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Thyroid hormone dysfunction is frequently observed in patients with chronic illnesses including heart failure which increases risk of adverse events. This study examined effects of thyroid hormones (TH) on cardiac T-tubule (TT) integrity, Ca 2+ sparks, and nanoscale organization of ion channels in excitation-contraction (EC)-coupling, including L-type calcium channel (Ca v 1.2), ryanodine receptor-type 2 (RyR2), and junctophilin-2 (Jph2). TH deficiency was established in adult female rats by propyl-thiouracil (PTU) ingestion for 8 weeks; followed by randomization to continued PTU without or with oral triiodo-L-thyronine (T3; 10 ug/kg/d) for two additional weeks (PTU+T3). Confocal microscopy of isolated cardiomyocytes (CM) showed significant misalignment of TTs, and increased Ca 2+ sparks in thyroid-deficient CMs. Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis of STochastic Optical Reconstruction Microscopy (STORM) images showed decreased (p<0.0001) RyR2 cluster number per cell area in PTU CMs compared to euthyroid (EU) control myocytes, and this was normalized by T3-treatment. Ca v 1.2 channels and Jph2 localized within 210 nm radius of the RyR2 clusters were significantly reduced in PTU myocytes, and these values were increased with T3 treatment. A significant percentage of the RyR2 clusters in the PTU myocytes had neither Ca v 1.2 or Jph2, suggesting fewer functional clusters in EC-coupling. Nearest neighbor distances between RyR2 clusters were greater (p<0.001) in PTU cells compared to EU and T3-treated CMs that corresponds to disarray of TTs at the sarcomere z-discs. These results support a regulatory role of T3 in the nanoscale organization of RyR2 clusters and co-localization of Ca v 1.2 and Jph2 in optimizing EC-coupling.

Objective: This study aims to determine if a novel imaging protocol (ultralow-dose dynamic expiratory computed tomography [CT] with repeated imaging) identifies tracheomalacia (TM) more reliably than traditional dynamic tracheal CT., Methods: We performed a retrospective evaluation of 184 consecutive ultralow-dose dynamic CTs for TM during 2017. The protocol obtains images during 1 inspiration and 2 forced expirations. Tracheal narrowing during both expirations (airway narrowing [percentage] during first dynamic expiration CT [DE1], airway narrowing [percentage] during second dynamic expiration CT [DE2]) was reported as a percentage of inspiratory area. We identified maximum narrowing of each patient's sequence (maximum narrowing [percentage] on either dynamic expiration CT [DEmax] = greatest narrowing of DE1 or DE2) and compared DE1, DE2, and DEmax in individual studies and between patients. Outcomes included frequency of TM, tracheal narrowing, and severity. Reliability was assessed by comparing tracheal area narrowing and TM grade., Results: There was significantly more airway narrowing using 2 expiratory image acquisitions. Average DEmax tracheal area was 12% narrower than DE1 alone and 21% worse than DE2 alone (both P < 0.001). Using DEmax, TM was diagnosed 35% more often than DE1 alone and 31% more often than DE2 alone ( P < 0.001). DEmax identified more severe distribution of TM compared with DE1 or DE2 alone ( P < 0.001). Reliability between DE1 and DE2 was good for tracheal narrowing and moderate for TM grade. The mean effective radiation dose was 2.41 millisievert (mSv) for routine inspiration CT and 0.07 mSv for each dynamic expiration CT (total effective radiation, 2.55 mSv)., Conclusions: Dynamic expiration CT with 2 expiratory image acquisitions enhanced evaluation of TM, minimally increased radiation dose, and should be considered as a noninvasive screening option., Competing Interests: S.L.C. and B.C.B. have received funding from Siemens Healthineers and Society of Thoracic Radiology. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. No conflicts of interest were declared for the remaining authors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Increased left ventricular wall thickness is a hallmark of cardiac amyloidosis (CA). Several other disease states, including hypertrophic cardiomyopathy (HCM), share this common feature. Myocardial strain has emerged as a diagnostic and prognostic tool to differentiate causes of increased left ventricular wall thickness. We sought to determine if regional strain differences were present in CA when compared with HCM when indexed to wall thickness as well as adjusting for important factors such as ejection fraction (EF), age, sex, and hypertension., Methods: We performed a multicenter, retrospective analysis of 122 patients in 3 groups: CA (n=40), HCM (n=44), and controls (n=38). Using commercially available software, we determined peak systolic strain measurements in the base, mid, and apical segments in all 3 cardinal directions of radial strain, circumferential strain, and longitudinal strain. The regional strain was indexed to wall thickness to create a strain to wall thickness (STT) ratio. Analysis of Variance was performed to examine the association of each strain parameter with the disease group, adjusting for age, sex, hypertension, and EF. Multinomial logistic regression was performed to determine which combination of variables can potentially be used to best model the disease group., Results: Ratios of STT at all 3 levels were significantly different with respect to the cardinal directions of radial, circumferential, and longitudinal strain in a multivariable analysis adjusting for age, sex, and hypertension. Specifically, with respect to the basal segments, the STT ratio across CA, HCM, and normal were significantly different in radial (1.13±0.34 vs. 3.79±0.22 vs. 4.12±0.38; P <0.0001), circumferential (-0.79±0.10 vs. -1.62±0.07 vs. -2.25±0.11; P <0.0001), and longitudinal directions (-0.41±0.09 vs. -1.03±0.06 vs. -1.41±0.10; P <0.0001). When adjusting for age, sex, hypertension and EF, only the base was significantly different between the CA and HCM groups in the radial (1.49±0.37 vs. 3.53±0.24; P <0.0001), circumferential -1.04±0.10 vs. -1.44±0.06; P <0.005), and longitudinal (-0.55±0.10 vs -0.94±0.06; P =0.007) directions. Using multinomial logistic regression, the use of age, left ventricular EF, global longitudinal strain, and basal radial strain yielded a diagnostic model with an area under the receiver operating characteristic curve (AUC) of 0.98. A model excluding age, despite being likely an independent predictor in our cohort, yielded an overall AUC of 0.90. When excluding age, the overall AUC was 0.91 and specifically when discriminating CA from HCM was 0.95., Conclusions: Regional myocardial strain indexed to wall thickness with an STT ratio can differentiate between etiologies of increased left ventricular wall thickness. Differences in myocardial deformation may be independent of wall thickness. Differences in basal strain when indexed to wall thickness in all 3 cardinal directions between CA and HCM are independent of EF. Multinomial logistic regression analysis using strain parameters differentiates CA and HCM with excellent diagnostic accuracy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background:  Coronavirus disease 2019 (COVID-19) is associated with venous and arterial thromboembolism (VTE and ATE) and all-cause mortality (ACM) in hospitalized patients. High-quality data are needed on postdischarge outcomes in patients with cardiovascular disease., Objectives:  To analyze outcomes and identify risk factors for ATE, VTE, and ACM in a high-risk subgroup of hospitalized COVID-19 patients with baseline cardiovascular disease., Methods:  We investigated postdischarge rates and associated risk factors of ATE, VTE, and ACM in 608 hospitalized COVID-19 patients with coronary artery disease, carotid artery stenosis (CAS), peripheral arterial disease (PAD), or ischemic stroke., Results:  Through 90 days postdischarge, outcome rates were: ATE 27.3% (10.2% myocardial infarction, 10.1% ischemic stroke, 13.2% systemic embolism, 12.7% major adverse limb event); VTE 6.9% (4.1% deep vein thrombosis, 3.6% pulmonary embolism); composite of ATE, VTE, or ACM 35.2% (214/608). Multivariate analysis showed significant association between this composite endpoint and age >75 years (odds ratio [OR]: 1.90, 95% confidence interval [CI]: 1.22-2.94, p  = 0.004), PAD (OR: 3.23, 95% CI: 1.80-5.81, p ≤ 0.0001), CAS (OR: 1.74, 95% CI: 1.11-2.75, p  = 0.017), congestive heart failure (CHF) (OR: 1.84, 95% CI: 1.02-3.35, p  = 0.044), previous VTE (OR: 3.08, 95% CI: 1.75-5.42, p  < 0.0001), and intensive care unit (ICU) admission (OR: 2.93, 95% CI: 1.81-4.75, p  < 0.0001)., Conclusion:  COVID-19 inpatients with cardiovascular disease experience high rates of ATE, VTE, or ACM through 90 days postdischarge. Age >75 years, PAD, CAS, CHF, previous VTE, and ICU admission are independent risk factors., Competing Interests: A.C.S. has consulting for Janssen, Boehringer Ingelheim, Bayer, Bristol-Myers Squibb, Portola, and ATLAS Group and received research funding from Janssen and Boehringer Ingelheim. M.G. receives research grant support and honoraria from Janssen. M.M. has consulted for Bayer and Pfizer and received support for congress attendance from Bayer, Pfizer, and Leo. E.A. has consulted for Bayer and received support for congress attendance from Bayer and Boehringer Ingelheim. The remaining authors have nothing to disclose., (Thieme. All rights reserved.)

Aims: Programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors have had a major impact on the approach to care of patients with lung cancer. An important issue that is not known is whether they benefit men and women the same. We conducted a meta-analysis of all randomised controlled trials evaluating PD-1/PD-L1 inhibition in patients with non-small cell lung cancer (NSCLC) to determine if clinical response and survival are influenced by gender., Materials and Methods: A PubMed search was carried out to identify all randomised controlled trials evaluating PD-1/PD-L1 inhibitors compared with conventional chemotherapy in NSCLC. Random-effects meta-analysis and meta-regression were performed to assess overall survival and progression-free survival (PFS) and whether there were differences in these outcomes between men and women., Results: In total, 12 studies with data for overall survival and 11 studies with data for PFS were included. Immunotherapy showed a statistically significant benefit over chemotherapy for overall survival (pooled hazard ratio = 0.72, 95% confidence interval = 0.65-0.81, P < 0.001) and progression-free survival (pooled hazard ratio = 0.62, 95% confidence interval = 0.54-0.72, P < 0.001). We did not find a statistically significant difference between men and women in terms of overall survival (males versus females: pooled hazard ratio = 0.74, 95% confidence interval = 0.66-0.83 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.63-0.82, P = 0.709) or progression-free survival (males versus females: pooled hazard ratio = 0.63, 95% confidence interval = 0.53-0.75 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.58-0.88, P = 0.372)., Conclusion: This is the first systematic review and meta-analysis investigating the effect of gender and response to PD-1/PD-L1 checkpoint inhibitors in patients solely with NSCLC. We examined 9270 and 6193 patients in terms of overall survival and PFS, respectively. Although there are significant biological differences between men's and women's immune responses, we have shown that these drugs offer the same survival benefit in patients with NSCLC regardless of gender., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: During the first wave of the coronavirus disease (COVID-19) pandemic in New York City, the number of mechanically ventilated COVID-19 patients rapidly surpassed the capacity of traditional intensive care units (ICUs), resulting in health systems utilizing other areas as expanded ICUs to provide critical care. Objectives: To evaluate the mortality of patients admitted to expanded ICUs compared with those admitted to traditional ICUs. Methods: Multicenter, retrospective, cohort study of mechanically ventilated patients with COVID-19 admitted to the ICUs at 11 Northwell Health hospitals in the greater New York City area between March 1, 2020 and April 30, 2020. Primary outcome was in-hospital mortality up to 28 days after intubation of COVID-19 patients. Results: Among 1,966 mechanically ventilated patients with COVID-19, 1,198 (61%) died within 28 days after intubation, 46 (2%) were transferred to other hospitals outside of the Northwell Health system, 722 (37%) survived in the hospital until 28 days or were discharged after recovery. The risk of mortality of mechanically ventilated patients admitted to expanded ICUs was not different from those admitted to traditional ICUs (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.95-1.20; P  = 0.28), while hospital occupancy for critically ill patients itself was associated with increased risk of mortality (HR, 1.28; 95% CI, 1.12-1.45; P  < 0.001). Conclusions: Although increased hospital occupancy for critically ill patients itself was associated with increased mortality, the risk of 28-day in-hospital mortality of mechanically ventilated patients with COVID-19 who were admitted to expanded ICUs was not different from those admitted to traditional ICUs.

Importance: Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown., Objective: To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19., Design, Setting, and Participants: The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US., Interventions: Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status., Main Outcomes and Measures: The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data., Results: Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71)., Conclusions and Relevance: In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients., Trial Registration: ClinicalTrials.gov Identifier: NCT04401293.

Objective: The aim of the study was to present: (1) physiatric care delivery amid the SARS-CoV-2 pandemic, (2) challenges, (3) data from the first cohort of post-COVID-19 inpatient rehabilitation facility patients, and (4) lessons learned by a research consortium of New York and New Jersey rehabilitation institutions., Design: For this clinical descriptive retrospective study, data were extracted from post-COVID-19 patient records treated at a research consortium of New York and New Jersey rehabilitation inpatient rehabilitation facilities (May 1-June 30, 2020) to characterize admission criteria, physical space, precautions, bed numbers, staffing, employee wellness, leadership, and family communication. For comparison, data from the Uniform Data System and eRehabData databases were analyzed. The research consortium of New York and New Jersey rehabilitation members discussed experiences and lessons learned., Results: The COVID-19 patients (N = 320) were treated during the study period. Most patients were male, average age of 61.9 yrs, and 40.9% were White. The average acute care length of stay before inpatient rehabilitation facility admission was 24.5 days; mean length of stay at inpatient rehabilitation facilities was 15.2 days. The rehabilitation research consortium of New York and New Jersey rehabilitation institutions reported a greater proportion of COVID-19 patients discharged to home compared with prepandemic data. Some institutions reported higher changes in functional scores during rehabilitation admission, compared with prepandemic data., Conclusions: The COVID-19 pandemic acutely affected patient care and overall institutional operations. The research consortium of New York and New Jersey rehabilitation institutions responded dynamically to bed expansions/contractions, staff deployment, and innovations that facilitated safe and effective patient care., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4. Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 0.5 mg/kg (CrCl 15-30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge., Competing Interests: M.G.: research grant from Janssen; M.C.: speakers bureau Sanofi; A.T.: educational grant: Janssen, research grant: Janssen, Bristol Meyers Squibb, Idorsia, consultant: Recovery Force, J.M.K.: consultant for Bayer Healthcare, Jansen, the ATLAS Group, AMAG pharmaceuticals, Agile Therapeutics for advisory and steering committee activities. Data and safety monitoring committees for Cystic Fibrosis Foundation Therapeutics, Novo Nordisk, Pfizer, Genentech, and BioMarin pharmaceuticals. M.B.: research grant support to CPC Clinical Research from Amgen, AstraZeneca, Bayer, Janssen, Merck, NovoNordisk; J.L.H.: consultancies with the ATLAS Group, Bayer Healthcare, Boehringer Ingelheim, and Population Health Research Institute; J.I.W.: consultant for Anthos, ATLAS Group, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Johnson and Johnson, Merck, Pfizer, PhaseBio, and Servier, institutional research grants from Bayer and Boehringer Ingelheim; A.C.S.: Janssen, Boehringer Ingelheim, Bayer, BMS, Portola, ATLAS Group: consultancy; Janssen, Boehringer Ingelheim: research funding. D.G., W.D., J.W., S.K., G.S., J.M.L., A.M., E.G., P.A.L., K.C., M.L., C.P.S., H.R., K.O., W.R.H., R.A.D., V.E.A.: no conflict of interest., (Thieme. All rights reserved.)

Patients with coronavirus disease 2019 (COVID-19) can have increased risk of mortality shortly after intubation. The aim of this study is to develop a model using predictors of early mortality after intubation from COVID-19. A retrospective study of 1945 intubated patients with COVID-19 admitted to 12 Northwell hospitals in the greater New York City area was performed. Logistic regression model using backward selection was applied. This study evaluated predictors of 14-day mortality after intubation for COVID-19 patients. The predictors of mortality within 14 days after intubation included older age, history of chronic kidney disease, lower mean arterial pressure or increased dose of required vasopressors, higher urea nitrogen level, higher ferritin, higher oxygen index, and abnormal pH levels. We developed and externally validated an intubated COVID-19 predictive score (ICOP). The area under the receiver operating characteristic curve was 0.75 (95% CI 0.73-0.78) in the derivation cohort and 0.71 (95% CI 0.67-0.75) in the validation cohort; both were significantly greater than corresponding values for sequential organ failure assessment (SOFA) or CURB-65 scores. The externally validated predictive score may help clinicians estimate early mortality risk after intubation and provide guidance for deciding the most effective patient therapies., (© 2021. The Author(s).)

Purpose: To identify preferences of patients and referring physicians for direct patient communication and notification of radiologic study results., Methods: An anonymous survey was conducted of patients undergoing outpatient radiologic imaging studies and their referring physicians. The voluntary surveys elicited responses regarding preferences on a 5-point Likert scale (Strongly disagree, disagree, neutral, agree and strongly agree), as well as indicated by responding yes or no to specific questions., Results: 368 patients completed the survey. 81.5% of patient responders preferred all results communicated from the radiologist within the same day. 65.9% of patients preferred same day results if normal vs 65.8% if abnormal. 34.5% preferred to wait and review normal results with the referring physician. 41.5% preferred to wait and review abnormal results with the referring physician. It was found that patients were more likely to strongly agree with waiting to review results with the referring physician if the results were abnormal, as opposed to normal (18.5% vs 11.9%, respectively; P < 0.014). 64% of physicians did not want results reviewed with their patients; 87.6% did not want a report sent to the patient by the radiologist, even after report was sent to their office. 66.4% of patients surveyed indicated that waiting for imaging results gives them anxiety., Conclusions: 58-82% of patients preferred same day radiologist communication of their results while 55-87.6% of physicians did not prefer same day radiologist communication of results directly with their patients. 66.4% of patients surveyed indicated that waiting for imaging results gives them anxiety., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To identify maternal and peripartum characteristics in twin gestations that are associated with postpartum hemorrhage (PPH) in which one or more units of packed red blood cells (PRBCs) were either administered or recommended but declined (PPH + PRBC). Methods: This retrospective cohort study evaluated all women with twin gestations who delivered at greater than 23 weeks of gestational age at a single, tertiary medical center from 2011 to 2016. Patients were included if they had documentation of estimated blood loss (EBL) at delivery and complete inpatient medical records available for review. Patients with incomplete records or an intrauterine fetal demise of one or both twins were excluded. The primary outcome was PPH + PRBC. Secondary outcomes included PPH with delivery EBL ≥1500 ml, PPH with atony and uterotonic administration, PPH with maternal hemorrhagic morbidity (MHM), and PPH with severe maternal morbidity (SMM). MHM was a composite outcome defined as PPH associated with any of the following: atony requiring uterotonics, any PRBC transfusion (≥1 unit), uterine or hypogastric artery ligation, hysterectomy, compression sutures, intrauterine balloon tamponade, uterine artery embolization, and/or exploratory laparotomy. SMM was a composite outcome defined as PPH associated with any of the following: administration of ≥4 units of PRBC, administration of ≥2 units of PRBC, and ≥2 units of fresh frozen plasma (FFP), return to operating room for any major procedure (excludes dilation and curettage), any peripartum hysterectomy, uterine artery embolization, intrauterine balloon tamponade or compression suture placed and administration of ≥2 units of PRBC, and/or intensive care unit (ICU) admission for invasive monitoring/treatment. A multivariable logistic regression analysis was performed. Results: A total of 1081 women with twin gestations were included. PPH + PRBC occurred in 4.4% ( n  = 48), delivery EBL ≥1500 ml occurred in 3.9% ( n  = 42), and atony with uterotonic administration occurred in 12.1% ( n  = 131) of the study population. The rate of MHM and SMM were 13.9% ( n  = 150) and 1.9% ( n  = 20), respectively. Although the rate of cesarean delivery was high overall (83.2%), it was nearly universal in the PPH + PRBC group (97.9%; p  < .02). PPH + PRBC occurred at a rate of 0.5% ( n  = 1/182) among vaginally delivered twins compared to 5.2% ( n  = 47/899) among those delivered by cesarean ( p  < .03). The final multivariable logistic regression model to predict PPH + PRBC identified six significant maternal and peripartum factors: nulliparity, either pregestational or gestational diabetes, intrapartum magnesium sulfate, admission hematocrit <30%, admission platelets <100 000/µL and administration of general anesthesia. Conclusions: A number of maternal and peripartum factors are associated with PPH in twin gestations. Optimization of maternal hematologic parameters and chronic medical conditions, and reduction in the rate of cesarean delivery in twin pregnancies may decrease the risk of postpartum hemorrhage.

Background: Serum Peanut-specific-IgE (PN-sIgE) and peanut-component-resolved-diagnostics (CRD) are often ordered simultaneously in the evaluation for peanut allergy. Results often guide the plans for peanut oral challenge. However, the clinical utility of CRD at different total PN-sIgE levels is unclear. A commonly used predefined CRD Ara h2 cutoff value in the literature predicting probability of peanut challenge outcomes is 0.35kUA/L. Objective: To examine the utility of CRD in patients with and without a history of clinical reactivity to peanut (PN). Methods: This was a retrospective chart review of 196 children with PN-sIgE and CRD testing, of which, 98 patients had a clinical history of an IgE-mediated reaction when exposed to PN and 98 did not. The Fisher's exact test was used to assess the relationship between CRD and PN-sIgE at different cutoff levels, McNemar test and Gwet's approach (AC1 statistic) were used to examine agreement between CRD and PN-sIgE, and logistic regression was used to assess differences in the findings between patients with and without reaction history. Results: Ara h 1, 2, 3, or 9 (ARAH) levels ≤0.35 kUA/L were significantly associated with PN-sIgE levels <2 kUA/L rather than ≥2 kUA/L (p < 0.0001). When the ARAH threshold was increased to 1 kUA/L and 2 kUA/L, these thresholds were still significantly associated with PN-sIgE levels of <2, <5, and <14 kUA/L. These findings were not significantly different in patients with and without a history of clinical reactivity. Conclusion: ARAH values correlated with PN-sIgE. Regardless of clinical history, ARAH levels are unlikely to be below 0.35, 1, or 2 kUA/L if the PN-sIgE level is >2 kUA/L. Thus, if possible, practitioners should consider PN-sIgE rather than automatically ordering CRD with PN-sIgE every time. Laboratory procedures that allow automatically and reflexively adding CRD when the PN-sIgE level is ≤5 kUA/L can be helpful. However, further studies are needed in subjects with challenge-proven PN allergy.

Objective: In patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration., Methods: In this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures., Results: Twenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119)., Conclusions: Preliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

Objective: To estimate whether the urinary force of stream method is noninferior to a standard fill voiding trial for rate of catheterization within 6 weeks after apical prolapse surgery in those discharged without a catheter., Methods: A noninferiority randomized controlled trial was conducted in postoperative women comparing force of stream with standard fill voiding trials after vaginal, abdominal, or laparoscopic-robotic apical pelvic organ prolapse (POP) surgery. Before discharge, women in both groups were backfilled with 300 mL normal saline. Successful voiding criteria in the force of stream group was subjective force of stream of at least 50 using a visual analog scale; reporting less than 50 prompted a bladder scan. Successful voiding was defined as a postvoid residual volume of less than 500 mL. For the standard fill voiding trial group, voiding two thirds of the instilled amount indicated success. The primary outcome was the rate of catheterization within the 6-week postoperative period after surgical repair of apical prolapse among those discharged without a urinary catheter. Secondary endpoints included trial of void failure rates. A sample size of 59 patients per group who passed trial of void at discharge was needed to achieve 80% power using a noninferiority margin (delta of 10%). Total enrollment of 169 patients was necessary to account for an estimated 30% trial of void failure rate., Results: From April 2016 and April 2017, 184 patients were enrolled (six enrolled before the trial registration date), with the first patient enrolled on April 1, 2016. One hundred seventy-four patients were randomized (86 in the force of stream group and 88 in the standard fill voiding trial group). No differences were observed in demographic or perioperative characteristics, except for stage 2 apical prolapse (52% in the force of stream group vs 36% in the standard fill voiding trial group). For the primary outcome, similar rates were found in those patients who passed their trial of void but subsequently needed catheterization for voiding dysfunction (force of stream 2.8% [2/71] vs standard fill voiding trial 3.1% [2/64]; difference -0.3%, 95% CI -8.69% to 8.08%). The incidence of trial of void failures at discharge was similar (force of stream 17.4% [15/86] vs standard fill voiding trial 26.4% [23/87]; risk ratio 0.65, 95% CI 0.37-1.18, P=nonsignificant)., Conclusion: Force of stream was noninferior to standard fill voiding trial when comparing the rate of catheter insertion during the 6-week postoperative period after apical POP surgery in those discharged without a catheter., Clinical Trial Registration: ClinicalTrials.gov, NCT02753920.

Cyanotic heart lesions are a complex subset of congenital heart disease (CHD) in which patients are desaturated until surgical repair or palliation. We hypothesized that a direct relationship would exist between degree of desaturation and presence of systemic inflammation and brain injury in unrepaired patients less than 1 year of age. The pre-operative desaturation with augmented systemic inflammation would predict a more complex post-operative course. Fifty patients with CHD were enrolled in this study and classified as cyanotic (O 2  ≤ 90%) or acyanotic (O 2  > 90%) based on SpO 2 . Serum inflammatory mediators measured included interleukins (IL)-6, IL-8, IL-12p70, IL-10, IL-1β, tumor necrosis factor (TNF)-α, interferon (INF)-γ; macrophage inhibitory factor (MIF) and a novel brain biomarker, phosphorylated neurofilament heavy subunit (pNF-H). Twenty-two cyanotic and 28 acyanotic subjects were enrolled with SpO 2 of 78 ± 18% and 98 ± 2% (p < 0.001), respectively, and mean age of 72 days (range 2-303) and 102 days (range 1-274), respectively. Cyanotic vs acyanotic subjects had elevated serum IL-6 (6.6 ± 7.6 vs 2.9 ± 2.9 pg/ml, p = 0.019) and pNF-H (222 ± 637 vs 57 ± 121 pg/ml, p = 0.046), and both biomarkers correlated with degree of desaturation (Spearman rank-order correlation ρ = - 0.30, p = 0.037 and ρ = - 0.29 p = 0.049, respectively). Post-operative inotrope scores at 24 h and duration of mechanical ventilation correlated inversely with pre-operative oxygen saturation (ρ = - 0.380, p = 0.014 and ρ = - 0.362, p = 0.020, respectively). The degree of pre-operative desaturation correlated with a more complicated post-operative course supporting the need for advanced peri-operative therapy in this population.

Objectives: To determine whether a novel, noninvasive quantitative ultrasound (US) technique can detect differences in proximal and distal cervical tissue echogenicity in women with and without a shortened cervical length (CL)., Methods: We conducted a retrospective case-control study of singleton pregnancies at 16 to 26 weeks' gestation in which a transvaginal US examination was performed to measure CL from 2013 to 2015. Initial CLs in cases and controls were less than 2.5 cm and 2.5 cm or greater, respectively. For each US image, a region of interest was selected in the proximal and distal cervical stroma, in both the anterior and posterior cervical lips. The Floyd-Steinberg dithering algorithm transformed grayscale pixels in each region of interest into a binary map. A histogram tabulated the number of black and white pixels, allowing determination of the percent echogenicity. The difference in the percent echogenicity was calculated by subtracting the distal cervical echogenicity (average of anterior and posterior lips) from the proximal cervical echogenicity (average of anterior and posterior lips)., Results: Ultrasound images from 177 women were analyzed. There was a difference in the percent echogenicity (P < .0001) when comparing women with a short cervix (mean ± SD, 9.8 ± 10.1; n = 102) to women with a normal CL (17.2 ± 9.5; n = 75). Differences were attributable to changes in proximal (P < .008) rather than distal cervical echogenicity. Regardless of CL, the proximal cervix was more echogenic than the distal cervix., Conclusions: A quantitative US analysis of cervical tissue can detect differences in echogenicity between the proximal and distal cervix in the second trimester. Proximal cervical echogenicity is lower with CL of less than 2.5 cm compared to a normal CL., (© 2018 by the American Institute of Ultrasound in Medicine.)

Purpose: Stereotactic body radiation therapy (SBRT) is a common treatment option for patients with metastatic tumors of the spine. The optimal treatment-, tumor-, and patient-specific characteristics necessary to achieve durable outcomes remain less well understood given the heterogeneous nature of the patient population this modality typically serves. The objective of this analysis was to better understand the determinants underlying SBRT spine treatment outcomes., Methods and Materials: A total of 127 patients with 287 spine tumors were treated between March 2010 and May 2015. The median total doses for single-fraction and hypofractionated courses of treatment were 16 Gy (range, 16-20 Gy) and 24 Gy (range, 16-40 Gy), respectively. Radiologic local control and numeric pain score data were measured, and univariate and multivariate analyses were done to determine factors predictive of treatment response., Results: Median follow-up was 5.9 months (range, 1-61 months). Radiologic local control was achieved in 84.7% of patients at 6 months and in 74.7% of patients at 1 year. Local control was found to be affected by the Spinal Instability Neoplastic Score, and was worse in patients with scores ≥7 (hazard ratio [HR]: 4.25; 95% confidence interval [CI], 1.57-11.51). Patients who required upfront surgical intervention to alleviate spinal cord compression, address mechanical spinal instability, or both had worse local control than those who did not require surgery (HR: 2.32; 95% CI, 1.04-5.17). Patients treated with a hypofractionated course compared with a single fraction had worse radiologic local control (HR: 2.63; 95% CI, 1.27-5.45). No patients developed radiation-induced myelitis after treatment, and the vertebral compression fracture rate was 9.1% after SBRT., Conclusions: Patients with potentially unstable spines or needing upfront spinal surgery before SBRT are less likely to achieve durable radiologic local control. Additionally, patients treated with single-fraction regimens have improved local control compared with those treated with hypofractionated radiation.

Objective: The objective of this study was to determine the effect, if any, of maternal body mass index (BMI) and amniotic fluid index (AFI) on the accuracy of sonographic estimated fetal weight (EFW) at 40 to 42 weeks' gestation., Methods: This was a retrospective cohort study of singleton gestations with ultrasound performed at 40 to 42 weeks from 2010 to 2013. In this study, patients with documented BMI and sonographic EFW and AFI, concurrently, within 7 days of delivery were included. Chronic medical conditions and fetal anomalies were excluded from this study. The primary variable of interest was the rate of substantial error in EFW, defined as absolute percentage error (APE) >10%., Results: A total of 1,000 pregnancies were included. Overall, the APE was 6.0 ± 4.5% and the rate of substantial error was 17.4% ( n  = 174). There was no significant difference in APE or rate of substantial error between BMI groups. In the final multivariable logistic regression model, the rate of substantial error was increased in women with oligohydramnios (OR 1.79; 95% CI: 1.10-2.92). Furthermore, oligohydramnios was significantly more likely to overestimate EFW while polyhydramnios was more likely to underestimate EFW. Maternal BMI did not affect the accuracy of sonographic EFW., Conclusion: Sonographic EFW may be affected by extremes of AFI in the postdates period. Maternal BMI does not affect EFW accuracy at 40 to 42 weeks., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Pregnant women with chronic hypertension are at risk for increased blood pressure and superimposed preeclampsia (SPE) in late pregnancy. Alterations in the renin-aldosterone system are a feature of normal pregnancy; however, their role in chronic hypertension with and without SPE is less clear. We performed a prospective, longitudinal trial of 108 women with chronic hypertension and measured plasma renin activity (PRA), 24-hour urine sodium, urine potassium, and urine aldosterone (Ualdo) at 12, 20, 28, and 36 weeks and postpartum. SPE developed in 34% of pregnancies. PRA was lower in women who developed SPE at weeks 28 (5.99 versus 6.22 ng/mL per hour; P <0.001) and 36 (5.71 versus 7.74 ng/mL per hour; P =0.002). Ualdo was lower in women with SPE compared with those without SPE at 28 weeks (59.6 versus 81.3 μg/d; P =0.039). Mean arterial pressure was inversely related to both PRA ( r =-0.23; P <0.0001) and Ualdo ( r =-0.11; P =0.029). PRA and Ualdo were positively associated with each other ( r =0.5327; P <0.0001) after adjusting for urine potassium, urine sodium, serum potassium, and mean arterial pressure. PRA and Ualdo were lower in women of black race compared with other racial groups ( P <0.001). Our results demonstrate that in women with chronic hypertension PRA and Ualdo increase in early pregnancy and subsequently decrease in women who develop SPE. These findings are consistent with the hypothesis that sodium retention may contribute to the elevation in blood pressure in SPE., (© 2018 American Heart Association, Inc.)

Objectives: To determine the effect, if any, of an increasing maternal body mass index (BMI) on sonographically diagnosed oligohydramnios in late gestation and how it subsequently affects obstetric and neonatal outcomes., Methods: This retrospective cohort study evaluated all women with singleton gestations who had a sonographic examination at 40 to 42 weeks' gestational age at North Shore University Hospital from 2010 through 2013. Underweight women (prepregnancy BMI < 18.5 kg/m 2 ) were excluded because of higher rates of oligohydramnios and fetal growth restriction. Patients were classified into 5 groups by late-pregnancy BMI. The primary variable of interest was the diagnosis of oligohydramnios (amniotic fluid index < 5 cm). Secondary variables of interest included the mode of delivery and indication for primary cesarean delivery. A multivariable logistic regression analysis was performed., Results: Oligohydramnios was identified in 189 of 1671 patients (11.3%). There was no significant difference in the amniotic fluid index between BMI groups. The rate of primary cesarean delivery increased with each successive BMI group (P < .001) such that women in the class III obesity group had an approximately 3-fold higher rate of primary cesarean delivery than women in the normal BMI group and a 2-fold higher rate than women in the overweight BMI group. In the final multivariable logistic regression model, a high BMI, nulliparity, and excessive gestational weight gain were associated with primary cesarean delivery. However, oligohydramnios did not contribute significantly to the model., Conclusions: The maternal BMI is not associated with oligohydramnios in late gestation. An increasing maternal BMI significantly increases the risk of primary cesarean delivery., (© 2017 by the American Institute of Ultrasound in Medicine.)

Background:  In a normal pregnancy, cervical collagen fibers remain organized in predictable patterns throughout most of the gestation. Cervical remodeling reflects a rearrangement of collagen fibers in which they become increasingly disordered and contribute to the pathogenesis of spontaneous preterm birth. Quantitative ultrasound analysis of cervical tissue echotexture may have the capacity to identify microstructural changes before the onset of cervical shortening., Objective:  The primary objective of this study was to examine the utility of a novel quantitative sonographic marker, the cervical heterogeneity index (HI), which reflects the relative organization of cervical collagen fibers. Also, we aimed to determine an optimal HI cut-point to predict spontaneous preterm birth., Study Design:  This retrospective cohort study employed a novel image-processing technique on transvaginal ultrasound images of the cervix in gestations between 14 and 28 completed weeks. The transvaginal sonography images were analyzed in MATLAB (MathWorks, Natick, MA) using a custom image-processing technique that assessed the relative heterogeneity of the cervical tissue., Results:  A total of 151 subjects were included in the study. The mean HI in subjects who delivered preterm and at term was 8.28 ± 3.73 and 12.35 ± 5.80, respectively ( p  < 0.0001). Thus, decreased tissue heterogeneity was associated with preterm birth, and increased tissue heterogeneity was associated with delivery at term. In our study population, preterm birth was associated with a short cervix (<2.5 cm), history of preterm birth and lower HI, and our findings indicate that HI may improve prediction of preterm birth., Conclusion:  Quantitative ultrasound measurement of the cervical HI is a promising, noninvasive tool for early prediction of spontaneous preterm birth., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Subcutaneous immunotherapy (SCIT) has been used to treat allergic rhinitis for over a century, and current regimens have wide variability with an array of practice styles and dosing strategies. Although there are some statements about contraindications and cautions, no specific formal age- or weight-based dosing guidelines are utilized when administering SCIT., Objective: The primary objective of this study was to estimate the overall incidence rate of any reaction to SCIT and to consider the severity of the reaction by grade in children and adults., Methods: A retrospective chart review was conducted to document the number and severity of episodes of systemic reactions (SRs) in pediatric and adult subjects. Crude incidence rates were estimated as the number of SRs relative to the total injections administered. Adjusted incidence rate ratios were generated using a generalized estimating equation approach, which accounted for multiple visits within subjects., Results: The incidence rate for any SR was 0.2%. The unadjusted incidence rate of any SR was significantly higher in children compared with adults (P < .001), although not significant when adjusted for asthma, gender, and phase of SCIT (P < .054). However, the incidence rate for grade 1 and 2 SRs in children was 1.89 times the incidence rate for adults, adjusting for these variables (P < .015)., Conclusions: These results suggest that current SCIT practices are associated with a higher rate of SRs, specifically of grade 1 and 2 SRs, in children than adults. Further studies are necessary to evaluate if changes in dosing strategies for children, such as a lower starting dose, a decrease in target maintenance dose, or a slower build-up phase, are warranted., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The potential role of systemic inflammation on brain injury in newborns with congenital heart disease (CHD) was assessed by measuring levels of central nervous system (CNS)-derived proteins in serum prior to and following cardiac surgery. A total of 23 newborns (gestational age, 39±1 weeks) with a diagnosis of CHD that required cardiac surgery with cardiopulmonary bypass (CPB) were enrolled in the current study. Serum samples were collected immediately prior to surgery and 2, 24 and 48 h following CPB, and serum levels of phosphorylated neurofilament-heavy subunit (pNF-H), neuron-specific enolase (NSE) and S100B were analyzed. Systemic inflammation was assessed by measuring serum concentrations of complement C5a and complement sC5b9, and the following cytokines: Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL12p70, interferon γ and tumor necrosis factor (TNF)-α. Analysis of cord blood from normal term deliveries (n=26) provided surrogate normative values for newborns. pNF-H and S100B were 2.4- to 2.8-fold higher (P<0.0001) in patient sera than in cord blood prior to surgery and remained elevated following CPB. Pre-surgical serum pNF-H and S100B levels directly correlated with interleukin (IL)-12p70 (ρ=0.442, P<0.05). pNF-H was inversely correlated with arterial pO 2 prior to surgery (ρ=-0.493, P=0.01) and directly correlated with arterial pCO 2 post-CPB (ρ=0.426, P<0.05), suggesting that tissue hypoxia and inflammation contribute to blood brain barrier (BBB) dysfunction and neuronal injury. Serum IL12p70, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher in patients than in normal cord blood and levels of these cytokines increased following CPB (P<0.001). Activation of complement was observed in all patients prior to surgery, and serum C5a and sC5b9 remained elevated up to 48 h post-surgery. Furthermore, they were correlated (P<0.05) with low arterial pO 2 , high pCO 2 and elevated arterial pressure in the postoperative period. Length of mechanical ventilation was associated directly with post-surgery serum IL-12p70 and IL-8 concentrations (P<0.05). Elevated serum concentrations of pNF-H and S100B in neonates with CHD suggest BBB dysfunction and CNS injury, with concurrent hypoxemia and an activated inflammatory response potentiating this effect.

Reperfusion injury following acute myocardial infarction is associated with significant morbidity. Activation of neuronal or non-neuronal cholinergic pathways in the heart has been shown to reduce ischemic injury and this effect has been attributed primarily to muscarinic acetylcholine receptors. In contrast, the role of nicotinic receptors, specifically alpha-7 subtype (α7nAChR) in the myocardium remains unknown which offers an opportunity to potentially repurpose several agonists/modulators that are currently under development for neurologic indications. Treatment of ex vivo and in vivo rat models of cardiac ischemia/reperfusion (I/R) with a selective α7nAChR agonist (GTS21) showed significant increases in left ventricular developing pressure, and rates of pressure development without effects on heart rate. These positive functional effects were blocked by co-administration with methyllycaconatine (MLA), a selective antagonist of α7nAChRs. In vivo , delivery of GTS21 at the initiation of reperfusion, reduced infarct size by 42% (p<0.01) and decreased tissue reactive oxygen species (ROS) by 62% (p<0.01). Flow cytometry of MitoTracker Red stained mitochondria showed that mitochondrial membrane potential was normalized in mitochondria isolated from GTS21 treated compared to untreated I/R hearts. Intracellular ATP concentration in cultured cardiomyocytes exposed to hypoxia/reoxygenation was reduced (p<0.001), but significantly increased to normoxic levels with GTS21 treatment, and this was abrogated by MLA pretreatment. Activation of stress-activated kinases, JNK and p38MAPK, were significantly reduced by GTS21 in I/R. We conclude that targeting myocardial 17nAChRs in I/R may provide therapeutic benefit by improving cardiac contractile function through a mechanism that preserves mitochondrial membrane potential, maintains intracellular ATP and reduces ROS generation, thus limiting infarct size.

Background: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder worldwide. Although thoracic complications are frequent in CLL, only limited data exist regarding the etiologies of these complications., Materials and Methods: A retrospective chart review was performed on all patients admitted to a tertiary care, CLL referral center, with CLL and a respiratory complaint from 2001 through 2013, to categorize pulmonary complaints and diagnoses., Results: There were 277 patients with CLL admitted on 409 occasions with respiratory complaints. The median age was 73 years, with a male to female ratio of 2:1. The majority of patients had a high-risk Rai classification and had received prior treatment. Common presenting symptoms included dyspnea, cough, and sputum production. The most common diagnoses were pneumonia (62.8%), with an identified organism in 44.7%, pleural effusions (31.8%), lung cancer (6.9%), and leukemic infiltrates (5.9%). Invasive procedures were performed 138 times: 70 bronchoscopies, 24 surgical lung biopsies, 10 computed tomography-guided lung biopsies, and 34 thoracenteses. In-hospital mortality was 24.9%. In a multivariable analysis, an elevated blood urea nitrogen level and creatinine, thrombocytopenia, and a presenting symptom of dyspnea correlated significantly with in-hospital mortality., Conclusion: Thoracic manifestations in CLL are common among hospitalized patients. Although infectious pneumonia remains most common, unusual or opportunistic infections may be increasing, and direct lung damage owing to CLL itself or to newer biologic agents are being diagnosed with lung tissue sampling. Recognition of these complications will allow earlier diagnosis, which may change management including removal of offending biologic agents or augmentation of treatment for CLL when infiltrative leukemic cells are present., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Inflammation in traumatic spinal cord injury (SCI) has been proposed to promote damage acutely and oppose functional recovery chronically. However, we do not yet understand the signals that initiate or prolong inflammation in persons with SCI. High-Mobility Group Box 1 (HMGB1) is a potent systemic inflammatory cytokine-or damage-associated molecular pattern molecule (DAMP)-studied in a variety of clinical settings. It is elevated in pre-clinical models of traumatic spinal cord injury (SCI), where it promotes secondary injury, and strategies that block HMGB1 improve functional recovery. To investigate the potential translational relevance of these observations, we measured HMGB1 in plasma from adults with acute (≤ 1 week post-SCI, n = 16) or chronic (≥ 1 year post-SCI, n = 47) SCI. Plasma from uninjured persons (n = 51) served as controls for comparison. In persons with acute SCI, average HMGB1 levels were significantly elevated within 0-3 days post-injury (6.00 ± 1.8 ng/mL, mean ± standard error of the mean [SEM]) or 4-7 (6.26 ± 1.3 ng/mL, mean ± SEM), compared with controls (1.26 ± 0.24 ng/mL, mean ± SEM; p ≤ 0.001 and p ≤ 0.01, respectively). In persons with chronic SCI who were injured for 15 ± 1.5 years (mean ± SEM), HMGB1 also was significantly elevated, compared with uninjured persons (3.7 ± 0.69 vs. 1.26 ± 0.24 ng/mL, mean ± SEM; p ≤ 0.0001). Together, these data suggest that HMGB1 may be a common, early, and persistent danger signal promoting inflammation in individuals with SCI.

Objective: To determine whether women with sonographically identified uterine fibroids are at higher risk for a short cervix., Methods: This retrospective cohort study evaluated all women with singleton gestations who had a routine second-trimester ultrasound at 17-23 weeks gestational age from 2010 to 2013. When fibroids were noted, their presence, number, location and size were recorded. Exclusion criteria included a history of cervical conization or loop electrosurgical excision procedure (LEEP), uterine anomalies, maternal age greater than 40 years, and a previously placed cerclage. The primary variable of interest was short cervix (<25 mm). Secondary variables of interest included gestational age at delivery, mode of delivery, indication for cesarean, malpresentation, birth weight, and Apgar scores. A multivariable logistic regression analysis was performed., Results: Fibroids were identified in 522/10 314 patients (5.1%). In the final multivariable logistic regression model, short cervix was increased in women with fibroids (OR 2.29, 95% CI: 1.40, 3.74). The number of fibroids did not affect the frequency of short cervix. Fibroids were significantly associated with preterm delivery (<37 weeks), primary cesarean, breech presentation, lower birth weight infants, and lower Apgar scores., Conclusions: Women with uterine fibroids may be at higher risk for a short cervix. Fibroids are also associated with several adverse obstetric and neonatal outcomes.

Objective: To examine clinical and demographic characteristics of a population-based cohort of patients with uterine carcinosarcoma (UCS), to assess access to treatment and survival patterns., Methods: Surveillance, Epidemiology and End Results database was queried for patients diagnosed in 1999-2010 and treated with surgery with or without adjuvant radiation therapy (aRT). The Kaplan-Meier method was used to estimate survival functions, and Cox proportional hazards regression - to analyze the effect of covariates on survival., Results: 2342 patients were eligible. African Americans presented with more advanced AJCC stages than other races (35.4% vs. 29.1%; p<0.01). African Americans vs. others, and women diagnosed in 1999-2004 vs. in 2005-2010, received aRT at a similar rate: 36.5% vs. 39.9% (p=NS), and 39.5% vs. 38.9% (p=NS), respectively. There was a trend towards higher aRT utilization among patients younger than 65 vs. older (41.4% vs. 37.5%; p<0.06). We observed better overall and cause-specific survival in the aRT group: 42 vs. 22 (p<0.0001) and 57 vs. 28months (p<0.0001), respectively. Black race, diagnosis in 1999-2004, advanced stage and age≥65years carried a higher risk of UCS death., Conclusions: We observed greater survival rate in the aRT group. African Americans were more likely to present with later stage disease and die of UCS than non-African Americans. Age and stage, but not race, influenced receipt of aRT. Patients treated more recently survived longer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Many intervertebral disc diseases cause low back pain (LBP). Proinflammatory cytokines and matrix metalloproteinases (MMPs) participate in disc pathology. In this study, we examined levels of serum cytokines and MMPs in human subjects with diagnoses of disc herniation (DH), spinal stenosis (SS), or degenerative disc disease (DDD) relative to levels in control subjects. Comparison between subjects with DH and those with other diagnoses (Other Dx, grouped from SS and DDD) was performed to elaborate a pathological mechanism based on circulating cytokine levels., Methods: Study participants were recruited from a spine neurosurgery practice (n = 80), a back pain management practice (n = 27), or a control cohort (n = 26). Serum samples were collected before treatment and were assayed by multiplex assays for levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ, tumor necrosis factor-α, MMP-1, MMP-3, and MMP-9. Inflammatory and degradative mediator levels were compared for subjects with LBP and control subjects, by diagnosis and by treatment groups, controlling for effects of sex, age, and reported history of osteoarthritis. Spearman's correlation coefficient was used to examine relationships with age, body mass index (BMI), symptom duration, and smoking history., Results: Serum levels of IL-6 were significantly higher in subjects with LBP compared with control subjects. Participants with LBP due to Other Dx had significantly higher levels of IL-6 than DH and controls. Serum levels of MMP-1 were significantly lower in LBP subjects, specifically those with DH, than in control subjects. Positive correlations were found between IL-6 levels and BMI, symptom duration, and age. MMP-1 levels were positively correlated with age., Conclusions: The findings of the present clinical study are the results of the first examination of circulating cytokine levels in DDD and SS and provide evidence for a more extensive role of IL-6 in disc diseases, where patients with DDD or SS have higher serum cytokine levels than those with DH or control subjects. These findings suggest that LBP subjects have low-grade systemic inflammation, and biochemical profiling of circulating cytokines may assist in refining personalized diagnoses of disc diseases.

This study updates assessment of post-transplant outcomes in IgAN patients in the modern era of immunosuppression. Using UNOS/OPTN data, patients ≥18 yr of age with first kidney transplant (1/1/1999 to 12/31/2008) were analyzed. Multivariable Cox regression models and propensity score-based matching techniques were used to estimate hazard ratios (HRs) for death-censored allograft survival (DCGS) and patient survival in IgAN compared to non-IgAN. Results of multivariable regression were stratified by donor type (living vs. deceased). A total of 107, 747 recipients were included (4589 with IgAN and 103 158 with non-IgAN). Adjusted HR for DCGS showed no significant difference between IgAN and non-IgAN. IgAN had higher patient survival compared to non-IgAN (HR 0.54, 95% CI 0.47-0.62, p < 0.0001 for deceased donors; HR 0.42, 95% CI 0.33-0.54, p < 0.0001 for living donors). Propensity score-matched analysis was similar, with no significant difference in DCGS between matched groups and higher patient survival in IgAN patients compared to non-IgAN group (HR 0.54, 95% CI 0.47, 0.63; p-value <0.0001). IgAN patients with first kidney transplant have superior patient survival and similar graft survival compared to non-IgAN recipients. Results can be used in prognostication and informed decision-making about kidney transplantation in patients with IgAN., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Although race and ethnic background are known to be important factors in the completion of advance directives, there is a dearth of literature specifically investigating the effect of race and ethnicity on advance directive completion rate after palliative care consultation (PCC)., Method: A chart review of all patients seen by the PCC service in an academic hospital over a 9-month period was performed. Data were compiled using gender, race, ethnicity, religion, and primary diagnosis. For this study, advance directives were defined as: "Do Not Resuscitate" (DNR) and/or "Do Not Intubate" (DNI)., Results: Of the 400 medical records reviewed, 57% of patients were female and 71.3% documented their religion as Christian. The most common documented diagnosis was cancer (39.5%). Forty-seven percent reported their race as white. White patients completed more advance directives than did nonwhite patients both before (25.67% vs. 12.68%) and after (59.36% vs. 40.84%) PCC. There was a significantly higher proportion of whites who signed an advance directive after a PCC than of nonwhites (p = 0.021); of the 139 whites who did not have an advance directive at admission, 63 signed an advance directive after a PCC compared with 186/60 nonwhites (45% vs. 32%, respectively, p = 0.021). Further analysis revealed that African Americans differed from whites in the likelihood of advance directive execution rates pre-PCC, but not post-PCC., Significance of Results: This study demonstrates the impact of a PCC on the completion of advance directives, on both whites and nonwhites. The PCC Intervention significantly reduced differences between whites and African Americans in completing advance directives, which have been consistently documented in the end-of-life literature.

Macrophage migration inhibitory factor (MIF) is a multifunctional protein that exhibits an intrinsic thiol protein oxidoreductase activity and proinflammatory activities. In the present study to examine intracellular MIF redox function, exposure of MIF-deficient cardiac fibroblasts to oxidizing conditions resulted in a 2.3-fold increase (p < 0.001) in intracellular ROS that could be significantly reduced by adenoviral-mediated reexpression of recombinant MIF. In an animal model of myocardial injury by ischemia/reperfusion (I/R), MIF-deficient hearts exhibited higher levels of oxidative stress than did wild-type hearts, as measured by significantly higher oxidized glutathione levels (decreased GSH/GSSG ratio), increased protein oxidation, reduced aconitase activity, and increased mitochondrial injury (increased cytochrome c release). The increased myocardial oxidative stress after I/R was reflected by larger infarct size (INF) in MIF-deficient hearts versus wild-type (WT) hearts (21 ± 6% vs. 8 ± 3% INF/LV; p < 0.05). In vivo hemodynamic measurements showed that left ventricular (LV) contractile function of MIF-deficient hearts subjected to 15-min ischemia failed to recover during reperfusion compared with WT hearts (LV developed pressure and ± dP/dt; p = 0.02). These data represent the first in vivo evidence in support of a cardioprotective role of MIF in the postischemic heart by reducing oxidative stress.

Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells and plasma levels of the chemokine stromal cell-derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.

Background: Thrombotic complications occur in adult patients undergoing stem cell transplantation (SCT), especially following high dose chemo-radiotherapy. There is little published information in children on the impact of SCT on coagulation, as well as potential correlations between altered coagulation and SCT-associated thrombosis and organ failure., Procedure: Forty three pediatric subjects who underwent allogeneic SCT were prospectively evaluated for congenital thrombophilia, anticoagulant levels, coagulation activation, and fibrinolysis at pre-established set points encompassing the period from the 2 to 4 weeks prior to conditioning to 28 days post-transplantation., Results: A significant decrease of protein C and antithrombin levels was found in 39% and 31% of subjects respectively, between SCT days +6 and +7. A peak in plasminogen activator inhibitor-1 levels in 31% of subjects was noted between days +9 and +10. No subject experienced a thrombotic event or other SCT-related organ failure. Antithrombin deficiency correlated with underlying malignancy, donor HLA-mismatch, and TBI, whereas decreased PC activity demonstrated a trend of association with lack of T-cell depletion and TBI. Prophylactic heparin did not influence the pattern of acquired hemostatic abnormalities observed in this cohort., Conclusions: Children undergoing allogeneic SCT develop a state of acquired thrombophilia in the early post-transplantation period. Although no SCT-related thromboembolic events were observed, our results provide new information about the hemostatic changes in children undergoing allogeneic SCT and their potential clinical triggers. The significance of these findings requires further prospective evaluation in a larger cohort of patients., ((c) 2007 Wiley-Liss, Inc.)

Objectives: To determine whether children with celiac disease (CD) fail to show a response to hepatitis B virus (HBV) vaccine more frequently than children without CD., Patients and Methods: This was a prospective study that compared the response to HBV, tetanus, rubella, and Haemophilus influenzae type b (Hib) vaccines between children with CD and age- and sex-matched control subjects., Results: The study population included 26 patients with CD and 18 age- and sex-matched controls. All had received the full complement of childhood vaccinations. A significantly higher proportion of subjects in the CD group (14 of 26) failed to respond to HBV vaccine compared with controls (2 of 18; 53.9% vs 11.1%; P < 0.05). Patients with CD were 8.33 times more likely to test negative for hepatitis B surface antigen than control subjects (95% CI, 1.5-46.5). By contrast, all of the subjects in both groups tested positive for rubella antibodies; only 1 subject in the CD group tested negative for tetanus antibody versus none in the control group (3.9% vs 0%; P = 1.0). The percentage of subjects who tested negative for Hib antibodies was similar in the 2 groups (CD, 33.3%; control, 44.4%; P = 0.53)., Conclusions: More than 50% of children with CD do not show a response to standard vaccination regimens for HBV. Given the large number of children with CD throughout the world, this observation suggests that there is a large HBV-susceptible population despite widespread vaccination. Current immunization strategies may need to be reassessed to protect this population and achieve the goal of universal protection.

Objective: To evaluate the inter-patient and intra-patient reproducibility of the glycemic response to a mixed meal in individuals with type 2 diabetes mellitus (DM)., Subjects/setting: Six individuals with DM were admitted to the General Clinical Research Center for 6 days., Intervention: Subjects consumed 3 different meal plans consisting of 4 meals daily (breakfast, lunch, dinner and snack) on 2 separate occasions. Serum insulin and glucose levels were sampled at 19 time points every day. The glycemic response (GR) to a meal was calculated as the area under the glucose response curve after consumption of a given meal. In addition, the incremental area under the curve (IGR) was calculated assuming a pre-prandial (baseline) glucose value before each meal as zero., Results: Intra-patient correlation coefficients (R) of GR for meals in subjects with DM were quite good, ranging 0.69-0.94. The range of the inter-patient coefficients of variation (CV) for the same meals was 21.5-30.4%. For IGR, the R values ranged from 0.64 to 0.91 for 8 out of 12 meals, confirming good intra-patient reproducibility for these meals. CV for IGR ranged from 31% to 113%., Conclusions: For patients with DM, the GR of individual meals exhibits excellent intra-patient reproducibility, allowing prediction of the glycemic response to a given meal in an individual subject. However, significant inter-patient variability of the GR precludes its use for the prediction of post-prandial glucose concentrations in groups of patients with diabetes.

Objective: To determine age-related concentrations of brain-type natriuretic peptide in preterm infants using bedside Triage brain-type natriuretic peptide test and correlate it to the presence or absence of the patent ductus arteriosus and ventilatory support., Methods: Serum brain-type natriuretic peptide levels were measured in infants who were born at <32 weeks' gestation from birth to 2 months of age. Serial echocardiograms were performed, until closure of the patent ductus arteriosus, or until discharge. Brain-type natriuretic peptide levels were correlated to the day of life, gestational age, presence or absence of the patent ductus arteriosus, and the degree of ventilatory support. Nineteen preterm infants (gestational age: 24-31 weeks; birth weight: 645-1670 g) were enrolled prospectively during the first 2 weeks of life. Serum brain-type natriuretic peptide levels (pg/mL) were determined in 177 blood samples, and 87 paired echocardiograms were performed., Results: Significant negative correlation was found between brain-type natriuretic peptide levels and the day of life and remained significant when the patients were stratified by gestational age (< or =28 weeks and >28 weeks). Higher brain-type natriuretic peptide levels correlated with increasing grade of the patent ductus arteriosus. Significant differences in brain-type natriuretic peptide levels were seen with increasing ventilatory support. Comparisons between the size of patent ductus arteriosus and the degree of ventilatory support to brain-type natriuretic peptide levels revealed that the size of the patent ductus arteriosus was the major determinant of both brain-type natriuretic peptide levels and the degree of ventilatory support., Conclusions: Similar to term infants, brain-type natriuretic peptide levels of preterm infants are related to the chronological age and decline during the first month of life. Rapid bedside Triage brain-type natriuretic peptide is a potentially valuable and practical assay in determining the hemodynamic changes in preterm infants.

Objective: To evaluate the clinicopathologic features and prognosis of patients with orbital lymphomas., Methods: Clinical and pathologic data of 35 patients with biopsy-proven orbital lymphoma diagnosed at a tertiary care hospital from 1992 to 2001 were reviewed. Lymphomas were divided into low-grade and high-grade lymphomas. Survival of patients was compared according to age, gender, disease site, extent of disease, tumor grade, and treatment modality by using log rank test., Results: Median patient age was 75 years (23-94) and the male-to-female ratio was 1:2.9. Twenty-three patients (66%) were diagnosed with low-grade lymphoma, and 12 patients (34%) were found to have high-grade lymphoma. Among low-grade lymphomas, marginal zone lymphoma (n=6), follicle center cell lymphoma (n= 6), and small lymphocytic lymphoma (n=5) were common entities, whereas diffuse large cell B-cell lymphoma (n=5) was the most common entity in patients with high-grade lymphoma. Disease was clinically localized in 74% of patients at the time of diagnosis. Radiation alone or with chemotherapy was the primary treatment modality in 83% of patients. All except one patient had an objective response to therapy. Over the median follow-up period of 47 months (range, 1.5-141 months), disease recurred in 37% patients who achieved a complete response. The estimated 5- and 10-year survival rates were 64% and 42%, respectively. Overall, 13 (37%) patients died, 6 with high-grade and 7 with low-grade lymphoma. No clinical variable was found to be prognostically significant with respect to survival., Conclusions: Orbital lymphoma is a disease of the elderly with a female preponderance. It tends to be localized to the orbit at the time of diagnosis and responds well to local or systemic therapy.

In order to determine variables that correlate with malignant pleural effusion and mortality in patients with lymphoproliferative disorders and pleural effusion, a retrospective study was performed. Clinical data of hospitalized patients with a lymphoid malignancy and pleural effusion who underwent thoracentesis from January 1993 to December 2002 were collected. A logistic regression analysis was carried out to determine prognostic variables that predict malignant pleural effusion and hospital mortality. There were 86 patients who were admitted on 91 occasions. The median age was 70 years (range 4 - 92) and the male:female ratio was 44:42. Sixty-four patients (74%) had advanced disease, 43 (50%) had received prior chemotherapy and 9 (10%) were in remission. Of 91 cases of pleural effusions, 44 (48%) were bilateral, 80 (88%) were exudates and 48 (53%) were due to malignant involvement of pleura. In multivariate analysis, symptomatic pleural effusion (odds ratio 10.3, 95% confidence interval 1.7 - 98.3), pleural fluid mesothelial cell count < 5% (odds ratio 8.0, 95% confidence interval 1.4 - 58.2), pleural fluid:serum lactate dehydrogenase (LDH) > or =1 (odds ratio 6.4, 95% confidence interval 1.2 - 45.6) and pleural fluid lymphocyte percentage > or =50 (odds ratio 6.4, 95% confidence interval 1.2 - 50) were significantly correlated with malignant effusion. A secondary cancer (odds ratio 11.9, 95% confidence interval 2.3 - 88.8), pleural fluid:serum LDH > or =1 (odds ratio 10.9, 95% confidence interval 2.6 - 64.9), and pneumonia (odds ratio 6.4, 95% confidence interval 1.7 - 28.6) were significantly correlated with hospital mortality. In conclusion, malignant pleural effusion is the common etiology of pleural effusion in patients with lymphoid malignancy. Many clinical and cytochemical markers have discriminatory values in identifying malignant effusion. A high pleural fluid to serum LDH level correlates with malignant pleural involvement and hospital mortality.

Objective: To evaluate agreement among various methods for measuring oxyhemoglobin (O2Hb) saturation in adult hypoxic patients with sickle cell disease (SCD) during painful vaso-occlusive crisis and to compare those results with a control group., Patients and Methods: The hemoglobin oxygen saturation was determined simultaneously by pulse oximetry (SpO2), co-oximetry [SO2 (functional oxyhemoglobin saturation) and FO2Hb (oxyhemoglobin fraction)] and by calculation (SaO2) using a normal O2Hb dissociation curve in 18 adult patients with SCD during vaso-occlusive crisis and 12 non-SCD patients with various cardiopulmonary diagnoses. The method proposed by Bland and Altman was used to evaluate agreement of various methods in each of the two groups., Results: Mean differences between various methods in patients with SCD were significantly larger than the control group. Limits of agreement (LOA) were also wider in the SCD group than in the control group. Mean bias between SpO2 and SO2, and SpO2 and FO2Hb in patients with SCD were -3.1 +/- 4.4 (LOA: -11.9 to 5.7) and 2 +/- 4.1 (LOA: -6.2 to 10.2) respectively, compared with -1.4 +/- 1.4 (LOA: -4.2 to 1.4) and 1.2 +/- 1.5 (LOA: -1.9 to 4.3) in the control group. A mean bias of -4.5 +/- 4 (LOA: -12.5 to 3.5) between SpO2 and SaO2 was noted in patients with SCD compared with -0.1 +/- 2.1 (LOA: -4.3 to 4.1) in the control group. The width of LOA for various methods in patients with SCD ranged from 9.8 to 17.6 compared with 1.3 to 8.4 in the control group., Conclusion: Patients with SCD during vaso-occlusive crisis have discrepancies in O2Hb saturation measurements by various methods. Abnormal pulse oximetry values in these patients should be interpreted cautiously and supplemented by arterial blood gas analysis and co-oximetry., (Copyright 2005 Blackwell Munksgaard.)

Immune thrombocytopenia (ITP) has a favorable prognosis in children. Only a small number of children go on to develop chronic ITP. However, at the time of diagnosis, it is not possible to predict the course of the disease. In order to determine prognostic factors that could predict the disease course at diagnosis, we retrospectively evaluated various clinical variables in 103 pediatric patients with newly diagnosed ITP at our institution from 1995 to 2001. Sixty-eight (66%) patients had a mean platelet volume (MPV) of <8 fL on admission. Of 72 patients who had a follow-up period of at least 6 months, 54 (75%) achieved a durable remission within 6 months and 18 (25%) developed chronic ITP. In univariate analysis, a low admission MPV (<8), history of viral prodrome, and a low admission platelet count (<10 x 10(9)/L) predicted for a favorable outcome. Age and sex did not correlate with remission. In multivariate analysis, a low admission MPV and a history of a viral prodrome were the only independent factors correlated with a durable CR. The adjusted odds ratio for achieving a durable remission was 8.9 (95% CI: 1.54-51.8) for history of a viral prodrome and 14 (95% CI: 2.52-83.3) for low admission MPV value. In conclusion, our study showed that a majority of the children with newly diagnosed ITP presented with a low MPV value. A history of viral illness and a low admission MPV were found to be independent prognostic variables that predicted for the achievement of a durable CR in childhood ITP., (2004 Wiley-Liss, Inc.)

Bronchial-associated lymphoid tissue (BALT) lymphoma is a distinct subgroup of low-grade B-cell extranodal non-Hodgkin's lymphoma, classified as marginal-zone lymphoma. This study was performed in order to assess the natural history of this rare entity. We evaluated retrospectively the clinical data of 22 patients with biopsy-proven BALT lymphoma at two tertiary-care institutions from 1996 to 2002. Immunophenotyping was done to confirm the abnormal populations of B-lymphoid cells in all cases, and clonality was determined by flow cytometry or molecular studies. There were 11 men and 11 women in the sample, median age 61 years (range 21-80 years); nine were asymptomatic at diagnosis. All 13 symptomatic patients had non-specific pulmonary complaints. On computed tomographic examination of the chest, 11 patients had bilateral disease, 12 had lung nodules, and 10 had a mass or air-space consolidation. In all but one case the disease was localised to the lung at diagnosis and none had peripheral blood or bone marrow involvement. Out of 22 patients, 20 received treatment in various combinations, 12 had chemotherapy and/or rituximab, six had surgery, and two received radiation therapy as primary treatment. A complete response (CR) was achieved in nine patients and a partial response was obtained in 10 patients. Seven of 10 patients who had unilateral disease achieved a CR. The estimated progression-free survival was 53 months. All patients were alive during the median follow-up period of 36 months (range 12-76 months). It appears that BALT lymphoma tends to be localised to lung at the time of diagnosis, responds well to local or systemic therapy, and has a favourable prognosis.

Perturbations in sex hormones occur in adults with liver disease; however, little is known about how liver disease affects hormone levels in children. To address this issue, we recruited 19 patients with portal hypertension and 21 non-hormone-deficient short children as controls. Serum sex hormones, sex hormone binding globulin (SHBG), IGF-I, IGFBP-3, gonadotropins, and thyroid hormones were measured; growth and pubertal status were recorded. There was no significant difference between groups for any of the sex hormones, SHBG, gonadotropins, or thyroid hormones. In contrast, IGF-I and IGFBP-3 were significantly lower among patients than controls, despite the fact that height SDS for the control group was significantly lower. We conclude from this cross-sectional study that children with portal hypertension do not have clinical evidence of growth failure or abnormal puberty, despite subtle changes in the growth axis.

Objective: To evaluate the activation of clotting systems in patients with sickle cell disease (SCD) by measuring the plasma D-dimer level and to determine the effect of low-dose warfarin on D-dimer level during vaso-occlusive crisis., Methods: Plasma D-dimer level was measured in 65 blood samples of 37 adult patients with SCD who were hospitalized for vaso-occlusive painful crisis. D-dimer level of patients who were on low-dose warfarin was compared with those patients who were not on any anticoagulation treatment. Analysis of variance (anova) was carried out to determine factors significantly associated with low D-dimer level in patients with SCD. The following factors were included in the anova model; warfarin, homozygous hemoglobin S, history of blood transfusion in past 3 months, hydroxyurea, hemoglobin S%, hemoglobin F%, white blood cell counts, hemoglobin level, platelet count, and plasma fibrinogen level., Results: Overall median D-dimer level in 65 samples was 2.7 microg fibrinogen equivalent units (FEU)/mL (0.34-4). Patients who were on low-dose warfarin had a median D-dimer level of 0.81 microg FEU/mL (0.34-1.8) compared with 3.1 microg FEU/mL (0.94-4) in those patients who were not on anticoagulation treatment. Using anova to model D-dimer levels, only warfarin was significantly correlated with low D-dimer levels after controlling for other variables., Conclusions: Patients with SCD during vaso-occulsive painful crisis have an elevated D-dimer level. Low-dose anticoagulation treatment is associated with a significant reduction in the D-dimer levels.

Background: Although pulmonary complications account for significant morbidity and mortality in patients with chronic lymphocytic leukemia (CLL), to the authors' knowledge there are sparse data available in published literature. The authors evaluated pulmonary complications in patients with CLL and identified prognostic variables that predict hospital mortality in these patients., Methods: Clinical data were analyzed retrospectively from patients with CLL who required hospitalization for a respiratory illness at a tertiary care institution from January 1993 to December 2001. A logistic regression analysis with a backward elimination procedure was carried out to determine prognostic variables that predict hospital mortality., Results: There were 110 patients who were admitted on 142 occasions with a pulmonary complication. The median age was 75 years (range, 43-97 years), and the male:female ratio was 1.7:1.0. Among 142 admissions, 68% were high risk according to the Rai criteria, 68% of patients admitted had received prior therapy for CLL, and 35% had received treatment within 3 months of admission. The most common pulmonary complications were pneumonias (75%), malignant pleural effusion/and or lung infiltrate due to CLL (9%), pulmonary leukostasis (4%), Richter transformation or nonsmall cell lung carcinoma (3%), and upper airway obstruction (2%). Forty-four of 110 patients (40%) died. In multivariate analysis, admission absolute neutrophil counts /= 20 mg/dL (odds ratio, 3.0; 95% CI, 1.1-8.3) were correlated significantly with mortality., Conclusions: Pneumonia was the major pulmonary complication in hospitalized patients with CLL. Severe neutropenia and high BUN levels were correlated significantly with increased mortality., (Copyright 2003 American Cancer Society.)

Change in proportion of metaphases with a Ph chromosome is often used to measure effect of treatment in chronic myelocytic leukemia, but this method requires analysis of dividing cells. Dual-color fluorescence in situ hybridization (D-FISH) analysis of bone marrow (BM) or blood (PB), can be used to establish the proportion of interphase nuclei with BCR/ABL fusion. We studied the correlation of these three measures with each other and with response classification categories. In a clinical trial to test rIFN(-) versus rIFN(-) +Ara-C (N = 65 patients), we defined for each cytogenetic and FISH parameter, the patient's "best response" over time and at any given time. The strength and nature of agreement among the three measurements were determined by regression, correlation, and kappa statistic. Correlations between cyBM versus D-FISH-BM, cyBM versus D-FISH-PB and D-FISH-BM vs. D-FISH-PB were fairly strong. Regression showed cyBM values were significantly higher than those of D-FISH-PB or D-FISH-BM. No difference between D-FISH-PB and D-FISH-BM was apparent. When numerical responses (BR%) were classified into response categories (CR, PR, MR, NR), levels of agreement were weak to moderate. We observed a trend toward disagreement between cyBM and each D-FISH method, with cyBM tending to "downgrade" response category. Whether analyzed using actual numerical values or classified into response categories, cyBM differed from D-FISH-BM or D-FISH-PB. The results indicate that mixing data of different methods to measure treatment response within or between patients may be misleading clinical index.