Citations

A 39-year-old 75 kg man with Type I Glanzmann's thrombasthenia developed recurring severe therapy-refractory nosebleeds, associated with nasal septal deformity, synechial scarring, and previous radiotherapy. During a 21 month period he required 16 hospitalizations for treatment of severe epistaxis. At initial hospitalization it was observed that his epistaxis ceased shortly after transfusion of 10 bags (units) of plasma cryoprecipitate (cryo), although transfusion with HLA-matched apheresis platelets from 3 donors, and topical therapy (cautery, packing), had been ineffective. Serum anti-platelet antibodies were not detectable by indirect immunofluorescence. During 9 subsequent hospitalizations his epistaxis stopped promptly (usually within 1 hour) following cryo transfusion (10 or 20 bags), including 6 occasions when cryo was the only therapy. On 6 additional occasions his epistaxis did not stop following cryo transfusion, but did stop after subsequent platelet transfusions or topical therapy. Eventually he underwent nasal septal reconstructive surgery surgery, and severe epistaxis has not recurred. Hemostatic studies, before and after cryo transfusions on 5 occasions, did not show improvement of platelet aggregation defects nor of Ivy bleeding times, although occasionally the volume of blood emanating from bleeding time punctures appeared decreased following cryo transfusion. Platelet glycoprotein (GP) IIb/IIIa antigen was measured in aliquots of 10 of the pools of cryo received by the patient (representing 100 bags of total volume 2200 ml), using an immunoradiometric assay (Nichols et al, Blood 68:300a, 1986). On average, the transfused cryo pools contained GP IIb/IIIa equivalent to 1.1 x 108 platelets/ml (range 0.6-1.7 x 108/ml. Our recently reported studies of blood bank cryo documented similar GP IIb/IIIa levels, and revealed that >93% of GP IIb/IIIa in cryo is present in the form of sedimentable membranous platelet macroparticles and microparticles. We hypothesize that the GPIIb/IIla-bearing platelet particles in transfused cryo might account for the improvement in hemostasis we frequently observed. We conclude that cryo transfusion deserves further study as a potentially useful therapeutic adjunct in promoting hemostasis in individuals with Glanzmann's thrombasthenia.

AbstractSymptomatic hyperviscosity is a well‐established phenomenon in Waldenström macroglobulinemia (WM). Monoclonal IgM can variably impact intrinsic serum viscosity, leading to widely disparate symptomatic thresholds for development of hyperviscosity‐related symptoms. Data regarding the predictors of symptomatic hyperviscosity and outcomes related to this complication remain scarce and a recent study proposed that IgM >6000 mg/dL be considered a new criterion for initiating therapy in otherwise asymptomatic (smoldering) WM to pre‐empt hyperviscosity‐related injury. Herein, we attempt to identify predictors of the development of symptomatic hyperviscosity and its impact in patients with WM. Of 997 WM patients evaluated from January, 1996 through June, 2017, symptomatic hyperviscosity was observed in 130 (13%) patients. Overall survival (OS) of these 130 patients was similar to that of patients without symptomatic hyperviscosity (median: 11.5 vs 11.6 years; P = 0.63). On multivariate‐analysis, only viscosity >1.8 cp (risk ratio: 4.0, P = 0.02) assessed at the time of WM diagnosis was an independent predictor for the development of subsequent symptomatic hyperviscosity. Among patients with smoldering WM and IgM >6000 mg/dL at diagnosis (n = 13) who were managed expectantly, the median time‐to‐initial therapy was 6.9 years and only 15% developed hyperviscosity‐related symptoms subsequently. In summary, the occurrence of symptomatic hyperviscosity does not impact OS. Serum viscosity at diagnosis of WM, and not IgM concentration, represents the single most important independent predictor for development of subsequent hyperviscosity‐related symptoms. Patients with smoldering WM and high serum IgM can be safely observed in the absence of any indications per the Consensus recommendations to initiate WM‐directed therapy.

Abstract BACKGROUND Return to the operating room (ROR) has been put forth by the National Quality Forum and the American College of Surgeons as a surgical quality indicator. However, current quality metrics fail to consider the nature and etiology of the ROR. OBJECTIVE To provide a comprehensive description of all reoperations after neurosurgical procedures and assess the validity of ROR as a quality measure in neurosurgery. METHODS We retrospectively analyzed all neurosurgical procedures performed in a high-volume, tertiary care academic medical center between June 1, 2014 and December 31, 2016. Based on a system constructed and validated at our institution, we classified RORs into (a) unplanned related, (b) planned return due to complications, (c) planned-staged return, or (d) unrelated return. RESULTS A total of 9200 unique neurosurgical cases were identified, of which 788 had an ROR within 45 d (8.6%). Median time to ROR (interquartile range) was 9 d (4-15). Specifically, 4.2% were planned-staged returns, 3.4% were unplanned related, 0.3% were unrelated, and 0.6% were planned because of previous complications. Cranial procedures had the highest unplanned ROR rate (4.2%), followed by spinal (2.8%) and peripheral nerve (0.4%). The most common reason for an unplanned ROR was wound complication/surgical site infection (34.3%), followed by hematoma evacuation (13.9%) and cerebrospinal fluid (CSF) leak (11.3%). CONCLUSION Unplanned RORs were relatively rare and most commonly associated with wound complication, postoperative hematoma, and CSF leak. To better reflect surgical quality, ROR metrics should indicate whether the return was planned or unrelated.

Introduction and Objective: Conflicting data exists regarding the impact of body mass index (BMI) on postoperative outcomes following surgery for renal malignancies (RM). Herein, we investigated associations between obesity, hypoalbuminemia, and/or significant weight loss in the preoperative period, and risk complications and mortality within 30 days of radical (RN) or partial nephrectomy (PN). Materials and Methods: Review of the American College of Surgeons National Surgical Quality Improvement Program database identified 8,618 patients treated with PN or RN for RM between 2005 and 2012. Univariate and multivariable logistic regression models were developed to assess associations between hypoalbuminemia (<3.5 g/dl), >10% weight loss within 6 months of surgery, obesity (BMI >30 kg/m 2 ), and 30-day major complications and mortality. Results: Median BMI was 29.2 kg/m 2 with 24.9%, 11.9%, and 8.2% having class I, II, and III obesity, respectively. Weight loss of >10% was observed in 2.6% and 15.4% had preoperative albumin<3.5 g/dl. There were 1,802 complications (20.9%) and 88 deaths within 30 days (1.0%). On multivariable analysis, BMI ≥40 kg/m 2 (OR 1.3, p = 0.04), >10% weight loss (OR 1.9, p < 0.001) and hypoalbuminemia (OR 1.5, p < 0.001) were independently associated with 30-day complications, while only >10% weight loss was independently associated with 30-day mortality (OR 2.4, p = 0.03). Conclusions: Extreme obesity, hypoalbuminemia, and significant weight loss were independently associated with risk of significant complications following PN or RN while only significant preoperative weight loss was associated with early mortality, underscoring the need to further understand the utility of moderating these risk factors in the perioperative period.

Objective: The aim of this study was to conduct a prospective, multicenter survey of patients regarding postoperative opioid use to inform development of standardized, evidence-based, procedure-specific opioid prescribing guidelines. Summary of Background Data: Previous work has shown significant variation in the amount of opioids prescribed after elective procedures, calling for optimization of prescribing. Methods: Adults (n = 3412) undergoing 25 elective procedures were identified prospectively from 3 academic centers (March 2017 to January 2018) to complete a 29-question telephone interview survey 21 to 35 days post-discharge (n = 688 not contacted, n = 107 refused). Discharge opioids were converted into Morphine Milligram Equivalents (MMEs). Results: Of the 2486 patients who completed the survey, 91.2% received opioids at discharge [median 225 (interquartile range, IQR 125 to 381) MME]. A median of 43 (0 to 184) MMEs were consumed after discharge with 77.3% of patients having leftover opioids at the time of the survey. In total, 61.5% of prescribed opioids were unused; 31.4% of patients used no opioids, and 52.6% required <50 MME. Overall, 90.6% of patients were satisfied with their postdischarge pain control. While 28.3% reported being prescribed too many opioids, 9.0% felt they were not prescribed enough. Only 9.6% of patients disposed of remaining opioids. Of the 2068 opioid-naive respondents (83.2%), 33.6% consumed no opioids (range 5.2% to 80.0% by procedure) and 57.0% (65.7% nonorthopedic) consumed <50 MME. Utilization data and predictors of low/high opioid consumption informed development of postoperative prescribing guidelines. Conclusion: A large proportion of postoperative patients reported using no or few opioids following discharge. Guidelines were developed to minimize opioid prescribing and identify patients requiring low doses or additional multimodal pain control.

Purpose Overall survival (OS) is the definitive and best-established primary efficacy end point to evaluate diffuse large B-cell lymphoma (DLBCL) therapies, but it requires prolonged follow-up. An earlier end point assessed post-treatment would expedite clinical trial conduct and accelerate patient access to effective new therapies. Our objective was to formally evaluate progression-free survival (PFS) and PFS at 24 months (PFS24) as surrogate end points for OS in first-line DLBCL. Patients and Methods Individual patient data were analyzed from 7,507 patients from 13 multicenter randomized controlled trials of active treatment in previously untreated DLBCL, published after 2002, with sufficient PFS data to predict treatment effects on OS. Trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS was evaluated using both linear regression ( R2WLS) and Copula bivariable ( R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80 and neither < 0.7, with lower-bound 95% CI > 0.60. Results Trial-level surrogacy for PFS was strong ( R2WLS = 0.83; R2Copula = 0.85) and met the predefined criteria for surrogacy. At the patient level, PFS strongly correlated with OS. The surrogate threshold effect had a hazard ratio of 0.89. Surrogacy was consistent across comparisons with or without rituximab and with rituximab maintenance trials. Trial-level surrogacy for PFS24 was relatively strong ( R2WLS = 0.77; R2Copula = 0.78) but did not meet prespecified criteria. At the patient level, PFS24 significantly correlated with OS. The surrogate threshold effect had an odds ratio of 1.51. Conclusion This large pooled analysis of individual patient data supports PFS as a surrogate end point for OS in future randomized controlled trials evaluating chemoimmunotherapy in DLBCL. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before OS results are mature.

Purpose: Hospital readmissions after surgery are a focus of quality improvement efforts. Although some reflect appropriate care, others are potentially preventable readmissions (PPRs). We aim to describe the burden, timing, and factors associated with readmissions after complex cancer surgery. Methods: The Nationwide Readmissions Database (2013) was used to select patients undergoing a complex oncologic resection, which was defined as esophagectomy/gastrectomy, hepatectomy, pancreatectomy, colorectal resection, lung resection, or cystectomy. Readmissions within 30 days from discharge were analyzed. International Classification of Diseases (9th revision) primary diagnosis codes were reviewed to identify PPRs. Multivariable logistic regression analyses identified demographic, clinical, and hospital factors associated with readmissions. Results: Of the 59,493 eligible patients, 14% experienced a 30-day readmission, and 82% of these were deemed PPRs. Half of the readmissions occurred within the first 8 days of discharge. Infections (26%), GI complications (17%), and respiratory conditions (10%) accounted for most readmissions. Factors independently associated with an increased likelihood of readmission included Medicaid versus private insurance (odds ratio [OR], 1.32; 95% CI, 1.17 to 1.48), higher comorbidity score (OR, 1.5; 95% CI, 1.33 to 1.63), discharge to a facility (OR, 1.39; 95% CI, 1.29 to 1.51), prolonged length of stay (OR, 1.42; 95% CI, 1.32 to 1.52), and occurrence of a major in-hospital complication (OR, 1.24; 95% CI, 1.16 to 1.34). Conclusion: One in seven patients undergoing complex cancer surgery suffered a readmission within 30 days. We identified common causes of these and identified patients at high risk for such an event. These data can be used by physicians, administrators, and policymakers to develop strategies to decrease readmissions.