Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis.

Palmitoylethanolamide (PEA) emerged over the years as a promising approach in the management of chronic pain. Despite the fact that the efficacy of micron-size PEA formulations appears to be time-dependent, the optimal timing has not yet been elucidated. This systematic review and meta-analysis aim to estimate the possible advantage of an extended treatment in the relief of chronic pain. The literature search was conducted consulting scientific databases, to identify clinical trials in which micron-size PEA was administered for at least 60 days, and pain assessed by the Visual Analogue Scale (VAS) or Numeric Rating Scale (NRS). Nine studies matched the required criteria, for a total of 742 patients involved. The meta-analysis showed a statistically and clinically significant pain intensity reduction after 60 days of micron-size PEA supplementation, compared to 30 days (1.36 points, p < 0.01). The secondary analysis revealed a weighted NRS/VAS score decrease of 2.08 points within the first month of treatment. These two obtained scores corresponded to a 35.1% pain intensity reduction within the first month, followed by a further 35.4% during the second month. Overall, these results confirm the clinically relevant and time-depended pain-relieving effect of micron-size PEA and therefore the advantage of an extended treatment, especially in patient with incomplete pain management.

Prevalence of FMS Diagnosis According to ACR 2016 Revised Criteria in a Pain Therapy Centre in Italy: Observational Study.

Background and Objectives: Fibromyalgia syndrome (FMS) is a multifaceted disease with a strong preference for the female sex. It is characterised by chronic widespread pain, sleep-wake disorders, fatigue, cognitive disturbances, and several other somatic symptoms. Materials and Methods: In this prospective observational study, we analysed data regarding 302 patients who were referred to our pain centre for a first clinical assessment evaluation and were then inspected for the physician-based 2016 revision of the ACR diagnostic criteria for FMS, regardless of the final diagnosis previously made by the pain therapist. Results: Among the 280 patients who adhered to the 2016 ACR questionnaire, 20.3% displayed positive criteria for FMS diagnosis. The level of agreement between the FMS discharge diagnosis made by the pain clinician and the ACR 2016 criteria-positivity was moderate (kappa = 0.599, with moderate agreement set at a kappa value of 0.6). Only four patients (1.7%) diagnosed as suffering from FMS at discharge did not satisfy the minimal 2016 ACR diagnostic criteria. Conclusions: This prospective observational study confirmed the diagnostic challenge with FMS, as demonstrated by the moderate grade of agreement between the FMS diagnosis at discharge and the positivity for 2016 ACR criteria. In our opinion, the use of widely accepted diagnostic guidelines should be implemented in clinical scenarios and should become a common language among clinicians who evaluate and treat patients reporting widespread pain and FMS-suggestive symptoms. Further methodologically stronger studies will be necessary to validate our observation.

Anti-CGRP and Anti-CGRP Receptor Monoclonal Antibodies for Migraine Prophylaxis: Retrospective Observational Study on 209 Patients.

BACKGROUND: Migraine is a neurological disorder characterized by attacks of head pain with prevalent unilateral localization, moderate to high intensity and specifically associated accompanying symptoms. METHODS: In this retrospective observational study, we analyzed data regarding 209 patients who had previously been diagnosed with migraine and who were prescribed, between 2019 and 2022, subcutaneous injections of anti-CGRP monoclonal antibodies (mAbs) fremanezumab or galcanezumab or anti-CGRP receptors mAb erenumab regardless of the concomitant assumption of any other acute-phase or prophylactic migraine medication. RESULTS: Regarding efficacy, in the 205 analyzed patients, the change from baseline in terms of MIDAS, HIT-6, MMDs and MAD scores was statistically significant for erenumab and galcanezumab, while for fremanezumab a statistical significance was not achieved likely due to the small sample size. In the treated population, 36 patients (17.5%) reported AEs (pain during injection, transient injection site erythema, nausea, constipation and fatigue). Only 5 patients (2.4%) discontinued the treatment for AEs while 15 patients (7.3%) left for lack of efficacy. CONCLUSIONS: this retrospective study comes out in favor of both significant efficacy and safety of anti-CGRP and anti-CGRP receptors mAbs in migraine patients. Further methodologically stronger studies are necessary to validate our observation.

Major vessel resection for complete cytoreduction in primary advanced and recurrent ovarian malignancies: A case series and systematic review of the literature - pushing the boundaries in oncovascular surgery.

INTRODUCTION: Oncovascular surgery (the removal of major blood vessels infiltrated by cancer) is challenging but can be key to achieve complete cytoreduction in patient with advanced ovarian cancer. The aim of this study was to review the literature on oncovascular surgery in ovarian cancer and to report the details of all the cases performed at our institution. METHODS: We retrospectively reviewed the database of ovarian cancer patients who underwent debulking surgery at the Department of Obstetrics and Gynecology of Verona University between January 2021 and 2023. Patients with at least one major vessel resection during cytoreduction were identified. We then systematically review the literature searching Pubmed and Embase from inception to January 2023 to report all cases of surgery for ovarian cancer with concomitant major vessel resection. RESULTS: Five patients with advanced/recurrent ovarian cancer underwent major vascular resection at our institution. Vascular involvement was preoperatively identified in all cases and no case of vascular resection was performed after accidental injury. The major vessels removed were the inferior vena cava (n = 2), the common iliac veins (n = 2), the external iliac arteries (n = 2), the left common iliac artery (n = 1), and the left external iliac vein (n = 1). All patients underwent other non-gynecological cytoreductive procedures prior to vessel removal and had R0 obtained. Three (60%) patients experienced one or more postoperative complications. The literature search identified a total of seven cases of major vessels resection in ovarian cancer surgery. A single or multiple major vessels were removed in two (28.6%) and five (72.4%) cases, respectively. All the seven patients underwent vascular reconstruction. Four (57.1%) patients reported postoperative complications. Overall, 66.7% of the 12 total identified patients were free from disease at the last follow-up [median 15.5 months (range 5-25)]. CONCLUSIONS: Oncovascular surgery is feasible in selected patients with ovarian cancer, provided that a multidisciplinary approach with customized care is available.

Challenges in diagnosis and treatment of multiple atypical parathyroid tumors in a patient with extrapyramidal symptoms: case report and literature review.

Background: Atypical parathyroid tumors (APTs) are rare entities. We report the case of a patient with multiple APT presenting with extrapyramidal symptoms and a delayed hypercalcemic crisis. Case Description: A 72-year-old man presented to a tertiary referral center's emergency room (ER) following two episodes of temporary loss of consciousness. He had a history of ideomotor sluggishness, lethargy, extrapyramidal symptoms and dysphagia, which started 6 months prior. Serum calcium levels at presentation were normal. Four days later the patient developed a rapidly evolving respiratory failure requiring orotracheal intubation, severe hypercalcemia (up to 19.8 mg/dL) and increased serum parathyroid hormone (PTH) (151 pmol/L). A neck ultrasound (US) showed two lesions posteroinferiorly to the right and left thyroid lobe. Since hypercalcemia proved to be refractory to medical therapy, the patient underwent urgent bilateral neck exploration with subtotal parathyroidectomy for suspect parathyroid carcinoma (PC). Histopathological examination showed three nodular lesions consistent with a diagnosis of APT in each excised parathyroid. Four months after surgery, the patient is alive and well with no signs of recurrence. Neurological follow-up visits documented the absence of extrapyramidal signs. Conclusions: Our patient showed an unusual presentation of primary hyperparathyroidism (PHPT) sustained by multiple concurrent APTs. A low suspicion threshold should be maintained to avoid delay in diagnosis. The present case adds to the body of literature on APTs, contributing to a greater understanding of this rare disease.

Analysis of P(v-a)CO2/C(a-v)O2 Ratio and Other Perfusion Markers in a Population of 98 Pediatric Patients Undergoing Cardiac Surgery.

BACKGROUND: The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO2) are the most commonly used perfusion markers, but they are not completely reliable in identifying a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO2/C(a-v)O2] can be a good index to predict the development of LCOS in the aforementioned patients, so as to treat it promptly. METHODS: This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Integrated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analyses were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to the intensive care unit, before and after extubation, and at any time of instability or modification of the patient's clinical and therapeutic conditions. RESULTS: The data analysis shows that 46.9% of the children developed LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO2/C(a-v)O2 ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. CONCLUSIONS: This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO2, and oxygen extraction ratio-ERO2) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with hemodynamic instability before surgery.

Postoperative pulmonary complications and mortality after major abdominal surgery. An observational multicenter prospective study.

BACKGROUND: Postoperative pulmonary complications (PPCs) significantly contribute to postoperative morbidity and mortality. We conducted a study to determine the incidence of PPCs after major elective abdominal surgery and their association with early and 1-year mortality in patient without pre-existing respiratory disease. METHODS: We conducted a multicenter observational prospective clinical study in 40 Italian centers. 1542 patients undergoing elective major abdominal surgery were recruited in a time period of 14 days and clinically managed according to local protocol. The primary outcome was to determine the incidence of PPCs. Further, we aimed to identify independent predictors for PPCs and examine the association between PPCs and mortality. RESULTS: PPCs occurred in 12.6% (95% CI 11.1-14.4%) of patients with significant differences among general (18.3%, 95% CI 15.7-21.0%), gynecological (3.7%, 95% CI 2.1-6.0%) and urological surgery (9.0%, 95% CI 6.0-12.8%). PPCs development was associated with known pre- and intraoperative risk factors. Patients who developed PPCs had longer length of hospital stay, higher risk of 30-days hospital readmission, and increased in-hospital and one-year mortality (OR 3.078, 95% CI 1.825-5.191; P<0.001). CONCLUSIONS: The incidence of PPCs in patients without pre-existing respiratory disease undergoing elective abdominal surgery is high and associated with worse clinical outcome at one year after surgery. General surgery is associated with higher incidence of PPCs and mortality compared to gynecological and urological surgery.

Changes in emergency psychiatric consultations in time of COVID-19: a retrospective observational study in the Verona Academic Hospital over the two pandemic years 2020-2021.

BACKGROUND: During the first months of the COVID-19 pandemic, local health authorities in most Italian regions prescribed a reduction of ordinary outpatient and community mental health care. The aim of this study was to assess the impact of the COVID-19 pandemic on access to the emergency departments (ED) for psychiatric consultation in the pandemic years 2020 and 2021 compared to 2019. METHODS: This is a retrospective study conducted by using routinely collected administrative data of the two EDs of the Verona Academic Hospital Trust (Verona, Italy). All ED psychiatry consultations registered from 01.01.2020 to 31.12.2021 were compared with those registered in the pre-pandemic year (01.01.2019 to 31.12.2019). The association between each recorded characteristic and the year considered was estimated by chi-square or Fisher's exact test. RESULTS: A significant reduction was observed between 2020 and 2019 (-23.3%) and between 2021 and 2019 (-16.3%). This reduction was most evident in the lockdown period of 2020 (-40.3%) and in the phase corresponding to the second and third pandemic waves (-36.1%). In 2021, young adults and people with diagnosis of psychosis showed an increase in requests for psychiatric consultation. CONCLUSIONS: Fear of contagion may have been an important factor in the overall reduction in psychiatric consultations. However, psychiatric consultations for people with psychosis and for young adults increased. This finding underlines the need for mental health services to implement alternative outreach strategies aimed to support, in times of crisis, these vulnerable segments of the population.

American Society of Anesthesiologists (ASA) physical status system predicts the risk of postoperative Clavien-Dindo complications greater than one at 90 days after robot-assisted radical prostatectomy: final results of a tertiary referral center.

To test the hypothesis of an association between the American Society of Anesthesiologists (ASA) physical status classification system and the risk of 90-days postoperative complications after robot-assisted radical prostatectomy (RARP), graded using the Clavien-Dindo classification system (CDS). In a period ranging from January 2013 to October 2020, 1143 patients were evaluated. ASA classification was computed by trained anesthesiologists. Postoperative complications at 90 days after RARP were grouped as greater than one (CDS between 2 and 4a) versus up to one (CDS between 0 and 1). The risk association was computed using logistic regression models. According to ASA physical status classification system, patients were distributed as follows: 102 (8.9%) ASA 1, 934 (81.7%) ASA 2, and 107 (9.4%) ASA 3. Overall, 90-days postoperative complications occurred in 277 (24.2%) cases, of which 137 (12%) were graded as CDS 1 vs. 105 (9.2%) CDS 2 vs. 17 (1.5%) CDS 3a vs. 15 (1.3%) CDS 3b vs. 3 (0.3%) CDS 4a. ASA 2 and 3 patient categories were more likely to have 90-days postoperative complications CDS > 1 (12.5% and 16.8%, respectively) compared to ASA 1 patients (4.9%). The risk association was stronger for ASA 3 (odds ratio, [OR]: 4.085; 95%CI: 1.457-11.455; p = 0.007) than for ASA 2 (OR: 2.907; 95%CI: 1.106-7.285; p = 0.023) patient categories. After adjustment for clinical, pathological, and perioperative covariates, including pelvic lymph node dissection (performed vs. not performed), either ASA 2 or 3 categories remained independent predictors of 90-days postoperative complications CDS > 1. The risk of 90-days postoperative complications CDS > 1 after RARP increased as the ASA physical status deteriorated independently by performing or not an extended pelvic lymph node dissection. In the ASA 3 patients category, RARP should be performed at tertiary referral centers to safely manage the risk of postoperative complications.

Epicardial adipose tissue volume and CT-attenuation as prognostic factors for pulmonary embolism and mortality in critically ill patients affected by COVID-19.

BACKGROUND/OBJECTIVES: The aim of this post-hoc analysis was to evaluate if epicardial adipose tissue (EAT) quantity and quality, as evaluated by computed tomography (CT), have a different role in the risk of mortality and pulmonary embolism in critically ill COVID-19 patients admitted to an intensive care unit (ICU). SUBJECTS/METHODS: CT derived EAT volume and density, as well as anthropometric and blood biomarkers, were evaluated in a sample of 138 subjects, 109 men and 29 women, for whom CT images and information on pulmonary embolism were available from a total of 313 subjects who were consecutively admitted to the ICU for COVID-19 from the REINSURE-ARDS prospective registry. RESULTS: A total of 28 patients (20.3%) died during the first 28 days after ICU admission. 26 subjects out of 138 had pulmonary embolism (18.8%). Age, weight, BMI, IL-6 levels and pulmonary embolism prevalence were significantly higher across EAT volume tertiles. Subjects who died in the first 28 days from ICU admission were older, had higher EAT volume, D-dimer, LDH and IL-6 level. After adjustment for age and gender, participants in tertile 3 of EAT volume had lower survival at 28 days from ICU admission as compared to subjects in the tertile 1, HR 2.95 (95% C.I. 1.02-8.49), but after adjusting for potential confounders the relation was no longer significant. No relation between EAT density and mortality was observed. From a binary logistic regression, subjects in tertile 3 of EAT volume and in tertile 1 of EAT density showed a 4 times and 3.6 times increased risk of pulmonary embolism, respectively. CONCLUSIONS: ICU subjects affected by severe COVID-19 with higher EAT volume and low EAT density should be carefully monitored and managed with a prompt and aggressive approach, to prevent serious and life-threatening consequences and the increase of hospital treatment costs.

Bipolar Spectrum Symptoms in Patients with Fibromyalgia: A Dimensional Psychometric Evaluation of 120 Patients.

BACKGROUND: Fibromyalgia Syndrome (FMS) is characterized by chronic widespread pain, fatigue, unrefreshing sleep and cognitive dysfunction. Depressive and manic symptoms are often reported in FMS patients' history. The aim of this study was to evaluate the prevalence of bipolar spectrum symptoms (BSS) and to correlate these with quality of life (QoL) scores and antidepressant treatment. METHODS: From October 2017 to July 2018, a battery of QoL questionnaires (FIQ, PSQI and SF-12) was administered to 120 FMS patients after a clinical examination. The MOODS-SR lifetime questionnaire was then remotely administered to the patients included in the study. RESULTS: The presence of depressive and manic lifetime symptoms was found, in line with the results of the available literature. A correlation was found between the history of depressive symptoms and the severity of FIQ and SF-12 scores. Despite a low statistical strength, a trend toward a correlation between a history of manic symptoms and SNRI treatment was detected. CONCLUSIONS: The correlation between the MOOD-depressive domains and poor QoL is in line with the available literature. Further studies are needed to corroborate these findings and to elucidate the relationship between manic symptoms and SNRI treatment.

The Effects of Temperature Management on Brain Microcirculation, Oxygenation and Metabolism.

PURPOSE: Target temperature management (TTM) is often used in patients after cardiac arrest, but the effects of cooling on cerebral microcirculation, oxygenation and metabolism are poorly understood. We studied the time course of these variables in a healthy swine model. METHODS: Fifteen invasively monitored, mechanically ventilated pigs were allocated to sham procedure (normothermia, NT; n = 5), cooling (hypothermia, HT, n = 5) or cooling with controlled oxygenation (HT-Oxy, n = 5). Cooling was induced by cold intravenous saline infusion, ice packs and nasal cooling to achieve a body temperature of 33-35 °C. After 6 h, animals were rewarmed to baseline temperature (within 5 h). The cerebral microvascular network was evaluated (at baseline and 2, 7 and 12 h thereafter) using sidestream dark-field (SDF) video-microscopy. Cerebral blood flow (laser Doppler MNP100XP, Oxyflow, Oxford Optronix, Oxford, UK), oxygenation (PbtO2, Licox catheter, Integra Lifesciences, USA) and lactate/pyruvate ratio (LPR) using brain microdialysis (CMA, Stockholm, Sweden) were measured hourly. RESULTS: In HT animals, cerebral functional capillary density (FCD) and proportion of small-perfused vessels (PSPV) significantly decreased over time during the cooling phase; concomitantly, PbtO2 increased and LPR decreased. After rewarming, all microcirculatory variables returned to normal values, except LPR, which increased during the rewarming phase in the two groups subjected to HT when compared to the group maintained at normothermia. CONCLUSIONS: In healthy animals, TTM can be associated with alterations in cerebral microcirculation during cooling and altered metabolism at rewarming.

Oxycodone-Naloxone Combination Hinders Opioid Consumption in Osteoarthritic Chronic Low Back Pain: A Retrospective Study with Two Years of Follow-Up.

Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release (27 patients, OXN patients) or Oxycodone Controlled Release (26 patients, OXY patients). The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction.

Persistent Idiopathic Facial Pain (PIFP) in Patients Referred to a Multidisciplinary Centre in Italy: A Retrospective Observational Study.

BACKGROUND: Persistent Idiopathic Facial Pain (PIFP), previously named Atypical Facial Pain (AFP) is a poorly understood condition, often diagnosed after several inconclusive investigations. The aim of this retrospective study was to evaluate the demographic and clinical characteristics of patients with PIFP referred to a Facial Pain Center. METHODS: Between May 2011 and September 2014, data on 41 PIFP patients were analyzed regarding temporal, topographical and descriptive pain features, including onset, localization, pain descriptors and intensity. Pharmacological pain treatments were also registered. Finally, the presence and type of previous minor oro-surgery procedures in the painful area were investigated. RESULTS: Demographic and clinical characterization were similar to PIFP patients reported in literature. The presence of previous minor oro-surgery procedures in the painful area was reported in most of these patients, in particular endodontic treatments and tooth extractions. CONCLUSIONS: This retrospective analysis showed a high prevalence of minor oro-surgery procedures in our population, while its role in PIFP pathophysiology remains unknown. A new classification of PIFP built around the main discriminant factor of presence of these procedures in the painful area could be considered while available data were still insufficient to define specific diagnostic criteria.

Severe systemic disease of the American Society of Anesthesiologists' (ASA) physical status system classification associated with delayed length of hospital stay in 1329 consecutive patients treated with radical prostatectomy for clinical prostate cancer.

BACKGROUND: The investigate the associations of the ASA physical status system with clinical, pathological, and perioperative features of prostate cancer (PCa) patients treated with radical prostatectomy (RP) that eventually associated with pelvic lymph node dissection (PLND). METHODS: We performed a retrospective analysis of prospective collected data from January 2013 to October 2020, including1329 patients. The ASA system was preoperatively assessed for each patient. Evaluated clinical factors were grouped as preoperative, perioperative, and pathological and were statistically associated with the ASA system. Continuous variables were represented as medians with relative interquartile ranges (IQR) and categorical factors were assessed as frequencies (percentages). Associations and risk of each ASA Class with population features were assessed by the multinomial logistic regression model (univariate and multivariate analysis). All tests were two-sided with P<0.05 considered to indicate statistical significance. RESULTS: Postoperative complications at discharge occurred in 27.2%. The distribution of the ASA physical status system was as follows: ASA I 108 patients (8.1%), ASA II 1081 subjects (81.3%) and ASA III 140 cases (10.5%). Median length of hospital state (LOHS) was the same for ASA groups I and II (4 days), but longer (5 days) for the ASA group III. On MVA, the risk of delayed hospital stay was associated only with ASA III patients and was independent from age and BMI. Clavien-Dindo complications greater than 2 did not show any independent association with the ASA system. CONCLUSIONS: The ASA preoperative physical status system predicted the likelihood of longer LOHS.

Bioethics in an oncological surgery unit during the COVID-19 pandemic: the Verona experience.

The spread of COVID-19 has overwhelmed medical facilities across the globe, with patients filling beds in both regular wards and in intensive care units. The repurposing of hospital facilities has resulted in a dramatic decrease in the capacity of hospitals-in terms of available beds, surgical facilities, and medical and nursing staff- to care for oncology patients. The Italian National Board of Bioethics provided precise and homogeneous guidelines for the allocation of the scarce resources available. In our experience, strictly following these general guidelines and not considering the clinical vocation of each single health care center did not allow us to resume usual activities but generated further confusion in resource allocation. To face the scarcity of available resources and guarantee our patients fair access to the health care system we created a surgical triage with four fundamental steps. We took into consideration " well defined and widely accepted clinical prognostic factors " as stated by the Italian Society of Anesthesia and Resuscitation. We were able to draw up a list of patients giving priority to those who theoretically should have a greater chance of overcoming their critical situation. The age criterion has also been used in the overall evaluation of different cure options in each case, but it has never been considered on its own or outside the other clinical parameters. Although not considered acceptable by many we had to forcefully adopt the criterion of comparison between patients to give priority to those most in need of immediate care.

Early Lung Ultrasound Findings in Patients With COVID-19 Pneumonia: A Retrospective Multicenter Study of 479 Patients.

OBJECTIVES: Lung ultrasound (LUS) holds the promise of an accurate, radiation-free, and affordable diagnostic and monitoring tool in coronavirus disease 2019 (COVID-19) pneumonia. We sought to evaluate the usefulness of LUS in the diagnosis of patients with respiratory distress and suspicion of interstitial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, in comparison to other imaging modalities. METHODS: This was a multicenter, retrospective study. LUS was performed, on Emergency Department (ED) arrival of patients presenting for possible COVID-19 evaluation, by trained emergency physicians, before undergoing conventional radiologic examination or while waiting for the report. Scans were performed using longitudinal transducer orientation of the lung regions. CXR was interpreted by radiologists staffing ED radiology. Subjects were divided into two group based on molecular test results. LUS findings were compared to COVID test results, nonlaboratory data, and other imaging for each patient. Categorical variables were expressed as percentages and continuous variables as median ± standard error. RESULTS: A total of 479 patients were enrolled, 87% diagnosed with SARS-CoV-2 by molecular testing. COVID positive and COVID negative patients differed with respect to sex, presence of fever, and white blood cells count. Most common findings on lung point of care ultrasound (POCUS) for COVID-positive patients were B-lines, irregular pleural lines, and small consolidation. Normal chest X-ray was found in 17.89% of cases. CONCLUSIONS: This 479 patient cohort, with COVID-19, found LUS to be noninferior to chest X-ray (CXR) for diagnostic accuracy. In this study, COVID-positive patients are most likely to show B lines and sub-pleural consolidations on LUS examination.

Fatal cytokine release syndrome by an aberrant FLIP/STAT3 axis.

Inflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune responses can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, a protein that controls caspase-8 death pathways, was highly expressed in myeloid cells of COVID-19 lungs. FLIP controlled CRS by fueling a STAT3-dependent inflammatory program. Indeed, constitutive expression of a viral FLIP homolog in myeloid cells triggered a STAT3-linked, progressive, and fatal inflammatory syndrome in mice, characterized by elevated cytokine output, lymphopenia, lung injury, and multiple organ dysfunctions that mimicked human CRS. As STAT3-targeting approaches relieved inflammation, immune disorders, and organ failures in these mice, targeted intervention towards this pathway could suppress the lethal CRS inflammatory state.

American Society of Anesthesiologists' (ASA) Physical Status System and Risk of Major Clavien-Dindo Complications After Robot-Assisted Radical Prostatectomy at Hospital Discharge: Analysis of 1143 Consecutive Prostate Cancer Patients.

Objective: To test the hypothesis of associations of preoperative physical status system with major postoperative complications at hospital discharge in prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). Materials and Methods: In a period ranging from January 2013 to October 2020, 1143 patients were evaluated. The physical status was assessed by the American Society of Anesthesiologists' (ASA) system, which was computed trained anesthesiologists. The Clavien-Dindo system was used to classify postoperative complications, which were coded as major if greater than 1. Results: ASA physical status system included class I in 102 patients (8.9%), class II in 934 subjects (81.7%), and class III in 107 cases (9.4%). Clavien-Dindo complications were distributed as follows: grade 1: 141 cases (12.3%), grade 2: 108 patients (9.4%), grade 3a: 5 subjects (0.4%), grade 3b: 9 patients (0.8%), and grade 4a: 3 cases (0.3%). Overall, major complications were detected in 125 cases (10.9%). On multivariate analysis, major Clavien-Dindo complications were predicted by ASA score grade II (adjusted odds ratio, OR = 2.538; 95%CI 1.007-6.397; p = 0.048) and grade III (adjusted OR 3.468; 95%CI 1.215-9.896; p = 0.020) independently by pelvic lymph node dissection (PLND) and/or blood lost. Conclusion: In RARP surgery, the risk of major postoperative Clavien-Dindo complications increased as the physical status system deteriorated independently by performing or not a PLND and/or large intraoperative blood lost. The ASA score system was an effective predictor of major Clavien-Dindo complications, which delayed LOHS in RARP surgery. Confirmatory studies are required. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01577-9.

Outcomes of COVID-19 patients intubated after failure of non-invasive ventilation: a multicenter observational study.

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06-4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04-1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.