How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Embolizing Papillary Fibroelastoma of the Mitral Valve

We report a case of myocardial infarction secondary to coronary embolization of a papillary fibroelastoma of the anterior mitral leaflet. The patient underwent successful operation. The English literature describes only 9 other surgically excised papillary fibroelastomas of the mitral valve. In 5 of these cases, the patient presented with signs of cerebral or coronary embolization. Our case further confirms that intracardiac papillary fibroelastomas pose a major threat of systemic embolization and that the clinician should be alert to the possibility of this condition, particularly in young patients who present with myocardial infarction or other conditions that could have arisen from systemic embolization. (Texas Heart Institute Journal 1991;18:62-6

Molecular characterization of extrahepatic cholangiocarcinoma: perihilar and distal tumours display divergent genomic and transcriptomic profiles

Background: Extrahepatic cholangiocarcinoma (ECC) is classified into two subtypes based on anatomic origin: distal extrahepatic (DECC) and perihilar (PHCC) cholangiocarcinoma. This study aimed to shed light on its genomic and transcriptomic profiles. Research design and methods: The genomic alterations of 99 ECC (47 PHCC and 52 DECC) were investigated by next-generation sequencing of 96 genes. A subgroup of cases, representative of each subtype, was further investigated using transcriptomic analysis. Bioinformatics tools were applied for clustering and pathway analysis and defining the immune composition of the tumor microenvironment. Results: PHCC had more frequent KRAS mutations (p=0.0047), whereas TP53 mutations were more common in DECC (p=0.006). Potentially actionable alterations included high-tumor mutational burden and/or microsatellite instability (7.1%), PI3KCA mutations (8.1%), and MYC (10.1%) and ERBB2 amplification (5.1%). The transcriptomic profiles showed the presence of three distinct clusters, which followed the anatomic origin and differed in the type of intra-tumor immune cells. DECC appeared to contain two distinct tumor subgroups, one enriched for druggable alterations and one lacking actionable opportunities. Conclusions: This study provides new insights into the molecular landscape and the actionable alterations of ECC. Our findings represent a step toward improved ECC molecular taxonomy and future therapeutic strategies for precision oncology

Reduced Annexin A1 Expression Associates with Disease Severity and Inflammation in Multiple Sclerosis Patients.

Chronic neuroinflammation is a key pathological hallmark of multiple sclerosis (MS) that suggests that resolution of inflammation by specialized proresolving molecules is dysregulated in the disease. Annexin A1 (ANXA1) is a protein induced by glucocorticoids that facilitates resolution of inflammation through several mechanisms that include an inhibition of leukocyte recruitment and activation. In this study, we investigated the ability of ANXA1 to influence T cell effector function in relapsing/remitting MS (RRMS), an autoimmune disease sustained by proinflammatory Th1/Th17 cells. Circulating expression levels of ANXA1 in naive-to-treatment RRMS subjects inversely correlated with disease score and progression. At the cellular level, there was an impaired ANXA1 production by CD4+CD25- conventional T and CD4+RORγt+ T (Th17) cells from RRMS subjects that associated with an increased migratory capacity in an in vitro model of blood brain barrier. Mechanistically, ANXA1 impaired monocyte maturation secondarily to STAT3 hyperactivation and potently reduced T cell activation, proliferation, and glycolysis. Together, these findings identify impaired disease resolution pathways in RRMS caused by dysregulated ANXA1 expression that could represent new potential therapeutic targets in RRMS

Reato colposo

Si tratta di un volume monografico-tematico sul "reato colposo" della nuova serie dell'enciclopedia del diritto

A prospective non-randomized controlled, multicenter trial comparing Appendectomy and Conservative Treatment for Patients with Uncomplicated Acute Appendicitis (the ACTUAA study)

Purpose: Acute appendicitis (AA) is among the most common causes of lower abdominal pain and admissions to the emergency department. Over the past 20 years, there has been a renewed interest in the conservative management of uncomplicated AA, and several studies demonstrated that an antibiotic-first strategy is a viable treatment option for uncomplicated AA. The aim of this prospective non-randomized controlled, multicenter trial is to compare antibiotic therapy and emergency appendectomy as treatment for patients with uncomplicated AA confirmed by US and/or CT or MRI scan. Methods: All adult patients in the age range 18 to 65 years with suspected AA, consecutively admitted to the Surgical Department of the 13 participating Italian Hospitals, will be invited to take part in the study. A multicenter prospective collected registry developed by surgeons, radiologists, and pathologists with expertise in the diagnosis and treatment of uncomplicated acute appendicitis represents the best research method to assess the long-term role of antibiotics in the management of the disease. Comparison will be made between surgical and antibiotic-first approaches to uncomplicated AA through the analysis of the primary outcome measure of complication-free treatment success rate based on 1-year follow-up. Quality of life, length of hospital stay, pain evaluation, and time to return to normal activity will be evaluated as secondary outcome measures. Trial registration: Clinicaltrials.gov ID: NCT03080103

Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry

Background: In 2010, the EUPHAS 2 collaborative group created a registry with the purpose of recording data from critically ill patients suffering from severe sepsis and septic shock treated with polymyxin-B hemoperfusion (PMX-HP) for endotoxin removal. The aim of the registry was to verify the application of PMX-HP in the daily clinical practice. Methods: The EUPHAS 2 registry involved 57 centers between January 2010 and December 2014, collecting retrospective data of 357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and septic shock caused by proved or suspected infection related to Gram negative bacteria. All patients received atleast one cycle of extracorporeal endotoxin removal by PMX-HP. Results: Septic shock was diagnosed in 305 (85.4 %) patients. The most common source of infection was abdominal (44.0 %) followed by pulmonary (17.6 %). Gram negative bacteria represented 60.6 % of the pathogens responsible of infection. After 72 h from the first cycle of PMX-HP, some of the SOFA score components significantly improved with respect to baseline: cardiovascular (2.16 \ub1 1.77 from 3.32 \ub1 1.29, p < 0.0001), respiratory (1.95 \ub1 0.95 from 2.40 \ub1 1.06, p < 0.001) and renal (1.84 \ub1 1.77 from 2.23 \ub1 1.62, p = 0.013). Overall 28-day survival rate was 54.5 % (60.4 % in abdominal and 47.5 % in pulmonary infection). Patients with abdominal infection treated with PMX-HP within 24 h from the diagnosis of septic shock had a 28-day survival rate of 64.5 %. Patients showing a significantly cardiovascular improvement after PMX-HP had a 28-survival rate of 75 % in comparison to the 39 % of patients who did not (p < 0.001). Cox regression analysis found the variation of cardiovascular, respiratory and coagulation SOFA to be independent covariates for 28-day survival. In European patients were observed a higher 28-day (58.8 vs. 34.5 %, p = 0.003), ICU (59 vs. 36.7 %, p = 0.006) and hospital survival rate (53.2 vs. 35 %, p = 0.02) than in Asian patients. However, the two populations were highly heterogeneous in terms of source of infection and severity scores at admission. Conclusion: The EUPHAS 2 is the largest registry conducted outside Japan on the clinical use of PMX-HP in septic patients. Data analysis confirmed the feasibility of PMX-HP to treat septic patients in daily clinical practice, showing clinical benefits associated with endotoxin removal without significant adverse events related to the extracorporeal technique

Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): a randomised, controlled, open-label, phase 3b trial

Background Treatment with natalizumab once every 4 weeks is approved for patients with relapsing-remitting multiple sclerosis, but is associated with a risk of progressive multifocal leukoencephalopathy. Switching to extended-interval dosing is associated with lower progressive multifocal leukoencephalopathy risk, but the efficacy of this approach is unclear. We aimed to assess the safety and efficacy of natalizumab once every 6 weeks compared with once every 4 weeks in patients with relapsing-remitting multiple sclerosis.Methods We did a randomised, controlled, open-label, phase 3b trial (NOVA) at 89 multiple sclerosis centres across 11 countries in the Americas, Europe, and Western Pacific. Included participants were aged 18-60 years with relapsing-remitting multiple sclerosis and had been treated with intravenous natalizumab 300 mg once every 4 weeks with no relapses for at least 12 months before randomisation, with no missed doses in the previous 3 months. Participants were randomly assigned (1:1), using a randomisation sequence generated by the study funder and contract personnel with interactive response technology, to switch to natalizumab once every 6 weeks or continue with once every 4 weeks. The centralised MRI reader, independent neurology evaluation committee, site examining neurologists, site backup examining neurologists, and site examining technicians were masked to study group assignments. The primary endpoint was the number of new or newly enlarging T2 hyperintense lesions at week 72, assessed in all participants who received at least one dose of assigned treatment and had at least one postbaseline MRI, relapse, or neurological examination or efficacy assessment. Missing primary endpoint data were handled under prespecified primary and secondary estimands: the primary estimand included all data, regardless of whether participants remained on the assigned treatment; the secondary estimand classed all data obtained after treatment discontinuation or study withdrawal as missing. Safety was assessed in all participants who received at least one dose of study treatment. Study enrolment is closed and an open-label extension study is ongoing. This study is registered with EudraCT, 2018-002145-11, and ClinicalTrials.gov, NCT03689972.Findings Between Dec 26, 2018, and Aug 30,2019,605 patients were assessed for eligibility and 499 were enrolled and assigned to receive natalizumab once every 6 weeks (n=251) or once every 4 weeks (n=248). After prespecified adjustments for missing data, mean numbers of new or newly enlarging T2 hyperintense lesions at week 72 were 0.20 (95% CI 0.07-0-63) in the once every 6 weeks group and 0.05 (0.01-0-22) in the once every 4 weeks group (mean lesion ratio 4.24 [95% CI 0.86-20-85]; p=0.076) under the primary estimand, and 0.31 (95% CI 0.12-0-82) and 0.06 (0.01-0-31; mean lesion ratio 4.93 [95% CI 1.05-23.20]; p=0.044) under the secondary estimand. Two participants in the once every 6 weeks group with extreme new or newly enlarging T2 hyperintense lesion numbers (>= 25) contributed most of the excess lesions. Adverse events occurred in 194 (78%) of 250 participants in the once every 6 weeks group and 190 (77%) of 247 in the once every 4 weeks group, and serious adverse events occurred in 17 (7%) and 17 (7%), respectively. No deaths were reported. There was one case of asymptomatic progressive multifocal leukoencephalopathy (without clinical signs) in the once every 6 weeks group, and no cases in the once every 4 weeks group; 6 months after diagnosis, the participant was without increased disability and remained classified as asymptomatic.Interpretation We found a numerical difference in the mean number of new or newly enlarging T2 hyperintense lesions at week 72 between the once every 6 weeks and once every 4 weeks groups, which reached significance under the secondary estimand, but interpretation of statistical differences (or absence thereof) is limited because disease activity in the once every 4 weeks group was lower than expected. The safety profiles of natalizumab once every 6 weeks and once every 4 weeks were similar. Although this trial was not powered to assess differences in risk of progressive multifocal leukoencephalopathy, the occurrence of the (asymptomatic) case underscores the importance of monitoring and risk factor consideration in all patients receiving natalizumab. Copyright (C) 2022 Elsevier Ltd. All rights reserved