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A 56-year-old man developed disseminate lymphadenopathies, associated with hepato-splenomegaly, fever, nocturnal sweating and weight loss. Imaging studies in particular FDG-PET/CT raised the suspicion of a malignant disease. But blood flow cytometry assay for B/T cell clonality was negative and fine-needle biopsy of enlarged laterocervical lymph node showed a not specific "reactive hyperplasia". Four months later, the patient developed a non-itching rash; since a further anamnestic investigation revealed an history of high-risk sexual intercourse, the patient underwent serological tests for Treponema pallidum that were positive at high titer, after a first negative screening. Made the diagnosis of secondary syphilis, the patient responded to the treatment with benzyl penicillin with complete resolution of symptoms. This case highlights the importance of carefully screening the patients with suspected lymphoadenopathies also for lue, particularly in presence of behavioral risk factors.

We present the case of a 58-year-old woman who developed hypokalaemia and metabolic alkalosis 2 weeks after therapy with colistimethate sodium for the treatment of chronic lower limb ulcer infection by extensively drug-resistant (XDR) Pseudomonas aeruginosa. The metabolic changes observed resembled Bartter syndrome, a group of congenital disorders affecting the distal segments of the renal tubules. The metabolic abnormalities reversed spontaneously 6 days after drug discontinuation. Acquired forms of Bartter syndrome have been reported during courses of antibiotic therapy; however, to our knowledge, this is the first documented case associated with colistimethate therapy in an adult.

OBJECTIVES: Historically, only 10% of patients with hepatocellular carcinoma (HCC) are diagnosed with early-stage, potentially curable disease. In this study, chronic hepatitis virus-infected patients were prospectively screened to determine: (i) the proportion of patients diagnosed with potentially curable HCC, and (ii) survival following curative therapy. METHODS: The study included 8900 chronic hepatitis virus-infected patients enrolled in a prospective screening programme, of whom 1335 (15.0%) were infected with hepatitis B virus (HBV), 7120 (80.0%) with hepatitis C virus (HCV), and 445 (5.0%) with both HBV and HCV. Screening was conducted every 6 months and included serum alpha-fetoprotein (AFP) measurement and ultrasonography. Curative treatments included liver transplantation, resection, radiofrequency ablation and/or ethanol injection. RESULTS: Hepatocellular carcinoma was diagnosed in 765 (8.6%) patients. Of 1602 patients with cirrhosis, 758 (47.3%) developed HCC. Curative treatment was possible in 523 (68.4%) of the 765 HCC patients. Two- and 5-year rates of overall survival in the curative treatment group were 65% and 28%, respectively, compared with 10% and 0% in the advanced disease group (P < 0.001). CONCLUSIONS: Prospective screening of patients at high risk for the development of HCC increases the proportion of patients diagnosed with potentially curable disease. This may result in an increase in the number of longterm survivors. Screening strategies should focus on patients with chronic HBV or HCV infection who have progressed to cirrhosis because more than 40% of these patients will develop HCC.

Objectives The study aims to evaluate the incidence of infectious complications (namely meningitis) within 30 days after endoscopic endonasal transspheinodal neurosurgery (EETS) in patients receiving an ultra-short peri-operative chemo-prophylaxis regimen with 2 doses of 1st generation cephalosporin or macrolide. Patients and methods We retrospectively analyzed the clinical records of 145 patients who received an ultra-short chemoprophylaxis with two doses of an antibiotic, given 30 min before and 8 h after EETS, over a 30-month time-frame. Ninety-seven patients (66.89%) received endovenous cefazolin, a 1st generation cephalosporin, administered at a dosage of 1000 mg, and 48 patients (33.10%) with an history of allergy to various agents, received endovenous clarithromycin at a dosage of 500 mg. Results No case of peri- and post-operative meningitis occurred in patients receiving the 2 doses of antibiotic. Only one patient (0.68%) developed cerebral fluid leakage on the 7th postoperative day, which required the switching to a broad-spectrum antibiotic prophylaxis for one week; this patient received the ultrashort prophylaxis with a macrolide. In addition, 7 patients (4.82%) developed minor infectious complications such as low-grade fever (3 cases, all of them receiving cefazolin), enlarged submandibular and cervical lymphnodes (3 cases, all of them receiving cefazolin), and upper and lower respiratory tract infection (1 case receiving clarithromycin). The cost of this prophylaxis regimen ranged from 7.76 Euro (cefazolin) to 39.54 Euro (clarithromycin). Conclusions This study suggested that an ultra-short single-antibiotic prophylaxis is a safe, cheap and effective regimen to prevent post-operative meningitis in patients undergoing EETS and who do not require lumbar drainage after surgery. In these patients also the rate of minor infective complications was acceptable when compared with the previous more expensive regimen based on 3rd generation cephalosporin plus aminoglycoside or alone, that could be suitable only for at-risk patients (e.g. smokers, cerebrospinal leak or Cushing's diseases).

The reverse seroconversion to hepatitis B virus infection has been sporadically described in onco-haematological patients receiving cytotoxic therapy or allogeneic bone marrow transplantation and can be associated with the development of acute icteric hepatitis. We present a male HBsAg-negative, anti-HBc-positive patient with Hairy Cell Leukemia who developed acute B hepatitis more than 1 year after the last course of 2-CdA and 6 months after splenectomy, while the patient was receiving therapy with alphaIFNr. The acute B hepatitis promptly responded to lamivudine therapy followed by viral clearance.

Hepatitis C virus infection and diabetes mellitus are two major public health problems worldwide and the burden of these diseases is expected to increase in the near future. Hepatitis C virus is associated to autoimmune disorders of several organs (e.g. thyroid and kidney) and has recently been reported to be associated also to metabolic disorders including type 2 diabetes mellitus. Biologically, the homologies between the hepatitis C virus polyprotein and the pancreas antigens could underlie a mechanism of molecular mimicry that could lead to autoimmune diabetes (type 1 diabetes mellitus and latent autoimmune diabetes of adults). Here we review the data on the potential relationship between HCV-related chronic liver disease and autoimmune mediated diabetes mellitus.

Hepatitis C virus (HCV) affects millions of individuals worldwide. In most cases, HCV infection progresses to chronic liver disease and, subsequently, to liver cirrhosis and hepatocellular carcinoma. HCV is transmitted by the parenteral route, for example by transfusion of blood or blood products, injection during drug abuse, etc., and by the inapparent parenteral route (penetration of the virus through difficult-to-identify microlesions present on the skin or mucosae), for example, sexual exposure or household exposure to infected contacts, etc. The cost of chronic hepatitis C and its sequelae is high in both financial and human terms. At present, only anti-HCV screening of blood/organ/tissue donors and universal precautions for the prevention of blood-borne infections are recommended for HCV prevention. Before the discovery of the main aetiological agent of non-A, non-B hepatitis (HCV), several randomised controlled clinical trials demonstrated that standard intramuscular immunoglobulin exerted a preventive effect on post-transfusional and sexual and /or horizontal transmission of non-A, non-B hepatitis. When serological tests for HCV infection became available, bimonthly inoculation of standard unscreened intramuscular immunoglobulin (prepared from plasma pools containing about 2% of anti-HCV-positive units) was demonstrated to significantly prevent sexually transmitted HCV infection. The immunoglobulin used contained high titres of anti-HCV neutralising antibodies (anti-E2 neutralisation of binding assay), whereas currently available commercial screened immunoglobulin (prepared from anti-HCV-negative blood units) did not. This finding suggested that anti-HCV neutralising antibodies are concentrated only in anti-HCV-positive units (which are currently discarded). Thus, anti-HCV hyperimmune globulin (HCIg) can be produced only from anti-HCV-positive units. The neutralising titre can be increased by the exclusive use of units with higher titres of neutralising antibodies. Unlike other hyperimmune globulins, which are produced from a limited number of selected donors, HCIg should be produced from a large number of units so as to contain neutralising antibodies to the different HCV strains. HCIg will have a number of advantages: (i) it is easy to produce and inexpensive; (ii) it has a long half-life, allowing infrequent administration; (iii) new additional viral inactivation procedures have been introduced to eradicate transmission of infection, and (iv) it may be possible to neutralise all the emerging HCV strains. HCIg could be used in all individuals at risk of HCV infection (sexual partners, haemodialysis patients, etc), in preventing reinfection of transplanted livers, and perhaps also in the treatment of chronic hepatitis C, alone or associated with other drugs.

Lamivudine can select resistant hepatitis B virus (HBV) tyrosine-methionine-aspartate-aspartate aminoacid motif (YMDD) mutants, which usually disappear in few months after lamivudine withdrawal. We report an unusual case of a male adult patient who showed a prolonged persistence of the M204I mutation up to 24 months after lamivudine withdrawal followed by the emergence of new distinct YMDD mutants (namely M204V, V207L). Only 42 months after lamivudine withdrawal wild-type YMDD motif became dominant over the YMDD mutants. To our knowledge, a so prolonged persistence of a YMDD mutant and also the emergence of new YMDD mutants many months after drug withdrawal are unusual.

{Background: The aim of this study is to evaluate the rate of infectious complications post endoscopic transspheinodal neurosurgery in patients receiving a new antibiotic chemoprophylaxis regimen. Methods: Clinical records of 170 patients who received prophylaxis with a third-generation cephalosporin plus aminoglycoside (160 cases) or alone (10 cases) were retrospectively analyzed. Twenty-eight patients (16.4\%) had CSF leakage. The postsurgical follow-up ranged from 3 months to 4 years. Results: Of 170 patients, 2 (1.17\%) developed infectious complications: 1 case of meningitis by Staphylococcus epidermidis and 1 case of sphenoid sinusitis (without microbiological diagnosis). In addition, asymptomatic sphenoid sinusitis was diagnosed in 2 other patients. The cost ranged from 22.50 to 33.34 euros/d. Conclusions: The rate of infectious complications was very low in patients receiving prophylaxis with a third-generation cephalosporin plus aminoglycoside or alone; because of the broad-spectrum of antibiotics and their high cost, this regimen could be used in at-risk patients (eg, smokers, patients with cerebrospinal leak, or patients with Cushing diseases). (c) 2007 Elsevier Inc. All rights reserved.}

We report the case of a 42-year-old woman with chronic hepatitis C (genotype 1), who in June 2004 started therapy with pegylated interferon alpha (PEG-IFNalpha) plus ribavirin. Two months later, she discontinued treatment because of polydipsia, polyuria and vomiting leading to a marked dehydration. Biochemical data showed type 1 diabetes mellitus with ketoacidosis, and insulin therapy was started. The patient, who before starting PEG-IFN alpha plus ribavirin therapy tested negative for glutamic acid decarboxylase antibodies (GADAb) and islet cell (ICAb) antibodies, became strongly positive for both autoimmune markers. This case confirms that patients with chronic hepatitis C who do not have baseline markers of pancreatic autoimmunity may develop severe ketoacidosis during treatment with PEG-IFNalpha, as well as with standard IFNalpha. In order to avoid this complication, as no guidelines are available and the pancreatic autoimmunity markers are not routinely analysed, we suggest frequent monitoring (e.g., every one to two weeks) of glycaemic values: e.g., every one to two weeks during the first 3 months (when this complication occurs most frequently) and monthly thereafter so as to identify diabetes at an early stage and before the onset of the appearance of severe ketoacidosis, which is life-threatening.

In a study of 87 patients with chronic hepatitis C, 12 months9 treatment with interferon alfa-2b at a dose of 6 million units (MU) three times per week seemed to be more effective than treatment with 3 MU three times a week for two months plus 1.5 MU three times a week for 10 months in increasing the percentage of long term responders. The percentage of patients in whom alanine amino-transferase activities returned to normal was highest in the 6 MU group, as was the percentage of responders who sustained this normal activity after treatment. Side effects were moderate and self-limited in most patients.

The sexual transmission of hepatitis C virus (HCV) has long been debated. The prevalence of infected at-risk partners varies from 0% to 30%. In a prospective study, the risk of infection was quantified in steady heterosexual partners and the prophylactic effect of normal human polyvalent immune serum globulin (ISG) was evaluated. A total of 899 at-risk partners of HCV-infected patients were enrolled in a single-blind randomized controlled trial and assigned to receive every 2 months 4 mL of intramuscular ISG from unscreened donors (450 partners) or placebo (499 partners). Seven partners developed acute HCV infection (increased aminotransferase levels and appearance of HCV-RNA): six of the placebo group (incidence density [ID] 12.00/1,000 person year; 95% confidence interval [CI] 3.0 to 21.61), and only one of the ISG-treated group (ID 1.98/1,000 person year; 95% CI 0 to 5.86). The risk of infection was significantly higher in controls versus treated individuals (p = 0.03). Six couples had genotype 1b (85%), and one couple had genotype la; HCV sequence homology strongly supported sexual transmission. Our trial demonstrates that HCV infection can be sexually transmitted and quantifies the risk of sexual transmission: for every year of at-risk sexual relationship, almost 1% of the partners became infected. Intramuscular ISG is safe and well tolerated. Unlike ISG from screened donors, ISG from donors unscreened for anti-HCV contains high titers of anti-gpE1/gpE2 neutralizing antibodies and high neutralizing activity. Anti-HCV hyperimmune globulin could be prepared from anti-HCV-positive blood units and could be used to protect sexual partners and in other at-risk situations of exposure to HCV infection.

Objectives: To estimate the risk of sexual transmission of hepatitis C and to assess the value of prophylaxis with periodic intramuscular immune serum globulin administration. Methods: Of 1102 steady heterosexual partners of patients with antibodies to the hepatitis C virus (HCV), 899 were enrolled in a single-blind, randomized, controlled trial. All the partners tested negative for antibodies to HCV and had normal baseline serum aminotransferase concentrations. The partners were assigned to receive 4 mL of 16% polyvalent immune serum globulin prepared from unscreened donors every 2 months (n=450) or a placebo (n=449). Tests for HCV infection were performed every 4 months. Results: Eight hundred eighty-four partners completed the study. Seven partners became infected with HCV: 6 in the control group (incidence density, 12.00 per 1000 person-years; 95% confidence interval, 3.0-21.61) and 1 in the immune serum globulin group (incidence density, 1.98 per 1000 person-years; 95% confidence interval, 0-5.86). The risk of infection was significantly higher for partners in the control group ( P =.03): for each year approximately 1% of the partners became infected. Sequence homology studies strongly suggest the sexual transmission of HCV. All immune serum globulin lots used had high enzyme-linked immunosorbent assay titers of neutralizing antibodies to HCV envelope glycoproteins and high neutralization titers in the neutralization of binding assay. Conclusions: Hepatitis C can be sexually transmitted. Immune serum globulin prepared from unscreened donors significantly reduced the risk. The treatment was safe and well tolerated. Because only immune serum globulin from unscreened donors (and not from those screened for HCV) contain anti-HCV neutralizing antibodies, hyperimmune anti-HCV immune serum globulin should be prepared from blood testing positive for antibodies to HCV, which is currently discarded. Arch Intern Med. 1997;157:1537-1544

The effects of interferon-alpha (IFN-alpha), given at a dosage of 6 MU thrice weekly for 12 months, on gonadal function were investigated in 18 males affected by chronic hepatitis C. Periodically, all patients were clinically monitored and questioned about sexual function. Gonadotropin and serum androgen concentrations (follicle-stimulating hormone, luteinizing hormone, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and sex hormone binding globulin) were tested every 3 months. Ten of 18 patients (55%) responded to IFN-alpha therapy. Serum total testosterone and sex hormone binding globulin values decreased slightly at the third month of treatment, then returned to baseline values. Serum free testosterone and other sex hormones remained essentially unchanged during IFN-alpha therapy. Four patients (22.2%) complained of sexual dysfunction (impaired libido, erectile failure, and impaired ejaculation), which was unrelated to any significant hormonal change and resolved after IFN therapy was stopped. Serum sex hormones values did not differ between responders and nonresponders to IFN-alpha. This study indicates that 12 months treatment with 6 MU of IFN-alpha thrice weekly does not significantly affect gonadal function in men with chronic hepatitis C. The sexual dysfunction observed could be ascribed to such other side effects of IFN as asthenia, fatigue, or anxiety, or it could have a psychologic basis.