Author(s) Chichareon P.; Modolo R.; Kogame N.; Takahashi K.; Wykrzykowska J. et al.
Source Journal of the American College of Cardiology; Oct 2019; vol. 74 (no. 13)
DOI 10.1016/j.jacc.2019.08.754
Background: Diabetes has been well recognized as a strong predictor of adverse outcomes after percutaneous coronary intervention (PCI), but studies in the era of drug-eluting stents and potent P2Y12 inhibitors have shown conflicting results. We assessed ischemic and bleeding outcomes after contemporary PCI according to diabetic status.

Method(s): We studied 15,957 patients in the GLOBAL LEADERS study with known baseline diabetic status. The primary endpoint was all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was major bleeding defined as Bleeding Academic Research Consortium (BARC) type 3 or 5.

Result(s): A quarter of the study cohort had diabetes (4,038 of 15,957), and these patients had a significantly higher risk for the primary endpoint at 2 years compared with those without diabetes (adjusted hazard ratio [HR]: 1.36; 95% confidence interval [CI]: 1.14 to 1.61). The difference was driven by a significantly higher risk for all-cause mortality at 2 years in patients with diabetes (adjusted HR: 1.44; 95% CI: 1.18 to 1.75). The risk for BARC type 3 or 5 bleeding was comparable between the 2 groups (adjusted HR: 1.18; 95% CI: 0.92 to 1.50). The antiplatelet strategy (experimental vs. reference strategy) had no significant effect on the rates of the primary endpoint and secondary safety endpoint at 2 years in patients with and without diabetes.

​Conclusion(s): Patients with diabetes had a higher risk for ischemic events after PCI than those without diabetes, while bleeding risk was comparable. The outcomes of patients with diabetes following PCI were not affected by the 2 different antiplatelet strategies. Categories: CORONARY: Pharmacology/PharmacotherapyCopyright © 2019

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Author(s) Ryan N.A.J.; Crosbie E.J.; Evans D.G.; Glaire M.A.; Blake D. et al.
Source Genetics in Medicine; Oct 2019; vol. 21 (no. 10); p. 2167-2180
Purpose: Endometrial cancer (EC) is often the sentinel cancer in women with Lynch syndrome (LS). However, efforts to implement universal LS screening in EC patients have been hampered by a lack of evidence detailing the proportion of EC patients that would be expected to screen positive for LS.

Method(s): Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I2 score was used to assess heterogeneity across studies.

​Result(s): Fifty-three studies, including 12,633 EC patients, met the inclusion criteria. The overall proportion of endometrial tumors with microsatellite instability or mismatch repair (MMR) deficiency by immunohistochemistry (IHC) was 0.27 (95% confidence interval [CI] 0.25-0.28, I2: 71%) and 0.26 (95% CI 0.25-0.27, I2: 88%), respectively. Of those women with abnormal tumor testing, 0.29 (95% CI 0.25-0.33, I2: 83%) had LS-associated pathogenic variants on germline testing; therefore around 3% of ECs can be attributed to LS. Preselection of EC cases did increase the proportion of germline LS diagnoses.

Conclusion(s): The current study suggests that prevalence of LS in EC patients is approximately 3%, similar to that of colorectal cancer patients; therefore our data support the implementation of universal EC screening for LS.Copyright © 2019, The Author(s).

Author(s) Choudhury A.; Garg S.; Smith J.; Sharp A.; Nabais De Araujo S. et al.
Source BMJ Open; 2019; vol. 9 (no. 10)
Objective To prospectively evaluate safety and efficacy of the ultrathin strut biodegradable polymer-coated Supraflex sirolimus-eluting stent (S-SES) in real world' patient population requiring percutaneous coronary intervention (PCI).

Methods National, prospective, multicentre, single-arm, all-comers, observational registry of 469 patients treated with S-SES from July 2015 and November 2016 in 11 centres in UK. Primary endpoint was target lesion failure (TLF) at 12 months (cardiac death, target vessel myocardial infarction (MI) or clinically driven target lesion revascularisation (TLR)). Secondary endpoints included safety and performance outcomes at 12 months-overall stent thrombosis (ST), all-cause mortality, any MI, target vessel failure (TVF) and major adverse cardiac events (MACE-composite of cardiac death, MI, emergent or repeat revascularisation).

Results At 12 months, the primary endpoint occurred in 11 (2.4%) of 466 patients, consisting of 4 (0.9%) cardiac deaths, 3 (0.6%) target vessel MI and 7 (1.5%) TLR. Secondary endpoints findings included all-cause mortality in 6 (1.3%), TVF of 14 (3%), no definite ST, 1 (0.2%) probable ST and 3 (0.6%) possible ST. Overall MACE was observed in 18 (3.9%).

​Conclusions The S-FLEX UK registry showed that the S-SES is safe with a low incidence of TLF in routine clinical practise in patients with coronary artery disease being treated by PCI.Copyright © 2019 Author(s).

• Available in full text at BMJ open from Europe PubMed Central - Open Access

Author(s) Hajibandeh S.; Clark M.C.; Barratt O.A.; Taktak S.; Henley N. et al.
Source Surgical Laparoscopy, Endoscopy and Percutaneous Techniques; Oct 2019; vol. 29 (no. 5); p. 321-327
Objective:The objective of this study was to evaluate the comparative efficacy of gallbladder retrieval via the epigastric and umbilical port during laparoscopic cholecystectomy. Method(s):We systematically searched MEDLINE, EMBASE, CINAHL, CENTRAL, the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov, ISRCTN Register, and bibliographic reference lists. Postoperative pain intensity, port-site infection, hernia, bleeding, and retrieval time were outcome parameters. Combined overall effect sizes were calculated using fixed-effect or random-effects models.

Result(s):We identified 5 randomized controlled trials and 1 prospective cohort study reporting a total of 2394 patients who underwent laparoscopic cholecystectomy with retrieval of the gallbladder via the umbilical port (n=1194) or epigastric port (n=1200). Our initial analysis demonstrated that gallbladder retrieval via the umbilical port was associated with a nonsignificant reduction in pain assessed by visual analogue scale at 24 hours [mean difference (MD): -0.49, 95% confidence interval (CI): -1.06 to 0.08, P=0.09] compared with the epigastric port. However, after sensitivity analysis and eliminating the source of heterogeneity, it reached statistical significance (MD: -0.66, 95% CI: -0.85 to -0.48, P<0.00001). Moreover, gallbladder retrieval via the umbilical port was associated with significantly shorter retrieval time (MD: -1.83, 95% CI: -3.18 to -0.49, P=0.008) but similar risk of port-site infection (odds ratio: 1.99, 95% CI: 0.53-7.44, P=0.31) and hernia (odds ratio: 0.33, 95% CI: 0.03-3.20, P=0.34).

​Conclusion(s):Our analysis demonstrated that retrieval of the gallbladder via the umbilical port may be associated with less postoperative pain in patients undergoing laparoscopic cholecystectomy compared with epigastric port retrieval. It may also be associated with shorter gallbladder retrieval time. However, the available evidence is limited.Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Author(s) Ismail D.; Owen C.M.
Source Clinical and Experimental Dermatology; Oct 2019; vol. 44 (no. 7); p. 753-758
Publication Date Oct 2019
DOI 10.1111/ced.13894
Background: Lichen sclerosus (LS) is a chronic inflammatory dermatosis with a predilection for the anogenital region, which mainly affects prepubertal girls and postmenopausal women. The cause is unknown, but a number of potential aetiological factors have been identified.

Aim(s): To examine a cohort of patients with prepubertal-onset vulval LS (VLS) and assess baseline characteristics, clinical presentation, potential precipitating and predisposing factors, and response to treatment. Method(s): Data were collected from case notes on patients aged < 18 years diagnosed with prepubertal-onset VLS attending a specialist vulval dermatology service. Data included clinical presentation, comorbidities, family history, therapy and response to treatment.

Result(s): In total, 26 paediatric patients were identified. The median age at onset of symptoms was 5 years (range 2-8.5 years). Many previously identified potential aetiological factors for the development of VLS were identified, including family history, trauma, autoimmune disease and hormonal factors. A significant proportion of patients had a history of urinary tract symptoms, including incontinence and urinary tract infection. Most patients responded well to a standard course of induction topical therapy followed by maintenance therapy, but some, including three patients with ongoing urinary incontinence and three postpubertal patients, continued to have active disease.

​Conclusion(s): A detailed assessment is essential in patients with VLS so that potential predisposing factors and comorbidities can be identified and managed. Urinary incontinence may be implicated in the development of paediatric VLS and may prevent adequate disease control. Paediatric VLS can persist through puberty, thus long-term follow-up is advised.Copyright © 2019 British Association of Dermatologists

• Available in full text at Clinical and experimental dermatology from Wiley Online Library Medicine and Nursing Collection 2019 - NHS

​Author(s) Takahashi K.; Chichareon P.; Modolo R.; Kogame N.; Tijssen J.G.P. et al.
Source Journal of the American College of Cardiology; Oct 2019; vol. 74 (no. 16); p. 2015-2027
DOI 10.1016/j.jacc.2019.08.997
Background: Data on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse. Objective(s): This post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI.

Method(s): The GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding.

Result(s): Among the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; pinteraction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; pinteraction = 0.754).

​Conclusion(s): Long-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).Copyright © 2019 American College of Cardiology Foundation

Author(s) Chichareon P.; Modolo R.; Kogame N.; Takahashi K.; van Klaveren D. et al.
Source Journal of the American College of Cardiology; Oct 2019; vol. 74 (no. 13)
DOI 10.1016/j.jacc.2019.08.512
Background: The logistic clinical SYNTAX score combined anatomic SYNTAX score and 7 variables to predict 2-year all-cause mortality after percutaneous coronary intervention (PCI). The score was derived from 7 stent trials in which new-generation drug-eluting stent and potent antiplatelet inhibitors were not widely utilized. The original logistic clinical SYNTAX score has been shown to overestimate 2-year all-cause mortality in the GLOBAL LEADERS study. This study aimed to revise and update the logistic clinical SYNTAX score to predict 2-year all-cause mortality after contemporary PCI using the population in the GLOBAL LEADERS study.

Method(s): The authors analyzed 15,883 patients in the GLOBAL LEADERS study who underwent PCI. The original model of the logistic clinical SYNTAX score was revised by re-estimating the predictor effects in Cox regression model (revised model). The authors updated the score by combining the original model with additional independent predictors of 2-year mortality identified in the GLOBAL LEADERS study population (updated model). Internal validation with bootstrap method was used to quantify and correct for overfitting and optimism.

Result(s): This study has identified 5 additional independent predictors of 2-year all-cause mortality: hemoglobin level; white blood cell count; chronic obstructive pulmonary disease; prior stroke; and current smoker. The updated model (C-index: 0.78; 95% confidence interval [CI]: 0.76 to 0.80) better discriminated 2-year all-cause mortality than the previous version (C-index: 0.75; 95% CI: 0.73 to 0.77), in an internal validation using bootstrap method. The updated model performed better in differentiating mortality among non-high-risk patients. The calibration of both models was appropriate. Currently the updated model is tested in an external validation cohort of 10,724 patients.

​Conclusion(s): By adding 5 predictors to the logistic clinical SYNTAX score, the score better predicts 2-year all-cause mortality after PCI. The score can be used for risk stratification and prediction in patients undergoing PCI in the contemporary practice. Categories: CORONARY: Stents: Drug-ElutingCopyright © 2019

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Author(s) Anderson S.; Garg S.; Saluja S.; Aghamohammadzadeh R.; Thiru S. et al.
Source Journal of the American College of Cardiology; Oct 2019; vol. 74 (no. 13)
DOI 10.1016/j.jacc.2019.08.990
Background: The impact of socioeconomic class on outcomes of percutaneous coronary intervention (PCI) in populations with access to universal unrestricted health care is limited. Furthermore, prior reports have focused mainly on patients with ST-segment elevation myocardial infarction (STEMI).

Method(s): We performed a retrospective analysis of centrally tracked outcomes from index PCI procedures entered in the British Cardiovascular Intervention Society database between 2007 and 2014 stratified according to quintiles of index of multiple deprivation (IMD; from the least deprived to the most deprived). The analyses were restricted to procedures performed in England. The primary endpoint was 30-day all-cause mortality, with secondary endpoints of mortality at 1 and 5 years. Hazard ratios (HRs) for mortality were determined from multivariate Cox regression models allowing for clustering by hospital.

Result(s): Among 437,024 eligible patients with 1.78 million person-years of observation, 40% of patients had PCI for stable coronary artery disease (CAD), 37.7% with non-STEMI, and 21.6% were treated for STEMI. A total of 52,258 patients (11.9%) died during a median of 3.5 years (interquartile range: 1.8 to 5.5 years) of follow-up. There was a trend toward an increase in crude mortality rates (per 1,000 person-years) with increasing quintile of IMD (from 26.7 per 1,000 in least deprived to 28.5 per 1,000 in the most deprived; p for trend <0.0001. When assessed by indication for PCI, only those undergoing intervention for non-STEMI or unstable angina had increased mortality rates as IMD worsened. In an age-, sex-, and indication for PCI-adjusted Cox regression multivariate analysis, mortality rates at 30 days were 14% greater (HR: 1.14; 95% confidence interval [CI]: 1.06 to 1.24; p < 0.0001) in patients from the most deprived areas compared with those with the least deprived IMD. These findings were similar for mortality at 1 year (HR: 1.09; 95% CI: 1.04 to 1.14) and at 5 years (HR: 1.10; 95% CI: 1.06 to 1.16).

​Conclusion(s): This very large, real-world dataset of patients demonstrates that deprivation is an independent marker of mortality following presentation with non-STEMI, and efforts should be directed at overcoming this. Reassuringly, in the setting of universal health care, deprivation does not influence outcomes from stable or STEMI presentation. Categories: OTHER: Political, International and Societal IssuesCopyright © 2019

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