Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

BACKGROUND: Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. METHODS: Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. RESULTS: Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). CONCLUSIONS: Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.     

Regulation of the small GTPase RhoA by syndecan-4 and integrins in focal adhesion formation

Introduction The transmembrane heparan sulfate proteoglycan, syndecan‐4, and integrins are important receptors for focal adhesion (FA) formation on fibronectin (FN) substrates. The small GTPase RhoA is also known to regulate FA and stress fiber formation. It has been suggested that syndecan‐4 and integrins co‐operatively regulate the assembly of FA in a Rho‐dependent manner, but the mechanism is unclear. Here, we examined the function of RhoA and the Rho effector kinases ROCKs in syndecan‐4 signalling on the process of FA formation and the possible mechanism by which syndecan‐4 may regulate RhoA activity. Methods Primary rat embryonic fibroblasts (REFs) were seeded on FN or ‘RGD’‐containing integrin‐binding domain of FN and lysed at various time points. The amount of active form of RhoA in each lysate was analysed by pull‐down experiments. Results and discussion The relative activities of RhoA showed one peak in the process of FA formation on FN, whereas no peak was obtained on the integrin‐binding domain. The one peak of RhoA activity on integrin‐binding domain was restored by addition of heparin‐binding domain into medium. These results suggested that a signal through syndecan‐4 link to the Rho pathway. Both ROCK‐I and ‐II isozymes were present in REF cell lysates and each could be specifically immunoprecipitated. The ROCK kinase activities in immunoprecipitates were analysed using GST‐myosin light chain as a substrate. The amount of ROCK‐I and ‐II activities changed through the adhesion process on FN and appeared to be independently regulated. Therefore, one or both ROCKs may be downstream of a syndecan‐4‐mediated signalling response through RhoA. The core protein of syndecan‐4 can directly bind to and activate PKC‐α. We found that PKC‐α could phosphorylate Rho‐Guanine Nucleotide Dissociation Inhibitor (GDI) in vitro. It has been suggested that PKC‐α‐mediated phosphorylation of Rho GDI stimulates GDI dissociation, thereby resulting in Rho activation. It is possible that syndecan‐4 regulates Rho/ROCK pathway through PKC‐α activation on the process of FA formation.     

Laparoscopic Cholecystectomy in Obese and Nonobese Patients

Background: From November 1997 to November 1998, 145 cases of laparoscopic cholecystectomy (LC) have been attempted at the District General Hospital of Corfu. Methods: 23 (15.8%) were obese (Group I, BMI >30) and 122 (84.2%) were nonobese patients (Group II, BMI ≤30). One-fifth of these patients suffered from acute cholecystitis. Results: Operative time averaged 95 minutes in Group 1 and 78 minutes in Group II. There were no deaths. There were no significant differences between the obese and nonobese groups in conversion to open procedure (Group1: 0%, Group II: 2.4%), intraoperative and postoperative complications (Group I: 4.3%, Group II: 4.0%), operating time, and length of postoperative hospitalization. Conclusion: LC was a safe and effective treatment for obese patients with symptomatic cholelithiasis.     

Magnetic Metal Oxide-Based Photocatalysts with Integrated Silver for Water Treatment

In this review, the most recent advances in the field of magnetic composite photocatalysts with integrated plasmonic silver (Ag) is presented, with an overview of their synthesis techniques, properties and photocatalytic pollutant removal applications. Magnetic attributes combined with plasmonic properties in these composites result in enhancements for light absorption, charge-pair generation-separation-transfer and photocatalytic efficiency with the additional advantage of their facile magnetic separation from water solutions after treatment, neutralizing the issue of silver’s inherent toxicity. A detailed overview of the currently utilized synthesis methods and techniques for the preparation of magnetic silver-integrated composites is presented. Furthermore, an extended critical review of the most recent pollutant removal applications of these composites via green photocatalysis technology is presented. From this survey, the potential of magnetic composites integrated with plasmonic metals is highlighted for light-induced water treatment and purification. Highlights: (1) Perspective of magnetic properties combined with plasmon metal attributes; (2) Overview of recent methods for magnetic silver-integrated composite synthesis; (3) Critical view of recent applications for photocatalytic pollutant removal.     

Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta‐analysis

Schwannomatosis is a genetic disorder characterized by the occurrence of multiple peripheral schwannomas. Segmental schwannomatosis is diagnosed when schwannomas are restricted to 1 extremity and is thought to be caused by genetic mosaicism. We studied 5 patients with segmental schwannomatosis through microstructural magnetic resonance neurography and mutation analysis of NF2, SMARCB1, and LZTR1. In 4 of 5 patients, subtle fascicular nerve lesions were detected in clinically unaffected extremities. Two patients exhibited LZTR1 germline mutations. This appears contrary to a simple concept of genetic mosaicism and suggests more complex and heterogeneous mechanisms underlying the phenotype of segmental schwannomatosis than previously thought. Ann Neurol 2016;80:625–628     

The value of transesophageal echocardiography in the investigation and management of cryptogenic cerebral ischemia: a single-center experience

The diagnostic utility of transesophageal echocardiography (TEE) has often been challenged in patients with cryptogenic stroke (CS). We estimated the prevalence of different findings on TEE examination of CS patients, their impact on secondary stroke prevention and the presence of potential age or gender disparities. We reviewed all TEE examinations that were performed in a single echocardiography laboratory during a 7-year-old period to identify CS patients that underwent investigation with TEE. Of the 518 total TEE examinations, we identified 88 CS patients. TEE revealed abnormal findings in 69.3 % of them. Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) were identified in 30.6 and 22.7 % of the patients. Ascending aorta and aortic arch atheromatosis was present in 26.1 % of the patients, with complex atheromatosis diagnosed in 14.7 % of them. Cardiac myxomas were uncovered in 2.3 %. Thrombi in the left atrium and in cardiac valves were reported in 3.4 and 2.3 % of the patients, respectively. Based on TEE findings, the therapeutic management would be very likely modified in 9.1 % of the patients. Subgroup analysis revealed no gender disparities on the prevalence of TEE findings and in secondary stroke prevention, while linear regression analyses revealed significant associations of age with the prevalence of PFO, ASA, aorta atheromatosis and complex aorta atheromatosis. TEE examination should be included in the diagnostic work-up of all CS patients, irrespective of age and gender status, since it can reveal potential sources of embolism and has a significant impact for secondary stroke prevention.     

Race and Health Disparities in Patient Refusal of Surgery for Early-Stage Non-Small Cell Lung Cancer: A SEER Cohort Study

Introduction  

Several factors, including race, age, stage, comorbid conditions, social support, and socioeconomic status, have been linked to the likelihood of a patient having surgery for early-stage non-small cell lung cancer (NSCLC). The aim of the present study is to determine the influence of race and health disparities on refusal of recommended potentially curative surgery.     

Selective hepatic arterial infusion of In-111-DTPA-Phe<Superscript>1</Superscript>-octreotide in neuroendocrine liver metastases

Purpose  The aim of this study is to evaluate the effectiveness of ¹¹¹In-DTPA-Phe¹-octreotide infusions after selective catheterization of the hepatic artery in inoperable metastasised liver, sst₂ receptor-positive neuroendocrine tumours due to the effect of ¹¹¹In Auger electron emission, minimising in parallel the toxicity of non-target tissue. Methods  The average dose per session administered monthly to each patient (17 cases in total) was 6.3 ± 2.3 GBq. Repetitions did not exceed 12-fold, except in one case (15 sessions). Response assessment was classified according to the Response Evaluating Criteria in Solid Tumours. CT/MRI scans were performed as baseline before, during and after the end of treatment, and monthly ultrasound images for follow-up measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function. Results  Complete response was achieved in one (5.9%) patient and partial in eight (47.0%), and disease stabilization in 3 (17.7%) patients; five (29.4%) did not respond. A 32-month median survival time was estimated in 12 (70.5%). Nine of these 12 surviving had a mean target diameter shrinkage from 144 ± 81 to 60 ± 59 mm. Grade 1 erythro-, leuko- and thrombo-cytopenia occurred in three (17.6%) cases. Conclusion  In unresectable metastatic liver lesions positive for somatostatin receptors repeated, transhepatic high doses of ¹¹¹In-DTPA-Phe¹-octreotide show an effective therapeutic outcome. Given the locoregional modality character of the administration technique plus the extremely short range of ¹¹¹In Auger and internal conversion electrons emission, no nephro-, liver- or myelo-toxicity has so far been observed.     

Multifocal Versus Solitary Papillary Thyroid Carcinoma

Background

Papillary Thyroid Carcinoma (PTC) which accounts for >85 % of all thyroid cancers in iodine-rich areas, appears either as a single tumor or as two or more, neoplastic foci within the thyroid gland (Multifocal PTC). We present the comparative results between solitary and MFC PTC.

Materials and methods

Demographics, tumor characteristics (size, laterality, foci number, histologic subtype) and TNM staging were compared between solitary and MFPTC patients. The presence of lymphocytic or Hashimoto’s thyroditis was also recorded.

Results

From January 2008 to December 2012, among 647 PTC patients, 241(37.2 %) had MFPTC 177 females (73.4 %) and 64 males (26.6 %), mean age 48.5 years (range 12–87). Mean number of tumor foci was 3.3 (range 2–26). MFPTC patients presented with more advanced T stage (28.2 vs. 18.7 %, p = 0.01) and more LN metastases (28.6 vs. 15.5 %, p < 0.001). Foci number correlates with male gender and LN metastases (p = 0.014 and p = 0.019, respectively). Central (N1a) or lateral (N1b) LN involvement correlates strongly with male gender (p  = 0.024) and younger age (p < 0.001). The follicular variant was the next most frequent histologic subtype associated with extremely rare LN metastases.

Conclusion

MFPTC comprises a more aggressive form of papillary thyroid cancer since it is associated with more frequent N1a/ N1b disease and occurs more frequently in T3/T4 patients. MFPTC foci number correlates with male gender and LN metastases.

     

Peripheral levels of matrix metalloproteinase-9, interleukin-6, and C-reactive protein are elevated in patients with acute coronary syndromes: correlations with serum troponin I

BACKGROUND: Acute coronary syndromes (ACS) are characterized by activation of systemic and local inflammatory mediators. The interrelation between these soluble inflammatory markers and their association with markers of myocardial necrosis have not been extensively studied. HYPOTHESIS: The study was undertaken to evaluate the association of the systemic levels of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted with ACS. METHODS: Analysis of serum concentrations of the above inflammatory markers was performed in 53 patients with unstable angina (UA) and in 15 with non-ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and 34 patients with stable coronary artery disease. RESULTS: Compared with patients with stable angina, those with ACS had elevated admission levels of MMP-9 (p = 0.04), CRP (p < 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared with patients with UA, those with NSTEMI also had higher levels of IL-6 (p < 0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). CONCLUSIONS: In patients with ACS, the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6 are significantly elevated, specifically in association with serum troponin I. Systemic and local markers of inflammatory activity may be directly associated with myocardial injury.