Climate change and its implications for kidney health.

PURPOSE OF REVIEW: Extremes of weather as a result of climate change are affecting social, economic and health systems. Kidney health is being threatened by global warming while treatment of kidney disease is contributing to increasing resource utilization and leaving a substantial carbon footprint. Improved physician awareness and patient education are needed to mitigate the risk. RECENT FINDINGS: Rising temperatures are changing kidney disease patterns, with increasing prevalence of acute kidney injury, chronic kidney disease and kidney stones. These issues disproportionately affect people suffering from social inequality and limited access to resources. SUMMARY: In this article, we review the effects of climate change on kidney stones, and acute and chronic kidney injury. Finally, we discuss the impact of renal replacement therapies on the environment and proposed ways to mitigate it.

Thiazides do not affect mortality but may reduce CV events vs. nondiuretic antihypertensive drugs at up to 5 y.

SOURCE CITATION: Reinhart M, Puil L, Salzwedel DM, et al. First-line diuretics versus other classes of antihypertensive drugs for hypertension. Cochrane Database Syst Rev. 2023;7:CD008161. 37439548.

Evaluation of a pilot emergency department linkage to care program for patients previously diagnosed with Hepatitis C.

There is a significant number of Emergency Department (ED) patients with known chronic hepatitis C virus (HCV) infection who have not been treated with directly acting antivirals. We implemented a pilot ED-based linkage-to-care program to address this need and evaluated the impact of the program using the HCV Care Continuum metrics. Between March 2015 and May 2016, dedicated patient care navigators identified HCV RNA-positive patients in an urban ED and offered expedited appointments with the on-site viral hepatitis clinic. Patient demographics and care continuum outcomes were abstracted from the EMR and analysed to determine significant factors influencing linkage-to-care (LTC) and treatment initiation rates. The ED linkage-to-care program achieved a 43% linkage-to-care rate (165/384), 22% treatment rate (84/384) and 16% sustained virologic response rate (63/384). Significant associations were found between linkage-to-care and increasing age (OR = 1.03), Medicare insurance (OR = 2.21) and having a primary care physician (PCP) (OR = 4.03). For patients who were linked, the odds of initiating treatment were also positively significantly associated with increasing age (OR = 1.04) and having a PCP (OR = 2.77). For patients who initiated treatment, the odds of sustained virologic response were marginally associated with having a PCP (OR = 4.92).Our ED linkage-to-care program utilized care coordination to successfully link nearly half of approached HCV RNA-positive patients to care. This design can be feasibly replicated by other EDs given limited non-clinical training required for linkage-to-care staff. Adoption of similar programs in other EDs may improve the rates of LTC and treatment initiation for previously diagnosed HCV patients.

Trifluridine/Tipiracil and Regorafenib in Patients with Metastatic Colorectal Cancer: A Retrospective Study at a Tertiary Oncology Center.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) and regorafenib prolong survival for patients with refractory metastatic colorectal cancer (mCRC); limited comparative effectiveness data exist. MATERIALS AND METHODS: A retrospective, longitudinal cohort study of patients with mCRC who initiated FTD/TPI or regorafenib (index therapy) between 2012 and 2017 at a U.S. tertiary oncology center, Dana-Farber Cancer Institute, was conducted. Using best tumor response assessments, real-world overall response rates (rwORR) and disease control rates (rwDCR) were described and analyzed using logistic regression. Survival rate was examined for each month after index therapy using Kaplan-Meier. Overall survival (OS) was assessed using Cox proportional hazards models. Subgroup analyses among patients with index therapy as second- or third-line were performed. RESULTS: One hundred twenty-six and 95 patients were treated with FTD/TPI or regorafenib as index therapy, respectively. Patients treated with FTD/TPI versus regorafenib had a better response (rwORR 52.5% vs. 34.2%; adjusted odds ratio [OR] = 2.6; all p value <.05; rwDCR 64.2% vs. 46.1%; adjusted OR = 2.5; all p value <.05). Similar findings were observed for FTD/TPI versus regorafenib as second- or third-line therapy (rwORR 54.8% vs. 25.9%; adjusted OR = 4.1; all p value <.05; rwDCR 69.0% vs. 37.0%; adjusted OR = 4.9; all p value <.05). A greater proportion of patients treated with FTD/TPI versus regorafenib survived at 3 months (86.2% vs. 73.4%; p value = .016) and 4 months (79.6% vs. 65.8%; p value = .017). Adjusted OS hazard ratio for FTD/TPI versus regorafenib was 0.80, p value = .157. CONCLUSION: Patients treated with FTD/TPI had better tumor response and disease control than patients treated with regorafenib. Subgroup analysis in second- or third-line suggests that early use of FTD/TPI may have clinical benefits. IMPLICATIONS FOR PRACTICE: In this retrospective cohort study, patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil (FTD/TPI) were significantly less likely than those treated with regorafenib to have dose modifications and more likely to have higher real-world objective response rate (rwORR) and real-world disease control rate (rwDCR) while treated. Patients treated with FTD/TPI versus regorafenib had significantly higher odds of having rwORR or rwDCR in adjusted analyses. Monthly survival rates were higher overall in patients treated with FTD/TPI versus regorafenib in the first 6 months of follow-up, particularly at months 3 and 4. This study offers insight into patients' treatment experience in real-world clinical settings.

Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.

Resource utilization across the continuum of HIV care: An emergency department-based cohort study.

BACKGROUND: The objective of this study was to determine the healthcare resource utilization for people living with HIV (PLWH) presenting to the emergency department (ED) across the HIV Care Continuum. METHODS: This prospective study enrolled PLWH presenting to an urban ED between June 2016 and March 2017. Subjects were categorized as being linked to care, retained in care, on antiretroviral therapy (ART), and virally suppressed (<200 copies/ml). Data on ED visit rates, duration of stay, and hospital admission rates were compared to local metrics. RESULTS: Overall, 94.3% of 159 enrollees had been linked to care, 75.5% retained in care, 81.1% on ART, and 62.8% virally suppressed. Compared to the general population of the city and of the ED, participants had a higher ED visit rate (3.0 v. 1.2 visits per person-per year) in the past two years, a higher median duration of ED stay (12.6 v. 7.6 h), and a higher hospital admission rate (36.5% v. 24.9%) during their index ED visit. Viral suppression was negatively associated with admission (OR = 0.35, 95% CI: 0.17, 0.72). Forty-eight (30.2%) participants who had at least eight ED visits in the past two years were more likely to have a diagnosed mental health disorder (79.2% v. 62.2%, p=0.036). CONCLUSIONS: Our results showed that PLWH use more ED resources than the general population and a better engagement in HIV care is linked to lesser ED resource utilization for PLWH, indicating the importance of improved HIV care engagement in healthcare utilization management.

LGBT cultural competency, patient exposure, and curricular education among student pharmacists.

BACKGROUND: Pharmacists are positioned in unique and important roles in health care in their ability to care for the lesbian, gay, bisexual, and transgender (LGBT) population. For example, pharmacists are a highly prevalent, accessible provider type, and informal surveys have shown that LGBT patients may be more comfortable asking their pharmacists sensitive medication questions rather than their primary provider. OBJECTIVES: To demonstrate gaps in LGBT cultural competency among student pharmacists and propose specific recommendations on the number of LGBT patient exposures and educational hours that can significantly improve LGBT cultural competency. METHODS: Student pharmacists (N = 275) at 3 universities in the United States completed a survey comprising demographics, experiential variables (i.e., number of LGBT patients and LGBT hours), and the 7-point Likert LGBT-Development of Clinical Skills Scale (LGBT-DOCSS). LGBT-DOCSS scores were stratified by 1-point increments, and experiential variable means were computed per each stratification to characterize the mean LGBT patients and hours of student pharmacists with higher scores and those with lower scores. RESULTS: Student pharmacists reported low numbers of annual LGBT patients (Mean = 3.82, SD = 9.54), annual LGBT curricular hours (Mean = 0.55, SD = 0.95), and annual LGBT extracurricular hours (Mean = 2.50, SD = 15.42). They reported very high attitudinal awareness (Mean = 6.19, SD = 1.02), moderate knowledge (Mean = 5.00, SD = 1.25), and low clinical preparedness (Mean = 3.26, SD = 1.33). Student pharmacists who cared for 25 or more LGBT patients and received 10 or more LGBT total hours reported significantly higher preparedness, knowledge, and overall cultural competency. CONCLUSION: Student pharmacists have shortcomings in LGBT cultural competency and limited LGBT patient exposure and education. To improve LGBT cultural competency, pharmacy schools and accrediting bodies should consider ensuring that student pharmacists receive at least a total of 25 LGBT patient contacts and 10 LGBT formal education hours across their pharmacy education.

Real-World Adherence in Patients with Metastatic Colorectal Cancer Treated with Trifluridine plus Tipiracil or Regorafenib.

BACKGROUND: Trifluridine and tipiracil (FTD + TPI) and regorafenib (REG) are approved treatments for the treatment of refractory metastatic colorectal cancer (mCRC). This study assesses adherence and duration of therapy with FTD + TPI versus REG and explores the effect of sequencing on adherence. MATERIALS AND METHODS: Adults diagnosed with mCRC were identified in the IQVIA Real-World Data Adjudicated Claims: U.S. database (October 2014-July 2017). The observation period spanned from the index date (first dispensing of FTD + TPI or REG) to the earliest of a switch to another mCRC agent, the end of continuous enrollment, or the end of data availability. Medication possession ratio (MPR), proportion of days covered (PDC), and persistence and time to discontinuation (gap ≥45 days) were compared between FTD + TPI and REG users and among switchers (FTD + TPI-to-REG vs. REG-to-FTD + TPI). RESULTS: A total of 469 FTD + TPI and 311 REG users were identified. FTD + TPI users had higher compliance with an MPR ≥80% (odds ratio [OR], 2.47; p < .001) and PDC ≥80% (OR, 2.77; p < .001). FTD + TPI users had better persistence (82.8% vs. 68.0%; p < .001) and lower risk of discontinuation (hazard ratio [HR], 0.76; p = .006). Among switchers (96 FTD + TPI-to-REG; 83 REG-to-FTD + TPI), those switching from FTD + TPI to REG were more likely to have an MPR ≥80% (OR, 2.91; p < .001) and PDC ≥80% (OR, 4.60; p < .001) compared with REG-to-FTD + TPI switchers while treated with these drugs. Additionally, FTD + TPI-to-REG switchers had a lower risk of first treatment discontinuation (HR, 0.66; p = .009). CONCLUSION: FTD + TPI users had significantly higher adherence and persistence, and patients who were treated with FTD + TPI before switching to REG also had higher adherence and persistence outcomes. IMPLICATIONS FOR PRACTICE: Trifluridine plus tipiracil (FTD + TPI) and regorafenib (REG) prolong survival in refractory metastatic colorectal cancer (mCRC) but have different tolerability profiles. This study assessed real-world adherence to treatment with FTD + TPI versus REG and compared outcomes among patients who switched from FTD + TPI to REG and vice versa. FTD + TPI was associated with significantly higher medication adherence and longer time to discontinuation than REG. Patients treated with FTD + TPI prior to switching to REG also showed higher adherence outcomes. Findings could help inform decision making regarding the choice and sequencing of treatment with FTD + TPI versus REG in patients with mCRC.

How much is needed? Patient exposure and curricular education on medical students' LGBT cultural competency.

BACKGROUND: For medical students, providing exposure to and education about the lesbian, gay, bisexual, and transgender (LGBT) patient population are effective methods to increase comfort, knowledge, and confidence in caring for LGBT people. However, specific recommendations on the number of patient exposures and educational hours that relate to high LGBT cultural competency are lacking. METHODS: Medical students (N = 940) at three universities across the United States completed a survey consisting of demographics, experiential variables (i.e., number of LGBT patients and LGBT hours), and the 7-point Likert LGBT-Development of Clinical Skills Scale (LGBT-DOCSS). LGBT-DOCSS scores were stratified by 1-point increments, and experiential variable means were computed per each stratification to characterize the mean LGBT patients and hours of medical students with higher scores and those with lower scores. RESULTS: Medical students reported caring for some LGBT patients annually (M = 6.02, SD = 20.33) and receiving a low number of annual LGBT curricular hours (M = 2.22, SD = 2.85) and moderate number of annual LGBT extracurricular hours (M = 6.93, SD = 24.97). They also reported very high attitudinal awareness (M = 6.54, SD = 0.86), moderate knowledge (M = 5.73, SD = 1.01), and low clinical preparedness (M = 3.82, SD = 1.25). Medical students who cared for 35 or more LGBT patients and received 35 or more LGBT total hours reported significantly higher preparedness and knowledge. CONCLUSIONS: Medical students have shortcomings in LGBT cultural competency and limited LGBT patient exposure and education. To improve LGBT cultural competency, medical schools and accrediting bodies should consider providing medical students with at least a total of 35 LGBT patient contacts and 35 LGBT education hours (10 h of required curricular education and 25 h of supplemental education).

A phase 2 trial of regorafenib as a single agent in patients with chemotherapy-refractory, advanced, and metastatic biliary tract adenocarcinoma.

BACKGROUND: Biliary tract cancers are rare, aggressive neoplasms. Most patients present with advanced/unresectable or metastatic disease at diagnosis, and no second-line regimen has demonstrated clinical benefit. This was a phase 2 study evaluating the efficacy and safety of regorafenib in patients who had advanced/unresectable or metastatic disease after receiving standard therapy. METHODS: In this single arm-study, patients with advanced/unresectable or metastatic biliary tract cancer who failed at least 1 line of systemic chemotherapy received regorafenib once daily on a schedule of 21-days on/7-days off in a 28-day cycle. Patients initially received a standard 160 mg dose. After toxicity assessments in the first 3 patients, the dose was reduced to 120 mg for subsequent patients, as preplanned. The primary endpoint was progression-free survival (PFS). Secondary objectives included overall survival (OS), the objective response rate, and the disease control rate. RESULTS: Forty-three patients received at least 1 dose of regorafenib, and 34 patients who received at least 1 cycle of treatment were evaluable for tumor response. The median PFS was 15.6 weeks (90% confidence interval, 12.9-24.7 weeks), and the median OS was 31.8 weeks (90% confidence interval, 13.3-74.3 weeks), with survival rates 40% at 12 months and 32% at 18 months. A partial response was achieved in 5 patients (11%), and 19 had stable disease (44%), for a disease control rate of 56%. The toxicity profile was as expected, with grade 3 and 4 adverse events reported in 40% of patients. The most common toxicities were hypophosphatemia (40%), hyperbilirubinemia (26%), hypertension (23%), and hand-foot skin reaction (7%). CONCLUSIONS: The current results suggest promising efficacy of regorafenib in patients with chemotherapy-refractory, advanced/metastatic biliary tract cancer, warranting further studies to confirm its clinical efficacy. There is a clear unmet need for effective therapies in patients who have advanced and metastatic biliary tract cancer.

Increasing HIV testing engagement through provision of home HIV self-testing kits for patients who decline testing in the emergency department: a pilot randomisation study.

OBJECTIVE: Up to 60% of patients decline routine HIV testing offer in US emergency departments (EDs). The objective of this study is to determine whether the provision of HIV self-testing (HIVST) kit would increase engagement of HIV testing among these HIV test 'Decliners'. METHODS: Patients who declined a test offered in an ED-based triage nurse-driven HIV screening programme were enrolled and randomised to either the HIVST or the control group. The patients in the HIVST group received HIVST kits to take home, were encouraged to report test results to an established internet-based STI/HIV testing recruitment website 'I Want the Kit' (IWTK) and received five referral cards for their peers to request HIVST kits from IWTK. The control group received pamphlets about publicly available HIV testing sites. HIV testing from both groups after enrolment was determined via telephone follow-up at 1 month. Testing rate ratio (RR) was determined using χ2 tests. RESULTS: Fifty-two patients were randomised to the HIVST group and 48 to the control group. Among all 64 patients completing any follow-up, 14/29 (48%) patients in the HIVST group tested themselves at home with the provided kit. Four of these had never had an HIV test. Only 2/35 (6%) in the control group reported having an HIV test after enrolment (RR: 8.45 (95% CI: 2.09 to 34.17)). 57% (8/14) in the HIVST group reported test results to IWTK. CONCLUSION: Provision of HIVST kits supplements ED-based screening programme and significantly improved engagement of HIV testing among those test 'Decliners' in the ED. TRIAL REGISTRATION NUMBER: NCT03021005, results.

Advanced liver fibrosis and care continuum in emergency department patients with chronic hepatitis C.

BACKGROUND: FIB-4, a non-invasive serum fibrosis index (which includes age, ALT, AST, and platelet count), is frequently available during ED visits. Our objective was to define 1-year HCV-related care outcomes of ED patients with known HCV, for the overall group, and both those with and without advanced fibrosis. METHODS: As part of an ongoing HCV linkage-to-care (LTC) program, HCV-infected ED patients were identified retrospectively via medical record review. Components of FIB-4 were abstracted, and patients with an FIB-4 > 3.25 were classified with advanced fibrosis and characterized with regards to downstream HCV care continuum outcomes at one-year after enrollment. RESULTS: Of the 113 patients with known HCV, 38 (33.6%) had advanced fibrosis. One-year outcomes along the HCV care continuum after ED encounter for 'all' 113, 75 'without advanced fibrosis', and 38 'advanced fibrosis' patients, respectively, were as follows: agreeing to be linked to care [106 (93.8%), 72 (96.0%), 34 (89.5%)]; LTC [38 (33.6%), 21 (28.0%), 17 (44.7%)]; treatment initiation among those linked [16 (42.1%), 9 (42.9%), 7 (41.2%)]; sustained virologic response 4 weeks post-treatment among those treated [15 (93.8%), 9 (100.0%), 6 (85.7%)]; documented all-cause mortality [10 (8.8%), 3 (4.0%), 7 (18.4%)]. Notably, 70% of those who died had advanced fibrosis. For those with advanced liver fibrosis, all-cause mortality was significantly higher, than those without (18.4% versus 4.0%, p = 0.030). CONCLUSIONS: Over one-third of HCV-infected ED patients have advanced liver fibrosis, incomplete LTC, and higher mortality, suggesting this readily-available FIB-4 might be used to prioritize LTC services for those with advanced fibrosis.

A review: Percutaneous pulmonary artery stenosis therapy: state-of-the-art and look to the future.

Stenosis, or narrowing, of the branches of the pulmonary artery is a type of CHD that, if left untreated, may lead to significant complications. Ideally, interventions to treat stenosis occur before significant complications or long-term sequelae take place, often within the first 2 years of life. Treatment depends on specifics of the condition, the presence of other malformations, and age of the child. Research and recent innovation to address these shortcomings have provided physicians with safer and more effective methods of treatment. This has further continued to push the ceiling of pulmonary arterial stenosis treatment available for patients. Despite continuous advancement in angioplasty - such as conventional and cutting balloon - and stenting, each treatment method is not without its unique limitations. New technological developments such as bioresorbable stents can accommodate patient growth and pulmonary artery stenosis treatment. As more than a decade has passed since the review by Bergersen and Lock, this article aims to provide a contemporary summary and investigation into the effectiveness of various therapeutic tools currently available, such as bare metal stents and potential innovations including bioresorbable stents.

Palladium-catalyzed acid-free Fujiwara-Moritani alkenylation of 4-thiazolidinones.

Herein, we report a facile method for the alkenylation of a 4-thiazolidinone motif without using external acid and high-pressure gas, which are required in conventional Fujiwara-Moritani reactions. Mild reaction conditions, one-pot synthesis, and utilization of an oxidant made this process more feasible in comparison with previously reported methods. Functionalization of the slightly more acidic [Formula: see text] C-H bond with the less acidic [Formula: see text] C-H bond yielded the alkenylated motif. This pathway opens new possibilities for organic synthesis.

Molecular targeted therapy in hepatocellular carcinoma: from biology to clinical practice and future.

OPINION STATEMENT: Hepatocellular carcinoma (HCC) is one of the most lethal cancers globally, particularly in certain regions of the world. Although the major risk factors for HCC have been identified, the specific mechanisms driving hepatocarcinogenesis remain unclear. Sorafenib is the only systemic therapy that has demonstrated an overall survival benefit in patients with advanced HCC and does so primarily through antiangiogenic activity. However, that actual benefit is still relatively small. Extensive research has focused on targeting dysfunctional molecular pathways in HCC. Despite promising preclinical and early-phase studies, other agents have failed to expand upon the efficacy of sorafenib in large-scale randomized trials. As the development of treatment options in the post-sorafenib setting is ongoing, more efforts are being focused on (1) evaluation of molecular agents targeting pathogenic, HCC-specific pathways; (2) the combination of targeted and cytotoxic therapies in selected subgroups; and (3) the combination of systemic and locoregional therapies in various settings. This article provides a review of recently completed and ongoing studies of molecular targeted agents in HCC, including a brief description of the biologic rationale behind these agents.

Evaluating Effectiveness of an Online LGBTQIA+ Health Course for Medical Students.

BACKGROUND AND OBJECTIVES: Despite the increasing number of sexual and gender minority (SGM) patients in the United States and designation by the National Institutes of Health as a population with health disparities, available tools are lacking to train medical students on appropriate care for this population. Therefore, we developed and implemented a novel, self-directed, 2-week online elective for undergraduate medical students. The objective of our study was to evaluate the effectiveness of this course in increasing medical students' competency and confidence in caring for SGM patients. METHODS: We developed the curriculum using Kern's six-step model for curriculum development. We created anonymous pre- and postcourse surveys using the standardized Lesbian, Gay, Bisexual, Transgender Development of Clinical Skills Survey (LGBT-DOCSS) questionnaire to assess cultural competence, as well as a 5-point Likert-scored survey to assess self-perceived confidence in the care of SGM patients. We tested the statistical significance in pre- and postsurvey scores via paired sample t tests in R (R Project for Statistical Computing). RESULTS: We found statistically significant increases in the LGBT-DOCSS categories of clinical preparedness (P<.001), basic knowledge (P<.001), overall competency (P<.001), and self-perceived confidence in caring for SGM patients (P<.001, N=33). CONCLUSIONS: The course represents an effective solution for increasing medical students' self-perceived competence and confidence in caring for SGM patients. The flexibility and ease of the online format may be appealing to both students and institutions, and ultimately can serve to increase access to crucial content that is largely absent from current undergraduate medical education. Future evaluation efforts will be required to determine whether the course impacts long-term behavioral changes and outcomes.

Differences in the association between epidural analgesia and length of stay by surgery type: an observational study.

INTRODUCTION: Despite a decline in the use of thoracic epidural analgesia related in part to concerns for delayed discharge, it is unknown whether changes in length of stay (LOS) associated with epidural analgesia vary by surgery type. Therefore, we determined the degree to which the association between epidural analgesia (vs no epidural) and LOS differed by surgery type. METHODS: We conducted an observational study using data from 1747 patients who had either non-emergent open abdominal, thoracic, or vascular surgery at a single tertiary academic hospital. The primary outcome was hospital LOS and the incidence of a prolonged hospital LOS defined as 21 days or longer. Secondary endpoints included escalation of care, 30-day all-cause readmission, and reason for epidural not being placed. The association between epidural status and dichotomous endpoints was examined using logistic regression. RESULTS: Among the 1747 patients, 85.7% (1499) received epidural analgesia. 78% (1364) underwent abdominal, 11.5% (200) thoracic, and 10.5% (183) vascular surgeries. After adjustment for differences, receiving epidural analgesia (vs no epidural) was associated with a 45% reduction in the likelihood of a prolonged LOS (p<0.05). This relationship varied by surgery type: abdominal (OR 0.42, 95% CI 0.23 to 0.79, p<0.001), vascular (OR 1.66, 95% CI 0.17 to 16.1, p=0.14), and thoracic (OR 1.07, 95% CI 0.20 to 5.70, p=0.93). Among abdominal surgical patients, epidural analgesia was associated with a median decrease in LOS by 1.4 days and a 37% reduction in the likelihood of 30-day readmission (adjusted OR 0.63, 0.41 to 0.97, p<0.05). Among thoracic surgical patients, epidural analgesia was associated with a median increase in LOS by 3.2 days. CONCLUSIONS: The relationship between epidural analgesia and LOS appears to be different among different surgical populations.

How predictive is peer review for gauging impact? The association between reviewer rating scores, publication status, and article impact measured by citations in a pain subspecialty journal.

BACKGROUND: Peer review represents a cornerstone of the scientific process, yet few studies have evaluated its association with scientific impact. The objective of this study is to assess the association of peer review scores with measures of impact for manuscripts submitted and ultimately published. METHODS: 3173 manuscripts submitted to Regional Anesthesia & Pain Medicine (RAPM) between August 2018 and October 2021 were analyzed, with those containing an abstract included. Articles were categorized by topic, type, acceptance status, author demographics and open-access status. Articles were scored based on means for the initial peer review where each reviewer's recommendation was assigned a number: 5 for 'accept', 3 for 'minor revision', 2 for 'major revision' and 0 for 'reject'. Articles were further classified by whether any reviewers recommended 'reject'. Rejected articles were analyzed to determine whether they were subsequently published in an indexed journal, and their citations were compared with those of accepted articles when the impact factor was <1.4 points lower than RAPM's 5.1 impact factor. The main outcome measure was the number of Clarivate citations within 2 years from publication. Secondary outcome measures were Google Scholar citations within 2 years and Altmetric score. RESULTS: 422 articles met inclusion criteria for analysis. There was no significant correlation between the number of Clarivate 2-year review citations and reviewer rating score (r=0.038, p=0.47), Google Scholar citations (r=0.053, p=0.31) or Altmetric score (p=0.38). There was no significant difference in 2-year Clarivate citations between accepted (median (IQR) 5 (2-10)) and rejected manuscripts published in journals with impact factors >3.7 (median 5 (2-7); p=0.39). Altmetric score was significantly higher for RAPM-published papers compared with RAPM-rejected ones (median 10 (5-17) vs 1 (0-2); p<0.001). CONCLUSIONS: Peer review rating scores were not associated with citations, though the impact of peer review on quality and association with other metrics remains unclear.

PD-1 Blockade Induces Reactivation of Nonproductive T-Cell Responses Characterized by NF-κB Signaling in Patients with Pancreatic Cancer.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) trials have evaluated CTLA-4 and/or PD-(L)1 blockade in patients with advanced disease in which bulky tumor burden and limited time to develop antitumor T cells may have contributed to poor clinical efficacy. Here, we evaluated peripheral blood and tumor T cells from patients with PDAC receiving neoadjuvant chemoradiation plus anti-PD-1 (pembrolizumab) versus chemoradiation alone. We analyzed whether PD-1 blockade successfully reactivated T cells in the blood and/or tumor to determine whether lack of clinical benefit could be explained by lack of reactivated T cells versus other factors. EXPERIMENTAL DESIGN: We used single-cell transcriptional profiling and TCR clonotype tracking to identify TCR clonotypes from blood that match clonotypes in the tumor. RESULTS: PD-1 blockade increases the flux of TCR clonotypes entering cell cycle and induces an IFNγ signature like that seen in patients with other GI malignancies who respond to PD-1 blockade. However, these reactivated T cells have a robust signature of NF-κB signaling not seen in cases of PD-1 antibody response. Among paired samples between blood and tumor, several of the newly cycling clonotypes matched activated T-cell clonotypes observed in the tumor. CONCLUSIONS: Cytotoxic T cells in the blood of patients with PDAC remain sensitive to reinvigoration by PD-1 blockade, and some have tumor-recognizing potential. Although these T cells proliferate and have a signature of IFN exposure, they also upregulate NF-κB signaling, which potentially counteracts the beneficial effects of anti-PD-1 reinvigoration and marks these T cells as non-productive contributors to antitumor immunity. See related commentary by Lander and DeNardo, p. 474.