Citations

AbstractObjectivesWe performed a systematic review and meta‐regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM).MethodsResponse outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression‐free survival (PFS). We used random‐effect meta‐regression models and conducted sensitivity analyses based on definition of CR and study quality.ResultsSeventy‐two trials were included in the systematic review, 63 of which contributed data in meta‐regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] −0.06, 0.10), in patients undergoing ASCT (−.11, 95% CI −0.44, 0.22) and in trials comparing ASCT with non‐ASCT patients (.04, 95% CI −0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results.ConclusionsThis meta‐regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM.

Abstract Rationale Patients with sarcoidosis may have an increased risk of infection similar to other immune-mediated disorders. However, the data are still limited. Objectives To investigate the risk of hospitalized infection among patients with sarcoidosis, using a population-based cohort. Methods Using the Rochester Epidemiology Project record-linkage system, a cohort of incident cases of sarcoidosis in Olmsted County, Minnesota from 1976 to 2013 was identified. Diagnosis was confirmed by individual medical record review. For each patient with sarcoidosis, a sex- and age-matched comparator without sarcoidosis was randomly selected from the same population. Medical records of cases and comparators were individually reviewed for hospitalized infection that occurred after the index date. The cumulative incidence of hospitalized infection overall and by type of infection, adjusted for the competing risk of death, was estimated. Cox models were used to compare the rate of first hospitalized infection between cases and comparators and to evaluate the association between use of immunosuppressive agents and hospitalized infection among cases. Results Three hundred and forty-five cases and 345 comparators were identified. Patients with sarcoidosis had a higher risk of a hospitalized infection with a hazard ratio (HR) of 2.00 (95% confidence interval [CI], 1.41–2.84), adjusted for age, sex, and calendar year of index date. Use of oral glucocorticoids was a significant predictor of hospitalized infection with an HR of 3.03 (95% CI, 1.33–6.90) for oral glucocorticoids not exceeding 10 mg/day and an HR of 4.48 (95% CI, 1.54–13.03) for oral glucocorticoids greater than 10 mg/day. Conclusions Patients with sarcoidosis are at increased risk of hospitalized infection. Glucocorticoid therapy is strongly associated with this increased risk.

BackgroundSyncope is a common reason for outpatient transthoracic echocardiography (TTE). We studied the applicability of pediatric appropriate use criteria (AUC) on initial outpatient evaluation of children (≤18 years) with syncope.MethodsData were obtained before (Phase I, April–September 2014) and after (Phase II, January‐April 2015) the release of the AUC document from six participating pediatric cardiology centers. Site investigators determined the indication for TTE and assigned appropriateness rating based on the AUC document: Appropriate (A), May Be Appropriate (M), Rarely Appropriate (R), or “unclassifiable” (U) if it did not fit any scenario in the AUC document.ResultsOf the total 4562 TTEs, 310 (6.8%) were performed for syncope: 174/2655 (6.6%) Phase I and 136/1907 (7.1%) Phase II, P=.44. Overall, 168 (50.5%) were for indications rated A, 63 (18.9%) for M, 79 (23.7%) for R, and 23 (6.9%) for U. Release of AUC did not change the appropriateness of TTEs [A=51.6% vs 49.0%, P=.63, R=20.2% vs 28.3%, P=.09]. Overall syncope‐related R indications formed 15.7% of R indications for all the echocardiograms performed in the entire Pediatric Appropriate Use (PAUSE) study (11.9% Phase I and 22.4% Phase II, P=.002). TTEs were normal in majority of the patients except 7 that had incidental findings.ConclusionsIn conclusion, syncope is a common reason for indications rated R and release of the AUC document did not improve appropriate utilization of TTE in syncope. Targeted educational interventions are needed to reduce unnecessary TTEs in children with syncope.

AbstractBackgroundIn an open‐label study of 26 patients with IBS‐C and chronic constipation, treatment with a vibrating (VIBRANT) capsule twice a week for 7.5 weeks resulted in 88.5% responders. Effects on colonic transit are unclear. We aimed to compare effects of VIBRANT and sham capsule treatment on colonic transit in patients with functional constipation.MethodsPatients with functional constipation (Rome III criteria) were randomized to VIBRANT or sham capsule treatment for 8 weeks and underwent scintigraphic colonic transit measurements during week 8. We estimated the overall rate of colonic transit from the slope of progression of colonic geometric center over 48 hours. The capsule was activated 8 hours after ingestion, and the vibration sequence included 240 cycles.Key ResultsThere were no significant group differences in overall colonic transit [GC48, 2.76 (IQR 2.42‐4.03) for sham group and 3.46 (2.55‐4.61) for active treatment group (P=.13)]. Additionally, the progression of the isotope through the colon was numerically faster, though not significantly different (slope, P=.14) in the VIBRANT capsule group compared to the sham group. Three participants in the VIBRANT capsule group had accelerated colonic transit at 32 hours and faster colonic transit slope compared to the 95th percentile of the sham group.Conclusions and InferencesAlthough there were no group differences between VIBRANT and sham capsule treatment on colonic transit, at least one (and possibly three) of 12 patients receiving the VIBRANT capsule had faster colonic transit. The vibration parameters to accelerate colonic transit in patients with functional constipation require further optimization.

BACKGROUND. No laboratory test can predict the risk of nonrelapse mortality (NRM) or severe graft-versus-host disease (GVHD) after hematopoietic cellular transplantation (HCT) prior to the onset of GVHD symptoms. METHODS. Patient blood samples on day 7 after HCT were obtained from a multicenter set of 1,287 patients, and 620 samples were assigned to a training set. We measured the concentrations of 4 GVHD biomarkers (ST2, REG3α, TNFR1, and IL-2Rα) and used them to model 6-month NRM using rigorous cross-validation strategies to identify the best algorithm that defined 2 distinct risk groups. We then applied the final algorithm in an independent test set ( n = 309) and validation set ( n = 358). RESULTS. A 2-biomarker model using ST2 and REG3α concentrations identified patients with a cumulative incidence of 6-month NRM of 28% in the high-risk group and 7% in the low-risk group ( P < 0.001). The algorithm performed equally well in the test set (33% vs. 7%, P < 0.001) and the multicenter validation set (26% vs. 10%, P < 0.001). Sixteen percent, 17%, and 20% of patients were at high risk in the training, test, and validation sets, respectively. GVHD-related mortality was greater in high-risk patients (18% vs. 4%, P < 0.001), as was severe gastrointestinal GVHD (17% vs. 8%, P < 0.001). The same algorithm can be successfully adapted to define 3 distinct risk groups at GVHD onset. CONCLUSION. A biomarker algorithm based on a blood sample taken 7 days after HCT can consistently identify a group of patients at high risk for lethal GVHD and NRM. FUNDING. The National Cancer Institute, American Cancer Society, and the Doris Duke Charitable Foundation.

The epidemiology of infections after living donor liver transplantation (LDLT) is limited. We aimed to study the epidemiology and risk factors of infections after LDLT. The medical records of 223 adult patients who underwent LDLT from January 1, 2000 to August 31, 2015 were reviewed for all infections occurring up to 1 year. We estimated the cumulative incidence of infection using the Kaplan‐Meier product limit method. Risk factors were analyzed with time‐dependent Cox regression modeling. The majority of patients were Caucasian (94.6%) and male (64.6%), and the median age at transplantation was 55 years. The most common indication for transplantation was primary sclerosing cholangitis (37.7%). A total of 122 patients developed an infection during the follow‐up period (1‐year cumulative event rate of 56%), with the majority (66%) of these occurring within 30 days after transplantation.Enterococcus sp. was the most frequent pathogen identified. Multivariate analysis showed that increased Model for End‐Stage Liver Disease (MELD) score (per 10‐point change: hazard ratio [HR], 1.59), history of recurrent infections prior to transplant (HR, 2.01), Roux‐en‐Y anastomosis (HR, 2.37), increased log‐number of packed red blood cell transfusions (HR, 1.39), and biliary complications (HR, 4.26) were independently associated with a higher risk of infection. Infections occur commonly after LDLT, with most infections occurring early and being related to the hepatobiliary system. Higher MELD scores, the type of biliary anastomosis, presence of biliary complications, and prior pretransplant infections are independently associated with a higher risk for infections.Liver Transplantation 23 465–4772017 AASLD.

Objective: To describe the practice of intubation of the critically ill at a single academic institution, Mayo Clinic’s campus in Rochester, Minnesota, and to report the incidence of immediate postintubation complications. Patients and Methods: Critically ill adult (≥18 years) patients admitted to a medical–surgical intensive care unit from January 1, 2013, to December 31, 2014, who required endotracheal intubation included. Results: The final cohort included 420 patients. The mean age at intubation was 62.9 ± 16.3 years, with 58% (244) of the cohort as male. The most common reason for intubation was respiratory failure (282 [67%]). The most common airway device used was video laryngoscopy (204 [49%]). Paralysis was used in 264 (63%) patients, with ketamine as the most common sedative (194 [46%]). The most common complication was hypotension (170 [41%]; 95% confidence interval [CI]: 35.7-45.3) followed by hypoxemia (74 [17.6%]; 95% CI: 14.1-21.6), with difficult intubation occurring in 20 (5%; 95% CI: 2.9-7.3). Conclusion: We found a high success rate of first-pass intubation in critically ill patients (89.8%), despite the procedure being done primarily by trainees 92.6% of the time; video was the preferred method of laryngoscopy (48.6%). Although our difficult intubation (4.8%) and complication rates typically associated with the act of intubation such as aspiration (1.2%; 95% CI: 0.4-2.8) and esophageal intubation (0.2%; 95% CI: 0.01-1.3) are very low compared to other published rates (8.09%), postintubation hypotension (40.5%) and hypoxemia (17.6%) higher.

Abstract BACKGROUND: Intraneural perineuriomas are rare, benign lesions produced by the neoplastic proliferation of perineurial cells. They typically present in adolescents and affect nerves of the limbs. In our experience, we have not encountered a single case of classic intraneural perineurioma at an intradural location. OBJECTIVE: To determine whether intraneural perineuriomas could occur intradurally, given the prevalence of intradural nerve sheath tumors, and explain our findings with an anatomic perspective. METHODS: We retrospectively reviewed the high-resolution magnetic resonance images of 56 patients from an institutional registry of patients with intraneural perineurioma. All cases were analyzed for signs of proximal extension toward spinal nerves, roots, and spinal cord. A literature review was performed. The clinical, radiological, and histopathological features of potential intradural lesions were critically appraised against strict criteria for a diagnosis of classic intraneural perineurioma. RESULTS: Fifteen of 56 (27%) patients with intraneural perineurioma had a proximal localization in the lumbosacral or brachial plexus. Not a single case occurred proximal to the dorsal root ganglia (DRG). One case of trigeminal intraneural perineurioma occurred distal to the gasserian ganglion. A literature review did not reveal any convincing cases of classic intraneural perineuriomas occurring in an intraspinal intradural location and revealed only 1 possible case in an intracranial intradural location. CONCLUSION: Based on our study, the occurrence of classic intraneural perineuriomas intradurally is exceedingly rare, if at all present. This may be related to the paucity of perineurial cells at the nerve root level and reciprocal interactions between neuroglial cells at the central-to-peripheral transition zones.