Peak insulin drip rate associated with decreased infections post-solid organ transplant.

Infection and rejection outcomes were retrospectively analyzed in patients following liver transplant and separately following heart transplant with patients being stratified by their severity of immediate postoperative insulin resistance as measured by the peak insulin drip rate that was required to reduce glucose levels. For each group, these peak insulin drip rates were divided into quartiles (Q). In liver transplant patients (n = 207), those in Q4 (highest infusion rate) had significantly fewer infections up to 6 months post-transplant (42.3% vs. 60.0%, p = .036) and borderline fewer rejection episodes (25.0% vs. 40.0%, p = .066) compared to Q1-Q3 patients. To confirm these unexpected results, a subsequent similar analysis in heart transplant (n = 188) patients again showed that Q4 patients had significantly fewer infections up to 6 months (19.1% vs. 53.9%, p < .0001) compared to Q1-Q3 patients. Logistic regression in a subset of 103 cardiac transplant patients showed that the maximum glucose during surgery, prior MI, and hypertension were associated with severe insulin resistance (SIR) status, while the presence of pre-existing diabetes and BMI were not. We hypothesize that patients are who are able to mount a more robust counter-regulatory response that causes the insulin resistance may be healthier and thus able to mount a better response to infections.

Short-term multifactorial intervention (STEMI): An approach using structured blood glucose monitoring (BGM) and conventional therapies in persons with diabetes.

Background: Achieving glucose and glycosylated hemoglobin (HbA1c) targets have been shown to reduce long-term microvascular complications of diabetes; however, suboptimal glucose control is common. We tested whether glucose control could be improved within 8 weeks by employing structured blood glucose monitoring (BGM) qid in addition to seven times per day prior to visits for diabetes education and medication management that occurred every 2-4 weeks. Methods: This single-center, prospective study was conducted on 78 adults with either type 1 diabetes (T1D) or type 2 diabetes (T2D), HbA1c >8%, and serum creatinine (sCr) <2.0 mg/dl. HbA1c was checked at baseline, Week 2, Week 4, and at Week 8. Patients were evaluated by a physician and a certified diabetes educator (CDE) at baseline, Week 2, and Week 4 for treatment adjustments and lifestyle advice based on a review of BGM done qid plus 7-point profiles conducted before Weeks 2, 4, and 8. Study outcomes were change in HbA1c from baseline to Week 8 and change in mean glucose on the 7-point profile from Week 2 to Week 8. These were compared using one-way repeated measures ANOVA. Results: Of the 78 patients, 64.1% had T2D, 50% were women, and 72% were Caucasian. Mean age (±SD) was 51.3.5 ± 11.1 years, and median diabetes duration was 9 (5-17) years. The percentage of patients using insulin increased from 58.9% at baseline to 67.9% at Week 8. The mean (±SD) HbA1c was 9.53% (±1.71) at baseline, declined -1.38% from baseline to week 8 (CI -1.62 to -0.14, P < 0.001). The mean (±SD) glucose on the 7-point profile was 187 (±52) mg/dl at Week 2, and 157 (±5) mg/dl at Week 8. (P < 0.01). Conclusions: An intensive glucose optimization program using structured BGM qid plus 7-point profiles, diabetes education, and conventional anti-diabetic therapies was successful in reducing HbA1c by 1.38% over 8 weeks in patients with poor glucose control.

Continuous glucose monitoring for inpatient diabetes management: an update on current evidence and practice.

Over the last few years, several exciting changes in continuous glucose monitoring (CGM) technology have expanded its use and made CGM the standard of care for patients with type 1 and type 2 diabetes using insulin therapy. Consequently, hospitals started to notice increased use of these devices in their hospitalized patients. Furthermore during the coronavirus disease 2019 (COVID) pandemic, there was a critical need for innovative approaches to glycemic monitoring, and several hospitals started to implement CGM protocols in their daily practice. Subsequently, a plethora of studies have demonstrated the efficacy and safety of CGM use in the hospital, leading to clinical practice guideline recommendations. Several studies have also suggested that CGM has the potential to become the standard of care for some hospitalized patients, overcoming the limitations of current capillary glucose testing. Albeit, there is a need for more studies and particularly regulatory approval. In this review, we provide a historical overview of the evolution of glycemic monitoring in the hospital and review the current evidence, implementation protocols, and guidance for the use of CGM in hospitalized patients.

ECTOPIC ADRENOCORTICOTROPIC HORMONE SYNDROME DUE TO METASTATIC PROSTATE CANCER WITH NEUROENDOCRINE DIFFERENTIATION.

OBJECTIVE: Neuroendocrine differentiation of prostate cancer can result in ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) and Cushing syndrome. The aim of this report is to highlight this unusual mechanism of hypercortisolism and its management. METHODS: We report a 73-year-old patient with a history of prostate adenocarcinoma who presented with severe weakness, hyperglycemia, and hypokalemia caused by EAS. RESULTS: Diagnostic workup showed elevated 24-hour urine cortisol and ACTH levels consistent with EAS. Fluorodeoxyglucose positron emission tomography-computed tomography revealed a hypermetabolic mass in the prostate and metastatic lesions to the liver and bones. Liver biopsy was consistent with small cell carcinoma with positive immunostaining for ACTH. Pleural fluid analysis was consistent with high-grade neuroendocrine carcinoma. The patient underwent chemotherapy with carboplatin and etoposide. Hypercortisolism was treated with ketoconazole, metyrapone, mifepristone, and spironolactone. He suffered complications including opportunistic infections, deep venous thrombosis, and delirium. Given his poor prognosis and clinical decline, the patient opted for comfort measures only in a hospice facility. CONCLUSION: Treatment-related neuroendocrine differentiation of prostate cancer is an emerging entity that may be associated with paraneoplastic syndromes including EAS.

Development of a Predictive Model for Hyperglycemia in Nondiabetic Recipients After Liver Transplantation.

BACKGROUND: Posttransplant hyperglycemia has been associated with increased risks of transplant rejection, infections, length of stay, and mortality. METHODS: To establish a predictive model to identify nondiabetic recipients at risk for developing postliver transplant (LT) hyperglycemia, we performed this secondary, retrospective data analysis of a single-center, prospective, randomized, controlled trial of glycemic control among 107 adult LT recipients in the inpatient period. Hyperglycemia was defined as a posttransplant glucose level greater than 200 mg/dL after initial discharge up to 1 month following surgery. Candidate variables with P less than 0.10 in univariate analyses were used to build a multivariable logistic regression model using forward stepwise selection. The final model chosen was based on statistical significance and additive contribution to the model based on the Bayesian Information Criteria. RESULTS: Forty-three (40.2%) patients had at least 1 episode of hyperglycemia after transplant after the resolution of the initial postoperative hyperglycemia. Variables selected for inclusion in the model (using model optimization strategies) included length of hospital stay (odds ratio [OR], 0.83; P < 0.001), use of glucose-lowering medications at discharge (OR, 3.76; P = 0.03), donor female sex (OR, 3.18; P = 0.02) and donor white race (OR, 3.62; P = 0.01). The model had good calibration (Hosmer-Lemeshow goodness-of-fit test statistic = 9.74, P = 0.28) and discrimination (C-statistic = 0.78; 95% confidence interval, 0.65-0.81, bias-corrected C-statistic = 0.78). CONCLUSIONS: Shorter hospital stay, use of glucose-lowering medications at discharge, donor female sex and donor white race are important determinants in predicting hyperglycemia in nondiabetic recipients after hospital discharge up to 1 month after liver transplantation.

Type B Insulin Resistance in Peru.

Type B insulin resistance (IR) is a rare autoimmune disease characterized by the presence of insulin receptor autoantibodies, resulting in a marked IR inducing hyperglycemia. Our first case is a 42-year-old female with a history of RA, SLE and Hashimoto-thyroiditis that presented with cachexia, acanthosis-nigricans, hirsutism, negative anti-insulin-ab and glucose level between 400 to 700 mg/dl, despite a total insulin dose of 1000 IU/day. She received pulses of cyclophosphamide along with prednisone. One year later the patient was off insulin and with HbA1c of 5.6%. The second case is a 42-year-old female patient that presented with polyuria, polydipsia, cachexia, acanthosis-nigricans, negative glutamic-acid-decarboxilase-ab and positive TPO-ab. She received IV infusion of regular insulin at a rate of 500 UI/d. Two years later she was off insulin with HbA1C of 5.6%. As summary, we reported a case of a disease remitted after receiving immunosuppressive therapy and a case of disease remitted spontaneously.

Inhospital Mortality in Patients with Type 2 Diabetes Mellitus: A Prospective Cohort Study in Lima, Peru.

Objective. To estimate cause of death and to identify factors associated with risk of inhospital mortality among patients with T2D. Methods. Prospective cohort study performed in a referral public hospital in Lima, Peru. The outcome was time until event, elapsed from hospital admission to discharge or death, and the exposure was the cause of hospital admission. Cox regression was used to evaluate associations of interest reporting Hazard Ratios (HR) and 95% confidence intervals. Results. 499 patients were enrolled. Main causes of death were exacerbation of chronic renal failure (38.1%), respiratory infections (35.7%), and stroke (16.7%). During hospital stay, 42 (8.4%) patients died. In multivariable models, respiratory infections (HR = 6.55, p < 0.001), stroke (HR = 7.05, p = 0.003), and acute renal failure (HR = 16.9, p = 0.001) increased the risk of death. In addition, having 2+ (HR = 7.75, p < 0.001) and 3+ (HR = 21.1, p < 0.001) conditions increased the risk of dying. Conclusion. Respiratory infections, stroke, and acute renal disease increased the risk of inhospital mortality among hospitalized patients with T2D. Infections are not the only cause of inhospital mortality. Certain causes of hospitalization require standardized and aggressive management to decrease mortality.

Beta-cell function and insulin resistance among Peruvian adolescents with type 2 diabetes.

OBJECTIVE: To characterize and compare the beta-cell function and insulin resistance among Peruvian adolescents with type 2 diabetes (T2D) and their non-diabetic, overweight and lean peers. METHODS: Cross-sectional study of 54 adolescents aged 10-19 years, distributed in three sex- and age-matched groups (n = 18): (i) adolescents with T2D; (ii) overweight adolescents without T2D; and (iii) lean adolescents without T2D, at the Diabetes, Obesity and Nutrition Research Center in Lima, Peru. Fasting glucose, insulin, C-peptide, and glycated hemoglobin were measured for all participants. In addition, a two-hour oral glucose tolerance test (OGTT, 1.75 mg of glucose/kg body weight) was performed, during which glucose and C-peptide were quantified. The homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) were derived for all participants, and beta-cell function was further examined by the area under the curve (AUC) of C-peptide. RESULTS: The median HOMA-IR score was higher in adolescents with T2D compared to lean adolescents (6.1 vs. 2.1; p = 0.002), but was not different from that of overweight adolescents (6.1 vs. 4.0; p = 0.322). The median HOMA-B was higher in overweight adolescents than in lean adolescents (256.9 vs. 134.2; p = 0.015), and adolescents with T2D (256.9 vs. 119.8; p = 0.011). The mean AUC of glucose in adolescents with T2D was 1.8-fold higher than that of overweight adolescents, and 1.9-fold higher than that of lean adolescents (p < 0.001). Although the median AUC of C-peptide in adolescents with T2D was lower than that of overweight and lean adolescents, this difference was not statistically significant (230.7 vs. 336.6 vs. 267.3 nmol/l120 min, respectively; p = 0.215). CONCLUSION: Among Peruvian adolescents with T2D, insulin resistance is the most prominent characteristic, rather than beta-cell dysfunction.

Blood Accessibility to Fibrin in Venous Thrombosis is Thrombus Age-Dependent and Predicts Fibrinolytic Efficacy: An In Vivo Fibrin Molecular Imaging Study.

Fibrinolytic therapy of venous thromboembolism (VTE) is increasingly utilized, yet limited knowledge is available regarding in vivo mechanisms that govern fibrinolytic efficacy. In particular, it is unknown how age-dependent thrombus organization limits direct blood contact with fibrin, the target of blood-based fibrinolytic agents. Utilizing high-resolution in vivo optical molecular imaging with FTP11, a near-infrared fluorescence (NIRF) fibrin-specific reporter, here we investigated the in vivo interrelationships of blood accessibility to fibrin, thrombus age, thrombus neoendothelialization, and fibrinolysis in murine venous thrombosis (VT). In both stasis VT and non-stasis VT, NIRF microscopy showed that FTP11 fibrin binding was thrombus age-dependent. FTP11 localized to the luminal surface of early-stage VT, but only minimally to subacute VT (p<0.001). Transmission electron microscopy of early stage VT revealed direct blood cell contact with luminal fibrin-rich surfaces. In contrast, subacute VT exhibited an encasing CD31+ neoendothelial layer that limited blood cell contact with thrombus fibrin in both VT models. Next we developed a theranostic strategy to predict fibrinolytic efficacy based on the in vivo fibrin accessibility to blood NIRF signal. Mice with variably aged VT underwent FTP11 injection and intravital microscopy (IVM), followed by tissue plasminogen activator infusion to induce VT fibrinolysis. Fibrin molecular IVM revealed that early stage VT, but not subacute VT, bound FTP11 (p<0.05), and experienced higher rates of fibrinolysis and total fibrinolysis (p<0.05 vs. subacute VT). Before fibrinolysis, the baseline FTP11 NIRF signal predicted the net fibrinolysis at 60 minutes (p<0.001). Taken together, these data provide novel insights into the temporal evolution of VT and its susceptibility to therapeutic fibrinolysis. Fibrin molecular imaging may provide a theranostic strategy to identify venous thrombi amenable to fibrinolytic therapies.

[Tuberculous spondylitis in adults: a case series from a reference hospital in Lima, Peru]. / Espondilitis tuberculosa en adultos: revisión de una serie de casos en un hospital de tercer nivel, Lima-Perú

We describe the demographic and clinical characteristics of adult patients with tuberculous spondylitis as well as an exploratory analysis that seeked to establish patient characteristics that contributed to the development of this disorder at a reference hospital in Lima. This is a case-series descriptive study where data collection from 33 medical records of patients from 1999 to 2009 was done. Eighteen (55%) were male. Median age was 31 years (IQR 23 to 51 years). Median time of symptoms was 3 months (IQR 1 to 8 months). The most frequent symptom was back pain in 28 (85%). The most frequently affected areas were the thoracic spine involved in 28 (60%) cases and lumbar spine in 13 (28%). Pulmonary tuberculosis was present in fourteen (42%) cases. Twenty four (73%) patients received first line treatment. Treatment duration was 10.5 ± 4.2 months. Clinical and diagnostic characteristics were similar to previous Peruvian case reports and current literature.

Espondilitis tuberculosa en adultos: revisión de una serie de casos en un hospital de tercer nivel, Lima-Perú / Tuberculous spondylitis in adults: a case series from a reference hospital in Lima, Peru

Describimos las características clínicas y demográficas en pacientes adultos con espondilitis tuberculosa así como un análisis exploratorio que buscó establecer características que contribuyeron al desarrollo de esta enfermedad, en un hospital de tercer nivel de Lima. Realizamos un estudio tipo serie de casos y describimos 33 casos recolectados entre 1999-2009. 18 pacientes (55 por ciento) fueron varones, la media de edad fue 31 años (IQ 23 a 51 años) y un tiempo de enfermedad de 3 meses (IQ 1 a 8 meses). El principal síntoma fue lumbalgia en 28 (85 por ciento). Los segmentos más comprometidos fueron el torácico en 28 (60 por ciento) casos y lumbar en 13 (28 por ciento). Tuberculosis pulmonar se encontró en 14 (42 por ciento) casos. Veinticuatro (73 por ciento) recibieron esquema I. La duración de tratamiento fue 10,5 ± 4,2 meses . Las características clínicas, diagnósticas fueron similares a series nacionales previas e internacionales.

We describe the demographic and clinical characteristics of adult patients with tuberculous spondylitis as well as an exploratory analysis that seeked to establish patient characteristics that contributed to the development of this disorder at a reference hospital in Lima. This is a case-series descriptive study where data collection from 33 medical records of patients from 1999 to 2009 was done. Eighteen (55 percent) were male. Median age was 31 years (IQR 23 to 51 years). Median time of symptoms was 3 months (IQR 1 to 8 months). The most frequent symptom was back pain in 28 (85 percent). The most frequently affected areas were the thoracic spine involved in 28 (60 percent) cases and lumbar spine in 13 (28 percent). Pulmonary tuberculosis was present in fourteen (42 percent) cases. Twenty four (73 percent) patients received first line treatment. Treatment duration was 10.5 ± 4.2 months. Clinical and diagnostic characteristics were similar to previous Peruvian case reports and current literature.