Potential biomarkers in endometrial cancer: a narrative review.

CONTEXT: Every year, approximately 0.4 million women suffer from endometrial cancer (EC) worldwide and it has become the most common gynecological malignancy. Almost 66% of EC cases are diagnosed at an early stage and can be cured by performing surgery while those at an advanced stage turns out to be fatal. Biomarkers of endometrial cancer would be very valuable for screening of women who are at high risk and in detecting the chance of recurrence of disease. OBJECTIVE: The current article has reviewed studies published on expression of biomarkers and susceptibility to EC. METHODS: Google Scholar and PubMed were used as searching platforms and we have majorly considered the literature from last 10 years. RESULTS: Potential biomarkers of EC identified from various studies were summarised.

Transurethral lidocaine (100 mg) bladder irrigation (TULI100) reduces the incidence of catheter related bladder discomfort in transurethral resection of bladder tumors: A randomized, double blind, controlled trial.

BACKGROUND: Transurethral resection of bladder tumors (TURBT) surgeries requires post-resection catheterization for continuous irrigation of the bladder. This indwelling catheter is associated with distressing catheter-related bladder discomfort (CRBD) and increases postoperative pain and agitation. OBJECTIVES: To prove the hypothesis that transurethral 100 mg lidocaine irrigation at the end of TURBT can reduce the frequency of moderate-to-severe postoperative CRBD. METHODS: 116 patients scheduled for TURBT were screened, 94 were recruited and completed the study. American Society of Anesthesiologists Physical Status I-II adult patients, 20-75 years of age undergoing elective TURBT surgery under general anesthesia were included. Transurethral normal saline with 0.01% lidocaine (100 mg in 1 L NS) was used for irrigation 30 min before the completion of surgery in group L, while only normal saline was used for transurethral irrigation in group N. The main outcomes were frequency of CRBD, pain and patient satisfaction at 0, 1, 2, and 6 h postoperatively. RESULTS: A total of 94 patients were analyzed in the study. The incidence of moderate-severe CRBD was significantly lower in group L as compared to group C at 0, 1, and 2 h (65.9% vs. 31.9%, p = 0.01; 31.9% vs. 10.6%, p = 0.012; 21.3% vs. 2.1%, p = 0.004, respectively). At the 6-h mark, the incidence of CRBD was lower in group L, although this did not achieve statistical significance (6.38% vs. 2.1%; p = 0.613). CONCLUSION: Irrigation with 0.01% lidocaine (100 mg) towards the end of TURBT reduces the incidence of moderate-severe CRBD by 52% and increases patient satisfaction.

Comparative evaluation of ultrasound guided supraclavicular and infraclavicular subclavian venous catheterizations in adult patients.

Background and Aims: Ultrasound-guided subclavian vein cannulation has two approaches: supraclavicular and infraclavicular. The aim of this study was to compare the ease of cannulation by recording the puncture time of the subclavian vein with the two approaches in adult patients. Material and Methods: This study was approved by our institutional ethics committee, and a written informed consent was obtained from the patients. This prospective randomized trial recruited patients aged 18 to 80 years with definite indications of subclavian vein cannulation. Real-time in-plane ultrasound-guided technique was used, and the subclavian vein was punctured at the junction of the brachiocephalic and IJV in supraclavicular approach (SC) and in oblique axis below the border of the clavicle in infraclavicular approach (IC). Results: A total of 96 patients were randomly allocated equally into two groups of 48 each, but only 45 patients in each group could be successfully cannulated. Median puncture times were comparable; 15 (9-39) s in SC and 21 (5-80) s in IC group. The first attempt success rate was 82.2% and 62.2%, and the mean total access time was 99.11 ± 34.66 s and 103.44 ± 50.27 s in SC and IC approaches, respectively and were comparable. The attempts of needle puncture were significantly higher in IC approach (1.40 ± 0.54 vs 1.20 ± 0.46 in SC approach; P = 0.04). The complication rates were comparable and less than 5%. Conclusion: Ease of cannulation of the subclavian vein using ultrasound-guided supraclavicular and infraclavicular approach is comparable as no statistically significant difference is noted in the puncture time and first-attempt success rate. The increased number of needle punctures reported in our study with the IC approach did not translate to an increased complication rate.

Application of the Risk Stratification Index to Multilevel Models of All-condition 30-Day Mortality in Hospitalized Populations Over the Age of 65.

BACKGROUND: The Risk Stratification Index (RSI) is superior to Hierarchical Conditions Categories (HCC) in patient-level regressions but has not been applied to assess hospital effects. OBJECTIVE: The objective of this study was to measure the accuracy of RSI in modeling 30-day hospital mortality across all conditions using multilevel logistic regression. SUBJECTS AND DATA SOURCES: A 100% sample of Medicare inpatient stays from 2009 to 2014, restricted to patients greater than 65 years of age in general hospitals, resulting in 64 million stays at 3504 hospitals. RESEARCH DESIGN: We calculated RSI and HCC scores for patient stays using multilevel logistic regression in 3 populations: all inpatients, surgical, and nonsurgical. Correlations of risk-standardized mortality rates with rates of specific case types assessed case-mix balance. Patient stay volume was included to assess smaller hospitals. RESULTS: We found a negligible correlation of all-conditions risk-standardized mortality rates with hospitals' proportions of orthopedic, cardiac, or pneumonia cases. RSI outperformed HCC in multilevel regressions containing both patient and hospital-level effects. C-statistics using RSI were 0.87 for the all-inpatients group, 0.87 for surgical, and 0.86 for nonsurgical stays. With HCC they were 0.82, 0.82, and 0.81. Akaike Information Criteria and Bayesian Information Criteria values were higher with HCC. RSI shifted 41% of hospitals' rankings by >1 decile. Hospitals with smaller volumes had higher 30-day observed and standardized mortality: 11.2% in the lowest volume quintile versus 8.5% in the highest volume quintile. CONCLUSION: RSI has superior accuracy and results in a significant shift in rankings compared with HCC in multilevel models of 30-day hospital mortality across all conditions.

Comparative evaluation of optic nerve sheath diameter in patients undergoing laparoscopic cholecystectomy using low and standard pressures of gas insufflations.

Background and Aims: Intra-abdominal insufflation of CO2 is associated with an increase of intracranial pressure (ICP). We conducted this randomized control trial to compare the impact of low vs standard pressure pneumoperitoneum on ICP through the ultrasonographic estimation of the optic nerve sheath diameter (ONSD). Material and Methods: Patients of age group 18-80 years planned for laparoscopic cholecystectomy were randomly allocated into two groups; group S (standard pressure of 12-16 mmHg) and group L (low pressure of 8-10 mmHg) on the basis of intra-abdominal pressures used for the surgery. All were administered general anesthesia and end-tidal carbon dioxide (ETCO2) was maintained between 35 and 40 mmHg and peak airway pressures less than 35 cmH2O. ONSD was measured in either eye at a point 3 mm posterior to the globe at following time intervals; baseline, 5 min after induction, 10 min after insufflation, 10 min after reverse Trendelenburg, intraoperatively during surgery and after exsufflation in the supine position. Results: The demographic profile and operative times were comparable. ONSD was measured in 100 patients in each group for both the eyes and no patient had values above the cutoff value of 5.0 mm. No significant difference in the ONSD was observed at the above mentioned time intervals between the groups. There was a statistically significant lower value of the heart rate and mean arterial pressure in the low-pressure group. Conclusion: Intra-abdominal insufflation of CO2 at standard and low pressures does not increase ICP in short duration surgeries and thus both the pressures can be safely used in adult patients operated in reverse Trendelenburg position. Advantages of low pressure were limited to better hemodynamic control.

Evidence for underuse of effective medical services around the world.

Underuse-the failure to use effective and affordable medical interventions-is common and responsible for substantial suffering, disability, and loss of life worldwide. Underuse occurs at every point along the treatment continuum, from populations lacking access to health care to inadequate supply of medical resources and labour, slow or partial uptake of innovations, and patients not accessing or declining them. The extent of underuse for different interventions varies by country, and is documented in countries of high, middle, and low-income, and across different types of health-care systems, payment models, and health services. Most research into underuse has focused on measuring solutions to the problem, with considerably less attention paid to its global prevalence or its consequences for patients and populations. Although focused effort and resources can overcome specific underuse problems, comparatively little is spent on work to better understand and overcome the barriers to improved uptake of effective interventions, and methods to make them affordable.

Levers for addressing medical underuse and overuse: achieving high-value health care.

The preceding papers in this Series have outlined how underuse and overuse of health-care services occur within a complex system of health-care production, with a multiplicity of causes. Because poor care is ubiquitous and has considerable consequences for the health and wellbeing of billions of people around the world, remedying this problem is a morally and politically urgent task. Universal health coverage is a key step towards achieving the right care. Therefore, full consideration of potential levers of change must include an upstream perspective-ie, an understanding of the system-level factors that drive overuse and underuse, as well as the various incentives at work during a clinical encounter. One example of a system-level factor is the allocation of resources (eg, hospital beds and clinicians) to meet the needs of a local population to minimise underuse or overuse. Another example is priority setting using tools such as health technology assessment to guide the optimum diffusion of safe, effective, and cost-effective health-care services. In this Series paper we investigate a range of levers for eliminating medical underuse and overuse. Some levers could operate effectively (and be politically viable) across many different health and political systems (eg, increase patient activation with decision support) whereas other levers must be tailored to local contexts (eg, basing coverage decisions on a particular cost-effectiveness ratio). Ideally, policies must move beyond the purely incremental; that is, policies that merely tinker at the policy edges after underuse or overuse arises. In this regard, efforts to increase public awareness, mobilisation, and empowerment hold promise as universal methods to reset all other contexts and thereby enhance all other efforts to promote the right care.

Drivers of poor medical care.

The global ubiquity of overuse and underuse of health-care resources and the gravity of resulting harms necessitate an investigation of drivers to inform potential solutions. We describe the network of influences that contribute to poor care and suggest that it is driven by factors that fall into three domains: money and finance; knowledge, bias, and uncertainty; and power and human relationships. In each domain the drivers operate at the global, national, regional, and individual level, and are modulated by the specific contexts within which they act. We discuss in detail drivers of poor care in each domain.

Evidence for overuse of medical services around the world.

Overuse, which is defined as the provision of medical services that are more likely to cause harm than good, is a pervasive problem. Direct measurement of overuse through documentation of delivery of inappropriate services is challenging given the difficulty of defining appropriate care for patients with individual preferences and needs; overuse can also be measured indirectly through examination of unwarranted geographical variations in prevalence of procedures and care intensity. Despite the challenges, the high prevalence of overuse is well documented in high-income countries across a wide range of services and is increasingly recognised in low-income countries. Overuse of unneeded services can harm patients physically and psychologically, and can harm health systems by wasting resources and deflecting investments in both public health and social spending, which is known to contribute to health. Although harms from overuse have not been well quantified and trends have not been well described, overuse is likely to be increasing worldwide.

Comparison of an Updated Risk Stratification Index to Hierarchical Condition Categories.

BACKGROUND: The Risk Stratification Index and the Hierarchical Condition Categories model baseline risk using comorbidities and procedures. The Hierarchical Condition categories are rederived yearly, whereas the Risk Stratification Index has not been rederived since 2010. The two models have yet to be directly compared. The authors thus rederived the Risk Stratification Index using recent data and compared their results to contemporaneous Hierarchical Condition Categories. METHODS: The authors reimplemented procedures used to derive the original Risk Stratification Index derivation using the 2007 to 2011 Medicare Analysis and Provider review file. The Hierarchical Condition Categories were constructed on the entire data set using software provided by the Center for Medicare and Medicaid Services. C-Statistics were used to compare discrimination between the models. After calibration, accuracy for each model was evaluated by plotting observed against predicted event rates. RESULTS: Discrimination of the Risk Stratification Index improved after rederivation. The Risk Stratification Index discriminated considerably better than the Hierarchical Condition Categories for in-hospital, 30-day, and 1-yr mortality and for hospital length-of-stay. Calibration plots for both models demonstrated linear predictive accuracy, but the Risk Stratification Index predictions had less variance. CONCLUSIONS: Risk Stratification discrimination and minimum-variance predictions make it superior to Hierarchical Condition Categories. The Risk Stratification Index provides a solid basis for care-quality metrics and for provider comparisons.

Validation and Calibration of the Risk Stratification Index.

BACKGROUND: The Risk Stratification Index was developed from 35 million Medicare hospitalizations from 2001 to 2006 but has yet to be externally validated on an independent large national data set, nor has it been calibrated. Finally, the Medicare Analysis and Provider Review file now allows 25 rather than 9 diagnostic codes and 25 rather than 6 procedure codes and includes present-on-admission flags. The authors sought to validate the index on new data, test the impact of present-on-admission codes, test the impact of the expansion to 25 diagnostic and procedure codes, and calibrate the model. METHODS: The authors applied the original index coefficients to 39,753,036 records from the 2007-2012 Medicare Analysis data set and calibrated the model. The authors compared their results with 25 diagnostic and 25 procedure codes, with results after restricting the model to the first 9 diagnostic and 6 procedure codes and to codes present on admission. RESULTS: The original coefficients applied to the 2007-2012 data set yielded C statistics of 0.83 for 1-yr mortality, 0.84 for 30-day mortality, 0.94 for in-hospital mortality, and 0.86 for median length of stay-values nearly identical to those originally reported. Calibration equations performed well against observed outcomes. The 2007-2012 model discriminated similarly when codes were restricted to nine diagnostic and six procedure codes. Present-on-admission models were about 10% less predictive for in-hospital mortality and hospital length of stay but were comparably predictive for 30-day and 1-yr mortality. CONCLUSIONS: Risk stratification performance was largely unchanged by additional diagnostic and procedure codes and only slightly worsened by restricting analysis to codes present on admission. The Risk Stratification Index, after calibration, thus provides excellent discrimination and calibration for important health services outcomes and thus appears to be a good basis for making hospital comparisons.

Comparison of short-axis out-of-plane versus long-axis in-plane ultrasound-guided radial arterial cannulation in adult patients: a randomized controlled trial.

BACKGROUND: The current available literature is not unanimous in reporting the utility of short-axis and long-axis techniques for radial artery cannulation in both adults and children. This study was designed to compare short-axis out-of-plane (SA-OOP) and long-axis in-plane (LA-IP) techniques in ultrasound-guided radial artery cannulation in adults. METHODS: In this prospective randomized controlled trial, 150 adult patients of American Society of Anesthesiologists physical status I-III aged between 18 and 70 years were included. All patients were randomized into two groups (group SA-OOP) and (group LA-IP) of 75 each undergoing ultrasound-guided radial artery cannulation. The primary outcome was successful cannulation in the first attempt. Secondary outcomes included antero-posterior arterial diameter, skin-to-artery distance, ultrasonic localization time, cannulation time, no of attempts to cannulate artery, cannula insertion failure, and vascular complications. RESULTS: First-attempt arterial cannulation was successful in 80 % of patients in the SA-OOP group as opposed to 82.6 % patients in the LA-IP group (p = 0.67). The time to cannulate the artery was similar between the two groups, but the time to localize artery was significantly higher in the long-axis technique (p < 0.001). CONCLUSIONS: The first-attempt cannulation success rate and cannulation time in adult patients are similar in ultrasound-guided radial artery cannulation with both short-axis as well as long-axis techniques. Trial registration Clinical Trial Registry of India (CTRI/2015/02/005552).

Effect of Intensive Education and Training of Nurses on Ventilator-associated Pneumonia and Central Line-associated Bloodstream Infection Incidence in Intensive Care Unit at a Tertiary Care Center in North India.

OBJECTIVE: The aim was to analyze the impact of education and training of nurses on the incidence of ventilator-associated pneumonia (VAP) and central line-associated bloodstream infection (CLABSI). PATIENTS AND METHODS: A prospective observational study at a tertiary care hospital included adult patients with Intensive Care Unit stay >48 h. The study was done in three phases: in Phase 1, baseline VAP and CLABSI incidence was calculated; in Phase 2, education and training of nurses; and in Phase 3, data were recollected for the incidence of VAP and CLABSI. RESULTS: The baseline incidence of VAP in Phase 1 was 28.86/1000 ventilator days and that of CLABSI was 7.89/1000 central-line days. In Phase 3, the incidence of VAP increased to 35.06 and that of CLABSI decreased significantly, 1.73. CONCLUSION: Intensive education and training sessions with feedback from nurses over a period of 6 months led to significant reduction in the incidence of CLABSI; however, the incidence of VAP increased.

Perioperative use of transthoracic echocardiography in a patient with congenitally corrected transposition of great arteries, atrial septal defect and severe pulmonary stenosis for lower segment cesarean section.

A 25-year-old female with congenitally corrected transposition of great arteries (CCTGAs), atrial septal defect, and severe pulmonary stenosis underwent lower segment cesarean section at 34 weeks of gestation using combined spinal epidural anesthesia (CSEA). We used transthoracic echocardiography (TTE) for intraoperative monitoring of the cardiovascular system because these patients are reported to have a high prevalence of myocardial perfusion defects, regional wall motion abnormalities, and impaired ventricular contractility. Scanning was done at four different time intervals; preoperatively, after initiation of CSEA, after delivery of child and postoperatively (6 and 24 h postdelivery) to detect regional wall motion and valvular abnormalities, calculate ejection fractions and optimize fluid administration. In this case report, we thus discuss the anatomical defects of CCTGA, physiologic concerns and emphasize on the use of TTE for perioperative management of such cases.

Esculetin induces antiproliferative and apoptotic response in pancreatic cancer cells by directly binding to KEAP1.

BACKGROUND: A handful of studies have exploited antitumor potential of esculetin, a dihydroxy coumarine derivative; the targets to which it binds and the possible downstream mechanism for its cytotoxicity in cancer cells remain to be elucidated. Using pancreatic cancer cell lines as a model system, herein the study was initiated to check the efficacy of esculetin in inhibiting growth of these cancer cells, to decipher mechanism of its action and to predict its direct binding target protein. METHODS: The cytotoxicity of esculetin was determined in PANC-1, MIA PaCa-2 and AsPC-1 cell lines; followed by an inspection of intracellular levels of ROS and its associated transcription factor, p65-NF-κB. The interaction between transcription factor, Nrf2 and its regulator KEAP1 was studied in the presence and absence of esculetin. The effect of Nrf2 on gene expression of antioxidant response element pathway was monitored by real time PCR. Thereafter, potential binding target of esculetin was predicted through molecular docking and then confirmed in vitro. RESULTS: Esculetin treatment in all three pancreatic cancer cell lines resulted in significant growth inhibition with G1-phase cell cycle arrest and induction of mitochondrial dependent apoptosis through activation of caspases 3, 8 and 9. A notable decrease was observed in intracellular ROS and protein levels of p65-NF-κB in PANC-1 cells on esculetin treatment. Antioxidant response regulator Nrf2 has been reportedly involved in crosstalk with NF-κB. Interaction between Nrf2 and KEAP1 was found to be lost upon esculetin treatment in PANC-1 and MIA Paca-2 cells. Nuclear accumulation of Nrf2 and an upregulation of expression of Nrf2 regulated gene NQO1, observed on esculetin treatment in PANC-1 further supported the activation of Nrf2. To account for the loss of Nrf2-KEAP1 interaction on esculetin treatment, direct binding potential between esculetin and KEAP1 was depicted in silico using molecular docking studies. Pull down assay using esculetin conjugated sepharose beads confirmed the binding between esculetin and KEAP1. CONCLUSIONS: We propose that esculetin binds to KEAP1 and inhibits its interaction with Nrf2 in pancreatic cancer cells. This thereby promotes nuclear accumulation of Nrf2 in PANC-1 cells that induces antiproliferative and apoptotic response possibly by attenuating NF-κB.

Design, synthesis and evaluation of novel indandione derivatives as multifunctional agents with cholinesterase inhibition, anti-ß-amyloid aggregation, antioxidant and neuroprotection properties against Alzheimer's disease.

A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)-1H-indene-1,3(2H)-diones were designed, synthesized and appraised as multifunctional anti-Alzheimer agents. In vitro studies of compounds 27-38 showed that these compounds exhibit moderate to excellent AChE, BuChE and Aß aggregation inhibitory activity. Notably, compounds 34 and 38 appeared as most active multifunctional agents in the entire series and exhibited excellent inhibition against AChE (IC50=0.048µM: 34; 0.036µM: 38), Aß aggregation (max% inhibition 82.2%, IC50=9.2µM: 34; max% inhibition 80.9%, IC50=10.11µM: 38) and displayed significant antioxidant potential in ORAC-FL assay. Both compounds also successfully diminished H2O2 induced oxidative stress in SH-SY5Y cells. Fascinatingly, compounds 34 and 38 showed admirable neuroprotective effects against H2O2 and Aß induced toxicity in SH-SY5Y cells. Additionally, both derivatives showed no considerable toxicity in neuronal cell viability assay and represented drug likeness properties in the primarily pharmacokinetics study. All these results together, propelled out that compounds 34 and 38 might serve as promising multi-functional lead candidates for treatment of AD in the future.

Development of cyanopyridine-triazine hybrids as lead multitarget anti-Alzheimer agents.

A series of new cyanopyridine-triazine hybrids were designed, synthesized and screened as multitargeted anti-Alzheimer's agents. These molecules were designed while using computational techniques and were synthesized via a feasible concurrent synthetic route. Inhibition potencies of synthetic compounds 4a-4h against cholinesterases, Aß1-42 disaggregation, oxidative stress, cytotoxicity, and neuroprotection against Aß1-42-induced toxicity of the synthesized compounds were evaluated. Compounds 4d and 4h showed promising inhibitory activity on acetylcholinesterase (AChE) with IC50 values 0.059 and 0.080µM, respectively, along with good inhibition selectivity against AChE over butyrylcholinesterase (BuChE). Molecular modelling studies revealed that these compounds interacted simultaneously with the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The mixed type inhibition of compound 4d further confirmed their dual binding nature in kinetic studies. Furthermore, the results from neuroprotection studies of most potent compounds 4d and 4h indicate that these derivatives can reduce neuronal death induced by H2O2-mediated oxidative stress and Aß1-42 induced cytotoxicity. In addition, in silico analysis of absorption, distribution, metabolism and excretion (ADME) profile of best compounds 4d and 4h revealed that they have drug like properties. Overall, these cyanopyridine-triazine hybrids can be considered as a candidate with potential impact for further pharmacological development in Alzheimer's therapy.

Using the first drop of blood for monitoring blood glucose values in critically ill patients: An observational study.

CONTEXT: Using the first drop or second drop of blood while measuring blood glucose (BG) values. OBJECTIVE: The study was planned to compare the BG values from the first and second drops of blood. RESEARCH SETTINGS: The study was conducted at the Main Intensive Care Unit, PGIMER, Chandigarh, India. RESEARCH DESIGN: This study was a comparative study. MATERIALS AND METHODS: Ninety patients aged 2-93 years were enrolled in this study. BG values from the first and second drops of blood were taken and compared. STATISTICAL ANALYSIS USED: Agreement between two drops was assessed using Bland-Altman analysis. A bias of <10 mg/dl was considered clinically acceptable. Linear regression of the mean difference (bias) with the BG readings was performed. RESULTS: One thousand four hundred and seven pairs of BG readings were taken from the enrolled patients. BG values had a bias of 3.9 ± 14.9 mg/dl. Nearly 96.7% of BG readings were within the limits of agreement. The absolute difference between first and second drops of blood was calculated; nearly 75.4% of the readings had fallen between 0 and 10 mg/dl, i.e. clinically acceptable range. CONCLUSION: There is no compete concordance of values of blood glucose between the first and the second drops of blood; any of the drops can be used for measuring BG values as the difference is not statistically significant. However, if hands are visibly clean and to decrease the blood loss in the critically ill patients where the BG values are measured frequently, using the first drop of blood is advised.