Lymphocyte apoptosis in children with central nervous system tuberculosis: a case control study

<p>Abstract</p> <p>Background</p> <p>Studies of the apoptosis mechanisms involved in the pathogenesis of tuberculosis have suggested that <it>Mycobacterium tuberculosis </it>can actively interfere with the apoptosis of infected cells. <it>In vivo </it>studies have been performed in adult populations but have not focused on this process in children. In the present study, we analyzed spontaneous T lymphocyte (PBT) apoptosis in the peripheral blood of children with central nervous system tuberculosis (CNS TB), before and after chemotherapy, and compared the results with healthy controls.</p> <p>Methods</p> <p>A case-control study was conducted from January 2002 to June 2009. It included 18 children with CNS TB and 17 healthy controls. Spontaneous apoptosis of PBTs, including CD4⁺, CD8⁺and CD8⁺/CD28⁺T cells, was evaluated after 24 and 72 h of culture in complete medium, using the Annexin V detection test. Analysis was conducted before and after chemotherapy, and expression of the apoptotic markers CD95 (Fas) and Fas ligand (FasL) was evaluated.</p> <p>Results</p> <p>Higher percentages of apoptotic T cells and CD4 lymphocytes were isolated from children with acute phase CNS TB than from children in the control group (p < 0.05). This difference significantly decreased after 60 days of specific treatment. In children with CNS TB, high levels of Fas ligand expression were detected in lymphocyte populations, associated with a high percentage of Fas positive cells, before and after treatment. In contrast to the CD4+ apoptosis profile, we did not find any significant difference in total CD8⁺cell apoptosis between children with acute phase disease and the control group. However, the percentage of apoptotic CD8⁺/CD28⁺T cells was significantly higher in the children with acute phase disease than in the healthy controls.</p> <p>Conclusions</p> <p>Our findings indicate that CNS TB in pediatric patients increases the sensitivity of CD4 and CD8⁺/CD28⁺T cells to apoptosis, suggesting a hypoergic status of this infection. This could play a key role in the immunopathogenesis of this complicated form of TB. Interestingly, specific chemotherapy is able to normalize both apoptosis sensitivity and T-cell activation.</p

Alveolar&ndash;Arterial Gradient Is an Early Marker to Predict Severe Pneumonia in COVID-19 Patients

Background: One of the main challenges in the management of COVID-19 patients is to early assess and stratify them according to their risk of developing severe pneumonia. The alveolar&ndash;arterial oxygen gradient (D(A-a)O2) is defined as the difference between the alveolar and arteriolar concentration of oxygen, an accurate index of the ventilatory function. The aim of this study is to evaluate D(A-a)O2 as a marker for predicting severe pneumonia in COVID-19 patients, in comparison to the PaO2/FiO2. Methods: This retrospective, multicentric cohort study included COVID-19 patients admitted to two Italian hospitals between April and July 2020. Clinical and laboratory data were retrospectively collected at the time of hospital admission and during hospitalization. The presence of severe COVID-19 pneumonia was evaluated, as defined by the Infectious Diseases Society of America (IDSA) criteria for community-acquired pneumonia (CAP). Patients were divided in severe and non-severe groups. Results: Overall, 53 COVID-19 patients were included in the study: male were 30/53 (57%), and 10/53 (19%) had severe pneumonia. Patients with severe pneumonia reported dyspnea more often than non-severe patients (90% vs. 39.5%; p = 0.031). A history of chronic obstructive pulmonary disease (COPD) was recalled by 5/10 (50%) patients with severe pneumonia, and only in 6/43 (1.4%) of non-severe cases (p = 0.023). A ROC curve, for D(A-a)O2 &gt;60 mmHg in detecting severe pneumonia, showed an area under the curve (AUC) of 0.877 (95% CI: 0.675&ndash;1), while the AUC of PaO2/FiO2 &lt; 263 mmHg resulted 0.802 (95% CI: 0.544&ndash;1). D(A-a)O2 in comparison to PaO2/FiO2 had a higher sensibility (77.8% vs. 66.7%), positive predictive value (75% vs. 71.4%), negative predictive value (94% vs. 91%), and similar specificity (94.4% vs. 95.5%). Conclusions: Our study suggests that the D(A-a)O2 is more appropriate than PaO2/FiO2 to identify COVID-19 patients at risk of developing severe pneumonia early

Outbreak of Brucella melitensis infection in Eastern Sicily: risk factors, clinical characteristics and complication rate

Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58\ub142.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/ Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended

Invasive cryptococcal disease in COVID-19: systematic review of the literature and analysis

: During the Coronavirus Disease 2019 (COVID-19) pandemic, an increasing number of fungal infections associated with SARS-CoV-2 infection have been reported. Among them, cryptococcosis could be a life-threatening disease. We performed a Systematic Review (PRISMA Statement) of cryptococcosis and COVID-19 co-infection, case report/series were included: a total of 34 cases were found, then we added our case report. We collected patients' data and performed a statistical analysis comparing two groups of patients sorted by outcome: "dead" and "alive". Three cases were excluded for lack of information. To compare categorical data, we used a Fisher-exact test (α=0.05). To compare quantitative variables a U Mann-Whitney test was used (α=0.05), with a 95% Confidence Interval. A total of 32 co-infected patients were included in the statistical analysis. Mortality rate was 17/32 (53.1%): these patients were included in "dead" group, and 15/32 (46.9%) patients survived and were included in "alive" group. Overall, males were 25/32 (78.1%), the median age was 60 years (IQR 53-70) with non-statistically significant difference between groups (p=0.149 and p=0.911, respectively). Three variables were associated with mortality: ARDS, ICU admission and inadequate treatment. Overall, 21 out of 24 (87.5%) patients were in ARDS with a statistically significant difference among two groups (p=0.028). ICU admission for COVID-19 was observed in 18/26 (69.2%), more frequently among dead group (p=0.034). Finally, 15/32 (46.9%) patients had adequate treatment (amphotericin B + flucytosine for invasive cryptococcosis) mostly among alive patients (p=0.039). In conclusion, mortality due to cryptococcal infection among COVID-19 patients remains high but an early diagnosis and appropriate treatment could reduce mortality