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The case here reported reflects the difficulty in diagnosing meningeal extramedullary hematopoiesis (EMH), which clinically appeared concomitantly with primary cerebral lymphoma and occurred in a patient with HIV infection and severe pancytopenia. Pancytopenia secondary to HIV infection could be hypothesized as a predisposing factor for the ectopic development of hematopoietic tissue outside the bone marrow. Although rare, intracranial EMH should always be considered in the differential diagnosis of headache and other endocranial hypertension symptoms in patients with chronic bone marrow dysfunction

Background: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients., Methods: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival., Results: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline., Conclusions: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Toscana virus (TOSV) is a Phlebotomus-transmitted RNA virus and a frequent cause of human meningitis and meningoencephalitis in Southern Europe during the summer season. While evidence for TOSV-related central nervous system (CNS) cases is increasing, little is known about the host defenses against TOSV. We evaluated innate immune response to TOSV by analyzing frequency and activation of blood antigen-presenting cells (APCs) and cytokine levels in plasma and cerebrospinal fluid (CSF) from patients with TOSV neuroinvasive infection and controls. An altered frequency of different blood APC subsets was observed in TOSV-infected patients, with signs of monocytic deactivation. Nevertheless, a proper or even increased responsiveness of toll-like receptor 3 and 7/8 was observed in blood APCs of these patients as compared to healthy controls. Systemic levels of cytokines remained low in TOSV-infected patients, while levels of anti-inflammatory and antiviral mediators were significantly higher in CSF from TOSV-infected patients as compared to patients with other infectious and noninfectious neurological diseases. Thus, the early host response to TOSV appears effective for viral clearance, by proper response to TLR3 and TLR7/8 agonists in peripheral blood and by a strong and selective antiviral and anti-inflammatory response in the CNS.

Background: Acute bacterial meningitis is a rare but extremely severe disease. The aim of this study was to investigate whether neutrophil gelatinase-associated lipocalin (NGAL) is present and measurable in cerebrospinal fluid (CSF) and if its assessment may be useful for identifying patients with bacterial meningitis., Methods: Eligible specimens were all consecutive CSFs of patients with suspect acute bacterial meningitis that were referred from the Unit of Infectious Diseases for routine chemical and morphological analysis over a three months period. CSF measurements consisted in NGAL, glucose, and total protein concentrations, along with cell count and differential., Results: Eighty eight CSFs were received throughout the study period, 58 (66%) with CSF findings compatible with bacterial meningitis. The values of white blood cells (WBC), polymorphonuclear (PMN) and mononuclear (MONO) leukocytes, red blood cells (RBC), total proteins, and NGAL were significantly increased in positive CSFs, whereas that of glucose did not significantly differ. A significant correlation was found between CSF concentration of NGAL and CSF values of PMN, WBC, RBC and total proteins, but not with that of glucose and MONO. The concentration of NGAL in CSF showed an area under the curve (AUC) of 0.94 for identifying positive CSFs, with specificity and sensitivity of 1.00 and 0.741 at a diagnostic threshold of 13 ng/mL., Conclusions: NGAL is present in CSF of patients with bacterial meningitis and its measurement may be helpful for identifying positive CSFs.

The case here reported reflects the difficulty in diagnosing meningeal extramedullary hematopoiesis (EMH), which clinically appeared concomitantly with primary cerebral lymphoma and occurred in a patient with HIV infection and severe pancytopenia. Pancytopenia secondary to HIV infection could be hypothesized as a predisposing factor for the ectopic development of hematopoietic tissue outside the bone marrow. Although rare, intracranial EMH should always be considered in the differential diagnosis of headache and other endocranial hypertension symptoms in patients with chronic bone marrow dysfunction.

Since the introduction of more effective antiretroviral therapy in HIV treatment, an increase in survival and in the quality of patients' life has been observed, due to the dramatic reduction in commonly occurring opportunistic diseases. The appearance of new clinical cases has, however, been observed, previously unrecorded probably due to the quicker negative evolution of AIDS. Pathologies such as lypodistrophy, cardiomyopathy, immune disease, are extremely widespread and partly linked to the natural history of HIV infections, and partly to the side effects of the treatments. Among such diseases, femoral head necrosis seems to occur fairly frequently and is characterised by a quick evolution. The emergence of coxalgia in HIV patients requires an early diagnosis through NMR or bone scan. Given the usual evolution of this pathology and the problems related to antiviral treatment, conservative treatment seems to have little possibility of success. A surgical replacement becomes essential in cases of invalidating necrosis, but there are still unresolved questions as regards risks of infection, bone integration, as well as local and systemic reactions to the prosthetic debris.

Up to the present, pancreatic complications due to cryptosporidium parvum infection have been described only in a few patients with acquired immunodeficiency syndrome (AIDS). We report our experience with 3 subjects with AIDS who presented with acute or chronic pancreatitis related to cryptosporidiosis. All 3 patients had abdominal pain resistant to analgesics, increased serum amylase and abnormalities at both sonography and computed tomography. Endoscopic retrograde cholangiopancreotography revealed papillary stenosis in all patients; one patient also had stenosis of the Wirsung duct. Cryptosporidium was found in both bile and stool samples in all patients, while viral cultures were negative, even in the 2 patients who had cytomegalovirus retinitis. Endoscopic sphincterotomy temporally relieved abdominal pain in all patients, but did not prevent either acute or recurrent pancreatic inflammation. Several antibiotic therapeutic protocols were ineffective against the parasite.

The importance of Rhodococcus equi infection, an uncommon human pathogen that almost exclusively affects immunocompromised hosts, has greatly increased following the advent of acquired immune deficiency syndrome (AIDS) epidemics. Until the present time, 38 cases of R. equi infection have been described in human immunodeficiency virus (HIV)-infected patients; we now report a further five personal cases. R. equi was acquired via respiratory exposure to animals in less than half of the patients, and caused invasive pulmonary infection (91%), bacteraemia and sometimes bloodstream dissemination. R. equi was easily cultured from sputum or blood, but its diagnosis was often difficult due to microbiological and clinical similarities with other pathogens. The persistence of the micro-organism inside macrophages and its high tissular load represent the major limitation to an effective treatment. Several antibiotics are active in vitro, but their efficacy in vivo depends on macrophage uptake and/or bactericidal activity. Treatment should start with at least two intravenous bactericidal antibiotics for 3-4 weeks, and then continue with oral therapy for a period of up to several months with at least two intracellularly active drugs. Surgical resection of the lesions may be beneficial in selected cases.

Sixty patients with endoscopically confirmed active variceal bleeding entered a randomized controlled clinical trial aimed at comparing the efficacy of octreotide vs. terlypressin in the control of acute variceal hemorrhage (period I, 24 h) and in the prevention of early rebleeding (period II, 6 days). Of the sixty 30 received octreotide (period I, 100 micrograms bolus followed by continuous intravenous infusion at 25 micrograms/h; period II, 100 micrograms t.i.d. subcutaneously), and 30 received terlypressin (period I, 2 mg intravenous bolus every 4 h; period II, 2nd day, 2 mg every 6 h; from 3th to 7th days, 1 mg every 6 h). Control of bleeding was achieved in 23 (76.6%) patients receiving octreotide and in 16 (53%) treated with terlypressin (NS); none of these patients suffered rebleeding during treatment. No significant difference in mortality was observed between the two groups during the hospitalization period. Complications due to therapy were lower with octreotide than with terlypressin (P < 0.01). Under the same effectiveness conditions the cost/benefit ratio must be taken into account.

We discuss here our experience with Mycobacterium avium complex (MAC) infection in 446 HIV-positive patients. MAC was found in 13 cases (2.9%): 10 males, 3 females, age range 21-47 years. Infection was disseminated in 10 cases and limited to the lung in 3. CD4+ cells were, on average, 48 per microliters. At clinical onset, all patients suffered from fever and weight loss, 10 from anemia, and 5 from diarrhea. MAC was found in its disseminated form in cultures of blood (10 patients), stool (5 patients) and urine (1 patient). Broncho-alveolar lavage seemed to be the most specific diagnostic method for lung infection. Twelve patients were treated with a multi-drug regimen consisting of an association of 4 or 5 antibiotics, selected on the basis of antibiogram, from the following: clofazimine, rifabutin, ciprofloxacin, ethambutol, isoniazid, amikacin and piazofolin. Mean survival of patients was 91.7%, 83.4%, 71.8% and 58.4% at 4, 5, 6 and 7 months of treatment respectively. Although the mean survival of the treated group is similar to that of untreated patients, multi-drug therapy seems to improve quality of life inasmuch as it brings temperature to normal and enables weight gain. Dissemination was never observed after treatment in patients with pulmonary infection only.

Preliminary data suggest that rifaximin a new non-absorbable rifamycin-derivate, has beneficial effects on chronic portal systemic encephalopathy (PSE). To compare the efficacy and safety of rifaximin vs neomycin in the treatment of the hyperammoniemic state of PSE, 30 cirrhotic patients with grade I to III of PSE were randomly allocated to one of two groups: group A (15 patients) receiving rifaximin (400 mg/8h) and group B (15 patients) neomycin (1gr/8h). The duration of treatment was 21 consecutive days. Age, sex, hepatic and renal function, level of PSE, EEG and number connection test were similar in both groups. A significant decrease in blood ammonia levels was observed at the end of the treatment period in both groups; moreover rifaximin produced an earlier reduction of blood ammonia levels. The neuropsychic syndrome related to the PSE improved in both groups without significant difference. No side effects attributable to therapy were observed in the rifaximin group. These results indicate that, rifaximin is at least as effective as neomycin in the achievement and maintenance of low blood ammonia levels in cirrhotics with chronic PSE.

Between August 1985 and June 1987, 809 subjects at risk for AIDS have been studied. 231 (28.5%) were seropositive for human immunodeficiency virus (HIV) antibodies. The seropositivity rate was 41% among drug addicts, 20.5% among homosexual/bisexual males, 19.7% among sexual partners of seropositive individuals. None of 62 subjects belonging to the health care personnel who interacted with seropositive patients and none of the 26 relatives of HIV-infected subject, have been found to be seropositive. Moreover the HIV seropositivity in the population of Parma was only 0.01%. Among the seropositive subjects, 155 (67.1%) were asymptomatic; 2 (0.8%) showed acute infection (a mononucleosis-like syndrome in both, associated with aseptic meningitis in one); 57 (24.6%) had PLG, 7 (3.4%) ARC, 9 (3.8%) full-blown AIDS (8 of these latter are dead).

In January 1984 a hepatitis B vaccination campaign was started in health care workers of Hospital of Parma. Within 3 years, of the 953 subjects submitted to serologic screening, 446 were eligible and 409, serum negative for HBV, completed the vaccination. 202 received HB-VAX vaccine (M.S.D.) intramusculary into the buttock at 0.1 and 6 months, and 208 received HEVAC-B vaccine (Pasteur) into deltoid region at 0, 1, 2 and 12 months. After the booster injection, percent of seroconversion (anti-HBs greater than 10 UI/l) and anti-HBs antibody titres were significantly (p less than 0.01) higher in HEVAC-B recipients (95.6%, mean anti-HBs titres = 6400 UI/l), than in the subjects vaccined with HB-VAX (77.1%, mean anti-HBs titres = 2703 UI/l). There was no significative difference in immune response in both groups with respect to age, sex or occupational category. Three hepatitis B infections were identified in HB-VAX recipients, but no one in individuals vaccined with HEVAC-B. No participants had serious adverse effects, minor side effects occurred with equal frequency in both groups. In general, both plasma-derived vaccines have proved to be highly immunogenic, safe and well tolerated in health care workers, however HEVAC-B vaccine, since contains S and pre-S ag, has shown a more satisfactory immunogenic effect.

Expression of hepatitis delta virus (HDV) markers was investigated in sera from 310 patients with acute hepatitis, 63 chronic hepatitis B surface antigen (HBsAg) carriers and 76 drug addicts positive for at least one serological hepatitis B virus (HBV) marker. Acute HDV infection occurred in 17.1% of the patients with acute hepatitis. Among 40 cases of coinfection, hepatitis was severe in ten and fulminant in three. Only two of the 13 superinfected patients showed a severe hepatitis, but a high percentage (78%) of them developed chronic hepatitis one year after HDV infection. Also in our area parenteral drug addiction represents the main factor of risk for HDV infection. The high prevalence of HDV infection in our area points to the necessity for serological screening for HDV markers in patients with acute and chronic hepatitis.

Thirty members of the staff and fifty-one patients of Parma hemodialysis unit, serum negative for HBV markers, having completed the vaccination (HB-vax vaccine) against hepatitis B, were followed for two years after booster dose. After the third injection, the response to HB vaccine was significantly higher (p less than .0005) in staff members, than in patients. In the staff group, 83.3% were responders at mean titers of anti-HBs of 2703 mUI/ml; only 51% of patients developed anti-HBs at mean titres of 287 mUI/ml. As to either sex or age, no significant differences were observed in the two groups. Among hemodialysis patients the higher response (71.4%) was noted in the less than 40 aged individuals in comparison with those 40-60 (56.9%) or greater than 60 aged (38%). The persistence of the immunisation in both groups appeared to be statistically correlated to the anti-HBs titres after booster injection. At the end of the follow-up, 63.3% of the staff vaccinated members, but only 15.6% of the patients still had protective titre. No ill-effects induced by vaccine developed. Hepatitis B infection was only observed in one non responder member of the staff. The study demonstrates a low response to HB-vaccine and a rapid decrease of anti-HBs titre in the hemodialysis patients, thus leading to the need of frequent revaccination.