Effectiveness and safety of Argon Plasma Coagulation in patients with haemoptysis caused by an endobronchial malignancy.

BACKGROUND: Patients with central neoplasms and haemoptysis show low survival rates. Symptom control without recurrence 48 hours after bronchoscopic interventions may improve the prognosis of these patients. Bronchoscopic Argon Plasma Coagulation (APC) is a useful technique for endobronchial management of haemoptysis in patients with central malignancies. Nevertheless, limited data are available in the literature on its efficacy and safety and the main predictors of success are still unclear. MATERIALS AND METHODS: An observational, prospective, single-center cohort study was carried out to assess the efficacy (i.e. immediate bleeding cessation without recurrence during the following 48 hours) of bronchoscopic APC in the treatment of patients with haemoptysis caused by endobronchial malignancies and the main predictors of success. RESULTS: A total of 76 patients with median age 75 years (IQR: 65-79) were enrolled. 67 (88.2%) patients had bleeding cessation without recurrence 48 hours after bronchoscopic APC. A low rate of non-serious adverse events (5.3%) was recorded and a low (7.6%) recurrence rate of haemoptysis at 3.5 months after the procedure was also shown. No clinical, demographic and endoscopic variables related to a successful procedure at 48 hours were found. CONCLUSIONS: This study demonstrates that bronchoscopic APC is an effective procedure in the treatment of patients with haemoptysis caused by endobronchial malignancies, regardless of the clinical characteristics of the patients, the endoscopic and histological features of the neoplasm and the severity of the symptom. Furthermore, it shows a low rate of complications and long-term efficacy in bleeding control.

Switching of biological therapy to dupilumab in comorbid patients with severe asthma and CRSwNP.

PURPOSE: Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally. METHODS: We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms. Patients were switched to dupilumab and outcomes were evaluated at baseline (T0), at 3 months (T1), at 6 months (T2), at 12 months (T3) and finally at 18 months (T4). Data were collected at each time point including blood tests measuring eosinophil levels and total IgE, SNOT22, ACT, NPS score, rhinomanometry, olfactory testing, and nasal cytology. RESULTS: The results showed an overall improvement in all the outcomes. Peripheral eosinophilia was observed consistently with existing literature. All patients registered an improvement in sinonasal outcomes, while only one patient had a worsening of asthma. Three patients interrupted the therapy due to various causes: poor asthma control, onset of psoriasis and thrombocytopenia. CONCLUSIONS: The response to a biologic treatment for CRSwNP control may be heterogenous and it seems that patients may benefit from switching improving control in equal measure in the upper and lower airway. Further studies to explore the endotype/phenotype which best fits with each biologic are mandatory to personalize the therapy.

Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS).

BACKGROUND: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. METHODS: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. RESULTS: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. CONCLUSION: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.

Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study.

BACKGROUND: The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks. METHODS: ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only. RESULTS: Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430-890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: - 94.9%; severe AER: - 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: - 95.9%; severe AER: - 97.5%) and bio-experienced patients (any AER: - 92.4%; severe AER: - 94.0%). CONCLUSIONS: Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients' eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04272463.

Long-term outcomes of combination biologic therapy in uncontrolled severe asthma: a case study.

INTRODUCTION: Treatment with biologics has significantly reduced the social and economic burden of severe asthma. However, some patients may still feature a suboptimal control of their symptoms while on therapy. In this subset of asthmatic patients, a benefit from a dual biologic therapy has sporadically been reported in literature. Our aim is to add our experience to the limited body of evidence supporting combination biologic therapies. CASE STUDY: Here we present the case of a 68-year-old nonsmoker female, with an allergic and eosinophilic corticosteroid-dependent severe asthma. She displayed well controlled comorbidities and good adherence to the inhaled therapy. Omalizumab was started in 2008 with an initial remarkable clinical improvement. After nine years of biologic therapy, she reported a gradual worsening of her symptoms and exacerbations. Mepolizumab was then added in 2019. RESULTS: The addition of Mepolizumab resulted in a meaningful amelioration of her quality of life, asthma control, number of exacerbations and 6-minute-walking-distance at 3-year follow-up. The average Prednisone dosage was tapered from 25 mg to 20 mg daily. No adverse events were observed since the introduction of the second biologic. CONCLUSION: Our experience indicates that Mepolizumab may be beneficial and safe as an add-on biologic in a patient whose allergic and eosinophilic asthma remains uncontrolled despite treatment with an anti-IgE strategy. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes published so far are replicable on a larger scale.

A tailored approach to refractory severe Mepolizumab-associated headache: a case study.

INTRODUCTION: Biologic drugs have been shown to reduce asthma exacerbations, improve lung function and quality of life, reduce oral corticosteroid use in appropriately selected patients. Mepolizumab has been demonstrated to have a safety profile that is similar to placebo, however, when present side effects may lead to treatment discontinuation. Among these, headache is one of the most common. CASE STUDY: We hereby describe the case of a never-smoking male patient with an eosinophilic corticosteroid-dependent severe asthma. He displayed well controlled comorbidities and good adherence to the inhaled therapy. Mepolizumab was started in 2017 with an initial remarkable clinical improvement. After three doses of biologic therapy, he reported a severe orthostatic headache associated with vomiting, unresponsive to analgesic drugs, that required hospitalization. No other cause than treatment with Mepolizumab was found to be plausibly associated with this new-onset headache. The therapeutic regimen was modified by administering Mepolizumab for two consecutive months alternated with a one-month break. RESULTS: The patient did not experience any further episodes of headache, while maintaining a good and stable control of his asthma. We were able to taper oral corticosteroids, and no flares-ups occurred in the following 5 years. CONCLUSION: Our experience indicates that a tailored strategy for managing severe asthmatic patients, who have experienced side effects from biologic drugs, can be effective in maintaining drug efficacy while minimizing side effects. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes here described are replicable on a larger scale.

Does the severity of asthma affect exercise capacity and daily physical activity?

OBJECTIVE: Exercise capacity, daily physical activity, and psychological profile are crucial aspects in the management of asthmatic patients. Whether these features are expressed in a different way in mild-moderate (MMA) and severe asthma (SA) is unknown. METHODS: In this observational cross-sectional study, patients matching the American Thoracic Society/European Respiratory Society (ATS/ERS) definition for SA underwent incremental cardiopulmonary exercise testing (CPET), full lung function testing, and an evaluation of daily step count and physical activity. Questionnaires on quality of life, general fatigue, and presence of anxiety and depression traits (Hospital Anxiety and Depression Scale - HADS) were administered. Patients were compared with a cohort of age- and gender-matched MMA patients. RESULTS: We enrolled 16 SA, 17 MMA patients, and 16 healthy subjects. Compared to MMA, SA subjects showed a median (interquartile range) reduced peak oxygen consumption during CPET (20.4 (17.2-23.3) vs. 25.6 (18.5-30.3) ml/min/kg; p = 0.019), a reduced resting lung function (FEV1% of predicted 77 (67-84) vs. 96 (84-100); p < 0.001) and a pronounced anxiety trait at HADS (9.5 (3-11.7) vs. 4.0 (2.0-7.5); p = 0.023). In addition, SA patients showed a significantly higher reduction in inspiratory capacity from rest to peak (310 (160-520) vs. 110 (-65-325) ml; p = 0.031). We found no significant differences in mean daily step count or quality of life. CONCLUSIONS: Compared to MMA, SA patients present a reduced exercise capacity and a more pronounced anxiety trait, but not worse daily physical activity or quality of life. These aspects should be considered in the clinical management and research development of SA.

Xpert MTB/RIF in the Diagnosis of Mediastinal Tuberculous Lymphadenitis by Endoscopic Ultrasound-Guided Needle Aspiration Techniques: A Systematic Review and Meta-Analysis.

BACKGROUND: Lymphadenopathy is one of the most prevalent clinical manifestations of extrapulmonary tuberculosis. Endosonography is the recommended technique in the diagnostic work-up of mediastinal lymphadenopathies. Xpert MTB/RIF assay is a self-contained cartridge-based fully automated DNA testing platform which can accurately detect both tuberculosis and mycobacterial resistance to rifampicin. A few studies assessed its accuracy for mediastinal lymph node aspirates collected using endosonography. A systematic review of observational studies was performed to provide a pooled estimate of sensitivity and specificity of Xpert MTB/RIF in the diagnosis of mediastinal tuberculous lymphadenitis using endoscopic ultrasound-guided needle aspiration techniques. METHODS: A search of the scientific evidence was carried out using PubMed, Embase, and Scopus. Articles describing observational studies on Xpert MTB/RIF in the diagnosis of mediastinal tuberculous lymphadenitis using endoscopic ultrasound-guided needle aspiration techniques were selected. RESULTS: Eight studies met the inclusion criteria. The overall pooled sensitivity was 61% (95% CI = 55-68%; I2 = 66.3%; p = 0.004), overall pooled specificity was 89% (95% CI = 85-91%; I2 = 90.1%; p < 0.0001). Area under the sROC curve was 0.68. Only one study reported data on rifampin resistance detection and showed a sensitivity of 83.3% and a specificity of 16%. CONCLUSIONS: Xpert MTB/RIF shows a good accuracy in the diagnosis of mediastinal mycobacterial lymphadenitis by endosonographic needle aspiration techniques. It should be always recommended for suspected mediastinal tuberculosis.

Observational, Multicenter Study on the Efficacy, Tolerability, and Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis Older than 80 Years.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) primarily affects old patients. Old age is a predictor of mortality. Nintedanib, the only antifibrotic drug approved in Italy for patients aged >80 years, can slow the progression of IPF by reducing the rate of decline in forced vital capacity (FVC) and the risk of exacerbations. OBJECTIVES: The primary aim of the study was to compare the decline of FVC after 12 months of nintedanib in patients aged >80 years versus younger patients. Differences related to other functional data, safety, tolerability, hospitalizations, exacerbations, and mortality were evaluated. METHODS: An observational, retrospective, multicenter study was carried out in Italy. RESULTS: 159 (122 [76.7%] males) patients were recruited: 106 (66.7%) aged ≤80 years and 53 (33.3%) aged >80 years. FVC decline after 12 months of therapy was not significantly different (-45 mL [-170; 75] vs. -20 mL [-138; 110] mL; p: 0.51). No differences were found for other functional data. Diarrhea was the most frequent adverse event (AE). Rate and type of any AEs, permanent/temporary dose reduction, or drug discontinuation were not significantly different between patients aged ≤80 vs. >80 years. Furthermore, acute exacerbations, hospitalization, and mortality were not significantly different. CONCLUSIONS: Nintedanib is effective and safe in patients with IPF aged >80 years, and no significant differences were found when clinical outcomes were compared with those of younger patients. Thus, older age should not be a barrier for the early prescription of antifibrotic treatment in IPF patients.

Bronchoscopy in the post-acute phase of COVID-19: an observational study.

BACKGROUND: Bronchoscopy is a useful technique adopted in the management of patients with COVID-19. 10-40% of COVID-19 survivors experience persistent symptoms. A comprehensive description of the utility and safety of bronchoscopy in the management of patients with COVID-19 sequelae is lacking. The aim of the study was to evaluate the role of bronchoscopy in patients with suspected post-acute sequelae of COVID-19. METHODS: An observational, retrospective study was carried out in Italy. Patients requiring bronchoscopy for suspected COVID-19 sequelae were enrolled. RESULTS: 45 (21, 46.7%, female) patients were recruited. Bronchoscopy was more frequently indicated for patients with a previous critical disease. The most frequent indications were tracheal complications, mostly performed in patients who were hospitalized during the acute phase than treated at home (14, 48.3% VS. 1, 6.3%; p-value: 0.007) and persistent parenchymal infiltrates, more frequent in those treated at home (9, 56.3% VS. 5, 17.2%; p-value: 0.008). 3 (6.6%) patients after the first bronchoscopy required higher oxygen flow. Four patients were diagnosed with lung cancer. CONCLUSION: Bronchoscopy is a useful and safe technique in patients with suspected post-acute sequelae of COVID-19. The severity of acute disease plays a role in the rate and indications of bronchoscopy. Endoscopic procedures were mostly performed for tracheal complications in critical, hospitalized patients and for persistent lung parenchymal infiltrates in mild-moderate infections treated at home.

Mediastinal lymphadenopathies and skin lesions in a 49-year-old Sinhalese man.

Leprosy is a neglected disease sporadically reported in high-income countries. Skin lesion and peripheral nerve involvement represent most common manifestations. Mediastinal lymphadenopathy in the absence of superficial lymph nodes involvement is very rare. Atypical or rare clinical presentations of disease may delay diagnosis and therapy and cause potential life-threatening manifestations and disabilities. We describe the case of a 49-year-old Sinhalese man who was admitted to our hospital with a one-month history of peripheral neurological symptoms and skin lesions on lower limbs. CT scan showed the presence of mediastinal lymphadenopathies without lung parenchymal and superficial lymph nodes involvement. Endobronchial ultrasound-guided transbronchial needle aspiration showed the presence of granulomas while skin biopsy revealed dermo-hypodermic granulomas with perineural lymphohistiocytic inflammatory reaction. Fite-Faraco staining demonstrated the presence of acid-fast bacilli in both lymph nodal and skin biopsy and polymerase chain reaction was positive for Mycobacterium leprae. Multibacillary leprosy was then diagnosed.

Excess Total Mortality in Italy: An Update to February 2023 with Focus on Working Ages.

BACKGROUND: Italy had a persistent excess of total mortality up to July 2022. This study provides updated estimates of excess mortality in Italy until February 2023. METHODS: Mortality and population data from 2011 to 2019 were used to estimate the number of expected deaths during the pandemic. Expected deaths were obtained using over-dispersed Poisson regression models, fitted separately for men and women, including calendar year, age group, and a smoothed function of the day of the year as predictors. The excess deaths were then obtained by calculating the difference between observed and expected deaths and were computed at all ages and working ages (25-64 years). RESULTS: We estimated 26,647 excess deaths for all ages and 1248 for working ages from August to December 2022, resulting in a percent excess mortality of 10.2% and 4.7%, respectively. No excess mortality was detected in January and February 2023. CONCLUSIONS: Our study indicates substantial excess mortality beyond those directly attributed to COVID-19 during the BA.4 and BA.5 Omicron wave in the latter half of 2022. This excess could be attributed to additional factors, such as the heatwave during the summer of 2022 and the early onset of the influenza season.

No Excess Total Mortality in Italy in the First Semester of 2023 at All Ages and in the Working Age Population.

BACKGROUND: Italy experienced a sustained excess in total mortality between March 2020 and December 2022, resulting in approximately 226,000 excess deaths. This study extends the estimate of excess mortality in the country until June 2023, evaluating the persistence of excess mortality. METHODS: We used mortality and population data from 2011 to 2019 to establish a baseline for expected deaths during the pandemic. Over-dispersed Poisson regression models were employed, stratified by sex, to predict expected deaths. These models included calendar year, age group, and a smoothed function for the day of the year as predictors. Excess mortality was then calculated for all ages and working ages (25-64 years). RESULTS: From January to June 2023, we found a reduction in the number of deaths compared to the expected ones: 6,933 fewer deaths across all age groups and 1,768 fewer deaths in the working age category. This corresponds to a 2.1% and 5.2% decrease in mortality, respectively. CONCLUSIONS: The excess mortality observed in Italy from March to December 2022 was no longer observed in the first six months of 2023.

ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study.

BACKGROUND: Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness. METHODS: ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only. RESULTS: Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400-850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5-25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1-13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (- 93.3%) and to 0.06 for severe exacerbations (- 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0-10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index. CONCLUSIONS: We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463.

Sarcopenia in idiopathic pulmonary fibrosis: a prospective study exploring prevalence, associated factors and diagnostic approach.

BACKGROUND: Sarcopenia gained importance in the evaluation of patients with chronic respiratory diseases, including idiopathic pulmonary fibrosis (IPF), since it may impact negatively on clinical outcomes. AIM: Aim of this study is to evaluate the prevalence and factors associated with sarcopenia, defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) 2019 definition, and to evaluate the prevalence of the single criteria that define the EWGSOP2 definition (muscle strength, muscle quantity and physical performance), in a cohort of consecutive patients with IPF prospectively followed up in 9 hospitals in Northern Italy between December 2018 and May 2021. METHODS: Enrolled patients underwent an extensive pulmonary and nutritional assessment, including bioelectrical impedance analysis, dynamometry and 4-m gait speed test, both at IPF diagnosis and at 6-month follow-up. RESULTS: Out of the 83 patients (81% males, mean age 72.5 years) with IPF at disease diagnosis enrolled in the study, 19 (22.9%) showed sarcopenia, including 2 (2.4%) with severe sarcopenia, 5 (6.0%) with confirmed sarcopenia and 12 (14.5%) with probable sarcopenia. Sarcopenia was associated with a significantly higher severity of the disease and sedentary lifestyle, while no differences were observed in regards to body mass index, history of weight loss and comorbidities between patients with and without sarcopenia. Out of the 64 patients without sarcopenia at baseline, 16 cases showed alteration of muscle quantity and/or physical performance. In the 51 patients with complete data at 6-month follow-up, there were no cases of severe sarcopenia, 1 case (2.0%) showed confirmed sarcopenia, while the prevalence of probable sarcopenia was 19.6% (10 cases). No differences in regards to antifibrotic treatment received and onset of gastrointestinal side effects were observed between patients with and without sarcopenia at follow-up. CONCLUSIONS: The prevalence of sarcopenia in patients with IPF both at diagnosis and at 6-month follow-up was low but not negligible and was associated with higher severity of the disease and sedentary lifestyle. In IPF patients, a comprehensive diagnostic work-up including all the criteria defining the EWGSOP2 definition might be more useful than a series testing for prompt recognition of nutritional and physical performance abnormalities.

One-year cognitive follow-up of COVID-19 hospitalized patients.

BACKGROUND AND PURPOSE: Cognitive dysfunction has been observed following recovery from COVID-19. To the best of our knowledge, however, no study has assessed the progression of cognitive impairment after 1 year. The aim was to assess cognitive functioning at 1 year from hospital discharge, and eventual associations with specific clinical variables. METHODS: Seventy-six patients (aged 22-74 years) who had been hospitalized for COVID-19 were recruited. Patients received neuropsychological assessments at 5 (n = 76) and 12 months (n = 53) from hospital discharge. RESULTS: Over half (63.2%) of the patients had deficits in at least one test at 5 months. Compared to the assessment at 5 months, verbal memory, attention and processing speed improved significantly after 1 year (all p < 0.05), whereas visuospatial memory did not (all p > 0.500). The most affected domains after 1 year were processing speed (28.3%) and long-term visuospatial (18.1%) and verbal (15.1%) memory. Lower PaO2 /FiO2 ratios in the acute phase were associated with worse verbal long-term memory (p = 0.029) and visuospatial learning (p = 0.041) at 5 months. Worse visuospatial long-term memory at 5 months was associated with hyposmia (p = 0.020) and dysgeusia (p = 0.037). CONCLUSION: Our study expands the results from previous studies showing that cognitive impairment can still be observed after 1 year. Patients with severe COVID-19 should receive periodic cognitive follow-up evaluations, as cognitive deficits in recovered patients could have social and occupational implications.

Accuracy and Predictors of Success of EUS-B-FNA in the Diagnosis of Pulmonary Malignant Lesions: A Prospective Multicenter Italian Study.

BACKGROUND: The role of endoscopic ultrasound with bronchoscope fine-needle aspiration (EUS-B-FNA) in the diagnosis of suspected malignant pulmonary lesions adjacent to the esophagus has been poorly investigated. The aim of the present study was to assess the accuracy of EUS-B-FNA for the diagnosis and molecular profiling of paraesophageal pulmonary lesions, as well as its predictors of success. MATERIALS AND METHODS: Patients who underwent EUS-B-FNA for the diagnosis of paraesophageal lesions were consecutively enrolled in four Italian centers. Demographic, clinical, procedural, pathological, and molecular characteristics of the malignant samples were collected. The primary outcome was the diagnostic accuracy for pulmonary malignancies. Secondary outcomes were diagnostic yield and predictors of success for diagnosis and molecular profiling. RESULTS: 107 adult patients (60 [56.1%] males; median (interquartile range) age: 69 [60-70] years) were enrolled. The diagnostic accuracy of EUS-B-FNA was 95.3% in the overall cohort and 95.2% in the 99 patients with a final diagnosis of malignancy. Neither clinical nor procedural variables significantly affected the diagnostic accuracy, whereas rapid on-site evaluation (ROSE), performed by pathologists or trained pulmonologists, was a strong predictor for a complete molecular profiling (OR [95% CI]: 12.9 [1.2-137.4]; p value: 0.03). CONCLUSION: EUS-B-FNA is a safe and accurate method for the diagnosis of paraesophageal pulmonary lesions. The presence of ROSE is relevant for a complete molecular profiling in this selected cohort of patients with advanced lung cancer.

Left pleural effusion in a young woman with genital tuberculosis.

Disseminated tuberculosis is a rare form of tuberculosis that can cause severe illness if diagnosed and treated late. We present the case of a young Senegalese woman who had a miscarriage due to a pelvic inflammatory disease, followed by the development of a left pleural effusion. Despite laparoscopic findings and a salpinx biopsy that revealed necrotizing granulomas, only microbiological examinations of pleural biopsies revealed the final diagnosis of disseminated, drug-sensitive tuberculosis.

Excess total mortality during the Covid-19 pandemic in Italy: updated estimates indicate persistent excess in recent months.

BACKGROUND: New releases of daily mortality data are available in Italy; the last containing data up to 31 January 2022. This study revises previous estimates of the excess mortality in Italy during the Covid-19 pandemic. METHODS: Excess mortality was estimated as the difference between the number of registered deaths and the expected deaths. Expected deaths in March-December 2020, January-December 2021 and January 2022 were estimated separately by sex, through an over-dispersed Poisson regression model using mortality and population data for the period 2011-2019. The models included terms for calendar year, age group, a smooth function of week of the year and the natural logarithm of the population as offset term. RESULTS: We estimated 99,334 excess deaths (+18.8%) between March and December 2020, 61,808 deaths (+9.5%) in 2021 and 4143 deaths (+6.1%) in January 2022. Over the whole pandemic period, 13,039 excess deaths (+10.2%) were estimated in the age group 25-64 years with most of the excess observed among men [10,025 deaths (+12.6%) among men and 3014 deaths (+6.3%) among women]. CONCLUSIONS: Up to 31 January 2022, over 165 thousand excess deaths were estimated in Italy, of these about 8% occurred among the working age population. Despite high vaccination uptake, excess mortality is still observed in recent months.

No excess mortality among working-age Italians during the Omicron wave of Covid-19.

BACKGROUND: This study provides updated estimates of the excess deaths in Italy with a focus on the working-age population. METHODS: Over-dispersed Poisson regression models, fitted on 2011-2019 mortality data, and including terms for age, calendar year and a smooth function of the week of the year, were used to estimate the expected number of deaths during the Covid-19 pandemic. The excess deaths were then obtained by the difference between observed and expected deaths and reported according to the pandemic periods defined by the predominant circulating variant of SARS-CoV-2. RESULTS: Around 170,700 excess deaths at all ages were estimated between March 2020 and March 2022 in Italy with most of the excess occurring during the pre-Delta and Delta period, and 2930 excess deaths (+2.5%) during the Omicron wave. The excesses among the working age population were: 10,425 deaths (+11.8%) during the pre-Delta period, 2460 (+9.4%) during the Delta wave, 283 (+2.2%) during the transition period to Delta. Mortality was lower than expected during the Omicron wave (-6.1%). CONCLUSIONS: Over the periods preceding the Omicron wave, Covid-19 caused around 12,800 excess deaths among individuals of working age, accounting for over 10% excess death. This excess was no longer observed during the Omicron wave.