Transplant hepatology and diversity: A decade-long analysis (2013-2022).

Diversity among physicians has been shown to positively impact patient care. Physicians from minority backgrounds are more likely to serve underserved communities and be involved in health disparities research. Efforts to increase the proportion of underrepresented minorities and women in medicine will help prepare a physician workforce that best cares for a diversifying nation. The purpose of this paper was to highlight trends in sex and ethnic representation among incoming U.S. transplant hepatology trainees over a 10-year period.

Continuous positive airway pressure reduces the incidence of atrial fibrillation in patients with obstructive sleep apnea: A Meta-Analysis and Systematic Review.

INTRODUCTION: Obstructive sleep apnea (OSA) and atrial fibrillation (AF) are disorders that have increased in the United States during recent years. Earlier investigations have shown that underlying undiagnosed and unmanaged OSA plays a significant role in high rates and also as a trigger for newly diagnosed AF. Since the introduction of continuous positive airway pressure (CPAP) as a main therapy for OSA, more studies have evaluated the effect of CPAP on the development or recurrence of AF in OSA patients. However, sample sizes in a limited number of studies have been too small to conclude whether CPAP therapy has a significant effect on the development of AF in patients with OSA. The authors report results of their systematic review and meta-analysis summarizing what is currently known about the efficacy of CPAP for mitigating AF in patients with OSA. METHOD: The authors systematically reviewed the published reports on CPAP use and the incidence of AF from PubMed, Google Scholar, EMBASE, Web of Science, meeting abstracts, and Cochrane databases published between January 2015 and November 2021. Study data were extracted by two reviewers and a random-effects meta-analysis was performed using RevMan version 5.4. RESULTS: A total of 17 studies that met inclusion criteria were identified Studies included a total of 6,523 patients, 3,248 (49.8%) who used CPAP and 3,275 (50.2%) who did not use CPAP. In a random effects model, patients treated with CPAP showed a decrease in the incidence of AF (OR, 0.51; 95% CI; 0.27; 0.97, p = 0.04). High heterogeneity among the included studies was also observed (I2 = 97%). CONCLUSION: Our results add to the increasing evidence that CPAP therapy may reduce the incidence of development of AF in patients with OSA. Prospective future studies and clinical trials are needed to refine our understanding of the relationship between OSA and AF and how CPAP may reduce cardiovascular disease development.

Self-Induced Euglycemic Diabetic Ketoacidosis: When to Stop the Drip.

Diabetic ketoacidosis (DKA) is a well-known, serious complication that many patients with type 1 and 2 diabetes face due to either a relative or absolute insulin deficiency. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have gained increased popularity due to their diabetic, cardiovascular, and renal benefits. An associated complication of SGLT2 inhibitors is euglycemic DKA. A 56-year-old male with a history of type 2 diabetes mellitus and peripheral neuropathy presented with right foot pain secondary to a diabetic foot ulcer. The ulcer was present for one year, but the patient noticed increased pain and purulent discharge over the three days prior to presentation. While being treated inpatient for the foot ulcers, the patient repeatedly refused to receive standard hospital diabetes management of insulin injections. He instead insisted to take his home medications against medical advice, which were metformin and Glyxambi® (empagliflozin/linagliptin, Boehringer Ingelheim, Ingelheim am Rhein, Germany). His diabetic foot ulcer was medically managed with IV antibiotics.  On day 4 of admission, his anion gap increased to 23 mEq/L, and serum bicarbonate (CO2) decreased to 8 mEq/L, raising concerns of diabetic ketoacidosis. His glucose was 141 mg/dL, his beta-hydroxybutyrate was high at 5.5 mmol/L. An arterial blood gas (ABG) test demonstrated anion gap metabolic acidosis with secondary respiratory alkalosis. A urinalysis demonstrated glucose 1000 mg/dL and ketones of 150 mg/dL. The patient was diagnosed with euglycemic DKA. Due to the patient having normal glucose levels, an insulin drip and a 5% dextrose with 0.45% normal saline drip were started. Basic metabolic profiles were ordered every four hours, with glucose checks every hour. Once the anion gap was closed and his urinary ketones disappeared, the patient transitioned to subcutaneous insulin. He was able to be discharged home with basal subcutaneous insulin and metformin with instructions to avoid SGLT2 inhibitors in the future.  Unfortunately, there are currently no guidelines from endocrinology or internal medicine societies regarding the management of euglycemic DKA. As the typical DKA diagnostic criteria of elevated blood glucose level are not present, it is easy to overlook euglycemic DKA. As these SGLT2 inhibitors become more prevalent, careful monitoring of all potential side effects as well as the contraindications are prudent to successful management of complex disease states.

A Meta-Analysis Comparing Venoarterial (VA) Extracorporeal Membrane Oxygenation (ECMO) to Impella for Acute Right Ventricle Failure.

The right ventricular complication happens when the right ventricle (RV) fails to move sufficient blood through the pulmonary circle to enable enough left ventricular pumping. A significant pulmonary embolism/right-sided myocardial infarction may cause this to develop suddenly in a previously healthy heart, but many of the patients treated in the critical care unit have gradual, compensated RV failure as a result of chronic heart and lung disease. RV failure management aims to decrease afterload and improve right-side filling pressures. Vasoactive medications have a lower effect on lowering vascular obstruction in the pulmonary circulation than in the systemic circle because the vascular tone is lower in the pulmonary circulation. Any factors that induce an elevation in pulmonary vascular tone must be addressed, and selective pulmonary vasodilators must be administered in a prescription that does not result in systemic hypotension or compromise oxygenation. The system-based systolic arterial pressure should be kept near the RV systolic pressure to ensure RV perfusion. When these efforts prove futile, judicious application of inotropic medications for better RV contractility may help ensure cardiac output. After obtaining the finest medical treatment, certain individuals may need the implantation of a mechanical circulatory support device. This meta-analysis is intended to compare the Impella and venoarterial (VA) extracorporeal membrane oxygenation (ECMO) mechanical supports for patients with acute right ventricular failure. This comparison should demonstrate the best mechanical support between the two through thorough analysis. The analysis was begun by data collection from relevant sites; PUBMED and EMBASE were searched in collaboration with Google Scholar. Keywords were searched: Impella for acute right ventricle failure and VA ECMO for acute right ventricle failure. The results that were close to the search titles had their respective articles downloaded for further scrutiny. The search finally brought 1001 related articles that were exposed to further analysis to find more refined and closer articles within the needs of this meta-analysis. After extensive scrutiny, 23 articles were found to be the best for these analyses. The data showed that VA ECMO had better results than Impella for acute RV failure. However, the data were not statistically significant, as either the numbers of the studies were not enough or the null hypothesis was true and there was no true difference between them. More studies will be needed to confirm this.

Primary Combined Hepatocellular-Cholangiocarcinoma: A Case of Underdiagnosed Primary Liver Cancer.

Combined hepatocellular-cholangiocarcinoma (CHC) is a rare primary tumor of the liver. Histologically, it comprises components of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) but is associated with a worse prognosis. International guidelines regarding its management are scarce, with surgical management (major hepatectomy) being the treatment of choice. In this report, we present a challenging case of a 73-year-old male with primary CHC who was not a surgical candidate but underwent hepatic artery radioembolization instead.

Use of N-Acetylcysteine in Amphetamine-Induced Acute Liver Failure.

Acute liver failure (ALF) is a serious complication of many drugs. Amongst recreational drugs, cocaine, amphetamines and ecstasy (methylenedioxymethamphetamine) have been known to cause ALF as a complication. However, the true effects and management on the liver of such cases have not been well reported and treatment of such conditions needs prompt action. N-acetylcysteine (NAC) is a known hepatoprotective agent but remains controversial in the use of recreational drug-induced acute liver injury. We present a case of ALF secondary to amphetamine ingestion, with a rapid recovery after administration of intravenous NAC.

A Case of Ochrobactrum intermedium Bacteremia Secondary to Cholangitis With a Literature Review.

Ochrobactrum species are gram-negative, non-lactose fermenting, aerobic bacilli closely related to Brucella genus. Ochrobactrum intermedium (O. intermedium) is an emergent human pathogen that is difficult to differentiate from other Ochrobactrum species by conventional methods. It is known to infect immunocompromised hosts, has the propensity for abscess formation, and is known for its multidrug resistance. We describe the case of an 84-year-old woman with a background of primary sclerosing cholangitis who presented with fatigue, fever, and syncope. Blood cultures grew O. intermedium. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were consistent with cholangitis. Cultures from the biliary duct confirmed the same microorganism. The patient was successfully treated with minocycline. Although rare, O. intermedium should be considered as a differential diagnosis in patients with biliary and gut pathology, particularly in immunocompromised patients.

Predicting QT interval prolongation in patients diagnosed with the 2019 novel coronavirus infection.

INTRODUCTION: 2019 novel coronavirus (COVID-19) patients frequently develop QT interval prolongation that predisposes them to Torsades de Pointes and sudden cardiac death. Continuous cardiac monitoring has been recommended for any COVID-19 patient with a Tisdale Score of seven or more. This recommendation, however, has not been validated. METHODS: We included 178 COVID-19 patients admitted to a non-intensive care unit setting of a tertiary academic medical center. A receiver operating characteristics curve was plotted to determine the accuracy of the Tisdale Score to predict QT interval prolongation. Multivariable analysis was performed to identify additional predictors. RESULTS: The area under the curve of the Tisdale Score was 0.60 (CI 95%, 0.46-0.75). Using the cutoff of seven to stratify COVID-19, patients had a sensitivity of 85.7% and a specificity of 7.6%. Risk factors independently associated with QT interval prolongation included a history of end-stage renal disease (ESRD) (OR, 6.42; CI 95%, 1.28-32.13), QTc ≥450 ms on admission (OR, 5.90; CI 95%, 1.62-21.50), and serum potassium ≤3.5 mmol/L during hospitalization (OR, 4.97; CI 95%, 1.51-16.36). CONCLUSION: The Tisdale Score is not a useful tool to stratify hospitalized non-critical COVID-19 patients based on their risks of developing QT interval prolongation. Clinicians should initiate continuous cardiac monitoring for patients who present with a history of ESRD, QTc ≥450 ms on admission or serum potassium ≤3.5 mmol/L.

An Early Presentation of Buried Bumper Syndrome.

Percutaneous endoscopic gastrostomy (PEG) is a well-established and successful method of nutritional delivery. Complications, although rare, are divided into early or late. Buried bumper syndrome (BBS) is usually a late complication of PEG tube insertion and can cause many issues such as pressure necrosis, peritonitis, and septic shock. Endoscopic evaluation is the definitive diagnosis, and treatment depends on each patient and the degree of depth of disc migration. We present to you a case of buried bumper syndrome in a 66-year-old female that was initially thought to be complicated with peritonitis, and surprisingly occurring only one week after initial PEG tube placement.

Pre-Operative Predictors of Concurrent Choledocholithiasis in Patients With Acute Calculus Cholecystitis: An External Validity Analysis.

Introduction Patients that are presented with acute calculus cholecystitis (AC) and elevated liver enzymes markers (LEM), often require evaluation for concurrent choledocholithiasis (CDL). Currently, evaluation guidelines follow the American Society of Gastroenterology Endoscopy (ASGE) recommendations. Objectives The aim of the study was to externally validate both ASGE and the Chisholm predictors in a community hospital patient cohort. Methods We conducted a retrospective study of patients who presented to Ascension Saint John hospital with AC and elevated LEM over a period of two years. Sensitivity (SEN), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) were used to test the external validity of ASGE and Chisholm algorithms. Results A total of 132 patients' charts were reviewed, and 87 patients included. Chisholm predictors SEN, SP, PPV and NPV were 50%, 82%, 18%, and 95% respectively versus 100%, 19%, 8%, 100% for the ASGE predictors model. In the ASGE module, SP and PPV can be significantly improved to 60% and 13%, respectively, by changing a few risk categories including age and LEM range. Conclusions External validation of the Chisholm module in our patient cohort showed that it would lead to a low referral rate for unnecessary imaging and thus might be more cost-effective, especially when compared to current ASGE recommendations which would have a higher referral rate. On the other hand, current ASGE recommendations successively labeled all the patients with CDL, while the Chisholm module missed around 50 percent. We also observed that with the current ASGE module, the referral rate for further imaging and diagnostic tests can be possibly improved by adjusting a few of the predictors including the age and the abnormal liver transaminases range, but this observation is arbitrary and will need to be validated in a larger cohort study.

Primary Leiomyosarcoma of the Mesentery: A Case Report With Review of Literature.

Mesenteric leiomyosarcoma (LMS) is a rare gastrointestinal mesenchymal tumor. It was often misdiagnosed as a gastrointestinal stromal tumor (GIST) until the introduction of immunohistochemistry staining (IHC) in 1998. Currently, a positive IHC staining for smooth muscle markers represents the main diagnostic modality. Herein, we present a case of Mesenteric LMS in a 68-year-old woman, who presented with nausea, vomiting, and abdominal pain and was found to have a right-sided mesenteric tumor encasing the right ureter, with right hydroureteronephrosis. The patient underwent surgical removal of the tumor and IHC stains were compatible with LMS. She achieved remission until she developed recurrence 12 months after initial diagnosis and subsequently expired due to postoperative complications when re-resection was attempted. Typically, mesenteric LMS carries a poor prognosis with a propensity for hematogenous metastasis. In the absence of a standardized protocol for therapy, early surgical resection is the only known curative modality but with a high risk of recurrence.

A Case of A Mesenteric Cyst Mimicking a Biloma.

Mesenteric cysts are a rare entity, with approximately 1,000 cases reported in the literature. Its etiology is unknown but was theorized to be a benign ectopic lymphatic proliferation in the mesentery. Imaging with surgical excision and pathologic microscopic evaluation is needed for diagnosis, but no specific guidelines for its management have been documented. Per most cases in the literature, drainage of mesenteric cysts is suboptimal and associated with increased risk of recurrence and infection, making surgical resection the treatment of choice. With its varying locations and presentations, diagnosis can be tricky especially given the rarity of its occurrence. Differential diagnosis includes pancreatic pseudocyst, hemangioma, choledochal cyst, hydatid cyst, cystic teratoma, etc. We present a 35-year-old woman who came in with worsening right upper quadrant (RUQ) pain due to chronic cholelithiasis and was found to have a large RUQ cystic mass adherent to the gallbladder, suggesting possible biloma or pancreatic pseudocyst; however, tissue analysis was positive for a mesenteric cyst.

Augmentation Cystoplasty of Diseased Porcine Bladders with Bi-Layer Silk Fibroin Grafts.

IMPACT STATEMENT: The search for an ideal "off-the-shelf" biomaterial for augmentation cystoplasty remains elusive and current scaffold configurations are hampered by mechanical and biocompatibility restrictions. In addition, preclinical evaluations of potential scaffold designs for bladder repair are limited by the lack of tractable large animal models of obstructive bladder disease that can mimic clinical pathology. The results of this study describe a novel, minimally invasive, porcine model of partial bladder outlet obstruction that simulates clinically relevant phenotypes. Utilizing this model, we demonstrate that acellular, bi-layer silk fibroin grafts can support the formation of vascularized, innervated bladder tissues with functional properties.

Repair of injured urethras with silk fibroin scaffolds in a rabbit model of onlay urethroplasty.

BACKGROUND: Preclinical validation of scaffold-based technologies in animal models of urethral disease is desired to assess wound healing efficacy in scenarios that mimic the target patient population. This study investigates the feasibility of bilayer silk fibroin (BLSF) scaffolds for the repair of previously damaged urethras in a rabbit model of onlay urethroplasty. MATERIALS AND METHODS: A focal, partial thickness urethral injury was created in adult male rabbits (n = 12) via electrocoagulation and then onlay urethroplasty with 50 mm2 BLSF grafts was carried out 2 wk after injury. Animals were randomly divided into three experimental groups and harvested at 2 wk after electrocoagulation (n = 3), and 1 (n = 3) or 3 (n = 6) months after scaffold implantation. Outcome analyses were performed preoperatively and at 2 wk after injury in all groups as well as at 1 or 3 mo after scaffold grafting and included urethroscopy, retrograde urethrography (RUG), and histological and immunohistochemical analyses. RESULTS: At 2 wk after electrocoagulation, urethroscopic and RUG evaluations confirmed urethral stricture formation in 92% (n = 11/12) of rabbits. Gross tissue assessments at 1 (n = 3) and 3 (n = 6) mo after onlay urethroplasty revealed host tissue ingrowth covering the entire implant site. At 3 mo post-op, RUG analyses of repaired urethral segments demonstrated a 39% reduction in urethral stenosis detected following electrocoagulation injury. Histological and immunohistochemical analyses revealed the formation of innervated, vascularized neotissues with α-smooth muscle actin+ and SM22α+ smooth muscle bundles and pan-cytokeratin + epithelium at graft sites. CONCLUSIONS: These results demonstrate the feasibility of BLSF matrices to support the repair of previously damaged urethral tissues.

Bilayer silk fibroin grafts support functional oesophageal repair in a rodent model of caustic injury.

Surgical repair of caustic oesophageal injuries with autologous gastrointestinal segments is often associated with dysmotility, dysphagia and donor site morbidity, and therefore alternative graft options are needed. Bilayer silk fibroin (BLSF) scaffolds were assessed for their ability to support functional restoration of damaged oesophageal tissues in a rat model of onlay oesophagoplasty. Transient exposure of isolated oesophageal segments with 40% NaOH led to corrosive oesophagitis and a 91% reduction in the luminal cross-sectional area of damaged sites. Oesophageal repair with BLSF matrices was performed in injured rats (n = 27) as well as a nondiseased cohort (n = 12) for up to 2 months after implantation. Both implant groups exhibited >80% survival rates, displayed similar degrees of weight gain, and were capable of solid food consumption following a 3-day liquid diet. End-point µ-computed tomography of repaired sites demonstrated a 4.5-fold increase in luminal cross-sectional area over baseline injury levels. Reconstructed oesophageal conduits from damaged and nondiseased animals produced comparable contractile responses to KCl and electric field stimulation while isoproterenol generated similar tissue relaxation responses. Histological and immunohistochemical evaluations of neotissues from both implant groups showed formation of a stratified, squamous epithelium with robust cytokeratin expression as well as skeletal and smooth muscle layers positive for contractile protein expression. In addition, synaptophysin positive neuronal junctions and vessels lined with CD31 positive endothelial cells were also observed at graft sites in each setting. These results provide preclinical validation for the use of BLSF scaffolds in reconstructive strategies for oesophageal repair following caustic injury.

Bi-layer silk fibroin grafts support functional tissue regeneration in a porcine model of onlay esophagoplasty.

Partial circumferential, full thickness defects of the esophagus can occur as a result of organ perforation or tumour resection, or during surgical reconstruction of strictured segments. Complications associated with autologous tissue flaps conventionally utilized for defect repair necessitate the development of new graft options. In this study, bi-layer silk fibroin (BLSF) scaffolds were investigated for their potential to support functional restoration of partial circumferential defects in a porcine model of esophageal repair. Onlay thoracic esophagoplasty with BLSF matrices (~3 x 1.5 cm) was performed in adult swine (N = 6) for 3 months of implantation. All animals receiving BLSF grafts survived with no complications and were capable of solid food consumption. Radiographic esophagrams revealed preservation of organ continuity with no evidence of contrast extravasation or strictures. Fluoroscopic analysis demonstrated peristaltic contractions. Ex vivo tissue bath studies displayed contractile responses to carbachol, electric field stimulation, and KCl while isoproterenol produced tissue relaxation. Histological and immunohistochemical evaluations of neotissues showed a stratified, squamous epithelium, a muscularis mucosa composed of smooth muscle bundles, and a muscularis externa organized into circular and longitudinal layers, with a mix of striated skeletal muscle fascicles interspersed with smooth muscle. De novo innervation and vascularization were observed throughout the graft sites and consisted of synaptophysin-positive neuronal boutons and vessels lined with CD31-positive endothelial cells. The results of this study demonstrate that BLSF scaffolds can facilitate constructive remodeling of partial circumferential, full thickness esophageal defects in a large animal model. Copyright © 2017 John Wiley & Sons, Ltd.

Acellular bi-layer silk fibroin scaffolds support functional tissue regeneration in a rat model of onlay esophagoplasty.

Surgical management of long-gap esophageal defects with autologous gastrointestinal tissues is frequently associated with adverse complications including organ dysmotility, dysphagia, and donor site morbidity. In order to develop alternative graft options, bi-layer silk fibroin (SF) scaffolds were investigated for their potential to support functional tissue regeneration in a rodent model of esophageal repair. Onlay esophagoplasty was performed with SF matrices (N = 40) in adult rats for up to 2 m of implantation. Parallel groups consisted of animals implanted with small intestinal submucosa (SIS) scaffolds (N = 22) or sham controls receiving esophagotomy alone (N = 20). Sham controls exhibited a 100% survival rate while rats implanted with SF and SIS scaffolds displayed respective survival rates of 93% and 91% prior to scheduled euthanasia. Animals in each experimental group were capable of solid food consumption following a 3 d post-op liquid diet and demonstrated similar degrees of weight gain throughout the study period. End-point µ-computed tomography at 2 m post-op revealed no evidence of contrast extravasation, fistulas, strictures, or diverticula in any of the implant groups. Ex vivo tissue bath studies demonstrated that reconstructed esophageal conduits supported by both SF and SIS scaffolds displayed contractile responses to carbachol, KCl and electrical field stimulation while isoproterenol produced tissue relaxation. Histological (Masson's trichrome and hematoxylin and eosin) and immunohistochemical (IHC) evaluations demonstrated both implant groups produced de novo formation of skeletal and smooth muscle bundles positive for contractile protein expression [fast myosin heavy chain (MY32) and α-smooth muscle actin (α-SMA)] within the graft site. However, SF matrices promoted a significant 4-fold increase in MY32+ skeletal muscle and a 2-fold gain in α-SMA+ smooth muscle in comparison to the SIS cohort as determined by histomorphometric analyses. A stratified squamous, keratinized epithelium expressing cytokeratin 5 and involucrin proteins was also present at 2 m post-op in all experimental groups. De novo innervation and vascularization were evident in all regenerated tissues indicated by the presence of synaptophysin (SYP38)+ boutons and vessels lined with CD31 expressing endothelial cells. In respect to SIS, the SF group supported a significant 4-fold increase in the density of SYP38+ boutons within the implant region. Evaluation of host tissue responses revealed that SIS matrices elicited chronic inflammatory reactions and severe fibrosis throughout the neotissues, in contrast to SF scaffolds. The results of this study demonstrate that bi-layer SF scaffolds represent promising biomaterials for onlay esophagoplasty, capable of producing superior regenerative outcomes in comparison to conventional SIS scaffolds.