Medicine by Alexandros G. Sfakianakis: 08/18/18

Σάββατο 18 Αυγούστου 2018

Immunotherapy in Prostate Cancer: Teaching an Old Dog New Tricks

Abstract

Immunotherapy is rapidly transforming cancer care across a range of tumor types. Although Sipuleucel-T represented the first successful vaccine for the treatment of established cancer, other immunotherapeutic approaches for prostate cancer such as checkpoint inhibitors have been relatively disappointing to date. However, significant promise is on the horizon as there is a wide array trials evaluating immunotherapy in prostate cancer patients. These include both immune checkpoint inhibitors and antigen-specific approaches including vaccines, antibody-drug conjugates, and antitumor antibodies. Furthermore, a better understanding of the key mechanisms that promote the immunosuppressive microenvironment of prostate cancer is emerging. These insights may eventually make it possible to determine which patients will benefit from immunotherapy. This review will discuss the successes and failures of immunotherapy in prostate cancer. We will also present key lessons learned from completed trials and highlight important ongoing studies.

Long-term Effects of Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients with Acute Lymphoblastic Leukemia

Abstract

Purpose of Review

Allogeneic hematopoetic stem cell transplantation (HSCT) is a curative option for children and adolescents with high-risk leukemia. Although acute complications were reduced during the last decade, considerable late effects are still limiting the overall success rate. This article emphasizes the specific pediatric aspects of long-term aftercare following myeloablative HSCT and provides an organ-based overview that covers main clinical patterns, incidence, and risk factors enhanced by current references and screening guidelines.

Recent Findings

In the last years, several attempts were made to separate pediatric outcome data from findings in adults. It turned out that not only the indication for but also the time and the procedures of HSCT substantially differ. Nearly any organ might be affected after the complex transplantation process and includes endocrinopathies, musculoskeletal disorders, cardiopulmonary complications, and secondary malignancies.

Summary

Patients after HSCT in childhood have a high risk for developing a wide range of late sequelae and may benefit from regular screening and early intervention. The occurrence and patterns of late effects depend on the intensity and severity of conditioning and are strongly associated with patient's age at transplant and beginning of complications.

Adoptive Cell Therapy in Treating Pediatric Solid Tumors

Abstract

Purpose of Review

This review will discuss the challenges facing adoptive cell techniques in the treatment of solid tumors and examine the therapies that are in development for specifically pediatric solid tumors.

Recent Findings

Targeting solid tumors with adoptive cell therapy has been limited by the inhibitory tumor microenvironment and heterogeneous expression of targetable antigens. Many creative strategies to overcome these limitations are being developed but still need to be tested clinically. Early phase clinical trials in neuroblastoma with GD2 CAR T cells are promising but results need to be validated on a larger scale. Most research in other pediatric solid tumors is still in early stages.

Summary

Adoptive cell therapy represents a useful tool to improve the outcomes of many pediatric solid tumors but significant study is still required. Several clinical trials are ongoing to test therapies that have shown promise in the lab.

Immune Checkpoint Inhibitor Toxicity

Abstract

Purpose of review

Immune checkpoint inhibitors have revolutionised the treatment of multiple malignancies and have a growing list of indications. As our familiarity with these agents grows, so does our understanding of their unique spectrum of toxicities. Here, we will review the literature regarding the toxicities of checkpoint inhibitors and address challenges encountered in day-to-day clinical practice.

Recent findings

Inhibitors of the PD-1/PD-L1 axis are considerably less toxic than the anti-CTLA-4 antibody ipilimumab. The combination of ipilimumab and anti-PD-1 agents is being trialled in multiple malignancies and is associated with increased toxicity. There is accumulating evidence suggesting a potential correlation between a subset of toxicities and clinical benefit in several tumour types, although conflicting data exists. Retrospective series have shown that anti-PD-1 can be safely administered to patients with prior high-grade toxicity from ipilimumab or combination immunotherapy.

Summary

The management of checkpoint inhibitor toxicity is complex and requires collaboration with our subspecialty colleagues. Identifying predictive biomarkers of both efficacy and toxicity would likely help guide treatment decisions, and should be a research priority in the years ahead.

Endoscopic Treatment of Early-Stage Esophageal Cancer

Abstract

Purpose of Review

Esophageal cancer is a leading cause of global cancer-related mortality. Here, we discuss the major endoscopic treatment modalities for management of early esophageal cancer (EEC).

Recent Findings

Advances in endoscopic imaging and therapy have shifted the paradigm of managing early esophageal cancers. Though esophagectomy remains the preferred management for advanced cancers, guidelines now recommend endoscopic resection followed by ablative therapy for early (Tis and T1a) cancers. Available data suggests endoscopic treatment is comparable to surgery with regard to overall and cancer-specific survival with lower procedural morbidity and mortality.

Summary

Endoscopic modalities are emerging as frontline treatment options for patients with early esophageal cancers. Accurate clinical staging with assessment of disease extent, tumor grade, and risk of nodal metastases is crucial when determining eligibility for endoscopic management of EEC. High-quality routine surveillance endoscopy is critical in patients who have undergone resection and/or ablation.

The content of dioxins and furans in soils, bottom sediments of water bodies, and tissues of small mammals near the landfill site with municipal solid wastes (Moscow, Russia)

Abstract

For the first time, the levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were characterized in the tissues of wild small mammals living in contaminated sites near a municipal solid waste landfill (Moscow, Russia). The Ural field mice Sylvaemus uralensis, the bank voles Clethrionomys glareolus, and the common shrews Sorex araneus were trapped at 1- and 5-km distances from the landfield "Salariyevo." High-resolution chromatography-mass spectrometry was used to measure the levels of 17 PCDD/Fs congeners in the animal organisms and natural objects (soils, bottom sediments). The values of the total toxic equivalencies (WHO-TEQ₀₅) for animals were many times higher than those for soils and bottom sediments. The octo-substituted congeners dominated in the samples from the habitat, whereas the highly toxic 2,3,7,8-substituted ones — in the mammalian tissues. The levels of WHO-TEQ₀₅ were comparable in the soil samples collected at 1- and 5-km distances from the dump body. The levels of WHO-TEQ₀₅ in tissues of mammals caught 1 km from the dump were much higher than those of the distant territory inhabitants. The maximum WHO-TEQ₀₅ levels were found in the shrews, and this has been considered in terms of nutrition characteristics. The data obtained will be used to assess the risks of chronic exposure to low doses of PCDD/Fs contaminating the environment near landfills.

Polyallylamine hydrochloride coating enhances the fluorescence emission of Human Serum Albumin encapsulated gold nanoclusters

Publication date: Available online 18 August 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Ben Allan Russell, Barbara Jachimska, Yu Chen

Abstract

Protein encapsulated gold nanoclusters have received much attention due to the possibility of using them as a non-toxic fluorescent probe or marker for biomedical applications, however one major disadvantage currently is their low brightness and quantum yield in comparison to currently used fluorescent markers. A method of increasing the fluorescence emission of Human Serum Albumin (HSA) encapsulated gold nanoclusters (AuNCs) via a Polyallylamide hydrochloride (PAH) coating is described. PAH molecules with a molecular weight of ~17,500 Da were found to enhance the fluorescence emission of HSA-AuNCs by 3-fold when the protein/polymer concentration ratio is 2:1 in solution. Interestingly, the fluorescence lifetime of the AuNCs was found to decrease while the native tryptophan (TRP) fluorescence lifetime also decreased during the fluorescence emission intensity enhancement caused by the PAH binding. Coinciding with the decrease in fluorescence lifetime, the zeta potential of the system was observed to be zero during maximum fluorescence intensity enhancement, causing the formation of large aggregates. These results suggest that PAH binds to the HSA-AuNCs acting as a linker; causing aggregation and rigidification, which results in a decrease in separation between native TRP of HSA and AuNCs; improving Förster Resonance Energy Transfer (FRET) and increasing the fluorescence emission intensity. These findings are critical to the development of brighter protein encapsulated AuNCs.

Graphical Abstract

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Detection of tris(2,3-dibromopropyl) phosphate and other organophosphorous compounds in Arctic rivers

Abstract

The flame-retardant tris(2,3-dibromopropyl) phosphate (TDBrPP) was in the 1970s banned for uses in textiles that may be in contact with the skin, owing to strong suspicions that the substance was a human carcinogen. The substance is looked for but rarely detected in samples from the built and natural environments, but there are indications that TDBrPP is still in use. Here, we report the measurement of a polymer-water partition coefficient (K_pw) for two types of silicone rubber (SR), allowing quantitative estimation of freely dissolved concentrations of TDBrPP by passive sampling in water. We found levels of 100 to 200 pg/L in two Arctic rivers that were sampled during a 2014–2015 survey of contamination using passive samplers in Norwegian and Russian rivers draining into the Barents Sea. We also report the widespread presence of other organophosphorus flame retardants in this survey of eight rivers that drain into the Barents Sea.

Topical glycopyrronium tosylate (DRM04) for the treatment of primary axillary hyperhidrosis: Pooled results from the ATMOS-1 and ATMOS-2 phase 3 randomized controlled trials

Introduction: The impact of hyperhidrosis on quality of life is comparable to, or greater than, psoriasis or eczema. Glycopyrronium tosylate (GT; formerly DRM04) is a cholinergic receptor antagonist developed for topical application for the treatment of primary axillary hyperhidrosis. ATMOS-1 (NCT02530281) and ATMOS-2 (NCT02530294) were designed to assess the efficacy and safety of GT in patients with primary axillary hyperhidrosis.

Multicenter clinical study proving antiseptic, bactericide and fungicide efficacy in a talc containing 17% sulfur in the treatment of patients with interdigital mycosis of the feet

Introduction: Set as an infection caused by fungi that use the keratin of skin, nails and hair as nutrients, the superficial mycosis develop under favorable conditions, such as heat and humidity, and stand out among the dermatologic diseases most prevalent in Brazil. One of the most common superficial mycoses is interdigital mycosis, characterized by flaking, cracks and itching between the toes, and the use of products with drying and antiseptic action is recommended to contribute to the decrease in the incidence of the disease.

Pseudocellulitis and gemcitabine, a recently described entity: Case report and literature review

Case report: A 55-year-old woman presents with a dermatosis disseminated to the abdomen and left pelvic extremity, constituted by two erythematous and edematous plaques, with a diameter of 30 × 15 cm in the abdomen and 20 × 15 cm in the thigh, well circumscribed with "peau d'orange" appearance. The evolution was of sudden development 2 days before presenting to consultation, with mild pain and pruritus, without any previous treatment. Patient refered 2 previous similar episodes, presenting after administration of chemotherapy, with 2 cycles of clindamycin and remission of symptoms after 7 days.

Chronic spontaneous urticaria treated with omalizumab (Xolair): A proposal of standardized tapering protocol before withdrawal to achieve the minimal effective dosage

Background: Chronic spontaneous urticaria (CSU) may represent a therapeutic challenge, although the recombinant humanized monoclonal antibody omalizumab has demonstrated a high effectiveness in the treatment of antihistamines-resistant CSU. There are no clear recommendations regarding the optimal duration of the treatment or the way to taper down the drug. The objective of our study was to describe our experience with a standardized tapering protocol of omalizumab before withdrawal.

Quality Improvement Project: Improving intake forms to make them more readable for patients in an urban clinic setting

In the landscape of increasing demands on physician and staff time, intake forms are frequently utilized to gather information before the start of the clinical encounter. These forms typically contain information on reason for visit, allergies, current medications, pertinent health history, abbreviated review of systems and important social history. We assessed a sample of the intake forms at our clinic and found that 63% of the time the forms were not filled out at all. A resident poll showed that 75% of residents felt the forms were not useful.

Transdermal effectiveness of a lipid-based antimicrobial emulsion

A proprietary lipid-based emulsion (ML:8) with established antimicrobial efficacy was investigated. To model a clinical situation in which bacteria have penetrated the integumentary barrier, a reference strain of Staphylococcus aureus (NCTC 8255-4) was inoculated into the subdermal compartment of isolated sheets of pig skin mounted between two chamber-halves to permit separate access to surface and to subdermal compartments. The objective was to evaluate transdermal efficacy of a range of concentrations of ML:8 through porcine skin in vitro.

Tie-over bolsters versus quilting sutures for the closure of full-thickness skin grafts

Background: Full-thickness skin grafting is a well established and preferred technique in the reconstruction of various tissue defects and wounds. However, lack of uniformity in the procedure of closing and securing the grafts has led to a wide-range of different techniques.

The use of intralesional triamcinolone as treatment of primary cutaneous B-cell lymphomas

Primary cutaneous B-cell lymphomas (PCBCLs) are benign malignancies which rarely disseminate, with 5-year disease-specific survival ranging from 94% to 100%. They are commonly treated with excision, radiation, or chemotherapy, alone or in combination. Intralesional corticosteroid injection is an alternative that is cost-effective with minimal side-effects, although it is less-frequently utilized as a primary mode of treatment. The present study was undertaken to evaluate the experience of an academic medical center in using intralesional corticosteroid injection as first-line therapy for PCBCL.

The rodent, the Hedgehog, and the man with nosocomephobia

A 71-year-old Caucasian gentleman presented in 2004 with a basal cell carcinoma (BCC) on his right cheek. A wide excision was arranged but was rescheduled and subsequently cancelled by the patient. He was noted to have a severe hospital phobia (nosocomephobia) related to childhood experiences concerning medical care of his parents. He declined all efforts to provide treatment and accepted the consequences. He represented 12 years later with a large tumor involving his right cheek, nose and sight threating eyelid involvement.

The Onychomycosis/Onychodystrophy Dermoscopy study (OMODO)—A comparative prospective study of onychoscopy features

Background: Onychomycosis (OM) and traumatic onychodystrophy (OD) are common causes of toenail dystrophy. Their treatment and prognosis differ, so early diagnosis is essential and questionable without mycology. Onychoscopy may prove useful in this setting. Although, few studies have addressed this issue and none directly compared OM and OD onychoscopic findings. We aimed to identify and describe onychoscopic patterns associated with OM and OD, proposing an onychoscopy-based algorithm to guide their differential.

Application of paclobutrazol: a strategy for inducing lodging resistance of wheat through mediation of plant height, stem physical strength, and lignin biosynthesis

Abstract

Lodging is a major constraint contributing to poor grain yield and quality of wheat (Triticum aestivum L.) worldwide. The use of plant growth regulators is becoming a foremost agro-chemical approach for minimizing the risk of lodging in cereal crops. The present study was conducted to examine the effects of the paclobutrazol application on culm physical strength, lignin content, and lodging resistance of wheat. Wheat seeds were soaked in paclobutrazol at the concentrations of 0 (CK, as control), 200 (PB1), 300 (PB2), and 400 (PB3) mg L⁻¹. Our results showed that paclobutrazol resulted in a dose-dependent decrease of plant height, internode length, and center of gravity height. Paclobutrazol treatments evidently increased the culm diameter, culm filling degree, and wall thickness of basal internodes, resulting in greater stalk-breaking strength and lodging resistance index (CLRI), where their maximum values were obtained with PB1 treatment. In addition, the activities of lignin-related enzymes were improved by paclobutrazol, particularly at low concentration, which increased the lignin accumulation of the basal internodes of wheat, subsequently improving the capability of stalk lodging resistance. Moreover, the correlation analysis revealed significant correlations between stem diameter, culm filling degree, and lignin with stalk bending strength and CLRI. The paclobutrazol concentration ≥ 300 mg L⁻¹ (PB2 and PB3 treatments) showed inhibitive effects on various culm morphological traits. These results suggest that not only the plant height, but also the lignin contents and physical strength of internodes are closely related with the lodging resistance of wheat, and reduction in plant height along with improved culm morphological characteristics and higher lignin accumulation in basal internodes could effectively relieve the risk of lodging.

Effects of combined exposure to perfluoroalkyl acids and heavy metals on bioaccumulation and subcellular distribution in earthworms ( Eisenia fetida ) from co-contaminated soil

Abstract

The effects of combined exposure to perfluoroalkyl acids (PFAAs) and heavy metals (HMs) including cadmium (Cd), copper (Cu), zinc (Zn), nickel (Ni), and lead (Pb) on earthworms (Eisenia fetida) were investigated. The results have demonstrated that the concentrations of labile acid exchangeable Cd, Zn, Ni, Pb, and Cu in soil were enhanced in addition of PFAAs. With PFAAs, the uptake of Cd, Zn, Ni, Pb, and Cu in earthworms was increased compared to those without PFAAs with the order of Cd > Zn > Pb > Ni > Cu. In the presence of HMs, the average biota-to-soil accumulation factors (BSAFs) of PFAAs in earthworms were decreased by 0.498–0.729 times for perfluorooctane sulfonate (PFOS) and 0.606–0.978 times for perfluorooctanoic acid (PFOA), indicating decrease rates of PFOS were higher than those of PFOA. And different levels of HMs led to insignificant different responses on the inhibiting effects of PFAAs uptake in earthworms. The increase of Cd in fraction C (associated with cytosol) and decrease of PFAAs in fraction C and fraction P (associated with tissue fragments, cell membranes, and intact cells) especially for fraction C were revealed when they were combined, suggesting cytosolic PFAAs and Cd were susceptibly mutual effected. This study indicated that PFAAs and metals mutually affected their bioaccumulation and subcellular distribution in earthworms, which will help to understand the fate and risks of PFAAs and metals in co-contaminated soil.

A new approach for excess sludge reduction by manganese dioxide oxidation: performance, kinetics, and mechanism studies

Abstract

A considerable amount of excess sludge, a kind of hazardous waste, is produced from the conventional wastewater treatment systems such as activated sludge process, and efficient sludge reduction processes are needed. A new chemical method for sludge reduction was proposed by using manganese dioxide as oxidant in this study. A favorable condition for sludge reduction is determined as manganese dioxide dosage of 0.165 g g⁻¹ wet sludge, sulfuric acid concentration of 3 mol L⁻¹, and reduction temperature of 90 °C for 90 min, where the sludge reduction efficiency can reach 73.30%. Reaction kinetic study revealed that the sludge reduction rate was controlled by the surface chemical reaction and the reaction followed a shrinking core kinetic model with apparent activation energy of 37.76 kJ mol⁻¹. Furthermore, reaction process analysis indicated that the sludge hydrolysis included two steps, i.e., floc destruction and microbial cell disruption. Considering the high efficiency and short treatment time, manganese dioxide oxidation is suggested to be a feasible method for disintegration of excess activated sludge.

Effect of Bacillus cereus peptide conjugated with nanoporous silica on inactivation of Listeria monocytogenes in apple juice, as an ecofriendly preservative

Abstract

Bacteriocins are ribosomally synthesized antimicrobial proteins/peptides. They are of great interest in the food processing industries as potential natural preservative agent to control food-borne pathogens. Bacillus spp. are one among the potential probiotics receiving more attention since they produce a broad spectrum of antimicrobial bioactive peptides. In this study, a small-scale medium composition and bioprocessing parameters were statistically optimized to increase the yield of bacteriocin namely cerein from Bacillus cereus NS02 showing antagonism against a wide range of food-borne pathogens. The cerein was partially purified, characterized, and evaluated for their optimal reaction condition. It was subjected to surface adsorption onto food-grade silica to evaluate its maximal adsorption, reached at 4 h, 40 °C, pH 6–7, and at the initial concentration of 200 AU mL⁻¹. The effectiveness of silica-adsorbed and silica-free cerein was checked in Listeria monocytogenes inoculated fresh apple juice and demonstrated biopreservative activity. In juice treated with silica-cerein, the colony forming unit (CFU) was found to be less in count on the 15th day of storage at 4 °C whereas, free-cerein was found to contain 3.8 log CFU mL⁻¹. While, on the same day of storage, the control juice contained the strength of 14.6 log CFU mL⁻¹. Based on the above, this study concludes that the identified heat stable low molecular weight peptide cerein from B. cereus NS02 could serve as a potential biopreservative with effective antilisterial activity in the food system. However, a more detailed study is required to determine if their quality change especially the effect of cerein in organoleptic and nutritional properties of food beyond their addition is necessary, before it is to be exploited as an ecofriendly biopreservative.

Proposed Response Assessment and Endpoints for Meningioma Clinical Trials: Report from the Response Assessment in Neuro-Oncology (RANO) Working Group

Abstract

No standard criteria exist for assessing response and progression in clinical trials involving patients with meningioma and there is no consensus on the optimal endpoints for trials currently underway. As a result, there is substantial variation in the design and response criteria of meningioma trials, making comparison between trials difficult. In addition, future trials should be designed with accepted standardized endpoints. The Response Assessment in Neuro-Oncology Meningioma Working Group is an international effort to develop standardized radiologic criteria for treatment response for meningioma clinical trials. In this proposal, we present the recommendations for response criteria and endpoints for clinical trials involving patients with meningiomas.

Leptin is a physiological regulator of skeletal muscle angiogenesis and is locally produced by PDGFRα and PDGFRβ expressing perivascular cells

Abstract

Skeletal muscle capillarity is characteristically reduced in mature leptin receptor-deficient (Lepr^db) mice, which has been attributed to the capillary loss that occurs secondary to metabolic dysfunction. Despite wide recognition of leptin as a pro-angiogenic molecule, the contribution of this adipokine has largely been overlooked in peripheral tissues. Moreover, prior documentation of leptin production within skeletal muscle indicates a potential paracrine role in maintaining local tissue homeostasis. Thus, we hypothesized that leptin is a physiological local paracrine regulator of skeletal muscle angiogenesis and that its production may be modulated by nutrient availability. Lepr^db mice exhibited impaired angiogenesis during normal developmental maturation of skeletal myocytes, corresponding with an inability to increase vascular endothelial growth factor-A (VEGFA) mRNA and protein levels between 4 and 13 weeks. In cultured murine and human skeletal myocytes, recombinant leptin increased VEGFA mRNA levels. Leptin mRNA was detectable in skeletal muscle, increasing with prolonged high-fat feeding in mice, and with adiposity in human subjects. Platelet-derived growth factor receptor (PDGFR)α− and PDGFRβ− expressing perivascular cell populations were identified as leptin producing within skeletal muscle of mice and humans. Furthermore, in response to 2 weeks of high-fat feeding, PDGFRβ+ but not PDGFRα+ cells increased leptin production. We conclude that leptin is a physiological regulator of the capillary network in skeletal muscle and stimulates VEGFA production by skeletal myocytes. PDGFRβ expressing perivascular cells exhibit the capacity to act as local "nutrient-sensors" that couple nutrient status to leptin production in skeletal muscle.

Trend of the environmental supervision on submarine pipeline installation

Crude oil removal from aqueous solution using raw and carbonized Xanthoceras sorbifolia shells

Abstract

Fruit shell residue from Xanthoceras sorbifolia was investigated as a potential biosorbent to remove crude oil from aqueous solution. The shell powder and its carbonized material were compared while assessing various factors that influenced oil removal capacity. The structure and sorption mechanism were characterized using scanning electron microscopy and Fourier-transform infrared spectroscopy. The oil removal capacity of the raw material (75.1 mg g⁻¹) was better than the carbonized material (49.5 mg g⁻¹). The oil removal capacity increased with greater saponin content, indicating that hydrophobic and lipophilic surface characteristics of the saponins improved adsorption by the raw X. sorbifolia shell. An orthogonal experimental design was used to optimize the adsorption. Using 4 g L⁻¹ of raw X. sorbifolia shell (particle size of < 0.15 mm), the highest crude oil removal efficiency was obtained using an initial oil concentration of 400 mg L⁻¹, adsorption temperature of 30 °C, adsorption time of 10 min at a shaking speed of 150 rpm. The adsorption of crude oil onto X. sorbifolia shell was best described using a pseudo-second-order kinetic model. Raw X. sorbifolia shell material was more efficient than the carbonized material at crude oil removal from aqueous solution. This was attributable to the functional groups of saponins in raw X. sorbifolia shell. This study highlights that some agricultural and forest residues could be a promising source of low-cost biosorbents for oil contaminants from water—without requiring additional processing such as carbonization.

Arundo donax L. stem-derived biochar increases As and Sb toxicities from nonferrous metal mine tailings

Abstract

Toxic metal(loid)s released from tailing residues of mining operations have become a global issue with regard to environmental impacts. Biochar derived from the agriculture waste is considered as a cost-effective and stable material, which could be applied for remediation of sites contaminated with toxic metal(loid)s. In the present study, tailings were amended for 90 days with increasing concentrations of Arundo donax L. stem-derived biochar (ASBC; at 0, 1, 3, and 5%). The 7-day wheat seed germination toxicity test was then used to assess the bioavailability of toxicants in aqueous leachates of the biochar-amended tailing samples. Concentrations of As, Cd, Cu, Pb, and Sb in leachates and the Community Bureau of Reference chemical fractions were determined using ICP-OES. The results indicated that tailing leachates were phytotoxic, an effect that was partially decreased due to increasing concentrations of ASBC, with maximum effects (∼47% of tailing phytotoxicity) occurring at 3% ASBC. Results of further fractionation analyses indicated that increasing concentrations of ASBC amendment decreased the mobile fractions of Cd, Cu, and Pb in tailing samples, but increased the mobilities of As and Sb. A novel approach using the relative toxicity index (= sum of toxicities of individual potentially toxic elements) indicated that the toxicity of the tailings decreased when As was not present, since As decreased the biochar-reduced toxicity. Our results suggest that the ability of using biochar to decrease toxicity in tailings (by sequestration of cationic metals such as Cd, Cu, and Pb) is limited by its inability to immobilize oxyanionic metalloids such as As and Sb.

Éruption lichénoïde cutanéo-muqueuse sous anti-PD-1

Publication date: Available online 17 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): M. Amini-Adle, B. Balme, M. Locatelli-Sanchez, P.-J. Souquet, S. Dalle

Étude rétrospective d’une série de pemphigus paranéoplasiques

Publication date: Available online 17 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): M. Fournet, P. Roblot, P. Levillain, G. Guillet, L. Machet, L. Misery

Résumé

Contexte

Le pemphigus paranéoplasique (PPN) est une maladie très rare et de mauvais pronostic associant un pemphigus, particulier par certains critères cliniques, immunologiques et histologiques, à une néoplasie.

Méthodes

Nous avons rétrospectivement analysé les dossiers de patients présentant un PPN dans la région Poitou-Charentes entre 2000 et 2015.

Résultats

Sept patients présentaient neuf néoplasies diagnostiquées de 4 mois avant à 25 mois après l'apparition des lésions cutanées (6/7) ou muqueuses (6/7) de pemphigus. Les lésions étaient cliniquement polymorphes. L'examen histologique révélait une acantholyse épidermique (7/7), des nécroses kératinocytaires (4/7) et une dermite lichénoïde d'interface (5/7). On mettait en évidence des dépôts d'IgG et de C3 intercellulaires ou le long de la jonction dermo-épidermique en immunofluorescence directe (IFD) (7/7), des anticorps anti-substance intercellulaire en immunofluorescence indirecte (IFI) sur vessie de rat (4/6), un immunotransfert reconnaissant les cibles antigéniques du PPN (2/4). La durée du suivi allait de 1 à 132 mois, la survie à 1 an était de 85,7 %.

Discussion

Les présentations cliniques et histopathologiques observées chez nos patients sont polymorphes, avec un chevauchement entre les manifestations cliniques et histologiques de PPN et de pemphigus classique. Le pronostic est meilleur dans notre série que dans la littérature. Les néoplasies associées sont diverses. Il semble exister des associations fortuites de pemphigus à des néoplasies, de meilleur pronostic que les véritables PPN. Un nouveau consensus pour les critères diagnostiques du PPN est nécessaire, qui aiderait les praticiens à diagnostiquer le PPN de manière plus homogène pour réaliser des études pronostiques ou des essais thérapeutiques.

Summary

Context

Paraneoplastic pemphigus (PNP) is a rare condition associated with poor prognosis. It associates polymorphic mucocutaneous manifestations with neoplasia. Diagnosis is difficult because of the various clinical and histological features involved and the lack of specificity of immunological examinations.

Methods

We retrospectively analyzed the records of patients presenting with PNP in the Poitou-Charentes region between 2000 and 2015.

Results

Seven patients were included. They presented 9 neoplasias (1 lymphoma, 1 melanoma, and 7 carcinomas) diagnosed from 4 months before to 25 months after the occurrence of cutaneous (6/7) and/or mucosal (6/7) polymorphic lesions. Histological examination revealed epidermal acantholysis (7/7), keratinocytic necrosis (4/7), and interface lichenoid dermatitis (5/7). Intercellular deposits of IgG and C3 or along the dermo-epidermal junction were detected with direct immunofluorescence (IF) (7/7). Four of 6 patients tested had positive indirect IF on rat bladder epithelium. Follow-up ranged from 1–132 months with a one-year survival of 85.7%.

Discussion

The clinical and histopathological presentations observed in our patients were polymorphic, with overlap between the clinical and histological features of PNP and classical pemphigus. Prognosis and survival appear better in our series than in the literature. It is possible that in some cases, the association of pemphigus with neoplasia was fortuitous, which might account for the better prognosis. A new consensus on the diagnostic criteria for PNP is needed to help practitioners to consensually diagnose it for prognostic or therapeutic trials.

A Bayesian assessment of occupational health surveillance in workers exposed to silica in the energy and construction industry

Abstract

Medical records generated during occupational health surveillance processes have large amounts of unexploited information that can help to reduce silica-related health risks and many occupational diseases. The methodology applied in this study consists in analyzing through machine learning techniques a database with 70,000 medical examinations from workers in the energy and construction industry in Spain. First, a general unsupervised Bayesian model is built and node force analysis is used to identify the factors with the greatest impact on the worker's health surveillance process. Second, a predictive Bayesian model is created and mutual information is employed to assess the more relevant factors affecting the medical capability of workers exposed to silica dust. The lung auscultation and the breathing exploration are the two factors that influence the most the medical capability of silica-exposed employees. Probabilistic inference shows a remarkable gender effect, where women present more resilience towards occupational diseases than men showing a higher proportion of normal results in certain key factors, such as body mass index (♀49.73%, ♂25.17%) or spirometry (♀53.73%, ♂48.91%). Finally, environmental conditions demonstrate to have a major influence on spatial variability of occupational diseases. The design of health prevention programs based on geographical variations can be crucial to the attainment of an ongoing and sustained healthier workforce with a reduction in the number of chronic workplace illnesses.