Rate of Inpatient Hypoglycemia Following a 1:1 Dose Interchange Between Concentrated Insulin Glargine to Insulin Detemir.

BACKGROUND: Insulin remains a mainstay of treating hyperglycemia in an acute setting. Insulin glargine 300 units/mL (Toujeo, iGlar300) has a different pharmacokinetic profile than 100 units/mL basal insulins, such as insulin detemir (iDet100) and iGlar100. While conversion from iGlar300 to iGlar100 requires a 20% dose decrease, there is currently no recommended interchange from iGlar300 to iDet100. OBJECTIVE: Compare the incidence of hypoglycemia in patients who received a 1:1 unit interchange from home iGlar300 or iGlar100 to iDet100 while admitted. METHODS: A retrospective study was conducted to evaluate adults within a multi-site network admitted between May and December 2019. Patients were included if they received at least one dose of iDet100 following interchange from home iGlar300 or iGlar100. The primary endpoint was the incidence of hypoglycemic events following a 1:1 interchange of iGlar300 vs. iGlar100 to inpatient iDet100. Secondary outcomes include overall hypoglycemic events, time to hypoglycemia, and doses given before hypoglycemia. RESULTS: Of 615 patients, 394 received a 1:1 unit interchange to iDet100 (52 from iGlar300 and 342 from iGlar100). Incidence of hypoglycemic events was significantly higher in those with a 1:1 interchange from iGlar300 versus iGlar100 (36.5% vs. 18.7%, p = 0.007). Significant differences were observed in overall hypoglycemic events, time to hypoglycemia, and number of doses given before hypoglycemic event. CONCLUSION AND RELEVANCE: A 1:1 unit interchange from iGlar300 to iDet100 led to a higher incidence of hypoglycemic events compared to those interchanged from iGlar100. Dose reduction should be considered when transitioning from home iGlar300 to iDet100 in the inpatient setting.

Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition.

Child undernutrition is a global health issue associated with a high burden of infectious disease. Undernourished children display an overabundance of intestinal pathogens and pathobionts, and these bacteria induce enteric dysfunction in undernourished mice; however, the cause of their overgrowth remains poorly defined. Here, we show that disease-inducing human isolates of Enterobacteriaceae and Bacteroidales spp. are capable of multi-species symbiotic cross-feeding, resulting in synergistic growth of a mixed community in vitro. Growth synergy occurs uniquely under malnourished conditions limited in protein and iron: in this context, Bacteroidales spp. liberate diet- and mucin-derived sugars and Enterobacteriaceae spp. enhance the bioavailability of iron. Analysis of human microbiota datasets reveals that Bacteroidaceae and Enterobacteriaceae are strongly correlated in undernourished children, but not in adequately nourished children, consistent with a diet-dependent growth synergy in the human gut. Together these data suggest that dietary cross-feeding fuels the overgrowth of pathobionts in undernutrition.

Thermodynamics of the Lévy spin glass.

We investigate the Lévy glass, a mean-field spin-glass model with power-law distributed couplings characterized by a divergent second moment. By combining extensively many small couplings with a spare random backbone of strong bonds the model is intermediate between the Sherrington-Kirkpatrick and the Viana-Bray models. A truncated version where couplings smaller than some threshold ε are neglected can be studied within the cavity method developed for spin glasses on locally treelike random graphs. By performing the limit ε→0 in a well-defined way we calculate the thermodynamic functions within replica symmetry and determine the de Almeida-Thouless line in the presence of an external magnetic field. Contrary to previous findings we show that there is no replica-symmetric spin-glass phase. Moreover we determine the leading corrections to the ground-state energy within one-step replica symmetry breaking. The effects due to the breaking of replica symmetry appear to be small in accordance with the intuitive picture that a few strong bonds per spin reduce the degree of frustration in the system.

Fibromuscular dysplasia of the renal artery responsible for renovascular hypertension: a histological presentation based on a series of 102 patients.

BACKGROUND: Fibromuscular dysplasia (FMD) is a rare non-atherosclerotic and non-inflammatory disease in the arterial system. The purpose of the study was a retrospective analysis of FMD in the renal artery. PATIENTS AND METHODS: A total number of 102 patients (mean age: 36.9 years) who suffered from renovascular hypertension underwent a surgical therapy. The operative specimens of the renal arteries were analysed with the lightmicroscop using histological and immunohistochemical methods. RESULTS: 101 patients (99.02%) presented a medial FMD (extensive-medial subtype in 56 patients, 54.9%, subadventitial subtype in 29 patients, 28.4% and combined subtype in 16 patients, 15.7%). In 1 patient (0.98%) an adventitial FMD was found. We observed the following complications: true and dissecting aneurysms (75 patients, 74.5%), arterio-venous fistulae (2 patients, 1.96%) and chronic thrombosis (10 patients, 9.8%). CONCLUSIONS: With the progress in angioplasty, not all patients suffering from FMD undergo a primary surgical therapy and therefore this lesion is less seen in the daily work of the histopathologist.

[Radiologic-histopathologic correlation of microcalcifications from 11g vacuum biopsy: analysis of 3196 core biopsies]. / Radiologisch-histopathologische Korrelation von Mikrokalzifikationen in 11-G-Vakuumbiopsaten - eine Analyse von insgesamt 3196 Proben.

PURPOSE: To perform a statistical evaluation of microcalcifications (MC) from suspicious breast lesions detected by radiography and histopathology. MATERIALS AND METHODS: Histological and radiological detection of calcifications were compared from 116 biopsies in 96 women. Lesions with identical description of calcifications detected in histopathology and radiography were considered concordant, patients with obvious discrepancies discordant. If histological and radiological groups of calcifications were identical in number but differed in location, the case was considered pseudo-concordant. RESULTS: Histopathology classified 24 of 116 lesions as malignant and 92 as benign. A total of 3196 core biopsies were examined, 851 of these contained groups of calcifications or single calcifications. Both modalities detected 579 calcifications, with 169 exclusively detected by radiography and 103 exclusively by histopathology. In 35 cases (30 %) radiologic and pathologic results were concordant, in 6 cases pseudo-concordant (4 %) and in 75 cases (65 %) discordant. The case-based Kappa coefficient was - 0.09 (- 0.24 to 0.07). The 122 calcifications not detected by histopathology were few or single calcifications at the edge of the core that were probably lost during processing, 18 were possible artefacts. Six cores contained calcium oxalate, 3 contained milk of calcium. In 6 cases malignant disease was found after the first examination, hence the cores were not searched thoroughly for the missing calcifications. In the remaining 14 cases, no calcifications were found despite complete processing of the tissue. In 49 of 103 cases of radiologically undetected microcalcifications, the retrospect analysis showed dense tissue areas that probably contained the calcification. The remaining 54 cases contained calcifications, which were too small to be detected radiologically. SUMMARY: Discordant results from pathological and radiological examinations of biopsies can mainly be explained by calcifications at the edge of the specimen lost during processing, which are therefore not detected in histopathology, and calcifications too small to be visualized radiologically.

Sebaceous glands in the uterine cervix: two new cases.

The authors report on two new cases of sebaceous glands in the uterine cervix. This extremely rare histological observation was found on biopsy specimens of the uterine cervix because of unclear colposcopic findings and of recurrent CIN II. The etiology of this entity is discussed including a brief review of the medical literature.

Variable extension of the transitional zone in the medial structure of carotid artery tripod.

BACKGROUND: The goal of our study was to demonstrate the extension of the transitional zone (TZ) between elastic and muscular medial structure in carotid artery tripod. PATIENTS AND METHODS: A histologic study of 56 probes from 8 carotid artery tripods was performed. The probes were obtained from autopsies of 4 adults (mean age: 47.5 years, range 38 to 55 years) and were taken from 7 different topographic sites. RESULTS: At each level of the CCA (at 1 cm and 2 cm proximal to the bifurcation as well as at the bifurcation) we observed an elastic arterial type in 24 (42.8%) probes with 11 to 20 (medium 15.0) elastic fibers per view field (200 x magnification) in the media. In contrast the histologic structure of the ICA and ECA varied as follows: in 8 sections (14.3%) elastic arterial type with 11 to 16 (medium 13.1) elastic fibers, in 11 sections (19.6%) muscular arterial type with 2 to 5 (medium 3.5) elastic fibers and in 9 sections (16.1%) a transitional arterial type with 6 to 8 (medium 6.7) elastic fibers in the media. Atherosclerotic lesions have prevented the assessment of the arterial type in 4 probes (7.1%). The TZ in the medial structure of carotid artery tripods is exclusively localized in the ICA/ECA but not in the CCA. The ICA/ECA presented a TZ with a length up to 0.5 cm (4 probes; 25%), up to 1.5 cm (4 probes; 25%) and longer than 1.5 cm (6 probes; 37.5%). CONCLUSIONS: In this study we confirmed that in the carotid artery tripod, a TZ--an arterial segment with transition from elastic to muscular type--does exist, involving a variable length. Furthermore studies on the impact of the biomechanical properties of the TZ as a potential factor in atherosclerotic disease are justified. In addition, the complex biomechanical behavior of the TZ should be considered prior to interventional procedures.

Cardiac ion channel expression and contractile function in mice with deletion of thyroid hormone receptor alpha or beta.

Cardiac myocytes express the two thyroid hormone receptors (T(3)Rs), T(3)Ralpha and T(3)Rbeta. However, which isoform contributes to specific, T(3)-induced alterations of cardiac function remains unclear. Here, we used individual T(3)R isoform knockout (KO) mice to study the effects of T(3)Ralpha and T(3)Rbeta in the heart. Our findings indicate that potassium channel genes that code for K(+) channels involved in action potential repolarization, like KV 4.2 and minK, are T(3)Ralpha targets. Both are markedly regulated by thyroid status. The recently identified cyclic nucleotide-gated channels, HCN2 and HCN4, are targets of T(3)Ralpha and are unchanged in a euthyroid T(3)Rbeta KO. However, these transcripts respond markedly to altered T(3) signaling concomitant with bradycardia in T(3)Ralpha KO and hypothyroid animals, as well as tachycardia in hyperthyroid T(3)Rss KO mice. SERCA2a and myosins are T(3) regulated and were also targets of T(3)Ralpha, and the papillary muscles of alphaKO animals showed a slowed rate of force development. Because of the absence of significant cardiac effects in euthyroid T(3)Rss KO mice, we determined messenger RNA levels for both T(3)Ralpha and T(3)Rss in the heart. We found that T(3)Rss is present at a 1:3 ratio to T(3)Ralpha1. We conclude that the cardiac phenotype regulated by T(3) is predominantly mediated by T(3)Ralpha and that the lack of T(3)Ralpha cannot be compensated by T(3)Rss in the heart.

The transitional zone in the tunica media of renal arteries has a maximal length of 10 millimetres.

BACKGROUND: The goal of our study was to demonstrate and to determine the length of the transitional zone in the tunica media in renal arteries. The majority of renal artery atherosclerotic stenotic lesions occurs in this segment. PATIENTS AND METHODS: Anatomical and histological studies were performed on 26 renal arteries from 13 adults at autopsy (mean age 61.6 years, range 33 to 87 years). RESULTS: In the macroscopical examination the right renal arteries (RRA) were longer with a median 53.8 mm (range 38 to 65 mm) than the left renal arteries (LRA) with a median 47.6 mm (range 35 to 63 mm), the circumferences were nearly the same: RRA 10.9 mm (range 5 mm to 15 mm) and LRA 11 mm (range 5 mm to 15 mm). Probes for histological examinations were taken from three different regions of each renal artery (origin, 5 mm and 10 mm distal to the origin). We observed a typical elastic arterial structure at the origin and muscular types at the distal 10 mm region. At the distal 5 mm region variable ratios of elastic tissue (ET) and smooth muscle cells (SMC) were found as follows: 15 arteries presented an equal ratio of EM:SMC, 7 arteries presented ET > SMC and 4 arteries presented ET < SMC ratios. CONCLUSIONS: In this study we confirmed that in renal arteries, a transitional zone (TZ) that is an arterial segment with transition from elastic to muscular type, does exist, involving the maximal length of 10 mm. Further studies on the impact of the biomechanical properties of the transitional zone as a potential localizing factor in renal atherosclerotic disease are justified. In addition, the complex biomechanical behavior of the TZ of the arterial wall should be taken into consideration when interventional procedures are planned.

Characterization of excitatory prostanoid receptors in the human umbilical artery in vitro.

1. 5-HT and the prostanoid TP receptor agonists, U46619 and I-BOP, constricted the human umbilical artery with pEC50 values of 7.3+/-0. 2, 6.7+/-0.1, and 7.3+/-0.2, respectively. The selective TP receptor antagonist, GR32191 (0.1 microM), shifted the concentration-effect curves to U46619 and I-BOP to the right, but had no effect on the response to 5-HT. 2. The natural prostaglandins, PGF2alpha and PGE2, caused concentration-dependent contraction with pEC50 values of 5.2+/-0.2 and 4.9+/-0.2, respectively. PGD2 was a partial agonist with a pEC50 of 5.24+/-0.03. GR32191 (0.1 microM) inhibited the responses to all of these compounds suggesting that they produce contraction by acting at TP receptors. 3. Sulprostone failed to elicit contraction in the human umbilical artery at concentrations up to 4.4 microM suggesting the absence of EP1 and EP3 receptors. Despite this, 17-phenyltrinor PGE2 and GR63799 both induced contraction at concentrations above 1 microM, but the effects were sensitive to GR32191 (0.1 microM). 4. Fluprostenol had no effect on the human umbilical artery at concentrations up to 17 microM suggesting the absence of FP receptors. Cloprostenol was ineffective in two tissues, but caused contraction in one tissue at the highest concentration tested (1.7 microM). However, this response was abolished in the presence of GR32191 (0.1 microM). 5. The effects of four TP receptor antagonists were assessed by global non-linear regression analysis. GR32191, SQ29548, SQ30741, and ICI192605 competitively inhibited responses to U46619 with pKb values of 8.0+/-0.1, 7.6+/-0.1, 7.0+/-0. 2 and 8.1+/-0.1, respectively. 6 These results suggest that the human umbilical artery functionally expresses TP receptors, but not EP1, EP2 or FP receptors.

Takayasu's arteritis and fibromuscular dysplasia as causes of acquired atypical coarctation of the aorta: retrospective analysis of seven cases.

Coarctation of the aorta usually occurs in the aortic isthmus: however, 2% of all coarctation is localized at atypical sites such as the aortic arch and the thoracic and/or abdominal aorta. Causal therapy involves vascular surgery, and during the procedure, biopsies of the involved vessels should be taken to establish the etiology. This study involved the retrospective analysis of clinical and histopathological findings for seven patients who underwent vascular surgical procedures (age range, 10-37 years; male/female ratio 3:4). Histopathological analysis of specimens revealed two pathological processes taking place with different localization in the aortic wall as the cause of the atypical coarctation of the aorta: (1) fibrosis/scarification in the tunica media and adventitia compatible with chronic lesions of Takayasu's arteritis (four cases); (2) fibromuscular dysplasia in the tunica media (three cases).

Carcinoma of the breast and pacemaker generators.

A 90-year-old woman developed intraductal adenocarcinoma (TNM classification pT2, G2) of the left breast 18 years after initial pacemaker implantation deep to the left breast. There was no evidence of local or distant metastasis and she was treated with local excision and tamoxifen.

Comparison analysis of illicit cocaine samples.

A rapid method for comparison analysis of illicit cocaine samples has been developed. The raw data are obtained by capillary gas chromatography using a nitrogen-phosphorus detector. The area ratios of four alkaloids (tropacocaine, norcocaine, cis-cinnamoylcocaine, and trans-cinnamoylcocaine) to cocaine are calculated for each sample. These ratios are compiled in a computer database which allows easy comparison of samples and makes possible reliable conclusions regarding their commonality of origin.