Chance, determinism, and unsettledness

Abstract

A previously unrecognised argument against deterministic chance is introduced. The argument rests on the twin ideas that determined outcomes are settled, while chancy outcomes are unsettled, thus making cases of determined but chancy outcomes impossible. Closer attention to tacit assumptions about settledness makes available some principled lines of resistance to the argument for compatibilists about chance and determinism. Yet the costs of maintaining compatibilism may be higher with respect to this argument than with respect to existing incompatibilist arguments.

Clinical and molecular implications of structural changes to desmosomes and corneodesmosomes

Abstract

Desmosomes provide the main intercellular adhesive properties between epidermal keratinocytes. Their distribution becomes uneven in severe dermatitis, multiple allergies and metabolic wasting syndrome due to desmoglein 1 deficiency and the loss of intercellular adhesion or acantholysis. When keratinocytes differentiate from granular cells into cornified cells, desmosomes are transformed into corneodesmosomes and can provide stronger intercellular adhesion. Degradation of corneodesmosomes is a tightly regulated process involving a number of proteases and their inhibitors. Peripheral corneodesmosomes are protected from proteolytic degradation by the tight junction-related structures around them, and this construction provides the basis for the normal basket weave-like structure of the stratum corneum. In Netherton syndrome, which is caused by an absence of the protease inhibitor lymphoepithelial Kazal-type-related inhibitor, premature degradation of corneodesmosomes occurs due to the overactivation of proteases involved in corneodesmosome degradation. Inflammatory peeling skin disease is caused by the absence of corneodesmosin, a unique component of corneodesmosomes. In this disease, corneodesmosomes are structurally abnormal, and their adhesiveness is compromised, which leads to intercellular splitting between the stratum corneum and stratum granulosum. The better we understand desmosome and corneodesmosome ultrastructure in normal and diseased skin, the clearer the physiological and pathological mechanisms of epidermal integrity become.

Possible role of plasmacytoid dendritic cells in pityriasis lichenoides

Summary

Background

Plasmacytoid dendritic cells (pDCs) and their product, type I interferons (IFNs), have been implicated in the pathogenesis of several skin disorders characterized by an interface dermatitis (ID) pattern, such as lichen planus (LP). A type I IFN signature has previously been documented in pityriasis lichenoides (PL). Although pDCs are known to be the main source and most potent producers of local type I IFNs, their role in PL has not been investigated.

Aim

To investigate the role of pDCs in PL.

Methods

In total, 20 cases of PL and 20 comparable cases of LP were immunohistochemically tested for pDC occurrence and type I IFN production using anti-blood-derived dendritic cell antigen-2 (BDCA2; a specific pDC marker) and anti-myxovirus protein A (anti-MxA) antibodies (indirect marker of pDC activity), respectively. MxA is a well-established surrogate marker for local type 1 IFN production. A semiquantitative scoring system was used.

Results

pDCs were present in all 40 cases with no statistically significant difference between the two groups. MxA expression was intense and diffuse in the majority of PL and LP cases.

Conclusions

pDCs constitute a central component of the inflammatory infiltrate in PL, suggesting that PL shares with the other entities that exhibit an ID a common pDC-driven process through type I IFN production, which ultimately leads to the cytotoxic attack.

Still optimistic about HANDOC

Too much optimism in the HANDOC score

Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia

To the Editor—We appreciate the comments from Abers and Musher [1] in response to our recent article describing the association between procalcitonin and etiology in community-acquired pneumonia [2]. We agree with them that withholding antibiotics from a patient with bacterial pneumonia has the potential to harm the patient and should be avoided. Based on the principle of never missing bacterial pneumonia, nearly all adults with pneumonia diagnosed in the United States are empirically treated with antibiotics [3, 4]. However, many adults with pneumonia seem to have nonbacterial disease [2, 3], meaning that many do not benefit from antibiotics.

Procalcitonin as a Marker of Etiology in Community-Acquired Pneumonia

To the Editor—Ongoing analysis of data from the landmark Etiology of Pneumonia in the Community (EPIC) study of pneumonia in adults [1] continues to yield important and useful results. Self et al [2] have most recently analyzed procalcitonin levels in patients hospitalized for community-acquired pneumonia (CAP). They found that, with the usually accepted cutoff of 0.25 ng/mL, the sensitivity of a positive result in detecting bacterial pneumonia was 76.3%.

Gender Differences in the Association Between Synthetic Cannabinoid Use and Teen Dating Violence Victimization

Violence and Gender , Vol. 0, No. 0.

Alleviation of iron toxicity in Schinus terebinthifolius Raddi (Anacardiaceae) by humic substances

Abstract

One of the industrial pillars of Espírito Santo state, South East of Brazil, is iron-mining products processing. This activity brings to a high level of coastal pollution due to deposition of iron particulate on fragile ecosystems as mangroves and restinga. Schinus therebinthifolius (aroeira) is a widespread restinga species. This work tested iron toxicity alleviation by vermicompost humic substances (HS) added to aroeira seedlings in hydroponic conditions. Catalase, peroxidase, and ascorbate peroxidase are antioxidant enzymes that work as reactive oxygen species (ROS) scavengers: they increase their activity as an answer to ROS concentration rise that is the consequence of metal accumulation or humic substance stimulation. S. terebinthifolius seedlings treated with HS and Fe augmented their antioxidant enzyme activities significantly less than seedlings treated separately with HS and Fe; their significantly lower Fe accumulation and the slight increase of root and leaf area confirm the biostimulating effect of HS and their role in blocking Fe excess outside the roots. The use of HS can be useful for the recovery of areas contaminated by heavy metals.

Accuracy of the Compressed Sensing Accelerated 3D-FLAIR Sequence for the Detection of MS Plaques at 3T [ADULT BRAIN]

BACKGROUND AND PURPOSE:

The use of 3D FLAIR improves the detection of brain lesions in MS patients, but requires long acquisition times. Compressed sensing reduces acquisition time by using the sparsity of MR images to randomly undersample the k-space. Our aim was to compare the image quality and diagnostic performance of 3D-FLAIR with and without compressed sensing for the detection of multiple sclerosis lesions at 3T.

MATERIALS AND METHODS:

Twenty-three patients with relapsing-remitting MS underwent both conventional 3D-FLAIR and compressed sensing 3D-FLAIR on a 3T scanner (reduction in scan time 1 minute 25 seconds, 27%; compressed sensing factor of 1.3). Two blinded readers independently evaluated both conventional and compressed sensing FLAIR for image quality (SNR and contrast-to-noise ratio) and the number of MS lesions visible in the periventricular, intra-juxtacortical, infratentorial, and optic nerve regions. The volume of white matter lesions was measured with automatic postprocessing segmentation software for each FLAIR sequence.

RESULTS:

Image quality and the number of MS lesions detected by the readers were similar between the 2 FLAIR acquisitions (P = .74 and P = .094, respectively). Almost perfect agreement was found between both FLAIR acquisitions for total MS lesion count (Lin concordance correlation coefficient = 0.99). Agreement between conventional and compressed sensing FLAIR was almost perfect for periventricular and infratentorial lesions and substantial for intrajuxtacortical and optic nerve lesions. Postprocessing with the segmentation software did not reveal a significant difference between conventional and compressed sensing FLAIR in total MS lesion volume (P = .63) or the number of MS lesions (P = .15).

CONCLUSIONS:

With a compressed sensing factor of 1.3, 3D-FLAIR is 27% faster and preserves diagnostic performance for the detection of MS plaques at 3T.

Resting-State Functional MRI: Everything That Nonexperts Have Always Wanted to Know [REVIEW ARTICLE]

SUMMARY:

Resting-state fMRI was first described by Biswal et al in 1995 and has since then been widely used in both healthy subjects and patients with various neurologic, neurosurgical, and psychiatric disorders. As opposed to paradigm- or task-based functional MR imaging, resting-state fMRI does not require subjects to perform any specific task. The low-frequency oscillations of the resting-state fMRI signal have been shown to relate to the spontaneous neural activity. There are many ways to analyze resting-state fMRI data. In this review article, we will briefly describe a few of these and highlight the advantages and limitations of each. This description is to facilitate the adoption and use of resting-state fMRI in the clinical setting, helping neuroradiologists become familiar with these techniques and applying them for the care of patients with neurologic and psychiatric diseases.

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology.

MATERIALS AND METHODS:

Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient.

RESULTS:

All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N-acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed.

CONCLUSIONS:

Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment.

Review of the Imaging Features of Benign Osteoporotic and Malignant Vertebral Compression Fractures [REVIEW ARTICLE]

SUMMARY:

Vertebral compression fractures are very common, especially in the elderly. Benign osteoporotic and malignant vertebral compression fractures have extremely different management and prognostic implications. Although there is an overlap in appearances, characteristic imaging features can aid in the distinction between these 2 types of compression fractures. The aim of this review is to characterize the imaging features of benign and malignant vertebral compression fractures seen with CT, PET, SPECT, and MR imaging.

Development of High Signal Intensity within the Globus Pallidus and Dentate Nucleus following Multiple Administrations of Gadobenate Dimeglumine [PATIENT SAFETY]

BACKGROUND AND PURPOSE:

Previous studies have evaluated various gadolinium based contrast agents and their association with gadolinium retention, however, there is a discrepancy in the literature concerning the linear agent gadobenate dimeglumine. Our aim was to determine whether an association exists between the administration of gadobenate dimeglumine and the development of intrinsic T1-weighted signal in the dentate nucleus and globus pallidus.

MATERIALS AND METHODS:

In this single-center, retrospective study, the signal intensity of the globus pallidus, dentate nucleus, thalamus, and middle cerebellar peduncle was measured on unenhanced T1-weighted images in 29 adult patients who had undergone multiple contrast MRIs using exclusively gadobenate dimeglumine (mean, 10.1 ± 3.23 doses; range, 6–18 doses). Two neuroradiologists, blinded to the number of prior gadolinium-based contrast agent administrations, separately placed ROIs within the globi pallidi, thalami, dentate nuclei, and middle cerebellar peduncles on the last MR imaging examinations. The correlations between the globus pallidus:thalamus and the dentate nucleus:middle cerebellar peduncle signal intensity ratios with the number of gadolinium-based contrast agent administrations and cumulative dose were tested with either 1-tailed Pearson or Spearman correlations. A priori, P < .05 was considered statistically significant.

RESULTS:

Both the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncle ratios showed significant correlation with the number of gadolinium-based contrast agent administrations (r = 0.39, P = .017, and r = 0.58, P = .001, respectively). Additionally, the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncle ratios showed significant correlation with the cumulative dose of gadobenate dimeglumine (r = 0.48, P = .004, and r = 0.43, P = .009, respectively). Dentate nucleus hyperintensity was qualitatively present on the last MR imaging in 79.3%–86.2% of patients and in all patients who had received >10 doses.

CONCLUSIONS:

At high cumulative doses (commonly experienced by patients, for example, with neoplastic disease), gadobenate dimeglumine is associated with an increase in the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncles signal intensity ratios.

T2 Relaxometry MRI Predicts Cerebral Palsy in Preterm Infants [PEDIATRICS]

BACKGROUND AND PURPOSE:

T2-relaxometry brain MR imaging enables objective measurement of brain maturation based on the water-macromolecule ratio in white matter, but the outcome correlation is not established in preterm infants. Our study aimed to predict neurodevelopment with T2-relaxation values of brain MR imaging among preterm infants.

MATERIALS AND METHODS:

From January 1, 2012, to May 31, 2015, preterm infants who underwent both T2-relaxometry brain MR imaging and neurodevelopmental follow-up were retrospectively reviewed. T2-relaxation values were measured over the periventricular white matter, including sections through the frontal horns, midbody of the lateral ventricles, and centrum semiovale. Periventricular T2 relaxometry in relation to corrected age was analyzed with restricted cubic spline regression. Prediction of cerebral palsy was examined with the receiver operating characteristic curve.

RESULTS:

Thirty-eight preterm infants were enrolled for analysis. Twenty patients (52.6%) had neurodevelopmental abnormalities, including 8 (21%) with developmental delay without cerebral palsy and 12 (31.6%) with cerebral palsy. The periventricular T2-relaxation values in relation to age were curvilinear in preterm infants with normal development, linear in those with developmental delay without cerebral palsy, and flat in those with cerebral palsy. When MR imaging was performed at >1 month corrected age, cerebral palsy could be predicted with T2 relaxometry of the periventricular white matter on sections through the midbody of the lateral ventricles (area under the receiver operating characteristic curve = 0.738; cutoff value of >217.4 with 63.6% sensitivity and 100.0% specificity).

CONCLUSIONS:

T2-relaxometry brain MR imaging could provide prognostic prediction of neurodevelopmental outcomes in premature infants. Age-dependent and area-selective interpretation in preterm brains should be emphasized.

Iodine Extravasation Quantification on Dual-Energy CT of the Brain Performed after Mechanical Thrombectomy for Acute Ischemic Stroke Can Predict Hemorrhagic Complications [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Intracerebral hemorrhage represents a potentially severe complication of revascularization of acute ischemic stroke. The aim of our study was to assess the capability of iodine extravasation quantification on dual-energy CT performed immediately after mechanical thrombectomy to predict hemorrhagic complications.

MATERIALS AND METHODS:

Because this was a retrospective study, the need for informed consent was waived. Eighty-five consecutive patients who underwent brain dual-energy CT immediately after mechanical thrombectomy for acute ischemic stroke between August 2013 and January 2017 were included. Two radiologists independently evaluated dual-energy CT images for the presence of parenchymal hyperdensity, iodine extravasation, and hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations performed until patient discharge were reviewed for intracerebral hemorrhage development. The correlation between dual-energy CT parameters and intracerebral hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact test. Receiver operating characteristic curves were generated for continuous variables.

RESULTS:

Thirteen of 85 patients (15.3%) developed hemorrhage. On postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation were present in 100% of the patients who developed intracerebral hemorrhage and in 56.3% of the patients who did not (P = .002 for both). Signs of bleeding were present in 35.7% of the patients who developed intracerebral hemorrhage and in none of the patients who did not (P < .001). Median maximum iodine concentration was 2.63 mg/mL in the patients who developed intracerebral hemorrhage and 1.4 mg/mL in the patients who did not (P < .001). Maximum iodine concentration showed an area under the curve of 0.89 for identifying patients developing intracerebral hemorrhage.

CONCLUSIONS:

The presence of parenchymal hyperdensity with a maximum iodine concentration of >1.35 mg/mL may identify patients developing intracerebral hemorrhage with 100% sensitivity and 67.6% specificity.

Cutaneous sarcoidosis during rituximab treatment for microscopic polyangiitis: an uncommon adverse effect?

A novel mutation in TRPS1 in a patient with tricho-rhino-phalangeal syndrome type 1, accompanied by vesicoureteral reflux

Trichophyton verrucosum : an atypical infection on the pubis

Improvement of psoriasiform eruptions after resection of breast cancer

Progressive nodular histiocytosis improved by methotrexate

Dermoscopic characteristics of transient acantholytic dermatosis (Grover’s disease)

Herpes simplex virus reactivation: is it common or rare in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms?

Granulomatous reaction to permanent eyebrow makeup successfully treated with topical steroids in combination with topical tacrolimus

Comparative study of the clinical, histological, and biological characteristics of squamous cell carcinomas in areas previously treated with photodynamic therapy

Abstract

Background

Although photodynamic therapy (PDT) is an effective treatment option for non-melanoma skin cancer, the development of aggressive tumours in PDT-treated areas has been described.

Objectives

To evaluate the clinical, histological, and biological characteristics of squamous cell carcinomas (SCCs) in areas previously treated with PDT vs those arising in areas never treated with this therapeutic modality.

Materials & methods

Aretrospective observational studywas designed. We collected all cases of invasive SCCs in areas previously treated with PDT. The control group consisted of an equivalent number of SCCs randomly selected from the database of our pathology department. Expression of specific markers implicated in SCC progression, including p53, Ki67, COX-2, cyclin D1, E-cadherin, EGFR, survivin, and pERK, was analysed.

Results

A total of 699 patients were treated with PDT for non-melanoma skin cancer during the course of the study. Ten invasive SCCs arising in areas previously treated with methylaminolevulinate-PDT were diagnosed in six patients. The control group consisted of 10 invasive SCCs from 10 patients never treated with PDT. In the PDT group, the mean tumour size was significantly lower and the absence of ulceration was more frequent than in the control group (p<0.024 and p = 0.035, respectively). Adiffuse survivin staining pattern was observed in 90% of tumours in the PDT group versus 50% in the comparative group (p = 0.141).

Conclusion

The number of SCCs arising in areas previously treated with PDT was very low and did not differ significantly from that of SCCs developing in non-PDT-treated areas.

Pyoderma gangrenosum developing over a skin ulcer due to arteriovenous malformation

Clinical assessment of skin phototypes: watch your words!

Abstract

Background

Fitzpatrick skin phototype classification is widely used to assess risk factors for skin cancers. This skin type evaluation is easy to use in clinical practice but is not always applied as initially described, nor practiced in a standardisedway. This can have implications on the results of relevant dermato-epidemiological studies.

Objectives

To demonstrate, in a large multinational setting, that the phrasing of questions on sun sensitivity can have a strong impact on the perception and reporting of skin phototype, as well as the importance of a standardised procedure for phototype assessment.

Materials & methods

Using data collected from 48,258 screenees of the Euromelanoma campaign in six European countries from 2009 to 2011, we analysed the impact of change in the question phrasing on phototype classification in each country.

Results

Changing the wording of a question to assess the phototype of a person also significantly influenced the classification of phototypes in different countries (p<0.001 for each country). The difference essentially corresponded to a shift towards a less sun-sensitive skin type when a shorter question that did not include skin colour description was used. The only exception was Portugal where phototype was not patient-assessed and classification shifted towards a more sun-sensitive phototype. Results were statistically significant and highly consistent, irrespective of gender.

Conclusions

The phrasing of questions on skin type is important and substantially influences reporting. A standardized procedure to classify phototypes should be used in order to obtain comparable data between studies.

Cutaneous drug reactions: chemotherapy-induced hyperpigmentation

Nail apparatus melanoma in a Japanese population: a comparative study of surgical procedures and prognoses in a large series of 151 cases

Abstract

Background

Nail apparatus melanoma (NAM) is a rare subtype of malignant melanoma with a prevalence that varies among populations. Conservative surgical approaches for thin to intermediate NAMs have recently been reported, however, their adoption is controversial, and resulting long-term prognoses are unknown.

Objectives

The purpose of this study was to determine the prognosis of NAM in a sample Asian population, and to investigate whether there is a difference in the local control and overall survival (OS) rates according to the extent of resection of the primary tumour.

Materials & methods

We performed a retrospective study of NAM patients treated at five medical institutions in Japan between 2000 and 2013. Outcomes according to surgery (amputation vs. resection) and tumour thickness were compared.

Results

We identified 151 cases of NAM in 83 men and 68 women; the thumb (n = 50; 33.1%) and hallux (n = 55; 36.4%) were the most common sites. No local recurrence was detected following any of the surgical procedures; Kaplan-Meier survival analysis revealed that the surgical procedure type was not significantly associated with disease-free survival (p = 0.786) or OS (p = 0.997). Five-year OS rates according to tumour thickness were 100% for in situ, 94.4% for ≤1-mm, 91.7% for 1.01-2.0-mm, 72.7% for 2.01-4.0-mm, and 47.6% for ≥4.01-mm tumours.

Conclusion

Surgical procedure type does not influence survival as long as total primary tumour resection is accomplished. The prognosis of NAMis comparable to that of other types of melanoma.

Comparison of allergen responses based on the TRUE Test and IQ Chamber system in Korean patients

Abstract

Background

A comparison between responses to allergens based on the TRUE Test® (TT) and IQ® Chamber (IQC) in Europeans has been previously reported, however, no such study has been performed in Asians.

Objectives

To compare allergen responses using the TT and IQC (using the Korean standard series) in order to gather more information regarding the positive response rates for each allergen and the clinical value of IQC.

Materials & methods

Suspected contact dermatitis patients were enrolled and tested with 18 allergens using the TT and IQC.

Results

The test was performed in 214 patients. Simultaneous positive results for both tests were recorded in 242 cases (positive concordance rate: 66.7%). IQC yielded more positive results. Allergens with a high positive concordance rate were nickel sulphate (82.1%), thimerosal (78.6%), and p-phenylenediamine (73.3%). IQC mostly showed similar or higher positive rates than TT, with high concordance.

Conclusions

We recommend the IQC method as a screening test in patients with suspected contact dermatitis. To compensate for possible false positive results, careful history taking and a different patch test should be performed when appropriate.

Angiomyxolipoma of the thumb

sQUIZ your knowledge! Persistent facial plaques

Multiple myeloma presenting with acquired cutis laxa and primary systemic amyloidosis

Eosinophilic annular erythema localized on the neck

Fatal venous embolism in a patient with advanced extramammary Paget disease

Clinical outcomes of primary cutaneous anaplastic large cell lymphoma: data from a single Japanese centre

Chemically and size-resolved particulate matter dry deposition on stone and surrogate surfaces inside and outside the low emission zone of Milan: application of a newly developed “Deposition Box”

Abstract

The collection of atmospheric particles on not-filtering substrates via dry deposition, and the subsequent study of the particle-induced material decay, is trivial due to the high number of variables simultaneously acting on the investigated surface. This work reports seasonally resolved data of chemical composition and size distribution of particulate matter deposed on stone and surrogate surfaces obtained using a new method, especially developed at this purpose. A "Deposition Box" was designed allowing the particulate matter dry deposition to occur selectively removing, at the same time, variables that can mask the effect of airborne particles on material decay. A pitched roof avoided rainfall and wind variability; a standardised gentle air exchange rate ensured a continuous "sampling" of ambient air leaving unchanged the sampled particle size distribution and, at the same time, leaving quite calm condition inside the box, allowing the deposition to occur. Thus, the "Deposition Box" represents an affordable tool that can be used complementary to traditional exposure systems. With this system, several exposure campaigns, involving investigated stone materials (ISMs) (Carrara Marble, Botticino limestone, Noto calcarenite and Granite) and surrogate (Quartz, PTFE, and Aluminium) substrates, have been performed in two different sites placed in Milan (Italy) inside and outside the low emission zone. Deposition rates (30–90 μg cm⁻² month⁻¹) showed significant differences between sites and seasons, becoming less evident considering long-period exposures due to a positive feedback on the deposition induced by the deposited particles. Similarly, different stone substrates influenced the deposition rates too. The collected deposits have been observed with optical and scanning electron microscopes and analysed by ion chromatography. Ion deposition rates were similar in the two sites during winter, whereas it was greater outside the low emission zone during summer and considering the long-period exposure. The dimensional distribution of the collected deposits showed a significant presence of fine particles in agreement with deposition rate of the ionic fraction. The obtained results allowed to point out the role of the fine particles fraction and the importance of making seasonal studies.

Retrospective audit of patients referred for further treatment following Mohs surgery for non-melanoma skin cancer

Abstract

Background/Objectives

To describe the characteristics, subsequent management and outcomes of patients referred for further management following Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).

Methods

Retrospective analysis of patients referred to a quaternary cancer centre from 2000 to 2015.

Results

In total, 83 lesions in 82 patients were referred for further management; 52 (62%) were SCC and 80 (96%) were located in the head and neck. Reasons for referral included high-risk disease for consideration for adjuvant radiotherapy (37/83, 45%), inadequate resection (28/83, 34%) or recurrence following previous MMS (15/83, 17%). Fewer than 40% of the 69 referrals received from MMS surgeons included photos or an operative report and diagram.

There was discordance in pathology opinion in 11 (13%) of cases. Histopathology from MMS was reviewed in eight cases and there was discordance with the in-hospital pathology opinion in six of these. In-hospital re-excision was performed in 19 cases and in five of these the pathology report on the paraffin-sectioned re-excised tissue was discordant with prior MMS assessment. Significantly, two cases were associated with a misinterpretation of lymphocytic infiltrate as residual disease in patients with chronic lymphocytic leukaemia (CLL).

Conclusion

This study highlights some of the challenges and limitations of MMS. Early referral for multidisciplinary management is recommended when MMS resection margins are inadequate or uncertain, especially for high-risk SCC. We recommend that referrals be accompanied by histological material, as well as a detailed report with operative photos and diagrams. CLL can pose an intraoperative diagnostic challenge. Discrepancies in the interpretation of MMS slides present an opportunity for improvement, and our findings support the role of ongoing quality assurance programs.

Aesthetic Refinements after Radial Free Flap Phalloplasty: Optimizing the Donor Site and the Phallus

Background: Phalloplasty with radial forearm flap is the gold standard for female-to-male sex reassignment surgery. However, it leaves a stigmatizing forearm scar, and as the new phallus is created with the forearm's skin and fat, it does not look like that of a biological man. The aesthetic appearance of the donor site and the neophallus can be optimized after phalloplasty. In this study, we review refinement techniques (RTs) performed after radial forearm flap phalloplasty. Methods: We present a historical cohort of patients who underwent the following RTs: forearm fat grafting and localized laser in the forearm's scars, and micropigmentation of the neophallus. Patient's aesthetic satisfaction was evaluated using the Patient and Observer Scar Assessment Scale for the forearm's refinements and the Male Genital Self-Image Scale for the neophallus. Results: Between January 2014 and January 2016, 8 patients underwent forearm fat grafting with localized laser, and 7 patients micropigmentation of the neophallus after radial flap phalloplasties. All Patient and Observer Scar Assessment Scale parameters showed a statistically significant reduction between preoperative and postoperative values. Male Genital Self-Image Scale survey showed that all patients felt positively about their genitals after micropigmentation. Patients who underwent refinement procedures were highly satisfied with the aesthetic outcome and felt more confident. They also claim that they would choose to have the refinement procedure done again. Conclusions: The proposed RTs are minimally invasive interventions to complement and enhance female-to-male sex reassignment surgery with very few complications and excellent aesthetic results of both the forearm scars and the constructed phallus.

A Systematic Review of Autologous Platelet-Rich Plasma and Fat Graft Preparation Methods

Background: The addition of platelet-rich plasma (PRP) to adipose tissue may improve fat graft survival, although graft retention rates vary markedly between studies. To what extent this outcome heterogeneity reflects differing methodological factors remains unknown. This systematic review aims to synthesize and critically review methodological approaches to autologous PRP and fat cotransplantation in both human and animal studies. Methods: In accordance with PRISMA guidelines, Ovid MEDLINE, Scopus, and Cochrane Library databases were searched from inception to April 2017. Data were extracted from all in vivo studies involving autologous PRP and fat cotransplantation. A secondary aim was to assess reporting of technical detail; authors were not contacted to provide missing data. Results: From 335 articles, 23 studies were included in the qualitative synthesis. Some 21 were performed in humans and 2 in rabbits. Six studies were randomized control trials; the remainder reported on observational data. Methods of PRP extraction and activation varied markedly between studies. Fat graft preparation was comparatively more consistent. Methods of PRP and fat mixing differed significantly, especially with regards to relative volume/volume ratios. Conclusions: Our study represents the first systematic review of methodological factors in autologous PRP and fat cotransplantation. It demonstrates that technical factors in graft preparation and administration vary significantly between in vivo studies. Such methodological heterogeneity may explain observed differences in experimental and clinical outcomes. Reporting of key procedural information is inconsistent and often inadequate. These issues make meaningful evaluation of the PRP-enhanced fat grafting literature difficult and may limit its translation into clinical practice.

Treatment of persistent organic pollutants in wastewater using hydrodynamic cavitation in synergy with advanced oxidation process

Abstract

Persistent organic pollutants (POPs) are very tenacious wastewater contaminants. The consequences of their existence have been acknowledged for negatively affecting the ecosystem with specific impact upon endocrine disruption and hormonal diseases in humans. Their recalcitrance and circumvention of nearly all the known wastewater treatment procedures are also well documented. The reported successes of POPs treatment using various advanced technologies are not without setbacks such as low degradation efficiency, generation of toxic intermediates, massive sludge production, and high energy expenditure and operational cost. However, advanced oxidation processes (AOPs) have recently recorded successes in the treatment of POPs in wastewater. AOPs are technologies which involve the generation of OH radicals for the purpose of oxidising recalcitrant organic contaminants to their inert end products. This review provides information on the existence of POPs and their effects on humans. Besides, the merits and demerits of various advanced treatment technologies as well as the synergistic efficiency of combined AOPs in the treatment of wastewater containing POPs was reported. A concise review of recently published studies on successful treatment of POPs in wastewater using hydrodynamic cavitation technology in combination with other advanced oxidation processes is presented with the highlight of direction for future research focus.

Efficacy and Safety of Titanium Miniplates in Septorhinoplasty

This case series evaluates the efficacy and safety of titanium miniplates for cartilaginous graft fixation in patients undergoing septorhinoplasty.

The Epidemic of Guns

The shooting in Las Vegas, Nevada, that left 59 people dead, 10 times that number wounded, and thousands of people with the psychological distress from being present at the scene during and after the massacre has once again raised the issue of what we as a nation can and should do about guns. The solution lies in not just focusing on Las Vegas and the hundreds of other mass shootings that have occurred in the United States in the last 14 months, but rather to underscore that on average almost 100 people die each day in the United States from gun violence. The 36 252 deaths from firearms in the United States in 2015 exceeded the number of deaths from motor vehicle traffic crashes that year (36 161). That same year, the US Centers for Disease Control and Prevention reported that 5 people died from terrorism. Since 1968, more individuals in the United States have died from gun violence than in battle during all the wars the country has fought since its inception.

January-February Issue Highlights

W-Plasty vs Straight-Line Trichophytic Closure in Rhytidectomy

This cohort study of rhytidectomy compares W-plasty and the more traditional straight-line trichophytic closure techniques for aesthetic outcomes for scars along the posterior occipital hairline.

Suturing Technique for the Correction of the Obtuse Nasolabial Angle—Reply

In Reply We thank Drs D'Ascanio and Piazza for pointing us in the direction of the history of techniques dealing with the obtuse nasolabial angle. We had not found these articles in our literature search because of their early year of publication. Nevertheless, it is very interesting to read that a similar technique was already described in 1943 by Aufricht and republished by Daley in 1944. Furthermore, it is pleasing to know that that technique is successfully being used by the associates of "Valerio Micheli-Pellegrini" Study Center. First, it shows us the relevance of the described problem, and second, the tenability of the technique.

Association of Frontal and Lateral Facial Attractiveness

This study examines the association between frontal and lateral facial attractiveness and identifies anatomical features that may influence discordance between frontal and lateral facial beauty.

The Intercrural Fascia Graft in Primary Rhinoplasty

This Surgical Pearl presents a description and video of the technique of the intercrural fascia graft in primary rhinoplasty.

Opioid Use After Rhinoplasty

This case series examines patient use of an opioid-based drug after rhinoplasty to establish an optimal pain management regimen that also mitigates the misuse or diversion of physician-prescribed opioid medications.

Algorithm-Based Levator Aponeurectomy—Reply

In Reply We thank Innocenti et al for their comment on our article. Although we do agree that long-term follow-up is necessary to establish the longevity of each procedure, there is no consensus in the literature regarding the necessary minimum follow-up time for upper-eyelid ptosis repair procedures. Several prior published reports of ptosis repair techniques have had similar or less follow-up time compared with our study. In addition, Doxanas did not notice late recurrences of ptosis at 3 or more years after surgery. Frueh et al suggested that late recurrences may be related to the use of dissolvable sutures to repair or advance the aponeurosis. We use nondissolving sutures. In the study by Innocenti et al, it is unclear what type of sutures was used. In addition, it is unclear if their 7.5% recurrence rate represented late recurrences or if the failures occurred earlier and remained stable at 3 years. Using dissolvable sutures, Tucker and Verhulst noted stabilization of height in most eyelids at 6 weeks after surgery.

Technical Refinements and Outcomes of the Modified Anterior Septal Transplant

This case series describes the novel anterior septal transplant technique, which consists of complete resection of the caudal septum and reconstruction with extended spreader grafts and a columellar strut, without a separate caudal septal replacement graft.

Mental Health and Nasal Function—Reply

In Reply Mental health is complex, and there may be various domains that influence perception of nasal function. For instance, our research suggests that there is an association between mental well-being and self-esteem, but not between mental well-being and body dysmorphia. Dr Bartley's suggestion about the association between anxiety and a worse perception of nasal function is well worth consideration, especially given that patients with anxiety often experience symptoms of dyspnoea. Our study did not evaluate anxiety as a factor influencing perception of nasal function, nor was hyperventilation assessed during the objective nasal function testing, and this makes it difficult for us to comment on the association.

Standardized Cosmesis and Health Nasal Outcomes Survey

This study reports on the development and testing of a new patient-reported outcome measure to evaluate both functional and cosmetic rhinoplasty patients, the Standardized Cosmesis and Health Nasal Outcomes Survey.

Characteristics, Diagnosis, and Management of Ehlers-Danlos Syndromes

This review summarizes characteristics, assessment, and management of Ehlers-Danlos syndromes, which can be associated with surgical complications and should be identified preoperatively to facilitate optimal treatment.

Understanding Facial Perception Before and After Blepharoplasty

This web-based survey study examines the effect of blepharoplasty on facial perceptions and measures patient-reported ratings of fatigue before and after surgery to compare observer and patient perceptions.

A New Method for Photocephalometry

This Research Letter presents a simple technique for obtaining pre- and postoperative cephalometric measurements from digital facial photographs using an adhesive ruler affixed to sunglasses.

Long-term Outcomes in Subtotal Septal Reconstruction in Rhinoplasty

This study reviews the long-term outcomes of subtotal septal reconstruction in rhinoplasty and provides objective evidence of functional and aesthetic improvement.

Algorithm-Based Levator Aponeurectomy

To the Editor We read with great interest the article titled "Role of algorithm-based levator aponeurectomy in small-incision external ptosis surgery for involutional ptosis" by Repp et al. The authors clearly described a new surgical algorithm for treatment of involutional ptosis considering the biomechanical property of the superior levator complex. Aponeurotic ptosis is the most common type of acquired ptosis, resulting from involutional changes of the levator aponeurosis as a consequence of its gradual stretching or attenuation of its strength. We congratulate Repp et al for the new technique proposed to control the aponeurosis to standardize the amount of stress placed on it among different patients. The algorithm is very interesting because it allows calculation of the amount of aponeurosis resection needed, minimizing the variable depending on the operator, and thus standardizing the method of surgical correction.

Hybrid Cartilage-Modifying Otoplasty Technique and Outcomes

This observational study compares preoperative and postoperative measurements of the ears of patients who underwent hybrid cartilage-modifying otoplasty.

Suturing Technique for the Correction of the Obtuse Nasolabial Angle

To the Editor We read the article, "The Columella Retraction Suture: A Powerful Suture Technique," by Nolst Trenité and Nolst Trenité, and watched the related video. We congratulate the authors on their work; however, some aspects should be underlined in their study.

Virtual Surgery for the Nasal Airway

This cross-sectional study examines survey data from surgeons to determine whether virtual surgery planning via computational fluid dynamics for nasal airway obstruction procedures affects surgeon decision making.

Degradation behavior of triclosan by co-exposure to chlorine dioxide and UV irradiation: influencing factors and toxicity changes

Abstract

This study investigated the transformation of triclosan (TCS) following co-exposure to UV irradiation and ClO₂. Special attention was given to understand the influencing of water quality parameters and toxicity changes during the co-exposure process. The results show that the co-exposure process prompted TCS elimination quickly and effectively, with more than 99% of TCS degraded under the experimental conditions. The molar yield ratios of 2,4-dichlorophenol/TCS (2,4-DCP/TCS) were calculated to be 35.81–74.49%; however, the by-product of 2,8-dichlorodibenzop-dioxin (2,8-Cl₂DD) was not detected. The TCS degradation was sensitive to ClO₂ dosage, pH, H₂O₂, and natural organic matter (NOM), but not to the carbonate (CO₃²⁻) concentration. Neutral and slightly alkaline condition were favorable to TCS elimination. The TCS removal rate increased from 85.33 to 99.75% when the ClO₂ concentration increased from 0.25 to 1.5 mg L⁻¹. TCS degradation can be promoted at low NOM level (1, 3, and 5 mg L⁻¹), whereas was inhibited at high NOM concentrations of 7 and 9 mg L⁻¹. While adding H₂O₂, the degradation rate of TCS increased with increasing H₂O₂ concentration from 1 to 3 mg L⁻¹; however, too low or overdosed H₂O₂ (0.5 and 5 mg L⁻¹) hindered TCS degradation. Based on the results of a microtox bioassay, the toxicity did not change following the co-exposure process.

Can Cd translocation in Oryza sativa L. be attenuated by arbuscular mycorrhizal fungi in the presence of EDTA?

Abstract

Arbuscular mycorrhizal (AM) fungi play an important role in plant tolerance of heavy metal contamination. In this study, a pot experiment was conducted to illustrate the effects of the two AM fungi species Funneliformis mosseae (Fm) and Rhizophagus irregularis (Ri) on plant growth of Oryza sativa L. either with or without ethylenediamine tetraacetate (EDTA) addition and during exposure to five Cd concentrations (in the range of 0–5 mg kg⁻¹). The results showed that Fm inoculation achieved greater mycorrhizal colonization and mycorrhizal dependency indexes than Ri inoculation. In addition, the effects of AM fungi on Cd biosorption and translocation in rice were also investigated in the presence of EDTA. Despite cooperative adsorption, the Freundlich isotherm could describe the biosorption effects of Cd on rice roots regardless of AM fungi inoculation or EDTA addition. Cd concentrations in mycorrhizal roots increased but decreased in mycorrhizal shoots in contrast to the control treatment. Although EDTA addition negatively inhibited the uptake of Cd to mycorrhizal shoots, lower translocation factor (TF) and bioconcentration factor (BCF) were still observed in treatments with EDTA compared to control treatment. Our findings suggest that Ri and Fm inoculation enhanced Cd immobilization in the roots, thus preventing Cd entry into the food chain during exposure to low and high Cd stress, respectively.

Enhanced reductive dechlorination of 1,1,1-trichloroethane using zero-valent iron-biochar-carrageenan microspheres: preparation and microcosm study

Abstract

In this study, a composite remediation material for the enhanced reductive dechlorination (ERD) of 1,1,1-trichloroethane (1,1,1-TCA) in aqueous solution was prepared. This material was comprised of biochar as the carrier and adsorbent, and carrageenan (CG) as the embedding medium to entrap the organic carbon sources and zero-valent iron (ZVI). We determined the suitable biochar dosage and organic carbon source in the composite alongside the optimal preparation conditions. Furthermore, using an anaerobic microcosm study, we discussed the performance and possible mechanisms of the composite on 1,1,1-TCA removal in aqueous solution. From this, we found that the suitable dosage of biochar in water during the preparation of composite microspheres was 0.2% (w/v). Under this condition, the biochar had a strong capacity to adsorb 1,1,1-TCA with a removal efficiency of 84.2%. Soluble starch was selected as the appropriate organic carbon source, because starch-microspheres show an excellent slow-release effect in water. The optimal preparation conditions of microspheres were identified as follows: 2% CG (w/v) colloidal solution, 6% CaCl₂ (w/v) solution, and a 12-h curing time. After 25-day incubation with the composite prepared under optimized conditions, the removal efficiency of 1,1,1-TCA was 95.68%, which was 24.69% higher than that observed in the microcosm with a commercial remediation material. The scanning electron microscopy (SEM) images show that the amounts of ZVI and soluble starch inside the microsphere decreased obviously, while the biochar amount remained about the same. This indicates that 1,1,1-TCA in aqueous solution was mainly removed via soluble starch-enhanced biotic reductive dechlorination and ZVI-enhanced abiotic reductive dechlorination. The changes in microbial community structure demonstrate that the composite stimulated the activities of functional anaerobic bacteria, in particular, regarding dechlorination and fermentation abilities in the microcosm, therefore enhancing the anaerobic biodegradation of 1,1,1-TCA. This study suggests that the composite, entrapping biochar, ZVI, and organic carbon source in CG microspheres can significantly enhance the reductive dechlorination of 1,1,1-TCA in aqueous solution. We anticipate this novel remediation material could be successfully applied to the in situ ERD remediation of natural groundwater mainly contaminated with 1,1,1-TCA.

Letter to the Editor on “Chrysotile and rock wool fibers induce chromosome aberrations and DNA damage in V79 lung fibroblast cells”

Angiomatosis of the Orbit: Clinical, Imaging, and Histologic Findings.

Angiomatosis is a complex vascular malformation that denotes a clinically extensive hemangioma, which either involves multiple tissue planes or extensively infiltrates 1 type of tissue. It is a rare condition characterized by diffuse proliferation of blood vessels admixed with fat and fibrotic tissue. Typically, this process involves the limbs in multiple tissue planes, including dermis, subcutis, muscle, and bone. In this report, the authors present the first case of angiomatosis infiltrating the orbit, controlled effectively with a combination of systemic steroids, radiation, and beta-blocker therapy. The characteristic imaging and histologic features and management options are discussed. (C) 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Apocrine Cystadenoma of the Eyelid: A Rare Palpebral Neoplasm. Report of 2 Cases.

The authors report 2 cases of apocrine cystadenoma of the eyelid, 1 of which was studied with immunohistochemical and other special stains. While a previous report describes the tumor in a palpebro-orbital location, no other detailed descriptions of a purely eyelid location are present in the literature. Apocrine cystadenoma occupies an unusual portion of the spectrum of Moll gland tumors of the eyelid. It has no definitive clinical characteristics and may be diagnosed pathologically by hematoxylin-eosin-stained sections. (C) 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

A Common Procedure With an Uncommon Pathology: Triamcinolone Acetonide Eyelid Injection.

Local corticosteroid injections are frequently employed by ophthalmologists to treat a variety of ocular, periocular, and orbital inflammatory conditions. Triamcinolone acetonide is a slowly dissolving crystalline corticosteroid that is often used for this purpose because of its prolonged anti-inflammatory effect. On occasion, previously injected corticosteroid material persists in tissues longer than anticipated, creating nodules that may masquerade as other disease conditions, or appearing incidentally in excised lesions on histopathologic examination. The histopathologic features of corticosteroid residues are unfamiliar to most ophthalmic pathologists and general pathologists. These features are described herein. Triamcinolone acetonide deposits in the skin appear as pale eosinophilic lakes of acellular frothy material on hematoxylin-eosin staining and are occasionally surrounded by a mild inflammatory reaction. (C) 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Apremilast Use in a Case of Cicatricial Ectropion Secondary to Severe Lamellar Ichthyosis.

Ichthyosis is a cutaneous disorder characterized by excessive amounts of dry thickened skin surface scales. Ocular manifestations of ichthyosis include cicatricial ectropion, which may cause exposure keratoconjunctivitis and rarely corneal perforation. Topical emollients, anti-inflammatory ointments, and systemic retinoids have been used to control the disease process, while surgical correction with donor graft has been reserved for severe cases involving corneal exposure. The authors report a case of a Caucasian male with lamellar ichthyosis with severe bilateral upper and lower eyelid cicatricial ectropion and corneal ulceration requiring surgical correction. Treatment with apremilast, a novel phosphodiesterase-4 inhibitor, for the treatment of a concomitant plaque psoriasis achieved good control of his skin diseases and minimized the recurrence of eyelid ectropion. (C) 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Lymphedema-Distichiasis Syndrome in a Male Patient Followed for 16 Years.

Distichiasis is a challenging condition that may require multiple surgical interventions. Besides ophthalmologic concerns in children, distichiasis may be part of the lymphedema-distichiasis syndrome, which presents with lymphedema of variable time of onset. Other significant systemic disorders such as coarctation of the aorta and varicose veins have been reported in association with this syndrome and must be reviewed for proper patient care. The authors report the case of a 22-year-old male patient who had been treated for distichiasis and followed for 16 years. At his initial evaluation, at 6 years of age, he presented solely with ocular complaints due to distichiasis. Only after 13 years of repeated ophthalmic treatments and continuous follow up, lymphedema was observed. Lymphedema-distichiasis syndrome diagnosis must be considered in children with distichiasis, even in the absence of lymphedema. (C) 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Association of Involutional Lower Eyelid Entropion with Reduced Upper Eyelid Position Relative to the Corneal Light Reflex: Quantification of Facial Asymmetry.

Purpose: To investigate the association between upper eyelid position relative to the corneal light reflex (MRD1) and to delineate an association between eyelid height and involutional lower eyelid entropion. Methods: Retrospective study of patients presenting for entropion repair to an academic ophthalmic plastic surgery service. A total of 111 patients were included in the study; 95 had unilateral involutional lower eyelid entropion, and 16 had bilateral lower eyelid entropion. Patients with a history of previous eyelid surgery, trauma, upper eyelid entropion, or cicatricial changes were excluded from the study. Results: Of the 95 patients with unilateral involutional lower eyelid entropion, 45 (47.4%) had a lesser MRD1 on the side ipsilateral to the involutional lower eyelid entropion. In this unilateral group, the mean MRD1 (+/- standard deviation) on the ipsilateral to the involutional lower eyelid entropion was 2.9 (+/-1.2) mm, while the mean MRD1 on the contralateral side was 3.3 (+/-1.0) mm. This difference was 0.4 mm and was statistically significant (p

Mesenchymal Chondrosarcoma of the Lacrimal Gland.

A 23-year-old woman presented with right-sided painless proptosis that developed in 12 months. MRI studies demonstrated a well-delineated tumorous enlargement of the right lacrimal gland with homogenous signal intensity and compressing the globe. The tumor was removed totally and in 1 piece with the tentative diagnosis of a pleomorphic adenoma. Pathologic examination revealed biphasic neoplastic elements, which were composed of the cartilaginous matrix and small round cell component. Immunohistopathological examination showed positive CD99 staining and negative reaction to S100, panCK, and CD15. The patient then received a total of 64 Gy orbital radiotherapy in 32 fractionations. There has been no recurrence or metastasis during 14 months of follow up. This case showed that mesenchymal chondrosarcoma may arise from the lacrimal gland and must be considered in the differential diagnosis of lacrimal gland tumors in young adults. (C) 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Adenocarcinoma of Pigmented Ciliary Epithelium in a Child With Aicardi Syndrome and Congenital Microphthalmia With Cyst.

A 5-year-old girl with Aicardi syndrome and microphthalmia with cyst of the OD presented with progressive enlargement of the cyst causing pain. Microophthalmia with inferior cyst (35 x 25 x 12 mm) was noted at birth, and Aicardi syndrome was diagnosed at 10 months by the presence of the classic triad of callosal agenesis, infantile spasms, and chorioretinal lacunae. She underwent enucleation with cyst resection, and subsequent reconstruction with a dermis fat graft. Histopathologic study revealed adenocarcinoma of the pigmented ciliary epithelium. Full-body metastatic workup was negative. Adenocarcinoma of the pigmented ciliary epithelium is an extremely rare eye tumor with only 4 documented cases in the literature, none arising in a microophthalmic eye with cyst. Aicardi syndrome is also a rare disease that has been associated with increased incidence of malignancy and ocular abnormalities, but has never been described in association with microophthalmia with cyst or with adenocarcinoma of the pigmented ciliary epithelium. Herein, the authors present a review of the case and relevant literature. (C) 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Meningoencephalocele and Cerebrospinal Fluid Leak Complicating Orbital Decompression.

A 51-year-old man who had undergone right orbital decompression 5 months earlier developed a meningoencephalocele extending in the right sphenoid sinus through a skull base defect of the right ethmoid, sphenoid, and frontal bones. The authors report the third case to their knowledge of meningoencephalocele with cerebrospinal fluid leak after orbital decompression and discuss its management and measures that can be taken to prevent this rare but serious complication. (C) 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Atypical Presentation of Squamous Papilloma.

No abstract available

Sphenoid Dysplasia: A Rare Presentation of Infantile Myofibroma.

The authors report a case of isolated congenital orbital myofibroma causing sphenoid dysplasia and presenting as global restriction of extraocular motility and ptosis in a neonate. Sphenoid wing dysplasia is most commonly associated neurofibromatosis 1 but this patient had no evidence of neurofibromatosis on clinical examination and genetic testing. Congenital orbital myofibroma can have secondary effects on bone and likely the lesion was present early in development leading to aplasia of the sphenoid bone. To the best of the authors' knowledge, this is the first reported case of sphenoid wing aplasia secondary to congenital orbital myofibroma independent of neurofibromatosis 1. (C) 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Application of experimental design for the optimization of artificial neural network-based water quality model: a case study of dissolved oxygen prediction

Abstract

This paper presents an application of experimental design for the optimization of artificial neural network (ANN) for the prediction of dissolved oxygen (DO) content in the Danube River. The aim of this research was to obtain a more reliable ANN model that uses fewer monitoring records, by simultaneous optimization of the following model parameters: number of monitoring sites, number of historical monitoring data (expressed in years), and number of input water quality parameters used. Box–Behnken three-factor at three levels experimental design was applied for simultaneous spatial, temporal, and input variables optimization of the ANN model. The prediction of DO was performed using a feed-forward back-propagation neural network (BPNN), while the selection of most important inputs was done off-model using multi-filter approach that combines a chi-square ranking in the first step with a correlation-based elimination in the second step. The contour plots of absolute and relative error response surfaces were utilized to determine the optimal values of design factors. From the contour plots, two BPNN models that cover entire Danube flow through Serbia are proposed: an upstream model (BPNN-UP) that covers 8 monitoring sites prior to Belgrade and uses 12 inputs measured in the 7-year period and a downstream model (BPNN-DOWN) which covers 9 monitoring sites and uses 11 input parameters measured in the 6-year period. The main difference between the two models is that BPNN-UP utilizes inputs such as BOD, P, and PO₄³⁻, which is in accordance with the fact that this model covers northern part of Serbia (Vojvodina Autonomous Province) which is well-known for agricultural production and extensive use of fertilizers. Both models have shown very good agreement between measured and predicted DO (with R² ≥ 0.86) and demonstrated that they can effectively forecast DO content in the Danube River.

Teratogenic effects induced by chitosan oligosaccharide in Wistar female rat Rattus norvegicus

Abstract

The aim of this research is to investigate the teratogenic effects of chitosan oligosaccharide in Wistar female rats (Rattus norvegicus). Chitosan LD50 value was calculated by probit analysis. High dose, 1/10 LD50 which equal to 150 mg/kg body weight, and low dose, 1/30 LD50 which equal to 50 mg/kg body weight, were administrated orally to Wistar female rats to examine the teratogenic effect during organogenesis period from 6th day to 15th day of gestation. Treated and control rats were sacrificed and their foetuses were examined for external, skeletal and visceral anomalies, number and length of foetuses and their weights. Obtained results showed toxicity and teratogenic effects of chitosan on treated rats and their progenies, i.e. high fetal mortality, offspring's weight and length reduction, and high incidence of fetal external, skeletal and visceral abnormalities. This suggested that chitosan is a teratogenic compound, restricted to current results from orally treated Wistar rats.

Adverse Events in Facial Implant Surgery and Associated Litigation

This cross-sectional study examines complications and litigation following facial implant surgery.

ICT, openness and CO 2 emissions in Africa

Abstract

This study investigates how information and communication technology (ICT) complements globalisation in order to influence CO₂ emissions in 44 Sub-Saharan African countries over the period 2000–2012. ICT is measured with internet penetration and mobile phone penetration whereas globalisation is designated in terms of trade and financial openness. The empirical evidence is based on the generalised method of moments. The findings broadly show that ICT can be employed to dampen the potentially negative effect of globalisation on environmental degradation like CO₂ emissions. Practical, policy and theoretical implications are discussed.

Comparison of Enalapril, Candesartan and Intralesional Triamcinolone in Reducing Hypertrophic Scar Development: An Experimental Study

Abstract

Background

The purpose of this study was to compare the effects of oral enalapril, an angiotensin-converting enzyme inhibitor (ACE-I), oral candesartan, an angiotensin receptor blocker (ARB), and intralesional corticosteroid treatments in reducing scar formation.

Methods

Twenty male rabbits were divided into five study groups: A (sham), B (control), C (ACE-I), D (ARB) and E (intralesional corticosteroid). The rabbit ear hypertrophic scar model was used. The hypertrophic scars were photographed and analyzed with the program ImageJ quantitatively to determine the degree of collagen fibers. The scar elevation index (SEI) was calculated at the end of the 40th day. Tissue samples were stained with hematoxylin and eosin and Masson's trichrome and examined under light microscopy for the determination of fibroblast number, epithelization, vascularization, inflammation and fibrosis.

Results

The SEI was the highest in the control group with the highest number of fibroblasts under the epithelium. In the steroid group, the SEI was significantly lower than both the ACE-I (p: 0.02) and ARB (p: 0.001) groups. The density of type 1 collagen fibers was the lowest in the control group, whereas type 3 collagen fibers were highest in that group. The ACE-I and ARB groups were similar regarding densities of type 1 and type 3 collagen fibers. The density of type 1 collagen fibers was the highest in the steroid group, whereas the density of type 3 collagen fibers was the lowest in that group.

Conclusions

Enalapril, candesartan and intralesional steroid therapies were all effective in reducing scar tissue development; however, enalapril and steroid groups revealed better results.

No Level Assigned

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

Therapieoptionen bei Sarkomen an der Wirbelsäule

Zusammenfassung

Hintergrund

Sarkome an der Wirbelsäule stellen aufgrund ihrer Heterogenität, Seltenheit und anatomischen Lage eine große Herausforderung für die Behandelnden dar.

Fragestellung

Diskutiert werden die Behandlungsmöglichkeiten (State-of-the-art).

Material und Methode

Es werden die aktuelle Literatur, Expertenmeinungen und Konsensempfehlungen internationaler Expertengremien diskutiert.

Ergebnisse

Es gibt folgende Konsensus-Empfehlungen: a) Osteosarkom: kombinierte Therapie: neoadjuvante Chemotherapie/En-bloc-Resektion/Strahlenresistenz; b) Ewing-Sarkom: kombinierte Therapie: neo- und adjuvante Chemotherapie/Restaging und Bestimmung des Regressionsgrads vor En-bloc-Resektion zwingend/En-bloc-Resektion und/oder Radiotherapie; c) Chondrosarkom: wenn möglich En-bloc-Resektion. Intensitätsmodulierte Radiotherapie scheint selektiv eine primäre oder adjuvante Option zu sein.

Etablierte Operationsverfahren (En-bloc-Resektion) kombiniert mit neuen Techniken (Implantate, Materialen/3D-Navigation), präziseren Bestrahlungsoptionen (intensitätsmodulierte Photonenbestrahlung) und Anwendung von Partikelstrahlung lassen eine Verbesserung der Therapieergebnisse erwarten.

Schlussfolgerung

Das beste Outcome haben Patienten, welche von Beginn an (bereits zur Biopsie) einem ausgewiesenen Tumorzentrum zugewiesen werden. Das Behandlungskonzept ist immer multidisziplinär.

Molecular characterization of a series of 990 index patients with albinism

Summary

Albinism is a clinically and genetically heterogeneous disease characterized by variable degrees of hypopigmentation and by nystagmus, foveal hypoplasia, and chiasmatic misrouting of the optic nerves. The wide phenotypic heterogeneity impedes the establishment of phenotype-genotype correlations. In order to obtain a precise diagnosis we screened the 19 known albinism genes in 990 index patients using targeted next generation sequencing (NGS) and high resolution comparative genomic hybridization. A molecular diagnosis was obtained in 72.42% of patients. 245 new pathogenic variants were identified. Intragenic rearrangements represented 10.8% of all pathogenic alleles. NGS panel analysis allowed establishing a diagnosis for the rarest forms of the disease which could not be diagnosed otherwise. Because of the clinical overlap between the different forms of the disease, diagnosis nowadays clearly relies on molecular grounds.

This article is protected by copyright. All rights reserved.

EVITA - A double-blind, vehicle controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity

Abstract

Background

Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab.

Patients and Methods

Patients receiving 1st line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary endpoints comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash.

Results

A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anti-cancer treatment was comparable in both arms.

Conclusion

The primary endpoint of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.

Transcriptional Regulation of the Mannan Utilization Genes in the Alkaliphilic Bacillus sp. N16-5

Abstract

Bacillus sp. N16–5 is an alkaliphile with great ability of utilizing mannan. Its mannan utilization gene cluster has been identified in a previous study. The ManR protein encoded by the cluster was predicted to be a LacI family regulator, and the transcription level of the mannan utilization gene cluster was upregulated after the manR gene was deleted, indicating that ManR is the repressor of this cluster. The transcription of the related genes was downregulated when manH, encoding the extracellular substrate-binding domain of the manno-oligosaccharide transporter, was deleted. Furthermore, isothermal titration calorimetry revealed that mannotetraose and mannopentose are ligands of ManR. These results all corroborate the hypothesis that the mannan utilization gene cluster is repressed by the transcription regulator ManR, and that the repression is removed when it binds to manno-oligosaccharides, which are generated by mannan degradation and transported into the cell by a specific transporter.

Extended-spectrum β-lactamase-producing Escherichia coli contributes to the survival of cefotaxime-susceptible E. coli under high concentrations of cefotaxime by acquisition of increased AmpC expression

Abstract

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-E) are becoming increasingly widespread in Vietnam. Antibiotics are detected in many Vietnamese foods; however, the effect of ESBL-E and antibiotic consumption on intestinal bacteria has not been studied sufficiently. Here, we investigated the effect of oral administration of ESBL-E (TB19) and cefotaxime on luminescence-emitting cefotaxime-sensitive E. coli (X14). Mice were given water containing TB19 and then received three injections of 1.0 × 10⁸ CFU of X14 harboring a luciferase gene. The mice were administered 100 μg of cefotaxime and luminescent bacteria were monitored over 24 h, following which luminescent bacteria were isolated from mouse feces. Luminescence continued to be detected in mice administered TB19 24 h after cefotaxime ingestion. Fecal analysis revealed two types of luminescent colonies, cefoxitin-resistant E. coli (X14-R) and Pseudomonas aeruginosa. Pulse-field gel electrophoresis confirmed that X14-R was a clonal strain of X14, suggesting that X14 survived using ESBLs originating from TB19 and acquired cefoxitin resistance due to cefotaxime consumption. Moreover, in vitro analysis of X14 indicated that expression of the ampC gene was upregulated by cefotaxime. Overall, ESBL-E and cefotaxime promoted the expansion of cefoxitin-resistant E. coli in the absence of plasmid-mediated gene transfer.

Multi-platform Next-generation Sequencing Identifies Novel RNA Molecules and Transcript Isoforms of the Endogenous Retrovirus Isolated from Cultured Cells

Abstract

In this study, we applied short- and long-read RNA sequencing techniques, as well as PCR analysis to investigate the transcriptome of the porcine endogenous retrovirus (PERV) expressed from cultured porcine kidney cell line PK-15. This analysis has revealed six novel transcripts and eight transcript isoforms, including five length and three splice variants. We were able to establish whether a deletion in a transcript is the result of the splicing of mRNAs or of genomic deletion in one of the PERV clones. Additionally, we re-annotated the formerly identified RNA molecules. Our analysis revealed a higher complexity of PERV transcriptome than it was earlier believed.

Closing in on the Reservoir: Proactive Case Detection in High-Risk Groups as a Strategy to Detect Plasmodium falciparum Asymptomatic Carriers in Cambodia

Abstract

Background

In the frame of elimination strategies of Plasmodium falciparum (Pf), active case detection has been recommended as complementary approach to the existing passive case detection programs. We trialed a polymerase chain reaction (PCR)–based active detection strategy targeting asymptomatic individuals, named proactive case detection (PACD), with the aim of assessing its feasibility, the extra yield of Pf infections, and the at-risk population for Pf carriage status.

Methods

A pilot of PACD was conducted in 3 villages in Chey Saen district (Preah Vihear province, Cambodia), from December 2015 to March 2016. Voluntary screening and treatment, following health promotion sensitization, was used as mobilization strategy.

Results

A total of 2802 persons were tested, representing 54% of the population. PACD (n = 30) and the respective reactive case detection (RACD) (n = 3) identified 33 Pf carriers, approximately twice as many as the Pf infections (n = 17) diagnosed in passive case detection and respective RACD, by health centers and village malaria workers using PCR, in the same villages/period. Final positivity rate was 1.07% (30/2802). People spending nighttime in forests and plantations were found to be at increased risk for Pf infection (odds ratio [OR], 3.4 [95% CI, 1.6–7.2], P = .002 and OR, 2.3 [95% CI, 1.1–4.9], P = .03, respectively).

Conclusions

We demonstrated the usefulness of the PACD component in identifying Pf asymptomatic carriers. Social mobilization and promotion led to good attendance of specific risk groups, identified to be, in the Cambodian context, individuals spending nighttime in forest and plantations.

Sero-efficacy of Vi-polysaccharide tetanus-toxoid typhoid conjugate vaccine (Typbar-TCV)

Abstract

Background

Salmonella Typhi is the major cause of enteric fever in lower income countries. New conjugate vaccines show promise as public health interventions, however there are no efficacy data available from endemic areas.

Methods

Data were obtained from a previously published phase 3 randomised controlled trial comparing Vi-polysaccharide tetanus-toxoid conjugate vaccine (Typbar-TCV; Bharat Biotech Intl Ltd, India): (Vi-TT) with Vi-polysaccharide (Typbar; Bharat Biotech Intl Ltd, India): (Vi-PS) in participants aged 2- 45 years. An additional open-label arm administered Vi-TT to children aged 6 months to 23 months. The proportion of participants with presumed clinical or subclinical infection ('seroincidence'), was determined using mixture models and compared using relative risks.

Results

81/387 (21%) participants were classified as having presumed typhoid infection during the 2 year period post-vaccination.Seroincidence was lower in those randomised to Vi-TT than Vi-PS in those aged 2-45 years; 21/155 (13.5%) vs 47/129 (36.4%); RR 0.372 (95%CI 0.235–0.588), p<0.0001 and in those aged 2-15 years RR 0.424 (95%CI 0.231–0.778), p=0.0039. There was no difference in seroincidence in those receiving Vi-TT aged 2-45 years and those aged 6-23 months; 21/155 (13.5%) vs 13/103 (12.6%); RR 1.073 (0.563, 2.046), p=0.8293. Vaccine seroefficacy was 85% (95%CI 80–88%).

Conclusion

This is the first field estimate of the seroefficacy of a Vi-TT vaccine and shows that Typbar TCV substantially reduces the number of serologically defined (sub)clinical infections in infants, children and adults. These results support the recent World Health Organisation recommendations for deployment of typhoid conjugate vaccines in high burden areas.

Usefulness of the serial measurement of Vi antibodies

Typhoid feverVi antibodiesconjugate Vi Vaccinevaccine efficacy

Alternative soilless media using olive-mill and paper waste for growing ornamental plants

Abstract

Peat-based growing media are not ecologically sustainable and peat extraction threatens sensitive peatland ecosystem. In this study, olive-stone waste (OSW) and paper waste (PW) were used in different ratios—as growing media—for ornamental crop production, as peat (P) substitutes. Marigold (Calendula officinalis L.), petunia (Petunia x hybrita L.) and matthiola (Matthiola incana L.) plants were grown in (1) P (100%), (2) P:OSW (90%:10%), (3) P:OSW (70%:30%), and (4) P:OSW:PW (60%:20%:20%). The physicochemical properties of these substrates and the effects on plant growth were determined. The addition of 10–30% OSW into the substrate increased marigold height compared to plants grown in 100% peat. No differences in plant size, plant biomass (leaves and flowers), and dry matter content were found. Adding PW, in combination with OSW, maintained marigold height and total number of flowers produced to similar levels as in plants grown in 100% peat. In matthiola, adding 30% OSW into the substrate reduced plant size and fresh weight, but not plant height. No differences were observed when plants grew in lower OSW (i.e., 10%) content. Petunia's height, its total number of flowers and flower earliness (flower opening) were increased in the presence of OSW compared to the plants grown in 100% peat. The addition of OSW did not affect petunia's size and fresh weight among treatments. The addition of PW suppressed several plant growth-related parameters for both matthiola and petunia. The insertion of OSW did not change leaf chlorophyll content whereas the presence of PW decreased chlorophylls for marigold, petunia, and matthiola. Both OSW and PW altered the content of total phenolics and antioxidant capacity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) in leaves and flowers for marigold and petunia. Both 30% OSW and PW increased antioxidative enzyme metabolism due to the increased damage index and lipid peroxidation observed in plants. Leaf N and P content decreased in PW-based media, while matthiola displayed visual phytotoxicity symptoms when PW was added into the substrate. The present work indicates that up to 30% of OSW can replace peat for marigold and petunia growing and only up to 10% of OSW for matthiola, while the addition of PW on top of OSW is not recommended, so further research is needed.

Histopathological findings in pregnancy associated cutaneous hyperpigmentation.

Abstract

Hyperpigmentation in pregnancy is a common phenomenon, experienced to some degree by up to 90% of pregnant women. It mainly involves sun-exposed areas, but it can extend to non-exposed zones. Cases with extensive hyperpigmentation are rarely reported. In this paper, we describe the case of a 30-year-old phototype V woman in her 37^th week of pregnancy, who presented with brownish hyperpigmentation of the skin in extensive areas, including both axillae, the abdomen, and the lowest part of the back. In the abdomen, there was a reinforcement of the hyperpigmentation through the linea nigra and the umbilicus. The hyperpigmentation affected the buttocks as well and involved the intertriginous area between them. Histopathologic analysis showed a hyperpigmented basal layer of the epidermis with no melanocytic atypia or melanocytic nests. Histochemical staining for iron did not show any deposits. Immunohistochemical studies for HMB-45, Melan A, and SOX10 demonstrated an increased number of melanocytes. There was hyperpigmentation of basal layer keratinocytes.. We also performed immunohistochemical stains for estrogen and progesterone receptors, which were both negative. The patient was examined 3 months after delivery, evidencing a significant clearing of the lesions.

Severe and recurrent levamisole-induced cutaneous vasculopathy

Abstract

Levamisole-induced vasculopathy is a thrombotic and necrotic vasculitis usually seen in cocaine users due to adulteration of the drug with this veterinary medication. Some cases can be severe or very extensive, which could lead to sepsis and death.

Angiosarcoma following treatment of basal cell carcinoma: a report of two cases

Divided nevus of the penis

Diphenylcyclopropenone-induced psoriatic koebnerization

Cover

A Diffuse Fine Papular and Pustular Rash in a Man With Advanced Human Immunodeficiency Virus and Diabetes

(See pages 477–8 for the Answer to the Photo Quiz.)

A Diffuse Fine Papular and Pustular Rash in a Man With Advanced Human Immunodeficiency Virus and Diabetes

(See pages 475–6 for Photo Quiz.)

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In the Literature

Estradiol Levels Are Altered in Human Immunodeficiency Virus–Infected Pregnant Women Randomized to Efavirenz-Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy

Abstract

Background

Combination antiretroviral therapy (cART) use in pregnancy has been associated with hormonal dysregulation. We performed a secondary retrospective analysis of longitudinal progesterone and estradiol levels in pregnancy using specimens from the Protease Inhibitors to Reduce Malaria Morbidity in HIV-infected Pregnant Women study, which randomized Ugandan human immunodeficiency virus (HIV)–infected ART-naive women to initiate either lopinavir/ritonavir (LPV/r)–based or efavirenz (EFV)–based cART.

Methods

Three hundred twenty-six women (160 randomized to the EFV arm and 166 women to the LPV/r arm) with at least 1 plasma sample collected during pregnancy were included. Enrollment samples collected prior to cART initiation were used as a cART-naive comparator group. Hormone levels were quantified by enzyme-linked immunosorbent assay.

Results

Estradiol levels were differentially affected by the 2 cART regimens. Exposure to LPV/r was associated with an increase in estradiol (P < .0001), whereas exposure to EFV was associated with a decrease in estradiol (P < .0001), relative to the cART-naive gestationally matched comparator group. Lower estradiol levels correlated with small for gestational age (SGA) (P = .0019) and low birth weight (P = .019) in the EFV arm, while higher estradiol levels correlated with SGA in the LPV/r arm (P = .027). Although progesterone levels were similar between treatment arms, we observed an association between SGA and lower progesterone in the LPV/r arm (P = .04). No association was observed between hormone levels and preterm birth in either arm. Levels of progesterone and estradiol were lower in cases of stillbirth, and levels of both hormones declined immediately prior to stillbirth in 5 of 8 cases.

Conclusions

Combination ART regimens differentially affect estradiol levels in pregnancy, a hormone critical to the maintenance of a healthy pregnancy. Identifying cART regimens that minimize perinatal HIV transmission without contributing to hormonal dysregulation represents an urgent public health priority.

Clinical Trials Registration

NCT00993031.

Risk of Pelvic Inflammatory Disease in Relation to Chlamydia and Gonorrhea Testing, Repeat Testing, and Positivity: A Population-Based Cohort Study

Abstract

Background

There is uncertainty around whether the risks of pelvic inflammatory disease (PID) differ following Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea) infection. We quantified the risk of PID associated with chlamydia and gonorrhea infection and subsequent repeat infections in a whole-population cohort.

Methods

A cohort of 315123 Western Australian women, born during 1974–1995, was probabilistically linked to chlamydia and gonorrhea testing records and to hospitalizations and emergency department presentations for PID from 2002 to 2013. Time-updated survival analysis was used to investigate the association between chlamydia and gonorrhea testing, and positivity, and risk of PID.

Results

Over 3199135 person-years, 120748 women had pathology test records for both chlamydia and gonorrhea, 10745 chlamydia only, and 653 gonorrhea only. Among those tested, 16778 (12.8%) had ≥1 positive chlamydia test, 3195 (2.6%) ≥1 positive gonorrhea test, and 1874 (1.6%) were positive for both. There were 4819 PID presentations (2222 hospitalizations, 2597 emergency presentations). Adjusting for age, Aboriginality, year of follow-up, health area, and socioeconomic status, compared to women negative for chlamydia and gonorrhea, the relative risk (adjusted incidence rate ratio) of PID was 4.29 (95% confidence interval [CI], 3.66–5.03) in women who were both chlamydia and gonorrhea positive; 4.54 (95% CI, 3.87–5.33) in those only gonorrhea positive; and 1.77 (95% CI, 1.61–1.94) in those only chlamydia positive.

Conclusions

Gonorrhea infection conferred a substantially higher risk than chlamydia of hospitalization or emergency department presentation for PID. The emergence of gonorrhea antimicrobial resistance may have a serious impact on rates of PID and its associated reproductive health sequelae.

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection

Abstract

Background

Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI.

Methods

A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results.

Results

The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY).

Conclusions

Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI.

Genomic Investigation of a Putative Endoscope-Associated Carbapenem-Resistant Enterobacter cloacae Outbreak Reveals a Wide Diversity of Circulating Strains and Resistance Mutations

Abstract

A genomic epidemiologic investigation of a putative carbapenem-resistant Enterobacter cloacae outbreak revealed few plausible instances of nosocomial transmission, highlighting instead the frequent importation of E. cloacae into our hospital. Searching for genetic determinants of carbapenem resistance demonstrated that most resistance is due to convergent mutations in phylogenetically diverse E. cloacae.

The Influence of Reported Penicillin Allergy

prophylaxisantibioticsurgical site infectionsallergyvancomycin

The Impact of a Reported Penicillin Allergy on Surgical Site Infection Risk

Abstract

Background

A reported penicillin allergy may compromise receipt of recommended antibiotic prophylaxis intended to prevent surgical site infections (SSIs). Most patients with a reported penicillin allergy are not allergic. We determined the impact of a reported penicillin allergy on the development of SSIs.

Methods

In this retrospective cohort study of Massachusetts General Hospital hip arthroplasty, knee arthroplasty, hysterectomy, colon surgery, and coronary artery bypass grafting patients from 2010 to 2014, we compared patients with and without a reported penicillin allergy. The primary outcome was an SSI, as defined by the Centers for Disease Control and Prevention's National Healthcare Safety Network. The secondary outcome was perioperative antibiotic use.

Results

Of 8385 patients who underwent 9004 procedures, 922 (11%) reported a penicillin allergy, and 241 (2.7%) had an SSI. In multivariable logistic regression, patients reporting a penicillin allergy had increased odds (adjusted odds ratio, 1.51; 95% confidence interval, 1.02–2.22) of SSI. Penicillin allergy reporters were administered less cefazolin (12% vs 92%; P < .001) and more clindamycin (49% vs 3%; P < .001), vancomycin (35% vs 3%; P < .001), and gentamicin (24% vs 3%; P < .001) compared with those without a reported penicillin allergy. The increased SSI risk was entirely mediated by the patients' receipt of an alternative perioperative antibiotic; between 112 and 124 patients with reported penicillin allergy would need allergy evaluation to prevent 1 SSI.

Conclusions

Patients with a reported penicillin allergy had a 50% increased odds of SSI, attributable to the receipt of second-line perioperative antibiotics. Clarification of penicillin allergies as part of routine preoperative care may decrease SSI risk.

A 12-Year Follow-up on the Long-Term Effectiveness of the Quadrivalent Human Papillomavirus Vaccine in 4 Nordic Countries

Abstract

Background

The long-term effectiveness of the quadrivalent human papillomavirus (qHPV) vaccine was assessed by monitoring the combined incidence of cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ (AIS), and cervical cancer related to HPV16 or HPV18.

Methods

Women from Nordic countries of Denmark, Iceland, Norway, and Sweden who received a 3-dose regimen of the qHPV vaccine in the beginning of FUTURE II (Females United to Unilaterally Reduce Endo/Ectocervical Disease; V501-015, base study NCT00092534) are followed through different national registries. Effectiveness analyses were conducted approximately 2 years following completion of the base study and occur approximately every 2 years thereafter for 10 years (ie, 14 years from day 1 of the base study). Vaccine effectiveness against HPV16/18-related CIN2 or worse (CIN2+) was estimated by comparing the observed incidence with the expected incidence of CIN2+ in an unvaccinated cohort using historical registry data.

Results

In the per-protocol population (2084 women) analysis of effectiveness after the first 12 years, there were no breakthrough cases of HPV16/18 CIN2+ after 9437 person- years of follow-up. Statistical power was sufficient to conclude that qHPV vaccine effectiveness remains above 90% for at least 10 years. The number of person-years during the follow-up interval of 10–12 years is continuing to accrue and shows a trend toward continuing effectiveness of the vaccine during that period.

Conclusion

The qHPV vaccine shows continued protection in women through at least 10 years, with a trend for continued protection through 12 years of follow-up.

Clinical Trials Registration

NCT00092534.

Study Identification

V501-015

Antimicrobial Resistance Gene Acquisition and Depletion Following Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

Abstract

Fecal microbiota transplantation (FMT) may be a novel approach to eliminate multidrug-resistant bacteria from the gut and to prevent future infections. Using whole metagenome sequencing data from 8 FMT donor–recipient pairs, we identified 37 and 95 antimicrobial resistance genes that were acquired by or removed from FMT recipients, respectively.

Comparison of a Novel Human Rabies Monoclonal Antibody to Human Rabies Immunoglobulin for Postexposure Prophylaxis: A Phase 2/3, Randomized, Single-Blind, Noninferiority, Controlled Study

Abstract

Background

Lack of access to rabies immunoglobulin (RIG) contributes to high rabies mortality. A recombinant human monoclonal antibody (SII RMAb) was tested in a postexposure prophylaxis (PEP) regimen in comparison with a human RIG (HRIG)–containing PEP regimen.

Methods

This was a phase 2/3, randomized, single-blind, noninferiority study conducted in 200 participants with World Health Organization category III suspected rabies exposures. Participants received either SII RMAb or HRIG (1:1 ratio) in wounds and, if required, intramuscularly on day 0, along with 5 doses of rabies vaccine intramuscualarly on days 0, 3, 7, 14 and 28. The primary endpoint was the ratio of the day 14 geometric mean concentration (GMC) of rabies virus neutralizing activity (RVNA) as measured by rapid fluorescent focus inhibition test for SII RMAb recipients relative to HRIG recipients.

Results

One hundred ninety-nine participants received SII RMAb (n = 101) or HRIG (n = 98) and at least 1 dose of vaccine. The day 14 GMC ratio of RVNA for the SII RMAb group relative to the HRIG group was 4.23 (96.9018% confidence interval [CI], 2.59–6.94) with a GMC of of 24.90 IU/mL (95% CI, 18.94–32.74) for SII RMAb recipients and 5.88 IU/mL (95% CI, 4.11–8.41) for HRIG recipients. The majority of local injection site and systemic adverse reactions reported from both groups were mild to moderate in severity.

Conclusions

A PEP regimen containing SII RMAb was safe and demonstrated noninferiority to HRIG PEP in RVNA production. The novel monoclonal potentially offers a safe and potent alternative for the passive component of PEP and could significantly improve the management of bites from suspected rabid animals.

Clincical Trials Registration

CTRI/2012/05/002709.

Epidemiology and Antimicrobial Resistance Characteristics of the Sequence Type 131-H30 Subclone Among Extraintestinal Escherichia coli Collected From US Children

Abstract

Background

Escherichia coli sequence type (ST) 131-H30 is a globally important pathogen implicated in rising rates of multidrug resistance among E. coli causing extraintestinal infections. Previous studies have focused on adults, leaving the epidemiology of H30 among children undefined.

Methods

We used clinical data and isolates from a case-control study of extended-spectrum cephalosporin-resistant E. coli conducted at 4 US children's hospitals to estimate the burden and identify host correlates of infection with H30. H30 isolates were identified using 2-locus genotyping; host correlates were examined using log-binomial regression models stratified by extended-spectrum cephalosporin resistance status.

Results

A total of 339 extended-spectrum cephalosporin-resistant and 1008 extended-spectrum cephalosporin-susceptible E. coli isolates were available for analyses. The estimated period prevalence of H30 was 5.3% among all extraintestinal E. coli isolates (95% confidence interval [CI], 4.6%–7.1%); H30 made up 43.3% (81/187) of extended-spectrum β-lactamase (ESBL)–producing isolates in this study. Host correlates of infection with H30 differed by extended-spectrum cephalosporin resistance status: Among resistant isolates, age ≤5 years was positively associated with H30 infection (relative risk [RR], 1.83 [95% CI, 1.19–2.83]); among susceptible isolates, age ≤5 years was negatively associated with H30 (RR, 0.48 [95% CI, .27–.87]), while presence of an underlying medical condition was positively associated (RR, 4.49 [95% CI, 2.43–8.31]).

Conclusions

ST131-H30 is less common among extraintestinal E. coli collected from children compared to reported estimates among adults, possibly reflecting infrequent fluoroquinolone use in pediatrics; however, it is similarly dominant among ESBL-producing isolates. The H30 subclone appears to disproportionately affect young children relative to other extended-spectrum cephalosporin-resistant E. coli.

Evidence of Sexually Transmitted Disease Testing Outside of Primary Human Immunodeficiency Virus Care for People Living With Human Immunodeficiency Virus in San Francisco, California

To the Editor—Using data from the Medical Monitoring Project (MMP), Mattson and colleagues found that a low proportion of sexually active adults in human immunodeficiency virus (HIV) care were screened for sexually transmitted diseases (STDs) in the prior 12 months in their primary care setting [1]. Sexually transmitted disease testing was far below recommended guidelines for sexually active persons living with HIV [2]. Reading this article encouraged us to examine our local MMP data to determine whether STD testing rates among MMP participants in San Francisco were similar and to examine whether the proportion of persons screened for STDs was underestimated because data collection in MMP was limited to medical chart abstraction from the participants' place of primary HIV care. Mattson et al noted this restriction as a limitation of their study.