Lihi Atzmony

Thrombosis associated with acute cytomegalovirus infection: A meta-analysis

BACKGROUND Thrombosis associated with acute cytomegalovirus (CMV) infection has been reported in the medical literature almost 100 times thus far. Still, the clinical characteristics of patients with both conditions have never been systematically reviewed and described. METHODS A literature search was conducted for all (n=97) reports concerning thrombosis associated with acute CMV infection. The current knowledge concerning this unique association and previous clinical experience are presented here. RESULTS The incidence of thrombosis among acute CMV infection hospitalized patients was 6.4%, and the incidence of acute CMV infection among thrombosis hospitalized patients was 1.9-9.1%. Most (n=64; 65.9%) reported patients were immunocompetent. Mean age of reported patients was 39.7 ± 14.9 years. Female-male ratio was 1:1. DVT/PE, splanchnic vein thrombosis and splenic infarction were the most prevalent thromboses associated with acute CMV infection. While DVT/PE was more prevalent among immunocompromised patients, splanchnic vein thrombosis was more prevalent among immunocompetent patients. Inherited predispositions for thrombosis were significantly more prevalent among immunocompetent patients. Immunocompromised patients were treated with antiviral agents significantly more often. Duration of anticoagulation therapy varied significantly between reported patients. In-hospital mortality rates were 4.9-22.2%. CONCLUSIONS We believe physicians should be alert for symptoms and signs of thrombosis in patients with acute CMV infection, and for symptoms and signs of acute CMV infection in patients with thrombosis.

Takotsubo cardiomyopathy and QT interval prolongation: who are the patients at risk for torsades de pointes? ☆

OBJECTIVES QT interval prolongation is prevalent among patients with Takotsubo cardiomyopathy (TC), whereas torsades de pointes (TdP) has rarely been reported in these patients. We studied all peer-reviewed reports on TC-associated QT interval prolongation and all peer-reviewed reports on TC-associated TdP to characterize the clinical circumstances leading to TdP in patients with TC. METHODS The literature search yielded 14 reports on TC-associated TdP and 26 reports on TC-associated QT interval prolongation. Overall, 15 patients with TC-associated TdP and 86 patients with TC-associated QT interval prolongation were reported. We systematically reviewed each report and recorded the risk factors for TdP as well as the clinical circumstances of TC. RESULTS The prevalence of the male sex was higher among patients with TC-associated TdP relative to patients with TC-associated QT interval prolongation (26.7% vs 5.8%; P = .01). There was a trend in the mean maximal corrected QT interval being longer among patients with TC-associated TdP relative to patients with TC-associated QT interval prolongation (679.9 +/- 230.6 vs 555.9 +/- 63.8 milliseconds; P = .06). There were no differences between patients with TC-associated TdP and patients with TC-associated QT interval prolongation in mean age, maximal troponin levels, and lowest ejection fraction. Overall, 12 (80.0%) patients with TC-associated TdP had risk factors for TdP other than the female sex and systolic dysfunction, including suspicion of congenital long QT syndrome, bradycardia, hypokalemia, recent conversion from atrial fibrillation to sinus rhythm, and using QT prolonging agents. CONCLUSIONS Men with TC-associated QT interval prolongation are at risk for TdP. Most patients with TC-associated TdP have risk factors for TdP other than the female sex and systolic dysfunction.

Incidence of cytomegalovirus-associated thrombosis and its risk factors: a case-control study.

INTRODUCTION Cytomegalovirus (CMV)-associated thrombosis has been reported sporadically in the medical literature until now. However, thrombosis incidence and its risk factors have never been studied in a cohort of patients with acute CMV infection. MATERIALS AND METHODS A retrospective case-control study. Medical charts and imaging study reports of all consecutive patients diagnosed with acute CMV infection during the years 2005-2006 in a tertiary medical center were reviewed for the presence of arterial and/or venous thromboses, and their acquired as well as inherited predispositions. The control group included age-matched and sex-matched consecutive patients, in whom acute CMV infection was excluded. Laboratory tests used for acute CMV infection diagnosis/exclusion were also matched, including serology, antigenemia, and PCR. RESULTS Included were 140 patients with acute CMV infection (study group) and 140 consecutive matched patients in whom acute CMV infection was excluded (control group). Among the control group, none of the patients had thrombosis, while among the study group, nine (6.4%; p=0.003) patients had thrombosis: five (3.6%; p=0.025) patients had arterial thrombosis and four (2.9%; p=0.045) patients had venous thrombosis. Binary logistic regression analysis showed that acute CMV infection was independently associated with thrombosis among the whole cohort (p=0.004), while use of oral contraceptives/hormones or pregnancy were independently associated with thrombosis among patients with acute CMV infection (p=0.043). CONCLUSIONS Thrombosis in patients with acute CMV infection is not rare. Acute CMV infection is associated with thrombosis independent of other risk factors for thrombosis. We hope to raise physicians awareness to the association between acute CMV infection and thrombosis.

New insights into folliculotropic mycosis fungoides (FMF): A single-center experience

BACKGROUND It is generally accepted that folliculotropic mycosis fungoides (FMF) is usually typified by indurated plaques and tumors mainly on the head/neck and an aggressive course. However, its clinical manifestations have long been recognized to be quite variable, and some studies indicate a better prognosis for certain presentations. OBJECTIVE We sought to summarize our experience with the clinicopathological presentations of FMF and impact on prognosis. METHODS Data were collected retrospectively for adults with FMF followed up prospectively at a tertiary medical center in 1995 through 2014. RESULTS In all, 34 patients presented with follicle-based patch/flat plaques, keratosis pilaris-like lesions, and/or acneiform lesions, defined clinically as early stage (IA, IB), and 15 presented with follicle-based infiltrated plaques and/or tumors, defined as advanced stage (IIB). The head/neck was involved in all tumor-stage cases, whereas early-stage lesions involved mainly the trunk/limbs. The tumor stage was characterized by more pruritus, heavier perifollicular infiltrates, greater vertical depth, and more frequent presence of eosinophils. On multivariate analysis, infiltrate density was the only significant histopathological discriminator between the stages. Estimated 5-year survival was 0.94 in the early-stage group and 0.69 in the tumor-stage group. LIMITATIONS Lack of long-term follow-up and relatively small sample are limitations. CONCLUSION FMF presents with 2 distinct patterns of clinicopathologic features, early stage and advanced stage, each with different prognostic implications.

C-reactive protein velocity following antibiotics in patients with chronic obstructive pulmonary disease exacerbation and community acquired pneumonia

INTRODUCTION Distinguishing community acquired pneumonia (CAP) from chronic obstructive pulmonary disease (COPD) exacerbation is a challenging task, since fever, productive cough, dyspnea, and leukocytosis are all common features of both conditions. Moreover, chest X-ray might not be sensitive enough. It is therefore quite common for physicians to prescribe unnecessary antibiotics for COPD exacerbation, leading to resistant bacteria and other related adverse affects. AIM To study whether CRP levels upon admission and the delta in CRP levels following initiation of antibacterial treatment, could provide an efficient tool for distinguishing CAP from COPD exacerbation. METHODS The study group included 36 COPD exacerbation and 49 CAP patients, admitted to a single Internal Medicine department during the years 2004-2006. All patients were treated with cephalosporins and macrolides upon admission. RESULTS CRP levels upon admission were significantly higher among CAP patients than among COPD exacerbation patients (111.5+/-104.4 vs. 34.9+/-28.6 mg/l, p<0.0001). CRP levels on the second day of hospitalization, following antibiotic administration to all patients, made a sharp incline in 36.7% of CAP patients compared to only 5.9% of COPD exacerbation patients (p=0.005), and remained unchanged in 61.8% of COPD patients compared to 16.3% of CAP patients (p=0.0006). CONCLUSIONS CRP levels upon admission and the delta in CRP levels following initiation of antibacterial treatment could provide an efficient tool for distinguishing CAP from COPD exacerbation.

Inherited and acquired predispositions for thrombosis in immunocompetent patients with cytomegalovirus-associated thrombosis

BACKGROUND Thrombosis is a rare complication of cytomegalovirus (CMV) infection in immunocompetent patients. The clinical circumstances of this complication have never been studied, to the best of our knowledge. AIM We reviewed all reports on CMV-associated thrombosis in immunocompetent adults found in the literature, in search for thrombosis risk factors other than CMV. METHODS Our search yielded 32 case reports and case series on CMV-associated thrombosis in immunocompetent adults. Reports on immunocompromised patients, infants and elderly patients were excluded. All reports were reviewed for other, acquired as well as inherited, predispositions for thrombosis. RESULTS Reports on 39 immunocompetent adults were reviewed, mean age for which was 34.9+/-10.8years. Overall, 14 (35.9%) patients had one or more acquired predispositions for thrombosis; 16 (45.7%) of the 35 patients that were investigated for inherited thrombophilias had one or more inherited predispositions for thrombosis. Only 12 (34.3%) patients were found to have no acquired or inherited predispositions for thrombosis other than CMV. The most common (n=13; 33.3%) acquired predisposition for thrombosis was daily use of oral contraceptives. The most common (n=6; 17.1%) inherited predisposition for thrombosis was factor V Leiden mutation. CONCLUSIONS Most immunocompetent adults with CMV-associated thrombosis have other acquired or inherited predispositions for thrombosis. Hence, addressing these predispositions in patients with CMV-associated thrombosis may be of great clinical importance.

Treatment of pemphigus vulgaris and pemphigus foliaceus: a systematic review and meta-analysis.

BackgroundNo optimal therapeutic approach has been established for pemphigus.ObjectiveOur objective was to evaluate the efficacy, steroid-sparing effect, and safety of available treatment modalities.MethodsPubMed, LILACS (up to July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL, issue 5 of 12, May 2014), and the ClinicalTrials.gov registry and reference lists were searched for randomized controlled trials of any treatment modality for pemphigus vulgaris and pemphigus foliaceus. Data were extracted independently by two authors using predefined appraisal criteria and data fields.ResultsA total of 20 studies (826 participants) were included. Most were small and open-labeled; all but seven were not concealed for allocation. Owing to the variability in intervention arms, five meta-analyses were performed, each pooling the data of two to three trials. Studies excluded from the meta-analyses were described quantitatively. Azathioprine had a steroid-sparing effect but did not increase remission rate. Mycophenolate mofetil induced sustained remission more quickly than did placebo and delayed time to relapse but did not have a steroid-sparing effect or favorable remission rate. Cyclophosphamide had a steroid-sparing effect, though less than azathioprine, but did not affect the remission rate or time-to-disease control. Intravenous immunoglobulin had more favorable short-term efficacy than did placebo. Topical epidermal growth factor hastened lesion healing.ConclusionsAlthough some of the available therapeutic modalities for pemphigus are beneficial in terms of steroid-sparing, hastening response, or delaying relapse, none were found to increase the complete response rate compared with glucocorticoids alone, currently the mainstay of treatment. Multicenter randomized controlled trials and case control studies with uniform outcome measures are warranted.

Association of bullous pemphigoid with malignancy: A systematic review and meta-analysis

Background: Studies evaluating whether malignancy rate is increased in patients with bullous pemphigoid (BP) have reached conflicting results. Objective: We sought to determine whether BP is associated with malignancy. Method: Medline, EMBASE, the Cochrane library, and reference lists of included studies were searched for comparative studies that evaluated the relationship between BP and malignancy. Data were analyzed on the basis of study design: cross‐sectional, case control, and cohort. A meta‐analysis was performed by using a random effects model to estimate pooled odds ratio. Results: The review included 8 studies. No association between BP and overall cancer was found for any of the study designs. Although a single cohort study reported an association with lymphoid leukemia and kidney and larynx cancer, a pooled analysis of case‐control studies did not. A pooled analysis of cross‐sectional studies found a significant association between BP and hematologic malignancies. Limitations: The paucity of well‐designed studies hindered the possibility of proving or disproving the BP‐cancer association. Conclusion: We did not find an association of BP with overall malignancy, but a possible association with hematologic malignancy was observed.

Symptomatic venous thromboembolism in elderly patients following major orthopedic surgery of the lower limb is associated with elevated vitamin B12 serum levels

BACKGROUND Elevated vitamin B12 serum levels are associated with systemic inflammation and mortality. Since venous thromboembolism (VTE) is associated with systemic inflammation and mortality as well, we have hypothesized that it is also associated with elevated vitamin B12 serum levels in elderly patients following major orthopedic surgery of the lower limb. METHODS This is a retrospective study. Medical charts of consecutive elderly (≥65 years) patients admitted for rehabilitation following major orthopedic surgery of the lower limb during 2007-2009 were reviewed. The study group included symptomatic VTE patients. The control group included patients in whom VTE was excluded. Demographics, co-morbidities, VTE risk factors, vitamin B12 serum levels, and 1-year mortality were studied. RESULTS The cohort included 197 elderly patients (median age: 82 years): 140 (71.1%) women and 57 (28.9%) men. Overall, 20 (10.2%) patients had VTE (study group) and in 177 (89.8%) patients VTE was excluded (control group). Vitamin B12 serum levels were higher in the study group compared with the control group (median: 634 vs. 409 pg/dL, p=0.024). The incidence of elevated vitamin B12 serum levels (≥500 pg/dL) was higher in the study group compared with the control group (odds ratio 3.1, p=0.031). Elevated vitamin B12 serum levels were associated with VTE (odds ratio 5.3, p=0.011) and with 1-year mortality (odds ratio 6.6, p=0.015) independent of demographics, co-morbidities, and VTE risk factors. CONCLUSIONS Symptomatic VTE is associated with elevated vitamin B12 serum levels in elderly patients following major orthopedic surgery of the lower limb.

Cytomegalovirus colitis associated with arterial thromboembolism in an immunocompetent elderly man.

ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. This study was conducted within the CAALYX project, funded by the Commission of the European Union as part of its Sixth Framework Program (IST-2005-045215). Author Contributions: Alejandro Rodrı́guez-Molinero conceived the study and participated in study design, data analysis, interpretation of data, and preparation of the manuscript. Antonio Yuste participated in study design, interpretation of data and preparation. José R. Banegas contributed to the study design, interpretation of data and preparation of the manuscript. Sponsor’s Role: None.