Health related quality of life, physical function, and cognitive performance in mechanically ventilated COVID-19 patients: A long term follow-up study.

BACKGROUND: Survivors of severe COVID-19 related respiratory failure may experience durable functional impairments. We aimed at investigating health-related quality of life (HR-QoL), physical functioning, fatigue, and cognitive outcomes in COVID-19 patients who received invasive mechanical ventilation (IMV). METHODS: Case-series, prospective, observational cohort study at 18 months from hospital discharge. Patients referring to the Intensive Care Unit (ICU) of Humanitas Research Hospital (Milan, Italy) were recruited if they needed IMV due to COVID-19 related respiratory failure. After 18 months, these patients underwent the 6-min walking test (6MWT), the Italian version of the 5-level EQ-5D questionnaire (EQ-5D-5L), the Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire (FACIT-F), the Trail Making Test-B (TMT-B) and the Montreal Cognitive Assessment-BLIND test (MoCA-BLIND). RESULTS: 105 patients were studied. The population's age was 60 ± 10 years on average, with a median Frailty Scale of 2 (Hodgson et al., 2017; Carenzo et al., 2021a [2,3]). EQ-VAS was 80 [70-90] out of 100, walked distance was 406 [331-465] meters, corresponding to about 74 ± 19,1% of the predicted value. FACIT-F score was 43 [36-49] out of 52, and MoCa-BLIND score was 19 (DeSalvo et al., 2006; von Elm et al., 2008; Herdman et al., 2011; Scalone et al., 2015 [16-20]) out of 22. The median TMT-B time was 90 [62-120] seconds. We found a possible age and gender specific effect on HR-QoL and fatigue. CONCLUSIONS: After 18 months from ICU discharge, survivors of severe COVID-19 respiratory failure experience a moderate reduction in HR-QoL, and a severe reduction in physical functioning. Fatigue prevalence is higher in younger patients and in females. Finally, cognitive impairment was present at a low frequency.

Role of emergency teleradiology in a mass motorcycle event: the experience of the 2021 International Six Days of Enduro (ISDE).

PURPOSE: Provision of healthcare support at mass gathering sporting events is of paramount importance for the success of the event. Many of such events, like motorsports, have been increasingly taking place in remote and austere environments. In these settings, the use of first-line diagnostic tools, such as point of care ultrasound and portable X-ray, could aid in definitive care on the field for patients with minor trauma while also ensuring fast access to the appropriate level of care for patients requiring hospitalization. METHODS: As part of the ISDE 2021 medical response plan, a field hospital equipped with portable digital X-ray and telemedicine was established. Data on patient admission, triage, treatments, diagnostics, and outcomes were collected for analysis. RESULTS: During the 6-day competition, 79 patients sought medical care at the field hospital, with traumatic injuries accounting for 77% of cases. Of these, 47 were athletes and 32 were non-athletes. The majority (91%) arrived spontaneously, while 9% were transported directly. Upon admission, 68 patients were triaged as non-urgent (code 3) and 11 as urgent (code 2). Of those admitted, 69 received treatment and were discharged at the field hospital, while 10 were transferred elsewhere. Notably, four patients had major trauma, two had isolated fractures, and one needed a CT scan after losing consciousness. Overall, 29 missions were conducted on the race field, including 13 primary transports to local hospitals and 6 to the field hospital. Primary transport was primarily due to major trauma. Among 31 patients who had radiological exams, 11 (35.5%) had traumatic injuries. Of these, 5 were treated with braces and casts and discharged without hospitalization, 3 were advised for post-event care, and 3 were hospitalized. In contrast, patients with negative X-rays received on-site treatment, with 7 able to continue competing. CONCLUSIONS: In summary, the successful implementation of portable X-ray machines and teleradiology at remote and austere high-risk sporting events holds great promise for enhancing on-site medical capabilities, allowing clinicians informed decisions, avoiding unnecessary hospitalization, and allowing athletes to continue with their competition. Provided that challenges related to cost, safety, connectivity, and power supply are effectively addressed.

Reversible supraventricular tachycardia and left bundle branch block in a marathon runner with exertional heat stroke in the Po Valley.

We report the case of a 52-year-old marathon runner admitted to our emergency department for exertional heat stroke (EHS). The electrocardiogram (ECG) showed a supraventricular tachycardia, probably an atrial flutter with 2:1 block, conducted with left bundle branch block. After 10 minutes of aggressive fluid management and rapid external cooling, the ECG returned to normal. As the high-sensitivity cardiac troponin I was elevated, coronary angiography and an electrophysiological study were performed, revealing normal coronary arteries and excluding inducible arrhythmias. As reported in the current literature, our findings confirm that the electrocardiographic changes and elevation of cardiac markers in EHS do not reflect cardiac ischemia, but rather a myocardial injury due to the pathophysiological response to dehydration and hyperthermia, which markedly impaired stroke volume and cardiac output. EHS is a life-threatening condition with a complex pathophysiology caused by thermoregulatory failure. Diagnosis is not always straightforward, but early recognition and timely management (the "golden hour") with rapid cooling and intravenous fluids are crucial to prevent irreversible and fatal organ damage. EHS is defined by a rectal temperature > 40.5 °C with symptoms or signs of neurological dysfunction, such as confusion, drowsiness, or seizures, which can rapidly worsen with delirium, coma, and cardiac arrest. With this case report, we want to remind emergency physicians that early diagnosis and appropriate management of EHS can avoid death and inappropriate treatment. (www.actabiomedica.it).

Outcome prediction during an ICU surge using a purely data-driven approach: A supervised machine learning case-study in critically ill patients from COVID-19 Lombardy outbreak.

PURPOSE: COVID-19 disease frequently affects the lungs leading to bilateral viral pneumonia, progressing in some cases to severe respiratory failure requiring ICU admission and mechanical ventilation. Risk stratification at ICU admission is fundamental for resource allocation and decision making. We assessed performances of three machine learning approaches to predict mortality in COVID-19 patients admitted to ICU using early operative data from the Lombardy ICU Network. METHODS: This is a secondary analysis of prospectively collected data from Lombardy ICU network. A logistic regression, balanced logistic regression and random forest were built to predict survival on two datasets: dataset A included patient demographics, medications before admission and comorbidities, and dataset B included respiratory data the first day in ICU. RESULTS: Models were trained on 1484 patients on four outcomes (7/14/21/28 days) and reached the greatest predictive performance at 28 days (F1-score: 0.75 and AUC: 0.80). Age, number of comorbidities and male gender were strongly associated with mortality. On dataset B, mode of ventilatory assistance at ICU admission and fraction of inspired oxygen were associated with an increase in prediction performances. CONCLUSIONS: Machine learning techniques might be useful in emergency phases to reach good predictive performances maintaining interpretability to gain knowledge on complex situations and enhance patient management and resources.

Chemistry, pharmacology, and cellular uptake mechanisms of thiometallate sulfide donors.

BACKGROUND AND PURPOSE: A clinical need exists for targeted, safe, and effective sulfide donors. We recently reported that ammonium tetrathiomolybdate (ATTM) belongs to a new class of sulfide-releasing drugs. Here, we investigated the cellular uptake mechanisms of this drug class compared to sodium hydrosulfide (NaHS) and the effects of a thiometallate tungsten congener of ATTM, ammonium tetrathiotungstate (ATTT). EXPERIMENTAL APPROACH: In vitro H2 S release was determined by headspace gas sampling of vials containing dissolved thiometallates. Thiometallate and NaHS bioactivity was assessed by spectrophotometry-derived sulfhaemoglobin formation. Cellular uptake dependence on the anion exchange protein (AE)-1 was investigated in human red blood cells. ATTM/glutathione interactions were assessed by LC-MS/MS. Rodent pharmacokinetic and pharmacodynamic studies focused on haemodynamics and inhibition of aerobic respiration. KEY RESULTS: ATTM and ATTT both exhibit temperature-, pH-, and thiol-dependence of sulfide release. ATTM/glutathione interactions revealed the generation of inorganic and organic persulfides and polysulfides. ATTM showed greater ex vivo and in vivo bioactivity over ATTT, notwithstanding similar pharmacokinetic profiles. Cellular uptake mechanisms of the two drug classes are distinct; thiometallates show dependence on AE-1, while hydrosulfide itself was unaffected by inhibition of this pathway. CONCLUSIONS AND IMPLICATIONS: The cellular uptake of thiometallates relies upon a plasma membrane ion channel. This advances our pharmacological knowledge of this drug class, and further supports their utility as cell-targeted sulfide donor therapies. Our results indicate that, as a more stable form, ATTT is better suited as a copper chelator. ATTM, a superior sulfide donor, may additionally participate in intracellular redox recycling. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.

Immunostimulants in respiratory diseases: focus on Pidotimod.

Usefulness of Pidotimod and its role as immunostimulant, has been discussed, we know, for several decades. Nevertheless, there is still much to know. Understanding its mechanisms and its potential usefulness in airway infections and its prevention, asthma both Th2 and non Th2 type, bronchiectasis, as adjuvant in vaccination and in allergen immunotherapy still remains to clearly unveil. The aim of this paper was to provide a useful updated review of the role of the main available immunostimulants, giving particular focus on Pidotimod use and its potentials utility in respiratory diseases. Pidotimod showed its usefulness in reducing need for antibiotics in airway infections, increasing the level of immunoglobulins (IgA, IgM, IgG) and T-lymphocyte subsets (CD3+, CD4+) endowed with immunomodulatory activity that affect both innate and adaptive immune responses. Higher expression of TLR2 and of HLA-DR molecules, induction of dendritic cell maturation and release of pro-inflammatory molecules, stimulation of T lymphocyte proliferation and differentiation toward a Th1 phenotype, as well as an increase of the phagocytosis have been demonstrated to be associated with Pidotimod in in vitro studies. All these activities are potentially useful for several respiratory conditions such as asthma, COPD, and recurrent respiratory tract infections.

Immunological mechanisms underlying chronic rhinosinusitis with nasal polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and quality-of-life impacting disorder, with an underlying immunological mechanism similar to other conditions such as eosinophilic asthma or atopic eczema. Areas covered: This review article summarizes the most recent evidence on the main immunological mechanisms involved in the pathogenesis and the perpetuation of CRSwNP, with a particular focus on the key role of epithelium-derived inflammation as a consequence of the interaction with the airborne environment. Expert commentary: The increase in knowledge of the immunology of CRSwNP leads to the development of therapeutical strategies based upon the use of biologic agents that, according to a personalized and precision medicine approach, will provide each single patient with the most suitable immunological treatment.

A critical appraisal on AIT in childhood asthma.

ABSTRACT: Allergen immunotherapy (AIT) is the only disease-modifying treatment approved for allergic rhinitis and allergic asthma and represents a suitable therapeutic option, especially in childhood, to modify the progression of respiratory allergic diseases. Starting from the previous "generic class effect" evaluation, as testified by the numerous meta analyses, AIT is now considered a product-specific pathogenic-oriented treatment. BACKGROUND: AIT was empirically proposed more than one century ago in the subcutaneous form (SCIT), but the IgE-mediated mechanism of allergy was elucidated only after 50 years of clinical use of the treatment. The sublingual administration (SLIT) was developed during the 1980 ties, to achieve an improvement in safety and convenience. While SCIT is approved in the United States for the treatment of asthmatic patients with more than 12 years, so far few trials evaluated the clinical efficacy and safety of SLIT in children with allergic asthma, although the indications and some aspects remain unclear. Certainly, due to compliance problems, the age below 3 years may be reasonably considered a practical contraindication. CONCLUSIONS: Given that some specific AIT products are effective and approved as drugs (AIFA, EMA, FDA), the use in children is still debated. Some aspects still need robust confirm: (a) the safety of AIT in asthma; (b) the optimal regimen of administration; (c) the role of AIT as preventative treatment for asthma development.