Peri-partum respiratory management of pregnant women with neuro-muscular disorders: a prospective observational study (IT-NEUMA-Pregn study).

BACKGROUND: Pregnant women with neuromuscular diseases (NMDs) often display respiratory muscle impairment which increases the risk for pulmonary complications (PCs). The aim of this study was to identify pregnant NMDs patients with pulmonary risk factors and to apply in these women non-invasive ventilation (NIV) combined with mechanical insufflation-exsufflation (MI-E) in the peri-partum period. METHODS: We conducted a multicenter observational study on women with NMDs undergoing cesarean section or spontaneous labor in a network of 7 national hospitals. In these subjects we applied a protocol for screening and preventing PCs, and we evaluated PCs rate, maternal and neonatal outcome. RESULTS: Twenty-four patients out of the 94 enrolled pregnant women were at risk for PCs and were trained or retrained to use NIV and/or MI-E before delivery. After delivery, 17 patients required NIV with or without MI-E. Despite nine out of the 24 women at pulmonary risk developed postpartum PCs, none of them needed reintubation nor tracheostomy. In addition, the average birth weight and Apgar score were normal. Only one patient without pulmonary risk factors developed postpartum PCs. CONCLUSION: This study showed the feasibility of applying a protocol for screening and treating pregnant NMDs women with pulmonary risk. Despite a PCs rate of 37% was observed in these patients, maternal and neonatal outcome were favorable.

Cardiogenic Pulmonary Edema in Emergency Medicine.

Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung's alveolar spaces due to an elevated cardiac filling pressure. All cardiac diseases, characterized by an increasing pressure in the left side of the heart, can cause CPE. High capillary pressure for an extended period can also cause barrier disruption, which implies increased permeability and fluid transfer into the alveoli, leading to edema and atelectasis. The breakdown of the alveolar-epithelial barrier is a consequence of multiple factors that include dysregulated inflammation, intense leukocyte infiltration, activation of procoagulant processes, cell death, and mechanical stretch. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Some studies claim that these patients may have higher levels of surfactant protein B in the bloodstream. The correct approach to patients with CPE should include a detailed medical history and a physical examination to evaluate signs and symptoms of CPE as well as potential causes. Second-level diagnostic tests, such as pulmonary ultrasound, natriuretic peptide level, chest radiograph, and echocardiogram, should occur in the meantime. The identification of the specific CPE phenotype is essential to set the most appropriate therapy for these patients. Non-invasive ventilation (NIV) should be considered early in the treatment of this disease. Diuretics and vasodilators are used for pulmonary congestion. Hypoperfusion requires treatment with inotropes and occasionally vasopressors. Patients with persistent symptoms and diuretic resistance might benefit from additional approaches (i.e., beta-agonists and pentoxifylline). This paper reviews the pathophysiology, clinical presentation, and management of CPE.

Effectiveness of Intranasal Analgesia in the Emergency Department.

In the Emergency Department (ED), pain is one of the symptoms that are most frequently reported, making it one of the most significant issues for the emergency physician, but it is frequently under-treated. Intravenous (IV), oral (PO), and intramuscular (IM) delivery are the standard methods for administering acute pain relief. Firstly, we compared the safety and efficacy of IN analgesia to other conventional routes of analgesia to assess if IN analgesia may be an alternative for the management of acute pain in ED. Secondly, we analyzed the incidence and severity of adverse events (AEs) and rescue analgesia required. We performed a narrative review-based keywords in Pubmed/Medline, Scopus, EMBASE, the Cochrane Library, and Controlled Trials Register, finding only twenty randomized Clinical trials eligible in the timeline 1992-2022. A total of 2098 patients were analyzed and compared to intravenous analgesia, showing no statistical difference in adverse effects. In addition, intranasal analgesia also has a rapid onset and quick absorption. Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while providing effective pain relief. Intravenous is simple to administer, non-invasive, rapid onset, and quick absorption; it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management.

The Anti-Viral Activity of Stem Cells: A Rational Explanation for their Use in Clinical Application.

It is well established the importance of stem cells (SCs) in tissue growth, regeneration and repair, given their ability to self-renew and differentiate into mature cells. Stem cells are present in all individuals and are potentially active to the end of life. However, less is known about their unique function within the immune system as immune regulators and their important task in viral protection. Antiviral resistance is a common mechanism in all cells though stem cells utilize an antiviral RNA interference (RNAi) mechanism, while adult cells react by using the interferondependent repression pathway via interferon-associated protein-based response to induce an antiviral response. Therefore, the idea behind this review is to highlight the mechanisms of viral evasion of host defense, which would then allow us to highlight the rationale use of autologous stem cells and their biochemical and immunological ability to reset the subverted immune responses. Recently, scientists have highlighted their use in the field of immune-therapy, establishing the possibilities of using them outside the conventional protocol with the advancement in manipulating these cells in such a way that specific body activity can be restored. This paper describes the remarkable SCs profile and discusses some ideas regarding their promising use in vivo.

Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection.

Many factors may influence the risk of being infected by SARS-CoV-2, the coronavirus responsible for coronavirus disease 2019 (COVID-19). Exposure to the virus cannot explain the variety of an individual's responses to the virus and the high differences of effect that the virus may cause to some. While a person's preexisting condition and their immune defenses have been confirmed to play a major role in the disease progression, there is still much to learn about hosts' genetic makeup towards COVID-19 susceptibility and risk. The host genetic makeup may have direct influence on the grade of predisposition and outcomes of COVID-19. In this study, we aimed to investigate the presence of relevant genetic single nucleotide polymorphisms (SNPs), the peripheral blood level of IL6, vitamin D and arterial blood gas (ABG) markers (pH, oxygen-SpO2 and carbon dioxide-SpCO2) on two groups, COVID-19 (n = 41, study), and the healthy (n = 43, control). We analyzed cytokine and interleukin genes in charge of both pro-inflammatory and immune-modulating responses and those genes that are considered involved in the COVID-19 progression and complications. Thus, we selected major genes, such as IL1ß, IL1RN (IL-1 ß and α receptor) IL6, IL6R (IL-6 receptor), IL10, IFNγ (interferon gamma), TNFα (tumor necrosis factor alpha), ACE2 (angiotensin converting enzyme), SERPINA3 (Alpha-1-Antiproteinase, Antitrypsin member of Serpin 3 family), VDR (vitamin D receptor Tak1, Bsm1 and Fok1), and CRP (c-reactive protein). Though more research is needed, these findings may give a better representation of virus pleiotropic activity and its relation to the immune system.

Characteristics of Hepatitis B Virus Genotype and Sub-Genotype in Hepatocellular Cancer Patients in Vietnam.

Untreated chronic hepatitis B virus (HBV) infection can lead to chronic liver disease and may progress to cirrhosis or hepatocellular carcinoma (HCC). HBV infection has been prevalent in Vietnam, but there is little information available on the genotypes, sub-genotypes, and mutations of HBV in patients with HBV-related HCC confirmed by histopathological diagnosis. We studied the molecular characteristics of HBV and its genetic variants in Vietnamese HCC patients after liver tumor resection. We conducted a descriptive cross-sectional study on 107 HBV-related HCC hospitalized patients from October 2018 to April 2019. The specimens collected included EDTA anticoagulant blood and liver tissues. Extracted HBV DNA was subjected to whole genome sequencing by the Sanger method. We discovered 62 individuals (57.9%) with genotype B and 45 patients (42.1%) with genotype C, with only sub-genotypes B4 and C1. Among the mutations, the double mutation, A1762T-G1764A, had the most significant frequency (73/107 samples; 68.2%) and was higher in genotype C than in genotype B (p < 0.001). The most common genotypes found in HCC patients in this investigation were B and C, with sub-genotypes B4 and C1 for each. The prevalence of genotype B4 was greater in HBV-infected Vietnamese HCC patients.

New Translational Trends in Personalized Medicine: Autologous Peripheral Blood Stem Cells and Plasma for COVID-19 Patient.

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), still remains a severe threat. At the time of writing this paper, the second infectious wave has caused more than 280,000 deaths all over the world. Italy was one of the first countries involved, with more than 200,000 people reported as infected and 30,000 deaths. There are no specific treatments for COVID-19 and the vaccine still remains somehow inconclusive. The world health community is trying to define and share therapeutic protocols in early and advanced clinical stages. However, numbers remain critical with a serious disease rate of 14%, ending with sepsis, acute respiratory distress syndrome (ARDS), multiple organ failure (MOF) and vascular and thromboembolic findings. The mortality rate was estimated within 2-3%, and more than double that for individuals over 65 years old; almost one patient in three dies in the Intensive Care Unit (ICU). Efforts for effective solutions are underway with multiple lines of investigations, and health authorities have reported success treating infected patients with donated plasma from survivors of the illness, the proposed benefit being protective antibodies formed by the survivors. Plasma transfusion, blood and stem cells, either autologous or allograft transplantation, are not novel therapies, and in this short paper, we propose therapeutic autologous plasma and peripheral blood stem cells as a possible treatment for fulminant COVID-19 infection.

An Alternative "Trojan Horse" Hypothesis for COVID-19: Immune Deficiency of IL-10 and SARS-CoV-2 Biology.

The coronavirus disease 2019 (COVID-19) pandemic has been a challenge for emergency care units worldwide due to the large numbers of patients, the scarcity of information, the medical resources, and the uncertainty regarding the disease's etiology and pathogenesis. The transmission of the virus and a probable post-pandemic of SARS-CoV-2 will depend on how deep this disease, the duration of immunity and the degree of cross immunity between SARS-CoV-2 and other pathogens either bacteria or fungi can be understood. Most mortalities have been related to an atypical pneumonia consisted of a sudden worsening of general condition of the admitted positive COVID-19 patients. The severe thromboembolism, often characterized by violent pulmonary and systemic complications, have been described with a blend of inflammatory-infectious patterns that rapidly shifted into a typical systemic inflammatory response syndrome (SIRS) or into an acute respiratory distress syndrome (ARDS) that eventually concluded into a multi-organ failure (MOF) and death. The fatality rate reported in our Covid-19 structure, SG Moscati Hospital of Taranto province in Italy, was higher in elderly male people with preexisting chronic pulmonary disease (COPD), patients with cancer and preexisting cardio-vascular diseases (CVD). We assumed a different theoretical position to clarify the higher mortality seen among those patients that was not as obvious as it appeared, we thus offered different pathophysiological picture that could help to recent solutions in therapy and prevention.

Immunity Profiling of COVID-19 Infection, Dynamic Variations of Lymphocyte Subsets, a Comparative Analysis on Four Different Groups.

BACKGROUND: A novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) emerged in December 2019 in China, spreading worldwide. The aim of the present investigation was to evaluate the immunological response and the clinical subset of peripheral lymphocyte subset alteration in COVID-19 infection. METHODS: the study was conducted on four different clinical groups (n = 4; total n = 138). Each individual was assigned to different groups based on specific criteria evaluated at the admission such as fever, dyspnea, arterial blood gas analysis (ABG), oral-nasopharyngeal swab/RT-PCR, and thoracic CT-scan. Treatment was performed only after blood samples were collected from each patient (PP and PP) at day 1. The blood samples were analyzed and tested the same day (CBC and Flowcytometry). The positive-positive group (PP n = 45; F = 18/ M = 27; median age = 62.33), comprised individuals affected by COVID-19 who showed fever, dyspnea (ABG = pO2 < 60), confirmed positive by oral-nasopharyngeal swab/RT-PCR and with CT-scan showing ground-glass opacities. The negative-positive (NP; n = 37; F = 11/M = 26; median age = 75.94) or "COVID-like" group comprised individuals with fever and dyspnea (ABG = pO2 < 60), who tested negative to nasopharyngeal swab/RT-PCR, with CT-scans showing ground-glass opacities in the lungs. The negative-affected group (NA; n = 40; F = 14/M = 26; median age = 58.5) included individuals negative to COVID-19 (RT-PCR) but affected by different chronic respiratory diseases (the CT-scans didn't show ground-glass opacities). Finally, the negative-negative group (NN; n = 16; F = 14/M = 2) included healthy patients (NN; n = 16; median age = 42.62). Data and findings were collected and compared. RESULTS: Lymphocytes (%) cells showed a decline in COVID-19 patients. The subsets showed a significant association with the inflammatory status in COVID-19, especially with regard to increased neutrophils, T-killer, T-active, T-suppressor, and T-CD8+CD38+ in individuals belong to the either COVID-19 and Covid-like NP group. CONCLUSIONS: Peripheral lymphocyte subset alteration was associated with the clinical characteristics and progression of COVID-19. The level of sub-set cells T-lymphocytes (either high or low) and B-lymphocytes could be used as an independent predictor for COVID-19 severity and treatment efficacy.

The Vitamin D, IL-6 and the eGFR Markers a Possible Way to Elucidate the Lung-Heart-Kidney Cross-Talk in COVID-19 Disease: A Foregone Conclusion.

BACKGROUND: Based on recent findings, we speculated the existence of the lung, heart, and kidney axis as the main pathway for the COVID-19 disease progression. METHODS: This paper reports on an observational study conducted by a team of researchers and doctors of the 118-Pre-Hospital and Emergency Department of SG Moscati of Taranto City in Italy. The study was conducted on a totality of 185 participants that were divided into three groups. The study group included COVID-19 affected patients (PP n = 80), the first control group included patients with different pathologies (non-COVID-19 NNp n = 62) of the SG Moscati Hospital, and the second control group included healthy individuals (NNh n = 43). The core of the current trial was focused on assessing the level of the vitamin D (serum 25(OH) D concentration), IL-6, and the renal glomerular filtrate (eGFR) in COVID-19 disease and non-COVID-19 patients in both groups. RESULTS: It was observed that the majority of COVID-19-infected patients showed a progressive multi-organ involvement, especially in regard to the lung, kidney, and heart. The majority of the COVID-19 patients exhibited preexisting comorbidities which include cardiovascular, respiratory, and renal disorders accompanied by a severely low level of vitamin D, extremely high level of IL-6, and low glomerular filtration rate (eGFR). The significant overall damages exerted by the immune-mediated responses under the hyper-expression of proinflammatory cytokines and interleukins, such as IL-6, may be facilitated by either a decreased level of vitamin D or the ageing process. The reduced presence of vitamin D was often found together with a reduced functionality of renal activity, as revealed by the low eGFR, and both were seen to be concomitant with an increased mortality risk in patients with lung disorders and heart failure (HF), whether it is showed at baseline or it develops during manifestation of COVID-19. Therefore, the documentation of the modifiable risk factors related to SARS-CoV-2 and lung impairment in older patients with kidney and heart disease may help the clinician to better manage the situation. CONCLUSIONS: This paper addresses how a low level of vitamin D and older age may be indicative of systemic worsening in patients with COVID-19, with a goal of providing a broader context in which to view a better therapeutic approach.

Sars-CoV-2 Virus Infection May Interfere CD34+ Hematopoietic Stem Cells and Megakaryocyte-Erythroid Progenitors Differentiation Contributing to Platelet Defection towards Insurgence of Thrombocytopenia and Thrombophilia.

To date, several cases of thrombosis have been confirmed to be related to Sars-CoV-2 infection. Multiple attempts detected the prolonged occurrence of Sars-CoV-2 viral RNA (long COVID) in whole blood suggesting that virus byproducts may remain within cells and tissues well over the disease has finished. Patients may develop severe thrombocytopenia, acute anemia of inflammation and, systemic thrombosis with the fatal course of disease, which is suggestive of further interferences of Sars-CoV-2 on hematopoietic stem cells (HSCs) within the differentiation process towards erythroid and megakaryocytic cells. Therefore, we speculated whether Sars-CoV-2 propagates in or compartmentalizes with hematopoietic progenitor, erythroid, and megakaryocytic cells as the main cause of thrombotic events in either COVID-19 patients or vaccinated individuals. Results: The Sars-CoV-2 RNA replication, protein translation and infectious particle formation as the spike proteins in hematopoietic cell lines take place via the angiotensin-converting enzyme 2 (ACE2) entry pathway within primary CD34+ HSCs inducing, ex vivo, the formation of defected erythroid and megakaryocytic cells that eventually become targets of humoral and adaptive immune cells. Conclusions: Viral particles from affected CD34+ HSCs or the cellular component of RBC units and eventually platelets, present the greatest risk for sever thrombosis-transmitted Sars-CoV-2 infections.

The 15-Months Clinical Experience of SARS-CoV-2: A Literature Review of Therapies and Adjuvants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19) that emerged in December 2019 in Wuhan, China, and rapidly spread worldwide, with a daily increase in confirmed cases and infection-related deaths. The World Health Organization declared a pandemic on the 11th of March 2020. COVID-19 presents flu-like symptoms that become severe in high-risk medically compromised subjects. The aim of this study was to perform an updated overview of the treatments and adjuvant protocols for COVID-19. METHODS: A systematic literature search of databases was performed (MEDLINE PubMed, Google Scholar, UpToDate, Embase, and Web of Science) using the keywords: "COVID-19", "2019-nCoV", "coronavirus" and "SARS-CoV-2" (date range: 1 January 2019 to 31st October 2020), focused on clinical features and treatments. RESULTS: The main treatments retrieved were antivirals, antimalarials, convalescent plasma, immunomodulators, corticosteroids, anticoagulants, and mesenchymal stem cells. Most of the described treatments may provide benefits to COVID-19 subjects, but no one protocol has definitively proven its efficacy. CONCLUSIONS: While many efforts are being spent worldwide in research aimed at identifying early diagnostic methods and evidence-based effective treatments, mass vaccination is thought to be the best option against this disease in the near future.

Toxic megacolon in ulcerative rectocolitis. Current trends in clinical evaluation, diagnosis and treatment.

Toxic megacolon is a clinical condition associated to high risk of colonic perforation, that significantly increases--even triplicates--the megacolon-related mortality when causing diffuse peritonitis. Abdominal and pelvic helical CT scan proved to be a fundamental diagnostic tool, in defining the colic dilatation and perforation. Conservative treatment is initially indicated in the event of toxic megacolon arising at the onset of a severe or toxic colitis. However it should be avoided when the toxic megacolon appears on corticosteroid therapy. Non operative management must not exceed 48 hours. The rationale of this strategy lies on the fact that early surgery is burdened by a mortality rate that, although moderate, is still higher than medical treatment. Nevertheless, successful conservative management does not exempt from surgery, which must be performed as soon as possible, in an elective setting, to prevent the recurrence of toxic megacolon. In emergency total colectomy and end ileostomy is the gold standard procedure. Bowel continuity will be restored, evaluating case by case, by performing an ileorectal anastomosis or proctectomy and ileoanal pouch anastomosis. Primary ileorectal anastomosis should be reserved to selected cases. In the elective setting, after proper therapy and regression of toxic megacolon, proctocolectomy and ileoanal pouch anastomosis is indicated.

Postsplenectomy type-1 hypersensitivity response: a correlation between IL-4 and IgE serum levels.

Authors demonstrated the presence of allergic manifestations in splenectomized patients following traumatic rupture of this organ. In particular, allergic diathesis, as supported by serum IgE increase, was exclusively found in patients with preserved T helper (h)-2 lymphocyte function. Th-2 function was monitored by measuring serum levels of interleukin (IL)-4, a cytokine involved in IgE synthesis. On the opposite, in splenectomized individuals with a reduced Th-2 function as supported by lower IL-4 serum levels, no IgE increase and allergic manifestations were detectable. On these grounds, authors hypothesize that allergic manifestations may be correlated to splenectomy since its exeresis may favor the persistence of antigens in the blood. Consequentially, in patients with a preserved Th-2 function, antigenic overload may lead to IgE increase and allergy onset.

[Conservative treatment of the splenic traumas]. / Trattamenti conservativi dei traumi splenici.

Authors hope for a growing diffusion of conservative treatments for lien's lesions, to avoid the asplenia syndrome, and the unfavourable implications derive from, above all immunodepression that increases septic risk. They report their experience about conservative choices for spleens traumatic injures and emphasize the absolute need of select the appropriate patients for those procedure, that must require: haemodynamics stability; not geriatric age; type I and II, according to Buntain's classifications, ien's lesions, and attentive selection of the patients carriers of type III lesions; absence of preceding spleens injures, opportunity of monitor patients, in immediate postoperative, in intensive care units. Authors suggest that one of the essential condition for the correct selection and achievement of conservative treatments of traumatic lien's injures, is the team work of the surgeon, of the anesthesiologist, of the radiologist. Conclude maintain that, conservative procedure for lien's lesions, must find a growing diffusion, but mention that is appropriate to not extend those treatments indications over the encoded ones.