Pros of Inpatient Sodium Glucose Cotransporter-2 Inhibitor Use.

OBJECTIVE: Sodium-glucose-cotransporter 2 (SGLT-2) inhibitors are widely used for diabetes management especially because their effects go beyond glucose control. More recently, their indications and usage have expanded to heart failure (HF) and renal dysfunction therapy in patients both with and without diabetes. Beneficial effects, especially for HF readmission, accrue very early in their treatment trajectory, and this has promoted their use in the hospital setting. Data on their safety and efficacy for inpatient use are accumulating but have lagged behind the outpatient data for their use. The objective of this counterpoint piece is to highlight areas of benefit for starting or continuing SGLT-2 inhibitors in the inpatient setting. METHODS: Discussion after literature review of available studies with a focus on HF outcomes and SGLT-2 inhibitor use. RESULTS: The benefits of starting or continuing an SGLT-2 inhibitor in the inpatient setting are well documented, mainly in HF. Similar data are not available for glucose or renal outcomes alone. Starting in the hospital allows the ability to titrate medications with similar effects, such as diabetes and HF agents, as well as reducing treatment inertia to obtain and start new medications after patients are discharged home. It is important to choose patients appropriately and hold these drugs when patients are without nutrition or on low-carbohydrate diets which can lead to diabetic ketoacidosis. CONCLUSION: In the right setting, using an SGLT-2 inhibitor in the hospital can affect multiple aspects of a patient's treatment trajectory and should be a consideration.

An Emergency Department-Based Intensive Care Unit is Associated with Decreased Hospital and Intensive Care Unit Utilization for Diabetic Ketoacidosis.

BACKGROUND: Many emergency department (ED) patients in diabetic ketoacidosis (DKA) are admitted to an inpatient intensive care unit (ICU), while ICU capacity is under increasing strain. The Emergency Critical Care Center (EC3), a hybrid ED-ICU setting, opened with the goal of providing rapid initiation of ICU care in the ED. OBJECTIVE: We sought to evaluate the impact of an ED-ICU on disposition and safety outcomes for adult ED patients in DKA. METHODS: This was a retrospective pre-post cohort of ED visits from 2012-2018 at a single academic medical center. Adult ED patients in DKA (pH < 7.30, HCO3 < 18 mEq/L, anion gap > 14, and glucose > 250 mg/dL) immediately before (pre-EC3) and after (post-EC3) opening of an ED-ICU were identified. ED disposition and safety data were collected and analyzed. RESULTS: We identified 631 patient encounters: 217 pre-EC3 and 414 post-EC3. Baseline demographics were similar between cohorts. Fewer patients in the post-EC3 cohort were admitted to an ICU (11.6% vs. 23.5%, p < 0.001, number needed to treat [NNT] = 8) or general floor bed (58.0% vs. 73.3%, p < 0.001, NNT = 6), and more were discharged from the ED (27.1% vs. 1.4%, p < 0.001, NNT = 4). Rates of hypokalemia (10.1% vs. 6.0%, p = 0.08) and admission to non-ICU with transfer to ICU within 24 h (0.5% vs. 0%, p = 0.30) did not differ. CONCLUSION: Management of patients with DKA in an ED-ICU was associated with decreased ICU and hospital utilization with similar safety outcomes. Managing rapidly reversible critical illnesses in an ED-ICU may help obviate increasing strain facing many health care systems.

Inpatient Glycemic Management in the Setting of Renal Insufficiency/Failure/Dialysis.

PURPOSE OF THIS REVIEW: Chronic diabetic nephropathy and renal dysfunction from other causes are common in hospitalized patients with diabetes. Available diabetes management guidelines aim to reduce hyperglycemia and hypoglycemia, both independent risk factors for hospital outcomes. Renal dysfunction, which increases the risk of hypoglycemia, adds a layer of complexity in diabetes management. Therefore, modified glucose goals and treatment regimens may be required. RECENT FINDINGS: Recent prospective and retrospective studies provide direction on safe insulin therapy for diabetes inpatients with renal compromise. Studies of newer diabetes pharmacotherapy provide data on oral agent use in the inpatient setting. Diabetes therapy should be modified with changing renal function. Glucose management in patients on peritoneal or hemodialysis is challenging. Reducing weight-based doses of insulin and use of newer insulins can reduce hypoglycemia risk. Safety and efficacy of DPP-4 inhibitors has been evaluated in the hospital and nursing home setting. Metformin, SGLT-2 inhibitors, and GLP1 receptor agonists can be used in several stages of renal dysfunction prior to and at discharge.

THE EFFICACY AND SAFETY OF CO-ADMINISTRATION OF SITAGLIPTIN WITH METFORMIN IN PATIENTS WITH TYPE 2 DIABETES AT HOSPITAL DISCHARGE.

OBJECTIVE: Few randomized controlled trials have focused on the optimal management of patients with type 2 diabetes (T2D) during the transition from the inpatient to outpatient setting. This multicenter open-label study explored a discharge strategy based on admission hemoglobin A1c (HbA1c) to guide therapy in general medicine and surgery patients with T2D. METHODS: Patients with HbA1c ≤7% (53 mmol/mol) were discharged on sitagliptin and metformin; patients with HbA1c between 7 and 9% (53-75 mmol/mol) and those >9% (75 mmol/mol) were discharged on sitagliptinmetformin with glargine U-100 at 50% or 80% of the hospital daily dose. The primary outcome was change in HbA1c at 3 and 6 months after discharge. RESULTS: Mean HbA1c on admission for the entire cohort (N = 253) was 8.70 ± 2.3% and decreased to 7.30 ± 1.5% and 7.30 ± 1.7% at 3 and 6 months ( P<.001). Patients with HbA1c <7% went from 6.3 ± 0.5% to 6.3 ± 0.80% and 6.2 ± 1.0% at 3 and 6 months. Patients with HbA1c between 7 and 9% had a reduction from 8.0 ± 0.6% to 7.3 ± 1.1% and 7.3 ± 1.3%, and those with HbA1c >9% from 11.3 ± 1.7% to 8.0 ± 1.8% and 8.0 ± 2.0% at 3 and 6 months after discharge (both P<.001). Clinically significant hypoglycemia (<54 mg/dL) was observed in 4%, 4%, and 7% among patients with a HbA1c <7%, 7 to 9%, and >9%, while a glucose <40 mg/dL was reported in <1% in all groups. CONCLUSION: The proposed HbA1c-based hospital discharge algorithm using a combination of sitagliptin-metformin was safe and significantly improved glycemic control after hospital discharge in general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood glucose; DPP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration rate; HbA1c = hemoglobin A1c; T2D = type 2 diabetes.

The Two-Bag Method for Treatment of Diabetic Ketoacidosis in Adults.

BACKGROUND: The "two-bag method" of management of diabetic ketoacidosis (DKA) allows for titration of dextrose delivery by adjusting the infusions of two i.v. fluid bags of varying dextrose concentrations while keeping fluid, electrolyte, and insulin infusion rates constant. OBJECTIVE: We aimed to evaluate the feasibility and potential benefits of this strategy in adult emergency department (ED) patients with DKA. METHODS: This is a before-and-after comparison of a protocol using the two-bag method operationalized in our adult ED in 2015. A retrospective electronic medical record search identified adult ED patients presenting with DKA from January 1, 2013 to June 30, 2016. Clinical and laboratory data, timing of medical therapies, and safety outcomes were collected and analyzed. RESULTS: Sixty-eight patients managed with the two-bag method (2B) and 107 patients managed with the one-bag method (1B) were identified. The 2B and 1B groups were similar in demographics and baseline metabolic derangements, though significantly more patients in the 2B group received care in a hybrid ED and intensive care unit setting (94.1% vs. 51.4%; p < 0.01). 2B patients experienced a shorter interval to first serum bicarbonate ≥ 18 mEq/L (13.4 vs. 20.0 h; p < 0.05), shorter duration of insulin infusion (14.1 vs. 21.8 h; p < 0.05), and fewer fluid bags were charged to the patient (5.2 vs. 29.7; p < 0.01). Frequency of any measured hypoglycemia or hypokalemia trended in favor of the 2B group (2.9% vs. 10.3%; p = 0.07; 16.2% vs. 27.1%; p = 0.09; respectively), though did not reach significance. CONCLUSIONS: The 2B method appears feasible for management of adult ED patients with DKA, and use was associated with earlier correction of acidosis, earlier discontinuation of insulin infusion, and fewer i.v. fluid bags charged than traditional 1B methods, while no safety concerns were observed.

PATHOPHYSIOLOGY AND MANAGEMENT OF HYPOGLYCEMIAIN END-STAGE RENAL DISEASE PATIENTS: A REVIEW.

OBJECTIVE: This review focuses on hypoglycemia in patients with end-stage renal disease (ESRD). It discusses the pathophysiology of glucose metabolism in the kidney, the impact of dialysis on glucose and insulin metabolism, and the challenges of glucose monitoring in ESRD. The clinical relevance of these changes is reviewed in relation to altered blood glucose targets and modification of antidiabetes therapy to prevent hypoglycemia. Based on current data and guidelines, recommendations for the outpatient and inpatient setting are provided for diabetes management in ESRD. METHODS: PubMed, OVID, and Google Scholar were searched to identify related articles through May 2016 using the following keywords: "glucose metabolism," "kidney," "diabetes," "hypoglycemia," "ESRD," and "insulin" in various combinations for this review. RESULTS: In ESRD, a combination of impaired insulin clearance, changes in glucose metabolism, and the dialysis process make patients vulnerable to low blood glucose levels. Hypoglycemia accounts for up to 3.6% of all ESRD-related admissions. At admission or during hospitalization, hypoglycemia in ESRD has a poor prognosis, with mortality rates reported at 30%. Several guidelines suggest a modified hemoglobin A1c (A1c) goal of 7 to 8.5% (53 to 69 mmol/mol) and an average blood glucose goal of 150 to 200 mg/dL. Noninsulin antidiabetes agents like dipeptidyl peptidase 4 inhibitors, repaglinide, and glipizide in appropriate doses and reduction of insulin doses up to 50% may help decrease hypoglycemia. CONCLUSION: Patients with ESRD are at high risk for hypoglycemia. Increased awareness by providers regarding these risks and appropriate diabetes regimen adjustments can help minimize hypoglycemic events. ABBREVIATIONS: ADA = antidiabetes agent BG = blood glucose CKD = chronic kidney disease DPP-4 = dipeptidyl peptidase 4 eGFR = estimated glomerular filtration rate ESRD = end-stage renal disease GFR = glomerular filtration rate HD = hemodialysis NPH = neutral protamine Hagedorn PD = peritoneal dialysis SA = short acting SU = sulfonylurea.

Postmarket Surveillance of Point-of-Care Glucose Meters through Analysis of Electronic Medical Records.

BACKGROUND: The electronic medical record (EMR) holds a promising source of data for active postmarket surveillance of diagnostic accuracy, particularly for point-of-care (POC) devices. Through a comparison with prospective bedside and laboratory accuracy studies, we demonstrate the validity of active surveillance via an EMR data mining method [Data Mining EMRs to Evaluate Coincident Testing (DETECT)], comparing POC glucose results to near-in-time central laboratory glucose results. METHODS: The Roche ACCU-CHEK Inform II(®) POC glucose meter was evaluated in a laboratory validation study (n = 73), a prospective bedside intensive care unit (ICU) study (n = 124), and with DETECT (n = 852-27 503). For DETECT, the EMR was queried for POC and central laboratory glucose results with filtering based on of bedside collection timestamps, central laboratory time delays, patient location, time period, absence of repeat testing, and presence of peripheral lines. RESULTS: DETECT and the bedside ICU study produced similar estimates of average bias (4.5 vs 5.0 mg/dL) and relative random error (6.3% vs 5.6%), with overlapping CIs. For glucose <100 mg/dL, the laboratory validation study estimated a lower relative random error of 3.6%. POC average bias correlated with central laboratory turnaround times, consistent with 4.8 mg · dL(-1) · h(-1) glycolysis. After glycolysis adjustment, average bias was estimated by the bedside ICU study at -0.4 mg/dL (CI, -1.6 to 0.9) and DETECT at -0.7 (CI, -1.3 to 0.2), and percentage POC results occurring outside Clinical Laboratory Standards Institute quality goals were 2.4% and 4.8%, respectively. CONCLUSIONS: This study validates DETECT for estimating POC glucose meter accuracy compared with a prospective bedside ICU study and establishes it as a reliable postmarket surveillance methodology.

Stress Hyperglycemia During Surgery and Anesthesia: Pathogenesis and Clinical Implications.

Numerous studies have demonstrated an association between hyperglycemia in the perioperative period and adverse clinical outcomes. Many patients who experience hyperglycemia while hospitalized do not have a known history of diabetes and experience a transient phenomenon often described as "stress hyperglycemia" (SH). We discuss the epidemiology and pathogenesis of SH as well as evidence to date regarding predisposing factors and outcomes. Further research is needed to identify the long-term sequelae of SH as well as perioperative measures that may modulate glucose elevations and optimal treatment strategies.

Medications that Regulate Gastrointestinal Transit Influence Inpatient Blood Glucose.

Objective: A multitude of factors affect a hospitalized individual's blood glucose (BG), making BG difficult to predict and manage. Beyond medications well established to alter BG, such as beta-blockers, there are likely many medications with undiscovered effects on BG variability. Identification of these medications and the strength and timing of these relationships has potential to improve glycemic management and patient safety. Materials and Methods: EHR data from 103,871 inpatient encounters over 8 years within a large, urban health system was used to extract over 500 medications, laboratory measurements, and clinical predictors of BG. Feature selection was performed using an optimized Lasso model with repeated 5-fold cross-validation on the 80% training set, followed by a linear mixed regression model to evaluate statistical significance. Significant medication predictors were then evaluated for novelty against a comprehensive adverse drug event database. Results: We found 29 statistically significant features associated with BG; 24 were medications including 10 medications not previously documented to alter BG. The remaining five factors were Black/African American race, history of type 2 diabetes mellitus, prior BG (mean and last) and creatinine. Discussion: The unexpected medications, including several agents involved in gastrointestinal motility, found to affect BG were supported by available studies. This study may bring to light medications to use with caution in individuals with hyper- or hypoglycemia. Further investigation of these potential candidates is needed to enhance clinical utility of these findings. Conclusion: This study uniquely identifies medications involved in gastrointestinal transit to be predictors of BG that may not well established and recognized in clinical practice.

Feasibility and Performance of Continuous Glucose Monitoring to Guide Computerized Insulin Infusion Therapy in Cardiovascular Intensive Care Unit.

BACKGROUND: We evaluated the feasibility of real-time continuous glucose monitoring (CGM) for titrating continuous intravenous insulin infusion (CII) to manage hyperglycemia in postoperative individuals in the cardiovascular intensive care unit and assessed their accuracy, nursing acceptance, and postoperative individual satisfaction. METHODS: Dexcom G6 CGM devices were applied to 59 postsurgical patients with hyperglycemia receiving CII. A hybrid approach combining CGM with periodic point-of-care blood glucose (POC-BG) tests with two phases (initial-ongoing) of validation was used to determine CGM accuracy. Mean and median absolute relative differences and Clarke Error Grid were plotted to evaluate the CGM accuracy. Surveys of nurses and patients on the use of CGMs experience were conducted and results were analyzed. RESULTS: In this cohort (mean age 64, 32% female, 32% with diabetes) with 864 paired POC-BG and CGM values analyzed, mean and median absolute relative difference between POC-BG and CGM values were 13.2% and 9.8%, respectively. 99.7% of paired CGM and POC-BG were in Zones A and B of the Clarke Error Grid. Responses from nurses reported CGMs being very or quite convenient (n = 28; 93%) and it was favored over POC-BG testing (n = 28; 93%). Majority of patients (n = 42; 93%) reported their care process using CGM as being good or very good. CONCLUSION: This pilot study demonstrates the feasibility, accuracy, and nursing convenience of adopting CGM via a hybrid approach for insulin titration in postoperative settings. These findings provide robust rationale for larger confirmatory studies to evaluate the benefit of CGM in postoperative care to improve workflow, enhance health outcomes, and cost-effectiveness.

Management of Individuals With Diabetes at High Risk for Hypoglycemia: An Endocrine Society Clinical Practice Guideline.

CONTEXT: Hypoglycemia in people with diabetes is common, especially in those taking medications such as insulin and sulfonylureas (SU) that place them at higher risk. Hypoglycemia is associated with distress in those with diabetes and their families, medication nonadherence, and disruption of life and work, and it leads to costly emergency department visits and hospitalizations, morbidity, and mortality. OBJECTIVE: To review and update the diabetes-specific parts of the 2009 Evaluation and Management of Adult Hypoglycemic Disorders: Endocrine Society Clinical Practice Guideline and to address developing issues surrounding hypoglycemia in both adults and children living with diabetes. The overriding objectives are to reduce and prevent hypoglycemia. METHODS: A multidisciplinary panel of clinician experts, together with a patient representative, and methodologists with expertise in evidence synthesis and guideline development, identified and prioritized 10 clinical questions related to hypoglycemia in people living with diabetes. Systematic reviews were conducted to address all the questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. RESULTS: The panel agreed on 10 questions specific to hypoglycemia risk and prevention in people with diabetes for which 10 recommendations were made. The guideline includes conditional recommendations for use of real-time continuous glucose monitoring (CGM) and algorithm-driven insulin pumps in people with type 1 diabetes (T1D), use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia, use of long-acting and rapid-acting insulin analogs, and initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia. Strong recommendations were made for structured diabetes education programs for those at high risk for hypoglycemia, use of glucagon preparations that do not require reconstitution vs those that do for managing severe outpatient hypoglycemia for adults and children, use of real-time CGM for individuals with T1D receiving multiple daily injections, and the use of inpatient glycemic management programs leveraging electronic health record data to reduce the risk of hypoglycemia. CONCLUSION: The recommendations are based on the consideration of critical outcomes as well as implementation factors such as feasibility and values and preferences of people with diabetes. These recommendations can be used to inform clinical practice and health care system improvement for this important complication for people living with diabetes.

Knowledge and attitudes of lower Michigan primary care physicians towards dietary interventions: A cross-sectional survey.

Background: Dietary interventions are first-line therapies for the prevention and management of many chronic diseases, yet primary care physicians prescribe these interventions infrequently. Objectives: This study investigates primary care physicians' current knowledge and opinions regarding the delivery of dietary interventions. This work aims to identify modifiable barriers to prescribing dietary interventions to prevent and treat diet-related diseases. Methods: We designed and fielded an anonymous, cross-sectional survey of faculty and resident physicians across the Internal Medicine, Family Medicine, and Pediatrics departments in three academic and community hospitals in lower Michigan. Data were collected between January 15 and April 15, 2019. Self-rated knowledge and attitudes were measured on a 5-point Likert scale. Objective scores were calculated for each question as percentage answered correctly among all respondents. Objective knowledge scores were compared based on participants' years in practice. Results: Response rate was 23% (356 responses). The sample was 62.3% female and 75.3% non-Hispanic White, and 56.7% were age 40 or younger. Average objective knowledge score was 70.3% (±17.2) correct. Mean self-rated knowledge score was 2.51 (±0.96) on a scale of 1(Poor) - 5(Excellent). Overall agreement with a statement of importance of dietary interventions was 3.99 (±0.40) on a scale of 1 (strongly disagree) to 5 (strongly agree). A majority (91.7%) of respondents indicated they would like more opportunities to learn about the evidence supporting dietary interventions. Conclusions: Physicians desire to incorporate dietary interventions into their practice. Findings encourage the development of educational strategies to support dietary intervention use among primary care physicians.

Hospital Diabetes Meeting 2022.

The annual Virtual Hospital Diabetes Meeting was hosted by Diabetes Technology Society on April 1 and April 2, 2022. This meeting brought together experts in diabetes technology to discuss various new developments in the field of managing diabetes in hospitalized patients. Meeting topics included (1) digital health and the hospital, (2) blood glucose targets, (3) software for inpatient diabetes, (4) surgery, (5) transitions, (6) coronavirus disease and diabetes in the hospital, (7) drugs for diabetes, (8) continuous glucose monitoring, (9) quality improvement, (10) diabetes care and educatinon, and (11) uniting people, process, and technology to achieve optimal glycemic management. This meeting covered new technology that will enable better care of people with diabetes if they are hospitalized.

Severe hyperglycemia and insulin resistance in patients with SARS-CoV-2 infection: a report of two cases.

BACKGROUND: Severe insulin resistance is an uncommon finding in patients with type 2 diabetes but is often associated with difficult to managing blood glucose. While severe insulin resistance is most frequently seen in the setting of medication side effects or rare genetic conditions, this report of two cases highlights the presence of severe insulin resistance in the setting of severe COVID-19 and explores how this may contribute to the poor prognosis of patients with diabetes who become infected with SARS-CoV-2. CASE PRESENTATION: Here we present the cases of two African-American women with pre-existing type 2 diabetes who developed severe COVID-19 requiring mechanical ventilation and concurrent severe insulin resistance with total daily insulin dose requirements of greater than 5 unit/kg. Both patients received aggressive insulin infusion and subcutaneous insulin therapy to obtain adequate glucose management. As their COVID-19 clinical course improved, their severe insulin resistance improved as well. CONCLUSIONS: The association between critical illness and hyperglycemia is well documented in the literature, however severe insulin resistance is not commonly identified and may represent a unique clinical feature of the interaction between SARS-CoV-2 infection and type 2 diabetes.

Improving Hospital Glucometrics, Workflow, and Outcomes with a Computerized Intravenous Insulin Dose Calculator Built into the Electronic Health Record.

OBJECTIVE: To adjust for dynamic insulin requirements in critically ill patients, intravenous (IV) insulin infusions allow for titration of the dose according to a prespecified algorithm. Despite the adaptability of IV insulin protocols, human involvement in dose calculation allows for error. We integrated a previously validated IV insulin calculator into our electronic health record (Epic) and instituted it in the cardiovascular intensive care unit (CVICU). We aim to describe the design of the calculator, the implementation process, and evaluate the calculator's impact. METHOD: Employing an aggressive training program and user acceptance testing prior to significant elbow support at the time of institution, we successfully integrated the insulin calculator in our CVICU. We evaluated the glucometrics before and after implementation as well as nursing satisfaction following calculator implementation. RESULTS: Overall, our implementation led to increased frequency of blood sugar at various glycemic targets, a trend toward less hypoglycemia or hyperglycemia. For severe hypoglycemia, our preintervention cohort had 0.02% of blood sugars less than 40 mg/dL but no blood sugars less than 40 mg/dL were identified in our patient's postintervention. For the CVICU target blood glucose of 70-180 mg/dL, 87.97% blood sugars at baseline met goal compared to 91.39% at one month, 91.24% at three months, and 90.87% at six months postintervention. CONCLUSION: By utilizing an aggressive education campaign championing superusers and making adjustments to the calculator based on early problems that were encountered, we were able to improve glycemic control and limit glucose variability at our institution.

Managing Hyperglycemia in the COVID-19 Inflammatory Storm.

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) is now at global pandemic levels causing significant morbidity and mortality. Patients with diabetes are particularly vulnerable and more likely to get severe complications when infected with this virus. Although the information continues to emerge, here we provide our perspective on initial outcomes observed in hospitalized patients with diabetes and the potential role played by the proinflammatory metabolic state in these patients that promotes fertile ground for the virus' inflammatory surge, resulting in severe insulin resistance and severe hyperglycemia. The rapidly evolving renal failure, hypotension, pressor and steroid use, and variable nutritional support further complicates their management. Thus, timely implementation of glucose management protocols addressing these complex scenarios while also following COVID-19-related trajectories in inflammatory biomarkers and being cognizant of the health care provider exposure may substantially affect morbidity and mortality.

Food Retention at Endoscopy Among Adults Using Glucagon-Like Peptide-1 Receptor Agonists.

This cross-sectional study investigates the association between glucagon-like peptide-1 receptor agonists and food retention during esophagogastroduodenoscopy.

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports.

BACKGROUND: Since 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug's AEs (which may change during a drug's life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O'Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed. METHODS: In July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles' references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized. RESULTS: One hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing's syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis. CONCLUSIONS: The spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.

Hypoglycemia in Hospitalized Hemodialysis Patients With Diabetes: An Observational Study.

INTRODUCTION: Hypoglycemia and hyperglycemia affect outcomes in hospitalized patient. Patients with diabetes and end stage renal disease are prone to hypoglycemia and few studies have evaluated glucometrics to identify the incidence and risk factors for hypoglycemia in this population. METHODS: We designed an observational retrospective review of 150 insulin requiring inpatients with diabetes receiving hemodialysis. We collected demographics, baseline characteristics, and glucometric data focusing on episodes of hypoglycemia with glucose cutoffs <70, <54, and <40 mg/dl. Detailed glucose and insulin data for 24 hours before and after hemodialysis was analyzed for each patient in context of a hypoglycemic episode. T-tests, one-way ANOVA, and chi-square tests were used for statistical analysis. RESULTS: At least one glucose value less than 70 mg/dl was observed in 51% of hemodialysis patients, less than 54 mg/dl in 28%, and less than 40 mg/dl in 11%. Patients with hypoglycemia had a higher HbA1c, standard deviation of glucose ( P = .0009) and higher total daily dose (TDD) of insulin by weight (0.34 units/kg vs 0.23 units/kg, P = .003). We observed a linear increasing risk for hypoglycemia with increasing TDD, with nearly 65% of hypoglycemic episodes occurring with TDD >0.20 units/kg. A majority (61%) of all hypoglycemic episodes occurred in the 24 hours prior to a hemodialysis session. Type 1 diabetes was independently associated with hypoglycemia. CONCLUSIONS: Hospitalized diabetes patients undergoing hemodialysis were found to have high rates of hypoglycemia. Our results support using a lower TDD of insulin in this population (<0.23 units/kg/day) and recommend special caution in those with type 1 diabetes.

Micromachined bulk PZT tissue contrast sensor for fine needle aspiration biopsy.

This paper describes a micromachined piezoelectric sensor, integrated into a cavity at the tip of a biopsy needle, and preliminary experiments to determine if such a device can be used for real-time tissue differentiation, which is needed for needle positioning guidance during fine needle aspiration (FNA) biopsy. The sensor is fabricated from bulk lead zirconate titanate (PZT), using a customized process in which micro electro-discharge machining is used to form a steel tool that is subsequently used for batch-mode ultrasonic micromachining of bulk PZT ceramic. The resulting sensor is 50 microm thick and 200 microm in diameter. It is placed in the biopsy needle cavity, against a steel diaphragm which is 300 microm diameter and has an average thickness of 23 microm. Devices were tested in materials that mimic the ultrasound characteristics of human tissue, used in the training of physicians, and with porcine fat and muscle tissue. In both schemes, the magnitude and frequency of an electrical impedance resonance peak showed tissue-specific characteristics as the needle was inserted. For example, in the porcine tissue, the impedance peak frequency changed approximately 13 MHz from the initial 163 MHz, and the magnitude changed approximately 1600 Omega from the initial 2100 Omega, as the needle moved from fat to muscle. Samples including oils and saline solution were tested for calibration, and an empirical tissue contrast model shows an approximately proportional relationship between measured frequency shift and sample acoustic impedance. These results suggest that the device can complement existing methods for guidance during biopsies.