Control In High-risk Patients Research Articles

Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-5-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: A multicentre, open-label, randomised, controlled, phase 3 trial.

6000 Background: Patients with N2-3 nasopharyngeal carcinoma have a high risk of failures, despite the current practice of concurrent adjuvant cisplatin-5-fluorouracil (PF) regime. Adjuvant PF regimen may not be adequate for tumor control of high risk patients, emphasizing the need for more effective regimen of adjuvant chemotherapy in N2-3 nasopharyngeal carcinoma. Methods: We conducted this multicentre, open-label, phase 3, randomised, controlled trial in four centers in China. Patients aged 18–65 years with stage T1–4N2–3 nasopharyngeal carcinoma were randomly assigned (1:1) to receive concurrent cisplatin (100mg/m2 intravenously) on days 1, 22, and 43 of radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously on day 1) (GP) once every 3 weeks or 5-fluorouracil (4 g/m2 in continuous intravenous infusion over 96 h) and cisplatin (80 mg/m2 on day 1 given intravenously) once every 4 weeks for three cycles. Randomisation was by a computer-generated random number code with a block size of six, stratified by treatment centre and nodal stage (N2 or N3). The primary endpoint was 3-year progression-free survival in the intention-to-treat population. This study is registered in ClinicalTrials.gov, NCT03321539. Results: From October 30, 2017 to July 9, 2020, 240 were randomly assigned to PF group (n = 120) or GP group (n = 120). After a median follow-up of 40 months (IQR: 32-48), the 3-year progression-free survival was 83.9% (95% CI 75.9–89.4) in GP group and 71.5% (62.5–78.7) in PF group (stratified HR 0.54; 95% CI, 0.32 to 0.93; p = 0.023). Significantly lower cumulative incidence of locoregional relapse (2.6% vs. 12.5%; HR 0.33; 95% CI, 0.12 to 0.90; Fine-Gray p = 0.030) and distant metastasis (10.4% vs. 20.1%; HR 0.50; 95% CI, 0.26 to 0.98; Fine-Gray p = 0.042) were also observed in GP group than PF group. However, there was no effect on early 3-year overall survival (90.7% vs. 94.0%; HR 1.12; 95% CI, 0.50 to 2.55; log-rank p = 0.779). Overall incidence of treatment-related adverse events was not significant different between the two treatment groups in the concurrent phase. In the adjuvant phase, significant higher incidence of grade 3-4 leucopenia (42 [41.2%] vs. 19 [16.8%], p < 0.001), neutropenia (33 [32.0%] vs. 10 [8.9%], p = 0.001) and thrombocytopenia (9 [8.7%] vs. 2 [1.8%], p = 0.044) was observed in GP group than PF group, whereas the frequency of diarrhea (6 [5.3%] vs. 0 [0%], p = 0.030) and mucositis (21 [18.6%] vs. 7 [6.8%], p = 0.010) was higher in PF group than in GP group. Conclusions: Concurrent adjuvant GP regimen significantly improved progression-free survival in patients with N2-3 nasopharyngeal carcinoma with acceptable toxicity. Long term follow-up is needed to confirm the ultimate therapeutic ratio. Clinical trial information: NCT03321539 .

Effects of the 2019 guideline-update on lipid therapy in patients with acute coronary syndromes

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): 2 Ludwig Boltzmann Institute for Cardiovascular Research. Background The European Society of Cardiology regularly updates its clinical practice guidelines. However, it is not well established whether guideline-changes have significant effects on actual clinical practice. Therefore, we retrospectively analyzed lipid therapy at discharge after acute coronary syndrome (ACS) in a one-year period until 3 months before and a one-year period starting 6 months after publication of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias, respectively. Methods and Results In total we included 702 patients that were discharged alive after treatment for ACS. 360 patients were treated in the period before and 342 were treated in the period after guideline change. 67.7 % of patients were male and 59.1% were treated for ST-elevation myocardial infarction (STEMI). After guideline change the proportion of patients that were discharged on high dose statin was significantly higher as compared to the period before the new guidelines were published (89.2 % vs 79.2 %; p=0.001). Ezetimibe was prescribed more often after the new guidelines (15.0 % vs 3.0 %; p<0.00001). Whereas proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were not prescribed at discharge in the earlier period, five patients were discharged on PCSK9i in the later period. The higher proportion of ezetimibe use and the introduction of PCSK9i resulted in an increased number of patients on high intensity treatment (high dose statin or moderate dose plus ezetimibe or PCSK9i: 92.4 % vs. 79.7 %; p<0.0001) in the period after the new guidelines. In 32.3 % of patients, cholesterol levels were available for the time period between one month and one year after discharge. Median on treatment LDL was significantly higher in the period before (64.4 IQR 47.4 – 94.2 mg/dL) than after the publication of the 2019 guidelines (46.2 IQR 33.8 – 61.8 mg/dl; p<0.00001). Conclusions The update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias was associated with a significant improve in the proportion of high dose statin and ezetimibe treatment in patients after ACS resulting in a significant lower LDL plasma level in a subgroup of patients. The change of these guidelines rapidly translated into clinical practice resulting in improved risk factor control in high-risk patients.

Postpartum Opioid Prescribing in Patients with Opioid Use Prior to Birth.

This study aimed to describe opioid prescribing patterns for pregnant patients with a history of or active opioid use to inform postpartum pain management strategies. We conducted a retrospective cohort analysis of all patients with a history of opioid use disorder (OUD) or chronic pain seen at a single outpatient clinic specializing in opioid use and OUD in pregnancy from January 2019 to August 2021. Patient characteristics, delivery outcomes, and opioid prescribing information were collected through electronic health record fields. We used descriptive statistics to characterize differences in receipt of an opioid prescription, prescription size, and receipt of a prescription refill across three patient groups: patients with OUD on medication, patients with OUD maintaining abstinence, and patients with chronic pain using opioids. In the study period, the institutional average rate of opioid prescribing after cesarean and vaginal birth were 80.0 and 2.8%, respectively. Of the 69 patients included in this study, 46 (66.7%) had a history of OUD on medication, 14 (20.3%) had a history of OUD maintaining abstinence, and 9 (13.0%) had a history of chronic pain. Receipt of an opioid prescription after childbirth was more common after cesarean birth (12/23, 52.2%) than vaginal birth (3/46, 6.5%). Refills were common in patients who received an opioid proscription (cesarean: 5/12, 41.7%; vaginal: 1/3, 33.3%). Compared with institutional averages, postpartum opioid prescribing rates for people with a history of OUD or chronic pain were 50 to 60% lower for cesarean birth and three times higher for vaginal birth. Future work is needed to balance opioid stewardship and harm reduction with adequate pain control in these high-risk populations. · Opioid prescribing rates for patients with OUD/chronic pain were 60% lower for cesarean birth than institutional averages.. · Opioid prescribing rates for patients with OUD/chronic pain were three times higher for vaginal birth than institutional averages.. · Refill rates following birth were high overall for cesarean (40%) and vaginal (33%) birth.. · More work is needed to balance opioid prescribing with adequate pain control in high-risk patients..

A review of ketogenic diets and their potential impact on COVID-19: Is there an interaction?

The aim of this review is to explore the potential significance of ketogenic diets (KDs) in the treatment and prevention of coronavirus, specifically focusing on their beneficial impacts on inflammation, immune responses, and the respiratory system. The study reviewed several COVID-19 observations and findings, particularly those concerning obesity as a contributing factor. As per the study, notable obesity is linked to an elevated chance of intensive care unit (ICU) admission requiring invasive mechanical ventilation in individuals with COVID-19. Additionally, the increasing weight gain associated with a SARS-CoV-2 infection prognosis may be attributed to various factors, including prolonged systemic inflammation, susceptibility to acute respiratory infections, and the influence of the viral disease. The article ultimately concludes that ketogenic diets may play a pivotal role in managing and preventing SARS-CoV-2 by diminishing the virus's impact on inflammatory responses, immune functionality, and respiratory system health. Furthermore, the article focuses on the link between extreme obesity and severe COVID-19 results, implying the need for weight control in high-risk patients.

CNS prophylaxis in aggressive B-cell lymphoma

The prevention of central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) continues to be one of the most contentious areas of lymphoma management. Outcomes for patients with secondary CNS lymphoma (SCNSL) have historically been very poor. However, in recent years improved responses have been reported with intensive immunochemotherapy approaches, and there is a growing interest in potential novel/cellular therapies. Traditional methods for selecting patients for CNS prophylaxis, including the CNS International Prognostic Index, are hampered by a lack of specificity, and there is accumulating evidence to question the efficacy of widely employed prophylactic interventions, including intrathecal and high-dose methotrexate (HD-MTX). Given the potential toxicity of HD-MTX in particular and the ongoing need to prioritize systemic disease control in high-risk patients, there is an urgent need to develop more robust methods for identifying patients at highest risk of CNS relapse, as well as investigating prophylactic interventions with greater efficacy. Here we review new evidence in this field from the last 5 years, focusing on the potential use of molecular diagnostics to improve the identification of high-risk patients, recent large data sets questioning the efficacy of HD-MTX, and the current approach to management of patients with SCNSL. We provide a suggested algorithm for approaching this very challenging clinical scenario.

Level of Control of Dyslipidemia Among Patients Followed in Family Medicine Clinics in Riyadh, Saudi Arabia.

BackgroundDyslipidemia is a well-established primary risk factor leading to atherosclerotic cardiovascular disease (ASCVD). Treatment with lifestyle modification and lipid-lowering agents has been shown to reduce ASCVD morbidity and mortality.ObjectivesTo explore the level of dyslipidemia control among patients followed in family medicine (FM) clinics and describe the prescribing pattern of lipid-lowering agents.Materials and methodsThis is a chart review cross-sectional observational study conducted over 382 patients who were followed in FM clinics at King Abdulaziz Medical City for National Guard, Riyadh, Saudi Arabia, from January 2016 to January 2019. The data were extracted from the electronic medical record system (BESTCare) and analyzed using Statistical Package for the Social Sciences (SPSS), version 23 (IBM Corp., Armonk, NY) to look for the association.ResultAll patients had a reduction in their lipid parameters over the three years follow-up period. The mean low-density lipoprotein cholesterol (LDL-C) for the total sample was (2.783 ± 0.850) mmol/L. 82.1% were using a statin alone, 6% were using statin plus fenofibrate, and 12.8% were switched from one statin to another. Those who had statin plus fenofibrate and those switched from one statin to another had the most reduction in their LDL, TC, and TG.ConclusionMost of the patients visiting the Ministry of National Guard - Health Affairs (MNG-HA), Riyadh, Saudi Arabia, showed a continuous reduction in their lipid profile over the follow-up period; with better control for high-risk patients. Many factors may have contributed to the reduction, like the number of clinic visits, dietician, and health educator visits, along with the type of medication used.

A split strategy to prevent cytomegalovirus after kidney transplantation using prophylaxis in serological high-risk patients and a pre-emptive strategy in intermediate-risk patients: Combining the best of two options?

Cytomegalovirus (CMV) remains an important challenge after kidney transplantation. Current Transplantation Society International Consensus Guidelines recommend antiviral prophylaxis or pre-emptive therapy for high-risk CMV-seronegative recipients with a CMV-seropositive donor (D+/R-) and moderate-risk CMV-seropositive recipients (R+). However, a split strategy according to CMV serostatus is not specifically mentioned. We evaluated a split strategy to prevent CMV infection after kidney transplantation in which D+/R- patients received valganciclovir (VGC) prophylaxis for 200days, and R+patients were treated pre-emptively according to CMV DNAemia. Patients were followed until 1-year post-transplant. Between April 2014 and March 2018, 40 D+/R- and 92 R+patients underwent kidney transplantation. Forty-six percent received antithymocyte globulin (ATG) induction, and 98% was treated with calcineurin inhibitors, mycophenolic acid (MPA), and steroids. No D+/R- patient developed CMV disease during prophylaxis (median 200days), but 15% developed post-prophylaxis or late-onset disease. Fifty-three percent developed neutropenia during prophylaxis, including 16/40 (40%) grade 3 or 4 neutropenia requiring reduction/discontinuation of MPA (30%) and/or VGC (35%), and an occasional need for granulocyte colony-stimulating factor (5%). In the R+group, 40% received antiviral therapy for a median duration of 21days; 5% developed early-onset CMV disease. Only 5% developed neutropenia. D+/R+status (hazard ratio (HR) 2.09,P=.004) and ATG use (HR 2.81, P<.0001) were risk factors for CMV reactivation. Prophylaxis leads to acceptable CMV control in high-risk patients but comes with a high risk of neutropenia. Pre-emptive therapy is effective and limits drug exposure in those at lower risk of CMV.

P1765COMBINING THE BEST OF TWO OPTIONS: A SPLIT STRATEGY WITH PROPHYLAXIS OR PRE-EMPTIVE THERAPY TO PREVENT CYTOMEGALOVIRUS AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Cytomegalovirus (CMV) remains an important challenge after kidney transplantation. Current Transplantation Society International Consensus Guidelines recommend antiviral prophylaxis or pre-emptive therapy for either high risk CMV-seronegative recipients of a CMV-seropositive donor (D+/R-) and moderate-risk CMV-seropositive recipients (R+). A split strategy according to CMV risk, however, is not specifically mentioned. Method We evaluated a split strategy to prevent cytomegalovirus infection after kidney transplantation. D+/R- patients received valganciclovir (VGC) prophylaxis during 200 days and R+ patients were treated pre-emptively according to CMV DNAemia. Results Between April 2014 and March 2018, 40 D+/R- and 92 R+ patients underwent kidney transplantation. Forty-six % received antithymocyte globuline (ATG) induction and 98 % were treated with calcineurin inhibitors, mycophenolic acid (MPA) and steroids. No D+/R- patient developed CMV disease during prophylaxis (median 200 days), 15 % developed late-onset disease. Fifty-three % developed neutropenia during prophylaxis, including 16/40 (40 %) grade 3 or 4 neutropenia requiring reduction/discontinuation of MPA (30 %) and/or VGC (30 %), and occasional need for granulocyte colony stimulating factors (5 %). In the R+ group, 40 % received antiviral therapy for a median duration of 21 days. Five percent developed CMV disease. Only 5 % developed neutropenia. D+/R+ status (hazard ratio (HR) 2.09, P 0.004) and ATG use (HR 2.81, P &amp;lt; 0.0001) were risk factors for CMV reactivation. Conclusion Prophylaxis leads to acceptable CMV control in high risk patients, but comes with a high risk of neutropenia. Pre-emptive therapy is effective and limits drug exposure in those at lower risk for CMV.

P573Effects of mobile text messaging on glycemic control in patients with coronary heart disease and diabetes mellitus: a randomized controlled trial

Abstract Background Mobile health interventions hold the prospect to support risk factor and lifestyle modification and are readily scalable in healthcare systems. Purpose We aim to assess whether text messaging program can improve glycemic control in high-risk patients with coronary heart disease (CHD) and diabetes mellitus (DM). Methods The study was a multi-centre randomised clinical trial conducted at 34 clinics in China. 502 individuals with both CHD and DM were recruited and randomly assigned to either the text messaging intervention (n=251) or control group (n=251). The control group received 2 thank-you messages per month in addition to usual care. The intervention group received 6 messages per week for 6 months. Messages provided educational and motivational information related to glucose monitoring, BP control, physical activity and lifestyle recommendations. The primary outcome was change in glycemic hemoglobin (HbA1C) from baseline to 6 months. Results Follow-up rate was 99%. At 6 months, HbA1C was significantly lower in intervention group compared to control group (mean HbA1C 6.7% vs. 7.2%, P&lt;0.001), with a mean change of −0.2% and 0.1% from baseline, respectively (mean absolute change −0.3% [95% CI −0.5 to 0.1]; P=0.003). Significantly more participants in intervention group achieved a HbA1c&lt;7% (69.3% vs. 52.6%; P=0.004), and change in FBG was larger in intervention group (−0.5 vs. 0.1 mmol/L; P=0.011). No differences in SBP, LDL-C, BMI and physical activity were observed. Almost all patients reported messages to be easy to understand (97.1%) and useful (94.1%). Table 1. Primary and Secondary Outcomes Analyses at 6 Month Follow-up Parameter Intervention (N=251) Control (N=251) Mean Difference in Change P value for Baseline 6 Months Mean Change Baseline 6 Months Mean Change (95% CI) Difference in Change Primary Outcome HbA1C level, %, mean (SD) 6.9 (1.4) 6.7 (1.3) −0.2 (1.0) 7.1 (1.4) 7.2 (1.5) 0.1 (1.1) −0.3 (−0.5, −0.1) 0.003 Secondary Outcomes HbA1C level&lt;7%, No. (%) 155 (62.0%) 174 (69.3%) – 139 (56.1%) 132 (52.6%) – 1.2 (1.1, 1.3)a 0.004 FBG, mmol/L, mean (SD) 8.1 (2.7) 7.5 (2.7) −0.5 (2.5) 8.5 (3.0) 8.6 (3.3) 0.1 (3.1) −0.6 (−1.1, −0.2) 0.011 SBP, mmHg, mean (SD) 135.9 (18.4) 134.7 (18.7) −1.4 (17.1) 135.9 (18.1) 132.2 (17.7) −3.5 (17.8) 2.4 (−0.8,5.5) 0.144 LDL-C, mmol/L, mean (SD) 2.6 (0.8) 2.5 (0.7) −0.1 (0.7) 2.6 (0.8) 2.5 (0.8) −0.1 (0.7) 0 (−0.1, 0.1) 0.828 BMI, mean (SD) 26.4 (3.2) 26.3 (3.5) −0.1 (2.1) 26.3 (3.2) 26.0 (3.4) −0.4 (2.5) 0.3 (−0.1, 0.7) 0.213 Physical activity (MET min/wk), 1386 1386 177 1386 1386 322 −70.7 0.784 median (IQR) (693–3066) (918–3612) (2840) (693–3066) (693–3002) (2635) (−574.9, 433.5) Conclusion Use of a simple, culturally sensitive mobile text-messaging program could be an effective and scalable way to improve disease self-management among patients with CHD and DM. Acknowledgement/Funding Research Special Fund for Public Welfare Industry of Health (201502009) from the National Health and Family Planning Commission of China

Weekly Screening for Multidrug-Resistant Organisms Identifies High Number of Colonizations in Patients Undergoing Stem Cell Transplantation

Introduction:Multidrug-resistant organisms (MDRO) are a challenge in patients undergoing stem cell transplant (SCT) which often result in an increase in mortality. To our knowledge, current literature defines only screening at the time of work-up for SCT-patients. The aims of the study were to assess the rate of MDRO colonization with weekly screening, rate of infection and the associated mortality in patients undergoing SCT.Patients and methods:Consecutive patients admitted at the SCT unit between January-18 to July-18 were reviewed in our institution. Screening consisted of rectal and perineal swab on admission and weekly until the date of discharge. In case of detection of MDRO , patients were isolated and infection control strategies were applied.Results:41 patients were analysed, with 47 admissions, 6 patients had 2 admissions. The median duration of hospitalization was 27 days/patient (range 8-100). 168 rectal-and perineal swab were performed with a median of 3 swabs/patient (range 1-7). Patient characteristics are shown in Table 1. 36 patients (87%) spiked fever in a median of 8,5 days after admission (1-38days). 24,4% (n=10) had a positive screening: 2/10 patients at baseline and 8/10 patients (80%) were detected for the first time beyond baseline screen. Rate of MDRO colonization was 3% per week (95%CI 1.4-5.4). MDRO identified were : 4 patients with Extended-spectrum beta-lactamases producing E. Coli (ESBL-EC), Multidrug-resistant (MR) Pseudomonas aeruginosa (n=3), Vancomycin-resistant Enterococci (n=2) and 1 patient with carbapenem-resistant Citrobacter freundii. 6/10 patients developed MDRO infection (60%), all with previous MDRO positive detection: MR-Pseudomonas aeruginosa in urine culture (n=3) 2 treated with ceftolozane/tazobactam, 1 with meropenem+amikacin; ESBL-EC in urine culture (n=2) both treated with meropenem and 1 with Klebsiella pneumoniae carbapenemase in urine culture treated with ceftazidime/avibactam. The infection rate was 4,6% (95% CI 3.9-5.2). In 80% patients (n=8) antibiotic treatment was guided by positive screening, 3 patients were admitted to intensive care unit for sepsis. No mortality was associated to MDRO.In 76%of patients (n=28) screening was negative for MDRO. 24/28 (85%) spiked fever with a median of 10 days after admission (1-38days). None MDRO-infections in negative-screened patients were detected.Conclusions :Weekly screening for MDRO identified a high number of MDRO colonizations allowing to apply early strategies of infection control in high risk patients . Besides, MDRO infection occurred only in patients previously colonized, therefore, 80% of our cohort could benefit from guided treatment by the time of the febrile episode. Early identification of MDRO colonization might have helped to reduce MDRO related mortality. However, these findings should be confirmed with further studies, comparing baseline with weekly MDRO screening strategies. DisclosuresNo relevant conflicts of interest to declare.

Role of alternative interventional procedures when endo- and epicardial catheter ablation attempts for ventricular arrhythmias fail.

Ventricular tachycardia (VT) refractory to antiarrhythmic drugs and standard percutaneous catheter ablation techniques portends a poor prognosis. We characterized the reasons for ablation failure and describe alternative interventional procedures in this high-risk group. Sixty-seven patients with VT refractory to 4±2 antiarrhythmic drugs and 2±1 previous endocardial/epicardial catheter ablation attempts underwent transcoronary ethanol ablation, surgical epicardial window (Epi-window), or surgical cryoablation (OR-Cryo; age, 62±11 years; VT storm in 52%). Failure of endo/epicardial ablation attempts was because of VT of intramural origin (35 patients), nonendocardial origin with prohibitive epicardial access because of pericardial adhesions (16), and anatomic barriers to ablation (8). In 8 patients, VT was of nonendocardial origin with a coexisting condition also requiring cardiac surgery. Transcoronary ethanol ablation alone was attempted in 37 patients, OR-Cryo alone in 21 patients, and a combination of transcoronary ethanol ablation and OR-Cryo (5 patients), or transcoronary ethanol ablation and Epi-window (4 patients), in the remainder. Overall, alternative interventional procedures abolished ≥1 inducible VT and terminated storm in 69% and 74% of patients, respectively, although 25% of patients had at least 1 complication. By 6 months post procedures, there was a significant reduction in defibrillator shocks (from a median of 8 per month to 1; P<0.001) and antiarrhythmic drug requirement although 55% of patients had at least 1 VT recurrence, and mortality was 17%. A collaborative strategy of alternative interventional procedures offers the possibility of achieving arrhythmia control in high-risk patients with VT that is otherwise uncontrollable with antiarrhythmic drugs and standard percutaneous catheter ablation techniques.

Management Strategies in Advanced Uterine Leiomyosarcoma: Focus on Trabectedin.

The treatment of advanced uterine leiomyosarcomas (U-LMS) represents a considerable challenge. Radiological diagnosis prior to hysterectomy is difficult, with the diagnosis frequently made postoperatively. Whilst a total abdominal hysterectomy is the cornerstone of management of early disease, the role of routine adjuvant pelvic radiotherapy and adjuvant chemotherapy is less clear, since they may improve local tumor control in high risk patients but are not associated with an overall survival benefit. For recurrent or disseminated U-LMS, cytotoxic chemotherapy remains the mainstay of treatment. There have been few active chemotherapy drugs approved for advanced disease, although newer drugs such as trabectedin with its pleiotropic mechanism of actions represent an important addition to the standard front-line systemic therapy with doxorubicin and ifosfamide. In this review, we outline the therapeutic potential and in particular the emerging evidence-based strategy of therapy with trabectedin in patients with advanced U-LMS.

Lipid control in high-risk patients: focus on PCSK9 inhibitors

Low-density lipoprotein (LDL)-cholesterol levels are strictly related to the risk of major cardiovascular events. Statins have been demonstrated to significantly reduce LDL-cholesterol levels, contributing to cardiovascular risk reduction especially in high-risk patients. However, low adherence to statins, due to adverse effects, is often observed and many patients in secondary prevention exhibit LDL-cholesterol levels >70 mg/dl. As a consequence, there is the need for new therapeutic approaches with different mechanisms of action to reach recommended lipid targets in high-risk patients. One potential approach is to inhibit PCSK9, a serum protein with an active role in controlling the expression of LDL receptors, by reducing their recycling and targeting it for lysosomal destruction. Monoclonal antibodies against PCSK9, in particular alirocumab and evolocumab, have been shown to reduce LDL substantially, either with or without concomitant statin therapy with good tolerability. Ongoing trials will further define the efficacy of these drugs as an emerging approach to the treatment of hypercholesterolemia in primary and secondary prevention of high-risk patients.

Factors Affecting Mortality and Treatment Completion of Tuberculosis Patients in Isfahan Province from 2006 to 2011.

Background:Regarding cases of infectious diseases tuberculosis (TB) is the most important cause of death and according to the DALY criteria, this disease has the seventh position in global disease ranking. In this study, we aim to determine the risk factors, which have a significant effect on the treatment completion and mortality of TB patients.Methods:This study is a retrospective cohort study. The sample is made up of registered TB patients in the Isfahan Province from 2006 to 2011. Information of the patients was collected from their files in health centers in the Isfahan Province. Variables such as age, sex, weight, nationality, residence, type of TB, imprisonment, human immunodeficiency virus, TB case were measured. Descriptive statistics (including frequency, percentage, mean and standard deviation) and statistical analysis (including Cox proportional hazard model) were used.Results:The result showed that imprisonment (hazard ratio [HR] = 4.76, P = 0.019), age (HR = 4.44, P = 0.001) and the TB case (HR = 2.73, P = 0.037) of pulmonary TB had significant impacts on mortality of the patients, also in the case of treatment completion, the TB case (HR = 0.34, P < 0.001) proved to have a significant impact on completion of the treatment. Type of extra-pulmonary TB in extra-pulmonary TB patients also had an effect on treatment completion.Conclusions:We can conclude that factors such as age, imprisonment, TB case and type of extra-pulmonary TB are effective on the treatment completion and mortality of the patients. It may be useful for policy makers to make more control of high-risk patients.

Misery perfusion, blood pressure control, and 5-year stroke risk in symptomatic major cerebral artery disease.

The benefit of strict blood pressure (BP) control in high-risk patients with symptomatic major cerebral artery disease and misery perfusion (MP) is controversial. Our purposes were (1) to determine whether MP is a predictor of a 5-year risk of subsequent stroke and (2) to investigate the relationships among BP during follow-up, MP, and the stroke risk. We studied 130 nondisabled patients with symptomatic major cerebral artery disease. Baseline hemodynamic measurements were obtained from (15)O-gas positron emission tomography, and patients received medical treatment and they were followed for 5 years or until stroke recurrence or death. During 5 years, strokes occurred in 6 of 16 patients with MP and in 15 of 114 without MP (log-rank test; P<0.01). There were 4 (25%) ipsilateral ischemic strokes in patients with MP and 4 in those without MP (P<0.001). The risk of ipsilateral ischemic stroke declined markedly after 2 years, and there was only 1 ipsilateral ischemic stroke in a patient without MP. Normal systolic BP (<130 mm Hg) was associated with an increased risk of ipsilateral ischemic strokes in patients with impaired perfusion (including MP), whereas systolic BP outside the 130 to 149 mm Hg range was associated with an increased risk of all strokes in patients without MP. Patients with MP showed a high-5-year stroke recurrence, but a large part of the 5-year stroke risk disappeared after 2 years. Aggressive BP control may be hazardous in patients with impaired perfusion, including MP.

Role of Single‐Pill Combination Therapy in Optimizing Blood Pressure Control in High‐Risk Hypertension Patients and Management of Treatment‐Related Adverse Events

Renin-angiotensin-aldosterone system (RAAS) inhibitors in combination with other antihypertensive drugs (eg, calcium channel blockers [CCBs] and/or diuretics) are a preferred treatment option for managing uncontrolled hypertension in high-risk patients with chronic kidney disease (CKD), diabetes, or heart failure because RAAS inhibitors provide cardiorenal benefits in addition to lowering blood pressure (BP). However, when prescribing antihypertensive therapies to high-risk patients, physicians must be aware of the risks of treatment-related adverse events of hyperkalemia and peripheral edema associated with RAAS inhibitors and CCBs, respectively. This review discusses the use of single-pill combination antihypertensive therapy to optimize BP control in high-risk patients with CKD, diabetes, and/or heart failure and provides strategies for preventing and managing hyperkalemia and peripheral edema in this group. Single-pill combination therapy can utilize different classes of antihypertensive drugs to reduce BP while mitigating the risks of treatment-related adverse events, reducing pill burden, lowering medical cost, and improving patient compliance.

Landscape of Combination Therapy – Which Way Forward? Proceedings of the Satellite Symposium Held at the ESH European Meeting on Hypertension and Cardiovascular Protection, 27 April 2012, London

Early combination therapy is more effective for hypertension control in high-risk patients than monotherapy, and current guidelines recommend the use of either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) for first-line therapy in patients younger than 55 years. Recent evidence shows that ACEIs reduce mortality, whereas ARBs show no apparent benefit despite their blood pressure lowering action. However, it is important to consider which blood pressure parameters should be targeted given that different drugs have distinct effects on key parameters. Remarkably, a high percentage of hypertensive patients whose treatment has brought these parameters within target ranges still remain at high risk of cardiovascular disease due to additional risk factors. Combination therapy with synergistic effects on blood pressure and metabolic control should thus be considered for the long-term treatment of hypertensive patients with co-morbid conditions.

The potential role of ductoscopy in modern breast diagnostics and therapy

Mammary ductoscopy is a modern, minimally invasive procedure that enables direct, in vivo observation of the mammary ductal system, primarily by nipple discharge. The rapidly developing device is suitable for aimed biopsy for further cytological or molecular examinations. High-tech equipments facilitate polypectomy or laser vaporization of certain intraluminal lesions, and play an important role in the direct surgical excision of the duct or the so-called terminal duct-lobular unit. The above listed facilitate the early diagnosis of malignancies even before imaging could detect them, and the control of high risk patients. Ductoscopy can foster surgical removal of ductal in situ tumors as anatomical units, thus enabling the optimization of radicality of breast conserving surgeries. Authors give a detailed description of the surgical techniques, and provide a wide review of the literature, for the first time in Hungarian language. Orv. Hetil., 2011, 152, 1284–1293.

Uterine sarcomas—Recent progress and future challenges

Uterine sarcomas are a group of rare tumours that provide considerable challenges in their treatment. Radiological diagnosis prior to hysterectomy is difficult, with the diagnosis frequently made post-operatively. Current staging systems have been unsatisfactory, although a new FIGO staging system specifically for uterine sarcomas has now been introduced, and may allow better grouping of patients according to expected prognosis. While the mainstay of treatment of early disease is a total abdominal hysterectomy, it is less clear whether routine oophorectomy or lymphadenectomy is necessary. Adjuvant pelvic radiotherapy may improve local tumour control in high risk patients, but is not associated with an overall survival benefit. Similarly there is no good evidence for the routine use of adjuvant chemotherapy. For advanced leiomyosarcoma, newer chemotherapy agents including gemcitabine and docetaxel, and trabectedin, offer some promise, while hormonal therapies appear to be more useful in endometrial stromal sarcoma. Novel targeted agents are now being introduced for sarcomas, and uterine sarcomas, and show some indications of activity. Non-pharmacological treatments, including surgical metastatectomy, radiofrequency ablation, and CyberKnife ® radiotherapy, are important additions to systemic therapy for advanced metastatic disease.

Prognostic Factors and Outcome Analysis of Submandibular Gland Cancer: A Clinical Audit

To retrospectively review a long-term, single-institution experience of subjects with submandibular gland malignancies treated with definitive locoregional therapy with an aim to identify clinicopathologic variables that correlate with outcomes. A comprehensive chart review of 47 patients presenting to the institute from 1993 to 2005 with a histologic diagnosis of submandibular salivary gland cancer was performed to extract demographic data, clinicopathological characteristics, and treatment details. Clinical and pathologic factors were correlated with locoregional control, distant metastases free survival, and disease-free survival using log-rank test and Cox proportional hazards model for univariate and multivariate analysis, respectively. With a median follow-up of 29 months (interquartile range, 13 to 64 months), the actuarial 5-year locoregional control, distant metastasis-free survival, and disease-free survivals of the entire cohort were 80.5%, 86.1%, and 71.8%, respectively. Overall stage grouping (P = .008), perineural invasion (P = .04), and radiotherapy dose (P = .033) were significant predictors of locoregional control. Overall stage grouping (P = .014) and T stage (P = .05) also affected disease-free survival. Extraglandular involvement showed a trend toward poorer outcome. Submandibular gland cancer is a rare disease with histologic diversity and variable clinical behavior. Overall stage grouping and perineural invasion remain the most significant predictors of outcome. Adequate doses of adjuvant radiotherapy improve locoregional control in high-risk patients.