Citations

Abstract Therapeutic strategies that target novel pathways are urgently needed for patients with relapsed/refractory multiple myeloma (RRMM). Ibrutinib is an oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in MM cells. This phase 1 dose‐escalation study examined various doses of ibrutinib in combination with standard doses of lenalidomide (25 mg) and dexamethasone (40 mg) using a standard 3 + 3 design in RRMM patients. The primary objective was to determine the maximum tolerated dose (MTD) of ibrutinib in combination with lenalidomide and dexamethasone. Patients ( n = 15) had received a median of 4 prior regimens, 53% were triple‐class exposed, 33% were penta‐exposed, and 54% were lenalidomide‐refractory. The MTD of ibrutinib was 840 mg ( n = 6) and only 1 dose‐limiting toxicity; a grade 3 rash possibly related to ibrutinib was noted. The most common ≥ grade 3 adverse events were rash in 2 (13%), lymphopenia in 2 (13%), leukopenia, neutropenia, thrombocytopenia, and anemia all occurring in 3 (20%) patients each. One patient achieved a partial response for an overall response rate of 7%. The clinical benefit rate was 80%. The median time to progression was 3.8 months. Ibrutinib, lenalidomide and dexamethasone appears to be a safe and well‐tolerated regimen with reasonable efficacy in heavily pretreated RRMM patients.

Introduction: Redo-Surgical valve replacement (Redo-SAVR) is the gold standard treatment for failed degenerated bioprosthetic valves. Recently approved less invasive Valve-In-Valve Transcatheter Aortic Valve Implantation (ViV-TAVI) procedure is becoming more popular but with limited evidence of its safety and efficacy compared to redo-SAVR. Hypothesis: We aimed to conduct the meta-meta analysis to evaluate the outcomes of ViV-TAVI compared to redo-SAVR. Methods: We conducted a systematic search of meta-analysis studies assessing outcomes of ViV-TAVR vs redo-SAVR using PubMed search engine and following PRISMA guidelines from inception to May 2021. A meta-meta-analysis was performed by obtaining a pooled odds ratio, 95% confidence interval (95%CI) using random-effects models to analyze outcomes of 30-day all-cause mortality and procedural mortality. Results: Nine meta-analysis studies were included. We found that there was a significantly lower odds of 30-day all-cause mortality (pooled OR:0.60; 95%CI:0.53-0.68; p<0.00001) with 0% heterogeneity (I2= 0%;p=0.53) in the ViV-TAVI compared to redo-SAVR. We also found a reduced risk of procedural mortality with ViV-TAVI compared to redo-SAVR (pooled OR:0.52; 95%CI:0.27-0.98; p=0.04) with 0% heterogeneity (I2= 0%;p=0.69) (Figure). Conclusions: ViV-TAVI is significantly associated with reduced risk of 30-day all-cause mortality, and procedural mortality compared to redo-SAVR. Our meta-meta-analysis supports that minimally invasive ViV-TAVI is a safe and better procedure for degenerated bioprosthetic valves in high-risk candidates.

Objective: To determine if gastrointestinal (GI) symptoms can predict deep endometriosis (DE) of the posterior pelvic compartment on magnetic resonance imaging (MRI). Methods: Patients with suspected endometriosis undergoing endometriosis protocol MRI at an academic center between 9/1/2015 and 7/31/2018 were identified. Presenting GI symptoms were collected via a standardized survey instrument prospectively at initial presentation. MRI and interdisciplinary conference notes were reviewed to identify posterior compartment DE (rectosigmoid, uterosacral ligaments, posterior cul de sac, and pelvic side walls). Associations between symptoms and DE were evaluated. Results: A total of 104 patients met inclusion criteria, and 89 (85.6%) presented with at least one GI symptom. Posterior compartment DE was identified on MRI in 47 patients (45.2%). The GI symptom that most strongly predicted DE was a bowel movement resulting in pain relief (OR 3.36, 95% CI 1.31–8.61, p = 0.012), with sensitivity, specificity, positive and negative predictive values 0.42, 0.82, 0.67, and 0.63, respectively. Other GI symptoms such as nausea, vomiting, rectal bleeding, change in frequency of bowel movements, and pain exacerbation by bowel movements did not significantly correlate to having DE. Of the 15 patients with no GI symptoms, 5 were found to have posterior compartment DE. Conclusion: In patients with suspected endometriosis, those who noted that bowel movements relieved their pain had more than three times the odds of having DE of the posterior compartment on MRI. Preoperative evaluation with MRI may be of value in these patients; however, lack of gastrointestinal symptoms does not exclude the possibility of posterior compartment DE.

OBJECTIVE The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

Abstract Background Pineoblastoma is a rare brain tumor usually diagnosed in children. Given its rarity, no pineoblastoma-specific trials have been conducted. Studies have included pineoblastoma accruing for other embryonal tumors over the past 30 years. These included only occasional children with pineoblastoma, making clinical features difficult to interpret and determinants of outcome difficult to ascertain. Patients and Methods Centrally or independently reviewed series with treatment and survival data from North American and Australian cases were pooled. To investigate associations between variables, Fisher’s exact tests, Wilcoxon-Mann-Whitney tests, and Spearman correlations were used. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analyses. Results We describe a pooled cohort of 178 pineoblastoma cases from Children’s Oncology Group (n = 82) and institutional series (n = 96) over 30 years. Children &lt;3 years of age have significantly worse survival compared to older children, with 5-year progression-free survival (PFS) and overall survival (OS) estimates of 13.5 ± 5.1% and 16.2 ± 5.3%, respectively, compared with 60.8 ± 5.6% and 67.3 ± 5.0% for ≥3 years old (both P &lt; .0001). Multivariable analysis showed male sex was associated with worse PFS in children &lt;3 years of age (hazard ratio [HR] 3.93, 95% CI 1.80-8.55; P = .0006), suggestive of sex-specific risks needing future validation. For children ≥3 years of age, disseminated disease at diagnosis was significantly associated with an inferior 5-year PFS of 39.2 ± 9.7% (HR 2.88, 95% CI 1.52-5.45; P = .0012) and 5-year OS of 49.8 ± 9.1% (HR 2.87, 95% CI 1.49-5.53; P = .0016). Conclusion Given the rarity of this tumor, prospective, collaborative international studies will be vital to improving the long-term survival of these patients.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte–predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

Patient safety is a core principle of anesthesia care worldwide. The specialty of anesthesiology has been a leader in medicine for the past half century in pursuing patient safety research and implementing standards of care and systematic improvements in processes of care. Together, these efforts have dramatically reduced patient harm associated with anesthesia. However, improved anesthesia patient safety has not been uniformly obtained worldwide. There are unique differences in patient safety outcomes between countries and regions in the world. These differences are often related to factors such as availability, support, and use of health care resources, trained personnel, patient safety outcome data collection efforts, standards of care, and cultures of safety and teamwork in health care facilities. This article provides insights from national anesthesia society leaders from 13 countries around the world. The countries they represent are diverse geographically and in health care resources. The authors share their countries’ current and future initiatives in anesthesia patient safety. Ten major patient safety issues are common to these countries, with several of these focused on the importance of extending initiatives into the full perioperative as well as intraoperative environments. These issues may be used by anesthesia leaders around the globe to direct collaborative efforts to improve the safety of patients undergoing surgery and anesthesia in the coming decade.