Citations

Abstract Background Endoscopic cyanoacrylate (glue) injection of fundal varices may result in life-threatening embolic adverse events through spontaneous gastrorenal shunts (GRSs). Balloon-occluded retrograde transvenous occlusion (BRTOcc) of GRSs during cyanoacrylate injection may prevent serious systemic glue embolization through the shunt. This study aimed to evaluate the efficacy and safety of a combined endoscopic–interventional radiologic (BRTOcc) approach for the treatment of bleeding fundal varices. Methods We retrospectively analysed the data of patients who underwent the combined procedure for acutely bleeding fundal varices between January 2010 and April 2018. Data were extracted for patient demographics, clinical and endoscopic findings, technical details, and adverse events of the endoscopic–BRTOcc approach and patient outcomes. Results We identified 30 patients (13 [43.3%] women; median age 58 [range, 25–92] years) with gastroesophageal varices type 2 (53.3%, 16/30) and isolated gastric varices type 1 (46.7%, 14/30) per Sarin classification, and median clinical and endoscopic follow-up of 151 (range, 4–2,513) days and 98 (range, 3–2,373) days, respectively. The median volume of octyl-cyanoacrylate: Lipiodol injected was 7 (range, 4–22) mL. Procedure-related adverse events occurred in three (10.0%) patients, including transient fever, non-life-threatening pulmonary glue embolism, and an injection-site ulcer bleed. Complete gastric variceal obturation was achieved in 18 of 21 patients (85.7%) at endoscopic follow-up. Delayed variceal rebleeding was confirmed in one patient (3.3%) and suspected in two patients (6.7%). Although no procedure-related deaths occurred, the overall mortality rate was 46.7%, primarily from liver-disease progression and co-morbidities. Conclusion The combined endoscopic–BRTOcc procedure is a relatively safe and effective technique for bleeding fundal varices, with a high rate of variceal obturation and a low rate of serious adverse events.

PolyQ ATXN3 is a pharmacodynamic marker for SCA3, and a SNP associated with the expanded allele may serve to specifically target mutant ATXN3 .

Abstract Aging is a physiological decline in both structural homeostasis and functional integrity, progressively affecting organismal health. A major hallmark of aging is the accumulation of senescent cells, which have entered a state of irreversible cell cycle arrest after experiencing inherent or environmental stresses. Although cellular senescence is essential in several physiological events, it plays a detrimental role in a large array of age‐related pathologies. Recent biomedical advances in specifically targeting senescent cells to improve healthy aging, or alternatively, postpone natural aging and age‐related diseases, a strategy termed senotherapy, have attracted substantial interest in both scientific and medical communities. Challenges for aging research are highlighted and potential avenues that can be leveraged for therapeutic interventions to control aging and age‐related disorders in the current era of precision medicine.

AbstractThe phase 3 FIRST trial demonstrated significant improvement in progression‐free survival (PFS) and overall survival (OS) with an immune‐stimulatory agent, lenalidomide, in combination with low‐dose dexamethasone until disease progression (Rd continuous) vs melphalan +prednisone + thalidomide (MPT) in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM). Rd continuous similarly extended PFS vs fixed‐duration Rd for 18 cycles (Rd18). Outcomes in the Canadian/US subgroup (104 patients per arm) are reported in this analysis. Rd continuous demonstrated a significant improvement in PFS vs MPT (median, 29.3 vs 20.2 months; HR, 0.69 [95% CI, 0.49‐0.97]; p = 0.03326) and an improvement vs Rd18 (median, 21.9 months). Median OS was 56.9 vs 46.8 months with Rd continuous vs MPT (p = 0.15346) and 59.5 months with Rd18. The overall response rate was higher with Rd continuous and Rd18 (78.8% and 79.8%) vs MPT (65.4%). In the 49.0%, 52.9%, and 29.8% of patients with at least very good partial response in the Rd continuous, Rd18, and MPT arms, respectively, the median PFS was 56.0, 30.9, and 40.2 months, respectively. The most common grade 3/4 treatment‐emergent adverse events were neutropenia (28.4%, 30.1%, and 52.0%), anemia (23.5%, 21.4%, and 23.5%), and infections (37.3%, 30.1%, and 24.5%) with Rd continuous, Rd18, and MPT, respectively. These results were consistent with those in the intent‐to‐treat population, confirming the benefit of Rd continuous vs MPT in the Canadian/US subgroup and supporting the role of Rd continuous as a standard of care for transplant‐ineligible patients with NDMM.

AbstractPurposeOvernight admission following anterior cruciate ligament reconstruction has implications on clinical outcomes as well as cost benefit, yet there are few validated risk calculators for reliable identification of appropriate candidates. The purpose of this study is to develop and validate a machine learning algorithm that can effectively identify patients requiring admission following elective anterior cruciate ligament (ACL) reconstruction. MethodsA retrospective review of a national surgical outcomes database was performed to identify patients who underwent elective ACL reconstruction from 2006 to 2018. Patients admitted overnight postoperatively were identified as those with length of stay of 1 or more days. Models were generated using random forest (RF), extreme gradient boosting (XGBoost), linear discriminant classifier (LDA), and adaptive boosting algorithms (AdaBoost), and an additional model was produced as a weighted ensemble of the four final algorithms.ResultsOverall, of the 4,709 patients included, 531 patients (11.3%) required at least one overnight stay following ACL reconstruction. The factors determined most important for identification of candidates for inpatient admission were operative time, anesthesia type, age, gender, and BMI. Smoking history, history of COPD, and history of coagulopathy were identified as less important variables. The following factors supported overnight admission: operative time > 200 min, age < 35.8 or > 53.5 years, male gender, BMI < 25 or > 31.2 kg/m2, positive smoking history, history of COPD and the presence of preoperative coagulopathy. The ensemble model achieved the best performance based on discrimination assessed via internal validation (AUC = 0.76), calibration, and decision curve analysis. The model was integrated into a web‐based open‐access application able to provide both predictions and explanations.ConclusionModifiable risk factors identified by the model such as increased BMI, operative time, anesthesia type, and comorbidities can help clinicians optimize preoperative status to prevent costs associated with unnecessary admissions. If externally validated in independent populations, this algorithm could use these inputs to guide preoperative screening and risk stratification to identify patients requiring overnight admission for observation following ACL reconstruction.Level of evidenceIV.