Myxovirus resistance protein A (MxA) expression in myositides: Sarcoplasmic expression is common in both dermatomyositis and lupus myositis.

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.

Dual-Innervated Gracilis Free Functional Muscle Transfers in Facial Palsy Patients: Comparing Long-Term Outcomes between One- versus Two-Stage Procedures.

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.

Lateral Tarsal Strip versus Tensor Fascia Lata Sling for Paralytic Ectropion: Comparison and Long-Term Outcomes.

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.

Dual Versus Single Innervation of Gracilis Free Functional Muscle Transfer in Facial Paralysis - Long-Term Resting and Dynamic Outcomes.

BACKGROUND: Comparing long-term tone and excursion between single- versus dual-innervated free functional muscle transfer (FFMT) in patients with longstanding facial paralysis. METHODS: Longstanding facial palsy patients treated with a FFMT innervated either by a nerve-to-masseter (single-innervation group) or by nerve-to-masseter and cross-facial-nerve graft (dual-innervation group) were included. One year minimal follow up was required. Outcome measures, based on standardized photos, 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 (Massachusetts Eye and Ear Infirmary, Boston, MA) and ImageJ (Rasband, W.S., ImageJ, U.S, National Institutes of Health, Bethesda, MD) were used for measurements. Between group and within group longitudinal comparisons were analyzed. RESULTS: At three years (single=24, dual=13), significance was found between groups in commissure position (single=26.42mm, dual=31.51mm, p<0.0001) and excursion with open mouth smile (single=31.32mm, dual=26.59mm, 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, while dual-innervation group revealed significant improvements (3.67mm and p<0.001, 3.17mm and p<0.001 respectively). Teeth exposure revealed an increase in the dual-innervation group (single=35.753 mm 2, dual=64.177 mm 2), albeit significance was not observed. CONCLUSIONS: Dually innervated FFMT revealed improvements in resting tone and teeth exposure with minimal decrease in smile excursion compared with single innervated FFMT.

Implementation and evaluation of a store-and-forward teledermatology workflow in a United States safety-net hospital urgent care emergency center: A retrospective cohort study.

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.

Development and Internal Validation of the Postoperative Analgesic Intake Needs Score: A Predictive Model for Post-Operative Narcotic Requirement after Spine Surgery.

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.

Perioperative Outcomes in Patients With Failing Single-Ventricle Physiology Undergoing Ventricular Assist Device Placement: A Single Institutional Experience.

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.

The Keloid Area and Severity Index (KASI): an objective tool for the evaluation of keloids.

To aid in the standardization of evaluating patients with multiple keloids, a Keloid Area and Severity Index (KASI) was developed using patient feedback, previous literature, and clinical expertise. The system was validated using intrarater and interrater reliability assessments. Here, we present a verified, reliable method of assessing keloid area and severity in clinical and research settings.

Bronchoalveolar Lavage Gram Stains for Early Bacterial Identification in Pneumonia: Should They Stay or Should They Go?

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.

CHRFAM7A: A human specific fusion gene, accounts for the translational gap for cholinergic strategies in Alzheimer's disease.

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 Aß 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 Aß 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.

Response to treatment in pediatric ocular myasthenia gravis.

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.

Randomized Controlled Trial of the Clinical Efficacy of Multiport Versus Uniport Wire-Reinforced Flexible Catheters for Labor Epidural Analgesia.

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.

Acute on chronic gastrointestinal bleeding: a unique clinical entity.

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.

Agreement between cytotechnologists and cytopathologists as a new measure of cytopathologist performance in gynecologic cytology.

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.

Postoperative Regimentation Of Treatment Optimizes Care and Optimizes Length of Stay (PROTOCOL) after pyloromyotomy.

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.

Impact of ethnicity in upper gastrointestinal hemorrhage.

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.

More favorable outcomes with peptic ulcer bleeding due to Helicobacter pylori.

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.

Androgen receptor gene and sex-specific Alzheimer's disease.

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.

Implication of common and disease specific variants in CLU, CR1, and PICALM.

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.

Predictors of liver transplant eligibility for patients with hepatocellular carcinoma in a safety net hospital.

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.