Citations

Abstract An anti-γM serum which distinguishes between 19SγM and a low-molecularweight γM from human serum (γMs-N) was prepared by immunizing a goat with normal human γM in Freund's complete adjuvant; it was absorbed with γG and hypogammaglobulinemic serum and was specific for γM. The reactivity of this antiserum was examined with 19SγM, with the γM monomer produced by reduction and alkylation (γMs-RA), and with the γM monomer prepared by reduction alone (γMs-R). In agar double diffusion the 19SγM band spurred over the bands formed by γMs-RA and γMs-R whereas the bands formed by γM monomers fused. Mixtures of 19SγM and γMs-RA formed concentric zones of precipitation in radial immunodiffusion and produced two bands in agar double diffusion. By quantitative precipitin analysis, with 19SγM the antiserum contained 30 µg Ab N/0.1 ml serum and with γMs-RA, 19 µg Ab N/0.1 ml. After absorption at equivalence with γMs-RA the antiserum still precipitated with 19SγM and Fc-γM but did not precipitate with Fab-γM. The precipitin reaction between 19SγM and the anti-γM serum absorbed with γMs-RA was inhibited by three γM subunits (γMs-RA, γMs-R, and γMs-N). Thus, the antiserum is reactive with an antigenic determinant on the Fc portion of the µ chain present on both 19SγM and the γM subunits. The difference in the reactivity of the antiserum with 19SγM and the γM subunits may be related to the number of specific antigenic determinants on these molecules.

Summary A naturally occurring low molecular weight γM protein (γMN) was isolated from the serum of a patient with type I dysgammaglobulinemia by preparative electrophoresis and gel filtration. This protein was compared to the macroglobulin (γM19) isolated from the patient’s serum and to the γM subunit (γMS) prepared by reduction and alkylation of γM19. The results indicate that γMN and γMS are similar in size and have the same antigenic determinants. These observations support the concept that the γMN is a naturally occurring subunit of γM19 and is very similar to γMS, γM19, γMN and γMS were also prepared from the patient’s serum after tetanus immunization and were found to bind radiolabeled tetanus toxoid. Most, but not all, controls did not show nonspecific binding of tetanus toxoid. These results suggest but do not conclusively establish the capacity of these γM proteins to bind antigen specifically.

Objectives: The primary objective of this study was to analyze the relationship of percentage of surgical overlap with patient outcomes to determine if a detrimental level of overlap exists. Background: Overlapping surgery is defined as 1 attending physician supervising 2 or more operative cases simultaneously, without the critical portions of the cases occurring concurrently. To date, no study has examined the relationship of percent overlap, or the percentage of 1 case that is spent overlapping with another, to outcomes, efficiency, safety, and complications. Methods: This study is a retrospective cohort study conducted at a large tertiary referral center. The primary outcomes of interest included operative duration, in-hospital mortality, 30-day readmission, and patient safety indicators (PSIs). The Cochran-Armitage test for trend was used to evaluate the outcomes of interest. P values of ≤0.05 were considered statistically significant. Results: A total of 87,426 cases were included in this study. There were 62,332 cases without overlap (Group 0), 10,514 cases with 1% to 25% overlap (Group 1), 5303 cases with 26% to 50% overlap (Group 2), 4296 cases with 51% to 75% overlap (Group 3), and 4981 cases with >75% overlap (Group 4). In-hospital mortality decreased as overlap increased (P trend<0.0001). Operative time increased with increasing overlap (P trend<0.0001) while readmission rates showed no statistical significance between groups (P trend=0.5078). Rates of PSIs were lower for Groups 1, 2, and 3 (1.69%, 2.01%, and 2.08%) when compared to Group 0 (2.24%). Group 4 had the highest rate of PSIs at 2.35% (P=0.0086). Conclusion: Overlapping surgery was shown to have reduced in-hospital mortality and similar PSI and readmission rates when compared to nonoverlapping cases. Operative time was shown to increase in overlapping surgeries when compared to nonoverlapping surgeries. The results from this study indicate that the percentage of surgical overlap does not detrimentally affect most patient outcomes, especially with overlap of <75%.

PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m 2 ) + gemcitabine (1,000 mg/m 2 ) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

AbstractPrimary pancreatic tumors in children are rare with an overall age‐adjusted incidence of 0.018 new cases per 100,000 pediatric patients. The most prevalent histologic type is the solid pseudopapillary neoplasm, followed by pancreatoblastoma. This paper describes relevant imaging modalities and presents consensus‐based recommendations for imaging at diagnosis and follow‐up.

Abstract Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE‐induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES. Based on these etiologies and the origin of eosinophils, HE and HES are divided into primary forms where eosinophils are clonal cells, reactive forms where an underlying reactive or neoplastic condition is detected and eosinophils are considered to be “non‐clonal” cells, and idiopathic HE and HES in which neither a clonal nor a reactive underlying pathology is detected. Since 2012, this classification and the related criteria have been widely accepted and regarded as standard. However, during the past few years, new developments in the field and an increasing number of markers and targets have created a need to update these criteria and the classification of HE and HES. To address this challenge, a Working Conference on eosinophil disorders was organized in 2021. In this conference, a panel of experts representing the relevant fields, including allergy, dermatology, hematology, immunology, laboratory medicine, and pathology, met and discussed new markers and concepts as well as refinements in definitions, criteria and classifications of HE and HES. The outcomes of this conference are presented in this article and should assist in the diagnosis and management of patients with HE and HES in daily practice and in the preparation and conduct of clinical trials.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Abstract Introduction Ischemic priapism remains a significant cause of morbidity among men. To date, the precise time when penile ischemia results in permanent, non-reversible cavernosal smooth muscle injury, compromising subsequent erectile integrity, remains ill-defined. Objectives To review the medical literature pertaining to ischemic priapism, focusing on factors that predict the exact timeline of irreversible cavernous tissue injury. Methods A comprehensive literature search was performed. Our search included both publications on animal models and retrospective clinical series through January 2022. Articles were eligible for inclusion if they contained original data regarding nonreversible tissue injury on histology and/or provided a timeline of erectile function loss or preservation and had full text available in English. Results Innovative studies in the 1990s using invitro models with strips of rabbit, rat, canine and monkey corpus cavernosal tissue demonstrated that anoxia eliminated spontaneous contractile activity and reduced tissue responsiveness to electrical field stimulation or pharmacological agents. The same models demonstrated that the inhibitory effects of field stimulated relaxation, were mediated by nitric oxide. Subsequent studies using similar models demonstrated that exposure of corpus cavernosum smooth muscle to an acidotic environment impairs its ability to contract. A pH of 6.9 was chosen for these experiments based on a case series of men with priapism, in whom a mean pH of 6.9 was measured in corporal blood after 4–6 hours of priapism. Invivo animal studies demonstrated that after erection periods of 6–8 hours, microscopy shows sporadic endothelial defects but otherwise normal cavernous smooth muscle. In these studies, greater durations of ischemic priapism were shown to result in more pronounced ultrastructural changes and presumably irreversibility. In studies involving human corporal tissues, samples were obtained from men who had experienced priapism for at least 12 hours. Overall, erectile function outcome data is deficient in priapism reporting, especially within treatment windows less than 6 hours. Some reports on ischemic priapism have documented good erectile function outcomes with reversal by 12 hours. Conclusion Based on our extensive review of animal models and clinical reports, we found that many clinical papers rely on the same small set of animal studies to suggest the time point of irreversible ischemic damage at 4–6 hours. Our review suggests an equal number of retrospective clinical studies demonstrate that ischemic priapism reversed within 6–12 hours may preserve erectile function in many patients.

Primary pancreatic tumors in children are rare with an overall age-adjusted incidence of 0.018 new cases per 100,000 pediatric patients. The most prevalent histologic type is the solid pseudopapillary neoplasm followed by pancreatoblastoma. This manuscript describes relevant imaging modalities and presents consensus-based recommendations for imaging at diagnosis and follow up.