Impact of etiology, sex, diabetes mellitus and remission status on erythrocytic profile in patients with cushing's syndrome: a large population database study.

PURPOSE: The study aimed to characterize the erythrocytic profile in patients with cushing's syndrome (CS) versus controls from the normal population according to etiology, sex, presence of diabetes mellitus (DM) and hypercortisolemia remission status. METHODS: This retrospective cohort analysis compared erythrocytic parameters between patients with CS of pituitary (CD) and adrenal (aCS) etiology and age, sex, body mass index (BMI) and socioeconomic status-matched controls in a 1:5 ratio. Laboratory values at baseline were calculated as mean values during the year preceding CS diagnosis, and over one year thereafter. RESULTS: The cohort included 397 CS patients (68.26% female; mean age 51.11 ± 16.85 years) and 1970 controls. Patients with CS had significantly higher baseline median levels of hemoglobin (Hgb) (13.70 g/dL vs. 13.12 g/dL [p < 0.0001]) and hematocrit (Hct) (41.64% vs. 39.80% [p < 0.0001]) compared to controls. These differences were observed for both CD and aCS and for both sexes. Patients who attained remission had Hgb and Hct levels comparable to controls (13.20 g/dL and 40.08% in patients with CD and aCS vs. 13.20 g/dL and 39.98% in controls). Meanwhile, those with persistent/recurrent disease maintained elevated levels. Patients with comorbid DM had similar Hgb but higher Hct (p = 0.0419), while patients without DM showed elevated erythrocytic values compared to controls (p < 0.0001). CONCLUSION: Our data illustrates that erythrocytic parameters are directly influenced by glucocorticoid excess as Hgb and Hct are higher in patients with CS, and normalize after remission. We have identified the influence of DM on erythrocytic parameters in patients with CS for the first time.

Glycemic Control Among Adults With Type 1 Diabetes During Passover: A Pre-Post Single-center Study.

OBJECTIVES: No data are available regarding glycemic control of patients with type 1 diabetes (T1D) during Passover. Our aim in this study was to assess the effect of Passover on diabetes management and glycemic control in adult patients with T1D with nutritional changes during Passover (observant) compared with patients who did not change their dietary habits during Passover (nonobservant). METHODS: Observational pre-post study of adult patients with T1D, followed in a diabetes clinic in Israel. Data were downloaded from insulin pumps and continuous glucose monitoring for 37 days: 2 weeks before Passover; 9 days of Passover; and 2 weeks thereafter. Differences in percentage of time spent above target (>10.0 to >13.9 mmol/L), at target (3.9 to 10.0 mmol/L) and below target (<3.9 to <3.0 mmol/L), were compared using paired t tests or paired signed rank tests. RESULTS: The study cohort included 43 patients (23 observant, 20 nonobservant). The average blood glucose was significantly higher during Passover compared with the period before Passover---in nonobservant patients 8.2±1.5 mmol/L and 7.9±1.3 mmol/L (p=0.043), respectively, and in observant patients 8.7±1.6 mmol/L and 8.4±1.6 mmol/L (p=0.048), respectively. Time above range 10 to 13.9 mmol/L was increased in observant patients during Passover, as compared with the period before Passover, was 24.9±16.2% and 20.6±12.4% (p=0.04), respectively. The dose of bolus insulin had increased significantly in observant patients: 27.4±13.9 units during Passover, as compared with 24.2±11.2 units before Passover (p=0.02). CONCLUSIONS: Passover alters glycemic control and insulin needs in Jewish patients with T1D. It is advisable to make specific adjustments to maintain the recommended glycemic control.

The Association Between Hypothyroidism Treatment and Mortality in Patients Hospitalized in Surgical Wards.

Limited data are available regarding the association between pre-admission thyroid-stimulating hormone (TSH) levels and prognosis in hospitalized surgical patients treated for hypothyroidism. We retrospectively evaluated a cohort of 1,451 levothyroxine-treated patients, hospitalized to general surgery wards. The 30-day mortality risk was 2-fold higher for patients with TSH of 5.0-10.0 mIU/L (adjusted OR, 2.3; 95% CI 1.1-5.1), and 3-fold higher for those with TSH > 10.0 mIU/L (3.4; 95% CI 1.3-8.7). Long-term mortality risk was higher in patients with TSH of 5.0-10.0 and above 10.0 mIU/L (adjusted HR, 1.2; 95% CI, 1.0-1.6, and 1.7; 95% CI 1.2-2.4, respectively). We found that in levothyroxine-treated adults hospitalized to surgical wards, increased pre-admission TSH levels are associated with increased short- and long-term mortality.

Cushing's syndrome in women: age-related differences in etiology and clinical picture.

OBJECTIVE: To evaluate the clinical presentation, biochemical profile, and etiology of Cushing's syndrome (CS) in women stratified by age. METHODS: Retrospective study of patients with CS, treated at Rabin Medical Center from 2000 to 2020, or Maccabi Healthcare Services in Israel from 2005 to 2017. Disease etiology, presentation and biochemical profile were compared according to age at diagnosis: ≤ 45, 46-64, or ≥ 65 years. Study was approved by the Ethics Review Boards of both facilities with waiver of consent. RESULTS: The cohort included 142 women (mean age, 46.0 ± 15.1 years):81 (57.0%) with Cushing's disease (CD), and 61 (43.0%) with adrenal CS. Pituitary etiology was more common among women < 45 (70.6%), compared with patients ≥ 65 years (31.6%) (P < 0.05). Among CS patients, hypercortisolism was diagnosed in the context of screening after an adrenal incidentaloma detection in 15.0% of patients < 45 and 53.8% of ≥ 65 years (P < 0.001). Weight gain was evident in 57.4% of women < 45 (56.3% CD, 60.0% CS), and 15.8% of women ≥ 65 years (50% CD, 0% CS) (P = 0.011). Mean UFC levels were highest for women < 45 (3.8 × ULN) and lowest for ≥ 65 years (2.3 × ULN) (P < 0.001). CONCLUSION: We have shown for the first time that women with CS ≥ 65 years of age more commonly have adrenal etiology. The initial presentation of CS also differs between age groups, where women < 45 years are likely to present with weight gain, while those ≥ 65 years are frequently diagnosed incidentally, when screening for hypercortisolism in the presence of an adrenal incidentaloma.

Rate of breast biopsy referrals in female BRCA mutation carriers aged 50 years or more: a retrospective comparative study and matched analysis.

PURPOSE: To evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population. METHODS: The study group consisted of 330 women with pathogenic variants (PVs) in BRCA1/2 attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients aged 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended by international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders. RESULTS: The total biopsy rate per 1000 follow-up years was 61.7 in the study group and 22.7 in the control group (p < 0.001). The corresponding positive biopsy rates per 1000 follow-up years were 26.4 and 2.0 (p < 0.001), and the positive biopsy percentages, 42.9% and 8.7% (p < 0.0001). CONCLUSION: Women aged 50 + years with PVs in BRCA1/2 attending a dedicated clinic have a 2.7 times higher biopsy rate per 1000 follow-up years, a 13.2 times higher positive biopsy rate per 1000 follow-up years, and a 4.9 times higher positive biopsy percentage than same-aged women in the general population.

Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing's Disease: Does Size Matter?

Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing's disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study.

The Association Between BMI and Mortality in Surgical Patients.

BACKGROUND: While obesity is commonly associated with increased morbidity and mortality, in patients with chronic diseases, it has have been associated with a better prognosis, a phenomenon known as the 'obesity paradox'. OBJECTIVE: We investigated the relationship between mortality, length of hospital stay (LOHS), and body mass index (BMI) in patients hospitalized to general surgical wards. METHODS: We extracted data of patients admitted to the hospital between January 2011 and December 2017. BMI was classified according to the following categories: underweight (< 18.5), normal weight (18.5-24.9), overweight (25-29.9), obesity (30-34.9) and severe obesity (≥ 35). Main outcomes were mortality at 30-day mortality and at the end-of-follow-up mortality), as well as LOHS. RESULTS: A total of 27,639 patients (mean age 55 ± 20 years; 48% males; 19% had diabetes) were included in the study. Median LOHS was longer in patients with diabetes vs. those without diabetes (4.0 vs 3.0 days, respectively), with longest LOHS among underweight patients. A 30-day mortality was 2% of those without (371/22,297) and 3% of those with diabetes (173/5,342). In patients with diabetes, 30-day mortality risk showed a step-wise decrease with increased BMI: 10% for underweight, 6% for normal weight, 3% for overweight, 2% for obese and only 1% for severely obese patients. In patients without diabetes, 30-day mortality was found to be 6% for underweight, 3% for normal weight and 1% across the overweight and obese categories. Mortality rate at the end-of-follow-up was 9% of patients without diabetes and 18% of those with diabetes (adjusted OR = 1.3, 95% CI, 1.2-1.5). In patients with diabetes, mortality risk showed an inverse association with respect to BMI: 52% for underweight, 29% for normal weight, 17% for overweight, 14% for obesity and 7% for severely obese patients, with similar trend in patients without diabetes. CONCLUSIONS: The results support the 'obesity paradox' in the general surgical patients as those with and without diabetes admitted to surgical wards, BMI had an inverse association with short- and long-term mortality.

Solid-organ transplant recipients with hyperglycemia on admission face worse outcomes.

OBJECTIVES: To evaluate the association between admission blood glucose (ABG) and mortality following hospitalization of solid-organ transplant recipients with and without diabetes. STUDY DESIGN: Descriptive, retrospective observational data extracted from electronic health records. METHODS: Observational data derived from the electronic health records of solid-organ transplant recipients who were hospitalized patients 18 years and older, admitted for any cause between January 2011 and December 2013. ABG levels were classified into categories: 70 to 110 mg/dL (normal), 111 to 140 mg/dL (mildly elevated), 141 to 180 mg/dL (moderately elevated), and greater than 180 mg/dL (markedly elevated). The main outcome was all-cause mortality. RESULTS: Our study included 832 patients (median [SD] age = 59 [14] years; 62% male; 68% kidney transplant recipients), 503 (61%) of whom did not have diabetes. Just over half of patients without diabetes had normal ABG (54%), whereas most of those with diabetes had moderately or markedly increased ABG (58%). In patients without diabetes, markedly elevated ABG was associated with increased 30-day mortality risk compared with normal ABG (adjusted odds ratio [aOR], 6.6; 95% CI, 1.9-22.1). The same pattern was evident with investigation of the mortality risk after 1 year (aOR, 5.9; 95% CI, 2.4-14.7) and 3 years (aOR, 10.2; 95% CI, 4.3-24.0). Among patients with diabetes, there was no difference in mortality risk with different ABG. With a competing risk model for 90-day readmission and mortality, there was no association between ABG and risk for readmissions in patients with or without diabetes. CONCLUSIONS: In organ transplant recipients admitted for any cause to a general ward, markedly elevated ABG in patients without diabetes was found to be independently associated with higher mortality risk compared with normal ABG levels. In patients with diabetes, there was no association between ABG level and mortality.

Low serum albumin levels predict short- and long-term mortality risk in patients hospitalised to general surgery wards.

BACKGROUND: Previous studies have reported conflicting results on the association between hypoalbuminaemia and morbidity and mortality in hospitalised patients. AIMS: To investigate the association of albumin levels on admission and change in levels during hospitalisation of patients in general surgery wards with hospitalisation outcomes. METHODS: Historical prospective data of patients hospitalised between January 2011 and December 2017. Albumin levels were classified as follows: marked hypoalbuminaemia (<2.5 mg/dL), mild hypoalbuminaemia (2.5-3.5 mg/dL), normal albumin (3.5-4.5 mg/dL) and hyperalbuminaemia (>4.5 mg/dL). Main outcomes were length of hospitalisation, 30-days and long-term mortality. RESULTS: The cohort included 17 930 patients (mean age 58 ± 20 years, 49% male). Most had normal albumin levels on admission (n = 11 087, 62%), 16% had mild hypoalbuminaemia (n = 2824) and 3% had marked hypoalbuminaemia (n = 529). Hyperalbuminaemia on admission was evident in 20% of the patients (n = 3490). Follow-up time was up to 7.2 years (median ± SD = 3 ± 2 years). Compared to 30-day mortality with normal albumin on admission (2%), mortality was higher with mild (9%) and marked hypoalbuminaemia (22%) and lower with hyperalbuminaemia (0.4%). The mortality rate at the end of follow up was 14% with normal albumin levels, and 35% and 58% with mild and marked hypoalbuminaemia respectively. Patients with hyperalbuminaemia on admission and before discharge had the best short- and long-term survival. This pattern was similar when analysed separately in different age groups. In patients with hypoalbuminaemia on admission, normalisation of albumin levels before discharge was associated with lower short- (12% vs 1%) and long-term mortality risk (42% vs 17%). CONCLUSIONS: Low albumin levels on admission to general surgery wards are associated with increased short- and long-term mortality. Normalisation of albumin levels before discharge was associated with lower mortality, compared to hypoalbuminaemia before discharge.

Glycemic variability and mortality in patients hospitalized in general surgery wards.

BACKGROUND: Glucose variability is common among hospitalized patients, but the prognostic implications among patients hospitalized in surgical wards are unknown. The objective of this study was to investigate the association between glucose variability, length of stay, and mortality. METHODS: Historical prospectively collected data of patients ≥18 years of age, hospitalized in general surgery wards between January 2011 and December 2017. Glucose variability was assessed by coefficient of variance and standard deviation of glucose values during hospitalization. The main outcomes were length of stay and 30-day and end-of-follow-up mortality. RESULTS: The cohort included 8,894 patients (mean age 63 ± 19 years, 48% male, mean follow-up 3.0 ± 1.8 years). A total of 2,012 (23%) patients had diabetes mellitus. The mean length of stay was longer with a higher coefficient of variance or standard deviation in patients without and with diabetes mellitus. The 30-day mortality was 6%, associated with a higher versus a lower coefficient of variance (9% vs 3%) and standard deviation (9% vs 3%) in patients without diabetes mellitus and with diabetes mellitus (9% vs 5%; 8% vs 5%, respectively). Mortality at the end of follow-up was increased in patients without diabetes mellitus with a higher coefficient of variance (27% vs 18%) and standard deviation (29% vs 17%) and in patients with diabetes mellitus (33% vs 24% and 32% vs 21%, respectively). Multivariate analysis indicated an increased risk for 30-day and end-of-follow-up mortality, in both groups. Adjustment for glucocorticoid treatment or hypoglycemia did not affect the results. In patients with a high or low coefficient of variance, mortality was higher with median glucose levels during hospitalization ≥180 mg/dl, compared with <180 mg/dl. CONCLUSION: In patients with and without diabetes mellitus hospitalized in general surgery wards, increased glucose variability is associated with longer hospitalization and increased short-term and long-term mortality.

The Pattern of Elevated Liver Function Tests in Nonalcoholic Fatty Liver Disease Predicts Fibrosis Stage and Metabolic-Associated Comorbidities.

BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) and with abnormal liver function tests (LFTs) most commonly present with elevated hepatocellular enzymes (H pattern), but a subset of patients is found to have elevated cholestatic enzymes (C pattern) or a mixed (M) pattern. AIMS AND METHODS: To determine whether the epidemiologic background and comorbidities, as well as the degree of liver fibrosis, differ between NAFLD patients with different patterns of elevated LFTs by retrospectively analyzing data of 106 patients with a biopsy-proven diagnosis of NAFLD. The pattern of elevated LFTs was determined by adopting the "R-Ratio" formula commonly used for drug-induced liver injury. RESULTS: Advanced fibrosis (F > 2) was found in 15 out of 48 (31.3%) patients with a C pattern of elevated LFTs as compared to 2 out of 44 (4.5%) in M patients and 2 out of 11 (18.2%) in H patients (p = 0.004). Group C patients are older and also had a higher prevalence of diabetes, a higher mean hemoglobin A1c, and a higher prevalence of hypertension, as well as a trend for a higher prevalence of hypertriglyceridemia. CONCLUSIONS: Using a simple formula incorporating routine LFTs can help to categorize NAFLD patients as low or high risk for advanced fibrosis stage and metabolic-associated comorbidities.

Prognostic Value of the Detection of Lymphovascular Invasion in Hormone Receptor-Positive Early Breast Cancer in the Era of Molecular Profiling.

BACKGROUND: Lymphovascular invasion (LVI) is considered a negative prognostic factor in early breast cancer, but its role in decision-making regarding adjuvant chemotherapy is unclear in the current era of molecular profiling. This study sought to evaluate the association of LVI status with the recurrence score (RS) on the multigene Oncotype DX (ODX) assay and its impact on outcome. METHODS: Patients with early estrogen receptor-positive breast cancer who underwent ODX analysis in 2005-2012 were retrospectively identified. Clinical data were collected from the medical records. The Cox proportional-hazards ratio was used to determine recurrence rates. The prognostic significance of LVI was evaluated by competing risks analysis. RESULTS: LVI was detected in 38 of 657 patients (6%). LVI was not associated with ODX RS (p = 0.225). However, it was significantly associated with other known prognostic factors and with worse 5-year disease-free survival (HR 2.93; 95% CI 1.02-8.39; p = 0.04). Overall survival (OS) analysis according to the ODX subgroups showed that the presence of LVI was associated with worse 5-year OS (p = 0.04) only in the intermediate-risk group, while LVI had no effect on the low- or high-risk groups. CONCLUSIONS: Although LVI was not significantly associated with a higher ODX RS, it may infer a worse outcome, especially in ODX intermediate-risk patients.

Predictors of hypoglycemia in hospitalized patients with diabetes mellitus.

Hypoglycemia is common among hospitalized patients with diabetes mellitus (DM), and is associated with increased morbidity and mortality. Identify pre-admission risk factors associated with in-hospital hypoglycemia. Historical prospectively collected data of adult DM patients hospitalized to medical wards between 2011 and 2013. Hypoglycemia and serious hypoglycemia were defined as at least one blood glucose measurement ≤ 70 and < 54 mg/dl, respectively, during hospitalization. The primary outcome was in-hospital hypoglycemia. The cohort included 5301 patients (mean age 73 ± 13 years, 51% male), including 792 patients (15%) with hypoglycemia, among them 392 patients (7%) with serious hypoglycemia. Patients with hypoglycemia or serious hypoglycemia during hospitalization were older, compared to patients without hypoglycemia and more likely to have chronic renal failure and cerebrovascular disease. Malignancy and female gender were risk factors for hypoglycemia, but not for serious hypoglycemia, while congestive heart failure was associated with increased risk only for serious hypoglycemia. Diabetes mellitus' duration over 10 years was associated with an almost threefold increased risk for hypoglycemia, compared to DM duration less than a year. Insulin treatment and glycated hemoglobin > 9% were also more common in patients with hypoglycemia. Insulin treatment was associated with a fourfold increase in the risk for hypoglycemia among all glycated hemoglobin categories. Our results identified several risk factors for in-hospital hypoglycemia in patients with DM. These findings may lead to appropriate monitoring and early intervention to prevent hypoglycemia and to reduce morbidity and mortality associated with in-hospital hypoglycemia.

Early Breast Cancer in the Elderly: Characteristics, Therapy, and Long-Term Outcome.

OBJECTIVE: The number of older adults diagnosed with breast cancer is increasing. However, data on breast cancer characteristics, treatment, and survival in elderly women are sparse. METHODS: The database of a tertiary cancer center was searched for all women aged ≥65 years who were diagnosed with early breast cancer in 2004-2007. Patients were divided into 2 age groups: 65-75 years and >75 years. Data on tumor, treatment, and outcome parameters were compared. RESULTS: The cohort included 390 patients. The older group underwent more mastectomies but less axillary surgery or adjuvant systemic therapy. Median overall survival (OS) was 9.5 years in the older group and not reached in the younger group; the 8-year disease-free survival rates were 85 and 88%, respectively (p = 0.27). Both age and tumor subtype had an effect on OS and recurrence rates (p < 0.001 for OS; p = 0.16 for recurrence). The worst outcome was noted in women aged >75 years with triple-negative (TN) disease. CONCLUSION: The treatment approach was different between both age groups, despite similar tumor characteristics. TN subtype presented as the most aggressive disease in both age groups. Physicians should be alert to these findings and select treatment on a case-by-case basis.

Body mass index and mortality in patients with and without diabetes mellitus.

OBJECTIVE: Investigate the association between body mass index (BMI), length of stay (LOS), and mortality in hospitalized patients with and without diabetes mellitus (DM). METHODS: Historical prospectively collected data of adult patients hospitalized between 2011 and 2013. Body mass index was calculated according to measurement or self-report on admission and classified as follows: underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), obese (30-34.9), and severely obese (≥35). The main outcomes were LOS, in-hospital, and end-of-follow-up mortality. RESULTS: Cohort included 24 233 patients (53% male; mean age ± SD, 65 ± 18), including 7397 patients with DM (31%). Among patients with normal BMI, LOS was shorter compared with underweight patients, but it was longer compared with overweight and obese patients. Following multivariate adjustment, this difference remained significant only for patients with DM. There was a significant interaction between DM status and BMI group, in the models for in-hospital and end-of-follow-up mortality. Compared with normal BMI, in-hospital mortality risk was increased by 80% and 100% for the underweight with and without DM, respectively. For patients with and without DM, in-hospital mortality risk was 30% to 40% lower among overweight and obese patients, and there was no difference between severely obese and normal weight patients. At the end-of-follow-up, mortality risk was 1.6-fold and 1.7-fold higher among underweight patients with and without DM, respectively. For overweight, obese, and severely obese patients, mortality risk was decreased by 30% to 40% in those with DM and by 20% to 30% in those without DM. CONCLUSIONS: In hospitalized patients with and without DM, there was an inverse association between BMI and mortality.

Long-term outcomes in older patients with hyperglycemia on admission for ischemic stroke.

AIMS: Evaluate the association between admission blood glucose (ABG) and mortality in older patients with or without diabetes mellitus (DM) hospitalized for acute ischemic stroke (AIS). METHODS: Observational data of patients ≥65years, admitted for AIS between January 2011 and December 2013. ABG levels were classified to categories: ≤70 (low), 70-110 (normal), 111-140 (mildly elevated), 141-180mg/dl (moderately elevated) and >180mg/dl (markedly elevated). Main outcome was all-cause mortality at the end-of-follow-up. RESULTS: Cohort included 854 patients, 347 with (mean±SD age 80±8, 44% male), and 507 without DM (mean±SD age 78±8, 53% male). There was a significant interaction between DM, ABG and mortality at end-of-follow-up (p≤0.05). In patients without DM there was a dose-dependent association between ABG category and mortality: adjusted hazard ratios (95% CI) compared to normal ABG were 1.8 (1.2-2.8), 2.9 (1.6-5.2) and 4.5 (2.1-9.7), respectively, for mildly, moderately and markedly elevated ABG. In patients with DM there was no association between ABG and mortality. There was no interaction between DM, ABG and in-hospital mortality or length of stay (LOS). Irrespective of DM status, compared to normal ABG levels, increased ABG category was associated with increased in-hospital mortality: adjusted odds ratios were 3.9 (1.1-13.4), 7.0 (1.8-28.1), and 20.3 (4.6-89.6) with mildly, moderately and markedly elevated ABG, respectively. Mean LOS was 6±5, 7±8, 8±7, and 8±8days, respectively. CONCLUSION: In older patients without DM hospitalized for AIS, elevated ABG is associated with increased long-term mortality. Irrespective of DM status, elevated ABG was associated with increased in-hospital mortality and LOS.

Pre-admission TSH levels predict long-term mortality in adults treated for hypothyroidism.

CONTEXT: Limited data is available regarding the association between pre-admission thyroid function and prognosis of hospitalized patients treated for hypothyroidism. OBJECTIVE: Evaluate an association between thyroid stimulating hormone (TSH) levels and mortality in hospitalized levothyroxine-treated patients. DESIGN AND SETTING: Observational data of patients admitted to medical wards between 2011 and 2013. TSH levels obtained up to 180 days prior to admission were stratified as follows: low (≤0.5 mIU/L), normal (0.5-5 mIU/L), high (>5 mIU/L). PATIENTS: Patients aged 60-80 years with available thyroid function tests were matched with controls without hypothyroidism. MAIN OUTCOME: All-cause mortality up to 66-months following discharge. RESULTS: One thousand and fifty seven patients (73% females, mean (SD) age 71 ± 6 years) were matched with controls without hypothyroidism. Mean hospital stay and in-hospital mortality were not different between groups. Mortality risk at the end-of-follow-up was 41% (438/1057) and 37% (392/1057) for patients with and without hypothyroidism (p < 0.05). TSH levels were classified as follows: low, 84 patients (8%); normal, 667 patients (63%); high, 306 patients (29%). Length of hospitalization and in-hospital mortality were not different between TSH categories. Mortality risk at the end-of-follow-up was 30, 39, and 50% with low, normal and elevated TSH, respectively. Adjusted hazard ratio (95% CI) of mortality at the end-of-follow-up was of 2.2 (1.2-3.8) for high vs. low TSH levels, and 1.4 (1.1-1.9) for high vs. normal TSH levels. CONCLUSION: In treated hypothyroid adult patients, increased TSH up to 6 months prior to admission is associated with increased mortality. Treatment should aim at achieving euthyroidism to improve survival.

Hyperglycemia on admission and hospitalization outcomes in patients with atrial fibrillation.

BACKGROUND: We evaluated the association of admission blood glucose (ABG) and mortality in patients with and without diabetes mellitus (DM) hospitalized for atrial fibrillation (AF). HYPOTHESIS: Hyperglycemia on admission is a bad prognostic marker in patients with AF. METHODS: Observational data were collected from electronic records of patients age ≥ 18 years hospitalized for AF in 2011-2013. Twelve-month data were available in all cases. ABG levels were classified as follows: 70 to 110 mg/dL, normal; 111 to 140 mg/dL, mildly elevated; 141 to 199 mg/dL, moderately elevated; ≥200 mg/dL, markedly elevated. Cox proportional hazards model was used to assess overall survival by ABG categories, adjusted for study variables. Primary outcome measure was mortality at end of follow-up. RESULTS: The cohort included 1127 patients (45% male; median age, 75 ± 13 years), of whom 331 had DM. Mortality rates by ABG levels were 19% (77/407 patients), normal ABG; 26% (92/353 patients), mildly elevated ABG; 28% (69/244 patients), moderately elevated ABG; and 41% (50/123 patients), markedly elevated ABG. Data were analyzed for the entire cohort following adjustment for age, sex, CHADS2 score, ischemic heart disease, smoking, and alcohol consumption. Compared with normal ABG, the adjusted hazard ratio for mortality was higher in patients with moderately elevated ABG (2.1, 95% confidence interval: 1.19-7.94, P < 0.05) and markedly elevated ABG (1.6, 95% confidence interval: 1.02-5.31, P < 0.05). CONCLUSIONS: In patients with and without DM hospitalized for AF, moderately to markedly elevated ABG levels are associated with increased mortality.

Blood glucose on admission and mortality in patients with venous thromboembolism.

AIMS: Evaluate association between admission blood glucose (ABG) and mortality in patients with or without diabetes mellitus (DM) hospitalized for venous thromboembolism (VTE). METHODS: Observational data derived from the electronic records of hospitalized patients ≥18years, admitted for VTE (including deep vein thrombosis and pulmonary embolism) between January 2011 and December 2013. ABG levels were classified to categories: ≤70 (low), 70-110 (normal), 111-140 (mildly elevated), 141-180mg/dl (moderately elevated) and>180mg/dl (markedly elevated). Main outcome was all-cause mortality at the end of follow-up. We had complete follow-up data at 12months for all patients; median follow-up time was 1126days. RESULTS: Cohort included 567 patients, 137 with (mean age 73, 45% male), and 430 without DM (mean age 65, 40% male). There was a significant interaction between DM, ABG and mortality (p≤0.05). In patients without DM there was a significant association between ABG and mortality: [hazard ratios 1.6, 2.3, and 4.7 respectively for mildly, moderately and markedly elevated ABG (p≤0.01)]. A significant association between ABG and mortality persisted following multivariable analysis only in patients with markedly elevated ABG (HR=2.3 95% CI 1.2-4.5). Similar results were evident in patients with deep vein thrombosis or pulmonary embolism. In patients with DM there was no significant association between ABG and mortality. CONCLUSION: In patients without DM hospitalized for VTE, markedly elevated ABG is associated with increased mortality.

Mortality Among Hospitalized Patients With Hypoglycemia: Insulin Related and Noninsulin Related.

CONTEXT: Hypoglycemia is common among hospitalized patients with and without diabetes mellitus. OBJECTIVE: Investigate the association between spontaneous or insulin-related hypoglycemia and mortality in hospitalized patients. DESIGN: Hypoglycemia was defined as blood glucose <70 mg/dl (3.9 mmol/l), including moderate (40 to 70 mg/dl, 2.2 to 3.9 mmol/l) and severe hypoglycemia (<40 mg/dl, 2.2 mmol/l). Use of insulin during hospitalization defined insulin-related hypoglycemia, thus patients were classified into 6 groups: non-insulin treated (NITC) and insulin-treated controls (ITC), insulin-related hypoglycemia (IH) or severe hypoglycemia (ISH), and non insulin-related hypoglycemia (NIH) and severe hypoglycemia (NISH). SETTING AND PATIENTS: Historical prospectively data of patients ≥ 18 years of age, hospitalized in medical wards for any cause between January 2011 and December 2013. MAIN OUTCOME MEASURE: All-cause mortality at the end of follow-up. RESULTS: The cohort included 33,675 patients, including 2605 with moderate hypoglycemia (IH, 1011; NIH, 1594) and 342 with severe hypoglycemia (ISH, 201; NISH,141). Overall end-of-follow-up mortality was 31.9% (NITC, 28.0%; ITC, 42.9%; NIH, 50.7%; IH, 55.3%; NISH, 70.9%; ISH, 69.1%). Compared with NITC, unadjusted hazard ratios (95% confidence intervals) for mortality were as follows: ITC, 1.7 (1.6 to 1.8), NIH, 2.2 (2.0 to 2.4), IH, 2.5 (2.2 to 2.7), NISH, 4.2 (3.5 to 5.2), and ISH, 3.8 (3.2 to 4.5); with P < 0.001. Following multivariate analysis, respective hazard ratios were 1.8, 2.1, 2.4, 3.2, and 3.6 (P < 0.001). Cause of admission did not affect the association. CONCLUSIONS: In hospitalized patients, hypoglycemia, either with insulin use or spontaneous, is associated with increased short- and long-term mortality.