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(1) Background: Few data are available on the risk of airway dysfunction in protease inhibitor (PI*) M heterozygotes carrying rare null or deficient allelic variants of the gene SERPINA-1 (PI*MR). (2) Methods: In this observational study, in a cohort of PI*MR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PI*MZ and PI*MS patients. (3) Results: A total of 60 patients were recruited; 35 PI*MR, 11 PI*MZ and 14 PI*MS. At the annual follow-up, the PI*MR and PI*MZ patients demonstrated a significantly higher FEV1 decline than the PI*MS group (p = 0.04 and p = 0.018, respectively). The PI*MR patients showed a significant increase in DLCO annual decline in comparison with the PI*MS group (p = 0.02). At baseline, the PI*MR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV1, FEV1/FVC and DLCO (p = 0.0004, p < 0.0001, p = 0.007, respectively) and, at the one-year follow-up, they displayed a significantly higher FEV1 and DLCO decline (p = 0.0022, p = 0.011, respectively). PI*MR heterozygotes with COPD showed a significantly higher FEV1, FEV1/FVC and DLCO annual decline in comparison with healthy PI*MR (p = 0.0083, p = 0.043, p = 0.041). (4) Conclusions: These results suggest that PI*MR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored. [ABSTRACT FROM AUTHOR]

Patients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing 2 days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. We suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of available SARS-CoV-2 vaccines and novel vaccinomics developments. [ABSTRACT FROM AUTHOR]

Introduction: Primary paraganglioma of the lung is a rare tumor of which few cases are reported in literature. Both solitary and diffuse primary pulmonary paragangliomas are described. The solitary form of this tumor is rare. Case presentation: We report the case of a 63-year-old Caucasian man with cough, intermittent palpitations and dyspnea. A contrast-enhanced computed tomography scan of his chest revealed a rounded, high-density lesion with irregular profiles measuring 24mm in diameter in the middle lobe. The lesion was suggestive of malignancy. Fine-needle aspiration cytology was performed. The results of the cytological tests were positive for malignant cells. Surgical resection was the choice of treatment. The results of the biochemical tests and postoperative histological examination allowed a definitive diagnosis: primary pulmonary paraganglioma. Conclusions: Paragangliomas are identified and characterized with the use of computed tomography and other imaging methods, but for a definitive diagnosis, histopathological evaluation is necessary. We report a rare case of a primary pulmonary paraganglioma that was treated surgically. This case report adds valuable knowledge to the literature on pulmonary paragangliomas. [ABSTRACT FROM AUTHOR]

The Renaissance theory, transmission and practices of extempore counterpoint have been increasingly attracting the attention of scholars over the last few decades. Within the Spanish musical tradition, a variety of historical sources, such as counterpoint treatises and actas capitulares, are providing an insight into how these crafts were actually taught and performed by learned musicians and singers in chapels. In addition to this tradition of extempore contrapunto, which I define as the ‘learned oral tradition of polyphonic music’, some Spanish sources suggest the existence of an ‘unlearned oral tradition of polyphonic music’, usually performed by non-professional musicians and by men and women without any formal notion of music theory. The music of this ‘unlearned’ tradition was often considered an essentially ‘artless’ repertory and was related, to some extent, to the term ‘fabordón’. While the skills necessary to sing extempore contrapunto were formally studied by professional musicians and practised in chapels, the unlearned tradition of polyphony, that is the capacity to perform simple consonances within a chordal and homophonic style on an existing tune or cantus firmus, was generally transmitted and sung by ear (‘por uso’). It can be seen as belonging to the oral tradition of common people who sung profane or devotional polyphonic songs ‘by ear’, but was also employed in churches where singers, monks and clergymen were accustomed to sing the psalm tones ‘a fabordón’. In this article I examine the various sources that describe this unlearned oral tradition of polyphonic music. [ABSTRACT FROM PUBLISHER]

Simple Summary: Modern profiling technologies have led to relevant progress toward precision medicine and disease management. A new trend in patient classification is to integrate multiple data types for the same subjects to increase the chance of identifying meaningful phenotype groups. However, these methodologies are still in their infancy, with their performance varying widely depending on the biological conditions analyzed. We developed MOUSSE, a new unsupervised and normalization-free tool for multi-omics integration able to maintain good clustering performance across a wide range of omics data. We verified its efficiency in clustering patients based on survival for ten different cancer types. The results we obtained show a higher average score in classification performance than ten other state-of-the-art algorithms. We have further validated the method by identifying a list of biological features potentially involved in patient survival, finding a high degree of concordance with the literature. High-throughput technologies make it possible to produce a large amount of data representing different biological layers, examples of which are genomics, proteomics, metabolomics and transcriptomics. Omics data have been individually investigated to understand the molecular bases of various diseases, but this may not be sufficient to fully capture the molecular mechanisms and the multilayer regulatory processes underlying complex diseases, especially cancer. To overcome this problem, several multi-omics integration methods have been introduced but a commonly agreed standard of analysis is still lacking. In this paper, we present MOUSSE, a novel normalization-free pipeline for unsupervised multi-omics integration. The main innovations are the use of rank-based subject-specific signatures and the use of such signatures to derive subject similarity networks. A separate similarity network was derived for each omics, and the resulting networks were then carefully merged in a way that considered their informative content. We applied it to analyze survival in ten different types of cancer. We produced a meaningful clusterization of the subjects and obtained a higher average classification score than ten state-of-the-art algorithms tested on the same data. As further validation, we extracted from the subject-specific signatures a list of relevant features used for the clusterization and investigated their biological role in survival. We were able to verify that, according to the literature, these features are highly involved in cancer progression and differential survival. [ABSTRACT FROM AUTHOR]

Presents error analysis and regularity tests for the implementation of double adaptive quadrature. Inclusion of local error estimates; Detection of numerical difficulties in the integral and function; Performance of numerical testing on set of functions; Effectiveness and efficiency of the device.

Background: Non-invasive ventilation (NIV) is associated with improvement of both morbility and mortality in patients affected by neuromuscular diseases with chronic respiratory failure. Several studies have also shown that long-term NIV positively impacts the patient's quality of life and perception of disease status. Its effectiveness is likely related to the adherence to NIV. Several factors, patient- and not patient-related, may compromise adherence to NIV, such as physical, behavioral, familiar, and social issues. Few data are currently available on the role of psychological factors in influencing NIV adherence. Materials and methods: In this pilot study, we evaluated the adherence to NIV in a group of 15 adult patients with neuromuscular diseases (Duchenne muscular dystrophy, myotonic dystrophy, and amyotrophic lateral sclerosis) in relation to their grade of depression assessed by the Beck Depression Inventory (BDI) questionnaire. Other data were collected, such as clinical features (age and sex), use of anxiolytic drugs, the presence of a family or professional caregiver, the quality of patient–physician relationship, the beginning of psychological support after BDI screening, and the family acceptance of NIV. NIV adherence was definied as the use of NIV for at least 4 h per night on 70% of nights in a month. Results: The overall rate of NIV adherence was 60%. Based on the BDI questionnaire, patients who were non-adherent to NIV had a higher rate of depression, mainly observed in the oldest patients. The acceptance of NIV by the family and positive physician–patient interaction seem to favor NIV adherence. Conclusion: Depression can interfere with NIV adherence in patients with neuromuscolar diseases. [ABSTRACT FROM AUTHOR]

Pulmonary involvement occurs in 3 to 10% of the cases of Plasmodium falciparum malaria and represents the most severe complication of this infection, with a lethality of about 70%. The antigens released by the parasite play an important role in the induction and worsening of lung damage. Capillary endothelial cells, which control the flux of fluids to the interstitial space, appear to be the most complicated structures. The clinical manifestations of pulmonary involvement may start suddenly at any time during the course of malaria, even after the disappearance of the circulating parasite. Hyperparasitemia predisposes to these factors. Treatment with corticosteroids is optional, and that is not often a benefit. [ABSTRACT FROM AUTHOR]

An abstract of the article "Pulmonary Rehabilitation in Patients With Parkinson Disease," by Giuseppe Fiorentino and colleagues is presented.

An abstract of the article "Effects of Aclidinium on Nocturnal Oxygen Saturation of COPD Patients (B-C Stages)," by Giuseppe Fiorentino and colleagues is presented.

Introduction: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. Methods: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. Results: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan–Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29–0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09–0.39; p < 0.0001). Conclusions: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the presence of subclinical cardiac dysfunction in recovered coronavirus disease 2019 (COVID-19) patients, who were stratified according to a previous diagnosis of pulmonary embolism (PE) as a complication of COVID-19 pneumonia. Out of 68 patients with SARS-CoV-2 pneumonia followed up for one year, 44 patients (mean age 58.4 ± 13.3, 70% males) without known cardiopulmonary disease were divided in two groups (PE+ and PE−, each comprising 22 patients) and underwent clinical and transthoracic echocardiographic examination, including right-ventricle global longitudinal strain (RV-GLS), and RV free wall longitudinal strain (RV-FWLS). While no significant differences were found in the left- or right-heart chambers' dimensions between the two study groups, the PE+ patients showed a significant reduction in RV-GLS (−16.4 ± 2.9 vs. −21.6 ± 4.3%, p < 0.001) and RV-FWLS (−18.9 ± 4 vs. −24.6 ± 5.12%, p < 0.001) values compared to the PE- patients. According to the ROC-curve analysis, RV-FWLS < 21% was the best cut-off with which to predict PE diagnosis in patients after SARS-CoV-2 pneumonia (sensitivity 74%, specificity 89%, area under the curve = 0.819, p < 0.001). According to the multivariate logistic regression model, RV-FWLS < 21% was independently associated with PE (HR 34.96, 95% CI:3.24–377.09, p = 0.003) and obesity (HR 10.34, 95% CI:1.05–101.68, p = 0.045). In conclusion, in recovered COVID-19 patients with a history of PE+, there is a persistence of subclinical RV dysfunction one year after the acute phase of the disease, detectable by a significant impairment in RV-GLS and RV-FWLS. A reduction in RV-FWLS of lower than 21% is independently associated with COVID-related PE. [ABSTRACT FROM AUTHOR]

Introduction: Primary paraganglioma of the lung is a rare tumor of which few cases are reported in literature. Both solitary and diffuse primary pulmonary paragangliomas are described. The solitary form of this tumor is rare.Case Presentation: We report the case of a 63-year-old Caucasian man with cough, intermittent palpitations and dyspnea. A contrast-enhanced computed tomography scan of his chest revealed a rounded, high-density lesion with irregular profiles measuring 24mm in diameter in the middle lobe. The lesion was suggestive of malignancy. Fine-needle aspiration cytology was performed. The results of the cytological tests were positive for malignant cells. Surgical resection was the choice of treatment. The results of the biochemical tests and postoperative histological examination allowed a definitive diagnosis: primary pulmonary paraganglioma.Conclusions: Paragangliomas are identified and characterized with the use of computed tomography and other imaging methods, but for a definitive diagnosis, histopathological evaluation is necessary. We report a rare case of a primary pulmonary paraganglioma that was treated surgically. This case report adds valuable knowledge to the literature on pulmonary paragangliomas. [ABSTRACT FROM AUTHOR]

Non-invasive ventilatory support (NVS) is a technique used to reduce respiratory work in neuromuscular diseases, preventing the progression of respiratory failure. NVS is usually administered via a nasal or an oronasal mask, causing discomfort, especially in patients ventilated for more than 16 h/day. Intermittent abdominal pressure ventilation (IAPV) differs completely from conventional NVS and consists of a portable ventilator and a corset with Velcro closures as the interface. In our study, the practicability and efficacy of IAPV were studied in three Italian centers monitoring 28 neuromuscular patients using IAPV who were then retrospectively analyzed. The primary outcomes were an improvement in hypoxemia and the normalization of hypercapnia, and the secondary outcome was an improvement in quality of life. Data were collected at baseline (T0) and after two hours of ventilation (T1), with follow-ups at three months (T2) and six months (T3). Statistical significance was found for PaCO2 over time (F (2.42) = 7.63, p = 0.001) and PaO2 (W = 0.539, p = 0.033). The time of NVS usage also significantly affected the quality of life (F (2.14) = 6.90, p = 0.010), as seen when comparing T0 and T3. As an alternative ventilation method, IAPV is still relevant today and could become a key part of daytime support, especially for patients who do not tolerate standard daytime NVS with an oral interface. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection is characterized by several clinical manifestations, ranging from the absence of symptoms to severe forms that necessitate intensive care treatment. It is known that the patients with the highest rate of mortality develop increased levels of proinflammatory cytokines, called the "cytokine storm", which is similar to inflammatory processes that occur in cancer. Additionally, SARS-CoV-2 infection induces modifications in host metabolism leading to metabolic reprogramming, which is closely linked to metabolic changes in cancer. A better understanding of the correlation between perturbed metabolism and inflammatory responses is necessary. We evaluated untargeted plasma metabolomics and cytokine profiling via 1H-NMR (proton nuclear magnetic resonance) and multiplex Luminex assay, respectively, in a training set of a limited number of patients with severe SARS-CoV-2 infection classified on the basis of their outcome. Univariate analysis and Kaplan–Meier curves related to hospitalization time showed that lower levels of several metabolites and cytokines/growth factors, correlated with a good outcome in these patients and these data were confirmed in a validation set of patients with similar characteristics. However, after the multivariate analysis, only the growth factor HGF, lactate and phenylalanine retained a significant prediction of survival. Finally, the combined analysis of lactate and phenylalanine levels correctly predicted the outcome of 83.3% of patients in both the training and the validation set. We highlighted that the cytokines and metabolites involved in COVID-19 patients' poor outcomes are similar to those responsible for cancer development and progression, suggesting the possibility of targeting them by repurposing anticancer drugs as a therapeutic strategy against severe SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Highlights: What are the main findings? Pneumothorax/pneumomediastinum developed without positive pressure ventilation among COVID-19 patients had high fatality. Presence of comorbidity, bilateral pneumothorax, and fever were related with in-hospital mortality among COVID-19 associated spontaneous pneumothorax/pneumomediastinum patients The CoBiF score (Co = comorbidity, Bi = bilateral pneumothorax, F = fever) well-predicted the early mortality of these patients. What is the implication of the main finding? The CoBiF score was validated in multinational cohorts, and it could improve early recognition and treatment of COVID-19 pneumothorax. Objectives: Pneumothorax and pneumomediastinum are associated with high mortality in invasively ventilated coronavirus disease 2019 (COVID-19) patients; however, the mortality rates among non-intubated patients remain unknown. We aimed to analyze the clinical features of COVID-19-associated pneumothorax/pneumomediastinum in non-intubated patients and identify risk factors for mortality. Methods: We searched PubMed Scopus and Embase from January 2020 to December 2021. We performed a pooled analysis of 151 patients with no invasive mechanical ventilation history from 17 case series and 87 case reports. Subsequently, we developed a novel scoring system to predict in-hospital mortality; the system was further validated in multinational cohorts from ten countries (n = 133). Results: Clinical scenarios included pneumothorax/pneumomediastinum at presentation (n = 68), pneumothorax/pneumomediastinum onset during hospitalization (n = 65), and pneumothorax/pneumomediastinum development after recent COVID-19 treatment (n = 18). Significant differences were not observed in clinical outcomes between patients with pneumomediastinum and pneumothorax (±pneumomediastinum). The overall mortality rate of pneumothorax/pneumomediastinum was 23.2%. Risk factor analysis revealed that comorbidities bilateral pneumothorax and fever at pneumothorax/pneumomediastinum presentation were predictors for mortality. In the new scoring system, i.e., the CoBiF system, the area under the curve which was used to assess the predictability of mortality was 0.887. External validation results were also promising (area under the curve: 0.709). Conclusions: The presence of comorbidity bilateral pneumothorax and fever on presentation are significantly associated with poor prognosis in COVID-19 patients with spontaneous pneumothorax/pneumomediastinum. The CoBiF score can predict mortality in clinical settings as well as simplify the identification and appropriate management of patients at high risk. [ABSTRACT FROM AUTHOR]

• Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly. • Many in-vivo and in-vitro studies suggest a possible role of intravenous fosfomycin for the treatment of CRAB infections. • Cefiderocol-containing regimens were independently associated with survival and clinical success, whilst colistin-based regimens were associated with death and clinical failure. • The study data showed clinical features and use of different antibiotic regimens with a possible role for fosfomycin in combination for treatment of severe infections caused by CRAB. Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections. This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model. One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n =54), colistin (n =48) or ampicillin/sulbactam (n =18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success. Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB. [ABSTRACT FROM AUTHOR]

Mechanical ventilation started with negative-pressure ventilation (NPV) during the 1950s to assist patients with respiratory failure, secondary to poliomyelitis. Over the years, technological evolution has allowed for the development of more comfortable devices, leading to an increased interest in NPV. The patients affected by neuromuscular diseases (NMD) with chronic and acute respiratory failure (ARF) may benefit from NPV. The knowledge of the available respiratory-support techniques, indications, contraindications, and adverse effects is necessary to offer the patient a personalized treatment that considers the pathology's complexity. [ABSTRACT FROM AUTHOR]

Telomerase and telomeric complex have been linked to a variety of disease states related to neurological dysfunction. In amyotrophic lateral sclerosis (ALS) patients, telomerase activity, as human telomerase reverse transcriptase (hTERT) expression, has not been characterized yet. Here, for the first time, we characterized telomerase and related pathway in blood sample and spinal cord from ALS patients compared with healthy controls. We found that hTERT expression level was significantly lower in ALS patients and was correlated either to p53 mRNA expression or p21 expression, pointing out the hypothesis that telomerase inhibition could be a pathogenetic contributor to neurodegeneration in ALS. As a consequence of the reduced telomerase activity, we identified shorter telomeres in leukocytes from sporadic ALS patients compared with healthy control group. [ABSTRACT FROM AUTHOR]

We established a technique to achieve low temperature hermetic sealing of surface micromachined channels by exploiting stiction. Using a wing-shaped structural layer, microchannels automatically seal during the drying step that follows the sacrificial etch. This avoids the need of plugging layers to close the apertures of the sacrificial etch. To demonstrate the technique, we designed a surface micromachined channel with a structural layer made of polycrystalline silicon carbide (poly-SiC). This layer integrates an array of anchored pillars to achieve long and wide microchannels (5.4 mm × 0.43 mm × 0.001 mm). To dimension the sealing-wing, we estimate the minimum adhesion energy between the poly-SiC and silicon. This is done by analytical modeling and experimental characterization of test structures in the shape of centrally-supported circular plates. The bending and adhesion of the sealing-wing is followed in situ by optical microscopy. The closed microchannels are annealed at 100 °C. Some structures are exposed to thermal stress at 760 °C. The results are inspected by white light interferometry, scanning electron microscopy, and helium leak testing. Microchannels result hermetically sealed showing leak rates below the detection limit (4×10-9 Pa·m3/s). The seal is effective to at least 600 kPa. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we present different devices, working as hydrogen sensors, based on single palladium nanowire and realized combining focused ion beam and dielectrophoresis techniques. The combination of these two techniques consists in the employ of focused ion beam for electrode patterning onto silicon/silicon dioxide substrates, followed by the assembly of a single palladium nanowire applying between electrodes an electric field at fixed frequency (dielectrophoresis) to a palladium nanoparticles solution. The nanowire morphology can be branched or not, depending on the applied frequency value. The devices are characterized in hydrogen environment at room temperature and their responses are compared. [Copyright &y& Elsevier]

Keywords: biomarkers; Covid-19 vulnerability; homocysteine (Hcy); MTHFR677C>T mutations; MTHFR gene; predictor parameters EN biomarkers Covid-19 vulnerability homocysteine (Hcy) MTHFR677C>T mutations MTHFR gene predictor parameters e354 e357 4 08/06/21 20210815 NES 210815 To the Editor, The Covid-19 pandemic is a global challenge, with rapidly increasing cases from the high infective aetiological agent, the Covid-19 virus. For both infected patients and/or those awaiting diagnostic confirmation of Covid-19 disease, these biomarkers may predict risk stratification and determine patient management. [Extracted from the article]

Background: Generally, alpha-1 antitrypsin deficiency (AATD) is suspected in young patients with pulmonary emphysema or chronic obstructive pulmonary disease (COPD). Patients often suffer from diagnostic gaps and are misdiagnosed with chronic obstructive pulmonary disease (COPD), asthma, and airway hyperresponsiveness (AHR), as AATD may present with nonspecific respiratory symptoms. It is never too late to suspect AATD, especially in a patient with an unusual medical history. In recent years, evidence is beginning to emerge that there may be value in identifying and treating patients who do not already have deterioration of functional parameters.Case Presentation: We describe a case of a 69-year-old Caucasian female patient, late diagnosis of AATD, with both severe bronchial hyperreactivity and numerous exacerbations due to the peculiar clinical history and the presence of a rare mutation; although not presenting forced expiratory volume in 1 second (FEV1) between 30 and 65%, the patient was treated with alpha-1 antitrypsin (AAT) augmentation therapy and achieved clinical and functional improvement.Conclusion: AATD should always be suspected. The Alpha-1 Foundation recommendations for the diagnosis and management of AATD in adult patients indicate that treatment should be provided for patients with FEV1 between 30 and 65%. It may be useful to evaluate and treat patients based on clinical symptoms, even outside the established parameters, in particular cases. [ABSTRACT FROM AUTHOR]

Measures implemented in many countries to contain the COVID-19 pandemic resulted in a change in lifestyle with unpredictable consequences on physical and mental health. We aimed at identifying the variables associated with psychological distress during the lockdown between April and May 2020 in the Italian academic population. We conducted a multicenter cross-sectional online survey (IO CONTO 2020) within five Italian universities. Among about 240,000 individuals invited to participate through institutional communications, 18 120 filled the questionnaire. Psychological distress was measured by the self-administered Hospital Anxiety and Depression Scale (HADS). The covariates collected included demographic and lifestyle characteristics, trust in government, doctors and scientists. Associations of covariates with influenza-like symptoms or positive COVID-19 test and with psychological distress were assessed by multiple regression models at the local level; a meta-analysis of the results was then performed. Severe levels of anxiety or depression were reported by 20% of the sample and were associated with being a student or having a lower income, irrespective of their health condition and worries about contracting the virus. The probability of being severely anxious or depressed also depended on physical activity: compared to those never exercising, the highest OR being for those who stopped during lockdown (1.53; 95% CI, 1.28 to 1.84) and the lowest for those who continued (0.78; 95% CI, 0.64 to 0.95). Up to 21% of severe cases of anxiety or depression might have been avoided if during lockdown participants had continued to exercise as before. Socioeconomic insecurity contributes to increase mental problems related to the COVID-19 pandemic and to the measures to contain it. Maintaining or introducing an adequate level of physical activity is likely to mitigate such detrimental effects. Promoting safe practice of physical activity should remain a public health priority to reduce health risks during the pandemic. [ABSTRACT FROM AUTHOR]

In recent months, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. COVID-19 patients show mild, moderate or severe symptoms with the latter ones requiring access to specialized intensive care. SARS-CoV-2 infections, pathogenesis and progression have not been clearly elucidated yet, thus forcing the development of many complementary approaches to identify candidate cellular pathways involved in disease progression. Host lipids play a critical role in the virus life, being the double-membrane vesicles a key factor in coronavirus replication. Moreover, lipid biogenesis pathways affect receptor-mediated virus entry at the endosomal cell surface and modulate virus propagation. In this study, targeted lipidomic analysis coupled with proinflammatory cytokines and alarmins measurement were carried out in serum of COVID-19 patients characterized by different severity degree. Serum IL-26, a cytokine involved in IL-17 pathway, TSLP and adiponectin were measured and correlated to lipid COVID-19 patient profiles. These results could be important for the classification of the COVID-19 disease and the identification of therapeutic targets. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Prone positioning (PP) has demonstrated to be a safe adjunctive therapy for severe acute respiratory distress syndrome (ARDS). There is limited evidence of PP effects on awake patients. This study aimed to investigate the effects and feasibility of PP on coronavirus disease 2019 (COVID-19)-associated awake patients with ARDS in a subintensive setting of care. MATERIAL AND METHODS: This is a single-center case-control study involving patients with severe COVID-19 infection. A total of 29 patients underwent noninvasive ventilation, and PP was initiated 12 h from admission; 18 patients tolerated prone and side positioning for at least 10 h/d and cycled their position every 2 h, and 11 patients had no complaints with PP RESULTS: A total of 29 patients (25 men and 4 women) with a median age of 64 years showed the average baseline white blood cell count of 8.45x109 cells/L, C-reactive protein of 10.1 mg/L, lactate dehydrogenase of 366 mU/mL, and interleukin-6 of 172 pg/mL. Basal pO2/FiO2 ratio (P/F) was 95 (±56.5) and showed no linear correlation with any of the inflammatory markers tested. Computed tomography findings included ground-glass opacities in 100% (29/29) of patients. Consolidation/atelectasis was found in 58% (17/29) of patients. P/F was homogeneously distributed at baseline in patients with PP (96.5) and without PP (95). P/F during PP increased significantly compared with noncompliant controls (288 vs. 202; p=0.0002). Total duration of respiratory failure was significantly shorter in patients with PP (14 vs. 21 days; p=0.002). The number of days to recover from respiratory failure inversely correlated with PP P/F independently from baseline P/F CONCLUSION: COVID-19 can lead to a severe impairment of gas exchange regardless of inflammatory status. Therefore, respiratory support may play a major role in COVID-19 treatment. We documented substantial efficacy of PP when started early and for at least 10 h/d. On awake patients, PP feasibility strictly depends on patient's compliance. The interface should be carefully chosen to best fit every patient. [ABSTRACT FROM AUTHOR]

Background: Continuous external negative pressure (CENP) during positive pressure ventilation can recruit dependent lung regions. We hypothesised that CENP applied regionally to the thorax or the abdomen only, increases the caudal end-expiratory transpulmonary pressure depending on positive end-expiratory pressure (PEEP) in lung-injured pigs. Eight pigs were anesthetised and mechanically ventilated in the supine position. Pressure sensors were placed in the left pleural space, and a lung injury was induced by saline lung lavages. A CENP shell was placed at the abdomen and thorax (randomised order), and animals were ventilated with PEEP 15, 7 and zero cmH2O (15 min each). On each PEEP level, CENP of − 40, − 30, − 20, − 10 and 0 cmH2O was applied (3 min each). Respiratory and haemodynamic variables were recorded. Electrical impedance tomography allowed assessment of centre of ventilation. Results: Compared to positive pressure ventilation alone, the caudal transpulmonary pressure was significantly increased by CENP of ≤ 20 cmH2O at all PEEP levels. CENP of – 20 cmH2O reduced the mean airway pressure at zero PEEP (P = 0.025). The driving pressure decreased at CENP of ≤ 10 at PEEP of 0 and 7 cmH2O (P < 0.001 each) but increased at CENP of – 30 cmH2O during the highest PEEP (P = 0.001). CENP of – 30 cmH2O reduced the mechanical power during zero PEEP (P < 0.001). Both elastance (P < 0.001) and resistance (P < 0.001) were decreased at CENP ≤ 30 at PEEP of 0 and 7 cmH2O. Oxygenation increased at CENP of ≤ 20 at PEEP of 0 and 7 cmH2O (P < 0.001 each). Applying external negative pressure significantly shifted the centre of aeration towards dorsal lung regions irrespectively of the PEEP level. Cardiac output decreased significantly at CENP -20 cmH2O at all PEEP levels (P < 0.001). Effects on caudal transpulmonary pressure, elastance and cardiac output were more pronounced when CENP was applied to the abdomen compared with the thorax. Conclusions: In this lung injury model in pigs, CENP increased the end-expiratory caudal transpulmonary pressure. This lead to a shift of lung aeration towards dependent zones as well as improved respiratory mechanics and oxygenation, especially when CENP was applied to the abdomen as compared to the thorax. CENP values ≤ 20 cmH2O impaired the haemodynamics. [ABSTRACT FROM AUTHOR]

Post-obstructive pneumonia can be caused by the obstruction of the airway secondary to an aspirated solid foreign body; they can be silent or lead to serious symptoms. In our report we show a patient affected by chronic obstructive pulmonary disease and obstructive sleep apnea syndrome treated with non-invasive ventilation and oxygen at home, that presented an acute respiratory failure with hypercapnia. The silent aspiration of a foreign body determined the worsening of hypoxia and hypercapnia owing to bronchial stenosis of the right lower lobe, and radiographic findings including pulmonary infiltrates: the patient had accidentally aspirated an olive from a "pizza with escarole"! [ABSTRACT FROM AUTHOR]

We have recently demonstrated in a double-blind randomized trial the beneficial effects of L -Arginine in patients hospitalized for COVID-19. We hypothesize that one of the mechanisms underlying the favorable effects of L -Arginine is its action on inflammatory cytokines. To verify our hypothesis, we measured longitudinal plasma levels of pro-inflammatory and anti-inflammatory cytokines implied in the pathophysiology of COVID-19 in patients randomized to receive oral L -Arginine or placebo. The study was successfully completed by 169 patients. Patients in the L -Arginine arm had a reduced respiratory support evaluated at 10 and 20 days; moreover, the time to hospital discharge was significantly shorter in the L -Arginine group. The assessment of circulating cytokines revealed that L -Arginine significantly reduced the circulating levels of pro-inflammatory IL-2, IL-6, and IFN-γ and increased the levels of the anti-inflammatory IL-10. Taken together, these findings indicate that adding L -Arginine to standard therapy in COVID-19 patients markedly reduces the need of respiratory support and the duration of in-hospital stay; moreover, L -Arginine significantly regulates circulating levels of pro-inflammatory and anti-inflammatory cytokines. [Display omitted] [ABSTRACT FROM AUTHOR]

Alpha 1 antitrypsin deficiency is responsible for various respiratory diseases in homozygous patients with severe protein deficiency. Sometimes the pulmonary impairment is found even in patients with intermediate deficit, with heterozygous condition. We describe the case of a woman with chronic obstructive pulmonary disease and emphysema with frequent exacerbations for over 10 years. After a diagnostic assessment, the woman with rare heterozygous mutation was treated with augmentation therapy obtaining a clinical and functional improvement. Early diagnosis in these patients is therefore essential to avoid exposure to smoking or to provide additional motivation for cessation to reduce the risk of lung damage. [ABSTRACT FROM AUTHOR]

Intra-hospital transport is often needed for diagnostic and therapeutic procedures that cannot be performed at the bedside. However, moving patients from the safe environment of an Intensive Care Unit (ICU) can lead to a variety of complications and adverse events, the risk is even higher in ventilated patients. This review is intended as a guide on how to prevent and avoid these adverse events during intra-hospital transport of patients on non-invasive ventilation (NIV). Greater attention should be paid to NIV indications and the selection of the patients to be transported. Detailed planning, preparation, and communication between the ward of origin and destination site, appropriate equipment, skilled staff, and continuous monitoring are the key major determinants of success in transporting critically ill patients on NIV. These points are discussed and analyzed in detail. [ABSTRACT FROM AUTHOR]

Background In patients with obstructive sleep apnea syndrome ( OSAS), repetitive hypoxia due to sleep-induced apnea adversely affects the interaction between myocardial oxygen demand and supply, resulting in the development of subclinical cardiac dysfunction. The purpose of the study was to analyze the different involvement of left and right heart myocardial function in patients with OSAS treated with noninvasive ventilation ( NIV). Methods Conventional Doppler echocardiography, Doppler myocardial imaging ( DMI), and two-dimensional speckle tracking echocardiography (2DSTE) of left ( LV) and right ventricular ( RV) longitudinal and right atrial ( RA) deformation were performed in 55 patients with OSAS undergoing NIV (M/F 38/17; mean age 67.8 ± 11.2 years). LV and RV global longitudinal strain ( GLS) was calculated by averaging local strain along the entire right and left ventricle, before and during NIV, and after 6 months of nocturnal NIV therapy. Results LV morphology was comparable before and during NIV, whereas LV ejection fraction and LV DMI early diastolic peak velocity were significantly improved in patients with OSAS during NIV, as was LV regional peak myocardial strain (P < 0.001). RV diameters were slightly increased in patients with OSAS during ventilation, whereas pulmonary artery systolic pressure ( PASP), RV GLS, and regional peak myocardial RV strain were significantly reduced during ventilation (P < 0.0001). RA transverse diameters and RA area were also slightly increased during NIV, whereas RA lateral wall strain was reduced (P < 0.001). Acute RV myocardial impairment completely reversed at follow-up, with a decrease in PASP and subsequent increase in both RV and RA myocardial performance. Conclusions Conventional 2DSTE is a useful tool for assessing left and right heart morphology and myocardial deformation in patients with OSAS and for monitoring both acute and chronic effects of NIV. [ABSTRACT FROM AUTHOR]

Pompe disease (glycogenosis type II) is a rare autosomal recessive lysosomal storage disorder due to mutations of the GAA gene, leading to the deficiency of acid α-glucosidase and consequent glycogen storage in various tissues, mainly in the skeletal muscle, heart and liver. The consequent clinical picture is mainly due to the muscle and heart involvement, although clinical manifestations may be multi-systemic. The phenotype of patients is heterogeneous and the severity is inversely related to the residual enzymatic activity of acid α-glucosidase. More than 200 different mutations of GAA gene have been described and genotype/phenotype correlations have been established for some of them. Traditionally three forms have been described, i.e. early onset classical and non-classical forms and late onset attenuated forms. A severe hypertrophic cardiomyopathy in combination with conduction disorder in newborns represents a typical feature in the classic infantile presentation, while clinical picture in late onset forms is dominated by skeletal muscle dysfunction, resulting in mobility and respiratory problems. Enzyme replacement therapy with recombinant human GAA is the approved therapeutic approach in Pompe disease patients. Clinical trials on enzyme replacement therapy (ERT) support the efficacy in improving survival and hypertrophic cardiomyopathy, while efficacy seems to be variable on manifestations due to skeletal muscle involvement, mainly in late-onset patients. Considering the limitations of ERT and its high costs, innovative therapeutic approaches are now under development. [ABSTRACT FROM AUTHOR]

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism. [ABSTRACT FROM AUTHOR]

Simple Summary: Several studies have explored the role of the inflammatory cells and cytokines involved in the protection or pathogenesis of coronavirus disease 2019. Unfortunately, the results have been controversial, and further studies are needed to better understand not only the roles but also the balance of these parameters, which are crucial data to improve prevention and treatment. As COVID-19 has a well-determined phasic progression and rapidly deteriorates approximately seven days after the onset of symptoms, it is extremely necessary to detect the clinical signs that are predictive of the outcome as early as possible. To this end, in this preliminary study, we evaluated the data relating to the monocyte intracellular TNF-α expression and lymphocyte subpopulations in peripheral blood collected from patients at admission and every day of hospitalization until day 7. Our findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcome of the coronavirus disease 2019. In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19. [ABSTRACT FROM AUTHOR]