An Evaluation of Risk Factors for Intracranial Metastases of Sarcomas: A Systematic Review and Meta-Analysis.

INTRODUCTION: Sarcomas, a group of neoplasms comprising both tissue and bone soft tissue tumors, has an increasing prevalence in recent years. Prognosis significantly hinges on early detection and if not detected early may consequently metastasize. This review will be the first systematic review and meta-analysis characterizing the presentation and progression of brain metastases from bone and soft tissue cancers. METHODS: The PubMed, Scopus, and Web of Science databases were queried to identify studies reporting the incidence of intracranial brain metastases from primary sarcoma to the present. Abstract and full-text screening of 1822 initial articles returned by preliminary search yielded 28 studies for inclusion and data extraction. Qualitative assessment of the studies were conducted in accordance with the Newcastle-Ottawa Scale criteria. Meta-analyses were applied to assess risk factors on outcomes. RESULTS: The average age within the cohort was 27.9 years with a male and female prevalence of 59.1% and 40.9%, respectively. The odds rato for living status (dead/alive) were calculated for several risk factors - male/female [OR 1.14, 95% CI 0.62, 2.07], single/multiple metastases [OR 0.67, 95% CI 0.35, 1.28], lung metastases/not [OR 1.63, 95% CI 0.85, 3.13], surgery/no surgery [OR 0.49, 95% CI 0.20, 1.21]. The standardized mean differences for duration from diagnoses to metastases were likewise analyzed - male/female [SMD 0.13, 95% CI -0.15, 0.42], single/multiple metastases [SMD 0.11, 95% CI -0.20, 0.42], lung metastases/not [SMD -0.03, 95% CI -0.38, 0.32], surgery/no surgery [SMD 0.45, 95% CI -0.18,1.09]. The standardized mean differences for duration from metastases to death were analyzed - lung metastases/not [SMD 0.43, 95% CI -0.08, 0.95]. CONCLUSION: Our study observed no statistically significant differences in mortality rate among several patient risk factors. Consequentially, there lacks a clear answer as to whether or not an association between mortality rates exists with these patient factors. As such, it is important to continue research in brain-metastasizing sarcomas despite their relative rarity.

Biochemical, Biomarker, and Behavioral Characterization of the GrnR493X Mouse Model of Frontotemporal Dementia.

Heterozygous loss-of-function mutations in the progranulin gene (GRN) are a major cause of frontotemporal dementia due to progranulin haploinsufficiency; complete deficiency of progranulin causes neuronal ceroid lipofuscinosis. Several progranulin-deficient mouse models have been generated, including both knockout mice and knockin mice harboring a common patient mutation (R493X). However, the GrnR493X mouse model has not been characterized completely. Additionally, while homozygous GrnR493X and Grn knockout mice have been extensively studied, data from heterozygous mice is still limited. Here, we performed more in-depth characterization of heterozygous and homozygous GrnR493X knockin mice, which includes biochemical assessments, behavioral studies, and analysis of fluid biomarkers. In the brains of homozygous GrnR493X mice, we found increased phosphorylated TDP-43 along with increased expression of lysosomal genes, markers of microgliosis and astrogliosis, pro-inflammatory cytokines, and complement factors. Heterozygous GrnR493X mice did not have increased TDP-43 phosphorylation but did exhibit limited increases in lysosomal and inflammatory gene expression. Behavioral studies found social and emotional deficits in GrnR493X mice that mirror those observed in Grn knockout mouse models, as well as impairment in memory and executive function. Overall, the GrnR493X knockin mouse model closely phenocopies Grn knockout models. Lastly, in contrast to homozygous knockin mice, heterozygous GrnR493X mice do not have elevated levels of fluid biomarkers previously identified in humans, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in both plasma and CSF. These results may help to inform pre-clinical studies that use this Grn knockin mouse model and other Grn knockout models.

Apnea Testing on Conventional Mechanical Ventilation During Brain Death Evaluation.

INTRODUCTION: The use of continuous positive airway pressure has been shown to improve the tolerance of the apnea test, a critical component of brain death evaluation. The ability to deactivate the apnea backup setting has made apnea testing possible using several conventional mechanical ventilators. Our goal was to evaluate the safety and efficacy of apnea testing performed on mechanical ventilation, compared with the oxygen insufflation technique, for the determination of brain death. METHODS: This was a retrospective study. In 2016, our institution approved a change in policy to permit apnea testing on conventional mechanical ventilation. We examined the records of consecutive adults who underwent apnea testing as part of the brain death evaluation process between 2016 and 2022. Using an apnea test technique was decided at the discretion of the attending physician. Outcomes were successful apnea test and the occurrence of patient instability during the test. This included oxygen desaturation (SpO2) < 90%, hypotension (mean arterial pressure < 65 mm Hg despite titration of vasopressor), cardiac arrhythmia, pneumothorax, and cardiac arrest. RESULTS: Ninety-two adult patients underwent apnea testing during the study period: 58 (63%) with mechanical ventilation, 32 (35%) with oxygen insufflation, and 2 (2%) lacked documentation of technique. Apnea tests could not be completed successfully in 3 of 92 (3%) patients-two patients undergoing the oxygen insufflation technique (one patient with hypoxemia and one patient with hypotension) and one patient on mechanical ventilation (aborted for hemodynamic instability). Hypoxemia occurred in 4 of 32 (12.5%) patients with oxygen insufflation and in zero patients on mechanical ventilation (p = 0.01). Hypotension occurred during 3 of 58 (5%) tests with mechanical ventilation and 4 of 32 (12.5%) tests with oxygen insufflation (p = 0.24). In multivariate analysis, the use of oxygen insufflation was an independent predictor of patient instability during the apnea test (odds ratio 37.74, 95% confidence interval 2.74-520.14). CONCLUSIONS: Apnea testing on conventional mechanical ventilation is feasible and offers several potential advantages over other techniques.

Clinical outcomes of hepatocellular carcinoma surveillance in Melbourne, Australia.

BACKGROUND: Ultrasound surveillance for hepatocellular carcinoma (HCC) may improve early tumour detection but may additionally result in surveillance-related harm through increased evaluation of non-HCC lesions. The incidence of these outcomes has not been reported outside North America. AIMS: We aimed to report the outcomes of HCC surveillance with respect to both surveillance-related benefits and harms. METHODS: We reviewed all HCC surveillance ultrasounds at a large Victorian tertiary hospital network in 2017 and followed their outcomes until 2021. Surveillance-related benefits were defined as early-stage HCC detection. Surveillance-related harm was defined as contrast imaging, biopsies or surgery performed to evaluate non-HCC liver lesions or false-positive alpha-fetoprotein levels. RESULTS: Five hundred and fifty-three patients were included (mean age 54.5 ± 12.3 years, males 67.5%, cirrhosis 50.3%). The most common liver disease aetiology was hepatitis B (53.9%). Over a median of 4.7 years follow-up, early-stage HCC was detected in 3.3% (5.4% in cirrhotic vs 1.1% in non-cirrhotic patients, P < 0.01). 75% of all HCCs were early-stage. Surveillance-related harm occurred in 12.5% (15.5% in cirrhotic vs 9.5% in non-cirrhotic patients, P < 0.04), although most harm was mild (12.1%). In subgroup analysis, the detection of early-stage HCC ranged between 0% (screened outside of guideline criteria and alcoholic cirrhotic patients) and 7.2% (hepatitis C cirrhosis). Harm occurred between 9% (non-cirrhotic hepatitis B) and 20.8% (thrombocytopenia). CONCLUSION: In our study, HCC surveillance was associated with early tumour detection, although many patients experienced mild surveillance-related harm. Novel surveillance strategies and pathways are required to improve detection in high-risk patients and minimise harm in low-risk patients.

The Role of Mental Health Conditions in Early Detection and Treatment of Veterans With Alzheimer's Dementia.

INTRODUCTION: The benefits of early detection of Alzheimer's disease (AD) have become increasingly recognized. Veterans with mental health conditions (MHCs) may be less likely to receive a specific AD diagnosis compared to veterans without MHCs. We investigated whether rates of MHCs differed between veterans diagnosed with unspecified dementia (UD) vs. AD to better understand the role MHCs might play in establishing a diagnosis of AD. MATERIALS AND METHODS: This retrospective analysis (2015-2022) identified UD and AD with diagnostic code-based criteria. We determined the proportion of veterans with MHCs in UD vs. AD cohorts. Secondarily, we assessed the distribution of UD/AD diagnoses in veterans with and without MHCs. RESULTS: We identified 145,309 veterans with UD and 33,996 with AD. The proportion of each MHC was consistently higher in UD vs. AD cohorts: 41.4% vs. 33.2% (depression), 26.9% vs. 20.3% (post-traumatic stress disorder), 23.4% vs. 18.2% (anxiety), 4.3% vs. 2.1% (bipolar disorder), and 3.9% vs. 1.5% (schizophrenia). The UD diagnostic code was used in 84% of veterans with MHCs vs. 78% without MHCs (P < .001). CONCLUSIONS: Mental health conditions were more likely in veterans with UD vs. AD diagnoses; comorbid MHC may contribute to delayed AD diagnosis.

Treatment Response Imaging in Prostate Cancer.

Objective criteria for measuring treatment response in prostate cancer are critical to clinical research and practice. The Prostate Cancer Working Group 3 criteria are widely accepted relying only on conventional imaging for radiographic treatment response. Prostate-specific membrane antigen PET/computed tomography was proven to be superior to conventional imaging in initial diagnosis and biochemical recurrence of prostate cancer. Moreover, there is growing evidence of its role in treatment response assessment in prostate cancer. This study will review the different criteria for imaging treatment response on conventional and advanced molecular imaging for different therapies, and the future perspective in posttherapy imaging.

Development of a Visually Calculated SUVmean (HIT Score) on Screening PSMA PET/CT to Predict Treatment Response to 177Lu-PSMA Therapy: Comparison with Quantitative SUVmean and Patient Outcomes.

177Lu-PSMA therapy is an effective treatment in patients with metastatic castration-resistant prostate cancer. SUVmean is a valuable screening biomarker to assess the suitability for 177Lu-PSMA therapy but requires quantitative software. This study aims to develop a simple, clinically applicable prostate-specific membrane antigen PET/CT score that encompasses the elements of SUVmean without requiring additional quantification. Methods: Datasets from ethics-approved trials of patients with metastatic castration-resistant prostate cancer after androgen receptor signaling inhibition and taxane chemotherapy (or unfit for taxane), who were treated with 177Lu-PSMA-617 and 177Lu-PSMA I&T with a pretreatment screening with 68Ga-PSMA-11 PET/CT, and clinical outcome data, including a prostate-specific antigen (PSA) 50% response rate (PSA50), PSA progression-free survival (PSA-PFS), and overall survival (OS), were included. The screening 68Ga-PSMA-11 PET/CT of all participants was analyzed both semiquantitatively and visually. Semiquantitative analysis was used to derive the SUVmean Visual analysis of the 68Ga-PSMA-11 PET/CT images involved a binary visual heterogeneity assessment (homogeneous or heterogeneous), allocating a tumor SUVmax range (<15, 15-29, 30-49, 50-79, or ≥80). A 4-category score incorporating both heterogeneity and intensity of tumors (HIT) was then developed as a combination of heterogeneity and intensity (SUVmax range). The SUVmax was less than 15 for score 1, 15-79 with heterogeneous intensity for score 2, 15-79 with homogeneous intensity for score 3, and 80 or greater for score 4. This score was evaluated according to clinical outcomes (PSA50, PSA-PFS, and OS) and compared with SUVmean Results: Data from 139 participants were analyzed. In total, 75 (54%) patients achieved a PSA50 with a median PSA-PFS of 5.5 mo (95% CI, 4.1-6.0 mo) and an OS of 13.5 mo (95% CI, 11.1-17.9 mo). SUVmean was associated with PSA50 and survival outcomes when analyzed as a continuous variable or as quartiles. The PSA50 for HIT scores 1-4 was 0%, 39%, 65%, and 76%, respectively. The HIT score was strongly related to PSA-PFS and OS (log-rank test, P < 0.001 and P = 0.002). The median PSA-PFS for HIT scores 1-4 was 1.0, 4.1, 6.0, and 8.5, respectively, and the median OS was 7.6, 12.0, 18.5, and 16.9 mo, respectively. Cohen κ between readers for the HIT score was 0.71. Conclusion: A prostate-specific membrane antigen PET/CT score incorporating HIT derived from tools on a standard PET workstation is comparable with quantitative SUVmean as a prognostic tool following 177Lu-PSMA therapy.

Explainable Machine Learning Model to Preoperatively Predict Postoperative Complications in Inpatients With Cancer Undergoing Major Operations.

PURPOSE: Preoperative prediction of postoperative complications (PCs) in inpatients with cancer is challenging. We developed an explainable machine learning (ML) model to predict PCs in a heterogenous population of inpatients with cancer undergoing same-hospitalization major operations. METHODS: Consecutive inpatients who underwent same-hospitalization operations from December 2017 to June 2021 at a single institution were retrospectively reviewed. The ML model was developed and tested using electronic health record (EHR) data to predict 30-day PCs for patients with Clavien-Dindo grade 3 or higher (CD 3+) per the CD classification system. Model performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), and calibration plots. Model explanation was performed using the Shapley additive explanations (SHAP) method at cohort and individual operation levels. RESULTS: A total of 988 operations in 827 inpatients were included. The ML model was trained using 788 operations and tested using a holdout set of 200 operations. The CD 3+ complication rates were 28.6% and 27.5% in the training and holdout test sets, respectively. Training and holdout test sets' model performance in predicting CD 3+ complications yielded an AUROC of 0.77 and 0.73 and an AUPRC of 0.56 and 0.52, respectively. Calibration plots demonstrated good reliability. The SHAP method identified features and the contributions of the features to the risk of PCs. CONCLUSION: We trained and tested an explainable ML model to predict the risk of developing PCs in patients with cancer. Using patient-specific EHR data, the ML model accurately discriminated the risk of developing CD 3+ complications and displayed top features at the individual operation and cohort level.

[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

Automated Plaque Detection and Agatston Score Estimation on Non-Contrast CT Scans: A Multicenter Study.

Coronary artery calcification (CAC) is a strong and independent predictor of cardiovascular disease (CVD). However, manual assessment of CAC often requires radiological expertise, time, and invasive imaging techniques. The purpose of this multicenter study is to validate an automated cardiac plaque detection model using a 3D multiclass nnU-Net for gated and non-gated non-contrast chest CT volumes. CT scans were performed at three tertiary care hospitals and collected as three datasets, respectively. Heart, aorta, and lung segmentations were determined using TotalSegmentator, while plaques in the coronary arteries and heart valves were manually labeled for 801 volumes. In this work we demonstrate how the nnU-Net semantic segmentation pipeline may be adapted to detect plaques in the coronary arteries and valves. With a linear correction, nnU-Net deep learning methods may also accurately estimate Agatston scores on chest non-contrast CT scans. Compared to manual Agatson scoring, automated Agatston scoring indicated a slope of the linear regression of 0.841 with an intercept of +16 HU (R2 = 0.97). These results are an improvement over previous work assessing automated Agatston score computation in non-gated CT scans.

SuperMap algorithm: an efficient, safe and accurate modality for mapping and eliminating challenging cardiac arrhythmias.

Even with the development of advanced catheter-based mapping systems, there remain several challenges in the electrophysiological evaluation and elimination of atrial arrhythmias. For instance, atrial tachycardias with irregular rates cannot be reliably mapped by systems that require stability in order to sequentially gather data points to be organized thereafter. Separately, these arrhythmias often arise following initial ablation for atrial fibrillation, posing logistic challenges. Here, we present the available literature summarizing the use of a non-contact mapping catheter, the AcQMap catheter, in conjunction with SuperMap, an algorithm that compiles a large number of non-contact data points from multiple catheter positions within the atria. These studies demonstrate the efficiency, safety and accuracy of this technology.

Irregular heart rhythms (arrhythmias) are often treatable with medications, but sometimes require expert evaluation in a cardiac electrophysiology laboratory. They are often studied and treated using thin, flexible catheters which enter the body through blood vessels in the leg and reach the internal walls of the heart. Time, expertise and specialized equipment are necessary to identify characteristics specific to each patient's arrhythmia. For each arrhythmia, a unique electrical blueprint is created before trying to eliminate it. The fleeting nature of certain arrhythmias can make it difficult to generate these blueprints, and many take a lot of time to accurately identify, leading to procedural challenges. Here we evaluate studies discussing the use of a new catheter (AcQMap) and its accompanying strategy for identifying arrhythmias. Unlike traditional catheters that require direct contact with the internal walls of the heart, the AcQMap catheter floats within these blood-filled chambers and does not touch the walls when obtaining data points. Instead, using ultrasound waves and electrical signals, it can generate data points to create blueprints. This technology also uses a new algorithm that enables the catheter to move freely within the heart, obtaining numerous data points and grouping them together to create maps efficiently and safely, even for fleeting or challenging arrhythmias.

Alfred Washington Adson: Perspectives on Intracranial Neurosurgery and the Responsibilities of the Neurosurgeon.

In a period when the budding field of neurosurgery was believed to have little promise, Dr Alfred Washington Adson founded and led the first neurosurgical department at Mayo Clinic. He was not without reservations-surgical intervention for neurological conditions was rarely pursued because of poor outcomes and high complication rates, and Dr Adson acknowledged his early concerns about the future of neurosurgery in his memoirs. However, his education, mentorship, his training, and his first neurosurgical cases helped to shape the impact he ultimately had on the field and his legacy as a neurosurgeon. Dr Adson trained with several renowned Mayo general surgeons, notably his mentor Dr Emil Beckman, whose desire for operative precision shaped Dr Adson's drive to develop his own skills as a surgeon. Two years into his residency, he became the youngest staff surgeon and was tasked with managing the neurosurgical cases at Mayo. The five neurosurgical cases overseen by Dr Adson in the next year illuminated the opportunity for neurosurgery to drastically improve the lives of patients. Dr Adson, given the option of continuing as either a general surgeon or a neurosurgeon, ultimately chose to pursue neurosurgery. This article seeks to provide a historical perspective on the neurosurgeon Dr Alfred Washington Adson using primary and secondary accounts from the Mayo archives, highlighting his contributions to the early understanding of intracranial pathology and how his early experiences as a trainee developed into a personal passion for self-improvement, education, and advocacy for health care in America.

Characterisation of social media conversations on syphilis: an unobtrusive observational study.

BACKGROUND: Conversations around disease conducted through social media provide a means for capturing public perspectives that may be useful in considering public health approaches. Syphilis is a sexually transmitted disease that is re-emerging. We sought to characterise online discourse on syphilis using data collected from the social media platform, Twitter. METHODS: We extracted English-language tweets containing the word 'syphilis' posted on Twitter in 2019. Tweet identification number and URL, date and time of posting, number of retweets and likes, and the author's screen name, username and biographical statement were included in the dataset. A systematically sampled 10% subset of the data was subjected to qualitative analysis, involving categorisation on content. All tweets assigned to the category of medical resource were assessed for clinical accuracy. The engagement ratio for each category was calculated as (retweets+likes):tweets. RESULTS: In 2019, 111,388 tweets mentioning syphilis were posted by 69,921 authors. The most frequent content category - totalling 5370 tweets (48%) - was a joke. Of 1762 tweets (16%) categorised as a medical resource, 1484 (84%) were medically correct and 240 (14%) were medically incorrect; for 38 (2%), medical accuracy could not be judged from the information posted. Tweets categorised as personal experiences had the highest engagement ratio at approximately 19:1. Medical resource tweets had an engagement ratio of approximately 7:1. CONCLUSIONS: We found medical information about syphilis was limited on Twitter. As tweets about personal experiences generate high engagement, coupling an experience with information may provide opportunity for public health education.

Contemporary approach to cardiogenic shock care: a state-of-the-art review.

Cardiogenic shock (CS) is a time-sensitive and hemodynamically complex syndrome with a broad spectrum of etiologies and clinical presentations. Despite contemporary therapies, CS continues to maintain high morbidity and mortality ranging from 35 to 50%. More recently, burgeoning observational research in this field aimed at enhancing the early recognition and characterization of the shock state through standardized team-based protocols, comprehensive hemodynamic profiling, and tailored and selective utilization of temporary mechanical circulatory support devices has been associated with improved outcomes. In this narrative review, we discuss the pathophysiology of CS, novel phenotypes, evolving definitions and staging systems, currently available pharmacologic and device-based therapies, standardized, team-based management protocols, and regionalized systems-of-care aimed at improving shock outcomes. We also explore opportunities for fertile investigation through randomized and non-randomized studies to address the prevailing knowledge gaps that will be critical to improving long-term outcomes.

Assessing the defecation practices of unsheltered individuals and their contributions to microbial water quality in an arid, urban watershed.

Outdoor defecation by people experiencing homelessness is frequently perceived as a potentially large source of human fecal pollution and a significant source of health risk in urban waterbodies with recreational contact. The goal of this study was to count the number of people experiencing homelessness and quantifies their sanitation habits in an urban river corridor setting, then use this information for estimating human fecal pollutant loading on a watershed scale. Two types of census counts were conducted including periodic point-in-time counts over six years and weekly counts of encampments. While the population census varied from count-to-count, the range of population estimates in the river corridor varied from 109 to 349 individuals during the six-year span, which mirrored the weekly counts of encampments. A face-to-face survey of people experiencing homelessness assessed the sanitation habits of the unsheltered population (N = 63), including outdoor defecation frequency and containment practices. Overall, 95 % of survey respondents reported defecating outdoors; 36 % practiced outdoor defecation between 4 and 7 days/week and 27 % practiced outdoor defecation <1 day/week. Of those that did practice outdoor defecation, 75 % contained their feces in a bucket or bag, thereby limiting fecal material contributions to the river; 6.7 % reported defecating on low ground near the river that could wash off when flood waters rise during a storm event. Only a single survey respondent reported defecating directly into the river. Based on literature values for average HF183 output for an adult human, and the average rainfall in the urban watershed, the total watershed contribution of HF183 averaged 1.2 × 1010 gene copies per storm event (95 % CI: 0.9 × 1010-1.6 × 1010) along the 41 km stretch of river in this study. This human fecal loading estimate is at least two orders of magnitude less than cumulative HF183 loading from all human sources measured at the bottom of the watershed.

Assessment of Blood Loss during Neuroendovascular Procedures.

(1) Background: Neuroendovascular procedures have generally been considered to have minor or inconsequential blood loss. No study, however, has investigated this question. The purpose of this study is to quantify the blood loss associated with neuroendovascular procedures and identify predictors of blood loss, using hemoglobin change as a surrogate for blood loss. (2) Methods: A retrospective review of 200 consecutive endovascular procedures (diagnostic and therapeutic) at our institution from January 2020 to October 2020 was performed. Patients had to have pre- and post-operative hematocrit and hemoglobin levels recorded within 48 h of the procedure (with no intervening surgeries) for inclusion. (3) Results: The mean age of our cohort was 60.1 years and the male representation was 52.5%. The mean pre-operative hemoglobin/hematocrit was significantly lower among females compared to males (12.1/36.2 vs. 13.0/38.5, p = 0.003, p = 0.009). The mean hemoglobin decrease was 0.5 g/dL for diagnostic angiograms compared to 1.2 g/dL for endovascular interventions (p < 0.0001), and 1.0 g/dL for all procedures combined. In a multivariate linear regression analysis, pre-operative antiplatelet/anticoagulant use was associated with a statistically significant decrease in hemoglobin. (4) Conclusions: Our data support that blood loss from diagnostic angiograms is marginal. Blood loss in endovascular interventions, however, tends to be higher. Pre-operative blood antiplatelet/anticoagulant use and increasing age appear to increase bleeding risk and may require closer patient monitoring.

The structure of tyrosine-10 favors ionic conductance of Alzheimer's disease-associated full-length amyloid-ß channels.

Amyloid ß (Aß) ion channels destabilize cellular ionic homeostasis, which contributes to neurotoxicity in Alzheimer's disease. The relative roles of various Aß isoforms are poorly understood. We use bilayer electrophysiology, AFM imaging, circular dichroism, FTIR and fluorescence spectroscopy to characterize channel activities of four most prevalent Aß peptides, Aß1-42, Aß1-40, and their pyroglutamylated forms (AßpE3-42, AßpE3-40) and correlate them with the peptides' structural features. Solvent-induced fluorescence splitting of tyrosine-10 is discovered and used to assess the sequestration from the solvent and membrane insertion. Aß1-42 effectively embeds in lipid membranes, contains large fraction of ß-sheet in a ß-barrel-like structure, forms multi-subunit pores in membranes, and displays well-defined ion channel features. In contrast, the other peptides are partially solvent-exposed, contain minimal ß-sheet structure, form less-ordered assemblies, and produce irregular ionic currents. These findings illuminate the structural basis of Aß neurotoxicity through membrane permeabilization and may help develop therapies that target Aß-membrane interactions.

Headache Disorders: Differentiating Primary and Secondary Etiologies.

In the initial assessment of a headache patient, several dangerous secondary etiologies must be considered. A thorough history and physical examination, along with a comprehensive differential diagnosis may alert a physician to the diagnosis of a secondary headache particularly when it is accompanied by certain clinical features. Evaluation and workup include a complete neurological examination, consideration of neuroimaging, and serum/spinal fluid analysis if indicated. Careful attention to the patients' history and physical examination will guide the diagnostic work-up and management. In this review, we summarize the diagnostic workup of various primary and secondary headache etiologies. Although most headaches are primary in nature, it is essential to screen for headache "red flags", as they can suggest life threatening secondary etiologies. When secondary causes are suspected, appropriate neuroimaging can further differentiate the underlying cause. The appropriate imaging is dependent on the most likely secondary etiology, which is deduced from history and physical examination. When no red flags are present, primary headaches are more likely. These can be differentiated by frequency, location, duration, triggers, and presence of aura. The different clinical presentations for secondary headaches, as well as the distinguishing features for primary headaches are outlined in this review.

Risks Associated with Surgical Management of Lumbosacral Transitional Vertebrae: Systematic Review of Surgical Considerations and Illustrative Case.

BACKGROUND: Lumbosacral transitional vertebrae (LSTV) are congenital anomalies of the L5-S1 segments characterized by either sacralization of the most caudal lumbar vertebra or lumbarization of the most cephalad sacral vertebra. This variation in anatomy exposes patients to additional surgical risks. METHODS: In order to shed light on surgical considerations reported for lumbar spine cases involving LSTV as described in the extant literature, we performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We also present a case example in which wrong level surgery was avoided due to anatomical understanding of LSTV. RESULTS: A 48-year-old female presented with severe back pain after sustaining a fall from ten feet. The patient exhibited full motor function in all extremities but had begun to experience urinary retention. On initial imaging read, the patient was suspected to have an L1 burst fracture. A review of the imaging demonstrated a transitional vertebra. Therefore, based on the last rib corresponding to T12, the fractured level was L2. This case illustrates the risk LSTV carries for wrong site surgery; appropriate levels were then decompressed and instrumented. On systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a three database literature search identified 39 studies describing 885 patients with LSTV and relevant surgical considerations. The primary indications for surgery were for disc herniation (37%), Bertolotti's syndrome (35%), and spinal stenosis (25%). This cohort displayed a mean follow-up time of 23 months. Reherniation occurred in 12 patients (5.5%). Medical management through steroid injection was 24, 72% (n = 80) for the sample. Wrong level surgery occurred in 1.4% (n = 12) of patients. CONCLUSIONS: LSTV represents a constellation of changes in anatomy beyond just a sacralized or lumbarized vertebra. These anatomical differences expose the patient to additional surgical risks. This case and review of the literature highlight avoidable complications and in particular wrong level surgery.

Update on sex specific risk factors in cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide and accounts for roughly 1 in 5 deaths in the United States. Women in particular face significant disparities in their cardiovascular care when compared to men, both in the diagnosis and treatment of CVD. Sex differences exist in the prevalence and effect of cardiovascular risk factors. For example, women with history of traditional cardiovascular risk factors including hypertension, tobacco use, and diabetes carry a higher risk of major cardiovascular events and mortality when compared to men. These discrepancies in terms of the relative risk of CVD when traditional risk factors are present appear to explain some, but not all, of the observed differences among men and women. Sex-specific cardiovascular disease research-from identification, risk stratification, and treatment-has received increasing recognition in recent years, highlighting the current underestimated association between CVD and a woman's obstetric and reproductive history. In this comprehensive review, sex-specific risk factors unique to women including adverse pregnancy outcomes (APO), such as hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus, preterm delivery, and newborn size for gestational age, as well as premature menarche, menopause and vasomotor symptoms, polycystic ovarian syndrome (PCOS), and infertility will be discussed in full detail and their association with CVD risk. Additional entities including spontaneous coronary artery dissection (SCAD), coronary microvascular disease (CMD), systemic autoimmune disorders, and mental and behavioral health will also be discussed in terms of their prevalence among women and their association with CVD. In this comprehensive review, we will also provide clinicians with a guide to address current knowledge gaps including implementation of a sex-specific patient questionnaire to allow for appropriate risk assessment, stratification, and prevention of CVD in women.