Long term predictors of breathlessness, exercise intolerance, chronic fatigue and well-being in hospitalized patients with COVID-19: A cohort study with 4 months median follow-up.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) is an emerging healthcare burden. We therefore aimed to determine predictors of different functional outcomes after hospital discharge in patients with COVID-19. METHODS: An ambidirectional cohort study was conducted between May and July 2020, in which PCR-confirmed COVID-19 patients underwent a standardized telephone assessment between 6 weeks and 6 months post discharge. We excluded patients who died, had a mental illness or failed to respond to two follow-up phone calls. The medical research council (MRC) dyspnea scale, metabolic equivalent of task (MET) score for exercise tolerance, chronic fatigability syndrome (CFS) scale and World Health Organization-five well-being index (WHO-5) for mental health were used to evaluate symptoms at follow-up. RESULTS: 375 patients were contacted and 153 failed to respond. The median timing for the follow-up assessment was 122 days (IQR, 109-158). On multivariate analyses, female gender, pre-existing lung disease, headache at presentation, intensive care unit (ICU) admission, critical COVID-19 and post-discharge ER visit were predictors of higher MRC scores at follow-up. Female gender, older age >67 years, arterial hypertension and emergency room (ER) visit were associated with lower MET exercise tolerance scores. Female gender, pre-existing lung disease, and ER visit were associated with higher risk of CFS. Age, dyslipidemia, hypertension, pre-existing lung disease and duration of symptoms were negatively associated with WHO-5 score. CONCLUSIONS: Several risk factors were associated with an increased risk of PACS. Hospitalized patients with COVID-19 who are at risk for PACS may benefit from a targeted pre-emptive follow-up and rehabilitation programs.

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis, first update.

OBJECTIVES: Cytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to update the data in a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients. METHODS: Data sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google from 8th October 2020 till 24th February 2021. Eligible studies were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. The participants were hospitalized COVID-19 patients, and intervention was tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs with a random effects model and evaluated inconsistency between studies with I2. We assessed the certainty of evidence using the GRADE approach. RESULTS: Of 1600 citations, eight RCTs and 28 cohorts were eligible. The eight RCTs had low risk of bias, and with 6311 patients they examined the effect of tocilizumab on short-term mortality; pooled RR was 0.91 (95%CI 0.78-1.07, I2 25%). Only the REMAP-CAP and RECOVERY trials, with the majority of their patients on concomitant corticosteroids, showed lower 30-day mortality with tocilizumab use: RR 0.74 (95%CI 0.59-0.93) and 0.89 (95%CI 0.81-0.97), respectively. Seven RCTs, with 5391 patients, examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.84 (95%CI 0.76-0.93), I2 0%, with a corresponding number needed to treat of 20 (95%CI 14.3-33.3). Eight RCTs, with 5340 patients, examined the effect of tocilizumab on a composite of poor outcome; pooled RR was 0.82 (95%CI 0.76-0.90, I2 3%). Data from the RCTs showed a lower risk of infections and no higher risk of serious adverse events with tocilizumab: pooled RR 0.67 (95%CI 0.45-0.99, eight RCTs) and 0.85 (95%CI 0.63-1.16, seven RCTs), respectively. Among 28 cohorts with 15 484 patients, the pooled adjusted RR for mortality was 0.53 (95%CI 0.43-0.67, I2 76%). CONCLUSIONS: Cumulative high-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized patients with severe COVID-19. Moderate-certainty evidence shows that tocilizumab reduces the risk of poor outcome and the risk of secondary infections in hospitalized COVID-19 patients. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.

Temporal Trends of Infective Endocarditis in North America From 2000 to 2017-A Systematic Review.

BACKGROUND: The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America. METHODS: A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included. RESULTS: Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%. CONCLUSIONS: The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE.

Workup and Management of Native and Prosthetic Valve Endocarditis.

Infective endocarditis (IE) is associated with significant serious adverse outcomes including death. IE usually presents with diverse clinical picture and syndromic diagnoses including heart failure, stroke, and peripheral embolization. Given variable, vague, and syndromic presentations, the diagnosis of IE may be delayed for days to weeks. Maintaining a high index of suspicion among clinicians is the key to early recognition of the disease and prompt initiation of antimicrobial therapy to prevent IE-associated mortality and morbidity. Blood culture and echocardiography remain essential tools in the diagnosis of infective endocarditis. However, advances in molecular techniques, serology testing, computed tomography scan, and nuclear medicine have led to growth in the available tools that may aid in early diagnosis of infective endocarditis. Antimicrobial agents are the mainstay of IE therapy; however, as many as 50% of endocarditis cases will undergo valve surgery, even on an urgent or emergent basis.

Indications of Surgery in Infective Endocarditis.

PURPOSE OF THE REVIEW: Infective endocarditis (IE) is a serious disease with significant morbidity and mortality. Valve surgery is fundamental in the standard of care of selected IE patients. Indeed, valve surgery can be a lifesaving procedure in critically ill endocarditis patients. Our goal from this review is to discuss the indications of surgery in IE population and international cardiac societies' guideline recommendations. RECENT FINDINGS: Though IE is an uncommon disease, its incidence is noted to be on rise in some parts of the world, and the disease is expected to continue to be a major health problem. Antimicrobials remain the mainstay of IE therapy, but as many as 50% of endocarditis patients will undergo surgical intervention. Heart failure most commonly from acute valvular insufficiency, uncontrolled and persistent infection, and recurrent embolic events are the major indications for valve surgery in IE population. Heart failure is by far the most common indication for surgery in IE patients. Despite the fact that many IE patients will require surgical interventions, most of the international societies' recommendations to perform valve surgery are based on observational studies or experts' opinion. Surgery plays a major role in the management of IE patients, and it is most commonly performed in patients with heart failure, persistent or uncontrolled infection, and recurrent emboli. Most of the current evidence supporting surgical intervention in IE patients is based on observational studies and experts' opinion. Randomized clinical trials are urgently needed to guide surgical therapy in IE.

Temporal trends in infective endocarditis epidemiology from 2007 to 2013 in Olmsted County, MN.

BACKGROUND: The aim of this study is to determine if there have been contemporary shifts in infective endocarditis (IE) epidemiology in our local population; an analysis of cases from 2007 to 2013 was conducted. METHODS: This is a population-based review of all adults (≥18 years) residing in Olmsted County, MN, with definite or possible IE using the Rochester Epidemiology Project from January 1, 2007, to December 31, 2013. RESULTS: We identified 51 cases of IE in Olmsted County, MN, between 2007 and 2013. Median age of IE cases was 68.8 years (interquartile range 55.6-76.5), and 41% were females. Age- and sex-adjusted incidence of IE was 7.4 (95% CI 5.3-9.4) cases per 100,000 person-years. From a multivariable Poisson regression model, incidence of IE did not change significantly during the study period (P = .222) but was significantly higher in males and those of older age (P < .001). The annual incidences (per 100,000 person-years) were 2.5 for Staphylococcus aureus, 1.1 for viridans group streptococci, 1.6 for Enterococcus species, and 0.8 for coagulase-negative staphylococci. Only 19.6% (10/51) of Olmsted County patients underwent valve surgery between 2007 and 2013 as compared with 44.4% (197/444) of non-Olmsted County patients treated at Mayo Clinic Rochester. CONCLUSION: In this population-based study, no significant change in the overall incidence of IE in Olmsted County, MN, between 2007 and 2013 was seen, and it was similar to that seen between 1970 and 2006. Male gender and older age were associated with increased IE risk. With a lesser extent of cases attributable to viridans group streptococcal IE compared with previous years, S aureus was the predominant pathogen in IE cases during 2007 to 2013. The relatively low valve surgery rate was disparate from that reported from large, tertiary care centers (including our own) with non-population-based cohorts, which are subject to referral bias and can influence the expected characterization of IE.

Global and regional burden of infective endocarditis, 1990-2010: a systematic review of the literature.

Infective endocarditis (IE) is a life-threatening disease associated with serious complications. The GBD 2010 (Global Burden of Disease, Injuries, and Risk Factors) study IE expert group conducted a systematic review of IE epidemiology literature to inform estimates of the burden on IE in 21 world regions in 1990 and 2010. The disease model of IE for the GBD 2010 study included IE death and 2 sequelae: stroke and valve surgery. Several medical and science databases were searched for IE epidemiology studies in GBD high-, low-, and middle-income regions published between 1980 and 2008. The epidemiologic parameters of interest were IE incidence, proportions of IE patients who developed stroke or underwent valve surgery, and case fatality. Literature searches yielded 1,975 unique papers, of which 115 published in 10 languages were included in the systematic review. Eligible studies were population-based (17%), multicenter hospital-based (11%), and single-center hospital-based studies (71%). Population-based studies were reported from only 6 world regions. Data were missing or sparse in many low- and middle-income regions. The crude incidence of IE ranged between 1.5 and 11.6 cases per 100,000 people and was reported from 10 countries. The overall mean proportion of IE patients that developed stroke was 0.158 ± 0.091, and the mean proportion of patients that underwent valve surgery was 0.324 ± 0.188. The mean case fatality risk was 0.211 ± 0.104. A systematic review for the GBD 2010 study provided IE epidemiology estimates for many world regions, but highlighted the lack of information about IE in low- and middle-income regions. More complete knowledge of the global burden of IE will require improved IE surveillance in all world regions.

Cangrelor versus clopidogrel in percutaneous coronary intervention: a systematic review and meta-analysis.

AIMS: Cangrelor is a new antiplatelet agent that has been used in percutaneous coronary intervention (PCI) with mixed results. We aimed to review the evidence on the efficacy of cangrelor in comparison to clopidogrel in reducing ischaemic endpoints at 48 hours in patients undergoing PCI in large randomised trials. METHODS AND RESULTS: In three large clinical trials involving 25,107 participants, the risk of the primary composite efficacy endpoint of death, MI and ischaemia-driven revascularisation at 48 hours, (pooled OR 0.94; 95% CI: 0.77-1.14, p=0.51, I2=68%), death from all cause (pooled OR 0.72, 95% CI: 0.36-1.43, p=0.34, I2=52%), myocardial infarction (pooled OR 0.94, 95% CI: 0.77-1.14, p=0.51, I2=68%) was not significantly different between cangrelor and clopidogrel. Likewise, severe or life-threatening bleeding was similar between cangrelor and clopidogrel (pooled OR 1.21, 95% CI: 0.70-2.12, p=0.50, I2=0%). The risk of stent thrombosis (pooled OR 0.59, 95% CI: 0.43-0.81, p=0.001, I2=0%), Q-wave myocardial infarction (pooled OR 0.53, 95% CI: 0.30-0.92, p=0.02, I2=0%) and ischaemia-driven revascularisation (pooled OR 0.71, 95% CI: 0.52-0.98, p=0.04, I2=0%) was lower in the cangrelor group. CONCLUSIONS: Based on this meta-analysis, we did not find any difference in the risk of the primary composite efficacy endpoint of all-cause death, ischaemia-driven revascularisation, and myocardial infarction at 48hours between cangrelor and clopidogrel use. Given that cangrelor was associated with a lower risk of stent thrombosis, ischaemia-driven revascularisation and Q-wave myocardial infarction compared to clopidogrel, cangrelor can be considered as a suitable alternative during PCI.

Temporal trends in the incidence of surgical site infections in patients undergoing coronary artery bypass graft surgery: a population-based cohort study, 1993 to 2008.

OBJECTIVE: To determine the incidence of and temporal trends in surgical site infections (SSIs) in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: A population-based cohort study was conducted to describe the epidemiologic features of SSI in Olmsted County, Minnesota, between January 1, 1993, and December 31, 2008, using the Rochester Epidemiology Project. Period-specific incidence rates (in-hospital or within 30 days outside the hospital) were calculated. Logistic regression analysis was used to adjust for potential confounders that could affect temporal trends in SSI incidence rates. RESULTS: During the 16-year study, of 1424 residents of Olmsted County who underwent CABG surgery, 1189 (83%) had isolated CABG and 235 (17%) had combined CABG and valve surgery. The overall SSI incidence rate was 7.0% (95% confidence interval [CI], 5.7%-8.4%). The incidence rate of superficial sternal SSI was 2.0% (95% CI, 1.2%-2.7%) and of deep sternal SSI was 1.5% (95% CI, 0.9%-2.2%). The leg harvest site infection rate was 3.6% (95% CI, 2.6 %-4.5%). The incidence rate decreased over time with a statistically significant linear trend. The adjusted odds ratio (95% CI) of SSI showed a decreasing linear trend: 0.39 (0.19-0.81) vs 0.50 (0.27-0.93) vs 0.83 (0.48-1.42) vs reference for 2005-2008 vs 2001-2004 vs 1997-2000 vs 1993-1996. CONCLUSION: In this population-based surveillance study of patients undergoing CABG surgery, the incidence of SSI decreased markedly between 1993 and 2008 in patients in Olmsted County. The factors responsible for this decrease are the focus of ongoing investigations.

Association between preoperative statin therapy and postoperative infectious complications in patients undergoing cardiac surgery: a systematic review and meta-analysis.

Infectious complications of cardiac surgery are often severe and life threatening. Statins having both immunomodulatory and anti-inflammatory effects were intuitively thought to influence the development of postsurgical infections. We sought to systematically examine whether any association exists between statin use and risk of infectious complications in patients undergoing cardiac surgery. We searched Ovid MEDLINE, Ovid EMBASE, Thomson Scientific Web of Science, and Elsevier Scopus from inception through February 2011 for comparative studies examining the association between statin use and risk of postoperative infections in patients undergoing cardiac surgery. We contacted a study's author for missing information. We conducted a random-effects meta-analysis of individual studies' odds ratios (adjusted for potential confounders). We identified 6 cohort studies for inclusion, 3 of which were conducted in Canada and 3 of which were conducted in the United States. Four were single-center studies, and 2 were population based. Exposure ascertainment was based on a review of admission medication list or prescription databases. Infectious outcomes were heterogeneous and included surgical site infections within 30 days, serious infections (sepsis), or any other postoperative infection. Statin use in the preoperative period was associated with a trend toward reduction in the incidence of postoperative infections in patients who underwent cardiac surgery (odds ratio, 0.81 [95% confidence interval, 0.64-1.01]; [Formula: see text]; [Formula: see text]). Heterogeneity was explained by country effect. Studies performed in Canada showed weaker associations than studies performed in the United States. This difference could not be attributed to study quality alone. We did not find good evidence to support an association between statin use and postoperative infectious complications. However, the trend toward statistical significance for this association indicates that further investigation is warranted.

Conclusion about the association between valve surgery and mortality in an infective endocarditis cohort changed after adjusting for survivor bias.

OBJECTIVE: Survivor bias commonly weakens observational studies, even those published in premier journals. It occurs because patients who live longer are more likely to receive treatment than those who die early. We sought to quantify the effect of survivor bias on the association between valve surgery and mortality in infective endocarditis (IE). STUDY DESIGN AND SETTING: The study cohort included 546 IE patients. We compared the hazard ratios (HR) resulting from two propensity score analysis approaches that adjusted for survivor bias (time-dependent variable and matching on follow-up time) with those achieved using the same models but without that adjustment (time-fixed variable). RESULTS: In the total cohort, the HR of surgery in the time-dependent model was 1.9 (95% confidence interval [CI] = 1.1-3.2; P = 0.03) vs. 0.9 (95% CI = 0.5-1.4; P = 0.53) in the time-fixed model. In the propensity score-matched subset, the HR of surgery was 1.3 (95% CI = 0.5-3.1; P = 0.56) and 0.8 (95% CI = 0.4-1.7; P = 0.57) in the subset with and without matching on follow-up time, respectively. CONCLUSION: Adjusting for survivor bias changed the conclusion about the association between valve surgery and mortality in IE. Researchers should be aware of this bias when evaluating observational studies of treatment efficacy.

Infectious pericarditis: an experience spanning a decade.

BACKGROUND: Although recent literature suggests a changing spectrum for infectious pericarditis (IP), this view has not been proven. In this report, we aim to review the features of IP in cases from a large tertiary centre. METHODS: A retrospective review of our institution's database was conducted to identify cases with IP between January 1994 and December 2004. All pericardial biopsy tissue results from the same period were also reviewed. RESULTS: One hundred and thirty-eight cases were identified, of which 14 cases were identified by pathology. The mean age was 53 +/- 18 years, and 74% were men. The most frequently identified causative organisms were Propionibacterium acnes (P. acnes), staphylococci and streptococci. A common predisposing factor was an immune-compromised state, followed by cardiac surgery. Fifty-five patients were treated with antibiotics (medical group) while 63 cases (surgical group) underwent surgical drainage (pericardial window) and/or pericardiectomy. In comparison to the medical group, the surgical group was more critically ill and immunocompromised (40% versus 24%, respectively). There were 52 late deaths during follow-up. Mortality in the medical group was 67% while in the surgical group it was 24% (P < 0.0001). CONCLUSIONS: In contradistinction to the literature reports, the most prevalent organism for IP was P. acnes. Patients managed aggressively with both antibiotics and surgery, demonstrated lower mortality rates. Therefore, clinicians should maintain a high index of suspicion for IP so that timely and appropriate mortality-reducing strategies can be offered.

Stenotrophomonas maltophilia infections of intact skin: a systematic review of the literature.

To highlight the importance of intact skin infection syndromes caused by Stenotrophomonas maltophilia, we review 17 reported cases. Skin infection syndrome presentations included metastatic cellulitis (58%), primary cellulitis (23%), and ecthyma gangrenosum (17%). Associated risk factors were hematologic malignancies and chemotherapy (94%), neutropenia (94%), presence of central venous catheter (17%), and exposure to broad-spectrum antibiotics (84%). The diagnosis was supported by cultures of skin biopsy specimens (35%), blood cultures (24%), or both (41%). Trimethoprim-sulfamethoxazole was the treatment of choice (76%), and outcomes were favorable (71%).

The role of valve surgery in infective endocarditis management: a systematic review of observational studies that included propensity score analysis.

BACKGROUND: The potential role of valve surgery in infective endocarditis (IE) management is controversial. No randomized trials have been conducted to date; accordingly, some studies use propensity score analysis (PSA) to minimize selection bias in observational studies. METHODS: A systematic review of the literature addressing the role of valve surgery in IE was performed. Studies in which PSA was applied to the management of IE were identified using Medline, Web of Science, Zetoc, and Article First from inception to June 2007. Cohort studies that compared valve surgery (combined with antimicrobial therapy) to antimicrobial therapy alone and used PSA to adjust for selection bias were eligible. Methodological details and outcomes were compared to assess methodological quality. RESULTS: Six cohort studies that enrolled a total of 3,409 patients with either native valve endocarditis (NVE) or prosthetic valve endocarditis (PVE) were eligible. The proportions of IE cases undergoing valve surgery ranged from 28.9% to 41.7% for PVE and from 20.8% to 49.3% for NVE. Two studies suggested a statistically significant survival benefit with surgery in patients with NVE. Data from 2 other patient cohorts (PVE and NVE) revealed conflicting results. No statistically significant associations were found in the remaining studies. CONCLUSIONS: There are several limitations of available cohort studies that assess the role of valve surgery in IE. Well-designed prospective studies that address these limitations are needed to further define the role of surgery in IE. Until then, careful scrutiny is warranted when making management decisions in complicated, left-sided IE.

Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis.

OBJECTIVE: To estimate the association between antioxidant use and primary cancer incidence and mortality and to evaluate these effects across specific antioxidant compounds, target organs, and participant subgroups. METHODS: Multiple electronic databases (MEDLINE, Cochrane Controlled Clinical Trials Register, EMBASE, Science Citation Index) were searched from their dates of inception until August 2005 to identify eligible randomized clinical trials. Random effects meta-analyses estimated pooled relative risks (RRs) and 95% confidence intervals (CIs) that described the effect of antioxidants vs placebo on cancer incidence and cancer mortality. RESULTS: Twelve eligible trials, 9 of high methodological quality, were identified (total subject population, 104,196). Antioxidant supplementation did not significantly reduce total cancer incidence (RR, 0.99; 95% CI, 0.94-1.04) or mortality (RR, 1.03; 95% CI, 0.92-1.15) or any site-specific cancer incidence. Beta carotene supplementation was associated with an increase in the incidence of cancer among smokers (RR, 1.10; 95% CI, 1.03-1.10) and with a trend toward increased cancer mortality (RR, 1.16; 95% CI, 0.98-1.37). Selenium supplementation was associated with reduced cancer incidence in men (RR, 0.77; 95% CI, 0.64-0.92) but not in women (RR, 1.00; 95% CI, 0.89-1.13, value for interaction, P< .001) and with reduced cancer mortality (RR, 0.78; 95% CI, 0.65-0.94). Vitamin E supplementation had no apparent effect on overall cancer incidence (RR, 0.99; 95% CI, 0.94-1.04) or cancer mortality (RR, 1.04; 95% CI, 0.97-1.12). CONCLUSION: Beta carotene supplementation appeared to increase cancer incidence and cancer mortality among smokers, whereas vitamin E supplementation had no effect. Selenium supplementation might have anticarcinogenic effects in men and thus requires further research.

A systematic review of population-based studies of infective endocarditis.

BACKGROUND: We sought to summarize and critically appraise the literature on the epidemiology of infective endocarditis (IE) in the general population. METHODS: We retrieved population-based IE surveys by searching MEDLINE and EMBASE. Two reviewers independently extracted relevant data. We performed a metaregression to determine if temporal trends of IE characteristics exist. RESULTS: Fifteen population-based investigations with 2,371 IE cases from seven countries (Denmark, France, Italy, the Netherlands, Sweden, United Kingdom, and United States) from 1969 to 2000 were eligible. Different case definitions and procedures were used to capture all IE cases, including census of existing diagnoses, record-linkage system, and direct contact survey. In the unadjusted regression, there was a decline in the proportion of IE patients with underlying rheumatic heart disease (RHD; 12%; 95% confidence interval [CI], - 21 to - 3%; p = 0.01) and an increase in the proportion of patients undergoing valve surgery (9%; 95% CI, 3 to 16%) per decade. After adjusting for country, the decline in IE cases with underlying RHD became nonsignificant, but the proportions of IE patients undergoing valve surgery increased 7% per decade (95% CI, - 4 to 14%; p = 0.06), and those with underlying prosthetic valve increased 7% per decade (95% CI, - 1 to 16%; p = 0.07). There were no significant temporal trends in the causative organisms. CONCLUSION: Evidence from well-planned, representative IE epidemiologic surveys is scarce in many countries. Available studies suggest a changing distribution of underlying valvular heart disease in patients with IE and an increase in its surgical treatment.

Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis.

BACKGROUND: The results from small clinical studies suggest that therapy with adult bone marrow (BM)-derived cells (BMCs) reduces infarct size and improves left ventricular function and perfusion. However, the effects of BMC transplantation in patients with ischemic heart disease remains unclear. METHODS: We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort studies of BMC transplantation to treat ischemic heart disease. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes. RESULTS: Eighteen studies (N = 999 patients) were eligible. The adult BMCs included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived circulating progenitor cells. Compared with controls, BMC transplantation improved left ventricular ejection fraction (pooled difference, 3.66%; 95% confidence interval [CI], 1.93% to 5.40%; P<.001); reduced infarct scar size (-5.49%; 95% CI, -9.10% to -1.88%; P = .003); and reduced left ventricular end-systolic volume (-4.80 mL; 95% CI, -8.20 to -1.41 mL; P = .006). CONCLUSIONS: The available evidence suggests that BMC transplantation is associated with modest improvements in physiologic and anatomic parameters in patients with both acute myocardial infarction and chronic ischemic heart disease, above and beyond conventional therapy. Therapy with BMCs seems safe. These results support conducting large randomized trials to evaluate the impact of BMC therapy vs the standard of care on patient-important outcomes.

A predictive model of recurrent lower extremity cellulitis in a population-based cohort.

BACKGROUND: Cellulitis is common and recurs in some patients. The study described herein derived a predictive model for the recurrence of lower extremity cellulitis in a population-based cohort. METHODS: We conducted a retrospective, population-based cohort study using the Rochester Epidemiology Project. We reviewed the medical records of Olmsted County, Minnesota, residents with lower extremity cellulitis occurring from January 1, 1999, to June 30, 2000. Univariate and multivariate Cox proportional hazards analyses were performed to evaluate risk factors in patients who experienced recurrent lower extremity cellulitis within 2 years. A predictive model was developed to estimate risk of recurrence based on a score of risk factors identified by multivariate analysis. RESULTS: A total of 209 episodes met the definition of lower extremity cellulitis. Thirty-five patients (16.7%) experienced recurrence within 2 years. Multivariate analysis identified tibial area involvement, prior malignancy, and dermatitis affecting the ipsilateral limb as independent risk factors for recurrence, with hazard ratios of 5.02, 3.87, and 2.99 (P<.01), respectively. A score calculated from these variables (a count of 0, 1, 2, or 3) was developed to measure risk of recurrence. Based on the predictive model, the estimated probability of recurrence (95% confidence interval [CI]) within 2 years was 5.0% (95% CI, 1.6%-8.2%), 17.3% (95% CI, 11.1%-23.0%), 50.6% (95% CI, 34.2%-63.0%), or 92.8% (95% CI, 51.9%-98.9%) for a score of 0, 1, 2 or 3, respectively. CONCLUSIONS: We derived a model including tibial area involvement, history of cancer, and dermatitis to predict recurrence of lower extremity cellulitis. Potential interventions can be incorporated into treatment to diminish the proclivity for recurrence in high-risk patients.