Phosphodiesterases S-sulfhydration contributes to human skeletal muscle function.

The increase in intracellular calcium is influenced by cyclic nucleotides (cAMP and cGMP) content, which rating is governed by phosphodiesterases (PDEs) activity.Despite it has been demonstrated a beneficial effect of PDEs inhibitors in different pathological conditions involving SKM, not much is known on the role exerted by cAMP-cGMP/PDEs axis in human SKM contractility. Here, we show that Ssulfhydration of PDEs modulates human SKM contractility in physiological and pathological conditions. Having previously demonstrated that, in the rare human syndrome Malignant Hyperthermia (MH), there is an overproduction of hydrogen sulfide (H2S) within SKM contributing to hyper-contractility, here we have used MH negative diagnosed biopsies (MHN) as healthy SKM, and MH susceptible diagnosed biopsies (MHS) as a pathological model of SKM hypercontractility. The study has been performed on MHS and MHN human biopsies after diagnosis has been made and on primary SKM cells derived from both MHN and MHS biopsies. Our data demonstrate that in normal conditions PDEs are S-sulfhydrated in both quadriceps' biopsies and primary SKM cells. This post translational modification (PTM) negatively regulates PDEs activity with consequent increase of both cAMP and cGMP levels. In hypercontractile biopsies, due to an excessive H2S content, there is an enhanced Ssulfhydration of PDEs that further increases cyclic nucleotides levels contributing to SKM hyper-contractility. Thus, the identification of a new endogenous PTM modulating PDEs activity represents an advancement in SKM physiopathology understanding.

Cave canem: HBO2 therapy efficacy on Capnocytophaga canimorsus infections: a case series.

BACKGROUND: Dog bites are a frequent injury, but the incidence and type of lesions vary across countries. Although only few patients develop complications, the treatment of advanced injuries has a considerable medical, social and economic impact. A frequently isolated pathogen in dog bite wounds is Capnocytophaga canimorsus, a bacterium that can cause sepsis or meningitis. Hyperbaric oxygen (HBO2) therapy has been shown to be useful in treating anaerobic infections, most likely because it creates an inhospitable environment for the bacterium and enhances the patient's immune response. AIM: We present a case series of C. canimorsus infections treated with HBO2 in adjunction to antibiotic therapy. Furthermore, we tested the in vitro activity of ceftaroline against C. canimorsus, alone and in association with hyperbaric oxygen therapy. METHODS: We included nine (9) patients admitted to the surgery department of "A. Cardarelli" Hospital (Naples) after dog bite, from 2010 to 2016. All were initially treated with antibiotics and required transfer to the intensive care unit due to worsening conditions. C. canimorsus was isolated from wounds, and HBO2 therapy was administered in adjunction to antibiotics, until clinical improvement and microbiological test negativity. We tested the activity of hyperbaric oxygen therapy in adjunction to ceftaroline on cultured plates with C. canimorsus versus ceftaroline alone. Minimal inhibitory concentration was evaluated. CONCLUSIONS: Our findings confirm the utility of HBO2 therapy after biting injuries. Indeed, increased oxygen supply to the wound (as well as in vitro) may be toxic for bacteria, can improve healing and may improve the effectiveness of antibiotics.

Serratus anterior plane block and postoperative pain control in obese patients undergoing S-ICD implantation: A case series and literature analysis.

We report five case series of obese patients with severe left ventricular ejection fraction impairment undergoing Serratus Anterior Plane Block during S-ICD Implantation. This anesthesia approach has a reduced impact on the patient's hemodynamics and adequately manages postprocedural pain. Abstract: Subcutaneous implantable cardioverter-defibrillator (S-ICD) procedures are frequently performed under analgosedation or general anesthesia, leading to prolonged postoperative hospital stays and increased costs. This anesthetic technique may also have a greater hemodynamic impact, particularly in obese and cardiac patients. However, an alternative anesthetic technique can be employed: ultrasound-guided serratus anterior plane block (US-SAPB). We analyzed the anesthetic clinical course in 5 patients, 3 males and 2 females, who were obese (BMI ≥ 30) and underwent S-ICD implantation for primary prevention using a two-incision intermuscular technique and ultrasound-guided serratus anterior plane block. All patients had a left ventricular ejection fraction less than or equal to 35%. It significantly facilitated pain control during the procedure and, especially, in the postoperative phase. However, the data available in the literature are mostly derived from case reports and small comparative studies. Therefore, further studies with a larger sample size and direct comparison with general anesthesia or deep sedation are needed.

Chronic Pelvic Pain in Congestion Pelvic Syndrome: Clinical Impact and Electromyography Pelvic Floor Activity Prior to and after Endovascular Treatment.

BACKGROUND: This study aims to characterize the clinical impact of endovascular treatment in Chronic Pelvic Pain (CPP) patients due to Pelvic Congestion Syndrome (PCS) and to assess the diagnostic value of surface electromyography (sEMG) studies of pelvic floor musculature (PFM) in PCS patients pre- and post-endovascular treatment. Between January 2019 and July 2023, we studied consecutive patients who were referred for interventional radiology assessment and treatment to a tertiary trauma care hospital, had evidence of non-obstructive PCS from Magnetic Resonance Imaging (MRI), had sEMG of PFM and who had undergone endovascular treatment. The primary outcome was clinical, defined as a change in symptom severity after endovascular treatment. The secondary outcome was a difference in the sEMG values pre- and post-endovascular therapy. RESULTS: We included 32 women (mean age 38 years). CPP was the leading symptom in 100% patients, followed by dysmenorrhea (75%) and post-coital pain (68.7%). Endovascular therapy included ovarian vein embolization in 28 patients (87.5%) and internal iliac vein embolization in only 2 patients (6.2%). After a median of 8 (range 6-10) months from endovascular treatment, 29 (90%) of patients reported an improvement of the main symptoms, and 15 (46%) were symptom-free. The sEMG values did not show a statistical difference pre- and post-PCS endovascular treatment. CONCLUSIONS: Endovascular treatment appeared to be highly effective in CPP due to PCS and was associated with a low rate of complication. sEMG study could be useful in revealing alterations of PFM electrophysiology, but a difference pre- and post-embolization in PCS patients was not demonstrated.

Efficacy and Adverse Effects of IV Morphine for Burn Pain Management in the Emergency Department: An Observational Study.

INTRODUCTION: The management of pain following a burn is extremely complex because of the multifactorial nature of burn pain (nociceptive and neuropathic). In the pre-hospital setting and emergency department (ED), the main goal of acute pain management is to reduce the patient's pain, allowing them to maintain function and to prevent the chronification of pain. Opioids are used as first-line treatment in management of burn pain. The aim of our study was to evaluate the efficacy and adverse effects of intravenous (IV) morphine for burn pain management in the ED and to evaluate pain management in the pre-hospital setting. METHODS: In this single-center observational study, patients presenting with second- and third-degree burns were enrolled in our ED. Numerical Rating Scale (NRS) and Burn Specific Pain Anxiety Scale (BSPAS) were performed at ED admission and after 1 h. Pain medications administered before arrival in the ED were reported by the rescue team. All patients received IV acetaminophen every 8 h and IV morphine according NRS. RESULTS: Thirty patients were included in this study. At the time of arrival to the ED, > 90% of the patients reported severe pain; 95.8% of them received IV morphine to achieve pain relief. After 1 h, > 65% of patients had NRS < 3. The total amount of IV morphine was 18.12 ± 4.26 mg in the first hour. No adverse events were recorded. The BSPAS on admission to the ED was 34.8 ± 5.6, indicating severe anxiety. After 1 h, BSPAS was 12.8 ± 4.8, indicating mild anxiety. CONCLUSION: IV morphine used for burn pain management in the emergency setting significantly improves patient outcomes in terms of pain. IV morphine also reduced anxiety scores at 1 h.

The management of pain following a burn is extremely complex because of the multifactorial nature of burn pain. The main goal of acute pain management is to reduce the patient's pain, allowing them to maintain function and to prevent the chronification of pain. Opioids are used as first-line treatment in management of burn pain. In this single-center observational study, patients presenting with severe burns were enrolled in our hospital. Pain intensity and anxiety level were evaluated at admission and after 1 h. We evaluated pain treatment using intravenous (IV) morphine. Thirty patients were included in this study. At the time of arrival in hospital, almost all patients reported severe pain and received IV morphine to achieve pain relief. After 1 h, > 65% of patients had no pain. No adverse events were recorded related to morphine administration. The anxiety level improved after pain treatment. Finally, IV morphine used for burn pain management in the emergency setting significantly improves patient outcomes in terms of pain and reduced agitation.

Enzymatic Debridement in Severe Burn COVID-19 Patients: A Case Series.

The presence of a high number of positive SARS-CoV-2 patients is found daily in the emergency room database, finding evidence of infection also in trauma and burns. Surgical debridement remains the gold standard for eschar removal, but it does not come without complications such as bleeding and high heat loss. In recent years, there has been an increase in the use of enzymatic debridement techniques, replacing surgical escharotomy. Early eschar removal is proven to be important; it has been proved that an early and effective burn treatment in COVID-19 patients can reduce other infection. Five clinical cases of patients arrived at our COVID-19 Major Burns Intensive Care Unit. On admission, burns extension and depth were assessed by an expert burn surgeon. We evaluated eschar removal modality, adverse events, and potential side effects. Enzymatic debridement was efficient in all patients treated with complete eschar removal, and no serious adverse events. All patients were treated within 24 hours of arrival at our facility with Nexobrid by specialized personnel in deep sedation and with O2 support using a face mask or nasal goggles. The use of enzymatic debridement in COVID-19-positive burn patients within dedicated pathways through nonsurgical treatment optimizes the treatment time. We believe that the use of enzymatic debridement could be a valid therapeutic option in burn patients, even with SARS-CoV-2 infection, and its use, when indicated, is safe and effective for the patient and optimizes the use of instrumental and human resources in a pandemic emergency.

Non invasive hemodynamic monitoring for fluids and blood resuscitation during placenta praevia accreta cesarean delivery: a retrospective observational study.

BACKGROUND: We carry out a retrospective observational analysis of clinical records of patients with major placenta praevia who underwent cesarean section surgery over a period of 20 months in our hospital. Out of a total of 40 patients, 20 were subjected to Goal-Directed Therapy (GDT) implemented with non-invasive hemodynamic monitoring using the EV1000 ClearSight system (Group I) and 20 to standard hemodynamic monitoring (Group II). Given the risk of conspicuous blood loss, this study evaluate the impact on maternal and fetal health of GDT relative to standard hemodynamic monitoring. RESULTS: Average total infusion of fluids was 1600 +/- 350 ml. Use of blood products occurred in 29 patients (72,5%), of which 11 had a hysterectomy and 8 were treated with Bakri Balloons. For 2 patients > 1000 mL of concentrated red blood cells were used. When stroke volume index SVI dropped below 35 mL/m2/beat, it responded well to the infusion of at least 2 crystalloid boluses (5 ml/kg) in 7 patients. Cardiac index (CI) increased in 8 patients in concomitance with a reduction in medium arterial pressure (MAP), but the use of ephedrine (10 mg iv) re-established acceptable baseline values. Group I means are higher than Group II means for MAP, lower for RBC usage, end-of-surgery maternal lactates and fetal pH, and for LOS. Statistical analysis determines that the null hypotheses of equalities between Groups I and II can be rejected for all measures apart from MAP at baseline and induction. Proportions of serious complications in Groups I and II are respectively 10% and 32% and Boschloo's test rejects the null of equality of proportions against the alternative hypothesis of lower proportion of occurrence in Group I than in Group II. CONCLUSIONS: Hypovolemia can lead to vasoconstriction and inadequate perfusion with decreased oxygen delivery to organs and peripheral tissues and ultimately cause organ dysfunction. Despite the small sample size due to the rarity of the pathology, our statistical analysis finds evidence in favor of more favorable clinical outcomes for patients who received GDT implemented with non-invasive hemodynamic monitoring infusion relative to patients who received standard hemodynamic monitoring.

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19.

The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex, and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five single nucleotide polymorphisms (SNPs) correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target.

SARS-CoV-2 in Urine May Predict a Severe Evolution of COVID-19.

We hypothesized that the spread of SARS-CoV-2 in urine during a severe COVID-19 infection may be the expression of the worsening disease evolution. Therefore, the aim of this study was to verify if the COVID-19 disease severity is related to the viral presence in urine samples. We evaluated the clinical evolution in acute COVID-19 patients admitted in the sub-intensive care and intensive care units between 28 of December 2020 and 15th of February 2021 and being positive for SARS-CoV-2 RNA in the respiratory tract, including repeated endotracheal aspirates (ETA), sputum, nasopharyngeal swabs (NPS) and urine. We found that those subjects with SARS-COV-2 in the urine at admittance (8 out of 60 eligible patients) had a more severe disease than those with negative SARS-CoV-2 in urine. Further, they showed an increase in fibrinogen and (C-reactive Protein) CRP serum levels, requiring mechanic ventilation. Of those with positive SARS-CoV-2 in the urine, 50% died. According to our preliminary results, it seems that the presence of SARS-CoV-2 in the urine characterizes patients with a more severe disease and is also related to a higher death rate.

Releasing Burn-Induced Compartment Syndrome by Enzymatic Escharotomy-Debridement: A Case Study.

Burn-induced compartment syndrome represents a serious and acute condition in deep circumferential burns of the extremities which, if left untreated, can cause severe complications. The surgical escharotomy that releases the high subdermal pressure is the therapeutic treatment of choice for burn-induced compartment syndrome. Guidelines for escharotomy indications and timing include pressure greater than 30 mm Hg and 6 Ps (Pain, Pallor, Paresthesia, Paralysis, Pulseless, and Poikilothermia). Nevertheless, despite the need for an early as possible pressure release, escharotomy is often delayed when a capable surgeon is not available, or if the indication is not completely clear to justify potential risks associated with surgical escharotomy. Early treatment of circumferential burns of the extremities with a Bromelain-based enzymatic agent NexoBrid® may represent a less traumatic and invasive procedure to reduce intra-compartmental pressure, replacing surgical escharotomy. This case study of 23 patients describes the variation of compartmental pressure in patients with circumferential burns of the extremities treated with NexoBrid® enzymatic escharotomy-debridement. All the patients were treated with NexoBrid® within 2 to 22 hours post-injury in our Burn Intensive Care Center. The excessive pressure recorded before treatment returned to normal below 30 mm Hg and an approximately 60% reduction of the compartmental pressure was observed in most cases within 1 hour from NXB application. On NexoBrid® removal after 4 hours complete debridement-escharotomy of the burns was achieved. Enzymatic escharotomy-debridement appears to be a useful and safe method to reduce postburn compartmental pressure. Additional randomized, well-controlled powered studies are needed to further support these results.