Granulocyte-colony stimulating factors as adjunctive therapy for diabetic foot infections.

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) increases the release of neutrophil endothelial progenitor cells from the bone marrow and improves neutrophil functions, which are often impaired in people with diabetes. OBJECTIVES: To examine the effects of adjunctive G-CSF compared with placebo or no growth factor added to usual care on rates of infection, cure and wound healing in people with diabetes who have a foot infection. SEARCH METHODS: In March 2013, for this second update, we searched the Cochrane Wounds Group Specialised Register (searched 14 March 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 2); Ovid MEDLINE (1948 to March Week 1 2013); Ovid EMBASE (1974 to 2013 March 13); Ovid MEDLINE (In-Process march 13,2013); and EBSCO CINAHL (1982 to 28 February 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated the effect of adding G-CSF to usual care in people with a diabetic foot infection. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility, methodological quality and extracted data. We reported risk ratio (RR) or, for continuous outcomes, mean differences (MD), with 95% confidence intervals (CI). In the case of low or no heterogeneity we pooled studies using a fixed-effect model. MAIN RESULTS: We identified and included five eligible trials with a total of 167 patients. The investigators administered various G-CSF preparations, at different doses and for different durations of time. Adding G-CSF did not significantly affect the likelihood of resolution of infection or wound healing, but it was associated with a significantly reduced likelihood of lower extremity surgical interventions (RR 0.38; 95 % CI 0.21 to 0.70), including amputation (RR 0.41; 95 % CI 0.18 to 0.95). Moreover, providing G-CSF reduced the duration of hospital stay (MD -1.40 days; 95% CI -2.27 to -0.53 days), but did not significantly affect the duration of systemic antibiotic therapy (MD -0.27 days; 95% CI -1.30 to 0.77 days). AUTHORS' CONCLUSIONS: The available evidence is limited, but suggests that adjunctive G-CSF treatment in people with a diabetic foot infection, including infected ulcers, does not appear to increase the likelihood of resolution of infection or healing of the foot ulcer. However, it does appear to reduce the need for surgical interventions, especially amputations, and the duration of hospitalisation. Clinicians might consider adding G-CSF to the usual treatment of diabetic foot infections, especially in patients with a limb-threatening infection, but it is not clear which patients might benefit.

Antimicrobial prophylaxis in colorectal surgery: focus on ertapenem.

Despite improvement in infection control measures and surgical practice, surgical site infections (SSIs) remain a major cause of morbidity and mortality. In colorectal surgery, perioperative administration of a suitable antimicrobial regimen that covers both anaerobic and aerobic bacteria is universally accepted. In a prospective, double-blind, randomized study ertapenem was recently found to be more effective than cefotetan, a parenteral cephalosporin so broadly used as to be considered as gold standard in the prevention of SSIs following colorectal surgery. In this adequate and well controlled study, the superiority of ertapenem over cefotetan was clearly demonstrated from the clinical and bacteriological points of view. However, data that directly compares ertapenem with other antimicrobial regimen effective in preventing SSIs following colorectal surgery are lacking; furthermore, the possible risk of promotion of carbapenem resistance associated with widespread use of ertapenem prophylaxis as well as the ertapenem effects on the intestinal gut flora are of concern. Further comparative studies of ertapenem versus other widely used prophylactic regimens for colorectal surgery in patients submitted to mechanical bowel preparation versus no preparation as well as further research on adverse events of antibiotic prophylaxis, including emergence of resistance and Clostridium difficile infection, seem warranted.

Granulocyte-colony stimulating factors as adjunctive therapy for diabetic foot infections.

BACKGROUND: G-CSF increases the release of neutrophil endothelial progenitor cells from the bone marrow, and improves neutrophil functions, which are often impaired in people with diabetes. OBJECTIVES: To examine the effects of adjunctive G-CSF compared with placebo or no growth factor added to usual care on rates of infection, cure and wound healing in people with diabetes who have a foot infection. SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Register (Searched 16/3/09); the Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 1 2009); Ovid MEDLINE (1950 to March Week 1 2009); Ovid EMBASE (1980 to 2009 Week 11); EBSCO CINAHL (1982 to March Week 2 2009); LookSmart's Find Articles (January 1990 to January 2008); conference proceedings and references lists in the included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated the effect of adding G-CSF to usual care in people with a diabetic foot infection. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility, methodological quality and extracted data. Relative risk (RR), or for continuous outcomes, mean differences (MD), with 95% confidence intervals (CI) were reported. In the case of low or no heterogeneity studies were pooled using a fixed-effect model. MAIN RESULTS: We identified and included five eligible trials with a total of 167 patients. The investigators administered various G-CSF preparations, at different doses and for different durations of time. Adding G-CSF did not significantly affect the likelihood of resolution of infection or wound healing, but it was associated with a significantly reduced likelihood of lower extremity surgical interventions (RR 0.37; 95 % CI 0.20 to 0.68), including amputation (RR 0.41; 95 % CI 0.18 to 0.95). Moreover, providing G-CSF reduced the duration of hospital stay (MD, -1.40 days; 95 % CI, -2.27 to -0.53 days), but did not significantly affect the duration of systemic antibiotic therapy (MD, -0.27 days; 95 % CI, -1.30 to 0.77 days). AUTHORS' CONCLUSIONS: The available evidence is limited, but suggests that adjunctive G-CSF treatment in people with a diabetic foot infection, including infected ulcers, does not appear to increase the likelihood of resolution of infection or healing of the foot ulcer. However, it does appear to reduce the need for surgical interventions, especially amputations, and the duration of hospitalisation. Clinicians might consider adding G-CSF to the usual treatment of diabetic foot infections, especially in patients with a limb-threatening infection, but it is not clear which patients might benefit.

Perioperative antibiotic prophylaxis: a critical review.

BACKGROUND: The value of perioperative prophylaxis is established for clean-contaminated procedures. For clean surgery, prophylaxis traditionally has been reserved for prosthetic device implantation procedures. METHODS: Review of pertinent English-language literature. CURRENT RECOMMENDATIONS: Evidence suggests that prophylactic antibiotics are advisable for at least some non-prosthetic procedures and that glycopeptides might have a role for major prosthetic surgery in units with a high prevalence of methicillin-resistant Staphylococcus aureus. In clean-contaminated surgery, cefazolin is recommended, although not for colorectal procedures or obstetric/gynecologic surgery that requires anti-anaerobic coverage. CONCLUSION: Antibiotic prophylaxis is generally overprescribed (i.e., given for too long). Short-duration prophylaxis is effective and safe.

Association between Enterococcus bacteraemia and death in neutropenic patients with haematological malignancies.

Fatality rates and prognostic factors for mortality due to Enterococcus spp. bacteraemia have not yet been fully defined in the setting of neutropenic patients affected with haematological malignancies. We have performed a retrospective, multi-centre cohort study on 98 episodes of Enterococcus bacteraemia occurring in patients hospitalised from January 1984 to December 2001 at the oncohaematology units in two tertiary-care hospitals (Verona Hospital and Vicenza Hospital, in north-east Italy). E. faecalis was isolated in 52 cases (53%), E. faecium in 39 (39.8%), E. avium in four, E. durans in one, and untyped Enterococcus spp. in two other cases; vancomycin resistance was detected in 15 (15.3%) isolates. A global mortality rate of 41.8% (41/98 cases) was revealed; Enterococcus spp. bacteraemia was associated with a fatal outcome in 29/98 cases (29.5%). The following variables were independently associated with an increased risk of death by multivariate analysis of survival: age > or =50 years (OR 3.74; 95% CI 1.35-10.32), pneumonia (OR 4.70; 95% CI 1.67-13.20), and shock (OR 13.7; 95% CI 1.23-152.43), while the initial phase of haematological disease (responsive to chemotherapy) appeared to be protective (OR 0.23; 95% CI 0.008-0.64, P level 0.005); however, pneumonia alone (OR 7.2, 95% CI 2.52-20.88) was independently associated with fatal outcome by multivariate analysis for death related to enterococcal bacteraemia. In our experience, the poor outcome proper to enterococcal bacteraemia appears to be directly related to underlying disease, patient's age, presence of pneumonia and shock; in contrast, severe neutropaenia, antibiotic resistance, and species of Enterococcus do not appear to affect the fatality rate significantly.

Erysipelas and cellulitis: clinical and microbiological spectrum in an Italian tertiary care hospital.

Patients hospitalized in the authors' institution for erysipelas or cellulitis between January 1995 and December 2002 were included in this retrospective review. Two hundred cases of soft tissue infections were hospitalized during the study period. The mean age of the patients was 58 years. The most commonly involved site was the leg (66%), followed by the arm (24%) and face (6%). Most patients (71%) had a recognized risk factor for soft tissue infection. Fever was present in 71% of cases, with a mean duration of 3 days. Blood cultures were positive in 3 out of 141 (2%) cases, whereas cutaneous swabs were positive in 73 out of 92 (79%) cases. On admission, white blood cells counts (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were elevated above normal levels in 100 out of 191 (50%) cases, 151 out of 176 (85%) cases, and 150 out of 154 (97%) cases, respectively. Patients with a hospital stay of more than 10 days had significantly higher CRP and ESR values than patients hospitalized for 10 days or less (P<0.01). A single antibiotic was used as treatment in 115 cases, whereas in the remaining 85 cases a combination of two antibiotics was administered. The most commonly used antibiotics were amoxicillin-clavulanic acid as single agent and penicillin with clindamycin as combination therapy. The mean duration of hospitalization was 7 days for patients treated with a single antibiotic and 11 days for patients treated with an antibiotic combination. A recurrence of infection occurred in 34 (17%) patients. Soft tissue infections are common and have a high degree of morbidity and require prolonged hospitalization and antibiotic treatment. Microbiological diagnosis is difficult and treatment is based on empiric evidence. ESR and CPR levels on admission may predict the severity of the disease and duration of hospitalization.

Prophylaxis of Candida infections in adult trauma and surgical intensive care patients: a systematic review and meta-analysis.

OBJECTIVE: To determine whether systemic antifungal prophylaxis decreases infectious morbidity and mortality in nonneutropenic, critically ill, trauma and surgical intensive care unit (ICU) adult patients. DESIGN: Systematic review and meta-analysis of randomized clinical trials. We used a fixed effect model, with risk ratio (RR) and 95% confidence intervals (CI). PARTICIPANTS: Patients admitted to ICU after surgery or trauma, with multiple risk factors for fungal infections. INTERVENTIONS: Nine studies (seven double blind) with a total of 1,226 patients compared ketoconazole (three) or fluconazole (six) to placebo (eight) or no treatment (one). RESULTS: Prophylaxis with azole was associated with reduced rates of candidemia (RR 0.30, 95% CI 0.10-0.82), mortality attributable to Candida infection (RR 0.25, 95% CI 0.08-0.80), and overall mortality (RR 0.60, 95% CI 0.45-0.81). Time to event analysis showed a significantly lower probability of fungal infections in treated patients. There was no evidence of statistical heterogeneity between studies, and publication bias assessment gave a negative results. There was, however, wide variability in the definition and reporting of some relevant clinical outcomes (e.g., confirmed or suspected infections, colonization) and pooling of these outcome measures was not feasible. CONCLUSIONS: Prophylaxis of candidal infection among critically ill ICU patients has beneficial effect on certain outcome measures, but additional data from well designed clinical trials and long-term epidemiological observations are needed to provide firm recommendations for the selection of subgroups of patients who would most benefit from prophylaxis and to determine the effect of prophylaxis on fungal resistance patterns.

Are granulocyte colony-stimulating factors beneficial in treating diabetic foot infections?: A meta-analysis.

OBJECTIVE: To assess the value of granulocyte colony-stimulating factor (G-CSF) as adjunctive therapy for diabetic foot infections. RESEARCH DESIGN AND METHODS: We systematically searched the medical literature (including Medline, Embase, LookSmart, and the Cochrane Library) for prospective randomized studies that used G-CSF as an adjunct to standard treatment for diabetic foot infections. Using a conventional meta-analysis, we pooled the relative risks (RRs) for outcomes of interest, including resolution of infection, wound healing, duration of antibiotic therapy, and need for various surgical interventions, using a fixed-effects model. RESULTS: Five randomized trials, with a total of 167 patients, met our inclusion criteria. The methodological quality of the studies was satisfactory. The investigators administered various G-CSF preparations parenterally for between 3 and 21 days. The meta-analysis revealed that adding G-CSF did not significantly affect the resolution of infection or the healing of the wounds but was associated with a significantly reduced likelihood of lower extremity surgical interventions (RR 0.38 [95% CI 0.20-0.69], number of patients who needed to be treated: 4.5), including amputation (0.41 [0.17-0.95], number of patients who needed to be treated: 8.6). There was no evidence of heterogeneity among the studies or of publication bias, suggesting that these conclusions are reasonably generalizable and robust. CONCLUSIONS: Adjunctive G-CSF treatment does not appear to hasten the clinical resolution of diabetic foot infection or ulceration but is associated with a reduced rate of amputation and other surgical procedures. The small number of patients who needed to be treated to gain these benefits suggests that using G-CSF should be considered, especially in patients with limb-threatening infections.

Alcohol is an important co-factor for both steatosis and fibrosis in Northern Italian patients with chronic hepatitis C.

BACKGROUND/AIMS: Steatosis in patients with chronic hepatitis C (CHC) may be the result of both viral and host factors. To evaluate: (1) the relationship between steatosis and either host or viral factors; (2) the correlation between steatosis and fibrosis in patients with CHC. METHODS: A consecutive series of 349 patients were evaluated for steatosis. At liver biopsy, patients were tested for virological, and laboratory analysis and questioned for alcohol consumption. RESULTS: Logistic regression analysis demonstrated that steatosis was independently associated with genotype 3a (odds ratio, OR 3.5), alcohol intake at the time of biopsy (OR 2.6) and age >35 years (OR 2.7). In multivariate analysis the presence of fibrosis was associated with past alcohol abuse (OR 3.7), and age older than 44 years (OR 2.2). Overall, a weak correlation was found between grade of steatosis and fibrosis score (r=0.861, P=0.05), which disappeared excluding patients without past or current alcohol intake. A direct correlation emerged between grade of steatosis and both 'grading' and 'staging' only in patients with genotypes other than 3a. CONCLUSIONS: Genotype 3a is the main risk factor for steatosis in patients with CHC. The grade of steatosis correlated with both grading and staging only in patients with genotypes other than 3a and this relationship is strictly linked to alcohol consumption.

Prophylaxis with cefazolin plus clindamycin in clean-contaminated maxillofacial surgery.

PURPOSE: Infections after maxillofacial surgery are usually due to aerobic and anaerobic gram-positive cocci and gram-negative bacilli. Various antimicrobials, including cephalosporins, beta-lactams/beta-lactamase inhibitors, aminoglycosides, lincosamides, and fluoroquinolones, have been tested for use for perioperative prophylaxis in maxillofacial surgery. However, the best regimen has not been determined. We tested the safety and the efficacy of clindamycin plus cefazolin as perioperative prophylaxis for patients undergoing major maxillofacial procedures. PATIENTS AND METHODS: Intravenous cefazolin and clindamycin in 3 doses were administered to 155 patients undergoing major maxillofacial procedures. After surgery, patients were monitored for the presence of infection and side effects. RESULTS: No patient experienced a fever or infection after surgery. No side effects related to these antibiotics were observed. CONCLUSIONS: The antibiotics used as prophylaxis in maxillofacial surgery should possess an adequate coverage against gram-positive aerobic and anaerobic cocci as well as gram-negative bacilli. Prophylaxis with cefazolin plus clindamycin in major maxillofacial seems safe and effective.

Diagnosing and treating diabetic foot infections.

Foot infections are a common, complex and costly complication of diabetes. We have made considerable progress in establishing consensus definitions for defining infection. Similarly, we have learned much about the appropriate ways to diagnose both soft tissue and bone infections. Accompanying these advances have been improvements in our knowledge of the proper approaches to antibiotic (and surgical) therapy for diabetic foot infections. Furthermore, investigators have explored the value of various adjunctive therapies, especially granulocyte colony stimulating factors and hyperbaric oxygen, for improving outcomes. This paper presents a summary of a minisymposium on infection of the diabetic foot that was held at the fourth International Symposium on the Diabetic Foot, in Noordwijkerhout, The Netherlands.

Candidal prosthetic hip infection in a patient with previous candidal septic arthritis.

We describe the case of a patient with chronic monocytic leukemia who underwent total hip arthroplasty (THA) for hip arthrosis. The patient has a history of Candida albicans arthritis of the same joint 5 months before THA surgery. Seven months after the prosthetic joint surgery, the patient developed a C albicans prosthetic infection that was successfully treated with amphotericin B and prosthesis removal. At surgery, the patient was believed cured of the candidal infection. Risk of infection after prosthetic joint surgery in patients with previous fungal joint infections has not been fully investigated. A lengthy infection-free follow-up period is probably necessary but may not be sufficient to prevent the occurrence of postoperative infections in these patients.

Occult hepatitis B virus infection does not affect liver histology or response to therapy with interferon alpha and ribavirin in intravenous drug users with chronic hepatitis C.

BACKGROUND: the frequency and the impact of occult HBV infection in patients with chronic hepatitis C infection is still a matter of some controversy. OBJECTIVES: our aim was to evaluate the prevalence of occult HBV infection and assess its impact on liver biochemistry, HCV viral titre, liver histology and on outcome of therapy in patients with chronic hepatitis C. STUDY DESIGN: paired liver biopsies and serum samples were collected from 51 patients (84% IVDUS) with HBsAg negative chronic hepatitis C, and tested for HBV-DNA with nested PCR. Liver biopsies were further studied histologically, with morphometric analyses and immunostaining techniques. Twenty-five were treated with alpha Interferon and ribavirin and followed for at least 18 months. RESULTS: HBV DNA was detected in 29.4% of liver tissue specimens and in only one (1.9%) serum sample. Three liver specimens were positive for surface gene, nine for core gene, three for both and none for the X gene. No significant difference in mean transaminase values, HCV viral titre, HCV genotype, or grading and staging and morphometric analysis was observed in patients with or without HBV DNA. Moreover, all 51 liver specimens were negative for both HBsAg and HBcAg. Sustained response to combination therapy was achieved in 40% of patients with and in 53% of patients without HBV DNA in the liver specimens (P=NS). CONCLUSIONS: HBV DNA is frequently found in the liver of patients with chronic hepatitis C. However, the lack of any significant impact on HCV viral titre, liver enzymes, histological parameters and response to therapy, suggests that in most cases HBV DNA detected in the liver by PCR may be either an integrated or low level replicative form.

A multicentre study of patient survival, disability, quality of life and cost of care: among patients with AIDS in northern Italy.

OBJECTIVE: To describe the epidemiological, clinical and economic changes that occurred in the HIV epidemic in Italy prior to and after the introduction of highly active antiretroviral therapy (HAART). DESIGN: A prospective, observational, multicentre case-control study was conducted comparing data, collected over 6 months, from an AIDS cohort in 1998 with that of a cohort in 1994. Out of 77 patients with AIDS in the 1998 cohort, 74 survived. These 74 patients were matched for severity of illness with 74 patient survivors from the 1994 cohort to enable valid comparisons of mortality, disability-dependency (DD), health-related QOL (HR-QOL), and direct costs. RESULTS: Overall, a considerable difference was observed in mortality (33.8% in 1994 vs 3.9% in 1998) between unmatched patients of the two cohorts. As for matched patients, the number of hospital admissions was 1.7 in 1994 and 0.8 in 1998; the average length of stay was 28.1 days in 1994 and 12.6 days in 1998. The direct cost per patient per year was euro15 390 and euro11 465 for the 1994 and 1998 cohorts, respectively (1999 values). The 1998 patient cohort had significantly better HR-QOL at 6 months in two domains of the instrument used (emotional reaction and energy) and the percentage of totally dependent patients was significantly lower compared with the 1994 cohort (1.4% vs 6.8%). CONCLUSIONS: This is the first study to present a comprehensive comparison of direct costs, DD and HR-QOL of patients with AIDS between two time periods. The use of a case-control design has enabled changes in costs and outcomes to be linked to the introduction of HAART in Italy in 1997.

Regional and systemic prophylaxis with teicoplanin in total knee arthroplasty: a tissue penetration study.

Five patients undergoing total knee arthroplasty (TKA) received 800 mg intravenous teicoplanin systemically 2.5 hours before surgery and 15 patients received 200 mg teicoplanin into a foot vein in the leg to be treated. Samples of bone, synovia, subcutaneous tissue, and skin were collected at 20, 40, and 60 minutes after tourniquet inflation and at the end of surgery. None of the study subjects experienced adverse effects, adverse events, or infections during the postoperative and follow-up period. Mean teicoplanin concentration in the collected tissue ranged from 1.52 to 5.81 mg/L after regional prophylaxis and from 0.9 to 2.94 mg/L after systemic prophylaxis. Bone and soft tissue penetration of teicoplanin after regional prophylaxis with 200 mg is at least comparable with that achieved after systemic prophylaxis with 800 mg. Regional prophylaxis in TKA appears to be safe and valuable. Higher dosages of teicoplanin seem to be needed to ensure coverage against coagulase negative staphylococci.

Outpatient therapy for febrile neutropenia: clinical and economic implications.

Although febrile episodes in neutropenic patients remain a potentially life-threatening complication of anticancer chemotherapy, considerable progress has been achieved in understanding this issue. Febrile neutropenic patients represent a heterogeneous population that displays a very variable risk for serious medical complications. It has also been ascertained that in low-risk patients, the standard of care can be safely and effectively shifted from traditional hospital-based, parenteral, empiric, broad-spectrum antibacterial therapy to outpatient treatment, even for the entire duration of the febrile episode. Furthermore, in the last years some risk assessment models have been developed to identify, at the onset of febrile episodes, low-risk neutropenic patients who are most likely to have a favourable outcome (and who can effectively and safely be treated on an outpatient basis). With respect to traditional hospital-based therapy, the outpatient treatment of low-risk patients is associated with several advantages, including a conspicuous cost saving. Some strategies for inpatient therapy, such as switching from intravenous to oral antibacterials and early discharge, can allow some cost containment; however, the most substantial decrease in costs can be obtained by using outpatient treatment over the entire febrile episode, especially by using oral antibacterials. In spite of the considerable number of clinical studies published over the past 20 years, only limited pharmacoeconomic data on this issue are available. Future comparative studies between outpatient and inpatient treatment of febrile neutropenia, in addition to clinical outcomes (e.g. survival, time to clinical response), should therefore include the following: (i) a detailed analysis of total costs, specifying the setting of outpatient treatment and the method of administration of antimicrobial agents (home nursing, self administration or treatment at infusion centres or at a low-care unit of the hospital); (ii) cost of inpatient treatment if outpatient therapy fails; and (iii) out-of-pocket expenses incurred by the patients.

Prevalence and clinical significance of circulating cryoglobulins in HIV-positive patients with and without co-infection with hepatitis C virus.

Although hepatitis C virus (HCV) is a recognized cause of circulating cryoglobulins, the role of human immunodeficiency virus (HIV) in the pathogenesis of cryoglobulinemia has not been investigated extensively. To evaluate the prevalence of circulating cryoglobulins and to assess the relationship with clinical and virological parameters, 162 HIV-positive subjects (84 anti-HCV(+)) were tested for cryoglobulins, C3, C4, RF, autoantibodies, HIV-viral titer, and CD4(+) count. Anti-HCV-positive subjects were tested for HCV-RNA, HCV-viral titer, and HCV genotype. All patients were examined for the presence of signs or symptoms of vasculitis and tested for cryoglobulins using a standard biochemical assay. Cryoglobulins were found in 30 (18.5%) cases. Of the 30 positive cases, 29 (96.7%) were anti-HCV-positive and 28 (93.3%) HCV-RNA-positive. The presence of cryoglobulins was significantly associated (P < 0.01) with HCV-RNA positivity (OR = 27), liver cirrhosis (OR = 16), decreased levels of C3 (OR = 8.6), C4 (OR = 13.6), increased levels of IgG and IgM (OR = 6.1 and 7.9, respectively), and RF positivity (OR = 6.3), but was unrelated to CD4(+) cell count, HIV viral load, diagnosis of AIDS, HCV viral load and the presence of autoantibodies. Interestingly, the presence of cryoglobulins was not significantly associated with signs and symptoms commonly associated with cryoglobulinemia. In conclusion, HIV infection does not seem to play a significant role in the production of circulating cryoglobulins, which strongly correlates with HCV co-infection and liver cirrhosis. Typical signs and symptoms of cryoglobulinemia do not correlate with the detection of circulating cryoglobulins in HIV and HCV patients.