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Introduction: This study addresses the gap in research comparing the effectiveness between home and in-office narrowband ultraviolet B (NB-UVB) phototherapy for the treatment of mycosis fungoides (MF). Elderly and disabled patients with this condition disproportionally lack access to home units due to insurance denial., Materials and Methods: A retrospective review included patients diagnosed with MF or Sezary syndrome who underwent either in-office or home UVB between 2016 and 2023. Eighty-four patients used home NB-UVB, while 75 used in-office. Clinical characteristics, treatment response, and access were evaluated., Results: Overall, there was no significant difference in response rates between home and in-office NB-UVB phototherapy. Subgroup analysis based on adjuvant treatment revealed a significant difference in clinical response rates for patients using NB-UVB with topicals (p = 0.008) and NB-UVB with multiple systemic therapies (p = 0.04). Financial and time constraints were the most common cause of treatment discontinuation for in-office patients (28%)., Conclusions: The effectiveness of home NB-UVB treatment is comparable, if not superior, to in-office treatment, likely attributed to treatment ease in access and compliance. Medicare and other health insurance companies should expand coverage to include home-based phototherapy for patients with MF, a potentially fatal cancer with a relative paucity of effective alternate therapies., (© 2024 The Author(s). Photodermatology, Photoimmunology & Photomedicine published by John Wiley & Sons Ltd.)

Background:  In facial reanimation, dual-innervated gracilis free functional muscle transfers (FFMTs) may have amalgamated increases in tone, excursion, synchroneity, and potentially spontaneity when compared with single innervation. The ideal staging of dual-innervated gracilis FFMTs has not been investigated. We aim to compare objective long-term outcomes following one- and two-stage dual-innervated gracilis FFMTs., Methods:  Included were adult patients with facial paralysis who underwent either one- (one-stage group) or two-stage (two-stage group) dual-innervated gracilis FFMT with ≥1 year of postoperative follow-up. Facial measurements were obtained from standardized photographs of patients in repose, closed-mouth smile, and open-mouth smile taken preoperatively, 1 year postoperatively, and 3 years postoperatively. Symmetry was calculated from the absolute difference between the paralyzed and healthy hemiface; a lower value indicates greater symmetry., Results:  Of 553 facial paralysis patients, 14 were included. Five and nine patients were in the one- and two-stage groups, with mean follow-up time, respectively, being 2.5 and 2.6 years. Within-group analysis of both groups, most paralyzed-side and symmetry measurements significantly improved over time with maintained significance at 3 years postoperatively in closed and open-mouth smile (all p ≤ 0.05). However, only the two-stage group had maintained significance in improvements at 3 years postoperatively in paralyzed-side and symmetry measurements in repose with commissure position (median change [interquartile range, IQR], 7.62 [6.00-10.56] mm), commissure angle (median change [IQR], 8.92 [6.18-13.69] degrees), commissure position symmetry (median change [IQR], -5.18 [-10.48 to -1.80] mm), commissure angle symmetry (median change [IQR], -9.78 [-11.73 to -7.32] degrees), and commissure height deviation (median change [IQR], -5.70 [-7.19 to -1.64] mm; all p ≤ 0.05). In the between-group analysis, all measurements were comparable in repose, closed-mouth smile, and open-mouth smile (all p  > 0.05)., Conclusion:  Long-term outcomes demonstrate that both one- and two-stage dual-innervated gracilis FFMTs significantly improve excursion, but only two-stage reconstruction significantly improves resting tone., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The purpose of this study was to compare long-term tone and excursion in single- versus dual-innervated free functional muscle transfer (FFMT) in patients with longstanding facial paralysis., Methods: Patients with longstanding facial palsy treated with an FFMT innervated either by a nerve-to-masseter graft (single-innervation group) or nerve-to-masseter and cross-facial-nerve grafts (dual-innervation group) were included. One-year minimum follow-up was required. Outcome measures, based on standardized photographs, included excursion, smile angle, teeth exposure, commissure height deviation, and upper lip height deviation in repose and in closed and open-teeth smile preoperatively and at 3 months, 1 year, and 3 years postoperatively. Emotrics software and ImageJ software were used to take measurements. Between-group and within-group longitudinal comparisons were analyzed., Results: At 3 years (single, n = 24; dual, n = 13), significance was found between groups in commissure position (single, 26.42 mm versus dual, 31.51 mm; P < 0.0001) and excursion with open-mouth smile (single, 31.32 mm versus dual, 26.59 mm; P < 0.001). Single-innervation FFMT within-group analysis lacked significant improvement in commissure height deviation and upper lip height deviation at 3 years in repose, whereas the dual-innervation group revealed significant improvements (3.67 mm [ P < 0.001], 3.17 mm [ P < 0.001], respectively). Teeth exposure revealed an increase in the dual-innervation group (single, 35.753 mm 2 versus dual, 64.177 mm 2 ), but significance was not observed., Conclusion: Dual-innervated FFMT revealed improvements in resting tone and teeth exposure with minimal decrease in smile excursion compared with single-innervated FFMT., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Introduction/aims: Myxovirus resistance protein A (MxA) is a type I interferon (IFN1) pathway activation marker and MxA sarcoplasmic expression is currently recognized as a highly specific marker for dermatomyositis (DM). However, we have frequently observed endothelial tubuloreticular inclusions (TRI), another surrogate IFN1 activation marker, in a variety of overlap myositides. The aim of this study was to examine MxA expression in those myositides., Methods: We retrospectively performed MxA immunostaining on a wide range of myositides., Results: MxA sarcoplasmic expression was present in DM (94.4%, 17/18), active lupus myositis (LM, 80%,16/20), inactive LM (36%, 4/11), antisynthetase syndrome (ASyS, 20%, 2/10), systemic sclerosis (13%, 2/15), Sjogren's syndrome (7.7%, 1/13), and human immunodeficiency virus (HIV) myositis (5.6%, 1/18) and was absent in immune-mediated necrotizing myopathy (IMNM, 0/16) and hydroxychloroquine myopathy (0/5). The sensitivity and specificity of MxA sarcoplasmic expression for LM and DM combined compared with all other myositides were 84.6% (95% CI: 69.5-94.1) and 92.1 (95% CI: 83.6-97.0), respectively, and superior to TRIs. MxA capillary expression was nonspecific. Histologically, 35% of LM cases demonstrated a unique panfascicular necrotizing myopathy pattern. The remainder of the LM cases had significant morphological overlap with DM/ASyS (20%), IMNM (20%), or polymyositis (15%)., Discussion: MxA sarcoplasmic expression is highly prevalent in LM and DM and is a useful marker in differentiating DM and LM from other myositides. LM can manifest in various pathology patterns that need to be differentiated from DM, IMNM, ASyS, and polymyositis., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Background: Paralytic ectropion increases risk for corneal injury in facial palsy patients. Although a lateral tarsal strip (LTS) provides corneal coverage through superolateral lower eyelid pull, the unopposed lateral force may result in lateral displacement of the lower eyelid punctum and overall worsening asymmetry. A tensor fascia lata (TFL) lower eyelid sling may overcome some of these limitations. This study quantitatively compares scleral show, punctum deviation, lower marginal reflex distance, and periorbital symmetry between the two techniques., Methods: Retrospective review was performed on facial paralysis patients who underwent LTS or TFL sling surgery with no prior lower lid suspension procedures. Standardized preoperative and postoperative images in primary gaze position were used to measure scleral show and lower punctum deviation using ImageJ, and lower marginal reflex distance using Emotrics., Results: Of 449 facial paralysis patients, 79 met inclusion criteria. Fifty-seven underwent LTS surgery and 22 underwent TFL sling surgery. Compared with preoperatively, lower medial scleral show improved significantly with both LTS (10.9 mm 2 ; P < 0.01) and TFL (14.7 mm 2 ; P < 0.01). The LTS group showed significant worsening of horizontal and vertical lower punctum deviation when compared with the TFL group (both P < 0.01). The LTS group was unable to achieve periorbital symmetry between the healthy and paralytic eye across all parameters measured postoperatively ( P < 0.01); and the TFL group achieved symmetry in medial scleral show, lateral scleral show, and lower punctum deviation., Conclusion: In patients with paralytic ectropion, TFL sling provides similar outcomes to LTS, with the added advantages of symmetry without lateralization or caudalization of the lower medial punctum., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Study Design: Retrospective Cohort., Objective: The aim of this study was to develop a clinical tool to pre-operatively risk-stratify patients undergoing spine surgery based on their likelihood to have high postoperative analgesic requirements., Methods: A total of 1199 consecutive patients undergoing elective spine surgery over a 2-year period at a single center were included. Patients not requiring inpatient admission, those who received epidural analgesia, those who had two surgeries at separate sites under one anesthesia event, and those with a length of stay greater than 10 days were excluded. The remaining 860 patients were divided into a derivation and validation cohort. Pre-operative factors were collected by review of the electronic medical record. Total postoperative inpatient opioid intake requirements were converted into morphine milligram equivalents to standardize postoperative analgesic requirements., Results: The postoperative analgesic intake needs (PAIN) score was developed after the following predictor variables were identified: age, race, history of depression/anxiety, smoking status, active pre-operative benzodiazepine use and pre-operative opioid use, and surgical type. Patients were risk-stratified based on their score with the high-risk group being more likely to have high opioid consumption postoperatively compared to the moderate and low-risk groups in both the derivation and validation cohorts., Conclusion: The PAIN Score is a pre-operative clinical tool for patients undergoing spine surgery to risk stratify them based on their likelihood for high analgesic requirements. The information can be used to individualize a multi-modal analgesic regimen rather than utilizing a "one-size fits all" approach.

Background: Teledermatology (TD) is an important method for increasing access to care in outpatient settings. However, less is known regarding its use in emergency/urgent care centers., Objective: To evaluate the effect of TD on urgent care emergency center (UCEC) dwell time and postencounter utilization., Study Type and Methods: This retrospective cohort study evaluated patients in a safety-net hospital (Parkland Health, Dallas, Texas, USA) UCEC, who (1) received a TD consult in 2018, (2) were referred to dermatology clinic in 2017, or (3) were referred to dermatology clinic in 2018 without a TD consult., Results: We evaluated 2024 patients from 2017 to 2018. Of the 973 referred to dermatology clinic in 2018, 332 (34%) received TD consultations. Mean dwell time for patients receiving TD was longer versus the 2017 cohort (303 vs 204 minutes, respectively). Patients receiving TD consultation with inflammatory skin conditions had lower odds of dermatology clinic visits compared with those that did not (odds ratio, 0.5; 95% CI, 0.3-0.8). Teledermatology was not associated with differences in repeat UCEC utilization., Limitations: Single institution study and inability to account for differences in patient complexity., Conclusion: TD increases dwell time in a safety-net hospital's UCEC but can reduce dermatology clinic utilization for patients with inflammatory skin conditions., Competing Interests: Dr Chong is an investigator for Biogen Inc. He is a consultant for Bristol Myers Squibb, EMD Serono, Horizon Therapeutics, and Biogen Inc. He receives royalties from MAPI Research Trust. Drs Carr, Alame, Mauskar, Metzger, Neal, Reisch, and Dominguez have no conflicts of interest to declare., (© 2023 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Objective: To address the current lack of specified data existing regarding the perioperative characteristics and outcomes in a novel patient population, which may bridge the current understanding of how patient characteristics and perioperative management may influence the postoperative hospital course before cardiac transplantation., Design: A retrospective electronic chart review included all patients with failing single- ventricle (SV) physiology receiving ventricular assist device (VAD) support at a high-volume pediatric VAD center between April 5, 2010, and December 1, 2020, using institution-based electronic medical records for retrospective analysis., Setting: At a single pediatric hospital., Participants: Fourteen pediatric patients with failing SV physiology receiving ventricular assist device therapy (SVAD)., Interventions: None., Measurements and Main Results: Preoperative, intraoperative, and postoperative patient demographic and medical data were obtained from prior inpatient progress notes, laboratory values, anesthetic records, cardiac catheterization reports, echocardiography reports, and postoperative surgical notes entered during inpatient encounters at the time of SVAD placement. Between April 5, 2010, and December 1, 2020, 16 VAD device implants supported 14 pediatric patients with failing SV physiology. Most patients presented with a preoperative diagnosis of hypoplastic left heart syndrome (N = 9, 64.3%). A total of 6 patients expired on VAD therapy (43%), 7 (50%) survived to receive a cardiac transplant, and 1 patient currently remains on device therapy., Conclusion: Although our institutional approach represents a single perspective, we anticipate that our experience institutional experience may prove helpful to others caring for peditric patients with single ventricle physiology undergoing ventricular assist device placement and promote collaborative efforts to improve their care., Competing Interests: Conflict of Interest None., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The primary endpoint was to determine the sensitivity and specificity of the bronchoalveolar lavage Gram stain in predicting culture results. Secondary endpoints included determining the proportion of Gram stains from bronchoalveolar lavages that accurately identify culture isolates and the duration of antibiotic treatment before bronchoalveolar lavage collection., Design: Retrospective, observational study., Setting: Four ICUs at a single academic medical center., Subjects: Patients at least 18 years old admitted to an ICU with a diagnosis of pneumonia, collection of a bronchoalveolar lavage sample, and receipt of antibiotics., Measurements and Main Results: Two-hundred five isolates were included. Gram stains for Gram-positive and Gram-negative isolates showed high specificity, 97.3% and 100%, respectively, but lower sensitivity at 61.9% and 54.2%, respectively. The positive predictive value and negative predictive value were 77.2% and 95.7% for Gram-positive isolates and 100% and 84.4% for Gram-negative isolates, respectively. Gram stains correctly identified isolates on the bronchoalveolar lavage culture in 61.9% of Gram-positive organisms and in 54.2% of Gram-negative organisms., Conclusions: Gram stains accurately identified causative organisms in a limited number of patients making the utility of the Gram stain an uncertain modality for predicting causative respiratory pathogens from bronchoalveolar lavage samples., Competing Interests: The authors have disclosed that they do not have any conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Cholinergic neuronal loss is one of the hallmarks of AD related neurodegeneration; however, preclinical promise of α7 nAChR drugs failed to translate into humans. CHRFAM7A, a uniquely human fusion gene, is a negative regulator of α7 nAChR and was unaccounted for in preclinical models., Methods: Molecular methods: Function of CHRFAM7A alleles was studied in vitro in two disease relevant phenotypic readouts: electrophysiology and Aβ uptake. Genome edited human induced pluripotent stem cells (iPSC) were used as a model system with the human context. Double blind pharmacogenetic study: We performed double-blind pharmacogenetic analysis on the effect of AChEI therapy based on CHRFAM7A carrier status in two paradigms: response to drug initiation and DMT effect. Mini Mental Status Examination (MMSE) was used as outcome measure. Change in MMSE score from baseline was compared by 2-tailed T-test. Longitudinal analysis of clinical outcome (MMSE) was performed using a fitted general linear model, based on an assumed autoregressive covariance structure. Model independent variables included age, sex, and medication regimen at the time of the first utilized outcome measure (AChEI alone or AChEI plus memantine), APOE4 carrier status (0, 1 or 2 alleles as categorical variables) and CHRFAM7A genotype., Findings: The direct and inverted alleles have distinct phenotypes. Functional CHRFAM7A allele classifies the population as 25% non-carriers and 75% carriers. Induced pluripotent stem cell (iPSC) models α7 nAChR mediated Aβ neurotoxicity. Pharmacological readout translates into both first exposure (p = 0.037) and disease modifying effect (p = 0.0048) in two double blind pharmacogenetic studies., Interpretation: CHRFAM7A accounts for the translational gap in cholinergic strategies in AD. Clinical trials not accounting for this uniquely human genetic factor may have rejected drug candidates that would benefit 25% of AD. Reanalyses of the completed trials using this pharmacogenetic paradigm may identify effective therapy., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Juvenile myasthenia gravis (JMG), a pediatric autoimmune neuromuscular junction disorder, includes generalized (GMG), and ocular (OMG) variants. We sought to determine whether differences existed between OMG and GMG children regarding demographics or treatment response., Methods: We performed retrospective analysis of 60 children with JMG seen between 1990 and 2018. Osserman scores were used to define OMG and GMG. The myasthenia scale of Millichap and Dodge was used to assess treatment responses., Results: There were no differences between GMG and OMG regarding time interval from disease onset to prednisone initiation (P = .42), or treatment response according to Millichap and Dodge (P = .12). Compared with GMG, OMG children showed younger age of disease onset and better outcomes after treatment. No OMG patients progressed to generalized disease during the follow-up period., Discussion: Compared with GMG, OMG patients had earlier disease onset and improved outcomes after treatment., (© 2019 Wiley Periodicals, Inc.)

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10 -7 ), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Background: The purpose of this prospective, randomized, controlled trial was to determine whether multiple ports improve the analgesic efficacy of wire-reinforced flexible catheters used for labor epidural analgesia (LEA)., Methods: Six hundred fifty laboring patients were randomized to receive epidural analgesia using either a multiport or uniport wire-reinforced flexible catheter. The primary outcome was analgesic success, defined as the incidence of adequate analgesia following the initial bolus given to initiate LEA. Secondary outcomes included the number of patients requiring clinician interventions during maintenance of LEA; anesthetic success, defined as the incidence of adequate anesthesia following the initial bolus given to establish surgical anesthesia for cesarean delivery; and maternal satisfaction with the overall quality of LEA., Results: There was no significant difference in analgesic success at initiation of LEA between the uniport and the multiport wire-reinforced flexible catheter (93.6% vs 89.5%, respectively; difference of 4.1% [95% confidence interval, -0.4% to 8.5%]; P = .077). There was also no difference in the number of patients requiring clinician interventions during maintenance of LEA and in anesthetic success at the establishment of surgical anesthesia for cesarean delivery between the 2 catheter types., Conclusions: Multiple ports do not appear to improve the analgesic efficacy of wire-reinforced flexible catheters used for LEA.

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10 -4 ) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10 -8 ) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10 -10 , odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAF controls = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10 -10 , OR = 1.43, MAF cases = 0.011, MAF controls = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10 -14 , OR = 1.67, MAF cases = 0.0143, MAF controls = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Background: Although objective measures of cytotechnologist (CT) and cytopathologist (CP) performance exist, challenges remain. Two assumptions deserve examination: CPs' interpretations are correct, and CTs and CPs render interpretations independently of each other. This study presents a CT-CP interpretation comparison and provides insight into these assumptions., Methods: Every gynecologic cytology specimen examined by both a CT and a CP from December 2004 to March 2015 was extracted from the laboratory information system; glandular interpretations were excluded. Excel and SAS were used for CT-CP pair analysis. CT-CP pairs with fewer than 32 specimens (the lowest quartile) were excluded. For the remaining CT-CP pairs, 30 specimens or 10% of the specimens (whichever was higher) were randomly selected for comparison by a weighted κ statistic. κ values greater than 0.6 represented good agreement within CT-CP pairs., Results: This study evaluated 7116 of 53,241 gynecologic cytology specimens (13.4%) that received CT and CP interpretations. This resulted in 155 pair-specific κ values from 15 CTs and 16 CPs. In aggregate, the κ values had a mean of 0.64, a standard deviation of 0.14, a median of 0.65, and a range of 0.27 to 0.91. Nine CTs exhibited good agreement in the majority of their pair-specific κ values with CPs (high-concordance CTs; 88 pair-specific κ values). This allowed us to identify outlier CPs who did not demonstrate good agreement with high-concordance CTs (16 of 88 pair-specific κ values [18.2%])., Conclusions: Laboratories can use this κ to determine when CP levels of agreement with CTs depart from those of their peers. Adding this to established metrics can give a more nuanced impression of CP performance. Cancer Cytopathol 2017;125:576-80. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Gastrointestinal bleeding is defined in temporal-spatial terms-as acute or chronic, and/or by its location in the gastrointestinal tract. Here, we define a distinct type of bleeding, which we have coined 'acute on chronic' gastrointestinal bleeding. We prospectively identified all patients who underwent endoscopic evaluation for any form of gastrointestinal bleeding at a University Hospital. Acute on chronic bleeding was defined as the presence of new symptoms or signs of acute bleeding in the setting of chronic bleeding, documented as iron deficiency anemia. Bleeding lesions were categorized using previously established criteria. We identified a total of 776, 254, and 430 patients with acute, chronic, or acute on chronic bleeding, respectively. In patients with acute on chronic gastrointestinal bleeding, lesions were most commonly identified in esophagus (28%), colon and rectum (27%), and stomach (21%) (p<0.0001 vs locations for acute or chronic bleeding). In those specifically with acute on chronic upper gastrointestinal bleeding (n=260), bleeding was most commonly due to portal hypertensive lesions, identified in 47% of subjects compared with 29% of acute and 25% of chronic bleeders, (p<0.001). In all patients with acute on chronic bleeding, 30-day mortality was less than that after acute bleeding alone (2% (10/430) vs 7% (54/776), respectively, p<0.001). Acute on chronic gastrointestinal bleeding is common, and in patients with upper gastrointestinal bleeding was most often a result of portal hypertensive upper gastrointestinal tract pathology. Reduced mortality in patients with acute on chronic gastrointestinal bleeding compared with those with acute bleeding raises the possibility of an adaptive response., Competing Interests: Competing interests: None declared., (Copyright © 2017 American Federation for Medical Research.)

Background/purpose: A non-standardized approach to caring for infants after pyloromyotomy for pyloric stenosis was associated with prolonged postoperative length of stay (pLOS) at our institution. We studied the impact of a standardized postoperative care protocol on pLOS, patients' clinical course, and nursing care., Methods: A retrospective chart review identified that 27% of infants who underwent uncomplicated pyloromyotomy had prolonged pLOS, defined as more than one postoperative midnight. A comprehensive postoperative care protocol was developed for infants undergoing pyloromyotomy. Patients were recruited prospectively and those with complications were excluded. A sample size of 70 in each cohort (historic and prospective) allowed 80% power to detect a 50% reduction in the proportion of patients with prolonged pLOS (α=0.05). The prospective group and historic cohort were compared using nonparametric statistics., Results: The historic cohort had 70 patients and the prospective cohort had 66. Protocol implementation resulted in fewer patients with prolonged pLOS, shorter time to feeds, fewer feeds to discharge, less emesis, and improved nursing documentation., Conclusion: Implementation of a postoperative care protocol improved various aspects of patient care and nursing care studied. Protocols outline a patient's course and serve as a common platform for communication among care providers; they can facilitate, expedite, and enhance patient care., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Goals: To examine ethnicity's role in the etiology and outcome of upper gastrointestinal hemorrhage (UGIH)., Background: UGIH is a serious condition with considerable associated morbidity and mortality., Materials and Methods: We analyzed 2196 patients admitted with acute UGIH between January 2006 and February 2012. Complete clinical data were gathered prospectively and entered into our GI Bleed Registry, which captures demographic and clinical variables. Results were analyzed using the χ² analyses and the analysis of variance techniques with Tukey multiple comparisons., Results: Among 2196 patients, 620 (28%) were black, 625 (29%) white, 881 (40%) Hispanic, and 70 (3%) were members of other ethnicities. Gastroduodenal ulcers (25%), esophageal varices (25%), and esophagitis (12%) were the most frequently identified causes of UGIH. Blacks experienced a high rate of gastroduodenal ulcers (199/620), whereas Hispanics most commonly had esophageal varices. In all ethnicities, the most common cause of bleeding in patients younger than 35 or older than 65 years was gastroduodenal ulcer disease. However, among patients aged 35 to 64 years, there were differences in the etiology of UGIH. Blacks aged 50 to 64 years frequently experienced gastroduodenal ulcers, whereas Hispanics aged 35 to 49 years typically had esophageal varices. Rebleeding rates were significantly lower in whites (5.8%) than in Hispanics (9.9%) or blacks (8.7%) (P=0.02)., Conclusions: By examining a diverse population, we conclude that UGIH may follow trends. Hispanics were likely to have esophageal varices and higher rebleeding rates, whereas blacks were likely to have ulcers and the highest mortality. Whites were equally likely to have ulcers or varices, but a lower rate of rebleeding.

Background: Acute upper gastrointestinal bleeding is a common complication of peptic ulcer disease, often caused by Helicobacter pylori and nonsteroidal anti-inflammatory drug (NSAID) use. The purpose of this study was to determine whether the cause and biologic behavior of ulcers associated with acute upper gastrointestinal bleeding might lead to divergent patient outcomes., Methods: In this Institutional Review Board-approved study, we compared clinical features and outcomes of patients with acute upper gastrointestinal bleeding due to ulcers categorized into 4 groups: Helicobacter pylori positive or negative combined with NSAID usage positive or negative. Likelihood chi-squared analyses were utilized for group comparisons and stepwise multiple logistic regression models were utilized to determine which factors were related to bleeding outcomes., Results: Of 2242 patients with upper gastrointestinal bleeding, 575 (26%) had gastroduodenal ulcer disease, and of those with appropriate diagnostic testing, approximately half (228, 10% overall) had evidence of Helicobacter pylori infection and half (216, 10% overall) had no evidence of Helicobacter pylori infection. Patients without Helicobacter pylori infection had significantly more comorbid conditions than those with Helicobacter pylori and higher Charlson Index comorbidity scores (2.6 ± 2.6 [mean and SD] vs 1.9 ± 2.3, P = .003). Hospital length of stay was significantly longer for Helicobacter pylori-negative patients (mean 11.4 ± 21.7 vs 6 ± 8.5 days and median 5.5 vs 3 days, P <.001 and <.001, respectively). Rebleeding events within 30 days were more frequent in Helicobacter pylori-negative patients than Helicobacter pylori-positive patients (11% vs 5%, P = .009). Rebleeding was most frequent in patients without Helicobacter pylori and with no reported use of NSAIDS (18%, P = .01)., Conclusions: Helicobacter pylori-negative ulcers were associated with poorer outcomes regardless of use of NSAIDs. Patients with ulcers negative for Helicobacter pylori and no history of NSAID use had the worst outcomes and had more severe systemic disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD) (onset at 65 years of age or older) compared with men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular, and inflammatory changes. These all together have been suggested as risk factors for late-onset AD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients and normal control subjects by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, sex, and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex-specific phenotypic effect., (Published by Elsevier Inc.)

Two recent genome-wide association studies (GWAS) for late onset Alzheimer's disease (LOAD) revealed 3 new genes: clusterin (CLU), phosphatidylinositol binding clathrin assembly protein (PICALM), and complement receptor 1 (CR1). In order to evaluate association with these genome-wide association study-identified genes and to isolate the variants contributing to the pathogenesis of LOAD, we genotyped the top single nucleotide polymorphisms (SNPs), rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), and sequenced the entire coding regions of these genes in our cohort of 342 LOAD patients and 277 control subjects. We confirmed the association of rs3851179 (PICALM) (p = 7.4 × 10(-3)) with the disease status. Through sequencing we identified 18 variants in CLU, 3 of which were found exclusively in patients; 8 variants (out of 65) in CR1 gene were only found in patients and the 16 variants identified in PICALM gene were present in both patients and controls. In silico analysis of the variants in PICALM did not predict any damaging effect on the protein. The haplotype analysis of the variants in each gene predicted a common haplotype when the 3 single nucleotide polymorphisms rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), respectively, were included. For each gene the haplotype structure and size differed between patients and controls. In conclusion, we confirmed association of CLU, CR1, and PICALM genes with the disease status in our cohort through identification of a number of disease-specific variants among patients through the sequencing of the coding region of these genes., (Published by Elsevier Inc.)

Background: Liver transplantation for patients with hepatocellular carcinoma (HCC) affords excellent long-term survival but is limited to patients with early stage tumors. Predictors for orthotopic liver transplantation eligibility are not well defined for patients in a safety-net hospital system., Aims: To clarify the clinical presentation of HCC and define predictors for early stage disease in a racially diverse safety-net hospital system., Methods: We retrospectively reviewed records of patients with HCC presenting to a large urban county hospital between January 1998 and October 2007. Logistic regression analysis was used to find predictors of OLT eligibility., Results: Of the 266 patients with HCC, 62% had multiple tumors, 47% had portal vein thrombosis and only 22% were potential liver transplant candidates based on Milan criteria. Male gender (OR 0.33; 95% CI 0.17-0.65) and AFP levels > 20 ng/mL (OR 0.22; 95% CI 0.11-0.45) were negative predictors of liver transplant eligibility. Age, race, and underlying viral liver disease were not significant predictors of early tumor stage., Conclusions: A minority of HCC patients in a safety-net hospital are eligible for liver transplant at the time of diagnosis. Men have more advanced tumors at presentation, which may be related to more aggressive tumor biology or differential rates of HCC surveillance.

Background: Student recruiting is a top priority for surgical educators. Efforts have focused on improving the junior clerkship, but earlier interventions might prove to be more effective. This study was performed to determine students' perceptions of surgeons across all 4 years, with special emphasis on the effect of the 3(rd)-year clerkship., Study Design: During 2004 to 2007, medical students at all levels were surveyed with 21 statements about surgeons' behavior, lifestyle issues, and potential as role models. Subjects responded anonymously using a 5-point Likert scale (1 = strongly agree). Surveys were administered annually to medical student year 1 (MS1), MS2, and MS4, and before and after the clerkship to MS3. Data were analyzed using chi-square contingency table analyses., Results: Three-thousand and sixty surveys were analyzed (MS1, n = 833; MS2, n = 670; MS3, n = 1,193; and MS4, n = 364). Responses among MS1 and MS2 confirm that students enter medical school with negative impressions of surgeons. The surgical clerkship had a positive impact, but this effect was lost by senior year. Changes in perceptions were statistically significant for 20 of 21 statements. This is underscored by the fact that the proportion of students applying to general surgery from our medical school remains essentially unchanged (2004, 5.3%; 2005, 7.4%; 2006, 10%; 2007, 7.4%; and 2008, 6%)., Conclusions: These data suggest that the junior surgery clerkship has a favorable but transient impact on the negative perceptions that medical students have about surgeons. Perceptions return to negative values within 1 year of the clerkship. Recruiting efforts should be focused on earlier interaction with students rather than concentrating on a 2- to 3-month rotation in the junior year., (Copyright (c) 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Often data collection for clinical studies is an afterthought. The results of such an approach are incomplete or confusing data that can, as a worst case, result in scrapping and restarting the entire study. We discuss the planning process for data collection and storage to include encounter form development; data flow and capture; data checking, verification, and validation; advantage of relational databases over spreadsheets; data security; and aspects of a complete data system.

Background & Aims: N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure., Methods: In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation., Results: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031)., Conclusions: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.

Background: The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established., Objective: To investigate the effectiveness of CDR-SOB scores in staging dementia severity compared with the global CDR score., Design: Retrospective study., Setting: Texas Alzheimer's Research Consortium minimum data set cohort., Participants: A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis., Main Outcome Measures: Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample., Results: Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.0, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, kappa scores ranged from 0.86 to 0.94 (P < .001 for all), with 93.0% of the participants falling within the new staging categories., Conclusions: The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided.

Objective: To determine whether variables in the surgery resident selection process will predict attrition or performance during residency training., Design: Retrospective study., Setting: A university residency program., Participants: A total of 111 categorical surgery residents matched during a 10-year period (1991-2000)., Main Outcome Measures: Satisfactory outcome included successful completion of training and the American Board of Surgery examinations on the first attempt. Participants with a satisfactory outcome were stratified into good or marginal performance based on adverse actions during residency., Results: Of 111 residents studied, 28 (25.2%) had an unsatisfactory outcome; attrition occurred in 25 (22.5%). Univariate analysis identified the following variables as predictors of unsatisfactory outcome: age at entry older than 29 years (P = .005), female sex (P = .02), courses repeated (P = .01), "C" grades on transcript (P = .01), no participation in team sports (P = .02), and lack of superlative comments in the dean's letter (P = .03). The following variables were retained in the multivariate model: age older than 29 years (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02-0.47; P = .003), summary comments in the dean's letter (OR, 4.57; 95% CI, 2.00-10.43; P < .001), participation in team sports (OR, 4.96; 95% CI, 1.36-18.05; P = .02), and merit scholarship in medical school (OR, 0.25; 95% CI, 0.08-0.78; P = .02)., Conclusions: Attrition can be predicted from factors identified on residency applications, with nonacademic factors being more important. Among residents who completed the program, no predictors of performance were identified.

A critical component essential to good research is the accurate and efficient collection and preparation of data for analysis. Most medical researchers have little or no training in data management, often causing not only excessive time spent cleaning data but also a risk that the data set contains collection or recording errors. The implementation of simple guidelines based on techniques used by professional data management teams will save researchers time and money and result in a data set better suited to answer research questions. Because Microsoft Excel is often used by researchers to collect data, specific techniques that can be implemented in Excel are presented.

Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen-induced ALF at 22 tertiary care centers in the United States. Detailed prospective data were gathered on 662 consecutive patients over a 6-year period fulfilling standard criteria for ALF (coagulopathy and encephalopathy), from which 275 (42%) were determined to result from acetaminophen liver injury. The annual percentage of acetaminophen-related ALF rose during the study from 28% in 1998 to 51% in 2003. Median dose ingested was 24 g (equivalent to 48 extra-strength tablets). Unintentional overdoses accounted for 131 (48%) cases, intentional (suicide attempts) 122 (44%), and 22 (8%) were of unknown intent. In the unintentional group, 38% took two or more acetaminophen preparations simultaneously, and 63% used narcotic-containing compounds. Eighty-one percent of unintentional patients reported taking acetaminophen and/or other analgesics for acute or chronic pain syndromes. Overall, 178 subjects (65%) survived, 74 (27%) died without transplantation, and 23 subjects (8%) underwent liver transplantation; 71% were alive at 3 weeks. Transplant-free survival rate and rate of liver transplantation were similar between intentional and unintentional groups. In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States. Susceptible patients have concomitant depression, chronic pain, alcohol or narcotic use, and/or take several preparations simultaneously. Education of patients, physicians, and pharmacies to limit high-risk use settings is recommended.

Purpose: The pilocytic astrocytoma (PA) is the most common childhood brain tumor. This report examines the MIB-1 labeling index (LI) as a predictor of progression-free survival (PFS) among childhood PAs., Patients and Methods: Consecutive PAs were examined to determine whether the MIB-1 LI was associated with tumor progression. Other variables evaluated included tumor location, use of adjuvant therapy, extent of resection, and age at diagnosis., Results: One hundred forty-one children were identified (mean +/- SD age, 7.6 +/- 4.7 years; range, 0.43 to 18.56 years); 118 children had adequate tissue for MIB-1 immunohistochemistry. The 5-year PFS was 61.25%. By log-rank analysis, an MIB-1 LI of more than 2.0 was associated with shortened PFS (P =.035). Patients with PAs who underwent complete surgical resection, had tumors located in the cerebellum, and were treated with surgery only also had more prolonged PFS (P =.001 for all). Tumors in the optic pathways were associated with a shorter PFS (P =.001). Restricting the evaluation of MIB-1 LI to only incompletely resected tumors revealed an insignificant trend of MIB-1 LI of more than 2.0 having a shortened PFS. Multivariate analysis demonstrated completely resected tumors and tumors located in the cerebellum as less likely to progress (P =.001 and.019, respectively)., Conclusion: Children with PAs with an MIB-1 LI of more than 2.0 have a shortened PFS. PAs that are completely resected and are located in the cerebellum have a prolonged PFS. This initial study suggests that the MIB-1 LI identifies a more aggressive subset of PAs. Further work should focus on elucidating features of pilocytic astocytomas that will identify prospectively children at risk for progression.

In this study we tested the hypothesis that synapse loss contributes to decreased regional cerebral blood flow (rCBF) in Alzheimer disease (AD). We compared antemortem rCBF and postmortem analysis of synaptophysin, as a measure of synapse loss, in 13 cases of AD. rCBF studies were performed using inhaled xenon gas (Xe-133), which yields quantitative results. Synapse loss was evaluated in postmortem brain samples using an enzyme-linked immunosorbant assay (ELISA) that measures synaptophysin, with results expressed as picomoles synaptophysin/10 mg brain. Synaptophysin was expressed either as concentration (QS method) or as the ratio of the concentration to the combined results in frontal, temporal and parietal lobe (RS method). There was no correlation between synapse loss and rCBF using the QS method and only borderline significance between right SPECT and right temporal synaptophysin using the RS method. The results of this study suggest that synapse loss may be a minor contributor to the decreased rCBF observed in AD., (Copyright 2003 S. Karger AG, Basel)

Background: Nonperioperative strokes are rare yet potentially devastating events for children with central nervous system (CNS) tumors. The incidence of and risk factors for nonperioperative strokes in children with CNS tumors is unknown., Methods: The authors performed a retrospective review of children from their institution with CNS tumors. The incidence of stroke in the nonperioperative period and the influence of patient demographic factors, coexisting genetic diseases, tumor type, and treatment modality on the subsequent occurrence of a stroke were determined., Results: Eight hundred seven consecutive patients from the authors' institution with CNS tumors were observed for a combined 3224 nonperioperative years. Thirteen patients (1.6%) had a nonperioperative stroke, for an incidence of 4.03 strokes/1000 years of nonperioperative patient follow-up. Eight patients were males, and the median age at diagnosis of a CNS tumor was 4.8 years (range, 0.3-18.6 years). The median duration from diagnosis of a CNS tumor until the occurrence of stroke was 2.3 years (range, 0.3-15.8 years). Among numerous potential risk factors individually examined by chi-square analysis, only treatment with radiation therapy was associated with the subsequent development of a stroke (chi-square, P = 0.007). By logistic regression analysis, treatment with radiation therapy and a diagnosis of an optic pathway glioma were the only statistically significant variables associated with a stroke., Conclusions: Strokes are much more common among children with CNS tumors. Children treated with radiation therapy and those with optic pathway gliomas have a higher association with the occurrence of a subsequent nonperioperative stroke. Because children with optic pathway gliomas may be at particularly high risk of stroke after radiation therapy, the desired beneficial therapeutic effects of irradiation must always be weighed against its potentially adverse effects, including stroke., (Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10353)

Acute chest syndrome (ACS) in patients with sickle cell disease (SCD) has historically been managed with oxygen, antibiotics, and blood transfusions. Recently high-dose corticosteroid therapy was shown to reduce the duration of hospitalization in children with SCD and vaso-occlusive crisis. Therefore, we chose to assess the use of glucocorticoids in ACS. We conducted a randomized, double-blind placebo-controlled trial to evaluate the efficacy and toxicity of intravenous dexamethasone (0.3 mg/kg every 12 hours x 4 doses) in children with SCD hospitalized with mild to moderately severe ACS. Forty-three evaluable episodes of ACS occurred in 38 children (median age, 6.7 years). Twenty-two patients received dexamethasone and 21 patients received placebo. There were no statistically significant differences in demographic, clinical, or laboratory characteristics between the two groups. Mean hospital stay was shorter in the dexamethasone-treated group (47 hours v 80 hours; P = .005). Dexamethasone therapy prevented clinical deterioration and reduced the need for blood transfusions (P < .001 and = .013, respectively). Mean duration of oxygen and analgesic therapy, number of opioid doses, and the duration of fever was also significantly reduced in the dexamethasone-treated patients. Of seven patients readmitted within 72 hours after discharge (six after dexamethasone; P = .095), only one had respiratory complications (P = 1.00). No side effects clearly related to dexamethasone were observed. In a stepwise multiple linear regression analysis, gender and previous episodes of ACS were the only variables that appeared to predict response to dexamethasone, as measured by lengh of hospital stay. Intravenous dexamethasone has a beneficial effect in children with SCD hospitalized with mild to moderately severe acute chest syndrome. Further study of this therapeutic modality is indicated., (Copyright 1998 by The American Society of Hematology)

Objective: To characterize leg muscle abnormalities in patients with ALS using MRI, and to correlate MRI with standard neurologic measures of motor neuron dysfunction., Methods: Eleven ALS patients were studied twice (once at baseline and again after 4 months) and compared with eight normal control subjects. MRI data of the lower extremities were compared with tibialis anterior compound muscle action potential amplitude (CMAPa) and foot dorsiflexion maximal voluntary isometric contraction (MVIC)., Results: Muscle MRI was abnormal by visual inspection in six of 11 patients. The mean muscle T1 time and muscle volume were not different in patients compared with normal control subjects (p > 0.1). However, the mean T2 times were increased in the patients compared with normal control subjects (p = 0.009). T1 times did not correlate with CMAPa or MVIC. Muscle volume correlated with MVIC (r = 0.73 to 0.78, p < 0.02) but not with CMAPa (p > 0.05). There was a strong negative correlation (r < -0.8, p < or = 0.01) between muscle T2 time and MVIC and CMAPa. Also, the change in T2 relaxation time correlated with the change in CMAPa as the disease progressed (r = -0.63, p = 0.037)., Conclusion: Of the MRI characteristics studied, T2 relaxation time was the best indicator of motor neuron dysfunction and may have a role in objective evaluation of motor neuron dysfunction.

Objectives: There is no accepted urodynamic definition of outlet obstruction in women. Currently, the diagnosis is made on the basis of history and radiographic and endoscopic findings. The goal of this study is to design a pressure-flow nomogram (PdetQmax/Qmax) and define cut-off values for obstruction., Methods: Two groups were studied prospectively in an open study: 124 control and 35 clinically obstructed patients. All had a complete history, physical examination, normal neurologic evaluation, cystoscopy, voiding cystography, and urodynamics-with-pressure-flow study. Pressure-flow plot and receiver operator characteristic curves (ROCs) were constructed to determine optimal cut-off values to predict obstruction for peak flow rate (Qmax) and detrusor pressure at maximal flow (PdetQmax)., Results: The etiology of obstruction was previous anti-incontinence surgery (n = 13), large cystocele (n = 11), urethral stricture (n = 6), and other (n = 5). On the basis of ROC curves, using cut-off values of Qmax of 15 mL/s or less and 12 mL/s or less, sensitivity was 85.7% and 71.4%, and specificity 78.2% and 90.3%, respectively. Using cut-off values of PdetQmax of more than 25 and more than 30 cm H2O, sensitivity was 74.3% and 71.4%, and specificity 79.8% and 88.7%, respectively. Using a combined cut-off value of Qmax of 1 5 mL/s or less and PdetQmax of more than 20 cm H2O, sensitivity was 74.3% and specificity was 91.1%., Conclusions: Based on this prospective, controlled study, preliminary cut-off values were obtained for refining the definition of outlet obstruction in women.

Cysteamine bitartrate capsules (Cystagon) have been approved by the US Food and Drug Administration for use in patients with nephropathic cystinosis. Plasma cysteamine concentrations were virtually identical at various times following ingestion of either cysteamine hydrochloride or Cystagon capsules in 24 normal control subjects. A transfer study was done with eight cystinosis patients who had been receiving either cysteamine hydrochloride or phosphocysteamine for many years. The plasma cysteamine concentration was significantly higher 2h after Cystagon and the leukocyte cystine content was significantly lower at all times after Cystagon compared to older forms of the drug. These differences are probably the result of greater patient compliance in taking the capsules compared to the older, liquid forms of the drug. A new method for following the course of renal glomerular deterioration in diseases such as cystinosis has been published recently. This method was used to re-analyse data on the efficacy of cysteamine treatment and to re-analyse new data on treating cystinosis patients with either of two doses of cysteamine (1.30 g/m2 per day and 1.95 g/m2 per day). This new method agrees well with other methods and shows that both doses of drug are equally effective in maintaining glomerular function.

Objective: To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications., Design: A placebo-controlled, randomized trial., Setting: Outpatient setting of specialty clinics in Dallas and Temple, Texas., Interventions: Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously., Patients: 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis., Measurements: Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry., Results: In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia., Conclusions: Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.

This report describes growth and nutrition data from the feasibility phase of a clinical trial that was designed to evaluate the effect of diet protein modification in infants with chronic renal insufficiency (CRI). The purpose of the proposed trial was to compare the safety (effect on growth in length) and efficacy [effect on glomerular filtration rate (GFR)] of a diet with a low protein: energy (P:E) ratio versus a control diet in such patients. Twenty-four infants with GFRs less than 55 ml/min per 1.73 m2 were randomly assigned at 8 months of age to receive either a low-protein (P:E ratio 5.6%) or control protein (P:E ratio 10.4%) formula, which resulted in average protein intakes of 1.4 and 2.4 g/kg per day in the low and control groups, respectively. Overall energy intakes over a 10-month period of study averaged 92% +/- 12% recommended dietary allowance (RDA) for length in the low-protein group and 92 +/- 15% RDA in the control group. Weight for age standard deviation scores (SDS) were comparably low in both groups at the time of randomization (low-protein--2.0 +/- 1.3, control -1.9 +/- 1.1) and at the end of the study (low -1.9 +/- 1.2, control -1.7 +/- 0.9). Length for age SDS at entry tended to be lower in the low-protein group but were not significantly different in the two groups (low -2.2 +/- 1.4 vs. control -1.7 +/- 1.4). However, at 18 months the low-protein group had a significantly lower SDS for length (-2.6 +/- 1.2 vs. -1.7 +/- 1.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Investigators in 13 pediatric nephrology centers reviewed clinical and pathological features in 218 children and adolescents with IgA nephropathy (IgAN), with particular emphasis on 80 patients who had follow-up periods of at least 4 years. Potential prognostic markers in the 80 children were compared between 12 (15%) who developed end-stage renal disease (ESRD) versus 68 who did not. The relationship between clinical and pathological features and the subsequent development of ESRD was examined using stepwise linear discriminant analysis in addition to standard univariate analysis. Seven variables were found to be predictive of ESRD: the presence of glomerular sclerotic changes, especially when this was associated with proliferation or sclerosis in 20% or more of the glomeruli; black race; hypertension at biopsy; proteinuria at biopsy; age at presentation; crescents; male sex. Using the resulting discriminant function, development of ESRD could be correctly predicted in 95% of the subjects. We conclude that ESRD is more common in American children with IgAN than was realized previously. Risk factors previously documented in adult studies have been confirmed, especially the presence of glomerular sclerosis, proteinuria, and hypertension.

The effects of etomidate, a nonbarbiturate cerebral metabolic depressant, on cerebral metabolism and blood flow were studied in 29 dogs during cerebral hypoperfusion. Three groups of animals were studied during a 45-minute normotensive and a 30-minute hypotensive period: 10 control animals without etomidate, 11 animals receiving a 0.1-mg/kg etomidate bolus followed by an infusion of 0.05 mg/kg/min etomidate (low-dose group), and eight animals receiving doses of etomidate sufficient to suppress electroencephalographic bursts (high-dose group). The mean arterial pressure fell to similar levels (p less than 0.05) during hypotension in all three groups (40 +/- 5, 38 +/- 3, and 27 +/- 6 mm Hg, respectively). The mean cerebral oxygen extraction fraction rose (p less than 0.05) from 0.23 +/- 0.02 to 0.55 +/- 0.08 in the five control animals tested and from 0.33 +/- 0.02 to 0.53 +/- 0.02 in the seven animals tested in the low-dose group, but did not increase (p greater than 0.05) in the four animals tested in the high-dose group (0.24 +/- 0.03 to 0.23 +/- 0.05). Mean cerebral blood flow levels decreased in all groups during hypotension (p less than 0.05): 42 +/- 3 to 21 +/- 4 ml/100 gm/min (52% +/- 12% decrease) in the five animals tested in the control group, 60 +/- 8 to 24 +/- 6 ml/100 gm/min (56% +/- 13% decrease) in the four animals tested in the low-dose group, and 55 +/- 8 to 22 +/- 3 ml/100 gm/min (60% +/- 4% decrease) in the four animals tested in the high-dose group. In summary, the cerebral oxygen extraction fraction increased in the control animals and low-dose recipients during hypotension, suggesting the presence of threatened cerebral tissue. In contrast, the cerebral oxygen extraction did not change during hypotension when high-dose etomidate was administered. It is concluded that high-dose etomidate may preserve the cerebral metabolic state during hypotension in the present model.

Objective: To compare a solution of 3% dextran-60 (D60) in Ringer's lactate (RL) with RL alone as maintenance fluids for abdominal aortic surgery., Design: Randomized control trial of 20 consecutive patients undergoing elective aortic reconstructive surgery., Setting: A surgical ICU in a university hospital., Patients: Consecutive patients, mean age 64 yr. Five patients had abdominal aneurysm, 12 had aortic obstruction disease, and three had aortic renal bypass surgery. These patients were followed for 1 month., Interventions: Pulmonary artery occlusion pressure of at least 10 mm Hg and a urine output greater than 30 mL/h were used to guide the intraoperative fluid infusion rates, which were 36 and 104 mL/kg of D60 and RL, respectively (ratio 1:2.9)., Measurements and Main Results: Body weight at 24 hr had increased more with RL (7.8 kg) than with D60 (3.2 kg) infusion (p less than .01), despite intraoperative urine volumes of 151 and 92 mg/kg with RL and D60, respectively. Total intravascular albumin decreased from 0.7 g/kg (1.4 to 0.7 g/kg) in both groups, corresponding to a plasma volume (PV) loss of 13 mg/kg without fluid infusions. A total intravascular dextran of 0.5 g/kg resulted in a PV expansion at 1 hr of 4.4 mL/kg above preoperative level, in sharp contrast to 7.0 mL/kg decrease in PV with RL. Of the intraoperative 3% D60 and RL infused, an estimated 51% D60 and 6% RL remained as PV expansion at 1 hr., Conclusions: A diluted colloid solution in Ringer's lactate is of significant value in maintaining intravascular volumes and hemodynamics during and after major operative procedures.

Hypertensive putaminal hemorrhage remains a major cause of hemorrhagic stroke carrying extremely high morbidity. Considerable controversy remains regarding the optimal form of therapy. Between 1983 and 1989 we conducted a prospective randomized trial with three treatment strategies: best medical management, best medical management plus intracranial pressure monitoring, and surgical evacuation. Only patients with significant deficit harboring a putaminal hematoma at least 3.0 cm in diameter were entered. The study was interrupted after 21 patients had been studied (9, best medical management; 4, intracranial pressure monitoring; and 8, surgical evacuation). No differences were found among groups for age, admission blood pressure, and time interval between onset of symptoms and arrival at hospital. None of the subjects were capable of returning to prestroke activity. Fifteen (71%) died or remained vegetative at 6 months, and only 4 (19%) were capable of independent life at home. Of the 9 patients in the best medical management arm, 7 were dead or vegetative. In the surgical group, 4 patients died and only 2 were capable of independent life. These results suggest that current medical and neurosurgical therapies remain ineffective in preventing the devastating neurologic consequences of hypertensive putaminal hemorrhage.

Bacterial LPS and TNF induce vascular endothelial cells to express a variety of response molecules. LPS that is partially deacylated (dLPS) by a human neutrophil enzyme blocks the ability of LPS, but not TNF, to augment one of these responses, the expression of endothelial cell surface molecules that promote neutrophil adherence (J. Exp. Med. 1987; 165:1393-1402). We show that dLPS can inhibit the ability of LPS, but not TNF, to elicit the expression of plasminogen activator inhibitor-1 (PAI-1), prostacyclin, and PGE2 by human umbilical vein endothelial cells. dLPS also prevented the accumulation of specific PAI-1 mRNA in response to LPS, but not to TNF. Neither the LPS- or TNF-induced expression of PAI-1 nor the dLPS inhibition of the LPS response was mediated by prostanoids. These results indicate that dLPS can specifically block a variety of endothelial cell responses to LPS and provide support for the hypotheses 1) that dLPS and LPS may interact with a common target molecule on or in endothelial cells, and 2) that dLPS, produced by enzymatic deacylation of LPS in vivo, could inhibit endothelial cell stimulation by LPS and thereby limit the host inflammatory response to invasive gram-negative bacteria.