Surgical therapy for end-stage achalasia: prevalence and risk factors for esophageal carcinoma development, clinical and functional long-term results of conservative surgery and esophagectomy

La chirurgia conservativa o l’esofagectomia, possono essere indicate per il trattamento della disfagia nell’acalasia scompensata. L’esofagectomia è inoltre finalizzata alla prevenzione dello sviluppo del carcinoma esofageo. Gli obiettivi erano: a) definire prevalenza e fattori di rischio per il carcinoma epidermoidale; b) confrontare i risultati clinici e funzionali di Heller-Dor con pull-down della giunzione esofagogastrica (PD-HD) ed esofagectomia. I dati in analisi, ricavati da un database istituito nel 1973 e finalizzato alla ricerca prospettica, sono stati: a) le caratteristiche cliniche, radiologiche ed endoscopiche di 573 pazienti acalasici; b) il risultato oggettivo e la qualità della vita, definita mediante questionario SF-36, dopo intervento di PD-HD (29 pazienti) e dopo esofagectomia per acalasia scompensata o carcinoma (20 pazienti). Risultati: a) sono stati diagnosticati 17 carcinomi epidermoidali ed un carcinosarcoma (3.14%). Fattori di rischio sono risultati essere: il diametro esofageo (p<0.001), il ristagno esofageo (p<0.01) e la durata dei sintomi dell’acalasia (p<0.01). Secondo l’albero di classificazione, soltanto i pazienti con esito insufficiente del trattamento ai controlli clinico-strumentali ed acalasia sigmoidea presentavano un rischio di sviluppare il carcinoma squamocellulare del 52.9%. b) Non sono state riscontrate differenze statisticamente significative tra i pazienti sottoposti ad intervento conservativo e quelli trattati con esofagectomia per quanto concerne l’esito dell’intervento valutato mediante parametri oggettivi (p=0.515). L’analisi della qualità della vita non ha evidenziato differenze statisticamente significative per quanto concerne i domini GH, RP, PF e BP. Punteggi significativamente più elevati nei domini RE (p=0.012), VT (p<0.001), MH (p=0.001) e SF (p=0.014) sono stati calcolati per PD-HD rispetto alle esofagectomie. In conclusione, PD-HD determina una miglior qualità della vita, ed è pertanto la procedura di scelta per i pazienti con basso rischio di cancro. A coloro che abbiano già raggiunto i parametri di rischio, si offrirà l’esofagectomia o l'opzione conservativa seguita da protocolli di follow-up.Conservative surgery or esophagectomy, may be indicated for therapy of dysphagia in end-stage achalasia. Esophagectomy is also aimed to prevent the development of carcinoma which may occur in end-stage achalasia. Aims of the study were: a) to determine prevalence and risk factors for epidermoid carcinoma development; b) to compare clinical and functional results after pull-down Heller-Dor (PD-HD) and esophagectomy. Data in the analysis, extracted from a database started in 1973 and finalized to prospective clinical research, were: a) clinical, radiological and endoscopic features of 573 achalasia patients; b) objective outcome and quality of life, assessed by means of SF-36 questionnaire, after PD-HD (29 patients) and esophagectomy for end stage achalasia or for cancer (20 patients). Results: a) Seventeen epidermoid carcinomas and one carcinosarcoma were diagnosed (3.14%). At multivariate analysis esophageal diameter (p<0.001), residual barium column (p<0.01) and duration of dysphagia (p<0.01) were independent risk factors. According to classification tree, patients with poor outcome at the last clinical-radiological control and sigmoid esophagus experienced a risk of epidermoid carcinoma development equal to 52.9%. b) No statistically significant differences were observed with regards to the objective evaluation of dysphagia, reflux symptoms and esophagitis (p=0.515). No statistically significant differences were calculated between the two groups as it concerns the domains general health, physical functioning, role physical and bodily pain. Significant differences with regards to the domains role emotional (p=0.012), vitality (p<0.001), mental health (p=0.001) and social functioning (p=0.014) were observed in favour of PD-HD. In conclusion, PD-HD achieved better quality of life than esophagectomy. PD-HD is the procedure of choice for patients with low or null risk for cancer. Patients, who overcome the risk parameters, should be offered esophagectomy or conservative treatment followed by strict endoscopic surveillance

Risk factors for postoperative depression in 150 subjects treated for drug-resistant focal epilepsy.

Objective.The primary goal was to identify risk factors for post-surgical depression in subjects operated on for drug-resistant epilepsy. Secondary goals were to confirm the high rate of depression in subjects suffering from epilepsy (prior to surgery) and to look for first post-surgical depressive episode.Methods.Case series study of 150 subjects surgically treated for partial epilepsy (side of surgery: 72 right, 78 left; site of surgery: 97 Unilobar Temporal, 17 Unilobar Frontal, 14 Posterior, 22 Multilobar). All subjects routinely had three psychiatric evaluations: before surgery (baseline) and at 6 and 12 months after surgery. Psychiatric diagnoses were made according to DSM-IV-TR criteria. Bivariate (Fisher exact test and Kruskal–Wallis rank sum test) and multivariate (logistic regression model fitting) analyses were performed.Results.Thirty-three (22%) subjects had post-surgical depressive episodes, 31 of them in the first 6 months. Fourteen out of 33 experienced depression for the first time. Post-surgical depressive episodes are not associated with gender, outcome on seizures, side/site of surgical resection, histological diagnosis, psychiatric diagnoses other than depression. Depressive episodes before surgery and older age at surgery time are risk factors for post-surgical depression (p = 0.0001 and 0.01, respectively, at logistic regression analysis). No protective factors were identified.Conclusions.Our data show that lifetime depressive episodes and older age at surgery time are risk factors for post-surgery depression. Moreover, a prospective study could be useful in order to assess whether depression is really a consequence of surgery

Therapeutic alternatives in chronic thromboembolic pulmonary hypertension: from pulmonary endarterectomy to balloon pulmonary angioplasty to medical therapy. State of the art from a multidisciplinary team

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with a very complex pathophysiology differing from other causes of pulmonary hypertension (PH). It is an infrequent consequence of acute pulmonary embolism that is frequently misdiagnosed. Pathogenesis has been related to coagulation abnormalities, infection or inflammation, although these disturbances can be absent in many cases. The hallmarks of CTEPH are thrombotic occlusion of pulmonary vessels, variable degree of ventricular dysfunction and secondary microvascular arteriopathy. The definition of CTEPH also includes an increase in mean pulmonary arterial pressure of more than 25 mmHg with a normal pulmonary capillary wedge of less than 15 mmHg. It is classified as World Health Organization group 4 PH, and is the only type that can be surgically cured by pulmonary endarterectomy (PEA). This operation needs to be carried out by a team with strong expertise, from the diagnostic and decisional pathway to the operation itself. However, because the disease has a very heterogeneous phenotype in terms of anatomy, degree of PH and the lack of a standard patient profile, not all cases of CTEPH can be treated by PEA. As a result, PH-directed medical therapy traditionally used for the other types of PH has been proposed and is utilized in CTEPH patients. Since 2015, we have been witnessing the rebirth of balloon pulmonary angioplasty, a technique first performed in 2001 but has since fallen out fashion due to major complications. The refinement of such techniques has allowed its safe utilization as a salvage therapy in inoperable patients. In the present keynote lecture, we will describe these therapeutic approaches and results

Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, Real-World Study

Introduction In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and &gt;= 3 (late add-on) prior antiseizure medications. Results A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12 months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p &lt; 0.001). Sustained seizure response was reached by 97/161 (60.3%) of patients in the early add-on group and 286/833 (34.3%) of patients in the late add-on group (p &lt; 0.001). Sustained seizure freedom was achieved by 51/161 (31.7%) of patients in the early add-on group and 91/833 (10.9%) of patients in the late add-on group (p &lt; 0.001). During the 1-year study period, 29 (16.5%) patients in the early add-on group and 241 (28.3%) in the late add-on group discontinued BRV (p = 0.001). Adverse events were reported by 38.7% and 28.5% (p = 0.017) of patients who received BRV as early and late add-on treatment, respectively. Conclusion Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study)

Background Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58–85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P&lt;0.0001); incidental diagnosis of lung cancer (HR: 1.71; P&lt;0.0001); and lung cancer resection (HR: 2.79; P&lt;0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P&lt;0.0001); incidental diagnosis of lung cancer (HR: 2.00; P&lt;0.0001); and lung cancer resection (HR: 2.07; P&lt;0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). Conclusions The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Background: The aim of this study in patients with acute posterior ischemic stroke (PS) and atrial fibrillation (AF) were to evaluate the risks of recurrent ischemic event and severe bleeding and these risks in relation with oral anticoagulant therapy (OAT) and its timing. Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of: stroke recurrence, TIA, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2,470 patients were available for the analysis: 473 (19.1%) with PS and 1,997 (80.9%) AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Conclusions: Patients with posterior or anterior stroke and AF appear to have similar risks of ischemic or hemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT

The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction

Abstract Background: Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF. Methods: We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding). Results: The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84–1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03–1.77). Conclusions: In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly