A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine's behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.

Utility of a Third Heplisav-B Dose in Patients With Inflammatory Bowel Disease Without Immunity After 2-Dose Heplisav-B Vaccination.

INTRODUCTION: Hepatitis B virus (HBV) vaccination is recommended in patients with inflammatory bowel disease (IBD). Although the 2-dose Heplisav-B vaccine has proven effective, more than 20% of patients with IBD do not seroconvert. We prospectively evaluated the effectiveness of a third Heplisav-B dose in patients with IBD lacking HBV immunity despite 2-dose vaccination. METHODS: Adults with IBD who had received 2-dose Heplisav-B vaccination between 2018 and 2023 were identified. Seroconversion was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L measured at ≥4 weeks after vaccination. Patients who did not seroconvert were prospectively offered a third Heplisav-B dose, followed by repeat HBsAb measurement. Demographic, clinical, medication, and vaccination data were compared between those who did and did not seroconvert. RESULTS: Of 192 patients identified, 71.9% (138/192) seroconverted after 2-dose Heplisav-B vaccination. The 54 patients (28.1%) who did not seroconvert were more likely to be male, have diabetes, chronic kidney disease, or elevated Charlson Comorbidity Index. Of the 54 patients, 30 (55.6%) elected to receive a third Heplisav-B dose, with 56.7% (17/30) achieving seroconversion (median HBsAb titer 376 IU/L, IQR 47-1,000 IU/L) despite a median intervaccination time of 416 days (IQR 90.8-667.8). No differences were noted between patients who did vs did not seroconvert after third-dose vaccination. DISCUSSION: In patients with IBD lacking HBV immunity despite 2-dose Heplisav-B vaccination, administration of a third dose resulted in a 56.7% seroconversion rate. Our results suggest that administration of an additional Heplisav-B dose may be an effective strategy in patients lacking immunity despite primary 2-dose vaccination.

Validation of prediction tools for GI bleeding in patients on dual anti-platelet therapy after percutaneous coronary intervention.

BACKGROUND AND AIMS: The management of dual anti-platelet therapy after percutaneous coronary intervention (PCI) and GI bleeding (GIB) remains a clinical dilemma. We sought to identify predictors of GIB and recurrent bleeding and to determine whether recurrent bleeding increases the risk of major adverse cardiovascular events (MACEs). METHODS: In this single-center retrospective study, patients undergoing PCI were identified. The primary and secondary endpoints were GIB at 180 days and recurrent bleeding or MACE at 365 days. Logistic regression was used to identify predictors of GIB and recurrent bleeding. Cox proportional hazards modeling was used to determine whether recurrent bleeding can predict a MACE. RESULTS: Five hundred thirty-six patients were included. On multivariable analysis, PCI for acute coronary syndrome was associated with a 95% increased odds of GIB (P < .001). The P2Y12 inhibitor was continued in >90% of patients, which trended toward significance for recurrent bleeding (P < .10). The HAS-BLED score (Hypertension, Abnormal renal and liver function, Stroke, Bleeding tendency or predisposition, Labile INRs, Elderly, Drugs), including a labile international normalized ratio and prior major bleeding, was strongly associated with recurrent bleeding (P ≤ .009). Recurrent bleeding was associated with a 115% increased risk of MACEs (P = .02). We derived a novel risk score, named the SIGE score ([S]TEMI at PCI, having a labile [I]NR at PCI, index [G]IB within 180 days of PCI, and previous precatheterization [E]ndoscopy within 6 months), to predict recurrent bleeding at 365 days with a high predictive accuracy (area under the curve, .773; 95% confidence interval, .702-.845). CONCLUSIONS: The SIGE score may help to predict recurrent bleeding, which was shown to be associated with an increased risk of MACEs. Further external validation is needed.

Development of a Risk Stratification Model for Pre-liver-Transplant Screening Colonoscopy.

BACKGROUND AND AIMS: Colonoscopies are routinely obtained before liver transplantation, although their utility is a highly debated topic in the literature. We aimed to determine the risk factors in patients with decompensated cirrhosis (DC) for post-colonoscopy complications (PCC). MATERIALS AND METHODS: We performed a single-center retrospective study of patients with DC undergoing colonoscopy as part of their pre-liver-transplant evaluation. The primary composite outcome was defined as a complication occurring within 30 days of the colonoscopy. Complications included acute renal failure, new or worsening ascites or hepatic encephalopathy, gastrointestinal bleeding, or any cardiopulmonary or infectious complication. Logistic regression analysis was utilized to derive a risk score in predicting the primary composite outcome. RESULTS: The strongest predictors of post-colonoscopy complication were MELD-Na ≥21 [aOR 4.0026 ( P =0.0050)] and history of any infection in the 30 days before colonoscopy [aOR 8.4345 ( P =0.0093)]. The area under the receiver operating characteristic curve of the final model was 0.78. The predicted risk of any complication at the lowest quartile was 16.2% to 39.4%, and the observed risk was 30.6% (95% CI: 15.5-45.6%), while the predicted risk at the highest quartile was 71.9% to 97.1%, and the observed risk was 81.3% (95% CI: 67.7-95%). CONCLUSION: In this cohort of patients with DC undergoing colonoscopy for pre-liver-transplant evaluation, a history of ascites, spontaneous bacterial peritonitis, and MELD-Na were found to be predictive of PCC. This risk score may help to predict PCC in patients with DC undergoing a pre-transplant colonoscopy. External validation is recommended.

IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas.

INTRODUCTION: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model. MATERIALS AND METHODS: We inoculated A375 and G361 human melanoma cell lines into NOD/SCID gamma mice (n = 64). We established a control group, a group treated with MSCs, a group treated with MSCs plus RT, and a group treated with RT. We assessed the immunohistochemical expression of IMP3, E-cadherin, N-cadherin, PARP1, HIF-1α, and the proliferation marker Ki-67. Additionally, we performed a retrospective study including 114 histological samples of patients diagnosed with malignant cutaneous superficial spreading melanoma (n = 104) and nodular melanoma (n = 10) with at least 5 years of follow-up. RESULTS: Most morphological and immunohistochemical features show statistically significant differences between the 2 cell lines. The A375 cell line induced the formation of metastases, while the G361 cell line provoked tumor formation but not metastases. All three treatments reduced the cell proliferation evaluated by the Ki-67 nuclear antigen (p = 0.000, one-way ANOVA test) and reduced the number of metastases (p = 0.004, one-way ANOVA test). In addition, the tumor volumes reduced in comparison with the control groups, 31.74% for RT + MSCs in the A357 tumor cell line, and 89.84% RT + MSCs in the G361 tumor cell line. We also found that IMP3 expression is associated with greater tumor aggressiveness and was significantly correlated with cell proliferation (measured by the expression of Ki-67), the number of metastases, and reduced expression of adhesion molecules. CONCLUSIONS: The combined treatment of RT and MSCs on xenografted melanomas reduces tumor size, metastases frequency, and the epithelial to mesenchymal transition/PARP1 metastatic phenotype. This treatment also reduces the expression of molecules related to cellular proliferation (Ki-67), molecules that facilitate the metastatic process (E-cadherin), and molecules related with prognosis (IMP3).

Radiographic evaluation of radial flexion osteotomy effect on static scapholunate instability: a preliminary cadaveric study.

INTRODUCTION: The optimal treatment of chronic scapholunate instability has yet to be established. Scapholunate ligament grafts are still far from being the ideal solution. We conducted an experimental study to evaluate whether flexion-opening wedge osteotomy of the distal radius improves misalignment and avoids rotatory subluxation of the scaphoid in a cadaveric model of static scapholunate dissociative instability. MATERIALS AND METHODS: Radiographic studies were performed on 15 cryopreserved specimens after recreating a model of scapholunate instability by division of the scapholunate interosseous ligament (SLIL) and secondary stabilizers, taking radiographs at baseline, after the instability model, and after distal radius osteotomy. Static and dynamic (under controlled tendon traction) anteroposterior and lateral views were obtained to measure the length (in mm) of the carpal scaphoid and scapholunate interval, scapholunate angle, radio-lunate angle, and palmar tilt of the distal joint surface of the radius and to measure the dorsal scaphoid translation by the concentric circles method. The Wilcoxon test was used for statistical comparisons. RESULTS: The scapholunate interval was significantly decreased after osteotomy in all static anteroposterior views and in all lateral views under tendon traction. Dorsal scaphoid translation was significantly reduced in static lateral view in extension and in dynamic lateral view under 5-pound flexor carpi radialis tendon tension controlled by a digital dynamometer. CONCLUSIONS: Flexion-addition osteotomy of the distal radius appears to improve carpal alignment parameters in a cadaveric model of static scapholunate instability, achieving similar values to those obtained before instability.

Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US.

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). RESULTS: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). CONCLUSION: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. IMPACT AND IMPLICATIONS: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.

Density mapping of nerve endings in the skin of the palm and flexor retinaculum of the hand. Application to open carpal tunnel release.

In order to re-evaluate the safest area to incise skin and the flexor retinaculum (FR) when performing a carpal tunnel release (CTR), we carried out a mapping study of the nerve endings in the skin and FR on cadaver specimens, which, unlike previous studies for the first time, includes histomorphometry and image digital analysis. After dividing the skin and FR into 20 and 12 sections, respectively, we carried out a histomorphological analysis of nerve endings. The analysis was performed by two neutral observers on 4-µm histological sections stained with hematoxylin-eosin (H-E), and Klüver-Barrera with picrosirius red (KB + PR) methods. A semi-automatic image digital analysis was also used to estimate the percentage of area occupied per nerve. We observed a lower quantity of nerve endings in the skin of the palm of the hand in line with the ulnar aspect of the 4th finger. The ulnar aspect of the FR was the most densely innervated. However, there are no statistically significant differences between sections in the percentage of area occupied per nerve both in the skin and in the FR. We concluded that there is not a safe area to incise when performing carpal tunnel surgery, but taking into account the quantity of nerve endings present in skin and FR, we recommend an incision on the axis of the ulnar aspect of 4th finger when incising skin and on the middle third of the FR for CTR.

Factors That Influence the Speed and Completion of Double Balloon Enteroscopy in Patients with Arteriovenous Malformations.

BACKGROUND: Double balloon enteroscopy remains a resource and time-intensive procedure that is not available in many endoscopy units. AIMS: We aimed to identify variables impacting the speed and completion of double balloon enteroscopy. METHODS: We retrospectively reviewed 550 patients. Using a mean time and distance for both the antegrade and retrograde approach, we determined the procedure speed and assessed factors that influenced it. In addition, we assessed the factors that contributed to a complete double balloon enteroscopy. RESULTS: A total of 386 antegrade and 164 retrograde double balloon enteroscopies were performed. Greater than 10 AVMs requiring treatment was a negative predictor (AOR 0.25, CI 0.11-0.51, p < 0.001), whereas age greater than 60 years (AOR 2.66, CI 1.18-6.65, p = 0.025) was a positive predictor of a fast antegrade enteroscopy. For retrograde, prior abdominal surgery was the only factor that trended to significance (AOR 0.38, CI 0.14-0.99, p = 0.052). A total of 120 combined procedures were performed. Female gender (AOR 2.62, CI 1.16-6.24, p = 0.02), history of prior abdominal surgery (AOR 0.31, CI 0.13-0.70, p = 0.006) and Boston bowel pre-preparation score of greater than 6 (AOR 4.50, CI 1.59-14.30, p = 0.006) were the only significant predictors of a complete procedure. CONCLUSION: By applying double balloon enteroscopy speed, a novel method of measuring procedure efficiency, we were able to more reliably identify the factors that will negatively impact the speed and success of the procedure.

Clinical Characteristics and Computed Tomography Findings in Adult Patients With an Aberrant Right Subclavian Artery: A Single-Center Retrospective Cohort Study.

OBJECTIVE: We sought to determine the prevalence and possible features associated with symptoms in adult patients diagnosed with an aberrant right subclavian artery (ARSA). METHODS: In this single-center retrospective study, 386 adult patients were diagnosed with ARSA on chest CT scans performed between June 2016 and April 2021. Patients were grouped by the presence of symptoms, which included dysphagia, shortness of breath, cough, and upper airway wheezing. Four cardiothoracic radiologists reviewed the chest CT scans to assess features of ARSA. Agreement and multivariable logistic regression analyses were performed to determine interobserver variability and features associated with the presence of symptoms, respectively. RESULTS: The prevalence of ARSA was 1.02% and 81.3% of patients were asymptomatic. Shortness of breath (74.6%) was the most common symptom. Interobserver agreement was acceptable with most variables having an interclass correlation coefficient or κ >0.80. A patient's height > 158 cm (OR: 2.50, P = 0.03), cross-sectional area > 60 mm 2 of ARSA at the level of the esophagus (OR: 2.39, P = 0.046), and angle >108 degrees formed with the aortic arch (OR: 1.99, P = 0.03) were associated with the presence of symptoms on multivariable logistic regression. A distance increase per 1 mm between ARSA and trachea (OR: 0.85, P = 0.02) was associated with decreased odds of symptoms. CONCLUSIONS: Aberrant right subclavian artery is an incidental finding in most adult patients. The cross-sectional area at the level of the esophagus, angle formed with the medial wall of the aortic arch, distance between the ARSA and the trachea, and a patient's height were features associated with the presence of symptoms.

Effects of emotional congruency and task complexity on decision-making.

The heuristic approach to decision-making holds that the selection process becomes more efficient when part of the information available is ignored. One element involved in selecting information is emotional valence. If emotional congruency is related to simplified decision-making strategies, then the interaction of this factor with task complexity should exist. The present study explored how factors of this nature influence decision-making efficiency. We hypothesized that emotional congruency would have a positive effect on task execution and that the magnitude of that effect would increase with greater task complexity because in that condition the amount of information to be processed is greater, meaning that a heuristic approach to the problem would be more efficient. We design a decision in browser decision-making task in which participants had to select emotional images to gain points. Depending on the correlation between emotional valence and in-task image value, we defined three emotional congruency conditions: direct, null, and inverse. Our results show that distinct types of emotional congruency have differential effects on behavior. While direct congruency-enhanced overall decision-making performance, inverse congruency interacted with task complexity to modify the pace at which task feedback affected behavior.

Cocaine-induced locomotor stimulation involves autophagic degradation of the dopamine transporter.

Cocaine exerts its stimulant effect by inhibiting dopamine reuptake leading to increased dopamine signaling. This action is thought to reflect binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share the behavioral actions of cocaine. We previously showed that toxic levels of cocaine induce autophagic neuronal cell death. Here, we show that subnanomolar concentrations of cocaine elicit neural autophagy in vitro and in vivo. Autophagy inhibitors reduce the locomotor stimulant effect of cocaine in mice. Cocaine-induced autophagy degrades transporters for dopamine but not serotonin in the nucleus accumbens. Autophagy inhibition impairs cocaine conditioned place preference in mice. Our findings indicate that autophagic degradation of DAT modulates behavioral actions of cocaine.

Simple risk score to predict the likelihood of a positive EUS in idiopathic acute pancreatitis.

BACKGROUND AND AIMS: We sought to derive a risk score, DORM65, of known variables to predict the likelihood of a positive EUS in patients with idiopathic acute pancreatitis (IAP). METHODS: A retrospective cohort study of 180 patients with IAP was performed across 3 tertiary care centers between January 2018 and December 2021. Multivariate logistic regression modeling was performed to predict a positive EUS. Accuracy of the models was assessed by the area under the receiver-operating characteristic curve (AUROCC). RESULTS: The diagnostic yield of EUS was 58.9% (95% confidence interval [CI], 51.7-66.1). The DORM65 scores of 5 predictors present before EUS with the best discrimination were a delayed EUS (defined as ≥82 days from the last episode of AP), obesity, not having had a repeated transabdominal US, male sex, and age ≥65 years at the time of EUS. For those at the lowest risk score group, the positive EUS rate was 13.0% compared with 100% in those at the highest risk group (relative risk, 7.67; P < .001). A score of 3 or more had a positive predictive value of 86.0% with a sensitivity of 34.9% and specificity of 91.9%. The model had a high predictive accuracy (AUROCC, .774; 95% CI, .707-.841). Adding 3 additional predictors (no cholecystectomy, no MRCP, and a single episode of AP) did not increase the accuracy significantly (AUROCC, .805; 95% CI, .742-.867). CONCLUSIONS: DORM65 is easily calculated and accurately predicts a positive EUS in patients with IAP. Further validation is needed.

Incidentalomas are associated with an increase in liver transplantation in patients with cirrhosis: a single-center retrospective study.

BACKGROUND: Incidentalomas, defined as incidental findings on imaging, are a growing concern. Our aim was to determine the impact and outcomes of extrahepatic incidentalomas on liver transplantation. METHODS: Patients at a large liver transplant center, who had an initial MRI for hepatocellular carcinoma screening between January 2004 and March 2020 were identified. Clinical data were collected retrospectively. Survival analysis, utilizing Kaplan Meier estimates and Cox proportional hazards regression analysis, was utilized to determine factors associated with liver transplantation. RESULTS: 720 patients were included. NASH (24.9%), HCV (22.1%) and alcohol (20.6%) were the most common causes of cirrhosis. 79.7% of patients had an extrahepatic incidentaloma. Older age and having received a liver transplant by the end of the study were associated with an incidentaloma. MELD was not associated with the presence of an incidentaloma. On univariate Cox proportional hazards regression, male sex, history of moderate alcohol use, smoking history, MELD, and incidentalomas were predictors of liver transplantation. On multivariate analysis, only MELD and the presence of an incidentaloma were found to be significant. Discovery of an incidentaloma was associated with a 30% increase in the risk of liver transplantation. Median time to transplantation did not differ based on the presence on an incidentaloma. Patients with cirrhosis from alcohol or HCV had a significantly shorter median time to transplantation than those with NASH. Renal and pancreatic lesions comprised 91% of all incidentalomas. CONCLUSIONS: In this single-center retrospective study, extrahepatic incidentalomas were common in patients with cirrhosis. The finding of an incidentaloma was associated with a higher risk of liver transplantation despite a similar median time to transplantation if no incidentaloma was discovered.

Colchicine as an Alternative First-Line Treatment of Sclerosing Mesenteritis: A Retrospective Study.

BACKGROUND: Sclerosing mesenteritis is a rare condition characterized by chronic inflammation and fibrotic changes of the mesentery. AIMS: To determine the long-term management and outcomes of patients with sclerosing mesenteritis. METHODS: Patients with biopsy-proven sclerosing mesenteritis at the Mayo Clinic between January 2006 and December 2016 were identified. Clinical data were collected retrospectively. RESULTS: One hundred and three patients were identified, median age 68.0 years (range 35.0-85.3). Most patients were symptomatic (87.4%) at presentation. Patients received no treatment (52.4%), medical therapy (42.7%) or surgery (4.9%) on initial diagnosis. The most common initial regimens were prednisone plus tamoxifen (41.9%), prednisone alone (23.3%), and prednisone plus colchicine (11.6%) with 55.6%, 57.2%, and 60% of patients improving, respectively, p = 0.85 for a difference in response rates. At least half of the patients responded to prednisone plus tamoxifen, prednisone plus colchicine, or prednisone alone at 6.0, 7.2, and 8.4 months, respectively. At a median follow-up of 45.6 months (95% CI 24.1-69.7), 65.4% of patients were receiving medical therapy. Of those receiving tamoxifen-based, steroid-based, or steroid-sparing regimens, 100%, 87.5%, and 77.8% had improved by their last follow-up appointment respectively, p = 0.15. CONCLUSION: Prednisone plus colchicine has a similar efficacy to prednisone plus tamoxifen for the initial and long-term treatment of sclerosing mesenteritis. The majority of patients were initiated on medical therapy over the long term with most reporting symptomatic improvement within a year. Death from SM was rare.

Endoscopic ultrasound-guided biliary drainage in benign biliary pathology with normal foregut anatomy: a multicenter study.

BACKGROUND AND AIMS: Biliary drainage using endoscopic ultrasound (EUS-BD) has been developed as a novel technique to obtain biliary access and drainage when ERCP fails. Numerous studies have demonstrated its safety and efficacy specifically pertaining to those with malignant distal biliary obstruction or altered foregut anatomy. The aim of this study is to evaluate the safety and efficacy of EUS-BD in benign indications in patients with normal foregut anatomy. METHODS: We performed a retrospective comparative study from 5 academic medical centers (2008-2018) involving patients with benign biliary obstruction and native foregut anatomy who had an initial failed ERCP with subsequent attempt at biliary decompression via EUS-BD or by repeating ERCP. RESULTS: 36 patients (mean age 61.6 ± 2.2, 38.9% female) who underwent attempted EUS-BD following initial failed ERCP were compared to 50 patients (mean age 62.7 ± 2.3, 73.5% female) who underwent repeat ERCP following an initial failed cannulation. EUS-BD was technically successful in 28 (77.8%) patients with rendezvous being the most common approach (86.1%). A higher level of pre-procedural bilirubin was found to be associated with technical success of EUS-BD (3.65 ± 0.63 versus 1.1 ± 0.4, p value 0.04). Success of repeat ERCP following failed cannulation was 86%. Adverse events were significantly more frequent in the EUS-BD cohort when compared to the repeat ERCP (10 (27.8%) versus 4 (8.0%), p = 0.02, OR 4.32. CONCLUSIONS: EUS-BD remains a viable therapeutic option in the setting of benign biliary disease, with success rates of 77.8%. Adverse events were significantly more common with EUS-BD vs. repeat ERCP, emphasizing the need to perform in expert centers with appropriate multidisciplinary support and to strongly consider the urgency of biliary decompression before considering same session EUS-BD after failed initial biliary access.

A comparison of clinical outcomes and cost utility among laparoscopy, enteroscopy, and temporary gastric access-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy.

BACKGROUND AND AIMS: Gastric Access Temporary for Endoscopy (GATE), also known as EUS-Directed Trangastric ERCP (EDGE), has demonstrated advantages over device-assisted enteroscopy (DAE) and laparoscopic-assisted ERCP (LA-ERCP) for patients with Roux-en-Y gastric bypass (RYGB) anatomy. We aimed to directly compare clinical outcomes and cost utility among the three ERCP modalities. METHODS: Patients with RYGB anatomy who had DAE, LA-ERCP, or GATE from 2009 to 2019 at 2 tertiary centers were included in our review. We measured outcomes in three areas: success rate, post-procedural adverse events (AEs) and hospitalization, and cost utility per Medicare/Medicaid insurance payments. RESULTS: Cohort Total 130 patients (70 underwent DAE, 42 LA-ERCP, and 18 GATE). Success rate DAE was successful in 59% of patients, compared to success rates of 98 and 100% for LA-ERCP and GATE, respectively (p < 0.001). For DAE, 62% of unsuccessful cases required rescue therapy. Adverse events and hospitalization Patients who underwent GATE had the lowest rate of hospitalization post procedure (44% vs. 77% and 100% for DAE and LA-ERCP, respectively, p < 0.01) and spent the least amount of time hospitalized (median time 0 days vs 2 and 3 days for DAE and LA-ERCP, respectively, p < 0.0001). GATE had lower AE rates than LA-ERCP (6 vs 31%, p = 0.046), and both had similar rates to DAE. Cost utility LA-ERCP carried the highest total procedural and hospitalization cost per Medicare/ Medicaid insurance payments (median payment difference of $9.7 K vs GATE and $7.9 K vs DAE, p < 0.01 for both). Procedural and hospitalization costs were similar between GATE and DAE (p = 0.76). CONCLUSIONS: GATE is a safe modality for ERCP with high success rates in RYGB patients and exhibits the lowest hospitalization time and rate of adverse events when compared to DAE and LA-ERCP. GATE is similar to DAE from a cost utility approach, and both are less costly than LA-ERCP.

Expression of Musashi-1 Increases in Bone Healing.

Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze the expression of MSI1 in an experimental model of rat femoral bone fractures. We also analyze the relation between MSI1 expression and the expression of two osteogenic markers: periostin (POSTN) and runt-related transcription factor 2 (RUNX2). We use histological, immunohistochemical, and qPCR techniques to evaluate bone healing and the expression of MSI1, POSTN, and RUNX2 over time (4, 7, and 14 days). We compare our findings with non-fractured controls. We find that in bone calluses, the number of cells expressing MSI1 and RUNX2 increase over time and the intensity of POSTN expression decreases over time. Within bone calluses, we find the presence of MSI1 expression in mesenchymal stromal cells, osteoblasts, and osteocytes but not in hypertrophic chondrocytes. After 14 days, the expression of MSI1, POSTN, and RUNX2 was significantly correlated. Thus, we conclude that musashi-1 potentially serves in the osteogenic differentiation of mesenchymal stromal cells and bone healing. Therefore, further studies are needed to determine the possibility of musashi-1's role as a clinical biomarker of bone healing and therapeutic agent for bone regeneration.

Anatomic study of pedicled bipolar teres major transfer for irreparable posterosuperior rotator cuff tears.

BACKGROUND: Treatment of rotator cuff (RC) tears has not included bipolar muscle-tendon transfers to date. The objective of this study was to verify the feasibility of pedicled bipolar teres major (TM) transfer over and under the long head of the triceps brachii (LHT) and compare its versatility with monopolar transfer in a model of supraspinatus (SS) tears in cadavers. METHODS: In 6 shoulders of cryopreserved cadavers, we re-created complete SS tears, conducting monopolar and bipolar TM transfers over and under LHT. We compared the morphology of the SS and TM, defect coverage, angle between the transferred TM and major SS axis, and axillary nerve overlap with each technique. RESULTS: The TM and SS were morphologically similar. Defect coverage was significantly lower with monopolar transfer (12 ± 4 mm) than with bipolar transfer (39 ± 9 mm under the LHT, P = .003, and 38 ± 8 mm over the LHT, P = .004). The bipolar transfer course over the LHT was the nearest to the SS axis (39° ± 11°, P = .005). We found a greater axillary nerve overlap with bipolar transfer under the LHT (27 ± 8 mm) than with bipolar transfer over the LHT (1 ± 2 mm, P = .005) or monopolar transfer (0 mm, P < .001). CONCLUSION: Bipolar TM transfer is possible without neurovascular pedicle interference, obtaining greater RC defect coverage and the closest path to the SS axis when conducted over the LHT compared with monopolar or bipolar transfer under the LHT. Accordingly, it can be considered an alternative option for the treatment of posterosuperior RC defects.

Identification of peptide sequences that selectively bind to pentaerythritol trinitrate hemisuccinate-a surrogate of PETN, via phage display technology.

The present research investigates the identification of amino acid sequences that selectively bind to a pentaerythritol tetranitrate (PETN) explosive surrogate. Through the use of a phage display technique and enzyme-linked immunosorbent assays (ELISA), a peptide library was tested against pentaerythritol trinitrate hemisuccinate (PETNH), a surrogate of PETN, to screen for those with amino acids having affinity toward the explosive. The results suggest that the library contains peptides selective to PETNH. Following three rounds of panning, clones were picked and tested for specificity toward PETNH. ELISA results from these samples show that each phage clone has some level of selectivity for binding to PETNH. The peptides from these clones have been sequenced and shown to contain certain common amino acid segments among them. This work represents a technological platform for identifying amino-acid sequences selective toward any bio-chem analyte of interest.