Trends in radiation dose for low grade gliomas across the United States.

PURPOSE: Adjuvant radiation is often used in patients with low grade gliomas with high-risk characteristics with a recommended dose of 45-54 Gy. We used the National Cancer Database (NCDB) to see which doses were being used, and if any difference was seen in outcome. METHODS: We queried the NCDB for patients with WHO Grade 2 primary brain tumors treated with surgery and adjuvant radiotherapy. We divided the cohort into dose groups: 45-50 Gy, 50.4-54 Gy, and > 54 Gy. Multivariable logistic regression was used to identify predictors of low and high dose radiation. Propensity matching was used to account for indication bias. RESULTS: We identified 1437 patients meeting inclusion criteria. Median age was 45 years and 62% of patients were > 40 years old. Nearly half of patients (48%) had astrocytoma subtype and 70% had subtotal resection. The majority of patients (69%) were treated to doses between 50.4 and 54 Gy. Predictors of high dose radiation (> 54 Gy) were increased income, astrocytoma subtype, chemotherapy receipt, and treatment in later year (2014). The main predictors of survival were age > 40, astrocytoma subtype, and insurance type. Patients treated to a dose of > 54 Gy had a median survival of 73.5 months and was not reached in those treated to a lower dose (p = 0.0041). CONCLUSIONS: This analysis shows that 50.4-54 Gy is the most widely used radiation regimen for the adjuvant treatment of low-grade gliomas. There appeared to be no benefit to higher doses, although unreported factors may impact interpretation of the results.

Factors associated with drug survival on first biologic therapy in patients with rheumatoid arthritis: a population-based cohort study.

Lack of sufficient head-to-head trials comparing biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), makes the choice of the first bDMARD a matter of rheumatologist's preference. Longer drug survival on the first bDMARD usually correlates with early remission. We aimed to identify factors associated with longer drug survival. We conducted a population-based retrospective longitudinal cohort study. We identified RA patients using the relevant International Classification of Disease 9th codes. "True" RA patients were defined as patients fulfilling, additionally, at least one of the following: receiving conventional DMARDs (cDMARDs), being positive for rheumatoid factor or anti-cyclic citrullinated peptide, or being diagnosed by a rheumatologist. We compared drug survival times and identified factors associated with longer drug survival. We identified 4268 true RA patients between the years of 2000-2017. 820 patients (19.2%) received at least one bDMARD. The most commonly prescribed bDMARDs were etanercept (352, 42.9%), adalimumab (143, 17.4%), infliximab (142, 17.3%) and tocilizumab (58, 7.1%). Infliximab was associated with the longest drug survival (47.1 months ± 46.3) while golimumab was associated with the shortest drug survival (14.9 months ± 15.1). Male gender [hazard ratio (HR) = 0.76, 95% confidence interval (CI), 0.63-0.86, p = 0.001], concurrent conventional DMARDs use (HR = 0.79, 95% CI 0.68 - 0.98, p = .031) and initiating bDMARD therapy in earlier calendric years (HR = 1.12, 95% CI 1.10 -1.18, p = 0.0001) were associated with longer drug survival. Male gender, concomitant cDMARDs and initiating biologic therapy at earlier calendric years are associated with longer drug survival.

Clinical characteristics and prognostic factors of Hurthle cell carcinoma: a population based study.

BACKGROUND: Thyroid Hurthle cell carcinoma (HCC) is a rare disease with high risk of invasion and metastasis and poor prognosis. The clinical characteristics, prognosis and treatment of HCC are still controversial, and clinical data are still limited to some case reports. Therefore, understanding the characteristics and survival factors of HCC is clinically necessary. METHODS: This study collected data from HCC patients diagnosed pathologically from 2004 to 2015, including basic population characteristics, tumor characteristics, and epidemiological and survival data. The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to conduct a population cohort study. RESULTS: A total of 2101 HCC patients with an average age of 55.42 ± 15.27 years were enrolled in this study. Of them, 1740 (82.82%) patients had local disease, 245 (11.66%) had regional disease, and 89 (4.24%) had distant disease. Total thyroidectomy was performed in 1669 (79.44%) patients, partial thyroidectomy was performed in 382 (18.18%) patients, and radioactive iodine (RAI) was used in 1155 (54.97%) patients. The 5-year and 10-year cancer-specific survival rate was 95.4 and 92.6%, respectively. The distant disease group had significantly more male patients, multifocal tumors, and extensive tumors compared to the local disease group. Multivariate survival analysis showed that age (P < 0.05), SEER stage (P < 0.001), and T-stage (P = 0.001) had significant effects on survival. There was no significant difference in survival between total and partial thyroidectomy (P = 0.078), or between RAI and non-RAI (P = 0.733). CONCLUSION: Male gender, multifocal tumors, and extended tumors are associated with increased risk of late stage HCC. Age over 45 years, distant SEER stage, and late T-stage are independent risk factors for mortality in HCC.

Profile of cell proliferation and apoptosis activated by the intrinsic and extrinsic pathways in the prostate of aging rats.

BACKGROUND: Estrogens acting through the receptors ERα and ERß participate in prostate normal growth and cancer. ERß is highly expressed in the prostate epithelium, playing pro-apoptotic, anti-proliferative, and pro-differentiation roles. Apoptosis is activated by the intrinsic pathway after castration and by the extrinsic pathway after ERß agonist treatment. This differential activation of apoptotic pathways is important since a major problem in the treatment of prostate cancer is the recurrence of tumors after androgen withdrawal. However, a comprehensive study about the pattern of apoptosis in the aging prostate is lacking, a knowledge gap that we aimed to address herein. METHODS: Cellular age-related proliferative and apoptotic profiles of prostate tissue obtained from aging Wistar rats were evaluated. Cell death (caspase-3, -8, -9, TNFα) was assessed by immunohistochemistry, immunofluorescence, and TUNEL. Cell proliferation (MCM7) and cell survival factors (ERK1/2, p-ERK1/2, p-Akt, and NF-κB) were determined by immunohistochemistry. RESULTS: As the rats aged, the number of proliferating cells gradually reduced in the normal epithelium of all prostate lobes, while increasing in focal areas of intraepithelial proliferation. Interestingly, in areas of intraepithelial proliferation, we observed a reduction in the number of cells positive for caspase-3, -8, and -9. Regardless the animal's age, few prostate epithelial cells were positive for caspase-3, caspase-9, and TUNEL. In contrast, a progressive increase was seen in the positivity for caspase-8, especially in the atrophic epithelium of ventral prostate, which coincided with a reduction in TNFα immunoreaction. However, morphology of most caspase-8 positive cells suggests that they were not apoptotic. We also found reduced ERß expression in the same areas. Possibly, low levels of the pro-apoptotic inductors TNFα and ERß direct caspase-8 activity to an alternative pro-survival role in the atrophic epithelium. This hypothesis is supported by the increased expression of the key survival factors (ERK1/2, p-ERK1/2, p-Akt, and NF-κB) in these areas. CONCLUSIONS: Our findings reveal that, as the animals age, there is an increase of proliferation in restricted areas of the prostate epithelium, and a concomitant reduction of the apoptosis rate with an increase in cell survival induced by caspase-8, indicating a focused and spontaneous disruption of tissue homeostasis.

Risk stratification of survival in injured patients with cardiopulmonary resuscitation within the first hour of arrival to trauma centre: retrospective analysis from the national trauma data bank.

BACKGROUND: The purpose of this study was to evaluate overall survival and associated survival factors for patients with trauma who had cardiopulmonary resuscitation (CPR) within 1 hour after arrival to a hospital. METHODS: Retrospective patient data was retrieved from the 2007-2010 edition of the US National Trauma Data Bank. Inhospital survival was the primary outcome; only patients with a known outcome were included in the analysis. Summary statistics and univariate analyses were first reported. Eighty per cent of the patients were then randomly selected and used for multivariate logistic regression analysis. The identified risk factors were further assessed for discrimination and calibration with the remaining patients with trauma using area under the curve (AUC) analysis and a Hosmer-Lemeshow test. RESULTS: From 19 310 total cases that were reviewed, only 2640 patients required CPR within 1 hour of hospital arrival and met the additional inclusion criteria. Of these patients, 2309 (87.5%) died and 331 (12.5%) survived to discharge. There were statistical differences for race (p=0.003), initial systolic BP (p<0.001), initial pulse (p<0.001), cause of injury (p<0.001), presence of head injury (p=0.02), Injury Severity Score (ISS) (p<0.001), Glasgow Coma Scale (GCS) total score (p<0.001) and GCS motor score (p<0.001); though not all were clinically significant. The multiple logistic regression model (AUC=0.72) identified lower ISS, higher GCS motor score, Caucasian race, American College of Surgeons (ACS) level 2 trauma designation and higher initial SBP as the most predictive of survival to hospital discharge. CONCLUSION: Approximately 13% of patients who had CPR within an hour of arrival to a trauma centre survived their injury. Therefore, implementation of an aggressive first hour in-hospital resuscitation strategy may result in better survival outcomes for this patient population.

Lymph node evaluation for colon cancer in routine clinical practice: a population-based study.

BACKGROUND: Guidelines recommend that 12 or more lymph nodes (lns) be evaluated during surgical resection of colon cancer. Here, we report ln yield and its association with survival in routine practice. METHODS: Electronic records of treatment were linked to the population-based Ontario Cancer Registry to identify all patients with colon cancer treated during 2002-2008. The study population (n = 5508) included a 25% random sample of patients with stage ii or iii disease. Modified Poisson regression was used to identify factors associated with ln yield; Cox models were used to explore the association between ln yield and overall (os) and cancer-specific survival (css). RESULTS: During 2002-2008, median ln yield increased to 17 from 11 nodes (p < 0.001), and the proportion of patients with 12 or more nodes evaluated increased to 86% from 45% (p < 0.001). Lymph node positivity did not change over time (to 53% from 54%, p = 0.357). Greater ln yield was associated with younger age (p < 0.001), less comorbidity (p = 0.004), higher socioeconomic status (p = 0.001), right-sided tumours (p < 0.001), and higher hospital volume (p < 0.001). In adjusted analyses, a ln yield of less than 12 nodes was associated with inferior os and css for stages ii and iii disease [stage ii os hazard ratio (hr): 1.36; 95% confidence interval (ci): 1.19 to 1.56; stage ii css hr: 1.52; 95% ci: 1.26 to 1.83; and stage iii os hr: 1.45; 95% ci: 1.30 to 1.61; stage iii css hr: 1.54; 95% ci: 1.36 to 1.75]. CONCLUSIONS: Despite a temporal increase in ln yield, the proportion of cases with ln positivity has not changed. Lymph node yield is associated with survival in patients with stages ii and iii colon cancer. The association between ln yield and survival is unlikely to be a result of stage migration.

Age at cancer diagnosis, amenability to medical interventions, and racial/ethnic disparities in cancer mortality.

PURPOSE: Racial disparities in cancer mortality may be greater for cancers that are amenable to available early detection and treatment (amenability level). We investigated whether these patterns vary by age at cancer diagnosis. METHODS: Using 5-year relative survival rates (5Y-RSR), we classified 51 cancer sites into least amenable, partly amenable, and mostly amenable cancers (<40%, 40-69%, ≥70% 5-YRS, respectively). We examined whether racial disparities in mortality rates (African-Americans, Asian/Pacific Islanders, Hispanics, whites), as estimated through Cox regression models, were modified by age at diagnosis and amenability level in 516,939 cancer cases diagnosed in 1995-1999. RESULTS: As compared with whites, all racial minority groups experienced higher cancer mortality rates in the youngest age group of 20-34 years. African-Americans and Hispanics diagnosed with partly and mostly amenable cancers had higher mortality rates relative to whites with cancers of the same amenability levels; further, these differences decreased in magnitude or reversed in direction with increasing age. In contrast, the racial differences in mortality were smaller and remained fairly constant across age groups for least amenable cancers. For example, in the youngest (20-34) and oldest (80-99) age groups, the adjusted hazard ratios (HRs) for African-Americans versus whites with least amenable cancers were, respectively, 1.26 (95% CI 1.02, 1.55) and 0.90 (95% CI 0.85, 0.96), while the HRs for African-Americans versus whites with mostly amenable cancers were 2.77 (95% CI 2.38, 3.22) and 1.07 (95% CI 0.98, 1.17). CONCLUSIONS: Cancer survival disadvantage for racial minorities is larger in younger age groups for cancers that are more amenable to medical interventions.

Systematic Review and Meta-analysis of Factors Influencing Survival Following Abdominal Aortic Aneurysm Repair.

BACKGROUND: Predicting long-term survival following repair is essential to clinical decision making when offering abdominal aortic aneurysm (AAA) treatment. A systematic review and a meta-analysis of pre-operative non-modifiable prognostic risk factors influencing patient survival following elective open AAA repair (OAR) and endovascular aneurysm repair (EVAR) was performed. METHODS: MEDLINE, Embase and Cochrane electronic databases were searched to identify all relevant articles reporting risk factors influencing long-term survival (≥1 year) following OAR and EVAR, published up to April 2015. Studies with <100 patients and those involving primarily ruptured AAA, complex repairs (supra celiac/renal clamp), and high risk patients were excluded. Primary risk factors were increasing age, sex, American Society of Anaesthesiologist (ASA) score, and comorbidities such as ischaemic heart disease (IHD), cardiac failure, hypertension, chronic obstructive pulmonary disease (COPD), renal impairment, cerebrovascular disease, peripheral vascular disease (PVD), and diabetes. Estimated risks were expressed as hazard ratio (HR). RESULTS: A total of 5,749 study titles/abstracts were retrieved and 304 studies were thought to be relevant. The systematic review included 51 articles and the meta-analysis 45. End stage renal disease and COPD requiring supplementary oxygen had the worst long-term survival, HR 3.15 (95% CI 2.45-4.04) and HR 3.05 (95% CI 1.93-4.80) respectively. An increase in age was associated with HR of 1.05 (95% CI 1.04-1.06) for every one year increase and females had a worse survival than men HR 1.15 (95% CI 1.07-1.27). An increase in ASA score and the presence of IHD, cardiac failure, hypertension, COPD, renal impairment, cerebrovascular disease, PVD, and diabetes were also factors associated with poor long-term survival. CONCLUSION: The result of this meta-analysis summarises and quantifies unmodifiable risk factors that influence late survival following AAA repair from the best available published evidence. The presence of these factors might assist in clinical decision making during discussion with patients regarding repair.

Does the diameter of abdominal aortic aneurysm influence late survival following abdominal aortic aneurysm repair? A systematic review and meta-analysis.

BACKGROUND: Studies reporting the influence of preoperative abdominal aortic aneurysm diameter on late survival following abdominal aortic aneurysm repair have not been consistent. AIM: To report the influence of abdominal aortic aneurysm diameter on overall long-term survival following abdominal aortic aneurysm repair. METHODS: Embase, Medline and the Cochrane electronic databases were searched to identify articles reporting the influence of abdominal aortic aneurysm diameter on late survival following open aneurysm repair and endovascular aneurysm repair published up to April 2015. Data were extracted from multivariate analysis; estimated risks were expressed as hazard ratio. RESULTS: A total of 2167 titles/abstracts were retrieved, of which 76 studies were fully assessed; 19 studies reporting on 22,104 patients were included. Preoperative larger abdominal aortic aneurysm size was associated with a worse survival compared to smaller aneurysms with a pooled hazard ratio of 1.14 (95% CI: 1.09-1.18), per 1 cm increase in abdominal aortic aneurysm diameter. Subgroup analysis of the different types of repair was performed and the hazard ratio (95% CI), for open aneurysm repair and endovascular aneurysm repair were 1.08 (1.03-1.12) and 1.20 (1.15-1.25), respectively, per 1 cm increase. There was a significant difference between the groups p < 0.02. CONCLUSIONS: This meta-analysis suggests that preoperative large abdominal aortic aneurysm independently influences overall late survival following abdominal aortic aneurysm repair, and this association was greater in abdominal aortic aneurysm repaired with endovascular aneurysm repair.

Mortality and Survival Factors in Patients with Moderate and Severe Pneumonia Due to COVID-19.

During the pandemic, some mortality-related factors were age, sex, comorbidities (obesity, diabetes mellitus, and hypertension), recovery time, hospitalizations, and biochemical markers. The present work aimed to identify the mortality and survival factors in adults with moderate and severe pneumonia due to COVID-19 during the first and second waves of the pandemic in Mexico at a third-level hospital (High-Specialty Regional Hospital of Ixtapaluca (HRAEI), Ixtapaluca, Estado de Mexico, Mexico). A database was generated using information from the electronic clinical records of patients hospitalized from December 2021 to August 2022. Survival analysis was performed associating age, sex, longer recovery times, and some drugs. The risk factors found were age in the patients between 40 and 60 years (OR = 1.70), male sex (OR = 1.53), the presence of comorbidities (OR = 1.66) and hypertension (OR = 2.19), work occupation (construction workers OR = 5.22, factory workers OR = 3.13, unemployed OR = 2.93), the prehospital use of metamizole sodium (OR = 2.17), cough (OR = 1.73), and in-hospital oxygen therapy (reservoir mask OR = 6.6). The survival factors found in this study were working in the healthcare field (OR = 0.26), the prehospital use of certain medications (paracetamol OR = 0.65, dexamethasone OR = 0.55, and azithromycin OR = 0.47), presenting ageusia (OR = 0.5) and hyporexia (OR = 0.34), and the time using in-hospital oxygen therapy (device 1 OR = 0.72). Prehospital treatment needs to be reevaluated as dexamethasone and azithromycin proved to be protective factors. Likewise, providing aggressive oxygen therapy during hospital admission decreased mortality risk.

The Prediction of Survival Outcome and Prognosis Factor in Association with Comorbidity Status in Patients with Colorectal Cancer: A Research-Based Study.

Colorectal carcinoma (CRC) is rising exponentially in Asia, representing 11% of cancer worldwide. This study analysed the influence of CRC on patients' life expectancy (survival and prognosis factors) via clinicopathology data and comorbidity status of CRC patients. Methodology: A retrospective study performed in HUSM using clinical data from the Surgery unit from 2015 to 2020. The demographic and pertinent clinical data were retrieved for preliminary analyses (data cleansing and exploration). Demographics and pathological characteristics were illustrated using descriptive analysis; 5-year survival rates were calculated using Kaplan−Meier methods; potential prognostic variables were analysed using simple and multivariate logistic regression analysis conducted via the Cox proportional hazards model, while the Charlson Comorbidity Scale was used to categorize patients' disease status. Results: Of a total of 114 CRC patients, two-thirds (89.5%) were from Malay tribes, while Indian and Chinese had 5.3% each. The 50−69.9 years were the most affected group (45.6%). Overall, 40.4% were smokers (majorly male (95.7%)), 14.0% ex-smokers, and 45.6% non-smokers (p-value = 0.001). The Kaplan−Meier overall 5-year median survival time was 62.5%. From the outcomes, patients who were male and >70 years had metastasis present, who presented with per rectal bleeding and were classified as Duke C; and who has tumour in the rectum had the lowest survival rate. Regarding the prognosis factors investigated, "Gender" (adjusted hazard ratio (HR): 2.62; 95% CI: 1.56−7.81, p-value = 0.040), "Presence of metastases" (HR: 3.76; 95% CI: 1.89−7.32, p-value = 0.010), "Metastasis site: Liver" (HR: 5.04; 95% CI: 1.71−19.05, p-value = 0.039), "Lymphovascular permeation" (HR: 2.94; 95% CI: 1.99−5.92, p-value = 0.021), and "CEA-level" (HR: 2.43; 95% CI: 1.49−5.80, p-value = 0.001) remained significant in the final model for multiple Cox proportional hazard regression analyses. There was a significant mean association between tumour grades and the patient's comorbidity status. Conclusions: Histopathological factors (gender, metastases presence, site of metastases, CEA level, and lymphovascular permeation) showed the best prognosis-predicting factors in CRC.

Clinical features, prognostic factors, and survival of patients with antisynthetase syndrome and interstitial lung disease.

Objective: This study aimed to analyze the clinical features and prognostic factors of imaging progression and survival in patients with antisynthetase syndrome (ASS) complicated by interstitial lung disease (ILD) in a large Chinese cohort. Methods: Medical records, imaging, and serological data of 111 patients with ASS-ILD (positive for at least one of the following autoantibodies: anti-Jo1, anti-PL7, anti-PL12, and anti-EJ) from the Affiliated Yantai Yuhuangding Hospital of Qingdao University database were retrospectively investigated. According to the changes in high-resolution computed tomography (HRCT) outcomes at 1 year follow-up, Patients were categorized into three groups: the regression, stability, and deterioration groups. Univariate analysis was performed to evaluate the possible prognostic factors of ILD outcome and death, and multivariate analysis was performed to determine the independent predictors of ASS-ILD outcome and death by logistic regression. Results: The number of CD3-CD19+ cells and initial glucocorticoid dosage were correlated with imaging progression, and may be independent risk factors for ILD deterioration. Dyspnea as the first symptom, hypohemoglobinemia, the serum ferritin level, oxygen partial pressure at diagnosis, and different treatment types were important factors affecting survival, and the initial serum ferritin level may be an independent risk factor for survival. Conclusions: The clinical characteristics of patients with ASS-ILD with different antisynthetase antibody subtypes are different. An increase in the CD3-CD19+ cell level is an independent risk factor for the deterioration of HRCT imaging. Early intensive treatment with high-dose glucocorticoids can effectively improve imaging prognosis of ILD. Patients with significantly elevated serum ferritin levels should be treated intensively.

Prognostic Survival Factors in Acute Liver Failure Patients in India.

BACKGROUND: Acute liver failure (ALF) is characterized by severe and sudden liver cell dysfunction. Baseline demographic, clinical, and biochemical factors associated with the survival of ALF patients were identified in a few selected Western studies, but very few studies have been done in India. The aim of the current study is to provide an overview of the factors associated with the survival of ALF patients and to suggest an optimum cutoff value for clinically significant parameters. MATERIALS AND METHODS: The patients suffering from ALF were reviewed in this study. The factors studied were age, sex, total serum bilirubin, serum creatinine, serum albumin, urea, aspartate aminotransferase, alanine aminotransferase (ALT), and recent hepatitis E virus infection. RESULTS: Total n = 41; Male 73%; median age 43 years. The median survival time of patients in the age group of 18-40 years was 238 days. The median survival time of patients >40 years of age was 129.10 days. Elevated serum urea and serum ALT levels at the time of admission were found to be significant predictors of mortality in patients suffering from ALF in our study. In Receiver Operator Characteristic (ROC) curve analysis, the optimum cutoff value of urea was found to be 42 mg/dL, and ALT was found to be 400 IU/L. CONCLUSIONS: Elevated serum urea and serum ALT levels at the time of admission were found to be significant predictors of mortality in patients suffering from ALF in our study. The use of these two parameters, along with King's criteria for the prognosis of ALF, can be more useful in the management of such patients in India.

Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study.

Background: Elderly patients infected with COVID-19 are reported to be facing a substantially increased risk of mortality. Clinical characteristics, treatment options, and potential survival factors remain under investigation. This study aimed to fill this gap and provide clinically relevant factors associated with survival of elderly patients with COVID-19. Methods: In this multi-center study, elderly patients (age ≥65 years old) with laboratory-confirmed COVID-19 from 4 Wuhan hospitals were included. The clinical end point was hospital discharge or deceased with last date of follow-up on Jul. 08, 2020. Clinical, demographic, and laboratory data were collected. Univariate and multivariate analysis were performed to analyze survival and risk factors. A metabolic flux analysis using a large-scale molecular model was applied to investigate the pathogenesis of SARS-CoV-2 with regard to metabolism pathways. Results: A total of 223 elderly patients infected with COVID-19 were included, 91 (40.8%) were discharged and 132 (59.2%) deceased. Acute respiratory distress syndrome (ARDS) developed in 140 (62.8%) patients, 23 (25.3%) of these patients survived. Multivariate analysis showed that potential risk factors for mortality were elevated D-Dimer (odds ratio: 1.13 [95% CI 1.04 - 1.22], p = 0.005), high immune-related metabolic index (6.42 [95% CI 2.66-15.48], p < 0.001), and increased neutrophil-to-lymphocyte ratio (1.08 [95% 1.03-1.13], p < 0.001). Elderly patients receiving interferon atmotherapy showed an increased probability of survival (0.29 [95% CI 0.17-0.51], p < 0.001). Based on these factors, an algorithm (AlgSurv) was developed to predict survival for elderly patients. The metabolic flux analysis showed that 12 metabolic pathways including phenylalanine (odds ratio: 28.27 [95% CI 10.56-75.72], p < 0.001), fatty acid (15.61 [95% CI 6.66-36.6], p < 0.001), and pyruvate (12.86 [95% CI 5.85-28.28], p < 0.001) showed a consistently lower flux in the survivors vs. the deceased subgroup. This may reflect a key pathogenic mechanism of COVID-19 infection. Conclusion: Several factors such as interferon atmotherapy and recreased activity of specific metabolic pathways were found to be associated with survival of elderly patients. Based on these findings, a survival algorithm (AlgSurv) was developed to assist the clinical stratification for elderly patients. Dysregulation of the metabolic pathways revealed in this study may aid in the drug and vaccine development against COVID-19.

High-intensity focused ultrasound ablation for advanced pancreatic cancer.

AIMS: The aim of this study was to evaluate the efficacy, safety, and survival factors of high-intensity focused ultrasound (HIFU) ablation in the treatment of advanced pancreatic cancer. SUBJECTS AND METHODS: A retrospective analysis was conducted between September 2010 and March 2016. Advanced pancreatic cancer patients with HIFU treatment were enrolled in the analysis to evaluate the efficacy of local ablation, pain relief, and relative complications of HIFU therapy. The main factors that affected Overall survival rate (OSR) and median survival time (MST) were also analyzed. RESULTS: Eighty-six patients received HIFU treatment, with a total of 93 treatments performed, and 83 cases were evaluated. Complete response rate (RR) was 3.6% (3/83) and partial RR was 79.5% (66/83). After HIFU treatment, pain reduction was observed in 74 patients, and the total remission rate was 97.6% (74/76). The total MST was 9.9 months (2-58.7 months), the total OSR in 1 and 2 years was 41.5% and 9.6%, respectively. Minor complications occurred in 97.7% (42/43) patients, including transient fever, abdominal pain, skin burn, and amylase elevation. The univariate analysis showed that the clinical stage, treatment method, ablation efficacy, and combined treatment were significant prognostic factors. CONCLUSION: HIFU can significantly alleviate cancer-related pain and prolong the survival time of patients with pancreatic cancer.

Autocrine embryotropins revisited: how do embryos communicate with each other in vitro when cultured in groups?

In the absence of the maternal genital tract, preimplantation embryos can develop in vitro in culture medium where all communication with the oviduct or uterus is absent. In several mammalian species, it has been observed that embryos cultured in groups thrive better than those cultured singly. Here we argue that group-cultured embryos are able to promote their own development in vitro by the production of autocrine embryotropins that putatively serve as a communication tool. The concept of effective communication implies an origin, a signalling agent, and finally a recipient that is able to decode the message. We illustrate this concept by demonstrating that preimplantation embryos are able to secrete autocrine factors in several ways, including active secretion, passive outflow, or as messengers bound to a molecular vehicle or transported within extracellular vesicles. Likewise, we broaden the traditional view that inter-embryo communication is dictated mainly by growth factors, by discussing a wide range of other biochemical messengers including proteins, lipids, neurotransmitters, saccharides, and microRNAs, all of which can be exchanged among embryos cultured in a group. Finally, we describe how different classes of messenger molecules are decoded by the embryo and influence embryo development by triggering different pathways. When autocrine embryotropins such as insulin-like growth factor-I (IGF-I) or platelet activating factor (PAF) bind to their appropriate receptor, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway will be activated which is important for embryo survival. On the other hand, the mitogen-activated protein kinase (MAPK) pathway is activated when compounds such as hyaluronic acid and serotonin bind to their respective receptors, thereby acting as growth factors. By activating the peroxisome-proliferator-activated receptor family (PPAR) pathway, lipophilic autocrine factors such as prostaglandins or fatty acids have both survival and anti-apoptotic functions. In conclusion, considering different types of messenger molecules simultaneously will be crucial to understanding more comprehensively how embryos communicate with each other in group-culture systems. This approach will assist in the development of novel media for single-embryo culture.

Survival of T- and B-Phenotype Diffuse Aggressive Non-Hodgkin's Lymphomas.

Survival of immunophenotyped non-Hodgkin's lymphomas (NHLs) diagnosed as diffuse mixed, diffuse large and large cell immunoblastic by the working formulation was evaluated based on phenotypic categories. These subtypes were grouped as diffuse aggressive NHLs due to their similarities, and categorized into T- and B-phenotype NHLs. There were 45 (57.7%) cases of T-NHL and 33 (42.3%) B-NHL. Major clinical factors such as sex, age, stage, B-symptoms and site of disease, as well as performance status (PS), LDH, primary site and number of extra-nodal sites involved showed equal distributions between T- and B-NHLs. Combination chemotherapeutic regimens based on doxorubicin were used in 84% of these cases. Complete remission was achieved in 73.6% of T-NHL and 74.1% of B-NHL. Median survival for the T- and B-NHL was the same over 30 months. Projected survival at 5 years was also similar, T-NHL (35%) and B-NHL (38%). Unilaterally, survival was adversely affected in stage III/IV of T-NHL and for age over 65 years for B-NHL. Survival was unfavorable for the B-NHL without B-symptoms when compared to T-NHLs. Multivariately, only sex, B-symptoms and PS significantly (P < 0.05) affected the survival of T-NHL. Although the overall results indicate that the response and survival of T- and B-NHL are similar, the differences observed on the effect of sex, age, stage, B-symptoms and PS on survival of T- and B-NHLs imply that, their influence on T-NHLs was different from that for B-NHLs. Therefore we suggest that separate prognostic models are needed for the T- and B-phenotype NHLs.

Impact of conditioning hyperglycemic on myocardial infarction rats: Cardiac cell survival factors.

While clinical data have suggested that the diabetic heart is more susceptible to ischemic heart disease (IHD), animal data have so far pointed to a lower probability of IHD. Thus, the aim of this present review is to look at these conflicting results and discuss the protective mechanisms that conditioned hyperglycemia may confer to the heart against ischemic injury. Several mechanisms have been proposed to explain the cardioprotective action of high glucose exposure, namely, up-regulation of anti-apoptotic factor Bcl-2, inactivation of pro-apoptotic factor bad, and activation of pro-survival factors such as protein kinase B (Akt), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α and protein kinase C-ε. Indeed, cytosolic increase in Ca(2+) concentration, the mitochondrial permeability transition pore, plays a key role in the genesis of ischemic injury. Previous studies have shown that the diabetic heart decreased Na(+)/Ca(2+) and Na(+)/H(+) exchanger activity and as such it accumulates less Ca(2+) in cardiomyocyte, thus preventing cardiac injury and the associated heart dysfunctions. In addition, the expression of VEGF in diabetic animals leads to increased capillary density before myocardial infarction. Despite poor prognostic in the long-term, all these results suggest that diabetes mellitus and consequently hyperglycemia may indeed play a cardioprotective role against myocardial infarction in the short term.

Elevated neutrophil gelatinase-associated lipocalin contributes to erlotinib resistance in non-small cell lung cancer.

PURPOSE: The EGFR tyrosine kinase inhibitors (TKIs) demonstrate efficacy in NSCLC patients whose tumors harbor activating EGFR mutations. However, patients who initially respond to EGFR TKI treatment invariably develop resistance to the drugs. Known mechanisms account for approximately 70% of native and acquired EGFR TKI resistance. In the current study we investigated a novel mechanism of NSCLC resistance to erlotinib. EXPERIMENTAL DESIGN: The mechanisms of acquired erlotinib resistance were evaluated by microarray analysis in thirteen NSCLC cell lines and in vivo in mice. Correlations between plasma neutrophil gelatinase associated lipocalin (NGAL) levels, erlotinib response and the EGFR mutational status were assessed in advanced stage NSCLC patients treated with erlotinib. RESULTS: In 5 of 13 NSCLC cell lines NGAL was significantly upregulated. NGAL knockdown in erlotinib-resistant cells increased erlotinib sensitivity in vitro and in vivo. NGAL overexpression in erlotinib-sensitive cells augmented apoptosis resistance. This was mediated by NGAL-dependent modulation of the pro-apoptotic protein Bim levels. Evaluation of the plasma NGAL levels in NSCLC patients that received erlotinib revealed that patients with lower baseline NGAL demonstrated a better erlotinib response. Compared to patients with wild type EGFR, patients with activating EGFR mutations had lower plasma NGAL at baseline and weeks 4 and 8. CONCLUSIONS: Our studies uncover a novel mechanism of NGAL-mediated modulation of Bim levels in NSCLC that might contribute to TKI resistance in lung cancer patients. These findings provide the rationale for the further investigations of the utility of NGAL as a potential therapeutic target or diagnostic biomarker.

Non-trauma related paediatric abdominal surgical emergencies in Lagos, Nigeria: Epidemiology and indicators of survival.

BACKGROUND: Pediatric surgical emergencies are associated with higher morbidity and mortality. The aim of this study is to describe the epidemiology of non-trauma related pediatric abdominal surgical emergencies in our centre and determine the indicators for survival in a cohort of patients. PATIENTS AND METHODS: A retrospective study of children aged 1 day to 15 years who presented with non-trauma related abdominal emergencies at the Lagos University Teaching Hospital (LUTH). RESULTS: There were 129 children. The median age at presentation was 5 months (range: 1 day-15 years). There were 104 males and 25 females. Sixty-four (49.6%) patients presented within 48 hours of the onset of the symptoms while 65 (50.4%) presented after 48 hours. Intestinal obstruction is the commonest indication for pediatric emergency surgery in our centre accounting for 76 patients (58.9%). Appendicitis is the second most common indication for emergency surgery with 13 patients (10.1%). Thirteen patients (10.1%) had postoperative complications. There were 13 deaths in all (10.1% mortality rate). Eleven out of 43 (25.6%) neonates died compared with 2 (2.3%) out of 86 patients in the other age groups (P=0.002). Seven out of 107 (6.5%) patients that had surgery within 72 hours died while 5/22 (22.7%) patients died who had surgery after 72 hours (P=0.003). There were 4 mortalities (28.6%) among patients with postoperative complications compared with 9 (7.8%) mortalities among 116 patients without any postoperative complications (Pp=0.001). CONCLUSION: Intestinal obstruction is the commonest pediatric surgical emergency seen in LUTH. Neonatal age, admission to surgery intervention time >72 hours, and severe postoperative complications are associated with high mortality.