A exoneração do passivo restante : questões controversas

Atendendo à fragilidade da nossa economia, não será de estranhar que nos deparemos hodiernamente com um número crescente de insolvências, quer de empresas, quer de pessoas singulares. Assim, com a entrada em vigor do Código de Insolvência e da Recuperação de Empresas aprovado pelo D.L n. º 53/2004, de 18 de março, o legislador adotou medidas de regulação de endividamento, entre as quais se pretende destacar a exoneração do passivo restante, prevista nos arts. 235. º e seguintes do CIRE. No fundo, a introdução deste mecanismo conforma o princípio do ressarcimento dos credores, ao mesmo tempo que atribui aos devedores a possibilidade de reabilitação económica. Cumpre igualmente alertar para o facto de no atual panorama mundial, em pleno contexto de pandemia, o número de insolvências de pessoas singulares está a aumentar e assim continuará com a perda de emprego por arrastamento das insolvências de empresas. Desta senda, move-nos uma pura curiosidade intelectual sobre o tema, bem como a extrema relevância atual do mesmo, o que, desde logo, nos compele ao seu aprofundamento. Comprometemo-nos, num primeiro momento, a analisar o instituto da exoneração do passivo restante, nomeadamente, os seus fundamentos e pressupostos, bem como a tramitação subjacente. Dissecaremos ainda algumas das questões mais controversas e dicotómicas que este instituto convoca, através de uma análise detalhada da jurisprudência e doutrina portuguesas, sendo que, paralelamente, propomo-nos a analisar identicamente determinada legislação e doutrina estrangeira, apondo uma comparação de soluções. Por último, será intento traçar possíveis posições acerca das divergências avançadas ao longo da investigação.Given the fragility of our economy, it is not surprising that we are facing an increasing number of insolvencies, both of companies and individuals. Thus, with the entry of the Insolvency Code approved by the Decree-Law number 53/2004, of March 18th, the legislator adopted measures to regulate indebtedness, among which is the Exemption from Remaining Liabilities, provided for in articles 235. º and following of the Insolvency Code. In essence, the introduction of this mechanism conforms to the principle of compensating creditors while giving debtors the possibility of economic rehabilitation. We should also point out that in the current global scenario, during a pandemic, the number of insolvencies of individuals is increasing and will continue to do so with the loss of jobs as a result of business insolvencies. In this way, we are moved by a pure intellectual curiosity about the theme, as well as its extreme relevance today, which immediately compels us to deepen it. We undertake, in a first step, to analyze the institute of Exemption from Remaining Liabilities, namely, its foundations, assumptions, as well as the underlying procedure. We will also dissect some of the most controversial and dichotomous issues raised by this institute through a detailed analysis of Portuguese jurisprudence and doctrine and in parallel, we propose to analyze certain foreign legislation and doctrine and compare solutions. Finally, it will be an attempt to outline possible positions about the problems advanced throughout the research

Upregulated proteasome subunits in COVID-19 patients: a link with hypoxemia, lymphopenia and inflammation

Severe COVID-19 disease leads to hypoxemia, inflammation and lymphopenia. Viral infection induces cellular stress and causes the activation of the innate immune response. The ubiquitin-proteasome system (UPS) is highly implicated in viral immune response regulation. The main function of the proteasome is protein degradation in its active form, which recognises and binds to ubiquitylated proteins. Some proteasome subunits have been reported to be upregulated under hypoxic and hyperinflammatory conditions. Here, we conducted a prospective cohort study of COVID-19 patients (n = 44) and age-and sex-matched controls (n = 20). In this study, we suggested that hypoxia could induce the overexpression of certain genes encoding for subunits from the α and β core of the 20S proteasome and from regulatory particles (19S and 11S) in COVID-19 patients. Furthermore, the gene expression of proteasome subunits was associated with lymphocyte count reduction and positively correlated with inflammatory molecular and clinical markers. Given the importance of the proteasome in maintaining cellular homeostasis, including the regulation of the apoptotic and pyroptotic pathways, these results provide a potential link between COVID-19 complications and proteasome gene expressionThis research was funded by Health Research Fund (Fondo de Investigación Sanitario [FIS])-European Regional Development Fund (FEDER), Spain through PI19/01612 (F.G.-R.) and COV20/00207 and PI19-01363 (C.C.-Z.) and ISCIII (CP18/00028), co-funded by ESF, “Investing in your future

Diagnostic yield of early repeat colonoscopy after suboptimal bowel preparation in a fecal immunochemical test-based screening program

Background Current guidelines regarding surveillance after screening colonoscopy assume adequate bowel preparation. However, follow-up intervals after suboptimal cleansing are highly heterogeneous. We aimed to determine the diagnostic yield of early repeat colonoscopy in patients with suboptimal bowel preparation in fecal immunochemical test (FIT)-based screening colonoscopy. Methods An observational study including patients who underwent colonoscopy with suboptimal bowel preparation after positive FIT screening and then repeat colonoscopy within 1 year. Suboptimal preparation was defined as a Boston Bowel Preparation Scale (BBPS) score of 1 in any segment. Patients with a BBPS score of 0 in any segment or incomplete examination were excluded. The adenoma detection rate (ADR), advanced ADR (AADR), and colorectal cancer rate were calculated for the index and repeat colonoscopies. Results Of the 2474 patients with FIT-positive colonoscopy at our center during this period, 314 (12.7%) had suboptimal preparation. Of the 259 (82.5%) patients who underwent repeat colonoscopy, suboptimal cleansing persisted in 22 (9 %). On repeat colonoscopy, the ADR was 38.7% (95% CI 32.6% to 44.8%) and the AADR was 14.9% (95%CI 10.5% to 19.4%). The per-adenoma miss rate was 27.7% (95 %CI 24.0% to 31.6%), and the per-advanced adenoma miss rate was 17.6% (95%CI 13.3% to 22.7%). After repeat colonoscopy, the post-polypectomy surveillance recommendation changed from 10 to 3 years in 14.7% of the patients with previous 10-year surveillance recommendation. Conclusions Patients with suboptimal bowel preparation on FIT-positive colonoscopy present a high rate of advanced adenomas in repeat colonoscopy, with major changes in post-polypectomy surveillance recommendations

Risk Factors for Metachronous Colorectal Cancer or Advanced Adenomas After Endoscopic Resection of Highrisk Adenomas

Background & aims: Among the characteristics of high-risk adenomas (HRAs), some may predict a higher risk of metachronous advanced lesions. Our aim was to assess which HRA characteristics are associated with high risk of metachronous colorectal cancer (CRC) or advanced adenomas (AAs). Methods: We systematically searched Pubmed, EMBASE, and Cochrane for cohort studies and clinical trials of CRC or AA incidence at surveillance stratified by baseline lesion size, histology, and multiplicity. We calculated pooled relative risks (RRs) using a random-effects model. Heterogeneity was assessed with the I2 statistic. Results: Fifty-five studies were included, with 936,540 patients with mean follow-up 5.4 ± 2.9 years. CRC incidence per 1000 person-years was 2.6 (2.1-3.0) for adenomas ≥20 mm, 2.7 (2.2-3.2) for high-grade dysplasia (HGD), 2.0 (1.8-2.3) for villous component, 0.8 (0.1-1.4) for ≥5 adenomas, 1.0 (0.7-1.2) for ≥3 adenomas. Metachronous CRC risk was higher in adenomas ≥20 mm vs 10 to 19 mm (RR, 2.08; 95% confidence interval [CI], 1.20-3.61), HGD vs low-grade dysplasia (RR, 2.89; 95% CI, 1.88-4.44), villous vs tubular (RR, 1.75; 95% CI, 1.33-2.31). No significant differences in CRC risk were found in ≥3 adenomas vs 1 to 2 (RR, 1.24; 95% CI, 0.84-1.83), nor in ≥5 adenomas vs 3 to 4 (RR, 0.79; 95% CI, 0.30-2.11). Compared with normal colonoscopy, RR for CRC risk was 2.61 (95% CI, 2.06-3.32) for ≥10mm, 6.62 (95% CI, 4.60-9.52) for HGD, 3.58 (95% CI, 2.24-5.73) for villous component, and 2.03 (95% CI, 1.40-2.94) for ≥3 adenomas. Similar trends were seen for metachronous AAs. Conclusion: Metachronous CRC risk is highest in patients with baseline adenomas with ≥20 mm or HGD. Multiplicity does not seem to be associated with substantially higher CRC risk in the near term

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias. A Randomized Trial.

Background: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. Objective: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. Design: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136) Setting: Spanish colorectal cancer screening program. Participants: 3213 persons with a positive fecal immunochemical test. Intervention: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. Measurements: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. Results: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. Limitations: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. Conclusion: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. Primary Funding Source: Medtronic

Variation in Colonoscopy Performance Measures According to Procedure Indication

BACKGROUND & AIMS: Most fulfillment and benchmarking information for colonoscopy quality indicators has been obtained from studies of primary screening colonoscopies. We analyzed differences in the fulfillment of colonoscopy quality indicators based on the indication for endoscopy. METHODS: We performed an observational, multicenter, cross-sectional study of 14,867 patients who underwent endoscopy procedures for gastrointestinal symptoms (40.3%), a positive result from a fecal immunochemical test (36.0%), postpolypectomy surveillance (15.3%), or primary screening (8.4%), from February 2016 through December 2017 at 14 centers in Spain. We evaluated rates of adequate colon cleansing, cecal intubation, adenoma detection, and colorectal cancer detection, among others. We used findings from primary screening colonoscopies as the reference standard. RESULTS: Fewer than 90% of patients had adequate bowel preparation; 83.1% of patients with gastrointestinal symptoms had adequate bowel preparation (odds ratio [OR] compared with patients with primary screening colonoscopies, 0.62; 95% CI, 0.49–0.78) and 85.3% of patients receiving postpolypectomy surveillance had adequate bowel preparation (OR, 0.71; 95% CI, 0.55–0.91). The cecal intubation rate was also lower in patients with gastrointestinal symptoms (93.1%) (OR, 0.34; 95% CI, 0.22–0.52). The adenoma detection rate was higher in patients with a positive result from a fecal immunochemical test (46.4%) (OR, 2.01; 95% CI, 1.71–2.35) and in patients undergoing postpolypectomy surveillance (48.2%) (OR, 1.41; 95% CI, 1.20–1.67). The highest proportion of patients with colorectal cancer was in the gastrointestinal symptom group (5.1%) (OR, 5.24; 95% CI, 2.30–11.93) and the lowest was in patients undergoing surveillance (0.8%) (OR, 0.83; 95% CI, 0.32–2.14). CONCLUSIONS: Fulfillment of colonoscopy performance measures varies substantially by indication. Policies addressing performance measures beyond colonoscopy screening procedures should be developed. Benchmarking recommendations could be adjusted according to colonoscopy indication

Factors associated with lesion detection in colonoscopy among different indications

Background and objective: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. Methods: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. Results: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). Conclusions: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications

Exercise Ventilatory Inefficiency in Post-COVID-19 Syndrome: Insights from a Prospective Evaluation

The present study was partially granted by Gerencia Regional de Salud de Castilla y León under grant number GRS COVID 111/A/20 and a grant from the Spanish Society of Cardiology SEC/FEC-INVCLI 2.Introduction: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. This study sought to identify clinical sequelae and their potential mechanism. Methods: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up. An outpatient group was also evaluated. They underwent serial testing with a cardiopulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis, and quality of life questionaries. Results: Patients with dyspnea (n = 41, 58.6%), compared with asymptomatic patients (n = 29, 41.4%), had a higher proportion of females (73.2 vs. 51.7%; p = 0.065) with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in the transthoracic echocardiogram and pulmonary function test. Patients who complained of persistent dyspnea had a significant decline in predicted peak VO2 consumption (77.8 (64–92.5) vs. 99 (88–105); p 50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest a potential ventilation/perfusion mismatch or hyperventilation syndrome.Fac. de MedicinaTRUEJunta de Castilla y León. Gerencia Regional de Salud de Castilla y LeónSociedad Española de Cardiologíapu

External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

Background: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. Methods: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. Results: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5–6.6), 9.4 (95% CI, 8.5–10.6), and 14 months (95% CI, 11.8–16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3–8.1), 12.7 (95% CI, 11.3–14.3), and 18.3 months (95% CI, 14.6–24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591–0.631) and 0.673 (95% CI, 0.636–0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). Conclusions: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design