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Total proctocolectomy with ileal pouch-anal anastomosis has become the standard procedure for patients with medically refractory ulcerative colitis, although a subset will develop de novo Crohn's disease.In this study, we investigated the association of preoperative C-reactive protein levels with the development of de novo Crohn's disease after ileal pouch-anal anastomosis.A prospectively maintained database of patients undergoing ileal pouch-anal anastomosis was reviewed.Preoperative C-reactive protein levels were compared between patients who developed de novo Crohn's disease and those who did not. De novo Crohn's disease was defined as small-bowel inflammation proximal to the ileal pouch or perianal disease identified more than 3 months after ileostomy closure. To minimize the heterogeneity of the timing of preoperative C-reactive protein measurement and the severity of ulcerative colitis, only hospitalized patients who had proctocolectomy for severe ulcerative colitis were included in the study.Development of de novo Crohn's disease was analyzed.Of 105 patients, 23 (22%) developed de novo Crohn's disease. Having C-reactive protein in the third tertile significantly increased the risk of developing de novo Crohn's disease (HR 3.44, 95% CI 1.10- 10.70, p = 0.03) compared to in the first tertile. In a multivariable model, a C-reactive protein in the third or second tertile vs the first tertile and younger age was associated with the development of de novo Crohn's disease.Limited to only hospitalized patients with severe ulcerative colitis.In hospitalized patients undergoing ileal pouch-anal anastomosis for medically refractory ulcerative colitis, higher preoperative C-reactive protein levels appear to increase the risk of developing de novo Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B750.LA MAGNITUD DE LA ELEVACIÓN PREOPERATORIA DE LA PROTEÍNA C REACTIVA SE ASOCIA CON APARICIÓN DE UNA ENFERMEDAD DE CROHN DE NOVO DESPUÉS DE UNA ANASTOMOSIS DE BOLSA ILEAL AL ANO EN PACIENTES CON COLITIS SEVERAANTECEDENTES:La proctocolectomía total con anastomosis bolsa ileal-anal se ha convertido en el procedimiento estándar para los pacientes con colitis ulcerativa refractaria al tratamiento médico, aunque un subgrupo desarrollará una enfermedad de Crohn de novo.OBJETIVO:En este estudio investigamos la asociación de los niveles de proteína C reactiva preoperatoria con el desarrollo de la enfermedad de Crohn de novo, después de la anastomosis bolsa ileal-anal.DISEÑO:Se revisó una base de datos recolectada en forma prospectiva, de pacientes sometidos a anastomosis bolsa ileal-anal.PACIENTES:Se compararon los niveles de proteína C reactiva preoperatoria entre los pacientes que desarrollaron la enfermedad de Crohn de novo y los que no la desarrollaron. La enfermedad de Crohn de novo se definió como una inflamación del intestino delgado proximal a la bolsa ileal o una enfermedad perianal identificada más de 3 meses después del cierre de la ileostomía. Para minimizar la heterogeneidad del momento de la medición de la proteína C reactiva preoperatoria y la gravedad de la colitis ulcerativa, solo se incluyeron en el estudio los pacientes hospitalizados que se sometieron a una proctocolectomía por colitis ulcerativa grave.PRINCIPALES MEDIDAS DE RESULTADO:se analizó el desarrollo de la enfermedad de Crohn de novo.RESULTADOS:De 105 pacientes, 23 (22%) desarrollaron enfermedad de Crohn de novo. Tener una proteína C reactiva en el tercer tercil aumentó significativamente el riesgo de desarrollar la enfermedad de Crohn de novo (HR 3,44, IC del 95%: 1,10-10,70, p = 0,03) en comparación con el primer tercil. En un modelo multivariable, una proteína C reactiva en el tercer o segundo tercil frente al primer tercil y una edad más joven se asoció con el desarrollo de la enfermedad de Crohn de novo.LIMITACIONES:Limitado solo a pacientes hospitalizados con colitis ulcerativa grave.CONCLUSIONES:En pacientes hospitalizados sometidos a anastomosis bolsa ileal-anal por colitis ulcerativa refractaria al tratamiento médico, niveles más elevados de proteína C reactiva preoperatoria parecen aumentar el riesgo de desarrollar enfermedad de Crohn de novo. Consulte Video Resumen en http://links.lww.com/DCR/B750. (Traducción-Eduardo Londoño-Schimmer).

AIM Tumour necrosis factor inhibitors (TNFi) have revolutionized the management of moderate to severe ulcerative colitis (UC) since their approval for UC in 2005. However, many patients ultimately require surgery with ileal pouch-anal anastomosis (IPAA). Development of de novo Crohn's disease (CD) following IPAA is an increasingly common and devastating complication, sometimes progressing to pouch failure. The aim of this study was to evaluate the association of preoperative TNFi exposure and the development of de novo CD after IPAA. METHOD A prospective single-centre inflammatory bowel disease (IBD) registry was searched for consecutive patients with UC undergoing IPAA during a 25-year period ending July 2018. Patients with preoperative CD or IBD-unclassified were excluded. De novo CD was diagnosed upon endoscopic evidence of five or more mucosal ulcers proximal to the ileal pouch any time after surgery and/or pouch fistula occurring more than three months after ileostomy closure. RESULTS The study cohort consisted of 400 patients with a median follow-up of 44.0 (IQR 11-113) months. Sixty-two (16%) patients developed de novo CD 28.0 (IQR 6-67) months following ileostomy closure. Survival analysis of TNFi era patients revealed a significant increase in de novo CD risk in those with preoperative TNFi exposure. Multivariable proportional hazards modelling revealed two independent predictors for de novo CD development: older age was protective (HR 0.89 per 5-year increase; P = 0.009) and preoperative TNFi exposure was hazardous (HR 2.10; P = 0.011). CONCLUSION This prospective study is the first to suggest an association between preoperative TNFi exposure and the development of de novo CD.

Background Severity of illness in COVID-19 is consistently lower in women. A focus on sex as a biological factor may suggest a potential therapeutic intervention for this disease. We assessed whether adding progesterone to standard of care (SOC) would improve clinical outcomes of hospitalized men with moderate to severe COVID-19. Research Question Does short-term subcutaneous administration of progesterone safely improve clinical outcome in hypoxemic men hospitalized with COVID-19? Study Design and Methods We conducted a pilot, randomized, open-label, controlled trial of subcutaneous progesterone in men hospitalized with confirmed moderate to severe COVID-19. Patients were randomly assigned to receive SOC plus progesterone (100 mg subcutaneously twice daily for up to 5 days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status on day 7. Length of hospital stay and number of days on supplemental oxygen were key secondary outcomes. Results Forty-two patients were enrolled from April 2020 to August 2020; 22 were randomized to the control group and 20 to the progesterone group. Two patients from the progesterone group withdrew from the study before receiving progesterone. There was a 1.5-point overall improvement in median clinical status score on a seven-point ordinal scale from baseline to day 7 in patients in the progesterone group as compared with control subjects (95% CI, 0.0-2.0; P = .024). There were no serious adverse events attributable to progesterone. Patients treated with progesterone required three fewer days of supplemental oxygen (median, 4.5 vs 7.5 days) and were hospitalized for 2.5 fewer days (median, 7.0 vs 9.5 days) as compared with control subjects. Interpretation Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to SOC, may represent a safe and effective approach for treatment in hypoxemic men with moderate to severe COVID-19. Trial Registry ClinicalTrials.gov; No.: NCT04365127; URL: www.clinicaltrials.gov .

Objective: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC). Methods: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution. Results: There was a 17.3% decrease in stroke code activations across LAC in 2020 compared to 2019 (1,786 vs. 2,159, respectively, χ2 goodness of fit test p < 0.0001) across 9 participating comprehensive stroke centers. Patients who did not receive any reperfusion therapy decreased by 16.6% in 2020 (1,527) compared to 2019 (1,832). Patients who received only intravenous thrombolytic (IVT) therapy decreased by 31.8% (107 vs. 157). Patients who received only mechanical thrombectomy (MT) increased by 3% (102 vs. 99). Patients who received both IVT and MT decreased by 31.8% (45 vs. 66). Recanalization treatment times in 2020 were comparable to 2019. CSCs serving a higher proportion of Latinx populations in the eastern parts of LAC experienced a higher incidence of MT in 2020 compared to 2019. Mild increase in stroke severity was seen in 2020 compared to 2019 (8.95 vs. 8.23, p = 0.046). A higher percentage of patients were discharged home in 2020 compared to 2019 (59.5 vs. 56.1%, p = 0.034), a lower percentage of patients were discharged to skilled nursing facility (16.1 vs. 20.7%, p = 0.0004), and a higher percentage of patients expired (8.6 vs. 6.3%, p = 0.008). Conclusion: LAC saw a decrease in overall stroke code activations in 2020 compared to 2019. Reperfusion treatment times remained comparable to prepandemic metrics. There has been an increase in severe stroke incidence and higher volume of thrombectomy treatments in Latinx communities within LAC during the pandemic of 2020. More patients were discharged home, less patients discharged to skilled nursing facilities, and more patients expired in 2020, compared to the same time frame in 2019.

PURPOSE: The aim of this study is to characterize and compare changes in gene expression patterns of paired axillary lymph node (ALN) metastases from estrogen receptor (ER) positive and triple negative (TNBC) primary breast cancer (PBC). METHODS: Patients with stage 2-3 PBC with macrometastasis to an ALN were selected. Gene expression of 2,567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Changes in gene expression between ER/PR positive, HER2 negative PBC and their paired ALN metastases were compared with TNBC and their paired ALN metastases. RESULTS: Fourteen pairs of ER positive and paired ALN metastasis were analyzed. Compared with the PBC, ALN metastasis had 673 significant differentially expressed genes, including 348 upregulated genes and 325 downregulated genes. Seventeen pairs of TNBC and paired ALN metastasis were analyzed. ALN metastasis had 257 significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. When gene expression of the ALN for ER positive PBC was compared to that of TNBC, 97 genes were upregulated in both, and 115 genes were similarly downregulated. Common upregulated genes were associated with cell death, necrosis, and homeostasis. Common downregulated genes were those of migration, degradation of extracellular matrix, and invasion. CONCLUSION: Although ER positive PBC and TNBC have a distinct gene expression profiles and distinct changes from PBC to ALN metastases, a significant number of genes are similarly up- or downregulated. Understanding the role of these common genomic changes may provide clues to understanding the metastatic process itself.

Background: Depression is a common complication of pregnancy and vitamin D deficiency is one biological risk factor for postpartum depression (PPD). Materials and Methods: We evaluated the ratio of 24,25(OH)(2)D and 25(OH)D serum concentrations referred to as the Vitamin D Metabolite Ratio (VMR), a new candidate biomarker during pregnancyand its relationship with PPD. Women were enrolled in the first trimester of pregnancy and followed through four timepoints. Results: A total of 89 women had complete depression, biomarker and demographic data and 34% were at risk for PPD (CES-D≥16). Stepwise multiple logistic regression models for PPD risk were carried out with eight predictors. Results showed that only lower VMR, OR = 1.43, 95% CI 1.10–1.86, p = 0.007, and Hispanic/Latina identification, OR = 3.83, 95% CI 1.44–10.92, p = 0.007 were significantly associated with higher PPD risk. Conclusion: Routine prenatal screening for vitamin D metabolites, particularly in Hispanic/Latina women, may identify women at risk for PPD.

Background: Limited data exists regarding sex differences in outcome and predictive accuracy of intensive care unit-based scoring systems when applied to cardiac intensive care unit patients. Methods: We reviewed medical records of patients admitted to cardiac intensive care unit from 1 January 2011–31 December 2016. Sex differences in mortality rates and the performance of intensive care unit-based scoring systems in predicting in-hospital mortality were analyzed. Calibration was assessed by the Hosmer-Lemeshow test and locally weighted scatterplot smoothing curves. Discrimination was assessed using the c statistic and receiver-operating characteristic curve. Results: Among 6963 patients, 2713 (39%) were women. Overall in-hospital and cardiac intensive care unit mortality rates were similar in women and men (9.1% vs 9.4%, p=0.67 and 5.9% vs 6%, p=0.88, respectively) and in age and major diagnosis subgroups. Of the scoring systems, Acute Physiology and Chronic Health Evaluation III and Sequential Organ Failure Assessment had poor calibration (Hosmer-Lemeshow p value 0.8). In the subgroups of acute myocardial infarction and heart failure patients, all scores had good calibration (Hosmer-Lemeshow p>0.001) and discrimination (C statistic >0.8) while in diagnosis subgroups with highest mortality, the calibration varied among scores and by sex, and discrimination was poor. Conclusions: No sex differences in mortality were seen in cardiac intensive care unit patients. The mortality predictive value of intensive care unit-based scores is limited in both sexes and variable among different subgroups of diagnoses.

Aims To gather the best available evidence regarding Ki-67% values in large-cell neuroendocrine carcinoma (LCNEC) and determine whether certain cut-off values could serve as a prognostic feature in LCNEC. Methods and results Aperio ScanScope AT Turbo, eSlide Manager and ImageScope software (Leica Biosystems) were used to measure Ki-67% in 77 resected LCNEC diagnosed by World Health Organisation (WHO) criteria. Cases were stratified into six classes by 10% Ki-67 increments. Using the Kaplan-Meier method, overall (OS) and disease-free survivals (DFS) were compared by AJCC stage, by six Ki-67% classes and with Ki-67% cut-points ≥20% and ≥40%. Tumours were from 0.9 to 11.5 cm and pathological stages 1-3. The system measured Ki-67% positivity using 4072-44 533 tumour nuclei per case (mean 16610 ± 8039). Ki-67% ranged from 1 to 64% (mean = 26%; median = 26%). Only 16 (21%) tumours had Ki-67% ≥40%. OS ranged from 1 to 298 months (median follow-up = 25 months). DFS ranged from 1 to 276 months (median follow-up = 9 months). OS and DFS differed across AJCC stage (overall log-rank P = 0.038 and P = 0.037). However, neither OS nor DFS significantly correlated with Ki-67% when six or two classes were used with either ≥20% Ki-67 or ≥40% Ki-67 as cut-point. A literature review identified 14 reports meeting our inclusion criteria with ≥10 LCNEC. Reported Ki-67% ranged from 2% to 100%. Problems contributing to variability in Ki-67% measurements are discussed. Conclusion Our findings caution against a blanket use of 20%, 40% or other Ki-67% cut-points for LCNEC diagnosis or prognostication.

Postpartum depression (PPD) is a common pregnancy complication. The association between cesarean delivery (CD) and PPD has shown conflicting results in prior studies, although emergent CD appears to be a clear risk factor. Establishing PPD risk is critical and may, however, be related to the unplanned nature of the CD, rather than the surgery itself. Our objective was to determine whether women who underwent unplanned CD were more likely than those with vaginal delivery to have higher depressive symptoms and thus screen positive for PPD risk in the immediate postpartum period.This cohort study was conducted at a community medical center using data for deliveries between 8/2015-1/2016. Women were screened in the hospital for depressive symptoms (PPD risk) using the Edinburgh Postnatal Depression Scale (EPDS) within 4 days post-delivery. Logistic regression, adjusting for maternal race/ethnicity and parity, was performed to evaluate the association between delivery route (vaginal vs planned vs unplanned CD) and PPD risk (EPDS ≥ 10).A total of 2094 women had complete data for analysis. Overall, 44 women (2.1%) screened positive for PPD risk. Logistic regression results showed that unplanned CD was significantly associated with PPD risk (OR = 2.28, 95% CI 1.13-4.57,Unplanned CD may be an independent risk factor for PPD risk in the immediate postpartum period. This finding might explain why some previous studies have demonstrated different results with regards to risk of CD where the unplanned nature of the delivery was not accounted for.

Objective Few studies examine the impact of surgical trainee involvement on tumor-free margins in breast conserving surgery (BCS). Our objective was to investigate the impact of resident and fellow involvement on positive margins rates following BCS for invasive breast cancer (BC). Design We identified female patients who had BCS for BC between January 2005 to December 2015. Setting Tertiary care hospital. Participants Around 1089 patients were identified from a prospectively maintained database. Results Of 1089 patients, mean age was 63 (range 43-99) years. Around 768 patients (70.1%) required preoperative localization, and 328 patients (29.9%) had a palpable cancer. Nonpalpable cancers had a smaller volume of specimen tissue excised (p = 0.0005) compared to palpable cancers, and no significant difference was observed in the positive margin rate between the nonpalpable group compared to the palpable group (24.7% nonpalpable vs. 25.3% palpable, p = 0.88). Nonpalpable cancer positive margin rates were 23.9% (n = 102/427) for cases performed by an attending surgeon, 25.0% (n = 15/60) with a junior resident (PGY 2-3), 28.6% (n = 8/28) with a senior resident (PGY 4-5), and 25.7% (n = 65/253) with a fellow, which were not statistically significant (p = 0.89). Palpable cancer positive margin rates were 27.6% (n = 47/170) for cases performed by an attending, 13.9% (n = 5/36) with an intern (PGY-1), 40.9% (n = 9/22) with a junior resident, 0% (n = 0/8) with a senior resident, and 23.9% (n = 22/92) with a fellow, which were also not significantly different (p = 0.07). Conclusion Resident and fellow participation in BCS for BC does not appear to impact the rate of positive margins.

The COVID-19 pandemic has significantly impacted the service delivery model (SDM) of clinical genetic counseling across the United States and Canada. A cross-sectional survey was distributed to 4,956 genetic counselors (GCs) from the American Board of Genetic Counselors and Canadian Association of Genetic Counselors mailing lists in August 2020 to assess the change in utilization of telehealth for clinical genetic counseling during the COVID-19 pandemic compared with prior to the pandemic. Data from 411 eligible clinical genetic counselors on GC attitudes and their experiences prior to and during the pandemic were collected and analyzed to explore the change in SDM, change in appointment characteristics, change in billing practices, GC perceived benefits and limitations of telehealth, and prediction of future trends in SDM in the post-pandemic era. The study showed the overall utilization of audiovisual and telephone encounters increased by 43.4% and 26.2%, respectively. The majority of respondents who provided audiovisual and telephone encounters reported increased patient volume compared with prior to the pandemic, with an average increase of 79.4% and 42.8%, respectively. There was an increase of 69.4% of GCs rendering genetic services from home offices. The percentage of participants who billed for telehealth services increased from 45.7% before the pandemic to 80.3% during the pandemic. The top GC perceived benefits of telehealth included safety for high-risk COVID patients (95.2%) and saved commute time for patients (94.7%). The top GC perceived limitations of telehealth included difficulty to conduct physician evaluation/coordinating with healthcare providers (HCP) (73.7%) and difficulty addressing non-English speaking patients (68.5%). Overall, 89.6% of GCs were satisfied with telehealth; however, 55.3% reported uncertainty whether the newly adopted SDM would continue after the pandemic subsides. Results from this study demonstrate the rapid adoption of telehealth for clinical genetic counseling services as a result of the COVID-19 pandemic, an increase in billing for these services, and support the feasibility of telehealth for genetic counseling as a longer term solution to reach patients who are geographically distant.

Objectives: We sought to examine alcohol use disorder (AUD) among general hospital medical inpatients with respect to identification, service utilization, and initiation of medication-assisted treatment. Methods: We performed a retrospective chart review for all adult inpatients over one full calendar year. Subjects were separated into two categories: patients with chart documentation of an AUD diagnosis and those without such documentation. We extracted from the electronic health record and analyzed information on demographics, service utilization, and treatment initiation of medication-assisted treatment for AUD such as naltrexone, disulfiram, or acamprosate. Results: The study revealed three main findings: 1) Less than one percent of patients discharged from the hospital in one full calendar year had an identified AUD diagnosis. 2) Patients with an AUD diagnosis had a significantly higher number of emergency department (ED) visits and longer hospital length of stay (LOS) but did not have significantly higher 30-day hospital readmissions, compared to patients with no AUD diagnosis. 3) Among patients diagnosed with AUD, only 1.8% received FDA-approved medication-assisted treatment for AUD. Conclusions: The AUD identification rate we detected was markedly lower than prevalence rates reported in the literature. Patients who were identified with AUD had higher counts of ED visits and longer LOS. Initiation rates of medication-assisted treatment for AUD were low. The study findings suggest that concerted efforts are needed to improve detection and diagnosis of AUD in order to support the delivery of effective AUD treatment including the initiation of evidence-based pharmacotherapy for AUD in the general hospital setting.

Background Transversus abdominis plane blocks are increasingly used to achieve opioid-sparing analgesia after colorectal surgery. Traditionally, bupivacaine was the long-acting analgesic of choice, but the addition of dexamethasone and/or epinephrine to bupivacaine may extend block duration. Liposomal bupivacaine has also been suggested to achieve an extended analgesia duration of 72 hours but is significantly more expensive. Objective The purpose of this study was to compare pain control between laparoscopic transversus abdominis plane blocks using liposomal bupivacaine versus bupivacaine with epinephrine and dexamethasone. Design This was a parallel-group, single-institution, randomized clinical trial. Settings The study was conducted at a single tertiary medical center. Patients Consecutive patients between October 2018 to October 2019, ages 18 to 90 years, undergoing minimally invasive colorectal surgery with multimodal analgesia were included. Interventions Patients were randomly assigned 1:1 to receive a laparoscopic transversus abdominis plane block with liposomal bupivacaine or bupivacaine with epinephrine and dexamethasone. Main outcome measures The primary outcome was total oral morphine equivalents administered in the first 48 hours postoperatively. Secondary outcomes included pain scores, time to ambulation and solid diet, hospital length of stay, and complications. Results A total of 102 patients (50 men) with a median age of 42 years (interquartile range, 29-60 y) consented and were randomly assigned. The primary end point, total oral morphine equivalents administered in the first 48 hours, was not significantly different between the liposomal bupivacaine group (median = 69 mg) and the bupivacaine with epinephrine and dexamethasone group (median = 47 mg; difference in medians = 22 mg, (95% CI, -17 to 49 mg); p = 0.60). There were no significant differences in pain scores, time to ambulation, time to diet tolerance, time to bowel movement, length of stay, overall complications, or readmission rate between groups. There were no treatment-related adverse outcomes. Limitations This study was not placebo controlled or blinded. Conclusions This first randomized trial comparing laparoscopic transversus abdominis plane block with liposomal bupivacaine or bupivacaine with epinephrine and dexamethasone showed that a liposomal bupivacaine block does not provide superior or extended analgesia in the era of standardized multimodal analgesia protocols.See Video Abstract at http://links.lww.com/DCR/B533. Estudio prospectivo y randomizado de bloqueo del plano muscular transverso del abdomen realizado por el cirujano con bupivacana versus bupivacana liposomal estudio tingle ANTECEDENTES:El bloqueo anestesico del plano muscular transverso del abdomen se utiliza cada vez mas para lograr una analgesia con menos consumo de opioides despues de cirugia colorrectal. Tradicionalmente, la Bupivacaina era el analgesico de accion prolongada de eleccion, pero al agregarse Dexametasona y/o Adrenalina a la Bupivacaina se puede prolongar la duracion del bloqueo. Tambien se ha propuesto que la Bupivacaina liposomal logra una duracion prolongada de la analgesia de 72 horas, pero es significativamente mas cara.OBJETIVO:Comparar el control del dolor entre bloqueo laparoscopico del plano de los transversos del abdomen usando Bupivacaina liposomal versus Bupivacaina con Adrenalina y Dexametasona.DISENO:Estudio clinico prospectivo y randomizado de una sola institucion en grupos paralelos.AJUSTE:Centro medico terciario unico.PACIENTES:Todos aquellos pacientes entre 18 y 90 anos sometidos a cirugia colorrectal minimamente invasiva con analgesia multimodal, entre octubre de 2018 a octubre de 2019 incluidos de manera consecutiva.INTERVENCIONES:Los pacientes fueron seleccionados aleatoriamente 1:1 para recibir un bloqueo laparoscopico del plano de los transversos del abdomen con Bupivacaina liposomal o Bupivacaina con Adrenalina y Dexametasona.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el total de equivalentes de morfina oral administradas en las primeras 48 horas despues de la operacion. Los resultados secundarios incluyeron puntuaciones de dolor, inicio de dieta solida, tiempo de inicio a la deambulacion, la estadia hospitalaria y las complicaciones.RESULTADOS:Un total de 102 pacientes (50 hombres) con una mediana de edad de 42 anos (IQR 29-60) fueron incluidos aleatoriamente. El criterio de valoracion principal, equivalentes de morfina oral total administrada en las primeras 48 horas, no fue significativamente diferente entre el grupo de Bupivacaina liposomal (mediana = 69 mg) y el grupo de Bupivacaina con Adrenalina y Dexametasona (mediana = 47 mg; diferencia en medianas = 22 mg, IC del 95% [-17] - 49 mg, p = 0,60). No hubo diferencias significativas en las puntuaciones de dolor, tiempo de inicio a la deambulacion, el tiempo de tolerancia a la dieta solida, el tiempo hasta el primer evacuado intestinal, la duracion de la estadia hospitalaria, las complicaciones generales o la tasa de readmision entre los grupos. No hubo resultados adversos relacionados con el tratamiento.LIMITACIONES:Este estudio no fue controlado con placebo ni de manera cegada.CONCLUSIONES:Este primer estudio prospectivo y randomizado que comparo el bloqueo del plano de los musculos transversos del abdomen por via laparoscopica, utilizando Bupivacaina liposomal o Bupivacaina con Adrenalina y Dexametasona, demostro que el bloqueo de Bupivacaina liposomal no proporciona ni mejor analgesia ni un efecto mas prolongado.Consulte Video Resumen en http://links.lww.com/DCR/B533.

BACKGROUND Resection of liver metastasis in small bowel neuroendocrine tumors (SBNET) may improve survival, however, factors influencing prognosis are unclear. We evaluated how the extent of resection influences outcomes. METHODS Patients with SBNET with liver metastasis from 1990 to 2013 who underwent resection of the primary tumor were identified. Outcomes among patients undergoing complete resection (CR), partial resection (PR), or no resection (NR) of liver metastases with resection of the primary tumor only were compared. RESULTS One hundred eleven patients met the criteria. The median number of liver lesions was seven and median lesions resected was one. Fifty (45%) patients had NR, 41 (36.9%) underwent CR, and 20 (18.1%) underwent PR. The 5-year overall survival (OS) was 79.4% for NR, 84.7% for PR, and 100% for CR, demonstrating a trend that CR was best, followed by PR then NR (P = .02). 10-year OS showed no significant differences (72.7% NR; 84.7% PR; 82.5% CR; P = .10). Greater than 10 liver lesions (hazard ratio [HR] 3.6; P = 0.04) or receiving chemotherapy (HR 3.7; P = .03) were negative predictors of survival. CONCLUSION The extent of resection of liver disease in SBNET influenced survival at 5 years but not at 10 years. In addition, more than 10 liver lesions and chemotherapy were predictors of mortality.

Donor-derived cell-free DNA (dd-cfDNA) became Medicare reimbursable in the United States in October 2017 for the detection of rejection in kidney transplant recipients based on results from its pivotal validation trial, but it has not yet been externally validated. We assessed 63 adult kidney transplant recipients with suspicion of rejection with dd-cfDNA and allograft biopsy. Of these, 27 (43%) patients had donor-specific antibodies and 34 (54%) were found to have rejection by biopsy. The percentage of dd-cfDNA was higher among patients with antibody-mediated rejection (ABMR; median 1.35%; interquartile range [IQR]: 1.10%-1.90%) compared to those with no rejection (median 0.38%, IQR: 0.26%-1.10%; P < .001) and cell-mediated rejection (CMR; median: 0.27%, IQR: 0.19%-1.30%; P = .01). The dd-cfDNA test did not discriminate patients with CMR from those without rejection. The area under the ROC curve (AUC) for CMR was 0.42 (95% CI: 0.17-0.66). For ABMR, the AUC was 0.82 (95% CI: 0.71-0.93) and a dd-cfDNA ≥0.74% yielded a sensitivity of 100%, specificity 71.8%, PPV 68.6%, and NPV 100%. The dd-cfDNA test did not discriminate CMR from no rejection among kidney transplant recipients, although performance characteristics were stronger for the discrimination of ABMR.

Transversus abdominis plane block may improve analgesia after colorectal surgery; however, techniques remain unstandardized and results are conflicting.The purpose of this study was to compare laparoscopic and ultrasound-guided transversus abdominis plane block with no block in minimally invasive colorectal surgery.This was a randomized controlled trial.The study was conducted at an urban teaching hospital.Patients undergoing laparoscopic colorectal surgery were included.The intervention included 2:2:1 randomization to laparoscopic, ultrasound-guided, or no transversus abdominis plane block.Morphine use in the first 24 hours after surgery was measured.The study cohort included 107 patients randomly assigned to laparoscopic (n = 41), ultrasound-guided (n = 45), or no transversus abdominis plane block (n = 21). Mean age was 50.4 years (SD ± 18 y), and 50 patients (47%) were men. Laparoscopic transversus abdominis plane block was superior to ultrasound-guided (p = 0.007) and no transversus abdominis plane block (p = 0.007), with median (interquartile range) total morphine used in the first 24 hours postoperatively of 17.6 mg (6.6-33.9 mg), 34.0 mg (16.4-44.4 mg), and 31.6 mg (18.4-44.4 mg). At 48 hours, laparoscopic transversus abdominis plane block remained superior to ultrasound-guided (p = 0.03) and no transversus abdominis plane block (p = 0.007) with median (interquartile range) total morphine used at 48 hours postoperatively of 26.8 mg (15.5-45.8 mg), 44.0 mg (27.6-70.0 mg), and 60.8 mg (34.8-78.8 mg). Mean hospital stay was 5.1 ± 3.1 days without any intergroup differences. Overall complications were similar between groups.Treatment teams were not blinded and there was operator dependence of techniques and variable timing of the blocks.Laparoscopic transversus abdominis plane block is superior to ultrasound-guided and no transversus abdominis plane block in achieving pain control and minimizing opioid use in the first 24 hours after colorectal surgery. A large, multicenter, randomized trial is needed to confirm our findings. See Video Abstract at http://links.lww.com/DCR/A822.

Liver biopsies are commonly performed in heart transplant candidates to confirm congestive hepatopathy (CH) and to assess the degree of fibrosis. Heterogeneity of fibrosis is frequent in CH, making it difficult to stage fibrosis. In this study, we evaluated the prevalence of heterogeneity of fibrosis and nodular regenerative hyperplasia (NRH) in liver biopsies with CH secondary to heart failure. Fifty liver biopsies with CH secondary to heart failure were reviewed. The fibrosis was scored on trichrome stain as follows: stage 0 for no fibrosis, stage 1 for zone 3 fibrosis, stage 2 for zone 3 and portal fibrosis, stage 3 for bridging fibrosis, and stage 4 for cirrhosis. Both stage 3 and stage 4 fibrosis were classified as advanced fibrosis. A predominant pattern of fibrosis and a secondary pattern of fibrosis, defined as a different stage of fibrosis seen in at least 10% of the biopsy material, if present, were recorded. A biopsy was considered to show heterogenous fibrosis if there was at least a 2 stage difference between the predominant and secondary patterns. Thirteen biopsies (26%) showed heterogenous fibrosis. Sixteen biopsies (32%) showed some evidence of advanced fibrosis: 5 had uniform advanced fibrosis, 4 had predominant pattern of advanced fibrosis, and advanced fibrosis was focal in 7 biopsies from 6 patients. NRH-type changes were seen in 9 of 50 biopsies (18%). In conclusion, our study showed heterogenous fibrosis in the liver biopsy of a quarter of patients with CH due to heart failure, highlighting the limitations of fibrosis assessment in the biopsies, and suggests that correlation with the complete clinical information is essential for management decisions.

Background A growing body of evidence has demonstrated racial disparities in bariatric surgery (BS) outcomes. We aimed to investigate the impact of race on postoperative percent excess weight loss (%EWL) and patient satisfaction. Methods Single center retrospective study of patients who underwent BS January 2012 to November 2017. Statistical analysis utilized Chi-squared, ANOVA and multivariable regression. Results A total of 378 patients were included. African American patients lost significantly less weight compared to Caucasian and Hispanic patients (39.0 %EWL, 53.4 %EWL and 52.3 %EWL, respectively). A significant difference remained after adjustment for possible confounders. No difference in postoperative satisfaction was found. Conclusions Our study adds to the existing literature demonstrating racial disparities in BS postoperative EWL, despite adjusting for possible confounders, while contributing to the limited literature examining Hispanic patients. Furthermore, we examined an understudied outcome in postoperative patient satisfaction and found no racial disparity despite disparity in EWL.

Our aim was to investigate the newest generation anti-cyclic citrullinated peptide (CCP) antibody 3.1 assay in diagnosing rheumatoid arthritis (RA) compared with other autoimmune and non-autoimmune diseases. We performed a retrospective observational chart review of patients with a positive CCP level over a one-year period at a single academic institution and assessed the associated diagnoses after at least six-months of follow-up. Of the 281 CCP positive patients during that period, 48% had a diagnosis of RA. The positive predictive value of RA in patients with a high CCP 3.1 assay was 0.619 compared to 0.248 with a low positive CCP 3.1 assay (P

As human and chimpanzee genomes show high homology for IGF1 and PRL, we analyzed the sera of 367 healthy chimpanzees obtained during routine physical examinations in a single colony and measured chimpanzee insulin-like growth factor (IGF)-1 and prolactin (PRL) levels across the lifespan using standard human immunoassays. Assuming chimpanzee IGF-1 levels peak during puberty as in humans, we randomly defined puberty as the age at which most IGF-1 levels were equal to or above the 90th percentile for each sex (males, ages ≥7.00 but

Background: Until now, quality of life (QOL) outcomes after modified selective neurectomy for postfacial paralysis synkinesis (PFPS) have not been assessed. Objective: To evaluate QOL outcomes amon...

Objectives Heart Failure is a chronic syndrome affecting over 5.7 million in the US and 26 million adults worldwide with nearly 50% experiencing depressive symptoms. The objective of the study is to compare the effects of two evidence-based treatment options for adult patients with depression and advanced heart failure, on depressive symptom severity, physical and mental health related quality of life (HRQoL), heart-failure specific quality of life, caregiver burden, morbidity, and mortality at 3, 6 and 12-months. Methods Trial design. Pragmatic, randomized, comparative effectiveness trial. Interventions. The treatment interventions are: (1) Behavioral Activation (BA), a patient-centered psychotherapy which emphasizes engagement in enjoyable and valued personalized activities as selected by the patient; or (2) Antidepressant Medication Management administered using the collaborative care model (MEDS). Participants. Adults aged 18 and over with advanced heart failure (defined as New York Heart Association (NYHA) Class II, III, and IV) and depression (defined as a score of 10 or above on the PHQ-9 and confirmed by the MINI International Neuropsychiatric Interview for the DSM-5) selected from all patients at Cedars-Sinai Medical Center who are admitted with heart failure and all patients presenting to the outpatient programs of the Smidt Heart Institute at Cedars-Sinai Medical Center. We plan to randomize 416 patients to BA or MEDS, with an estimated 28% loss to follow-up/inability to collect follow-up data. Thus, we plan to include 150 in each group for a total of 300 participants from which data after randomization will be collected and analyzed. Conclusions The current trial is the first to compare the impact of BA and MEDS on depressive symptoms, quality of life, caregiver burden, morbidity, and mortality in patients with depression and advanced heart failure. The trial will provide novel results that will be disseminated and implemented into a wide range of current practice settings. Registration ClinicalTrials.Gov Identifier: NCT03688100.

Introduction: Low-flow, low-gradient aortic stenosis (LFLG-AS) is associated with impaired left ventricular (LV) function and afterload mismatch. Indications and timing for transcatheter aortic valve replacement (TAVR) in LFLG-AS do not account for the presence of subclinical LV remodeling. We evaluated whether combining LV global longitudinal strain (GLS) and CT-derived extracellular volume (ECV), both markers of LV remodeling, provides incremental prediction of adverse outcomes in patients with LFLG-AS undergoing TAVR. Methods: We retrospectively evaluated patients with LFLG-AS undergoing TAVR in whom pre-TAVR CT-based ECV measurements were available. GLS was measured in pre-TAVR echocardiograms using speckle tracking. Cox regression analysis was performed with a primary outcome of heart failure hospitalization (HFH) or death. Four sub-groups were identified for analysis based on optimal cutoff points: Group 1 (n=64): ECV< 33 + GLS≥

Due to the low incidence of male breast cancer (BC), there are few studies evaluating outcomes. We evaluated the clinicopathologic features and outcomes of male BC. Male patients with BC from January 2006 to December 2018 were identified. Of 49 patients, mean age was 64 (range 33-94) years. Of the 27 (55.1%) patients who had genetic testing, 9 (33.3%) had a Breast Cancer gene (BRCA) 1 or 2 mutation. The majority of patients had a mastectomy (n = 43/49, 87.8%) and had invasive ductal carcinoma (n = 47/49, 95.9%). 20 patients (n = 20/43, 46.5%) had positive lymph nodes. 41 (n = 41/47, 87.2%) patients had estrogen receptor positive disease. The majority of patients were pathologic stage 2 (n = 21/46, 45.7%), followed by stage 1 (n = 15/46, 32.6%), stage 3 (n = 6/46, 13.0%), and stage 4 (n = 4/46, 8.7%). Eight patients had the 21-gene recurrence score performed. Of patients with stage 1-3 BC, 10 (n = 10/43, 23.3%) patients had recurrence. With median follow-up of 4.1 (range .6-10.6) years, 5-year overall survival was 82.9% and 5-year disease-free survival was 65.9%. In conclusion, our cohort of patients with male BC had a high incidence of BRCA mutations and most commonly had high-grade estrogen positive stage 2 tumors. Breast conserving surgery was utilized in 4% of patients and genomic testing utilized in 55% of patients.

BackgroundThe impact of CD4+ T-cell count and highly active antiretroviral therapy (HAART) on the rate of surgical site infection (SSI) in patients with human immunodeficiency virus (HIV) undergoing total hip arthroplasty is still unclear. The goals of this study were to assess the rate of perioperative infection at a large tertiary care referral center and to identify risk factors in HIV+ patients undergoing total hip arthroplasty (THA).MethodsThis study was a prospective, observational study at a single medical center from 2000–2017. Patients who were HIV+ and underwent THA were followed from the preoperative assessment period, through surgery and for a 2-year follow-up period.ResultsSixteen of 144 HIV+ patients (11%) undergoing THA developed perioperative surgical site infections. Fourteen patients (10%) required revision THA within a range of 12 to 97 days after the initial surgery. The patients’ mean age was 49.6 ± 4.5 years, and the most common diagnosis prompting THA was osteonecrosis (96%). Patients who developed SSI had a lower waist-hip ratio (0.86 vs. 0.93,p= 0.047), lower high density lipoprotein cholesterol (45.8 vs. 52.5,p= 0.015) and were more likely to have post-traumatic arthritis (12.5% vs. 0%,p= 0.008). Logistic regression analysis demonstrated that current alcohol use and higher waist-hip ratio were significant protectors against infection (p< 0.05). No other demographic, medical, immunologic parameters, or specific HAART regimens were associated with perioperative infection.ConclusionsImmunologic status as measured by CD4+ cell count, HIV viral load, and medical therapy do not appear to influence the development of SSI in HIV+ patients undergoing THA. Metabolic factors and post-traumatic arthritis may influence the increased rate of infection in HIV+ patients following THA.

Objective: Chronic rhinosinusitis (CRS) has long been associated with vocal dysfunction. However, studies quantifying the presence of voice dysfunction in CRS patients or the effects of functional endoscopic sinus surgery (FESS) are sparse. The goal of this study was to determine the voice-related quality of life in patients undergoing FESS for CRS using the validated Voice Related Quality of Life Survey (VRQL). We correlated the preoperative VRQL scores to the Sino-Nasal Outcome Test (SNOT-22) scores, and we determined the effect of FESS on postoperative VRQL scores. Methods: Consecutive patients undergoing FESS were preoperatively administered both the VRQL and the SNOT-22 surveys. Spearman (ρ) and Pearson ( r) correlation coefficients were calculated. The VRQL was mailed to patients postoperatively between 3 and 6 months. The paired t-test was used to compare pre- and post-FESS scores. Results: A total of 102 patients were enrolled, and 81 patients completed the two surveys. A total of 51 (62.9%) patients had raw VRQL score ≥ 10, signifying presence of significant vocal symptoms. The mean ± standard deviation (SD) raw VRQL score of the entire study population was 12.4 ± 4.6, and the mean SNOT-22 score was 37.8 ± 19.2. The Spearman correlation coefficient between VRQL and the total SNOT-22 score was 0.34 ( P =.002), and the Pearson correlation coefficient was 0.36 ( P = .001). Both correlations were similar, demonstrating that increasing severity of CRS symptoms correlates with decreasing voice-related quality of life (QOL). Seventy patients completed the postoperative survey for an 86% retention rate. Thirty-six of these patients had abnormal preoperative VRQL scores, and these patients improved significantly after FESS. The mean preoperative versus postoperative raw scores were 15.2 ± 5.6 versus 12.5 ± 4.1, respectively ( P = .003). Conclusion: This study demonstrates the increasing presence of vocal complaints with increasing severity of CRS. It also demonstrates that VRQL scores improve after FESS in those patients with preoperative vocal complaints. Level of Evidence: IV

Supplemental Digital Content is available in the text., Background. Higher Banff inflammation and chronicity scores on kidney transplant biopsies are associated with poorer graft survival, although histology alone has limitations in predicting outcomes. We investigated if integrating donor-derived cell-free DNA (dd-cfDNA, Allosure; CareDx, Inc.) with Banff biopsy scores into a predictive model for estimated glomerular filtration rate over time can improve prognostic assessment versus histology alone. Methods. We identified 180 kidney transplant patients with dd-cfDNA assessed within 1 mo of biopsy. Using linear mixed–effects models, a prediction model of Banff histology scores and dd-cfDNA on estimated glomerular filtration rate over time was derived. Nested models were compared using the likelihood-ratio test, Akaike Information Criterion, and Bayesian Information Criterion to assess if inclusion of dd-cfDNA into a model consisting of Banff biopsy scores would improve model fit. Results. Univariate models identified significant covariate-by-time interactions for cg = 3 versus

Context Combination therapy with somatostatin receptor ligand (SRL) plus pegvisomant for patients with acromegaly is recommended after a maximizing dose on monotherapy. Lower-dose combination regimens are not well studied. Objective To compare cost-effectiveness and efficacy of 3 lower-dose combination regimens in controlled and uncontrolled acromegaly Design and Setting Prospective, randomized, open-label, parallel arm study at a tertiary referral pituitary center. Patients Adults with acromegaly regardless of response to prior SRL and biochemical control status at baseline, stratified by an SRL dose required for insulin-like growth factor (IGF)-I normalization during any 3-month period within 12 months preceding enrollment. Intervention Combination therapy for 24 to 32 weeks on arm A, high-dose SRL (lanreotide 120 mg/octreotide long-acting release [LAR] 30 mg) plus weekly pegvisomant (40-160 mg/week); arm B, low-dose SRL (lanreotide 60 mg/octreotide LAR 10 mg) plus weekly pegvisomant; or arm C, low-dose SRL plus daily pegvisomant (15-60 mg/day) Main Outcome Measure Monthly treatment cost in each arm in participants completing ≥ 24 weeks of therapy. Results Sixty patients were enrolled and 52 were evaluable. Fifty of 52 (96%) demonstrated IGF-I control regardless of prior SRL responsiveness (arm A, 14/15 [93.3%]; arm B, 22/23 [95.7%]; arm C, 14/14 [100%]). Arm B was least costly (mean, $9837 ± 1375 per month), arm C was most expensive (mean, $22543 ± 11158 per month), and arm A had an intermediate cost (mean, $14261 ± 1645 per month). Approximately 30% of patients required pegvisomant dose uptitration. Rates of adverse events were all Conclusions Low-dose SRL plus weekly pegvisomant represents a novel dosing option for achieving cost-effective, optimal biochemical control in patients with uncontrolled acromegaly requiring combination therapy.

Background Mentoring is an essential component of cardiothoracic surgery training, yet trainees report varied experiences despite substantial efforts to enhance mentorship opportunities. This study aimed to evaluate mentorship effectiveness and identify gaps in mentorship education. Methods A survey was distributed to cardiothoracic surgical trainees in Accreditation Council for Graduate Medical Education–accredited programs (n = 531). Responses to 16 questions concerning trainee experiences, expectations, and perspectives on mentorship were collected. An 11-component mentorship effectiveness tool generated a composite score (0 to 55), with a score of 44 or lower indicating less effective mentorship. Results Sixty-seven residents completed the survey (12.6%), with most (83.6%) reporting a current mentor. Trainees with mentors cited “easy to work with and approachable” (44 of 58; 75.9%) as the major criterion for mentor selection, whereas trainees without a mentor reported an inability to identify one who truly reflected the resident’s needs (6 of 11; 45.5%). Resident age, gender, race or ethnicity, marital status, family status, postgraduate year, and training program type or size were not associated with having a mentor (P = .15 to .73). The median mentorship effectiveness score was 51 (interquartile range, 44, 55). More than one-third of residents (25 of 67) had either no mentor (n = 6) or less effective mentorship (n = 16), or both (n = 3). Resident and program characteristics were not associated with mentorship effectiveness (P = .39 to .99). Finally, 61.2% of residents had not received education on effective mentorship, and 53.8% did not currently serve as a mentor. Conclusions Many resident respondents have either no mentor or less effective mentorship, and most reported not having received education on mentorship. Addressing these gaps in mentorship training and delivery should be prioritized.

There is no clear study identifying the microbiome of the appendix. However, in other diverticular conditions, such as diverticulosis, methanogens appear important. We investigated whether patients who had undergone appendectomies had decreased levels of exhaled methane (CH4). Consecutive patients who underwent breath testing (BT) from November 2005 to October 2013 were deterministically linked to electronic health records. The numbers of patients with CH4 ≥ 1 ppm (detectable) and ≥ 3 and ≥ 10 ppm (excess) were compared between patients who did and did not undergo appendectomy using a multivariable model adjusted for age and sex. Of the 4977 included patients (48.0 ± 18.4 years, 30.1% male), 1303 (26.2%) had CH4 ≥ 10 ppm, and 193 (3.9%) had undergone appendectomy. Appendectomy was associated with decreased odds of CH4 ≥ 1, ≥ 3, and ≥ 10 ppm (ORs (95% CI) = 0.67 (0.47–0.93), p = 0.02; 0.65 (0.46–0.92), p = 0.01; and 0.66 (0.46–0.93), p = 0.02, respectively). Additionally, the percentage of CH4 producers increased 4-fold from the first to ninth decade of life. This is the first study to report that appendectomy is associated with decreased exhaled CH4. The appendix may play an active physiologic role as a reservoir of methanogens.

Background: Severity of illness and mortality from coronavirus disease 2019 (COVID-19) is consistently lower in women than in men. While this outcome difference is not well understood, focus on sex as a biologic factor may suggest potential therapeutic intervention for this disease. We assessed whether adding progesterone, a steroid hormone with immune-modulatory properties, to standard of care, would improve clinical outcomes of hospitalized men with moderate to severe COVID-19. Method: We conducted a Phase 1, randomised, open-label, controlled trial at a large academic hospital in Los Angeles, CA, USA, of subcutaneous progesterone in men hospitalized with confirmed COVID-19 and evidence of lower respiratory tract involvement. Patients were randomly assigned (1:1), using block randomization and a computer-generated randomization sequence, to receive standard of care (SOC) plus progesterone (100 mg subcutaneously twice daily for up to five days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status based on a 7-point ordinal scale noted at baseline compared to that on Day 7 of the trial. Control patients with significant clinical deterioration or absence of clinical improvement by Day 7 were permitted to cross over to receive progesterone therapy. Intention to treat analysis was performed and the patient’s last clinical assessment prior to receiving the study drug was imputed as the Day 7 assessment. Findings: Forty-two patients were enrolled in the study from April 27 to August 20, 2020; 22 were randomised to the control group and 20 to the progesterone group. Of the 20 patients in the progesterone group, two withdrew from the study prior to receiving progesterone and were excluded from analysis. There was an overall improvement in clinical status from baseline to Day 7 in patients in the progesterone group as compared to controls (95% CI: 0-2; P = 0·010). There were no serious adverse events attributable to progesterone. Interpretation: Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to standard of care may represent a safe and novel approach for the treatment in men with moderate to severe COVID-19. Trial Registration: This trial was registered at ClinicalTrials.gov, NCT04365127. Funding Statement: The Institut Biochimique SA (IBSA, Lugano, Switzerland) Declaration of Interests: SG, YM, SP, TK, DN, JH, SC, RIG, JM, CB, ML, VT report grants and nonfinancial support from Institut Biochimique SA (IBSA, Lugano, Switzerland), during the conduct of the study; SG,SP report patent pending on method of use of progesterone agonist for treatment of COVID-19 VT reports grants from NIH/NIAID ACTT (ACTT 1-3), outside the submitted work. DS, HG declare no competing interests. Ethics Approval Statement: This study was approved by the Cedars-Sinai Institutional Review Board (IRB).

Outcomes based on menopausal status of breast cancer (BC) patients who are BRCA mutations carriers (BRCAm) are not well known. A prospective database identified 88 BRCAm with BC from 2005 to 2015. Of the 88 patients, 68 (77.3%) women were premenopausal (Pre-M) and 20 (22.7%) were postmenopausal (Post-M). In the Pre-M group, 52.9 per cent of patients had triple-negative (TN) BC, whereas in the Post-M group, there were more estrogen receptor +(65%; P = 0.129) and less TN (25%; P = 0.041) tumors. Median tumor size was significantly larger in the Pre-M group compared with the Post-M group ( P

Data from pathology reports of estrogen receptor positive (ER+) breast cancers with Ki67 < 14% (luminal-A; n = 128) and Ki67 ≥ 14% (luminal-B; n = 100) were entered into the automatic recurrence score (RS) calculator accessible at the University of Pittsburgh Department of Pathology website. Using RS obtained with Magee equations #1 and #3, an average modified Magee recurrence score (AMM RS) was calculated for each tumor. The AMM RS and the Oncotype DX RS (Onco RS) were compared per tumor and associated with follow-up. AMM RS and Onco RS agreed in 64.9% (148 of 228) breast cancers (70.3% luminal-A and 58% luminal-B). There was only one two-step (low risk by Onco/high risk by AMM) RS disagreement. This luminal-B patient is alive without recurrence and free of tumor at 46 months postdiagnosis. Low-risk/intermediate-risk disagreements comprised 94.7% (36 of 38) and 69% (29 of 42) of the RS disagreements in the luminal-A and luminal-B groups, respectively (P = 0.004). In luminal-A, there were only two intermediate/high-risk disagreements; both high-risk ratings were by Onco RS. In luminal-B, there were 12 intermediate/high-risk disagreements; 11 of the high-risk ratings were by Onco RS. 100% (3 of 3) luminal-A tumors and 75% (6 of 8) luminal-B tumors that were high risk by AMM RS were also high risk by Onco RS. Eight tumors recurred and/or metastasized. AMM RS and Onco RS disagreed in only two of these eight tumors. The high percentage of tumors scored as intermediate risk (50% by AMM RS and 39% by Onco RS) is a major limitation of both scoring algorithms.

This study provides a comprehensive analysis of total hip arthroplasty (THA) revisions in the U.S. from 2007 to 2013.International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify all THA revisions in the Nationwide Inpatient Sample (NIS) from 2007 to 2013. The diagnoses leading to the revisions, types of revisions, major inpatient complications, and hospital and patient characteristics were compared between 2007 and 2013. Multivariable logistic regression models were used to calculate adjusted odds ratios (ORs) for complications in 2013 versus 2007.This study identified 320,496 THA revisions performed between 2007 and 2013. From 2007 to 2013, the THA revision rate adjusted for U.S. population growth increased by 30.4% in patients between 45 and 64 years of age and decreased in all other age groups. The rate of surgically treated THA dislocations decreased by 14.3% from 2007 to 2013 (p0.0001). The mean length of the hospital stay and hospital costs for THA revision were significantly lower in 2013 than in 2007 (4.6 versus 5.8 days and $20,463 versus $25,401 both p0.0001). A multivariable model showed that the odds of a patient undergoing THA revision having the following inpatient complications were significantly lower in 2013 than in 2007: deep vein thrombosis (OR = 0.57, p = 0.004), pulmonary embolism (OR = 0.45, p = 0.047), myocardial infarction (OR = 0.52, p = 0.003), transfusion (OR = 0.64, p0.0001), pneumonia (OR = 0.56, p0.0001), urinary tract infection (OR = 0.66, p0.0001), and mortality (OR = 0.50, p = 0.0009). Notably, the odds of being discharged to a skilled nursing facility were also lower in 2013 than in 2007 (OR = 0.71, p0.0001).The THA revision rate has significantly increased in patients between 45 and 64 years of age. However, the rate of surgically treated THA dislocations has decreased significantly. This may indicate that evolving techniques and implants are improving stability. The rate of inpatient complications following THA revision also decreased significantly from 2007 to 2013.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Measuring IGF-1, a biomarker for GH activity, is critical to evaluating disordered hypothalamic-pituitary GH axis. Inconsistent IGF-1 measurements among different immunoassays are well documented. We switched from Immulite 2000 immunoassay to narrow-mass-extraction, high-resolution liquid chromatography mass-spectrometry (LC-MS) compliant with recent consensus recommendations on assay standardization. Comparability of these two assays in patients with pituitary disease in a clinical practice setting is not known. We sought to compare IGF-1 levels on Immulite 2000 and LC-MS in samples from naive and treated patients with secretory and non-secretory pituitary masses. We prospectively collected serum samples from 101 patients treated at the Cedars-Sinai Pituitary Center between February 2012 and March 2014. We intentionally recruited more patients with acromegaly or GH deficiency to ensure a clinically representative cohort. Samples were classified as in or out of the respective reference ranges. Bland–Altman analysis was used to assess agreement between assays. Twenty-four percent of samples were classified differently as below, in, or above range. Agreement between the assays was poor overall, with a significant bias for immunoassay reporting higher values than LC-MS. This pattern was also observed in patients with acromegaly and those with ≥ 2 pituitary hormone deficiencies. IGF-1 results may differ after switching from an older immunoassay to a consensus-compliant assay such as LC-MS. Clinicians should consider the potential impact of assay switching before altering treatment due to discrepant results, particularly in patients monitored over time, such as those with acromegaly and GH deficiency.

Remission from Cushing disease (CD) after pituitary adenoma resection may be predicted by a postoperative reduction in serum cortisol level. A 2008 consensus statement recommends assessing morning cortisol levels during the first postoperative week, and replacing glucocorticoid (GC) if cortisol nadir of 2 or 5 µg/dL is achieved. We sought to evaluate adherence to consensus recommendations following adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma resection at our tertiary medical center, and assess time to cortisol nadir to better define the window for assessment and intervention.We retrospectively analyzed data extracted from in-hospital electronic medical records for CD surgeries between January 1991 and September 2015. We compared cortisol levels and collection times, ACTH measurement, and postoperative and discharge GC treatment before and after consensus statement publication in July 2008.107 surgeries were performed in 92 patients with CD. After 2008, more surgeries had at least one cortisol value assessed (67.9% before vs. 91.3% after, p = 0.033), with median initial cortisol measurement at 14 h post-surgery. However, ACTH measurement remained unchanged (42.9% vs. 43.5%; p 0.99). Cortisol collection during GC treatment tended to increase (32.7% vs. 57.1%; p = 0.068). Of surgeries performed without prior GC treatment, 31.7 and 55.0% had a cortisol nadir of 2 and 5 µg/dL, respectively, within 72 h postoperative.Our physicians were more diligent in measuring in-hospital postoperative cortisol levels consistent with 2008 consensus recommendations. Better management of cortisol measurements and their timing is an opportunity for improvement.

BACKGROUND Geriatric femoral neck fractures are associated with substantial morbidity and medical cost. We evaluated the incidence and management trends of femoral neck fractures in recent years in the U.S. METHODS Patient data from 2003 through 2013 were obtained from the Nationwide Inpatient Sample database. Femoral neck fractures in patients ≥65 years old were identified and grouped using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes for internal fixation, hemiarthroplasty, or total hip arthroplasty (THA). The nationwide incidence of femoral neck fractures was calculated and presented as an age-adjusted population rate. Univariable methods were used for trend analysis and comparisons between groups. Logistic regression modeling was used to analyze complications. RESULTS From 2003 to 2013, we identified 808,940 femoral neck fractures in patients ≥65 years old. The national age-adjusted incidence of femoral neck fractures decreased from 242 per 100,000 U.S. adults in 2003 to 146 in 2013. The proportion of fractures managed operatively with THA increased over time (5.9% in 2003 versus 7.4% in 2013; p < 0.001). Concurrently, the use of hemiarthroplasty declined (65.1% versus 63.6%; p < 0.001). In 2013, the median age of the patients treated with THA was significantly younger (77.3 years) compared with that in the hemiarthroplasty and internal fixation groups (83.2 and 82.0 years). The THA group had significantly higher median initial hospital costs ($17,097) compared with the hemiarthroplasty and internal fixation groups ($14,776 and $10,462). CONCLUSIONS In the last decade, the total number and population rate of femoral neck fractures in the elderly declined significantly. There was a modest but significant increase in the utilization of THA. CLINICAL RELEVANCE This report identifies the changing trends in clinical practice in the treatment of geriatric femoral neck fractures in the U.S. Treating physicians should be aware of these trends, which include a decreasing national incidence of geriatric femoral neck fractures as well as an increase in the use of THA.

Small bowel neuroendocrine tumors (SBNET) account for most gastrointestinal neuroendocrine tumors. Patients often present with late-stage disease; however, there is little information regarding factors that contribute to recurrence. Database review identified 301 patients diagnosed with SBNET between 1990 and 2013. Univariate analysis included patients who underwent complete resection. Survival was estimated by the Kaplan–Meier method. A total of 147 patients met study criteria. Average age was 60 years (range 21–91); 49 per cent were male. Thirty-seven (25.3%) patients had laparoscopic resection, and 29 (19.9%) patients had only small bowel disease, whereas 108 (72.6%) had nodal metastasis. Five-year overall and disease-free survival were 97.5 and 73.5 per cent. Forty-seven (32%) patients had recurrence. The recurrence group was more likely to have an open operation (59.6 vs 32%, P < 0.01), mesenteric invasion, or lymphatic metastasis (87.2 vs 67%, P < 0.01) compared with the no-recurrence group. Cox regression analysis showed that variables associated with recurrence included nodal disease (HR 9.06, P = 0.03), lymphovascular invasion (LVI) (3.95, P < 0.01), perineural invasion (PNI) (3.48, P < 0.01), and mesenteric involvement (3.77, P = 0.03). Patients with SBNET presenting with nodal metastasis, mesenteric involvement, LVI, or PNI have a higher risk of recurrence. Closer surveillance should be considered after operative resection.

Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Design: Prospective controlled study in an outpatient clinic. Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches., In a pilot study, the HPA axis was dysfunctional and downregulated in PTSD subjects vs matched healthy control subjects, suggesting the potential of endocrine targeting approaches in PTSD patients.

Background We report clinical experience with combined heart and kidney transplantation (HKTx) over a 23-year time period. Methods From June 1992 to August 2015, we performed 83 combined HKTx procedures at our institution. We compared the more recent cohort of 53 HKTx recipients (group 2, March 2009 to August 2015) with the initial 30 previously reported HKTx recipients (group 1, June 1992 to February 2009). Pre-operative patient characteristics, peri-operative factors, and post-operative outcomes including survival were examined. Results The baseline characteristics of the two groups were similar, except for a lower incidence of ethanol use and higher pre-operative left-ventricular ejection fraction, cardiac output, and cardiac index in group 2 when compared with group 1 (P = .007, .046, .037, respectively). The pump time was longer in group 2 compared with group 1 (153.30 ± 38.68 vs 129.60 ± 37.60 minutes; P = .007), whereas the graft ischemic time was not significantly different between the groups, with a trend to a longer graft ischemic time in group 2 versus group 1 (195.17 ± 45.06 vs 178.07 ± 52.77 minutes; P = .056, respectively). The lengths of intensive care unit (ICU) and hospital stay were similar between the groups (P = .083 and .39, respectively). In addition, pre-operative and post-operative creatinine levels at peak, discharge, 1 year, and 5 years and the number of people on post-operative dialysis were similar between the groups (P = .37, .75, .54, .87, .56, and P = .139, respectively). Overall survival was not significantly different between groups 2 and 1 for the first 5 years after transplant, with a trend toward higher survival in group 2 (P = .054). Conclusions The most recent cohort of combined heart and kidney transplant recipients had similar ICU and hospital lengths of stay and post-operative creatinine levels at peak, discharge, and 1 and 5 years and a similar number of patients on post-operative dialysis when compared with the initial cohort. Overall survival was not significantly different between the later and earlier groups, with a trend toward higher overall survival at 5 years in the more recent cohort of patients. In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation is safe to perform and has excellent outcomes.

Thromboembolic (TE) events and hemorrhagic complications continue to remain as frequent adverse events and causes of death after mechanical circulatory support device (MCSD) implantation. To counterbalance this postimplant multifactorial hypercoagulable state, antithrombotic therapy given postimplant must be individually tailored to keep patient adequately anticoagulated yet normocoagulable. Prior studies describing different anticoagulation protocols do not define normocoagulability for patients on MCSDs. We evaluated the role of thromboelastography platelet mapping (TEG PM) in defining "normocoagulability" for MCS patients on anticoagulant (warfarin) and antiplatelet agents. Ninety-eight MCSD patients who underwent TEG PM assay at our institution from 2012 to 2014 were included for retrospective analysis. Eleven (11.2%) subjects developed at least one TE event during the study period. Of the 13 TE events, 8 occurred in patients with total artificial heart (TAH). TEG parameters closest to the event or when patient was clinically adequately anticoagulated and corresponding international normalized ratio (INR) were measured. Thromboelastography coagulation index (CI) appears to be the single most statistically significant parameter that can be used to designate a patient as normocoagulable. Based on our results, patients with HeartMate II (HM II) and Heart Ware (HW) devices should be maintained at a CI value of less than or equal to 1.5 whereas patients with TAH devices should be maintained at a CI less than or equal to 1.2. The CI should be correlated with the degree of Vitamin K-dependent coagulation factor inhibition that is achieved using device-specific goal INR ranges. A recent modification, TEG PM assesses the effects of antiplatelet drug. Maximal amplitude arachidonic acid (MA-AA) < 50 and maximal amplitude adenosine diphosphate (MA-ADP) < 50 are desired for normocoagulable state.

Alcohol use disorders (AUDs) are common among persons with major depressive disorder (MDD) and have an adverse impact on course of illness and patient outcomes. The aim of this study was to examine whether AUD adversely impacted patient-centered outcomes in a sample of research subjects evaluated as part of a large clinical trial for depression. The outcomes of interest to this post hoc analysis are quality of life (QOL), functioning, and depressive symptom severity.We analyzed 2280 adult MDD outpatient research subjects using data from the Sequenced Treatment Alternatives to Relieve Depression trial. We compared entry and post-selective serotonin reuptake inhibitors (SSRI) treatment QOL, functioning, and depressive symptom severity scores between 121comorbid MDD with AUD (MDD + AUD) subjects and 2159 MDD-no-AUD subjects, and also differences between subjects categorized as remitters versus nonremitters within each group at exit.At entry, MDD + AUD subjects reported similar QOL, functioning, and depressive symptom severity compared with the MDD-no-AUD subjects. After treatment with citalopram, both groups showed significant improvements throughout treatment; however, 36% to 55% of subjects still suffered from severely impaired QOL and functioning at exit.The overall study population demonstrated a significant response to treatment with large effect sizes in depressive symptom reduction, but to a lesser extent in QOL and functioning. Findings suggest that subjects with MDD + AUD benefited equally as MDD-no-AUD from treatment with selective serotonin reuptake inhibitors (SSRI) medication, yet both groups continue to experience reduced QOL and functioning after treatment. Monitoring QOL and functioning is critical to determine whether interventions that improve clinical outcomes also impact patient-centered outcomes, and our analysis suggests that there is a pressing need for innovative interventions that effectively improve these outcomes.

Objectives Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) often have high comorbidity, consequently influencing patient-reported outcomes of depressive symptom severity, quality of life (QOL), and functioning. We hypothesized that the combined effects of concurrent PTSD and MDD would result in worse treatment outcomes, whereas individuals who achieved MDD remission would have better treatment outcomes. Methods We analyzed 2280 adult participants who received level 1 treatment (citalopram monotherapy) in the Sequenced Treatment Alternatives to Relieve Depression study, including 2158 participants with MDD without comorbid PTSD and 122 participants with MDD with comorbid PTSD (MDD + PTSD). Post hoc analysis examined the proportion of participants whose scores were within normal or severely impaired for functioning and QOL. Remission status at exit from MDD was also determined. Results At entry, participants with MDD + PTSD experienced significantly worse QOL, functioning, and depressive symptom severity compared with participants with MDD without comorbid PTSD. Although both groups had significant improvements in functioning and QOL posttreatment, the participants with MDD + PTSD were less likely to achieve remission from MDD. Conclusions Findings suggested that participants with MDD + PTSD are at a greater risk for severe impairment across all domains and less likely to achieve remission from MDD after treatment with citalopram monotherapy. As such, the use of patient-reported measures of QOL and functioning may inform practicing clinicians' and clinical trial researchers' abilities to develop appropriate interventions and monitor treatment efficacy. More importantly, we encourage clinicians and health care providers to routinely screen for PTSD in patients with MDD because this at-risk group requires tailored and specific pharmacotherapy and psychotherapy interventions beyond traditionally standard treatments for depression.

Black Americans suffer disproportionately from hypertension and hypertensive heart disease. Out-of-office blood pressure (BP) is more predictive for cardiovascular complications than clinic BP; however, the relative abilities of clinic and out-of-office BP to predict left ventricular hypertrophy in black and white adults have not been established. Thus, we aimed to compare associations of out-of-office and clinic BP measurement with left ventricular hypertrophy by cardiac magnetic resonance imaging among non-Hispanic black and white adults. In this cross-sectional study, 1262 black and 927 white participants of the Dallas Heart Study ages 30 to 64 years underwent assessment of standardized clinic and out-of-office (research staff-obtained) BP and left ventricular mass index. In multivariable-adjusted analyses of treated and untreated participants, out-of-office BP was a stronger determinant of left ventricular hypertrophy than clinic BP (odds ratio per 10 mm Hg, 1.48; 95% CI, 1.34–1.64 for out-of-office systolic BP and 1.15 [1.04–1.28] for clinic systolic BP; 1.71 [1.43–2.05] for out-of-office diastolic BP, and 1.03 [0.86–1.24] for clinic diastolic BP). Non-Hispanic black race/ethnicity, treatment status, and lower left ventricular ejection fraction were also independent determinants of hypertrophy. Among treated Blacks, the differential association between out-of-office and clinic BP with hypertrophy was more pronounced than in treated white or untreated participants. In conclusion, protocol-driven supervised out-of-office BP monitoring provides important information that cannot be gleaned from clinic BP assessment alone. Our results underscore the importance of hypertension management programs outside the medical office to prevent hypertensive heart disease, especially in high-risk black adults. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00344903.