Evaluation of the response rate of chemo-radiation and brachytherapy in patients with locally advanced carcinoma cervix in a tertiary care center

Background: Incidence and mortality estimates are used to measure the burden of cancer in a population and survival estimates are ideal for evaluating the outcome of cancer control activities. Survival studies evaluate the quality and quantity of life of a group of patients after diagnosing the disease. The patient survival after the diagnosis of cervical cancer is indirectly influenced by socio-economic factors. The present study was carried out with an aim to evaluate the success rate of chemo-radiation followed by brachytherapy to the patients of locally advanced carcinoma (Ca.) cervix in a tertiary care center.Methods: All cases were staged according to the International Federation of Gynaecologists and Oncologists (FIGO) staging system. To illustrate the observed survival of cancer patients Kaplan-Meier curve was plotted. All the patients, except one, completed chemo-radiation and were retrospectively analyzed for the presence of local residual disease, local recurrence, distant metastases, radiation reactions, disease-free survival, and overall survival.Results: There were 22 patients of Carcinoma cervix reported in the radiation oncology department in the year 2018 and 2019. The overall treatment time ranged from 30 days to 178 days, with a median of 63 days. All the patients had a complete response after the treatment. The median follow-up time for all the patients was 15 months. Three patients had a metastatic recurrence and one patient developed distant metastases as well as local recurrence. Overall survival rate was 100% while the disease-free survival rate was 81.82%.Conclusions: The response to chemo-radiation in the treatment of locally advanced Carcinoma cervix is comparable to historic data and is well tolerated

Extracorporeal membrane oxygenation in severe influenza infection with respiratory failure: A systematic review and meta-analysis

Introduction: Extracorporeal membrane oxygenation (ECMO) has been extensively used for potentially reversible acute respiratory failure associated with severe influenza A (H1N1) pneumonia; however, it remains an expensive, resource-intensive therapy, with a high associated mortality. This systematic review and meta-analysis aims to summarize and pool outcomes data available in the published literature to guide clinical decision-making and further research. Methods: We conducted a systematic search of MEDLINE (1966 to April 15, 2015), EMBASE (1980 to April 15, 2015), CENTRAL, and Google Scholar for patients with severe H1N1 pneumonia and respiratory failure who received ECMO. The study validity was appraised by Newcastle-Ottawa Scale. The primary outcome was all-cause mortality. The secondary outcomes were duration of ECMO therapy, mechanical ventilation, and Intensive Care Unit (ICU) length of stay. Results: Of 698 abstracts screened and 142 full-text articles reviewed, we included 13 studies with a total of 494 patients receiving ECMO in our final review and meta-analysis. The study validity was satisfactory. The overall mortality was 37.1% (95% confidence interval: 30-45%) limited by underlying heterogeneity (I2 = 65%, P value of Q statistic = 0.006). The median duration for ECMO was 10 days, mechanical ventilation was 19 days, and ICU length of stay was 33 days. Exploratory meta-regression did not identify any statistically significant moderator of mortality (P < 0.05), except for the duration of pre-ECMO mechanical ventilation in days (coefficient 0.19, standard error: 0.09, Z = 2.01, P < 0.04, R2 = 0.16). The visual inspection of funnel plots did not suggest the presence of publication bias. Conclusions: ECMO therapy may be used as an adjunct or salvage therapy for severe H1N1 pneumonia with respiratory failure. It is associated with a prolonged duration of ventilator support, ICU length of stay, and high mortality. Initiating ECMO early once the patient has been instituted on mechanical ventilation may result in improved survival

Effect of antiplatelet therapy on mortality and acute lung injury in critically ill patients: A systematic review and meta-analysis

Aim: Platelet function is intricately linked to the pathophysiology of critical Illness, and some studies have shown that antiplatelet therapy (APT) may decrease mortality and incidence of acute respiratory distress syndrome (ARDS) in these patients. Our objective was to understand the efficacy of APT by conducting a meta-analysis. Materials and Methods: We conducted a meta-analysis using PubMed, Central, Embase, The Cochrane Central Register, the ClinicalTrials.gov Website, and Google Scholar. Studies were included if they investigated critically ill patients receiving antiplatelet therapy and mentioned the outcomes being studied (mortality, duration of hospitalization, ARDS, and need for mechanical ventilation). Results: We found that there was a significant reduction in all-cause mortality in patients on APT compared to control (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.70–0.97). Both the incidence of acute lung injury/ARDS (OR: 0.67; 95% CI: 0.57–0.78) and need for mechanical ventilation (OR: 0.74; 95% CI: 0.60–0.91) were lower in the antiplatelet group. No significant difference in duration of hospitalization was observed between the two groups (standardized mean difference: −0.02; 95% CI: −0.11–0.07). Conclusion: Our meta-analysis suggests that critically ill patients who are on APT have an improved survival, decreased incidence of ARDS, and decreased need for mechanical ventilation

Tri- modality therapy in advanced esophageal carcinoma: long- term results and insights from a developing world, institutional cohort

Objective: To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). Methods: Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. Results: The median OS was 71.4 months (interquartile range: 19.6–∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89–0.98); 0.94 (0.89–0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09–0.53); 0.30 (0.12–0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01–1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08–6.57)] and adventitial involvement [2.54 (1.36–4.72)] also influenced OS, while involved margins [3.12 (1.24–7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44–0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57–0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the periesophageal and perigastric (greater and lesser curvature) regions, respectively. Conclusion: NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. Advances in knowledge: The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS

N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction.

BACKGROUND: Recent evidence suggests a role for lung microbiome in occurrence of chronic lung allograft dysfunction (CLAD). However, the mechanisms linking the microbiome to CLAD are poorly delineated. We investigated a possible mechanism involved in microbial modulation of mucosal response leading to CLAD with the hypothesis that a Proteobacteria dominant lung microbiome would inhibit N-myc-interactor (NMI) expression and induce epithelial to mesenchymal transition (EMT). METHODS: Explant CLAD, non-CLAD, and healthy nontransplant lung tissue were collected, as well as bronchoalveolar lavage from 14 CLAD and matched non-CLAD subjects, which were followed by 16S rRNA amplicon sequencing and quantitative polymerase chain reaction (PCR) analysis. Pseudomonas aeruginosa (PsA) or PsA-lipopolysaccharide was cocultured with primary human bronchial epithelial cells (PBEC). Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate NMI expression and EMT in explants and in PsA-exposed PBECs. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of EMT regulator NMI. RESULTS: 16S rRNA amplicon analyses revealed that CLAD patients have a higher abundance of phyla Proteobacteria and reduced abundance of the phyla Bacteroidetes. At the genera level, CLAD subjects had an increased abundance of genera Pseudomonas and reduced Prevotella. Human CLAD airway cells showed a downregulation of the N-myc-interactor gene and presence of EMT. Furthermore, exposure of human primary bronchial epithelial cells to PsA resulted in downregulation of NMI and induction of an EMT phenotype while NMI upregulation resulted in attenuation of this PsA-induced EMT response. CONCLUSIONS: CLAD is associated with increased bacterial biomass and a Proteobacteria enriched airway microbiome and EMT. Proteobacteria such as PsA induces EMT in human bronchial epithelial cells via NMI, demonstrating a newly uncovered mechanism by which the microbiome induces cellular metaplasia