Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.

Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease.

Cryo-EM structures of human ABCA7 provide insights into its phospholipid translocation mechanisms.

Phospholipid extrusion by ABC subfamily A (ABCA) exporters is central to cellular physiology, although the specifics of the underlying substrate interactions and transport mechanisms remain poorly resolved at the molecular level. Here we report cryo-EM structures of lipid-embedded human ABCA7 in an open state and in a nucleotide-bound, closed state at resolutions between 3.6 and 4.0 Å. The former reveals an ordered patch of bilayer lipids traversing the transmembrane domain (TMD), while the latter reveals a lipid-free, closed TMD with a small extracellular opening. These structures offer a structural framework for both substrate entry and exit from the ABCA7 TMD and highlight conserved rigid-body motions that underlie the associated conformational transitions. Combined with functional analysis and molecular dynamics (MD) simulations, our data also shed light on lipid partitioning into the ABCA7 TMD and localized membrane perturbations that underlie ABCA7 function and have broader implications for other ABCA family transporters.

This is why we are staying: Job satisfaction among Physiotherapists in the Kimberley region of Western Australia.

INTRODUCTION: The Kimberley region of Western Australia (WA) is classified by the Modified Monash Model as MM6 & 7 ('Remote/Very Remote'). Many physiotherapists in the Kimberley are considered 'rural generalists' and require a diverse set of clinical and non-clinical skills to work successfully within this setting. OBJECTIVE: To understand physiotherapists' perspectives regarding job satisfaction within the Kimberley region a 'rural and remote' areas of Australia. DESIGN: An exploratory case study approach examined physiotherapists' job satisfaction in the Kimberley. Each participant completed a demographic survey and a one-on-one face-to-face interview lasting for approximately 60 minutes. Transcriptions were analysed and presented thematically. Eleven physiotherapists (nine women, two men, median age = 32 [27-60] years) participated in the study. Participants' median time working in the Kimberley was 2 (1-15) years; eight participants completed a rural placement, and eight participants had a rural background. FINDINGS AND DISCUSSION: Two overarching themes relating to job satisfaction emerged: 'personal factors' and 'workplace factors'. Furthermore, several sub-themes illustrated high levels of job satisfaction. Positive sub-themes relating to personal factors included 'belonging to the community and a rural lifestyle'. 'Diversity in caseloads' and 'workplace culture' were examples of positive workplace sub-themes. Subthemes that challenged the participants personally were 'family arrangements' including schooling, 'spousal employment and family separation' and the 'transiency and social issues' within these remote communities. Workplace challenges comprised of 'barriers to providing best practice' and the 'workforce and clinical experience' found within the Kimberley physiotherapy community and the wider health care workforce. The primary challenge of job satisfaction that encompassed both personal and workplace factors was 'accommodation', with 'cost', 'lack of availability', and 'perceived unsafe location' challenging physiotherapists' decisions to remain in the Kimberley. CONCLUSION: This study describes the many factors impacting job satisfaction among physiotherapists in a rural and remote location in WA Australia. These factors warrant consideration by organisations interested in improving recruitment and retention in this context. Improving recruitment and retention in physiotherapists in rural and remote Australia has the potential to positively influence health service provision, and therefore improve health outcomes for those living in rural and remote communities.

Accelerated atherosclerosis in beta-thalassemia.

Children with beta-thalassemia (BT) present with an increase in carotid intima-medial thickness, an early sign suggestive of premature atherosclerosis. However, it is unknown if there is a direct relationship between BT and atherosclerotic disease. To evaluate this, wild-type (WT, littermates) and BT (Hbbth3/+) mice, both male and female, were placed on a 3-mo high-fat diet with low-density lipoprotein receptor suppression via overexpression of proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutation (D377Y). Mechanistically, we hypothesize that heme-mediated oxidative stress creates a proatherogenic environment in BT because BT is a hemolytic anemia that has increased free heme and exhausted hemopexin, heme's endogenous scavenger, in the vasculature. We evaluated the effect of hemopexin (HPX) therapy, mediated via an adeno-associated virus, to the progression of atherosclerosis in BT and a phenylhydrazine-induced model of intravascular hemolysis. In addition, we evaluated the effect of deferiprone (DFP)-mediated iron chelation in the progression of atherosclerosis in BT mice. Aortic en face and aortic root lesion area analysis revealed elevated plaque accumulation in both male and female BT mice compared with WT mice. Hemopexin therapy was able to decrease plaque accumulation in both BT mice and mice on our phenylhydrazine (PHZ)-induced model of hemolysis. DFP decreased atherosclerosis in BT mice but did not provide an additive benefit to HPX therapy. Our data demonstrate for the first time that the underlying pathophysiology of BT leads to accelerated atherosclerosis and shows that heme contributes to atherosclerotic plaque development in BT.NEW & NOTEWORTHY This work definitively shows for the first time that beta-thalassemia leads to accelerated atherosclerosis. We demonstrated that intravascular hemolysis is a prominent feature in beta-thalassemia and the resulting increases in free heme are mechanistically relevant. Adeno-associated virus (AAV)-hemopexin therapy led to decreased free heme and atherosclerotic plaque area in both beta-thalassemia and phenylhydrazine-treated mice. Deferiprone-mediated iron chelation led to deceased plaque accumulation in beta-thalassemia mice but provided no additive benefit to hemopexin therapy.

Impacts of net zero policies on air quality in a metropolitan area of the United Kingdom: Towards world health organization air quality guidelines.

Climate change and air pollution are closely interlinked since carbon dioxide and air pollutants are co-emitted from fossil fuel combustion. Net Zero (NZ) policies aiming to reduce carbon emissions will likely bring co-benefits in air quality and associated health. However, it is unknown whether regional NZ policies alone will be sufficient to reduce air pollutant levels to meet the latest 2021 World Health Organisation (WHO) guidelines. Here, we carried out high resolution air quality modelling for in the West Midlands region, a typical metropolitan area in the UK, to quantify the effects of different NZ policies on air quality. Results show that NZ policies will significantly improve air quality in the West Midlands, with up to 6 µg m-3 (21%) reduction in annual mean NO2 (mostly through the electrification of vehicle fleet, EV) and up to 1.4 µg m-3 (12%) reduction in annual mean PM2.5 projected for 2030 relative to levels under a "business as usual" (BAU) scenario. Under BAU, 2030 PM2.5 concentrations in most wards would be below 10 µg m-3 whilst under the Net Zero scenario, those in all wards would be below 10 µg m-3. This means that the ward averages in the West Midlands would meet the UK PM2.5 of 10 µg m-3target a decade early under the Net Zero scenario. However, no ward-level-averaged annual mean PM2.concentrations meet the 2021 WHO Air Quality guideline level of 5 µg m-3 under any scenario. Similarly for NO2 only 18 wards (8% of the region's population) are predicted to have NO2 concentrations below the 2021 WHO guideline level (10 µg m-3). Decarbonisation policies linked to Net Zero deliver substantial regional air quality benefits, but are not in isolation sufficient to deliver clean air with air pollutant levels low enough to meet the 2021 WHO guidelines.

A Deep Learning Approach for Automatic and Objective Grading of the Motor Impairment Severity in Parkinson's Disease for Use in Tele-Assessments.

Wearable sensors provide a tool for at-home monitoring of motor impairment progression in neurological conditions such as Parkinson's disease (PD). This study examined the ability of deep learning approaches to grade the motor impairment severity in a modified version of the Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) using low-cost wearable sensors. We hypothesized that expanding training datasets with motion data from healthy older adults (HOAs) and initializing classifiers with weights learned from unsupervised pre-training would lead to an improvement in performance when classifying lower vs. higher motor impairment relative to a baseline deep learning model (XceptionTime). This study evaluated the change in classification performance after using expanded training datasets with HOAs and transferring weights from unsupervised pre-training compared to a baseline deep learning model (XceptionTime) using both upper extremity (finger tapping, hand movements, and pronation-supination movements of the hands) and lower extremity (toe tapping and leg agility) tasks consistent with the MDS-UPDRS. Overall, we found a 12.2% improvement in accuracy after expanding the training dataset and pre-training using max-vote inference on hand movement tasks. Moreover, we found that the classification performance improves for every task except toe tapping after the addition of HOA training data. These findings suggest that learning from HOA motion data can implicitly improve the representations of PD motion data for the purposes of motor impairment classification. Further, our results suggest that unsupervised pre-training can improve the performance of motor impairment classifiers without any additional annotated PD data, which may provide a viable solution for a widely deployable telemedicine solution.

Triamterene Functions as an Effective Nonsense Suppression Agent for MPS I-H (Hurler Syndrome).

Mucopolysaccharidosis I-Hurler (MPS I-H) is caused by the loss of α-L-iduronidase, a lysosomal enzyme that degrades glycosaminoglycans. Current therapies cannot treat many MPS I-H manifestations. In this study, triamterene, an FDA-approved, antihypertensive diuretic, was found to suppress translation termination at a nonsense mutation associated with MPS I-H. Triamterene rescued enough α-L-iduronidase function to normalize glycosaminoglycan storage in cell and animal models. This new function of triamterene operates through premature termination codon (PTC) dependent mechanisms that are unaffected by epithelial sodium channel activity, the target of triamterene's diuretic function. Triamterene represents a potential non-invasive treatment for MPS I-H patients carrying a PTC.

The influence of stormwater infiltration on downslope groundwater chemistry.

Stormwater infiltration basins have been used extensively around the world to restore urban hydrology towards more natural flow and water quality regimes. There is, however, significant uncertainty in the fate of infiltrated water and accompanying contaminants that depends on multiple factors including media characteristics, interactions with downslope vegetation, legacy contaminants, and presence of underground infrastructure. Understanding the influence of such factors is thus central to the design and siting of infiltration basins. An extensive field program was established to collect monthly data on ground water quality, including nutrients and major ion concentrations, in a bore network downstream of a stormwater infiltration basin in Victoria, Australia. The groundwater samples were analysed for temperature, pH, EC, turbidity, major ions (Na+, Ca2+, K+, Mg2+, Cl-, SO42-, NO3-, CO32-, HCO3-), NOx and heavy metals. The collected data were used to understand the origin and fate of water and solutes in the subsurface and their interactions with the soil matrix. The results revealed that Ca-HCO3, Na-Cl water types predominate in the study area, grouped in 3 clusters; shallow fresh groundwater in the vicinity of the basin (near basin), deep saline groundwater further downstream of the basin (near-stream) and a mid-section where rock-water interaction (Na-HCO3 water) through cation exchange control the chemistry of groundwater. The results also suggest that as the water moves downstream of the basin, it experiences significant evapotranspiration and concentration due to the presence of deep-rooted vegetation. The results suggest that while infiltration basins can remove infiltrated contaminants, the infiltrated stormwater can mobilise legacy contaminants such as nitrate. Overall, the efficacy of infiltration basins in urban regions depends substantially on the downstream vegetation, urban underground infrastructure and the presence of legacy contaminants in the soils. These all need to be considered in the design of stormwater infiltration basins.

Management of Transected Invasive Melanoma: A Single Institution Retrospective Review.

BACKGROUND: Deep transection of invasive melanoma precludes accurate measurement of Breslow depth, which may affect tumor staging. OBJECTIVE: To determine the frequency of upstaging of transected invasive melanomas after excision, characterize the impact on National Comprehensive Cancer Network (NCNN)-recommended treatment, and determine predictors of subsequent upstaging. MATERIALS AND METHODS: A retrospective review of invasive melanomas between January 2017 and December 2019 at a single institution. Deeply transected biopsy reports were compared with subsequent excisions to calculate the frequency of upstaging. RESULTS: Three hundred sixty (49.6%) of 726 invasive melanomas identified were transected. Forty-nine (13.6%) transected tumors had upstaging that would have altered NCCN-recommended management. "Broadly" transected tumors had upstaging that would have resulted in a change in the management in 5/23 cases (21.7%) versus 2/41 cases (4.9%) for "focally" transected tumors (p = .038). Breslow depth increased by 0.59 mm on average for "broad" transection versus 0.06 mm for "focal" transection (p =< .01). Of the 89 transected pT1a melanomas, specimens with gross residual tumor or pigment after biopsy were upstaged in 8/17 (47.1%) of cases versus 5/72 (6.9%) of specimens without (p =< .01). CONCLUSION: Upstaging of deeply transected invasive melanomas that would alter NCCN-recommended management occurred in 13.6% of cases. Broad transection and gross residual tumor or pigment after biopsy predicted higher likelihood of upstaging.

Defining self-disclosure of personal cancer coping experiences in oncology social workers' helping relationships: When cancer "hits home".

PURPOSE: Oncology social workers are increasingly finding themselves diagnosed with or caring for a loved one with cancer. Self-disclosure may be useful for building a therapeutic alliance. Yet, practice-informed guidelines for psychosocial oncology providers do not exist. RESEARCH APPROACH: Twenty-three psychosocial oncology providers diagnosed with and/or providing care to someone with cancer completed semi-structured interviews eliciting attitudes and utilization regarding self-disclosure. METHODOLOGICAL APPROACH: Interviews were digitally recorded and transcribed verbatim. Using grounded theory's constant comparative method, researchers conducted open and theoretical coding. FINDINGS: Participants expressed consensus in defining, and reported a range of evolving practices regarding, self-disclosure. Recommendations for responsible self-disclosure included self-awareness, ongoing assessment, supervision, and enhanced educational programming. INTERPRETATION AND IMPLICATION: Therapeutic tools must evolve as core features of psychosocial oncology care. A flexible and context-specific framework for clinician self-disclosure related to personal experiences with cancer can guide oncology social work practice.

Sinister sinusitis.

Two previously well Caucasian teenage girls with no significant travel or family history were admitted with sinusitis refractory to treatment with antibiotics. Both had progressive symptoms despite broad-spectrum antibiotics and developed involvement of other systems, ultimately requiring admission to the paediatric intensive care unit (PICU). They were subsequently diagnosed with the same condition and made an excellent recovery.The first girl, 14 years old, originally presented to her general practitioner with a sore throat, nasal congestion, and fever. Despite multiple courses of antibiotics over the following month she presented again multiple times with progressive symptoms including epistaxis, widespread myalgia and arthralgia, difficulty in breathing, haemoptysis, fatigue, and weight loss. Examination on admission found minimal discharge from her right tympanic membrane, ulcerated inferior turbinates with dried blood and yellow mucus in both nasal cavities, swollen tonsils without exudate, and an isolated aphthous ulcer on the tip of her tongue. She had small bilateral cervical lymph nodes. Examination of the cardiovascular system was unremarkable but on respiratory examination there was reduced air entry on the right side. Her abdomen was generally tender but soft with no organomegaly. A week into her admission she developed an oxygen requirement and increased work of breathing requiring intubation and ventilation.The second girl, 13 years old, presented to her local hospital with a 1-day history of epistaxis, right ear pain, and pain and swelling to the right periorbital tissues. Again, despite multiple courses of antibiotics, she had persistent symptoms and subsequently developed fever, fatigue, haemoptysis, and had a syncopal episode. She was admitted to her local district general hospital and, despite initial treatment, deteriorated over the following 2 weeks with persistent fever, new oxygen requirement, deteriorating renal function, and anaemia. She was transferred to a tertiary centre for respiratory support which escalated from Optiflow, through continuous then biphasic positive airway pressure, intubation and ventilation, and ultimately VV-ECMO.The investigations for both patients prior to admission to PICU at our centre are shown in table 1.

Reply to Aljabali et al. Comment on "Abbas et al. The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Medicina 2022, 58, 213".

We appreciate Ahmed Sami Aljabali and his colleagues for their interest and comments [...].

The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disease that leads to progressive proximal muscle weakness and muscle atrophy. To assess the beneficial and adverse effects of nusinersen, a promising intervention for SMA, we conducted a systematic search and meta-analysis of the published randomized control trials (RCTs) of nusinersen for SMA. Materials and methods: Utilizing the Preferred Reporting for Systematic Review and Meta-Analysis (PRISMA), we searched PubMed, Scopus, Web of Science, Cochrane Central, and Clinicaltrials.gov from inception to 22 July 2021. Results: Three RCTs satisfying the inclusion and exclusion criteria covered 274 patients: 178 patients in the nusinersen group. Our results show a significant risk difference (RD) in the motor milestone response (RD: 0.51; 95% CI: 0.39, 0.62; p < 0.00001) and improvement in the HINE-2 score (RD: 0.26; 95% CI: 0.12, 0.40; p < 0.0003) in the nusinersen group compared to the control group. Moreover, a significant decrease in the risk ratio (RR) for severe adverse events (RR: 0.72; 95% CI: 0.57, 0.92; p = 0.007) and any adverse event leading to treatment discontinuation (RR: 0.40; 95% CI: 0.22, 0.74; p = 0.004) was observed. An insignificant result was found for any adverse effects (RR: 0.93; 95% CI: 0.97, 1.01; p = 0.14) and for serious adverse effects (RR: 0.81; 95% CI: 0.60, 1.07; p = 0.14). Conclusions: This review provides evidence that nusinersen treatment was effective in treatment for infants with SMA and was associated with fewer severe adverse events; however, more RCTs are needed to establish evidence.

Prescription of analgesia in emergency medicine (POEM) secondary analysis: an observational multicentre comparison of pain relief provided to adults and children with an isolated limb fracture and/or dislocation.

BACKGROUND: Acute pain is a common reason for emergency department (ED) attendance. Royal College of Emergency Medicine (RCEM) pain management audits have shown national variation and room for improvement. Previous evidence suggests that children receive less satisfactory pain management than adults. METHODS: Prescription of analgesia in emergency medicine is a cross-sectional observational study of consecutive patients presenting to 12 National Health Service EDs with an isolated long bone fracture and/or dislocation, and was carried out between 2015 and 2017. Using the recommendations in the RCEM Best Practice Guidelines, pain management in ED was assessed for differences of age (adults vs children) and hospital type (children's vs all patients). RESULTS: From the total 8346 patients, 38% were children (median age 8 years). There was better adherence to the RCEM guidance for children than adults (24% (766/3196) vs 11% (579/5123)) for the combined outcome of timely assessment, pain score and appropriate analgesia. In addition, children were significantly more likely than adults to receive analgesia appropriate to the pain score (of those with a recorded pain score 67% (1168/1744) vs 52% (1238/2361)). Children's hospitals performed much better across all reported outcomes compared with general hospitals. CONCLUSIONS: In contrast to previous studies, children with a limb fracture/dislocation are more likely than adults to have a pain score documented and to receive appropriate analgesia. Unexpectedly, children's EDs performed better than general EDs in relation to timely and appropriate analgesia but the reasons for this are not apparent from the present study.

Cerebral Expression of Metabotropic Glutamate Receptor Subtype 5 in Idiopathic Autism Spectrum Disorder and Fragile X Syndrome: A Pilot Study.

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR5 expression provide conflicting findings about the nature of dysregulation of cerebral mGluR5 pathways in subtypes of ASD. The demonstration of reduced mGluR5 expression throughout the living brains of men with fragile X syndrome (FXS), the most common known single-gene cause of ASD, provides a clue to examine mGluR5 expression in ASD. We aimed to (A) compare and contrast mGluR5 expression in idiopathic autism spectrum disorder (IASD), FXS, and typical development (TD) and (B) show the value of positron emission tomography (PET) for the application of precision medicine for the diagnosis and treatment of individuals with IASD, FXS, and related conditions. Two teams of investigators independently administered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a novel, specific mGluR5 PET ligand to quantitatively measure the density and the distribution of mGluR5s in the brain regions, to participants of both sexes with IASD and TD and men with FXS. In contrast to participants with TD, mGluR5 expression was significantly increased in the cortical regions of participants with IASD and significantly reduced in all regions of men with FXS. These results suggest the feasibility of this protocol as a valuable tool to measure mGluR5 expression in clinical trials of individuals with IASD and FXS and related conditions.

Neonatal hypoglycemia and the CPT1A P479L variant in term newborns: A retrospective cohort study of Inuit newborns from Kivalliq Nunavut.

INTRODUCTION: Neonatal hypoglycemia (NH) in the first days of life can largely be prevented by recognizing those at risk and managing accordingly. The CPT1A P479L variant is prevalent in northern Indigenous populations and is a possible risk factor for hypoglycemia. We report on NH incidence in the Kivalliq region of Nunavut, where all Inuit newborns are screened for NH. METHODS: We reviewed clinical charts of 728 Inuit newborns from Kivalliq (January 1, 2010 to December 31, 2013) for blood glucose (BG) levels and infant/maternal characteristics, linking to CPT1A genotype; 616 newborns had BG data from 2 to 48 hours of life. NH was defined using Canadian Paediatric Society guidelines (≤2.0 mmol/L at 2 hours, <2.6 mmol/L at 2 to 48 hours). RESULTS: NH was documented in 21.4% overall, 24.4% of at-risk newborns and 19.5% of term newborns with no risk factors (≥37 weeks gestation, term-NRF). NH was documented in 22.0% of CPT1A P479L homozygous, 19.8% of P479L heterozygous and 4.8% of noncarrier term-NRF newborns. With multivariable logistic regression, the adjusted ORs for developing NH in term-NRF newborns was 4.97 for CPT1A P479L homozygotes (95% confidence interval [CI]:0.65-38.35, P=0.19) and 4.71 for P479L heterozygotes (95% CI:0.57-37.89, P=0.15). CONCLUSION: Term-NRF newborns had a higher NH incidence than previously reported, similar to that for at-risk newborns, possibly due to the CPT1A P479L variant. Since only Inuit newborns from Kivalliq are screened for NH, further study of long-term outcomes of NH in this population and the role of the P479L variant are warranted to determine if neonatal BG screening is indicated in all Inuit newborns.

Nuts, cereals, seeds and legumes proteins derived emulsifiers as a source of plant protein beverages: A review.

Milk beverages derived from plant-based protein have attracted the interest of consumers and researchers as a health-promoting functional food. It can also be considered as a substitute for animal milk due to various allergy concerns associated with dairy milk. The plant-based emulsions are directed to prevent diet-related chronic diseases including diabetes, cardiovascular, obesity and other disorders due to the presence of healthy long-chain unsaturated fatty acids as compared to bovine milk. Further, associations between nutritional contents (vitamins, minerals and low fat) and pharmacological properties of plant-based protein may have extra beneficial effects. The review aims to summarize the four different groups of plant sources (nuts, cereals, seeds and legumes) used for the preparation of plant-based milk beverages. In addition, it also provides a detailed review of the general characteristics and functional properties of these plant sources. Physicochemical composition, protein and fats quality, functional properties, effect of heat and high-pressure treatment is also provided in detail. It also covers fats digestibility, protein stability, protein solubility and digestibility. Furthermore, the effect of processing, possible comparative study and potential applications in healthcare have been discussed.

Negative predictive value of biopsy margins of dysplastic nevi: A single-institution retrospective review.

BACKGROUND: Biopsies of dysplastic nevi processed by bread-loafing allow for limited margin assessment; however, reported biopsy margins often influence management. OBJECTIVE: To evaluate the negative predictive value of biopsy margins of dysplastic nevi. METHODS: A retrospective search of a single academic institution's pathology database was conducted to identify all biopsy specimens of dysplastic nevi between January 1, 2015, and December 31, 2017. Biopsy specimen margin assessments were compared with excision pathology reports to calculate negative predictive value and to assess the frequency of residual nevus on excision after positive biopsy margins. RESULTS: A total of 1245 dysplastic nevi from 934 patients were identified. Clear biopsy margins had a negative predictive value for the absence of residual nevus on excision of 87.3% for dysplastic nevi of moderate atypia or greater. Residual nevus was identified on excision in 29.41% of cases of dysplastic nevi of moderate atypia or greater when initial biopsy margins were positive. LIMITATIONS: This was a retrospective, single-institution study. The calculations likely overestimate the true negative predictive value of biopsy margins because of processing of excision specimens by bread-loafing. CONCLUSIONS: This study provides additional evidence that reported biopsy margins are not representative of true margin status.

Negative Predictive Value of Biopsy Margins in Keratinocyte Carcinoma: A Literature Review.

BACKGROUND: Pathologists sometimes include commentary on margin involvement in shave biopsy reports of keratinocyte carcinoma (KC). This practice can lead to confusion regarding the need for further treatment. There is limited literature evaluating the reliability of reported histologic margin status in shave biopsies of KC. OBJECTIVE: To evaluate the negative predictive value (NPV) of reported clear shave biopsy margins in basal and squamous cell carcinomas to determine whether this assessment is a reliable predictor of complete tumor removal. METHODS: A literature review was performed using the PubMed database. The data were compiled, NPVs were calculated by the tumor subgroup, and a statistical analysis was performed. RESULTS: Four studies met inclusion criteria. Two hundred twenty-one KCs were identified (n = 221). All specimens had negative-reported histologic margins (39 squamous cell carcinoma [SCC] and 182 BCC). Fifty-five cases initially noted to have negative margins on biopsy were found to have residual tumor on subsequent analysis: 5 SCC and 50 BCC, translating to 12.8% of all SCC (5/39) and 27.5% for BCC (50/182). Negative predictive values were found to be 75.1% for all KCs, 87.2% for SCC, and 72.5% for BCC. CONCLUSION: Negative histologic margin status on shave biopsy specimens of KC has a poor NPV and is an inadequate predictor for complete tumor removal.

Heparin Treatment in Aneurysmal Subarachnoid Hemorrhage: A Review of Human Studies.

Aneurysmal subarachnoid hemorrhage (aSAH) remains a significant cause of stroke disability despite gradual reductions in physical morbidity and mortality. Heparin is an effective anti-inflammatory agent and may potentially prevent delayed neurological injury in the days to weeks after the hemorrhage. Various human studies have shown the safety of a continuous infusion of low-dose unfractionated heparin in the setting of subarachnoid hemorrhage as well as its efficacy in minimizing delayed neurological deficits including symptomatic cerebral vasospasm, vasospasm-related infarction, and cognitive dysfunction. Studies have also shown mixed results with low-molecular-weight heparin usage in this patient population. Heparin treatment is not associated with significant hemorrhagic complications; however, vigilance is essential for early detection of heparin-induced thrombocytopenia in order to prevent devastating sequelae. Multicenter randomized controlled trials are necessary for objective characterization of the effects of heparin.