Efficacy and safety of therapies for COVID-19 in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Clinical evidence suggests that pregnant women are more vulnerable to COVID-19, since they are at increased risk for disease progression and for obstetric complications, such as premature labor, miscarriage, preeclampsia, cesarean delivery, fetal growth restriction and perinatal death. Despite this evidence, pregnant women are often excluded from clinical trials, resulting in limited knowledge on COVID-19 management. The aim of this systematic review and meta-analysis is to provide better evidence on the efficacy and safety of available COVID-19 treatment in pregnant women. METHODS: Four authors searched major electronic databases from inception until 1 st November-2022 for controlled trials/observational studies, investigating outcomes after the administration of anti-SARS-CoV-2 treatments in pregnant women affected by COVID-19. The analyses investigated the cumulative incidence of delivery and maternal outcomes in pregnant women, comparing those taking active medication vs standard care. Risk ratios (RRs) with 95% confidence intervals were calculated. Statistical significance was assessed using the random effects model and inverse-variance method. This systematic review and meta-analysis was conducted in accordance with the updated 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol has been registered in Prospero (number registration: CRD42023397445). RESULTS: From initially 937 non duplicate records, we assessed the full texts of 40 articles, finally including ten studies. In six studies, including 1627 patients, the use of casirivimab/imdevimab (CAS/IMD), remdesivir, and IFN-alpha 2b significantly decreased the need of cesarean section ((RR = 0.665; 95%CI: 0.491-0.899; p = 0.008; I 2 = 19.5%;) (Table 1, (Fig. 1). Treatments did not decrease the risk of preterm delivery, admission to neonatal ICU, or stillbirth/perinatal loss (p-values > 0.50 for all these outcomes) and did not prevent the progression of disease towards severe degrees (k = 8; 2,374 pregnant women; RR = 0.778; 95%CI: 0.550-1.099; p = 0.15; I 2 = 0%). Moreover, the use of medications during pregnancy did not modify the incidence of maternal death in two studies (Table 2). CONCLUSIONS: To our analysis, CAS/IMD, remdesivir, and IFN alpha 2b reduced the number of cesarean sections but demonstrated no effect on disease progression and other obstetric and COVID-19 related outcomes. The inability to evaluate the influence of viral load on illness development in pregnant women was attributed to lack of data. In our systematic review, no major side effects were reported. Though, it is essential for the medical community to focus more on clinical trials and less on episodic case reports and case series, with standardization of fetal and maternal outcomes.

Immunogenicity and safety of the BNT162b2 COVID-19 mRNA vaccine in PLWH: A monocentric study in Bari, Italy.

In March, people living with HIV infection (PLWH) were included in the risk category of fragile people for severe COVID-19 receiving priority access to vaccination with BNT162b2 vaccine. The aim of the study was to evaluate the immunogenicity and safety of the two doses regimen. The antibodies titer for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) was evaluated after 21 days since the first administration (Time 1), 1 (Time 2), and 3 (Time 3) months post-vaccination. Information regarding virological and immunological conditions at baseline, previous SARS-CoV-2 state of infection, other immunodeficiencies, current antiretroviral therapy (ART), comorbidities, and severe adverse events (SAE) to vaccination was collected. Six hundred and ninety-seven patients were tested for quantitative anti-spike antibodies at Time 1, 577 patients had a second detection at Time 2, and 491 patients had the third detection. Baseline characteristics of the study population are reported in Table 1. At the time of vaccine administration, all patients were on ART (except one long-term nonprogressor); 632 (90.7%) patients had undetectable HIV-RNA; 12 (1.7%) patients were immunosuppressed due to chemotherapy or other immunosuppressive drugs; 345 (49.5%) patients had at least one COVID-19 related comorbidity and 155 (22.2%) had two or more comorbidities. No SAEs were reported. Final serological results are available for 694 patients after the first dose, 577 and 491 after the second and third ones, respectively; positive titer (values ≥ 50 AU/ml) was demonstrated in 653 (94.1%), 576 (99.8%), 484 (98.6%) patients, respectively. Only one patient was a nonresponder after completing vaccination, who was a newly diagnosed one for HIV infection. All vaccinations were well tolerated, with no SAEs. BNT162b2 mRNA vaccine was immunogenic and safe in PLWH.

Impact of antimalarial resistance and COVID-19 pandemic on malaria care among pregnant women in Northern Uganda (ERASE): protocol of a prospective observational study.

BACKGROUND: Uganda accounts for 5% of all malaria cases and deaths reported globally and, in endemic countries, pregnancy is a risk factor for both acquisition of P. falciparum infection and development of severe malaria. In recent years, malaria control has been threatened by COVID-19 pandemic and by the emergence, in Northern Uganda, of both resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. METHODS: In this facility-based, prospective, observational study, pregnant women will be recruited at antenatal-care visits and followed-up until delivery. Collected data will explore the incidence of asymptomatic parasitemia and malaria-related outcomes, as well as the attitudes towards malaria prevention, administration of intermittent preventive treatment, healthcare seeking behavior and use of insecticide-treated nets. A subpopulation of women diagnosed with malaria will be recruited and their blood samples will be analyzed for detection of genetic markers of resistance to artemisinin derivatives and sulfadoxine-pyrimethamine. Also, to investigate the impact of COVID-19 on malaria care among pregnant women, a retrospective, interrupted-time series will be conducted on at the study sites for the period January 2018 to December 2021. DISCUSSION: The present study will explore the impact of COVID-19 pandemic on incidence of malaria and malaria-related adverse outcomes, along with the prevalence of resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. To our knowledge, this is the first study aiming to explore the combined effect of these factors on a cohort of pregnant women. TRIAL REGISTRATION: This study has been registered on the ClinicalTrials.gov public website on 26th April, 2022. CLINICALTRIALS: gov Identifier: NCT05348746.

Impact of SARS-CoV-2 outbreak on heart and lung transplant: A patient-perspective survey.

BACKGROUND: The risk of COVID-19 is expected to be higher among solid organ transplant. The aim of the present study was to evaluate the incidence of COVID-19 and the impact of the SARS-CoV-2 outbreak on the personal hygiene and expectations in heart and lung transplant recipients. METHODS: A telephone survey of heart (n = 69) and lung (n = 41) transplant patients and a group of controls (n = 41) was conducted concerning personal hygiene before and after the outbreak; the impact on subjective expectations regarding graft outcome; symptoms possibly associated with SARS-CoV-2 infection; and diagnosis of COVID-19. RESULTS: Seventy nine percent of the patients declared they increased the use of face masks and handwash. Behavior at home regarding self-isolation did not change. About half the patients said they were afraid of the virus. A higher percentage of Lung transplant (LTX) were convinced that SARS-CoV-2 could have a negative impact on the outcome of their graft. 28% declared that they were afraid to come to the hospital for routine examinations and asked to postpone. Nine LTX and five Heart transplant (HTX) patients experienced symptoms that could have been associated with SARS-CoV-2 infection, but none of them underwent a nasopharyngeal swab. Only one LTX was diagnosed with the infection. CONCLUSIONS: In our study, we observed a low incidence of COVID-19 in heart and lung transplant patients (0.9%), similar to that of the general population of our Region. Isolation measures were already observed before the pandemic and were further strengthened in most cases. Particular attention should also be paid to new psychological and physical complications indirectly linked to the COVID-19 pandemic.

The Role of Galectins in Chronic Lung Allograft Dysfunction.

BACKGROUND: Galectins are proteins that bind ß-galactosides such as N-acetyllactosamine present in N-linked and O-linked glycoproteins and that seem to be implicated in inflammatory and immune responses as well as fibrotic mechanisms. This preliminary study investigated serum galectins as clinical biomarkers in lung transplant patients with chronic lung allograft dysfunction (CLAD), phenotype bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: Nineteen lung transplant patients [median age (IQR), 55 (45-62) years; 53% males] were enrolled in the study. Peripheral blood concentrations of galectins-1, 3 and 9 were determined with commercial ELISA kits. RESULTS: Galectin-1 concentrations were higher in BOS than in stable LTX patients (p = 0.0394). In logistic regression analysis, testing BOS group as dependent variable with Gal-1 and 3 as independent variables, area under the receiver operating characteristics (AUROC) curve was 98.9% (NPV 90% and PPV 88.9%, p = 0.0003). With the stable LTX group as dependent variable and Gal-1, 3 and 9 as independent variables, AUROC was 92.6% (NPV 100% and PPV 90%, p = 0.0023). In stable patients were observed an inverse correlation of Gal-3 with DLCO% and KCO%, and between Gal-9 and KCO%. CONCLUSION: Galectins-1, 3 and 9 are possible clinical biomarkers in lung transplant patients with diagnostic and prognostic meaning. These molecules may be directly implicated in the pathological mechanisms of BOS. The hypothesis that they could be new therapeutic targets in BOS patients is intriguing and also worth exploring.

Association between Glycosylated Hemoglobin Levels and Vaccine Preventable Diseases: A Systematic Review.

People with diabetes are at higher risk of serious complications from many vaccine-preventable diseases (VPDs). Some studies have highlighted the potential impact of glycosylated hemoglobin levels (HbA1c), but no systematic review has synthesized these findings. Of the 823 identified studies, 3 were included, for a total of 705,349 participants. Regarding the incidence of herpes zoster (HZ), one study found that higher HbA1c levels at the baseline (>10.3%) were associated with a significantly higher risk of HZ of 44%, compared to those with a good HbA1c control (6.7%). On the contrary, the second one reported that when compared to the reference group (HbA1c of 5.0-6.4%), participants with a HbA1c less than 5.0% were at higher risk of HZ of 63%, whilst participants with a HBA1c more than 9.5% had a similar risk. Finally, the third study observed that diabetes, defined using a value of HbA1c more than 7.5%, was associated with an increased risk of mortality in men with COVID-19. In conclusion, both high and low HBA1c levels appear to be associated with a higher risk of HZ. Regarding COVID-19, a value of HbA1c more than 7.5% was associated with a higher risk of death in COVID-19, but only in men.

Rapid de-escalation of anti-MRSA therapy guided by S. aureus nares screening for patients with pneumonia: protocol of a randomized controlled trial (SNAP study).

Introduction: The current Infectious Disease Society of America and American Thoracic Society (IDSA/ATS) guidelines recommend linezolid or vancomycin as an empiric treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in hospitalized patients with specific risk factors,. A nasal PCR-assay for MRSA, with its high negative predictive value, can guide a rapid antibiotic de-escalation avoiding unnecessary anti-MRSA treatment. The indiscriminate use of these drugs has contributed to the emergence of resistant S. aureus strains leading to adverse effects without any survival benefit, increasing hospital stays and associated costs. Aim of the study is the use of this diagnostic tool to reduce empirical anti-MRSA treatment duration in pneumonia, shortening antimicrobial therapy days while measuring in-hospital mortality, length of stay and adverse drug event incidence. Methods: It is a prospective, randomized single-center controlled trial planned to be conducted in the Azienda Consorziale Policlinico di Bari. The research project will have a duration of 12 months following the approval of the Ethical Committee of the University of Bari. The minimum sample size is 38 patients per group, for a total of 76 subjects, calculated assuming a standard deviation of 10, a power of 90%, a type I error of 5% and a 10% drop-out rate. We will enroll eligible patients ensuring their evidence-based management according to guidelines, we will perform a nasal swab for MRSA in patients in the experimental group and discontinue the empirical anti-MRSA therapy if the nasal swab result is negative. For both arms, follow-up visits will be on day 2, 5, 7, 14, and 28 relatives to the enrollment visit (day 0). Data will be collected on the clinical course of pneumonia and laboratory tests. Discussion: Our study will provide evidence on the duration (in days) of the antibiotic intake as a primary outcome of the study. Secondary outcome measures include in-hospital mortality, the length of stay and days of mechanical ventilation (in VAP), and the incidence of adverse events related to the administration of the therapy. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT06238297, identifier NCT06238297.

Knowledge, Attitudes, and Practices toward Antimicrobial Resistance among Young Italian Nurses and Students: A Multicenter, Cross-Sectional Study.

Background: Nurses play a pivotal role in combating antimicrobial resistance (AMR). However, the success of local and national AMR containment efforts hinges on the knowledge, attitude, and practice (KAP) of nursing staff and undergraduate students. Objectives: This study aims to explore the determinants of nurses' KAP regarding AMR, offering insights to control the emergence and spread of drug-resistant pathogens. Methods: This cross-sectional, multicenter survey involving Italian nurses, nursing students, and healthcare professionals was conducted administering an anonymous online questionnaire focusing on AMR. The median score of 12 was taken as the cutoff for "good KAP." The association between study variables and good KAP was assessed using chi-square or t-tests, followed by multivariable logistic regression analysis for statistically significant (p < 0.05) variables. Findings: Among 848 participants, 61.9% (n = 525) were students, and 39.6% (n = 336) scored as having "low KAP." High KAP was associated with being female and studying AMR independently. Conversely, living in southern Italy and receiving AMR training from pharmaceutical companies were associated with low KAP. Conclusions: Among Italian nurses, AMR awareness relies on those who have studied AMR as self-taught and is affected by gender and region. Italian universities lack in lectures on AMR management, and much needs to be done to improve awareness of antimicrobial stewardship among nonmedical health workers.

Cardiac Tuberculosis: A Case Series from Ethiopia, Italy, and Uganda and a Literature Review.

Extrapulmonary tuberculosis (TB) is estimated to account for up to 20% of active cases of TB disease, but its prevalence is difficult to ascertain because of the difficulty of diagnosis. Involvement of the heart is uncommon, with constrictive pericarditis being the most common cardiac manifestation. Diagnostic research for cardiac disease is frequently lacking, resulting in a high mortality rate. In addition to direct cardiac involvement, instances of cardiac events during antitubercular therapy are described. This case series describes five cases of TB affecting the heart (cardiac TB) from Italy and high-burden, low-income countries (Ethiopia and Uganda), including a case of Loeffler syndrome manifesting as myocarditis in a patient receiving antitubercular therapy. Our study emphasizes how cardiac TB, rare but important in high-burden areas, is a leading cause of pericardial effusion or pericarditis. Timely diagnosis and a comprehensive approach, including imaging and microbiological tools, are crucial. Implementing high-sensitivity methods and investigating alternative samples, such as detection of tuberculosis lipoarabinomannan or use of the GeneXpert assay with stool, is recommended in TB control programs.

COVID Perceptions among Pregnant Women Living in a Malaria Hyperendemic Rural Region in Uganda: A Cross-Sectional Study.

Both SARS-CoV2 and Plasmodium falciparum infection during pregnancy increases the risk for adverse maternal and fetal outcomes, including abortion, severe disease, and death. Indeed, although malaria and COVID-19 show an overlapping clinical presentation, they require a profoundly different approach. The aim of this study was to explore COVID-19 awareness among pregnant women living in a P. falciparum hyperendemic region in rural Uganda. This cross-sectional, prospective study was conducted in one Hospital and two Health Centers (HC) in Lango region, Uganda, from July 14, 2022, to March 14, 2023. Data about demographics, COVID-19 history, and COVID-19 and malaria perceptions were collected using RedCap mobile app platform. Study endpoint was a context-specific COVID-19 awareness score, accounting for the most common disease misconceptions. Association between study variables and good COVID-19 awareness was assessed by χ2 and t test, as appropriate, and variables found to be statistically significant were further explored in multivariate logistic regression analysis. A total of 888 pregnant women were recruited. Median age was 24 (interquartile range: 20-29) years, whereas 79% (n = 704) attained only primary education and 66.6% (n = 591) were used in agriculture. SARS-CoV2 vaccination rate was 92%. In multivariate analysis (Table 3), variables associated with high COVID knowledge were presenting at antenatal care visit in Atipe HC (adjusted odds ratio [aOR]: 8.1, 95% CI: 4.1-16.48) having a previous good knowledge about malaria (aOR: 1.76, 95% CI: 1.21-2.56). Among pregnant women living in rural Uganda, COVID-19 awareness relies on the overall educational level, malaria knowledge and reference HC. Among pregnant women living in P. falciparum endemic areas, community-level malaria awareness might guide educational interventions during future pandemics.

Stool Xpert MTB/RIF as a possible diagnostic alternative to sputum in Africa: a systematic review and meta-analysis.

Introduction: Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries. Methods: Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool. Results: overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1-74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97-100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis. Conclusions: Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples.

Impact of the COVID-19 pandemic on malaria in pregnancy indicators in Northern Uganda: a joinpoint regression analysis.

BACKGROUND: Pregnancy is both a risk factor for P. falciparum infection and development of severe malaria. In low- and middle-income countries, the COVID-19 pandemic severely impacted health systems, including utilization of maternal services. This study aimed to assess trends in delivering malaria in pregnancy-related health-care services before and during COVID-19 in Northern Uganda. METHODS: An interrupted time-series study comparing pre-COVID-19 (January 2018 to April 2020) and COVID-19 (May to December 2021) periods, based on the date the first COVID case was detected. The study involved 30 health facilities in Northern Uganda with 22,650 estimated pregnancies per year, 14% of which took place in hospital. Monthly data were sourced from District routinely collected indicators. Trends were analyzed by joinpoint regression models. RESULTS: From the onset of the COVID pandemic in Uganda (May 2020), we found a significant reduction in the number of women accessing a fourth antenatal care visit (from APC + 183.5 to + 4.98; p < 0.001) and taking at least three doses of intermittent preventive treatment in pregnancy (IPTp, from APC + 84.28 to -63.12; p < 0.001). However, we found no significant change in the trend of the total number of pregnant women managed as outpatients or hospitalized for malaria, as well as in the number of women attending their first antenatal visit and in the number of institutional deliveries. CONCLUSIONS: In our study, the COVID-19 pandemic significantly reduced access to ANC visits and IPTp uptake. However, the healthcare system maintained its capacity for managing malaria cases, first antenatal visits, and institutional deliveries.Trial registration: This study has been registered on the ClinicalTrials.gov public website on 26 April 2022. ClinicalTrials.gov Identifier: NCT05348746.

Subacute Cardiac Tamponade Due to Tuberculous Pericarditis Diagnosed by Urine Lipoarabinomannan Assay in a Immunocompetent Patient in Oyam District, Uganda: A Case Report.

BACKGROUND: Uganda ranks among the countries with the highest burden of TB the world and tuberculous pericarditis (TBP) affects up to 2% of people diagnosed with pulmonary tuberculosis worldwide. In Africa, it represents the most common cause of pericardial disease. Here, we present the case of a 21-year-old male patient who was diagnosed of cardiac tamponade due to tuberculous pericarditis with a positive urine LF-LAM. CASE REPORT: We report a case of a 21-year-old male living in Oyam district, Uganda, who presented to the emergency department with difficulty in breathing, easy fatigability, general body weakness, and abdominal pain. A chest X-ray showed the presence of right pleural effusion and massive cardiomegaly. Thus, percutaneous pericardiocentesis was performed immediately and pericardial fluid resulted negative both for gram staining and real-time PCR test Xpert MTB/RIF. The following day's urine LF-LAM test resulted positive, and antitubercular therapy started with gradual improvement. During the follow-up visits, the patient remained asymptomatic, reporting good compliance to the antitubercular therapy. CONCLUSION: Our case highlights the potential usefulness of a LF-LAM-based diagnostic approach, suggesting that, in low-resource settings, this test might be used as part of routine diagnostic workup in patients with pericardial disease or suspected extra-pulmonary tuberculosis.

Neurocysticercosis in Low- and Middle-Income Countries, a Diagnostic Challenge from Oyam District, Uganda.

BACKGROUND: In countries where Taenia solium is endemic, neurocysticercosis (NCC) is the leading identified cause of seizures, accounting for nearly 30% of all epilepsy cases and up to 2.8 million of Disability Adjusted Life Years. Diagnosis of this condition, however, is strictly reliant on either MRI or CT scan, which are poorly available in low- and middle-income countries (LMICs), creating challenges for proper case management and the acquisition of precise neuroepidemiologic data that may guide program and policy development. METHODS: Here, we report the case of a 73-year-old woman admitted in a rural hospital in Northern Uganda, who presented with seizures and a progressive inability to walk. She was then diagnosed with NCC after a brain CT scan. CONCLUSIONS: This case study represents a rare example of the detection of NCC in a rural district hospital, thus suggesting the potential feasibility of a CT-scan guided diagnostic approach in low resource settings.

Guinea Worm Disease: A Neglected Diseases on the Verge of Eradication.

BACKGROUND: Dracunculiasis, also known as Guinea worm disease (GWD), is a neglected tropical disease (NTD) caused by a parasite (Dracunculus medinensis). In the past, dracunculiasis was known as "the disease of the empty granary" because of the difficulties patients had in going to work in fields or to school when affected by this disease. In tropical areas, the condition has been widespread in economically disadvantaged communities, and has been associated with reduced economic status and low levels of education. METHODS: we searched PubMed, Scopus, Google Scholar, EMBASE, Cochrane Library, and WHO websites for literature addressing dracunculiasis published in the last 50 years. RESULTS: by development and optimization of multi-layered control measures, transmission by the vector has been interrupted, but there are foci in several African countries with a high risk of compromising the results obtained in the control of this neglected disease. CONCLUSION: this review features state-of-the-art data on the infection prevalence, geographical distribution, diagnostics, parasite-host interactions, and the pathology of dracunculiasis. Also described are the current state and future perspectives for vector control and elimination strategies.

Predictors for Pulmonary Tuberculosis Outcome and Adverse Events in an Italian Referral Hospital: A Nine-Year Retrospective Study (2013-2021).

Background: The COVID-19 pandemic has undone years of progress in providing essential TB services and controlling the TB burden. Italy, a low TB burden country, has an incidence of 7.1 cases per 100,000 people. To control the TB spreading in Italy is critical to investigate the characteristics of patients with the worst outcomes and the highest risk of adverse events related to antituberculosis therapy. Therefore, we conducted a large retrospective study in TB patients admitted to the Clinic of Infectious Diseases University of Bari, Italy, in order to describe the clinical presentation and the factors associated with adverse events and outcomes. Methods: We retrospectively evaluated the patients admitted to the Clinic of Infectious Diseases from January 2013 to 15 December 2021. We stratified our cohort into two groups: <65 years of age and ≥65 years in order to assess any differences between the two groups. Two logistic regression models were implemented considering the dependent variables as: (I) the adverse events; and (II) the unsuccessful treatments. Results: In total, 206 consecutive patients [60% (n = 124) M, median age 39 years, range 16-92] were diagnosed and admitted with TB at Clinic of Infectious Diseases. Of the whole sample, 151 (74%) were <65 years and 55 (26%) were ≥65. Statistically significant differences between the two groups were detected (p-value < 0.05) for nationality (p-value = 0.01), previous contact with TB patient (p-value = 0.00), type of TB (p-value = 0.00), unsuccessful treatment (p-value = 0.00), length of hospitalization (p-value = 0.02) and diagnostic delay (p-value = 0.01). Adverse events related to TB drug regimen were reported in 24% (n = 49). Age < 65 years (O.R. = 3.91; 95% CI 1.72-4.21), non-Italian nationality (O.R. = 4.45; 95% CI 2.22-4.98.), homeless (O.R. = 3.23; 95% CI 2.58-4.54), presence of respiratory symptoms (O.R. = 1.23; 95% CI 1.10-1.90), diagnostic delay (O.R = 2.55; 95% CI 1.98-3.77) resulted associated with unsuccessful treatment outcome (death, failure or lost to follow up). Finally, age < 65 years (O.R. = 1.73; 95% CI 1.31-2.49), presence of pulmonary TB (O.R. = 1.15; 95% CI 1.02-1.35), length of hospitalization (O.R. = 1.82; 95% CI 1.35-2.57) and TB culture positive (O.R. = 1.35; 95% CI 1.12-1.82) were associated with adverse events in our populations. Conclusions: The pharmacological approach alone seems insufficient to treat and cure a disease whose ethiopathogenesis is not only due to the Mycobacterium tuberculosis, but also to the poverty or the social fragility. Our data suggest that young foreigners, the homeless, and the people with low social and economic status are at higher risk of an unfavorable outcome in low incidence TB countries. Targeted actions to support this highly vulnerable population both in terms of outcome and occurrence of adverse events are needed.

Impact of a Multistep Bundles Intervention in the Management and Outcome of Gram-Negative Bloodstream Infections: A Single-Center "Proof-of-Concept" Study.

Background: This is a "proof-of-concept" study aiming to evaluate the impact of a multistep bundles intervention in the management and outcomes of patients with gram-negative bloodstream infections (GN-BSIs). Methods: This was a single-center, quasi-experimental design study. In the pre-phase (January 2019 to May 2020), patients were retrospectively enrolled. During the post-phase (June 2020 to September 2021), all patients were prospectively enrolled in a nonmandatory 3-step bundles intervention arm including (i) step 1: imaging to detect deep foci of infection, follow-up blood cultures and procalcitonin monitoring; (ii) step 2: early targeted antibiotic treatment and surgical source control; (iii) step 3: discontinuation of antibiotics within 7-10 days in case of uncomplicated BSI. Patients were followed up to 28 days from BSI onset. The primary outcome was 28-day mortality. Results: A total of 271 patients were enrolled: 127 and 144 in the pre- vs post-phase, respectively. Full application of step 1 (67% vs 42%; P < .001), step 2 (83% vs 72%; P = .031), and step 3 (54% vs 2%; P < .001) increased in the post-phase. Overall, the intervention reduced 28-day mortality (22% vs 35%, respectively; P = .016) and the median duration of total (11 vs 15 days; P < .001) and targeted (8 vs 12 days; P = .001) antibiotic therapy. Finally, the multivariate Cox regression confirmed the independent protective effect of adherence to step 1 (adjusted hazard ratio [aHR], 0.36; 95% CI, 0.20-0.63) and step 2 (aHR, 0.48; 95% CI, 0.29-0.81) on risk of 28-day mortality. Conclusions: Clinical management and outcomes of patients with GN-BSIs may be improved by providing a pre-established multistep bundles intervention.

Loa loa in the Vitreous Cavity of the Eye: A Case Report and State of Art.

Loa loa is a filarial nematode responsible for loiasis, endemic to West-Central Africa south of the Sahara and transmitted by flies. This study reports a case of L. loa in the vitreous cavity of the eye of a young patient, along with an in-depth literature review. A 22-year-old woman from Cameroon who migrated from Cameroon to Italy was referred to the Emergency Ophthalmology Department at Policlinico di Bari in July 2021 with the presence of a moving parasite in the subconjunctiva of the left eye. A recent onset of a papular lesion on the dorsal surface of the right wrist and a nodular lesion in the scapular region were detected. L. loa filariasis was diagnosed based on anamnestic data, clinical and paraclinical signs, and a parasitological test confirming the presence of microfilariae in two blood samples collected in the morning of two different days. Because of the unavailability of diethylcarbamazine (DEC), albendazole (ALB) 200 mg twice daily was administered for 21 days. A mild exacerbation of pruritus occurred during treatment, but resolved with the use of an antihistamine. A single dose of 12 mg ivermectin was prescribed at the end of the treatment with albendazole. Unlike other endemic parasite infections, L. loa is not included in the Global Program to Eliminate Lymphatic Filariasis, because it is not mentioned in the WHO and CDC list of neglected tropical diseases. This can result in an overall risk of lack of attention and studies on loiasis, with lack of data on global burden of the disease.

Regulatory and Effector Cell Disequilibrium in Patients with Acute Cellular Rejection and Chronic Lung Allograft Dysfunction after Lung Transplantation: Comparison of Peripheral and Alveolar Distribution.

BACKGROUND: The immune mechanisms occurring during acute rejection (AR) and chronic lung allograft dysfunction are a challenge for research and the balance between effector and regulatory cells has not been defined completely. In this study, we aimed to elucidate the interaction of effector cells, mainly Th17, Th1 and Th2, and regulatory cells including (CD4+CD25+CD127low/-) T reg cells and phenotypes of B regs, CD19+CD24hiCD38hi, CD19+CD24hiCD27hi and CD19+CD5+CD1d+. METHODS: Bronchoalveolar lavage cells (BAL) and peripheral blood mononuclear cells (PBMCs) from stable lung transplanted (LTx )subjects (n = 4), AR patients (n = 6) and bronchiolitis obliterans syndrome (BOS) (n = 6) were collected at the same time. Cellular subsets were detected through flow cytometry. RESULTS: A predominance of Th17 cells subtypes in the PBMCs and BAL and a depletion of Tregs, that resulted in decrease Treg/Th17 ratio, was observed in the AR group. CD19+CD24hiCD38hi Bregs resulted increased in BAL of AR patients. Th1 cells predominance and a reduction of Tregs cells was observed in BAL from AR patients. Moreover, multivariate analysis showed interdependences within studied variables revealing that effector cells and regulatory cells can effectively discriminate patients' immunological status. CONCLUSIONS: In AR, BOS and stable lung transplant, regulatory and effector cells clearly demonstrated different pathways of activation. Understanding of the balance of T cells and T and B regulatory cells can offers insights into rejection.

Portable Pocket-Sized Ultrasound Scanner for the Evaluation of Lung Involvement in Coronavirus Disease 2019 Patients.

Ultrasound imaging of the lung (LUS) and associated tissues has demonstrated clinical utility in coronavirus disease 2019 (COVID-19) patients. The aim of the present study was to evaluate the possibilities of a portable pocket-sized ultrasound scanner in the evaluation of lung involvement in patients with COVID-19 pneumonia. We conducted 437 paired readings in 34 LUS evaluations of hospitalized individuals with COVID-19. The LUS scans were performed on the same day with a standard high-end ultrasound scanner (Venue GO, GE Healthcare, Chicago, IL, USA) and a pocket-sized ultrasound scanner (Butterfly iQ, Butterfly Network Inc., Guilford, CT, USA). Fourteen scans were performed on individuals with severe cases, 11 on individuals with moderate cases and nine on individuals with mild cases. No difference was observed between groups in days since onset of symptoms (23.29 ± 10.07, 22.91 ± 8.91 and 28.56 ± 11.13 d, respectively; p = 0.38). No significant differences were found between LUS scores obtained with the high-end and the portable pocket-sized ultrasound scanner. LUS scores in individuals with mild respiratory impairment were significantly lower than in those with moderate and severe cases. Our study confirms the possibilities of portable pocket-sized ultrasound imaging of the lung in COVID-19 patients. Portable pocket-sized ultrasound scanners are cheap, easy to handle and equivalent to standard scanners for non-invasive assessment of severity and dynamic observation of lung lesions in COVID-19 patients.