Outcomes of patients hospitalized for acute pulmonary embolism by obstructive sleep apnea status.

Pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) is increasingly recognized in the aging population, especially with the rising obesity epidemic. The impact of OSA on inpatient mortality in PE is not well understood. We used the Nationwide Inpatient Sample databases from 2005 to 2016 to identify 755,532 acute PE patients (age≥18 years). Among these, 61,050 (8.1%) were OSA+. Temporal trends in length of stay, inpatient mortality, and its association with OSA in PE patients were analyzed. The proportion of PE patients who were OSA+ increased from 2005 to 2016. OSA+ PE patients were younger and predominantly men. Despite a higher prevalence of traditional risk factors for inpatient mortality in OSA+ patients, OSA was associated with a lower risk of mortality in PE patients (odds ratio, 95% confidence interval; p: unadjusted 0.56, 0.53-0.58; p < 0.0001 and adjusted 0.55, 0.52-0.58; p < 0.0001). Overall mortality and length of stay in PE patients decreased over time. Relative to OSA- patients, there was a slight increase in mortality among OSA+ PE patients over time, although the length of stay remained unchanged between the two groups. In conclusion, OSA+ PE patients had a lower inpatient mortality compared to OSA- patients despite a higher prevalence of traditional mortality risk factors. Secondary pulmonary hypertension related to OSA with preconditioning of the right ventricle to elevated afterload may potentially explain the protective effect of OSA on mortality in PE. However, mechanistic studies need to further elucidate the links behind this association.

Identification and Characterisation of a Novel Pathogenic Mutation in the Human Lipodystrophy Gene AGPAT2 : C48R: A Novel Mutation in AGPAT2.

Loss-of-function mutations in AGPAT2, encoding 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2), produce congenital generalised lipodystrophy (CGL). We screened the AGPAT2 gene in two siblings who presented with pseudoacromegaly, diabetes and severe dyslipidaemia and identified a novel mutation in AGPAT2 causing a single amino acid substitution, p.Cys48Arg. We subsequently investigated the molecular pathogenic mechanism linking both this mutation and the previously reported p.Leu228Pro mutation to clinical disease. Wild-type and mutant AGPAT2 were expressed in control and AGPAT2-deficient preadipocyte cell lines. mRNA and protein expression was determined, and the ability of each AGPAT2 species to rescue adipocyte differentiation in AGPAT2-deficient cells was assessed. Protein levels of both p.Cys48Arg and p.Leu228Pro AGPAT2 were significantly reduced compared with that of wild-type AGPAT2 despite equivalent mRNA levels. Stable expression of wild-type AGPAT2 partially rescued adipogenesis in AGPAT2 deficient preadipocytes, whereas stable expression of p.Cys48Arg or p.Leu228Pro AGPAT2 did not. In conclusion, unusually severe dyslipidaemia and pseudoacromegaloid overgrowth in patients with diabetes should alert physicians to the possibility of lipodystrophy. Both the previously unreported pathogenic p.Cys48Arg mutation in AGPAT2, and the known p.Leu228Pro mutation result in decreased AGPAT2 protein expression in developing adipocytes. It is most likely that the CGL seen in homozygous carriers of these mutations is largely accounted for by loss of protein expression.

Subpleural versus deep lung biopsies obtained during pleuroscopy for histological examination: an experimental animal study.

BACKGROUND: Lung biopsies obtained during medical pleuroscopy using coagulating forceps could represent a cost-effective alternative to surgical lung biopsies in patients with diffuse parenchymal lung diseases (DPLD). However, it is not clear whether these patients should undergo deeplung biopsies rather than more superficial subpleural lung biopsies. OBJECTIVES: The aim of this experimental animal study was to compare gross and microscopic features of deep and subpleural pleuroscopic lung biopsy samples. METHODS: Six male sheep (median weight 40 kg) underwent lung biopsies via pleuroscopy under general anesthesia. The following parameters were studied: weight, size, quality of the parenchyma and visceral pleura, parenchymal vessels and bronchial tissue. RESULTS: The mean number of biopsies taken per animal was 4.5 ± 1.22 and 4.83 ± 1.33 (p = 0.36) for deep and subpleural biopsies, respectively. The mean size of deep and subpleural biopsies was 1.758 ± 0.478 and 1.283 ± 0.851 cm(2), respectively (p = 0.0006). The mean weight of deep biopsies and subpleural biopsies was 0.156 ± 0.092 and 0.145 ± 0.047 mg, respectively (p = 0.83). No statistically significant difference was found between subpleural and deep biopsies regarding the mean quality scores of parenchyma-pleura (p = 0.36), vessels (p = 0.36), or bronchial tissue (p = 0.20). CONCLUSION: Both subpleural biopsies obtained during pleuroscopy and deep lung biopsy specimens obtained by electrocautery in animal subjects provided satisfactory material for histologic examination. Therefore, in DPLD, where the subpleural layers are involved, subpleural biopsies obtained during pleuroscopy might be sufficient for establishing an accurate diagnosis.

Prognostic value of postoperative and post-ablative serum thyroglobulin levels in patients with differentiated thyroid cancer.

BACKGROUND: The study was designed to examine the value of post-operative and post-ablative serum thyroglobulin levels and diagnostic whole body scan in predicting remission in patients with differentiated thyroid carcinoma. METHODOLOGY: Serum TG levels and diagnostic iodine-123 whole body scans performed prior to and 6-12 months after 131I ablation for DTC were evaluated in 100 consecutive patients at King Faisal Specialist Hospital Riyadh. Patients were followed up for a period of 7.6 years (range 7-10 years). All patients underwent total thyroidectomypriorto 131I ablation. RESULTS: Patients with serum TG levels < 8 ng/ml post thyroidectomy (50 patients) also maintained low TG < 8 ng/ml after 131I ablation and had better outcome (60%) remission. On the other hand DTC subjects with higher TG > 8 ng/ml post thyroidectomy (50 patients) 40% remained in remission X2 = 4.00, p = 0.046. For the group with initial high post-operative TG, it became < 8 ng/ml in 34/50 (68%) patients after ablation with 131I and in this subgroup, remission was seen in 16/34 (47%) of patients in contrast to 4/16 (25%) remission rate in those who continue to have TG > 8 ng/ml after ablation. At the end of follow up, 123I-WBS was positive in 4% and 10% of patients with initial TG < 8 ng/ml and TG > 8 ng/ml respectively; X2 = 1.38, p= 0.24. CONCLUSION: Post-operative and post-ablative serum TG levels -but not follow up diagnostic WBS- have predictive values and permit selection of patients with higher risk for persistent/recurrent disease.

The effect of vitamin D status on the severity of bone disease and on the other features of primary hyperparathyroidism (pHPT) in a vitamin D deficient region.

A clear relationship between vitamin D status and the clinical indices of primary hyperparathyroidism (pHPT) severity has not been convincingly established. We proposed that such a relationship might exist, in so far as vitamin D deficiency could contribute to the severity of metabolic bone disease and promote the growth of the parathyroid tumor. Accordingly, we undertook a retrospective study and analyzed the clinical, biochemical, radiological and histopathological findings in a group of 49 patients who underwent parathyroidectomy at our center. Patients who had skeletal X-rays were grouped, according to their X-ray findings, in group A (19 patients; 45%) if they had severe bone changes, or group B (23 patients; 55%) if they had mild or no bone changes. Patients were also stratified according to their 25-hydroxyvitamin D (25-OHD) levels in tertiles. The 2 groups were compared using Fisher's exact test or analysis of variance as appropriate. Group A patients were younger (p=0.001), had more musculoskeletal symptoms (p=0.0003), and complained more frequently of fatigue (p=0.02). They had higher alkaline phosphatase (AP; p=0.0002), PTH index (p=0.0007), and serum Ca level (p=0.006). There were more patients from the lower and middle vitamin D tertiles and fewer patients from the upper vitamin D tertile in group A (p=0.02). Post-operative severe hypo-calcemia was more prevalent in group A patients (p<0.0001). Resected parathyroid tumors were larger in size in group A patients (p=0.01), and weighed more (p=0.01). There was a positive correlation between the weight of the parathyroid tumor and the PTH index (p=0.002), and AP level (p=0.0007). We concluded that vitamin D deficiency is a contributing factor to both the severity of bone disease and the high activity of parathyroid tumors seen in many patients with pHPT in vitamin D deficient regions.

Impact of cervical lymph node dissection on serum TG and the course of disease in TG-positive, radioactive iodine whole body scan-negative recurrent/persistent papillary thyroid cancer.

In the management of papillary thyroid cancer (PTC), surgery is indicated for locoregional recurrent/persistent disease. In this study, we examined the effect of such surgery on serum TG and the course of the disease in 21 patients with PTC (mean age 38.5 yr), who after the initial surgery and radioactive iodine (RAI) ablation developed high TG (>10 ng/ml) and negative 123I whole body scan (DxWBS). All patients had neck persistent/recurrent PTC that was confirmed by ultrasound-guided fine needle aspiration. Prior to neck re-exploration, radiological studies (chest X-rays, CT scan of the chest, and fluoro-18-deoxyglucose positron emission tomography [FDG-PET]) showed no evidence of distant metastases. TG autoantibodies were negative in 19 patients. Second surgery consisted of unilateral (13 patients) or bilateral (8 patients) modified neck dissection. The mean+/-SE TG prior to neck re-exploration was 184.8+/-79.0 ng/ml and declined after surgery to 127.5+/-59.0 ng/ml (p=0.25). The corresponding TSH values were 150.6+/-23.0 and 143.4+/-20.0 mU/l, respectively (p=0.34). After a mean follow-up of 20.7+/-3 months, TG increased to 168+/-68.0 ng/ml. This increase, however, was NS (p=0.67). The corresponding TSH values were 143.4+/-20.0 and 132.0+/-22.0 mU/l (p=0.27). Following second surgery, only 4 patients achieved remission, the other 17 patients received one or more of the following therapies; RAI (10 patients), third surgery (5 patients), and/or external radiation (7 patients). Thirteen patients continued to have persistent disease and 4 patients showed progressive course of their disease (distant metastases or grossly palpable neck disease). In conclusion, second surgery for recurrent/persistent PTC leads to remission in only a minority of cases but the course of the disease tends to be stable in most cases.

Sulfonylurea signal transduction.

In the pancreatic beta cells the proximal step in sulfonylurea signal transduction is the binding of these clinically important drugs to high-affinity receptors in the beta cell membrane. Using HIT cells as a model system, we have established an extremely close correlation between the affinity of binding of glyburide and its analog, iodoglyburide, and the activation of various steps in stimulus-secretion coupling--inhibition of 86Rb+ efflux, increase in [Ca2+]i resulting from gating of voltage-gated calcium channels by cell depolarization, and the exocytosis of insulin. Two different L-type channel cDNAs have been identified in an HIT cell library, one neuroendocrine in type and one more cardiac-like. A HIT cell membrane protein of Mr 140,000, which we believe to be the high-affinity sulfonylurea receptor, can be covalently linked to 5(125)-iodo-2-hydroxyglyburide by ultraviolet irradiation. The receptor has been solubilized and retains binding activity and the same rank order of displacement of the 5(125)-iodo-2-hydroxyglyburide as observed with the native receptor. The Mr 140,000 protein has been partially purified and the amino acid sequences of three proteolytic fragments have been used to design oligonucleotides to screen HIT cell cDNA libraries. Since the binding constant of glyburide or iodoglyburide is closely correlated with the ability of these compounds to inhibit the ATP-sensitive K+ channel, increase [Ca2+]i, and elicit insulin secretion, we have identified the Mr 140,000 protein as the sulfonylurea receptor. Expression of the cloned cDNA should allow us to test this hypothesis directly.

Concomitant euthyroid Graves' ophthalmopathy and isolated ocular myasthenia gravis.

A 44 year old diabetic woman presented with diplopia and bilateral ptosis and mild exophthalmos. The patient was clinically euthyroid, the baseline thyroid function tests were normal, but the thyroid stimulating hormone response to thyrotrophin releasing hormone was flat. Computed tomographic scan and magnetic resonance imaging of the orbits showed left medial and inferior rectus muscle thickening, more prominent on the left side, consistent with Graves' disease. The tensilon stimulation test resulted in resolution of the ptosis and partial improvement of the ophthalmoplegia. The single fibre electromyography was consistent with a defect in neuromuscular transmission. However, forced duction test was normal and anti-acetylcholine receptor antibodies were undetectable. Significant improvement of the extraocular muscle function and resolution of the right ptosis had resulted from anticholinesterase therapy. These findings and the clinical response to therapy were consistent with concomitant euthyroid Graves' ophthalmopathy and ocular myasthenia gravis. Coexistent isolated ocular myasthenia gravis and Graves' ophthalmopathy is rare and should be considered in patients with findings of ocular myasthenia and extraocular muscle dysfunction.