Lung function trajectories from school age to adulthood and their relationship with markers of cardiovascular disease risk.

RATIONALE: Lung function in early adulthood is associated with subsequent adverse health outcomes. OBJECTIVES: To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function. METHODS: Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). We used multinomial logistic regression models to investigate early-life predictors of the derived trajectories. We then ascertained the extent of the association between the derived FEV1/FVC trajectories and blood pressure and echocardiographic markers of increased cardiovascular risk and stroke in ~3200 participants at age 24 years in one of our cohorts. RESULTS: We identified four FEV1/FVC trajectories with strikingly similar latent profiles across cohorts (pooled N=6377): above average (49.5%); average (38.3%); below average (10.6%); and persistently low (1.7%). Male sex, wheeze, asthma diagnosis/medication and allergic sensitisation were associated with trajectories with diminished lung function in all cohorts. We found evidence of an increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV1/FVC (with p values for the mean crude effects per-trajectory ranging from 0.10 to p<0.001). In this analysis, we considered trajectories as a pseudo-continuous variable; we confirmed the assumption of linearity in all the regression models. CONCLUSIONS: Childhood lung function trajectories may serve as predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood.

Determinants of lung function development from birth to age 5 years: an interrupted time series analysis of a South African birth cohort.

BACKGROUND: Early life is a key period that determines long-term health. Lung development in childhood predicts lung function attained in adulthood and morbidity and mortality across the life course. We aimed to assess the effect of early-life lower respiratory tract infection (LRTI) and associated risk factors on lung development from birth to school age in a South African birth cohort. METHODS: We prospectively followed children enrolled in a population-based cohort from birth (between March 5, 2012 and March 31, 2015) to age 5 years with annual lung function assessment. Data on multiple early-life exposures, including LRTI, were collected. The effect of early-life risk factors on lung function development from birth to age 5 years was assessed using the Generalised Additive Models for Location, Scale and Shape and Interrupted Time Series approach. FINDINGS: 966 children (475 [49·2%] female, 491 [50·8%] male) had lung function measured with oscillometry, tidal flow volume loops, and multiple breath washout. LRTI occurred in 484 (50·1%) children, with a median of 2·0 LRTI episodes (IQR 1·0-3·0) per child. LRTI was independently associated with altered lung function, as evidenced by lower compliance (0·959 [95% CI 0·941-0·978]), higher resistance (1·028 [1·016-1·041]), and higher respiratory rate (1·018 [1·063-1·029]) over 5 years. Additional impact on lung function parameters occurred with each subsequent LRTI. Respiratory syncytial virus (RSV) LRTI was associated with lower expiratory flow ratio (0·97 [0·95-0·99]) compared with non-RSV LRTI. Maternal factors including allergy, smoking, and HIV infection were also associated with altered lung development, as was preterm birth, low birthweight, female sex, and coming from a less wealthy household. INTERPRETATION: Public health interventions targeting LRTI prevention, with RSV a priority, are vital, particularly in low-income and middle-income settings. FUNDING: UK Medical Research Council Grant, The Wellcome Trust, The Bill & Melinda Gates Foundation, US National Institutes of Health Human Heredity and Health in Africa, South African Medical Research Council, Hungarian Scientific Research Fund, and European Respiratory Society.

Obstructive and restrictive spirometry from school age to adulthood: three birth cohort studies.

Background: Spirometric obstruction and restriction are two patterns of impaired lung function which are predictive of poor health. We investigated the development of these phenotypes and their transitions through childhood to early adulthood. Methods: In this study, we analysed pooled data from three UK population-based birth cohorts established between 1989 and 1995. We applied descriptive statistics, regression modelling and data-driven modelling to data from three population-based birth cohorts with at least three spirometry measures from childhood to adulthood (mid-school: 8-10 years, n = 8404; adolescence: 15-18, n = 5764; and early adulthood: 20-26, n = 4680). Participants were assigned to normal, restrictive, and obstructive spirometry based on adjusted regression residuals. We considered two transitions: from 8-10 to 15-18 and from 15-18 to 20-26 years. Findings: Obstructive phenotype was observed in ∼10%, and restrictive in ∼9%. A substantial proportion of children with impaired lung function in school age (between one third in obstructive and a half in restricted phenotype) improved and achieved normal and stable lung function to early adulthood. Of those with normal lung function in school-age, <5% declined to adulthood. Underweight restrictive and obese obstructive participants were less likely to transit to normal. Maternal smoking during pregnancy and current asthma diagnosis increased the risk of persistent obstruction and worsening. Significant associate of worsening in restrictive phenotypes was lower BMI at the first lung function assessment. Data-driven methodologies identified similar risk factors for obstructive and restrictive clusters. Interpretation: The worsening and improvement in obstructive and restrictive spirometry were observed at all ages. Maintaining optimal weight during childhood and reducing maternal smoking during pregnancy may reduce spirometry obstruction and restriction and improve lung function. Funding: MRC Grant MR/S025340/1.

Clinical features, socioeconomic status, management, short and long-term outcomes of patients with acute myocardial infarction: Phase I results of PEACE MENA registry.

BACKGROUND: The Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa (PEACE MENA) is a prospective registry program in Arabian countries that involves in patients with acute myocardial infarction (AMI) or acute heart failure (AHF). METHODS: This prospective, multi-center, multi-country study is the first report of the baseline characteristics and outcomes of inpatients with AMI who were enrolled during the first 14-month recruitment phase. We report the clinical characteristics, socioeconomic, educational levels, and management, in-hospital, one month and one-year outcomes. RESULTS: Between April 2019 and June 2020, 1377 patients with AMI were enrolled (79.1% males) from 16 Arabian countries. The mean age (± SD) was 58 ± 12 years. Almost half of the population had a net income < $500/month, and 40% had limited education. Nearly half of the cohort had a history of diabetes mellitus, hypertension, or hypercholesterolemia; 53% had STEMI, and almost half (49.7%) underwent a primary percutaneous intervention (PCI) (lowest 4.5% and highest 100%). Thrombolytics were used by 36.2%. (Lowest 6.45% and highest (90.9%). No reperfusion occurred in 13.8% of patients (lowest was 0% and highest 72.7%).Primary PCI was performed less frequently in the lower income group vs. high income group (26.3% vs. 54.7%; P<0.001). Recurrent ischemia occurred more frequently in the low-income group (10.9% vs. 7%; P = 0.018). Re-admission occurred in 9% at 1 month and 30% at 1 year, whereas 1-month mortality was 0.7% and 1-year mortality 4.7%. CONCLUSION: In the MENA region, patients with AMI present at a young age and have a high burden of cardiac risk factors. Most of the patients in the registry have a low income and low educational status. There is heterogeneity among key performance indicators of AMI management among various Arabian countries.

Clinical Features, Socioeconomic Status, Management, and Outcomes of Acute Heart Failure: PEACE MENA Registry Phase I Results.

INTRODUCTION: PEACE MENA (Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa) is a prospective registry in Arab countries for in-patients with acute myocardial infarction (AMI) or acute heart failure (AHF). Here, we report the baseline characteristics and outcomes of in-patients with AHF who were enrolled during the first 14 months of the recruitment phase. METHODS: A prospective, multi-centre, multi-country study including patients hospitalized with AHF was conducted. Clinical characteristics, echocardiogram, BNP (B-type natriuretic peptide), socioeconomic status, management, 1-month, and 1-year outcomes are reported. RESULTS: Between April 2019 and June 2020, a total of 1258 adults with AHF from 16 Arab countries were recruited. Their mean age was 63.3 (±15) years, 56.8% were men, 65% had monthly income ≤US$ 500, and 56% had limited education. Furthermore, 55% had diabetes mellitus, 67% had hypertension; 55% had HFrEF (heart failure with reduced ejection fraction), and 19% had HFpEF (heart failure with preserved ejection fraction). At 1 year, 3.6% had a heart failure-related device (0-22%) and 7.3% used an angiotensin receptor neprilysin inhibitor (0-43%). Mortality was 4.4% per 1 month and 11.77% per 1-year post-discharge. Compared with higher-income patients, lower-income patients had a higher 1-year total heart failure hospitalization rate (45.6 vs 29.9%, p=0.001), and the 1-year mortality difference was not statistically significant (13.2 vs 8.8%, p=0.059). CONCLUSION: Most of the patients with AHF in Arab countries had a high burden of cardiac risk factors, low income, and low education status with great heterogeneity in key performance indicators of AHF management among Arab countries.

A strategy to improve adherence to guideline-directed medical therapy (GDMT) and the role of the multidisciplinary team in a heart-failure programme.

BACKGROUND: Heart failure (HF) patients place a heavy burden on the healthcare system because of their frequent need for in-patient treatment, emergency room visits and subsequent hospital stays. To provide proper care and effective therapy, practitioners have streamlined delivery techniques such as clinical pathways, checklists and pocket manuals. However, a description of the establishment of a disease-management programme, including a multidisciplinary team of physicians, clinical pharmacists and nurse specialists is required. The aim of this study was to highlight the role of the multidisciplinary team in a heart-failure programme by assessing the improvement in adherence to guideline-directed medical therapy. METHODS: A retrospective, observational research was undertaken on patients with HF at a cardiac centre in Riyadh, to observe the HF patients' management before (January to December 2014) and after (January to December 2015) the establishment of a programme. RESULTS: The use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers was 75.59% in 2014 at discharge and 81.17% in 2015 (p = 0.249). Beta-blockers use at release increased from 87.83% in 2014 to 94.53% in 2015 (p = 0.021). The flu vaccine was given to 48.24% of patients in 2014 and 75.13% of the patients in 2015 (p < 0.001). The pneumococcal vaccine was administered to 44.22% of patients in 2014 and 75.13% of patients in 2015 (p < 0.001). The ejection fraction improved from 30.21% in the first month to 39.56% in the 12th month (p = 0.001) in patients managed in 2015. CONCLUSION: The multidisciplinary heart-failure programme resulted in a positive effect, in the form of improved patient care after including the clinical pharmacist and nurse specialist.

Evolution of Eczema, Wheeze, and Rhinitis from Infancy to Early Adulthood: Four Birth Cohort Studies.

Rationale: The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear. Objectives: To investigate within-individual patterns of morbidity of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood. Methods: We investigated onset, progression, and resolution of eczema, wheeze, and rhinitis using descriptive statistics, sequence mining, and latent Markov modeling in four population-based birth cohorts. We used logistic regression to ascertain if early-life eczema or wheeze, or genetic factors (filaggrin [FLG] mutations and 17q21 variants), increase the risk of multimorbidity. Measurements and Main Results: Single conditions, although the most prevalent, were observed significantly less frequently than by chance. There was considerable variation in the timing of onset/remission/persistence/intermittence. Multimorbidity of eczema+wheeze+rhinitis was rare but significantly overrepresented (three to six times more often than by chance). Although infantile eczema was associated with subsequent multimorbidity, most children with eczema (75.4%) did not progress to any multimorbidity pattern. FLG mutations and rs7216389 were not associated with persistence of eczema/wheeze as single conditions, but both increased the risk of multimorbidity (FLG by 2- to 3-fold, rs7216389 risk variant by 1.4- to 1.7-fold). Latent Markov modeling revealed five latent states (no disease/low risk, mainly eczema, mainly wheeze, mainly rhinitis, multimorbidity). The most likely transition to multimorbidity was from eczema state (0.21). However, although this was one of the highest transition probabilities, only one-fifth of those with eczema transitioned to multimorbidity. Conclusions: Atopic diseases fit a multimorbidity framework, with no evidence for sequential atopic march progression. The highest transition to multimorbidity was from eczema, but most children with eczema (more than three-quarters) had no comorbidities.

Ischemic cardiomyopathy versus non-ischemic cardiomyopathy in diabetic patients: clinical characteristics, management, and long-term outcomes.

BACKGROUND: Diabetes mellitus causes ischemic heart disease (IHD) through macrovascular or microvascular involvement. Diabetes-associated hypertension, dyslipidemia, and obesity further increase coronary artery disease risk and can cause left ventricular hypertrophy leading to heart failure with preserved ejection fraction independent of IHD. This study was undertaken to evaluate the differences in demographics, clinical characteristics, Echocardiographic parameters, management, and outcomes between non-ischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) patients in cohort of diabetes patients. METHODS: This retrospective study included diabetes patients with reduced ejection fraction (≤40) who were hospitalized with heart failure between January 2014 and February 2020. Patients were divided into two groups: group 1; ICM and group 2; NICM. Data obtained on above mentioned features including mortality and heart failure readmissions were compared between the two groups. RESULTS: A total of 612 diabetes patients admitted with acute heart failure were screened of which 442 were included. Group 1 (ICM) had 361 patients (81.7%) and group 2 (NICM) had 81 patients (18.3%). Patients in group 1 were older, predominantly males and with higher prevalence of hypertension, smoking and insulin dependent Diabetes while group 2 patients had higher BMI and higher prevalence of cardiac rhythm problems. No significant difference was detected in 5-year-mortality between the two groups (P=0.165). However, heart failure associated hospitalizations were higher in group 2 though it was not statistically significant (P=0.062). CONCLUSION: There was no difference in 5-years mortality between ICM and NICM in diabetes patients. However, NICM patients had higher prevalence of obesity and rhythm problems.

Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia.

Background: Chronic myeloid leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(9;22) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKIs) has changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, the mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find novel biomarkers of CML progression by employing whole-exome sequencing (WES). Materials and Methods: WES of accelerated phase (AP) and blast crisis (BC) CML patients was carried out, with chronic-phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing were carried out using Illumina platforms. Statistical analysis was carried out using SAS/STAT software version 9.4, and R package was employed to find mutations shared exclusively by all AP-/BC-CML patients. Confirmation of mutations was carried out using Sanger sequencing and protein structure modeling using I-TASSER followed by mutant generation and visualization using PyMOL. Results: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modeling studies showed that mutations induce structural changes in ANKRD36 protein. Conclusions: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in humans. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in the biology and progression of CML.

Effects of compressive lesions on intraoperative human spinal cord elasticity.

OBJECTIVE: Although evaluating tissue elasticity has various clinical applications, spinal cord elasticity (SCE) in humans has never been well documented. In this study, the authors aimed to evaluate the impact of compression on human SCE in vivo. METHODS: The authors prospectively assessed SCE using intraoperative shear wave elastography (SWE). All consecutive patients undergoing spinal cord (SC) decompression (laminectomy or corpectomy) between June 2018 and June 2019 were included. After intraoperative exposure of the patient's dura mater, at least three SWE measurements of the SC and its coverings were performed. Intraoperative neurological monitoring in the form of motor and somatosensory evoked potentials was utilized. Cases were divided into two groups based on the state of SC compression following bone removal (laminectomy or corpectomy): patients with adequate decompression (the decompressed SC group [DCG]) following bone removal and patients with remining compression, e.g., compressing tumor or instability (the compressed SC group [COG]). RESULTS: A total of 25 patients were included (8 females and 17 males) with a mean age of 48.28 ± 21.47 years. Most cases were degenerative diseases (10 cases) followed by tumors (6 cases), and the compression was observed at cervical (n = 14), thoracic (n = 9), and conus medullaris (n = 2) levels. The COG (6 cases) expressed significantly higher elasticity values, i.e., greater stiffness (median 93.84, IQR 75.27-121.75 kPa) than the decompressed SC in DCG (median 9.35, IQR 6.95-11.22 kPa, p < 0.001). Similarly, the compressed dura mater in the COG was significantly stiffer (mean ± SD 121.83 ± 70.63 kPa) than that in the DCG (29.78 ± 18.31 kPa, p = 0.042). Following SC decompression in COG, SCE values were significantly reduced (p = 0.006; adjusted for multiple comparisons). Intraoperative monitoring demonstrated no worsening from the baseline. CONCLUSIONS: The current study is to the authors' knowledge the first to quantitatively demonstrate increased stiffness (i.e., elasticity value) of the human SC and dura mater in response to external compression in vivo. It appears that SCE is a dynamic phenomenon and is reduced following decompression. Moreover, the evaluation of human SCE using the SWE technique is feasible and safe. Information from future studies aiming to further define SCE could be valuable in the early and accurate diagnosis of the compressed SC.

Phenotypic and molecular characterization of virulence factors of extra-intestinal pathogenic Escherichia coli isolated from patients of Peshawar, Pakistan.

Extra-Intestinal Escherichia coli (ExPEC) are important cause of Urinary Tract Infections (UTIs) and systemic infections. The purpose of this study was to investigate numerous ExPEC bacterial isolates for phenotypic virulence characteristics including hemolytic activity and resistance pattern and to observe their association with genetic traits via Polymerase Chain Reaction (PCR). A total of 367 ExPEC isolates were collected from patients admitted in Khyber Teaching Hospital (KTH) Peshawar, Pakistan. Standard techniques were used for identification of isolates, determination of hemolytic potential and antimicrobial susceptibility testing. PCR was used for screening of virulence genes using specific primers. A total of 367 ExPEC isolates were characterized, among which 62.7, 24.3, 7.1 and 6% were isolated from urine, pus, sputum and wound specimens, respectively. Majority of the isolates (82.8%) were hemolysin positive. Multi drug resistance pattern was shown by 41% of the isolates and harbored at least one virulence gene (71.7%), of which sat was the most prevalent (64.3%). The highest resistance was found to cefotaxime (99.2%), ampicillin (97.5%) and aztreonem (89.6%). 15 different virulence genes combinations were observed in the current study. A total of 16 virotypes (15 of positive virulence genes and one of no virulence gene) were observed in the current study. The current investigation showed a high prevalence of sat and hlyA genes among ExPEC isolate, suggesting a role of these genes in the pathogenesis of ExPEC.

Correction: Acute Myocardial Infarction and Acute Heart Failure in the Middle East and North Africa: Study Design and Pilot Phase Study Results from the PEACE MENA Registry.

[This corrects the article DOI: 10.1371/journal.pone.0236292.].

The Burden of Cardiovascular Disease Risk Factors in the Middle East: A Systematic Review and Meta-Analysis Focusing on Primary Prevention.

BACKGROUND: The increasing incidence of cardiovascular disease (CVD) threatens the Middle Eastern population. Several epidemiological studies have assessed CVD and its risk factors in terms of the primary prevention of CVD in the Middle East. Therefore, summarizing the information from these studies is essential. AIM: We conducted a systematic review to assess the prevalence of CVD and its major risk factors among Middle Eastern adults based on the literature published between January 1, 2012, and December 31, 2018, and carried out a meta-analysis. METHODS: We searched electronic databases such as PubMed/Medline, ScienceDirect, Embase and Google Scholar to identify literature published from January 1, 2012, to December 31, 2018. All the original articles that investigated the prevalence of CVD and reported at least one of the following factors were included: hypertension, diabetes, dyslipidaemia, smoking and family history of CVD. To summarize CVD prevalence, we performed a random-effects meta-analysis. RESULTS: A total of 41 potentially relevant articles were included, and 32 were included in the metaanalysis (n=191,979). The overall prevalence of CVD was 10.1% (95% confidence interval (CI): 7.1- 14.3%, p<0.001) in the Middle East. A high prevalence of CVD risk factors, such as dyslipidaemia (43.3%; 95% CI: 21.5-68%), hypertension (26.2%; 95% CI: 19.6-34%) and diabetes (16%; 95% CI: 9.9- 24.8%), was observed. The prevalence rates of other risk factors, such as smoking (12.4%; 95% CI: 7.7- 19.4%) and family history of CVD (18.7%; 95% CI: 15.4-22.5%), were also high. CONCLUSION: The prevalence of CVD is high (10.1%) in the Middle East. The burden of dyslipidaemia (43.3%) in this region is twice as high as that of hypertension (26.2%) and diabetes mellitus (16%). Multifaceted interventions are urgently needed for the primary prevention of CVD in this region.

Whole exome sequencing identifies a novel FANCD2 gene splice site mutation associated with disease progression in chronic myeloid leukemia: Implication in targeted therapy of advanced phase CML.

Tyrosine Kinase Inhibitors (TKIs) have significantly improved the clinical outcome of BCR-ABL+ Chronic Phase-Chronic Myeloid Leukemia (CP-CML). Nonetheless, approximately one-third of the CP-CML patient's progress to advanced phases of CML (accelerated and blast phase). Impaired DNA repair including mutations in Fanconi anemia (FA) pathway genes are responsible for progression of many cancers. Nevertheless, FA-pathways genes have never been reported in myeloid cancers. Hence, this study was aimed to discover DNA repair genes associated with CML progression. AP-CML patients were subjected to whole exome sequencing along with appropriate controls. A novel splice site FANCD2 mutation was detected. FANCD2 is a well-known FA-pathway gene with established role in DNA repair. This is first report of FA-pathway DNA repair genes in myeloid cancers that can serve as a novel marker of CML progression to clinically intervene CML progression. Further studies are needed to establish the functional role of FANCD2 in CML progression that can provide novel insights into CML pathogenesis. This study also indicates that a combination TKIs and Poly (ADP-ribose) polymerase (PARP) inhibitors like Olaparib (FDA approved anti-cancer drug for FA-pathway gene mutations) could improve the clinical outcome CML patients in accelerated and blast-crisis phases of the disease.

The Prognostic Impact of Pulse Pressure in Acute Heart Failure: Insights from the HEARTS Registry.

BACKGROUND: Low pulse pressure predicts long-term mortality in chronic heart failure, but its prognostic value in acute heart failure is less understood. The present study was designed to examine the prognostic value of pulse pressure in acute heart failure. METHODS: Pulse pressure was tested for its impact on short- and long-term mortality in all patients admitted with acute heart failure from October 2009 to December 2010 in eighteen tertiary centers in Saudi Arabia (n = 2609). All comparisons were based on the median value (50 mmHg). Heart failure with reduced ejection fraction was defined as less than 40%. RESULTS: Low pulse pressure was associated with increased short-term mortality in the overall population (OR = 1.61; 95 CI 1.17, 2.22; P 0.004 and OR = 1.51; 95% CI 1.13, 2.01; P = 0.005, for hospital and thirty-day mortality, respectively), and short-term and two-year mortality in the reduced ejection fraction group (OR = 1.81; 95% CI 1.19, 2.74; P = 0.005, OR = 1.69; 95% CI 1.17, 2.45; P = 0.006, and OR = 1.29; 95% CI 1.02, 1.61; P = 0.030 for hospital, thirty-day, and two-year mortality, respectively). This effect remained after adjustment for relevant clinical variables; however, pulse pressure lost its predictive power both for short-term and long-term mortality after the incorporation of systolic blood pressure in the model. Conversely, low pulse pressure was an independent predictor of improved survival at two and three years in heart failure with preserved ejection fraction (OR = 0.43; 95% CI 0.24, 0.78, P = 0.005 and OR = 0.49; 95% CI 0.28, 0.88; P = 0.016, respectively). CONCLUSION: In acute heart failure with reduced ejection fraction, the prognostic value of low pulse pressure was dependent on systolic blood pressure. However, it inversely correlated with long-term survival in heart failure with preserved ejection fraction.

Association between craniovertebral junction abnormalities and syringomyelia in patients with chiari malformation type-1.

OBJECTIVE: To assess the correlation between craniovertebral junction (CVJ) abnormalities and syringomyelia in patients with Chiari malformation type-1 (CM1). METHODS: This was a retrospective study including patients with CM1. Identification of cases was done by searching a radiology database at a university hospital from 2012 to 2017. Patients were divided into 2 groups based on whether CVJ abnormalities were present (CVJ+) or absent (CVJ-). The patients` demographic and clinical data were reviewed. All magnetic resonance imaging studies were examined by a certified neuroradiologist. RESULTS: Sixty-four consecutive patients with CM1 were included. The mean age was 24+/-17 years; 59% were females. The CVJ+ group had more female patients (p=0.012). The most frequent CVJ abnormality was platybasia (71%), followed by short clivus (44%) and cervical kyphosis (33%). The CVJ abnormalities were more in Syringomyelia cases (p=0.045). However, the results were not significant when hydrocephalus cases were excluded. CONCLUSION: Among CM1 patients, CVJ abnormalities were found more in patients with syringomyelia. Future studies with larger sample size are required to further study the correlation between CVJ abnormalities and both syringomyelia and hydrocephalus in CM1 patients.

Long term outcome of chronic myeloid leukemia patients treated with imatinib: Report from a developing country.

The outcome of chronic myeloid leukemia has been greatly improved by the use of Imatinib (IM), a selective BCR/ABL kinase inhibitor. The aim of present study was to report long term follow-up & outcome of IM-treated CML patients along with their clinicopathological features, risk group stratification, adverse events and to compare it with CML patients reported from western countries. The mean follow-up of 123 CML patients was 5.5 years in present study, who were treated with frontline IM 400mg daily in a tertiary care hospital in Pakistan. Risk stratification scores, response to treatment (ELN guidelines) and survival outcomes estimated by Kaplan-Meier analysis. Mean age: 35 years (9-67 years) and M: F: 1.5:1, mean follow up time: 5.5 years (1-15 years). Overall survival (OS): at 5.5, 8, 10 and 12 years were 93%, 88%, 81% and 73%, respectively. Progressions free survival (PFS) was 95%, 83%, 83% and 78% at 5.5, 8, 10 and 12 years, respectively. OS estimate by Sokal score was significant (P-value: 0.0019). Additional chromosomal aberrations: 1.6%. Eighteen (14.6%) patients progressed to AP/BC. Adverse events were moderate and tolerable. We present findings from a long term follow up of CML patients treated with IM in a developing country. CML mean age at onset was considerably lower than the western populations. Furthermore, 5.5 years OS are comparable to western CML population. IM in our patients as frontline choice proved to be very effective. IM was found to be well tolerated, safe with manageable moderate side effects.

Food and Migration: Dietary Acculturation among Migrants to the Kingdom of Saudi Arabia.

METHODS: A cross sectional study design was used based on 2 questionnaires; Rosenmoller et al's and the WHO STEPS surveillance tool for chronic disease surveillance. Data on length of residency, dietary patterns, anthropometric and biochemical measurements were collected by trained interviewers. Descriptive statistics were reported as a percentage or mean, as appropriate. Chi-square test, Fisher's exact test or independent t test, Univariate and Multivariate logistic regression analysis were used to compare the significance between variables. RESULTS: Both male and female participants showed a similar mean age (39.7 and 38.5 years). Approximately 61% of them had <5 year's duration of residency. Significant gender differences were observed in blood pressure and biochemical measurements, with men showing higher mean systolic and diastolic blood pressure and dyslipidemia than women (P < .001). Women had significantly higher BMI (P < .001), showed higher mean food practice (P < .001) and awareness scores than men. CONCLUSIONS: Migration into Saudi Arabia from this subgroup showed marked changes in the food practice; acquisition of unhealthy dietary practices also co-existed despite improved awareness and the presence of comorbidities. Findings from this study have relevance to other migrant communities and public health policy.

Acute myocardial infarction and acute heart failure in the Middle East and North Africa: Study design and pilot phase study results from the PEACE MENA registry.

BACKGROUND: This pilot study describes the overall design and results of the Program for the Evaluation and Management of the Cardiac Events registry for the Middle East and North Africa (MENA) Region. METHODS: This prospective, multi-center, multi-country study included patients hospitalized with acute myocardial infarction (AMI) and/or acute heart failure (AHF). We evaluated the clinical characteristics, socioeconomic and educational levels, management, in-hospital outcomes, and 30-day mortality rate of patients that were admitted to one tertiary-care center in each of 14 Arab countries in the MENA region. RESULTS: Between 22 April and 28 August 2018, 543 AMI and 381AHF patients were enrolled from 14 Arab countries (mean age, 57±12 years, 82.5% men). Over half of the patients in both study groups had low incomes with limited health care coverage, and limited education. Nearly half of the cohort had a history of diabetes mellitus, hypertension, or hypercholesterolemia. Among patients with ST-elevation myocardial infarctions, 56.4% received primary percutaneous interventions, 24% received thrombolysis, and 19.5% received no acute reperfusion therapy. The main causes of AHF were ischemic heart diseases (55%) and primary valvular heart diseases (15%). The in-hospital and 30-day mortality rates were 2.0% and 3.5%, respectively, for AMI, and 5.4% and 7.0%, respectively, for AHF. CONCLUSIONS: This pilot study revealed a high prevalence of cardiovascular risk factors in patients with AMI and AHF in Arab countries, and low levels of socioeconomic and educational status. Future phases of the study will improve our understanding of the impact that these factors have on the management and outcomes of cardiac events in these patient populations.

Age-Related Sex Differences in Clinical Presentation, Management, and Outcomes in ST-Segment-Elevation Myocardial Infarction: Pooled Analysis of 15 532 Patients From 7 Arabian Gulf Registries.

Background No studies from the Arabian Gulf region have taken age into account when examining sex differences in ST-segment-elevation myocardial infarction (STEMI) presentation and outcomes. We examined the relationship between sex differences and presenting characteristics, revascularization procedures, and in-hospital mortality after accounting for age in patients hospitalized with STEMI in the Arabian Gulf region from 2005 to 2017. Methods and Results This study was a pooled analysis of 31 620 patients with a diagnosis of acute coronary syndrome enrolled in 7 Arabian Gulf registries. Of these, 15 532 patients aged ≥18 years were hospitalized with a primary diagnosis of STEMI. A multiple variable regression model was used to assess sex differences in revascularization, in-hospital mortality, and 1-year mortality. Odds ratios and 95% CIs were calculated. Women were, on average, 8.5 years older than men (mean age: 61.7 versus 53.2 years; absolute standard mean difference: 68.9%). The age-stratified analysis showed that younger women (aged <65 years) with STEMI were more likely to seek acute medical care and were less likely to receive thrombolytic therapies or primary percutaneous coronary intervention and guideline-recommended pharmacotherapy than men. Women had higher crude in-hospital mortality than men, driven mainly by younger age (46-55 years, odds ratio: 2.60 [95% CI, 1.80-3.7]; P<0.001; 56-65 years, odds ratio: 2.32 [95% CI, 1.75-3.08]; P<0.001; and 66-75 years, odds ratio: 1.79 [95% CI, 1.33-2.41]; P<0.001). Younger women had higher adjusted in-hospital and 1-year mortality rates than younger men (P<0.001). Conclusions Younger women (aged ≤65 years) with STEMI were less likely to receive guideline-recommended pharmacotherapy and revascularization than younger men during hospitalization and had higher in-hospital and 1-year mortality rates.