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This study aimed to elucidate the pharmacokinetic/pharmacodynamic and pharmacodynamic/efficacy relationships of anifrolumab, a type I interferon receptor antibody, in patients with moderate to severe systemic lupus erythematosus. Data were pooled from the randomized, 52-week, placebo-controlled TULIP-1 and TULIP-2 trials of intravenous anifrolumab (150 mg/300 mg, every 4 weeks for 48 weeks). Pharmacodynamic neutralization was measured with a 21-gene type I interferon gene signature (21-IFNGS) in patients with high IFNGS. The pharmacokinetic/pharmacodynamic relationship was analyzed graphically and modeled with a nonlinear mixed-effects model. British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rates were compared across 21-IFNGS neutralization quartiles. Overall, 819 patients received ≥1 dose of anifrolumab or placebo, of whom 676 were IFNGS high. Over 52 weeks, higher average anifrolumab serum concentrations were associated with increased median 21-IFNGS neutralization, which was rapid and sustained with anifrolumab 300 mg (80%, weeks 12-52), lower and delayed with anifrolumab 150 mg (50%, week 52), and minimal with placebo. The proportion of patients with week 24 anifrolumab trough concentration exceeding the IC

To explore the feasibility of the Internet + nursing service mode in family rehabilitation of elderly patients with osteoarthritic diseases.The control group (n=50) received routine rehabilitation treatment procedures and discharge guidance. For the observation group (n=50), extended nursing rehabilitation service was conducted through the Internet + nursing service platform based on the routine treatment in the control group.(1) The compliance with follow-up of the patients in the observation group was significantly higher than that in the control group; (2) The total satisfaction of patients in the observation group was significantly higher than that in the control group; (3) The VAS (1 month: 4.36±1.15 vs. 5.86±1.61, p0.05; 3 months 4.36±1.15 vs. 5.86±1.61, p0.05), SAS (1 month: 37.21±14.16 vs. 49.31±13.45, p0.05; 3 months 26.73±8.25 vs. 40.33±9.50, p0.05), SDS (1 month: 32.36±10.15 vs. 46.32±12.61, p0.05; 3 months 27.11±8.08 vs. 40.62±11.40, p0.05) and PSQI (1 month: 13.64 ± 1.13 vs. 16.31 ± 3.45, p0.05; 3 months 11.54 ± 1.87 vs. 15.74 ± 1.36, p0.05) scores in the observational group were significantly lower than that in control group at one month and three months after discharge. The ADL (1 month: 86.86 ± 4.13 vs. 74.33 ± 3.44, p0.05; 3 months 90.34 ± 7.87 vs. 78.52 ± 6.36, p0.05) scores in the observational group were significantly higher than that in control group at one month and three months after discharge.The extended rehabilitation nursing management for family rehabilitation of elderly patients with osteoarthritic diseases through the Internet + nursing service is a family rehabilitation model suitable for elderly patients with osteoarthritic diseases in China and has positive significance in developing a diversified medical nursing model.

The purpose of this study was to determine the relationship between admission source and postoperative length of stay (LOS), index admission hospital charges, and discharge disposition, in patients undergoing shoulder arthroplasty.The New York Statewide Planning and Research Cooperative System (SPARCS) was used to identify all patients that underwent elective shoulder arthroplasty from 1994 through 2015. Patients were grouped into institutionalized (INS) versus non-institutionalized (n-INS) groups based on admission source. The two groups were compared regarding demographics, Charleston comorbidity index (CCI), postoperative blood transfusion requirement, LOS, and total charges.A total of 33,248 patients were identified (32,875 n-INS, 373 INS). Patientsin the INS cohort were significantly older (71.9 versus 68.1 years) and had a higher CCI (1.3 vs. 0.7). The mean LOS in the INS group was nearly 1 week longer(9.5 days vs. 2.8 days) and had a significantly higher postoperative blood transfusion rate (37.5% vs. 9.2%, odds ratio: 5.9). The mean total hospital charges in the INS group were also significantly higher ($63,988 vs. $36,826).Institutionalized patients undergoing shoulder arthroplasty have a protracted postoperative hospital course and this ultimately resulted in poorer outcomes and increased resource utilization.

mAbs have revolutionized the treatment of autoimmune disorders. Even though mAbs have shown impressive efficacy in blocking T cell or B cell activation and/or recruitment to sites of inflammation, this group of biologicals are not devoid of adverse effects. The most serious adverse effects include infusion reactions, including the activation of the complement pathway. In this study, we present a detailed structure–function study of an anti-CCL20 humanized IgG1 mAb that neutralizes CCL20 chemokine and prevents the recruitment of Th17 cells to sites of inflammation. We demonstrate that the anti-CCL20 Ab changes significantly following administration to humans and monkeys and exposure to human serum. Analysis of the drug product revealed that the anti-CCL20 Ab has unexpectedly high C1q binding. This high binding was linked to immune complex formation in vivo but not during in vitro serum incubation. The immune complex contained multiple complement components. Anti-CCL20 Ab-mediated, complement-dependent cytotoxicity occurred when the Ab bound to CCL20 tethered to the cell membrane of target cells. Taken together, these results provide a likely cause for the animal toxicity observed. In addition, anti-CCL20 revealed progressive acidification because of N100 (located in CDR) deamidation over time, which did not directly impact Ag binding. Our study demonstrates that the safety profiling of mAbs should include the evaluation of effector functions in addition to typical stressed conditions.

To determine whether patients who reported a discrete traumatic event precipitating the onset of femoroacetabular impingement syndrome (FAIS) reported similar patient-reported outcomes for the modified Harris Hip Score (mHHS) and the Non-Arthritic Hip Score (NAHS) following hip arthroscopy as patients with atraumatic hip pain associated with FAIS alone.A retrospective comparative therapeutic investigation of a prospectively collected database of cases performed by a single surgeon from 2010 to 2015 identified a group of patients who developed FAIS after a discrete traumatic event. This group was compared 1:2 with a body mass index and age-matched group of primary hip arthroscopies with atraumatic hip pain attributed to FAIS. Preoperative mHHS and NAHS were obtained and compared with those at 2-year follow-up. Clinical failure at 2 years was defined as any further ipsilateral hip surgery including revision arthroscopy and conversion to arthroplasty.In the traumatic etiology group, the mean mHHS and NAHS improved from 49.6 to 82.7 (P.001) and from 46.9 to 84.0 (P.001), respectively. The mean mHHS and NAHS in the atraumatic group improved from 51.5 to 85.82 (P.001) and from 49.3 to 85.2 (P.001), respectively. Survivorship at 2 years was 81.1% for traumatic etiology and 88.3% for atraumatic etiology; adjusted proportional hazards regression analysis demonstrated a difference in survivorship that was not statistically significant between the traumatic and atraumatic cohorts (hazard ratio 1.8, 95% confidence interval 0.8-4.0).The findings of this study demonstrate that patients presenting with FAIS and history of a traumatic hip injury can expect to experience similar good outcomes at 2 years following primary hip arthroscopy as compared with patients with atraumatic FAIS.Level III (Therapeutic) retrospective comparative study.

The purpose of this study is to analyze trends in the epidemiology of paediatric stress fractures. The New York Statewide Planning and Research Cooperative System database was queried for stress fractures in children between the ages of 6 and 18 years. After checking for monotonicity of the data, Spearman's correlation coefficient was calculated. Multivariate regressions were used to test for associations between demographic variables and risk of stress fracture. Analysis of 11 475 386 outpatient visits between 2000 and 2015 showed that the annual incidence of paediatric stress fractures increased from 1.37 cases per 100 000 outpatient visits in 2006 to 5.32 per 100 000 visits in 2015 (ρ = 0.876, P < 0.01). The mean age at the time of injury was 14.4 ± 2.8 years. Children younger than 14 years accounted for 33.6% of the cohort. Age, male sex, white ethnicity, and private insurance were statistically significant predictors of stress fractures in a multivariate model. This study is the first to document an increase in the annual incidence of paediatric stress fractures.

Aims The aim of this study was to investigate the effects of preoperative bisphosphonate treatment on the intra- and postoperative outcomes of arthroplasty of the shoulder. The hypothesis was that previous bisphosphonate treatment would adversely affect both intra- and postoperative outcomes. Patients and Methods A retrospective cohort study was conducted involving patients undergoing arthroplasty of the shoulder, at a single institution. Two patients with no previous bisphosphonate treatment were matched to each patient who had received this treatment preoperatively by gender, age, race, ethnicity, body mass index (BMI), and type of arthroplasty. Previous bisphosphonate treatment was defined as treatment occurring during the three-year period before the arthroplasty. The primary outcome measure was the incidence of intraoperative complications and those occurring at one and two years postoperatively. A total of 87 patients were included: 29 in the bisphosphonates-exposed (BP+) group and 58 in the non-exposed (BP-) group. In the BP+ group, there were 26 female and three male patients, with a mean age of 71.4 years (51 to 87). In the BP- group, there were 52 female and six male patients, with a mean age of 72.1 years (53 to 88). Results Previous treatment with bisphosphonates was positively associated with intraoperative complications (fracture; odds ratio (OR) 39.40, 95% confidence interval (CI) 2.42 to 6305.70) and one-year postoperative complications (OR 7.83, 95% CI 1.11 to 128.82), but did not achieve statistical significance for complications two years postoperatively (OR 3.45, 95% CI 0.65 to 25.28). The power was 63% for complications at one year. Conclusion Patients who are treated with bisphosphonates during the three-year period before shoulder arthroplasty have a greater risk of intraoperative and one-year postoperative complications compared with those without this previous treatment.

小儿特发性病态窦房结综合征是在儿童时期起病，表现为窦房结功能障碍的心律失常综合征，通常认为与遗传性因素有关。随着基因测序技术的发展，与特发性病态窦房结综合征相关的基因变异位点陆续被发现，人们对其发病机制的认识已深入到分子水平。本文报道1例智力障碍伴特发性病态窦房结综合征的病例，为GNB5基因移码变异c.136delG。该基因变异临床罕见，丰富了特发性窦房结综合征的基因和临床表型谱，为该病的精准诊断及遗传咨询提供依据。.

Introduction Evidence-based medicine (EBM) is pivotal in shaping patient care, yet it is challenging to incorporate into undergraduate medical education (UME) due to a lack of dedicated resources within the preclinical curriculum. To address this challenge, we used a peer-led approach to explain difficult concepts through language that students can understand at their shared level of understanding. Methods Four second-year medical students trained in EBM over 18 months by facilitating monthly journal clubs, ultimately leading to their involvement as peer-instructors. With input from a faculty expert, peer-instructors designed integrative PowerPoint modules and interactive problem sets on basic biostatistics and EBM principles. Assessment included formative quizzes with multiple attempts to achieve at least 80% to demonstrate mastery of core learning objectives. Afterwards, students were invited to provide feedback using a 5-point Likert scale survey. Results Of second-year students who participated, all 151 demonstrated 80% competency on each quiz. Eighty-seven (58%) students completed the survey on which, 77% agreed/strongly agreed that their level of understanding of EBM improved after the peer-led sessions, 76% agreed/strongly agreed that the sessions were more conducive to learning compared to traditional lectures, and 94% agreed/strongly agreed that the material covered was relevant to the USMLE Step 1. Discussion This peer-led approach has been rated as effective by learners, improving their ability to critically appraise and apply clinical evidence. To promote integration of EBM into UME, we have prepared modules, problem sets, quizzes, and an outline of the problem-solving sessions for universal adoption.

Background Uncorrected superior glenoid wear in patients managed with reverse total shoulder arthroplasty (rTSA) can result in increased complications, including baseplate failure. The present study quantifies the clinical and radiographic outcomes of patients with Favard type-E1, E2, and E3 glenoid deformity who were managed with rTSA with use of a superior or superior/posterior augmented glenoid baseplate. Methods We retrospectively reviewed the records for 68 patients with shoulder arthritis and Favard type-E1, E2, or E3 glenoid deformity who were managed with primary rTSA and a 10° superior augmented or 10° superior/8° posterior augmented baseplate. The mean duration of follow-up was 40 months (range, 24 to 85 months). Outcomes were assessed preoperatively and at the latest follow-up with shoulder range of motion and use of outcome scores including the Simple Shoulder Test (SST), University of California Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score, Constant score, and Shoulder Pain and Disability Index (SPADI) score. Radiographs were evaluated preoperatively and at the time of the latest follow-up. Differences in preoperative and postoperative range of motion and outcome metrics were assessed with use of a 2-tailed Student t test. Results The majority of patients experienced clinically meaningful improvements in terms of pain and function following rTSA with a superior or superior/posterior augment, with 94% of patients rating themselves as "much better" (73.5%) or "better" (20.5%) at the time of the latest follow-up. At least 88% of the patients exceeded the minimum clinically important difference (MCID) threshold, and 75% of patients exceeded the substantial clinical benefit (SCB) threshold, for each of the clinical outcome metrics and range of motion. Five complications were reported (prevalence, 7.4%), including acromial stress fracture (2 patients), posttraumatic scapular neck fracture (1 patient), chronic shoulder pain (1 patient), and aseptic glenoid loosening (1 patient). Conclusions The present short-term clinical and radiographic study demonstrated that shoulder arthropathy with superior glenoid wear patterns (Favard types E1, E2, and E3) can be successfully treated with rTSA with a superior or superior/posterior augmented baseplate. Longer-term clinical and radiographic follow-up is necessary to confirm that these promising short-term results are durable. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

We sought to identify the influence of shoulder arthroplasty (SA) type (primary anatomic, primary reverse, revision) and indication (fracture, arthritis) on the risk of postoperative packed red blood cell transfusion (pRBCT) and intravenous fluid bolus (IVFB).Patients who underwent SA from 2013 through 2016 at our institution were categorized into four groups: primary anatomic (pTSA; N = 298), primary reverse (pRTSA; N = 292), revision (RevSA; N = 133), and shoulder arthroplasty for fracture (SAF; N = 58). Basic demographics, intraoperative metrics, preoperative lab values, and postoperative interventions (pRBCT and IVFB) were retrieved from electronic records.There were 781 SAs, of which 176 cases involved at least one postoperative intervention: pRBCT (6.3%) or IVFB (18.8%). Compared to pTSA, the odds of pRBCT in pRTSA, revSA, and SAF were: 3.0 (95% CI 0.9-10.0), 3.4 (95% CI 0.9-2.7), and 8.6 (95% CI 2.2-32.9), respectively. Independent risk factors for pRBCT included increasing age (p = 0.003), underweight body mass index (p = 0.019), Charlson Comorbidity Index ≥ 3 (p = 0.002), inpatient discharge to higher level of care (p = 0.011), estimated blood loss (p = 0.003), and preoperative hemoglobin (p ≤ 0.001). Also, compared to pTSA, the odds for IVFB in pRTSA, revSA, and SAF were: 2.8 (95% CI 1.7-4.6), 2.2 (95% CI 1.2-4.0), and 4.7 (95% CI 2.2-9.9), respectively. Other independent risk factors for IVFB included female sex (0.002), CCI ≥ 3 (p = 0.017), and operative time (p = 0.047).Shoulder arthroplasty for fracture is an independent risk factor for higher risk of postoperative pRBCT and IVFB.

Background Short meal-to-bed time (MTBT) has been reported to relate to gastroesophageal reflux disease (GERD), but evidence is lacking in pregnant women. We aimed to assess the characteristics of GERD and the association between MTBT and GERD during pregnancy. Patients and methods A cross-sectional study was carried out on 400 pregnant women aged 18 years and older visiting the antenatal clinic of Gia-Dinh People's Hospital, Vietnam. GERD was defined as having troublesome heartburn and/or regurgitation at least once a week. Reflux-related insomnia was defined as having difficulties in initiating or maintaining sleep through the night. MTBT was defined as "short" if it was ≤2 hours in more than two thirds of days in a week. Results There were 154 (38.5%) patients with GERD and 20 (13.0%) patients with reflux-related insomnia. In multivariate analysis, there were 3 factors significantly associated with GERD: third trimester [odds ratio (OR)=1.66; 95% confidence interval (CI): 1.03-2.69], previous history of typical reflux symptoms (OR=9.05; 95% CI: 5.29-15.50), and short MTBT (OR=12.73; 95% CI: 2.92-55.45). The frequency of reflux symptoms progressively increased across subgroups of patients with no short MTBT, either daytime or nighttime short MTBT, and with both daytime and nighttime short MTBT. Nighttime MTBT was also a significant risk factor for reflux-related insomnia (OR=4.60; 95% CI: 1.64-12.92). Conclusions We reported for the first time that short MTBT was a predominant risk factor of GERD in pregnancy. This dieting habit was significantly associated with reflux symptom frequency and reflux-related insomnia.

A major factor that impacts the long-term outcome and complication rates of total shoulder arthroplasty is the preoperative posterior glenoid bone loss quantified by glenoid retroversion. The purpose of this study was to assess if glenoid retroversion varies significantly at different glenoid heights in Walch B2 and B3 glenoids. Patients with B2 and B3 glenoid types were included following retrospective review of 386 consecutive CT shoulder studies performed for arthroplasty preoperative planning. True axial CT reconstructions were created using a validated technique. Two readers independently measured the glenoid retroversion angles according to the Friedman method using the “intermediate” glenoid at three glenoid heights: 75% (upper), 50% (equator), and 25% (lower). The variances between the three levels for a given patient were calculated. Twenty-nine B2 and 8 B3 glenoid types were included. There was no significant difference in variance of glenoid version among the three levels in B2 or B3 groups. The mean variance in retroversion degree between equator-lower, upper-equator, and upper-lower glenoid was − 0.4, 0.3, and − 0.2 for B2; and − 0.2, 1.9, and 1.9 for B3 glenoid, respectively. The level of inter-reader agreement was fair to good for variance at equator-lower, and good to excellent for upper-equator and upper-lower glenoid. Glenoid version can be accurately measured at any level between 25 and 75% of glenoid height for Walch B2 and B3. We recommend that the glenoid equator be used as the reference to assure consistent and reliable version measurements in this group of patients.

Although germline alterations and somatic mutations in disease cells have been extensively analyzed, molecular changes in immune cells associated with disease conditions have not been characterized in depth. It is clear that our immune system has a critical role in various biological and pathological conditions, such as infectious diseases, autoimmune diseases, drug-induced skin and liver toxicity, food allergy, and rejection of transplanted organs. The recent development of cancer immunotherapies, particularly drugs modulating the immune checkpoint molecules, has clearly demonstrated the importance of host immune cells in cancer treatments. However, the molecular mechanisms by which these new therapies kill tumor cells are still not fully understood. In this regard, we have begun to explore the role of newly developed tools such as next-generation sequencing in the genetic characterization of both cancer cells and host immune cells, a field that is called immunogenomics/ immunopharmacogenomics. This new field has enormous potential to help us better understand changes in our immune system during the course of various disease conditions. Here we report the potential of deep sequencing of T-cell and B-cell receptors in capturing the molecular contribution of the immune system, which we believe plays critical roles in the pathogenesis of various human diseases.

B-cell receptors (BCRs) play a critical role in adaptive immunity as they generate highly diverse immunoglobulin repertoires to recognize a wide variety of antigens. To better understand immune responses, it is critically important to establish a quantitative and rapid method to analyze BCR repertoire comprehensively. Here, we developed "Bcrip", a novel approach to characterize BCR repertoire by sequencing millions of BCR cDNA using next-generation sequencer. Using this method and quantitative real-time PCR, we analyzed expression levels and repertoires of BCRs in a total of 17 peanut allergic subjects' peripheral blood samples before and after receiving oral immunotherapy (OIT) or placebo. By our methods, we successfully identified all of variable (V), joining (J), and constant (C) regions, in an average of 79.1% of total reads and 99.6% of these VJC-mapped reads contained the C region corresponding to the isotypes that we aimed to analyze. In the 17 peanut allergic subjects' peripheral blood samples, we observed an oligoclonal enrichment of certain immunoglobulin heavy chain alpha (IGHA) and IGH gamma (IGHG) clones (P = 0.034 and P = 0.027, respectively) in peanut allergic subjects after OIT. This newly developed BCR sequencing and analysis method can be applied to investigate B-cell repertoires in various research areas, including food allergies as well as autoimmune and infectious diseases.

Eukaryotic cell motility is crucial during development, wound healing, the immune response, and cancer metastasis. Some eukaryotic cells can swim, but cells more commonly adhere to and crawl along the extracellular matrix. We study the relationship between hydrodynamics and adhesion that describe whether a cell is swimming, crawling, or combining these motions. Our simple model of a cell, based on the three-sphere swimmer, is capable of both swimming and crawling. As cell-matrix adhesion strength increases, the influence of hydrodynamics on migration diminish. Cells with significant adhesion can crawl with speeds much larger than their nonadherent, swimming counterparts. We predict that, while most eukaryotic cells are in the strong-adhesion limit, increasing environment viscosity or decreasing cell-matrix adhesion could lead to significant hydrodynamic effects even in crawling cells. Signatures of hydrodynamic effects include dependence of cell speed on the medium viscosity or the presence of a nearby substrate and the presence of interactions between noncontacting cells. These signatures will be suppressed at large adhesion strengths, but even strongly adherent cells will generate relevant fluid flows that will advect nearby passive particles and swimmers., Note: four supplemental movies are provided

Laryngeal squamous cell carcinoma is one of the common head and neck cancers, and it ranks the second in the incidence of head and neck cancers. Smoking and alchol are considered the main causes of the disease in the past. Since 1982, when scholars first proposed that human papillonavirus(HPV) was associated with the development of laryngeal cancer, there have been a large number of studies on the correlation between HPV and laryngeal cancer, but the results are different. Therefore, this article summarizes the progress of related researches on the relationship between HPV and laryngeal cancer in recent years, and explores the impact of HPV on the treatment strategy of laryngeal cancer.喉鳞状细胞癌是头颈部常见肿瘤之一，在头颈恶性肿瘤发病率中居第2位，既往认为抽烟、喝酒是发生的主要病因，自1982年学者首次提出HPV与喉癌的发生有关之后，国内外开始有大量对HPV与喉癌的相关性研究，但结果有一定的差异。因此本文通过总结近年来HPV与喉癌关系的相关研究成果进展进行综述，探究HPV对喉癌治疗策略的影响。.

Accurate human leukocyte antigen (HLA) genotyping is critical in studies involving the immune system. Several algorithms to estimate HLA genotypes from whole-exome data were developed. We compared the accuracy of seven algorithms, including Optitype, Polysolver and PHLAT, as well as investigated patterns and possible causes of miscalls using 12 clinical samples and 961 individuals from the 1000 Genomes Project. Optitype showed the highest accuracy of 97.2% for HLA class I alleles at the second field resolution, followed by 94.0% in Polysolver and 85.6% in PHLAT. In Optitype, 34 (21.1%) of 161 miscalls were across different serological types, and common miscalls were HLA-A*26:01 to HLA-A*25:01, HLA-B*45:01 to HLA-B*44:15 and HLA-C*08:02 to HLA-C*05:01 with error rates of 4.1%, 10.0% and 4.1%, respectively. In Polysolver, 193 (55.9%) of 345 miscalls occurred across different serological alleles, and a specific pattern of genotyping error from HLA-A*25:01 to HLA-A*26:01 was observed in 93.3% of HLA-A*25:01 carriers, due to dropping of HLA-A*25:01 sequence reads during the extraction process of HLA reads. In PHLAT, 147 (59.8%) of 246 miscalls in HLA-A were due to erroneous assignment of multiple alleles to either HLA-A*01:22 or HLA-A*01:81. These results suggest that careful considerations needed to be taken when using exome-based HLA class I genotyping data and applying these results in clinical settings.

BACKGROUND The purpose of this study was to examine the geographic and demographic variations and time trends of different types of meniscal procedures in New York State to determine whether disparities exist in access to treatment. METHODS The New York Statewide Planning and Research Cooperative System (SPARCS) outpatient database was reviewed to identify patients who underwent elective, primary knee arthroscopy between January 1, 2003, and December 31, 2015, for 1 of the following diagnosis-related categories: Group 1, meniscectomy; Group 2, meniscal repair; and Group 3, meniscal allograft transplantation, with or without anterior cruciate ligament reconstruction (ACLR). The 3 groups of meniscal procedures were compared on geographic distribution, patient age, insurance, concomitant ACLR, and surgeon and hospital volume over the study period. RESULTS A total of 649,470 patients who underwent knee arthroscopy between 2003 and 2015 were identified for analysis. Both meniscectomies and meniscal repairs had a scattered distribution throughout New York State, with allograft volume concentrated at urban academic hospitals. The majority of patients who underwent any meniscal procedure had private insurance, with Medicaid patients having the lowest rates of meniscal surgery. At high-volume hospitals, meniscal repairs and allografts are being performed with increasing frequency, especially in patients

Little research has been conducted evaluating surgical trends during the past 10 years and subsequent procedure risk factors for patients undergoing bone-blocking procedures for the treatment of anterior shoulder instability. The Statewide Planning and Research Cooperative System database was queried between 2003 and 2014 to identify patients undergoing soft tissue or bone-blocking procedures for anterior shoulder instability in New York. Patient demographics and 1-year subsequent procedures were analyzed. Multivariate logistic regression analyses were conducted to identify 1-year subsequent procedure risk factors. From 2003 through 2014, a total of 540 patients had Latarjet procedures performed. During this period, the volume of Latarjet procedures increased by 950%, from 12 procedures in 2003 to 126 procedures in 2014. The volume of open Bankart repairs declined by 77%; arthroscopic Bankart repairs fluctuated, being up (328%) between 2003 and 2012 and then down (6%) between 2012 and 2014. Of the 540 patients, 2.4% (13 of 540) required intervention for recurrent shoulder instability events. Age older than 20 years and workers' compensation were identified as independent risk factors for reoperation. The number of bone-blocking procedures, such as the Latarjet, has increased by nearly 1000% during the past decade in New York. Only 2.4% (13 of 540) of the patients had subsequent shoulder instability interventions. [ Orthopedics . 2018; 41(3):e389–e394.]

Purpose To evaluate the cost-effectiveness of nonoperative management, primary SLAP repair, and primary biceps tenodesis for the treatment of symptomatic isolated type II SLAP tear. Methods A microsimulation Markov model was constructed to compare 3 strategies for middle-aged patients with symptomatic type II SLAP tears: SLAP repair, biceps tenodesis, or nonoperative management. A failed 6-month trial of nonoperative treatment was assumed. The principal outcome measure was the incremental cost-effectiveness ratio in 2017 U.S. dollars using a societal perspective over a 10-year time horizon. Treatment effectiveness was expressed in quality-adjusted life-years (QALY). Model results were compared with estimates from the published literature and were subjected to sensitivity analyses to evaluate robustness. Results Primary biceps tenodesis compared with SLAP repair conferred an increased effectiveness of 0.06 QALY with cost savings of $1,766. Compared with nonoperative treatment, both biceps tenodesis and SLAP repair were cost-effective (incremental cost-effectiveness ratio values of $3,344/QALY gained and $4,289/QALY gained, respectively). Sensitivity analysis showed that biceps tenodesis was the preferred strategy in most simulations (52%); however, for SLAP repair to become cost-effective over biceps tenodesis, its probability of failure would have to be lower than 2.7% or the cost of biceps tenodesis would have to be higher than $14,644. Conclusions When compared with primary SLAP repair and nonoperative treatment, primary biceps tenodesis is the most cost-effective treatment strategy for type II SLAP tears in middle-aged patients. Primary biceps tenodesis offers increased effectiveness when compared with both primary SLAP repair and nonoperative treatment and lower costs than primary SLAP repair. Level of Evidence Level III, economic decision analysis.

Background Gastrointestinal angiodysplasias (GIAD) are commonly diagnosed in the small bowel but can be located in other areas of the gastrointestinal tract. About half of patients diagnosed with GIAD have more than 1 lesion and 20% of patients have GIAD in both the small bowel and a source outside of the small bowel (nonisolated to small bowel GIAD or NISGIAD). The remaining patients with GIAD have lesions isolated to the small bowel (ISGIAD). Complications including rebleeding, hospitalization and mortality rates have not been previously analyzed between these 2 groups. Aim To compare rebleeding, hospitalization and mortality rates between ISGIAD and NISGIAD. The secondary goals were to evaluate comorbidities that may be associated with ISGIAD and/or NISGIAD, and to determine if any of these comorbidities are associated with a higher risk of rebleeding from GIAD. Materials and methods This was a retrospective study that included 425 patients who underwent video capsule endoscopy between 2006 and 2013. Patients underwent esophagogastroduodenoscopy and colonoscopy before video capsule endoscopy. The primary indications for workup included obscure gastrointestinal bleeding. After exclusion criteria, 87 patients diagnosed with GIAD remained, 57 patients with ISGIAD and 30 with NISGIAD. Categorical variables were compared by the Fisher exact test or χ test and continuous data were compared using the Student T test. Results Risk factors associated with rebleeding rates included coronary artery disease, chronic kidney disease, and congestive heart failure on multivariate analysis. Odds ratios for rebleeding was found in patients with NISGIAD (odds ratio, 4.222; P=0.036). There was no difference in hospitalization rates between patients with ISGIAD and NISGIAD. There was no statistically significant difference in mortality from any cause at 30, 60, and 90 days in patients with ISGIAD and NISGIAD. Conclusions In this retrospective analysis of GIAD at a single institution, patients with NISGIAD compared with ISGIAD had a 4 times odds of rebleeding within 1 year after capsule endoscopy. This is a novel study, as the distribution of GIAD has not been previously described as being a risk factor for rebleeding.

A placebo-controlled trial that compares the outcomes of immediate vs. deferred initiation of antiretroviral therapy in HIV +ve tuberculous meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol were investigated in the presence and absence of anti-HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact on the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low cerebrospinal fluid (CSF) and systemic exposures to rifampicin compared to previously reported HIV -ve cohorts. Elevated CSF concentrations of pyrazinamide, on the other hand, were strongly and independently correlated with increased mortality and neurological toxicity. The findings suggest that the current standard dosing regimens may put the patient at risk of treatment failure from suboptimal rifampicin exposure, and potentially increasing the risk of adverse central nervous system events that are independently correlated with pyrazinamide CSF exposure.

The MR1 antigen-presenting system is conserved among mammals and enables T cells to recognize small molecules produced by bacterial pathogens, including Mycobacterium tuberculosis (M.tb). However, it is not known whether MR1-mediated antigen presentation is important for protective immunity against mycobacterial disease. We hypothesized that genetic control of MR1 expression correlates with clinical outcomes of tuberculosis infection. We performed an MR1 candidate gene association study and identified an intronic single-nucleotide polymorphism (rs1052632) that was significantly associated with susceptibility to tuberculosis in a discovery and validation cohort of Vietnamese adults with tuberculosis. Stratification by site of disease revealed that rs1052632 genotype GG was strongly associated with the development of meningeal tuberculosis (odds ratio=2.99; 95% confidence interval (CI) 1.64-5.43; P=0.00006). Among patients with meningeal disease, absence of the G allele was associated with an increased risk of death (hazard ratio=3.86; 95% CI 1.49-9.98; P=0.005). Variant annotation tools using public databases indicate that rs1052632 is strongly associated with MR1 gene expression in lymphoblastoid cells (P=0.004) and is located within a transcriptional enhancer in epithelial keratinocytes. These data support a role for MR1 in the pathogenesis of human tuberculosis by revealing that rs1052632 is associated with MR1 gene expression and susceptibility to tuberculosis in Vietnam.

The role of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the pathophysiology of severe falciparum malaria remains unclear. We conducted a retrospective case-control study of Vietnamese adults with severe malaria to determine the relationship between outcome and admission plasma reactive nitrogen intermediates (RNI), the stable metabolites of NO. The study was designed to take into account the potential confounders of recent dietary nitrogen intake and renal function. Seventy-six patients who died from severe malaria were matched for age and sex with 76 survivors from a prospectively studied series of 560 patients. Median untransformed unadjusted plasma RNI levels were slightly higher in fatal cases (45 mumol/L, range 0-482) than in survivors (24.1 mumol/L, range 1.4-466) (P = 0.031, Wilcoxon signed-rank). There was a significant positive correlation between RNI levels and plasma creatinine (Spearman's rho = 0.35, P < 0.0001), and the addition of plasma creatinine as a covariate in a multivariate analysis abolished the trend towards higher RNI levels in fatal cases (P for the coefficient for RNI = 0.96). There was no association between RNI levels and either depth of coma on admission or time to regain consciousness. These findings do not support a pivotal role for systemic generation of NO in the pathogenesis of severe malaria in general, or cerebral malaria in particular.

Objective: The purpose of this study was to evaluate the safety and efficacy of hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind, placebo-controlled trial. Methods: Twenty-eight patients with type 2 SMA and 29 patients with type 3 SMA were randomly assigned (2:1) to receive HU or matching placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the first 2 months (T1–T2) and then every 2 months throughout treatment (T3–T10) and posttreatment periods (T11–T13). The primary outcome measures were the Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC). Results: Fifty-five patients completed this trial, which lasted from March 2007 to June 2009. Except for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had −1.88 for GMFM (p = 0.11), −0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function. Conclusion: Under the current regimen and schedule, HU brought about no improvement in patients with type 2 and 3 SMA, and its main side effect was neutropenia. Classification of evidence: This trial provides Class I evidence that HU 20 mg/kg/day does not effectively treat SMA.

Hidradenocarcinoma (HAC) is a rare adenexal tumor with a propensity for the head and neck region and extremities. We report a case of hidradenocarcinnoma in a 56-year-old woman with a mass on her right palm sampled by fine-needle aspiration and later confirmed on histological examination. Fine-needle aspiration cytology revealed a dual population of cells including polyhedral eosinophilic cells and glycogen containing cells with pale/clear cytoplasm. The nuclei were pleomorphic with prominent nucleoli. Occassional papillary structures were identified on the cell block material. A series of immunohistochemical stains were performed and an adnexal neoplasm was suggested. The mass was resected. On histologic sections, infiltration into the adjacent soft tissue was identified. After an additional series of immunohistochemical stains, the diagnosis was confirmed as a HAC. Herein, we present our findings and discuss the differential diagnoses.

BACKGROUND: WHO recommends screening for TB and evaluation for isoniazid preventive therapy (IPT) based on evidence that they reduce TB-related morbidity and mortality among HIV-infected persons. In Vietnam an IPT pilot was implemented in two provinces; TB screening treatment and outcomes were evaluated to inform the adoption and scale-up of IPT. METHODS: During April 2008 to March 2010 eligible HIV-infected persons aged >15 years with no previous or current TB treatment alcohol abuse or liver disease were screened for TB. If TB disease was ruled out based on symptoms chest x-rays and sputum smears isoniazid was administered for 9 months. RESULTS: Among 1281 HIV-infected persons who received initial eligibility screening 520 were referred to and evaluated at district TB clinics for TB disease or IPT eligibility. Active TB was diagnosed in 17 patients and all were started on treatment. Of 520 patients evaluated 416 (80.0%) initiated IPT: 382 (91.8%) completed IPT 17 (4.1%) stopped treatment 8 (1.9%) died 3 (0.7%) developed TB during IPT and 6 (1.4%) had unknown outcomes. No severe adverse events were reported. CONCLUSIONS: IPT treatment completion was high; no serious complications occurred. Improving and expanding intensified case-finding and IPT should be considered in Vietnam. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

For decades it has been common knowledge that there is a connection between rheumatoid factor–positive and antibodies against citrullinated peptide–positive rheumatoid arthritis (RA) and smoking1. Cigarette smoking is regarded as one of the major environmental factors suggested to play a critical role in the development of a variety of disorders including autoimmune diseases such as RA, systemic lupus erythematosus, systemic sclerosis, multiple sclerosis, and Crohn’s disease2. It is safe to say that there is a widespread appreciation of the odiousness of smoking. However, does smoking also have an effect on actual disease activity and on the prognosis of patient outcome? Some statistical procedures, as well as some people, may nourish the illusion that there really is such a thing as a one-and-only risk factor. However, is this the case in reality? Is life really that simple? Many aspects should be considered in relation to smoking and its consequences for patients with RA. Cigarette smoke represents a mixture of more than 4000 toxic substances including nicotine, polycyclic aromatic hydrocarbons, organic compounds, solvents, gas substances (primarily carbon monoxide), and free radicals. Extensive data suggest that smoking has a modulator role in the immune system contributing to a shift from Th type 1 to Th type 2 immune response3. Although there is consensus that smoking is highly likely to play a role in the pathogenesis of RA, does it also influence disease activity? The respective data … Address correspondence to Dr. B.F. Leeb, 2nd Dept. of Medicine, Center for Rheumatology, Lower Austria, Landstrasse 18, Karl Landsteiner Institute for Clinical Rheumatology, Stockerau, A-2000, Austria. E-mail: burkhard.leeb{at}stockerau.lknoe.at

International audience; A series of 16 flavonoids were isolated and prepared from bud exudate of Gardenia urvillei and Gardenia oudiepe, endemic to New Caledonia. Most of them are rare polymethoxylated flavones. Some of these compounds showed noticeable activity against Leishmania (Leishmania) amazonensis, Plasmodium falciparum and Trypanosoma brucei gambiense, in addition to tubulin polymerization inhibition at low micromolar concentration. We also provide a full set of NMR data as some of the flavones were incompletely described.

During inflammation, activated monocytes (Mo) migrate into tissues where they interact with extracellular matrix components such as hyaluronate (HA), produced in high amounts at inflammatory sites. We determined whether Mo that had invaded sites of cutaneous inflammation bind HA and express the putative HA receptors CD44 isoforms, ICAM-1, or receptor for hyaluronate-mediated motility (RHAMM). In cutaneous inflammation, activated infiltrating Mo displayed high HA avidity and expressed epitopes encoded by CD44s, CD44 variant exons v3, v4, v5, v6, v7, and v9, and ICAM-1, but not RHAMM. We further investigated how activation affects the avidity of Mo for HA and which receptors were responsible for such binding. Mo freshly purified from human peripheral blood bound little HA and expressed CD44s but no epitopes encoded by CD44v exons, ICAM-1, or RHAMM. During short-term tissue culture, Mo upregulated their HA avidity and expression of ICAM-1, CD44s, and epitopes encoded by CD44v, all of which were further augmented by IFN-γ or lipopolysaccharide, whereas RHAMM was not detectable. Thus in vitro activated Mo resembled Mo that had migrated to inflammatory sites in vivo . Lipolysaccharide or IFN-γ-induced HA binding was inhibited by more than 90% with monoclonal antibodies directed against N- terminal HA binding domains of CD44s, but not by monoclonal antibodies against CD44v epitopes or ICAM-1. In conclusion, we show that upon in vitro or in vivo activation, Mo enhance their capacity to bind HA. This is critically dependent upon the expression of CD44s epitopes. Regulated CD44–HA interactions may be important for the ability of Mo to migrate into and within sites of inflammation and for Mo effector functions.

Zymographic and immunological studies revealed that primarily tissue-type plasminogen activator and to a lesser extent urokinase-type plasminogen activator were present in fluids of pemphigus vulgaris (type Neumann) skin blisters. Furthermore, plasmin activity was detected in pemphigus blister fluids using chromogenic peptide substrate assays. In pemphigus, but not in control, suction blister fluids plasmin/alpha 2-antiplasmin and plasmin/alpha 2-macroglobulin complexes were found by immunoprecipitation or by testing in immunoassays after fractionation by molecular-sieve chromatography. Plasmin activity, detected by a low molecular weight chromogenic peptide assay, was ascribed to plasmin/alpha 2-macroglobulin complexes. Since formation of plasmin/inhibitor complexes requires active plasmin, the finding indicates previous activation of plasminogen in pemphigus lesions.

Background The rate of H. pylori infection in Vietnam is reportedly high, but the spectrum of H. pylori-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese H. pylori has also not been investigated in detail. Methods Individuals undergoing esophagogastroduodenoscopy were randomly recruited. H. pylori infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. H. pylori virulence factors were investigated by PCR and sequencing. Results Among the examined patients, 65.6% were infected with H. pylori. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all H. pylori-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of vacA m1, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among H. pylori isolates from Hanoi than among those from Ho Chi Minh. Conclusions H. pylori infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. vacA m1 is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.

The multifunctional cytokine, transforming growth factor beta (TGF-beta), was identified by immunocytochemistry in the brain tissues of four patients with acquired immune deficiency syndrome (AIDS), but not in control brain tissue. The TGF-beta staining was localized to cells of monocytic lineage as well as astrocytes, especially in areas of brain pathology. In addition, the brain tissues from the AIDS patients contained transcripts for human immunodeficiency virus 1 (HIV-1) by in situ hybridization, suggesting a correlation between the presence of HIV-1 in the brain and the expression of TGF-beta. However, the expression of TGF-beta was not limited to HIV-1-positive cells, raising the possibility of alternative mechanisms for the induction of TGF-beta in these AIDS patients' brains. To investigate these mechanisms, purified human monocytes were infected in vitro with HIV-1 and were shown to secrete increased levels of TGF-beta. In addition, HIV-1-infected monocytes released a factor(s) capable of triggering cultured astrocytes that are not infected with HIV-1 to secrete TGF-beta. The release of TGF-beta, which is an extremely potent chemotactic factor, may contribute to the recruitment of HIV-1-infected monocytic cells, enabling viral spread to and within the central nervous system (CNS). Moreover, TGF-beta augments cytokine production, including cytokines known to be neurotoxic. The identification of TGF-beta within the CNS implicates this cytokine in the immunopathologic processes responsible for AIDS-related CNS dysfunction.

The inflammatory lesions associated with Helicobacter pylori gastritis and duodenitis contain large numbers of mononuclear cells. The close proximity of H. pylori to gastric mucosa suggests that the organism interacts with mononuclear cells, thereby modulating the inflammatory response. To investigate the role of monocytes/macrophages in this response, we examined the effect of whole H. pylori bacteria, H. pylori surface proteins, and H. pylori lipopolysaccharide (LPS) on purified human monocytes. Whole H. pylori and the extracted LPS induced expression of the monocyte surface antigen HLA-DR and interleukin-2 receptors, production of the inflammatory cytokines interleukin 1 and tumor necrosis factor (peptide and messenger RNA), and secretion of the reactive oxygen intermediate superoxide anion. Since H. pylori in vivo does not invade mucosal tissue, we determined whether soluble constituents of the bacteria could activate monocytes. Soluble H. pylori surface proteins, which are enriched for urease and do not contain LPS, stimulated phenotypic, transcriptional, and functional changes consistent with highly activated monocytes. These findings indicate that H. pylori is capable of activating human monocytes by an LPS-independent as well as an LPS-dependent mechanism. H. pylori activation of resident lamina propria macrophages and monocytes trafficking through the mucosa, leading to the secretion of increased amounts of inflammatory cytokines and reactive oxygen intermediates, could play an important role in mediating the inflammatory response associated with H. pylori gastritis and duodenitis.

The following guidelines were developed for the medical assessment services of the German Pension Insurance Federal Institution. Starting from day-to-day practice, criteria and attributes to guide decisions for a systemisation of the sociomedical assessment of performance in breast cancer were compiled. The guidelines aim at standardising the sociomedical assessment of performance and help to make the decision-making process more transparent, e. g., for the assessment of applications for decreased earning capacity benefits. The guidelines summarise typical manifestations of breast cancer and describe the necessary medical information for the sociomedical assessment of performance. Relevant assessment criteria for the medical history, clinical examination, and for diagnostic tests are illustrated. The assessment of the individual's capacity is outlined, taking occupational factors into account. Following the determination of dysfunctions, the remaining abilities and disabilities, respectively, are deduced and compared with occupational demands. Finally, inferences are drawn regarding the occupational capacity of the individual.

Bacterial meningitis remains an important cause of morbidity and mortality in Vietnam. Diagnosis is hampered by the ready availability of antibiotics in the community, leading to late presentation, masked clinical signs, and poor organism detection during the microscopical examination and culture of cerebrospinal fluid (CSF). In order to improve organism detection at the Hospital for Tropical Diseases in Ho Chi Minh City, a diagnostic PCR-based protocol was developed. This protocol was followed in the investigation of CSF samples from 36 patients with clinical signs of bacterial meningitis. Each sample was first tested in a semi-nested PCR using primers for the 16sRNA gene common to all bacteria. The products of this reaction were then amplified using a 16sru8 primer and primers specific for Neisseria meningitidis, Haemophilus influenzae or Streptococcus spp. The samples found positive for Streptococcus were further investigated in a nested PCR using primers specific for the pneumolysin gene of S. pneumoniae. The sensitivity of detection was increased from 36% with culture to 44% with PCR. Although the sample size was small, the results indicate that PCR would be a feasible and useful adjunct in the diagnosis of bacterial meningitis, particularly in areas where community antibiotic use is common.

Summary In animals, high doses of intramuscular artemether and artemotil have been shown to cause an unusual pattern of selective damage to certain brainstem nuclei, especially those implicated in hearing and balance. We aimed to investigate whether a similar pattern arises in human adults. We examined the brainstems of adults who died after treatment with high dose artemether or quinine for severe falciparum malaria for evidence of a pattern of selective neuronal damage. Neuropathological findings were similar in recipients of quinine (n=15) and artemether (n=6; total artemether doses received 4–44 mg/kg). No evidence was recorded for artemether-induced neurotoxic effects.

Acrolein, an alpha,beta-unsaturated aldehyde, is by far the strongest electrophile present in cigarette smoke which is involved in several lung pathophysiological conditions. Acrolein depletes glutathione and creates thiol imbalance. Acrolein due to thiol imbalance as well as covalent modification of cysteine is known to inhibit the activity of redox sensitive transcription factors such as NF-kappaB and AP-1. Exposure of human type II lung epithelial (A549) cells to non-lethal dose of acrolein (150 fmol/cell for 1 h) depletes 80% of intracellular glutathione and increases the transcription of gamma-glutamylcysteine synthetase (gamma-GCS) at 6-12 h post-treatment, which helps in replenishing the glutathione to normal level. Acrolein treatment activates transcription of phase II genes in general, as indicated by an increase in mRNA for NAD (P) H:quinone oxidoreductase (NQO1). Western blot analysis revealed the increased level of the transcription factor, Nrf2 in the nuclear extract from acrolein treated cells. Electrophoretic mobility shift assay shows increased binding of nuclear proteins to human antioxidant response element (ARE) consensus sequence after treatment with acrolein. The involvement of Nrf2 in ARE mediated transcriptional activation in response to acrolein exposure has been confirmed by human NQO1-ARE reporter assay. The ability of acrolein to transcriptionaly activate genes responsible for phase II enzymes may form the basis of resistance against cell death and can have implications in cigarette smoke related lung carcinogenesis.

A prospective case-control study was conducted in a referral hospital in Ho Chi Minh City, Vietnam, to compare the clinical and laboratory features and outcome of severe falciparum malaria in injection drug abusers (IDAs) with those of patients who had acquired malaria by mosquito bite. From 1991 to 1996, 70 IDAs were admitted to the hospital, of whom at least 32 had acquired malaria by needle sharing. Although IDAs were more likely than control patients with severe malaria to be malnourished and to have coincident hepatitis B, hepatitis C, and human immunodeficiency virus infections, the overall rates of mortality, complications, and recovery were similar in the 2 groups. The route of malaria acquisition did not affect the outcome of severe malaria. The management of severe malaria in IDAs is similar to that for other patients.

Patients infected with the malaria parasite Plasmodium falciparum may develop a diffuse reversible encephalopathy, termed cerebral malaria. It is unclear how the intraerythrocytic parasite, which sequesters in the cerebral microvasculature but does not enter the brain parenchyma, induces this neurological syndrome. Adhesion of parasitized red blood cells in the brain microvasculature is mediated by specific receptors on the host endothelium, including intercellular adhesion molecule (ICAM)-1, CD36 and CD31. Leucocyte binding to cerebral endothelial cells in culture induces intracellular signalling via ICAM-1. The hypothesis that parasitized red blood cells binding to receptors on cerebral endothelial cells causes changes in the integrity of the blood-brain barrier was tested. Immunohistochemistry was used to examine the blood-brain barrier in human cerebral malaria, with antibodies to macrophage and endothelial activation markers, intercellular junction proteins, and plasma proteins. The distribution of the cell junction proteins occludin, vinculin and ZO-1 were altered in cerebral malaria cases compared to controls. While fibrinogen was the only plasma protein detected in the perivascular space, there was widespread perivascular macrophage activation, suggesting that these cells had been exposed to plasma proteins. It was concluded that functional changes to the blood-brain barrier occur in cerebral malaria, possibly as a result of the binding of parasitized red blood cells to cerebral endothelial cells. These changes require further examination in vitro.

The stereoacuity (SA) was measured by means of the Titmus test, Random Dot E stereotest and Yan's stereoscopic test charts in 90 cases of glaucoma or retinitis pigmentosa with visual field contraction and 28 normal subjects. Significant reduction in SA was observed in all patients with contracted visual field, and markedly so (130") in cases with bilateral or unilateral tubular vision. The SA was reduced with visual field loss of over 30% and there was a positive correlation between the SA reduction and the area of visual field loss.

The stereoacuity threshold (ST) was measured in 124 cases of correctable ametropia, comprising 100 cases of myopia (-0.75 to -13.00D) and 24 cases of hyperopia (+0.87 to +5.00D). The mean ST in myopia without and with correction was 97.73" and 8.25" respectively and in hyperopia without and with correction was 21.37" and 9.74" respectively, both differing significantly from the value of 5.15" in normal eyes. The results indicated that the ametropia could have affected ST through reduced visual acuity and possibly other factors.

The mechanism by which Helicobacter pylori, a noninvasive bacterium, initiates chronic antral gastritis in humans is unknown. We now show that H. pylori releases products with chemotactic activity for monocytes and neutrophils. This chemotactic activity was inhibited by antisera to either H. pylori whole bacteria or H. pylori-derived urease. Moreover, surface proteins extracted from H. pylori and purified H. pylori urease (a major component of the surface proteins) exhibited dose-dependent, antibody-inhibitable chemotactic activity. In addition, a synthetic 20-amino acid peptide from the NH2-terminal portion of the 61-kD subunit, but not the 30-kD subunit, of urease exhibited chemotactic activity for monocytes and neutrophils, localizing the chemotactic activity, at least in part, to the NH2 terminus of the 61-kD subunit of urease. The ability of leukocytes to chemotax to H. pylori surface proteins despite formyl-methionyl-leucyl-phenylalanine (FMLP) receptor saturation, selective inhibition of FMLP-mediated chemotaxis, or preincubation of the surface proteins with antiserum to FMLP indicated that the chemotaxis was not FMLP mediated. Finally, we identified H. pylori surface proteins and urease in the lamina propria of gastric antra from patients with H. pylori-associated gastritis but not from uninfected subjects. These findings suggest that H. pylori gastritis is initiated by mucosal absorption of urease, which expresses chemotactic activity for leukocytes by a mechanism not involving N-formylated oligopeptides.