Using ex vivo bioengineered lungs to model pathologies and screening therapeutics: A proof-of-concept study.

Respiratory diseases, claim over eight million lives annually. However, the transition from preclinical to clinical phases in research studies is often hindered, partly due to inadequate representation of preclinical models in clinical trials. To address this, we conducted a proof-of-concept study using an ex vivo model to identify lung pathologies and to screen therapeutics in a humanized rodent model. We extracted and decellularized mouse heart-lung tissues using a detergent-based technique. The lungs were then seeded and cultured with human cell lines (BEAS-2B, A549, and Calu3) for 6-10 days, representing healthy lungs, cancerous states, and congenital pathologies, respectively. By manipulating cultural conditions and leveraging the unique characteristics of the cell lines, we successfully modeled various pathologies, including advanced-stage solid tumors and the primary phase of SARS-CoV-2 infection. Validation was conducted through histology, immunofluorescence staining, and pathology analysis. Additionally, our study involved pathological screening of the efficacy and impact of key anti-neoplastic therapeutics (Cisplatin and Wogonin) in cancer models. The results highlight the versatility and strength of the ex vivo model in representing crucial lung pathologies and screening therapeutics during the preclinical phase. This approach holds promise for bridging the gap between preclinical and clinical research, aiding in the development of effective treatments for respiratory diseases, including lung cancer.

Association of childhood and adolescence obesity with incidence and mortality of adulthood cancers. A systematic review and meta-analysis.

Background: Prevalence and subsequent conditions of childhood and adolescent obesity are increasing. It has been seen that obesity in youth is associated with adulthood cancer. This systematic review and meta-analysis aimed to determine the pooled association of childhood obesity with cancers in adulthood. Methods: In this systematic review, international electronic databases such as Scopus, PubMed, Web of Science, and EMBASE were searched using relevant keywords until February 2022. All Cohort studies assessing the association of childhood and adolescent obesity (under 18 years old) with the incidence and mortality of all types of cancers were included. Two independent reviewers screened and carried out the quality assessment of included studies. Between-studies heterogeneity was assessed using the I squared and Cochran's Q tests. Random/fixed-effect meta-analyses were used to pool the appropriate effect sizes (Hazard ratios (HR)). Results: Overall, 46 studies were found to be relevant and were included in this study. Based on the random-effects model meta-analysis, childhood obesity increased the hazard of cancer incidence and mortality in adulthood by 33% (HR: 1.33, 95%CI (1.25, 1.41)) and by 28% (HR: 1.28, 95%CI (1.13, 1.42)), respectively. In the subgroups meta-analysis, the HR of childhood obesity and adulthood cancer incidence mortality in women was higher than in men (HR=1.39, 95%CI (1.25, 1.53) vs HR= 1.20, 95%CI (1.07, 1.32)) and (HR= 1.40, 95%CI (1.10, 1.69) vs HR=1.20, 95%CI (1.04, 1.36)) respectively. Conclusion: This study found that obesity in childhood and adolescence is associated with a significant increase in the incidence and mortality of cancers in adulthood. Prevention of childhood obesity, in addition to its short-term beneficial effects, can reduce the burden of cancer in adulthood. The data sets of this study are present in the Tables of the current manuscript. Moreover this study was registered online in PROSPERO (registration code: CRD42022331958). Systemic review registration: https://www.crd.york.ac.uk/Prospero/, identifier CRD42022331958.

Long-term full-scale intelligent quotient outcomes following pediatric and childhood epilepsy surgery: A systematic review and meta-analysis.

OBJECTIVE: Cognitive measures are an important primary outcome of pediatric, adolescents, and childhood epilepsy surgery. The purpose of this systematic review and meta-analysis is to assess whether there are long-term alterations (≥ 5 years) in the Full-Scale Intelligence Quotient (FSIQ) of pediatric patients undergoing epilepsy surgery. METHODS: Electronic databases (EMBASE, MEDLINE, and Scopus) were searched for English articles from inception to October 2022 that examined intelligence outcomes in pediatric epilepsy surgery patients. Inclusion criteria were defined as the patient sample size of ≥ 5, average follow- up of ≥5 years, and surgeries performed on individuals ≤ 18 years old at the time of surgery. Exclusion criteria consisted of palliative surgery, animal studies, and studies not reporting surgical or FSIQ outcomes. Publication bias was assessed using a funnel plot and the Quality in Prognosis Studies (QUIPS) toolset was used for quality appraisal of the selected articles. A random-effects network meta-analysis was performed to compare FSIQ between surgical patients at baseline and follow-up and Mean Difference (MD) was used to calculate the effect size of each study. Point estimates for effects and 95% confidence intervals for moderation analysis were performed on variables putatively associated with the effect size. RESULTS: 21,408 studies were screened for abstract and title. Of these, 797 fit our inclusion and exclusion criteria and proceeded to full-text screening. Overall, seven studies met our requirements and were selected. Quantitative analysis was performed on these studies (N = 330). The mean long-term difference between pre- and post- operative FSIQ scores across all studies was noted at 3.36 [95% CI: (0.14, 6.57), p = 0.04, I2 = 0%] and heterogeneity was low. CONCLUSION: To our knowledge, this is the first meta-analysis to measure the long-term impacts of FSIQ in pediatric and adolescent epilepsy patients. Our overall results in this meta-analysis indicate that while most studies do not show long-term FSIQ deterioration in pediatric patients who underwent epilepsy surgery, there was an increase of 3.36 FSIQ points, however, the observed changes were not clinically significant. Moreover, at the individual patient level analysis, while most children did not show long-term FSIQ deterioration, few had significant decline. These findings indicate the importance of surgery as a viable option for pediatric patients with medically refractory epilepsy.

Bilateral Central Retinal Vein Occlusion and Stevens-Johnson Syndrome Associated with Coronavirus-19: A Case Report.

Purpose: To report a case of bilateral central retinal vein occlusion (CRVO) associated with coronavirus-19 (COVID-19) infection. Methods: A 43-year-old man presented to the emergency department with flu-like symptoms, severe erythema, a rash on his face, and respiratory distress. He was admitted to the intensive care unit, and the reverse transcriptase-polymerase chain reaction test was positive for the severe acute respiratory syndrome coronavirus-2 virus. The routine blood work was unremarkable. The dermatologist noted positive Nikolsky's sign, and the patient was diagnosed with Stevens-Johnson syndrome (SJS), which affected 18% of his body and was later confirmed by skin biopsy. Later, he reported worsening vision. Results: Ophthalmic examination and fundus fluorescein angiography showed bilateral CRVO. Despite best medical efforts, including treatment with systemic dexamethasone and remdesivir, the patient died on the 6 days of his hospitalization. Conclusion: This was a rare bilateral CRVO and SJS case in a young patient, probably caused by the COVID-19 infection.

Strategies to overcome the side effects of chimeric antigen receptor T cell therapy.

Chimeric antigen receptor (CAR) therapy is a method directing T lymphocytes against antigens on the surface of tumors, increasing target cell elimination. Genetic engineering enhances the capability of immune cells to detect new antigens expressed on cell surfaces. CAR T cell therapy is a significant breakthrough for treating human malignancies; however, different side effects (e.g., cytokine release syndrome) restrict its application. Improving design and using various combined receptors enhance the performance of these cells. This review discusses limitations and risk factors associated with CAR T cell therapy. We also review some alternative approaches for developing the next generation of CAR T cells.