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OBJECTIVE External ventricular drainage (EVD) catheters are associated with complications such as EVD catheter infection (ECI), intracranial hemorrhage (ICH), and suboptimal placement. The aim of this study was to investigate the rates of EVD catheter complications and their associated risk factor profiles in order to optimize the safety and accuracy of catheter insertion. METHODS A total of 348 patients with urgently placed EVD catheters were included as a part of a prospective multicenter observational cohort. Strict definitions were applied for each complication category. RESULTS The rates of misplacement, ECI/ventriculitis, and ICH were 38.6%, 12.2%, and 9.2%, respectively. Catheter misplacement was associated with midline shift (p = 0.002), operator experience (p = 0.031), and intracranial length (p < 0.001). Although mostly asymptomatic, ICH occurred more often in patients receiving prophylactic low-molecular-weight heparin (LMWH) (p = 0.002) and those who required catheter replacement (p = 0.026). Infectious complications (ECI/ventriculitis and suspected ECI) occurred more commonly in patients whose catheters were inserted at the bedside (p = 0.004) and those with smaller incisions (≤ 1 cm) (p < 0.001). ECI/ventriculitis was not associated with preinsertion antibiotic prophylaxis (p = 0.421), catheter replacement (p = 0.118), and catheter tunneling length (p = 0.782). CONCLUSIONS EVD-associated complications are common. These results suggest that the operating room setting can help reduce the risk of infection, but not the use of preoperative antibiotic prophylaxis. Although EVD-related ICH was associated with LMWH prophylaxis for deep vein thrombosis, there were no significant clinical manifestations in the majority of patients. Catheter misplacement was associated with operator level of training and midline shift. Information from this multicenter prospective cohort can be utilized to increase the safety profile of this common neurosurgical procedure.

Background To identify pancreatectomy specific risk factors for myocardial infarction and cardiac arrest (MICA) and to assess whether addition of new information obtained during the hospitalization changes these risk factors. Methods Analysis was performed on elective pancreatectomy data from the ACS-NSQIP database (2014–2019). Risk factors were grouped into pre-operative, intra-operative, and postoperative phases. Factors were selected using a bootstrap resampling procedure to determine MICA association. Independent significance was assessed by logistic regression. Results In the first 30 days post-op, 650 of 39779 patients (1.88%) developed MICA. Some of the surgery specific, intra- and post-operative factors that were identified are: delayed gastric emptying (OR: 2.61; 95% CI: 2.12–3.21), total pancreatectomy (OR: 2.16; 95% CI: 1.29–3.42), pancreatic fistula (OR: 1.54; 95% CI: 1.25–1.90), post-operative transfusion (OR: 1.28; 95% CI: 1.03–1.58), and open approach (OR: 1.36; 95% CI: 1.05–1.77). Adding new variables improved statistical model performance and the c-statistic improved from 0.69 to 0.76 in the final analysis. Conclusion Surgery specific, intra-, and post-operative factors were associated with MICA. Addition of new information during the hospital course changed risk factors and the statistical prediction of MICA risk improved.

The excessive occlusal wear of complete-arch implant-supported prostheses made with metal and acrylic resin is a clinical complication that can require repeated maintenance in certain patients. A patient who presented with moderate occlusal wear of the prosthetic teeth and substantial fracture of the maxillary anterior acrylic resin base only 2 years after a previous replacement of the acrylic resin base and denture teeth is described. Because of the patient's history and existing wear, both the maxillary and mandibular prostheses were repaired by replacing the acrylic resin bases and resin denture teeth but with the addition of cast gold occlusal surfaces on the posterior prosthetic teeth. The provided treatment helped this patient, who was likely to need more frequent maintenance visits in the future because of his history of accelerated occlusal wear and increased occlusal force.

Background Necrotizing Enterocolitis (NEC) remains a significant cause of morbidity and mortality. Recently, there has been an increased recognition of the importance of intestinal immunity and the associations with antibiotics and enteral feeds in the pathophysiology of NEC. The primary purpose of this study is to examine the association of enteral feeds on the survival of premature neonates with NEC. Material and methods A retrospective review using the Vermont Oxford Network for a Level IV NICU from January 1, 2013 through December 31, 2019 was performed. All neonates had a gestational age between 22 to 29 weeks, weighed at least 300 grams (n = 653), had a reported enteral feed status and were treated for NEC (n = 43). Data analysis utilized two-tailed t-tests for NEC and infection rates then Fisher's exact tests for survival status. Results The incidence of NEC in the population was 6.6% (43/653). Of the 43 neonates treated for NEC, 27 were enterally fed, while the other 16 were not. All 27 neonates with NEC that were able to achieve enteral feeds survived and had an infection rate of 22.2%. Meanwhile, all 16 neonates with NEC that were unable to achieve enteral feeds died and had an infection rate of 62.5%. Conclusions There is a significant association between enteral feeds and NEC, survival, and infection rates in premature neonates. These findings support the importance of intestinal immunity and the microbiota in NEC. Given the limitations of the retrospective review, the profound survival advantage with enteral feeds reinforces the need for further study.

Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA+ mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after next-generation androgen receptor–directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA+ identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA+ by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

Objectives The aim of this study was to compare the incidence and prognostic significance of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) according to racial groups. Background PPM after TAVR may be of more concern in Asian populations considering their relatively small annular and valve sizes compared with Western populations. Methods TP-TAVR (Transpacific TAVR Registry) was an international multicenter cohort study of patients with severe aortic stenosis who underwent TAVR in the United States and South Korea from January 2015 to November 2019. PPM was defined as moderate (0.65-0.85 cm2/m2) or severe ( Results Among 1,101 eligible patients (533 Asian and 569 non-Asian), the incidence of PPM was significantly lower in the Asian population (33.6%; moderate, 26.5%; severe, 7.1%) than in the non-Asian population (54.5%; moderate, 29.8%; severe, 24.7%). The 1-year rate of the primary outcome was similar between the PPM and non-PPM groups (27.5% vs 28.1%; P = 0.69); this pattern was consistent between Asian (25.4% vs 25.2%; P = 0.31) and non-Asian (28.7% vs 32.1%; P = 0.97) patients. After multivariable adjustment, the risk for the primary outcome did not significantly differ between the PPM and non-PPM groups in the overall population (HR: 0.95; 95% CI: 0.74-1.21), in Asian patients (HR: 1.07; 95% CI: 0.74-1.55), and in non-Asian patients (HR: 0.86; 95% CI: 0.63-1.19). Conclusions In this study of patients with severe aortic stenosis who underwent TAVR, the incidence of PPM was significantly lower in Asian patients than in non-Asian patients. The 1-year risk for the primary composite outcome was similar between the PPM and non-PPM groups regardless of racial group. (Transpacific TAVR Registry [TP-TAVR]; NCT03826264 )

Background We investigated the evolving prevalence of mood and anxiety symptoms among healthcare workers from May, 2020 to January, 2021; risk factors for adverse outcomes; and characteristic modes of affective responses to pandemic-related stressors. Methods 2,307 healthcare workers (78.9% female, modal age 25-34) participated in an online survey assessing depression (Patient Health Questionnaire [PHQ-9]) and anxiety symptoms (Generalized Anxiety Disorder scale [GAD-7]), demographic variables, and self-reported impact of pandemic-related stressors. 334 subjects were reassessed ∼6 months later. Results The prevalence of clinically significant depression and anxiety was 45.3% and 43.3%, respectively, and a majority (59.9%–62.9%) of those individuals had persistent significant symptoms at 6-month follow-up. Younger age, female gender, and specific occupations (support staff > nurses > physicians) were associated with increased depressive and anxiety symptoms. The most important risk factors were social isolation and fear of contracting COVID-19. The prevalence of clinically significant mood and anxiety symptoms increased by 39.8% from May, 2020 to January, 2021. PHQ-9 and GAD-7 scores were highly correlated and associated with nearly identical risk factors, suggesting that they are not capturing independent constructs in this sample. Principal components analysis identified seven orthogonal symptom domains with unique risk factors. Conclusions Clinically significant mood and anxiety symptoms are highly prevalent and persistent among healthcare workers, and are associated with numerous risk factors, the strongest of which are related to pandemic stressors and potentially modifiable. Interventions aimed at reducing social isolation and mitigating the impact of fear of infection warrant further study.

Background The Surgeon General oversees the Commissioned Corps of the U.S. Public Health Service (USPHS) and is viewed as the “Nation’s Doctor,” responsible for providing the public with information on living healthier and safer lives. The Surgeon General’s influence is seen through public health initiatives such as warning labels on tobacco and alcohol products. The objectives of this paper are to describe the tradition of the Office of the Surgeon General as created by Dr John M. Woodworth and to describe the careers of Dr C. Everett Koop and Dr Richard H. Carmona—the only 2 surgeons by training to hold the role. Methods This is a historical literature review using a combination of primary and secondary sources. Results Dr Woodworth set the priorities and responsibilities of the Surgeon General’s Office: education, public service, sanitation, and public health. Dr Koop is widely regarded as the most influential Surgeon General of all time. He was both a pioneer in pediatric surgery and a highly influential public figure, issuing landmark reports on smoking, violence, and AIDS. Dr Carmona is a trauma surgeon by training and focused on the dangers of second-hand smoke as Surgeon General. Dr Carmona served in a more political role as Surgeon General, eventually running for Senate at the end of his term. Conclusion This brief review of the history of the Surgeon General’s Office highlights the contributions of the first Surgeon General and the only 2 surgeons who have held the position.

Purpose: This study provides a contemporary assessment of the treatment patterns, health care resource utilization (HRU) and costs among metastatic castration-sensitive prostate cancer (mCSPC) patients in the U.S. Materials and Methods: Adults with mCSPC were selected from Optum's de-identified Clinformatics® Data Mart Database (Commercial insurance/Medicare Advantage [COM/MA]; January 1, 2014–July 31, 2019) or Medicare Fee-for-Service (FFS; January 1, 2014–December 31, 2017). The index date was the first metastatic disease diagnosis date on/after the first prostate cancer diagnosis (without prior evidence of castration resistance). Patients were observed for 12 months pre-index (baseline) through their mCSPC period (from index until castration resistance or followup end). First-line (1L) mCSPC therapy was assessed during the mCSPC period; all-cause HRU and health plan-paid costs per-patient-per-year (PPPY) were measured during baseline and mCSPC periods. Results: Among 6,517 COM/MA and 13,324 Medicare-FFS mCSPC patients over ∼10 months (median mCSPC period), 38% and 48% remained untreated/deferred treatment, and 45% and 46% received 1L androgen deprivation therapy (ADT) monotherapy, respectively. 1L abiraterone acetate and docetaxel were used among 7% and 6% of COM/MA and 1% and 2% of Medicare-FFS patients, respectively. HRU increased from baseline to mCSPC period, resulting in increased health plan-paid costs from $21,201 to $108,767 in COM/MA and from $16,819 to $69,639 PPPY in Medicare-FFS. Conclusions: This study highlights the limited use of newer therapies that improve survival in men with mCSPC in the U.S. HRU and costs increased substantially after onset of metastasis. Given the emergence of newer effective mCSPC therapies, further evaluation of future real-world mCSPC treatment patterns and outcomes is warranted.

Objectives To compare the efficacy and safety of algenpantucel-L (HAPa; IND# 12311) immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC). Summary background data To date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene. Methods A multicenter, phase 3, open label, randomized (1:1) trial of patients with borderline resectable or locally advanced unresectable PDAC. Patients received neoadjuvant SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) followed by chemoradiation (standard group) or the same standard neoadjuvant regimen combined with HAPa immunotherapy (experimental group). The primary outcome was overall survival. Results Between May 2013 and December 2015, 303 patients were randomized from 32 sites. Median (IQR) overall survival was 14.9 (12.2-17.8) months in the standard group (N=158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) (hazard ratio [HR] 1.02, 95% CI 0.66-1.58; P = 0.98). Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% CI 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05). Conclusions Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation. Trial registration ClinicalTrials.gov Identifier: NCT01836432.

Background & aims Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. Aims evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria. Methods Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n = 48) or placebo (n = 46) for 6 months (double-blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open-label extension (continuous givosiran, n = 47/48; placebo crossover, n = 46/46). Endpoints included annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events. Results Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double-blind period, 0.0 in open-label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double-blind period) and 0.0 (open-label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long-term givosiran led to sustained lowering of delta-aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double-blind period. Conclusions Long-term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life.

Background Patient surveillance using repeated biomarker measurements presents an opportunity to detect and treat disease progression early. Frequent surveillance testing using biomarkers is recommended and routinely conducted in several diseases, including cancer and diabetes. However, frequent testing involves tradeoffs. Although surveillance tests provide information about current disease status, the complications and costs of frequent tests may not be justified for patients who are at low risk of progression. Predictions based on patients’ earlier biomarker values may be used to inform decision making; however, predictions are uncertain, leading to decision uncertainty. Methods We propose the Personalized Risk-Adaptive Surveillance (PRAISE) framework, a novel method for embedding predictions into a value-of-information (VOI) framework to account for the cost of uncertainty over time and determine the time point at which collection of biomarker data would be most valuable. The proposed sequential decision-making framework is innovative in that it leverages the patient’s longitudinal history, considers individual benefits and harms, and allows for dynamic tailoring of surveillance intervals by considering the uncertainty in current information and estimating the probability that new information may change treatment decisions, as well as the impact of this change on patient outcomes. Results When applied to data from cystic fibrosis patients, PRAISE lowers costs by allowing some patients to skip a visit, compared to an “always test” strategy. It does so without compromising expected survival, by recommending less frequent testing among those who are unlikely to be treated at the skipped time point. Conclusions A VOI-based approach to patient monitoring is feasible and could be applied to several diseases to develop more cost-effective and personalized strategies for ongoing patient care. Highlights In many patient-monitoring settings, the complications and costs of frequent tests are not justified for patients who are at low risk of disease progression. Predictions based on patient history may be used to individualize the timing of patient visits based on evolving risk. We propose Personalized Risk-Adaptive Surveillance (PRAISE), a novel method for personalizing the timing of surveillance testing, where prediction modeling projects the disease trajectory and a value-of-information (VOI)–based pragmatic decision-theoretic framework quantifies patient- and time-specific benefit-harm tradeoffs. A VOI-based approach to patient monitoring could be applied to several diseases to develop more personalized and cost-effective strategies for ongoing patient care.

Background Exercise may improve clinical and quality of life outcomes for men with prostate cancer. No randomized controlled trials (RCTs) have examined the feasibility, safety, and acceptability of remote exercise training in men with metastatic castrate‐resistant prostate cancer (mCRPC). Methods We conducted a pilot RCT (1:1:1 aerobic or resistance exercise 3x/week or usual care) to determine the feasibility, safety, and acceptability of remotely monitored exercise over 12 weeks in 25 men with mCRPC. A prescribed exercise program was based on baseline testing including high‐ and moderate‐intensity aerobic exercise or resistance exercise completed at a local exercise facility. Feasibility was based on attendance, adherence, and tolerance; safety on adverse events; and acceptability on participant interviews. Results Between March 2016 and March 2020, 25 patients were randomized (8 aerobic, 7 resistance, and 10 control). Twenty‐three men (82%) completed the 12‐week study. Men who completed the remote intervention attempted 90% and 96% of prescribed aerobic and resistance training sessions, respectively, and 86% and 88% of attempted sessions were completed as or more than prescribed. We observed changes in performance tests that corresponded with the exercise prescription. No safety concerns were identified. Ninety percent of participants interviewed were satisfied with the program and would recommend it to others. Conclusions Remotely monitored exercise training is feasible, safe, and acceptable in men with mCRPC; there was no difference in these outcomes by mode of exercise. Through this research, we provide direction and rationale for future studies of exercise and clinical outcomes in patients with metastatic prostate cancer., We conducted a 3‐arm pilot randomized controlled trial to determine the feasibility, safety, and acceptability of two modes of remotely monitored exercise (resistance or aerobic) over 12 weeks compared to usual care in 25 men with metastatic castrate‐resistant prostate cancer (mCRPC). We report that remotely monitored exercise training is feasible, safe, and acceptable in this patient population, with a high satisfaction rate. Through this research we provide direction and rationale for future studies of exercise and clinical outcomes for people with metastatic cancer.

Background Most previous studies support a direct link between total parasite load and the clinical severity of Plasmodium falciparum malaria infections. Methods We estimated P. falciparum parasite loads in 3 groups of children with malaria infections of differing severity: (1) children with World Health Organization–defined severe malaria (n = 1544), (2) children admitted with malaria but without features of severity (n = 200), and (3) children in the community with asymptomatic parasitemia (n = 33). Results Peripheral parasitemias were highest in those with uncomplicated malaria (geometric mean [GM] parasite count, 111 064/μL; 95% confidence interval, CI, 86 798–141 819/μL), almost 3 times higher than in those with severe malaria (39 588/μL; 34 990–44 791/μL) and >100 times higher than in those with asymptomatic malaria (1092/μL; 523–2280/μL). However, the GM P. falciparum histidine-rich protein 2 (PfHRP2) values (95% CI) increased with severity, being 7 (4–12) ng/mL in asymptomatic malaria, 843 (655–1084) ng/mL in uncomplicated malaria, and 1369 (1244–1506) ng/mL in severe malaria. PfHRP2 concentrations were markedly lower in the subgroup of patients with severe malaria and concomitant invasive bacterial infections of blood or cerebrospinal fluid (GM concentration, 312 ng/mL; 95% CI, 175–557 ng/mL; P < .001) than in those without such infections (1439 ng/mL; 1307–1584; P < .001). Conclusions The clinical severity of malaria infections related strongly to the total burden of P. falciparum parasites. A quantitative test for plasma concentrations of PfHRP2 could be useful in identifying children at the greatest clinical risk and identifying critically ill children in whom malaria is not the primary cause., Through a clinical surveillance study, we show that plasma levels of Plasmodium falciparum histidine-rich protein 2, a marker of total body parasite load, are strongly correlated with the severity of P. falciparum infections among children in Kilifi, Kenya.

This article tests the power transition theory using relative military power within a dyad pair. The author hypothesizes that when a dyad pair achieves relative military power parity, the two states are likely to initiate war. Furthermore, when a dyad pair no longer maintains relative military power parity, the probability of war between the two states decreases. Although the sample population used to test this hypothesis is small (n=3), the mixed-method analysis indicates support to the power transition theory. Furthermore, results are more substantial when using military expenditure and surplus domestic when compared to results using military personnel and surplus domestic product. No statistically significant difference exists (p=.99) when comparing military expenditure and surplus domestic product with a combination of military expenditure, military personnel, and surplus domestic product. These results indicate that relative military power possesses the potential to provide researchers an additional quantitative measure to test the power transition theory. Although these initial results are promising, further research is required to test a larger sample population of dyads.

Perioperative pain management remains an important focus of both patient and provider attention in orthopaedic trauma surgery. There is a constant effort to improve pain management while decreasing opioid consumption, and peripheral nerve blocks are a safe and effective way to achieve these two goals. This is particularly relevant because more procedures are being done in outpatient surgery centers, and the need to safely provide analgesia without the systemic risk of opioid medications is paramount. The primary goal of this article was to describe the diagnosis-based approach for the utilization of preoperative peripheral nerve blocks in perioperative care for orthopaedic trauma surgery procedures based on the experience and current practice at our center.

The Hospital Incident Command System (HICS) is an incident management system specific to hospitals based on the principles of Incident Command System (ICS), and it includes prevention, protection, mitigation, response, and recovery. It plays a crucial role in effective and timely response during the periods of disasters, mass casualties, and public health emergencies. In recent times, hospitals have used a customized HICS structure to coordinate effective responses to public health problems such as the Ebola outbreak in the US and SARS epidemic in Taiwan. The current COVID-19 pandemic has placed unprecedented challenges on the healthcare system, necessitating the creation of HICS that can help in the proper allocation of resources and ineffective utilization of healthcare personnel. The key elements in managing a response to this pandemic include screening and early diagnosis, quarantining affected individuals, monitoring disease progression, delivering appropriate treatment, and ensuring an adequate supply of personal protective equipment (PPE) to healthcare staff.

Background and objectives In a randomized double-blind, placebo-controlled trial, treatment with spironolactone in early-stage CKD reduced left ventricular mass and arterial stiffness compared with placebo. It is not known if these effects were due to BP reduction or specific vascular and myocardial effects of spironolactone. Design, setting, participants, & measurements A prospective, randomized, open-label, blinded end point study conducted in four UK centers (Birmingham, Cambridge, Edinburgh, and London) comparing spironolactone 25 mg to chlorthalidone 25 mg once daily for 40 weeks in 154 participants with nondiabetic stage 2 and 3 CKD (eGFR 30–89 ml/min per 1.73 m2). The primary end point was change in left ventricular mass on cardiac magnetic resonance imaging. Participants were on treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and had controlled BP (target ≤130/80 mm Hg). Results There was no significant difference in left ventricular mass regression; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was −3.8 g (95% confidence interval, −8.1 to 0.5 g, P=0.08). Office and 24-hour ambulatory BPs fell in response to both drugs with no significant differences between treatment. Pulse wave velocity was not significantly different between groups; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was 0.04 m/s (−0.4 m/s, 0.5 m/s, P=0.90). Hyperkalemia (defined ≥5.4 mEq/L) occurred more frequently with spironolactone (12 versus two participants, adjusted relative risk was 5.5, 95% confidence interval, 1.4 to 22.1, P=0.02), but there were no patients with severe hyperkalemia (defined ≥6.5 mEq/L). A decline in eGFR >30% occurred in eight participants treated with chlorthalidone compared with two participants with spironolactone (adjusted relative risk was 0.2, 95% confidence interval, 0.05 to 1.1, P=0.07). Conclusions Spironolactone was not superior to chlorthalidone in reducing left ventricular mass, BP, or arterial stiffness in nondiabetic CKD.

OBJECTIVE The present systematic review and pooled analysis aims to assess the incidence and risk factors for the development of retrograde ejaculation (RE) following first-time open anterior lumbar surgery. METHODS A systematic MEDLINE review via PubMed was performed, identifying 130 clinical papers relating to the topic. Eighteen publications were selected according to predetermined inclusion and exclusion criteria and were used to determine the incidence of RE. Only the publications that provided data on surgical risk factors present specifically in the men in the study were included in the analysis of risk factors. RESULTS Of the 2503 men included, there were 57 reported events of RE (2.3%). Of the cases for which long-term data were provided, 45.8% had resolved by final follow-up. There was a statistically significant increased risk associated with a transperitoneal as opposed to a retroperitoneal approach (8.6% vs 3.2%), as well as with the use of recombinant human bone morphogenetic protein–2 (rhBMP-2) in anterior lumbar interbody fusion (ALIF) as opposed to ALIF with bone graft or arthroplasty in controls (5.0% vs 1.8%). However, when excluding from analysis the patients operated on prior to the FDA’s 2008 warning that commented on the drug’s neuroinflammatory properties, there was no significant difference in rates of RE in patients receiving rhBMP-2 versus the control group (2.4% vs 2.5%). There was no significant difference in risk based on single- versus multilevel procedure or on ALIF versus arthroplasty. CONCLUSIONS In a pooled analysis of currently published data on men undergoing first-time open anterior lumbar surgery, this study found an overall incidence of RE of 2.3%. Nearly half of these patients recovered, reporting resolution of symptoms anywhere between 3 months and 48 months. Analysis of risk factors was limited by a paucity of published literature segregating data by sex. However, there was an increased risk associated with rhBMP-2 only when including data collected prior to the FDA warning on its detrimental properties. The authors therefore posit that the risk of RE is probably overestimated in the literature, given that the vast majority of the data available were collected prior to this warning and given the subsequent implementation of precautions when handling rhBMP-2.

Groundwater dependency is increasing globally, while millions of potentially contaminated sites are yet to be characterized for contamination levels. In particular, groundwater contamination due to light nonaqueous phase liquids (LNAPLs) continues to be a global challenge. Mathematical approaches (i.e., analytical, semi-analytical, empirical, numerical) are preferred for an initial site assessment to circumvent the high characterization costs and limited site data availability. However, the site-specific nature of contamination restricts the generalization of any single approach. Hence, the requirement is for an easy-to-use computing interface that provides site-specific data management, the selection and use of multiple-model interfaces for computing, and site characterization, with extension for the latest models as they become available. This work provides one such interface called CAST or Contamination Assessment and Site-management Tool. CAST is an open-source browser-based (online/offline) tool that provides an interface for six different analytical models (e.g., BIOSCREEN-AT), a MODFLOW based numerical model, and two empirical models (including a hybrid numerical-analytical model). Additionally, CAST includes interfaces for site data management, their evaluation, and scenario-based modeling. CAST's development is in a modular format, which simplifies the addition of new computing or data interfaces. Furthermore, the entire code-base of CAST is based on open-source (dominantly Python programming) libraries and standards. This further simplifies the modification or extension of this tool. This paper introduces CAST, its different computing, and data management interfaces and provides examples of the tool's functionality primarily for the initial evaluation of contaminated sites.

Objectives Ambulatory blood pressure (BP) control is worse in men compared with women with chronic kidney disease (CKD) and this may partially explain the faster CKD progression in men. This is the first study investigating possible sex differences in prevalence, control and phenotypes of hypertension in kidney transplant recipients (KTRs) with office-BP and 24-h ambulatory BP monitoring (ABPM). Methods This cross-sectional study included 136 male and 69 female stable KTRs who underwent office-BP measurements and 24-h ABPM. Hypertension thresholds for office and ambulatory BP were defined according to the 2017 ACC/AHA and 2021 KDIGO guidelines for KTRs. Results Age, time from transplantation, eGFR and history of major comorbidities did not differ between groups. Office SBP/DBP levels were insignificantly higher in men than women (130.3 ± 16.3/77.3 ± 9.4 vs. 126.4 ± 17.8/74.9 ± 11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ± 12.1/83.0 ± 8.2 vs. 124.6 ± 11.9/80.3 ± 9.3 mmHg; P = 0.032/P = 0.044). No significant between-group differences were detected for night-time BP. The prevalence of hypertension was similar by office-BP criteria (93.4 vs. 91.3%; P = 0.589), but higher in men than women with ABPM (100 vs. 95.7%; P = 0.014). The use of ACEIs/ARBs and CCBs was more common in men. Office-BP control was similar (43.3 vs. 44.4%, P = 0.882), but 24-h control was significantly lower in men than women (16.9 vs. 30.3%; P = 0.029). White-coat hypertension was similar (5.1 vs. 7.6%; P = 0.493), whereas masked hypertension was insignificantly more prevalent in men than women (35.3 vs. 24.2%; P = 0.113). Conclusion BP levels, hypertension prevalence and control are similar by office criteria but significantly different by ABPM criteria between male and female KTRs. Worse ambulatory BP control in male compared with female KTRs may interfere with renal and cardiovascular outcomes.

Androgen deprivation therapy remains the backbone therapy for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). In recent years, several treatments, including docetaxel, abiraterone + prednisone, enzalutamide, and apalutamide, have each been shown to demonstrate survival benefit when used upfront along with androgen deprivation therapy. However, treatment selection for an individual patient remains a challenge. There is no high level clinical evidence for treatment selection among these choices based on biological drivers of clinical disease. In August 2020, the Prostate Cancer Foundation convened a working group to meet and discuss biomarkers for hormone-sensitive prostate cancer, the proceedings of which are summarized here. This meeting covered the state of clinical and biological evidence for systemic therapies in the mHSPC space, with emphasis on charting a course for the generation, interrogation, and clinical implementation of biomarkers for treatment selection.

Background Children are important in community‐level influenza transmission. School‐based monitoring may inform influenza surveillance. Methods We used reported weekly confirmed influenza in Allegheny County during the 2007 and 2010‐2015 influenza seasons using Pennsylvania's Allegheny County Health Department all‐age influenza cases from health facilities, and all‐cause and influenza‐like illness (ILI)‐specific absences from nine county school districts. Negative binomial regression predicted influenza cases using all‐cause and illness‐specific absence rates, calendar week, average weekly temperature, and relative humidity, using four cross‐validations. Results School districts reported 2 184 220 all‐cause absences (2010‐2015). Three one‐season studies reported 19 577 all‐cause and 3012 ILI‐related absences (2007, 2012, 2015). Over seven seasons, 11 946 confirmed influenza cases were reported. Absences improved seasonal model fits and predictions. Multivariate models using elementary school absences outperformed middle and high school models (relative mean absolute error (relMAE) = 0.94, 0.98, 0.99). K‐5 grade‐specific absence models had lowest mean absolute errors (MAE) in cross‐validations. ILI‐specific absences performed marginally better than all‐cause absences in two years, adjusting for other covariates, but markedly worse one year. Conclusions Our findings suggest seasonal models including K‐5th grade absences predict all‐age‐confirmed influenza and may serve as a useful surveillance tool.

Online sources of health information are a significant means by which the public educates itself about health and wellness. The purpose of this study is to investigate how undergraduate students evaluate and assess health-related websites for accuracy, as well as the self-reported factors used in identifying whether a website is an accurate source of information. One hundred and fifty-seven students participated by reviewing a series of 10 health-related websites and indicated whether they believed the website to be an accurate source of health information. Students completed an open-ended question to self-report how they made this determination. Results indicate that students were not able to accurately distinguish between credible sources of web-based health information and those sources that were previously categorized as not being credible sources. Analysis of self-reported qualitative feedback gave rise to 6 factors used to determine the accuracy of the websites reviewed. While students report using these factors, and these factors are consistent with previous research, this does not appear then to be translating to successful determination of a source’s accuracy. Educating students in proper fact-checking and evaluation skills may be warranted to develop a generation of individuals who can be said to have better health literacy.

In a powder diffraction experiment the resolution function defines the instrumental contribution to the peak widths as a function of the Bragg angle. The Caglioti formula is frequently applied to model the instrumental broadening and used in structural refinement. The parameters in the Caglioti formula are linked to physically meaningful parameters for most diffraction geometries. However, this link is lost for the now very popular powder diffraction geometry using large 2D area detectors. Here we suggest a new physical model for the instrumental broadening specifically developed for powder diffraction data measured with large 2D area detectors. The model is verified using data from two synchrotron diffraction beamlines with the Pilatus2M and MAR345 detectors. Finally, a functional form is proposed to replace the Caglioti formula for this geometry in the Rietveld method and profile refinements.

Introduction Coronavirus disease 2019 (COVID‐19) adversely affects patients who are older, multimorbid, and from Black, Asian or minority ethnicities (BAME). We assessed whether being from BAME is independently associated with mortality in end‐stage kidney disease (ESKD) patients with COVID‐19. Methods Prospective observational study in a single UK renal center. A study was conducted between March 10, 2020 and April 30, 2020. Demographics, socioeconomic deprivation (index of multiple deprivation), co‐morbidities (Charlson comorbidity index [CCI]), and frailty data (clinical frailty score) were collected. The primary outcome was all‐cause mortality. Data were censored on the 1st June 2020. Findings Overall, 191 of our 3379 ESKD patients contracted COVID‐19 in the 8‐week observation period; 84% hemodialysis, 5% peritoneal dialysis, and 11% kidney transplant recipients (KTR). Of these, 57% were male and 67% were from BAME groups (43% Asian, 17% Black, 2% mixed race, and 5% other). Mean CCI was 7.45 (SD 2.11) and 3.90 (SD 2.10) for dialysis patients and KTR, respectively. In our cohort, 60% of patients lived in areas classified as being in the most deprived 20% in the United Kingdom, and of these, 77% of patients were from BAME groups. The case fatality rate was 29%. Multivariable cox regression demonstrated that BAME (hazard ratio [HR]: 2.37, 95% CI: 1.22–4.61) was associated with all‐cause mortality after adjustment for age, deprivation, co‐morbidities, and frailty. Associations with all‐cause mortality persisted in sensitivity analyses in patients from South Asian (HR: 2.52, 95% CI: 1.24–5.12) and Black (HR: 2.43, 95% CI: 1.04–5.67) ethnic backgrounds. Discussion BAME ESKD patients with COVID‐19 are just over twice as likely to die compared to White patients, despite adjustment for age, deprivation, comorbidity, and frailty. This study highlights the need to develop strategies to improve BAME patient outcomes in future outbreaks of COVID‐19.

BackgroundOur study examined whether the early-onset depression phenotype among young adults (probands) is associated with the metabolic syndrome (MetS) and its components, and if MetS characterizes unaffected but high-risk siblings of probands.MethodsWe studied three groups of young adults (Mage = 25 years, s.d. = 3.84 years): probands with histories of childhood onset depression – i.e. early-onset phenotype – (n = 293), their unaffected siblings (high-risk siblings, n = 273), and healthy controls (n = 171). Participants completed a full psychiatric interview, physical and laboratory assessments, and self-rating scales. MetS was defined using the criteria of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001).ResultsEarly-onset depression phenotype and being a high-risk sibling were associated with higher MetS composite scores relative to that of controls, but did not differ from one another. With regard to MetS components: Probands and siblings had similarly larger waist circumference and lower HDL than did controls, while siblings and controls had lower triglyceride levels than did probands but did not differ from one another. Groups did not differ on glucose levels and SBP.ConclusionsOur study extends the literature on the association between MetS and depression and underscores the importance of depression phenotypes: failure to account for the clinical heterogeneity of depression may partly underlie the inconsistent findings regarding its relation to MetS. The results also suggest that, in depression-prone populations, MetS may predate and possibly function as a risk factor for eventual depression.

International audience; Hypertension is common in kidney transplantation recipients and may be difficult to treat. Factors present before kidney transplantation, related to the transplantation procedure itself and factors developing after transplantation may contribute to blood pressure (BP) elevation in kidney transplant recipients. The present consensus is based on the results of three recent systematic reviews, the latest guidelines and the current literature. The current transplant guidelines, which recommend only office BP assessments for risk stratification in kidney transplant patients should be reconsidered, given the presence of white-coat hypertension and masked hypertension in this population and the better prediction of adverse outcomes by 24-h ambulatory BP monitoring as indicated in recent systematic reviews. Hypertension is associated with adverse kidney and cardiovascular outcomes and decreased survival in kidney transplant recipients. Current evidence suggests calcium channel blockers could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss, whereas no clear benefit is documented for renin-angiotensin system inhibitor use over conventional treatment in the current literature. Randomized control trials demonstrating the clinical benefits of BP lowering on kidney and major cardiovascular events and recording patient-related outcomes are still needed. These trials should define optimal BP targets for kidney transplant recipients. In the absence of kidney transplant-specific evidence, BP targets in kidney transplant recipients should be similar to those in the wider chronic kidney disease population.

Objectives The goal of this study was to test whether continuous automatic remote patient monitoring (RPM) linked to centralized analytics reduces nonactionable in-person patient evaluatio...

Major pelvic hemorrhage remains a considerable challenge of modern trauma care associated with mortality in over a third of patients. Efforts to improve outcomes demand continued research into the optimal employment of both traditional and newer hemostatic adjuncts across the full spectrum of emergent care environments. The purpose of this review is to provide a concise description of the rationale for and effective use of currently available adjuncts for the control of pelvic hemorrhage. In addition, the challenges of defining the optimal order and algorithm for employment of these adjuncts will be outlined. LEVEL OF EVIDENCE Review, level IV.

Drug Metabolism Reviews has an impressive track record of providing scientific reviews in the area of xenobiotic biotransformation over 47 years. It has consistently proved to be resourceful to many scientists from pharmaceutical industry, academia, regulatory agencies working in diverse areas including enzymology, pharmacology, pharmacokinetics, and toxicology. Over the last 5 years Drug metabolism Reviews has annually published an industry commentary aimed to highlight novel insights and approaches that have made significant impacts on the field of biotransformation (led by Cyrus Khojasteh). We hope to continue this tradition by providing an overview of advances made in the field of drug transporters during 2020. The field of drug transporters is rapidly evolving as they play an essential role in drug absorption, distribution, clearance, and elimination. In this review, we have selected outstanding drug transporter articles that have significantly contributed to moving forward the field of transporter science with respect to translation and improved understanding of diverse aspects including uptake clearance, clinical biomarkers, induction, proteomics, emerging transporters, and tissue targeting. The theme of this review consists of a synopsis that summarizes each article followed by our commentary. The objective of this work is not to provide a comprehensive review but rather to exemplify novel insights and state-of-the-art highlights of recent research that have advanced our understanding of drug transporters in drug disposition. We are hopeful that this effort will prove useful to the scientific community and as such request feedback, and further extend an invitation to anyone interested in contributing to future reviews.

The development and early morphological features of feline hip osteoarthritis (OA) are largely unknown. Tears in the acetabular labrum and at the chondrolabral transition zone are suggested to be important in the pathogenesis of human hip OA, but in cats such lesions have not been described. We investigated associations between computed tomography (CT)-detected joint changes and microscopic articular cartilage lesions, the distribution of detected changes, and histologically evaluated the acetabular margin (AM) in hip joints from 20 cats. Histologic evaluation was undertaken on at least one joint from each cat. CT-detected joint changes and articular cartilage lesions were graded and the histological appearance of CT-detected osteophytes evaluated. The majority of CT-detected lesions and cartilage lesions were mild. Whole-joint CT scores and AM osteophyte CT scores showed moderate to strong correlation with cartilage scores. The odds were higher for presence of CT-detected osteophytes in craniodorsal, cranial, cranioventral, ventral and dorsal AM regions. Peripheral acetabular regions showed higher cartilage lesion grades than central regions. Tears, seen as fissures/clefts, in labral and perilabral tissues were common. CT-detected AM osteophytes morphologically presented as pointed sclerotic bone, spur-shaped bone or rounded chondro-osteophytes. The results suggest that CT is a valuable tool for diagnosing early feline hip OA. CT-detected osteophytes showed variable histologic morphologies, which may implicate different disease mechanisms and/or disease stages. Tears in the AM could represent an early event in feline hip OA and this warrants further investigation.

A novel buprenorphine (BUP) extended-release formulation (BUP-XR) produced as a lipid-encapsulated, low viscosity BUP suspension for SC injection to control pain was evaluated for pharmacokinetics and safety in Sprague–Dawley rats given either 0.65 mg/kg (low dose) or 1.30 mg/kg (high dose). The 2 dosage groups each contained 6 male and 6 female rats to determine whether BUP-XR behaved differently in male or female animals. Blood samples were obtained from each animal before BUP-XR administration and at 6, 24, 48, 72, 96, and 168 h after administration. For necropsy and injection-site histopathology evaluation, 3 animals of each sex from each test group were euthanized on day 8, with the remaining animals euthanized on day 15. Mean plasma BUP concentration peaked from 6 to 24 h in all test groups, then declined in a linear fashion. Quantifiable plasma BUP was measured in all male rats at all time points except for one low dose group sample taken at 168 h. Female rats had quantifiable plasma BUP at all time points except for 1 low dose group sample at 72 and 96 h, and 2 low dose group samples at 168 h. The low dose groups, whether male or female, had lower mean plasma BUP levels at all time points as compared with their high dose counterparts, and female rats had lower mean plasma BUP levels than male rats at all time points. Results indicate that a single BUP-XR dose at either dose concentration can reliably provide plasma levels of BUP reported in the literature to be therapeutically relevant for up to 72 h, although lower plasma BUP levels can be anticipated in female rats compared with male counterparts. Mild to moderate injection-site granulomatous inflammation was observed in 6 of 12 rats in the low dose group and 7 of 12 in the high dose group. This reaction is characteristic of lipid material designed to persist in situ.

Background Few studies have evaluated the effect of hepatitis C (HCV) on primary total shoulder arthroplasty (TSA). Our purpose was to determine if HCV infection is associated with increased complication rates after TSA in United States (US) veterans and, secondarily, to determine if preoperative HCV treatment with direct-acting antivirals (DAAs) affects postoperative complication rates. Methods US Department of Veterans Affairs (VA) data sets were used to retrospectively identify patients without HCV, patients with untreated HCV, and patients with HCV treated with DAAs who underwent TSA from 2014 to 2019. Medical and surgical complications were assessed using International Classification of Diseases codes. Complication rates between patients with HCV (treated and untreated) and patients without HCV and between HCV-treated patients and HCV-untreated patients were compared at 90 days and 1 year after surgery. Results We identified 5774 primary TSAs that were performed at VA hospitals between 2014 and 2019. A minority (9.5%) of TSA patients had HCV, 23.4% of whom were treated preoperatively with DAAs. On multivariate analysis, HCV patients had increased odds of 1-year medical complications (odds ratio, 1.39; 95% confidence interval, 1.06-1.81, P = .016), when compared with patients without HCV. No statistically significant difference in complication rates was observed between HCV-treated and HCV-untreated patients. Discussion US veterans with a history of HCV are at an increased risk of developing medical but not surgical complications within the first year after TSA. Larger studies are necessary to evaluate the effects of DAA treatment on complication rates.

OBJECTIVES Hypertension is highly prevalent and independently associated with adverse outcomes in patients undergoing hemodialysis. Volume overload is the main mechanism of increased blood pressure (BP) in these individuals. This study examines the long-term effects of dry-weight reduction with a standardized lung-ultrasound (US)-guided strategy on ambulatory BP in hypertensive hemodialysis patients. METHODS This is the report of the 12-month follow-up of a randomized controlled trial in 71 clinically euvolemic, hemodialysis patients with hypertension. Patients were randomized to dry-weight reduction guided by prehemodialysis lung ultrasound and to standard care. A 48-h ambulatory BP monitoring (ABPM) was performed in all study participants at baseline and after 12 months. RESULTS During follow-up, a greater proportion of patients in the active group underwent dry-weight reduction compared with the control group (71.4% vs. 22.2%; P

Screening for occult coronary artery disease in potential kidney transplant recipients has become entrenched in current medical practice as the standard of care and is supported by national and international clinical guidelines. However, there is increasing and robust evidence that such an approach is out-dated, scientifically and conceptually flawed, ineffective, potentially directly harmful, discriminates against ethnic minorities and patients from more deprived socioeconomic backgrounds, and unfairly denies many patients access to potentially lifesaving and life-enhancing transplantation. Herein we review the available evidence in the light of recently published randomized controlled trials and major observational studies. We propose ways of moving the field forward to the overall benefit of patients with advanced kidney disease.

Background As right colon polyps are challenging to detect, a retroflexed view of right colon (RV) may be useful. However, cecal retroflexion (CR) without a RV to the hepatic flexure (HF) is inadequate. We aimed to determine the frequency of CR and quality of the RV in routine practice. Methods This prospective observational study performed at an academic medical center assessed colonoscopy inspection technique of endoscopists who had performed ≥ 100 annual screening colonoscopies. We video recorded ≥ 28 screening/surveillance colonoscopies per endoscopist and randomly evaluated 7 videos per endoscopist. Six gastroenterologists blindly reviewed the videos to determine if CR was performed and HF withdrawal time (cecum to HF time, excluding ileal/polypectomy time). Results Reviewers assessed 119 colonoscopies performed by 17 endoscopists. The median HF withdrawal time was 3 min and 46 s. CR was performed in 31% of colonoscopies. CR frequency varied between endoscopists with 9 never performing CR and 2 performing CR in all colonoscopies. When performed, nearly half (43%) of RVs did not extend to the HF with median RV duration of 16 s (IQR 9–30 s). Three polyps were identified in the RV (polyp detection rate of 8.1%), all identified prior to a forward view. Conclusions CR is performed infrequently in routine practice. When CR is performed, the RV is of low quality with a very short inspection duration and insufficient ascending colon examination. Further education is required to educate endoscopists in optimal technique to improve overall colonoscopy quality.

Wearable electronic devices are a convenient solution to pain intensity assessment as they can provide continuous monitoring for more precise medication adjustments. However, there is little evidence regarding the use of wearable electronic devices for chronic pain intensity assessment. Our primary objective was to examine the physiologic parameters used by wearable electronic devices for chronic pain intensity assessment. We initially inquired PubMed, CINAHL, and Embase for studies evaluating the use of wearable electronic devices for chronic pain intensity assessment. We updated our inquiry by searching on PubMed, Embase, Scopus, and Google Scholar. English peer-reviewed studies were included, with no exclusions based on time frame or publication status. Of 348 articles that were identified on the first inquiry, 8 fulfilled the eligibility criteria. Of 179 articles that were identified on the last inquiry, only 1 fulfilled the eligibility criteria. We found articles evaluating wristbands, smartwatches, and belts. Parameters evaluated were psychomotor and sleep patterns, space and time mobility, heart rate variability, and skeletal muscle electrical activity. Most of the studies found significant positive associations between physiological parameters measured by wearable electronic devices and self-reporting pain scales. Wearable electronic devices reliably reflect physiologic or biometric parameters, providing a physiological correlation for pain. Early stage investigation suggests that the degree of pain intensity can be discerned, which ideally will reduce the bias inherent to existing numeric/verbal scales. Further research on the use of these devices is vital.

Cardiac surgeries are known to produce moderate to severe pain. Pain management has traditionally been based on intravenous opioids. Poorly controlled pain can result in increased incidence of respiratory complications such as atelectasis and pneumonia leading to prolonged intubation and intensive care unit length of stay and subsequent prolonged hospital stay. Adequate perioperative analgesia improves hemodynamics and immunologic responses, which would result in better outcomes after cardiac surgery. Opioid sparing “Enhanced Recovery After Surgery” protocols are increasingly being incorporated into cardiac surgeries. This will reduce opioid requirements and opioid-related side effects and facilitate fast-tracking of patients. Regional analgesia can be provided by neuraxial blocks, fascial plane blocks, peripheral nerve blocks, or simply by the infiltration of the wound with local anesthetics for cardiac surgery. Neuraxial analgesia is provided through epidural, spinal, and paravertebral routes. Though they are being replaced by peripheral fascial plane blocks, epidural and spinal analgesia are still being used in some centers. In this article, neuraxial forms of analgesia are focused. We sought to review epidural analgesia and its impact in suppressing hemodynamic stress response, reducing pulmonary complications, and development of chronic pain. The relationship between intraoperative heparinization and potential neuraxial hematoma is discussed. Other neuraxial options such as spinal and paravertebral analgesia and their usefulness, benefits, and limitations are also reviewed.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the preferred method for diagnosing pancreatic masses. While the diagnostic success of EUS-FNA is widely accepted, the actual performance of EUS-FNA is not known. This study sought to define the EUS-FNA accuracy compared with the gold standard, surgically resected specimens. The study was a single institution, retrospective, and chart review of patients with surgically resected pancreatic specimens from 2005 to 2015 with a preoperative EUS-FNA or biliary brushing. Cytological reports were organized from least concerning (i.e., low chance of malignancy) to most concerning (high chance of malignancy) into eight cytologic categories. We identified 741 cytologic cases: 530 EUS-FNA and 211 endoscopic brushings. For EUS-FNA samples, 62.5% of "benign" samples proved to be "benign" on surgical pathology. A cytologic diagnosis of "suspicious for malignancy" or "positive for malignancy" were concordant with a cancer diagnosis on surgical pathology 93.3% and 98.0% of cases, respectively. EUS-FNA proved to be highly reliable at diagnosing malignancy for cytologic samples that were "suspicious" or "positive" for malignancy. Paired with supportive clinical data, these interpretations may be used to justify cancer treatment.

BACKGROUND Resuscitative endovascular occlusion of the aorta (REBOA) is used for temporary aortic occlusion of trauma patients in the management of noncompressible hemorrhage. Previous studies have focused on how to properly perform REBOA in the trauma environment to improve survival rates, but high-grade evidence defining the ideal patient population does not yet exist. This post hoc analysis of the Emergent Truncal Hemorrhage Control Study seeks to identify the most important clinical factors for physicians to consider when selecting for REBOA candidates and their potential survival following REBOA. METHODS Post hoc analysis of a large, multicenter, prospective observational study conducted at six level 1 trauma centers, 2017 to 2018, was performed. An onsite data collector documented all time points for REBOA patients since admission. Candidate predictors were demographics; injury severity; physiology preprocedure, during procedure, and postprocedure; cardiopulmonary resuscitation; and REBOA-specific variables (time to procedure, procedure-related time intervals, access site, technique, sheath size, catheter length, balloon volume, deployment zone). Predictive models for survival at three different time points along the trauma triage and REBOA process timeline ("Admission," "REBOA Initiation," and "Postaortic Occlusion") were devised by logistic regression. RESULTS Eighty-eight patients had REBOA placement. The Admission model selected age, Glasgow Coma Scale, and admission systolic blood pressure as significant predictors of survival (area under the receiver operating characteristic curve [AUROC], 0.86; 95% CI, 0.77-0.94). The REBOA Initiation and Postaortic Occlusion models selected age, Glasgow Coma Scale, and the systolic blood pressure measured just before balloon inflation as predictors for survival (AUROC, 0.87 [95% CI, 0.78-0.97] and AUROC, 0.90 [95% CI, 0.81-0.99], respectively). No REBOA procedural variables were identified as predictors of patient survival. CONCLUSION Only patient-specific criteria of age, neurologic status, and severity of shock predicted survival. The hemodynamic stability of the patient at the time REBOA is initiated is more important than how REBOA is initiated. These findings suggest that earlier preparation for REBOA placement may be a key to improved survival. LEVEL OF EVIDENCE Therapeutic, level IV.

This review discusses impact of advancements in biologic understanding of prostate cancer (PCa) on definition and diagnosis of castration-resistant PCa (CRPC), predictive factors for progression to CRPC and treatment strategies. More sensitive assays confirm that bilateral orchiectomy reduces serum testosterone (T) closer to 20 ng/dL than 50 ng/dL, and evidence suggests that achieving T 20 ng/dL improves outcomes and delays CRPC emergence. Regular T assessments will evaluate whether T is adequately suppressed in the setting of potential progression to CRPC, given that late dosing may result in T escape. More advanced imaging modalities and biomarker assays allow earlier detection of disease progression. Predictive factors for progression to CRPC include Gleason grade, extent of metastatic spread, germline hereditary factors such as gene mutations affecting androgen receptor amplification or DNA repair deficiency mutations, prostate-specific antigen kinetics, and biomarker analyses. Treatment options for CRPC have expanded beyond androgen deprivation therapy to include therapies that suppress T or inhibit its activity through varying mechanisms. Future directions include therapies with novel biological targets, drug combinations and personalized treatments. Advanced PCa management aims to delay progression to CRPC and prolong survival. With redefinition of castration and advancements in understanding of the biology of disease progression, diagnosis and treatment strategies should be re-evaluated. Definition of CRPC could be updated to reflect the T 20 ng/dL requirement as this is a 'true' castrate level and may improve outcomes. It is important that androgen deprivation therapy as foundational therapy is continued even as new CRPC therapies are introduced.

Background Genetic screening and testing has only recently become an accessible assessment for genetic risk. Unfortunately, these technologies have been underutilized in minority populations despite their usefulness for predicting diseases like sickle cell disease (SCD), often found in African American and Black and Hispanic populations. We surveyed prenatal patients to understand current choices, beliefs and experiences surrounding genetic screening and testing, specifically for sickle cell disease. Methods In this cross-sectional survey, we collected information from 322 women during prenatal visits from July 2019 through May 2021. Responses to questions about pregnancy screening and testing practices were analyzed for trends to identify barriers to care and education about testing and screening for sickle cell disease. Patients were asked to rate whether they agree or disagree with statements regarding sickle cell health behaviors. We used χ2 tests to compare categorical variables by self-reported race. Binary logistic regression was used to determine the odds ratios and confidence intervals for each outcome. Results Women were a mean (SD) age of 33.3 (6.1). 42.9% of patients self-identified as White while 41.3 of patients self- identified as African American/Black. Screening questions were adjusted for differences in race, insurance, and education levels to show significant differences in responses between African Americans/Blacks and Whites for screening for SCD (p=0.047, OR 95% CI= 0.455 [0.210-0.989]) and plans to meet with genetic counselors (p=0.049, OR 95% CI = 0.299 [0.090-0.993]). Regarding sickle cell health behaviors, only the responses to the statements about if sickle cell is not in their family, then it is likely not in themselves or their children, and partners' opinions about genetic screening remained significant (p=0.011 and p=0.081, respectively). Conclusions Our findings suggest gaps in screening, testing, and educational efforts between African American/Black and White patients, as well as differences in opinions regarding pregnancy management with a family history or gestational diagnosis of sickle cell disease. Future research should focus on decreasing these healthcare gaps and improving education that address concerns about SCD for relevant populations.

Recent efforts to quantify biogeochemical and ecological processes in oyster habitats have focused on provision of habitat and regulation of the nitrogen cycle. However, it is unclear how these two processes may interact. In this study, seasonal patterns of habitat use and nitrogen removal from natural oyster beds were quantified for comparison with nearby bare sediment in Green Hill Pond, a temperate coastal lagoon in Rhode Island USA. Relationships were tested between benthic macrofaunal abundance and nitrogen removal via denitrification and burial in sediments. Nitrogen removal by oyster bio-assimilation was quantified and compared with nearby oyster aquaculture. Despite limited differences in habitat use by macrofauna, there were fewer non-oyster benthic organisms (e.g., filter-feeders, detritivores) where oysters were present, possibly due to competition for resources. Additionally, low rugosity of the native oyster beds provided little refuge value for prey. There was a shift from net N removal via denitrification in bare sediments to nitrogen fixation beneath oysters, though this change was not statistically significant (t((96)) = 1.201; p = 0.233). Sediments contained low concentrations of N, however sediments beneath oysters contained almost twice as much N (0.07%) as bare sediments (0.04%; p < 0.001). There was no difference in tissue N content between wild oysters and those raised in aquaculture nearby, though caged oysters had more tissue per shell mass and length, and therefore removed more N on a shell length basis. These oyster beds lacked the complex structure of 3-dimensional oyster reefs which may have diminished their ability to provide habitat for refugia, foraging sites for macrofauna, and conditions known to stimulate denitrification.

Despite the implementation of mitigation measures, Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading worldwide, and has caused more than 1 million deaths so far. Although recent reports indicate that three vaccine candidates are effective against SARS-CoV-2, more time is needed to generate enough doses for the general population. Meanwhile, frontline healthcare workers are at high risk of SARS-CoV-2 exposure. To avoid collapse of the medical care system, there is a need to develop novel approaches to limit SARS-CoV-2 spread. Through a process called trained immunity, the Bacillus Calmette-Guerin (BCG) vaccine boosts the action of innate immune cells, resulting in a nonspecific reduction in the incidence of viral infections. Due to this immunomodulatory action, the BCG vaccine is currently used as a therapeutic in bladder cancer. Data collected from epidemiological and observational studies indicate that BCG vaccination might provide protection against COVID-19. While these observations do not provide evidence of causality and are limited by cofounding and intrinsic biases, it is crucial to explore the hypothesis that BCG vaccination may provide a nonspecific innate immune boost and therefore protect against COVID-19 in randomized controlled clinical trials, particularly for people at higher risk of developing COVID-19, such as frontline healthcare workers.

Introduction The Brain Injury Guidelines (BIG) direct surgeons to implement risk-stratified treatment plans for patients with traumatic brain injury (TBI). BIG categorize patients into one of three severity categories, from lowest to highest risk (BIG 1, BIG 2, and BIG 3). BIG empowers physicians to implement standardized treatment plans that limit unnecessary hospitalizations, repeat imaging, and neurosurgical consultation. These guidelines have been studied in Level I trauma centers, but their clinical application has never been studied in a Level III trauma center. In this pilot study, we sought to determine if the BIG can be implemented in a regional trauma center where patients with less severe brain injuries are locally evaluated and treated. Methods All TBI patients at a Level III trauma center were stratified using the BIG criteria, where BIG 1 and BIG 2 patients were managed locally and BIG 3 patients were transferred to a Level I trauma center. We conducted a retrospective review using the local trauma database and electronic medical records over a 1-year period when BIG were first protocolized. The primary endpoint included deaths, complications, readmissions, and length of stay. Results There were 6 (12.2%) BIG 1, 5 (10.2%) BIG 2, and 38 (77.6%) BIG 3 patients evaluated at the Level III trauma center. All BIG 1 and BIG 2 patients remained at the Level III trauma center, and 33 of the 38 BIG 3 patients were transferred. There were no complications, readmissions, or unexpected transfers within the BIG 1 or BIG 2 patient cohorts. Conclusion The BIG criteria can be successfully implemented in a Level III trauma center. A collaborative transfer agreement with a Level I trauma center reduces unnecessary transfers without negatively affecting patient care. The BIG criteria should be considered for well-developed regional trauma systems.

Diabetic kidney disease develops in about 40% of patients with diabetes and is the commonest cause of chronic kidney disease worldwide. Patients with chronic kidney disease, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular death. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with diabetic kidney disease dates back to studies that are now 20 or more years old. During the last few years sodium-glucose co-transporter-2 inhibitors have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with renin-angiotensin system blockers and sodium-glucose co-transporter-2 inhibitors, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of cardiovascular death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists reduce albuminuria and surrogate markers of cardiovascular disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In The FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease (FIDELIO-DKD) study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of diabetic kidney disease and the incidence of cardiovascular events with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of mineralocorticoid receptor antagonists, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic chronic kidney disease. Sin financiación 7.186 JCR (2021) Q1, 3/25 Transplantation 1.536 SJR (2021) Q1, 219/2489 Medicine (miscellaneous) No data IDR 2021 UEM

Background Coronary microvascular dysfunction (CMD) is common in end-stage renal disease (ESRD) and is an adverse prognostic marker. Coronary flow velocity reserve (CFVR) is a measure of coronary microvascular function and can be assessed using Doppler echocardiography. Reduced CFVR in ESRD has been attributed to factors such as diabetes, hypertension and left ventricular hypertrophy. The contributory role of other mediators important in the development of cardiovascular disease in ESRD has not been studied. The aim of this study was to examine the prevalence of CMD in a cohort of kidney transplant candidates and to look for associations of CMD with markers of anaemia, bone mineral metabolism and chronic inflammation. Methods Twenty-two kidney transplant candidates with ESRD were studied with myocardial contrast echocardiography, Doppler CFVR assessment and serum multiplex immunoassay analysis. Individuals with diabetes, uncontrolled hypertension or ischaemic heart disease were excluded. Results 7/22 subjects had CMD (defined as CFVR Conclusions Among kidney transplant candidates with ESRD, there is a high prevalence of CMD, despite the absence of traditional risk factors. Anaemia may be a potential driver of microvascular dysfunction in this population and requires further investigation.