Non-infected Cohort Research Articles

Chronic overlapping pain conditions increase the risk of long COVID features, regardless of acute COVID status.

Chronic overlapping pain conditions (COPCs) refer to conditions that have similar central nervous system pathophysiologic mechanisms driving widespread pain as well as common comorbid symptoms such as fatigue and problems with sleep, memory, and mood. If COPCs predict the onset of long COVID, this could offer a valuable orientation for long COVID-related research and clinical care. This retrospective cohort study aimed to determine whether having a COPC predicts the onset of long COVID features using US electronic health records and 1:1 propensity score matching without replacement. The study cohorts included (1) people with acute COVID (n = 1,038,402), (2) people with acute influenza (n = 262,092), and (3) a noninfected cohort comprising people with a routine healthcare encounter (n = 1,081,593). Having a COPC increased the risk of long COVID features in all 3 study cohorts. Among those with COVID, having a pre-existing COPC increased the risk by 1.47 (95% CI = 1.46, 1.47). In the influenza cohort, COPCs increased the risk by 1.39 (95% CI = 1.38, 1.40). In the noninfected cohort, COPCs increased the risk by 1.57 (95% CI = 1.56, 1.59). These findings reinforce the likelihood that nociplastic mechanisms play a prominent role in long COVID. Recognizing that this ubiquitous nonspecific syndrome occurs frequently in the population can inform precision medicine therapies that avoid the pitfalls of viewing long COVID exclusively in the framework of postinfectious disease.

Outcomes of Surgical Revascularization for Acute Limb Ischemia in COVID-19 Patients Comparing to Noninfected Cohort: A Single-Center Observational Prospective Study

The purpose of the study was to compare the clinical presentation, management, and outcomes of surgical revascularization for acute limb ischemia (ALI) in 2 groups of patients-with and without SARS-CoV-2 infection. During the 2years (01.01.2020-31.12.2021) all consecutive patients diagnosed with ALI and treated with urgent revascularization were prospectively enrolled. Based on the results of polymerase chain reaction swab for SARS-CoV-2 infection patients were allocated to group A-infected or group B-noninfected. Demographic characteristics, clinical, imaging, laboratory data, and details of treatment were collected prospectively. The composite endpoint of major amputation and/or death at 30days after surgery was defined as main study outcome. The postoperative ankle-brachial index value, reinterventions, complications, and length of hospital stay were considered as secondary outcomes. Overall, 130 patients (139 limbs with ALI) were analyzed-21 patients (23 limbs) in group A and 109 patients (116 limbs) in group B. The anatomical site of arterial occlusion, duration, and severity of ischemia did not differ significantly between the groups. Patients with COVID-19 had significantly shorter time from ALI onset till administration of the first dose of anticoagulant: 8 (2.5-24) hr vs. 15.7 (6-72) hr in group B, P=0.02. Vascular imaging was performed before intervention only in 5 (23.8%) infected patients compared to 78 (71.5%) patients in group B, P<0.001. The main outcome was registered in 38 (29.2%) patients, significantly more frequent in infected cohort: 12 (57.1%) patients in group A versus 26 (23.8%) in group B, P=0.003. Difference was preponderantly caused by high mortality in group A-9 (42.8%) patients, compared to 17 (15.5%) patients in group B, P=0.01. The difference in the rate of limb loss was not statistically significant: 4 (17.3%) limbs were amputated in COVID-19 patients and 12 (10.3%) limbs-in noninfected patients (P=0.3). Combination of ALI and COVID-19 resulted in increased 30-day mortality-risk ratio (RR) 2.7 (95% confidence interval [CI]: 1.42-5.31), P=0.002, but did not lead to significantly higher amputation rate-RR 1.6 (95% CI: 0.59-4.75), P=0.32. In group A initial admission of the patient in the intensive care unit was an independent risk factor for amputation/death. Excepting systemic complications which were more frequently registered among COVID-19 patients: 7 (33%) cases vs. 14 (12.8%) in group B, P=0.04; no differences in other secondary outcomes were observed between the groups. Study demonstrates the significant negative impact of COVID-19 upon the 30-day amputation-free survival in patients undergoing urgent surgical revascularization for ALI. The difference in outcome is influenced by higher rate of mortality among infected patients, rather than by the rate of limb loss. Severity of COVID-19, namely requirement of intensive care, mostly determines the outcome of ALI treatment.

176. The long-term outcomes of patients with early surgical site infections following instrumented lumbar fusions

176. The long-term outcomes of patients with early surgical site infections following instrumented lumbar fusions

Outcomes of patients with advanced urothelial cancer who develop infection while on treatment with pembrolizumab.

4573 Background: Over the past decade, studies have shown the benefit of immune checkpoint inhibitors (IO) in patients with advanced urothelial cancer. These agents work by reconditioning the adaptive anti-cancer immune response within the tumor microenvironment. Immune-related adverse events have been well documented, but there is limited data evaluating infections in patients treated with IO. We performed a retrospective analysis to assess the incidence of infection and its effect on morbidity and mortality in patients treated with pembrolizumab for advanced urothelial cancer. Methods: Data was collected from a network of 7 hospitals for patients who received pembrolizumab for advanced urothelial cancer from 1/1/2017-8/1/2021. Date of last follow up was 12/1/2021. Covariates compared among infected and non-infected cohorts included age, gender, race, comorbidities, ECOG, anti-infective therapy at IO initiation, and line of therapy (1L, 2L, &gt; 2L). Univariable analysis with reported odds ratio (OR) and 95% confidence interval (CI) was used to assess risk factors for infection. Outcome measures included all-cause emergency department (ED) visits, inpatient and intensive care unit (ICU) admissions, median number of IO cycles, and overall survival (OS). OS was evaluated using the Kaplan-Meier model. All analyses were deemed statistically significant if the p-value was &lt; 0.05. Results: A total of 51 patients were identified. Of these, 34 (66.7%) had at least one documented infection and 17 (33.3%) had no reported infections. Baseline characteristics were similar across cohorts. Compared to non-infected patients, infected patients received fewer cycles of IO (median 4 vs 8, p = 0.016). At last follow-up, 20 (58.8%) patients in the infected cohort and 4 (23.5%) in the non-infected cohort died (p = 0.017). Median OS was 7.4 months (95% CI: 3.4-24.9) among patients with infection while not reached in those without infection (p = 0.014). ED visits (p = 1.00), inpatient admissions (p = 0.21), and ICU admissions (p = 0.17) did not significantly differ between cohorts. Univariable analysis did not identify significant risks among covariates. Conclusions: The incidence of infection in patients treated with pembrolizumab for advanced urothelial cancer is high and associated with fewer cycles of IO therapy and shorter OS. Further study of infectious process prevention is of value to maximize immunotherapy benefit.

Hypertension and low cholesterol as risk factors for infection after primary inflatable penile prosthesis surgery

Background: Inflatable penile prosthesis (IPP) is an effective surgical intervention in the treatment of erectile dysfunction. However, infection is a devastating complication of IPP placement. We sought to evaluate the association between medical comorbidities, medications, and serum metabolic lab values, and infection following primary IPP placement in our ethnically diverse population. Methods: A retrospective chart review was performed on all men who had primary IPP placement between 2017–2019 at our institution. Variables collected included patient demographics, medical history, medication usage, and pre- and postoperative lab values, within six months of surgery, including hemoglobin A1c, total cholesterol, and low density lipoprotein. Rates of postoperative infection through 60 days were noted. Patients were grouped either into the infected or non-infected cohort based on postoperative infection status. A Student’s unpaired t-test was used to compare numerical variables and a Pearson chi-square test or Fisher’s exact test was used to compare categorical variables between the cohorts. Results: A total of 293 men underwent primary IPP placement, of whom 14 (4.8%) were in the infected cohort and 279 (95.2%) in the non-infected cohort. The infected cohort was more likely to have a history of hypertension (92.9% vs 74.2%, p = 0.026) and statins medication usage (78.6% vs 52.0%, p = 0.039) when compared to the non-infected cohort, respectively. The infected cohort had a significantly lower postoperative cholesterol value (136.3 mg/dL vs 170.0 mg/dL, p = 0.024) and postoperative low density lipoprotein (LDL) value (65.2 mg/dL vs 92.1 mg/dL, p = 0.020) when compared to the non-infected cohort, respectively. Conclusions: Hypertension and usage of statin medications were more common in men who developed infection following IPP placement. As hypertension can disrupt microvasculature over time, it may contribute to poor healing post-IPP placement. Future research is warranted to determine statins’ anti-inflammatory effect on wound healing and ability to fight infection.

Inflammation and Liver Cell Death in Patients with Hepatitis C Viral Infection.

Hepatitis C virus (HCV)-induced liver disease contributes to chronic hepatitis. The immune factors identified in HCV include changes in the innate and adaptive immune system. The inflammatory mediators, known as “inflammasome”, are a consequence of the metabolic products of cells and commensal or pathogenic bacteria and viruses. The only effective strategy to prevent disease progression is eradication of the viral infection. Immune cells play a pivotal role during liver inflammation, triggering fibrogenesis. The present paper discusses the potential role of markers in cell death and the inflammatory cascade leading to the severity of liver damage. We aim to present the clinical parameters and laboratory data in a cohort of 88 HCV-infected non-cirrhotic and 25 HCV cirrhotic patients, to determine the characteristic light microscopic (LM) and transmission electron microscopic (TEM) changes in their liver biopsies and to present the link between the severity of liver damage and the serum levels of cytokines and caspases. A matched HCV non-infected cohort was used for the comparison of serum inflammatory markers. We compared the inflammation in HCV individuals with a control group of 280 healthy individuals. We correlated the changes in inflammatory markers in different stages of the disease and the histology. We concluded that the serum levels of cytokine, chemokine, and cleaved caspase markers reveal the inflammatory status in HCV. Based upon the information provided by the changes in biomarkers the clinician can monitor the severity of HCV-induced liver damage. New oral well-tolerated treatment regimens for chronic hepatitis C patients can achieve cure rates of over 90%. Therefore, using the noninvasive biomarkers to monitor the evolution of the liver damage is an effective personalized medicine procedure to establish the severity of liver injury and its repair.

MO721THROMBOTIC EVENTS AFTER COVID-19 INFECTION IN HEMODIALYSIS PATIENTS*

Background and AimsThere is an increased risk of thrombotic complications in patients with COVID-19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new-onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID-19.MethodWe performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow-up due to kidney transplantation or death from non-thrombotic causes.Results185 prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS-CoV-2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID-19 survivors compared to the non-infected cohort (18.5% vs 1.9%, p=0.002) after a median follow-up of 7 months. Stroke incidence was 38.9 episodes/1000 patient-years in patients infected with SARS-CoV-2, compared to an incidence of 2.8 episodes/1000 patient-years in non-infected patients during the follow-up period. The median time from diagnosis of SARS-CoV-2 to the first thrombotic event was 62 days (interquartile range 5-118 days). Survival analysis with Kaplan-Meier curves revealed an increase in the rate of thrombotic events after SARS-CoV-2 compared to non-infected patients (see Figure 1). Mean survival from thrombotic event was 6.1±0.4 months in the COVID-infected group, compared to 6.97±0.04 months in the non-infected group (p<0.001). Multivariate regression analysis showed that COVID-19 infection increased risk for late thrombotic events adjusted for age, sex, hypertension, diabetes, antithrombotic treatment and previous thrombotic events (OR 26.4, 95% CI 2.5-280.6, p=0.01). Clinical and laboratory markers did not predict thrombotic events.MO721 Figure 1:Kaplan-Meier survival curves for freedom from thrombotic events, stratified by COVID-19 infection statusConclusionThere is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID-19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID-19.

Differences between infected and noninfected synovial fluid.

AimsThe diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF.MethodsIn all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups.ResultsA total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine).ConclusionMetabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF.Cite this article: Bone Joint Res 2021;10(1):85–95.

194. The fate of patients with early postoperative surgical site infections following instrumented lumbar fusion

BACKGROUND CONTEXT Acute postoperative surgical site infections (SSI) following instrumented lumbar fusions are a relatively infrequent occurrence. Treatment with aggressive surgical debridement and parenteral antibiotics are generally effective in leading to eradication of infection and maintenance of the instrumentation. However, it is not clear what the long-term effect may be on clinical outcome or more specifically the potential for development of a non-union or instrumentation loosening. PURPOSE To evaluate the long term clinical and radiographic outcomes of patients who underwent an instrumented lumbar fusion which was complicated by an acute postoperative surgical site infection that necessitated a surgical debridement and a prolonged course of parenteral antibiotics. STUDY DESIGN/SETTING A retrospective review of a cohort of consecutive patients treated a single institution. PATIENT SAMPLE A consecutive cohort of patients who underwent an elective lumbar decompression and instrumented fusion for lumbar stenosis complicated by an acute surgical site infection within the first 4 weeks postoperatively that required additional surgery to debride the wound and maintain the instrumentation. Patients underwent surgery over a 12-year period (2007-2016) at a tertiary spine referral center. Follow-up was a minimum of 2 years and a mean of 6.2 years. OUTCOME MEASURES Hospital length of stay, need for further surgery, clinical outcome measures: ODI, VAS (back), VAS (leg), patient-reported satisfaction, willingness to repeat index surgery and radiographic fusion rates. METHODS The clinical data base at our medical center was queried to identify acute surgical site infections occurring within 4 weeks following a posterior lumbar decompression and instrumented fusion. RESULTS A total of 1,602 patients underwent an instrumented lumbar fusion: 604 (38%) L4-5, 623 L3-5 (39%), 375 L2-5 (23%). An acute surgical site infection occurred in 39 patients (.024%). Significant risk factors (p 80, BMI > 30, Diabetes, osteoporosis and prior decompressive surgery. Notable nonsignificant risk factors included length of surgery, preoperative diagnosis (degenerative spondylolisthesis or degenerative scoliosis), use of iliac crest autograft or allograft, duration of postoperative suction drain, or occurrence of an incidental durotomy requiring repair. Mean length of hospital stay was significantly longer in patients with an SSI, 3.2 days vs 7.2 days (p=.02). Longer term follow-up revealed revision surgery to address symptomatic non-union was slightly greater in the SSI cohort, 6 patients (15%) vs 15 patients (12%) in the noninfected cohort, but this did not reach significance (p>.05). Radiographic evidence of non-union or loose instrumentation was not significantly different between the two cohorts. At 6-month follow-up, clinical outcomes were consistently better in the noninfected cohort: VAS back (p=.04), VAS leg (p=.03) and ODI (p=.04), as were patient reported satisfaction (p=.04) and willingness to repeat the index procedure (p=.04). By 1 year postoperatively and onward thereafter to the latest follow-up, no significant difference was noted in clinic outcomes, patient satisfaction, or willingness to repeat the index surgery. CONCLUSIONS In a single center study of 1,602 patients undergoing a posterior decompression and instrumented fusion for degenerative lumbar disease, acute postoperative surgical site infection occurred in 2% of cases. Older, obese, diabetic patients were more prone to an SSI and the initial 6-month clinical outcomes were inferior to patients without an infection. However, long-term clinical and radiographic follow-up showed no significant differences between those with and without an infection. As well, late revision rates were not greater in patients with history of an SSI. Recognition of a postoperative infection, especially in high risk patients, followed by prompt surgical intervention and appropriate parenteral antibiotics allows for maintenance of instrumentation and favorable clinical outcomes. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Prediction of 28-day mortality in acute decompensation of cirrhosis through the presence of multidrug-resistant infections at admission.

The aim of this study is to evaluate the epidemiology and impact of bacterial infections at admission in patients with acute decompensation (AD) of cirrhosis. A cohort with AD of cirrhosis (European Association for the Study of the Liver criteria) admitted at a tertiary center was evaluated between 2013 and 2014 for the presence of bacterial infections at admission. Clinical, demographic, and microbiological data were collected prospectively till death, transplant, or 90 days. Of 179 patients with AD, 102 (56.9%) had bacterial infections at admission. The commonest infections were spontaneous bacterial peritonitis (SBP) (n = 65; 63.7%), spontaneous bacteremia (n = 10; 9.8%), pneumonia (n = 9; 8.8%), urinary tract infection (n = 8; 7.8%), spontaneous bacterial empyema (n = 4; 3.9%), and cellulitis (n = 2; 1.9%). The commonest source was community acquired (n = 85; 83.3%). Serum albumin and sodium levels were lower in infected as compared with non-infected cohort (P = 0.015; for both). Escherichia coli was the commonest organism isolated from SBP (n = 14; 21.5%), urinary tract infection (n = 5; 45.5%), and bacteremia (n = 3; 20%). There was a trend toward higher 28-day mortality in infected cohort as compared with non-infected cohort (48 [52.7%] vs 28 [32%]; P = 0.152). Multidrug-resistant organisms (MDROs) were isolated in 63% of all culture-positive infections. The presence of MDRO was an independent predictor of 28-day mortality. Infections are the leading reason for the occurrence of AD; SBP is the most common infection, and E. coli is the commonest microorganism based on this single-center study of Indian patients with AD of cirrhosis. There is a high prevalence of MDROs among culture-positive infections that independently predict 28-day mortality in AD of cirrhosis.

Does external fixator pin site distance from definitive implant affect infection rate in pilon fractures?

IntroductionTibial pilon fractures are often treated with initial external fixation followed by delayed definitive fixation. It has been postulated that the external fixator pin site may correlate with infection risk. The purpose of this study was to determine whether external fixator pin-site distance from definitive implants impacts the risk of deep infection in pilon fractures. Materials and methodsA retrospective cohort study was completed at a single level 1 trauma center. All patients ages 15–65 who underwent open reduction and internal fixation (ORIF) of a distal tibial fracture (AO/OTA Classification 43) from 2007 to 2013 were included. The final study population was 133 patients. The impact of external fixation pin location (relative to the definitive implant location) on postoperative infection was measured. ResultsAs a continuous variable, the distance between the closest pin site and plate was 62.1 ± 44.1 mm in the infected cohort and 62.2 ± 49.7 mm in the non-infected cohort (p = 0.991). Further analysis was performed by grouping the distances into less than 0 mm (i.e. overlapping), >0.0 – 25.0 mm, >25.0 – 50.0 mm, >50.0 – 75.0 mm, >75.0 – 100.0 mm, and >100.0 mm of separation. No significant differences were noted with regards to the risk for infection. ConclusionsStaged care has been shown to be an effective treatment strategy for AO/OTA type 43 fractures. There are many variables to consider when placing an external fixator construct. In this cohort, pin site distance from definitive implant location was not associated with an increase in deep infections. Level of evidenceLevel III.

Risk Factors for Deep Infection Following Plate Fixation of Proximal Tibial Fractures.

The risk factors are unclear for deep surgical site infection after plate fixation of proximal tibial fractures. The objective of this study was to identify the patient and surgical procedure-related risk factors for infection using established criteria for deep surgical site infection. A total of 655 proximal tibial fractures were treated with open reduction and plate fixation at our center between 2004 and 2013. We identified 34 patients with deep surgical site infection. A control group of 136 patients was randomly selected from the non-infected cohort. Potential risk factors for deep surgical site infection were identified by reviewing surgical, medical, and radiographic records. Independent risk factors for infection were identified from multivariable logistic regression analysis using a stepwise procedure. The prevalence of deep surgical site infection was 5.2%, the mean age of affected patients was 55 years (range, 16 to 84 years), and 35% of patients were female. Twenty-eight of 34 deep infections were diagnosed within 2 months (acute onset), and only 6 infections were diagnosed >6 months after the index surgical procedure. Nine of the 28 acute-onset infections were treated with antibiotic therapy and debridement. Seventeen patients (50%) required muscle flap coverage, and 5 patients (15%) eventually required above-the-knee amputation. In the multivariable logistic regression analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs), independent predictors of infection were patient age of ≥50 years (OR, 3.6 [95% CI, 1.3 to 10.1]); obesity, defined as a body mass index of ≥30 kg/m(2) (OR, 6.5 [95% CI, 2.2 to 18.9]); alcohol abuse (OR, 6.7 [95% CI, 2.4 to 19.2]); OTA/AO-type-C fracture (OR, 2.8 [95% CI, 1.1 to 7.5]); use of a temporary spanning external fixator (OR, 3.9 [95% CI, 1.4 to 11.1]); and a 4-compartment fasciotomy (OR, 4.5 [95% CI, 1.3 to 15.7]). There is high morbidity associated with deep surgical site infection in plated proximal tibial fractures. Patients who are ≥50 years of age, obese patients, those with a history of alcohol abuse, or those with an OTA/AO-type-C fracture are at high risk for infection. Performing a fasciotomy also increases the risk of deep infection and should be implemented with meticulous technique when deemed necessary. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Association between Helicobacter pylori infection and the subsequent risk of end-stage renal disease: a nationwide population-based cohort study.

The association between Helicobacter pylori infection and end-stage renal disease (ESRD) events remains unknown. We assessed the relationship between H. pylori infection requiring hospital admission and the subsequent risks of ESRD. This was a retrospective cohort study in which data from the National Health Insurance system of Taiwan was used. The H. pylori-infected cohort comprised 20,068 patients. Each participant was frequency-matched by age and sex with 4 individuals from the general population without H. pylori-infected. Cox proportional hazards regression analysis was used to estimate the influence of H. pylori infection on the risk of ESRD. The overall incidence of ESRD was 3.72 times greater in the H. pylori-infected cohort than in the non-infected cohort (11.1 vs. 2.96 per 1000 person-years), with an adjusted HR of 2.58 [95% confidence interval (CI)=2.33-2.86]. The risk of ESRD markedly increased in patients with H. pylori infection combined with at least one of the following concomitant comorbidities: hypertension, diabetes, hyperlipidaemia and coronary artery disease. This is currently the largest nation-based study in which the risk of ESRD in H. pylori-infected patients was examined. H. pylori infection was associated with a subsequent risk of ESRD. H. pylori-infected patients with concomitant chronic kidney disease (CKD) or cardiovascular disease (CVD) risk factors were at higher risk of ESRD than were those who had a single CKD or CVD risk factor.

Survival of Patients With Biventricular Devices After Device Infection, Extraction, and Reimplantation

This study sought to compare outcomes in patients with biventricular device infections who undergo successful treatment including extraction and reimplantation to patients with biventricular devices never known to become infected. Infection of a cardiac implantable electronic device (CIED) is associated with substantial morbidity and mortality. Survival in patients with cardiac resynchronization therapy (CRT) device infections undergoing full system extraction is unknown. We extracted data on all patients undergoing extraction of a biventricular pacing device for an infectious indication at the Cleveland Clinic between February 16, 2000, and June 30, 2011. Survival of patients who presented with a CRT device infection, extraction, and successful reimplantation was compared to that of a large cohort of consecutive patients undergoing initial CRT implantation without a known history of subsequent device-related infection. In addition, long-term outcomes were compared between patients who were extracted and deemed to be cured with and without successful biventricular device reimplantation. In all, 151 patients underwent biventricular device extraction for infection, of whom 81 were successfully reimplanted. The noninfected cohort consisted of 879 patients. In a multivariate Cox regression model controlling for sex, a history of ischemic cardiomyopathy, creatinine, hemoglobin, beta-blocker use, angiotensin-converting enzyme inhibitor use, and diuretic use, no significant association between subsequent infection with reimplantation and all-cause mortality was noted (p= 0.21). There was a trend toward worse outcomes for patients extracted, deemed cured, and not reimplanted compared to patients with successful CRT reimplantation. Patients with a biventricular device infection who are successfully extracted, treated with antibiotics, and reimplanted with a biventricular device have outcomes similar to those of patients with biventricular devices not known to have become infected.

Heterologous Immunity Triggered by a Single, Latent Virus in Mus musculus: Combined Costimulation- and Adhesion- Blockade Decrease Rejection

The mechanisms underlying latent-virus-mediated heterologous immunity, and subsequent transplant rejection, especially in the setting of T cell costimulation blockade, remain undetermined. To address this, we have utilized MHV68 to develop a rodent model of latent virus-induced heterologous alloimmunity. MHV68 infection was correlated with multimodal immune deviation, which included increased secretion of CXCL9 and CXCL10, and with the expansion of a CD8dim T cell population. CD8dim T cells exhibited decreased expression of multiple costimulation molecules and increased expression of two adhesion molecules, LFA-1 and VLA-4. In the setting of MHV68 latency, recipients demonstrated accelerated costimulation blockade-resistant rejection of skin allografts compared to non-infected animals (MST 13.5 d in infected animals vs 22 d in non-infected animals, p<.0001). In contrast, the duration of graft acceptance was equivalent between non-infected and infected animals when treated with combined anti-LFA-1/anti-VLA-4 adhesion blockade (MST 24 d for non-infected and 27 d for infected, p = n.s.). The combination of CTLA-4-Ig/anti-CD154-based costimulation blockade+anti-LFA-1/anti-VLA-4-based adhesion blockade led to prolonged graft acceptance in both non-infected and infected cohorts (MST>100 d for both, p<.0001 versus costimulation blockade for either). While in the non-infected cohort, either CTLA-4-Ig or anti-CD154 alone could effectively pair with adhesion blockade to prolong allograft acceptance, in infected animals, the prolonged acceptance of skin grafts could only be recapitulated when anti-LFA-1 and anti-VLA-4 antibodies were combined with anti-CD154 (without CTLA-4-Ig, MST>100 d). Graft acceptance was significantly impaired when CTLA-4-Ig alone (no anti-CD154) was combined with adhesion blockade (MST 41 d). These results suggest that in the setting of MHV68 infection, synergy occurs predominantly between adhesion pathways and CD154-based costimulation, and that combined targeting of both pathways may be required to overcome the increased risk of rejection that occurs in the setting of latent-virus-mediated immune deviation.

Impact of the human immunodeficiency virus on early multidrug-resistant tuberculosis treatment outcomes in Botswana

The impact of the human immunodeficiency virus (HIV) on multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in sub-Saharan Africa, where extensive rollout of highly active antiretroviral therapy (HAART) has occurred, remains unclear. To compare the time to initial culture conversion among patients with and those without HIV infection in a setting of individualized MDR-TB care in Botswana. Prospective cohort study of MDR-TB patients receiving ambulatory, integrated TB-HIV care at two public clinics in Botswana. The time to culture conversion was compared by HIV status using Cox proportional hazard ratios (HRs). A total of 40 HIV-infected and 30 non-HIV-infected patients with MDR-TB and follow-up cultures were identified. The median time to initial culture conversion was 78 days (interquartile range [IQR] 42-186) for HIV-infected and 95 days (IQR 70-133) for non-HIV-infected individuals (log rank P > 0.5; unadjusted HR 0.9, 95%CI 0.5-1.5). Adjusting for age, sex, treatment history and number of active anti-tuberculosis drugs did not change this result (adjusted HR 0.8, 95%CI 0.4-1.4). We found no difference in the proportion of or time to initial sputum culture conversion between an HIV-infected and a non-infected cohort of MDR-TB patients in Botswana, suggesting that outcomes may be comparable in similar settings with access to individualized anti-tuberculosis treatment and HAART.

The burden of hepatitis C in Sweden: a national study of inpatient care

The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that serious liver complications (SLC) would increase in the 2000s. The aim of this study was to analyse the burden of HCV-associated inpatient care in Sweden, to demonstrate the changes over time and to compare the findings with a noninfected population. The HCV-cohort (n: 43,000) was identified from the national surveillance database 1990-2006, and then linked to national registers to produce an age-, sex-, and region-matched noninfected comparison population (n: 215,000) and to obtain information on demographics, cancers, inpatient care and prescriptions. Cox regression was used to estimate the likelihood (hazard ratios) for admission to hospital in the HCV compared with the noninfected cohort. The hazard ratios were 4.03 (95% CI: 3.98-4.08) for all care, 77.52 (71.02-84.60) for liver-related care and 40.74 (30.58-54.27) for liver cancer care. The admission rate in the HCV-cohort compared with the noninfected cohort, the rate ratio (age- and sex-adjusted) for all inpatient care was 5.91 (95% CI: 5.87-5.94), and the rate ratio for liver-related care was 70.05 (66.06-74.28). In the HCV-cohort, 45% of all episodes were for psychiatric, mostly drug-related, care. Inpatient care for SLC increased in the 2000s. To conclude, drug-related care was common in the HCV-infected cohort, the demand for liver-related care was very high, and SLC increased notably in the 2000s, indicating that the burden of inpatient care from serious liver disease in HCV-infected individuals in Sweden is an increasing problem.

Epidemic hepatitis C virus infection in Egypt: estimates of past incidence and future morbidity and mortality

Hepatitis C virus (HCV) infection is gaining increasing attention as a global health crisis. Egypt reports the highest prevalence of HCV worldwide, ranging from 6% to more than 40% among regions and demographic groups. Predicting the impact of the epidemic has been difficult because of the long-latency period and low-resource setting. Accordingly, we sought to estimate historic incidence and predict the future impact of HCV using Markov simulation modelling techniques. Age-specific HCV incidence rates (IRs) were estimated using previously acquired age-specific HCV prevalence data. Data for this analysis were from a highly detailed, community-based seroprevalence study from 2003. Future HCV-related morbidity and mortality were estimated using a computer cohort simulation of HCV natural history in the Egyptian population. Population and natural history parameters were defined using results from a meta-analysis and existing comprehensive literature reviews. Incidence model estimates ranged from 2.01 to 25.47 HCV cases per 1000 person-years (PYs). The highest IRs were calculated among those over 35 years of age. Our Markov model predicted 127,821 deaths from chronic liver disease and 117,556 deaths from hepatocellular carcinoma in Egypt over the next 20 years. During this period, it was estimated that HCV would yield 750,210 PY of decompensated cirrhosis, 132,894 PY of hepatocellular carcinoma, and a total loss of 32.86 million years of life compared to a non-infected cohort. Our results support the claim of high HCV incidence in Egypt and suggest that HCV may lead to a substantial health and, consequently, economic burden over the next 10-20 years.

Morbidly Obese, Diabetic, Younger, and Unilateral Joint Arthroplasty Patients Have Elevated Total Joint Arthroplasty Infection Rates

The study aims to delineate the deep infection rates and infection risk factors for primary total knee and total hip arthroplasty patients. A retrospective review was conducted on 6108 patients from 1991 to 2004. The deep infection cases were compared to the noninfected cohort whereby infection risk factors were identified. Of the 8494 joint arthroplasties, 43 (0.51%) developed a deep infection (30 total knee arthroplasties, 13 total hip arthroplasties). Patients with a body mass index greater than 50 had an increased odds ratio of infection of 21.3 ( P < .0001). Diabetic patients were 3 times as likely to become infected compared to nondiabetic patients ( P = .0027). Simultaneous bilateral total joint arthroplasties were found to have developed infection 3 times less frequently than those performed as unilateral procedures ( P = .0024). The average age in our infection cohort was 64.3 and 68.4 in the noninfected cohort. In this retrospective review study, obesity, diabetes, and younger age were found to be risk factors for joint arthroplasty infection.