Diagnosis and management of patients with stage III non­small cell lung cancer: A joint statement by the Lebanese Society of Medical Oncology and the Lebanese Pulmonary Society (Review).

Proper management of stage III non-small cell lung cancer (NSCLC) might result in a cure or patient long-term survival. Management should therefore be preceded by adequate and accurate diagnosis and staging, which will inform therapeutic decisions. A panel of oncologists, surgeons and pulmonologists in Lebanon convened to establish a set of recommendations to guide and unify clinical practice, in alignment with international standards of care. Whilst chest computerized tomography (CT) scanning remains a cornerstone in the discovery of a lung lesion, a positron-emission tomography (PET)/CT scan and a tumor biopsy allows for staging of the cancer and defining the resectability of the tumor(s). A multidisciplinary discussion meeting is currently widely advised for evaluating patients on a case-by-case basis, and should include at least the treating oncologist, a thoracic surgeon, a radiation oncologist and a pulmonologist, in addition to physicians from other specialties as needed. The standard of care for unresectable stage III NSCLC is concurrent chemotherapy and radiation therapy, followed by consolidation therapy with durvalumab, which should be initiated within 42 days of the last radiation dose; for resectable tumors, neoadjuvant therapy followed by surgical resection is recommended. This joint statement is based on the expertise of the physician panel, available literature and evidence governing the treatment, management and follow-up of patients with stage III NSCLC.

Genetic interactions of schizophrenia using gene-based statistical epistasis exclusively identify nervous system-related pathways and key hub genes.

Background: The relationship between genotype and phenotype is governed by numerous genetic interactions (GIs), and the mapping of GI networks is of interest for two main reasons: 1) By modelling biological robustness, GIs provide a powerful opportunity to infer compensatory biological mechanisms via the identification of functional relationships between genes, which is of interest for biological discovery and translational research. Biological systems have evolved to compensate for genetic (i.e., variations and mutations) and environmental (i.e., drug efficacy) perturbations by exploiting compensatory relationships between genes, pathways and biological processes; 2) GI facilitates the identification of the direction (alleviating or aggravating interactions) and magnitude of epistatic interactions that influence the phenotypic outcome. The generation of GIs for human diseases is impossible using experimental biology approaches such as systematic deletion analysis. Moreover, the generation of disease-specific GIs has never been undertaken in humans. Methods: We used our Indian schizophrenia case-control (case-816, controls-900) genetic dataset to implement the workflow. Standard GWAS sample quality control procedure was followed. We used the imputed genetic data to increase the SNP coverage to analyse epistatic interactions across the genome comprehensively. Using the odds ratio (OR), we identified the GIs that increase or decrease the risk of a disease phenotype. The SNP-based epistatic results were transformed into gene-based epistatic results. Results: We have developed a novel approach by conducting gene-based statistical epistatic analysis using an Indian schizophrenia case-control genetic dataset and transforming these results to infer GIs that increase the risk of schizophrenia. There were ∼9.5 million GIs with a p-value ≤ 1 × 10-5. Approximately 4.8 million GIs showed an increased risk (OR > 1.0), while ∼4.75 million GIs had a decreased risk (OR <1.0) for schizophrenia. Conclusion: Unlike model organisms, this approach is specifically viable in humans due to the availability of abundant disease-specific genome-wide genotype datasets. The study exclusively identified brain/nervous system-related processes, affirming the findings. This computational approach fills a critical gap by generating practically non-existent heritable disease-specific human GIs from human genetic data. These novel datasets can train innovative deep-learning models, potentially surpassing the limitations of conventional GWAS.

Comparative Genomics Supports That Brazilian Bioethanol Saccharomyces cerevisiae Comprise a Unified Group of Domesticated Strains Related to Cachaça Spirit Yeasts.

Ethanol production from sugarcane is a key renewable fuel industry in Brazil. Major drivers of this alcoholic fermentation are Saccharomyces cerevisiae strains that originally were contaminants to the system and yet prevail in the industrial process. Here we present newly sequenced genomes (using Illumina short-read and PacBio long-read data) of two monosporic isolates (H3 and H4) of the S. cerevisiae PE-2, a predominant bioethanol strain in Brazil. The assembled genomes of H3 and H4, together with 42 draft genomes of sugarcane-fermenting (fuel ethanol plus cachaça) strains, were compared against those of the reference S288C and diverse S. cerevisiae. All genomes of bioethanol yeasts have amplified SNO2(3)/SNZ2(3) gene clusters for vitamin B1/B6 biosynthesis, and display ubiquitous presence of a particular family of SAM-dependent methyl transferases, rare in S. cerevisiae. Widespread amplifications of quinone oxidoreductases YCR102C/YLR460C/YNL134C, and the structural or punctual variations among aquaporins and components of the iron homeostasis system, likely represent adaptations to industrial fermentation. Interesting is the pervasive presence among the bioethanol/cachaça strains of a five-gene cluster (Region B) that is a known phylogenetic signature of European wine yeasts. Combining genomes of H3, H4, and 195 yeast strains, we comprehensively assessed whole-genome phylogeny of these taxa using an alignment-free approach. The 197-genome phylogeny substantiates that bioethanol yeasts are monophyletic and closely related to the cachaça and wine strains. Our results support the hypothesis that biofuel-producing yeasts in Brazil may have been co-opted from a pool of yeasts that were pre-adapted to alcoholic fermentation of sugarcane for the distillation of cachaça spirit, which historically is a much older industry than the large-scale fuel ethanol production.

Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer.

Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplatin on day 1 and gemcitabine on days 1 and 8 of each cycle of chemotherapy. Patients with nonsquamous histology received cisplatin or carboplatin with pemetrexed on day 1 of each cycle. Patients then proceeded to their planned surgery. Out of 15 patients accrued as part of stage 1 of the study, four had a radiologic response (1 complete response), lower than the minimum of six responses needed to continue to phase 2 of the study. The study was therefore terminated. Majority had adenocarcinoma histology and stage IIIA disease. The treatment was well tolerated with no unexpected side effects. Four patients (26.7%) had grade III/IV CTCAE toxicity. This study confirms that the preoperative administration of chemotherapy and avelumab is safe. There was no indication of increased surgical complications. The benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint.

Unique Presentation and Management Approach of Pleural Solitary Fibrous Tumor.

Solitary fibrous tumor (SFT) of the pleura is an uncommon tumor that is often discovered incidentally on a routine chest X-ray. We report a case of a young female with a large, sessile, hypervascularized SFT of the pleura presenting with cardiopulmonary shock to a rural hospital with limited therapeutic interventions. We propose, in this case report, a unique multidisciplinary approach for the management of such a critical patient and the safe resection of the tumor.

Salmonella typhi sternal wound infection.

Samonella typhi usually causes gastrointestinal infections. Few reports in the literature described skin and soft tissue infections related to Salmonella species, especially in immunocompetent patients. Our case exhibited sternal abscess growing Salmonella typhi.

Unusual case of difficult double-lumen endotracheal tube removal.

A reusable Robertshaw red rubber double-lumen endotracheal tube (DLT) was placed to facilitate lung isolation for thoracoscopy in a 49-year-old atopic patient. In spite of its smooth insertion, it was then not possible to remove the DLT. Direct laryngoscopy showed severe laryngeal edema. After 48 hours of medical treatment with steroids, the trachea was extubated. The laryngeal edema could have been the result of physical and chemical irritation by the reusable rubber DLT itself, or from the substances formed during repeated cleaning and sterilization of the DLT. Atopic patients who are prone to developing latex allergy are also more liable to develop severe reactions to chemical, mechanical, and physical irritation from reusable red rubber DLTs or from the chemical solution used for its cleaning and sterilization.

[Giant mediastinal cystic lymphangioma: clinical case and review of the literature]. / Lymphangiome kystique médiastinal géant. Un cas clinique et revue de la littérature.

Benign cystic lymphangioma is a relatively rare tumor of the human body. It's more frequent in young patients. It is usually localized in the neck but may have mediastinal or intra-abdominal localization. It's usually asymptomatic with good prognosis after total excision. We report in this article the case of a young man with a huge mediastinal cystic lymphangioma which was successfully operated and a review of the literature.

Current concepts in gastric cancer surgery.

OBJECTIVE: Current problems in gastric cancer surgery concern the extent of gastric resection, the need for abdominal evisceration, the degree of lymphadenectomy, and an optimal preoperative tumor staging procedure. METHODS: A retrospective clinical trial of 284 patients who underwent surgery at Ernst-Moritz-Arndt-University, Greifswald, Germany for gastric cancer between 1987 and 1996. Main outcome measures consist of epidemiological parameters, data on type of surgery, histopathology, postoperative complications, mortality and cancer survival. Statistical analysis between groups was performed using Chi square test (perioperative risk factors, tumor localization, and surgical treatment) and Mann Whitney U tests (Lauren classification). Survival was calculated according to the Kaplan Meier method. RESULTS: The results are in favor of subtotal gastrectomy performed for all T stages located in the distal or middle 3rd provided that a tumor-free margin of 5 cm in intestinal type and 10 cm in diffuse Lauren's type tumor can be achieved, since this operation carries the lowest postoperative risks and provides the best postoperative quality of life. Resection of adjacent organs are indicated only if they are invaded by the primary tumor (T4). They should not be resected as part of an extended lymphadenectomy procedure. The primary tumor site should guide the degree of lymph node removal. Multimodal therapeutic approaches and high postoperative morbidity and mortality after exploratory laparotomy justify the use of diagnostic laparoscopy in T3 and T4 stage tumors and if diagnostic scans suggest tumor spread. CONCLUSION: Even though surgery for gastric cancer is well standardized, a tailored surgical approach to different extents of gastric cancer appears justified.