Current Trends and Predictors of Case Outcomes for Malpractice in Colonoscopy in the United States.

BACKGROUND: Over 14 million colonoscopies are performed annually, and this procedure remains the largest contributor to malpractice claims against gastroenterologists. The aim of this study was to evaluate reasons for litigation and predictors of case outcomes. MATERIALS AND METHODS: Cases related to colonoscopy were reviewed within the Westlaw legal database. Patient demographics, reasons for litigation, case payouts, and verdicts were assessed. Multivariate regression was used to determine predictors of defendant verdicts. RESULTS: A total of 305 cases were included from years 1980 to 2017. Average patient age was 54.9 years (range, 4 to 93) and 52.8% of patients were female. Juries returned defendant and plaintiff verdicts in 51.8% and 25.2% of cases, respectively, and median payout was $995,000. Top reasons for litigation included delay in treatment (65.9%) and diagnosis (65.6%), procedural error (44.3%), and failure to refer (25.6%). Gastroenterologists were defendants in 71% of cases, followed by primary care (32.2%) and surgeons (14.8%). Cases citing informed consent predicted defendant verdict (odds ratio, 4.05; 95% confidence interval, 1.90-9.45) while medication error predicted plaintiff verdict (odds ratio, 0.18; 95% confidence interval, 0.04-0.59). Delay in diagnosis (P=0.060) and failure to refer (P=0.074) trended toward plaintiff verdict but did not reach significance. Most represented states were New York (21.0%), California (13.4%), Pennsylvania (13.1%), Massachusetts (12.5%). CONCLUSIONS: Malpractice related to colonoscopy remains a significant and has geographic variability. Errors related to sedation predicted plaintiff verdict and may represent a target to reduce litigation. Primary care physicians and surgeons were frequently cited codefendants, underscoring the significance of interdisciplinary care for colonoscopy.

Association of hospital factors and socioeconomic status with the utilization of minimally invasive surgery for colorectal cancer over a decade.

BACKGROUND: Surgical resection is a mainstay of treatment for colorectal cancer (CRC). Minimally invasive surgery (MIS) has been shown to have improved outcomes compared to open procedures for colorectal malignancy. While use of MIS has been increasing, there remains large variability in its implementation at the hospital and patient level. OBJECTIVE: The purpose of this study was to identify disparities in sex, race, location, patient income status, insurance status, hospital region, bed size and teaching status for the use of MIS in the treatment of CRC. METHODS: This was a retrospective cohort study using the Nationwide Inpatient Sample Database. Between 2008 and 2017, there were 412,292 hospitalizations of adult patients undergoing elective colectomy for CRC. The primary outcome was use of MIS during hospitalization. RESULTS: Overall, the frequency of open colectomies was higher than MIS (56.56% vs. 43.44%). Black patients were associated with decreased odds of MIS use during hospitalization compared to White patients (OR 0.921, p = 0.0011). As the county population where patients resided decreased, odds of MIS also significantly decreased as compared to central counties of metropolitan areas. As income decreased below the reference of $71,000, odds of MIS also significantly decreased. Medicaid and uninsured patients had decreased odds of MIS use during hospitalization compared to private insurance (OR 0.751, p < 0.0001 and OR 0.629, p < 0.0001 respectively). Rural and urban non-teaching hospitals were associated with decreased odds of MIS as compared to urban teaching hospitals (OR 0.523, p < 0.0001 and OR 0.837, p < 0.0001 respectively). Hospitals with a small bed size were also associated with decreased MIS during hospitalizations (OR 0.888, p < 0.0001). CONCLUSIONS: Marked hospital level and socioeconomic disparities exist for utilization of MIS for colorectal cancer. Strategies targeted at reducing these gaps have the potential to improve surgical outcomes and cancer survival.

Retrospective review of case records of snakebite presenting to a single tertiary care centre over a 5-year period.

Background Snakebite is a disease of the poor, and hospitals catering to these individuals are often resource-constrained. Lack of electronic medical records in these resource-limited settings makes the capture of data even harder. Methods Before establishing a snakebite registry in the region, we did a retrospective case record review of all snakebite victims (n=3229) over 5 years who presented to a single tertiary care centre, catering to one of the largest number of snakebite victims in the country. Results Of the 451 cases, 262 (58.1%) presented to the emergency department within 2 hours of the bite. In 170 instances, the snake was brought along and the species of the snake was recorded. Russell's viper was the most common (130; 76.5%). Blood products were used in 237 (52.5%) patients. Acute kidney injury occurred in 165 (36.6%) patients, of whom 37 (8.2%) required dialysis. The mean (SD) duration of hospital admission was 10.5 (7.4) days. There was a significant correlation between number of snakebites with rainfall and humidity. One hundred and seven cases (3.3%) of snakebite resulted in mortality. A majority of mortality records were not available (88%; 94/107), rendering us incapable of doing reliable mortality data correlations or interpretation. Conclusion Viperidae bites predominate in the region, with renal injury being the most common cause for morbidity. Region-specific, prospective snakebite mapping could be a cost-effective strategy that might help in vulnerability analysis of the region. A multi-centric region-specific snakebite registry encompassing not just the clinico-epidemiological characteristics of snakebite victims, but also the demographic data, the pre-hospital care and local remedial practices, geospatial distribution, anti-snake venom and blood product usage, will help in developing better healthcare strategies for snakebite victims in India.

The anti-tumor agent, Dp44mT, promotes nuclear translocation of TFEB via inhibition of the AMPK-mTORC1 axis.

Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and its analogues are potent anti-cancer agents through their ability to target lysosomes. Considering this, it was important to understand the mechanisms involved in the Dp44mT-mediated induction of autophagy and the role of 5'-adenosine monophosphate-activated protein kinase (AMPK) as a critical autophagic regulator. As such, this investigation examined AMPK's role in the regulation of the transcription factor EB (TFEB), which transcribes genes involved in autophagy and lysosome biosynthesis. For the first time, this study demonstrated that Dp44mT induces translocation of TFEB to the nucleus. Furthermore, Dp44mT-mediated nuclear translocation of TFEB was AMPK-dependent. Considering that: (1) the mammalian target of rapamycin complex 1 (mTORC1) plays an important role in the regulation of TFEB; and (2) that AMPK is a known regulator of mTORC1, this study also elucidated the mechanisms through which Dp44mT regulates nuclear translocation of TFEB via AMPK. Silencing AMPK led to increased mTOR phosphorylation, that activates mTORC1. Since Dp44mT inhibits mTORC1 in an AMPK-dependent manner through raptor phosphorylation, Dp44mT is demonstrated to regulate TFEB translocation through dual mechanisms: AMPK activation, which inhibits mTOR, and inhibition of mTORC1 via phosphorylation of raptor. Collectively, Dp44mT-mediated activation of AMPK plays a crucial role in lysosomal biogenesis and TFEB function. As Dp44mT potently chelates copper and iron that are crucial for tumor growth, these studies provide insight into the regulatory mechanisms involved in intracellular clearance and energy metabolism that occur upon alterations in metal ion homeostasis.

Laparoscopy improves failure to rescue compared to open surgery for emergent colectomy.

Emergent colectomy is performed in thousands of Americans each year and carries significant morbidity and mortality. Although laparoscopy has gained favor in the elective setting, its impact on failure to rescue has not been studied on a population level for emergent colectomy. The purpose of this study was to compare failure to rescue following laparoscopic versus open colectomy in the emergency setting. This was a retrospective cohort study of The American College of Surgeons National Surgical Quality Improvement Program. Adult patients undergoing emergent colectomy between 2005 and 2018 were selected and stratified into laparoscopic or open surgery groups using the Current Procedural Terminology codes. Propensity matching was performed based on the demographic and comorbidity data. Main outcomes were failure to rescue, mortality, overall morbidity, individual complications, and length of hospital stay. After matching, 11,484 cases were included for analysis, of which 3829 were laparoscopic. Overall, open colectomy conferred higher odds of failure to rescue (OR 1.71, 95% CI 1.42-2.08), mortality (OR 1.72, 95% CI 1.44-2.07), and morbidity (OR 1.73, 95% CI 1.60-1.88) vs laparoscopic cases. Open surgery significantly increased the risk of nearly all measured postoperative complications including return to operating room (OR 1.25, 95% CI 1.08-1.45), ventilator use > 48 h (OR 2.43, 95% CI 2.03-2.93), and septic shock (OR 2.34, 95% CI 1.97-2.80). Hospital length of stay was shorter for patients undergoing laparoscopic (10.4 days) vs open (12.3 days) colectomy (p < 0.0001). This study demonstrates the safety and efficacy of the laparoscopic approach for emergent colectomy vs open surgery. Laparoscopy was associated with improved complications rates, mortality, and failure to rescue, indicating that it is a promising option to improve patient outcomes during emergent colectomy.

Insurance status and level of education predict disparities in receipt of treatment and survival for anal squamous cell carcinoma.

INTRODUCTION: Anal squamous cell carcinoma (ASCC) is relatively rare, but its incidence and mortality have been steadily climbing in marginalized populations. We explored the impact of insurance status, education, and income on survival and receipt of chemoradiation therapy. METHODS: We included patients with ASCC from the Surveillance, Epidemiology, and End Results Program database from 2004 to 2016. Socioeconomic variables included insurance status, level of education, income, and unemployment rate. Cox proportional hazards and multivariate logistic regression were used to determine predictors of survival and receipt of chemoradiation. RESULTS: We included a total of 10,868 cases of ASCC. The median age was 55, 10.4 % were black, and 65.4 % were female. Overall, 74.1 % of patients received combination chemoradiation. In multivariate analysis, poorer survival was found for Medicaid (HR 1.52, 95 % CI 1.34-1.74) and uninsured (HR 1.68, 95 % CI 1.35-2.10) patients, and for communities with the lowest rates of high school education (HR 1.17, 95 % CI 1.02-1.38), lowest income (HR 1.29, 95 % CI 1.08-1.54), and highest unemployment (HR 1.21, 95 % CI 1.03-1.40). Patients were less likely to receive combination treatment if they were black (OR 0.76, 95 % CI 0.55-0.92), had Medicaid insurance (OR 0.54, 95 % CI 0.33-0.88) or lower education (OR 0.59, 95 % CI 0.46-0.76). CONCLUSION: Insurance status, level of education, income, and employment impact survival and receipt of treatment in patients with ASCC. Identifying high risk patients and developing targeted interventions to improve access to treatment is integral to reducing these disparities and improving cancer survival.

Regulation of autophagy and apoptosis by Dp44mT-mediated activation of AMPK in pancreatic cancer cells.

Upon activation, the 5'-adenosine monophosphate-activated protein kinase (AMPK) increases catabolism, while inhibiting anabolism. The anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), activates AMPK in multiple tumor cell-types (Biochim. Biophys Acta 2016;1863:2916-2933). This acts as an initial cell "rescue response" after iron-depletion mediated by Dp44mT. Considering Dp44mT-mediated AMPK activation, the role of AMPK on Dp44mT cytotoxicity was examined. Dp44mT increased the p-AMPK/AMPK ratio in multiple tumor cell-types over short (24 h) and longer (72 h) incubations. Notably, Dp44mT was more effective in inhibiting tumor cell proliferation after AMPK silencing, potentially due to the loss of AMPK-mediated metabolic plasticity that protects cells against Dp44mT cytotoxicity. The silencing of AMPK-increased cellular cholesterol and stabilized lysosomes against Dp44mT-mediated lysosomal membrane permeabilization. This was substantiated by studies demonstrating that the cholesterol-depleting agent, methyl-ß-cyclodextrin (MßCD), restores Dp44mT-mediated lysosomal membrane permeabilization in AMPK silenced cells. The increased levels of cholesterol after AMPK silencing were independent of the ability of AMPK to inhibit the rate-limiting step of cholesterol synthesis via the inactivating phosphorylation of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) at Ser872. In fact, Dp44mT did not increase phosphorylation of HMGCR at (Ser872), but decreased total HMGCR expression similarly in both the presence or absence of AMPK silencing. Dp44mT was demonstrated to increase autophagic initiation after AMPK silencing via an AMPK- and Beclin-1-independent mechanism. Further, there was increased cleaved caspase 3 and cleaved PARP after incubation of AMPK silenced cells with Dp44mT. Overall, AMPK silencing promotes Dp44mT anti-proliferative activity, suggesting a role for AMPK in rescuing its cytotoxicity by inhibiting autophagy and also apoptosis.

Abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions in cervical dystonia.

The cerebellum can influence the responsiveness of the primary motor cortex (M1) to undergo spike timing-dependent plastic changes through a complex mechanism involving multiple relays in the cerebello-thalamo-cortical pathway. Previous TMS studies showed that cerebellar cortex excitation can block the increase in M1 excitability induced by a paired-associative stimulation (PAS), while cerebellar cortex inhibition would enhance it. Since cerebellum is known to be affected in many types of dystonia, this bidirectional modulation was assessed in 22 patients with cervical dystonia and 23 healthy controls. Exactly opposite effects were found in patients: cerebellar inhibition suppressed the effects of PAS, while cerebellar excitation enhanced them. Another experiment comparing healthy subjects maintaining the head straight with subjects maintaining the head turned as the patients found that turning the head is enough to invert the cerebellar modulation of M1 plasticity. A third control experiment in healthy subjects showed that proprioceptive perturbation of the sterno-cleido-mastoid muscle had the same effects as turning the head. We discuss these finding in the light of the recent model of a mesencephalic head integrator. We also suggest that abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions of the integrator in cervical dystonia.

Rectal perfusion parameters normalised to tumour-free rectal wall can predict response to neoadjuvant chemoradiotherapy.

AIMS: To evaluate absolute changes in quantitative and semi-quantitative perfusion parameters using a newer approach of comparing these parameters with tumour-free normal rectal wall (i.e., relative/normalised change) in predicting complete pathological response to chemoradiotherapy. MATERIALS AND METHODS: Perfusion parameters measured before and after treatment of 10 patients with histopathologically proven rectal cancer that showed complete treatment response (Group 1) were compared with 10 patients with residual tumour on histopathology following treatment (Group 2). Quantitative perfusion MRI parameters (Ktrans: volume transfer coefficient reflecting vascular permeability, Kep: flux rate constant, Ve: extracellular volume ratio reflecting vascular permeability, integral of area under the curve (IAUC); Toft model) were quantified by manually delineating a region of interest in the upper, mid and lower third of the tumour (1 cm2), in addition similar parameters were obtained from the normal rectal wall at least 1 cm away from the potential resection margin, absolute as well as relative perfusion values normalised to that of the normal rectal wall were evaluated. The differences in absolute and normalised qualitative parameters were compared within each group using paired t-tests and between each group using analysis of variance (ANOVA). RESULTS: Wash-in, wash-out, positive enhancement integral (PEI), Ktrans, IAUC in the complete pathological responders when compared to the adjacent normal rectal wall showed ratios approaching 1, suggesting that rectal perfusion is similar to the adjacent normal rectal wall in complete pathological responders. The difference in the normalised values in the responders and non-responders was statistically significant. CONCLUSION: Perfusion parameters can be used in predicting response to treatment, when normalised to the adjacent normal rectal wall.

Non-invasive quantification of hepatic steatosis in living, related liver donors using dual-echo Dixon imaging and single-voxel proton spectroscopy.

AIM: To evaluate the diagnostic implications of hepatic fat fraction calculated using dual-echo Dixon imaging and (1)H magnetic resonance spectroscopy (MRS) to detect hepatic steatosis in potential liver donors using histopathology as the reference standard. MATERIALS AND METHODS: One hundred and forty-five potential liver donors were included in the study. Magnetic resonance imaging (MRI) was performed using a 1.5 T system using a three-dimensional dual-echo MRI sequence with automated reconstruction of in-phase (IP), out-of-phase (OP), fat-signal-only, and water-signal-only images. Hepatic fat fraction was calculated by drawing 15 regions of interest on the IP, OP, fat-only, and water-only images. Single-voxel MRS was performed at echo times (TEs) of 30 ms in the right and left lobes of liver. Liver fat fraction was calculated from water and fat peaks. One hundred and forty-five biopsies were prospectively evaluated for steatosis by a pathologist using traditional determination of the cell-count fraction. MRI and pathology values of steatosis were correlated using Pearson's correlation coefficient. The sensitivity and specificity of each of these methods was calculated using histopathology as the reference standard. Reproducibility was assessed in 40 patients who had repeat scanning within 4-40 days. Measurement error was calculated from the coefficient of variation (CoV) with histopathologically proven <5% fat (n=112). RESULTS: The Bland-Altman limits of agreement with 95% confidence intervals (CI) was -2.9 to 5.3%. The intraclass correlation coefficient (ICC) for interobserver variability and reproducibility was 0.94 (95% CI: 0.91-0.97), 0.92 (95% CI: 0.91-0.97). The CoV was 7.6% (95% CI: 3.4-11.85). The area under the receiver operating characteristic (ROC) curve (AUC) for Dixon imaging 0.89 (95% CI: 0.87-0.91), for MRS 0.88 (95% CI: 0.86-0.90). The sensitivity for detecting <5% fat was 84% and specificity was 90%. CONCLUSION: Combination of dual-echo Dixon imaging and proton MRS is a useful tool for the preoperative diagnosis of hepatic steatosis in potential living liver donors. This can help avoid unnecessary biopsies in these patients.

Alterations in ovarian cancer cell adhesion drive taxol resistance by increasing microtubule dynamics in a FAK-dependent manner.

Chemorefractory ovarian cancer patients show extremely poor prognosis. Microtubule-stabilizing Taxol (paclitaxel) is a first-line treatment against ovarian cancer. Despite the close interplay between microtubules and cell adhesion, it remains unknown if chemoresistance alters the way cells adhere to their extracellular environment, a process critical for cancer metastasis. To investigate this, we isolated Taxol-resistant populations of OVCAR3 and SKOV3 ovarian cancer cell lines. Though Taxol-resistant cells neither effluxed more drug nor gained resistance to other chemotherapeutics, they did display increased microtubule dynamics. These changes in microtubule dynamics coincided with faster attachment rates and decreased adhesion strength, which correlated with increased surface ß1-integrin expression and decreased focal adhesion formation, respectively. Adhesion strength correlated best with Taxol-sensitivity, and was found to be independent of microtubule polymerization but dependent on focal adhesion kinase (FAK), which was up-regulated in Taxol-resistant cells. FAK inhibition also decreased microtubule dynamics to equal levels in both populations, indicating alterations in adhesive signaling are up-stream of microtubule dynamics. Taken together, this work demonstrates that Taxol-resistance dramatically alters how ovarian cancer cells adhere to their extracellular environment causing down-stream increases in microtubule dynamics, providing a therapeutic target that may improve prognosis by not only recovering drug sensitivity, but also decreasing metastasis.

Therapeutic potency of saponin rich aqueous extract of Scoparia dulcis L. in alloxan induced diabetes in rats.

BACKGROUND: Diabetes mellitus is major metabolic disorders of carbohydrate metabolism. This leads to alter the multiple organ system. AIMS: To investigate the antidiabetic and antioxidant effects of the saponin rich aqueous extract of Scoparia dulcis (SRE-SD) using alloxan-induced hyperglycemic rat model. MATERIAL AND METHODS: The single dose of alloxan was injected for the induction of diabetes in rats. The SRE-SD and glibenclamide were administered for 15 consecutive days from the 3(rd) day of alloxan administration. Quantity of food and water intake was measured at day 0, and 18. Further, body weight was recorded and blood samples were collected at different time intervals that is, day 0, 3, 8, 13, and 18. The oxidative biomarkers (i.e. thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and nitrite (NO(2-)) levels were also estimated in the serum sample. RESULTS: The SRE-SD showed a remarkable dose and time-dependent changes in alloxan-induced rise in the level of food consumption and water intake, serum glucose level, TBARS, NO(2-) and fall in the level of GSH. Further, significant attenuation was observed at 20 and 30 mg/kg of SRE-SD treated group. CONCLUSIONS: These findings demonstrate that SRE-SD has both antidiabetic and antioxidant effects on the experimental model of diabetes in rat.

Duplex sonography in the planning and evaluation of arteriovenous fistulae for haemodialysis.

This paper describes how to perform duplex sonography in the planning and evaluation of arteriovenous fistulae in haemodialysis patients, discusses its roles in these settings, and presents a review of commonly encountered complications.

Precision of cerebrovascular reactivity assessment with use of different quantification methods for hypercapnia functional MR imaging.

BACKGROUND AND PURPOSE: Tools for noninvasive mapping of hemodynamic function including cerebrovascular reactivity are emerging and may become clinically useful to predict tissue at hemodynamic risk. One such technique assesses blood oxygen level-dependent (BOLD) MR imaging contrast in response to hypercapnia, but the reliability of its quantification is uncertain. The aim of this study was to prospectively investigate the intersubject and interhemispheric variability and short-term reproducibility of hypercapnia functional MR imaging (fMRI) in healthy volunteers and to assess the effects of different methods of quantification and normalization. MATERIALS AND METHODS: Sixteen healthy volunteers, (7 women and 9 men) underwent hypercapnia fMRI with a clinical 1.5T scanner; 8 underwent scanning twice. We determined BOLD amplitude changes using a visually defined block design or automated regression to end-tidal (ET) carbon dioxide (CO2). Absolute percent signal intensity changes (PSC) were extracted for whole-brain, gray matter, and middle cerebral artery territory, and also normalized to ETCO2 change. Intersubject and intrasubject (between hemispheres and sessions) coefficients of variation (COV) were derived. We assessed the effects of different quantification methods on reproducibility indices using the t test and U tests. RESULTS: The mean change in ETCO2 was 7.8 +/- 3.3 mm Hg. Averaged BOLD increases varied from 2.54% to 2.92%. Short-term reproducibility was good for absolute PSC (4.8% to 10%) but poor for normalized PSC (range, 24% to 27% COV). Intersubject reproducibility varied between 11% and 23% for absolute PSC and, again, was poorer for normalized data (32% to 39%). Interhemispheric reproducibility of absolute PSC was excellent ranging between 1.24 and 2.16% COV. CONCLUSIONS: In conclusion, quantification of cerebrovascular reactivity with use of hypercapnia fMRI was found to have good between-session and very good interhemispheric reproducibility. The technique holds promise as a diagnostic tool, especially for sensitive detection of unilateral disease.