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Nosocomial infections are public health threats with often grave human costs. Because implementing screening and best outbreak response practices is costly for health care organizations, allocating resources for interventions requires consensus among stakeholders with a plurality of perspectives about how to weigh prospective interventions' risks and benefits. Economic analysis can facilitate decision making but is relatively new in nosocomial infection prevention and control. This article describes features of and reasons for economic analysis in this specific area and focuses on emerging challenges in antimicrobial stewardship.

Background Mortality is a critical measure of disease impact. The European Union (EU) countries share the same regulatory framework but different implementation policies. Methods We extracted cumulative COVID-19 mortality data across the EU countries. We evaluated the 27 member states using the location quotient (LQ) to adjust for the expected mortality in the whole EU region, where an LQ 1 a less favorable outcome. We categorized EU members into 3 distinct profiles based on their LQ estimates: favorable profile, LQ ≤0.9; unfavorable profile, LQ >1.10; and average profile, LQ between 0.9 and 1.10. We compared LQ estimates and profiles with the prevaccination era that ended in December 2020 with the COVID-19 vaccine rollout. Results Twelve member states had a favorable profile, 4 had an average profile, and 11 had an unfavorable profile. In quantitative analysis, an improvement (negative LQ difference) was noted across countries with higher vaccination coverage (median, 71% fully vaccinated vs 57% for countries with positive LQ differences). There was a significant negative association between the share of fully vaccinated and LQ changes (ρ = –0.62, P Conclusions There is significant variability in mortality and impact of COVID-19 between countries, even if they share the same regulatory framework. Extending immunization coverage may lead the transition to a more favorable profile, and alter the trajectory of COVID-19 mortality.

Background Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is associated with significant morbidity, mortality, and hospitalization costs. Cefazolin and antistaphylococcal penicillins (ASPs), such as nafcillin, are the preferred treatments for MSSA bacteremia. The aim of this study was to compare the cost-effectiveness of each approach. Methods We constructed a decision-analytic model comparing the use of cefazolin with ASPs for the treatment of MSSA bacteremia. Cost-effectiveness was determined by calculating deaths averted and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Results In the base-case analysis, the cost associated with the cefazolin strategy was $38 863.1, and the associated probability of survival was 0.91. For the ASP strategy, the cost was $48 578.8, and the probability of survival was 0.81. The incremental difference in cost between the 2 strategies was $9715.7, with hospital length of stay being the main driver of cost, and the incremental difference in effectiveness was 0.10. Overall, cefazolin results in savings of $97 156.8 per death averted (ICER, $–97 156.8/death averted). In the probabilistic analysis, at a willingness-to-pay of $50 000, cefazolin had a 68% chance of being cost-effective compared with ASPs. In cost-effectiveness acceptability curves, the cefazolin strategy was cost-effective in 73.5%–81.8% of simulations compared with ASP for a willingness-to-pay ranging up to $50 000. Conclusions The use of cefazolin is a cost-effective strategy for the treatment of MSSA bacteremia and, when clinically appropriate, this strategy results in considerable health care cost-savings.

ImportanceStaphylococcus aureus bacteremia is associated with a significant burden of mortality, morbidity, and health care costs. Infectious disease consultation may be associated with reduced mortality and bacteremia recurrence rates.ObjectiveTo evaluate the cost-effectiveness of infectious disease consultation for Staphylococcus aureus bacteremia.Design, Setting, and ParticipantsIn this economic evaluation, a decision-analytic model was constructed comparing infectious disease consult with no consult. The population was adult hospital inpatients with Staphylococcus aureus bacteremia diagnosed with at least 1 positive blood culture. Cost-effectiveness was calculated as deaths averted and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Costs and outcomes were calculated for a time horizon of 6 months. The analysis was performed from a societal perspective and included studies that had been published by January 2022.InterventionsPatients received or did not receive formal bedside consultation after positive blood cultures for Staphylococcus aureus bacteremia.Main Outcomes and MeasuresThe main outcomes were incremental difference in effectiveness (survival probabilities), incremental difference in cost (US dollars) and incremental cost-effectiveness ratios (US dollars/deaths averted).ResultsThis model included 1708 patients who received consultation and 1273 patients who did not. In the base-case analysis, the cost associated with the infectious disease consult strategy was $54 137.4 and the associated probability of survival was 0.77. For the no consult strategy, the cost was $57 051.2, and the probability of survival was 0.72. The incremental difference in cost between strategies was $2913.8, and the incremental difference in effectiveness was 0.05. Overall, consultation was associated with estimated savings of $55 613.4/death averted (incremental cost-effectiveness ratio, −$55613.4/death averted). In the probabilistic analysis, at a willingness-to-pay threshold of $50 000, infectious disease consult was cost-effective compared with no consult in 54% of 10 000 simulations. In cost-effectiveness acceptability curves, the consult strategy was cost-effective in 58% to 73%) of simulations compared with no consult for a willingness-to-pay threshold ranging from $0 to $150 000.Conclusions and RelevanceThese findings suggest that infectious disease consultation may be a cost-effective strategy for management of Staphylococcus aureus bacteremia and that it is associated with health care cost-savings.

Background Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is associated with significant morbidity, mortality, and hospitalization costs. Cefazolin and antistaphylococcal penicillins (ASPs), such as nafcillin, are the preferred treatments for MSSA bacteremia. The aim of this study was to compare the cost-effectiveness of each approach. Methods We constructed a decision-analytic model comparing the use of cefazolin with ASPs for the treatment of MSSA bacteremia. Cost-effectiveness was determined by calculating deaths averted and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Results In the base-case analysis, the cost associated with the cefazolin strategy was $38 863.1, and the associated probability of survival was 0.91. For the ASP strategy, the cost was $48 578.8, and the probability of survival was 0.81. The incremental difference in cost between the 2 strategies was $9715.7, with hospital length of stay being the main driver of cost, and the incremental difference in effectiveness was 0.10. Overall, cefazolin results in savings of $97 156.8 per death averted (ICER, $–97 156.8/death averted). In the probabilistic analysis, at a willingness-to-pay of $50 000, cefazolin had a 68% chance of being cost-effective compared with ASPs. In cost-effectiveness acceptability curves, the cefazolin strategy was cost-effective in 73.5%–81.8% of simulations compared with ASP for a willingness-to-pay ranging up to $50 000. Conclusions The use of cefazolin is a cost-effective strategy for the treatment of MSSA bacteremia and, when clinically appropriate, this strategy results in considerable health care cost-savings.

We aimed to study the changing popularity of oral anticoagulants and the potential association between media coverage and real-world utilization practice, using time series analysis.In this STROBE-compliant study, we used Google Trends data to study public interest for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, and edoxaban) and warfarin in the United States (10-year coverage, beginning July 1st, 2008 ending June 30th, 2018). We validated our findings on a sample of 50 consecutive datasets (accumulated between July 6th, 2018 and October 19th, 2018), using the same search criteria. We used the LexisNexis Academic database to quantify monthly media coverage for DOACs and explored its association with interest by the public, using the cross-correlation coefficient function. Finally, we studied the association between public interest and real-world utilization data, including published US-wide data on ambulatory anticoagulation visits.The approval of dabigatran in 2010 marked an increasing public interest for DOACs. Dabigatran exhibited a steep rise early after Food and Drug Administration approval that peaks in 2011, to be surpassed sequentially by rivaroxaban (2012) and apixaban (2014). Apixaban has outperformed its competitors in popularity since mid-2017, and, by the end of the observation period, was close to warfarin that is on first place. Media coverage was low before approval of the first oral DOAC (dabigatran), increased thereafter (median 13 news articles per month vs 64, P < .001), with peaks on the approval dates (81 vs 48, P = .003). Media coverage had a weak immediate impact on DOACs public interest and public interest patterns preceded changes in ambulatory anticoagulation visits by up to 5 months.For a long-run observation period, a single Google Trends search will suffice to produce robust estimations of the relative popularity between treatment options, such as oral anticoagulants. Media coverage has limited immediate impact and relative public interest is a potential lead indicator of changes in actual utilization.

SUMMARY Bloodstream infections are associated with considerable morbidity and health care costs. Molecular rapid diagnostic tests (mRDTs) are a promising complement to conventional laboratory methods for the diagnosis of bloodstream infections and may reduce the time to effective therapy among patients with bloodstream infections. The concurrent implementation of antimicrobial stewardship programs (ASPs) may reinforce these benefits. The aim of this study was to evaluate the cost-effectivenesses of competing strategies for the diagnosis of bloodstream infection alone or combined with an ASP. To this effect, we constructed a decision-analytic model comparing 12 strategies for the diagnosis of bloodstream infection. The main arms compared the use of mRDT and conventional laboratory methods with or without an ASP. The baseline strategy used as the standard was the use of conventional laboratory methods without an ASP, and our decision-analytic model assessed the cost-effectivenesses of 5 principal strategies: mRDT (with and without an ASP), mRDT with an ASP, mRDT without an ASP, conventional laboratory methods with an ASP, and conventional laboratory methods without an ASP. Furthermore, based on the availability of data in the literature, we assessed the cost-effectivenesses of 7 mRDT subcategories, as follows: PCR with an ASP, matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) analysis with an ASP, peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with an ASP, a blood culture nanotechnology microarray system for Gram-negative bacteria (BC-GP) with an ASP, a blood culture nanotechnology microarray system for Gram-positive bacteria (BC-GN) with an ASP, PCR without an ASP, and PNA-FISH without an ASP. Our patient population consisted of adult inpatients in U.S. hospitals with suspected bloodstream infection. The time horizon of the model was the projected life expectancy of the patients. In a base-case analysis, cost-effectiveness was determined by calculating the numbers of bloodstream infection deaths averted, the numbers of quality-adjusted life years gained, and incremental cost-effectiveness ratios (ICERs). In a probabilistic analysis, uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. In the base-case analysis, MALDI-TOF analysis with an ASP was the most cost-effective strategy, resulting in savings of $29,205 per quality-adjusted life year and preventing 1 death per 14 patients with suspected bloodstream infection tested compared to conventional laboratory methods without an ASP (ICER, −$29,205/quality-adjusted life year). BC-GN with an ASP (ICER, −$23,587/quality-adjusted life year), PCR with an ASP (ICER, −$19,833/quality-adjusted life year), and PCR without an ASP (ICER, −$21,039/quality-adjusted life year) were other cost-effective options. In the probabilistic analysis, mRDT was dominant and cost-effective in 85.1% of simulations. Importantly, mRDT with an ASP had an 80.0% chance of being cost-effective, while mRDT without an ASP had only a 41.1% chance. In conclusion, our findings suggest that mRDTs are cost-effective for the diagnosis of patients with suspected bloodstream infection and can reduce health care expenditures. Notably, the combination of mRDT and an ASP can result in substantial health care savings.

Background Antimicrobial lock solutions are a low-cost strategy that can reduce the incidence of central line-associated bloodstream infection (CLABSI). The aim of this study was to evaluate the cost-effectiveness of antimicrobial locks for the prevention of CLABSI. Methods We constructed a decision-analytic model comparing antimicrobial lock solutions to heparin locks for the prevention of CLABSI in 3 settings: hemodialysis, cancer treatment, and home parenteral nutrition. Cost-effectiveness was determined by calculating CLABSIs prevented and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Results In probabilistic analysis, at a willingness to pay of $50000, antimicrobial lock solutions had a 96.24% chance of being cost-effective, compared with heparin locks in the hemodialysis setting, an 88.00% chance in the cancer treatment setting, and a 92.73% chance in the home parenteral nutrition setting. In base-case analysis, antimicrobial lock solutions resulted in savings of $68721.03 for the hemodialysis setting, $85061.41 for the cancer setting, and $78513.83 for the home parenteral nutrition setting per CLABSI episode prevented. Conclusions In 3 distinct and clinically important settings (hemodialysis, cancer treatment, and home parenteral nutrition), antimicrobial lock solutions are an effective strategy for the prevention of CLABSI, and their use can result in significant healthcare savings.

Sjogren's syndrome (SS) patients manifest high cell-free DNA (cf-DNA) levels in serum, associated with impaired DNaseI activity. Undegraded DNA may accumulate in tissues and act as an inflammasome-activating signal. Herein, we investigated the occurrence of aberrant DNA build-up in various biologic compartments of SS patients and its correlation with the activity of NLRP3 and AIM2 inflammasomes. For this purpose, we evaluated sera, PBMC, circulating monocytes and salivary glands (SG) from different SS patient subgroups and controls. We found that SS patients at high risk for lymphoma and those with established lymphoma display high serum cf-DNA levels, substantial extranuclear DNA accumulations in PBMC and SG tissues, a unique NLRP3 inflammasome gene signature in PBMC, and significantly increased serum IL-18 and ASC levels. In these patients, the circulating monocytes manifested NLRP3 inflammasome activation and increased response to NLRP3 stimuli, whereas SG-infiltrating macrophages exhibited signs of NLRP3 activation and pyroptosis. Cell-free nucleic acids isolated from patients' sera competently primed the activation of both NLRP3 and AIM2 inflammasomes in healthy monocytes. SS patients also manifested diminished DNaseI activity in serum and DNaseII expression in PBMC, which inversely correlated with indices of inflammasome activation. DNaseII gene-silencing in healthy monocytes led to cytoplasmic DNA deposition and activation of inflammasome-related genes and of caspase1. Our data reveal the occurrence of systemic NLRP3 inflammasome activation in severe SS, which is associated with widespread extranuclear accumulations of inflammagenic DNA and impaired DNA degradation. These findings can provide novel biomarkers and new therapeutic targets for the management of SS patients with adverse outcomes.

OBJECT The authors performed a prospective study to define the prevalence and microbiological characteristics of infections in patients undergoing craniotomy and to clarify the risk factors for post-craniotomy meningitis. METHODS Patients older than 18 years who underwent nonstereotactic craniotomies between January 2006 and December 2008 were included. Demographic, clinical, laboratory, and microbiological data were systemically recorded. Patient characteristics, craniotomy type, and pre- and postoperative variables were evaluated as risk factors for meningitis RESULTS Three hundred thirty-four procedures were analyzed (65.6% involving male patients). Traumatic brain injury was the most common reason for craniotomy. Almost 40% of the patients developed at least 1 infection. Ventilatorassociated pneumonia (VAP) was the most common infection recorded (22.5%) and Acinetobacter spp. were isolated in 44% of the cases. Meningitis was encountered in 16 procedures (4.8%), and CSF cultures were positive for microbial growth in 100% of these cases. Gram-negative pathogens (Acinetobacter spp., Klebsiella spp., Pseudomonas aeruginosa, Enterobacter cloaceae, Proteus mirabilis) represented 88% of the pathogens. Acinetobacter and Klebsiella spp. demonstrated a high percentage of resistance in several antibiotic classes. In multivariate analysis, the risk for meningitis was independently associated with perioperative steroid use (OR 11.55, p = 0.005), CSF leak (OR 48.03, p < 0.001), and ventricular drainage (OR 70.52, p < 0.001). CONCLUSIONS Device-related postoperative communication between the CSF and the environment, CSF leak, and perioperative steroid use were defined as risk factors for meningitis in this study. Ventilator-associated pneumonia was the most common infection overall. The offending pathogens presented a high level of resistance to several antibiotics.

Objectives:ICUs are a major reservoir of methicillin-resistant Staphylococcus aureus. Our aim was to estimate costs and effectiveness of methicillin-resistant Staphylococcus aureus prevention policies.Design and Interventions:We evaluated three up-to-date methicillin-resistant Staphylococcus aureus

Local thermal ablation may extend the scope of palliative therapy in patients with colorectal liver metastasis. We performed a retrospective, case-controlled study to compare patients with colorectal liver metastases that were treated with percutaneous radiofrequency (RF) or microwave (MW) thermal ablation, against the control group of chemotherapy alone.We described baseline demographics, ablation sessions, procedure duration and related complications. We compared outcomes of percutaneous thermal ablation versus chemotherapy alone (controls) in patients with colorectal liver metastasis. The control group assigned (non-ablated patients) had similar demographics and prior treatment profile when compared to ablated patients. Progression-free survival (PFS) and overall survival (OS) were estimated for the two groups.Twenty-eight cases with 57 baseline hepatic lesions (median age 68 years; male to female ratio 2:1) were evaluated and compared with 48 controls. A total of 55 sessions (52 RF, 3 MW) were performed among the cases, with minimal procedural time (median 8 min), zero mortality and no severe complications (3 cases of local hepatic hematoma not requiring hospitalization). Ablated patients had prolonged median PFS (19.4 months) and OS (27.5 months) when compared against controls (14.0 and 21.4 months, respectively). After adjusting for hepatic involvement, PFS estimates were comparable and OS was better for the ablated group. One and 2-year survival estimates were 0.96 and 0.79 for thermal ablation patients compared with 0.82 and 0.52 for controls (p=0.05 and p=0.07, respectively).Percutaneous thermal ablation may delay progression and death in colorectal cancer patients with metastatic liver disease.

Low-affinity variants FcγRIIIa-V158F and FcγRIIa- H131R may alter response to rituximab-based chemotherapy in diffuse large B-cell lymphoma (DLBCL) but available clinical evidence is inconclusive. Our purpose was to explore their association in terms of treatment response.We performed a meta-analysis of published literature to associate these variants with complete remission after upfront immunochemotherapy in DLBCL, and summarized the genetic risk using the model-free approach of generalized odds ratio (ORFcγRIIa-H131R was associated with an inferior response to treatment (ORFcγRIIa-H131R but not FcγRIIIa-V158F may modify treatment response in DLBCL.

Hematopoietic stem cell transplant (HSCT) recipients are at high risk of contracting Clostridium difficile infection (CDI). We systematically searched the PubMed and EMBASE databases through March 2014 and performed a random-effects meta-analysis to estimate the prevalence and trends of CDI over time. Among 48 eligible articles that included 12,025 patients at risk, we estimated that 7.9% (95% confidence interval [CI], 6.5% to 9.5%) of HSCT patients are diagnosed with CDI during the peri-transplantation and late post-transplantation periods, an estimation that is relatively consistent across studies (τ2 = .032). Prevalence of CDI is significantly higher among the 5120 allogeneic patients (9.3% [95% CI, 7.0% to 11.9%]), compared with the 4665 autologous patients (5.2% [95% CI, 3.8% to 6.9%]) (P = .02), and as many as 1 of 10 allogeneic transplant recipients are expected to be diagnosed with CDI compared with 1 of 20 autologous transplantation patients. However, this difference did not reach statistical significance when stratified data from the same centers were examined (P = .11). Importantly, we found an increasing trend of CDI diagnosis both worldwide (P = .02) and across studies conducted in North America (P = .03) over the last 34 years. Notably, studies with a follow-up period that extended through the late post-transplantation period (after day +100) had a similar prevalence of CDI as those that followed patients only during the peri-transplantation period (up to day +100) (P = .94). In summary, CDI is common in the hematopoietic transplantation setting and the majority of infections occur in the peri-transplantation period. The prevalence is almost 9-times higher than that reported among all hospital stays, with an increasing trend over time.

Image-guided radiofrequency ablation is a well-accepted technique of interventional oncology in adults. To evaluate the efficacy and safety of CT-guided radiofrequency ablation as a minimally invasive treatment for metastatic neoplasms in children. A total of 15 radiofrequency ablation sessions were performed in 12 children and young adults (median age 9.5; range 5–18 years) with metastatic malignancies. Seven children and young adults had secondary hepatic lesions, three had pulmonary and two had bone lesions. Radiofrequency ablation was performed under conscious sedation. The median lesion size was 1.7 cm (range 1.3–2.8 cm). The median time for ablation was 8 min (range 7–10 min). Radiofrequency procedures were technically successful in all tumors. Postablation imaging immediately after, and 1 month and 3 months after radiofrequency ablation showed total necrosis in all patients. At 6-month follow-up, three patients (all with lesion size >2 cm) had local recurrence and underwent a second radiofrequency ablation session. At 2-year follow-up no patient had recurrence of the treated tumor. Post-ablation syndrome occurred in four children. No major complication occurred. CT-guided radiofrequency tumor ablation was safe and efficient for palliative treatment in our cohort of patients.

BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of morbidity and mortality in NICUs and PICUs. Our objective was to assess the burden of MRSA colonization on admission, study the time trends, and examine the significance of MRSA colonization in this population. METHODS: PubMed and Embase databases were consulted. Studies that reported prevalence of MRSA colonization on ICU admission were selected. Two authors independently extracted data on MRSA colonization and infection. RESULTS: We identified 18 suitable articles and found an overall prevalence of MRSA colonization of 1.9% (95% confidence interval [CI] 1.3%–2.6%) on admission to the NICU or PICU, with a stable trend over the past 12 years. Interestingly, 5.8% (95% CI 1.9%–11.4%) of outborn neonates were colonized with MRSA on admission to NICU, compared with just 0.2% (95% CI 0.0%–0.9%) of inborn neonates (P = .01). The pooled acquisition rate of MRSA colonization was 4.1% (95% CI 1.2%–8.6%) during the NICU and PICU stay and was as high as 6.1% (95% CI 2.8%–10.6%) when the NICU population was studied alone. There was a relative risk of 24.2 (95% CI 8.9–66.0) for colonized patients to develop a MRSA infection during hospitalization. CONCLUSIONS: In the NICU and PICU, there are carriers of MRSA on admission, and MRSA colonization in the NICU is almost exclusively associated with outborn neonates. Importantly, despite infection control measures, the acquisition rate is high, and patients colonized with MRSA on admission are more likely to suffer a MRSA infection during hospitalization.

Objective. Biologic agents are increasingly used to treat patients with rheumatoid arthritis (RA). We aimed to review their association with opportunistic infections (OIs), including fungal, viral (with a focus on herpesvirus-related infections), tuberculosis and other mycobacterial infections. Methods. We searched PubMed and EMBASE through June 24, 2013, and complemented the search with the reference lists of eligible articles. The analysis included randomized trials on RA that compared any approved biologic agent with controls and reported the risk of OIs. Results. A total of 70 trials that included 32 504 patients (21 916 patients receiving biologic agents and 10 588 receiving placebo) were deemed eligible. Biologic agents increased the risk of OIs (pooled Peto odds ratio [OR], 1.79; 95% confidence interval [CI], 1.17–2.74; I 2 = 3%), resulting in 1.7 excess infections per 1000 patientstreated (number needed to harm, 582). A significant risk was noted for mycobacterial (OR, 3.73; 95% CI, 1.72–8.13; I 2 = 0), and viral (OR, 1.91; 95% CI, 1.02–3.58; I 2 = 0) infections. Interestingly, no significant differences were found for invasive and superficial fungal infections (1.31; 95% CI, .46–3.72), invasive fungal infections (2.85; .68–11.91), P. jirovecii pneumonia (1.77; .42–7.47), varicella-zoster virus (1.51; .71–3.22), as well as overall mortality attributed to OIs (1.91; .29– 12.64). Conclusions. Among patients with RA, biologic agents are associated with a small but significant risk of specific OIs. This increase is associated with mycobacterial diseases and does not seem to affect overall mortality. Because OIs are a relatively rare complication of biologic agents, large registries are needed to identify the exact effect in different OIs and to compare the different biologic agents.

To estimate the prevalence and significance of nasal methicillin-resistant Staphylococcus aureus colonization in the ICU and its predictive value for development of methicillin-resistant S. aureus infection.MEDLINE and EMBASE and reference lists of all eligible articles.Studies providing raw data on nasal methicillin-resistant S. aureus colonization at ICU admission, published up to February 2013. Analyses were restricted in the general ICU setting. Medical, surgical, and interdisciplinary ICUs were eligible. ICU studies referring solely on highly specialized ICUs populations and reports on methicillin-resistant S. aureus outbreaks were excluded.Two authors independently assessed study eligibility and extrapolated data in a blinded fashion. The two outcomes of interest were the prevalence estimate of methicillin-resistant S. aureus nasal colonization at admission in the ICU and the sensitivity/specificity of colonization in predicting methicillin-resistant S. aureus-associated infections.Meta-analysis, using a random-effect model, and meta-regression were performed. Pooled data extracted from 63,740 evaluable ICU patients provided an estimated prevalence of methicillin-resistant S. aureus nasal colonization at admission of 7.0% (95% CI, 5.8-8.3). Prevalence was higher for North American studies (8.9%; 95% CI, 7.1-10.7) and for patients screened using polymerase chain reaction (14.0%; 95% CI, 9.6-19). A significant per year increase in methicillin-resistant S. aureus colonization was also noted. In 17,738 evaluable patients, methicillin-resistant S. aureus infections (4.1%; 95% CI, 2.0-6.8) developed in 589 patients. The relative risk for colonized patients was 8.33 (95% CI, 3.61-19.20). Methicillin-resistant S. aureus nasal carriage had a high specificity (0.96; 95% CI, 0.90-0.98) but low sensitivity (0.32; 95% CI, 0.20-0.48) to predict methicillin-resistant S. aureus-associated infections, with corresponding positive and negative predictive values at 0.25 (95% CI, 0.11-0.39) and 0.97 (95% CI, 0.83-1.00), respectively.Among ICU patients, 5.8-8.3% of patients are colonized by methicillin-resistant S. aureus at admission, with a significant upward trend. Methicillin-resistant S. aureus colonization is associated with a more than eight-fold increase in the risk of associated infections during ICU stay, and methicillin-resistant S. aureus infection develops in one fourth of patients who are colonized with methicillin-resistant S. aureus at admission to the ICU.

Supplemental Digital Content is available in the text, The elderly population is particularly vulnerable to Clostridium difficile infection (CDI), but the epidemiology of CDI in long-term care facilities (LTCFs) is unknown. We performed a retrospective cohort study and used US 2011 LTCF resident data from the Minimum Data Set 3.0 linked to Medicare claims. We extracted CDI cases based on International Classification of Diseases-9 coding, and compared residents with the diagnosis of CDI to those who did not have a CDI diagnosis during their LTCF stay. We estimated CDI prevalence rates and calculated 3-month mortality rates. The study population consisted of 2,190,613 admissions (median age 82 years; interquartile range 76–88; female to male ratio 2:1; >80% whites), 45,500 of whom had a CDI diagnosis. The nationwide CDI prevalence rate was 1.85 per 100 LTCF admissions (95% confidence interval [CI] 1.83–1.87). The CDI rate was lower in the South (1.54%; 95% CI 1.51–1.57) and higher in the Northeast (2.29%; 95% CI 2.25–2.33). Older age, white race, presence of a feeding tube, unhealed pressure ulcers, end-stage renal disease, cirrhosis, bowel incontinence, prior tracheostomy, chemotherapy, and chronic obstructive pulmonary disease were independently related to “high risk” for CDI. Residents with a CDI diagnosis were more likely to be admitted to an acute care hospital (40% vs 31%, P

Context: Scanty reports have focused on FDG-PET after radiofrequency ablation (RFA), for recurrence of hepatic metastases. Objective: To assess FDG-PET diagnostic accuracy on detection of recurrent hepatic lesions. Methods: After a comprehensive search of PubMed and EMBASE, we performed a patient-based diagnostic meta-analysis of post-RFA FDG-PET. Results: Across nine included articles, independent, random-effects sensitivity and specificity were 0.73(0.50–0.88) and 0.85(0.72–0.93), respectively. A symmetrical SROC curve was produced with no significant heterogeneity. Specificity was optimal for surgical RFA and colorectal origin of metastases. Conclusion: Synthesis of published evidence suggests PET/CT as an appropriate tool for optimizing post-ablation follow-up.

Objective.To describe morbidity, organ damage, mortality, and cause of death in patients with antiphospholipid syndrome (APS).Methods.Descriptive analysis of 135 patients. Patients were clustered according to initial event: arterial thrombosis including stroke (AT; n = 46), venous thrombosis including pulmonary emboli (VT; n = 53), or pregnancy morbidity (PM; n = 36). Disease progression according to initial event and prevalence of organ damage was observed.Results.APS occurs among young individuals (mean age 33.3 ± 11.9 yrs). One-third of the patients have APS secondary to systemic lupus erythematosus (SLE) or SLE-like disease. A broad spectrum of clinical manifestations mark the disease onset even before diagnosis. The pattern of initial presentation is preserved with regard to second event; VT is followed by VT (84%), AT is followed by AT (95%), and PM is followed by PM (88.9%). The highest morbidity is attributed to neurologic damage. PM is more likely to be followed by a second event, yet is associated with less organ damage than AT and VT. After a mean followup of 7.55 years, 29% of patients experienced organ damage and 5 died, with Systemic Lupus International Collaborating Clinics score associated with increased mortality (HR 1.31, 95% CI 1.07–1.60, p = 0.01, per 1-unit increase); hematological malignancies occurred in 2 patients after a cumulative followup of 1020 person-years. Coexistent SLE adds significant damage in patients with APS.Conclusion.APS is a disease of young individuals, who experience increased morbidity. Neurologic damage is the most common cause of morbidity. AT at presentation as well as coexistent SLE are associated with poor outcome.

Supplemental Digital Content is available in the text, Clinical guidelines play a central role in day-to-day practice. We assessed the degree of incorporation of cost analyses to guidelines and identified modifiable characteristics that could affect the level of incorporation. We selected the 100 most cited guidelines listed on the National Guideline Clearinghouse (http://www.guideline.gov) and determined the number of guidelines that used cost analyses in their reasoning and the overall percentage of incorporation of relevant cost analyses available in PubMed. Differences between medical specialties were also studied. Then, we performed a case–control study using incorporated and not incorporated cost analyses after 1:1 matching by study subject and compared them by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement requirements and other criteria. We found that 57% of guidelines do not use any cost justification. Guidelines incorporate a weighted average of 6.0% (95% confidence interval [CI] 4.3–7.9) among 3396 available cost analyses, with cardiology and infectious diseases guidelines incorporating 10.8% (95% CI 5.3–18.1) and 9.9% (95% CI 3.9– 18.2), respectively, and hematology/oncology and urology guidelines incorporating 4.5% (95% CI 1.6–8.6) and 1.6% (95% CI 0.4–3.5), respectively. Based on the CHEERS requirements, the mean number of items reported by the 148 incorporated cost analyses was 18.6 (SD = 3.7), a small but significant difference over controls (17.8 items; P = 0.02). Included analyses were also more likely to directly relate cost reductions to healthcare outcomes (92.6% vs 81.1%, P = 0.004) and declare the funding source (72.3% vs 53.4%, P

Granulocyte-colony-stimulating factors are helpful for the support of patients receiving autologous hematopoietic stem cell transplantation, resulting in faster neutrophil recovery and lower incidence of febrile neutropenia (FN). Our aim was to evaluate the use of pegfilgrastim vs. filgrastim with regard to absolute neutrophil count (ANC) recovery, risk, and duration of FN and length of hospital stay. Mean difference was the summary effect for continuous data, and odds ratio for binary data, using random-effects modeling. MEDLINE, EMBASE, and the Cochrane Registry of Randomized Controlled Trials were included in the search. Randomized controlled trials (RCTs), case-control studies, and studies with historical control group for filgrastim were eligible. Of the initial 114 studies screened, 12 studies were analyzed (four were RCTs, including one phase III trial). The use of pegfilgrastim resulted in a one d gain in ANC recovery (mean difference -0.82, 95% CI -1.07 to -0.57, p < 0.001) and duration of FN (-0.67, 95% CI -1.28 to -0.06, p < 0.001) but had no effect on the risk of FN or length of stay. Pegfilgrastim was more expensive (baseline marginal cost €116.97, p < 0.001), which was largely determined by the treatment duration and pegfilgrastim cost. Non-randomized setting attenuated the effect on duration of FN whereas delayed onset of filgrastim injections (to pegfilgrastim) overestimated the protective effect on the risk of FN. Both drugs are at least equally effective, though methodology and disease stratification in published trials warrant further improvement.

Fluconazole is the first line of therapy for the management of candidiasis. However, fluconazole-resistant strains pose an emerging challenge in everyday clinical practice. In this study, we sought to determine whether cumulative length of hospital stay (CLOS) is a predictive factor for the acquisition of non-susceptible Candida strains to fluconazole. Thirty-three critically ill emergency surgery patients with 56 Candida isolates were enrolled in this prospective study. We divided our isolates according to their minimum inhibitory concentration (MIC) to fluconazole using 8 mcg/ml as a cutoff. We then compared the two groups with respect to basic demographics, antifungal agents prescribed, number of wide-spectrum antibiotics, duration of central venous catheter placement, elapsed time to positive culture, duration of prior hospital stay, and length of hospital stay. Non-susceptible fluconazole samples belonged to patients with a significantly longer prior hospital stay and a longer CLOS (P = 0.02 and 0.01, respectively). The difference between the 2 groups regarding non-albicans strains was statistically significant (P

In a previous retrospective study we have shown that circulating antibodies to endogenous erythropoietin (anti-EPO) are associated with HIV-1-related anemia. The present longitudinal cohort study was conducted to examine the effect of anti-EPO on the risk of developing anemia over time.The study population consisted of 113 HIV-1 seropositive patients, who were screened for the presence of anti-EPO, with a mean+/-SD follow up of 105+/-40 months, for a total of 2190 visits. Anti-EPO were detected with an ELISA assay.Anti-EPO were detected in 41% (46/113) at enrollment and 29% (320/1094) for all visits, and were associated with higher EPO levels for all visits (45.7+/-60.4 vs. 31.8+/-31.7 IU/ml, p0.001). After adjusting for other significant confounders, anti-EPO has been associated with increased risk of anemia both at enrollment (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.25-20.49) as well as for all visits ([OR], 2.15; 95% [CI]: 1.29-3.56). During follow up, a decline in prevalence of both anti-EPO and anemia was observed as the percentage of patients receiving HAART was increasing.Anti-EPO are an independent risk factor for anemia in HIV-1-infected patients. HAART seems to reduce both anti-EPO and anemia prevalence.

The predictive value of 18F-FDG PET in patients with relapsing/refractory lymphoma who are receiving high-dose chemotherapy and autologous stem cell transplantation (ASCT) remains a matter of debate. Seminal reports on pretransplant ASCT indicated an adverse prognosis in patients with positive FDG PET scans. The lack of a uniform outcome measure along with the mixed histologies in various studies have hampered efforts to quantify this prognostic value. A MEDLINE review of published trials up to April 2009 identified 16 studies involving pretransplant FDG PET scans in lymphoma. Where progression-free survival (PFS) and overall survival (OS) were set as the main outcome measures, time-to-event data analysis was used to calculate the overall prognostic value of a pretransplant FDG-PET scan. Pooled survival data from seven eligible studies suggested a worse PFS in patients with a positive FDG PET study (HR 3.23, 95% CI 2.14 to 4.87). The OS pooled from six eligible studies was also significantly worse among patients with a positive FDG PET study (HR 4.53, 95% CI 2.50 to 8.22). No statistically significant heterogeneity was observed between studies for either outcome. Despite the documented clinical heterogeneity between studies, meta-analysis data confirmed the prognostic impact of pretransplant FDG PET in patients with lymphoma and provided a uniform measure of the association for both progression and survival after ASCT.

Thrombocytopenia in Systemic Lupus Erythematosus is a common clinical manifestation affecting up to one third of patients in published cohorts. Antiplatelet antibodies, antithrombopoietin antibodies and faulty hemopoiesis have been implicated among other immunologic and non-immunologic causes. This mini review is an uptodate summary of these immunologic phenomena.

Objective To evaluate the expression profile of infiltrating macrophages and dendritic cells (DCs) as well as of interleukin-18 (IL-18) and IL-12 in the minor salivary gland (MSG) lesions of patients with Sjogren's syndrome (SS), and to assess the relationship of these factors with disease parameters. Methods Macrophages, DCs, T cells, B cells, proIL-18, mature IL-18, and IL-12 were detected by single- and double-labeling immunohistochemistry in MSG specimens from 21 patients with primary SS (13 of 21 tested for IL-12), 7 patients with secondary SS, and 9 disease control patients. Expression profiles were assessed for correlations with various disease parameters, including adverse predictors of lymphoma development. Results MSGs from patients with SS (but not from disease controls) manifested increased infiltration by macrophages and DCs, strong expression of IL-18 by macrophages (particularly in B cell–rich areas and in germinal center–like structures in primary SS), and expression of IL-12 by mononuclear cell infiltrates. In primary SS, high infiltration by macrophages correlated with SG enlargement (P = 0.01). The DC infiltration rate correlated positively with the macrophage infiltration rate (P = 0.04), occurrence of SG enlargement (P = 0.03), and presence of C4 hypocomplementemia (P = 0.05), and inversely with serum C4 complement levels (P = 0.001). The rate of infiltration by IL-18–expressing cells correlated positively with biopsy focus scores (P < 0.001), larger infiltrates of macrophages (P = 0.01), DCs (P = 0.01), and B cells (P = 0.02), and SG enlargement (P = 0.02), and negatively with serum C4 complement levels (P = 0.02). The rate of infiltration by IL-12–expressing cells correlated inversely with that by IL-18–expressing cells (P = 0.001), biopsy focus scores (P = 0.003), and SG enlargement (P = 0.01), and positively with serum C4 complement levels (P = 0.05). Conclusion In patients with primary SS, infiltration of the SG by macrophages and DCs and expression of IL-18 and IL-12 appear to play active roles in the expansion and organization of infiltrative injuries and have a correlation with certain predictors of lymphoma development.

Several factors including antibiotic use, immunosuppression and frequent hospitalizations make solid organ transplant (SOT) recipients vulnerable to Clostridium difficile infection (CDI). We conducted a meta-analysis of published studies from 1991-2014 to estimate the prevalence of CDI in this patient population. We searched PubMed, EMBASE and Google Scholar databases. Among the 75,940 retrieved citations, we found 30 studies coded from 35 articles that were relevant to our study. Based on these studies, we estimated the prevalence of CDI among 21,683 patients who underwent transplantation of kidney, liver, lungs, heart, pancreas, intestine or more than one organ and stratified each study based on the type of transplanted organ, place of the study conduction, and size of patient population. The overall estimated prevalence in SOT recipients was 7.4% [95%CI, (5.6-9.5%)] and it varied based on the type of organ transplant. The prevalence was 12.7% [95%CI, (6.4%-20.9%)] among patients who underwent transplantation for more than one organ. The prevalence among other SOT recipients was: lung 10.8% [95% CI, (5.5%-17.7%)], liver 9.1 % [95%CI, (5.8%-13.2%)], intestine 8% [95% CI, (2.6%-15.9%)], heart 5.2% [95%CI, (1.8%-10.2%)], kidney 4.7% [95% CI, (2.6%-7.3%)], and pancreas 3.2% [95% CI, (0.5%-7.9%)]. Among the studies that reported relevant data, the estimated prevalence of severe CDI was 5.3% [95% CI (2.3%-9.3%)] and the overall recurrence rate was 19.7% [95% CI, (13.7%-26.6%)]. In summary, CDI is a significant complication after SOT and preventive strategies are important in order to reduce the CDI related morbidity and mortality.

Background Autophagy and regulation of IL-23 signaling pathways have been implicated in the pathogenesis of Crohn's disease (CD). We studied the mode of inheritance and reviewed the association of 2 polymorphic variants of ATG16L1 and IL23R with CD. Methods We searched the PubMed and ISI Web of Science databases (up to May 2014) for pertinent articles. We included all studies that had a case-control design, with cases having CD and controls being healthy and reported full genotype frequencies for the ATG16L1 and/or IL23R variant of interest. We quantified the relative genetic risk using the model-free approach of the generalized odds ratio metric (ORG) and reported 95% precision estimates. Also, we explored the mode of inheritance using the degree of dominance h-index. Results Fifty-one studies fulfilled these requirements and were included in the analysis. These studies involved 12,762 patients and 16,735 controls evaluating the association of ATG16L1 (rs2241880 p.Thr300Ala) and 8110 patients and 11,900 controls evaluating the association of IL23R (rs11209026 p.Arg381Gln) with CD. The ATG16L1 variant rs2241880 was associated with increased susceptibility to CD (combined ORG = 1.38; 95% confidence interval, 1.29-1.48) and a nondominant mode of inheritance (suggesting that the effect of heterozygosity lies exactly in the middle of extreme homozygotes, h = 0). The IL23R variant rs11209026 was associated with significant protection (ORG = 0.46; 95% confidence interval, 0.41-0.53) and a recessive mode of inheritance, indicating that the effect of a heterozygous genotype would lie close to the wild-type homozygous genotype. In subgroup analysis, the significant effects persisted across Caucasian ancestry studies and pediatric populations but were lacking across studies in Asian populations. Conclusions The ATG16L1 variant rs2241880 was associated with 38% increase in the risk for CD for higher mutational load, whereas IL23R variant rs11209026 decreased the risk by 54% for higher mutational load. The mode of inheritance for ATG16L1 variant demonstrated perfect additivity for genetic risk, whereas it showed recessiveness for the IL23R variant. This analysis permits risk stratification for CD based on the mutational status and highlight the need for additional studies in certain populations.

BackgroundThe impact of Clostridium difficile colonization in C. difficile infection (CDI) is inadequately explored. As a result, asymptomatic carriage is not considered in the development of infection control policies and the burden of carrier state in long-term care facilities (LTCFs) is unknown.PurposeTo explore the epidemiology of C. difficile colonization in LTCFs, identify predisposing factors and describe its impact on healthcare management.Data sourcesPubMed, Embase and Web of Science (up to June 2014) without language restriction, complemented by reference lists of eligible studies.Study selectionAll studies providing extractable data on the prevalence of toxigenic C. difficile colonization among asymptomatic residents in LTCFs.Data extractionTwo authors extracted data independently.Statistical methodsThe pooled colonization estimates were calculated using the double arcsine methodology and reported along with their 95% random-effects confidence intervals (CIs), using DerSimonian-Laird weights. We assessed the impact of patient-level covariates on the risk of colonization and effects were reported as odds ratios (OR, 95% CI). We used the colonization estimates to simulate the effective reproduction number R through a Monte Carlo technique.ResultsBased on data from 9 eligible studies that met the specified criteria and included 1,371 subjects, we found that 14.8% (95%CI 7.6%-24.0%) of LTCF residents are asymptomatic carriers of toxigenic C. difficile. Colonization estimates were significantly higher in facilities with prior CDI outbreak (30.1% vs. 6.5%, p = 0.01). Patient history of CDI (OR 6.07; 95% CI 2.06-17.88; effect derived from 3 studies), prior hospitalization (OR 2.11; 95% CI 1.08-4.13; derived from 3 studies) and antimicrobial use within previous 3 months (OR 3.68; 95% CI 2.04-6.62; derived from 4 studies) were associated with colonization. The predicted colonization rate at admission was 8.9%.ConclusionAsymptomatic carriage of toxigenic C. difficile represents a significant burden in LTCFs and is associated with prior CDI outbreaks in the facility, a history of CDI, prior hospitalization and antimicrobial use. These findings can impact infection control measures at LTCFs.

Thrombocytopenia in Systemic Lupus Erythematosus (SLE) is a common clinical manifestation affecting up to one third of patients in published cohorts. Anti-platelet antibodies have been implicated in its pathogenesis, as sensitized platelets interact with macrophages through the Fc receptor eliminating them from circulation. Non-specific, immunecomplex mediated platelet destruction is also implicated as are antiphospholipid syndrome, thrombotic microangiopathies and hemophagocytic syndrome. A few cases of thrombocytopenia with amegakaryocytic hypoplasia due to antibodies against c-mpl receptor have recently been identified. Pathophysiology has recently been intrigued by frequent findings of anti-thrombopoietin antibodies and faulty hemopoiesis in SLE patients with cytopenias. More specifically, histologic data has shown dysplastic changes and stromal alteration suggesting that bone marrow is a target organ in SLE. Although thrombocytopenia, per se, is a benign complication, with hemorrhagic manifestations being infrequent, it is associated with a more active disease and worse outcome: it marks a subgroup of SLE patients, having a higher risk of irreversible end-organ events throughout their disease course. These patients exhibit a predilection to a distinct pattern of damage, rendering thrombocytopenia a quantitive and qualitative marker of impending damage. Immunosuppressive therapy is required to restore normal platelet counts and treat concomitant organ involvement of other systems. Common therapeutic modalities include corticosteroids, intravenous immunoglobulin (IVIG), cytotoxic agents (mainly cyclophosphamide), immunomodulators (azathioprine) and androgens (Danazol). More recently, B-lymphocyte depletion (anti- CD20 immunotherapy) and mycofenolate mofetil have been successfully used in refractory cases with splenectomy as a last resort should other options fail.

Objective. To assess the role of thrombocytopaenia as an independent predictor of outcome in patients with systemic lupus erythematosus (SLE). Methods. This was a single-centre, retrospective, matched case-control study (1:2). Fifty consecutive Greek SLE patients were selected at random who had developed thrombocytopaenia during the disease course (cases) were compared with 100 SLE patients with no history of thrombocytopaenia, and matched for age, sex and disease duration (controls). Overall damage was assessed at the end of follow-up, using Systemic Lupus International Collaborating Clinics index. Total number of irreversible organ-damage events for both groups were recorded. Rates for specific outcomes and incidence-rate ratios (IRRs) for damage were estimated. Multivariate analysis estimating influential clinical and immunological factors for outcome, including thrombocytopaenia, was performed. Results. After 583 person-years of follow-up for cases and 1155 for controls, we found that thrombocytopaenic individuals have a higher risk for damage (IRR 1.96, 1.52–2.53) compared with their matched controls and this effect persists throughout the course of their disease. They also have a predilection to certain types of damage involving heart and kidneys. Among other significant factors associated with damage in multivariate analysis (disease activity, serositis, anti-cardiolipin antibodies, central nervous system involvement), thrombocytopaenia appears as the most influential. Conclusion. Thrombocytopaenia is a quantitive and qualitative marker of impending damage in SLE patients.

A meta-analysis of case-control studies that investigated the association between the C677T and/or A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and acute lymphoblastic leukemia (ALL) was carried out. Pooled odds ratios (OR) of various genetic contrasts of each polymorphism were estimated using random (RE) and fixed effects (FE) models. Pooled ORs for combined genotypes and haplotypes were estimated after adjustment for study effect using a log-linear model and the expectation-maximization algorithm in combination with log-linear modeling, respectively. The recessive model for allele 1298C produced a rather marginal association: RE OR: 0.67; 95% confidence interval (CI): 0.46-0.99 and FE OR: 0.64; 95% CI: 0.49-0.84. In Caucasians, the results of the recessive model for allele 1298C was consisted with a protective effect of ALL development: FE OR: 0.63; 95% CI: 0.46-0.87. In childhood ALL, according to the results of the allele contrast and the recessive model for 677T allele it was conceivable that a protective effect exist: RE OR = 0.74; 95% CI: 0.57-0.96 and RE OR: 0.69; 95% CI: 0.51-0.94, respectively. The combined genotypes produced significant pooled OR for the 677CC/1298CC relative to 677CC/1298AA (OR: 0.54; 95% CI: 0.36-0.80). The haplotype 677C/1298C might be more protective to ALL relative to haplotype 677C/1298A (OR: 0.77; 95% CI: 0.61-0.97). When studies not in Hardy-Weinberg equilibrium (HWE) were corrected to account for departures from HWE, then, the pattern of results remained the same. Overall, there is high heterogeneity between the studies in both polymorphisms. A differential magnitude of effect in large versus small studies and alteration of early extremes effects existed.

Summary Immunologically mediated thrombocytopenia is a frequent clinical manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies targeting platelet membrane glucoproteins have a central role in peripheral platelet destruction. Autoantibodies against thrombopoietin are also present in about one-third of patients, but their pathogenetic role is obscure. Thirty-eight serum samples from SLE patients were tested for anti-platelet antibodies, anti-thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow histology was also assessed. Thirty-nine per cent of sera displayed anti-thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti-thrombopoietin antibodies were associated with lower thrombopoietin concentrations, and lower mean platelet values in long-term follow-up. Anti-platelet antibodies were present in about 40% of thrombocytopenic and non-thrombocytopenic individuals but were absent in patients who had recovered from thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were absent in control sera from patients with rheumatoid arthritis and primary Sjögren’s syndrome. Decreased bone marrow cellularity, normal or low number of hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent findings in thrombocytopenic SLE patients, suggesting a defect in megakaryopoiesis. These findings were not evident in specimens from patients with idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal cellularity and absence of stromal alterations. In conclusion, peripheral destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower effective circulating thrombopoetin and impaired compensatory response due to bone marrow damage interact in SLE and thrombocytopenia ensues.

Haematological abnormalities are common in systemic lupus erythematosus. Anaemia is found in about 50% of patients, with anaemia of chronic disease being the most common form. Impaired erythropoietin response and presence of antibodies against erythropoietin may contribute to the pathogenesis of this type of anaemia. Patients with autoimmune haemolytic anaemia usually belong to a distinct category, which is associated with anticardiolipin antibodies, thrombosis, thrombocytopenia, and renal disease, often in the context of secondary antiphospholipid syndrome. Autoantibodies, T lymphocytes, and deregulation of the cytokine network can affect bone marrow erythropoiesis, leading to anaemia.