Predictors of readmission and mortality in adults with diabetes or stress hyperglycemia after initial hospitalization for COVID-19.

INTRODUCTION: We previously reported predictors of mortality in 1786 adults with diabetes or stress hyperglycemia (glucose>180 mg/dL twice in 24 hours) admitted with COVID-19 from March 2020 to February 2021 to five university hospitals. Here, we examine predictors of readmission. RESEARCH DESIGN AND METHODS: Data were collected locally through retrospective reviews of electronic medical records from 1786 adults with diabetes or stress hyperglycemia who had a hemoglobin A1c (HbA1c) test on initial admission with COVID-19 infection or within 3 months prior to initial admission. Data were entered into a Research Electronic Data Capture (REDCap) web-based repository, and de-identified. Descriptive data are shown as mean±SD, per cent (%) or median (IQR). Student's t-test was used for comparing continuous variables with normal distribution and Mann-Whitney U test was used for data not normally distributed. X2 test was used for categorical variable. RESULTS: Of 1502 patients who were alive after initial hospitalization, 19.4% were readmitted; 90.3% within 30 days (median (IQR) 4 (0-14) days). Older age, lower estimated glomerular filtration rate (eGFR), comorbidities, intensive care unit (ICU) admission, mechanical ventilation, diabetic ketoacidosis (DKA), and longer length of stay (LOS) during the initial hospitalization were associated with readmission. Higher HbA1c, glycemic gap, or body mass index (BMI) were not associated with readmission. Mortality during readmission was 8.0% (n=23). Those who died were older than those who survived (74.9±9.5 vs 65.2±14.4 years, p=0.002) and more likely had DKA during the first hospitalization (p<0.001). Shorter LOS during the initial admission was associated with ICU stay during readmission, suggesting that a subset of patients may have been initially discharged prematurely. CONCLUSIONS: Understanding predictors of readmission after initial hospitalization for COVID-19, including older age, lower eGFR, comorbidities, ICU admission, mechanical ventilation, statin use and DKA but not HbA1c, glycemic gap or BMI, can help guide treatment approaches and future research in adults with diabetes.

Glycemic Gap Predicts Mortality in a Large Multicenter Cohort Hospitalized With COVID-19.

CONTEXT: Diabetes or hyperglycemia at admission are established risk factors for adverse outcomes during hospitalization for COVID-19, but the impact of prior glycemic control is not clear. OBJECTIVE: We aimed to examine the associations between admission variables, including glycemic gap, and adverse clinical outcomes in patients hospitalized with COVID-19 infection. METHODS: We examined the relationship between clinical predictors, including acute and chronic glycemia, and clinical outcomes, including intensive care unit (ICU) admission, mechanical ventilation (MV), and mortality among 1786 individuals with diabetes or hyperglycemia (glucose > 10 mmol/L twice in 24 hours) who were admitted from March 2020 through February 2021 with COVID-19 infection at 5 university hospitals in the eastern United States. RESULTS: The cohort was 51.3% male, 53.3% White, 18.8% Black, 29.0% Hispanic, with age = 65.6 ± 14.4 years, BMI = 31.5 ± 7.9 kg/m2, glucose = 12.0 ± 7.5 mmol/L [216 ± 135 mg/dL], and HbA1c = 8.07% ± 2.25%. During hospitalization, 38.9% were admitted to the ICU, 22.9% received MV, and 10.6% died. Age (P < 0.001) and admission glucose (P = 0.014) but not HbA1c were associated with increased risk of mortality. Glycemic gap, defined as admission glucose minus estimated average glucose based on HbA1c, was a stronger predictor of mortality than either admission glucose or HbA1c alone (OR = 1.040 [95% CI: 1.019, 1.061] per mmol/L, P < 0.001). In an adjusted multivariable model, glycemic gap, age, BMI, and diabetic ketoacidosis on admission were associated with increased mortality, while higher estimated glomerular filtration rate (eGFR) and use of any diabetes medication were associated with lower mortality (P < 0.001). CONCLUSION: Relative hyperglycemia, as measured by the admission glycemic gap, is an important marker of mortality risk in COVID-19.

Familial Dysalbuminemic Hyperthyroxinemia (FDH), Albumin Gene Variant (R218S), and Risk of Miscarriages in Offspring.

BACKGROUND: Familial dysalbuminemic hyperthyroxinemia (FDH) is a rare autosomal dominant disorder whose clinical characteristics remain incompletely understood, we investigated the role of albumin gene mutation in relation to miscarriage rate in a large pedigree of FDH followed up for 4 years. PATIENTS AND METHODS: The proband and extended family with unexplained miscarriage and hyperthyroxinemia were identified and genotypes in candidate genes and thyroid function tests (TFTs), including changes in TFTs during pregnancy were comprehensively assessed. We also evaluated the development and growth of children in this large FDH pedigree during four years follow-up. RESULT: The R218S variant in the albumin gene was identified in the proband and her relatives with hyperthyroxinemia who were diagnosed as FDH. Among the family members who underwent TFTs, 11 of 17 (65%) had similar changes in levels of thyroid hormone, with an estimated FDH heritability of 86%. Moreover, 32% (95% CI 16-54%) of FDH women experienced miscarriages at a rate that was substantially higher than the spontaneous abortion rate reported in the general population in China (7-14%). During the follow-up, results revealed that free triiodothyronine (fT3) and thyroid stimulating hormone (TSH) levels were normal during the entire gestational period; comparing to their age-adjusted peers, both FDH affected and FDH unaffected children in this pedigree appeared to have lower body weight and height. CONCLUSIONS: Albumin gene variant (R218S) not only causes FDH but also may be associated with a higher risk of miscarriages, although the growth of their children appears not to be affected by the age of 2 years.

First-Line Diagnostic Evaluation with MRI of Children Suspected of Having Acute Appendicitis.

Background Advances in abdominal MRI have enabled rapid, free-breathing imaging without the need for intravenous or oral contrast material. The use of MRI as the primary imaging modality for suspected appendicitis has not been previously studied. Purpose To determine the diagnostic performance of MRI as the initial imaging modality in children suspected of having acute appendicitis. Materials and Methods The study included consecutive patients 18 years of age and younger presenting with acute abdominal pain at a tertiary care institution from January 2013 through June 2016 who subsequently underwent an unenhanced MRI examination as the primary diagnostic imaging modality. Electronic medical records and radiology reports were retrospectively evaluated for the feasibility and diagnostic performance of MRI, with surgical pathology and follow-up electronic records as reference standards. Statistical analyses were performed by using simple binomial proportions to quantify sensitivity, specificity, and accuracy, and exact 95% confidence intervals (CIs) were obtained. Results After exclusions, 402 patients (median age: 13 years; interquartile range [IQR], 9-15 years; 235 female patients; 167 male patients) were included. Sedation for MRI was required in 13 of 402 patients (3.2%; 95% CI: 1.7%, 5.5%). The appendix was visualized in 349 of 402 patients (86.8%; 95% CI: 83.1%, 90%); for the remaining patients, a diagnosis was provided on the basis of secondary signs of appendicitis. The sensitivity, specificity, and accuracy of MRI as the primary diagnostic imaging modality for the evaluation of acute appendicitis were 97.9% (95 of 97; 95% CI: 92.8%, 99.8%), 99% (302 of 305; 95% CI: 97.2%, 99.8%), and 98.8% (397 of 402; 97.1%, 99.6%), respectively. Among patients with negative findings for appendicitis at MRI, an alternate diagnosis was provided in 113 of 304 patients (37.2%; 95% CI: 31.7%, 42.9%). Conclusion When performed as the initial imaging modality in children suspected of having acute appendicitis, MRI examinations had high diagnostic performance for the diagnosis of acute appendicitis and in providing alternative diagnoses. © RSNA, 2019 See also the editorial by Dillman and Trout in this issue.

Pediatric Diabetic Ketoacidosis With Hyperosmolarity: Clinical Characteristics and Outcomes.

OBJECTIVE: Studies of hyperglycemic emergencies with hyperosmolality, including hyperglycemic hyperosmolar state (HHS) and "mixed presentation" with features of diabetic ketoacidosis (DKA) and HHS, are lacking in children. Objectives were to determine the incidence of DKA, HHS, and mixed presentation in a pediatric population, to characterize complications, and to assess accuracy of associated diagnosis codes. METHODS: Retrospective cohort study of 411 hyperglycemic emergencies in pediatric patients hospitalized between 2009 and 2014. Hyperglycemic emergency type was determined by biochemical criteria and compared to the associated diagnosis code. RESULTS: Hyperglycemic emergencies included: 333 DKA, 54 mixed presentation, and 3 HHS. Altered mental status occurred more frequently in hyperosmolar events ( P<.0001), and patients with hyperosmolarity had 3.7-fold greater odds of developing complications compared to those with DKA ( P = .0187). Of those with DKA, 98.5% were coded correctly. The majority (81.5%) of mixed DKA-HHS events were coded incorrectly. Events coded incorrectly had 3.1-fold greater odds of a complication ( P = .02). CONCLUSION: A mixed DKA-HHS presentation occurred in 13.8% of characterized hyperglycemic emergencies, whereas HHS remained a rare diagnosis (0.8%) in pediatrics. Hyperosmolar events had higher rates of complications. As treatment of hyperosmolarity differs from DKA, its recognition is essential for appropriate management. ABBREVIATIONS: AMS = altered mental status; DKA = diabetic ketoacidosis; EMR = electronic medical record; HHS = hyperglycemic hyperosmolar state; ICD-9 = International Classification of Diseases, Ninth Revision; ISPAD = International Society of Pediatric and Adolescent Diabetes; NODM = new-onset diabetes mellitus; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.

Yoga as a Complementary Therapy for Adults with Type 2 Diabetes: Design and Rationale of the Healthy, Active, and in Control (HA1C) Study.

Diabetes is the seventh leading cause of death in the United States. For most patients, medication alone is not sufficient to achieve glycemic control; attention must also be paid to multiple healthy behaviors including diet, regular physical activity, and stress management. Yoga, a mindfulness practice with emphasis on relaxation, meditation, and deep breathing, may have special relevance to people with type 2 diabetes mellitus (T2DM). Yoga practice may positively affect stress and other self-care tasks that will contribute to improved glycemic control. The Healthy, Active, and in Control (HA1C) study is designed to examine the feasibility and acceptability of yoga among adult patients with T2DM. In this pilot randomized controlled trial, adults with T2DM were randomly assigned to either a 12-week Iyengar Yoga intervention given twice weekly, or a twice-weekly 12-week program of traditional exercise (e.g., walking, stationary cycling). Assessments are conducted at the end of treatment (12 weeks) and at 3 and 6 months postintervention. The HA1C study will assess feasibility and acceptability (e.g., attendance/retention rates, satisfaction with program), glycemic outcomes (e.g., HbA1c, fasting blood glucose, postprandial blood glucose), and changes in physiological (e.g., salivary cortisol) and behavioral factors (e.g., physical activity, diet) relevant to the management of T2DM. Focus groups are conducted at the end of the intervention to explore participants' experience with the program and their perception of the potential utility of yoga for diabetes management.

Pediatric Diabetes Outpatient Center at Rhode Island Hospital: The impact of changing initial diabetes education from inpatient to outpatient.

BACKGROUND: This study compared outcomes and costs for new-onset Type 1 diabetes mellitus (T1DM) patients educated at the outpatient versus inpatient settings. METHODS/DESIGN: Retrospective study examining the following variables: 1) hemoglobin A1c (HbA1c), 2) severe hypoglycemia, 3) admissions for diabetic ketoacidosis (DKA) or ER visits, and 4) healthcare cost. RESULTS: 152 patients with new-onset T1DM from September 2007-August 2009. There were no differences between outpatient group (OG) and inpatient group (IG) in mean HbA1c levels at 1, 2 and 3 years post-diagnosis (OG 8%, 8.5%, 9.3%; IG 8.3%, 8.9%, 9%, p=0.51). Episodes of severe hypoglycemia, DKA, and ER visits were not different between the two groups. Mean total hospital costs for OG and pure OG were significantly less than IG (OG: $2886 vs. IG: $4925, p<0.001), (pure OG: $1044 vs. IG: $4925, p<0.0001). CONCLUSION: Our study demonstrates that outpatient- based pediatric diabetes education lowers healthcare cost without compromising medical outcomes. [Full article available at http://rimed.org/rimedicaljournal-2017-02.asp].

Spinal Bone Texture Assessed by Trabecular Bone Score in Adolescent Girls With Anorexia Nervosa.

CONTEXT: Trabecular bone score (TBS) is a bone assessment tool that offers information beyond that afforded by dual-energy x-ray absorptiometry (DXA) bone mineral density (BMD) measurements. Adolescents with anorexia nervosa (AN) are known to exhibit compromised bone density and skeletal strength. OBJECTIVES: This study aimed to determine TBS among adolescents with AN and evaluate the correlation with anthropometric, clinical and densitometric variables. DESIGN: Areal BMD spinal measures were analyzed for TBS. Findings were compared with clinical (height, weight, body mass index [BMI], age, pubertal development, 25-hydroxyvitamin D) and self-reported data (illness duration, amenorrhea, exercise, fracture, family history of osteoporosis, and antidepressant use), and BMD measures by DXA and peripheral quantitative computed tomography (pQCT). SETTING AND PARTICIPANTS: This was an urban adolescent program consisting of 57 females with AN, age 11-18 y. INTERVENTIONS: Interventions included DXA (absolute BMD and Z-score), pQCT (volumetric BMD [vBMD] and stress-strain index [SSI]), laboratory evaluation, and questionnaire administration. MAIN OUTCOME MEASURES: Main outcome measures included TBS, areal and vBMD, SSI, fracture history, disease duration. RESULTS: The TBS of six participants (11%) showed degraded and 19 (33%) partially degraded microarchitecture. Spinal TBS was correlated (P < .05) with age, height, weight, BMI, pubertal stage, BMD, and body composition by DXA, and BMD and SSI by pQCT. TBS was not correlated with disease duration, fracture, vitamin D status, race, or ethnicity, and self-reported health data. CONCLUSIONS: TBS showed evidence of degraded microarchitecture in over 40% of this study sample, and strongly correlated with anthropometric data and measures of BMD and skeletal strength. TBS is a novel tool that captures another dimension of bone health in adolescents with AN.

The evolving use of radioiodine therapy in differentiated thyroid cancer.

The incidence of differentiated thyroid cancer has increased worldwide over the last three decades, but thyroid cancer-related mortality remains stable. Until recently, the standard treatment for most thyroid cancers has been near-total thyroidectomy followed by radioiodine remnant ablation. Observational data support lower recurrence rates and improved survival after radioiodine ablation in patients with high-risk cancers; however, a similar benefit has not been established for all patients with thyroid cancer. Risk stratification should be used to identify patients who are likely to benefit from radioiodine ablation and guide therapeutic decisions. For most patients who need radioiodine remnant ablation, preparation for therapy with recombinant human thyroid-stimulating hormone stimulation is as effective as thyroid hormone withdrawal. Lower therapeutic doses of radioiodine are recommended for the majority of thyroid remnant ablations. Higher doses are reserved for advanced disease at initial diagnosis, local recurrences that cannot be treated with surgery alone, and distant metastatic disease.

Glycemic control in familial vs. sporadic type 1 diabetes patients over 5 years.

BACKGROUND: Studies have shown that familial type 1 diabetes patients (FTID) have less severe metabolic derangement at presentation compared to sporadic patients (ST1D), but data on long-term metabolic control are lacking. OBJECTIVE/HYPOTHESIS: (1) FT1D will have less severe presentation and better HbA1c over 5 years compared to ST1D; (2) HbA1c in the offspring will correlate with parent HbA1c in parent-offspring group; and (3) HbA1c of the second affected sibling (SP2) will correlate with the first affected sibling (SP1) in sib-pairs. METHODS: Cohort of 33 parent-offspring and 19 sib-pairs; controls included 33 sporadic subjects matched by age, sex, ethnicity, puberty, and insulin regimen. Paired t-test and Pearson's correlation were used for statistical analysis. RESULTS: At diagnosis, mean age in FT1D vs. matched ST1D (7.7±4.9 vs. 7.6±4.5 years), mean HbA1c (9.6% vs. 10.7%), HCO3 (21 vs. 18 meq/L), glucose (428 vs. 463 mg/dL) and pH (7.35 vs. 7.36; p=ns) were not different. At 5 years, HbA1c (8.9% vs. 8.8%; p=0.81), clinic visits (12 vs. 12.5, p=0.68) and emergency room visits (0.48 vs. 0.24, p=0.10) were not different. In affected siblings, only HCO3 was different (SP1:18 vs. SP2: 24 meq/L; p<0.01). HbA1c for SP2 correlated positively with SP1 (r=0.67, p<0.01). Offspring HbA1c correlated positively with affected parents (9.3% vs. 8.6%, r=0.57, p=0.18) but was not significant. CONCLUSION: Metabolic control at diagnosis and at 5 years was similar in FT1D and ST1D. In sib-pairs, the second affected sibling had milder clinical presentation compared to the first affected sibling.

Therapeutic options for the prevention of type 2 diabetes mellitus in the metabolic syndrome.

The increasing prevalence of metabolic syndrome has created an impetus to prevent complications such as diabetes. There are no defined treatments for metabolic syndrome apart from addressing each of its components such as obesity, hypertension, dyslipidemia, and hyperglycemia. To evaluate diabetes-prevention strategies, we performed a Medline search and identified evidence suggesting that lifestyle intervention and certain medications can prevent diabetes. In addition, there are several agents on the horizon that seem promising. The mechanism responsible for diabetes prevention relates to improved insulin resistance as a result of weight loss or other processes. Lifestyle interventions and medications such as metformin are effective and safe in long-term prevention studies. However, the safety and efficacy of newer agents need clarification.

Regulatory T cells in Graves' disease.

CONTEXT: Graves' disease (GD) involves auto-immunity against thyroid cell antigens, but the reasons for induction of auto-immunity are uncertain. We wished to determine whether there was a deficiency of regulatory T cells in patients with active GD. DESIGN: Venous blood samples were obtained from patients with GD before and after treatment, and controls, and peripheral blood mononuclear cells were prepared. PATIENTS AND MEASUREMENTS: Regulatory T cells were enumerated by Fluorescent Activated Cell sorting (FACS) in nineteen patients with untreated GD, 9 patients 6-8 weeks post RAI therapy, and 30 control subjects. Twenty-one patients with active GD prior to control of hyperthyroidism, 23 euthyroid controls without known autoimmune thyroid disease, and 10 patients who were euthyroid 6-12 months after RAI treatment were studied for expression of genes found in regulatory T cells by real-time Polymerase Chain reaction (PCR). RESULTS: Percent distribution of CD4+, CD4+CD25+ and CD4+ CD25+(int-hi) CD127+(lo) regulatory T cells was similar in active GD patients and control subjects. The number of CD25+ and CD4+ CD25+(int-hi) CD127+(lo) cells was similar in GD patients and control subjects, but was lower in recently treated patients. Messenger RNA was prepared from PBMC, and reverse transcribed. Copy DNA abundance was evaluated by Real Time PCR using appropriate primers, for GAPDH (glyceraldehyde phosphate dehydrogenase) as a control housekeeping gene, and 5 genes related to function of regulatory T cells. Message RNA for Gadd45 alpha, Gadd45beta (growth arrest and damage inducible proteins), GITR (glucocorticoid inducible TNF receptor) and CD25 (IL-2R subunit) was more abundant in patients with active GD than in normal controls, and FoxP3 mRNA level was equal to that in controls. Message RNA levels in patients treated and euthyroid for 6 months were also greater than or equal to values in controls. CONCLUSION: This study provides evidence that there is no deficit in T regulatory cells during active GD, or during the months post therapy.

Mosquito larvicidal activity of oleic and linoleic acids isolated from Citrullus colocynthis (Linn.) Schrad.

In mosquito control programs, botanical origin may have the potential to be used successfully as larvicides. The larvicidal activity of crude acetone, hexane, ethyl acetate, methanol, and petroleum ether extracts of the leaf of Centella asiatica Linn., Datura metal Linn., Mukia scabrella Arn., Toddalia asiatica (Linn.) Lam, extracts of whole plant of Citrullus colocynthis (Linn.) Schrad, and Sphaeranthus indicus Linn. were assayed for their toxicity against the early fourth instar larvae of Culex quinquefasciatus (Diptera: Culicidae). The larval mortality was observed after 24 h exposure. All extracts showed moderate larvicidal effects; however, the highest larval mortality was found in whole plant petroleum ether extract of C. colocynthis. In the present study, bioassay-guided fractionation of petroleum ether extract led to the separation and identification of fatty acids; oleic acid and linoleic acid were isolated and identified as mosquito larvicidal compounds. Oleic and Linoleic acids were quite potent against fourth instar larvae of Aedes aegypti L. (LC50 8.80, 18.20 and LC90 35.39, 96.33 ppm), Anopheles stephensi Liston (LC50 9.79, 11.49 and LC90 37.42, 47.35 ppm), and Culex quinquefasciatus Say (LC50 7.66, 27.24 and LC90 30.71, 70.38 ppm). The structure was elucidated from infrared, ultraviolet, 1H-nuclear magnetic resonance, 13C-NMR, and mass spectral data. This is the first report on the mosquito larvicidal activity of the reported isolated compounds from C. colocynthis.

Mosquito larvicidal activity of isolated compounds from the rhizome of Zingiber officinale.

The larvicidal activity of a petroleum ether extract of Zingiber officinale Roscoe (Zingiberaceae) was evaluated against Aedes aegypti L. and Culex quinquefasciatus Say (Diptera). Bioassay-guided fractionation led to the isolation of 4-gingerol (1), (6)-dehydrogingerdione (2) and (6)-dihydrogingerdione (3); the latter has not previously been reported from Z. officinale. The structures were established from infrared (IR), ultraviolet (UV), (1)H-nuclear magnetic resonance (NMR), (13)C-NMR and mass spectral data. Following a 24 h exposure, compounds 1-3 exhibited larvicidal activities against fourth instar larvae of A. aegypti (LC(50) 4.25, 9.80, 18.20 ppm) and C. quinquefasciatus (LC50 5.52, 7.66, 27.24 ppm), respectively. The results show that the most effective compound was 4-gingerol.

HIV and obstetric complications and fetal outcomes in Vellore, India.

Antenatal prevalence is more than 1% in parts of India, yet little is known about the complications and fetal outcomes in this region. We reviewed the records of 23,386 women who delivered at the Christian Medical College Hospital in Vellore, India from 2000 through 2002. HIV-infected women were more likely than HIV-uninfected women to have pregnancy-induced hypertension, anaemia, breech presentations, stillborn babies and fetal deaths. HIV-infected women who did not receive mother-to-child transmission prophylaxis or had breech fetal presentation were more likely to have fetal deaths (P = 0.001). HIV prophylaxis and optimal prenatal care should be a priority for HIV-infected pregnant women in resource-limited countries.