SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups.

Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with "bystander hepatitis", cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.

A case of adenoviral covid-19 vector vaccine possibly linked to severe but reversible interstitial lung injury post-vaccination.

BACKGROUND: Several safe and effective vaccines against nCoV-19 have been developed to contain the pandemic with very few severe adverse-reactions reported. Vaccine-induced interstitial lung disease (ILD) is a very rare and difficult to recognise and diagnose adverse-reaction and is mostly associated with Influenza vaccines. METHODS: We report a 55-yr old male who presented with severe respiratory failure that required for several days oxygen supplementation with high flow nasal cannula, and myocardial infarction. Symptoms onset was eighteen days after the first shot of adenoviral AZD1222 vector vaccine. Possible SARS-CoV-2 natural infection post-vaccination was excluded with rigorous laboratory work-up including multiple nasopharengeal rt-qPCR tests for SARS-CoV-2 detection and close monitoring of his serum SARS-CoV-2 antibodies. Other potential infectious agents and alternate diagnoses were thoroughly investigated. RESULTS: Patient responded impressively to high dose steroids. A repeat chest CT nine days after the first one showed a remarkable resolution of the bilateral ground glass opacities. Except for his cardiology medication, no supplemental oxygen neither steroids were prescribed upon his discharge. On one month follow-up, no residual pulmonary dysfunction was noticed with patient preserving a SatO2 of 97-98% on ambient air. CONCLUSION: Vaccine-induced ILD might constitute a rare nCoV-19 post-vaccination adverse-event. According to current restricted data, when post-vaccination ILD is early suspected and recognised, then prompt implementation of steroid treatment reverses significantly the lung lesions without progression to fibrosis.

Controversies' clarification regarding ribavirin efficacy in measles and coronaviruses: Comprehensive therapeutic approach strictly tailored to COVID-19 disease stages.

BACKGROUND: Ribavirin is a broad-spectrum nucleoside antiviral drug with multimodal mechanisms of action, which supports its longevity and quality as a clinical resource. It has been widely administered for measles and coronavirus infections. Despite the large amount of data concerning the use of ribavirin alone or in combination for measles, severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019 (COVID-19) outbreaks, the conclusions of these studies have been contradictory. Underlying reasons for these discrepancies include possible study design inaccuracies and failures and misinterpretations of data, and these potential confounds should be addressed. AIM: To determine the confounding factors of ribavirin treatment studies and propose a therapeutic scheme for COVID-19. METHODS: PubMed database was searched over a period of five decades utilizing the terms "ribavirin" alone or combined with other compounds in measles, severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 infections. The literature search was performed and described according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles were considered eligible when they reported on ribavirin dose regimens and/or specified outcomes concerning its efficacy and/or possible adverse-effects. In vitro and animal studies were also retrieved. A chapter on ribavirin's pharmacology was included as well. RESULTS: In addition to the difficulties and pressures of an emerging pandemic, there is the burden of designing and conducting well-organized, double-blind, randomized controlled trials. Many studies have succumbed to specific pitfalls, one of which was identified in naturally ribavirin-resistant Vero cell lines in in vitro studies. Other pitfalls include study design inconsistent with the well-established clinical course of disease; inappropriate pharmacology of applied treatments; and the misinterpretation of study results with misconceived generalizations. A comprehensive treatment for COVID-19 is proposed, documented by thorough, long-term investigation of ribavirin regimens in coronavirus infections. CONCLUSION: A comprehensive treatment strictly tailored to distinct disease stages was proposed based upon studies on ribavirin and coronavirus infections.

Thymic Carcinoma With Multiple Paraneoplastic Disorders.

Thymic neoplasms are rare and may run an indolent course. Among them, thymic epithelial carcinoma is exceptional as it may be presented with extensive local invasion and distant metastases. There is a wide spectrum of autoimmune/paraneoplastic syndromes associated with thymic tumors including autoimmune diseases, some of which may precede the diagnosis of thymoma. This article describes a 37-year-old woman with metastatic malignant thymoma and a combination of manifestations from different organs. Vitiligo, Raynaud's phenomenon and anti-centromere antibodies were preceded while eosinophilia, interstitial lung disease, rash, thickening of the skin and asymptomatic cryoglobulinemia were diagnosed concomitantly with the neoplasm. We have reviewed the literature and found only twenty case reports with a cluster of three or more autoimmune/paraneoplastic syndromes in the same patient but none with this unique constellation of disorders. The diversity of thymoma's clinical presentation and laboratory/histological features may cause diagnostic dilemmas and therapeutic challenges.

Fatal Streptococcus pseudoporcinus disseminated infection in decompensated liver cirrhosis: a case report.

BACKGROUND: Streptococcus pseudoporcinus (S. pseudoporcinus) was first identified in 2006. It cross-reacts with Lancefield group B antigen agglutination reagents and has been misidentified as S. agalactiae. Sites of S. pseudoporcinus isolation include the female genitourinary tract, urine, wounds, and dairy products. The prevalence of vaginal colonization is reportedly between 1 and 5.4%. Two uneventful cases of soft tissue infection caused by S. pseudoporcinus were reported in the past. However, since late 2019, six cases of invasive S. pseudoporcinus infections have emerged in the literature, one of which was fatal. CASE PRESENTATION: We describe a fatal case of a Caucasian male with spontaneous bacterial peritonitis associated with bacteremia due to a multidrug-resistant S. pseudoporcinus strain in a patient with decompensated liver cirrhosis. Despite the patient's good general condition and stable blood test results when he had visited the outpatient clinic for large-volume paracentesis a few days before admission, this time he presented to the emergency department with a rapidly worsening clinical condition and with laboratory features consistent with multiple-organ dysfunction syndrome, and succumbed within a short period. CONCLUSIONS: Contrary to what was thought until recently, multidrug-resistant S. pseudoporcinus may cause invasive, disseminated, fatal disease in humans. According to current limited data, vancomycin, linezolid, daptomycin, levofloxacin, clindamycin, and tetracycline seem to be the most effective antimicrobial agents against multidrug-resistant strains, and should be the empirical choice in cases of disseminated S. pseudoporcinus infection until laboratory antimicrobial susceptibility results are available. Improvements and new approaches for bacterial identification in routine clinical microbiology laboratories may reveal the real spectrum of S. pseudoporcinus infections in humans, which is currently believed to be underestimated. SS. pseudoporcinus could emerge as a serious medical problem in the near future, similar to other ß-hemolytic streptococci.

Clinical characteristics and outcomes of measles outbreak in adults: A multicenter retrospective observational study of 93 hospitalized adults in Greece.

OBJECTIVES: Measles outbreaks are increasingly reported among countries that were close-to-eliminate measles infection. There are few reports of clinical characteristics of measles in adults in the contemporary literature. In this study we aim to describe the clinical characteristics and complications of measles infection in hospitalized adults during the recent epidemic in Greece. METHODS: A multicentre observational retrospective study was conducted in three tertiary hospitals in Greece. All adult hospitalized patients (≥18 years old) with serologically confirmed and/or clinical features compatible with measles were included. Pediatric patients and patients with missing data were excluded. RESULTS: In total, 93 patients, 40 males (43 %) and 53 females (57 %), mostly young patients were included. Most of them (87 %) had no past medical history. Among women, 4 were pregnant. 56 (60.2 %) and 25 (26.9 %) patients reported either unknown or incomplete vaccination for measles. Ribavirin was administered in 8 (8.6 %) patients. Pneumonitis and hepatic involvement were the most common complications, occurring in 43 (46.2 %) and 75 (80.6 %) patients respectively. Pneumonitis was significantly associated with male sex, older age, lower lymphocyte counts and higher C-reactive protein (CRP) on admission. One pregnant woman suffered spontaneous fetal miscarriage and one patient died due to acute respiratory distress syndrome (ARDS) and high-risk pulmonary embolism. CONCLUSION: Considerable proportions of incompletely vaccinated or unvaccinated adults have led to the re-emergence of measles in countries with reported close-to-elimination rates. Pneumonitis is a major complication among adults with measles. More studies are imperative in order to explore the role of immune paresis in measles.

The immunity features and defects against primary cytomegalovirus infection post-splenectomy indicate an immunocompromised status: A PRISMA-compliant meta-analysis.

BACKGROUND: To evaluate if splenectomy results in severely impaired immune responses against primary cytomegalovirus (CMV) infection compared to the general immunocompetent population. METHODS: We performed a systemic literature review to study CMV infections in splenectomized individuals, a special population group presently considered immunocompetent to viral infections. We retrieved 30 cases with established CMV infection post-splenectomy and we recorded their disease manifestations, laboratory findings, immunological studies, and histopathology reports. In addition, we retrieved numerous multidisciplinary articles in view of post-splenectomy immunology defects, as well as of immune responses to primary invading CMV in the absence of the spleen. Two clinical studies directly comparing splenectomized with nonsplenectomized individuals under severe iatrogenic immunosuppression as well as the numerically largest review articles of CMV infections in immunocompetent were retained. RESULTS: Splenectomy results in the loss of spleen's ability to fend-off blood-borne pathogens and impairs the link between innate and adaptive immunity. The major post-splenectomy immune-defects against CMV are: weakened, delayed or absent anti-CMV IgM, and compensatory marked IgG response; severely impaired B-cell and CD4, CD8 T-cells function responses; and post-splenectomy, bone marrow compensates for the absence of spleen's immune responses against CMV, mimicking a monoclonal T-cell lymphoproliferative process. CONCLUSION: The puzzled diagnosis of the CMV syndrome post-splenectomy is of the most challenging and misleading, resulting in risky and costly interventions and a subsequent prolonged hospitalization (2 months). The mounting multi-disciplinary literature evidence renders us to suggest that splenectomized individuals are not only prone to encapsulated bacteria but also behave as immunocompromised to CMV.

Severe pancytopenia and splenomegaly associated with felty's syndrome, both fully responsive solely to corticosteroids.

In severe cases of pancytopenia with subsequent infections due to long-term untreated Felty's syndrome, the initiation of immunosuppressive treatment with sole prednisone (1 mg/kg iv) should be considered, despite that, the low neutrocytes count would make one physician hesitant. A full resolution of whole blood count within 3 weeks and a 30% reduction in spleens sized was noted.

Cytomegalovirus infection in a splenectomized with ß-thalassemia major: immunocompetent or immunosuppressed?

We should possibly revise our knowledge about risk assessment of splenectomized individuals with ß-thalassemia major. Besides their known risk of certain bacterial infection, they might be also in a risk of life-threatening primary cytomegalovirus (CMV) infection and end-, multi-organ disease, in the context of their immunosuppression status. Prompt and appropriate treatment initiation can be life saving.

Listeria monocytogenes peritonitis: presentation, clinical features, treatment, and outcome.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious complication in cirrhotic patients. Gram (-) (E. coli, Klebsiella pneumoniae), and Gram (+) (Streptococci, Staphylococci) bacteria are most frequently cultured from patients'ascites. Listeria monocytogenes (Lm) is scarcely reported as a causative agent. OBJECTIVE: Our objective is to describe Lm peritonitis as a clinical entity, including its presentation, clinical features, treatment, and the potential factors that might affect survival outcome. DATA SOURCES: MEDLINE, Scholar.Google, Scopus databases, including English, Spanish, French, and German language papers published between 1966 and June 2011, and reference lists. DATA EXTRACTION: investigators abstracted details about medical history, disease presentation, laboratory data, treatment and outcome. DATA SYNTHESIS: One-hundred and twenty-eight cases with known survival outcome--eighty-six cirrhotics, seventeen individuals undergoing continuous ambulatory peritoneal dialysis and another twenty-five with other or no underline condition were reviewed. An additional number of twenty-five cases with unknown outcome were searched in Listeria studies published from 1990 to 2009 and were only used for calculating worldwide distribution. CONCLUSION: Cirrhotics, mostly alcoholics, presented with fever and abdominal pain. Those who succumbed had significantly higher peripheral WBC count (15622 vs. 8155 cells/mm(3), p = 0.01) and (%) polymorphonuclear cells in differential count (83.3 vs. 71%, p = 0.001). Higher mortality was experienced in those with comorbidities, and those who presented with encephalopathy. Lower mortality was experienced in patients on continuous ambulatory peritoneal dialysis. Ascites was neutrocytic in 86% of the samples. In the sum of the cases mortality was 27.3%, with significantly highest rates in the elderly, in patients with bacteremia, immunosuppression, hematological malignancies, and lowest rates in those who presented with abdominal pain and in diabetics (type I or II). The latter observation was surprising and could be considered a single fortuitous fact. Initial appropriate treatment was associated with significantly better outcome (p = 0.002) than inappropriate; combination therapy with an aminoglycoside was superior to monotherapy (p = 0.038).

Disseminated intravascular coagulation as the laboratory hallmark of acute Q fever.

A 37-y-old white male presented with high fever, constitutional symptoms, mild meningeal and pulmonary involvement. Laboratory investigation revealed thrombocytopenia and excessive prolongation of coagulation times (International normalized ratio-INR- up to 6) requiring transfusion with 14 units of fresh frozen plasma. Serology established acute Coxiella burnetti infection. Patient recovered on levofloxacin.

Possible green tea-induced thrombotic thrombocytopenic purpura.

PURPOSE: A case of a patient who developed thrombotic thrombocytopenic purpura (TTP) after consuming a weight-loss product containing green tea is reported. SUMMARY: A 38-year-old, 68-kg Caucasian woman arrived at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. She had no symptoms of infection and denied illegal drug use. Her medical history included hypothyroidism, for which she was treated with levothyroxine 150 microg daily for the past four years. She reported that she had been using a green tea preparation for the two months before admission to lose body weight. The daily preparation contained 200 mg of green tea extract 5:1, equivalent to 1 g of natural green tea. On clinical examination, the patient appeared acutely ill and was afebrile, with pallor, petechiae, and purpura of the extremities. Laboratory test results at the time of admission revealed that the patient had anemia and marked thrombocytopenia. A peripheral blood smear demonstrated a feature of microangiopathic hemolytic anemia. Immunoglobulin G autoantibodies against ADAM metallopeptidase with thrombospondin type 1 motif, 13 were detected. On hospital day 3, the patient appeared confused and exhibited aphasia that was initially transient but then recurrent. Brain computerized tomography did not exhibit focal pathology. Over the next few days, her neurologic symptoms subsided and her platelet count and hematocrit value gradually increased. Plasmapheresis was performed (12 procedures). Corticosteroid treatment was also initiated. After 20 days of hospitalization, the patient was discharged. CONCLUSION: A 38-year-old woman developed TTP after consuming a weight-loss product containing green tea extract for two months.

Atypical autoimmune polyglandular syndrome type 3 overlapped by chronic HCV infection resulting in carcinogenesis and fatal infection.

The case of a woman with insulin-dependent diabetes mellitus, autoimmune thyroiditis, atrophic gastritis, pernicious anemia, and immunologic thrombocytopenic purpura consisting of autoimmune polyglandular syndrome type 3 associated with a history of gonadal failure is reported. Hepatitis C viral infection added xerophthalmia, lymphocytic sialadenitis, and exacerbation of idiopathic thrombocytopenic purpura. This unique disease constellation was complicated with splenic marginal zone lymphoma and gastric carcinoids. A lung infection, initially treated on an outpatient basis, proved fatal to the patient.

Case report: mixed cholestatic/hepatocellular liver injury induced by the herbicide quizalofop-p-ethyl.

CONTEXT: Quizalofop-p-ethyl is an often applied, slightly toxic herbicide for which no severe toxicity has been reported in humans. CASE PRESENTATION: We present the case of a farmer exposed to quizalofop-p-ethyl who presented with obstructive cholestasis. A complete workup disclosed no other cause of liver pathology, but liver biopsy established drug-induced hepatotoxicity. The patient was treated with ursodeoxycholic acid and prednisolone, and was recovered fully 70 days after his exposure to the herbicide. The patient was followed for the next 9 months. CONCLUSION: Quizalofop-p-ethyl can induce a mixed cholestatic/hepatocellular liver injury. We discuss possible mechanisms implicated in liver injury after exposure to quizalofop-p-ethyl. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: In patients presenting with mixed cholestatic/ hepatocellular liver injury, occupational exposure to quizalofop-p-ethyl in the course of agricultural use should be investigated.

Unusual onset of varicella zoster reactivation with meningoencephalitis, followed by rhabdomyolysis and renal failure in a young, immunocompetent patient.

We present an unusual onset of meningoencephalitis due to VZV reactivation, with increased intrathecal production of IgG VZV antibodies and negative PCR, in a young, immunocompetent adult. Herpes zoster erupted 5 d later. Rare complication of VZV-related rhabdomyolysis occurred, with subsequent ARF, in combination with acyclovir and ceftriaxone. The patient recovered fully and remained healthy.