Changes in Sarcopenia Status Predict Survival Among Patients with Resectable Esophageal Cancer.

BACKGROUND: Sarcopenia is a predictor of survival in patients with esophageal cancer. The objective of this research was to obtain insight into how changes in sarcopenia influence survival in resectable esophageal cancer. PATIENTS AND METHODS: A retrospective cohort of patients with esophageal cancer undergoing tri-modality therapy was selected. Body composition parameters from the staging, post-neoadjuvant, and 1-year surveillance computed tomography (CT) scans were calculated. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and log-rank test, as well as multivariable Cox-proportional hazards models. RESULTS: Of 141 patients, 118 had images at all three timepoints. The median DFS and OS were 33.2 [95% confidence interval (CI) 19.1-73.7] and 34.5 (95% CI 23.1-57.6) months, respectively. Sarcopenia classified by the staging CT was present in 20 (17.0%) patients. This changed to 45 (38.1%) patients by the post-neoadjuvant scan, and 44 (37.3%) by the surveillance scan. In multivariable analysis, sarcopenia at the post-neoadjuvant scan was significantly associated with OS [hazards ratio (HR) 2.65, 95% CI 1.59-4.40; p < 0.001] and DFS (HR 1.80, 95% CI 1.03-3.13; p = 0.038). The net change in skeletal muscle index was associated with OS (HR 0.93, 95% CI 0.90-0.97; p < 0.001) and DFS (HR 0.94, 95% CI 0.91-0.98; p = 0.001). CONCLUSIONS: Patients who develop sarcopenia as a consequence of skeletal muscle wasting during neoadjuvant therapy are at risk for worse DFS and OS. Patients who have a net loss of muscle over time may be at high risk for early disease recurrence.

Optimizing management for early-stage esophageal adenocarcinoma: longitudinal results from a multidisciplinary program.

BACKGROUND: The management of early-stage esophageal cancer is nuanced. A multidisciplinary approach may optimize management through selection of candidates for surgical or endoscopic therapies. The objective of this research was to examine long-term outcomes of patients with early-stage esophageal cancer who undergo treatment with endoscopic resection or surgery. METHODS: Data on patient demographics, co-morbidities, pathology results, OS and RFS were obtained for both the endoscopic resection group and esophagectomy group. Univariate analysis of OS and RFS were conducted using the Kaplan-Meier method with calculation of the log-rank test. Multivariate cox-proportional hazards models were created for OS and RFS using a hypothesis-driven approach. A multivariate logistic regression model was created to identify predictors of esophagectomy among patients undergoing initial endoscopic resection. RESULTS: A total of 111 patients were included. The median OS for the surgery group was 67.0 months compared to 74.0 months in the endoscopic resection group (log-rank p = 0.93). The median RFS for the surgery group was 109.4 months compared to 63.3 months in the endoscopic resection group (log-rank p = 0.0127). On multivariable analysis, patients undergoing endoscopic resection had significantly worse RFS (HR 2.55, 95% CI 1.09-6.00; p = 0.032), but equivalent OS (HR 1.03, 95% CI 0.46-2.32; p = 0.941), compared to patients undergoing esophagectomy. High-grade disease (OR 5.43, 95% CI 1.13-26.10; p = 0.035) and submucosal involvement (OR 7.75, 95% CI 1.90-31.40; p = 0.004) were identified as significant predictors of proceeding to esophagectomy. CONCLUSIONS: Through a multidisciplinary approach, patients with early-stage esophageal cancer achieve excellent RFS and OS. Submucosal involvement and high-grade disease place patients at increased risk for local disease recurrence; these patients may undergo endoscopic resection safely if treated with a multidisciplinary approach incorporating endoscopic surveillance and surgical consultation. Further risk-stratification models may enable better patient selection and optimization of long-term outcomes.

Perivascular network segmentations derived from high-field MRI and their implications for perivascular and parenchymal mass transport in the rat brain.

A custom segmentation workflow was applied to ex vivo high-field MR images of rat brains acquired following in vivo intraventricular contrast agent infusion to generate maps of the perivascular spaces (PVS). The resulting perivascular network segmentations enabled analysis of perivascular connections to the ventricles, parenchymal solute clearance, and dispersive solute transport within PVS. Numerous perivascular connections between the brain surface and the ventricles suggest the ventricles integrate into a PVS-mediated clearance system and raise the possibility of cerebrospinal fluid (CSF) return from the subarachnoid space to the ventricles via PVS. Assuming rapid solute exchange between the PVS and CSF spaces primarily by advection, the extensive perivascular network decreased the mean clearance distance from parenchyma to the nearest CSF compartment resulting in an over 21-fold reduction in the estimated diffusive clearance time scale, irrespective of solute diffusivity. This corresponds to an estimated diffusive clearance time scale under 10 min for amyloid-beta which suggests that the widespread distribution of PVS may render diffusion an effective parenchymal clearance mechanism. Additional analysis of oscillatory solute dispersion within PVS indicates that advection rather than dispersion is likely the primary transport mechanism for dissolved compounds greater than 66 kDa in the long (> 2 mm) perivascular segments identified here, although dispersion may be significant for smaller compounds in shorter perivascular segments.

Rice anther tapetum: a vital reproductive cell layer for sporopollenin biosynthesis and pollen exine patterning.

The tapetum is the innermost layer of the four layers of the rice anther that provides protection and essential nutrients to pollen grain development and delivers precursors for pollen exine formation. The tapetum has a key role in the normal development of pollen grains and tapetal programmed cell death (PCD) that is linked with sporopollenin biosynthesis and transport. Recently, many genes have been identified that are involved in tapetum formation in rice and Arabidopsis. Genetic mutation in PCD-associated genes could affect normal tapetal PCD, which finally leads to aborted pollen grains and male sterility in rice. In this review, we discuss the most recent research on rice tapetum development, including genomic, transcriptomic and proteomic studies. Furthermore, tapetal PCD, sporopollenin biosynthesis, ROS activity for tapetum function and its role in male reproductive development are discussed in detail. This will improve our understanding of the role of the tapetum in male fertility using rice as a model system, and provide information that can be applied in rice hybridization and that of other major crops.

Sarcopenia reduces overall survival in unresectable oesophageal cancer: a systematic review and meta-analysis.

Sarcopenia measured through body composition analysis is emerging as an important prognosticator among various malignancies, including oesophageal cancer. Skeletal muscle index (SMI) as determined by the third lumbar vertebrae on cross-sectional CT images has been demonstrated as a predictor of overall survival in oesophageal cancer, using pre-defined cut off values for sarcopenia. However, this is largely within the setting of resectable disease. The primary objective of this systematic review and meta-analysis was to determine the effect of sarcopenia defined by SMI on overall-survival in patients with unresectable oesophageal cancer. On 30 January 2021, a systematic search of the literature was conducted to identify the role of SMI among patients with unresectable oesophageal cancer, with overall survival as the primary outcome. Databases included MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library. Inclusion criteria included age >18, diagnosis of oesophageal cancer, and non-operative management. A meta-analysis was conducted using RevMan 5.4.1 using an inverse variance, random effects model. After the removal of duplicates, 2755 unique search results were obtained. Manual screening of titles and abstracts resulted in 287 full text articles that were reviewed. Of these, five studies met the inclusion criteria with data evaluating the effect of sarcopenia defined by SMI on overall survival. A total of 783 patients, the majority of which were male (n = 638, 81%), with a mean age of 68 ± 2.3 years were included. 641 (82%) patients were diagnosed with squamous cell carcinoma. Sarcopenia, as determined by SMI using pre-defined cut-off values, was reported in 517 patients (66%). Meta-analysis demonstrated decreased overall survival in the sarcopenia group compared with the non-sarcopenia group (HR = 1.51; 95% CI 1.21-1.89; P = 0.0003; I2  = 0%; Figure 1). No significant publication bias was noted on assessment of funnel plot and Egger's test (P = 0.295). Sarcopenia as defined by SMI is predictive of overall survival among patients with nonoperative oesophageal cancer. Further analysis on the effect of sarcopenia on treatment related adverse effects and complications, particularly related to chemotherapy, radiotherapy, and oesophageal stenting, is needed to identify the degree of prognostication offered by body composition analysis. Studies on the modifiability of sarcopenia will help determine the utility of nutritional interventions.

Sarcopenia Determined by Skeletal Muscle Index Predicts Overall Survival, Disease-free Survival, and Postoperative Complications in Resectable Esophageal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Sarcopenia has been identified as a prognostic factor among certain types of cancer. In esophageal cancer, patients are at increased risk of malnutrition and sarcopenia, ultimately contributing to poor outcomes. A systematic review was conducted to determine whether sarcopenia, defined by the skeletal muscle index, is predictive of overall survival, disease-free survival, and postoperative complications in resectable esophageal cancer. MATERIALS AND METHODS: A systematic search of MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines up until January 2021. The primary outcome was overall survival; secondary outcomes included disease-free survival, pulmonary complications, and anastomotic leak. RESULTS: Twenty-one studies (4 prospective; 17 retrospective; 3966 patients) were included. Sarcopenia was present in 1940 (48.1%) patients and was associated with lower overall survival [hazard ratio (HR): 1.56; 95% confidence interval (CI): 1.25-1.95; P <0.00001; I2 =71%] and disease-free survival (HR: 1.73; 95% CI: 1.04-2.87; P =0.03; I2 =51%). A decrease in skeletal muscle index, independent of sarcopenia status, was associated with lower overall survival (HR: 1.81; 95% CI: 1.20-2.73; P =0.005; I2 =92%). Sarcopenia was associated with increased odds of pulmonary complications (odds ratio: 1.86; 95% CI: 1.29-2.66; P =0.0008; I2 =41%) and increased odds of anastomotic leak (odds ratio: 1.46; 95% CI: 1.11-1.93; P =0.008; I2 =0%). CONCLUSIONS: Sarcopenia is a predictor of overall survival, disease-free survival, and postoperative complications in patients with resectable esophageal cancer. Studies on the modifiability of sarcopenia in the preoperative period will help determine the utility of nutritional interventions.

Will weather stem the spread of the COVID-19 in Pakistan?

The pandemic of COVID-19 started spreading more exponentially across Pakistan since the end of February 2020. Numerous models and factors have been used to estimate predictions of the prevalence and severity of COVID-19 infections around the globe. While many factors play a role in the spread of COVID-19, climate and weather conditions are considered key elements in the transmission of COVID-19. Many researchers believe that recent increases in COVID-19 cases correlate strongly with local temperatures and factors (such as humidity, weather conditions, etc.) related to it. In this manuscript we test the hypothesis that SARS-CoV-2 spread is temperature-dependent by using the available data derived from Pakistan. The present review focuses on the relationship between temperature and COVID-19, examining the virus's viability and infectivity under various conditions. Our findings indicate that the trough and crest of the COVID-19 wave observed in 2020 are likely to repeat in the summer and winter of 2021, respectively. In Pakistan, temperatures, and humidity significantly affect the COVID-19 transmission and incidence. Like other types of beta-coronaviruses (ß-CoVs), the spread of COVID-19 may depend upon a great deal on temperature.

Bilateral Lung Transplant for Treatment of Idiopathic Pulmonary Fibrosis With Undetected Lung Adenocarcinoma: A Case Report.

BACKGROUND: Lung transplant has become a curative therapy for various forms of progressive lung disease refractory to medical management. Idiopathic pulmonary fibrosis (IPF) is a rare condition characterized by accumulation of activated fibroblasts and secretion of extracellular matrices within the lung parenchyma. End-stage IPF is a fatal condition, with limited medical therapies other than lung transplantation. IPF has been demonstrated as a known risk factor for the development of lung cancer, and current lung transplant standards define history of malignancy within the past five years as an absolute exclusion criterion. CASE REPORT: We present the case of a patient with biopsy-confirmed idiopathic pulmonary fibrosis treated with bilateral lung transplant, discovered to have stage four lung adenocarcinoma in the explanted lungs. The patient subsequently received pseudoadjuvant chemotherapy and remained recurrence-free until 23 months post-transplant. CONCLUSION: This case highlights the challenge of ruling out malignancy in patients with end-stage lung disease. There remains a paucity of clinical studies on lung transplantation for lung cancer and more evidence is required before supporting this clinical decision.

Gastric ischemic conditioning prior to esophagectomy reduces anastomotic leaks and strictures: a systematic review and meta-analysis.

BACKGROUND: Gastric ischemic conditioning (GIC) is a strategy to promote neovascularization of the gastric conduit to reduce the risk of anastomotic complications following esophagectomy. Despite a number of studies and reviews published on the concept of ischemic conditioning, there remains no clear consensus regarding its utility. We performed an updated systematic review and meta-analysis to determine the impact of GIC, particularly on anastomotic leaks, conduit ischemia, and strictures. METHODS: A systematic search of MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library was performed on February 5th, 2020 by a university librarian after selection of key search terms with the research team. Inclusion criteria included human participants undergoing esophagectomy with gastric conduit reconstruction, age ≥ 18, N ≥ 5, and GIC performed prior to esophagectomy. Our primary outcome of interest was anastomotic leaks. Our secondary outcome was gastric conduit ischemia, anastomotic strictures, and overall survival. Meta-analysis was performed with RevMan 5.4.1 using a Mantel-Haenszel fixed-effects model. RESULTS: A total of 1712 preliminary studies were identified and 23 studies included for final review. GIC was performed in 1178 (53.5%) patients. Meta-analysis revealed reduced odds of anastomotic leaks (OR 0.67; 95% CI 0.46-0.97; I2 = 5%; p = 0.03) and anastomotic strictures (OR 0.48; 95% CI 0.29-0.80; I2 = 65%; p = 0.005). Meta-analysis revealed no difference in odds of conduit ischemia (OR 0.40; 95% CI 0.13-1.23; I2 = 0%; p = 0.11) and no difference in odds of overall survival (OR 0.54; 95% CI 0.29-1.02; I2 = 22%; p = 0.06). CONCLUSION: GIC is associated with reduced odds of anastomotic leaks and anastomotic strictures and may decrease morbidity in patients undergoing esophagectomy. Further prospective randomized trials are needed to better identify the optimal patient population, timing, and techniques used to best achieve GIC.

Non-invasive assessment of exfoliated kidney cells extracted from urine using multispectral autofluorescence features.

Optimally preserved urinary exfoliated renal proximal tubule cells were assessed by multispectral imaging of cell autofluorescence. We demonstrated different multispectral autofluorescence signals in such cells extracted from the urine of patients with healthy or diseased kidneys. Using up to 10 features, we were able to differentiate cells from individuals with heathy kidneys and impaired renal function (indicated by estimated glomerular filtration rate (eGFR) values) with the receiver operating characteristic area under the curve (AUC) of 0.99. Using the same method, we were also able to discriminate such urine cells from patients with and without renal fibrosis on biopsy, where significant differences in multispectral autofluorescence signals (AUC = 0.90) were demonstrated between healthy and diseased patients (p < 0.05). These findings show that multispectral assessment of the cell autofluorescence in urine exfoliated proximal tubule kidney cells has the potential to be developed as a sensitive, non-invasive diagnostic method for CKD.

Transmediastinal penetrating trauma.

Penetrating transmediastinal injury (TMI) is associated with a high mortality rate and presents a challenging diagnostic scenario. Previous dogma mandated surgical exploration or extensive and invasive investigations for all patients sustaining transmediastinal penetrating trauma, regardless of hemodynamic status. Since the late 1990s, the paradigm has changed, with most centers adopting a tiered approach to management based on clinical presentation. Transmediastinal penetrating trauma is a rare injury pattern and can result from gunshot wounds, stab wounds, blast injuries, and other missiles. The most predominant source, however, remains gunshot wounds, accounting for the vast majority of these injuries. A systematic approach in the emergency department to diagnosis and management should be undertaken and patients in extremis or with hemodynamic compromise rapidly identified. The unstable patient forgoes further investigations and the surgeon must use knowledge about the hypothesized trajectory, results of limited imaging, chest tube output, and anticipation of resuscitative maneuvers to select the best operative approach. In patients who are sufficiently stable to undergo CT angiogram (CTA) of the chest, the trajectory of the missile or impalement can often be deduced and this is used to guide further investigation or operation. In those where ambiguity remains, more focused tests such as echocardiography, pericardial window, esophagoscopy or esophagography, and bronchoscopy can be used to assess the mediastinal structures. For the stable patient, management proceeds with cautious and expeditious investigations to determine the extent of underlying organ-specific injuries. Thus, in patients with this injury pattern, determination of the patient's clinical status is critical to determine the appropriate course of management.

Biological screening of Euphorbia helioscopia L.

The present research is preliminary biological screening of Euphorbia helioscopia L. (Euphorbiaceae). Dichloromethane and methanol extracts of the aerial parts of the plant were investigated for their antioxidant, antifungal, antibacterial and phytotoxic activities. Dichloromethane extract exhibited significant activity against Fusarium solani with 90% Inhibition, where as the same extract also showed non-significant activity against Salmonella typhi and Bacillus subtilis. Methanolic extract has promising radical-scavenging activity in this assay. Both the extracts have non-significant phytotoxicity against lemna minor.