Differential effect of endogenous glucagon-like peptide-1 on prandial glucose counterregulatory response to hypoglycaemia in humans with and without bariatric surgery.

AIM: To determine the effect of endogenous glucagon-like peptide 1 (GLP-1) on prandial counterregulatory response to hypoglycaemia after gastric bypass (GB). MATERIALS AND METHODS: Glucose fluxes, and islet-cell and gut hormone responses before and after mixed-meal ingestion, were compared during a hyperinsulinaemic-hypoglycaemic (~3.2 mmol/L) clamp with and without a GLP-1 receptor (GLP-1R) antagonist exendin-(9-39) infusion in non-diabetic patients who had previously undergone GB compared to matched participants who had previously undergone sleeve gastrectomy (SG) and non-surgical controls. RESULTS: Exendin-(9-39) infusion raised prandial endogenous glucose production (EGP) response to insulin-induced hypoglycaemia in the GB group but had no consistent effect on EGP response among the SG group or non-surgical controls (p < 0.05 for interaction). The rates of systemic appearance of ingested glucose or prandial glucose utilization did not differ among the three groups or between studies with and without exendin-(9-39) infusion. Blockade of GLP-1R had no effect on insulin secretion or insulin action but enhanced prandial glucagon in all three groups. CONCLUSIONS: These results indicate that impaired post-meal glucose counterregulatory response to hypoglycaemia after GB is partly mediated by endogenous GLP-1, highlighting a novel pathogenic mechanism of GLP-1 in developing hypoglycaemia in this population.

Effect of Dapagliflozin on Renal and Hepatic Glucose Kinetics in T2DM and NGT Subjects.

Acute and chronic SGLT-2 inhibition increase endogenous glucose production (EGP). However, the organ - liver versus kidney - responsible for the increase in EGP has not been identified. 20 T2DM and 12 NGT subjects received [3-3H]-glucose infusion (to measure total EGP) in combination with arterial and renal vein catheterization and PAH infusion for determination of renal blood flow. Total EGP, net renal arteriovenous balance, and renal glucose production were measured before and 4 hours after dapagliflozin and placebo administration. Following DAPA, EGP increased in both T2D and NGT from baseline to 240 minutes, while there was a significant time-related decrease after placebo in T2D. Renal glucose production at baseline was <5% of basal EGP in both groups and did not change significantly following DAPA in either NGT and T2D. Renal glucose uptake (sum of tissue glucose uptake plus glucosuria) increased in both T2D and NGT following DAPA (P<0.05 vs placebo). The increase in RGU was entirely explained by the increase in glucosuria. Single dose of dapagliflozin significantly increased EGP, which primarily is explained by an increase in hepatic glucose production, establishing the existence of a novel renal-hepatic axis.

Vagal activation alters prandial bile acid composition and glycemia in patients with hypoglycemia after Roux-en-Y gastric bypass surgery.

BACKGROUND: Altered prandial glycemic response after Roux-en-Y gastric bypass (RYGB) is exaggerated in patients with post-RYGB hypoglycemia. Increased contribution of glucagon-like peptide 1 (GLP-1) to prandial insulin secretion plays a key role in developing hypoglycemia after RYGB, but the role of nonhormonal gut factors remains unknown. Here, the effect of vagal activation on prandial bile acid (BA) composition in relation to glucose, insulin and gut hormone responses was examined in a small size group of nondiabetic subjects after RYGB with intact gallbladder compared to nonoperated controls. METHODS: Concentrations of blood glucose, hormones, and BAs were measured in two RYGB subjects with documented hypoglycemia (HGB), three asymptomatic RYGB-treated subjects (AGB), and four nonoperated controls with intact gallbladders during a meal-tolerance test with (MTT-Sham) and without (MTT) preceding modified sham feeding (chew and spit). KEY RESULTS: Meal ingestion raised serum total BAs in RYGB-treated subjects without any effect in nonoperated controls. Modified sham feeding similarly increased meal-induced responses of conjugated BAs (CBAs) in all subjects (p < 0.05 compared to MTT alone), whereas unconjugated BAs (UBAs), mainly deoxycholic and chenodeoxycholic acid, were raised only in the HGB group (p < 0.001 for interaction). Prandial UBAs had an inverse correlation with glucose nadir (r = -0.75, p < 0.05) and were directly associated with ISR and GLP-1 during MTT-Sham. CONCLUSIONS & INFERENCES: In this small cohort, vagal activation by modified sham feeding increases prandial CBAs in both operated and nonoperated subjects but enhances UBAs only in patients with documented post-RYGB hypoglycemia. Our findings highlight a potential role for nonhormonal gut factors, such as BA and gut microbiome, in glucose abnormalities after RYGB.

The effect of level of injury on diabetes incidence and mortality after spinal cord injury - a longitudinal cohort study.

STUDY DESIGN: Retrospective longitudinal cohort study of veterans with SCI. OBJECTIVES: Spinal cord injury (SCI) is associated with an increased risk of developing diabetes mellitus (DM), likely due to body composition alterations and autonomic nervous system dysfunction. These factors are more pronounced in persons with tetraplegia (TP) versus paraplegia (PP). However, the effect of level of injury (LOI) on DM incidence is largely unknown. Therefore, the objective is to examine the effect of LOI on DM incidence in persons with SCI. SETTING: South Texas Veterans Health Care System. METHODS: We obtained electronic record data on age, sex, race/ethnicity, LOI and HbA1c concentration from January 1st 2001 through December 31st 2021. Cox proportional hazard regression analyses were used to assess the association between LOI, DM and all-cause mortality. RESULTS: Among 728 non-diabetic veterans with SCI (350 TP/ 378 PP, 52 ± 15 years, 690 male/38 female) 243 developed DM, of which 116 with TP and 127 with PP. Despite chronological variations between TP and PP, DM risk over the entire follow-up did not differ between the groups (hazard ratio (HR): 1.06, 95% CI: 0.82-1.38). Mortality was higher in TP versus PP (HR: 1.40, 95% CI: 1.09-1.78). However, developing DM did not increase the risk of death, regardless of LOI (HR: 1.07, 95% CI: 0.83-1.37). CONCLUSION: Despite chronological variations between both groups, the level of injury had minimal effect on long-term DM development in this cohort of veterans with SCI. Sponsorship NIH (DK105379; MS), RR&D SPiRE (I21RX003724-01A1; MT and SH).

GLP-1 enhances beta-cell response to protein ingestion and bariatric surgery amplifies it.

OBJECTIVE: Protein ingestion stimulates ß-cell secretion and alters glucose flux. Enhanced action of glucagon-like peptide 1 (GLP-1) and increased plasma glucose excursion contribute to prandial hyperinsulinemia after gastric bypass surgery (GB) and sleeve gastrectomy (SG). We examined the contribution of endogenous GLP-1 to glucose kinetics and ß-cell response to protein ingestion under basal glucose concentrations in humans, and whether these responses are affected by rerouted gut after GB or SG. DESIGN: Glucose fluxes, insulin secretion rate (ISR), and incretin responses to a 50-gram oral protein load were compared between 10 non-diabetic individuals with GB, 9 matched subjects with SG and 7 non-operated controls (CN) with and without intravenous infusion of exendin-(9- 39) [Ex-9), a specific GLP-1 receptor (GLP-1R) antagonist. RESULTS: Blocking GLP-1R increased the plasma glucose concentration before and after protein ingestion in all 3 groups (p<0.05) and decreased ß-cell sensitivity to glucose in the first 30 minutes of protein ingestion (p<0.05). Reduction in the prandial ISR3h by Ex-9 infusion, however, only was observed in GB and SG (p<0.05 for interaction) and not in controls. Also, GLP-1R blockade increased post-protein insulin action in GB and SG, but not CN (p=0.09 for interaction). Endogenous glucose production (EGP) during the first 60 minutes after protein ingestion was increased in all 3 groups but EGP3h only was accentuated in GB by Ex-9 infusion (p<0.05 for interaction). CONCLUSION: These findings are consistent with both a pancreatic and extrapancreatic role for GLP-1 during protein ingestion in humans, and GLP-1 actions are exaggerated by bariatric surgery.

Endogenous glucagon-like peptide 1 diminishes prandial glucose counterregulatory response to hypoglycemia after gastric bypass surgery.

We have previously shown that prandial endogenous glucose production (EGP) during insulin-induced hypoglycemia is smaller in non-diabetic subjects with gastric bypass (GB), where prandial glucagon-like peptide 1 (GLP-1) concentrations are 5-10 times higher than those in non-operated controls. Here, we sought to determine the effect of endogenous GLP-1 on prandial counterregulatory response to hypoglycemia after GB. Glucose fluxes, and islet-cell and gut hormone responses before and after mixed-meal ingestion were compared during a hyperinsulinemic hypoglycemic (~3.2 mmol/l) clamp with and without a GLP-1 receptor (GLP-1R) antagonist exendin-(9-39) (Ex-9) in non-diabetic subjects with prior GB compared to matched subjects with SG and non-surgical controls. In this setting, GLP-1R blockade had no effect on insulin secretion or insulin action, whereas prandial glucagon was enhanced in all 3 groups. Ex-9 infusion raised prandial EGP response to hypoglycemia in every GB subject but had no consistent effects on EGP among subjects with SG or non-operated controls (P < 0.05 for interaction). These results indicate that impaired post-meal glucose counterregulatory response to hypoglycemia after GB is partly mediated by endogenous GLP-1, highlighting a novel mechanism of action of GLP-1R antagonists for the treatment of prandial hypoglycemia in this population.

Differential effect of gastric bypass versus sleeve gastrectomy on insulinotropic action of endogenous incretins.

OBJECTIVE: Prandial hyperinsulinemia after Roux-en-Y gastric bypass surgery (GB), and to lesser degree after sleeve gastrectomy (SG), has been attributed to rapid glucose flux from the gut and increased insulinotropic gut hormones. However, ß-cell sensitivity to exogenous incretin is reduced after GB. This study examines the effect of GB versus SG on prandial glycemia and ß-cell response to increasing concentrations of endogenous incretins. METHODS: Glucose kinetics, insulin secretion rate (ISR), and incretin responses to 50-g oral glucose ingestion were compared between ten nondiabetic participants with GB versus nine matched individuals with SG and seven nonoperated normal glucose tolerant control individuals (CN) with and without administration of 200 mg of sitagliptin. RESULTS: Fasting glucose and hormonal levels were similar among three groups. Increasing plasma concentrations of endogenous incretins by two- to three-fold diminished prandial glycemia and increased ß-cell secretion in all three groups (p < 0.05), but insulin secretion per insulin sensitivity (i.e., disposition index) was increased only in GB (p < 0.05 for interaction). However, plot of the slope of ISR (from premeal to peak values) versus plasma glucagon-like peptide-1 concentration was smaller after GB compared with SG and CN. CONCLUSIONS: After GB, increasing incretin activity augments prandial ß-cell response whereas the ß-cell sensitivity to increasing plasma concentrations of endogenous incretin is diminished.

C-reactive protein, D-dimer, erythrocyte sedimentation rate, and troponin in intensive care unit patients with COVID-19 in Iran.

Background: The coronavirus disease 2019 (COVID-19) pandemic in Iran has led to a lack of intensive care unit (ICU) facilities. This study examines C-reactive protein (CRP), D-dimer, erythrocyte sedimentation rate (ESR), and troponin in ICU patients with COVID-19 in comparison to COVID-19 patients admitted to the wards in Iran. Materials and Methods: In a case-control study, troponin, CRP, ESR, and D-dimer were compared in the case samples of 109 COVID-19 patients admitted to the ICU, and in the control group, 140 COVID-19 patients admitted to the wards. Results: The mean of CRP (P < 0.001) and D-dimer (P < 0.001) was higher, whereas troponin (P < 0.001) was lower in patients admitted to the ICU, but no significant difference was observed between the values of ESR (P = 0.292) in the two groups. Conclusion: This study showed that the values of CRP and D-dimer were higher in patients admitted to the ICU, but no significant difference was observed between the values of ESR in the two groups.

Bariatric Surgery Alters the Postprandial Recovery From Hypoglycemia, Mediated by Cholinergic Signal.

Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) surgeries increase prandial insulin and glucagon secretion but reduce the endogenous glucose production (EGP) response to hypoglycemia in comparison with control subjects who had not undergone gastric surgery (CN), suggesting that parasympathetic nervous system (PNS) plays a role. Here, we investigated the effect of acute PNS blockade on the post-meal counterregulatory response to insulin-induced hypoglycemia in GB and SG compared with CN. Glucose kinetics and islet cell secretion were measured in nine subjects without diabetes with GB and seven with SG and five CN during hyperinsulinemic-hypoglycemic clamp (∼3.2 mmol/L) combined with meal ingestion on two separate days with and without intravenous atropine infusion. Glucose and hormonal levels were similar at baseline and during steady-state hypoglycemia before meal ingestion in three groups and unaffected by atropine. Atropine infusion diminished prandial systemic appearance of ingested glucose (RaO) by 30%, EGP by 40%, and glucagon response to hypoglycemia by 90% in CN. In GB or SG, blocking PNS had no effect on the RaO or meal-induced hyperglucagonemia but increased EGP in SG without any effect in GB (P < 0.05 interaction). These findings indicate that cholinergic signal contributes to the recovery from hypoglycemia by meal consumption in humans. However, bariatric surgery dissipates PNS-mediated physiologic responses to hypoglycemia in the fed state. ARTICLE HIGHLIGHTS: Rerouted gut after Roux-en-Y gastric bypass (GB) and, to a lesser degree, after sleeve gastrectomy (SG) leads to larger glucose excursion and lower nadir glucose, predisposing individuals to hypoglycemia. Despite prandial hyperglucagonemia, endogenous glucose production response to hypoglycemia is reduced after GB or SG. Parasympathetic nervous system (PNS) activity plays a key role in regulation of glucose kinetics and islet cell function. We examined the effect of acute PNS blockade on counterregulatory glucose and islet cell response to meal ingestion during insulin-induced hypoglycemia among GB, SG, and control subjects who had not had gastric surgery. Our findings demonstrate that cholinergic signal is critical in the recovery from hypoglycemia by meal ingestion in humans who have not had gastric surgery, although prandial PNS-mediated physiologic responses to hypoglycemia are differentially changed by GB and SG.

Insulinotropic effect of endogenous incretins is greater after gastric bypass than sleeve gastrectomy despite diminished beta-cell sensitivity to plasma incretins.

Background/Aims: Prandial hyperinsulinemia after Roux-en Y gastric bypass surgery (GB), and to lesser degree after sleeve gastrectomy (SG), has been attributed to rapid glucose flux from the gut and increased insulinotropic gut hormones. However, ß-cell sensitivity to exogenous incretin is markedly reduced after GB. This study examines the effect of GB versus SG on prandial glycemia and ß-cell response to increasing concentrations of endogenous incretins. Methods: Glucose kinetics, insulin secretion rate (ISR), and incretin responses to 50-gram oral glucose ingestion were compared between 10 non-diabetic subjects with GB versus 9 matched individuals with SG and 7 non-operated normal glucose tolerant controls (CN) on two days with and without administration of 200 mg sitagliptin. Results: Fasting glucose and hormonal levels were similar among 3 groups. Increasing plasma concentrations of endogenous incretins by 2-3-fold diminished post-OGTT glycemia and increased ß-cell secretion in all 3 groups (p<0.05), but insulin secretion per insulin sensitivity (i.e., disposition index) was increased only in GB (p<0.05 for interaction). As a result, sitagliptin administration led to hypoglycemia in 3 of 10 GB. Yet, plot of the slope of ISR versus the increase in endogenous incretin concentration was smaller after GB compared to both SG and CN. Conclusion: Augmented glycemic-induced ß-cell response caused by enhanced incretin activity is unique to GB and not shared with SG. However, the ß-cell sensitivity to increasing concentrations of endogenous incretin is smaller after bariatric surgery, particularly after GB, compared to non-operated controls, indicating a long-term adaptation of gut-pancreas axis after these procedures. HIGHLIGHTS: What is known?: Glycemic effects of gastric bypass (GB) and sleeve gastrectomy (SG) is attributed to rapid nutrient flux and enhanced insulinotropic effects of gut hormones but ß-cell sensitivity to exogenous GLP-1 or GIP is diminished after GB. What the present findings add?: Post-OGTT ß-cell sensitivity to enhanced endogenous incretins by DPP4i is markedly reduced in bariatric subjects versus non-operated controls, and yet insulin secretory response (disposition index) is increased leading to hypoglycemia in GB and not SG. Significance?: Blunted sensitivity to GLP-1 may represent ß-cell adaptation to massive elevation in GLP-1 secretion following bariatric surgery to protect against hypoglycemia.The differential effect of enhanced concentrations of incretins on post-OGTT insulin response (disposition index) among GB versus SG highlights a distinct adaptive process among the two procedures.Augmented insulinotropic effects of gut hormones on postprandial insulin secretory response after GB despite a reduced beta-cell sensitivity to plasma concentrations of GLP-1 makes a case for non-hormonal mechanisms of GLP-1 action after GB.Better understanding of long-term effects of bariatric surgery on gut-pancreas axis activity is critical in development of GLP-1-based strategies to address glucose abnormalities (both hyperglycemia and hypoglycemia) in these settings.

Altered Insulin Clearance after Gastric Bypass and Sleeve Gastrectomy in the Fasting and Prandial Conditions.

Background: The liver has the capacity to regulate glucose metabolism by altering the insulin clearance rate (ICR). The decreased fasting insulin concentrations and enhanced prandial hyperinsulinemia after Roux-en-Y gastric-bypass (GB) surgery and sleeve gastrectomy (SG) are well documented. Here, we investigated the effect of GB or SG on insulin kinetics in the fasting and fed states. Method: ICR was measured (i) during a mixed-meal test (MMT) in obese non-diabetic GB (n = 9) and SG (n = 7) subjects and (ii) during a MMT combined with a hyperinsulinemic hypoglycemic clamp in the same GB and SG subjects. Five BMI-matched and non-diabetic subjects served as age-matched non-operated controls (CN). Results: The enhanced ICR during the fasting state after GB and SC compared with CN (p < 0.05) was mainly attributed to augmented hepatic insulin clearance rather than non-liver organs. The dose-response slope of the total insulin extraction rate (InsExt) of exogenous insulin per circulatory insulin value was greater in the GB and SG subjects than in the CN subjects, despite the similar peripheral insulin sensitivity among the three groups. Compared to the SG or the CN subjects, the GB subjects had greater prandial insulin secretion (ISR), independent of glycemic levels. The larger post-meal ISR following GB compared with SG was associated with a greater InsExt until it reached a plateau, leading to a similar reduction in meal-induced ICR among the GB and SG subjects. Conclusions: GB and SG alter ICR in the presence or absence of meal stimulus. Further, altered ICR after bariatric surgery results from changes in hepatic insulin clearance and not from a change in peripheral insulin sensitivity.

Prandial hepatic glucose production during hypoglycemia is altered after gastric bypass surgery and sleeve gastrectomy.

AIMS/HYPOTHESIS: Roux-en Y gastric bypass surgery (GB) and sleeve gastrectomy (SG) alter prandial glucose metabolism, producing lower nadir glucose values and predisposing susceptible individuals to prandial hypoglycemia. The glycemic phenotype of GB or SG is associated with prandial hyperinsulinemia and hyperglucagonemia along with an increased influx of ingested glucose. Following insulin-induced hypoglycemia, glucagon is the most important stimulus for hepatic glucose production (HGP). It is unclear whether prandial hyperglucagonemia after GB or SG changes HGP under hyperinsulinemic hypoglycemia conditions. This study examined the hypothesis that prandial glucose production is reduced after GB and SG during hypoglycemia. METHODS: Glucose kinetics and islet-cell and gut hormone secretion during hyperinsulinemic (120 mU.m-2.min-1) hypoglycemic clamp (~3.2 mM) were measured before and after mixed meal ingestion in 9 non-diabetic subjects with GB, 7 with SG, and 5 matched non-operated controls (CN). RESULTS: Systemic appearance of ingested glucose was faster in GB compared to SG, and in SG compared to CN (p < 0.05). Subjects with GB and SG had greater plasma glucagon levels after eating (AUCGlucagon) compared to CN (p < 0.05). But prandial HGP response during insulin-induced hypoglycemia (AUCHGP) was smaller and shorter in duration in surgical groups (p < 0.05). In the absence of meal stimuli, however, glucose counterregulatory response to hypoglycemia was comparable among the 3 groups during hyperinsulinemic clamp. CONCLUSION: After bariatric surgery, prandial glucose counterregulatory response to hypoglycemia is impaired. Considering post-meal hyperglucagonemia after GB or SG the blunted HGP response suggests a lower sensitivity of liver to glucagon that can predispose to hypoglycemia in this population.

Characterization of glucose metabolism in youth with vs. without cystic fibrosis liver disease: A pilot study.

Background: Diabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease. Methods: In this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained. Results: Participants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial ß-cell secretory response (AUC C-peptide 3h) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1). Conclusion: In this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.

Utility of Continuous Glucose Monitoring vs Meal Study in Detecting Hypoglycemia After Gastric Bypass.

CONTEXT: Gastric bypass (GB) increases postprandial glucose excursion, which in turn can predispose to the late complication of hypoglycemia. Diagnosis remains challenging and requires documentation of symptoms associated with low glucose and relief of symptom when glucose is normalized (Whipple triad). OBJECTIVE: To compare the yield of mixed meal test (MMT) and continuous glucose monitoring system (CGMS) in detecting hypoglycemia after GB. SETTING: The study was conducted at General Clinical Research Unit, Cincinnati Children's Hospital (Cincinnati, OH, USA). METHODS: Glucose profiles were evaluated in 15 patients with documented recurrent clinical hypoglycemia after GB, 8 matched asymptomatic GB subjects, and 9 healthy weight-matched nonoperated controls using MMT in a control setting and CGMS under free-living conditions. RESULTS: Patients with prior GB had larger glucose variability during both MMT and CGMS when compared with nonsurgical controls regardless of their hypoglycemic status. Sensitivity (71 vs 47%) and specificity (100 vs 88%) of MMT in detecting hypoglycemia was superior to CGMS. CONCLUSIONS: Our findings indicate that a fixed carbohydrate ingestion during MMT is a more reliable test to diagnose GB-related hypoglycemia compared with CGMS during free-living state.

Evaluation of the Association between Antiphospholipid Antibodies and ICU Admission Outcome in Critically Ill COVID-19 Patients in Iranian Population.

Background: The role of anti-phospholipid antibodies (aPLs) in the prognosis of COVID-19 patients is controversial. In order to prove the role of this factor, the necessary measures such as early initiation of anticoagulants should be started even in the early stages of the disease and in outpatients or the use of other drugs in addition to anticoagulants. We decided to investigate the role of these antibodies in ICU admission outcomes in critically ill COVID-19 patients. Methods: The case-control study was carried out in Isfahan, Iran, from March to September 2021. One hundred nine patients in the case group were selected, including patients admitted to the ICU with a COVID-19 diagnosis. The 140 patients in the control group were selected from hospitalized and outpatients with COVID-19 with PCR + and pulmonary involvement, similar to the case group without the need for ICU hospitalization. The anti B2GP1 (IgM, IgG) and anti-cardiolipin (IgM, IgG)) were compared in two groups. Results: The frequency percentage of patients in the abnormal group of anti-phospholipid antibodies was about 10% in total. No statistically significant difference in these aPLs in continued measures was observed between the two groups of patients admitted to the ICU and those outside the ICU. Also, in the logistics regression analysis, no significant association was observed. Conclusions: Therefore, the cause of coagulation in patients admitted to the ICU is not related to these aPLs. This means that aPLs could not be a good predictor of patient admission to the ICU.

Modeling organizational intelligence, learning, forgetting and agility using structural equation model approaches in Shiraz University of Medical Sciences Hospitals.

OBJECTIVES: Strengthening the organizational agility of the hospital can lead to decreased production costs and increased market share, better serving to patients' needs, introduction of new services and increased competitiveness; therefore, this study aimed to investigate the agility of Shiraz public teaching hospitals. RESULTS: The results showed that organizational intelligence had a positive and significant effect on organizational agility with a path coefficient of 0.172. Organizational forgetting and organizational learning also played a mediating role between organizational intelligence and organizational agility. This means that organizational intelligence had positive effect on organizational forgetting with path coefficient of 0.482, organizational forgetting on organizational learning with path coefficient of 0.40 and subsequently organizational learning on organizational agility with path factor of 0.07. Organizational forgetting also played a mediating role between organizational intelligence and organizational learning.

Risk factors of the efficacy of hepatitis B vaccine in health-care workers.

BACKGROUND: Conventional hepatitis B virus vaccination fails to achieve efficient protection in about 5%-10% of the world population. Different factors influence the immunogenicity of hepatitis B vaccine. This study aimed to evaluate these factors in health-care workers. MATERIALS AND METHODS: This was a descriptive study which was implemented among 140 of medical and dental staff working as health-care workers who were low responder after vaccination entered the study. RESULTS: Age (>40 years), weight (body mass index >25), immunodeficiency diseases, (primary immune deficiency and immunosuppressant drugs), diabetes mellitus, and smoking were the important factors. CONCLUSION: In the high-risk group of hepatitis B disease, the risk factors of immunogenicity must be evaluated at vaccination and check titers of antibody after vaccination.