Citations

Abstract Patients with multiple myeloma (MM) who do not respond to initial therapy have worse outcomes than primary responders, and effective treatments are lacking in this population. However, the outcomes of primary refractory disease in the modern treatment era have not yet been studied. We reviewed patients with MM treated with triplet/quadruplet therapy at our institution to assess the incidence of primary refractory disease and the impact of salvage therapies in this population. We identified 1127 patients, of whom 1086 were evaluated for hematologic responses after 4 to 6 cycles. Of these, 93.3% (1013) had evidence of response, whereas 6.7% (73) had primary refractory disease. With a median overall survival (OS) of 51.3 months, patients with primary refractory disease had an increased risk of shorter survival in univariable and multivariable analyses (hazard ratio [HR], 3.5 [95% confidence interval (CI), 2.5-4.9]; HR, 4.3 [95% CI, 2.6-6.9], respectively). In the subgroup analysis of patients with primary refractory disease, those who received second-line autologous stem cell transplantation (ASCT) had increased second progression-free survival (20.9 vs 8.1 months; P < .01) and second OS (74.7 vs 31.3 months; P = .02) compared with patients who did not. We conclude that early progression remains a significant factor for shorter OS in the current era, and salvage ASCT could be the most beneficial option for this population.

Abstract Background This is Part 2 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy (EL) using an Enhanced Recovery After Surgery (ERAS) approach. This paper addresses intra‐ and postoperative aspects of care. Methods Experts in aspects of management of high‐risk and emergency general surgical patients were invited to contribute by the International ERAS ® Society. PubMed, Cochrane, Embase, and Medline database searches were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized clinical trials, systematic reviews, meta‐analyses, and large cohort studies and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. Some ERAS ® components covered in other guideline papers are outlined only briefly, with the bulk of the text focusing on key areas pertaining specifically to EL. Results Twenty‐three components of intraoperative and postoperative care were defined. Consensus was reached after three rounds of a modified Delphi Process. Conclusions These guidelines are based on best available evidence for an ERAS ® approach to patients undergoing EL. These guidelines are not exhaustive but pull together evidence on important components of care for this high‐risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.

IMPORTANCE: Initial Society of Critical Care Medicine Discovery Viral Infection and Respiratory illness Universal Study (VIRUS) Registry analysis suggested that improvements in critical care processes offered the greatest modifiable opportunity to improve critically ill COVID-19 patient outcomes. OBJECTIVES: The Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 ICU Collaborative was created to identify and speed implementation of best evidence based COVID-19 practices. DESIGN, SETTING, AND PARTICIPANTS: This 6-month project included volunteer interprofessional teams from VIRUS Registry sites, who received online training on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury approach, a structured and systematic method for delivering evidence based critical care. Collaborators participated in weekly 1-hour videoconference sessions on high impact topics, monthly quality improvement (QI) coaching sessions, and received extensive additional resources for asynchronous learning. MAIN OUTCOMES AND MEASURES: Outcomes included learner engagement, satisfaction, and number of QI projects initiated by participating teams. RESULTS: Eleven of 13 initial sites participated in the Collaborative from March 2, 2021, to September 29, 2021. A total of 67 learners participated in the Collaborative, including 23 nurses, 22 physicians, 10 pharmacists, nine respiratory therapists, and three nonclinicians. Site attendance among the 11 sites in the 25 videoconference sessions ranged between 82% and 100%, with three sites providing at least one team member for 100% of sessions. The majority reported that topics matched their scope of practice (69%) and would highly recommend the program to colleagues (77%). A total of nine QI projects were initiated across three clinical domains and focused on improving adherence to established critical care practice bundles, reducing nosocomial complications, and strengthening patient- and family-centered care in the ICU. Major factors impacting successful Collaborative engagement included an engaged interprofessional team; an established culture of engagement; opportunities to benchmark performance and accelerate institutional innovation, networking, and acclaim; and ready access to data that could be leveraged for QI purposes. CONCLUSIONS AND RELEVANCE: Use of a virtual platform to establish a learning collaborative to accelerate the identification, dissemination, and implementation of critical care best practices for COVID-19 is feasible. Our experience offers important lessons for future collaborative efforts focused on improving ICU processes of care.

ABSTRACT Suprastimulation of pancreatic acinar cells with specific agonists inhibits zymogen secretion and induces the formation of large basolateral blebs. Currently the molecular mechanisms that mediate this dramatic morphologic response are undefined. Further, it is unclear if blebbing represents a terminal or reversible event. Using computer-enhanced video microscopy of living acini we have found that these large blebs form rapidly (within 2-3 minutes) and exhibit ameboid undulations. They are induced by small increases in agonist concentration and require an energy-dependent phosphorylation event. Remarkably, the blebs are rapidly absorbed when agonist levels are reduced, indicating that blebbing is a reversible response to a physiological stimulus, not a terminal event. Morphological methods show that these dramatic changes in cell shape are accompanied by a marked reorganization of actin and myosin II at the basolateral domain. During 30 minutes of suprastimulation, both basolateral actin and myosin II gradually increase to form a ring centered at the necks of the blebs. Immunocytochemical and biochemical studies with a phospho-specific antibody to the myosin regulatory light chain reveal an activation of myosin II in suprastimulated acini that is completely absent in resting cells. Studies using cytoskeletal antagonistic drugs indicate that bleb formation and motility require actin remodeling concomitant with an activation of myosin II. This aberrant activation and reorganization of the actin-myosin cytoskeleton is likely to have detrimental effects on acinar cell function. Additionally, this mechanism of bleb formation may be conserved among other forms of physiological blebbing events.

Since fibroids are known to be hormonally receptive tumors, it is biologically plausible that fibroids decrease in size after menopause. Patients may opt for more conservative therapy or expectant management if fibroid growth could be predicted[1](#ref-0001). Studies assessing fibroid growth in premenopausal patients have shown that individual tumors in a single uterus grow at different rates and can grow consistently or in short bursts 2 . These variations and the unknown effect of natural menopause make patient counseling difficult. Studies that include only symptomatic menopausal patients or those undergoing treatment can result in selection bias towards fibroids that are increasing in size 3,4 . The objective of our study was to estimate fibroid growth course before and after menopause among women not specifically seeking fibroid treatment. Our hypothesis was that fibroid growth would decline after menopause.

Background: Ultrasonography (US) is the first-line diagnostic tool used to assess fetal musculoskeletal (MSK) anomalies. Associated anomalies in other organ systems may benefit from evaluation via Magnetic Resonance Imaging (MRI). In this study, we compared the diagnostic accuracy of US and MRI to diagnose fetal MSK (primary objective) and non-MSK anomalies (secondary objective). We describe additional findings by low-dose computerized tomography (CT) in two cases incompletely characterized via US and MRI. Materials and Methods: This was an IRB-approved retrospective study of consecutive patients with suspected fetal MSK anomalies examined between December 2015 and June 2020. We compared individual MSK and non-MSK anomalies identified via US, MRI, and CT with postnatal outcomes. Sensitivity and specificity for US and MRI were calculated and compared. Results: A total of 31 patients with 112 MSK and 43 non-MSK anomalies were included. The sensitivity of MRI and US for MSK anomalies was not significantly different (76.6% vs. 61.3%, p = 0.3). Low-dose CT identified eight additional skeletal anomalies. MRI diagnosed a higher number of non-MSK anomalies compared to US (81.4% vs. 37.2%, p < 0.05). Conclusions: Fetal MRI and US have comparable sensitivity for MSK anomalies. In selected cases, low-dose CT may provide additional information. Fetal MRI detected a larger number of non-MSK anomalies in other organ systems compared to US. Multimodality imaging combining all the information provided by MRI, US, and CT, if necessary, ultimately achieved a sensitivity of 89.2% (95% CI: 83.4% to 95.0%) for the diagnosis of musculoskeletal anomalies and 81.4% for additional anomalies in other organs and systems.

Background Pediatric cardiac surgery is associated with abnormal coagulation, bleeding, and nearly ubiquitous transfusions. With the popularization of patient blood management, attempts are being made to decrease liberal transfusions by administering prothrombin complex concentrates (PCCs). The safety and efficacy of PCCs in adult cardiac surgery has been studied extensively, but only few reports address this in children. We performed an observational study focused on transfusion requirements after off-label use of activated PCC Factor Eight Inhibitor Bypassing Activity (FEIBA) as an adjunct to post-cardiopulmonary bypass (CPB) hemostatic protocol. Methods We reviewed the medical records of children ≤15 kg undergoing cardiac operations with CPB between May 2018 and March 2022. A propensity score (PS) analysis was performed to identify matched pairs of patients who did and did not receive FEIBA. Results Out of 210 patients who met the inclusion criteria, 44 patients received FEIBA. Propensity score-based analysis identified 40 matched pairs of patients with similar baseline characteristics. There was no statistically significant difference in the primary outcome—the volume of transfusion after CPB, which included all allogeneic blood products and salvaged washed red cells administered after protamine. Specifically, FEIBA patients were transfused 28 (22-34) mL/kg and controls were transfused 22 (11-49) mL/kg, P = .989. Upon arrival to ICU, the FEIBA group averaged an 8% lower international normalized ratio, compared with the controls ( P = .009) and a 1.08 g/dL higher hemoglobin ( P = .050). Neither difference remained significant on POD 1. Conclusions In this exploratory study, we found no change in transfusion requirements after CPB despite FEIBA administration.