Childhood lichen planus: A series of 42 patients

Abhinav Kumar, Vibhu Mendiratta, Shilpi Agarwal, Ram Chander, Sarita Sanke

Indian Journal of Paediatric Dermatology 2018 19(2):116-119

Background: Lichen planus (LP) is a papulosquamous disease of unknown etiology that is relatively uncommon in children. There is a paucity of data on the clinical profile of LP in children. Available case series are few and majority being retrospective. A cross-sectional observational study to evaluate the clinical profile of childhood LP was performed. Materials and Methods: All childhood cases (<18 years) with histopathologically confirmed diagnosis of LP were evaluated. Detailed clinical history, examination, and investigations were performed according to a proforma. Observation and Results: There were 42 children and childhood LP constituted 1.4% of the pediatric dermatoses. There were 26 females (61.9%) and 16 (38.1%) males with male to female ratio of 1:1.6. The age ranged from 2 to 18 years with a mean age of 11.6 ± 5.1 years. The duration of the disease ranged from 15 days to 5 years with a mean of 8.6 ± 9.4 months. History of recent hepatitis B vaccination was found in 6 (14.3%) patients, and exposure to X-ray radiation was seen in 3 (7.1%). The most common morphological presentation of LP was papules and plaques observed in 34 (81%) patients. Classical LP was the most common variant, found in 29 (69%) patients, followed by hypertrophic variant in 7 (16.7%) patients. Koebnerization was found in 31 (73.8%) patients. Oral mucosa involvement was seen in 28.6% of patients, nail in 42.85%, and scalp in 7.1% of patients. Conclusion: Childhood LP resembles adult LP in most of the aspects. However, etiological factors in childhood LP may be different. It is an under-reported disease. Large multi-centric prospective studies should be undertaken to acquire a better understanding of the clinical profile of childhood LP.

Co-occurrence of psoriasis, vitiligo, and lichen planus in a single patient

Swathi Neelagiri, B Janardhan, K Siva Rami Reddy, V Sreedhar

Indian Journal of Paediatric Dermatology 2018 19(2):157-160

Psoriasis is a common autoimmune skin disease affecting around 2%–3% of the world population. The disease has an autoimmune and complex genetic background. It may be associated with other autoimmune diseases such as vitiligo, lichen planus, discoid lupus erythematosus, and alopecia areata as reviewed in the literature. There are few case reports about the co-occurrence of one or two autoimmune diseases. Many speculations have been put forward about the pathogenesis of these conditions, but T-cell-mediated autoimmunity and true Koebner phenomenon background play a common etiological cause of co-occurrence of psoriasis, lichen planus, and vitiligo. We report a 9-year-old female patient who presented with psoriasis, lichen planus, and vitiligo lesions. Interestingly, she developed psoriatic plaques on the vitiligo patches in the knee. Histopathological diagnosis was consistent with the concurrence of psoriasis, lichen planus, and vitiligo.

Comorbidities in pediatric atopic dermatitis

Eliza I Pope, Aaron M Drucker

Indian Journal of Paediatric Dermatology 2018 19(2):102-107

Atopic dermatitis is a common chronic condition that often begins in early childhood. In addition to associations with other atopic conditions such as asthma, food allergy and hayfever, recent research has uncovered a number of other important potential comorbidities. In this review article, we summarize the reported comorbidities of pediatric atopic dermatitis including mental health disorders, infections, obesity, hypertension, injuries and anemia.

Waardenburg syndrome Type I

Virendra N Sehgal, Pardeep Venkatesh

Indian Journal of Paediatric Dermatology 2018 19(2):178-180

Treatment guidelines for atopic dermatitis by ISPD task force 2016

Deepak Parikh, Sandipan Dhar, Ramkumar Ramamoorthy, Sahana Srinivas, Rashmi Sarkar, Arun Inamadar, Manish Shah, Raghubir Banerjee, Amrinder Jit Kanwar, Vibhu Mendiratta, Renu George, Ram Gulati

Indian Journal of Paediatric Dermatology 2018 19(2):108-115

Lipoid proteinosis: A series of three cases

Astha Sharma, Lalit Kumar Gupta, Manisha Balai, Ashok Kumar Khare

Indian Journal of Paediatric Dermatology 2018 19(2):170-172

Lipoid proteinosis is a very rare progressive autosomal recessive disorder characterized by deposition of hyaline material in the skin, upper aerodigestive tract, and internal organs. Patients present with a history of repeated blistering, skin scarring, beaded eyelid papules, waxy papules over the body, and laryngeal and tongue infiltration leading to hoarseness of voice. This disorder is caused by mutations in the extracellular protein 1 gene present on chromosome 1q21. We report three cases of lipoid proteinosis, who presented to our outpatient department with aforementioned features.

Trichoscopy in pediatric age group

Subrata Malakar, Purva R Mehta, Samipa S Mukherjee

Indian Journal of Paediatric Dermatology 2018 19(2):93-101

Approach to trichology in the pediatric age group is based on the clinical expertise of the dermatologist and investigative techniques. Currently, the trichoscope is an indispensible, noninvasive tool in the diagnosis of trichological disorders. It not only highlights the subtle tricoscopic points invisible to the naked eye but also serves as a prognostic and monitoring tool in therapeutic management. Trichoscopy goes a long way in improving the diagnostic and clinical acumen of the physician. In the pediatric age group, trichoscopy deals with pattern analysis ranging from hair shaft patterns to follicular, perifollicular, and interfollicular patterns. It not only describes the key trichoscopic features of noncicatricial alopecias, cicatricial alopecias, and genetic hair shaft defects but also helps to delineate various trichological mimics from each other. For compiling data, all trichology cases presenting to a tertiary care center were examined and photographed with a Fotofinder, DermLite Foto II Pro, and DermLite DL 3N. All trichological data were analyzed, and interpretations were based on the literature available.

Therapy for involuting infantile hemangioma: Propranolol effectiveness

Luz Orozco-Covarrubias, Leticia Lara-Mendoza, Luis Martín Garrido-García, Ramón Ruiz-Maldonado

Indian Journal of Paediatric Dermatology 2018 19(2):120-123

Background/Objectives: The efficacy of propranolol as a treatment for infantile hemangiomas (IHs) has been documented. Until now, little has been written about the role of propranolol beyond the proliferation phase of IH. Our aim was to document propranolol efficacy and safety in the treatment of involutive IH. Patients and Methods: Two evaluations were conducted. Investigators evaluated the final clinical results by comparing clinical data at baseline and at the end of the study. Evaluators scored each panel of photographs and were blinded from any clinical information. Both groups used the same scoring system. Patients treated with propranolol in our department between 2009 and 2014 were reviewed. Results: A total of 15 patients with involuting IH treated with propranolol were eligible. Eleven (73%) were females, ranging in age between 16 and 110 months (median 41 months). The types of IH were mixed (n = 13) and superficial (n = 2). The median duration of the propranolol treatment was 20 months (range 6–33 months). The mean size reduction was from 6 cm ± 4.33 before the treatment to 3.98 ± 1.25 at the end of the treatment. The general mean involution according to the investigators' evaluation was 4.1 ± 2.7. The general mean involution according to the evaluators' evaluation was 4.9 ± 1.5. Telangiectasias showed no response. Recurrence was observed in one patient. Transient nightmares were documented in one patient, and nighttime awakenings were documented in another. The therapy was discontinued in neither of these patients. Conclusions: In our experience, propranolol was well tolerated and associated with limited adverse reactions. The use of oral propranolol was effective in the treatment of IH beyond the proliferative phase.

Neonatal purpura fulminans caused by rare Citrobacter species

Sanjiv Vijay Choudhary, Shivani Sanjeev Dhande, Taru Aghi, Prashant Mahajan

Indian Journal of Paediatric Dermatology 2018 19(2):164-166

A 23-day-old neonate, born of nonconsangious marriage, admitted to Neonatal Intensive Care Unit for hypernatremic dehydration with petechiae and ecchymotic patches and necrotic skin lesions for 10–12 days was referred to dermatology department. On the general examination, pulse was 158/min, and respiratory rate was 52/min, and systemic examination was normal. Hematological investigations showed pancytopenia. Bleeding time was normal but prothrombin time and activated partial thromboplastin time reports were prolonged. D-dimer levels were elevated. Urine and stool were normal. Blood culture and sensitivity report revealed the growth of Citrobacter species with sensitivity to ciprofloxacin, amikacin, tetracycline, and resistance to Imipenem. Histopathology revealed epidermal hyperkeratosis with epidermal-dermal splitting, vessels showing fibrin occlusion with red blood cell extravasation into the perivascular areas in dermis along with dermal necrosis. To the best of our knowledge, this might be the first case of purpura fulminans in a neonate caused by rare Citrobacter species.

A study of dermatoses in the early neonatal period from a tertiary care hospital in North West Punjab

Shiti Bose, Emy Abi Thomas, Anuradha Bhatia, Inderpreet Sohi

Indian Journal of Paediatric Dermatology 2018 19(2):124-129

Background: Neonatal life, as defined by the World Health Organization, constitutes the first 28 days of extrauterine life. The transition of neonatal skin from an aqueous to an air-dominant environment results in various changes, both physiological and pathological. Aims: This study was designed to find the prevalence and pattern of various physiological and pathological dermatoses as well as its relation to maternal and neonatal factors in the early neonatal period. Materials and Methods: This prospective study was done on 505 live born neonates at Christian Medical College and Hospital, Ludhiana. All consecutive live born babies and those presenting for follow-up within 7 days of birth were considered. Results: Out of 505 neonates that were examined, 284 (56.24%) were males and 221 (43.76%) were females. Physiological skin changes were seen in 460 (91.09%), the most common being physiological desquamation in 211 (41.78%) neonates followed by Milia in 199 (39.41%). Pathological changes were seen in 102 (20.20%) neonates of whom one had aplasia cutis congenita. The most common developmental abnormality was accessory nipple in 6 (1.19%) neonates. Icterus was most often seen in neonates delivered by normal vaginal delivery 134 (56.54%). Milia was more often seen in babies of multiparous mothers, 135 (67.84%) as compared to primiparous mothers. Conclusion: A good knowledge of neonatal dermatoses helps allay concerns in parents and treating physicians thereby avoiding diagnostic and therapeutic procedures, which may not be required, especially as most of the early neonatal dermatoses are transient in nature.

Varicella masquerading as pemphigus vulgaris

Ranjana Beniwal, Lalit Kumar Gupta, Ashok Kumar Khare, Asit Mittal, Sharad Mehta, Manisha Balai

Indian Journal of Paediatric Dermatology 2018 19(2):176-177

Geographic tongue in 8-month-old monozygotic twins: Case report with review of literature

Saru Thakur, Mudita Gupta, GR Tegta, Kuldeep Verma

Indian Journal of Paediatric Dermatology 2018 19(2):130-133

Geographical tongue is a benign inflammatory disorder of the tongue characterized by map like areas of erythema which are not constant in size, shape, or location. Positive family history may be reported in few cases, but so far there is a single case report of geographical tongue in monozygotic twins 5-year-old. We report a case of geographical tongue in monozygotic twins in infants 8-month-old, which is the first case in twins in infancy to the best of our knowledge.

Tufted angioma

Sharad Mehta, Manju Meena, Urvashi Goyal, Lalit Kumar Gupta, Ashok Kumar Khare, Asit Mittal

Indian Journal of Paediatric Dermatology 2018 19(2):182-183

Pityriasis rotunda in a child

Mrinal Gupta

Indian Journal of Paediatric Dermatology 2018 19(2):134-135

Pityriasis rotunda is an uncommon disorder of keratinization characterized by sharply defined hyper- or hypo-pigmented, perfectly circular, scaly patches with no inflammatory changes. The etiology of pityriasis rotunda remains unknown. Most authors believe that it is a form of acquired ichthyosis and it has been associated with a variety of conditions including tuberculosis, malnutrition, and malignancy. We report a case of pityriasis rotunda in a 7-year-old otherwise healthy female who was treated with topical retinoids and emollients with partial improvement.

Reiter's disease in a 8-year-old boy

Rohit Kapoor, Syed Md Azad, Anwesha Mukherjee, Sandipan Dhar

Indian Journal of Paediatric Dermatology 2018 19(2):154-156

An 8-year-old male child presented with complaints of pain abdomen and appearance of rashes all over the body, with pain and swelling of the left knee joint. The child was a known case of developmental delay with seizure disorder, and the rashes had appeared just after starting oral valproate. On examination, the child appeared well except for the rashes and local swelling with decreased range of motion in the left knee joint. Redness around the urethral meatus was also noted. Skin biopsy revealed features suggestive of reactive arthritis. The child responded well to nonsteroidal anti-inflammatory drugs.

Linear alopecia areata versus trichotillomania: The game of time

Samipa Samir Mukherjee, BS Chandrashekar

Indian Journal of Paediatric Dermatology 2018 19(2):136-138

Linear variant of alopecia areata (AA) is a rare entity posing as a diagnostic challenge owing to the ability to mimic multiple conditions ranging from trichotillomania, dermatitis artefacta to linear lupus erythematosus profundus. Awareness regarding this entity optimized with dermoscopy and histopathology examination is essential for an effective diagnosis and treatment. Herein, we describe a case of a 7-year-old female with linear AA simulating trichotillomania which we believe is the first reported case in pediatric age group in India.

Familial reactive perforating collagenosis in two siblings

Abhijna K Rai, Mamatha S Kusagur, KS Chandan

Indian Journal of Paediatric Dermatology 2018 19(2):161-163

Reactive perforating collagenosis (RPC) is a rare form of transepithelial elimination disorder, in which genetically altered collagen is extruded through the epidermis. Of the acquired and inherited form, the latter is extremely rare. Here, we present two cases of inherited form of RPC in siblings aged 4 and 7 years presented with a history of itchy raised lesions of 9 months and 3 years duration, respectively. Dermatological examination revealed multiple papules with a central keratotic plug distributed mainly over face and extensors of upper and lower extremities. Köebnerization was present. Skin biopsy revealed perforating collagen bundles in the upper dermis and epidermis.

Spiegler–Fendt sarcoid/lymphocytoma cutis: A focus on nomenclature and diagnosis

Virendra N Sehgal, Deepa Sehgal, Jangid B Lal, Sonal Sharma

Indian Journal of Paediatric Dermatology 2018 19(2):139-142

Spiegler–Fendt sarcoid/lymphocytoma cutis, presenting as an asymptomatic, slowly progressive, erythematous macule of the size of a guinea over the left cheek, is presented in a 7-year-old girl, the diagnosis of which was complimented by lymphocytic exocytosis with spongiosis of the epidermis. Immunohistochemistry revealed wide-ranging T-cell variations, which was more positive for T-cell markers, CD3, of which predominance of CD4 subset was seen, emphasizing its role as a diagnostic tool.

Furuncular myiasis in a 6-year-old boy

Manoj Kumar Sharma, Sumit Kumar Yadav, Ramesh Kumar, Suresh Jain

Indian Journal of Paediatric Dermatology 2018 19(2):167-169

Myiasis is caused by the invasion of tissues or organs of humans or animals by dipterous larvae. A 6-year-old boy presented with 1-month history of scalp ulcer that has initially started as a painful, itchy swelling in the vertex region. Cutaneous examination revealed live maggots in the ulcerous wound. Clinicians should be more alert to the possibility of myiasis in patients with furuncloid or boil-like lesions. Herein, we report this case because of its rarity.

Hemorrhagic varicella

S Nageswaramma, G Swarna Kumari, Bala Kumar Dorai

Indian Journal of Paediatric Dermatology 2018 19(2):143-145

Varicella is a benign disorder occurring commonly in children. Hemorrhagic varicella is a serious complication occurring in immunocompromised persons or those on immunosuppressive therapy. Our encounter with this case of Hemorrhagic varicella highlights that the rare hemorrhagic varicella can also occur in a chronic malnourished child. Prompt diagnosis and treatment with acyclovir leads to complete recovery.

Current Concepts in the Treatment of Resectable Pancreatic Cancer

Abstract

Purpose of Review

The diagnosis of pancreatic cancer carries with it a high mortality rate. Despite advances in the field, this has remained relatively unchanged over the last few decades. Current options for the treatment of resectable pancreatic ductal adenocarcinoma will be reviewed here in conjunction with the historical data that support them. We will focus on updates in treatment guidelines and ongoing clinical trials of interest.

Recent Findings

For localized disease, standard of care includes resection followed by adjuvant chemotherapy ± chemoradiation. Recently, a report was published supporting the use of doublet therapy with gemcitabine and capecitabine (as opposed to gemcitabine monotherapy), which prompted a practice-changing update to major treatment guidelines. Multiple trials using neoadjuvant treatment, novel therapies, and different forms of radiation are ongoing.

Summary

Although pancreatic cancer is an active area of research, outcomes remain dismal. Clinical trials will need to be more robust and innovative to drastically improve survival statistics.

Hematopoietic Stem Cell Transplantation for Adult Philadelphia-Negative Acute Lymphoblastic Leukemia in the First Complete Remission in the Era of Minimal Residual Disease

Abstract

Purpose of Review

The purpose of this review is to discuss the potential role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia-negative (Ph⁻) adult acute lymphoblastic leukemia (ALL) in first complete remission (CR1) in the era of minimal residual disease (MRD).

Recent Findings

Allo-HSCT continues to have a role in the therapy of a selected group of high-risk adult patients with ALL in CR1. Although the clinical significance of MRD has been studied less extensively in adults with ALL than in children, recent studies support its role as the strongest prognostic factor that can identify patients that are unlikely to be cured by standard chemotherapy and benefit from undergoing allo-HSCT. In addition, MRD status both pre- and post-HSCT has been found to correlate directly with the risk of relapse.

Summary

Currently, the clinical challenge consists on applying MRD and molecular failure to integrate novel agents and immunotherapy to lower MRD before allo-HSCT and to modulate the graft versus leukemia (GVL) effect after transplant.

Mesenchymal Chondrosarcoma: a Review with Emphasis on its Fusion-Driven Biology

Abstract

Mesenchymal chondrosarcoma is a rare but deadly form of chondrosarcoma that typically affects adolescents and young adults. While curative intent is possible for patients with localized disease, few options exist for patients in the unresectable/metastatic setting. Thus, it is imperative to understand the fusion-driven biology of this rare malignant neoplasm so as to lead to the future development of better therapeutics for this disease. This manuscript will briefly review the clinical and pathologic features of mesenchymal chondrosarcoma followed by an appraisal of existing data linked to the fusions, HEY1-NCOA2 and IRF2BP2-CDX1, and the associated downstream pathways.

Prevalence and Risk of Polypharmacy Among Elderly Cancer Patients Receiving Chemotherapy in Ambulatory Oncology Setting

Abstract

Purpose of Review

This was a single center, retrospective cross-sectional study looking into the incidence and types of drug-related problems (DRPs) detected among elderly cancer patients receiving at least three long-term medications concurrent with IV chemotherapy, and the types of intervention taken to address these DRPs. This paper serves to elucidate the prevalence and risk of polypharmacy in our geriatric oncology population in an ambulatory care setting, to raise awareness on this growing issue and to encourage more resource allocation to address this healthcare phenomenon.

Recent Findings

DRP was detected in 77.6% of elderly cancer patients receiving at least three long-term medications concurrent with IV chemotherapy, with an average incidence of three DRPs per patient. Approximately half of DRPs were related to long-term medications. Forty percent of DRPs required interventions at the prescriber level. The use of five or more medications was shown to almost double the risk of DRP occurrence (OR 1.862, P = 0.039). Out of the eight predefined categories of DRPs, underprescribing was the most common (26.7%), followed by adverse drug reaction (25.0%) and drug non-adherence (16.2%).

Summary

Polypharmacy leading to DRPs is a common occurrence in elderly cancer patients receiving outpatient IV chemotherapy. There should be systematic measures in place to identify patients who are at greater risk of inappropriate polypharmacy and DRPs, and hence more frequent drug therapy optimization and monitoring. The identification of DRPs is an important step to circumvent serious drug-related harm. Future healthcare interventions directed at reducing DRPs should aim to assess the clinical and economic impact of such interventions.

The objectivity of Subjective Bayesianism

Abstract

Subjective Bayesianism is a major school of uncertain reasoning and statistical inference. It is often criticized for a lack of objectivity: (i) it opens the door to the influence of values and biases, (ii) evidence judgments can vary substantially between scientists, (iii) it is not suited for informing policy decisions. My paper rebuts these concerns by connecting the debates on scientific objectivity and statistical method. First, I show that the above concerns arise equally for standard frequentist inference with null hypothesis significance tests (NHST). Second, the criticisms are based on specific senses of objectivity with unclear epistemic value. Third, I show that Subjective Bayesianism promotes other, epistemically relevant senses of scientific objectivity—most notably by increasing the transparency of scientific reasoning.

Kim, Sungmoon, Public Reason Confucianism: Democratic Perfectionism and Constitutionalism in East Asia

Philosophy of Gongfu Revealed through Confucius: Responses to Chenyang L i and Huaiyu W ang ’s Comments on My Book Confucius: The Man and the Way of Gongfu

François Noël’s Contribution to the Western Understanding of Chinese Thought: Taiji sive natura in the Philosophia sinica (1711)

Abstract

Jesuits in China adopted key Confucian terms to express Christian notions; for example, Tian 天 or Shangdi 上帝 was considered an equivalent for God, and guishen 鬼神 for angels. A Terms controversy started among the Jesuits and other missionaries and developed into the famous Rites Controversy. However, all the missionaries agreed in rejecting the Neo-Confucian concept of Taiji 太極, which was believed to be materialistic, pantheistic, or atheistic. The Flemish Jesuit François Noël (1651–1729), after a careful study of Neo-Confucian texts, interpreted Taiji with the Western concept of nature, and even claimed that it held theistic meaning. We shall analyze and evaluate here this early Western attempt in giving a positive meaning to Taiji.

Reply to: Cutaneous squamous cell carcinoma progression during imiquimod treatment

Successful treatment of severe psoriasis relapse with Secukinumab(IL17 A inhibitor) after abrupt Brodalumab (IL17 receptor inhibitor) discontinuation: A retrospective study evaluating long term efficacy and safety

History of plastic surgery: art, philosophy, and rhinoplasty

The two-hundredth anniversary of K. F. Graefe's "Rhinoplasty", E. Zeis' naming of the specialty of plastic surgery in 1838, and the continuing discussion on what is plastic surgery have prompted this historical-conceptual review with an analytic semantic insight into the meaning of the word "plastic". A literature search has revealed that this term has a dual content composed of an artistic and a philosophic aspect. Progressive development of these two connotations can be traced from their birth in the ceramics and myths of the ancient Greece to their metamorphoses in the fine arts, science, and plasticity philosophy of our days.

Stage IV Melanoma of Unknown Primary: A Population-Based Study in the United States from 1973 to 2014

Melanoma of unknown primary (MUP) is incompletely described on a population level.

Trichologic response of platelet-rich plasma in androgenetic alopecia is maintained during combination therapy

Low conversion rate of Quantiferon-TB Gold screening tests in patients treated with tumor necrosis factor inhibitors: A retrospective cohort study identifying an important practice gap

Melanoma staging: Varying precision and terminal digit clustering in Breslow thickness data is evident in a population based study

Errors in Breslow thickness reporting can give misclassification of T category, an important classifier in melanoma staging.

Risk of skin cancer in HIV-infected patients: a Danish nationwide cohort study

The risk of skin cancer in HIV-infected patients has not been extensively studied.

Drug survival of apremilast for psoriasis in a real-world setting

Non-malignant late cutaneous changes after allogeneic hematopoietic stem cell transplant in children

There are limited pediatric data on non-malignant cutaneous changes, including autoimmune conditions and permanent alopecia, after hematopoietic stem cell transplantation (HSCT).

The copper complexation ability of a synthetic humic-like acid formed by an abiotic humification process and the effect of experimental factors on its copper complexation ability

Abstract

Humic acids have an important impact on the distribution, toxicity, and bioavailability of hazardous metals in the environment. In this study, a synthetic humic-like acid (SHLA) was prepared by an abiotic humification process using catechol and glycine as humic precursors and a MnO₂ catalyst. The effect of physico-chemical conditions (ionic strength from 0.01 to 0.5 M NaNO₃, pH from 4 to 8, temperature from 25 to 45 °C, and humic acid concentration from 5 to 100 mg/L) on the complexation ability of SHLA for Cu²⁺ were investigated. A commercial humic acid (CHA, CAS: 1415-93-6) from Sigma-Aldrich was also studied for comparison. The results showed that for pH 4 to 8, the conditional stability constants (log K) of SHLA and CHA were in the range 5.63–8.62 and 4.87–6.23, respectively, and complexation capacities (CC) were 1.34–2.61 and 1.42–2.31 mmol/g, respectively. The Cu complexation ability of SHLA was higher than that of the CHA due to its higher number of acidic functional groups (SHLA 19.19 mmol/g; CHA 3.87 mmol/g), extent of humification and aromaticity (AL/AR: 0.333 (SHLA); 1.554 (CHA)), and O-alkyl functional groups (SHLA 15.56%; CHA 3.45%). The log K and complexation efficiency (fraction of metal bound to SHLA) of SHLA were higher at higher pH, lower ionic strength, higher temperature, and higher SHLA concentration. Overall, SHLA was a good and promising complexation agent for copper in both soil washing of copper contaminated soil and the treatment of copper-containing wastewater.

Impact of change in serum albumin level during and after chemoradiotherapy in patients with locally advanced esophageal cancer

Abstract

Background

In patients with locally advanced esophageal cancer treated by concurrent chemoradiotherapy (CCRT), baseline malnutrition and its progression have been shown to be associated with a poor outcome. We conducted this study to determine the variation in four blood test parameters including serum albumin level (ALB), creatinine (Cre), hemoglobin (Hb) and platelet (Plt) during CCRT for stage III esophageal cancer patients and its effect on patients' outcome.

Methods

One hundred eighty-three patients diagnosed with stage III esophageal cancer were retrospectively investigated. In addition to known prognostic factors, baseline level of the four blood test parameters and their variation at day 105 (ΔALB, ΔCre, ΔHb and ΔPlt, respectively) were analyzed.

Results

The median observation period for patients who survived was 57.2 months, and the 5-year overall survival rate was 35.6% (95% CI 34.2–36.9%). In multivariate analyses, baseline ALB (≥ 3.6 g/dL), higher ΔALB (≥ + 0.3 g/dL) were independent predictors for overall survival (p = 0.001 and < 0.001, respectively), in addition to other clinical factors including T stage and overall treatment time (OTT). For disease-free survival, ΔALB was only a predictor in hematological parameters (p = 0.001) in addition to T stage and OTT. No hematological and clinical parameters had significant correlation with local control in multivariate analysis. Furthermore, ΔALB showed significant correlation with OS and DFS in log-rank test (p = 0.002 and 0.002, respectively).

Conclusions

Our results suggest improvement in ALB after treatment might be a favorable prognostic factor in esophageal cancer patients treated by CCRT.

Stereological and molecular studies on the combined effects of photobiomodulation and human bone marrow mesenchymal stem cell conditioned medium on wound healing in diabetic rats

Publication date: Available online 26 March 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Abdollah Amini, Ramin Pouriran, Mohammad-Amin Abdollahifar, Hojjat Allah Abbaszadeh, Seyed Kamran Ghoreishi, Sufan Chien, Mohammad Bayat
We investigated the effects of conditioned medium (CM) from human bone marrow mesenchymal stem cells (h BMMSC)s and pulse wave photobiomodulation (PW PBM), applied alone or in combination, on the stereological parameters and gene expression of some growth factors, during wound healing in a streptozotocin (STZ)-induced rat model of type one diabetes mellitus (T1DM).T1DM was induced in 72 rats and two incisions were made in each animal. The rats were assigned to one of four groups: a control (placebo) group, a Laser group (890 nm, 80 Hz, 0.2 J/cm²); a CM group, and a combined CM + Laser group. On post-surgical days 4, 7, and 15, skin samples were extracted for stereology and reverse transcription PCR (RT-PCR) analyses of gene expression of basic fibroblast growth factor (bFGF), hypoxia-inducible factor (HIF-1α), and stromal cell-derived factor-1α (SDF-1α).The stereological examinations of the proximal and distal wounds revealed significantly enhanced healing in all the treated groups, compared to the control group. The extent of healing was significantly greater in the CM + Laser group than in the other treatment groups. The RT-PCR results also indicated greater gene expression in the CM + Laser and Laser groups than in the CM and control groups.Application of CM and PW PBM, alone or in combination accelerated the process of wound healing in T1DM rats. The results of combined application of CM and PW PBM, indicated a synergistic effect, and the combination treatment was statistically more effective than single applications of CM or PW PBM.

A novel stellerite-based photocatalytic composite and its enhanced disinfection application

Publication date: Available online 26 March 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Wanzhong Zhang, Haiyu Huang, Zhiming Sun, Shuilin Zheng, Caihong Yu
The aim of this work was to prepare, characterize and evaluate the potential of novel ZnO/stellerite composite photocatalysts against Staphylococcus aureus (S. aureus). SEM/EDS studies employed to study the surface morphological properties revealed stellerite as the catalysts carrier played a role of dispersant for ZnO nanoparticles. The XRD patterns of the ZnO/stellerite indicated hexagonal crystal structure with 20–30 nm size. It was found that the crystallite size of ZnO/stellerite was much smaller as compared to pure ZnO and increased with increasing ZnO loading amount. The results of optical properties of ZnO/stellerite showed smaller band gap in contrast to pure ZnO, investigated by UV–vis absorption. Due to the optimum ZnO loading, the as-prepared ZnO-20 composite had the highest BET surface area and the pore volume. Using the TG-DSC measurement, the high thermal stability of the product was studied for different temperature values. Antibacterial activity of ZnO/stellerite affected by the ZnO loading, concentration of samples and light conditions (under dark and UV irradiation conditions) was examined by disinfection of S. aureus. The as-prepared ZnO-20 composite with 100 mg/L was found to exhibit excellent inactivation efficiencies (87.65% in the dark and 97.67% under UV illumination) towards S. aureus. Compared with pure ZnO, the obtained composite photocatalysts showed significantly better antibacterial performance by studying the disinfection kinetics of S. aureus. Thus, the present study reveals that the novel ZnO/stellerite shows great potential for its use in the targeted disinfection applications.

Graphical abstract

Albizia chevalier based ag nanoparticles: Anti-proliferation, bactericidal and pollutants degradation performance

Publication date: Available online 26 March 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Shahid Ali Khan, Bello Aminu Bello, Jalaluddin Awllia Khan, Yasir Anwar, Muqtadir Baig Mirza, Fareed Qadri, Aliya Farooq, Ibrahim Khalil Adam, Abdullah Muhammad Asiri, Sher Bahadar Khan
The eco-friendly biosynthesis of silver nanoparticles (AgNps) from bark extract of Albizia chevalier are reported here for their anti-proliferative, antibacterial and pollutant degradation potentials. The synthesized AgNps were characterized by FTIR spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy dispersive X-rays spectrometry (EDS) and X-ray diffraction studies. The TEM and FESEM images show a monodispersed spherical shaped particles of approximately 30 nm. Crystalline peaks were obtained for the synthesized AgNps in XRD spectrum. The AgNps were investigated for in vitro anticancer and antibacterial activities and its potential to degrade 4-nitrophenol (4-NP) and congo red dye (CR). The MTT results shows a significant dose-dependent antiproliferation effect of the AgNps on the cell lines HepG2, MDA-MB-231 and MFC7. The effect was found more pronounced in MDA-MB-231 as compared to MFC-7 cell lines. The antibacterial results indicated 99 and 95% killing of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) respectively, after 24 h incubation with the AgNps. The AgNps were found to speed up the reductive degradation of 4-NP and CR dye, which give an alternative route for the removal of toxic organic pollutants from the wastewater. The synthesized AgNps were not only used as a bactericidal and anticancer agent, but also effectively used for the reductive degradation of carcinogenic compounds which are listed as the priority pollutants. Therefore, AgNps have the potential for the treatment of various cancers, bacterial infections and for industrial detoxification of wastewater.

Graphical abstract

Distribution and hydrogeochemical behavior of arsenic enriched groundwater in the sedimentary aquifer comparison between Datong Basin (China) and Kushtia District (Bangladesh)

Abstract

A prompt growth in research on arsenic occurrence and behavior in the environment has occurred over the last decade or so. High arsenic (As) in groundwater has become a major global concern due to its widespread occurrence. A comparative hydrogeochemical study was performed on the occurrence of high As groundwater in Datong Basin, China, and Kushtia District, Bangladesh. A total of 132 groundwater samples (83 from Datong Basin and 49 from Kushtia District) were collected to analyze the major hydrogeochemical components and trace elements in groundwater of both areas. Factor analysis (FA) was applied on the hydrochemical data to identify the major hydrogeochemical processes in sedimentary aquifers. High As groundwater was observed in the low-lying central parts of Datong Basin, which are composed of the Holocene alluvial and lacustrine aquifers. The elevated As concentrations ranged from 0.31 to 452 μg/L and distributed in depths between 20 and 45 m. As-enriched groundwater is mainly Na-HCO₃ type water and characterized by higher pH value, high Na⁺, low Ca²⁺, SO₄²⁻, and NO₃⁻ along with moderate TDS. The alkaline and reducing subsurface environment facilitate the leaching of As in sedimentary aquifers. The release and distribution of As in aquifers are resulted from the reduction of As-carrying crystalline iron (Fe) oxide/hydroxides and oxidation of organic matter. The aquifers of Kushtia District, Bangladesh, are unconsolidated, alluvial in nature, and developed from Holocene floodplain and Pleistocene deposits. High As (6.04–590.7 μg/L) groundwater occurs mainly in shallow aquifers. The Ca-HCO₃ type groundwater is distinguished by circum-neutral pH, medium-high EC, high HCO₃⁻, and low content of NO₃⁻, SO₄²⁻, K⁺, and Cl⁻. The reductive suspension of MnOOH increases the dissolved As loads and redox responsive elements such as SO₄²⁻ and pyrite oxidation act as the main mechanisms for As release in groundwater. As is mobilized by anaerobic leakage from the brown-clay and gray-sand into the sediment. Infiltration from irrigation return and surface wash water are the potential factors that remobilize As. The weak loading of Fe suggests that the release of Fe and As is decoupled in sedimentary aquifers of Kushtia District.

Screening of groundwater remedial alternatives for brownfield sites: a comprehensive method integrated MCDA with numerical simulation

Abstract

Brownfield sites pollution and remediation is an urgent environmental issue worldwide. The screening and assessment of remedial alternatives is especially complex owing to its multiple criteria that involves technique, economy, and policy. To help the decision-makers selecting the remedial alternatives efficiently, the criteria framework conducted by the U.S. EPA is improved and a comprehensive method that integrates multiple criteria decision analysis (MCDA) with numerical simulation is conducted in this paper. The criteria framework is modified and classified into three categories: qualitative, semi-quantitative, and quantitative criteria, MCDA method, AHP-PROMETHEE (analytical hierarchy process-preference ranking organization method for enrichment evaluation) is used to determine the priority ranking of the remedial alternatives and the solute transport simulation is conducted to assess the remedial efficiency. A case study was present to demonstrate the screening method in a brownfield site in Cangzhou, northern China. The results show that the systematic method provides a reliable way to quantify the priority of the remedial alternatives.

Characterization of isolated liver sinusoidal endothelial cells for liver bioengineering

Abstract

Background

The liver sinusoidal capillaries play a pivotal role in liver regeneration, suggesting they may be beneficial in liver bioengineering. This study isolated mouse liver sinusoidal endothelial cells (LSECs) and determined their ability to form capillary networks in vitro and in vivo for liver tissue engineering purposes.

Methods and results

In vitro LSECs were isolated from adult C57BL/6 mouse livers. Immunofluorescence labelling indicated they were LYVE-1⁺/CD32b⁺/FactorVIII⁺/CD31⁻. Scanning electron microscopy of LSECs revealed the presence of characteristic sieve plates at 2 days. LSECs formed tubes and sprouts in the tubulogenesis assay, similar to human microvascular endothelial cells (HMEC); and formed capillaries with lumens when implanted in a porous collagen scaffold in vitro. LSECs were able to form spheroids, and in the spheroid gel sandwich assay produced significantly increased numbers (p = 0.0011) of capillary-like sprouts at 24 h compared to HMEC spheroids. Supernatant from LSEC spheroids demonstrated significantly greater levels of vascular endothelial growth factor-A and C (VEGF-A, VEGF-C) and hepatocyte growth factor (HGF) compared to LSEC monolayers (p = 0.0167; p = 0.0017; and p < 0.0001, respectively), at 2 days, which was maintained to 4 days for HGF (p = 0.0017) and VEGF-A (p = 0.0051). In vivo isolated mouse LSECs were prepared as single cell suspensions of 500,000 cells, or as spheroids of 5000 cells (100 spheroids) and implanted in SCID mouse bilateral vascularized tissue engineering chambers for 2 weeks. Immunohistochemistry identified implanted LSECs forming LYVE-1⁺/CD31⁻ vessels. In LSEC implanted constructs, overall lymphatic vessel growth was increased (not significantly), whilst host-derived CD31⁺ blood vessel growth increased significantly (p = 0.0127) compared to non-implanted controls. LSEC labelled with the fluorescent tag DiI prior to implantation formed capillaries in vivo and maintained LYVE-1 and CD32b markers to 2 weeks.

Conclusion

Isolated mouse LSECs express a panel of vascular-related cell markers and demonstrate substantial vascular capillary-forming ability in vitro and in vivo. Their production of liver growth factors VEGF-A, VEGF-C and HGF enable these cells to exert a growth stimulus post-transplantation on the in vivo host-derived capillary bed, reinforcing their pro-regenerative capabilities for liver tissue engineering studies.

Occurrence and toxicological assessment of polycyclic aromatic hydrocarbons (PAHs) in marine sediments under mussel farming influence

Abstract

The use of marine resources for mussel culture has become increasingly important, particularly on the European Atlantic coast and notably in the Galician Rías in the northwest of Spain. Despite its importance, there is a lack of research and analysis in this area and of the potential problems that it could cause to the environment. This paper details the findings of a study that aimed to find the probable environmental impact of mussel culture activities and to evaluate the polycyclic aromatic hydrocarbon (PAH) content derived from this activity. The Ría de Arousa, where you can find over 70% of all installed rafts in Galicia, was selected for the present study, and nearly 40 marine sediment samples were collected there. The sediments were extracted by ASE (accelerated solvent extraction) procedure, and the quantification of PAHs was performed using gas chromatography coupled to mass spectrometry (GC-MS), with the aid of deuterated PAH internal standards. The total concentration of parental PAHs ranged from 11.66 to 30,272-ng g⁻¹ dry weight (d.w.), with a mean value of 3907-ng g⁻¹ d.w.; the concentration of alkyl PAHs varied from 3.72 to 1187-ng g⁻¹ d.w., with a mean value of 205.1-ng g⁻¹ d.w. Compositional patterns, principal component analysis (PCA) and hieratical cluster association (HCA) yielded a sediment classification where the mussel raft impact is pointed out. PAH ratios indicated a predominance of combustion sources, except in two samples, located in small harbors. Only one station showed total potential carcinogenic PAH values in the range that would frequently cause negative biological effects, and the toxic equivalent concentrations based on BaP equivalents identified another ten positions where biological effects would occur occasionally.

Effects of exogenous sulfur on growth and Cd uptake in Chinese cabbage ( Brassica campestris spp. pekinensis ) in Cd-contaminated soil

Abstract

Soil pollution with heavy metals has many adverse effects on ecosystem health as well as food security. A pot experiment was performed to investigate the effects of different valence states of exogenous sulfur (S) on the uptake of cadmium (Cd) in Chinese cabbage in Cd-contaminated soil. The results showed that S significantly promoted plant growth in Chinese cabbage, with the following order of magnitude for the different S treatments: sodium sulfite (Na₂SO₃) > sodium sulfate (Na₂SO₄) > powdered sulfur (S₀). Additionally, enzyme activity and the content of reductive substances in the leaves markedly increased, while malondialdehyde content significantly decreased; hence, S observably enhanced the ability of Chinese cabbage to tolerate Cd stress. S₀ significantly reduced soil pH, thus increasing the mobility and bioavailability of Cd in the soil, while Na₂SO₃ increased soil pH, and Na₂SO₄ had no effect on soil pH. The acid-soluble and oxidizable fractions of Cd in soil increased with the S₀ treatment. The applied Na₂SO₃ and Na₂SO₄ both increased the residual fraction of Cd in the soil, but they reduced the amount of the acid-extractable, reducible, and oxidizable Cd. The results showed that compared with S₀, the Na₂SO₃ and Na₂SO₄ treatments decreased the acid-extractable Cd concentrations by 6.3 and 4%, respectively, in the most contaminated soil. In conclusion, the influence of S on the bioavailability and speciation of Cd varied not only with the soil Cd content but also with the application rate and S valence state.

Assessment of the effects of different tree species on urban microclimate

Abstract

Trees in urban areas are important for their ecological functions in addition to their esthetic characteristics. Trees provide positive effects on urban microclimate by canopy, reflection, and transpiration activities; therefore, they help to decline formation of heat island. The objective of this study was to determine thermal effects of 15 different tree types: 4 coniferous and 11 deciduous species commonly found in the city of Erzurum located at the northeastern part of Turkey. The relationships between sky view factor and surface temperature regarding the differences in leaf density and tree species. In August 2016, the surface temperature of trees was measured using a thermal camera at 10:00 am and 4:00 pm hours. Sky view factor (SVF) was obtained by fisheye photos and physiologically characteristics of trees were determined. In all trees while the surface temperature was 20.1 °C at 10:00 am, it was 23.4 °C at 4:00 pm. Among the deciduous tree species, Betula verrucosa Ehrh. and Robinia pseudoacacia "Umbracuifera" had the lowest surface temperature; however, Abies concolor (Gord. & Glen.) had the lowest surface temperature among the coniferous tree species. The results indicated that the surface temperatures of different tree species varied considerably, and the SVF value had a significant effect on tree surface temperatures. However, it was obtained that the leaf types had no statistically significant effect on tree surface temperature.

Decision modelling of non-pharmacological interventions for individuals with dementia: a systematic review of methodologies

The main objective of this study is to conduct a systematic review to identify and discuss methodological issues surrounding decision modelling for economic evaluation of non-pharmacological interventions (NPI...

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Ahead of Print.

Using carbonized low-cost materials for removal of chemicals of environmental concern from water

Abstract

Adsorption on low-cost biochars would increase the affordability and availability of water treatment in, for example, developing countries. The aim of this study was to identify the precursor materials and hydrochar surface properties that yield efficient removal of compounds of environmental concern (CEC). We determined the adsorption kinetics of a mixture containing ten CECs (octhilinone, triclosan, trimethoprim, sulfamethoxasole, ciprofloxacin, diclofenac, paracetamol, diphenhydramine, fluconazole, and bisphenol A) to hydrochars prepared from agricultural waste (including tomato- and olive-press wastes, rice husks, and horse manure). The surface characteristics of the hydrochars were evaluated via diffuse reflectance infrared spectroscopy (DRIFTS), X-ray photoelectron spectroscopy (XPS), and N₂-adsorption. Kinetic adsorption tests revealed that removal efficiencies varied substantially among different materials. Similarly, surface analysis revealed differences among the studied hydrochars and the degree of changes that the materials undergo during carbonization. According to the DRIFTS data, compared with the least efficient adsorbent materials, the most efficient hydrochars underwent more substantial changes during carbonization.

Protective effect of grape or apple juices in bone tissue of rats exposed to cadmium: role of RUNX-2 and RANK/L expression

Abstract

The aim of this study was to investigate if grape or apple juices are able to protect bone tissue of rats exposed to cadmium. For this purpose, histopathological analysis and immunohistochemistry for RUNX-2 and RANK-L were investigated in this setting. A total of 20 adult Wistar rats were distributed into four groups (n = 5), as follows: control group, cadmium group, cadmium and grape juice group, and Cadmium and apple juice group. Control group received a single intraperitoneal (i.p.) water injection. Cadmium group received a single i.p. injection of cadmium chloride (1.2 mg/kg body weight) diluted in water. Cadmium and grape juice and cadmium and apple juice groups received a single i.p. injection of cadmium chloride (1.2 mg/kg body), and after 15 days, the rats were treated with grape or apple juices for 15 days, by gavage. All animals were euthanized 30 days after the beginning of experiment. Histopathological analysis in rat femur revealed extensive bone loss in rats intoxicated with cadmium. Grape or apple juices were able to increase bone formation. Cadmium inhibited RUNX-2 immunoexpression whereas cadmium increased RANK-L immunoexpression in rat bone cells. Grape or apple juices increased RUNX-2 and decreased RANK-L immunoexpression after cadmium intoxication. Taken together, our results demonstrate that grape or apple juices are able to exert therapeutic activity following cadmium intoxication in rat bone tissue as result of stimulatory effect of bone formation by RUNX-2 upregulation and RANK-L downregulation.

Caffeine levels as a predictor of Human mastadenovirus presence in surface waters—a case study in the Sinos River basin—Brazil

Abstract

The presence of caffeine in environmental water samples is almost entirely human-related, given that there are virtually no industrial or agricultural releases. Caffeine has already been proposed as an anthropogenic marker for wastewater contamination of surface waters. The aim of this study was to evaluate if caffeine concentrations in water can be a predictor of virological and bacteriological contamination. Water samples were taken at three sampling sites from urban water streams from the hydrographic basin of the Sinos River (Brazil) monthly in the period of May 9th, 2016 to April 11th, 2017 (n = 36). Concentrations of Human mastadenovirus (HAdV-F and HAdV-C), fecal coliforms, and caffeine were measured in all collected samples. Concentrations of caffeine in water were strongly correlated with HAdV-F (r_s = 0.704, p = 0.000). This study, for the first time, characterized caffeine concentrations in water as predictors of virus presence, with cut-off values presenting 92.9% specificity and 95.5% sensitivity for HAdV-F and 66.7% specificity and 80% sensitivity for HAdV-C. Considering its marked chemical stability and ease of quantification, caffeine concentrations can be used as a comprehensive marker of human contamination of water resources, also being predictive of bacteriological and virological concentrations.

Remediation of cadmium contaminated water and soil using vinegar residue biochar

Abstract

This study investigated a new biochar produced from vinegar residue that could be used to remediate cadmium (Cd)-contaminated water and soil. Aqueous solution adsorption and soil incubation experiments were performed to investigate whether a biochar prepared at 700 °C from vinegar residue could efficiently adsorb and/or stabilize Cd in water and soil. In the aqueous solution adsorption experiment, the Cd adsorption process was best fitted by the pseudo-second-order kinetic and Freundlich isotherm models. If the optimum parameters were used, i.e., pH 5 or higher, a biochar dosage of 12 g L⁻¹, a 10 mg L⁻¹ Cd initial concentration, and 15-min equilibrium time, at 25 °C, then Cd removal could reach about 100%. The soil incubation experiment evaluated the biochar effects at four different application rates (1, 2, 5, and 10% w/w) and three Cd contamination rates (0.5, 1, and 2.5 mg kg⁻¹) on soil properties and Cd fractionation. Soil pH and organic matter increased after adding biochar, especially at the 10% application rate. At Cd pollution levels of 1.0 or 2.5 mg kg⁻¹, a 10% biochar application rate was most effective. At 0.5 mg Cd kg⁻¹ soil, a 5% biochar application rate was most efficient at transforming the acid extractable and easily reducible Cd fractions to oxidizable and residual Cd. The results from this study demonstrated that biochar made from vinegar residue could be a new and promising alternative biomass-derived material for Cd remediation in water and soil.

Assessment of biotoxicity of Cu nanoparticles with respect to probiotic strains of microorganisms and representatives of the normal flora of the intestine of broiler chickens

Abstract

Copper nanoparticle Cu (d = 55 ± 15 nm) and CuO nanoparticles (d = 90 ± 10 nm) were used in the studies (OOO Platina, Russia). Using the method of pure cultures, we extracted Lactobacillus, Enterococcus, and Enterobacterium from the intestines of broilers. Additionally, strains of Bacillus subtilis 10641 and Bifidobacterium were involved in probiotic strains. The data obtained in the course of the study testify to the insignificant biotoxicity of copper nanoparticles with respect to representatives of the genera Lactobacillus (30 to 15 μg/ml) and Bifidobacterium (30 μg/ml), with the most sensitive bacteria being the genus Lactobacillus, for which a concentration of 7.5 μg/ml was subinhibitory. The second stage was the study using method of agar wells. In the course of the experiment, we obtained results confirming the data of the research by the serial dilution method. In this case, as in the first case, the data indicate the insignificant biotoxicity of copper nanoparticles in relation to representatives of the genera Lactobacillus and Bifidobacterium. We have studied the bioaccumulating ability of microorganisms of the studied metals. In all the studies carried out, as in the first series of experiments, representatives of the genera Lactobacillus and Bifidobacterium with the lowest bioaccumulative ability were the most sensitive to copper nanoparticles and were 3.1 and 8.2%, respectively. The use of nanoparticles as a component of the fodder additive in small concentrations does not adversely affect not only the probiotic strains, but also the main representatives of the normoflora (Lactobacillus, Enterococcus, and Enterobacterium) of the poultry, the positive effect of the copper nanoparticles being directly related to low level of dissociation of nanoparticles, since biologically active ions will be released much more slowly, thereby creating a prolonged effect of exposure.

The effect of platelet-rich plasma on motility changes in experimental caustic esophageal burn

Abstract

Background

Besides stricture formation, diminished esophageal motility after caustic esophageal burns also plays a role in the deterioration of the clinical course. In this study, we aimed to investigate the effect of caustic burn on the esophageal contractions and the effect of platelet-rich plasma (PRP) on these changes.

Methods

Twenty-one Wistar albino rats were divided into three groups [Sham operation (n = 8), caustic esophageal burn with NaOH (n = 6), PRP treatment after caustic burn (n = 7)]. After 3 weeks, esophagectomy was performed and contractions and EFS responses were evaluated in the organ bath.

Results

KCl- and acetylcholine-induced responses were reduced in the Burn group, but increased in Sham and PRP groups (p < 0.05). EFS responses were higher in Burn group compared to the other groups. Response with l-arginine was increased in Burn group, but decreased in PRP group. There was more decrease in the contraction in Sham and PRP groups compared to the Burn group after SNP (sodium nitroprusside) incubation (p < 0.05). L-NAME (Nω-Nitro-l-arginine methyl ester) did not change the EFS responses in the Burn group, but EFS responses were decreased significantly in Sham and PRP groups (p < 0.05). EFS responses were decreased in all groups, but more in the Sham and PRP groups after Y-27632 (Rho-kinase inhibitor) incubation (p < 0.05).

Conclusions

For the first time, we demonstrated that both cholinergic and non-adrenergic non-cholinergic mechanisms are responsible for the altered motility in corrosive esophageal injury. Our results suggest that PRP treatment may be helpful in regulating the esophageal motility and decreasing altered contractions in corrosive burns. This effect may also contribute to the reduction of stricture formation, especially by reducing inappropriate contractions of the esophageal wall during the post-burn healing phase.

Disposition ascriptions

Abstract

I argue that disposition ascriptions—claims like 'the glass is fragile'—are semantically equivalent to possibility claims: they are true when the given object manifests the disposition in at least one of the relevant possible worlds.

A consequentialist account of Narveson’s dictum

Abstract

In population ethics, Narveson's dictum states: morality favours making people happy, but is neutral about making happy people. The thought is intuitively appealing; for example, it prohibits creating new people at the expense of those who already exist. However, there are well-known obstacles to accommodating Narveson's dictum within a standard framework of overall betterness: any attempt to do so violates very plausible formal features of betterness (notably transitivity). Therefore, the prevailing view is that the dictum is off-limits to consequentialists, who are thereby committed to the unsavoury normative consequences of denying it. We argue against the prevailing view, by showing that Narveson's dictum can be accommodated within "multidimensional" consequentialism. The key move is to deny the normative preeminence of overall betterness, instead taking moral decision-making to rest directly on "respects" of betterness. The multidimensional approach permits a consequentialist account of Narveson's dictum in which betterness is well-behaved. It also yields a new way to think of the connection between goodness and rightness, thus revealing new terrain in the space of possible moral theories.

Rezidiviertes oder refraktäres klassisches Hodgkin-Lymphom

Zusammenfassung

Hintergrund

Das klassische Hodgkin-Lymphom ist mit risikoadaptierter Erstlinientherapie in den meisten Fällen heilbar. Neben der Reduktion möglicher therapieassoziierter Früh- und Langzeitschädigungen stellt v. a. die Therapie von Patienten mit rezidivierter oder primär refraktärer Erkrankung (r/r HL) eine klinische Herausforderung dar.

Methoden

Dieser Übersichtsartikel fasst die aktuell verfügbaren Daten zu Sicherheit und Effektivität verschiedener Therapieansätze beim r/r HL zusammen und gibt Handlungsempfehlungen für verschiedene klinische Situationen.

Ergebnisse

Bis zu 50 % der für eine intensivierte Therapie geeigneten Patienten erreichen nach einer Hochdosischemotherapie mit autologer Stammzelltransplantation (ASZT) eine langfristige Remission. Mehrfach rezidivierte, refraktäre, ältere oder multimorbide Patienten hatten bis vor einigen Jahren bei größtenteils palliativen Therapieoptionen eine schlechte Prognose. Das Anti-CD30-Antikörper-Wirkstoffkonjugat Brentuximab Vedotin (BV) ermöglicht eine zielgerichtete Therapie mit hohen Ansprechraten sowie teilweise dauerhaften kompletten Remissionen und ist nach ASZT oder zwei vorangegangen Therapien für das r/r HL zugelassen. Zuletzt wurden die beiden Anti-PD-1-Antikörper Nivolumab und Pembrolizumab als Immuncheckpointinhibitoren auch bei Patienten mit intensiv vorbehandeltem r/r HL untersucht. Beide Substanzen zeigten bei sehr guter Verträglichkeit deutlich höhere Ansprechraten als bei anderen malignen Erkrankungen und lange Remissionen. Nivolumab und Pembrolizumab wurden daher kürzlich für das r/r HL nach vorausgegangener Therapie mit BV zugelassen. Zudem zeigten weitere zielgerichtete Substanzen wie AFM13, Everolimus, Panobinostat oder Mocetinostat sowie auch Lenalidomid oder Bendamustin Aktivität bei intensiv behandelten Patienten.

Therapiealgorithmus für Patienten mit Hodgkin-Lymphom

Tumorassoziierte Fatigue beim Hodgkin-Lymphom

Zusammenfassung

Hintergrund

Da heutzutage die meisten Hodgkin-Patienten geheilt werden können, ist die Nachsorge der überwiegend jungen Langzeitüberlebenden in den Mittelpunkt gerückt. Zu den häufigsten Beeinträchtigungen zählt die tumorassoziierte Fatigue („cancer-related fatigue", CrF).

Fragestellung

Dieser Artikel gibt einen Überblick über die Häufigkeit, Entwicklung und den Verlauf von CrF beim Hodgkin-Lymphom (HL), deren langfristige Folgen für die soziale Reintegration sowie über bestehende therapeutische Optionen.

Material und Methoden

Mittels systematischer und manueller Literaturrecherche wurden relevante Publikationen sowie im Rahmen aktueller Studien getestete neue Therapieansätze für CrF zusammengefasst.

Ergebnisse

CrF ist bereits zum Zeitpunkt der Diagnosestellung vorhanden, wobei das Ausmaß der Fatigue mit fortschreitendem Stadium zunimmt. Unter laufender Therapie kommt es unabhängig vom Stadium und der erhaltenen Therapie zu einem starken Anstieg der Fatigue auf ein nahezu identisch hohes Niveau. Wichtigster prognostischer Faktor für den Verlauf und den Schweregrad der Langzeit-Fatigue ist die Baseline-Fatigue. Die Therapieintensität hingegen nimmt auf das Ausmaß und den Verlauf der Fatigue keinen Einfluss. In allen Stadien konnten mehrere Subgruppen mit unterschiedlichen Fatigue-Verläufen identifiziert werden. Patienten mit schwerer Fatigue bei Diagnosestellung müssen auch mit dauerhafter, schwerer Fatigue rechnen. In den anderen Subgruppen konnten hingegen teils wesentliche Verbesserungen beobachtet werden. Neben der Einschränkung der Lebensqualität hat das Leiden an Fatigue auch relevante sozioökonomische Folgen. Die Zahl der Überlebenden mit Fatigue, die sich nach 5 Jahren in einem festen Beschäftigungsverhältnis oder in Ausbildung befinden, ist fast 30 % niedriger verglichen mit Überlebenden ohne Fatigue. Mit körperlichen Trainingsprogrammen sowie verhaltenstherapeutischen Maßnahmen konnten bislang gute Erfolge in der Therapie von CrF erzielt werden.

Schlussfolgerungen

Der Leidensdruck der Betroffenen ist hoch. Weitere randomisierte, klinische Studien sind erforderlich, um die Therapieoptionen und somit das Outcome der Patienten zu verbessern.

Positronenemissionstomographie beim Hodgkin-Lymphom

Zusammenfassung

Hintergrund

Die FDG-PET (Fluordesoxyglucose-Positronenemissionstomographie) ist eine Standarduntersuchung in der Bestimmung des Stadiums und des Therapieansprechens des Hodgkin-Lymphoms geworden.

Ergebnisse

Im initialen Staging erlaubt die PET eine sichere Stadienzuordnung und bei unauffälligem osteomedullärem Befund den Verzicht auf die Knochenmarkbiopsie. Der prädiktive Wert der FDG-PET während und nach der Chemotherapie bietet weiteren, deutlichen Zugewinn an Information. PET-gesteuerte Therapieregime wurden eingeführt, die die PET schon nach 2 Zyklen Chemotherapie zur weiteren Therapiestratifizierung einsetzen. Sowohl Protokolle, die eine Intensivierung der Therapie aufgrund einer positiven PET nutzen, als auch die Deeskalation der Therapie wegen einer unauffälligen, negativen PET haben Erfolge gezeigt. So kann z. B. bei negativer FDG-PET nach 2 Zyklen effektiver Chemotherapie für fortgeschrittene Stadien die Therapie von üblicherweise 6 auf insgesamt nur 4 Zyklen verkürzt werden. Nach Chemotherapie kann in fortgeschrittenen Stadien bei negativer FDG-PET außerdem ohne Verlust an Therapiesicherheit auf eine ergänzende Bestrahlung verzichtet werden.

Ausblick

Für frühe und mittlere Stadien ist die Möglichkeit des Verzichts auf die Bestrahlung noch nicht gezeigt, jedoch werden belastbare Daten erwartet. Robuste und reproduzierbare Beurteilungskriterien für die PET sind heute Standard bei der Interpretation der Untersuchung, sowohl in wissenschaftlichen Studien als auch in der täglichen klinischen Routine. Die sog. 5‑Punkte-Deauville-Skala ist derzeitiger Standard zur visuellen Analyse. Die Konsequenzen aus der jeweiligen Zuordnung berücksichtigen dabei sowohl die vorangegangene als auch die folgende Behandlung.

Therapie des Hodgkin-Lymphoms in frühen und intermediären Stadien

Zusammenfassung

Hintergrund

In frühen und intermediären Stadien des Hodgkin-Lymphoms (HL) kann die überwiegende Zahl der Patienten durch eine risikoadaptierte Chemo- und Strahlentherapie (RT) geheilt werden. Allerdings trägt die therapieassoziierte Langzeittoxizität wesentlich zu Morbidität und Mortalität bei. Aktuelle Studien haben daher zum Ziel, die therapieassoziierte Toxizität unter Erhalt bzw. weiterer Verbesserung der erreichten Tumorkontrolle zu reduzieren.

Ziel

Ziel war die Entwicklung einer Therapieleitlinie für die frühen und intermediären Stadien des HL auf der Grundlage aktueller Studiendaten.

Methoden

Es erfolgte eine Analyse der Tumorkontrolle, des Gesamtüberlebens und der verfügbaren Toxizitätsdaten in aktuellen randomisierten Studien, Metaanalysen und relevanten retrospektiven Auswertungen.

Ergebnisse und Schlussfolgerung

In den frühen Stadien sind 2 Zyklen ABVD (Adriamycin, Bleomycin, Vinblastin, Dacarbazin) und 20 Gy Involved-Site-RT (IS-RT) aufgrund der hervorragenden Überlebensdaten (HD10) und der Etablierung des kleineres Bestrahlungsfelds der IS-RT Therapiestandard. In den intermediären Stadien kann mit 4 Zyklen ABVD und 30 Gy IF-RT (Involved-Field-RT) ein progressionsfreies Überleben (PFS) von bis zu 83 % erzielt werden. Eine signifikante Verbesserung der Tumorkontrolle wurde bei höherer Akuttoxizität mit 2 Zyklen BEACOPP_eskaliert (Bleomycin, Etoposid, Doxorubicin, Cyclophosphamid, Vincristin, Procarbazin, Prednison) und 2 Zyklen ABVD („2 + 2"; HD14) erreicht. Die in H10 angewandte ^18FFDG-PET-basierte Applikation von 2 Zyklen BEACOPP_eskaliert bei nach 2 Zyklen ABVD PET-positiven Patienten könnte bei einem signifikanten Teil der Patienten bei vergleichsweise gutem PFS die Therapieintensität reduzieren. Es bedarf jedoch weiterer Daten zur Etablierung dieses Ansatzes. Daher werden aktuell „2 + 2" + 30 Gy IS-RT bei Patienten bis 60 Jahre als Standard empfohlen. Die verfügbaren Daten unterstützen die Rolle der RT in der erzielten Tumorkontrolle. Eine ^18FFDG-PET-basierte RT kann als individueller Therapieansatz angewandt werden.

Neue Entwicklungen in der Therapie des fortgeschrittenen klassischen Hodgkin-Lymphoms

Zusammenfassung

Hintergrund

Das Gesamtüberleben von Patienten mit fortgeschrittenem Hodgkin-Lymphom (HL), die mit dem aktuellen Standard der Deutschen Hodgkin Studiengruppe (DHSG), bestehend aus der Interim-Positronen-Emissionstomographie(PET)-gesteuerten Gabe von 4 bis 6 Zyklen BEACOPP_eskaliert (Bleomycin, Etoposid, Doxorubicin, Cyclophosphamid, Vincristin, Procarbazin und Prednison in eskalierter Dosierung) plus Bestrahlung Positronen-Emissionstomographie-positiver Reste, behandelt werden, liegt bei mehr als 95 %. Es ist dennoch nötig, die Toxizität der Therapie weiter zu minimieren, ohne dabei Einbußen in der Effektivität zu erleiden. Langfristiges Ziel ist also die Reduktion von Nebenwirkungen bei gleichbleibend gutem Therapieerfolg.

Ziel

Ziel des vorliegenden Artikels ist es, eine Zusammenfassung über die gegenwärtigen Standardtherapien sowie neue Entwicklungen in der Behandlung des fortgeschrittenen HL zu geben.

Material und Methode

Mittels systematischer und manueller Literaturrecherche wurden relevante Publikationen sowie im Rahmen derzeit laufender Studien getestete neue Therapieansätze zusammengefasst.

Ergebnisse

Vergleiche von BEACOPP_eskaliert und ABVD (Doxorubicin, Bleomycin, Vinblastin, Dacarbazin) zeigen einen signifikanten und klinisch bedeutenden Überlebensvorteil für BEACOPP_eskaliert sowohl im Sinne des progressionsfreien Überlebens (PFS) als auch des Gesamtüberlebens (OS). Die Interim-PET-gesteuerte Gabe von 4−6 Zyklen BEACOPP_eskaliert ist sicher und hoch effektiv. Dennoch ist eine weitere Optimierung der Therapie, z. B. durch die Implementierung zielgerichteter Substanzen wie Brentuximab Vedotin, möglich. Daher wird derzeit eine BEACOPP-Variante namens BrECADD (Brentuximab Vedotin, Etoposid, Cyclophosphamid, Doxorubicin, Dacarbazin, Dexamethason) im Rahmen der HD21-Studie randomisiert mit herkömmlichem BEACOPP_eskaliert verglichen. Zuvor wurde im Rahmen einer Phase-II-Studie gezeigt, dass BrECADD bei Patienten mit fortgeschrittenem HL sicher angewendet werden kann.

Schlussfolgerungen

Langfristiges Ziel in der Behandlung des HL ist die Reduktion der Toxizität der Therapie ohne Verschlechterung der Tumorkontrolle und des lymphomspezifischen Outcomes. Dies kann möglicherweise durch die Implementierung zielgerichteter Substanzen in die Erstlinientherapie erreicht werden. Daher wird momentan die Brentuximab Vedotin enthaltende BEACOPP-Variante BrECADD im Rahmen der HD21-Studie randomisiert gegen konventionelles BEACOPP_eskaliert getestet.

Assessment of Severity of Illness and Monitoring Response to Treatment of Odontogenic Space Infection Using Serum Prealbumin

Abstract

Purpose

To assess Serum Prealbumin in the severity of illness and monitor response to treatment in odontogenic space infection.

Patients and Methods

This was a prospective cohort study comprising patients being managed for odontogenic space infection at the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria. The calculated sample size was 69. Clinical parameters (Swelling Size, Visual Analogue Scale for pain intensity, and Maximal Interincisal Distance) were measured on day 0, day 4, and day 8. Other clinical parameters were Number of Anatomic Spaces Involved, setting of treatment, and Length of Hospital Stay. Serum Prealbumin levels were also serially measured. The relationship between Serum Prealbumin level and the clinical parameters was established using Spearman's correlation test, independent t test, Friedman's test, and linear regression. Significance level was set at .05.

Results

The mean Serum Prealbumin level at presentation (day 0) was 19.19 ± 4.61 mg/dl, which was significantly lower among inpatients (p = 0.001). On days 0, 4, and 8, Serum Prealbumin negatively correlated with Number of Anatomic Spaces Involved (p < 0.001). Serum Prealbumin levels on days 0, 4, and 8 and response in Serum Prealbumin negatively correlated with Length of Hospital Stay. On each day, Serum Prealbumin negatively correlated with pain intensity and Swelling Size and positively correlated with mouth opening. The response in Serum Prealbumin also positively correlated with response in each of the three clinical parameters.

Conclusion

This study suggests that Serum Prealbumin is a reliable tool for grading severity of illness and monitoring response to treatment in odontogenic space infection.

Digging Deeper: Why Metaphysics is More Than a Toolbox

Abstract

Steven French (J Gen Philos Sci, https://ift.tt/2Gc0ihc, 2018) proposes a vindication of "scientifically disinterested" metaphysics that leaves little room to its original ambitions. He claims that (1) as a discipline that looks to find out truths about the world, it is untenable; and that (2) rather, its vindication lies in its use as a "toolbox" of concepts for a philosophical discipline that does have a claim at getting us closer to truth—the philosophy of science, and more specifically of physics. I respond to both his main claims. The first claim, I argue, neglects what I call (with Ralf Busse) "archaeological" metaphysics, which tries to impose some order on phenomena by "digging deeper" from the less to the more fundamental, or from the less to the more abstract questions. The second claim imposes a hierarchical relation between metaphysics and philosophy of science which should, I argue, be replaced with a more egalitarian picture of philosophy.

The expanding horizon of alkyl quinolone signalling and communication in polycellular interactomes

Abstract

Population dynamics within natural ecosystems is underpinned by microbial diversity and the heterogeneity of host-microbe and microbe-microbe interactions. Small molecule signals that intersperse between species have been shown to govern many virulence-related processes in established and emerging pathogens. Understanding the capacity of microbes to decode diverse languages and adapt to the presence of 'non-self' cells, will provide an important new direction to the understanding of the 'polycellular' interactome. Alkyl Quinolones (AQs) have been described in the ESKAPE pathogen Pseudomonas aeruginosa, the primary agent associated with mortality in patients with Cystic Fibrosis and the third most prevalent nosocomial pathogen worldwide. The role of these molecules in governing the physiology and virulence of P. aeruginosa and other pathogens has received considerable attention, while a role in interspecies and interkingdom communication has recently emerged. Herein we discuss recent advances in our understanding of AQ signalling and communication in the context of microbe-microbe and microbe-host interactions. The integrated knowledge from these systems-based investigations will facilitate the development of new therapeutics based on the AQ framework that serve to disarm the pathogenesis of P. aeruginosa and competing pathogens.

p xmMetabolites of endophytic fungi from Australian native plants as potential anticancer agents

Abstract

Interest in endophytes as natural sources for new medicines was inspired by the discovery of paclitaxel-producing endophytic fungi. This study investigated the anti-cancer activity of extracts of endophytes isolated from two Australian plants, Eremophila longifolia (EL) and Eremophila maculata (EM). Endophytes were isolated from surface-sterilised leaf tissue, grown as pure cultures and identified by sequencing of ITS regions of the ribosomal DNA. To determine cytotoxicity, two leukaemic (MOLT-4, T-cell leukaemia; PreB-697, Pre-B leukaemia), a lung cancer cell line (A549) and a normal human fibroblast cell line were treated with endophyte extracts to assess cytotoxicity in relation to alternariol monomethyl ether (AME) and alternariol (AOH). Endophyte extracts that showed cell cytotoxicity were analysed by UV HPLC to determine the metabolites. Pure AME and AOH, three extracts form Alternaria sp. (EM-6, EM-7 and EM-9) and one from Preussia minima sp. (EL-14) were cytotoxic to the cancer cell lines. All cytotoxic endophytes contained AME and AOH, the most cytotoxic endophyte EM-6 also contained two unique peaks. These data indicate that these four endophyte extracts may have anti-cancer properties due to the presence of AME and AOH, however the unique compounds found in the EM-6 extract may be exclusively cytotoxic and warrant further investigation.

Metabolic Engineering of E. coli for the Production of Isoprenoids

Abstract

Metabolic engineering is the practice of using directed genetic manipulations to rewire cellular metabolism primarily with the aim to transform the organism into a single-celled chemical factory. Using biological processes, we can produce more complex chemicals in a more sustainable way. This is particularly important for chemicals which are hard to synthesize using traditional chemistry. However, cells have evolved for growth and must be engineered to produce a single chemical at commercially viable levels. This review focuses on the strategies used to rewire cellular metabolism to produce chemicals using isoprenoid production in E. coli as an example which illustrates many of the challenges faced in metabolic engineering.

Prognostic Value of Contrast Enhancement and FLAIR for Survival in Newly Diagnosed Glioblastoma Treated With and Without Bevacizumab: Results from ACRIN 6686

Abstract

Background

ACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed glioblastoma. This study investigated whether changes in contrast-enhancing and FLAIR-hyperintense tumor assessed by central reading prognosticate overall survival (OS).

Methods

284 patients (171 men; median age 57 years, range 19-79; 159 on bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant temozolomide (22 weeks post- chemoradiation initiation). Four central readers measured bi-dimensional lesion enhancement (2D-T1) and FLAIR hyperintensity at both time points. Changes from baseline to pre-cycle 4 for both markers were dichotomized (increasing versus non-increasing). Cox proportional hazards model and Kaplan-Meier survival estimates were used for inference.

Results

Adjusting for treatment, increasing 2D-T1 (n=262, HR=2.07 [95% CI 1.48-2.91], p<0.0001) and FLAIR (n=273, HR=1.75 [1.26-2.41], p=0.0008) significantly predicted worse OS. Median OS (days) was significantly shorter for patients with increasing versus non-increasing 2D-T1 for both bevacizumab (443 vs. 535, p=0.004) and placebo (526 vs. 887, p=0.001). Median OS was significantly shorter for patients with increasing versus non-increasing FLAIR for placebo (595 vs. 872, p=0.001), and trended similarly for bevacizumab (499 vs. 535, p=0.0935). Adjusting for 2D-T1 and treatment, increasing FLAIR represented significantly higher risk for death (HR=1.59 [1.11-2.26], p=0.01).

Conclusions

Increased 2D-T1 significantly predicts worse OS in both treatment groups, implying absence of a substantial proportion of pseudoprogression 22 weeks after initiation of standard therapy. FLAIR adds value beyond 2D-T1 in predicting OS, potentially addressing the pseudoresponse effect by sub-stratifying bevacizumab-treated patients with non-increasing 2D-T1.

The T2-FLAIR Mismatch Sign as an Imaging Marker for Non-Enhancing IDH-mutant, 1p/19q-intact Lower Grade Glioma: A Validation Study

Abstract

Background

The purpose of this study was to assess the reproducibility of the previously described T2-FLAIR mismatch sign as a specific imaging marker in non-enhancing isocitrate dehydrogenase (IDH) mutant, 1p/19q non-codeleted lower grade glioma (LGG), encompassing both diffuse and anaplastic astrocytoma.

Methods

MR scans (n=154) from three separate databases with genotyped LGG were evaluated by two independent reviewers to assess (i) presence/absence of "T2-FLAIR mismatch" sign and (ii) presence/absence of homogenous signal on T2WI. Interrater agreement with Cohen's kappa (κ) was calculated, as well as diagnostic test performance of the T2-FLAIR mismatch sign to identify IDH-mutant astrocytoma.

Results

There was substantial interrater agreement for the T2-FLAIR mismatch sign [κ = 0.75 (0.64, 0.87)], but only fair agreement for T2 homogeneity [κ = 0.38 (0.25-0.52)]. The T2-FLAIR mismatch sign was present in 38 cases (25%) and had a positive predictive value of 100%, negative predictive value of 68%, a sensitivity of 51% and a specificity of 100%.

Conclusions

With a robust interrater agreement, our study confirms that among non-enhancing LGG the T2-FLAIR mismatch sign represents a highly specific imaging marker for IDH-mutant astrocytoma. This non-invasive marker may enable a more informed patient counsel and can aid in the treatment decision processes in a significant proportion of patients presenting with non-enhancing, LGG like lesions.

Population Description and Clinical Response Assessment for Spinal Metastases: Part 2 of the SPIne Response Assessment in Neuro-Oncology (SPINO) Group Report

Abstract

Background

Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group.

Methods

SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches.

Results

Published literature, expert survey and ongoing clinical trials were used in to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurologic and functional status and symptom severity.

Conclusions

Accurate description of patient population and therapy effects requires a combination of clinician-based and patient reported outcome (PRO) measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and post-operative spine SBRT.