Cutaneous granulomatous lesions in a patient with mucosa‐associated lymphoid tissue (MALT) lymphoma

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Inherited desmoplastic trichoepitheliomas

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Ingestion of plastic fragments by the Guri sea catfish Genidens genidens (Cuvier, 1829) in a subtropical coastal estuarine system

Abstract

One of the most recognized anthropogenic impacts in marine environments is solid waste pollution, especially plastic, which can be ingested by fish, thus interfering with their health. In this context, the aim of this study is to describe the ingestion of plastic fragments and to identify the possible effect of this contamination in the condition factor of Genidens genidens in the Laguna Estuarine System. The stomach contents of 92 G. genidens (26 juveniles and 66 adults) were analyzed. The Index of Relative Importance was performed to identify the contribution of each prey item. Condition factor (CF) was used to analyze the effect of plastic ingestion on the fish's body condition (by comparing individuals in the same ontogenetic phase). For the juveniles, eight items were observed, the most important of which were Penaeidae, followed by Portunidae and plastic. For the adults, 12 items were observed, the most important of which were Penaeidae, Portunidae, Polychaeta, and plastic. The analysis of CF demonstrated higher values for individuals without plastic in the stomach, which indicated a better health condition. The CF of a fish may be affected by variations in the physiological condition, environmental stresses, and nutritional and biological variations, and could be used to compare the body condition or health of a fish species. The ingestion of plastic could significantly influence the worst body condition of the individuals that were analyzed in the present study. The plastic pollution in marine coastal waters is associated with the appropriate waste management levels.

http://bit.ly/2Wt6VEp

Tanycytes: a rich morphological history to underpin future molecular and physiological investigations

Abstract

Tanycytes are located at the base of the brain and retain characteristics from their developmental origins – as radial glial cells ‐ throughout their life span. With transport mechanisms and modulation of tight junction proteins, tanycytes form a bridge connecting the cerebrospinal fluid with the external limiting basement membrane. They also retain the powers of self‐renewal and can differentiate to generate neurons and glia. Like radial glia, they are a heterogeneous family with distinct phenotypes. Although the four subtypes so far distinguished display distinct characteristics, further research is likely to reveal new subtypes. In preparation for this review we re‐visited the work of the pioneers in the field revealing forgotten work waiting to inspire new research with today's cutting‐edge technologies. We have conducted a systematic ultrastructural study of α‐tanycytes that resulted in a wealth of new information, generating numerous questions for future study. We also consider median eminence pituicytes, a closely‐related cell type to tanycytes, and attempt to relate pituicyte fine morphology to molecular and functional mechanism. Our rationale was that future research should be guided by a better understanding of the early pioneering work in the field, which may currently be overlooked when interpreting newer data or designing new investigations.

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M1b Disease in the 8th Edition of TNM Staging of Lung Cancer: Pattern of Single Extrathoracic Metastasis and Clinical Outcome

AbstractBackground.The 8th edition of TNM staging of non‐small cell lung cancer (NSCLC) has revised M classification and defined M1b disease with single extrathoracic metastasis, which is distinguished from M1c with multiple extrathoracic metastases. We investigated the prevalence, characteristics, and overall survival (OS) of M1b disease in patients with stage IV NSCLC.Methods.The study reviewed the medical records and imaging studies of 567 patients with stage IV NSCLC to determine M stage using the 8th edition of TNM staging. Clinical characteristics and OS were compared according to M stages.Results.Among 567 patients, 57 patients (10%) had M1b disease, whereas 119 patients (21%) had M1a disease and 391 patients (69%) had M1c disease. Squamous histology was more common in M1b (16%) than in M1a (6%) and M1c (6%; p = .03). The median OS of patients with M1b disease was 14.8 months, compared with 22.6 months for patients with M1a and 13.4 months for those with M1c disease (p < .0001). Significant OS differences of M1b compared with single‐organ M1c and multiorgan M1c groups were noted (single‐organ M1c vs. M1b: hazard ratio [HR], 1.49; p = .02; multiorgan M1c vs. M1b: HR, 1.57; p = .01) in multivariable analyses adjusting for smoking and systemic therapy types. Among patients with M1b disease, the brain was the most common site of single metastasis (28/57; 49%), followed by bone (16/57; 28%). Single brain metastasis was more frequently treated with local treatment (p < .0001).Conclusion.M1b disease was noted in 10% of patients with stage IV NSCLC. Squamous histology was more common in M1b group than others. The brain was the most common site of single metastasis and was often treated locally.Implications for Practice.The newly defined group of M stage consists of a unique subset among patients with stage IV non‐small cell lung cancer that can be studied further to optimize treatment approaches.

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Refining the Use of Adjuvant Oxaliplatin in Clinical Stage II or III Rectal Adenocarcinoma

AbstractBackground.Current guidelines include the use of adjuvant oxaliplatin in clinical stage II or III rectal adenocarcinoma. However, its efficacy is supported by a single phase II trial. We aimed to examine whether oxaliplatin confers survival benefit in this patient population.Methods.Using the National Cancer Database (2006–2013) we identified 6,868 individuals with clinical stage II or III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy. We used multivariate Cox regression to evaluate survival differences according to treatment intensity and change from clinical to pathological stage.Results.We demonstrated an association with improved overall survival with the use of doublet adjuvant chemotherapy in pathological stage III rectal adenocarcinoma (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67–0.92). This association was confirmed in patients with clinical stage III and subsequent pathological stage III disease (HR, 0.69; 95% CI, 0.57–0.83) and was not observed in patients who progressed from clinical stage II to pathological stage III disease. Doublet adjuvant chemotherapy was not associated with improved overall survival in patients with pathological stage 0 or I disease, regardless of their clinical stage.Conclusion.Adjuvant oxaliplatin following neoadjuvant chemoradiotherapy in rectal adenocarcinoma was confirmed in patients with clinical stage III and subsequent pathological stage III disease. Omission of oxaliplatin can be considered in pathological complete response or pathological stage I disease.Implications for Practice.Current guidelines include the use of oxaliplatin as part of adjuvant chemotherapy (AC) in patients with clinical stage II or III rectal adenocarcinoma (RAC). However, its efficacy is supported only by a single phase II trial. This study found an association with improved overall survival with the use of doublet AC in patients diagnosed with clinical stage III and subsequent pathological stage III, and not in patients with pathological stage 0 or I, regardless of their clinical stage. Therefore, omission of oxaliplatin can be considered in patients with either pathological complete response or pathological stage I RAC, thereby avoiding oxaliplatin‐induced neuropathy.

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Bridge: Person‐Centered Collaborative Care for Patients with Serious Mental Illness and Cancer

AbstractBackground.Individuals with serious mental illness (SMI) experience increased cancer mortality due to inequities in cancer treatment. Psychiatric care at cancer diagnosis may improve care delivery, yet models for integrating psychiatry and cancer care are lacking. We assessed the feasibility and acceptability of a person‐centered collaborative care trial for SMI and cancer.Subjects, Materials, and Methods.We developed the Bridge intervention for patients with SMI (schizophrenia, bipolar disorder, and severe major depression) and cancer. Bridge includes proactive identification of SMI, person‐centered care from a psychiatrist and case manager, and collaboration with oncology. We conducted a 12‐week, single‐group trial in patients with SMI and a new breast, gastrointestinal, lung, or head/neck cancer. We assessed the feasibility of patient identification, enrollment and study completion; evaluated acceptability and perceived benefit with exit interviews with patients, caregivers, and oncology clinicians; and examined change in psychiatric symptoms with the Brief Psychiatric Rating Scale (BPRS).Results.From November 2015 to April 2016, 30/33 eligible patients (90.9%) enrolled, and 25/29 (86.2%) completed assessments at all timepoints, meeting feasibility criteria. Of 24 patients, 23 (95.8%) found meeting with the psychiatrist helpful; 16/19 caregivers (84.2%) shared that Bridge addressed key caregiving challenges. Oncology clinicians evaluated Bridge as "very" or "most" useful for 94.3% of patients. Exit interviews with all participant groups suggested that Bridge fostered patient‐clinician trust, increased access to psychiatric treatment, and enabled patients to initiate and complete cancer treatment. Psychiatric symptoms on the BPRS improved from baseline to 12 weeks.Conclusion.Bridge is a feasible and acceptable care delivery model for patients with SMI, their caregivers, and oncology clinicians. Randomized trials are warranted to assess the efficacy of improving cancer outcomes in this underserved population.Implications for Practice.Serious mental illness affects 13 million U.S. adults who experience increased cancer mortality. To improve outcomes, new models of integrated oncology and mental health care are urgently needed. This study found that it was feasible to identify, enroll, and retain patients with serious mental illness and a new cancer in a trial of integrated mental health and cancer care (Bridge). Patients, caregivers, and oncologists reported that Bridge facilitated the initiation and completion of cancer care. Randomized trials are warranted to investigate the impact on cancer outcomes. Trial procedures may inform consent, engagement, and trial retention for patients with mental illness.

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Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study

AbstractBackground.NUT carcinoma is a rare aggressive disease caused by BRD4/3‐NUT fusion, and C‐MYC upregulation plays a key role in the pathogenesis. Here, we report on the clinicopathological characteristics of Korean patients with NUT carcinoma and the in vitro efficacy of MYC‐targeting agents against patient‐derived NUT carcinoma cell lines.Materials and Methods.Thirteen patients with NUT carcinoma were evaluated for p53, C‐MYC, epidermal growth factor receptor (EGFR), HER2, and programmed cell death ligand 1 (PD‐L1) by immunohistochemistry. The half maximal inhibitory concentration (IC50) values of NUT carcinoma cell lines (SNU‐2972‐1, SNU‐3178S, HCC2429, and Ty‐82) were determined using MYC‐targeting agents, including bromodomain and extraterminal (BET) inhibitors (I‐BET, OTX‐015, AZD5153) and histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin, panobinostat, CUDC‐907).Results.Primary tumor sites included head and neck (n = 9) and lung (n = 4). The patient age ranged from 8 to 73 years with the male/female ratio of 1.2:1. Nine patients died at 3–23.6 months (median, 10.6) after diagnosis. Eight patients had been misdiagnosed initially with other diseases. One patient with metastatic NUT carcinoma who received mass excision plus metastasectomy followed by chemoradiotherapy was a long‐term survivor (>27 months). Although expressions of C‐MYC (8/12, 73%) and p53 (12/12, 100%) were commonly observed, EGFR, HER2, and PD‐L1 expressions were observed in 2 of 7 (29%), 2 of 8 (25%), and 1 of 12 (8.3%) patients, respectively. BET and HDAC inhibitors showed variable but limited in vitro efficacy. However, a dual HDAC/PI3K inhibitor, CUDC‐907, was most potent against NUT carcinoma cells, with an IC50 of 5.5–9.0 pmol/L. Consistent with these findings, kinome short interfering RNA screening showed a positive hit for PI3KCA in NUT carcinoma cells. Panobinostat (IC50, 0.4–1.3 nmol/L) and a bivalent BET inhibitor, AZD5153 (IC50, 3.7–8.2 nmol/L), also showed remarkable efficacies.Conclusion.East Asian patients with NUT carcinoma showed dismal survival outcomes like Western patients, and CUDC‐907 might be promising in NUT carcinoma treatment.Implications for Practice.NUT carcinoma (NC) is a disease caused by BRD‐NUT fusion leading to C‐MYC upregulation. NC is often misdiagnosed and very aggressive, requiring development of effective therapeutic strategy. This article presents the clinicopathological features of the largest series of NCs in East Asians and preclinical sensitivities to MYC‐targeting agents in NC cell lines. Patients with NC had grave outcomes and poor response to treatment. Among MYC‐targeting agents, including BET and HDAC inhibitors, CUDC‐907 (a dual PI3K/HDAC inhibitor) was most effective against NC cells, followed by panobinostat (an HDAC inhibitor) and AZD5153 (a bivalent BET inhibitor). CUDC‐907 might be promising in NC treatment.

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Book Review:Prevention and Recovery from Eating Disorders in Type 1Diabetes:Injecting Hope

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Preoperative Angiography for Free Fibula Flap Harvest: A Meta-Analysis

J reconstr Microsurg
DOI: 10.1055/s-0038-1677012

Background The necessity for routine preoperative imaging for free fibula harvest is controversial. The primary objective of this meta-analysis is to determine if lower extremity angiography is necessary to detect abnormalities that may alter flap selection. The secondary objective is to determine if physical examination alone is sufficient to predict these abnormalities. Methods A literature search was performed using Cochrane, CENTRAL, MEDLINE, CINAHL, and EMBASE. Studies were selected for inclusion if they included patients undergoing free fibula flap harvest with preoperative imaging, with or without physical examination findings. Data extraction was performed independently and in duplicate, including a change in flap selection and the level of agreement between physical examination and imaging. Pooled proportions were calculated using a random-effects model and 95% confidence intervals (CI). Results Sixteen studies were included for analysis. Mean sample size was 42 patients (range: 5–123). Included studies were of low methodologic quality. Pooled proportion of patients who had flap selection change secondary to abnormalities identified on preoperative angiography was 20.1% (95% CI: 9.6–33.2%). A pooled proportion of 71.5% (95% CI: 5–88.7%) of cases requiring change in flap selection was missed by physical examination findings alone. Conclusions There is low-quality evidence suggesting a necessity for routine preoperative angiography for all patients undergoing free fibula flap harvest. Physical examination alone is insufficient in detecting vascular abnormalities that may result in limb compromise or an inability to successfully harvest a free fibula. Further investigation is warranted for cost-effectiveness of preoperative imaging protocols.
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Dissemination of resistance genes in duck/fish polyculture ponds in Guangdong Province: correlations between Cu and Zn and antibiotic resistance genes

Abstract

Duck/fish polyculture farming is a typical farming model in the Pearl River delta in southern China. We examined soil, water, and sediment samples from three duck-fish farms in Guangdong Province in September and December 2014. We determined the abundance of three metal resistance genes, 16S rDNA, and 23 antibiotic resistance genes encoding resistance to tetracycline, sulfonamides, quinolones, chloramphenicol, and β-lactamases. Microbial community structure was quantified by Illumina high-throughput sequencing of 16S rDNA genes. We found a prevalence of antibiotic resistance genes and the sul1, sul2, tetA, tetM, aac(6′)-Ib, and floR genes were the most abundant. Levels of Cu and Zn were significantly correlated with numerous ARG types and sul2, floR, and tetM were identified as potential antibiotic resistance gene indicators. Cu levels were significantly and positively correlated with the relative abundance of sul3, tetT, tetW, qnrB, qnrS, fexB, sul1, sul2, tetM, and qnrA. Zn was significantly correlated to relative abundance of sul2, sul3, tetM, tetA, tetT, tetW, qnrA, qnrB, qnrS, aac(6′)-Ib, qepA, bla_SHV, cmlA, floR, fexA, cfr, and fexB. The levels of Acinetobacter, Brevibacillus, and Wautersiella showed significant positive correlations with metal resistance genes as well as qnrB, oqxA, oqxB, and bla_SHV (p > 0.8). Sphingobacterium, Flavobacterium, Acidothermus, and Corynebacterium had significant correlations with abundance of tetracycline resistance genes, sulfonamide resistance genes, bla_TEM, bla_CTX, and cfr (p > 0.8). Sphingobacterium, Flavobacterium, Acidothermus, and Corynebacterium were most abundant in soil samples while Acinetobacter, Brevibacillus, and Wautersiella were most abundant in water samples. Dissemination of antibiotic resistance genes in aquaculture environments is extensive and tracing their origins is necessary to establish risk assessment methods required for aquatic environmental protection.

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Electrokinetic remediation of antibiotic-polluted soil with different concentrations of tetracyclines

Abstract

This study investigated the efficacy of electrokinetic remediation of soils polluted with different concentrations of tetracyclines (TCs). Three widely used TCs (oxytetracycline, chlortetracycline, and tetracycline) were selected, and concentrations of 0, 5, 10, 20, and 50 mg/kg (C0, C5, C10, C20, C50) were selected for comparison. Antibiotic-polluted soils with no electric field served as controls. The average removal rates of TCs in different treatments ranged from 25 to 48% after 7-day remediation. The contributing ratios of electrokinetics to TCs removal varied from 22 to 84%. The concentrations of NH₄⁺ increased in soils and electrolytes, which indicated the decomposition of TCs in the electric field. The highest removal amount of TCs was obtained in the C50 treatment, due to efficient reactions of TCs with oxidative radicals generated during the electrolysis. The fluctuant range of pH in the electrolytes was decreased with increasing concentration of TCs, while the soil pH was increased. The removal rate of antibiotic-resistant bacteria (ARB) in the C5 treatment was significantly higher than that in other treatments. The abundance of antibiotic resistance genes (ARGs) increased with the concentrations of TCs in soils. It might result from the induction of increasing selective pressure of antibiotics. Significant removal of ARGs occurred in the C50 treatment (38–60%). In terms of controlling ARB and ARGs, which were more resistant, the electrokinetic technology showed advantageous effects. Above all, electrokinetic technology provides an effective remediation method, especially for TC-polluted soil with a concentration of 20–50 mg/kg.

http://bit.ly/2B7Gjje

Plasma TNF‐α and adiponectin levels differentiate psoriatic arthritis from psoriasis patients

Abstract

Psoriasis (PsO) and psoriatic arthritis (PsA) are inflammatory disorders. Circulating biomarkers of inflammation such as interleukin‐6 (IL‐6), Tumor Necrosis Factor‐α (TNF‐α), and C‐reactive protein (CRP) have been associated with disease severity and progression of PsO and PsA. Adiponectin and leptin are adipose derived cytokines, recognized as key regulator of body weight and metabolism². Whether circulating levels of these inflammatory and metabolic biomarkers may predict the risk of PsA in psoriasis populations remains unclear.

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Physician Perceptions of Primary Care‐based Skin Cancer Screening in a Veterans Affairs Pilot Study

Abstract

Understanding primary care practitioner (PCP) barriers and facilitators to performing clinical skin examination (CSE) for skin cancer screening is necessary before widespread implementation. Time constraints, competing comorbidities, and patient embarrassment have been reported as obstacles. In 2016, the United States Preventative Services Task Force deemed the worldwide evidence as insufficient to assess the balance of benefits versus harms of skin cancer screening (I statement), neither recommending for nor against CSE. While the impact of primary care‐based skin cancer screening on melanoma incidence and mortality has been investigated, qualitative studies describing PCP feedback and diverse contextual factors that may help or hinder program implementation are lacking.

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Protective effects of quercetin supplementation against short-term toxicity of cadmium-induced hematological impairment, hypothyroidism, and testicular disturbances in albino rats

Abstract

The aim of this study was to evaluate the probable protective effect of quercetin (QUE) against cadmium (Cd)-induced sub-chronic toxicity in rats. Adult male rats were given either Cd (as cadmium chloride; 5 mg/kg) alone or in combination with QUE (50 mg/kg) daily for 4 weeks by oral gavage. At the end of the experimental period, Cd accumulation, and selected hematological, thyroid, and reproductive markers were assessed. Results revealed that Cd treatment significantly increased Cd concentrations in blood, thyroid gland, and testicular tissue of rats. Cd also caused a decline in hemoglobin content, hematocrit value, and total erythrocyte and leucocyte counts. Further, significant suppressions in the blood levels of hormones related to thyroid gland function, and male reproductive hormones (i.e., testosterone, luteinizing hormone and follicle-stimulating hormone), were observed in Cd-treated rats compared to the control. In parallel, low sperm count and sperm motility, increased sperm abnormalities, and marked pathology occurred in testis. Combination with QUE recorded amelioration of the deleterious effects of Cd, involving regulation of hematological toxicity and thyroid hormonal levels and subsequently modulation of testicular function. In conclusion, it appears that dietary QUE can rescue from Cd-induced hematological dysfunctions and testicular damage by reversing the hypothyroid state.

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JCD Editorial January 2019

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Issue Information

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Revisiting the Significance of Prominent C Cells in the Thyroid

Abstract

C cell hyperplasia is considered a precursor lesion for hereditary forms of medullary thyroid carcinoma. It has therefore been suggested as a morphological marker to distinguish hereditary from sporadic medullary thyroid carcinoma and to triage genetic testing in resource poor settings. However, numerous definitions for C cell hyperplasia have been suggested, and there is surprisingly little data regarding the number of C cells present in thyroid glands removed for conditions other than medullary carcinoma. We therefore sought to investigate the specificity of different criteria for C cell hyperplasia. We examined the number of C cells and solid cell nests (ultimobranchial body remnants) present in 118 completion thyroidectomy specimens from patients without medullary carcinoma and with no risk factors for MEN2. Morphological review was performed on all H&E-stained slides, and immunohistochemistry for calcitonin was performed on one block from each case. Solid cell nests were found in 4 (3.3%) of thyroids. Increased numbers of C cells sufficient to fulfil criteria for C cell hyperplasia were found in 5 (4.2%) to 36 (30.5%) cases depending on the criteria used. We conclude that large numbers of C cells are commonly found in thyroids not associated with medullary carcinoma. Therefore, regardless of which criteria are used, the presence of C cell hyperplasia is not a specific marker for hereditary medullary thyroid carcinoma.

http://bit.ly/2MEImjj

Spatiotemporal variability of heavy metals and identification of potential source tracers in the surface water of the Lhasa River basin

Abstract

The Lhasa River basin is the economic and population center of Tibet and has abundant resources. Due to its harsh weather condition, high elevation, and inconvenient accessibility, few studies have focused on heavy metal distributions in this region. In the present study, to investigate the dissolved trace metal pollution and its controlling factors, 57 water samples from the Lhasa River and its tributaries were collected during three water flow regimes in 2016. The data on the dissolved fraction revealed that the Lhasa River basin appeared to have no to low pollution levels. However, the Lhasa River water showed alkaline characteristics which may affect the presence of heavy metal elements in a dissolved fraction. The concentration of heavy metal elements in colloidal or particulate matter therefore needs attention. Multivariate analyses were performed to determine the significant relationship between the data and to identify controlling factors for dissolved heavy metals in the study area. The results suggested that Mn, Cd, Cu, and Zn originated from a natural geological background, whereas Pb originated from mining drainage and As was influenced by geothermal flows. The concentration of dissolved heavy metals in the Meldromarchu tributary was greatly affected by the mining drainage water, while that in the Tölungchu tributary was greatly influenced by the geothermal water sources. This paper provides the first comprehensive analysis of dissolved heavy metal pollution characteristics and the controlling factors of pollution during the three different water flow regimes of the Lhasa River basin.

http://bit.ly/2CQev2W

Previous, current, and cumulative dose effect of waterpipe smoking on LDL and total cholesterol

Abstract

The popularity of waterpipe smoking is dramatically increasing in Lebanon, reaching 36.9%, the highest among countries in the region. To the best of our knowledge, no studies have assessed the impact of waterpipe smoking on lipid levels in the Lebanese population. Therefore, the objective of the study was to evaluate the correlation between waterpipe smoking and LDL-C and total cholesterol levels in exclusive Lebanese waterpipe smokers compared to non-smokers. This cross-sectional study was conducted between October 2016 and February 2017, enrolling 308 patients (156 non-smokers and 147 waterpipe smokers) from four laboratories. Current and previous WS (beta = 66.64 and beta = 71.49) were significantly associated with higher LDL scores. Current WS was significantly associated with and total cholesterol levels (beta = 34.12). Cumulative WS (number of waterpipes per week × duration in years) was significantly associated with higher LDL-C and total cholesterol levels respectively (p < 0.001 for all 3 variables). The university level of education (beta = 8.89) and current alcohol drinking (beta = 8.81) were significantly associated with higher LDL scores. Our study demonstrated an association between previous or current waterpipe smoking and lipid level. Future research are needed to detect the direct cause of the relation between waterpipe smoking and CVD. Concerned authorities should set up awareness campaigns to increase alertness on dangers of WS and dependence, and encourage these young adults to embrace health-promoting behaviors.

http://bit.ly/2RYXfmz