Sex differences in ischemic stroke during COVID-19 first outbreak in northern Italy.

INTRODUCTION: COVID-19 pandemic had a great impact on outcome in SARS-CoV-2 positive patients with ischemic stroke during the first wave in Italy. Few data are available on outcome stratified by sex. METHODS: The Italian Society of Hospital Neuroscience conducted a multi-center, retrospective, observational study on neurological complications in COVID-19 patients with ischemic stroke. All the patients admitted from March 1st to April 30th, 2020 in 20 Neurology Units in Northern Italy were recruited. Demographical and clinical features, treatment and outcome data were compared focusing on sex differences. RESULTS: 812 patients with ischemic stroke were enrolled, of whom 129 with COVID-19; males were 53.8%. In-hospital mortality in COVID-19 patients was 35.3% in males and 27.9% in females while 8.5% in male and 5.8% in female patients without COVID-19. SARS-CoV-2 positive patients had a higher frequency of stroke of undetermined etiology, than negative ones (32.8% vs 22.5%; p = 0.02), especially in females compared to males (36.1% vs 27.9%), albeit without statistical significance. Male patients with SARS-CoV-2 were more likely to require cPAP (30.9% vs 14.8%; p = 0.03), endotracheal tube (14.9% vs 3.3%; p = 0.02) and reperfusion strategies (29.4% vs 11.5%; p = 0.01) than females, as well as to have a higher CRP and D-dimer. These elements together with older age, a total anterior circulation stroke and lymphopenia were predictors of a worse outcome. DISCUSSION: Our study detected some differences due to sex in ischemic stroke with and without COVID-19, supporting the possibility to perform sex analyses for SARS-CoV-2 positive patients for a better clinical management.

Discontinuity of marginal artery at splenic flexure and rectosigmoid junction: A systematic review and meta-analysis.

AIM: The aim of this study was to provide comprehensive evidence-based assessment of the discontinuity of the marginal artery at the splenic flexure (SF) and the rectosigmoid junction (RSJ). METHOD: A systematic review was conducted of literature published to 26 December 2022 in the electronic databases PubMed, SCOPUS and Web of Science to identify studies eligible for inclusion. Data were extracted and pooled into a meta-analysis using the Metafor package in R. The primary outcomes were the pooled PPEs of the marginal artery at the SF and the RSJ. The secondary outcome was the size of vascular anastomoses. RESULTS: A total of 21 studies (n = 2,864 patients) were included. The marginal artery was present at the splenic flexure in 82% (95% CI: 62-95) of patients. Approximately 81% (95% CI: 63-94%) of patients had a large macroscopic anastomosis, while the remainder (19%) had small bridging ramifications forming the vessel. The marginal artery was present at the RSJ in 82% (95% CI: 70-91%) of patients. CONCLUSION: The marginal artery may be absent at the SF and the RSJ in up to 18% of individuals, which may confer a higher risk of ischaemic colitis. As a result of high interstudy heterogeneity noted in our analysis, further well-powered studies to clarify the prevalence of the marginal artery at the SF and the RSJ, as well as its relationship with other complementary colonic collaterals (intermediate and central mesenteric), are warranted.

Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis.

Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

A real-world study of alemtuzumab in a cohort of Italian patients.

BACKGROUND AND PURPOSE: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. METHODS: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. RESULTS: We studied 322 patients (mean age 36.8 years, median EDSS score 3, median follow-up 1.94 years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p < 0.001). The number of previous-year relapses was associated with alemtuzumab ARR (adjusted risk ratio [RR] 1.38, p = 0.009). Progression-free survival was 94.5% after 1 year, and 89.2% after 2 years of alemtuzumab treatment. EDSS score improvement occurred in 13.5% after 1 year, and 20.6% after 2 years. Re-baselining patients after 6 months of alemtuzumab treatment, led to no evidence of disease activity status in 71.6% after 1 year and 58.9% after 2 years. CONCLUSIONS: Alemtuzumab decreases ARR independent of previous therapy, including patients with disease activity during natalizumab treatment. Overall, 90% of patients showed no disease progression, and 20% an improvement after 2 years of alemtuzumab.

SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy.

OBJECTIVE: To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. METHODS: In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. RESULTS: Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06-2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05-2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17-5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death. CONCLUSIONS: Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

Analysis of the Different Lymphatic Drainage Patterns during Sentinel Lymph Node Biopsy for Skin Melanoma.

In the last two decades, studies of lymphoscintigraphy imaging in lymphatic mapping reported an extreme heterogeneity of skin lymphatic drainage of some skin area, in contrast with the previous scientific literature. The aim of this study was to investigate the presence of any correlations between the topographical location of cutaneous melanoma and the topographical location of sentinel lymph nodes. Data from 165 patients undergoing sentinel lymph node biopsy between January 2013 and May 2021 were analyzed, demonstrating that melanomas in the Lumbar region presented a significant more heterogeneous drainage by site than those in the Scapular region (p < 0.01) and that melanomas in the Subscapular region were significantly more heterogeneous by laterality (unilateral vs. bilateral) than those in the Scapular region (p < 0.05). Results of this study supported the evidence of multiple lymphatic drainage as regards the sentinel node biopsy performed in skin melanoma located on the dorsal subscapular region and lumbar region. For this reason, the association of preoperative lymphoscintigraphy with another imaging evaluation is needed in these critical cutaneous areas. Recent technical developments enabling fluorescence lymphography together with indocyanine green have significantly improved the visualization of lymphatic drainage patterns at a microscopic level. In the preoperative phase, any doubt can be resolved by associating the SPET-CT scan to lymphoscintigraphy, while during the intraoperative phase, an additional evaluation with indocyanine green can be performed in doubtful cases. The aim of the duplex lymphatic mapping (pre and/or intraoperative) is an accurate search of sentinel nodes, in order to reduce the rate of false negatives.

A systematic review and meta-analysis of variants of the branches of the superior mesenteric artery: the Achilles heel of right hemicolectomy with complete mesocolic excision?

AIM: Dissection with subsequent ligation and resection of arteries at their origin (central vascular ligation) is essential for adequate oncological resection during right hemicolectomy with complete mesocolic excision. This technique is technically demanding due to the highly variable arterial pattern of the right colon. Therefore, this study aims to provide a comprehensive evidence-based assessment of the arterial vascular anatomy of the right colon. METHODS: A thorough systematic literature search through September 2020 was conducted on the electronic databases PubMed, Scopus and Web of Science to identify studies eligible for inclusion. Data were extracted and pooled into a meta-analysis using MetaXl software. RESULTS: A total of 41 studies (n = 4691 patients) were included. The ileocolic artery (ICA), right colic artery (RCA) and middle colic artery (MCA) were present in 99.7% (95% CI 99.4%-99.8%), 72.6% (95% CI 61.3%-82.5%) and 96.9% (95% CI 94.2%-98.8%) respectively of patients. Supernumerary RCA and MCA were observed in 3.2% and 11.4% respectively of all cases. The RCA shared a common trunk with the ICA and MCA in 13.2% and 17.7% respectively of patients. A retro-superior mesenteric vein course of the ICA and RCA was observed in 55.1% and 11.4% respectively of all cases. CONCLUSION: The vascular anatomy of the right colon displays several notable variations, namely the absence of some branches (RCA absent in 27.4% of cases), supernumerary branches, common trunks, and retro-superior mesenteric vein courses. These variations should be taken into consideration during right hemicolectomy with complete mesocolic excision to ensure adequate oncological resection while minimizing intra-operative complications.

Impact of SARS-CoV-2 infection on acute intracerebral haemorrhage in northern Italy.

INTRODUCTION: Growing evidence has been published as to the impact of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) on cerebrovascular events over the last few months, with considerable attention paid to ischemic strokes. Conversely, little is known about the clinical course of intracerebral haemorrhage (ICH) and simultaneous SARS-CoV-2 infection. METHOD: The Italian Society of Hospital Neurosciences (SNO) promoted a multicentre, retrospective, observational study (SNO-COVID-19), involving 20 Neurological Departments in Northern Italy. Clinical data on patients with acute cerebrovascular diseases, admitted from March 1st to April 30th, 2020, were collected. A comparison was made of the demographical and clinical features of both SARS-CoV-2 positive and negative patients with ICH. RESULTS: 949 patients were enrolled (average age 73.4 years; 52.7% males); 135 patients had haemorrhagic stroke and 127 (13.4%) had a primary ICH. Only 16 patients with ICH (12.6%) had laboratory confirmed SARS-CoV-2 infection, both symptomatic and asymptomatic. SARS-CoV-2 related pneumonia or respiratory distress (OR 5.4), lobar location (OR 5.0) and previous antiplatelet or anticoagulant treatment (OR 2.9) were the only factors significantly associated with increased mortality in ICH. SARS-CoV-2 infection, regardless of respiratory involvement, led to a non-significantly increased risk of in-hospital death (37.5% vs 23.4%, p = 0.2). DISCUSSION: ICH patients with COVID-19 did not experience an increase in mortality as striking as ischemic stroke. The inflammatory response and respiratory complications could justify the slight increase of death in ICH. Bleeding sites and previous antiplatelet or anticoagulant treatment were the only other predictors of a worse outcome.

Impact of SARS-CoV-2 on reperfusion therapies for acute ischemic stroke in Lombardy, Italy: the STROKOVID network.

Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62-80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5-270) minutes vs. 190 (IQR 150-245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82-13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10-0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions.

When Does the Cytokine Storm Begin in COVID-19 Patients? A Quick Score to Recognize It.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that is responsible for coronavirus disease 2019 (COVID-19), which has rapidly spread across the world, becoming a pandemic. The "cytokine storm" (CS) in COVID-19 leads to the worst stage of illness, and its timely control through immunomodulators, corticosteroids, and cytokine antagonists may be the key to reducing mortality. After reviewing published studies, we proposed a Cytokine Storm Score (CSs) to identify patients who were in this hyperinflammation state, and at risk of progression and poorer outcomes. We retrospectively analyzed 31 patients admitted to Infectious Disease Department in "St. Maria" Hospital in Terni with confirmed SARS-CoV-2 infections, and analyzed the "CS score" (CSs) and the severity of COVID-19. Then we conducted a prospective study of COVID-19 patients admitted after the definition of the CSscore. This is the first study that proposes and applies a new score to quickly identify COVID-19 patients who are in a hyperinflammation stage, to rapidly treat them in order to reduce the risk of intubation. CSs can accurately identify COVID-19 patients in the early stages of a CS, to conduct timely, safe, and effect administration of immunomodulators, corticosteroids, and cytokine antagonists, to prevent progression and reduce mortality.

Surgical anatomy of sigmoid arteries: A systematic review and meta-analysis.

BACKGROUND: The purpose of this systematic review and meta-analysis was to determine the prevalence of the number of sigmoid arteries (SA) and variations in their origins. METHODS: A thorough systematic search of literature through February 2020 was conducted on major electronic databases to identify eligible studies. Data were extracted and pooled into a meta-analysis using Metafor package in R. The primary outcome was the variations in the SA origin (according to modified Zebrowski classification), and the secondary outcome was the prevalence of the number of SA. RESULTS: A total of 22 studies (n = 2653 patients) were included. Type 1 modified Zebrowski (separated origins or common trunk of the SA originating from descending recto-sigmoid trunk (DRST)) was the most common origin type of the SA (pooled prevalence estimate (PPE) = 49.67% (95% CI 32. 67- 66.71)), while type 3 (separated origins or common trunk of 1 or 2 SA originating from DRST or superior rectal artery (SRA) and 1 or 2 SA originating from DRST or SRA) was the least common (PPE = 0.18%; 95% CI 0.00-2.82)). Of the Type 1 variants, the not specified (N.S) variant was by far the most prevalent. The number of SA ranged from one to five, with three being the mode (PPE = 42.3%). CONCLUSION: This is the most comprehensive analysis of arterial vascular anatomy of the sigmoid colon. In light of the highly variable anatomical pattern displayed by the SA, thorough pre-operative knowledge of their anatomy can be crucial in minimizing incidences of iatrogenic injury.

[Health professionals and the crime scene: analysis of operational strategies and development of a Data Collection tool]. / Sanitari e Scena del Crimine: analisi delle strategie operative ed elaborazione di uno strumento di raccolta dati.

The Emergency Medical Service team are often the first to arrive in situations that later turned out to be crime scenes. Therefore, multiple responsibilities derive from their actions, as there is the burden of assisting the parties involved by maintaining the integrity of forensic evidence while, at the same time, mitigating further harm or risks. The aforementioned, however, often lack any forensic training with the consequent risk of alteration of the area and loss of fundamental information for the purpose of further investigation. The purpose of this study, born from the interdisciplinary collaboration between nursing and forensic sciences, is aimed to guarantee the correct approach by emergency professionals at the Crime Scene; in the light of the data currently available regarding intervention strategies, a Data Collection Sheet was drawn up, whose non-immediate compilation would inevitably lead to the loss of important informations. This is a tool not intended for medical examiners, already trained in this field and equipped with elaborate survey cards, but rather an easy-to-use tool that is the prerogative of "laymen" that can prevent emergency healthcare professionals from losing crucial elements that will then be provided to the investigative bodies and consequently to the consultants or experts. The working method involved the research in Literature of already existing operational tools and a bibliographic review of texts, articles and protocols relating to the topic, as well as surveys carried out at national level via email with EMS Operations Centres about the use of a Crime Scene Report Card.

Routine drain or no drain after laparoscopic cholecystectomy for acute cholecystitis.

BACKGROUND: Laparoscopic cholecystectomy (LC) is considered to be the gold standard in the early management of acute cholecystitis however, recommendations for routine drain insertion in the acute setting are unavailable. STUDY DESIGN: A systematic review of literature review and metanalysis was conducted. All studies comparing drain versus no drain after LC for acute cholecystitis were included. RESULTS: Seven studies, with 1274 patients, were included. Postoperative wound infection rates (relative risk (RR) 0.30, 95% confidence interval (CI) 0.10 to 0.88; I2 = 0%) and postoperative abdominal collection requiring drainage (RR 1.20, 95% CI 0.35 to 4.12; I 2 = 0%) were lower in the no-drain group, but this was only significant for wounded infections on subgroup analysis of RCTs. Length of stay hospital (mean difference (MD) -0.49, 95% CI -0.89 to -0.09; I 2 = 69%) and operative time (MD -8.13, 95% CI -13.87 to -2.38; I 2 = 92%) were significantly shorter in the no drain group however this was in the context of significant heterogeneity. CONCLUSION: The available data suggests that acute cholecystitis is not an indication for routine drain placement after LC. However, these results must be interpreted with caution due to the limitations of the included studies. In effect, the main issue of this meta-analysis lies on the limitations of the included studies themselves, because of a considerable heterogeneity among the included works, particularly for the inclusion criteria of patients and reported severity of acute cholecystitis. Further work is required to produce evidence which will definitively alter clinical practice. LEVEL OF EVIDENCE: Level 2a (systematic review of cohort studies). Oxford CEBM levels of evidence.

Neurologic manifestations in 1760 COVID-19 patients admitted to Papa Giovanni XXIII Hospital, Bergamo, Italy.

OBJECTIVES: Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the major neurological complications in a large cohort of COVID-19 patients. METHODS: Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories. RESULTS: Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease [53 pts (38.7%)] including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases [31 (22.6%)] including 17 Guillain-Barrè syndromes; (c) altered mental status [49 (35.8%)] including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0-48.2; χ2= 14.306; p < 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5-37.5%; χ2= 7.055; p < 0.01). CONCLUSION: This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.

Anatomical variations of the pyramidalis muscle: a systematic review and meta-analysis.

PURPOSE: To provide a comprehensive evidence-based assessment of the anatomical characteristics of the pyramidalis muscle (PM). MATERIALS AND METHODS: A thorough systematic search of the literature through August 31st 2020 was conducted on major electronic databases PubMed, Scopus and Web of Science (WOS) to identify studies eligible for inclusion. Data were extracted and pooled into a meta-analysis using MetaFor package in R and MetaXL. A random-effects model was applied. The primary outcome of interest was the prevalence of PM. The secondary outcomes were the dimensions (length and width) of the PM. RESULTS: A total of 11 studies (n = 787 patients; 1548 sides) were included in the meta-analysis. The multinomial pooled prevalence estimate (PPE) for a bilateral absence of the PM was 11.3% (95% CI [7.2%, 16.2%], 82.3% (95% CI [76.2%, 87.6%]) for a bilateral presence, and 6.3% (95% CI [3.3%, 10.2%]) for a unilateral presence. Of four studies (n = 37 patients) that reported the side of a unilateral presence, the PPE of a unilateral right-side presence was 42.2% (95% CI [23.0%, 62.3%]) compared to 57.8% for a unilateral left-side presence (95% CI [37.7%, 77.0%]). The mean length of the PM displayed high levels of heterogeneity, ranging from 3.12 to 12.50 cm. CONCLUSION: The pyramidalis muscle is a rather constant anatomical structure being present in approximately 90% of individuals.

Cladribine vs other drugs in MS: Merging randomized trial with real-life data.

OBJECTIVE: Cladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data. METHODS: Data from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity. RESULTS: All weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis. CONCLUSION: In patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.

Intersigmoid Hernia: A Forgotten Diagnosis-A Systematic Review of the Literature over Anatomical, Diagnostic, Surgical, and Medicolegal Aspects.

INTRODUCTION: Intersigmoid hernia is a hernia of the small bowel into the intersigmoid fossa. It is well known to be a rare condition. Recent reports reveal that the preoperative differentiation of intersigmoid hernias is difficult and the diagnosis is often confirmed during the laparotomic exploration. Due to the vague clinical manifestation in most cases, the surgical treatment is frequently delayed. MATERIALS AND METHODS: In this study, we systematically reviewed the literature up to 2019 covering 114 studies and 124 patients with an intersigmoid hernia. The purpose of this work is to improve the understanding of the anatomical aspects, clinical presentation, diagnosis, and treatment of intersigmoid hernia so as to assist the preoperative differentiation of these hernias when presented as acute abdomen in the emergency department. RESULTS: The diameter of the intersigmoid recess was reported with mean 2.65 cm (range 1-10 cm, SD 1.15 cm) and the length of the incarcerated small intestine was between 3 cm (min) and 150 cm (max): mean 25.25 cm, SD 35.04 cm. The diameter of the sigmoid recess was greater in patients who underwent resection due to strangulation (mean 3.31 cm, SD 1.53 cm) compared to those who underwent only reduction of the hernia (mean 2.35 cm, SD 0.74 cm). The time from onset to operation was less in patients undergoing resection surgery due to throttling (mean 3.03 days, SD 3.01 days) compared to those who underwent only a reduction of hernia incarceration (mean 8.49 days, SD 6.83 days). CONCLUSION: Intersigmoid hernia is often a forgotten diagnosis and a clinical challange due to its anatomical characteristics.

First therapy choice in newly diagnosed Multiple Sclerosis patients: A multicenter Italian study.

BACKGROUND: The approval of an increasing number of disease modifying drugs for the treatment of Multiple Sclerosis (MS) creates new challenges for patients and clinicians on the first treatment choice. The main aim of this study was to assess factors impacting first therapy choice in a large Italian MS cohort. METHODS: Newly diagnosed relapsing-remitting (RR) MS patients (2010-2018) followed in 24 Italian MS centres were included in the study. We evaluated the association of baseline demographics, clinical and MRI characteristics to the first treatment choice by logistic regression models applied to pre-defined binary alternatives: dimethyl fumarate vs injectables (interferon and glatiramer acetate), teriflunomide vs injectables, fingolimod vs dimethyl fumarate and fingolimod vs natalizumab. RESULTS: We enrolled 3025 patients in the period between January 2010 and June 2018. Relapses in the previous year (OR = 2.75; p = 0.001), presence of spinal cord lesions (OR = 1.80; p = 0.002) and higher number (>9) of T2 lesions on the baseline brain MRI scan (OR = 1.65; p = 0.022) were the factors associated to dimethyl fumarate choice as first therapy vs an injectable drug. Older age (OR = 1.06; p < 0.001), male sex (OR = 2.29; p = 0.001) and higher EDSS (OR = 1.36; p < 0.001) were the factors associated with the choice of teriflunomide vs injectables. In more recent years, dimethyl fumarate (OR = 3.23; p < 0.001) and teriflunomide (OR = 2.53; p < 0.001) were chosen more frequently than injectables therapies. The main determinant for the choice of fingolimod as compared with dimethyl fumarate was a higher EDSS (OR = 1.56; p = 0.001), while there was a weak association with a longer disease duration (p = 0.068) and a longer time from onset to diagnosis (p = 0.085). Compared to fingolimod, natalizumab was preferred in patients with a younger age (OR = 0.95; p = 0.003) and higher EDSS (OR = 1.45; p = 0.007) and a shorter disease duration (OR = 0.52; p = 0.076). CONCLUSION: Many factors guided therapeutic decision for our Italian cohort of MS patients; they are mainly related to MS disease activity, baseline EDSS, disease duration and age.

Media-Based Research on Selfie-Related Deaths in Italy.

BACKGROUND: The incidence of taking selfies and sharing them on social media as well as selfie-related dangerous behaviors is increasing, particularly among young people, also leading to selfie-related trauma and death. This study was performed to obtain epidemiological characteristics of selfie-related mortality in Italy. METHODS: Scientific literature and Italian media were reviewed. RESULTS: Twelve victims from 11 events, from 2014 to 2018, were analyzed (sex, age, accident types, the nationality, the Italian region where the incident took place, if the person involved was indigenous or a tourist, the dynamics and the causa mortis, if other people have been involved in the selfie, and if other people were deceased). The majority of selfie victims were male teenagers, the average age was 23.6 years, the most preferred site of taking selfies was the natural environment followed by the railway one, the most frequently reported event or accident type was falling from a height, and the most frequent causes of selfie-related deaths were multitrauma and drowning. CONCLUSIONS: Selfie-related deaths in Italy appear to be an issue and appear to be increasing. Particularly, male teenagers and young adults are at high risk for selfie-related deaths. Measures should be taken to reduce their incidence.

Aberrant left hepatic arteries arising from left gastric arteries and their clinical importance.

BACKGROUND: The Aberrant Left Hepatic Artery (ALHA) is replaced when it does not originate from the hepatic artery proper and it is the only supply to that part of the liver, while an accessory artery coexists with a normal artery. The aim of this systematic review is to evaluate the incidence of ALHAs including the one arising from the Left Gastric Artery, also named Hyrtl's artery. METHODS: A literature search in PubMed, SCOPUS, WOS and Google Scholar was performed. The risk of bias was assessed by means of the AQUA tool. The main outcome was the prevalence of ALHA. Secondary outcomes were the prevalence of the accessory and replaced left hepatic arteries. A subgroup analysis was conducted by geographic region and type of evaluation. RESULTS: This review included 57 studies, with a total of 19,284 patients. The majority of the studies involved the use of radiological techniques -especially Angio-CT-and were performed in Asia. The overall risk of bias was moderate. The overall prevalence of the ALHA was 13.52%; the overall prevalence was 8.26% for the Replaced ALHA and 5.55% for the Accessory ALHA. In the 18 studies that employed Michels' classification, Type II had the lowest prevalence (0.36%) and Type VII the highest prevalence (6.62%). DISCUSSION: Some of the studies included did not distinguish between the ''replaced'' and ''accessory'' ALHA (34.25%). Some surgical dissection techniques proved insufficient for the localization of other hepatic arteries. These results suggest that an accurate preoperative radiological evaluation is needed to localize replaced arteries.