Tranexamic Acid in Upper Gastrointestinal Bleeding is Associated With Venous and Arterial Thromboembolic Events.

OBJECTIVES: To determine the risk difference of arterial and venous thromboembolic events between patients with upper gastrointestinal bleeding (UGIB) who received and did not receive tranexamic acid. DESIGN: Retrospective cohort study. SETTING: The TriNetX Analytics (Cambridge, MA) Research Network, a deidentified mixed electronic health record and claims-derived database with over 110 million patients, primarily located in the United States. PATIENTS: A total of 2,016,763 patients diagnosed with hematemesis or melena between October 31, 2003, and October 31, 2023. INTERVENTIONS: Receipt of tranexamic acid within 7 days of a UGIB diagnosis. MEASUREMENTS AND MAIN RESULTS: We measured the incidence of thromboembolic events, both venous (deep venous thrombosis [DVT] and pulmonary embolism [PE]) and arterial (cerebrovascular accident [CVA] and myocardial infarction [MI]), within either 7 days of tranexamic acid (for recipients) or 7 days of UGIB diagnosis (for nonrecipients). Subsequently, we developed similar subcohorts using propensity score matching (PSM) for demographic and comorbidity data and reexamined the incidence of thromboembolic events, both before and after excluding any patients with any prior episodes of the outcomes. In all analyses, tranexamic acid recipients experienced significantly more adverse thromboembolic outcomes, with the post-PSM cohorts' risk difference generating an odds ratio of 1.4 for MI (95% CI, 1.2-1.7), 1.6 in CVA (95% CI, 1.3-1.9), 1.8 in PE (95% CI, 1.5-2.3), and 2.1 in DVT (95% CI, 1.8-2.5); all p values of less than 0.001. CONCLUSIONS: Leveraging data from a large, multi-institutional database, we identified a correlation between tranexamic acid use in patients with UGIB and the occurrence of both venous and arterial thromboembolic events. Although the former is well-attested in the literature, the latter finding is more novel, underscoring the need for further prospective research to better characterize the risk-benefit profile of tranexamic acid in the management of gastrointestinal bleeding.

Risk of Primary Gastrointestinal Lymphoma in Patients With Inflammatory Conditions Exposed to Tumor Necrosis Factor Alpha Inhibitors and Immunomodulators: A Case-Control Study.

Introduction: The aim of this case-control study was to determine if exposure to tumor necrosis factor alpha inhibitors (TNFIs) or immunomodulators (thiopurines or methotrexate) was associated with development of primary gastrointestinal lymphoma (PGIL) in patients with chronic inflammatory conditions. Methods: Patients with PGIL and controls evaluated at a tertiary care center over 20 years were matched 1:3 using a medical record informatics search engine based on their chronic inflammatory condition (Crohn's disease [CD], ulcerative colitis [UC], rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis) and duration of follow-up. Patients who started on TNFI within 3 months of PGIL diagnosis were excluded. We extracted demographics, medical history, and medications used. Univariate models using conditional logistic regression were used due to the small number of matched pairs. Results: Twenty PGIL cases matched with 60 controls were followed for a mean 9.9 ±â€…6.9 and 9.7 ±â€…8.6 years, respectively. Mean age at time of PGIL diagnosis was 47.5 ±â€…22.0 (standard deviation) years and the majority (75%) were males. The most common inflammatory diagnosis was inflammatory bowel disease (80% of cases; 45% with UC and 35% with CD). Development of PGIL was not associated with TNFI (odds ratio [OR] = 2.6; 95% confidence interval [CI] 0.69-11.01; P = .18), but with use of TNFI in combination with thiopurines (OR = 8.93; 95% CI 1.43-80.25; P = .014). Risk of PGIL increased with every additional TNFI (2.277 (1.002-5.713); P = .0494). All cases exposed to multiple TNFI were also exposed to thiopurines. Use of thiopurines (alone or in combination) was the greatest risk factor (OR = 6.32; 95% CI 1.55-37.05; P = 0.006) to develop PGIL. Conclusions: TNFI therapy was not associated with increased risk for PGIL unless used in combination with thiopurines and with every switch to a different TNFI.

Transjejunal ERCP, EUS-guided gallbladder drainage, and cholecystoscopy with direct electrohydraulic lithotripsy with large gallstone removal in Roux-en-Y anatomy.

Video 1Transjejunal ERCP, EUS-guided gallbladder drainage, and cholecystoscopy with direct electrohydraulic lithotripsy with large gallstone removal in Roux-en-Y anatomy.

Effectiveness of the Reverse Sural Flap in Covering Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis.

Background: The reverse sural fasciocutaneous flap (RSFCF) has been used with success to cover noncomplicated foot and ankle soft tissue defects. However, there are some controversies when it is used in patients having chronic diabetic foot ulcers. This aim of this meta-analysis was to evaluate the efficacy of RSFCF in covering diabetic foot and ankle ulcers. Methods: A systematic review was undertaken from MEDLINE, EMBASE, Web of Science, Cochrane Library, and Google Scholar. Only diabetic foot and ankle ulcers were accepted for inclusion and all study designs were included. Proximally based flaps, nondiabetic ulcers, and assisted negative pressure therapy were excluded. Suitability for inclusion was assessed by 2 reviewers. The random-effect estimate was reported for the set outcomes whenever high heterogeneity was present. Metaregression analysis was performed to identify independent risk factors for failure. Results: The search identified 33 relevant studies comprising 187 patients and flap interventions; all but 1 were case-series. The weighted outcomes were as follows: (1) the flap healing rate was 93.3% while 6.6% resulted in total necrosis, (2) the rate of partial flap necrosis was 12%, (3) venous congestion was reported in 6.6% of cases, (4) the infection rate was 8.3%, and (5) the donor site morbidity was 4.6%. No association was found between pedicle width or presence of a subcutaneous pedicle tunnel and the primary outcome of total loss. Conclusions: This review demonstrated excellent results of the flap when covering complicated or large diabetic foot and ankle ulcers. When compared to those published in the literature, our results found RSFCF to be relatively less successful in diabetic wounds than in trauma patients but more successful than in those having associated osteomyelitis and those who were treated with random local flaps.

Historique: Le lambeau fascio-cutané sural inversé (LFCSI) a couvert avec succès des anomalies non compliquées des tissus mous du pied et de la cheville. Cependant, une controverse sévit quant à son utilisation chez les patients ayant des ulcères du pied causés par un diabète chronique. La présente méta-analyse visait à évaluer l'efficacité du LFCSI sur des ulcères du pied et de la cheville causés par un diabète. Méthodologie: Les chercheurs ont réalisé une analyse systématique dans MEDLINE, EMBASE, Web of Science, Bibliothèque Cochrane et Google Scholar. Ils n'ont inclus que les ulcères du pied et de la cheville causés par le diabète, mais accepté toutes les méthodologies d'étude. Ils ont exclu les lambeaux proximaux, les ulcères non diabétiques et la thérapie assistée par pression négative. Deux examinateurs ont évalué la pertinence de l'inclusion. Ils ont précisé l'évaluation à effets aléatoires des résultats cliniques observés dès qu'une forte hétérogénéité était constatée. La méta-analyse de régression a permis d'établir les facteurs de risque d'échec. Résultats: La recherche a permis d'extraire 33 études pertinentes incluant 187 patients et interventions par lambeaux, toutes étant des séries de cas, sauf une. Les résultats pondérés s'établissaient comme suit: a) taux de guérison des lambeaux de 93,3%, et 6,6% de nécrose totale, b) taux de nécrose partielle du lambeau de 12%, c) congestion veineuse dans 6,6% des cas, d) taux d'infection de 8,3% et e) atteinte au siège du donneur de 4,6%. Aucune association n'a été constatée entre la largeur du pédicule ou la présence d'un tunnel pédiculaire sous-cutané et le résultat primaire de perte totale du lambeau. Conclusions: La présente analyse a démontré d'excellents résultats du lambeau pour couvrir des ulcères étendus et complexes du pied et de la cheville causés par le diabète. Par rapport aux résultats figurant dans les publications, les LFCSI étaient relativement moins efficaces pour les plaies causées par le diabète que par un traumatisme, mais plus efficaces que celles également associées à l'ostéomyélite ou que les lambeaux locaux aléatoires.

Decreasing delirium through music listening (DDM) in critically ill, mechanically ventilated older adults in the intensive care unit: a two-arm, parallel-group, randomized clinical trial.

BACKGROUND: Delirium is a highly prevalent and morbid syndrome in mechanically ventilated intensive care unit (ICU) patients. Music is a promising non-pharmacological intervention with beneficial effects on anxiety and stress, while its effects on delirium duration and severity are not well understood. METHODS/DESIGN: Our study is a two-arm, randomized parallel-group, clinical trial to evaluate the efficacy of music intervention compared to a silence-track attention control on delirium/coma duration in mechanically ventilated critically ill older adults. One hundred sixty mechanically ventilated adults 50 years of age or older will be randomized to one of two arms within 72 h of ICU admission: (1) 1-h music listening sessions twice daily through noise-canceling headphones, or (2) 1-h sessions of a silence track twice daily through noise-canceling headphones. Our primary aim is to compare delirium/coma-free days after randomization during the 7-day study intervention phase using the Confusion Assessment Method for the ICU (CAM ICU) and the Richmond Agitation Sedation Scale (RASS) for delirium and coma. Secondary outcomes include pain and anxiety evaluated twice daily during the intervention phase and throughout the duration of ICU stay using the Critical Care Pain Observation Tool (CPOT) and visual analog scale-anxiety (VAS-A). Enrolled participants will be followed after hospital discharge to further measure cognition as well as screening for depression and anxiety using the following telephone-based instruments: Indiana University Telephone-Based Assessment of Neuropsychological Status (IU TBANS), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7). DISCUSSION: This randomized clinical trial will measure the efficacy of a music listening intervention for delirium and coma duration early in the intensive care unit among older adults. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04182334 .

Serum Biomarkers in Postoperative Delirium After Esophagectomy.

BACKGROUND: Esophagectomy is associated with postoperative delirium, but its pathophysiology is not well defined. We conducted this study to measure the relationship among serum biomarkers of inflammation and neuronal injury and delirium incidence and severity in a cohort of esophagectomy patients. METHODS: Blood samples were obtained from patients preoperatively and on postoperative days 1 and 3 and were analyzed for S100 calcium-binding protein B, C-reactive protein (CRP), interleukin (IL) 8 and IL-10, tumor necrosis factor-α, and insulin-like growth factor 1. Delirium was assessed twice daily using the Richmond Agitation Sedation Scale and Confusion Assessment Method for Intensive Care Unit. Delirium severity was assessed once daily with the Delirium Rating Scale-Revised-98. RESULTS: Samples from 71 patients were included. Preoperative biomarker concentrations were not associated with postoperative delirium. Significant differences in change in concentrations from preoperatively to postoperative day 1 were seen in IL-8 (delirium, 38.6; interquartile range [IQR], 29.3-69.8; no delirium, 24.8; IQR, 16.0-41.7, P = .022), and IL-10 (delirium, 26.1; IQR, 13.9-36.7; no delirium, 12.4; IQR, 7.7-25.7; P = .025). Greater postoperative increase in S100 calcium-binding protein B (Spearman r = 0.289, P = .020) and lower levels of insulin-like growth factor 1 were correlated with greater delirium severity (Spearman r = -0.27, P = .040). Greater CRP change quartiles were associated with higher delirium incidence adjusting for severity of illness (odds ratio, 1.68; 95% confidence interval, 1.03-2.75; P = .037) or comorbidities (odds ratio, 1.70; 95% confidence interval, 1.05-2.76, P = .030). CONCLUSIONS: Differences in change in serum CRP, IL-8, and IL-10 concentrations were associated with postoperative delirium, suggesting biomarker measurement early in the postoperative course is associated with delirium.

Single-Institution Experience with Selective Internal Radiation Therapy (SIRT) for the Treatment of Primary and Secondary Hepatic Tumors.

PURPOSE: We aim to provide results of the real-world experience of a single center in Lebanon on the use of radioembolization to treat liver-only or liver-dominant tumors.  Methods: This retrospective review included patients who were evaluated for radioembolization between January 2015 and June 2017 and who had a lung shunt fraction of 20% or less. Tumor responses were determined using the response evaluation criteria in solid tumors (RECIST). RESULTS: Of the 23 Arab patients with a median age of 64 years (range, 36-87 years), eight had hepatocellular carcinoma, four had cholangiocarcinoma, and 11 had liver-only or liver-dominant metastases from other primary cancers. Most (n=17) had multifocal lesions, and 13 had a history of branched (n=8) or main (n=5) portal vein thrombosis. When appropriate, the gastroduodenal artery and middle hepatic artery were embolized for consolidation of radiotherapy; 18 patients required arterial coil occlusion, two had their cystic artery occluded, and one developed cholecystitis, which was successfully treated with antibiotics and supportive care. Another patient developed a post-radioembolization complication-a peptic ulcer unrelated to arterial reflux of microspheres because both the gastroduodenal and right gastric arteries were occluded. The median time to progression was seven months (range, 3-36 months), and median overall survival from radioembolization was 12 months (range, 3-40 months). Tumor responses included five complete responses, 13 partial responses, one stable disease, and four cases of progressive disease.  Conclusion: Performing radioembolization in a non-referral, private center in Lebanon resulted in good patient outcomes with few complications.

A Rare Presentation of Gall Bladder Volvulus: A Case Report.

BACKGROUND Gall bladder volvulus is a rare clinical entity, with only around 500 cases reported in the literature. It is defined as the rotation of the gallbladder on its mesentery along the axis of the cystic pedicle, although cases of torsion of the gallbladder fundus itself have been reported. CASE REPORT A 78-year-old woman presented for severe right upper-quadrant abdominal pain that began acutely 3 days prior. Her pain was accompanied by nausea and vomiting. She also reported feeling chills. Abdominal X-ray revealed a 7-cm-diameter subhepatic opacity containing gas. Abdominal ultrasound and CT scan revealed a distended and displaced gallbladder located below the liver, in contact with the right kidney. Subsequently, open cholecystectomy was performed, and a distended, necrotic gallbladder was found twisted on its pedicle; thus, a gall bladder volvulus was diagnosed. CONCLUSIONS In our patient, the classic patient characteristics of an elderly thin female with kyphosis were present. However, the rest of the presentation was not typical of gallbladder volvulus due to the patient's delay in seeking treatment, and was representative of the necrotic phase of gallbladder torsion, in which the patient becomes ill-appearing, with fever and chills, with significant abdominal rigidity.

Correction: Genome-wide association analysis of HDL-C in a Lebanese cohort.

[This corrects the article DOI: 10.1371/journal.pone.0218443.].

Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling.

How individuals respond to chronic stress varies. Susceptible individuals ultimately develop depression; whereas resilient individuals live normally. In this study, our objective was to examine the effect of branched-chain amino acids (BCAA), commonly used by athletes, on susceptibility to stress. Male C57BL/6 mice were subjected to daily defeat sessions by a CD1 aggressor, for 10 days. On day11, the behavior of mice was assessed using the social interaction test, elevated plus maze and open field. Mice received the BCAA leucine, isoleucine or valine before each defeat session. Furthermore, we examined whether BCAA regulate brain derived neurotrophic factor (BDNF) signaling by using a brain-permeable tropomyosin receptor kinase B (TRKB) inhibitor, ANA-12. We also tested the effect of voluntary exercise and high protein diets on susceptibility to stress. Mice exposed to chronic stress displayed increased susceptibility and social avoidance. BCAA promoted resilience to chronic stress, rescued social avoidance behaviors and increased hippocampal BDNF levels and TRKB activation. Inhibition of TRKB signaling abolished the ability of BCAA to promote resilience to stress and to rescue social avoidance. Interestingly, we found that BCAA activate the exercise-regulated PGC1a/FNDC5 pathway known to induce hippocampal BDNF signaling. Although both voluntary exercise and BCAA promoted resilience to stress, combining them did not yield synergistic effects confirming that they affect similar pathways. We also discovered that high protein diets mimic the effect of BCAA by rescuing social deficits induced by chronic stress and increase Bdnf expression in the hippocampus. Our data indicate that BCAA, exercise and high protein diets rescue susceptibility to stress by activating the hippocampal BDNF/TRKB signaling.

Genome-wide association analysis of HDL-C in a Lebanese cohort.

Low serum levels of high-density lipoprotein cholesterol (HDL-C) have been shown to be a risk factor for coronary artery disease independent of low-density lipoprotein cholesterol (LDL-C) in different populations. In this study, we investigated genetic variants through genome-wide association studies to determine their association with HDL-C levels in a sample of 2,700 patients. We identified several SNPs associated with HDL-C levels in the Lebanese population using unadjusted and adjusted by biological factors models. We replicated the association of rs3764261 within CETP with HDL-C levels in the study population, and found other previously unidentified SNPs to be significant at the suggestive level, in both previously identified and unidentified genes. This paper reports the first genome-wide analysis of HDL-C in the Lebanese, Middle Eastern, population and supports the importance of genome-wide association studies across different and minor ethnicities to understand better the etiology of complex human diseases.