Mind the gap: IgG4-related disease mimicking infectious cerebral mass lesions.

BACKGROUND: Cerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units. CASE PRESENTATION: Our patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease. Steroid treatment determined conspicuous improvement and led to discharge of the patient. CONCLUSION: Parenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology.

Clinical characteristics, management and in-hospital mortality of patients with coronavirus disease 2019 in Genoa, Italy.

OBJECTIVES: To describe clinical characteristics, management and outcome of individuals with coronavirus disease 2019 (COVID-19); and to evaluate risk factors for all-cause in-hospital mortality. METHODS: This retrospective study from a University tertiary care hospital in northern Italy, included hospitalized adult patients with a diagnosis of COVID-19 between 25 February 2020 and 25 March 2020. RESULTS: Overall, 317 individuals were enrolled. Their median age was 71 years and 67.2% were male (213/317). The most common underlying diseases were hypertension (149/317; 47.0%), cardiovascular disease (63/317; 19.9%) and diabetes (49/317; 15.5%). Common symptoms at the time of COVID-19 diagnosis included fever (285/317; 89.9%), shortness of breath (167/317; 52.7%) and dry cough (156/317; 49.2%). An 'atypical' presentation including at least one among mental confusion, diarrhoea or nausea and vomiting was observed in 53/317 patients (16.7%). Hypokalaemia occurred in 25.8% (78/302) and 18.5% (56/303) had acute kidney injury. During hospitalization, 111/317 patients (35.0%) received non-invasive respiratory support, 65/317 (20.5%) were admitted to the intensive care unit (ICU) and 60/317 (18.5%) required invasive mechanical ventilation. All-cause in-hospital mortality, assessed in 275 patients, was 43.6% (120/275). On multivariable analysis, age (per-year increase OR 1.07; 95% CI 1.04-1.10; p < 0.001), cardiovascular disease (OR 2.58; 95% CI 1.07-6.25; p 0.03), and C-reactive protein levels (per-point increase OR 1.009; 95% CI 1.004-1.014; p 0.001) were independent risk factors for all-cause in-hospital mortality. CONCLUSIONS: COVID-19 mainly affected elderly patients with predisposing conditions and caused severe illness, frequently requiring non-invasive respiratory support or ICU admission. Despite supportive care, COVID-19 remains associated with a substantial risk of all-cause in-hospital mortality.

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.

Travel-related hepatitis E: a two-decade GeoSentinel analysis.

BACKGROUND: Hepatitis E virus (HEV) is widely distributed worldwide and is endemic in developing countries. Travel-related HEV infection has been reported at national levels, but global data are missing. Moreover, the global availability of HEV diagnostic testing has not been explored so far. The aim of this study is to describe the epidemiology of HEV infections in returning travellers and availability of HEV diagnostic testing in the GeoSentinel surveillance network. METHODS: This was a multicentre retrospective cross-sectional study. All confirmed and probable HEV travel-related infections reported in the GeoSentinel Network between 1999 and 2018 were evaluated. GeoSentinel sites were asked to complete a survey in 2018 to assess the availability and accessibility of HEV diagnostic procedures (i.e. serology and molecular tests) throughout the study period. RESULTS: Overall, 165 travel-related HEV infections were reported, mainly since 2010 (60%) and in tourists (50%). Travellers were exposed to hepatitis E in 27 countries; most travellers (62%) were exposed to HEV in South Asia. One patient was pregnant at the time of HEV infection and 14 had a concomitant gastrointestinal infection. No deaths were reported. In the 51% of patients with information available, there was no pre-travel consultation. Among 44 GeoSentinel sites that responded to the survey, 73% have access to HEV serology at a local level, while 55% could perform (at a local or central level) molecular diagnostics. CONCLUSION: Reported access to HEV diagnostic testing is suboptimal among sites that responded to the survey; this could negatively affect diagnosing HEV. Pre-travel consultations before travel to South Asia and other low-income and high-prevalence areas with a focus on food and water precautions could be helpful in preventing hepatitis E infection. Improved HEV diagnostic capacity should be implemented to prevent and correctly diagnose travel-related HEV infection.

COVID-19 in a MS patient treated with ocrelizumab: does immunosuppression have a protective role?

BACKGROUND: Coronavirus disease 19 (COVID-19) is a novel disease entity that is spreading throughout the world. It has been speculated that patients with comorbidities and elderly patients could be at high risk for respiratory insufficiency and death. Immunosuppression could expose infected patients to even higher risks of disease complications due to dampened immune response. However, it has been speculated that overactive immune response could drive clinical deterioration and, based on this hypothesis, several immunosuppressants are currently being tested as potential treatment for COVID-19. METHODS: In this paper we report on a patient that has been treated with ocrelizumab (a B-cell depleting monoclonal antibody) for primary progressive multiple sclerosis who developed COVID-19. RESULTS: Despite complete B cell depletion, patient symptoms abated few days after hospitalization, and he was discharged to home-quarantine. Phone interview follow-up confirmed that, after 14 days, no new symptoms occurred. DISCUSSION: This report supports the putative role of immunosuppressive therapy in COVID-19 affected patients.

Time to change the single-centre approach to management of patients with tuberculosis: a novel network platform with automatic data import and data sharing.

Time to change the single-centre approach to TB http://ow.ly/lCeM30hBcbB.

Varied spectrum of clinical presentation and mortality in a prospective registry of visceral leishmaniasis in a low endemicity area of Northern Italy.

BACKGROUND: Visceral Leishmaniasis (VL) is endemic in 88 countries, in areas of relatively low incidence with a relevant proportion of immune suppressed patients clinical presentation, diagnosis and management may present difficulties and pitfalls. METHODS: Demographic data, clinical, laboratory features and therapeutic findings were recorded in patients identified by a regional VL disease registry from January 2007 to December 2010. RESULTS: A total of 55 patients (36 adults mean age 48.7 years, 19 children median age 37.5 months) were observed presenting with 65 episodes. All childen were immunocompetent, whereas adults affected by VL included both immunocompetent (n°17) and immunesuppressed (n°19) patients. The clinical presentation was homogeneous in children with predominance of fever and hepato-splenomegaly. A wider spectrum of clinical presentations was observed in immunocompromised adults. Bone marrow detection of intracellular parasites (Giemsa staining) and serology (IFAT) were the most frequently used diagnostic tools. In addition, detection of urinary antigen was used in adult patients with good specificity (90%). Liposomal amphotericin B was the most frequently prescribed first line drug (98.2% of cases) with 100% clinical cure. VL relapses (n°10) represented a crucial finding: they occurred only in adult patients, mainly in immunocompromised patients (40% of HIV, 22% of non-HIV immunocompromised patients, 5,9% of immunocompetent patients). Furthermore, three deaths with VL were reported, all occurring in relapsing immunocompromised patients accounting for a still high overall mortality in this group (15.8%). CONCLUSIONS: The wide spectrum of clinical presentation in immunesuppresed patients and high recurrence rates still represent a clinical challenge accounting for high mortality. Early clinical identification and satisfactory treatment performance with liposomal amphotericin B are confirmed in areas with low-level endemicity and good clinical standards. VL needs continuing attention in endemic areas where increasing numbers of immunocompromised patients at risk are dwelling.

Hepatitis B Reactivation in a HBsAg-Negative, HBcAb-Positive Patient Receiving Fludarabine for the Treatment of Chronic Lymphocytic Leukaemia.

Hepatitis B virus (HBV) reactivation is an increasingly recognized cause of morbidity and mortality in patients undergoing chemotherapy. In haematology, the risk of reactivation of B hepatitis among HBsAg-positive patients has been documented; therefore, use of lamivudine prophylaxis is recommended before starting chemotherapy. Differently, for HBsAg-negative patients with markers of previous HBV infection (i.e., presence of isolated anti-HBc positivity) (anticore patients) management strategies are not univocal. We describe a rare case of HBV reactivation in an anticore patient after fludarabine therapy for chronic lymphocytic leukaemia. The patient fully recovered after a 6-month course of lamivudine with persistent HBV-DNA clearance and loss of HBsAg. The most important feature of this case is that fludarabine alone infrequently determines HBV reactivation, especially in anticore patients. Therefore, we suggest that patients candidates to receive fludarabine therapy should be considered for lamivudine prophylaxis, not only if HBsAg-positive, but even if anticore-positive only.

Insulin resistance predicts rapid virological response in non-diabetic, non-cirrhotic genotype 1 HCV patients treated with peginterferon alpha-2b plus ribavirin.

BACKGROUND/AIMS: The rapid decline in hepatitis C virus RNA is crucial for determining the outcome of therapy in patients with genotype 1 chronic hepatitis C. However, the variables influencing the early phase of viral decay are still largely unexplored. We aimed to assess which pre-treatment variable may predict rapid virologic response (RVR) and sustained virologic response (SVR). METHODS: We evaluated 90 consecutive non-diabetic patients with genotype 1 chronic hepatitis C without cirrhosis, treated with peginterferon alpha-2b plus ribavirin. Viral load (COBAS Amplicore, Roche) was measured at 1, 4 and 12 weeks after starting treatment, and then 24 weeks after the end of treatment. RESULTS: The overall SVR was 47%. The SVR in patients with RVR was 100%. Age, GGT levels, viral load, steatosis, fibrosis and HOMA-IR were significantly associated with RVR in univariate analysis. After logistic regression, HOMA-IR proved to be the strongest independent predictor of RVR (OR 0.37, 95% CI: 0.16-0.89; p=0.027), whereas fibrosis had a weaker independent association with RVR (OR 0.32, 95% CI: 0.1-1.04; p=0.057). Among the eight pre-treatment variables, both BMI and steatosis were significantly associated with HOMA-IR, either in univariate or in multivariate analyses. CONCLUSIONS: Our data suggest that insulin resistance is strongly associated with RVR, thus reflecting the important role played by metabolic factors in the early phase of viral kinetics. HOMA-IR would appear to be a useful tool in predicting RVR and should be evaluated at baseline in all chronic hepatitis C patients before initiating antiviral treatment.