Fever of unknown origin (FUO): which are the factors influencing the final diagnosis? A 2005-2015 systematic review.

BACKGROUND: The differential diagnosis of Fever of Unknown Origin (FUO) is very extensive, and includes infectious diseases (ID), neoplasms and noninfectious inflammatory diseases (NIID). Many FUO remain undiagnosed. Factors influencing the final diagnosis of FUO are unclear. METHODS: To identify factors associated with FUO diagnostic categories, we performed a systematic review of classical FUO case-series published in 2005-2015 and including patients from 2000. Moreover, to explore changing over time, we compared these case-series with those published in 1995-2004. RESULTS: Eighteen case-series, including 3164 patients, were included. ID were diagnosed in 37.8% of patients, NIID in 20.9%, and neoplasm in 11.6%, FUO were undiagnosed in 23.2%. NIIDs significantly increased over time. An association exists between study country income level and ID (increasing when the income decreases) and undiagnosed FUO (increasing when the income increases); even if not significant, the use of a pre-defined Minimal Diagnostic Work-up to qualify a fever as FUO seems to correlate with a lower prevalence of infections and a higher prevalence of undiagnosed FUO. The multivariate regression analysis shows significant association between geographic area, with ID being more frequent in Asia and Europe having the higher prevalence of undiagnosed FUO. Significant associations were found with model of study and FUO defining criteria, also. CONCLUSIONS: Despite advances in diagnostics, FUO still remains a challenge, with ID still representing the first cause. The main factors influencing the diagnostic categories are the income and the geographic position of the study country.

Different changes in mitochondrial apoptotic pathway in lymphocytes and granulocytes in cirrhotic patients with sepsis.

BACKGROUND & AIMS: Apoptosis regulates leucocyte response during bacterial infections. This study explored leucocyte apoptotic pathway in cirrhotic patients with or without infections or sepsis. METHODS: In cirrhotic patients with bacterial infection or sepsis, the expression of Caspase 9, Bcl-2 family proteins, which comprises pro-apoptotic molecules, such as Bax, and anti-apoptotic molecules, such as Bcl-2 and Bcl-xL, were measured in peripheral lymphocytes and granulocytes. Regulatory microRNAs MIR-15 and MIR-16 were also measured. RESULTS: This study enrolled 80 patients with cirrhosis, of whom 28 had no evidence of infections, 32 had bacterial infections and 20 had sepsis; reference values were obtained from 10 age-matched healthy subjects. An over-expression of Caspase-9 and pro-apoptotic protein Bax was found in lymphocytes of cirrhotic patients with infection or sepsis as compared with non-infected cases (P = 0.05 and 0.0001, respectively), while anti-apoptotic proteins Bcl-2 and Bcl-xL were downregulated. In granulocytes, lowest expression of pro-apoptotic protein Bax occurred in septic patients, while in cirrhotics with infections anti-apoptotic Bcl-2 and Bcl-xL were upregulated. Eight patients died; the survivors had less derangements in Bax, Bcl-2 and BcL-xL expression than non-survivors. The pro-apoptotic miRNA, MIR-15 and MIR-16, were upregulated in cirrhotics with bacterial infections. CONCLUSIONS: Overall, the data show in lymphocytes, and not in granulocytes, an activation of the pro-apoptotic pathway in cirrhotic patients with bacterial infections, which correlates with the severity of the infection and the outcome.

[HBV and pregnancy]. / Infezione da HBV in gravidanza.

The clinical course of HBV infection in pregnant women does not usually differ from the course in non-pregnant women. Hepatitis flare rarely occurs during pregnancy, but it is frequent after delivery. HBV carrier status is associated with a higher incidence of gestational diabetes mellitus, pre-term labour and miscarriage. In the case of HBV-infected women wishing to become pregnant, the therapy could be delayed after delivery if the liver disease is mild, while if the woman has a moderate/severe liver disease, or becomes pregnant while on treatment, the potential risks of the antivirals have to be compared with the risks of hepatitis flares with progression to hepatic decompensation without treatment. The availability of highly effective passive-active immunoprophylaxis of the neonate using hepatitis B immune globulin and hepatitis B vaccine has considerably reduced the incidence of the vertical transmission of HBV infection, but a residual risk exists in cases of high maternal HBV-DNA levels: in such cases, the administration of anti-viral therapy during the third trimester of pregnancy may further reduce the risk of neonatal infection.

Salvage therapy with tenofovir followed by adefovir maintenance in a cirrhotic patient with a lamivudine resistant HBV flare.

A 36 year old man with chronic hepatitis B and cirrhosis was admitted in our Department for the onset of jaundice, ascites and ALT flare (x 35 u.n.v.) while under lamivudine treatment. Serum HBV-DNA was 1.48 x 10(6) IU/ml and lamivudine (LAM) resistance mutations were present. Tenofovir (TDF) 300 mg/day was added to LAM after its off-label use was authorised. HBV-DNA decreased in a biphasic manner and became undetectable by day 45. A parallel improvement in ALT and bilirubin values was detected. Tenofovir was substituted with adefovir dipivoxil 10 mg/day. Ten months after this switch HBV-DNA remained undetectable. Tenofovir is an effective salvage therapy for critically ill patients with LAM-resistant HBV flares and can be switched to adefovir after HBV-DNA becomes undetectable. Local cost and reimbursement policies are important determinants in antiviral therapy.

[Cholera: recent acquisitions]. / Attualità sul colera.

Cholera is still a medical problem in several countries, leading to the death of a large number of affected individuals. Recent acquisitions on the epidemiology of Vibrio cholerae suggest that there is a risk of global spreading of the disease and of the development of new pathogenic strains. We have reviewed the most recent hypothesis on the ecology of cholera, in particular on the origin of epidemics. Recent developments in the fields of therapy and prophylaxis of cholera are also reported.

Fever of unknown origin: a systematic review of the literature for 1995-2004.

BACKGROUND: Fever of unknown origin (FUO) identifies a pattern of fever with temperature higher than 38.3 degrees C on several occasions over more than 3 weeks, in which the diagnosis remains uncertain after an initial diagnostic work-up. The identification of the cause of FUO is a challenge in clinical practice despite recent advances in diagnostic techniques. There are more than 200 reported causes of FUO and they can be classified in four diagnostic categories: infections, neoplasms, non-infectious inflammatory diseases and miscellaneous. METHODS: We performed a systematic research of the literature on classical FUO to retrieve the review articles and case series published from 1995 to 2004, including articles from developing countries. The case series were reviewed to identify the tests commonly used both to qualify a fever as FUO and to determine the cause of the FUO, and to design an updated flow chart for the diagnosis of classical FUO. RESULTS AND CONCLUSIONS: No standardized diagnostic strategy could be determined. The diagnostic process should be guided by the potential diagnostic clues (PDCs) emerging from the history, physical examination and baseline tests. A standardized flow chart can be applied only in absence of PDCs or when the PDCs are contradictory.Nuclear medicine techniques are a valuable aid in the search for the origin of FUO due to bacterial infections or in the absence of PDCs.

[Cutaneous myiasis from Cordylobia anthropophaga in a traveller returning from Senegal: a case study]. / Miasi cutanea da Cordylobia anthropophaga in un viaggiatore di ritorno dal Senegal.

Myiasis is the infestation of human or animal tissues by fly larvae. The disease is widespread especially in tropical countries. Here we report a case of myiasis due to Cordylobia anthropophaga that occurred in a traveller returning from Senegal. This case has some peculiar characteristics, regarding the site of the lesion and the clinical presentation.

[Risks of antibacterial agents in pregnancy]. / Rischi dei farmaci antibatterici in gravidanza.

Antimicrobial therapy in the pregnant woman has to consider the potential risks of antibacterial agents for the developing foetus and the mother. Extensive clinical experience shows that penicillins, cephalosporins and erythromycin (except erythromycin estolate) can be considered safe for the developing foetus and for the pregnant woman. Nitrofurantoin is a valid antibacterial option in pregnancy, except in the latter stages. Isoniazid and ethambutol are the safest drugs for the treatment of tuberculosis in pregnancy, but attention must be paid to the potential toxicity of isoniazid for the mother. For several other antimicrobial agents (aminoglycosides, fluoroquinolones, newer macrolides, metronidazole, rifampicin, vancomycin) a potential teratogenic or toxic risk has been documented in animal or human studies: however, their use during pregnancy is justified when there is no safer alternative. A few antibacterials should be absolutely avoided in pregnancy: tetracyclines, cotrimoxazole and chloramphenicol according to a teratogenic risk or a toxic risk for the foetus or the mother, and clindamycin according to its high risk/benefits ratio. The safety data in pregnancy of many other antibacterials, including carbapenems, ketolides and streptogramines, are very limited or lacking. More data on the risks of antibacterial agents are needed for an optimal therapy of bacterial infections in pregnancy.