Repair of post-bariatric surgery, recurrent, and de novo hiatal hernias improves bloating, abdominal pain, regurgitation, and food intolerance.

BACKGROUND: Post-bariatric surgery hiatal hernias are associated with a cluster of symptoms, including bloating (nausea/vomiting or fullness), abdominal pain, regurgitation, and food intolerance or dysphagia (BARF). OBJECTIVES: To report the short-term outcomes of repairing post-bariatric surgery hiatal hernias in patients with BARF. SETTING: Large, multispecialty group practice with university affiliation. METHODS: We reviewed the records of all consecutive patients who underwent repair of post-bariatric surgery hiatal hernias (2012-2020). Data are shown as means ± standard deviations. RESULTS: We repaired hiatal hernias in 52 patients (age, 57 ± 10 yr), 4 ± 3 years post sleeve gastrectomy (SG; n = 27), 11 ± 6 years following Roux-en-Y gastric bypass (RYGB; n = 24), and 11 years post duodenal switch with SG (DS-SG; n = 1). Diagnoses were made by upper gastrointestinal contrast study (80%), computed tomography (70%), and/or endoscopy (56%). Hernias in patients with SG were repaired by a posterior cruroplasty after reducing the neo-stomach into the abdomen (n = 11 SG patients; n = 1 DS-SG patient) or converting the SG to RYGB (n = 16). All 24 RYGB patients underwent hernia repair similarly. At 12 ± 10 months of follow-up, dysphagia or regurgitation improved in >80% of patients; nausea, vomiting, or abdominal pain improved in 70% of patients; and heartburn persisted in 56% of patients. Subsequent recurrent hernias that required operative repair developed in 3 patients. CONCLUSIONS: Hiatal hernias containing the neo-stomach present earlier after SG than RYGB. The diagnosis can be made with a combination of imaging studies and endoscopy. Repair of post-bariatric surgery hiatal hernias markedly improves symptoms of BARF in most patients.

Management of nonalcoholic fatty liver disease and the role of bariatric surgery: a brief review for surgeons.

Nonalcoholic fatty liver disease (NAFLD) is closely linked to the metabolic syndrome and is highly prevalent in bariatric patients. The criterion standard to diagnose NAFLD is a liver biopsy specifically to detect inflammatory changes characteristic of nonalcoholic steatohepatitis. Technologic advancements will improve the accuracy of current noninvasive modalities. Modification of risk factors via food management is important to prevent the progression of NAFLD to nonalcoholic steatohepatitis and cirrhosis. Several clinical trials are underway for pharmacologic treatment of NAFLD; currently the mainstay of treatment is insulin sensitizers and vitamin E. There is strong evidence bariatric surgery improves biochemical and histologic features of NAFLD and therefore, bariatric surgery should be considered as a treatment of NAFLD in patients with obesity. Gastric bypass exhibits antilipogenic, antiinflammatory, antioxidant, and antidiabetic properties in the livers of laboratory animals; thereby, providing a unique window to study regulation of body adiposity and insulin resistance.

Health-Related Quality of Life and Physiological Outcomes of Peroral Endoscopic Myotomy for Achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) has gained acceptance as a treatment for achalasia. The aim of this study was to assess symptomatic, quality of life (QoL), and physiological outcomes of POEM using standardized methods. MATERIALS AND METHODS: Patients who were planned to undergo POEM were evaluated pre- and postoperatively with timed barium esophagogram (TBE), high-resolution manometry (HRM), the achalasia symptom questionnaire (ASQ) (best score 10, worst score 31), and the short form (SF)-36 (best score 100, worst score 0). Nine patients completed postoperative HRM, TBE, and 48 hours esophageal pH monitoring. A P-value of <.05 was considered statistically significant. RESULTS: A total of 34 of 37 patients completed the POEM procedure. There was improvement in the ASQ scores and in QoL. HRM integrated relaxation pressures (IRPs) improved from 31.4 ± 10.8 mmHg preoperatively to 12.3 ± 6.7 mmHg postoperatively, and lower esophageal sphincter pressure (LESP) improved from 49.1 ± 16.9 mmHg preoperatively to 23.1 ± 9.4 mmHg postoperatively. Of the 7 patients who were evaluated with 48-hour pH monitoring postoperatively, 5 patients (71%) demonstrated pathological reflux with an average Demeester score of 23.1 ± 19.1. There was a negative linear correlation between LESP change and Demeester scores (r = -0.7, P = .03). CONCLUSION: The POEM procedure significantly improves achalasia-related symptoms and improves social functioning. Physiologically, there is reduction in both IRP and LESP. Postoperative pathological reflux is correlated with LESP reduction.

Computerized intensive insulin dosing can mitigate hypoglycemia and achieve tight glycemic control when glucose measurement is performed frequently and on time.

INTRODUCTION: Control of blood glucose (BG) in critically ill patients is considered important, but is difficult to achieve, and often associated with increased risk of hypoglycemia. We examined the use of a computerized insulin dosing algorithm to manage hyperglycemia with particular attention to frequency and conditions surrounding hypoglycemic events. METHODS: This is a retrospective analysis of adult patients with hyperglycemia receiving intravenous (IV) insulin therapy from March 2006 to December 2007 in the intensive care units of 2 tertiary care teaching hospitals. Patients placed on a glycemic control protocol using the Clarian GlucoStabilizer IV insulin dosing calculator with a target range of 4.4-6.1 mmol/L were analyzed. Metrics included time to target, time in target, mean blood glucose +/- standard deviation, % measures in hypoglycemic ranges <3.9 mmol/L, per-patient hypoglycemia, and BG testing interval. RESULTS: 4,588 ICU patients were treated with the GlucoStabilizer to a BG target range of 4.4-6.1 mmol/L. We observed 254 severe hypoglycemia episodes (BG <2.2 mmol/L) in 195 patients, representing 0.1% of all measurements, and in 4.25% of patients or 0.6 episodes per 1000 hours on insulin infusion. The most common contributing cause for hypoglycemia was measurement delay (n = 170, 66.9%). The median (interquartile range) time to achieve the target range was 5.9 (3.8 - 8.9) hours. Nearly all (97.5%) of patients achieved target and remained in target 73.4% of the time. The mean BG (+/- SD) after achieving target was 5.4 (+/- 0.52) mmol/L. Targeted blood glucose levels were achieved at similar rates with low incidence of severe hypoglycemia in patients with and without diabetes, sepsis, renal, and cardiovascular disease. CONCLUSIONS: Glycemic control to a lower glucose target range can be achieved using a computerized insulin dosing protocol. With particular attention to timely measurement and adjustment of insulin doses the risk of hypoglycemia experienced can be minimized.

Glycemic control and insulin safety: the impact of computerized intravenous insulin dosing.

The aim of this work was to evaluate our Glycemic Control Initiative that was put in place to improve blood glucose control in hyperglycemic intensive care patients and improve insulin safety by minimizing the risk of hypoglycemia. A computerized decision-support tool was developed for intravenous insulin dosing that provided an automated and standardized approach across the organization's intensive care units (ICUs). As a result of this, at 3 years post implementation, ICU patients are 2.28 times more likely to have blood glucose levels <150 mg/dL (odds ratio = 2.28; 95% confidence interval = 2.25-2.30; P < .001) compared with the baseline period. Although glycemic control was significantly improved, the patient safety risk from hypoglycemia did not increase, as rates of blood glucose <50 mg/dL decreased from 0.68% at baseline to 0.64% in 2007.

Antidiabetic therapy before and 1 year after discharge for patients manifesting in-hospital hyperglycemia.

BACKGROUND: While studies have evaluated the impact of hyperglycemia during hospitalization, little is known about its management before and after admission. METHODS: We sampled a managed care outpatient database (8547 patients) with linkage to inpatient data from June 1, 2003 to June 30, 2006, evaluating hyperglycemia management preadmission (PA), during index admission (IA), and postdischarge (PD). Antihyperglycemic medications used during PA, IA, and PD for up to 15 months were available for 2898 patients from this cohort. Diabetes mellitus (DM) status was determined from ICD-9 codes. RESULTS: Patients at IA had an average age of 60 +/- 18 years. Forty-one percent were men and 59% were women. Nearly 60% of patients either had DM or manifested hyperglycemia (blood glucose > 130 mg/dL): 19.5% (1627) had preexisting DM (DM+); 9.6% (801) were newly diagnosed with DM at IA; 28.6% (2391) did not have DM (DM-) but manifested hyperglycemia during hospitalization; and 36.9% (3083) remained normoglycemic. The DM status of 459 patients (5.4%) was unascertainable. For the previously diagnosed DM+ patients, antidiabetic therapy intensified more than 2-fold during IA, primarily with insulin. Postdischarge hyperglycemia management medication doubled, with increases seen in both oral hypoglycemic agents (OHAs) and insulin. Newly diagnosed DM+ patients were also treated primarily with insulin during hospitalization and reverted to OHAs PD. A minority of DM- patients received antidiabetic therapy during IA, primarily with insulin, but 4% were diagnosed DM+ in the 15-month period PD and treated primarily with OHAs. Among those normoglycemic in the hospital, 1% were diagnosed with DM and treated with OHAs PD. CONCLUSION: Hyperglycemia management was intensified for all DM+ patients, primarily with insulin in the hospital and both insulin and OHAs PD. A better understanding of this natural history and antidiabetic transitional care could facilitate better discharge planning and thus improve diabetes care.

Safety and effectiveness of a computerized subcutaneous insulin program to treat inpatient hyperglycemia.

BACKGROUND: This proof of concept study was designed to evaluate the safety and effectiveness of a computerized insulin program, the Clarian GlucoStabilizer Subcutaneous Insulin Program (CGS-SQ). This paper discusses the CGS-SQ's impact on the glycemic control of hospitalized patients with hyperglycemia. METHODS: Patients at Methodist and Indiana University Hospitals requiring subcutaneous insulin were treated using the CGS-SQ. This program calculates subcutaneous bolus insulin doses based on the current blood glucose (BG), using an insulin sensitivity factor, the number of grams of carbohydrates eaten, and an insulin-to-carbohydrate ratio, with a goal of maintaining the patient's BG in a prespecified target range. The target range, insulin sensitivity factor, and insulin-to-carbohydrate ratio are established by the physician. RESULTS: From April 2006 to September 2007, the CGS-SQ treated 1772 patients at Methodist and Indiana University Hospitals, with 46,575 BGs in its database. For these patients, the average BG was 158.3 mg/dl, 40.5% percent of BGs were in the default target range of 100-150 mg/dl, and 69.8% were in the wider range of 70-180 mg/dl. The hypoglycemia (BG <40 mg/dl) rate was 0.18%. CONCLUSIONS: The CGS-SQ provided a means to deliver insulin in a standardized manner, resulting in satisfactory BG control with a low hypoglycemia rate, thus serving as a tool for safe and effective insulin therapy for hospitalized patients.

Utilization of a computerized intravenous insulin infusion program to control blood glucose in the intensive care unit.

BACKGROUND: This proof of concept study was designed to evaluate the safety and effectiveness of an intravenous insulin dosing calculator, the Clarian GlucoStabilizer program, and to determine the feasibility of its use as part of a glycemic control program. This paper discusses the impact of the GlucoStabilizer program on the glycemic control of intensive care patients with hyperglycemia. METHODS: Patients admitted to the intensive care unit (ICU), requiring intravenous insulin, were treated using the GlucoStabilizer program. This program calculates an insulin drip rate based on the low and high blood glucose (BG) levels of the desired target range, the patient's current and previous BG levels, and an insulin sensitivity factor, with a goal of safely and expeditiously achieving and maintaining the patient's BG in the target range. RESULTS: From October 2004 through March 2006, the GlucoStabilizer program has been used to treat 2,398 patients in the ICUs, with 177,279 BG measurements in its database. In these patients, 61.0% of BGs have been in the target range of 80-110 mg/dL, while 90.9% have been in the wider range of 60-150 mg/dL. The average BG was 106.5 mg/dL (SD 39.1 mg/dL), and the frequency of hypoglycemia (BG <50 mg/dL) was 0.4%. These results compare favorably with the level of glycemic control in the 3 months before implementation of the GlucoStabilizer program. CONCLUSIONS: Use of the GlucoStabilizer program in the ICU resulted in improved glycemic control compared to the previous manually calculated glycemic control protocols.

Dominant-negative histone H3 lysine 27 mutant derepresses silenced tumor suppressor genes and reverses the drug-resistant phenotype in cancer cells.

Histone modifications and DNA methylation are epigenetic phenomena that play a critical role in many neoplastic processes, including silencing of tumor suppressor genes. One such histone modification, particularly at H3 and H4, is methylation at specific lysine (K) residues. Whereas histone methylation of H3-K9 has been linked to DNA methylation and aberrant gene silencing in cancer cells, no such studies of H3-K27 have been reported. Here, we generated a stable cell line overexpressing a dominant-negative point mutant, H3-K27R, to examine the role of that specific lysine in ovarian cancer. Expression of this construct resulted in loss of methylation at H3-K27, global reduction of DNA methylation, and increased expression of tumor suppressor genes. One of the affected genes, RASSF1, was shown to be a direct target of H3-K27 methylation-mediated silencing. By increasing DNA-platinum adduct formation, indicating increased access of the drug to target DNA sequences, removal of H3-K27 methylation resensitized drug-resistant ovarian cancer cells to the chemotherapeutic agent cisplatin. This increased platinum-DNA access was likely due to relaxation of condensed chromatin. Our results show that overexpression of mutant H3-K27 in mammalian cells represents a novel tool for studying epigenetic mechanisms and the Histone Code Hypothesis in human cancer. Such findings show the significance of H3-K27 methylation as a promising target for epigenetic-based cancer therapies.