Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1\u3b2, IL-6, IL-15 and TNF-\u3b1

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1\u3b2, IL-6, IL-10, IL-15, TNF-\u3b1, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1\u3b2 in lung samples obtained from the COVID-19 group (p\u2009<\u20090.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p\u2009<\u20090.001). TNF-\u3b1 showed a higher immunoreactivity in the COVID-19 group than in the control group (p\u2009<\u20090.001). CD8\u2009+\u2009T cells where more numerous in the lung samples obtained from the COVID-19 group (p\u2009<\u20090.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Oral ondansetron versus domperidone for acute gastroenteritis in pediatric emergency departments: Multicenter double blind randomized controlled trial

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis

Educational aspects of nursing to promote coping in patients with Amyotrophic Lateral Sclerosis: a literature review

reservedBackground: La Sclerosi Laterale Amiotrofica è una patologia dei motoneuroni, e come tale provoca una progressiva e inesorabile degenerazione dei tratti corticospinali, dei nuclei motori bulbari, dei neuroni delle corna anteriori o da una combinazione di questi. Ha eziologia sconosciuta e si manifesta principalmente con sintomi asimmetrici all’esordio, costituiti da crampi, debolezza e atrofia muscolare degli arti superiori e inferiori, porta alla morte nel 50% dei casi entro 3 anni dalla diagnosi, che avviene attraverso la risonanza magnetica nucleare. Non ha cura e il trattamento farmacologico, costituito da Riluzolo e Edaravone, forniscono solamente dei benefici limitati, ad essi vengono poi aggiunti farmaci specifici e mirati contro i sintomi. Obiettivo: L’obiettivo di questa ricerca è supportare il paziente dopo la diagnosi di SLA, individuando gli interventi che migliorano il benessere del paziente, favorendo l’accettazione delle modifiche che la patologia porterà allo stile di vita, evitando che si instauri depressione o ansia post-diagnosi. Materiali e metodi: È stata effettuata una revisione della letteratura tramite la banca dati PubMed, la ricerca è stata svolta analizzando gli studi pubblicati negli ultimi cinque anni. L’analisi e la selezione degli studi sono state sviluppate tramite il metodo PRISMA e hanno portato all’inclusione di dieci articoli che corrispondevano ai criteri di selezione. Risultati: Dalla ricerca sono emersi atteggiamenti negativi e ansiosi dei pazienti e dei caregiver nelle modalità di atteggiamento verso la patologia, si è notato che questi provocassero un peggioramento della patologia stessa e della percezione della qualità di vita. È stato dimostrato come un atteggiamento positivo e di accettazione, attraverso l’uso di strategie di coping attivo siano predittivi di maggior benessere dei soggetti. Conclusione: Dagli articoli selezionati per questa revisione di letteratura si evince che utilizzare strategie di coping che favoriscono l’accettazione, permette di rendere gli ostacoli provocati dalla malattia più tollerabili. La correlazione SLA–depressione/ansia non è ancora sufficientemente trattata in letteratura. È emersa inoltre la necessità di implementare l’offerta di gruppi di mutuo aiuto, in modo da offrire momenti di supporto e condivisione tra i pazienti, così come tra i caregiver.

Medication Errors in Pediatrics: Proposals to Improve the Quality and Safety of Care Through Clinical Risk Management

Medication errors represent one of the most common causes of adverse events in pediatrics and are widely reported in the literature. Despite the awareness that children are at increased risk for medication errors, little is known about the real incidence of the phenomenon. Most studies have focused on prescription, although medication errors also include transcription, dispensing, dosage, administration, and certification errors. Known risk factors for therapeutic errors include parenteral infusions, oral fluid administration, and tablet splitting, as well as the off-label use of drugs with dosages taken from adult literature. Emergency Departments and Intensive Care Units constitute the care areas mainly affected by the phenomenon in the hospital setting. The present paper aims to identify the risk profiles in pediatric therapy to outline adequate preventive strategies. Precisely, through the analysis of the available evidence, solutions such as standardization of recommended doses for children, electronic prescribing, targeted training of healthcare professionals, and implementation of reporting systems will be indicated for the prevention of medication error

Supporting Decision Making in Intensive Care: Ethical Principles for Managing Access to Care During the COVID-19 Pandemic

The pandemic from Covid-19 causes a health threat for many countries and requires an internationally coordinated response due to the high spread of the infection. the current local and international situation gives rise to logistical and ethical considerations regarding the imbalance between needs for assistance and availability of health resources in the continuation of the emergency. a shortage condition will require healthcare professionals to choose between patients who will have access to respiratory support and those who will have to continue without. the sharing of criterie for the introduction of patients to the different therapeutic paths is fundamental to prevent the onset of ethical issues. the present paper analyzes the critical issues related to the scarcity of healthcare resources and the limitation of access to intensive care with the aim of proposing ethically sustainable principles for the management of the current pandemic situatio

Spread of COVID-19 Infection in Long-Term Care Facilities of Trieste (Italy) during the Pre-Vaccination Era. Integrating Findings of 41 Forensic Autopsies with Geriatric Comorbidity Index as a Valid Option for the Assessment of Strength of Causation

Background: in 2020 a new form of coronavirus spread around the world starting from China. The older people were the population most affected by the virus worldwide, in particular in Ita-ly where more than 90% of deaths were people over 65 years. In these people, the definition of the cause of death is tricky due to the presence of numerous comorbidities. Objective: to deter-mine whether Covid-19 was the cause of death in a series of older adults residents of nursing care homes. Methods: 41 autopsies were performed from May to June 2020. External examina-tion, swabs, macroscopic and microscopic examination were performed. Results: the case series consisted of nursing home guests; 15 men and 26 women, with a mean age of 87 years. The av-erage number of comorbidities was 4. Based only on the autopsy results the defined cause of death was in 8% of the cases respiratory failure in subjects with histological signs of diffuse al-veolar damageCovid-19 in 8% of the cases, 31% died of acute respiratory failure due to bron-chopneumonia, 37% died of acute cardiac failure with one or more positive swabs for Covid-19SARS-CoV-2, 10% died of acute cardiac failure in patients without signs of SARS-CoV-2 infectionCovid-19, 3 cases of septic shock, 2 cases from malignant neoplastic disease and 1 case of massive digestive bleeding. Conclusions: The combined evaluation of the Geriatric Index of Comorbidity, swab result and autopsy results showed that only in 5 cases death was due to Covid-19, in the remaining 36 cases Covid-19 was not acknowledged as cause of deat

More than Pneumonia: Distinctive Features of SARS-Cov-2 Infection. From Autopsy Findings to Clinical Implications: A Systematic Review

Despite safety recommendations for the management of corpses with COVID-19 infection and the high number of deaths worldwide, the post-mortem investigation rate is extremely low as well as the scientific contributions describing the pathological features. The first results of post-mortem investigations provided interesting findings and contributed to promoting unexplored therapeutic approaches and new frontiers of research. A systematic review is provided with the aim of summarizing all autopsy studies up to February 2020 in which a complete post-mortem investigation in patients with COVID-19 disease was performed, focusing on histopathological features. We included case reports, case series, retrospective and prospective studies, letters to the editor, and reviews. A total of 28 studies fulfilled the inclusion criteria, producing a pooled dataset of 407 full autopsies. Analyzing the medical history data, only 12 subjects had died without any comorbidities (for 15 cases the data were not available). The post-mortem investigation highlighted that acute respiratory distress syndrome (ARDS) and multiple organ failure represent the main clinical features of COVID-19 disease, often leading to pulmonary thromboembolism and superimposed bronchopneumonia. The discussed data showed a strict relationship among the inflammatory processes, diffuse alveolar, and endothelial damage. In light of these results, the full autopsy can be considered as the gold standard to investigate unknown infections or pathogens resulting in death