Unusual arterial thrombotic events in Covid-19 patients.

INTRODUCTION: COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated. OBJECTIVES: To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event. MATERIAL AND METHODS: We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis. RESULTS: From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy. CONCLUSION: Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated.

[A case of community-acquired MRSA (CA-MRSA) sepsis complicated by meningoencephalitis and cerebral abscess, successfully treated with linezolid]. / Un caso di sespi da MRSA comunitario (CA-MRSA) complicata da meningoencefalite ed ascesso cerebrale trattato con successo con linezolid.

The authors describe a clinical case regarding a young female patient affected by sepsis due to methicillin-resistant Staphylococcus aureus (MRSA), associated to meningoencephalitis and cerebral abscess. The patient had no contact with hospitals in the months prior to illness and had always been healthy. She recovered thanks to linezolid therapy. The MRSA strain proved positive for Panton-Valentine leukocidin (PVL positive) and was therefore defined as community-acquired MRSA (CA-MRSA).

[Prevention of nosocomial infections: surveillance based on microbiological data]. / Effetti del monitoraggio sistematico sulla prevenzione delle infezioni ospedaliere: la sorveglianza basata sui dati del laboratorio di microbiologia.

BACKGROUND: In the C. Poma Hospital of Mantua we have been using a system of continuous surveillance of nosocomial infections based on microbiological data for the past 4 years. This monitoring estimates the incidence of the microorganisms found in cultures, especially those at risk of causing nosocomial infections. MATERIALS AND METHODS: Since June 2001 microbiological data have been registered using the Mercurio-Dianoema software and elaborated by means of Microsoft Excel in order to obtain information about isolated bacteria, especially those resistant to antibiotics. RESULTS: Surveillance in "critical" wards revealed the presence of Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans in the intensive care unit in the period 2003-2005. The most frequent bacteria in hemodialysis have been coagulase-negative Staphylococci and Staphylococcus aureus, with variable methicillin resistance. CONCLUSION: The analysis of microbiological data has promoted effective measures to reduce the incidence of these bacteria (increased rules of good practice, hand washing, etc.). If nosocomial infections or high-risk microorganisms occur, assessments are carried out; monitoring of the antibiotic resistance of the bacteria is very important.

[Epidemiologic surveillance of multi-drug resistant Pseudomonas aeruginosa in Mantova Hospital (Italy)]. / Sorveglianza epidemiologica di Pseudomonas aeruginosa multiresistente nell'Ospedale di Mantova.

For the period 2002-2005 we verified and compared the data of the prevalence and resistance of Pseudomonas aeruginosa (PA) isolated in Mantova Hospital (Italy) with the data from the international database. From the first six-month period of 2004 a significant increase was found (9% vs 28.8%) in the prevalence of multi-drug resistant PA (MDR-PA). The principal wards involved were the Intensive Care Unit and the Department of Respiratory Diseases. A significant increase in resistance rates was observed for all antimicrobials tested, in particular for aztreonam, ceftazidime, ciprofloxacin, gentamycin and imipenem. The lowest dual resistance rates were observed between amikacina with piperacillin/tazobactam, while the highest were for those that included ciprofloxacin and beta-lactams (aztreonam, cefepime). In this study we confirm the importance of continuous surveillance of laboratory data and tightening local control measures for nosocomial infections in order to prevent the spread and selection of MDR-PA.

Multiresistant Stenotrophomonas maltophilia tunneled CVC-related sepsis, treated with systemic and lock therapy.

In the last decade, a remarkable increase in the incidence of nosocomial Gram-negative infections has been observed. These pathogens represent a substantial problem in clinical practice, due to the high resistance profile of most commonly used antibiotics. This phenomenon is surely a co-factor that exposes these susceptible patients to infections caused by selected pathogens like multiresistant Gram-negative rods. A typical example is represented by VAP (ventilator-associated pneumonia) sustained by Acinetobacter spp., Pseudomonas aeruginosa, Bulkolderia cepacia. The Authors describe a case of a central venous cather (CVC)-related Stenotrophomonas maltophilia sepsis in a patient affected by solid tumor, successfully treated with systemic antibiotic therapy associated with "lock therapy". This combination was able to cure the infection, allowing the patient to continue chemotherapy and saving the in situ CVC. The surveillance of CVCs, good adherence to the protocols and guidelines and "good practice" are the cornerstones for the prevention of nosocomial infections.

Solar UV radiation: differential effectiveness of UVB subcomponents in causing cell death, micronucleus induction and delayed expression of heritable damage in human hybrid cells.

PURPOSE: To determine the effectiveness of two UV spectra with different UVB components for cell kill and micronucleus induction in irradiated human HeLaxskin fibroblast (CGL1) hybrid cells and their progeny. To determine the presence of reactive oxygen species (ROS) in the progeny of the irradiated cells at various post-irradiation times and their relationship with induced delayed biological effects. MATERIAL AND METHODS: A commercial solar ultraviolet simulator was used. Two different filters were employed: the first transmitted radiation with lambda>284nm and the second radiation with lambda>293nm. The resulting spectra have different UVB components (lambda between 284 and 320nm, 19 W/m(2), and between 293 and 320nm, 13 W/m(2)) and the same UVA component (lambda between 320 and 400nm, 135 W/m(2)). CGL1 cells were irradiated with various doses. Clonogenic survival and micronucleus formation were scored in the irradiated cells and their progeny. ROS were detected by incubation of cultures at various post-irradiation times with dichlorodihydrofluorescein diacetate followed by flow cytometric measurement of the final product, dichlorofluorescein. RESULTS: The biological effectiveness of the lambda>284nm spectrum was higher by a factor of 3 compared to the lambda>293nm spectrum for cell kill, and by a factor of 5 for micronucleus induction. No delayed cell death or micronucleus formation was found in the progeny of cells exposed to lambda>293nm, while a large and dose-dependent effect was found in the progeny of cells exposed to lambda>284nm for both of these endpoints. ROS levels above those in unirradiated controls were found only in the progeny of cells exposed to the lambda>284nm spectrum. CONCLUSIONS: The spectrum with lambda>284nm was more effective than that with lambda>293nm for induction of cell kill and micronucleus formation in the directly irradiated cells as well as induction of delayed effects in the progeny in the form of delayed reproductive death and micronucleus formation. The presence of ROS in the progeny of the irradiated cells may be the cause of the delayed effects.

Cell cycle effects of gemcitabine.

Gemcitabine (2',2'-difluoro-2'-deoxycytidine, or dFdC) is a promising anticancer agent with demonstrated clinical activity in solid tumours currently undergoing clinical trials. Despite extensive studies on the biochemical mechanism of action, cell cycle perturbations induced by dFdC have not yet been thoroughly investigated, apart from the expected inhibition of DNA synthesis. The aim of our study was to clarify whether cell population kinetics is a vital factor in the cytotoxicity of dFdC in single or repeated treatments and in the dFdC-cisplatin combination. Ovarian cancer cells growing in vitro were treated with dFdC for 1 hr in a range of concentrations from 10 nM to 10 microM. Cell kinetics was investigated by DNA-bromodeoxyuridine flow cytometry, using different experimental protocols to measure either the time course of DNA-synthesis inhibition or the fate of cells in G(1), S or G(2)M at the time of dFdC treatment or 24 hr later. A modified sulforhodamine B test was used to assess the growth inhibition caused by dFdC given alone or with cisplatin. Although dFdC promptly inhibited DNA synthesis, cytotoxicity on proliferating cells was not specific for cells initially in the S phase. DNA synthesis was restored after a G(1) block of variable, dose-dependent length, but recycling cells were intercepted at the subsequent checkpoints, resulting in delays in the G(2)M and G(1) phases. The activity of repeated treatment with dFdC + dFdC or dFdC + cisplatin was highly dependent on the interval length between them. These results suggest that the kinetics of cell recycling from a first dFdC treatment strongly affects the outcome of a second treatment with either dFdC itself or cisplatin.

Desynchronization rate in cell populations: mathematical modeling and experimental data.

We characterize the kinetics of two cancer cell lines: IGROV1 (ovarian carcinoma) and MOLT4 (leukemia). By means of flow cytometry, we selected two populations from exponentially growing in vitro cell lines, depending on the cells' DNA synthesis activity during a preceding labeling period. For these populations we determined the time course of the percentages of cells in different phases of the cycles, sampling every 3 hr for 60 hr. Initially, semi-synchronous populations quickly converged to a stable age distribution, which is typical of the cell line (at equilibrium); this desynchronization reflects the intercell variability in cell cycle duration. By matching these experimental observations to mathematical modelling, we related the convergence rate toward the asymptotic distribution (R) and the period of the phase-percentage oscillations (T), to the mean cell cycle duration and its coefficient of variation. We give two formulas involving the above-mentioned parameters. Since T and R can be drawn by fitting our data to an asymptotic formula obtained from the model, we can estimate the other two kinetic parameters. IGROV1 cells have a shorter mean cell cycle time, but higher intercell variability than the leukemia line, which takes longer to lose synchrony.

[Evaluation of the efficacy of a program to control nosocomial spread of methicillin-resistant Staphylococcus aureus]. / Valutazione dell'efficacia di un sistema di controllo della diffusione intraospedaliera di Staphylococcus aureus meticillino-resistente.

OBJECTIVE: To evaluate the efficacy of a program to control nosocomial spread of methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Analysis of the incidence of infection and contamination due to MRSA in patients admitted to the hospital of Cremona 6 months before and 3 years after the introduction of the guidelines (July 1997). RESULTS: During the 42 months of the study period, on 80705 admissions, 511 cases of MRSA contamination/infection were identified, the incidence being 0.57 cases per 100 admissions. The infection rate dropped from 0.34 (IC95%: 0.25-0.45) in the first 6 months of the study, before the introduction of guidelines, to 0.17 (IC95%: 0.14-0.20) in the following 3 years (p=0.01). Severe infection decreased from 0.18 to 0.1 per 100 admissions, with a 44% decrease (p=0.058), while mild infections diminished from 0.16 to 0.07 per 100 admissions (p=0.045). Methicillin resistance among nosocomial isolates of Staphylococcus aureus was reduced from 53 % to 35 % (p<0.0001). CONCLUSIONS: The introduction of a program to control the nosocomial spread of MRSA proved effective in reducing both the incidence of infection and the methicillin-resistance of Staphylococcus aureus isolates. The cost effectiveness of the program seems very favourable.

Prognostic factors correlated with survival in AIDS patients.

The authors present the AIDS cases (CDC '93) observed in Brescia from 1983 to 1994. They observed 1189 subjects (M 84%, F 16%) with a mean age of 32.7 years (intra-venous drug users 75.1%, heterosexuals 14%, homosexuals 9.6%). The mean survival observed was 56.7 weeks from the diagnosis of AIDS (mortality per year 78%). The most frequent AIDS-defining events were Visceral Candidiasis, P. carinii Pneumonia (PCP) and Neurotoxoplasmosis, while the longest and shortest mean survival was for Kaposi's Sarcoma (89 weeks) and Wasting Syndrome (8.4). The mean value of CD4+ lymphocyte counts on AIDS diagnosis was 72.6/microl (1166 cases) and the highest and lowest were in non-Hodgkin's Lymphoma (NHL; 147.6/microl) and Cryptosporidiosis (18.8/microl). Antiretroviral therapy had been given for at least a month in 41.4% subjects (mean treatment duration of 74.8 weeks). The Cox model has demonstrated the favourable effect on survival of high CD4+ lymphocyte counts on diagnosis, antiretroviral therapy, the diagnosis of Tuberculosis (TBC) and PCP as initial markers and the diagnosis of TBC, PCP or Cytomegalovirus infection (CMV) during the entire clinical evolution. Moreover, the unfavourable effect of high age, diagnosis of Progressive Multifocal Leucoencephalopathy (PML), Wasting Syndrome and NHL as initial markers and diagnosis of PML or NHL in any moment of the disease has been demonstrated.

Changing patterns of HIV transmission and better targeting for intervention strategies.

We considered the HIV population of our area, comparing demographic characteristics between 2 consecutive 6-year periods to assess the current patterns of HIV transmission. All HIV-positive patients referred to our hospital from January 1985 to December 1996 were included in the study and were classified into 2 periods: A (January 1985 to December 1990) and B (anuary 1991 to December 1996). The variables analysed were: sex, age at first visit, HIV risk category. A total of 4284 HIV subjects were observed, 2306 in period A vs 1978 in period B (P=ns). Males were 76.3% vs 75.2% (P=ns). Mean age for males was 27.4 vs 32.4 years (P < 0.001) and for females 25.4 vs 30.1 years (P < 0.001). Intravenous drug users (IVDUs) were 88.4% vs 65.4% (P < 0.001), 'heterosexuals' 14.3% vs 24.8% (P < 0.001), 'men who have sex with men' 2.4% vs 4.8% (P < 0.001). Mean age by the main risk groups was: IVDUs 25.9 vs 29.7 years (P < 0.001); heterosexuals 30.4 vs 36 years (P=0.007); 'men who have sex with men' 35 vs 35 years. In conclusion, our study confirms the emerging role of heterosexuals in the current HIV epidemic. People older than teenagers seem to have misperceived their own risk of HIV infection, given the increase in the mean age occurred in the most recent years. This trend suggests the need for prevention strategies focusing more on heterosexual transmission and older people.