Progressive improvement of impaired visual acuity during the first year after transsphenoidal surgery for non-functioning pituitary macroadenoma

Improvement of visual field defects continues even years after the initial surgical treatment. Because this process of continuing improvement has not been documented for visual acuity, we audited our data to explore the pattern of recovery of visual acuity until 1 year after transsphenoidal surgery for non-functioning pituitary macroadenoma. Retrospective follow-up study. Forty-three patients (mean age 56 +/- 14 years), treated by transsphenoidal surgery for non-functioning pituitary macroadenoma, were included in this analysis. Visual acuity improved significantly within 3 months after transsphenoidal surgery. The mean visual acuity increased from 0.65 +/- 0.37 to 0.75 +/- 0.36 (P <0.01) (right eye), and from 0.60 +/- 0.32 to 0.82 +/- 0.30 (P <0.01) (left eye). Visual acuity was improved 1 year after transsphenoidal surgery compared to the 3 months postoperative values. The mean visual acuity increased from 0.75 +/- 0.36 to 0.82 +/- 0.34 (P <0.05) (right eye), and from 0.82 +/- 0.30 to 0.88 +/- 0.27 (P <0.05) (left eye). Visual acuity improves progressively after surgical treatment for non-functioning pituitary macroadenomas, at least within the first year after transsphenoidal surger

Health, not weight loss, focused programmes versus conventional weight loss programmes for cardiovascular risk factors:A systematic review and meta-analysis

© 2019 The Authors. Published by BMC. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website:Background: Obesity is a cardiovascular disease risk factor. Conventional weight loss (CWL) programmes focus on weight loss, however 'health, not weight loss, focused' (HNWL) programmes concentrate on improved health and well-being, irrespective of weight loss. What are the differences in CVD risk outcomes between these programmes? Aim: To conduct a systematic review and meta-analysis to compare the effects of HNWL with CWL programmes on cardiovascular disease risk factors. Methods: We searched CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, ASSIA, clinical trial registers, commercial websites and reference lists for randomised controlled trials comparing the two programmes (initially searched up to August 2015 and searched updated to 5 April 2019). We used the Mantel-Haneszel fixed-effect model to pool results. Sub-group and sensitivity analyses that accounted for variations in length of follow-up, enhanced programmes and risk of bias dealt with heterogeneity. Results: Eight randomised controlled trials of 20,242 potential studies were included. Improvements in total cholesterol-HDL ratio (mean difference-0.21 mmol/L, 95% confidence interval [-3.91, 3.50]) and weight loss (-0.28 kg [-2.00, 1.44]) favoured HNWL compared to CWL programmes in the long term (53-104 week follow-up), whereas improvements in systolic (-1.14 mmHg, [-5.84, 3.56]) and diastolic (-0.15 mmHg, [-3.64, 3.34]) blood pressure favoured CWL programmes. These differences did not reach statistical significance. Statistically significant improvements in body satisfaction (-4.30 [-8.32,-0.28]) and restrained eating behaviour (-4.30 [-6.77,-1.83]) favoured HNWL over CWL programmes. Conclusions: We found no long-term significant differences in improved CVD risk factors; however, body satisfaction and restrained eating behaviour improved more with HNWL compared to CWL programmes. Yet firm conclusions cannot be drawn from small studies with high losses to follow-up and data sometimes arising from a single small study.Published versio

Analytical methods for inferring functional effects of single base pair substitutions in human cancers

Cancer is a genetic disease that results from a variety of genomic alterations. Identification of some of these causal genetic events has enabled the development of targeted therapeutics and spurred efforts to discover the key genes that drive cancer formation. Rapidly improving sequencing and genotyping technology continues to generate increasingly large datasets that require analytical methods to identify functional alterations that deserve additional investigation. This review examines statistical and computational approaches for the identification of functional changes among sets of single-nucleotide substitutions. Frequency-based methods identify the most highly mutated genes in large-scale cancer sequencing efforts while bioinformatics approaches are effective for independent evaluation of both non-synonymous mutations and polymorphisms. We also review current knowledge and tools that can be utilized for analysis of alterations in non-protein-coding genomic sequence

Mercury Spikes Indicate a Volcanic Trigger for the Late Ordovician Mass Extinction Event: An Example from a Deep Shelf of the Peri-Baltic Region.

The Late Ordovician mass extinction (LOME) was the second largest Phanerozoic crisis, but its cause remains elusive. Several triggering mechanisms have been proposed over the years, including bioevolutionary events, oceanographic changes, and geotectonic processes. Here, we report the presence of Hg spikes in the Zbrza PIG-1 borehole from the Upper Ordovician deep shelf sections of the peri-Baltic region. A strong positive anomaly in the lower late Katian (Hg/TOC = 2537.3 ppb/wt%) was noted. No correlation between Hg and TOC (R² = 0.07) was distinguished in the Hirnantian, although several positive anomalies were found. Because the Hg/Mo ratio showed trends very similar to those of Hg/TOC, it seems likely that TOC values reflect the redox conditions. In order to evaluate the role of anoxia in levels of Hg enrichment several redox indicators were measured. These showed that the elevated mercury values in the Hirnantian are not caused by anoxia/euxinia because euxinic biomarkers (maleimides and aryl isoprenoids) are present in very low abundance and pyrite framboids are absent. In total, positive Hg/TOC anomalies occur in the lower late Katian, at the Katian - Hirnantian boundary, and in the late Hirnantian. The lack of a strong Hg/TOC correlation, Ni enrichments, and the absence of 'anoxic indicators' (no biomarkers, no framboids, low Mo concentration) at these levels, supports the interpretation that Hg enrichment is due to enhanced environmental loading. We conclude that our Hg and Hg/TOC values were associated with volcanic pulses which triggered the massive environmental changes resulting in the Late Ordovician mass extinction

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies

ICAR: endoscopic skull‐base surgery

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Cytokine and Chemokine Concentrations as Biomarkers of Feline Mycobacteriosis

Abstract Mycobacteriosis is an emerging zoonotic disease of domestic cats and timely, accurate diagnosis is currently challenging. To identify differential cytokine/chemokine concentrations in serum/plasma of cats, which could be diagnostic biomarkers of infection we analysed plasma/serum from 116 mycobacteria-infected cats, 16 healthy controls and six cats hospitalised for unrelated reasons was analysed using the Milliplex MAP Feline Cytokine Magnetic Bead multiplex assay. Three cytokines; sFAS, IL-13 and IL-4 were reduced while seven; GM-CSF, IL-2, PDGF-BB, IL-8, KC, RANTES and TNF-α were elevated in mycobacteria-infected cats compared to healthy controls. However, IL-8 and KC concentrations were not significantly different from cats hospitalised for other reasons. Elevations in TNF-α and PDGF-BB may have potential to identify M. bovis and M. microti infected cats specifically while GM-CSF, IL-2 and FLT3L were increased in MTBC infected cats. This study demonstrates potential use of feline tuberculosis as a spontaneously occurring model of this significant human disease. Cytokine profiling has clear diagnostic potential for mycobacteriosis of cats and could be used discriminate tuberculous from non-tuberculous disease to rapidly inform on zoonotic risk. Future work should focus on the in-field utility of these findings to establish diagnostic sensitivity and specificity of these markers

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402