Cellulitis and soft tissue infection in patients with HIV disease: epidemiological and microbiological features

In order to assess the epidemiological, microbiological, and clinical features of cellulitis and soft tissue infection occurring during the course of HIV disease, clinical and laboratory data of 2221 hospitalizations carried out since 1991 were retrospectively examined, and 67 bacteriologically-proven episodes of cellulitis-soft tissue infection were identified (3.02% of overall admissions). Among the 92 cultured pathogens, Staphylococcus aureus was the most frequent (46 cases), followed by Pseudomonas spp., Escherichia coli, and Streptococcus pyogenes; 38.1% of patients had a polymicrobial infection. i.v. drug use (p<.02) and the male gender (p<.05), were significantly associated with the occurrence of these complications, while a great variation in the severity of underlying immunodeficiency was shown. An elevated rate (83.6%) of episodes of cellulitis or soft tissue infection were community-acquired in origin; the comprehensive frequency of these episodes significantly dropped during the highly active antiretroviral therapy (HAART) era (p<.01). Limbs were involved in over 80% of episodes, and an hematogenous dissemination of bacterial infection (which occurred in 25.4% of cases), proved significantly related to a CD4+ lymphocyte count <100 cells/microL (p<.03), and an absolute neutrophil count <1000 cells/microL (p<.05). S. aureus strains showed an elevated in vitro resistance rate to penicillin, ampicillin, and rifampin, and a 21.7% rate of methicillin-resistance, while among the 29 gram-negative microorganisms, resistance to ampicillin and first-generation cephalosporins, and that to amoxycillin-clavulanate and second-generation cephalosporin, occurred in over 90% and 60% of tested strains, respectively. All episodes of HIV-associated cellulitis and soft tissue infection were favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam and aminoglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in 4 patients only, 6-17 months after the initial episode. Cellulitis and soft tissue infection are underestimated complications of HIV disease, but they have a broad etiological and clinical spectrum, are predominantly community-acquired, and are responsible for an appreciable morbidity, due to the supporting role of i.v. drug addiction, and the frequent hematogenous dissemination (which proved to be significantly related to the progression of immunodeficiency and underlying disease). The frequent polymicrobial etiology requires a combination antimicrobial therapy (to be guided by in vitro susceptibility studies), which may avoid a complicated and recurrent disease course in the great majority of cases.     

Can Machine Learning Methods Produce Accurate and Easy-to-Use Preoperative Prediction Models of One-Year Improvements in Pain and Functioning After Knee Arthroplasty?

BackgroundApproximately 15%-20% of total knee arthroplasty (TKA) patients do not experience clinically meaningful improvements. We sought to compare the accuracy and parsimony of several machine learning strategies for developing predictive models of failing to experience minimal clinically important differences in patient-reported outcome measures (PROMs) 1 year after TKA.MethodsPatients (N = 587) in 3 large Veteran Health Administration facilities completed PROMs before and 1 year after TKA (92% follow-up). Preoperative PROMs and electronic health record data were used to develop and validate models to predict failing to experience at least a minimal clinically important difference in Knee Injury and Osteoarthritis Outcome Score (KOOS) Total, KOOS JR, and KOOS subscales (Pain, Symptoms, Activities of Daily Living, Quality of Life, and recreation). Several machine learning strategies were used for model development. Ten-fold cross-validation and bootstrapping were used to produce measures of overall accuracy (C-statistic, Brier Score). The sensitivity and specificity of various predicted probability cut-points were examined.ResultsThe most accurate models produced were for the Activities of Daily Living, Pain, Symptoms, and Quality of Life subscales of the KOOS (C-statistics 0.76, 0.72, 0.72, and 0.71, respectively). Strategies varied substantially in terms of the numbers of inputs required to achieve similar accuracy, with none being superior for all outcomes.ConclusionModels produced in this project provide estimates of patient-specific improvements in major outcomes 1 year after TKA. Integrating these models into clinical decision support, informed consent and shared decision making could improve patient selection, education, and satisfaction.Level of EvidenceLevel III, diagnostic study.     

Comparison of renal function after open radical cystectomy,extracorporeal robot assisted radical cystectomy,and intracorporeal robot assisted radical cystectomy

PurposeRenal function outcomes following robot-assisted radical cystectomy (RARC) have not been well established. We sought to compare long-term renal function outcomes between open radical cystectomy, RARC with extracorporeal urinary diversion and intracorporeal urinary diversion at a high volume institution.Materials and MethodsWe retrospectively reviewed our institutional bladder cancer database for patients who underwent RC from 2010 to 2019 with pre-operative estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m². Changes in renal function were assessed through locally weighted scatter plot smoothing and comparison of median eGFR between surgical groups. Chronic Kidney Disease Stage 3B was defined as eGFR < 45 ml/min/1.73m². Renal function decline was defined as a ≥10 ml/min/1.73m² drop in eGFR. Kaplan Meier method with log-rank was used to compare CKD 3B-free survival and renal function decline. Cox Proportional Hazards model was used to identify predictors of CKD 3B.ResultsSix hundred and forty four patients were included with median follow-up of 32 months (IQR 12–56). Preoperative characteristics were similar among the groups with no differences in median pre-operative eGFR (ORC: 74.6, extracorporeal urinary diversion: 74.3, intracorporeal urinary diversion: 71.6 ml/min/1.73m², P = 0.15). Median postoperative eGFR on follow up was not different between groups (P = 0.56). 33% of patients developed CKD 3B. There were no differences in CKD 3B-free survival by surgical approach (P = 0.23) or urinary diversion (P = 0.09). 64% of patients experienced renal function decline with a median time of 2.4 years (P 0.23). Predictors of CKD were pathologic T3 disease or greater (HR: 1.77, P = 0.01), ureteroenteric anastomotic stricture (HR: 2.80, P < 0.001), preoperative CKD Stage 2 (HR: 1.81, P =0.02), and preoperative CKD Stage 3A (HR: 5.56, P < 0.001).ConclusionRenal function decline is common after RC. Tumor stage, pre-operative eGFR, and ureteral stricture development, not surgical approach, influence renal function decline.     

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the best-characterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases.     

肢端型系统性硬皮病误诊1例

1　病例报告　女 ,45岁 ,因吞咽困难 16 mo伴发热 15 d,于1999- 0 7- 12入院 .于 16 mo前与人争吵后出现吞咽困难 ,以进食馒头、面条为著 ,剑突下有时出现梗噎感 ,随即呕吐 ,呕出所进食物及粘液 ,情绪波动可诱发症状加重 ,伴食欲减退、返酸 .15 d前无诱因出现不规则发热 ,T38～ 39℃ ,上腹痛加重 ,全身酸困不适 ,乏力、头晕、消瘦 .追问病史 ,患者 5 a前双手、足疼痛麻木 ,尤以受凉、精神刺激后明显 ,手指初发白 ,继而发紫 ,变红 ,且麻木疼痛加重 ,手足小关节渐僵硬、畸形 .曾到多家医院就诊 ,诊断 :“雷诺病、类风湿性关节炎”.2 a前出现…     

Autosomal recessive hypermyelinating neuropathy

We studied three patients from two kinships, affected by early onset hereditary motor and sensory neuropathy with probable autosomal recessive inheritance (HMSN type III). Morphological studies of sural nerve biopsies revealed an abnormal myelin proliferation. Two adult patients with long-term follow up, lost ability to walk at 28 and 22 years and showed severe involvement of the cranial nerves. Our observations suggest that hypermyelination neuropathy with early onset is a progressive disease with poor long-term prognosis. In one kinship the occurrence of the disease in two sibs of both sexes but not in parents, is consistent with an autosomal recessive inheritance. Familial cases of hypermyelination neuropathy have not been described in previous reports. Morphological aspects of this condition are compared with other forms of hypermyelination neuropathy.Supported by Telethon-Italy for the project: Chronic inflammatory polyradiculoneuropathy: electrophysiological and immunopathological studies