Incretin mimetics and acute pancreatitis: enemy or innocent bystander?

PURPOSE OF REVIEW: The incretin enhancers and mimetics, including dipeptidyl peptidase-4 (DPP-4) inhibitors, GLP-1 receptor agonists (GLP-1RA) and GLP-1/GIP co-agonists, have become mainstays in the treatment of type 2 diabetes (T2D). Recently, the approval of certain GLP-1RA and GLP-1/GIP co-agonists for the treatment of obesity has broadened their popularity and use. In this review, we summarize the evidence for an association of these drugs with acute pancreatitis and other adverse events of special interest to gastroenterologists. RECENT FINDINGS: In addition to pancreatic islets, GLP-1 receptors are expressed in the exocrine cells of the pancreas. There is inconsistent evidence for an association of DPP-4 inhibitors, GLP-1RA and co-agonists with risk for acute pancreatitis in individual trials. Meta-analyses of long-term randomized controlled trials indicate a small risk of acute pancreatitis associated with DPP-4 inhibitors but not GLP-1RA or co-agonists. Cholecystitis and cholelithiasis may be more common among those treated with GLP-1RA and GLP-1/GIP co-agonists. There is no evidence that any of these drugs are associated with an increased risk of pancreatic cancer. SUMMARY: While drugs that leverage the incretin system are increasingly being used for patients with T2D and obesity, caution in warranted in those with a history of pancreatitis and gallbladder disease.

Surveying the Knowledge and Practices of Primary Care Residents in Managing Adult Patients with Obesity.

BACKGROUND: The prevalence of obesity is increasing worldwide at an alarming rate, yet obesity remains under-addressed during clinic encounters. A lack of training in how to treat obesity is one crucial factor contributing to this deficiency. OBJECTIVE: This study explored resident physicians' perceptions of their education on obesity and its relationship with confidence and practice behaviors when caring for patients with obesity. DESIGN: A survey was distributed to residency directors to share with residents in their programs. Participation was voluntary and anonymous. Data was collected over a 3-month period. PARTICIPANTS: Residents in Family Medicine and Internal Medicine programs in West Virginia and Indiana who saw adult patients in an ambulatory care setting. MAIN MEASURES: The electronic survey queried the presence of a formal curriculum on Obesity Medicine (OM) and each resident's knowledge, confidence, practice behaviors, and attitudes pertaining to OM. KEY RESULTS: The survey was distributed to 490 residents in 12 programs. Response rate was 22.9% (112 resident physicians). All respondents felt that medical training in obesity should be strengthened. Residents who reported having a formal curriculum on OM were more likely than those without a curriculum to rate their confidence as "high" when discussing weight (35.0% vs. 16.7%, p = 0.03) and when counseling patients about diet and nutrition (37.5% vs. 18.1%, p = 0.02). They also more frequently reported learning enough from faculty to manage obesity (65.0% vs. 29.2%, p < 0.001). Residents with an OM curriculum reported discussing obesity as a problem with patients (100.0% vs. 86.1%, p = 0.01), and completing motivational interviews (90.0% vs. 58.3%, p = < 0.001), more frequently than their peers without a curriculum. CONCLUSIONS: Residents with a formal OM curriculum were more confident in addressing and discussing obesity with patients. Formal training in OM will strengthen resident training to better address and treat patients with obesity.

Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: a systematic review.

BACKGROUND: Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies. METHODS: We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment. RESULTS: Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation. CONCLUSIONS: Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops.

Islet autoantibodies are markers found in the blood when insulin-producing cells in the pancreas become damaged and can be used to predict future development of type 1 diabetes. We evaluated published literature to determine whether characteristics of islet antibodies (type, levels, numbers) could improve prediction and help understand differences in how individuals with type 1 diabetes respond to treatments. We found existing evidence shows that islet autoantibody type and number are most useful to predict disease progression before diagnosis. In addition, the age when islet autoantibodies first appear strongly influences rate of progression. These findings provide important information for patients and care providers on how islet autoantibodies can be used to understand future type 1 diabetes development and to identify individuals who have the potential to benefit from intervention or prevention therapy.

Health Care Disparities in Outpatient Diabetes Management During the Coronavirus Disease 2019 Pandemic: Where Do We Stand Now?

OBJECTIVE: We examined diabetes outpatient management during the first 2 years of the Coronavirus Disease 2019 pandemic in an endocrinology practice with a focus on health care disparities in outcomes. METHODS: We conducted a retrospective cohort study examining adults with diabetes during 3 time periods: T1 (March 2019-February 2020), T2 (March 2020-February 2021), and T3 (March 2021-February 2022). Clinical outcomes included body mass index (BMI), systolic blood pressure (SBP), Hemoglobin A1c (HgbA1c), low-density lipoprotein cholesterol (LDL), and urine albumin:creatinine ratio. Appointment types (virtual vs in-person) were also collected. RESULTS: Frequencies of HgbA1c, BMI, and SBP measurements reduced by 36.0%, 46.3%, and 48.5% in T2, respectively, and remaining 8.7% (HgbA1c), 13.4% (BMI), and 15.2% (SBP) lower at the end of the study period (P < .001) compared to prepandemic levels. However, the average HgbA1c and LDL slightly improved. Clinic appointments per patient increased during the pandemic, fueled by telehealth utilization. Women had fewer in-person visits during T2, those older than 65 had better HgbA1c, and the most socioeconomically deprived group had the worst HgbA1c during every time period. In addition, black patients had worse HgbA1c, LDL, and SBP values throughout the study, which did not worsen over the pandemic. CONCLUSION: While the frequency of health measurements had not fully recovered 2 years into the pandemic, this did not translate to worse diabetes management or a widening of pre-existing disparities. Our study emphasizes the role of equitable health care in minimizing inequalities in diabetes, particularly during times of crisis.

Multifocal C-cell Hyperplasia and Marked Hypercalcitoninemia in a Diabetic Patient Treated With Glucagon-Like Peptide-1 Agonist With Concurrent Multinodular Goiter and Hyperparathyroidism.

Thyroid C-cell hyperplasia (CCH) is divided into physiologic or reactive CCH and neoplastic CCH. Glucagon-like peptide-1 receptor agonists (GLP-1 Ra) is a group of medications used to treat type 2 diabetes that has documented C-cell stimulation effect in rodents, leading to subsequent CCH and medullary thyroid carcinoma (MTC) in rats and/or mice. Currently, there is no sufficient evidence supporting the association between GLP-1 Ra and human thyroid CCH and/or MTC. Here, we present a case of significant hypercalcitoninemia in a 53-year-old diabetic male patient receiving GLP-1 Ra treatment with concurrent multinodular goiter and hyperparathyroidism. Total thyroidectomy and central neck dissection revealed multifocal CCH involving bilateral thyroid lobes and several negative lymph nodes. Subsequent genetic testing did not detect germline mutation of RET gene. However, due to marked hypercalcitoninemia and massive thyromegaly, unsampled medullary thyroid microcarcinoma cannot be completely ruled out. The patient's postsurgical calcitonin level was back to normal. Our case indicates the significant clinical value of monitoring serum calcitonin levels in patients receiving GLP-1 Ra, especially in presence of other thyroid and/or parathyroid pathology that may be associated with increased calcitonin and/or CCH. Literature regarding the association between GLP-1 Ra and CCH is also reviewed.

High-dose intravenous hydrocortisone for the treatment of hyperthyroidism: a rare precipitant of thyrotoxicosis periodic paralysis.

Summary: Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism triggered by precipitants that increase the activity of the sodium-potassium pump in the skeletal muscle. In our case study, a previously healthy 34-year-old male presented to the emergency department with new onset thyrotoxicosis, secondary to Graves' disease. Given the severity of his triiodothyronine (T3) thyrotoxicosis, he was admitted and started on a high dose of beta-blocker, thioamides, and intravenous hydrocortisone. On the second day of his hospitalization, he developed acute flaccid paralysis of his lower extremities. Subsequent stroke workup was negative, and his electrolytes revealed severe hypokalemia and hyperglycemia consistent with TPP. He was treated with potassium and had a complete recovery of his paralysis and hypokalemia within hours. The patient has not had any recurrence since this singular episode in the hospital. This case highlights the scenario where the treatment of hyperthyroidism with high-dose corticosteroids to reduce the conversion of thyroxine to T3 inadvertently resulted in TPP. Clinicians should be aware of this potentially rare but serious consequence of using steroids to manage hyperthyroidism. Learning points: High-dose steroids used to treat hyperthyroidism in hospitalized patients may rarely precipitate thyrotoxic periodic paralysis (TPP) by inducing hypokalemia and hyperglycemia. TPP should be included in the differential diagnosis for acute flaccid paralysis in hospitalized patients with hyperthyroidism. Since TPP is associated with trans-cellular shifts in potassium instead of total body potassium depletion, conservative repletion of potassium is recommended to avoid rebound hyperkalemia.

A Reduced Pancreatic Polypeptide Response is Associated With New-onset Pancreatogenic Diabetes Versus Type 2 Diabetes.

PURPOSE: Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM). METHODS: Subjects with new-onset DM (<3 years' duration) in the setting of PDAC (PDAC-DM, n = 28), CP (CP-DM, n = 38), or T2DM (n = 99) completed a standardized mixed meal tolerance test, then serum PP concentrations were subsequently measured at a central laboratory. Two-way comparisons of PP concentrations between groups were performed using Wilcoxon rank-sum test and analysis of covariance while adjusting for age, sex, and body mass index. RESULTS: The fasting PP concentration was lower in both the PDAC-DM and CP-DM groups than in the T2DM group (P = 0.03 and <0.01, respectively). The fold change in PP at 15 minutes following meal stimulation was significantly lower in the PDAC-DM (median, 1.869) and CP-DM (1.813) groups compared with T2DM (3.283; P < 0.01 for both comparisons). The area under the curve of PP concentration was significantly lower in both the PDAC-DM and CP-DM groups than in T2DM regardless of the interval used for calculation and remained significant after adjustments. CONCLUSIONS: Fasting PP concentrations and the response to meal stimulation are reduced in new-onset DM associated with PDAC or CP compared with T2DM. These findings support further investigations into the use of PP concentrations to characterize pancreatogenic DM and to understand the pathophysiological role in exocrine pancreatic diseases (NCT03460769).

Recruitment and Retention Strategies for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: From the Type 1 Diabetes in Acute Pancreatitis Consortium.

ABSTRACT: Recruitment and retention of patients with acute pancreatitis (AP) in clinical studies can be challenging. While some obstacles are similar to other clinical conditions, some are unique to AP. Identifying potential barriers early and developing targeted solutions can help optimize recruitment and retention in AP studies. Such pre-emptive and detailed planning can help prospective, longitudinal studies focus on exocrine and endocrine complications of AP in accurately measuring outcomes. This article highlights the challenges in recruitment and retention strategies in AP studies and reviews available resources to create opportunities to address them. We describe the multifaceted approach used by the Recruitment and Retention Committee of the Type 1 Diabetes in Acute Pancreatitis Consortium, which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.

Outcomes of Initial Management Strategies in Patients With Autoimmune Lymphocytic Hypophysitis: A Systematic Review and Meta-analysis.

CONTEXT: Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown. OBJECTIVE: This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy. METHODS: A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model. RESULTS: We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low. CONCLUSION: Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.

Use of Continuous Etomidate Infusion to Rapidly Correct Hypercortisolism in a Patient With Disseminated Nocardiosis.

Cushing's syndrome (CS) is an immunocompromised state characterized by impaired cellular and adaptive immunity due to hypercortisolism. This imbalance in the immune system leads to a high risk of opportunistic infections which can potentially prove fatal. In such patients, mortality can be reduced with early diagnosis and effective management of the underlying hypercortisolism. In this case report, we describe how prompt reduction of cortisol levels using a low dose continuous etomidate infusion was pivotal in effective treatment of an opportunistic infection, disseminated nocardiosis, in a 29-year-old female with Cushing's syndrome. We also discuss how treatment with antibiotics including empiric therapy with Imipenem and sulfamethoxazole/trimethoprim (SMX/TMP) and definite therapy as per susceptibility testing, with amikacin, SMX/TMP, and doxycycline helped to prevent adverse outcomes. Through this case, we aim to emphasize that infiltrates or cavitary lesions on the computed tomography (CT) scan of the chest in a patient with Cushing's syndrome should raise concern for nocardiosis, and prompt management with antibiotics should be initiated. Similarly, disseminated nocardiosis should always raise concern for possible immune deficiency states like Cushing's syndrome. Our case is unique in detailing the significance of using etomidate to acutely lower cortisol levels in a patient with endogenous CS and widespread invasive opportunistic infection. The pharmacology aspects of the Etomidate, in this case, have been published in the Journal of Pharmacy Practice and cited appropriately in this article.

CURRENT KNOWLEDGE AND PRACTICES OF HEATH CARE PROFESSIONALS ON OPIOID-INDUCED ADRENAL INSUFFICIENCY.

Objective: Opioid-induced adrenal insufficiency (OIAI) is reported in up to 29% of chronic opioid users through suppression of the hypothalamus-pituitary-adrenal axis. Unrecognized adrenal insufficiency leads to increased morbidity and potentially death; thus, healthcare provider (HCP) awareness of OIAI is crucial. The aim of the present study was to assess the knowledge and current practices of HCPs regarding OIAI and to identify factors associated with decreased awareness. Methods: We carried out a cross-sectional, anonymous survey of HCPs in internal medicine specialties that prescribe or care for patients taking chronic opioids. Results: Of 91 (30%) participants who completed the survey, 51 (56%) were men and 52 (57%) were in training. Most responders were general internal medicine providers (n = 33, 36%), followed by endocrinologists (n = 13, 14%) and various other specialties (n = 45, 49%). While 61 (67%) of respondents prescribed opioids, only 17 (19%) were comfortable in their knowledge of opioid side effects. Among nonendocrine providers, 53 (68%) identified adrenal insufficiency as a known opioid-induced endocrinopathy. Compared to other providers, endocrinologists were more likely to recognize opioid-related endocrinopathies (69% versus 24%, P = .01) and to identify the correct symptoms for OIAI (38% versus 9%, P <.001). One in four nonendocrine providers reported discomfort in managing glucocorticoid replacement therapy. The majority (60%) of providers indicated that online resources and continuing medical education lectures would improve knowledge of OIAI. Conclusion: Our study identified several deficiencies in HCP knowledge of opioid-induced endocrine effects, especially in nonendocrine providers. As many symptoms of OIAI overlap with those of underlying conditions, OIAI could be potentially missed, highlighting the need to further educate providers about opioid-induced endocrinopathies. Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; CME = continuing medical education; HCP = healthcare professional; OIAI = opioid-induced adrenal insufficiency.

Inflammation-associated microRNA changes in circulating exosomes of heart failure patients.

OBJECTIVE: MiR-486 and miR-146a are cardiomyocyte-enriched microRNAs that control cell survival and self-regulation of inflammation. These microRNAs are released into circulation and are detected in plasma or in circulating exosomes. Little is known whether heart failure affects their release into circulation, which this study investigated. RESULTS: Total and exosome-specific microRNAs in plasma of 40 heart failure patients and 20 controls were prepared using the miRVana Kit. We measured exosomal and total plasma microRNAs separately because exosomes serve as cargos that transfer biological materials and alter signaling in distant organs, whereas microRNAs in plasma indicate the level of tissue damage and are mostly derived from dead cells. qRT-PCR was used to quantify miR-486, miR-146a, and miR-16. Heart failure did not significantly affect plasma miR-486/miR-16 and miR-146a/miR-16 ratio, although miR-146a/miR-16 showed a trend of elevated expression (2.3 ± 0.79, p = 0.27). By contrast, circulating exosomal miR-146a/miR-16 ratio was higher in heart failure patients (2.46 ± 0.51, p = 0.05). miR-146a is induced in response to inflammation as a part of inflammation attenuation circuitry. Indeed, Tnfα and Gm-csf increased miR-146a but not miR-486 in the cardiomyocyte cell line H9C2. These results, if confirmed in a larger study, may help to develop circulating exosomal miR-146a as a biomarker of heart failure.

Personal Attitudes Toward Weight in Overweight and Obese US Hemodialysis Patients.

OBJECTIVE: Overweight and obesity have become increasingly common among end-stage renal disease patients on hemodialysis. Yet, little attention has been given to what hemodialysis patients themselves think of their weight, how they perceive it affects their health, and their attitudes about or desire for weight reduction. We explored these issues using a survey that we designed specifically for the dialysis population. DESIGN AND METHODS: Sixty-six chronic hemodialysis patients from a US urban center with a body mass index ≥25 kg/m2 and stable weight were recruited to participate in a cross-sectional study. The 12-question weight-related survey was validated by retesting a random portion of the study population. RESULTS: Based on test-retest results, the survey had good to excellent validity. Seventy-nine percent of patients were black, 49% were male, 29% were overweight, and 71% were obese. In general, the patients underestimated their weight excess though 73% were interested in weight loss, of whom nearly half reported attempting to do so mostly through diet and exercise. The majority of participants interested in losing weight felt that doing so would improve their physical and emotional health. The most common barrier to weight reduction was a belief that it was too difficult (55%), followed by a lack of motivation, money, time, resources, and knowledge. Diet was the most common weight loss strategy (85%) considered, whereas bariatric surgery was the least common (6.1%). CONCLUSIONS: A majority of overweight and obese hemodialysis patients believe their excess weight is adversely impacting their health and quality of life and therefore wish to lose weight.

A case of extragastrointestinal stromal tumor complicated by severe hypoglycemia: a unique presentation of a rare tumor.

BACKGROUND: Non-Islet Cell Tumor Hypoglycemia (NICTH) is a rare paraneoplastic cause of hypoglycemia arising from excess tumor production of insulin-like growth factor. The objective of this report is to describe an unusual case of Extragastrointestinal Stromal Tumor (EGIST) associated NICTH. CASE PRESENTATION: A 64 year-old African female was brought to the emergency room with a 1-month history of recurrent syncope, weight loss, and abdominal bloating. Serum blood glucose was discovered to 39 mg/dL, when insulin, proinsulin, and C-peptide were suppressed. Computed tomography scan revealed a diffuse extraintestinal metastatic disease process, and a biopsy confirmed the diagnosis of an Extragastrointestinal Stromal Tumor (EGIST). IGF-I and II levels were 27 ng/ml and 262 ng/ml respectively, and the ratio of IGF-II to IGF-I was calculated as 9.7:1, suggestive of IGF-II-mediated NICTH. Acutely, the patient's hypoglycemia resolved with dextrose and glucagon infusion. Long-term euglycemia was achieved with prednisone and imatinib therapy. CONCLUSIONS: NICTH should be considered when hypoglycemia occurs in the setting of low serum insulin levels. Whereas definitive treatment of EGIST involves surgical resection, immunotherapy with tyrosine kinase inhibitors and corticosteroids have been shown to alleviate hypoglycemia in cases where surgery is delayed or not feasible.

Outcome of coronary artery bypass grafting in a tertiary-care center in Pakistan.

BACKGROUND: Coronary artery bypass grafting and percutaneous coronary intervention are revascularization options for significant coronary artery disease. While international data support the use of coronary artery bypass in high-risk groups, regional data on outcomes in these groups are rare. We conducted a retrospective study to determine the outcomes of patients undergoing coronary artery bypass for left main and multivessel disease. METHODS: Two thousand eight hundred and fifty-one patients undergoing coronary artery bypass at the Aga Khan University Hospital from 2006 to 2013 were included; patients undergoing redo surgery were excluded. Demographic data, comorbidities, angiography findings, in-hospital complications, one-month and one-year follow-up were analyzed. RESULTS: Of the 2851 patients, 568 had left main disease (group 1) and 2283 (group 2) had multivessel disease (≥2 vessels excluding the left main). Group 1 had significantly more chronic lung disease, cardiogenic shock, and congestive heart failure than group 2 (p < 0.001); 50.6% of patients were diabetic and 71.8% were hypertensive. Mortality was 5.1% and 2.2% during hospital stay, 6.5% and 2.6% at 30 days, and 6.7% and 2.7% at 1 year in groups 1 and 2, respectively. CONCLUSION: Our comparable results and international data advocate revision of the current practice of using percutaneous coronary intervention over coronary artery bypass in the developing world. Institutional results are essential to determine the outcome of coronary artery bypass in high-risk populations with a high burden of diabetes and hypertension. We noted increased complications and mortality in patients with left main rather than multivessel disease.

Depression in patients on hemodialysis and their caregivers.

Depression is recognized as the most common psychiatric problem in patients with end-stage renal disease. Stress negatively affects the quality of life of not only the patients on hemodialysis but also their caregivers. The objective of this study was to measure and compare the frequency of depression in these patients and their attendants, and to assess the associated risk factors in both groups. A cross-sectional study was conducted at our hemodialysis unit from June to September 2009. A total of 180 patients and 180 caregivers were enrolled and the Beck's Depression Inventory (BDI-II) questionnaire was administered. Of the 360 respondents, 201 (55.8%) were males and 264 (73.3) were married. According to the BDI scoring, 135 (75%) of the patients and 60 (33.4%) of the attendants were found to be moderately to severely depressed. Marriage (OR 1.817), low income status (OR 1.757) and unemployment (OR 4.176) correlated with increased depression grade, while gender and education level did not. Anemia was the only co-morbidity showing positive association with depression scores in the patients' group (P = 0.023). We conclude that the majority of the patients undergoing dialysis were depressed and were twice more likely to be depressed than their caregivers. In both groups, marriage and unemployment were associated with increased depressive symptoms, while household income showed negative association with depression. Gender and education level were not related to the depression scores.

Vitamin D levels in asymptomatic adults--a population survey in Karachi, Pakistan.

BACKGROUND: It is well established that low levels of 25(OH) Vitamin D (<30 ng/dL) are a common finding world over, affecting over a billion of the global population. Our primary objective was to determine the prevalence of vitamin D deficiency and insufficiency in the asymptomatic adult population of Karachi, Pakistan and the demographic, nutritional and co-morbidity characteristics associated with serum vitamin D levels. METHODS: A cross-sectional population survey was conducted at two spaced out densely populated areas of the city. Serum levels of 25OH vitamin D were measured and GFR as renal function was assessed by using 4 variable MDRD formula. RESULTS: Our sample of 300 had a median age of 48(interquartile range 38-55) years. The median level of serum vitamin D was 18.8 (IQ range 12.65-24.62) ng/dL. A total of 253 (84.3%) respondents had low levels (<30 ng/dL) of 25OH vitamin D. Serum PTH and vitamin D were negatively correlated (r = -0.176, p = 0.001). The median PTH in the vitamin D sufficiency group was 38.4 (IQ range28.0-48.8)pg/mL compared with 44.4 (IQ range 34.3-56.8) pg/mL in the deficiency group (p = 0.011).The median serum calcium level in the sample was 9.46(IQ range 9.18-9.68) ng/dL. Low serum levels of vitamin D were not associated with hypertension (p = 0.771) or with an elevated spot blood pressure (p = 0.164).In our sample 75(26%) respondents had an eGFR corresponding to stage 2 and stage 3 CKD. There was no significant correlation between levels of vitamin D and eGFR (r = -0.127, p-value = 0.277). Respondents using daily vitamin D supplements had higher 25 OH vitamin D levels (p-value = 0.021). CONCLUSION: We observed a high proportion of the asymptomatic adult population having low levels of vitamin D and subclinical deterioration of eGFR. The specific cause(s) for this observed high prevalence of low 25OH vitamin D levels are not clear and need to be investigated further upon.

Short-term complications after bilateral internal mammary artery grafting--a retrospective study.

OBJECTIVES: To analyze our experience of conducting Bilateral Internal Mammary Artery (BIMA) grafting, using both pedicled and free grafts for coronary revascularization, assessing the safety and efficacy of the procedure and comparing any differences observed between the two techniques of harvesting the grafts. METHODS: A retrospective cross sectional study was conducted in July 2010 in which all 48 patients undergoing bilateral internal mammary artery grafting for coronary bypass surgery at the Aga Khan University Hospital from 1996 to 2010 were reviewed and evaluated. The main outcome measures were perioperative mortality and early morbidity with particular reference to cerebrovascular accidents, sternal wound complications and re-opening for bleeding. Chi-square test was used to elicit any meaningful associations between patient characteristics and post-operative outcomes. RESULTS: Of the 48 patients undergoing bilateral IMA grafting, 46 were males and 2 females. The mean age was 48 +/- 9.4 years. Dyslipidaemia and smoking were the most common identifiable risk factors for coronary vascular disease. Following the 40 elective and 8 emergent surgeries, there was one hospital death. The most common post-operative complications were arrhythmias and wound infection. Diabetes and obesity were not observed to be associated with an increased risk of developing surgical site infection. CONCLUSIONS: Our study suggests that the short-term efficacy and the safety profile of bilateral IMA grafting for coronary revascularization is clinically acceptable. Long-term follow-up studies should be done to assess the cardiac event-free survival of these individuals evaluating its applicability as a routine for coronary artery bypass grafting in Pakistan.