A case report of T-box 1 mutation causing phenotypic features of chromosome 22q11.2 deletion syndrome

Abstract Background The heterozygous microdeletion of chromosome 22q11.2 results in a spectrum of disorders, including DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS), with phenotypic features that can include the classic triad of congenital heart disease (CHD), thymic aplasia and hypoparathyroidism. Such microdeletions are usually detectable by fluorescence in situ hybridization (FISH). Case presentation We report a case of a twenty-three year-old female who presented with clinical features of chromosome 22q11.2 deletion syndrome including cardiac anomalies, hypoparathyroidism and dysmorphic facial features. FISH did not reveal a 22q11.2 microdeletion. Further genetic analysis showed T box-1 (TBX1) heterozygous mutation. Conclusions The TBX1 gene plays a significant role in the development of fourth pharyngeal arch structures. Mutations of TBX1, which is found at chromosome 22q11.21 can be responsible for the development of syndromes classically associated with chromosome 22q11.2 deletions. This case emphasizes that the TBX1 gene, among other genes, can be responsible for the developmental anomalies seen in these syndromes.https://deepblue.lib.umich.edu/bitstream/2027.42/152180/1/40842_2019_Article_87.pd

FunnyBase: a systems level functional annotation of Fundulus ESTs for the analysis of gene expression

BACKGROUND: While studies of non-model organisms are critical for many research areas, such as evolution, development, and environmental biology, they present particular challenges for both experimental and computational genomic level research. Resources such as mass-produced microarrays and the computational tools linking these data to functional annotation at the system and pathway level are rarely available for non-model species. This type of "systems-level" analysis is critical to the understanding of patterns of gene expression that underlie biological processes. RESULTS: We describe a bioinformatics pipeline known as FunnyBase that has been used to store, annotate, and analyze 40,363 expressed sequence tags (ESTs) from the heart and liver of the fish, Fundulus heteroclitus. Primary annotations based on sequence similarity are linked to networks of systematic annotation in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and can be queried and computationally utilized in downstream analyses. Steps are taken to ensure that the annotation is self-consistent and that the structure of GO is used to identify higher level functions that may not be annotated directly. An integrated framework for cDNA library production, sequencing, quality control, expression data generation, and systems-level analysis is presented and utilized. In a case study, a set of genes, that had statistically significant regression between gene expression levels and environmental temperature along the Atlantic Coast, shows a statistically significant (P < 0.001) enrichment in genes associated with amine metabolism. CONCLUSION: The methods described have application for functional genomics studies, particularly among non-model organisms. The web interface for FunnyBase can be accessed at . Data and source code are available by request at [email protected]

A new model for diabetes-focused capacity building – lessons from Sri Lanka

Abstract Sri Lanka is experiencing a rapid increase in the number of people with diabetes mellitus (DM) due to population growth and aging. Physician shortages, outdated technology, and insufficient health education have contributed to the difficulties associated with managing the burden of disease. New models of chronic disease management are needed to address the increasing prevalence of DM. Medical students, business students, and faculty members from the University of Michigan partnered with the Grace Girls’ Home, Trincomalee General Hospital, and Selvanayakapuram Central Hospital to identify and train diabetes-focused medical assistants (MAs) to collect and enter patient data and educate patients about their disease. Return visits to these MAs were encouraged so that patient progress and disease progression could be tracked longitudinally. Data entry was conducted through a cloud-based mechanism, facilitating patient management and descriptive characterization of the population. We implemented this pilot program in June 2016 in coordination with Trincomalee General Hospital and Selvanayakapuram Central Hospital. Over a 12-month period, 93 patients were systematically assessed by the medical assistants. All patients received education and were provided materials after the visit to better inform them about the importance of controlling their disease. Fifteen percent (14/93) of patients returned for follow-up consultation. Trained MAs have the potential to provide support to physicians working in congested health systems in low-resource settings. Public investment in training programs for MAs and greater acceptance by physicians and patients will be essential for handling the growing burden associated with chronic illnesses like DM. Trained MAs may also play a role in improved patient education and awareness regarding diabetes self-management.https://deepblue.lib.umich.edu/bitstream/2027.42/146742/1/40842_2018_Article_74.pd

Identification of population characteristics through implementation of the Comprehensive Diabetic Retinopathy Program

Abstract Background Diabetic retinopathy is the most common cause of blindness in working-age adults. Characteristics of patients with diabetes presenting to a retina subspecialty clinic have not been adequately studied, limiting our ability to risk stratify patients with diabetic retinopathy. Our goal is to describe an innovative program that collects structured, longitudinal data on patients with diabetes in a retina clinic, and identifies population characteristics to define patient risk stratification. Methods Demographics, body-mass index, blood pressure, hemoglobin A1c, smoking history, diabetes type, diabetes duration, kidney disease history, and diagnosis codes were collected on all patients with diabetes at the Kellogg Eye Center retina clinic. A mixed effects negative binomial regression was then performed to assess visit frequency as a function of these variables. Visit frequency was used as a marker for cost of care. A subgroup of patients was surveyed about knowledge of diabetes management goals and barriers to better self-management. Results There were 2916 patients in the cohort with 1014 in the subgroup. The cohort was predominantly Caucasian (74.5%), with a mean age of 64 years (range 13–99) and a relatively even distribution of sex (53.2% men). The mean maximum hemoglobin A1c was 8.0% (range 4.3–15.7%), and 57.1% had a diagnosis of diabetic retinopathy. Patients averaged 3.9 visits (range 1–27) during the 18-month study period. Blood pressure and duration of diabetes were positively associated with visit frequency (p < 0.0001, p < 0.0001, respectively). Of the surveyed patients, 87.6% knew their goal hemoglobin A1c, while only 45.9% identified the correct blood pressure goal. The most common reported barrier to better self-management was “it’s just not working” (47.1%). Conclusions Implementation of this program enables the creation of a longitudinal dataset on patients with diabetes. Resulting data can be used to improve quality of care provided to patients at a retina clinic. The findings suggest considerable healthcare resources are being directed to a small patient population. This enhanced understanding of characteristics of patients with diabetes will improve efforts to preserve vision and utilize health system resources efficiently.https://deepblue.lib.umich.edu/bitstream/2027.42/149131/1/40842_2019_Article_79.pd

The relationship between diabetes mellitus and 30-day readmission rates

Abstract Background It is estimated that 9.3% of the population in the United States have diabetes mellitus (DM), 28% of which are undiagnosed. The high prevalence of DM makes it a common comorbid condition in hospitalized patients. In recent years, government agencies and healthcare systems have increasingly focused on 30-day readmission rates to determine the complexity of their patient populations and to improve quality. Thirty-day readmission rates for hospitalized patients with DM are reported to be between 14.4 and 22.7%, much higher than the rate for all hospitalized patients (8.5–13.5%). The objectives of this study were to (1) determine the incidence and causes of 30-day readmission rates for patients with diabetes listed as either the primary reason for the index admission or with diabetes listed as a secondary diagnosis compared to those without DM and (2) evaluate the impact on readmission of two specialized inpatient DM services: the Hyperglycemic Intensive Insulin Program (HIIP) and Endocrine Consults (ENDO). Methods For this study, DM was defined as any ICD-9 discharge diagnosis (principal or secondary) of 250.xx. Readmissions were defined as any unscheduled inpatient admission, emergency department (ED) visit, or observation unit stay. We analyzed two separate sets of patient data. The first pilot study was a retrospective chart review of all patients with a principle or secondary admission diagnosis of diabetes admitted to any adult service within the University of Michigan Health System (UMHS) between October 1, 2013 and December 31, 2013. We then did further uncontrolled analysis of the patients with a principal admitting diagnosis of diabetes. The second larger retrospective study included all adults discharged from UMHS between October 1, 2013 and September 30, 2014 with principal or secondary discharge diagnosis of DM (ICD-9-CM: 250.xx). Results In the pilot study of 7763 admissions, the readmission rate was 26% for patients with DM and 22% for patients without DM. In patients with a primary diagnosis of DM on index admission, the most common cause for readmission was DM-related. In the larger study were 37,702 adult inpatient discharges between October 1, 2013 and September 30, 2014. Of these, 20.9% had DM listed as an encounter diagnosis. Rates for all encounters (inpatient, ED and Observation care) were 24.3% in patients with DM compared to 17.7% in those without DM (p < 0.001). The most common cause for readmission in patients with DM as a secondary diagnosis to the index admission was infection-related. During the index hospital stay, only a small proportion of patients with DM (approximately 12%) received any DM service consult. Those who received a DM consult had a higher case mix index compared to those who did not. Despite the higher acuity, there was a lower rate of ED /observation readmission in patients followed by the DM services (6.6% HIIP or ENDO vs. 9.6% no HIIP or ENDO, p = 0.0012), though no difference in the inpatient readmission rates (17.6% HIIP or ENDO vs. 17.4% no HIIP or ENDO, p = 0.89) was noted. Conclusions Patients with both a primary or secondary diagnosis of DM have higher readmission rates. The reasons for readmission vary; patients with a principal diagnosis of DM have more DM related readmissions and those with secondary diagnosis having more infection-related readmissions. DM services were used in a small proportion of patients and may have contributed to lower DM related ED revisits. Further prospective studies evaluating the role of these services in terms of glucose management, patient education and outpatient follow up on readmission are needed to identify interventions important to reducing readmission rates.https://deepblue.lib.umich.edu/bitstream/2027.42/136189/1/40842_2016_Article_40.pd

Human Impacts on Forest Biodiversity in Protected Walnut-Fruit Forests in Kyrgyzstan

We used a spatially explicit model of forest dynamics, supported by empirical field data and socioeconomic data, to examine the impacts of human disturbances on a protected forest landscape in Kyrgyzstan. Local use of 27 fruit and nut species was recorded and modeled. Results indicated that in the presence of fuelwood cutting with or without grazing, species of high socioeconomic impor- tance such as Juglans regia, Malus spp., and Armeniaca vulgaris were largely eliminated from the landscape after 50–150 yr. In the absence of disturbance or in the presence of grazing only, decline of these species occurred at a much lower rate, owing to competi- tive interactions between tree species. This suggests that the current intensity of fuelwood harvesting is not sustainable. Conversely, cur- rent grazing intensities were found to have relatively little impact on forest structure and composition, and could potentially play a positive role in supporting regeneration of tree species. These results indicate that both positive and negative impacts on biodiversity can arise from human populations living within a protected area. Potentially, these could be reconciled through the development of participatory approaches to conservation management within this reserve, to ensure the maintenance of its high conservation value while meeting human needs

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Application of One-Step IADPSG Versus Two-Step Diagnostic Criteria for Gestational Diabetes in the Real World: Impact on Health Services, Clinical Care, and Outcomes

Purpose of Review This paper seeks to summarize the impact of the one-step International Association of Diabetes and Pregnancy Study Groups (IADPSG) versus the two-step gestational diabetes mellitus (GDM) criteria with regard to prevalence, outcomes, healthcare delivery, and long-term maternal metabolic risk. Recent Findings Studies demonstrate a 1.03–3.78-fold rise in the prevalence of GDM with IADPSG criteria versus baseline criteria. Women with GDM by IADPSG criteria have more adverse pregnancy outcomes than women with normal glucose tolerance (NGT). Treatment of GDM by IADPSG criteria may be cost effective. Use of the fasting glucose as a screen before the 75-g oral glucose tolerance test to rule out GDM with fasting plasma glucose (FPG) < 4.4 (80 mg/dl) and rule in GDM with FPG ≥ 5.1 mmol/l (92 mg/dl) reduces the need for OGTT by 50% and its cost and inconvenience. The prevalence of postpartum abnormal glucose metabolism is higher for women with GDM diagnosed by IADPSG criteria versus that for women with NGT. Summary Data support the use of IADPSG criteria, if the cost of diagnosis and treatment can be controlled and if lifestyle can be optimized to reduce the risk of future diabetes

Subcutaneous glucagon infusion and continuous glucose monitoring enable effective management of hypoglycemia in a patient with IGF-2-producing hemangiopericytoma

Abstract Background Ectopic insulin-like growth factor (IGF)-2 production is a rare complication of an array of epithelial and mesenchymal tumors, and can clinically manifest as life-threatening hypoglycemia. Case presentation A 49-year-old woman with 13-year history of metastatic hemangiopericytoma, previously treated with multiple rounds of chemotherapy and palliative radiation, presented to the emergency department after a hypoglycemic seizure. On arrival, glucose was 18 mg/dL (1.0 mmol/L) and required continuous dextrose infusion for maintenance within normal limits. Insulin was <2.0 μU/mL, C-peptide 0.1 ng/mL, and beta-hydroxybutyrate <0.2 mmol/L. Random cortisol was 21 μg/dL; sulfonylurea screen, and insulin antibodies were negative. IGF-2 level was 1320 ng/mL; IGF-1 was within normal limits and IGF binding protein (BP)-3 suppressed. Dexamethasone, started at 6 mg twice daily, allowed discontinuation of the glucose infusion. Given concern for nocturnal hypoglycemia, and patient interest in steroid-sparing anti-hypoglycemic regimen, she was also started on overnight continuous subcutaneous glucagon infusion via insulin pump. She was discharged with instructions to maintain a diet high in complex carbohydrates during the day, while utilizing glucagon pump at night. She was also started on continuous glucose monitoring system (CGMS) with an alarm to warn of hypoglycemia. Glucagon infusion rate was later titrated based on CGMS readings. Abdominal CT revealed increasing size of a right upper quadrant mass not previously subjected to radiotherapy. After radiation to this area, hypoglycemia improved, allowing further glucagon titration. In parallel, IGF-2 level declined to 380 ng/mL. Conclusions Ectopic IGF-2 production is a rare but often fatal complication of many cancers, and should be considered on the differential diagnosis in patients with malignancy and unexplained hypoglycemia. Once hypoglycemia is diagnosed, patients often have end-stage disease. While treatment of the causative tumor is the only definitive intervention, anti-hypoglycemia therapy is a life-saving, temporizing measure. In this case, the patient attained euglycemia and survived 3 months after presentation before ultimately succumbing to other malignancy-related complications. Given efficacy in management of hypoglycemia while awaiting definitive tumor-directed therapy, we submit nighttime subcutaneous glucagon infusion and CGMS are valuable additions to the physician’s armamentarium in managing this condition

Acute pseudogout of the foot following Parathyroidectomy: a case report

Abstract Background The current case report is the first in the literature to report the association between parathyroidectomy and an episode of probable pseudogout in the foot in a patient with diabetes mellitus. Case presentation The authors present a case of pseudogout of the left foot following a subtotal parathyroidectomy in an 80-year-old female with type 2 diabetes mellitus and primary hyperparathyroidism. Pseudogout, also known as calcium pyrophosphate dehydrate deposition disease, is an unusual metabolic sequela following parathyroidectomy. Pseudogout attacks have been noted in the immediate post-operative period following parathyroidectomy, but has rarely been identified in the foot. The diagnosis was challenging and there were multiple differential diagnoses that were entertained in this case. Conclusions This case illustrates the importance of reviewing the surgical history as there might be a link between the previous surgeries and current foot problems. This case also serves as a reminder of the importance of calcium and phosphate metabolism in podiatric health. Most specifically it demonstrates again the association of pseudogout and parathyroidectomy in a patient with diabetes mellitus. Although a rare occurrence, it is an important reminder that metabolic imbalances of calcium levels can manifest in any bone