N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study.

BACKGROUND: N-acetyl-cysteine (NAC) has been previously shown to exert beneficial effects in diverse respiratory diseases, through antioxidant and anti-inflammatory actions. Our aim was to evaluate NAC potential impact in hospitalised patients with COVID-19 pneumonia, in terms of progression to severe respiratory failure (SRF) and mortality. PATIENTS AND METHODS: This retrospective, two-centre cohort study included consecutive patients hospitalised with moderate or severe COVID-19 pneumonia. Patients who received standard of care were compared with patients who additionally received NAC 600 mg bid orally for 14 days. Patients' clinical course was recorded regarding (i) the development of SRF (PO2/FiO2 <150) requiring mechanical ventilation support and (ii) mortality at 14 and 28 days. RESULTS: A total of 82 patients were included, 42 in the NAC group and 40 in the control group. Treatment with oral NAC led to significantly lower rates of progression to SRF as compared to the control group (p < .01). Patients in the NAC group presented significantly lower 14- and 28-day mortality as compared to controls (p < .001 and p < .01 respectively). NAC treatment significantly reduced 14- and 28-day mortality in patients with severe disease (p < .001, respectively). NAC improved over time the PO2/FiO2 ratio and decreased the white blood cell, CRP, D-dimers and LDH levels. In the multivariable logistic regression analysis, non-severe illness and NAC administration were independent predictors of 28-days survival. CONCLUSION: Oral NAC administration (1200 mg/d) in patients with COVID-19 pneumonia reduces the risk for mechanical ventilation and mortality. Our findings need to be confirmed by properly designed prospective clinical trials.

Pneumococcal Otogenic Meningitis Complicated With Pneumocephalus and Coma State.

We herein describe the unusual case of a male patient with pneumococcal otogenic meningitis, which was complicated with non-traumatic pneumocephalus and coma, in the absence of head trauma or a neurosurgical procedure. The initiation of an aggressive, empirical scheme with wide-spectrum antibiotics was achieved to stop the progression of meningitis, pneumocephalus, and their underlying causes in this patient. We propose pathogenetic mechanisms to explain this life-threatening condition.

Fatal, paraparetic acute motor axonal neuropathy, early complicating chemotherapy with nab-paclitaxel.

So far, very few cases describing an interrelation between chemotherapy and Guillain-Barré syndrome have been published. We describe the first case of a paraparetic, pure acute motor axonal neuropathy variant of Guillain-Barré syndrome, early complicating protein-bound paclitaxel (nab-paclitaxel/abraxane) chemotherapy (first and sole session at a 350 mg dose) in a female patient with metastatic breast cancer. Although our patient was treated with the standard regimen of intravenous immunoglobulin for 5 days, she showed no evidence of motor improvement and died 1 month after the onset of the neurological deficit.

Serum cytokine profile in patients with hepatitis B e antigen-negative chronic active hepatitis B and inactive hepatitis B virus carriers.

An insufficient cellular immune response seems to be critical for the immunopathogenesis of chronic hepatitis B virus infection. We have previously demonstrated no differences of T-lymphocyte subsets in blood between inactive hepatitis B s antigen (HBsAg) carriers and patients with HBeAg-negative chronic active hepatitis B. This study investigated the peripheral blood cytokine profile in patients with HBeAg-negative chronic active hepatitis B infection (Group A, n = 21) and inactive HBsAg carriers (Group B, n = 13). Serum cytokines [interferon (IFN)-γ, tumor necrosis factor-α, interleukin (IL)-1b, IL-4, IL-12, IL-10, IL-2, IL-5, IL-8] were analyzed by using flow cytometry. Patients with chronic active disease presented with significantly decreased levels of IFN-γ and IL-10 compared to inactive carriers (P = 0.048 and P = 0.008, respectively). In HBeAg-negative chronic active hepatitis B patients, a significant negative correlation of IFN-γ levels with serum hepatitis B viral load was noted (P = 0.021). In conclusion, patients with HBeAg-negative chronic active hepatitis B and HBsAg inactive carriers display a different cytokine profile. Decreased Th1 response observed in patients with chronic active hepatitis B could be implicated in the persistence of virus replication and ongoing progression of liver disease.

Recurrent visceral leishmaniasis in an immunocompetent patient: a case report.

INTRODUCTION: Current treatment options for visceral leishmaniasis (pentavalent antimony, amphotericin B, liposomal amphotericin B and mitelfosine) achieve long-term clinical cure in the majority of immunocompetent patients. Disease relapse is usually provoked by T-cell number or function impairment (corticosteroid or cytotoxic therapy, transplant recipients, advanced human immunodeficiency virus disease). CASE PRESENTATION: We report a case of visceral leishmaniasis with multiple relapses in a 75-year-old Greek immunocompetent man. Visceral leishmaniasis relapses occurred despite appropriate treatment with liposomal amphotericin B 3mg/kg/day on days one to five, 14 and 21 (for the first episode and the first relapse) and mitelfosine 150mg/day for 28 days (for the second relapse). The third relapse was treated with high-dose liposomal amphotericin B (10mg/kg for two consecutive days), followed by a secondary prophylaxis of 3mg/kg once per month, which prevented disease reappearance during one year of follow-up. CONCLUSION: An unusual case of recurrent visceral leishmaniasis in an older immunocompetent patient was treated with high-dose liposomal amphotericin B and a monthly prophylaxis with no evidence of a relapse after one year of follow-up.

T-lymphocyte subsets in peripheral blood and liver tissue of patients with chronic hepatitis B and C.

AIM: To evaluate the immune response in peripheral blood and liver tissue, through the measurement of T-cell subsets, in patients with chronic hepatitis B (CHB) and C (CHC). PATIENTS AND METHODS: Thirty-four patients with CHB (21 with active HBV infection and 13 inactive HBV carriers) and 20 patients with CHC were included in the study. We also evaluated 21 biopsies from patients with active CHB infection and 20 patients with CHC. We measured CD3, CD4, CD8 and CD4/CD8 ratio in peripheral blood and liver tissue. RESULTS: We found no differences in the numbers of all T-lymphocyte subpopulations between patients with active HBV infection and inactive carriers. We found a significant increase in the absolute numbers of CD3(+), CD4(+) and CD8(+) T-lymphocytes in CHC compared to CHB patients (p=0.005, p=0.034 and p<0.0001 respectively). There was a significant increase in the number of CD3(+) and CD8(+) T-lymphocytes in the area of portal tracts (p=0.012 and p=0.009 respectively) and lobules (p=0.011 and p=0.01 respectively) in patients with CHC compared to those with CHB. In both groups there was a direct correlation between CD3(+) cells in portal tracts and HAI score (r=0.783, p=0.008), while we noted a correlation between CD8(+) cells in portal tracts and HAI score only in patients with CHC. Interface hepatitis correlated to CD3(+) cells in lobules of patients with CHC and CHB but a direct relationship between CD8(+) cells and HAI score was found only in those with CHC. CONCLUSION: Insufficient cellular immune response is critical for the ineffective virus clearance and liver damage in chronic hepatitis B, while in chronic hepatitis C, immune response, as represented by CD8(+) T-cells, is present in the peripheral blood and the liver. However, there is an immunological escape of HCV, which seems to survive in the presence of an adequate immune response. The significant correlation between portal and periportal CD8(+) T-lymphocyte expression and interface hepatitis may be considered evidence of the occurrence of cytotoxic immune-mediated toxicity.

Potential role of hepatic progenitor cells expression in cases of chronic hepatitis C and their relation to response to therapy: a clinicopathologic study.

BACKGROUND: This study investigates the correlation of hepatic progenitor cells (HPC) expression with treatment response in patients with chronic hepatitis C. DESIGN: The study comprised 77 liver biopsies with chronic hepatitis C (HCV). All patients were PCR-HCV (+) and received antiviral therapy with interferon or pegylated interferon alpha-2b and ribavirin. Twenty-nine patients were assigned as responders (group A), 29 as nonresponders (group B) and 19 as relapsers (group C). Ten normal liver biopsies were used as controls. Liver paraffin sections were subjected (a) to immunohistochemistry using antibodies for cytokeratins 19 (CK19) and 7 (CK7), alpha-fetoprotein (AFP), leukocyte common antigen (LCA) and CD34 antigen (b) to in situ hybridization for AFP mRNA and (c) to immunohistochemistry+in situ hybridization. Results were expressed as % of positive cells following morphometric analysis. RESULTS: HPC expression was present in all 87 specimens. In the control biopsies, rare HPC were detected. In the CH cases and according to AFP mRNA expression, the grade for % HPC expression was: group B: 53.2+/-2.6> group C: 48.37+/-1.8> group A: 31.4+/-1.6 (group A vs B P<0.01, group A vs C P<0.01, group B vs C P>0.05. Double stain revealed that HPC coexpressed CK19/AFP mRNA, CK7/AFP mRNa and AFP protein/AFP mRNA. HPC-percentages were directly correlated with total HAI score (P<0.01), fibrosis stage (P<0.01), and transaminase values (P<0.05). CONCLUSIONS: This study demonstrates that in cases of chronic hepatitis C, the significant association of HPC expression with the severity of disease and more specifically with the response to treatment implies that HPC development and proliferation may provide additional prognostic information and predict prognosis in such cases.

Prevalence of liver steatosis in patients with chronic hepatitis B: a study of associated factors and of relationship with fibrosis.

OBJECTIVES: The clinical significance of hepatic steatosis in chronic hepatitis B virus patients is poorly understood. The purpose of this study was to determine risk factors for liver steatosis in chronic hepatitis B patients and its relationship with fibrosis. METHODS: We retrospectively evaluated liver biopsies from patients with chronic hepatitis B treated in our department. Patients co-infected with other viruses (hepatitis C virus, HIV) or suffering from liver disease of any other cause were excluded from the study, as well as patients consuming alcohol above 30 g/day for males or 20 g/day for females. Liver steatosis, necroinflammation and fibrosis were assessed. RESULTS: A total of 233 patients with chronic hepatitis B were included in the study. The mean age was 44.7+/-16.2 years. There were 164 men (70.4%) and 69 women (29.6%). The majority of patients were HbeAg-negative, 196/233 (84.1%). Thirty-seven patients had cirrhosis (15.9%). Steatosis was present in 42 patients (18%). Steatosis was independently associated with fasting glucose level (P=0.019) and being overweight (body mass index >or=25; P=0.021). No correlation was found with stage of fibrosis, grade of inflammation, alcohol use or other parameters. Ninety-four out of 233 patients (40.3%) had advanced fibrosis. Patients with advanced fibrosis were older than those with minimal or no fibrosis (47.6+/-17 versus 42.3+/-15.2 years, P=0.024) and more frequently had a higher grade of necroinflammation activity (57/94 (60.6%) versus 26/139 (18.7%), P<0.0001). There was no significant association between advanced fibrosis and the presence of steatosis or mild alcohol consumption. CONCLUSION: Hepatic steatosis is present in 18% of our patients with biopsy-proven chronic hepatitis B. Steatosis is independently associated only with body mass index and fasting glucose level, risk factors for metabolic steatohepatitis, and was not correlated with the degree of fibrosis.

Liver steatosis is an independent risk factor for treatment failure in patients with chronic hepatitis C.

OBJECTIVES: Hepatic steatosis is a common feature of chronic hepatitis C. The purpose of this study was to determine factors related to the presence of steatosis and to define the role of steatosis in the response to antiviral treatment in chronic hepatitis C patients. METHODS: We retrospectively analysed all patients with chronic hepatitis C treated in a 5 year period in our department. Patients were included in the study only if a pretreatment liver biopsy specimen was available for evaluation. All patients treated either with interferon in combination with ribavirin, or with pegylated interferon in combination with ribavirin were included irrespectively of their response (early, end of treatment and/or sustained) to antiviral therapy. RESULTS: A total of 116 patients with chronic hepatitis C were included in the study with a mean age of 45.5 +/- 14.1 years. Steatosis was present in 52 patients (44.8%). On univariate analysis age, P = 0.04 and body mass index > or = 25, P = 0.004 were correlated with the presence of steatosis and on multivariate analysis only body mass index > or = 25, P = 0.032. Advanced fibrosis was not found associated with steatosis. Sixty patients out of 116 (51.7%) had sustained virological response (SVR). In particular 42 out of 64 patients with no steatosis (65.6%) had SVR compared to 20 out of 52 patients (38.4%) with any degree of steatosis (P = 0.009). Patients with genotype 2 or 3 had a more favourable outcome compared to patients with 1 or 4 genotypes, 63.2% vs 49.2%, P = 0.032. Also increased age (P = 0.0001), gamma glutamyltransferase (GGT) (P = 0.029), no history of intravenous drugs use (P = 0.001) and advanced fibrosis on pretreatment biopsy (P = 0.046) were correlated with treatment failure. On multivariate analysis significant independent association with SVR was found with the presence of steatosis on pretreatment biopsy (P = 0.004), increased GGT (P = 0.005) and genotype (P = 0.017). CONCLUSION: Steatosis in the liver biopsy performed before the beginning of antiviral treatment was found to be associated only to the body mass index of the patients and to be a strong independent factor for treatment failure.