Late-"de novo" paraesophageal hernia after Roux-en-Y gastric bypass (RYGB)-should it be repaired?

BACKGROUND: This study presents a case series of "de novo" paraesophageal hernia (dnPEH) in post-Roux-en-Y gastric bypass (RYGB) patients and analyzes the predisposing factors, symptoms, and outcomes after repair. This is a lesser known complication after RYGB and when symptomatic, may warrant surgery. METHODS: A retrospective review of data from a single academic institution from 2002 to 2022 was performed identifying patients who developed dnPEH after RYGB and compared them to patients with primary RYGB without post-operative symptomatic dnPEH. Patient characteristics from initial RYGB were analyzed to identify predisposing factors for dnPEH development. Additional information analyzed included time to dnPEH repair, indications for surgery, types of herniation, type of surgical repair, and symptom resolution. RESULTS: There were 6975 RYGB in the study period of which 6619 underwent RYGB alone at index surgery, with 31 of those patients developing late stage PEH requiring repair. Patients with older age (51.8 years with dnPEH vs 45.2 years without, p = 0.001) and increased weight loss at 1 year (33.4% vs 30.5%, p = 0.048) from index RYGB were more likely to develop dnPEH. The incidence of dnPEH was 31/6619 (0.47%). Late dnPEH after RYGB took an average of 74 months (45-102 months IQR) to develop symptoms and undergo repair. The most common symptoms were heartburn/reflux 19/31 (61.3%) and epigastric pain 13/31 (41.9%). Symptom resolution rate after repair was highest with 100% for globus and 89.5% heartburn/reflux. The most common form of dnPEH was pouch herniation in 25/31. Surgical repair most commonly included primary cruroplasty alone in 25/31 with additional mesh in 1 case. Recurrence rate was 2/31 (6.54%). CONCLUSION: Late dnPEH after RYGB is an emerging entity typically occurring years after index RYGB. Symptomatic patients with dnPEH warrant hernia repair and responded well to surgical repair in this case series.

Traditions and innovations in assessment of glomerular filtration rate using creatinine to cystatin C.

PURPOSE OF REVIEW: Glomerular filtration rate (GFR) is the best index for kidney function and estimated GFR (eGFR) calculated from endogenous filtration markers like serum creatinine and cystatin C is widely used in clinical practice for chronic kidney disease diagnosis and prognostication. We sought to review the evolution of GFR estimating equations, nuances of eGFR interpretation, and utility of eGFR in drug dosing. RECENT FINDINGS: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) serum creatinine eGFR equation was recently updated to exclude the race variable and the CKD-EPI creatinine-cystatin C equation demonstrated the highest reliability. Although calculated creatinine clearance by Cockcroft Gault has been traditionally used for drug dosing, the use of eGFR is slowly being adapted by the Food and Drug Administration for pharmacokinetic studies. However, the individual-level accuracy of eGFR using the CKD-EPI 2021 equations remained low, with the distribution of measured GFR at a given eGFR value spanning several CKD stages. SUMMARY: Although current methods of estimating GFR have improved in population measures of reliability, all have significant individual-level inaccuracies that can be an issue when clinical decision-making is contingent on the actual level of GFR. Modern methods of GFR measurements should be made widely available to enhance individualized patient decision-making.

Fertility and pregnancy outcomes in women with nonclassic 21-hydroxylase deficiency.

INTRODUCTION: Overall fertility and pregnancy outcomes in patients with nonclassic congenital adrenal hyperplasia (NCCAH) have been poorly studied. It has been suggested that hydrocortisone (HC) may decrease the time to conceive (TTC) and the rate of miscarriage in these patients. OBJECTIVES: To describe fertility and pregnancy outcomes in a large cohort of NCCAH women. The secondary objective was to identify factors that could impact reproductive outcomes, with a particular focus on HC dose and genetic status. DESIGN: Retrospective study in a referral center for congenital adrenal hyperplasia. PATIENTS AND MEASUREMENTS: One hundred seventy-three female patients with NCCAH confirmed by genetic testing, followed in our center between 2010 and 2019. RESULTS: Among the 173 patients, 95 women had a parental project, 86 of whom presented 176 pregnancies, 56% under glucocorticoid (GC) treatment and 44% without, and 76 women obtained 128 live births. Two-thirds of the patients regularized their cycle under GC treatment, with significant decrease of androgens and progesterone levels. This treatment was associated with a shortening of TTC (coef ß = -.196, information coefficient [IC] = [-10.7; -0.91], p = .021). Androgen levels and TTC were positively correlated to the rate of miscarriage (OR = 4.8, IC = [1.15; 20.34], p = .021 for testosterone, OR = 1.4, IC = [1.05; 1.81], p = .02 for androstenedione, and OR = 1.03, IC = [1.01; 1.06], p = .015 for TTC). There was no difference in terms of obstetric outcomes between patients with or without GC treatment. CYP21A2 genotype had no impact on pregnancy outcome or TTC. CONCLUSIONS: Infertility is relative in patients with NCCAH. HC seems beneficial for fertility and pregnancy outcomes, especially for patients with menstrual disorders and high preconceptional androgen levels.

Impact of sex differences on cardiac injury in critically ill patients with COVID-19.

BACKGROUND: COVID-19 infections are associated with accrued inflammatory responses which may result in cardiac injury. Immune response to infection appears different between men and women, suggesting that COVID-19 patients' outcomes may differ according to biological sex. However, the impact of biological sex on the occurrence of cardiac injury during intensive care unit (ICU) stay in COVID-19 patients remain unclear. METHODS: In this multicenter and prospective study, we included consecutive patients admitted to ICU for severe COVID-19 pneumonia, during the first two pandemic waves. Biological, electrocardiogram (ECG) and echocardiographic variables were collected on ICU admission. Cardiac injury was defined by increased troponin above 99th percentile of upper norm value and newly diagnosed ECG and/or echocardiographic abnormalities. The primary endpoint was the proportion of patients with cardiac injury during ICU stay according to biological sex. The impact of biological sex on other subsequent clinical outcomes was also evaluated. RESULTS: We included 198 patients with a median age of 66 (56-73) years, 147 (74%) patients were men and 51 (26%) were women. Overall, 119 (60%) patients had cardiac injury during ICU stay and the proportion of patients with cardiac injury during ICU stay was not different between men and women (60% vs. 61%, p = 1.00). Patients with cardiac injury during ICU stay showed more cardiovascular risk factors and chronic cardiac disease and had a higher ICU mortality rate. On ICU admission, they had a more marked lymphopenia (0.70 (0.40-0.80) vs. 0.80 (0.50-1.10) × 109/L, p < 0.01) and inflammation (C-Reactive Protein (155 (88-246) vs. 111 (62-192) mg/L, p = 0.03); D-Dimers (1293 (709-2523) vs. 900 (560-1813) µg/L, p = 0.03)). Plasmatic levels of inflammatory biomarkers on ICU admission correlated with SAPS-2 and SOFA scores but not with the different echocardiographic variables. Multivariate analysis confirmed cardiovascular risk factors (OR = 2.31; 95%CI (1.06-5.02), p = 0.03) and chronic cardiac disease (OR = 8.58; 95%CI (1.01-73.17), p = 0.04) were independently associated with the occurrence of cardiac injury during ICU stay, whereas biological sex (OR = 0.88; 95%CI (0.42-1.84), p = 0.73) was not. Biological sex had no impact on the occurrence during ICU stay of other clinical outcomes. CONCLUSIONS: Most critically ill patients with COVID-19 were men and experienced cardiac injury during ICU stay. Nevertheless, biological sex had no impact on the occurrence of cardiac injury during ICU stay or on other clinical outcomes. Clinical trial registration NCT04335162.

Does bioabsorbable mesh reduce hiatal hernia recurrence rates? A meta-analysis.

INTRODUCTION: The use of bioabsorbable mesh at the hiatus is controversial. Long-term data are scant. We evaluated the world literature and performed a meta-analysis to determine if these meshes were effective in reducing recurrence. METHODS: A literature search was performed using PubMed, MEDLINE, and ClinicalKey. We evaluated articles reporting on both Bio-A™ (polyglycolic acid:trimethylene carbonate-PGA:TMC) and Phasix™ (poly-4-hydroxybutyrate-P4HB) used at the hiatus. The DerSimonian-Laird random effects model was used to estimate the overall pooled treatment effect along with a 95% confidence interval (CI). Similar analysis was conducted to compare the clinical outcomes, i.e., recurrence rate, mean surgical time, mean hospital stays and mean follow-up duration between non-Mesh and Mesh group. The I2 statistic was computed to assess the heterogeneity in effect sizes across the studies. RESULTS: A total of 21 studies (12 mesh studies with 963 subjects and 9 non-mesh studies with 617 subjects) were included to conduct the meta-analysis. There was one article reporting outcomes on P4HB mesh (73 subjects) and 11 on PGA:TMC mesh (890 subjects). The bioabsorbable mesh group had a significantly lower recurrence rate compared to the non-mesh group (8% vs. 18%; 95%CI 0.08-0.17), pooled p-value < 0.0001. Surgery time was shorter in the mesh group compared to the non-mesh group (136.4 min vs. 150 min) but not statistically significant (p = 0.54). There tended to be a more extended follow-up period after surgery in the non-mesh group compared to the mesh group (27 vs. 25.8 months, range 10.8-54 months); but not statistically significant (ES: 27.4; 95%CI 21.6-33.3; p = 0.92). CONCLUSIONS: Hiatal hernia repair with bioabsorbable mesh is more effective at reducing hernia recurrence rate in the mid-term than simple suture cruroplasty. Further studies investigating the long-term outcomes and P4HB mesh are needed.

Persistent diaphragm dysfunction after cardiac surgery is associated with adverse respiratory outcomes: a prospective observational ultrasound study.

BACKGROUND: Transient diaphragm dysfunction is common during the first week after cardiac surgery; however, the precise incidence, risk factors, and outcomes of persistent diaphragm dysfunction are not well described. METHODS: In a single-centre prospective cohort study, we included all consecutive patients over 18 yr who underwent elective cardiac surgery. Diaphragm function was evaluated with ultrasound (M-mode) by recording the excursion of both hemidiaphragms at two different time points: preoperatively and after the seventh postoperative day in patients breathing without assistance. Significant diaphragm dysfunction after the seventh day of the index cardiac surgery was defined as a decrease in diaphragm excursion below the lower limit of normal: at rest, < 9 mm for women and < 10 mm for men; after a sniff test, < 16 mm for women and < 18 mm for men. RESULTS: Overall, 122 patients were included in the analysis. The median [interquartile range (IQR)] age was 69 [59-74] years and 96/122 (79%) were men. Ten (8%) patients had diaphragm dysfunction after the seventh postoperative day. We did not identify risk factors for persistent diaphragm dysfunction. Persistent diaphragm dysfunction was associated with a longer median [IQR] duration of noninvasive (8 [0-34] vs 0 [0-0] hr; difference in medians, 8 hr; 95% confidence interval [CI], 0 to 22; P < 0.001) and invasive mechanical ventilation (5 [3-257] vs 3[2-4] hr; difference in medians, 2 hr; 95% CI, 0.5 to 41; P = 0.008); a higher reintubation rate (4/10, 40% vs 1/112, 0.9%; relative risk, 45; 95% CI, 7.1 to 278; P < 0.0001), a higher incidence of pneumonia (4/10 [40%] vs 7/112 [6%]; relative risk, 6; 95% CI, 2 to 16; P < 0.001), and longer median [IQR] length of stay in the intensive care unit (8 [5-29] vs 4 [2-6] days; difference in medians, 4 days; 95% CI, 2 to 12; P = 0.002). CONCLUSION: The incidence of persistent diaphragm dysfunction was 8% in patients undergoing elective cardiac surgery and was associated with adverse respiratory outcomes. STUDY REGISTRATION: ClinicalTrials.gov (NCT04276844); prospectively registered 19 February 2020.

RéSUMé: CONTEXTE: Un dysfonctionnement transitoire du diaphragme est fréquent au cours de la première semaine après une chirurgie cardiaque. Toutefois, l'incidence précise, les facteurs de risque et les devenirs liés à un dysfonctionnement persistant du diaphragme ne sont pas bien décrits. MéTHODE: Dans une étude de cohorte prospective monocentrique, nous avons inclus tous les patients consécutifs de plus de 18 ans qui ont bénéficié d'une chirurgie cardiaque non urgente. La fonction du diaphragme a été évaluée à l'échographie (mode M) en enregistrant l'excursion des deux hémidiaphragmes à deux moments différents : avant l'opération et après le septième jour postopératoire chez les patients respirant sans assistance. Un dysfonctionnement significatif du diaphragme après le septième jour de la chirurgie cardiaque initiale a été défini comme une diminution de l'excursion diaphragmatique en dessous de la limite inférieure de la normale, soit : au repos, < 9 mm pour les femmes et < 10 mm pour les hommes; après un test de reniflement, < 16 mm pour les femmes et < 18 mm pour les hommes. RéSULTATS: Au total, 122 patients ont été inclus dans l'analyse. L'âge médian des patients (écart interquartile [ÉIQ]) était de 69 ans [59-74] ans et 96/122 (79 %) étaient des hommes. Dix (8 %) patients ont présenté un dysfonctionnement du diaphragme après le septième jour postopératoire. Nous n'avons pas identifié de facteurs de risque de dysfonctionnement persistant du diaphragme. Un dysfonctionnement persistant du diaphragme était associé à : une durée médiane [ÉIQ] de ventilation non invasive (8 [0­34] vs 0 [0­0] h; différence dans les médianes, 8 heures; intervalle de confiance [IC] à 95 %, 0 à 22; P < 0,001) et de ventilation mécanique invasive (5 [3­257] vs 3[2­4] h; différence dans les médianes, 2 heures; IC 95 %, 0,5 à 41; P = 0,008) plus longues, un taux de réintubation plus élevé (4/10, 40 % vs 1/112, 0,9 %; risque relatif, 45; IC 95 %, 7,1 à 278; P < 0,0001), une incidence plus élevée de pneumonie (4/10 [40 %] vs 7/112 [6 %]; risque relatif, 6; IC 95 %, de 2 à 16; P < 0,001), et une durée de séjour médiane [ÉIQ] plus longue à l'unité de soins intensifs (8 [5-29] vs 4 [2­6] jours; différence en médianes, 4 jours; IC 95 %, 2 à 12; P = 0,002). CONCLUSION: L'incidence de dysfonctionnement persistant du diaphragme était de 8 % chez les patients bénéficiant d'une chirurgie cardiaque non urgente et était associée à des issues respiratoires indésirables. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04276844); enregistrée prospectivement le 19 février 2020.

Using machine learning to develop a clinical prediction model for SSRI-associated bleeding: a feasibility study.

INTRODUCTION: Adverse drug events (ADEs) are associated with poor outcomes and increased costs but may be prevented with prediction tools. With the National Institute of Health All of Us (AoU) database, we employed machine learning (ML) to predict selective serotonin reuptake inhibitor (SSRI)-associated bleeding. METHODS: The AoU program, beginning in 05/2018, continues to recruit ≥ 18 years old individuals across the United States. Participants completed surveys and consented to contribute electronic health record (EHR) for research. Using the EHR, we determined participants who were exposed to SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine). Features (n = 88) were selected with clinicians' input and comprised sociodemographic, lifestyle, comorbidities, and medication use information. We identified bleeding events with validated EHR algorithms and applied logistic regression, decision tree, random forest, and extreme gradient boost to predict bleeding during SSRI exposure. We assessed model performance with area under the receiver operating characteristic curve statistic (AUC) and defined clinically significant features as resulting in > 0.01 decline in AUC after removal from the model, in three of four ML models. RESULTS: There were 10,362 participants exposed to SSRIs, with 9.6% experiencing a bleeding event during SSRI exposure. For each SSRI, performance across all four ML models was relatively consistent. AUCs from the best models ranged 0.632-0.698. Clinically significant features included health literacy for escitalopram, and bleeding history and socioeconomic status for all SSRIs. CONCLUSIONS: We demonstrated feasibility of predicting ADEs using ML. Incorporating genomic features and drug interactions with deep learning models may improve ADE prediction.

Sociodemographic characteristics differ across routine adult vaccine cohorts: An All of Us descriptive study.

BACKGROUND: The National Institutes of Health All of Us (AoU) Research Program is currently building a database of 1million+ adult subjects. With it, we describe the characteristics of those with documented vaccinations. OBJECTIVES: To describe the sociodemographic, health status, and lifestyle factors associated with vaccinations. METHODS: This is a retrospective study involving data from the AoU program (R2020Q4R2, N = 315,297). Five vaccine cohorts [influenza, hepatitis B (HBV), pneumococcal <65 years old, pneumococcal ≥65 years old, and human papillomavirus (HPV)] were generated based on vaccination history. The influenza cohort comprised participants with documented influenza vaccinations in electronic health records (EHRs) from September 2017 to May 2018. Other vaccine cohorts comprised participants with ≥1 lifetime record(s) of vaccination documented in the EHR by December 2018. The vaccine cohorts were compared to the overall AoU cohort. Descriptive statistics were generated using EHR- and survey-based sociodemographic, health, and lifestyle information. The SAMBA (0.9.0) R package was utilized to adjust for EHR selection and outcome misclassification biases to infer sources of disparity for pneumococcal vaccinations in older adults. RESULTS: Cohort counts were as follows: influenza (n = 15,346), HBV (n = 6323), pneumococcal <65 (n = 15,217), pneumococcal ≥65 (n = 15,100), and HPV (n = 2125). All vaccine cohorts had higher proportions of White and non-Hispanic/Latino participants compared to the overall AoU cohort. The largest differences were found in pneumococcal age ≥65, with 80.2% White participants compared to 52.9% in the overall study population. Multivariable analysis revealed that race/ethnic disparities in pneumococcal vaccination among older adults were explained by biological sex, income, health insurance, and education-related variables. CONCLUSION: Racial, ethnic, education, and income characteristics differ across the vaccine cohorts among AoU participants. These findings inform future utilization of large health databases in vaccine epidemiology research and emphasize the need for more targeted interventions that address differences in vaccine uptake.

Determinants of diaphragm inspiratory motion, diaphragm thickening, and its performance for predicting respiratory restrictive pattern in Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Respiratory status is a key determinant of prognosis in patients with Duchenne muscular dystrophy (DMD). We aimed to evaluate the determinants of diaphragm ultrasound and its performance in predicting restrictive respiratory patterns in DMD. METHODS: This was a retrospective study of DMD patients followed in our center and admitted for an annual checkup from 2015 to 2018. We included DMD patients who underwent diaphragm ultrasound and pulmonary functional tests. RESULTS: This study included 74 patients with DMD. The right diaphragm thickening fraction (TF) was significantly associated with age (P = .001), Walton score (P = .012), inspiratory capacity (IC) (P = .004), upright forced vital capacity (FVC) (P < .0001), supine FVC (P = .038), and maximal inspiratory pressure (MIP) (P = .002). Right diaphragm excursion was significantly associated with age (P < .0001), steroid use (P = .008), history of spinal fusion (P < .0001), body mass index (BMI) (P = .002), Walton score (P < .0001), IC (P < .0001), upright FVC (P < .0001), supine FVC (P < .0001), and MIP (P < .0001). A right diaphragm TF >28% and a right diaphragm excursion>25.4 mm were associated with an FVC >50% with, respectively, an area under the curve (AUC) of 0.95 (P = .001) and 0.93 (P < .001). A left diaphragm TF >26.8% and a left diaphragm excursion >21.5 mm were associated with an FVC >50% with, respectively, an AUC of 0.95 (P = .011) and 0.97 (P < .001). DISCUSSION: Diaphragm excursion and diaphragm TF can predict restrictive pulmonary insufficiency in DMD.

Suppression of tumorigenicity-2 (ST2) is a promising biomarker in heart transplantation.

BACKGROUND: To evaluate the association between donors' and recipients' serum levels of soluble ST2 (sST2) and recipients' outcome after heart transplantation (HT). METHODS: Blood samples were collected in 50 heart donors before organ procurement and in 50 recipients before HT (D0), a week after HT (D7) and at every first year's endomyocardial biopsy (EMB); sST2 levels were evaluated by ELISA. RESULTS: Donors who sustained a cardiac arrest, had significantly higher sST2 levels. Recipients on national high emergency waiting list had significantly higher preoperative sST2 levels compared to recipients who did not. Recipients with postoperative sepsis or continuous renal replacement therapy had significantly higher sST2 levels at D7. Recipients who needed a postoperative ECMO for allograft dysfunction had significantly higher sST2 levels in their corresponding donors. Recipients who died during the hospitalization after the transplantation had significantly higher sST2 levels at D7 compared to recipients who did not. No difference was observed in sST2 levels in recipients who had mild allograft rejection and recipient who did not. CONCLUSIONS: Higher sST2 levels in donors are associated to allograft dysfunction requiring ECMO in recipients; higher postoperative sST2 levels in recipients are associated with in-hospital mortality.

Anticancer drug-induced life-threatening ventricular arrhythmias: a World Health Organization pharmacovigilance study.

AIMS: With the explosion of anticancer drugs, an emerging concern is the risk for drug-induced sudden death (SD) via ventricular arrhythmias (VA). METHODS AND RESULTS: We used the international pharmacovigilance database VigiBase (n = 18 441 659 reports) to compare drug-induced long QT (diLQT, n = 18 123) and VA (n = 29 193) including torsade de pointes (TdP, n = 8163) reporting for 663 anticancer drugs vs. all other drugs until 01/01/2019. The analysis used the 95% lower-end credibility interval of the information component (IC025), an indicator for disproportionate Bayesian reporting; significant when IC025 >0. There were 2301 reports (13.8% fatal) for 40 anticancer drugs significantly associated with diLQT (with 27 also associated with VA or SD) and 9 drugs associated with VA without diLQT. Half of these (46.9%, 23/49) were associated with SD. Most (41%, 20/49) were kinase inhibitors, 8% (4/49) were hormonal therapies, 6% (3/49) were immunotherapies, 24% (12/49) were cytotoxics, and 20% (10/49) were miscellaneous. In VigiBase, reports of diLQT, TdP, or VA increased from 580 in the period 1967-83 to 15 070 in 2014-18 with the proportion related to anticancer drugs increasing from 0.9% (5/580) to 14.0% (2115/15 070) (P < 0.0001). Concordance between these VigiBase signals and data concerning diLQT and VA/TdP identified in CredibleMeds or US Food and Drug Administration (FDA) labels was moderate (κ = 0.47 and 0.40, P < 0.0001). Twenty-three drugs represent new signals, while 24 flagged by CredibleMeds or FDA had no signal in VigiBase. A three-level SD risk stratification relying on isolated long QT (low risk), associated with VA without SD (moderate risk), and VA with SD (high risk) is proposed. CONCLUSION: This list of liable anticancer drugs may prove useful for physicians and regulatory authorities to re-evaluate cardiac monitoring requirements. CLINICAL TRIAL REGISTRATION: NCT03530215.

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study.

Chimeric-antigen-receptor T cells directed against CD19 (CAR-T) are emerging hematological therapeutics with scarce data on its overall safety profile spectrum. To determine the clinical features and incidence of adverse-drug reactions (ADR) associated with CAR-T. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase and meta-analysis of data from CAR-T trials and cohorts in the literature was also performed through March, 2020. The primary objective was to identify ADR associated with approved CAR-T (axicabtagene-ciloleucel; tisagenlecleucel). We conducted a Bayesian disproportionate analysis with the 95% lower credibility-interval of information component (IC025 , significance > 0). We also performed a systematic-review and meta-analysis of CAR-T trials and cohorts in the literature to evaluate ADR incidence. Nine ADR classes were associated with CAR-T: Cytokine release syndrome (CRS, n = 1378, IC025  = 4.24), neurological disorders (n = 963, IC025  = 2.42), hematological disorders (n = 532, IC025  = 3.32), infections (n = 287, IC025  = 2.38), cardiovascular disorders (n = 256, IC025  = 2.81), pulmonary disorders (n = 186, IC025  = 3.80), reno-metabolic disorders (n = 123, IC025  = 1.89), hemophagocytic-lymphohistiocytosis (n = 36, IC025  = 5.01) and hepatic disorders (n = 32, IC025  = 2.49). ADR-related fatalities accounted for 99/1783 (5.5%) of the reports and 262/1783 (14.7%) for all-cause mortality. These ADR-related fatalities were associated with hemophagocytic-lymphohistiocytosis, cerebral vascular disorder, infections, and respiratory failure. In meta-analyses, the most frequent any-grade ADRs were CRS, hematological disorders, and neurological disorders. Fatal ADR were most found with neurological disorders, CRS, and infections. Note, CAR-T infusion may be associated with severe ADR mainly following the week of administration, though rarely fatal. Infections, hemophagocytic-lymphohistiocytosis and end organ failures including neurological or lung involvements require scrutiny.

Takotsubo syndrome after liver transplantation: An association with intraoperatively administered epinephrine and fentanyl.

Takotsubo syndrome (TTS) can develop after liver transplant (LT), but its predisposing factors are poorly understood. In this study, we aimed to determine if perioperative factors were associated with posttransplant TTS. Adult patients who underwent primary LT between 2006 and 2018 were included. Patients with and without TTS were identified and matched by propensity scores. Of 2181 LT patients, 38 developed postoperative TTS with a mean left ventricular ejection fraction of 25.5% (±7.8%). Multivariable logistic regression revealed two preoperative risk factors (alcoholic cirrhosis and model for end-stage liver disease-sodium scores) for TTS. Post-propensity match analyses showed that TTS patients had significantly higher doses of epinephrine and lower doses of fentanyl during LT compared with non-TTS patients. A higher dose of epinephrine and a lower dose of fentanyl was associated with a higher predicted probability of TTS. All TTS patients had full recovery of cardiac function and had comparable 1-year survival. In conclusion, TTS occurred at a rate of 1.7% after LT and was associated with two pretransplant risk factors. The higher doses of epinephrine and lower doses of fentanyl administered during LT were associated with posttransplant TTS. More studies on the relationship between intraoperative medications and TTS are warranted.

Simulation training for the endoscopic management of upper gastrointestinal bleeding: a nationwide survey of rural surgeons' needs and preferences analysis.

BACKGROUND: Published needs analyses of rural surgeons have identified a need for training in the endoscopic management of non-variceal upper gastrointestinal bleeding (NVUGIB). The study aim was to survey rural surgeons regarding their requirements and preferences for a simulation model on which they could rehearse the endoscopic management of NVUGIB. METHODS: Rural surgeons were contacted via the American College of Surgery Advisory Council listserv and invited to complete an online survey. RESULTS: A total of 66 responses were received, representing all 4 US regional divisions. Seventy-seven percent of respondents perform > 100 endoscopy cases per year. A majority have no experience with simulation models (77%), citing cost, time, and access to training courses as the three most limiting factors. Thirty-three percent lacked confidence in managing UGIBs, and 73% were interested in receiving additional training. Preference analysis revealed that respondents preferred a portable simulation model (81%) that costs between $500 and $1000 (46%), and requires 1-2 weeks of training (34%). Verbal feedback from an expert was viewed as the most helpful type of feedback (61%). CONCLUSION: Rural surgeons frequently perform flexible endoscopy in their practice and are interested in further training for the endoscopic management of NVUGIB. These results will be used to develop a simulation platform for training in the endoscopic management of NVUGIB that meets rural surgeons' needs.

Quadritherapy vs standard tritherapy immunosuppressant regimen after heart transplantation: A propensity score-matched cohort analysis.

After heart transplant, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting calcineurin inhibitors (CNIs) into EVL. The aim of this study was to describe the effects of combining low-dose EVL and CNIs in maintenance immunosuppression regimen (quadritherapy) and compare it with standard tritherapy associating standard-dose CNIs, mycophenolate mofetil, and corticosteroids. In the 3-year registry cohort of heart transplanted patients, those who received quadritherapy were compared with those who received tritherapy. EVL was added after 3 months posttransplant. Three analyses were performed to control for confounders: propensity score matching, multivariable survival, and inverse probability score weighting analyses. Among 213 patients who were included (75 with quadritherapy), propensity score matching selected 64 unique pairs of patients with similar characteristics. In the matched cohort (n = 128), quadritherapy was associated with fewer deaths (3 [4.7%] vs 17 [21.9%], P = .007) and biopsy-proven acute rejections (15 [23.4%] vs 31 [48.4%], P = .002). These results were confirmed in the overall cohort (n = 213), after multivariable and inverse probability score weighting analyses. Renal function and donor-specific HLA-antibodies remained similar in both groups. Low-dose combination quadritherapy was associated with fewer deaths and rejections, compared with standard immunosuppression tritherapy.

Favorable Outcomes of a Direct Heart Transplantation Strategy in Selected Patients on Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: Heart transplantation in patients supported by venoarterial extracorporeal membrane oxygenation has been associated with poor prognosis. A specific protocol for extracorporeal membrane oxygenation management encompassing patient selection, implantation strategy, and preoperative and perioperative treatment is applied at our institution. Our aim was to compare posttransplant outcomes of patients supported or not by extracorporeal membrane oxygenation at the time of heart transplantation. DESIGN: A large observational single-center retrospective study was conducted. The primary endpoint was overall survival after heart transplantation. Secondary endpoints included death-censored rejection-free survival and the frequency of extracorporeal membrane oxygenation-related complications. SETTING: One heart transplantation and extracorporeal membrane oxygenation high-volume center. PATIENTS: All consecutive patients over 18 years old with a first noncombined heart transplantation performed between 2012 and 2016 were included. INTERVENTIONS: None (retrospective observational study). MEASUREMENTS AND MAIN RESULTS: Among the 415 transplanted patients, 118 (28.4%) were on extracorporeal membrane oxygenation at the time of transplantation (peripheral, 94%; intrathoracic, 6%). Median time on extracorporeal membrane oxygenation before heart transplantation was 9 days (interquartile range, 5-15 d) and median follow-up post heart transplantation was 20.7 months. Posttransplant survival did not differ significantly between the two groups (1-yr survival = 85.5% and 80.7% in extracorporeal membrane oxygenation vs nonextracorporeal membrane oxygenation patients; hazard ratio, 0.69; 95% CI, 0.43-1.11; p = 0.12, respectively). Donor age, body mass index, creatinine clearance, and ischemic time were independently associated with overall mortality, but not extracorporeal membrane oxygenation at the time of heart transplantation. Rejection-free survival also did not significantly differ between groups (hazard ratio, 0.85; 95% CI, 0.60-1.23; p = 0.39). Local wound infection was the most frequent complication after extracorporeal membrane oxygenation (37% of patients). CONCLUSIONS: With the implementation of a specific protocol, patients bridged to heart transplantation on extracorporeal membrane oxygenation had similar survival compared with those not supported by extracorporeal membrane oxygenation.

Task Deconstruction of Colonic Endoscopic Submucosal Dissection (cESD): An Expert Consensus.

BACKGROUND: Slow adoption of colonic ESD (cESD) in the US is multifactorial due to: lack of clinical training construct (e.g., gastric ESD in Japan), complication risks, and technical difficulty. More than 28,000 patients/year undergo colonic resection for benign lesions that could be managed effectively with cESD. Selected patients could avoid surgery if procedural adoption of cESD increased due to more accessible training. Current US cESD training is scarce, and existing programs are piecemeal. There is a need to develop an effective national training program for practicing endoscopists. A prerequisite to training development is a comprehensive task list delineating procedural steps. The aim of this work was to describe an evidence-based method of deconstructing cESD into the essential steps to provide a task list to guide teaching and assessment. METHODS: Subject-matter experts (SMEs) performed a literature review to create an initial procedural step list. Eleven clinical cESD SMEs and four educational SMEs formed a 'cESD Working Group' to develop consensus regarding steps. Through a two-stage modified Delphi process, a consensus on a comprehensive standard cESD deconstructed task list was reached. The aim was to standardize cESD teaching to efficiently bring a novice to safe performance. RESULTS: A literature review identified eight initial cESD steps. First-round Delphi consensus was gained on seven steps. Semi-structured focus group discussions resulted in consensus on a modified version of 7 of the initial steps, with addition of two steps. Consensus on procedural actions needed to perform each step was achieved after the hands-on laboratory. The final result was a ten-step deconstructed task list for standard cESD. CONCLUSION: The development of a standardized cESD procedural task list provides a foundation to safely and efficiently teach cESD to practicing endoscopists. This list can be used to develop a training pathway to increase procedural adoption. Selected patients currently undergoing colonic resections could benefit from increased adoption of cESD.

Clinical Experience with the Gore Hybrid Vascular Graft in Complex Revascularizations Demonstrates Safety and Efficacy.

BACKGROUND: Arterial revascularizations can present significant challenges when vessels are disadvantaged and advances in technology present the surgeon with innovative opportunities. A number of studies have used the GORE® Hybrid Vascular Graft (GHVG), and we have been using this device in arterial revascularizations since it came to market. The aim of this study is therefore to present a large single-center experience using the GHVG. This series presents patients with complex revascularizations in multiple vascular beds. METHODS: We retrospectively analyzed a single-center series of 43 patients who received a total of 56 GHVGs in complex revascularization procedures at Houston Methodist Hospital from March 2012 to April 2017. We excluded 5 patients (7 grafts in total) because of loss of follow-up. An additional 8 patients were excluded from the analysis (11 grafts in total) secondary to mortalities unrelated to their grafts (7 patients died during index hospitalization and 1 patient died shortly after discharge). RESULTS: Our results demonstrated an 18-month primary patency, assisted primary patency, and secondary patency of 82, 86, and 96%, respectively. These complex revascularizations included a total of 56 devices placed. GHVGs were placed in the external iliac artery (27/56), renal artery (12/56), common femoral artery (6/56), superficial femoral artery (4/56), common iliac artery (3/56), grafts (3/56), profunda femoris artery (1/56), and the superior mesenteric artery (1/56). Early mortality in patients (7/8) was because of the nature of their disease and not related to the surgical intervention. CONCLUSIONS: The GHVG has the ability to create a sutureless anastomosis in a disadvantaged vessel or to promote a potentially better outcome by either avoiding prolonged ischemia to visceral branches or avoiding extensive abdominal or retroperitoneal exposure in an iliofemoral bypass. These results demonstrate the value of the GHVG in complex revascularizations not amenable to traditional open surgical bypass. LEVEL OF EVIDENCE: IV.

Effect of recipient gender and donor-specific antibodies on antibody-mediated rejection after heart transplantation.

Gender-difference regarding antibody-mediated rejection (AMR) after heart transplantation has been described. However, no study accounted for the presence of preformed donor-specific antibodies (pfDSA), a known risk factor of AMR, more common among women than men. In a single-institution 6-year cohort (2010-2015), time to AMR was assessed, comparing men with women by survival analysis with a 1-year death-censored follow-up. All AMRs were biopsy proven. Confounding variables that were accounted for included mean intensity fluorescence (MFI) of pfDSA, recipient age, HLA-, size- and sex-mismatch. 463 patients were included. Overall incidence of AMR was 10.3% at 1 year. After adjusting for confounding variables, independent risk factors of AMR were female recipient gender (adjusted hazard-ratio [adj. HR] = 1.78 [1.06-2.99]), P = .03) and the presence of pfDSA (adj. HR = 3.20 [1.80-5.70], P < .001). This association remained significant when considering pfDSA by their MFI; female recipient gender had an adj. HR = 2.2 (P = .026) and MFI of pfDSA (per 1 MFI-increase) adj. HR = 1.0002 (P < .0001). In this cohort, women were at higher risk of AMR than men and this risk increase was additive to that of pfDSA. These findings may suggest a gender-related difference in the severity of pfDSA.

Respiratory Variability of Pulmonary Velocity-Time Integral As a New Gauge of Fluid Responsiveness For Mechanically Ventilated Patients in the ICU.

OBJECTIVES: To evaluate reliability and feasibility of the respiratory variability of pulmonary velocity-time integral as a new dynamic marker of fluid responsiveness in mechanically ventilated patients. DESIGN: Prospective observational study. SETTING: Medical-surgical ICU of a general hospital. PATIENTS: Fifty mechanically ventilated patients with acute circulatory failure. INTERVENTIONS: Transthoracic echocardiography was performed at inclusion (transthoracic echocardiography baseline). Fluid therapy was prescribed to patients exhibiting one value greater than or equal to 13% among commonly used variables of fluid responsiveness: respiratory variability of aortic velocity-time integral, respiratory variability of inferior vena cava diameter, or pulse pressure variation. MEASUREMENTS AND MAIN RESULTS: Respiratory variability of pulmonary velocity-time integral was assessed at baseline. Respiratory variability of pulmonary velocity-time integral was significantly greater in patients who received fluid therapy (26.9 ± 12.5% vs 6.2 ± 4.3%; p < 0.0001). Respiratory variability of pulmonary velocity-time integral was correlated with respiratory variability of aortic velocity-time integral (r = 0.75; p < 0.0001), respiratory variability of inferior vena cava diameter (r = 0.42; p < 0.01), and pulse pressure variation (r = 0.87; p < 0.0001) at baseline and with the relative increase in cardiac output after fluid therapy (r = 0.44; p = 0.019). Fluid responsiveness was defined as a 10% increase in cardiac output after fluid therapy, assessed by a second transthoracic echocardiography. Respiratory variability of pulmonary velocity-time integral was associated with fluid responsiveness (adjusted odds ratio, 1.58; 95% CI, 1.08-2.32; p = 0.002). Area under the receiver operating characteristics curve was 0.972, and a value of respiratory variability of pulmonary velocity-time integral greater than or equal to 14% yielded a sensitivity of 92% and specificity of 87% to predict fluid responsiveness. Interobserver reproducibility was excellent (intraclass correlation coefficient = 0.94). CONCLUSIONS: Respiratory variability of pulmonary velocity-time integral is a simple and reliable marker of fluid responsiveness for ventilated patients in ICU.