The outbreak of coronavirus disease 2019 (COVID-19) has distressed our working practice. Infectious disease specialists, pneumologists and intensivists were not enough to face the enormous amount of ...patients that needed hospital care; therefore, many doctors have been recruited from other medical specialties trying to take care of as many patients as possible. The ‘call to duty’ of such doctors for urgent COVID-19 cases, however, diverted the attention from the care of patients with chronic conditions, which might have been neglected or undervalued. In this extremely difficult time, the standard of care of chronic patients has been reduced and this might have determined an increased rate of complications secondary to undermanagement. Thousands of patients with acute and chronic non-COVID-19 conditions have not accessed specialist care in the last weeks in Italy. Moreover, even those patients who have had scheduled an outpatient visit did not attend it for fear of leaving their home or due to the inability to go. During the pandemic, there was a drastic reduction in the number of hospital admissions for any medical conditions different from COVID-19. Self-presentation to the emergency department (ED) has been discouraged and the patients’ own fear of being infected by going to the hospital led to also a significant decrease in ED access. During the lockdown, in San Giuseppe Hospital MultiMedica IRCCS, Milan, the ED admissions dropped from the mean of 2361/month in December 2019–February 2020 to 1102 (− 53%) and 861 (− 63%) in March and April 2020, respectively. For all the above-mentioned reasons, it is possible that some clinical conditions will further progress with a significant increase in morbidity and mortality. To prevent this, it is essential that patients with chronic conditions should be at least monitored and managed with telephone or online health consultation, identifying those who need urgent access to care, prioritizing outpatient visits based on disease severity. Patients with mild conditions could be managed outside the hospital by implementing telemedicine and creating networks of general practitioners who can consult with in-hospital specialists.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chronic infection with the hepatitis C virus (HCV) is a major cause of liver disease worldwide and is also responsible for extrahepatic manifestations (EHMs) involving the skin, kidneys, salivary ...glands, eyes, thyroid, and immune system. Mixed cryoglobulinemia is the prototype EHM related to HCV infection. Although these HCV-related EHMs may contribute to significant rates of morbidity affecting patient's quality of life and survival, most of these complications can reverse after HCV eradication by interferon therapy. This notwithstanding, individual patients may have an irreversible injury in various organs that is not reversed by a cure of the HCV infection.
Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment ...where it arises-advanced chronic liver disease-to its heterogeneous clinical and biological behaviour. The advent, and good results, of immunotherapy for cancer called for the evaluation of its potential application also in HCC, where there is evidence of intra-hepatic immune response activation. Several studies advanced our knowledge of immune checkpoints expression in HCC, thus suggesting that immune checkpoint blockade may have a strong rationale even in the treatment of HCC. According to this background, initial studies with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, and nivolumab, a programmed cell death protein 1 (PD-1) antibody, showed promising results, and further studies exploring the effects of other immune checkpoint inhibitors, alone or with other drugs, are currently underway. However, we are still far from the identification of the correct setting, and sequence, where these drugs might be used in clinical practice, and their actual applicability in real-life is unknown. This review focuses on HCC immunobiology and on the potential of immune checkpoint blockade therapy for this tumour, with a critical evaluation of the available trials on immune checkpoint blocking antibodies treatment for HCC. Moreover, it assesses the potential applicability of immune checkpoint inhibitors in the real-life setting, by analysing a large, multicentre cohort of Italian patients with HCC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In the original publication of the article, the given name and family name of all the author were swapped. The correct author name is given in this erratum.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We describe a rare case of polyserositis with chylous ascites following nivolumab therapy, highlighting the challenges in recognizing and managing immune-related adverse events (irAEs) associated ...with immune checkpoint inhibitors (ICPIs).
Background & Aims
In the direct‐acting antiviral era, treatment of genotype‐3 HCV (HCV‐GT3) is still challenging. Real‐life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir ...(DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap.
Methods
Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV‐GT3 patients consecutively treated within the Lombardia web‐based Navigatore HCV‐Network; differences in SVR12 across regimens were evaluated by logistic regression.
Results
Of the 2082 subjects with HCV‐GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV‐positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV‐RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10HCV‐RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV‐RNA were independently associated with SVR12.
Conclusions
In a large real‐life setting of HCV‐GT3‐infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier‐to‐treat patients allows ribavirin‐free and shorter schedules without mining SVR12 in this <<difficult‐to‐treat>> genotype.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background/Aims: Cryoglobulinemic vasculitis remains an uncommon complication of hepatitis B virus infection. Methods: We report the case of a 40-years old female Chinese patient with chronic ...hepatitis B developing cryoglobulinemic vasculitis with multiple organ involvement (liver, kidney, and skin) coupled with weakness, arthralgias, haemolytic anaemia, and autoimmune thyroiditis. She received entecavir mono-therapy at dose adjusted for estimated glomerular filtration rate. Results: Within five months of entecavir treatment, hepatitis B viraemia decreased below the limit of detection with normal serum amino-transferase levels, HBeAg clearance occurred, vasculitis regressed with disappearance of purpura and ascites; in addition, renal function normalized and nephritic syndrome remitted. After a five-year follow-up, the patient is asymptomatic with intact kidney function, proteinuria in the normal range, and normal liver biochemistry, despite the antiviral treatment was withdrawn and the patient remained HBsAg positive. Conclusions: This is the second case of hepatitis B virus-related cryoglobulinemic vasculitis successfully treated with entecavir suggesting that effective antiviral therapy may counteract both the hepatic and extra-hepatic manifestations of infection by hepatitis B virus.
Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based ...on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis.
HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram.
After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively.
The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP