Cardiac surgery and acute hepatitis B - Use of the Seraph™ 100 hemofilter.

We present a case of a 55-year-old male, presenting with angina symptoms with electrocardiographic changes and a panfocal systolic murmur radiating to the carotids. He had a primary HBV infection 8 months ago, without antiviral treatment. Echocardiography showed critical aortic valve stenosis (area: 0.53 cm2/m2). No coronary lesions were found on coronary angiography. Blood analysis revealed AST/GOT of 96 U/L and ALT/GPT 150 U/L. The serological profile revealed positive IgM anti-HBc, anti-HBc, anti-HBs and anti-HBe antibodies, with an increasing viral load (VL). The abdominal ultrasound identified mild hepatic fibrosis (F3) with minimal steatosis. Mechanical aortic prosthetic valve replacement was performed under CPB. The Seraph™ 100 filter was incorporated into the CPB circuit to reduce the risk of HBV contamination, infection and liver failure. The postoperative VL was monitored (Table 1). Liver function tests showed peak levels of bilirubin 0.66 mg/dL, AST/GOT 58 U/L, ALT/GPT 74 U/L at 6 hours post-surgery, with recovery of normal ranges at 48 hours post-surgery.

Development and validation of a self-attention network-based algorithm to detect mediastinal lesions on computed tomography images.

Background: Diagnosis of mediastinal lesions on computed tomography (CT) images is challenging for radiologists, as numerous conditions can present as mass-like lesions at this site. This study aimed to develop a self-attention network-based algorithm to detect mediastinal lesions on CT images and to evaluate its efficacy in lesion detection. Methods: In this study, two separate large-scale open datasets [National Institutes of Health (NIH) DeepLesion and Medical Image Computing and Computer Assisted Intervention (MICCAI) 2022 Mediastinal Lesion Analysis (MELA) Challenge] were collected to develop a self-attention network-based algorithm for mediastinal lesion detection. We enrolled 921 abnormal CT images from the NIH DeepLesion dataset into the pretraining stage and 880 abnormal CT images from the MELA Challenge dataset into the model training and validation stages in a ratio of 8:2 at the patient level. The average precision (AP) and confidence score on lesion detection were evaluated in the validation set. Sensitivity to lesion detection was compared between the faster region-based convolutional neural network (R-CNN) model and the proposed model. Results: The proposed model achieved an 89.3% AP score in mediastinal lesion detection and could identify comparably large lesions with a high confidence score >0.8. Moreover, the proposed model achieved a performance boost of almost 2% in the competition performance metric (CPM) compared to the faster R-CNN model. In addition, the proposed model can ensure an outstanding sensitivity with a relatively low false-positive rate by setting appropriate threshold values. Conclusions: The proposed model showed excellent performance in detecting mediastinal lesions on CT. Thus, it can drastically reduce radiologists' workload, improve their performance, and speed up the reporting time in everyday clinical practice.

Promising anti-proliferative indolic benzenesulfonamides alter mechanisms with sulfonamide nitrogen substituents.

Agents that cause apoptotic cell death by interfering with tubulin dynamics, such as vinblastine and paclitaxel, are an important class of chemotherapeutics. Unfortunately, these compounds are substrates for multidrug resistance (MDR) pumps, allowing cancer cells to gain resistance to these chemotherapeutics. The indolesulfonamide family of tubulin inhibitors are not excluded by MDR pumps and have a promising activity profile, although their high lipophilicity is a pharmacokinetic limitation for their clinical use. Here we present a new family of N-indolyl-3,4,5-trimethoxybenzenesulfonamide derivatives with modifications on the indole system at positions 1 and 3 and on the sulfonamide nitrogen. We synthesized and screened against HeLa cells 34 novel indolic benzenesulfonamides. The most potent derivatives (1.7-109 nM) were tested against a broad panel of cancer cell lines, which revealed that substituted benzenesulfonamides analogs had highest potency. Importantly, these compounds were only moderately toxic to non-tumorigenic cells, suggesting the presence of a therapeutic index. Consistent with known clinical anti-tubulin agents, these compounds arrested the cell cycle at G2/M phase. Mechanistically, they induced apoptosis via caspase 3/7 activation, which occurred during M arrest. The substituents on the sulfonamide nitrogen appeared to determine different mechanistic results and cell fates. These results suggest that the compounds act differently depending on the bridge substituents, thus making them very interesting as mechanistic probes as well as potential drugs for further development.

Advances in Immunotherapy for Malignant Pleural Mesothelioma: From Emerging Strategies to Translational Insights.

MPM stands as a rare malignancy necessitating improved therapeutic strategies due to its limited treatment choices and unfavorable prognosis. The advent of immune checkpoint inhibitors has heralded a paradigm shift in the therapeutic landscape of MPM, offering promising avenues across diverse clinical scenarios. In the context of advanced stages of the disease, Immune check-point inhibitors targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-as-sociated protein 4 (CTLA-4), have exhibited encouraging potential in clinical trials, particularly manifesting efficacy among patients exhibiting disease progression following chemotherapy regimens. Innovative combination regimens, exemplified by the concurrent administration of nivolumab and ipilimumab, have demonstrated marked improvement in survival and patient's benefits. A deeper comprehension of the intricate genetic underpinnings of MPM, encompassing key mutations such as cyclin-dependent kinase inhibitor 2A (CDKN2A), neurofibromin 2 (NF2), and BRCA1-associated protein 1 (BAP1) mutations, has elucidated novel avenues for targeted therapeutic interventions. This review accentuates the transformative capacity of immunotherapy in revolutionizing the therapeutic outlook for MPM, thereby potentially translating into augmented survival rates and offering glimpses of new approaches on the horizon. Despite the persisting challenges, the synergistic crossroads of interdisciplinary research and collaborative clinical endeavors portend a hopeful landscape for MPM treatment.

El mesotelioma pleural maligno (MPM) es una neoplasia poco frecuente que requiere una mejora de las estrategias terapéuticas debido a sus limitadas opciones de tratamiento y a su pronóstico desfavorable. La llegada de los inhibidores de los puntos de control inmunitario ha supuesto un cambio de paradigma en el panorama terapéutico del MPM, ofreciendo vías prometedoras en diversos escenarios clínicos. En el contexto de los estadios avanzados de la enfermedad, los inhibidores de puntos de control inmunitario dirigidos contra la proteína de muerte celular programada 1 (PD-1) y la proteína 4 asociada a los linfocitos T citotóxicos (CTLA-4) han mostrado un potencial alentador en los ensayos clínicos, sobre todo por su eficacia en los pacientes con progresión de la enfermedad tras los regímenes de quimioterapia. Los regímenes combinados innovadores, ejemplificados por la administración concurrente de nivolumab e ipilimumab, han demostrado una mejora significativa de la supervivencia y de los beneficios para los pacientes. Una comprensión más profunda de los complejos fundamentos genéticos del MPM, que abarca mutaciones clave como el inhibidor de la cinasa dependiente de ciclina 2A (CDKN2A), la neurofibromina 2 (NF2) y las mutaciones de la proteína 1 asociada a BRCA1 (BAP1), ha dilucidado nuevas vías para el desarrollo de intervenciones terapéuticas dirigidas. Esta revisión acentúa la capacidad transformadora de la inmunoterapia para revolucionar las perspectivas terapéuticas en el MPM, lo que podría traducirse en un aumento de las tasas de supervivencia y ofrecer nuevos enfoques terapéuticos en el horizonte próximo. A pesar de los retos persistentes, el cruce sinérgico de la investigación interdisciplinar y los esfuerzos clínicos de colaboración auguran un panorama esperanzador en el tratamiento de los MPM.

Impact of radiological follow-up frequency on resected lung cancer: a propensity score matching analysis.

Background: Despite advances in lung cancer treatment and the subsequent improvement in oncological outcomes, the optimal frequency of radiological follow-up remains unclear. Current recommendations lack consensus and do not consider individual patient characteristics and tumor factors. This study aimed to examine the impact of radiological follow-up frequency on oncological outcomes following lung cancer resection. Methods: A prospective multicenter study, involving patients who underwent anatomical lung resection in the GEVATS database between December 2016 and March 2018. The relationship between surveillance frequency and oncological outcomes was evaluated. Two groups were established based on follow-up frequency: low frequency (LF) and high frequency (HF). Subgroup analyses were performed based on tumor stage, histology, lymphadenectomy, and adjuvant therapy. Propensity score matching (PSM) was applied to balance the groups. Results: A total of 1,916 patients were included in the study, LF 444 (23.17%), HF 1,472 (76.83%). Factors associated with HF surveillance included higher stage, adjuvant chemotherapy and adjuvant radiotherapy. Subanalyses were performed after PSM for various factors, revealing significant differences between LF and HF groups in cancer-specific survival among who received adjuvant therapy {LF 53.021 months [95% confidence interval (CI): 48.622-57.421] vs. HF 58.836 months (95% CI: 55.343-62.330); HR 0.453, 95% CI: 0.242-0.849; P=0.013}, as well as overall survival for patients with squamous cell carcinoma [LF 54.394 months (95% CI: 51.424-57.364) vs. HF 61.578 months (95% CI: 59.091-64.065); HR 0.491, 95% CI: 0.299-0.806; P=0.005] and those who received adjuvant therapy LF 50.176 months [95% CI: 45.609-54.742) vs. HF 57.189 months (95% CI: 53.599-60.778); HR 0.503, 95% CI: 0.293-0.865; P=0.013]. Conclusions: Findings suggest that high-frequency surveillance only improves survival outcomes in lung cancer patients who received adjuvant treatment or had squamous cell carcinoma. Therefore, future guidelines for lung cancer follow-up should consider individualizing the frequency of radiological surveillance based on patients' risk profiles.

Computing tools for effective field theories: SMEFT-Tools 2022 Workshop Report, 14-16th September 2022, Zürich.

In recent years, theoretical and phenomenological studies with effective field theories have become a trending and prolific line of research in the field of high-energy physics. In order to discuss present and future prospects concerning automated tools in this field, the SMEFT-Tools 2022 workshop was held at the University of Zurich from 14th-16th September 2022. The current document collects and summarizes the content of this workshop.

A proof of concept for matchete: an automated tool for matching effective theories.

Studying the impact of new-physics models on low-energy observables necessitates matching to effective field theories at the relevant mass thresholds. We introduce the first public version of Matchete, a computer tool for matching weakly-coupled models at one-loop order. It uses functional methods to directly compute all matching contributions in a manifestly gauge-covariant manner, while simplification methods eliminate redundant operators from the output. We sketch the workings of the program and provide examples of how to match simple Standard Model extensions. The package, documentation, and example notebooks are publicly available at https://gitlab.com/matchete/matchete.

[Questions and Answers in Lung Cancer]. / Preguntas y respuestas en cáncer de pulmón.

Over the past 2 decades, scientific evidence has strongly supported the use of low-radiation dose chest computed tomography (CT) as a screening technique for lung cancer. This approach has resulted in a significant reduction in mortality rates by enabling the detection of early-stage lung cancer amenable to potentially curative treatments. Regarding diagnosis, there are also novel methods under study, such as liquid biopsy, identification of the pulmonary microbiome, and the use of artificial intelligence techniques, which will play a key role in the near future. At present, there is a growing trend towards less invasive surgical procedures, such as segmentectomy, as an alternative to lobectomy. This procedure is based on 2 recent clinical trials conducted on peripheral tumors measuring less than 2 cm. Although these approaches have demonstrated comparable survival rates, there remains controversy due to uncertainties surrounding recurrence rates and functional capacity preservation. With regard to adjuvant therapy, immunotherapy, either as a monotherapy or in conjunction with chemotherapy, has shown encouraging results in resectable stages of locally advanced lung cancer, demonstrating complete pathologic responses and improved overall survival.After surgery treatment, despite the lack of solid evidence for long-term follow-up of these patients, clinical practice recommends periodic CT scans during the early years.In conclusion, there have been significant advances in lung cancer that have improved diagnostic techniques using new technologies and screening programs. Furthermore, the treatment of lung cancer is increasingly personalized, resulting in an improvement in the survival of patients.

Outcomes of Surgery for Metachronous Second Primary Non-small Cell Lung Cancer.

OBJECTIVE: The optimal surgical approach for second primary metachronous lung cancer (MPLC) remains unclear. Our aim is to evaluate the morbidity and prognostic value based on the extent of surgical resection in MPLC. METHODS: Retrospective study of 84 patients with a history of anatomical resection for lung cancer and MPLC surgically treated between January 2010 and December 2020. RESULTS: The interval between the initial primary tumor and the second was 50.38±32.89 months. The second resection was contralateral in 43 patients (51.2%) and ipsilateral in 41 (48.8%). Thirty-six patients (42.9%) underwent a second anatomical resection, and in 48 patients (57.1%), it was non-anatomical. Postoperative complications were observed in 29 patients (34.5%) after the second lung resection. According to the Clavien-Dindo classification, 95.2% were mild (Clavien-Dindo I-II), and a single patient died (1.2%) in the postoperative period (Grade V). Prolonged air leak (p=0.037), postoperative arrhythmias (p=0.019) and hospital stay showed significant differences depending on the extent of surgery in ipsilateral resections. The main histological type was adenocarcinoma (47.6%) and the median tumor size was 17.74±11.74mm. The overall survival was 58.07 months (95% CI 49.29-66.85) for patients undergoing anatomical resection and 50.97 months (95% CI 43.31-58.63) for non-anatomical without significant differences (p=0.144). The disease-free survival after the second surgery was 53.75 months (95% CI 45.28-62.23) for anatomical resection and 41.34 months (95% CI 33.04-49.65) for non-anatomical group. CONCLUSION: Second anatomical resections provide good long-term outcomes and have been shown to provide better disease-free survival compared to non-anatomical resections in properly selected patients.

Acute Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The Good, the Bad, and the Ugly of Isolated Extramedullary Relapse in a Latin American Population.

Hematopoietic stem cell transplantation (HSCT) is an effective therapy for acute leukemia (AL). Relapse represents the main cause of mortality. Isolated extramedullary relapse (iEMR) is atypical and has been related to better outcomes. Here we describe the clinical characteristics and outcomes of AL relapse after HSCT in our study population and analyze the impacts of different types of relapse on survival outcomes. This retrospective, multicenter study included 124 patients age ≥15 years with AL who underwent HSCT between 2004 and 2019. At diagnosis, 66.1% of the patients had lymphocytic AL, 19.7% presented with high-risk features, and 18.5% had extramedullary disease (EMD). At HSCT, 83.1% of the patients were in complete remission (CR), and 44.8% had negative measurable residual disease (MRD). The vast majority of donors were related (96%), including 48.4% HLA-matched and 47.6% haploidentical. Myeloablative conditioning was provided to 80.6% of patients. The median overall survival (OS) was 15 months (95% confidence interval [CI] 9.9 to 20.1 months). Factors associated with improved OS were adolescent and young adult (AYA) patient (P = .035), first or second CR (P = .026), and chronic graft-versus-host disease (GVHD) (P < .001). Acute GVHD grade III-IV (P = .009) was associated with increased mortality. The median relapse-free survival was 13 months (95% CI, 7.17 to 18.8 months); early disease status (P = .017) and chronic GVHD (P < .001) had protective roles. Sixty-eight patients (55%) relapsed after HSCT, with a median time to relapse of 6 months (95% CI, 3.6 to 8.4 months). iEMR was reported in 16 patients (23.5%). The most commonly involved extramedullary sites were the central nervous system and skin. Compared to patients with bone marrow relapse, all patients with iEMR had a diagnosis of acute lymphoid leukemia (P = .008), and 93.8% belonged to the AYA group; regarding pre-HSCT characteristics, iEMR patients had higher rates of negative MRD (P = .06) and a history of EMD (P = .009). Seventy-seven percent of relapsed patients received additional treatment with curative intent. The median OS after relapse (OSr) was 4 months (95% CI, 2.6 to 5.4 months). Factors related to increased OSr included lymphoid phenotype (P = .03), iEMR (P = .0042), late relapse (≥6 months) (P = .014), receipt of systemic therapy including second HSCT (P < .001), and response to therapy (P < .001). Rates of relapse and iEMR were higher than those previously reported in other studies. Advanced disease, reduced-intensity conditioning, and a diminished graft-versus-leukemia effect were factors influencing these findings. At relapse, presenting with iEMR after 6 months and receiving intensive therapy with adequate response were associated with better outcomes. Our results strongly suggest that a personalized approach to treating patients with HSCT is needed to counterbalance specific adverse factors and can positively impact clinical outcomes.

Nutritional counseling for cow's milk protein allergy in infants from birth to 2 y of ages: Scoping review.

OBJECTIVES: Cow's milk protein allergy (CMPA) is a clinical condition that requires appropriate nutritional counseling during breastfeeding and the introduction of complementary feeding. Using evidence-based dietetic advice is critical for correct growth and development during childhood. The aim of this study was to review the most recent literature on nutritional counseling aimed at infants between 0 and 2 y of age diagnosed with CMPA. METHODS: Six databases were searched and updated on August 22, 2020. Retrieved articles were screened in duplicate and independently by all the authors, and these were selected according to the following inclusion criteria: clinical trials, reviews, meta-analyses, and clinical practice guidelines published since 2013 on any dietetic intervention aimed at infant populations between 0 and 2 y of age with CMPA. Critical appraisal through the AGREE instrument and CASP tools enabled the risk of bias assessment. RESULTS: We obtained 2874 results, of which 40 were included for reviewing. The retrieved information enabled us to answer all the research questions, including aspects of the nutritional counseling aimed at mothers who breastfeed infants with CMPA, as well as infants during breastfeeding and the introduction of complementary feeding. We also reviewed the specific nutritional requirements of infants with CMPA to assess nutritional supplementation and the evidence available on the use of probiotics, prebiotics, and symbiotics. CONCLUSIONS: This scoping review collected, in a structured and comprehensive way, the most recent available information regarding nutritional counseling in CMPA for a successful dietetic intervention of the casuistry that may arise during early infancy.

Pilot randomised controlled trial of a patient navigation intervention to enhance engagement in the PrEP continuum among young Latino MSM: a protocol paper.

INTRODUCTION: Men who have sex with men (MSM) are one of the most at-risk group for contracting HIV in the USA. However, the HIV epidemic impacts some groups of MSM disproportionately. Latino MSM comprise 25.1% of new HIV infections among MSM between the ages of 13 and 29 years. The daily medication tenofovir/emtricitabine was approved by the Food and Drug Administration for pre-exposure prophylaxis (PrEP) in 2012 and has demonstrated strong efficacy in reducing HIV acquisition. METHODS AND ANALYSIS: Through extensive formative research, this study uses a pilot randomised controlled trial design and will examine the feasibility and acceptability of a patient navigation intervention designed to address multiple barriers to improve engagement in the PrEP continuum among 60 Latino MSM between the ages of 18 and 29 years. The patient navigation intervention will be compared with usual care plus written information to evaluate the feasibility and acceptability of the intervention and study methods and the intervention's potential in improving PrEP continuum behaviours. The results will be reviewed for preparation for a future full-scale efficacy trial. ETHICS AND DISSEMINATION: This study was approved by the institutional review board at San Diego State University and is registered at ClinicalTrials.gov. The intervention development process, plan and the results of this study will be shared through peer-reviewed journal publications, conference presentations and healthcare system and community presentations. REGISTRATION DETAILS: Registered under the National Institutes of Health's ClinicalTrials.gov (NCT04048382) on 7 August 2019 and approved by the San Diego State University (HS-2017-0187) institutional review board. This study began on 5 August 2019 and is estimated to continue through 31 March 2021. The clinical trial is in the pre-results stage.