A Genetic Risk Score for the Estimation of Weight Loss After Bariatric Surgery.

BACKGROUND: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most frequent bariatric surgery procedures worldwide. In this prospective study, we examined the association of a genetic risk score (GRS) with loss of excess weight after bariatric surgery. METHODS: A total of forty-seven morbidly obese Greek patients who underwent SG (81%) or RYGB were recruited, followed up for 2 years and genotyped. Weight loss after surgery was reported as the percentage of excess weight that was lost (%EWL) at 12 and 24 months after surgery. A GRS was constructed based on previously BMI- and WHR-related single nucleotide polymorphisms (SNPs) that were found significantly correlated with weight loss after bariatric surgery in our population. The level of post-surgery %EWL after 12 and 24 months was estimated through two multiple linear regression models that considered the effects of relevant genetic risk variants. RESULTS: The first proposed model suggested that the predictor variables of GRS, age, and BMI had a significant effect on %EWL12m. GRS was significantly associated with %EWL12m, indicating a 4.618% decrease of %EWL12m per score unit. The second model indicated a positive correlation between %EWL24m and %EWL12m, suggesting that while post-surgery weight loss increased during the first 12 months, an increase was expected in the next 12 months as well. GRS was also significantly associated with %EWL24m, indicating approximately 3% decrease of %EWL24m per score unit. CONCLUSION: GRS can be used in the future together with other preoperative parameters in order to predict the outcome of bariatric surgery.

Isolated right ventricular infarction during percutaneous coronary intervention.

Isolated right ventricular infarction (RVI) is an increasingly recognized cause of precordial ST-segment elevation (STE). A patient is described who developed STE in leads V1-V5 secondary to occlusion of the right ventricular branch during stent angioplasty to the right coronary artery. The pattern of precordial STE was thought to be suggestive of anteroseptal myocardial infarction because of progressive STE toward lead V3. Repeat angiography disclosed a patent left anterior descending artery. Subsequent scrutiny of the electrocardiogram (ECG) revealed that leads V2 and V3 were switched and ECG interpretation considering this technical error revealed STE in V2>V3, which favored RVI. Furthermore, the mean spatial ST vector was approximately +120° in the frontal plane producing ST-segment depression in lead I which argued against anteroseptal myocardial infarction and indicated right ventricular epicardial injury. This report highlights that analysis of the ECG using vector concepts is a useful adjunct to pattern recognition for the diagnosis of RVI.

Complex coronary artery anatomy in a patient with prolapsing left atrial myxoma.

The case of an asymptomatic patient with prolapsing left atrial myxoma, in whom preoperative coronary angiography revealed a rare coronary artery anatomy in the absence of atherosclerotic obstructive disease, is presented. There was a type IV dual left anterior descending (LAD) artery with intraseptal course of the right aortic sinus-connected (long) LAD artery and an ectopic left circumflex artery originating from the right aortic sinus and having a retroaortic course. The patient underwent successful surgical excision of the mass which was confirmed by histology to be cardiac myxoma. This particular coronary artery anatomy has only been described once, and this is the first reported case of its combination with cardiac myxoma. This report highlights the importance of differentiating between the possible courses of such ectopic coronary arteries. The angiographic signs which enabled differentiation of the intraseptal course of the long LAD artery from the malignant interarterial course with which it is frequently confused are presented.

24-h Intraocular pressure control with evening-dosed travoprost/timolol, compared with latanoprost/timolol, fixed combinations in exfoliative glaucoma.

PURPOSE: To evaluate 24-h efficacy of travoprost/timolol fixed combination (TTFC) vslatanoprost/timolol fixed combination (LTFC) in exfoliative glaucoma (XFG). DESIGN: A prospective, single-masked, crossover, active-controlled, randomized 24-h comparison. METHODS: After up to a 6-week medicine-free period, XFG patients were randomized to either TTFC or LTFC for 3 months, dosed each evening, and then changed to the opposite treatment for another 3 months. At the end of the washout, and both treatment periods, a 24-h intraocular pressure (IOP) curve was measured. RESULTS: In total, 40 patients completed the study. The TTFC group showed a lower mean absolute 24-h IOP (18.7±2.6 vs 19.6±2.6 mm Hg, P<0.001), maximum IOP (20.5±2.6 vs 21.5±2.6 mm Hg, P<0.001) and 24-h IOP range (3.4±1.3 vs 4.1±1.6 mm Hg, P=0.01). At individual time points, TTFC showed reduced IOPs compared with LTFC, after a Bonferroni correction, at 1000, 1800, and 2200 hours (P≤0.04). No statistical differences existed at hours: 0600, 1400, and 0200 (P≥0.05) and for the minimum IOP (P=0.09). CONCLUSIONS: This study suggests that evening-dosed TTFC may provide greater 24-h IOP reduction, primarily at the 1800 hours time point, compared with LTFC in XFG.

Management of advanced stage uterine sarcomas: a bone of contention.

Uterine sarcomas constitute a rare group of neoplasms characterized by an aggressive clinical course and poor prognosis. It is this rarity that has resulted in clinical-trial reports and literature reviews including a broad range of histological subtypes of sarcoma. This has a detrimental effect on interpretation and application of the results; the pathological subtype demands a tailored approach. Surgical resection remains the mainstay of treatment for non metastatic uterine sarcomas. Although adjuvant radiation therapy has reportedly been of little survival value, it appears to improve local control and may delay recurrence. The role of adjuvant chemotherapy has yet to be established; however, bearing in mind the limitations and assumptions in the pooling of data the therapeutic options should be based on the pathological subtype. Considering the poor overall survival in uterine sarcomas, the need for new therapeutic agents is critical. New drugs with possible activity in uterine sarcomas include trabectedin, temozolomide, liposomal doxorubicin and gemcitabine.

Ischemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart.

There is accumulating evidence showing that ischemic preconditioning (PC) may lose its cardioprotective effect in the diseased states. The present study investigated whether PC can be effective in hypothyroidism, a clinical condition which is common and often accompanies cardiac diseases such as heart failure and myocardial infarction. Hypothyroidism was induced in rats by 3-week administration of 6n-propyl-2-thiouracil in water (0.05 %). Normal and hypothyroid hearts (HYPO) were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischemia and 45 min of reperfusion. A preconditioning protocol (PC) was also applied prior to ischemia. HYPO hearts had significantly improved post-ischemic recovery of left ventricular developed pressure, end-diastolic pressure and reduced lactate dehydrogenase release. Furthermore, phospho-JNK and p38 MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold lower in HYPO as compared to normal hearts (P<0.05). A different response to PC was observed in normal than in HYPO hearts. PC improved the post-ischemic recovery of function and reduced the extent of injury in normal hearts but had no additional effect on the hypothyroid hearts. This response, in the preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller expression of the phospho-JNK and phospho-p38 MAPK levels at the end of reperfusion, as compared to non-PC hearts (P<0.05), while in HYPO hearts, no additional reduction in the phosphorylation of these kinases was observed after PC. Hypothyroid hearts appear to be tolerant to ischemia-reperfusion injury. This response may be, at least in part, due to the down-regulation of ischemia-reperfusion induced activation of JNKs and p38 MAPK kinases. PC is not associated with further reduction in the activation of these kinases in the hypothyroid hearts and fails to confer added protection in those hearts.

Second-line therapy with dorzolamide/timolol or latanoprost/timolol fixed combination versus adding dorzolamide/timolol fixed combination to latanoprost monotherapy.

OBJECTIVE: To evaluate open-angle glaucoma patients, who were insufficiently controlled on latanoprost monotherapy, to determine the 24 h intraocular pressure (IOP) efficacy and safety when changing them to dorzolamide/timolol (DTFC) or latanoprost/timolol fixed combination (LTFC) or adding DTFC. METHODS: A prospective, observer-masked, placebo-controlled, crossover, comparison. Consecutive adults with primary open-angle or exfoliative glaucoma who exhibit a mean baseline IOP >21 mm Hg on latanoprost monotherapy were randomised for 3 months to: DTFC, LTFC or DTFC and latanoprost. Patients were then crossed over to the next treatment for periods 2 and 3. At the end of the latanoprost run-in and after each 3-month treatment period, patients underwent 24 h IOP monitoring. RESULTS: 31 patients completed this study. All three adjunctive therapies significantly reduced the IOP at each time point and for the mean 24 h curve, except at 18:00 and 02:00 with DTFC and 02:00 with LTFC. When the three treatments were compared directly, the DTFC and latanoprost therapy demonstrated lower IOPs versus the other treatment groups, including: the mean 24 h pressure, maximum as well as minimum levels and individual time points following a modified Bonferroni correction (p<0.0032). CONCLUSIONS: This study showed DTFC, LTFC and the addition of DTFC to latanoprost significantly decrease the IOP compared with latanoprost alone, but the latter therapy regime yields the greatest IOP reduction.

Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00.

BACKGROUND: A randomized phase III trial in high-risk breast cancer patients was conducted, to further explore the impact of dose-density in the adjuvant treatment for breast cancer. The safety analysis is presented. PATIENTS AND METHODS: From October 2000 until June 2005, 1121 node-positive patients were randomized to sequential dose-dense epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, New Jersey, USA) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of 'intensified' combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF). Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments. RESULTS: Median dose intensity of epirubicin and paclitaxel was double in group A, as designed, with significantly less cycles administered at full dose (P < 0.001). Median cumulative dose of all drugs and total treatment duration, however, were identical between groups. Severe taxane-related toxic effects were more frequent in group A, while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects, including febrile neutropenia. The rates of secondary malignancies were low. CONCLUSION: Both regimens as used in the present study are well tolerated and safe. The rates of severe taxane-related toxic effects and thrombocytopenia, although low overall, are significantly increased with the dose-dense sequential regimen.