Subxiphoid thymectomy with a double sternum retractor: a pilot study.

Background: Our study aims to describe the experience of a single team in terms of the potential and benefits of subxiphoid thymectomy using a double sternum hook retractor. Methods: From November 2016 to July 2018, 34 patients have been undergone subxiphoid thymectomy at our Department. Twenty patients were diagnosed with Masaoka Stage I–III thymomas, 12 with thymic hyperplasia or cysts of the thymus, 2 with thymic tumors. All patients underwent a chest computed tomography (CT) with enhancement. 18-Fludeoxyglucose positron emission tomography (18FDG-PET) was performed when recurrence was suspected. Neurological examinations were set. Patients underwent video-assisted thoracoscopic surgery (VATS) subxiphoid thymectomy with a double sternum retractor. A retrospective analysis of clinical, perioperative data, and follow-up was performed. Incidence rates for death or recurrence were calculated. Average pain score (NRS scale), average mental health, and physical health scores (SF-12) were analyzed. Results: Thirty-four patients (mean age 54; 12 men and 22 women) with thymic neoformation (from 1.0 cm × 1.0 cm × 1.0 cm to 14.0 cm × 9.0 cm × 4.5 cm) were enrolled. All patients underwent subxiphoid thymectomy. No mortality or recurrence was observed. Median follow-up time was 17.9 months (range, 2.2–23.3 months). The morbidity rate was 9.7 events per 100 person-years. Average pain scores after surgery and after follow-up were 1.7±0.4 and 0.1±0.4, respectively; average mental health and physical health scores on the SF-12 scale were 45.6±2.4 and 33.6±2.4, respectively. Conclusions: Subxiphoid thymectomy is a high satisfaction approach with positive aesthetic outcomes and low pain. Double sternum retractors are especially useful for creating space during thymectomy. However, the qualified experience is needed

Budget Impact analysis of venetoclax for management of acute myeloid leukemia from the perspective of the social security and the private sector in Argentina

OBJECTIVE: This study aimed to estimate the budget impact of the incorporation of venetoclax for the treatment of patients with Acute Myeloid Leukemia (AML) over 75 years of age or those with comorbidities and contraindications for the use of intensive chemotherapy, from the perspective of the social security and the private third-party payers in Argentina. METHODS: A budget impact model was adapted to estimate the cost difference between the current scenario (azacitidine, decitabine and low doses of cytarabine) and the new scenario (incorporation of venetoclax) for a third-party payer over a time horizon of three years. Input parameters were obtained from a literature review, validated or complemented by expert opinion using a modified Panel Delphi approach. All direct medical costs were estimated by the micro-costing approach and were expressed in US dollars (USD) as of September 2020 (1 USD = 76.18 Argentine pesos). RESULTS: For a third-party payer with a cohort of 1,000,000 individuals covered, incorporating venetoclax was associated with an average budget impact per-member per-month (PMPM) of $0.11 USD for the social security sector and$0.07 USD for the private sector. The duration of treatment with venetoclax was the most influential parameter in the budget impact results. CONCLUSION: The introduction of venetoclax was associated with a positive and slight budget impact. These findings are informative to support policy decisions aimed to expand the current treatment landscape of AML

Comparison of uniportal robotic-assisted thoracic surgery pulmonary anatomic resections with multiport robotic-assisted thoracic surgery: a multicenter study of the European experience

Background: Robotic-assisted thoracic surgery (RATS) has seen increasing interest in the last few years, with most procedures primarily being performed in the conventional multiport manner. Our team has developed a new approach that has the potential to convert surgeons from uniportal video-assisted thoracic surgery (VATS) or open surgery to robotic-assisted surgery, uniportal-RATS (U-RATS). We aimed to evaluate the outcomes of one single incision, uniportal robotic-assisted thoracic surgery (U-RATS) against standard multiport RATS (M-RATS) with regards to safety, feasibility, surgical technique, immediate oncological result, postoperative recovery, and 30-day follow-up morbidity and mortality. Methods: We performed a large retrospective multi-institutional review of our prospectively curated database, including 101 consecutive U-RATS procedures performed from September 2021 to October 2022, in the European centers that our main surgeon operates in. We compared these cases to 101 consecutive M-RATS cases done by our colleagues in Barcelona between 2019 to 2022. Results: Both patient groups were similar with respect to demographics, smoking status and tumor size, but were significantly younger in the U-RATS group [M-RATS =69 (range, 39-81) years; U-RATS =63 years (range, 19-82) years; P<0.0001]. Most patients in both operative groups underwent resection of a primary non-small cell lung cancer (NSCLC) [M-RATS 96/101 (95%); U-RATS =60/101 (59%); P<0.0001]. The main type of anatomic resection was lobectomy for the multiport group, and segmentectomy for the U-RATS group. In the M-RATS group, only one anatomical segmentectomy was performed, while the U-RATS group had twenty-four (24%) segmentectomies (P=0.0006). All M-RATS and U-RATS surgical specimens had negative resection margins (R0) and contained an equivalent median number of lymph nodes available for pathologic analysis [M-RATS =11 (range, 5-54); U-RATS =15 (range, 0-41); P=0.87]. Conversion rate to thoracotomy was zero in the U-RATS group and low in M-RATS [M-RATS =2/101 (2%); U-RATS =0/101; P=0.19]. Median operative time was also statistically different [M-RATS =150 (range, 60-300) minutes; U-RATS =136 (range, 30-308) minutes; P=0.0001]. Median length of stay was significantly lower in U-RATS group at four days [M-RATS =5 (range, 2-31) days; U-RATS =4 (range, 1-18) days; P<0.0001]. Rate of complications and 30-day mortality was low in both groups. Conclusions: U-RATS is feasible and safe for anatomic lung resections and comparable to the multiport conventional approach regarding surgical outcomes. Given the similarity of the technique to uniportal VATS, it presents the potential to convert minimally invasive thoracic surgeons to a robotic-assisted approach

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe