197,108 research outputs found

    Review article: immune checkpoint inhibitors and the liver, from therapeutic efficacy to side effects

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    Background: Immune checkpoint inhibitors have revolutionised the oncological landscape in the last few years. Possible applications include the treatment of hepatocellular carcinoma and cholangiocarcinoma. Unfortunately, new immune-related adverse effects have been associated with the use of these agents and the liver is one of the organs most frequently involved. Aims: To provide a general overview of the potential impact of immune checkpoint inhibitors on the liver. Methods: We reviewed the literature and abstracts/presentations on immune checkpoint inhibitors at most relevant hepatology meetings over the last 5 years. Results: The role of immune checkpoint inhibitors has been investigated both for the treatment of viral hepatitis and primary liver cancer. Hepatocellular carcinoma and chronic hepatitis B show the greatest potential for treatment with these drugs in the near future. However, immune-related adverse events involving the liver are a growing concern related to their widespread use. Conclusions: Immune checkpoint inhibitors represent an exciting new class of drugs with currently limited application in malignant and non-malignant liver disease. Caution must be exercised on the emergence of potentially severe immune adverse reactions

    Hepatitis C: Is eradication possible?

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    Hepatitis C has a relevant global impact in terms of morbidity, mortality and economic costs, with more than 70 million people infected worldwide. In the resolution, “Transforming our world: the 2030 Agenda for Sustainable Development” was included as a focus area in the health-related goal with world leaders pledging to “combat” it by 2030. In response, WHO drafted the Global Viral Hepatitis Strategy carrying the ambitious targets to reduce the number of deaths by two-thirds and to increase treatment rates up to 80%. Despite the availability of highly effective therapeutic regimens based on direct-acting antivirals many barriers to HCV eradication still remain. They are related to awareness of the infection, linkage to care, availability of the therapeutic drug regimens and reinfection. Overall, if an effective prophylactic vaccine will not be available, HCV eradication appears difficult to achieve in the future

    Diagnostic utility of ultrasonography versus nerve conduction studies in mild carpal tunnel syndrome

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    Objective. To prospectively compare high-resolution ultrasonography (US) and nerve conduction velocity (NCV) in clinically diagnosed mild carpal tunnel syndrome (CTS). Methods. Eighty-five patients (70 women and 15 men, mean age 46.8 years) reported symptoms compatible with classic/probable CTS. The protocol included NCV of the median and ulnar nerves (distal motor latency [DML], sensory conduction velocity [SCV] from the third [M3 SCV] and fourth fingers [M4 SCV] to the wrist for the median nerve); electrophysiologic severity scale; self-administered Levine/Boston questionnaire (BQ); and cross-sectional area (CSA) measurement of the nerve at the tunnel inlet (CSA-I), at the middle (CSA-M), and at the outlet (CSA-O). Relationship between age, body mass index, duration of symptoms, CSAs, NCV, electrophysiologic severity scale, and BQ scores was calculated. Concordance between CSAs and NCV, sensitivity of NCV and US was also evaluated. Results. The mean values of CSA-I, CSA-M, and CSA-O were 10.3, 9.8, and 8.7 mm 2, respectively. Relationships were found between CSA-I and M3 SCV (r = -0.45), M4 SCV (r = -0.56), and median nerve DML (r = 0.29). Anomalous CSA-I, CSA-M, and CSA-O were found in 48, 25, and 26 patients, respectively; 55 (64.7%) had ≥1 abnormal CSA. NCV abnormalities were found in 67%. The sensitivity increased to 76.5% if US and NCV were considered together. The highest concordance to detect absence/presence of abnormalities was between CSA-I and NCV (77.6%; κ = 0.52). Conclusion. In mild cases of CTS, US did not detect more anomalies than NCV and vice versa, and no anomalies were detected with either diagnostic instrument in 23.5% of mild cases. © 2008, American College of Rheumatology

    Does the immune response play a role in the pathogenesis of chronic liver disease?

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    The pathogenesis and perpetuation of hepatocellular injury in chronic inflammatory liver disease is still unclear. Several pieces of circumstantial evidence point to the importance of antigen-specific immune responses. In chronic hepatitis B virus infection, the hepatitis B virus nucleoprotein appears to be a major target antigen for both helper and cytotoxic T lymphocytes. In autoimmune chronic active hepatitis, several autoantibodies have been identified that are associated with different disease subgroups and that may be helpful to distinguish this form of chronic active hepatitis from that caused by non-A, non-B agents. In primary biliary cirrhosis, antimitochondrial antibodies are almost invariably present and have now been characterized at the molecular level

    Factors influencing the diagnostic process of carpal tunnel syndrome

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    There are no studies regarding the course leading to carpal tunnel syndrome (CTS) diagnosis and factors influencing the diagnostic process. The study aim is to analyse CTS diagnostic path assessing whether the type of physician (general practitioners or specialist) may influence the manner and timing of diagnosis, and whether CTS severity at diagnosis may be predicted by factors related to Public Health Service and/or to patient. A medical history form was filled in by 375 consecutive patients with idiopathic CTS enrolled at an electromyography service. The patient answered a self-administered questionnaire on symptom severity and the neurophysiologist quantified clinical and electrophysiological CTS severity. The patients going directly to general practitioner were older and more blue collars, had minor education level, more symptom duration, more clinical and electrophysiological severity, more medical examination numbers, more time elapsing between first visit to a doctor and referral for EMG than those going to a specialist. But all variables are interrelated and when multivariate logistic regression analyses were performed, only patient age and some other few independent variables related to patient or health care but not to referring doctor could predict CTS severity at the diagnosis. Typology of the first doctor did not influence diagnostic path. The patients should reduce the time elapsing between CTS symptom onset and consulting doctor thus, permitting early treatments. Some corrective actions on diagnostic path may concern the public health service by reducing waiting lists to perform electrodiagnostic testing and giving greater information to population at risk. © 2012 Springer-Verlag Italia

    Production of human monoclonal antibodies to hepatitis C virus and their characterization

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    : Human monoclonal antibodies (hMAb) provide novel ways to probe the B-cell repertoire in health and disease. However, the development of hMAb technology has met with several difficulties owing to the instability of the cell lines, the low level of specific antibody secretion, and the poor cloning efficiency, particularly when using lymphoblastoid cells (1,2). In order to overcome these problems, some investigators have fused human B lymphocytes with human/mouse myeloma heterohybrids. However, in such systems, human chromosomes are unstable and may occasionally be deleted. Despite the potential emergence of technical pitfalls, B-cell immortalization with EBV has been extensively used for hMAb production, because of its simplicity and because EBV can bind to and penetrate in virtually all B lymphocytes, theoretically allowing the exploration of the whole B-cell repertoire. The most recent protocols have made use of techniques aimed at expanding the population of antigen-specific B-cell precursors and improving the capacity of B-cells to grow at low density. These methods will be discussed below

    Carpal tunnel syndrome incidence in a general population

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    Objective: To determine the incidence of carpal tunnel syndrome (CTS) in a general population of a restricted area in the middle part of Italy. Methods: Prospective study to identify cases of CTS, newly diagnosed on the basis of clinical symptoms and delay in distal conduction velocity of the median nerve. In the 8-year period from 1991 to 1998, cases were identified by electromyographic services in the Siena area of Local Health District No. 7 of Tuscany (Italy). This area has a population of 120,000. Results: In the 8-year period, 3,142 cases (79.7% women and 20.3% men; mean age, 55 years; range, 13 to 97 years) were identified. The mean annual crude incidence was 329 cases per 100,000 person-years, and the standardized incidence was 276. The sex-specific incidences were 139 for men and 506 for women. The mean annual incidence for men increased moderately but significantly during the study period, whereas that for women remained constant. The age-specific incidence for women increased gradually with age, reaching a peak between 50 and 59 years, after which it declined. In men, there was a bimodal distribution with peaks between 50 and 59 years and between 70 and 79 years. Rural and industrial areas had higher crude and age- and sex-specific incidences than did urban areas. Conclusions: The incidence in the Siena area is about threefold that reported in the Rochester area (Minnesota) and is similar to that of Marshfield (Wisconsin). The different results with respect to US reports may depend on case inclusion criteria and occupational activities of the population at risk
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