A customised fetal growth and birthweight standard for Qatar: a population-based cohort study.

OBJECTIVES: Customized birthweight centiles have improved the detection of small for gestational age (SGA) and large for gestational age (LGA) babies compared to existing population standards. This study used perinatal registry data to derive coefficients for developing customized growth charts for Qatar. METHODS: The PEARL registry data on women delivering in Qatar (2017-2018) was used to develop a multivariable linear regression model predicting optimal birthweight. Physiological variables included gestational age, maternal height, weight, ethnicity, parity, and sex of the baby. Pathological variables such as hypertension, preexisting and gestational diabetes and smoking were calculated and excluded to derive the optimal weight at term. RESULTS: The regression model found a term optimal birthweight of 3,235 g for a Qatari nationality mother with median height (159 cm), booking weight (72 kg), parity (1) and gestation at birth (276 days) at the end of an uncomplicated pregnancy. Constitutional coefficients significantly affecting birthweight were gestational age, height, weight, and parity. The main pathological factors were preexisting diabetes (increase by +175.7 g) and smoking (decrease by -190.9 g). The SGA and LGA rates in the entire cohort after applying the population-specific customized centiles were 11.1 and 12.2 %, respectively (contrasting with the Hadlock standard: SGA-26.3 % and LGA-1.8 %, and Fenton standard: SGA-12.9 % and LGA-4.0 %). CONCLUSIONS: Constitutional and pathological variations in fetal growth and birthweight apply in the maternity population in Qatar and have been quantified to allow the generation of customised charts for better identification of pregnancies with abnormal growth. Currently in-use population standards may misdiagnose many SGA and LGA babies.

Validation of a modified obstetric comorbidity index for prediction of postpartum adverse events including fetal morbidity - a retrospective cohort study from Qatar.

BACKGROUND: The Obstetric Comorbidity Index (OBCMI) is an internationally validated scoring system for maternal risk factors intended to reliably predict the occurrence of severe maternal morbidity (SMM). This retrospective cohort study applied the OBCMI to pregnant women in Qatar to validate its performance in predicting SMM and cumulative fetal morbidity. METHODS: Data from 1000 women who delivered in July 2021 in a large tertiary centre was extracted from medical records. The OBCMI index included maternal demographics, pre-existing comorbidities, and various current pregnancy risk factors such as hypertension, including preeclampsia, intrauterine fetal death, prolonged rupture of membranes and unbooked pregnancies. SMM was based on the ACOG consensus definition, and the cumulative fetal morbidity (CFM) included fetal distress in labour, low APGAR and umbilical artery (UA) pH, admission to neonatal intensive care (NICU), and hypoxic-ischemic encephalopathy (HIE). A c-statistic or area under curve (AUC) was calculated to determine the ability of OBCMI to predict SMM and CFM. RESULTS: The median OBCMI score for the cohort was 1 (interquartile range- 0 to 2); 50% of women scored 0, while 85% (n = 842) had a score ranging from 0 to 2. Ten women (1%) scored ≥ 7; the highest score was 10. The incidence of SMM was 13%. According to the modified scoring system, the mean OBCMI score in those who developed SMM was 2.18 (± 2.20) compared to a mean of 1.04 (± 1.40) in those who did not (median 1, IQR:1-3 versus median 0, IQR: 0-2; p < 0.001). The incidence of CFM was 11.3%. The incidence of low APGAR score, HIE and NICU admission was nearly 1 in 1000. Around 5% of the babies had fetal distress in labour and low UA pH. For every 1 unit increase in OBCMI score, the odds of SMM increased by 44% (OR 1.44 95% CI 1.30-1.59; p < 0.001; AUC 0.66), and CFM increased by 28% (OR 1.28 95% CI 1.15-1.42; p < 0.001; AUC 0.61). A cut-off score of 4 had a high specificity (> 90%); 1 in 4 and 1 in 6 women with OBCMI score ≥ 4 developed SMM and CFM, respectively. CONCLUSION: The OBCMI performed moderately well in predicting SMM in pregnant women of Qatar and can be effectively used as a risk assessment tool to red-flag high-risk cases so that appropriate and timely multidisciplinary care can be initiated to reduce SMM and maternal mortality. The index is also helpful in predicting fetal morbidity; however, further prospective studies are required to validate OBCMI for CFM.

Patient perceptions of advanced practice radiation therapists prescribing medication in radiation therapy.

INTRODUCTION: The purpose of this study was to determine patient perceptions of an advanced practice radiation therapist (APRT) prescribing medication for radiation therapy treatment-related side effects. By comprehending patient perceptions, it is important to implement change in order to improve patients' quality of life. METHODS: A literature review was conducted on advanced practice (AP) roles in Canada and world-wide; the roles searched were: APRT, nurse practitioner and pharmacist. The search focused on evidence demonstrating improvements made to patient care due to the implementation of these roles. Based on this review and input from a team of experts a qualitative semi-structured interview survey was designed, and pilot tested. The survey consisted of five open-ended questions, which were designed to determine patient satisfaction of an APRT prescribing medication over the course of their radiation therapy treatments. Patients undergoing head and neck radiation therapy treatments at a large, academic cancer centre were invited to participate. Six patients who had a head and neck APRT involved in their treatment were interviewed. A comprehensive thematic analysis was then conducted using the transcripts created from these interviews, which was followed by two independent blinded analyses to ensure validity of the results. DISCUSSION: The thematic analysis produced four salient themes which were: side effect management, care provided by the APRT in comparison to other healthcare workers, patients' access to care, and overall patient satisfaction. Common medications for head and neck radiation therapy treatment related side effects were discussed and these were: Magic Mouthwash, Xylocaine, Nystatin, Benadryl, Advil, Tylenol, Dexamethasone, Tantum, Biotene, Mucaine, Flamazine, Hydrocortisone, Ondansetron, Senokot, and narcotics. CONCLUSION: This study was valuable to understand patient experiences and provide evidence to change processes in order to improve quality of patient centered care. The study revealed that although patients were happy with the process of prescribing medication, they all agreed that having an advanced practice radiation therapist prescribe would improve care. Patient responses further demonstrated the need for future research in regards to side effect management as a whole by APRTs as well as how role clarification can impact patient perceptions of APRTs.

Genomic Newborn Screening for Pediatric Cancer Predisposition Syndromes: A Holistic Approach.

As next-generation sequencing (NGS) has become more widely used, germline and rare genetic variations responsible for inherited illnesses, including cancer predisposition syndromes (CPSs) that account for up to 10% of childhood malignancies, have been found. The CPSs are a group of germline genetic disorders that have been identified as risk factors for pediatric cancer development. Excluding a few "classic" CPSs, there is no agreement regarding when and how to conduct germline genetic diagnostic studies in children with cancer due to the constant evolution of knowledge in NGS technologies. Various clinical screening tools have been suggested to aid in the identification of individuals who are at greater risk, using diverse strategies and with varied outcomes. We present here an overview of the primary clinical and molecular characteristics of various CPSs and summarize the existing clinical genomics data on the prevalence of CPSs in pediatric cancer patients. Additionally, we discuss several ethical issues, challenges, limitations, cost-effectiveness, and integration of genomic newborn screening for CPSs into a healthcare system. Furthermore, we assess the effectiveness of commonly utilized decision-support tools in identifying patients who may benefit from genetic counseling and/or direct genetic testing. This investigation highlights a tailored and systematic approach utilizing medical newborn screening tools such as the genome sequencing of high-risk newborns for CPSs, which could be a practical and cost-effective strategy in pediatric cancer care.

Time-resolved fluorescence and diffuse reflectance for lung squamous carcinoma margin detection.

OBJECTIVES: A major challenge in non-small cell lung cancer surgery is the occurrence of positive tumor margins. This may lead to the need for additional surgeries and has been linked to poor patient prognosis. This study aims to develop an in vivo surgical tool that can differentiate cancerous from noncancerous lung tissue at the margin. METHODS: A time-resolved fluorescence and diffuse reflectance bimodal device was used to measure the lifetime, spectra, and intensities of endogenous fluorophores as well as optical properties of lung tissue. The tumor and fibrotic tissue data, each containing 36 samples, was obtained from patients who underwent surgical removal of lung tissue after being diagnosed with squamous carcinoma but before any other treatment was administered. The normal lung tissue data were obtained from nine normal tissue samples. RESULTS: The results show a statistically significant difference between cancerous and noncancerous tissue. The results also show a difference in metabolic related optical properties between fibrotic and normal lung tissue samples. CONCLUSIONS: This work demonstrates the feasibility of a device that can differentiate cancerous and noncancerous lung tissue for patients diagnosed with squamous cell carcinoma.

Perinatal outcomes in women with class IV obesity compared to women in the normal or overweight body mass index categories: A population-based cohort study in Qatar.

Background: The prevalence of childhood and adult obesity is rising exponentially worldwide. Class IV obesity (body mass index, BMI ≥50 kg/m2) is associated with a higher risk of adverse perinatal outcomes. This study compared these outcomes between women with class IV obesity and women in the normal or overweight categories during pregnancy. Methods: A retrospective cohort study was performed in Qatar, including women having singleton live births beyond 24 weeks of gestation, classified into two class IV obesity and normal/overweight (BMI between 18.5 and 30.0 kg/m2). The outcome measures included the mode of delivery, development of gestational diabetes and hypertension, fetal macrosomia, small for date baby, preterm birth and neonatal morbidity. Adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) were determined using multivariable logistic regression models. Results: A total of 247 women with class IV obesity were compared with 6797 normal/overweight women. Adjusted analysis showed that women with class IV obesity had 3.2 times higher odds of cesarean delivery (aOR: 3.19, CI: 2.26-4.50), 3.4 times higher odds of gestational diabetes (aOR: 3.39, CI: 2.55-4.50), 4.2 times higher odds of gestational hypertension (aOR: 4.18, CI: 2.45-7.13) and neonatal morbidity (aOR: 4.27, CI: 3.01-6.05), and 6.5 times higher odds of macrosomia (aOR 6.48, CI 4.22-9.99). Conclusions: Class IV obesity is associated with more adverse perinatal outcomes compared with the normal or overweight BMI categories. The study results emphasized the need for specialized antenatal obesity clinics to address the associated risks and reduce complications.

Maternal and neonatal outcomes associated with multiple repeat cesarean deliveries: A registry-based study from Qatar.

BACKGROUND: Cesarean delivery (CD) is associated with increased maternal and neonatal morbidity compared to vaginal delivery, particularly in cases classified as emergency procedures or when there are multiple CDs. This retrospective cohort study aims to examine the incidence of maternal and neonatal complications in women with multiple CDs. METHODS: This study used data from a national perinatal database obtained from a single tertiary maternity care hospital. Women who delivered a singleton live birth after 24 weeks of gestation by CD were stratified into five groups based on the number of CDs, with the last group having five or more CDs. The women were divided into those with five or more CDs (Group 5) versus those with fewer than five (Groups 1 to 4). The maternal outcomes included intra-operative surgical complications, blood loss, and intensive care unit (ICU) admission. The neonatal outcomes included preterm birth, neonatal ICU (NICU) admission, respiratory distress syndrome (RDS), and perinatal death. RESULTS: Of the 6,316 women in the study, 2,608 (41.3%) had a primary CD. 30.3%, 17.5%, and 7.3% of the cohort had their second, third, and fourth CDs, respectively. Women undergoing the 5th CD and above formed the remaining 3.5% (227). Women in Group 5 had the highest risk of suffering a surgical complication (3.1%, p = 0.015) and postpartum hemorrhage (7.5%, p = 0.010). 24% of babies in Group 5 were born preterm (p < 0.001). They also had a 3.5 times higher risk of having a surgical complication (RR = 3.5, 95% CI 1.6-7.6, p = 0.002), a 1.8 times higher risk of developing postpartum hemorrhage (RR = 1.8, 95% CI 1.1-2.9, p = 0.014), a 1.7 times higher risk of delivering between 32-37 weeks of gestation (RR = 1.7, 95% CI 1.3-2.2, p < 0.001), a higher risk of the baby getting admitted to NICU (RR = 1.3, 95% CI 1.0-1.6, p = 0.038), and developing RDS (RR = 1.5, 95% CI 1.2-2.0, p = 0.002) compared to Groups 1-4. The risks of neonatal outcomes such as NICU admission (RR 2.9, 95% CI 2.1-4.0) and RDS (RR 3.5, 95% CI 2.3-5.5) were much higher in elective CDs performed at term compared to preterm births (p < 0.001 for both). CONCLUSION: Maternal morbidity significantly increases with the increasing number of CD. The increased risk of RDS and NICU admissions in the neonate with multiple CDs reflects lower gestational age and birthweight in these groups-consideration of preoperative steroids for lung maturation in these women to reduce neonatal morbidity warrants further discussion.

The SGLT2 inhibitor canagliflozin suppresses growth and enhances prostate cancer response to radiotherapy.

Radiotherapy is a non-invasive standard treatment for prostate cancer (PC). However, PC develops radio-resistance, highlighting a need for agents to improve radiotherapy response. Canagliflozin, an inhibitor of sodium-glucose co-transporter-2, is approved for use in diabetes and heart failure, but is also shown to inhibit PC growth. However, whether canagliflozin can improve radiotherapy response in PC remains unknown. Here, we show that well-tolerated doses of canagliflozin suppress proliferation and survival of androgen-sensitive and insensitive human PC cells and tumors and sensitize them to radiotherapy. Canagliflozin blocks mitochondrial respiration, promotes AMPK activity, inhibits the MAPK and mTOR-p70S6k/4EBP1 pathways, activates cell cycle checkpoints, and inhibits proliferation in part through HIF-1α suppression. Canagliflozin mediates transcriptional reprogramming of several metabolic and survival pathways known to be regulated by ETS and E2F family transcription factors. Genes downregulated by canagliflozin are associated with poor PC prognosis. This study lays the groundwork for clinical investigation of canagliflozin in PC prevention and treatment in combination with radiotherapy.

The impact of abnormal maternal body mass index during pregnancy on perinatal outcomes: a registry-based study from Qatar.

OBJECTIVES: Abnormal body mass index (BMI) during pregnancy, a growing public health concern, increases maternal and neonatal complications. This study aimed to investigate the impact of abnormal BMI on perinatal outcomes compared to normal BMI. METHODS: A total of 14,624 women having singleton births were categorized as underweight (BMI<18.5 kg/m2), overweight (25.0-29.9 kg/m2), obesity class I (30.0-34.9 kg/m2), obesity class II (35.0-39.9 kg/m2), and obesity class III (≥40.0 kg/m2) and compared to those with normal BMI (18.5-24.9 kg/m2). Outcomes included gestational diabetes (GDM), gestational hypertension (GHT), postpartum haemorrhage (PPH), cesarean delivery (CD), preterm birth (PTB), low birth weight (LBW), congenital anomalies and neonatal intensive care unit admission. RESULTS: Women with increasing BMI had increasingly higher odds of developing specific adverse outcomes, the highest being in the class III obesity group (GDM-aOR 2.71, 95 % CI 2.25-3.27, p<0.001, GHT-aOR 5.32 95 % CI 3.49-8.11, p<0.001, CD-aOR 2.33 95 % CI 1.85-2.94, p<0.001, PPH-aOR 1.77 95 % CI 1.35-2.33, p<0.001). On the other hand, being underweight during pregnancy was associated with increased odds of PTB (aOR 2.09, 95 % CI 1.37-3.20, p=0.001), LBW (OR 1.88, 95 % CI 1.27-2.79, p=0.002) and congenital anomalies (aOR 2.52 95 % CI 1.12-5.64, p=0.025). Majority in the underweight category gained less than expected gestational weight gain during the pregnancy. CONCLUSIONS: The findings of this study have important implications for the clinical management of pregnant women with abnormal BMI. Interventions to improve maternal and neonatal outcomes must focus on enhancing pre-pregnancy BMI and maintaining adequate gestational weight gain.

Multivariate analysis of breast tissue using optical parameters extracted from a combined time-resolved fluorescence and diffuse reflectance system for tumor margin detection.

Significance: Breast conservation therapy is the preferred technique for treating primary breast cancers. However, breast tumor margins are hard to determine as tumor borders are often ill-defined. As such, there exists a need for a clinically compatible tumor margin detection system. Aim: A combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system has been developed to determine the optical properties of breast tissue. This study aims to improve tissue classification to aid in surgical decision making. Approach: Normal and tumor breast tissue were collected from 80 patients with invasive ductal carcinoma and measured in the optical system. Optical parameters were extracted, and the tissue underwent histopathological examination. In total, 761 adipose, 77 fibroglandular, and 347 tumor spectra were analyzed. Principal component analysis and decision tree modeling were performed using only TRF optical parameters, only DR optical parameters, and using the combined datasets. Results: The classification modeling using TRF data alone resulted in a tumor margin detection sensitivity of 72.3% and specificity of 88.3%. Prediction modeling using DR data alone resulted in greater sensitivity and specificity of 80.4% and 94.0%, respectively. Combining both datasets resulted in the improved sensitivity and specificity of 85.6% and 95.3%, respectively. While both sensitivity and specificity improved with the combined modeling, further study of fibroglandular tissue could result in improved classification. Conclusion: The combined TRF-DR system showed greater tissue classification capability than either technique alone. Further work studying more fibroglandular tissue and tissue of mixed composition would develop this system for intraoperative use for tumor margin detection.

Canagliflozin mediates tumor suppression alone and in combination with radiotherapy in non-small cell lung cancer (NSCLC) through inhibition of HIF-1α.

Non-small cell lung cancer (NSCLC) has a poor prognosis, and effective therapeutic strategies are lacking. The diabetes drug canagliflozin inhibits NSCLC cell proliferation and the mammalian target of rapamycin (mTOR) pathway, which mediates cell growth and survival, but it is unclear whether this drug can enhance response rates when combined with cytotoxic therapy. Here, we evaluated the effects of canagliflozin on human NSCLC response to cytotoxic therapy in tissue cultures and xenografts. Ribonucleic acid sequencing (RNA-seq), real-time quantitative PCR (RT-qPCR), metabolic function, small interfering ribonucleic acid (siRNA) knockdown, and protein expression assays were used in mechanistic analyses. We found that canagliflozin inhibited proliferation and clonogenic survival of NSCLC cells and augmented the efficacy of radiotherapy to mediate these effects and inhibit NSCLC xenograft growth. Canagliflozin treatment alone moderately inhibited mitochondrial oxidative phosphorylation and exhibited greater antiproliferative capacity than specific mitochondrial complex-I inhibitors. The treatment downregulated genes mediating hypoxia-inducible factor (HIF)-1α stability, metabolism and survival, activated adenosine monophosphate-activated protein kinase (AMPK) and inhibited mTOR, a critical activator of hypoxia-inducible factor-1α (HIF-1α) signaling. HIF-1α knockdown and stabilization experiments suggested that canagliflozin mediates antiproliferative effects, in part, through suppression of HIF-1α. Transcriptional regulatory network analysis pinpointed histone deacetylase 2 (HDAC2), a gene suppressed by canagliflozin, as a key mediator of canagliflozin's transcriptional reprogramming. HDAC2 knockdown eliminated HIF-1α levels and enhanced the antiproliferative effects of canagliflozin. HDAC2-regulated genes suppressed by canagliflozin are associated with poor prognosis in several clinical NSCLC datasets. In addition, we include evidence that canagliflozin also improves NSCLC response to chemotherapy. In summary, canagliflozin may be a promising therapy to develop in combination with cytotoxic therapy in NSCLC.

Breast tissue analysis using a clinically compatible combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system.

OBJECTIVE: This work aims to develop a clinically compatible system that can perform breast tissue analysis in a more time efficient process than conventional histopathological assessment. The potential for such a system to be used in vivo in the operating room or surgical suite to improve patient outcome is investigated. METHOD: In this work, 80 matched pairs of invasive ductal carcinoma and adjacent normal breast tissue were measured in a combined time-resolved fluorescence and diffuse reflectance (DA) system. Following measurement, the fluorescence intensity of collagen and flavin adenine dinucleotide (FAD); the fluorescence lifetime of collagen, nicotinamide adenine dinucleotide (NADH), and FAD; the DA; absorption coefficient; and reduced scattering coefficient were extracted. Samples then underwent histological processing and H&E staining to classify composition as tumor, fibroglandular, and/or adipose tissue. RESULTS: Statistically significant differences in the collagen and FAD fluorescence intensity, collagen and FAD fluorescence lifetime, DA, and scattering coefficient were found between each tissue group. The NADH fluorescence lifetime and absorption coefficient were statistically different between the tumor and fibroglandular groups, and the tumor and adipose groups. While many breast tissue analysis studies label fibroglandular and adipose together as "normal" breast tissue, this work indicates that some differences between tumor and fibroglandular tissue are not the same as differences between tumor and adipose tissue. Observations of the reduced scatter coefficient may also indicate further classification to include fibro-adipose may be necessary. Future work would benefit from the additional tissue classification. CONCLUSION: With observable differences in optical parameters between the three tissue types, this system shows promise as a breast analysis tool in a clinical setting. With further work involving samples of mixed composition, this combined system could potentially be used intraoperatively for rapid margin assessment.

Impact of timing and severity of COVID-19 infection in pregnancy on intrauterine fetal growth- a registry-based study from Qatar.

BACKGROUND: The novel coronavirus disease (COVID-19) pandemic has impacted pregnant women, increasing maternal and neonatal morbidity. The placenta is a potential target for the pathophysiological processes due to the increased thrombotic inflammatory activation and inadequate uteroplacental perfusion and oxygenation, potentially causing intrauterine growth restriction. This study investigates the impact of gestational age at diagnosis of COVID-19 and the presence of symptoms on intrauterine fetal growth in pregnant women. METHODS: A retrospective review of COVID-19 positive pregnant women in Qatar from March 2020 to March 2021 was conducted. They were divided based on trimester of pregnancy in which they were infected. The outcomes included birthweight, customised fetal birthweight centiles, small for gestational age (SGA) baby and daily growth increments, compared between the trimesters and between symptomatic and asymptomatic women. RESULTS: In our cohort, 218 women (20.5%) were infected in the first trimester, 399 (37.5%) in the second and 446 (42%) in the third. Women in the second trimester were significantly younger and symptomatic. Women infected in the first trimester were least likely to have diabetes. The mean birthweight, risk of SGA (11.5% vs 10% vs 14.6%, p = 0.302), and median customized growth centiles (47.6% vs 45.9% vs 46.1%)were similar between the groups. Symptomatic women had significantly lower mean birthweight (3147 gms vs 3222 gms) and median birthweight centiles (43.9% vs 54.0%)compared to the asymptomatic (p<0.05 for both). In women infected within 20 weeks of gestation, a delay in daily fetal growth increments was noted with symptomatic disease, although not statistically significant. CONCLUSION: This study shows that women with symptomatic disease had lower birth centiles and birth weights. This was regardless of the gestational age at which they were infected. Early symptomatic disease seems to have an impact on fetal growth velocity; however, larger studies are needed to corroborate these findings.

Association of single nucleotide polymorphisms with dyslipidemia and risk of metabolic disorders in the State of Qatar.

BACKGROUND: Dyslipidemia is recognized as one of the risk factors of cardiovascular diseases (CVDs), type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD). OBJECTIVE: The study aimed to investigate the association between selected single nucleotide polymorphisms (SNPs) with dyslipidemia and increased susceptibility risks of CVD, NAFLD, and/or T2DM in dyslipidemia patients in comparison with healthy control individuals from the Qatar genome project. METHODS: A community-based cross-sectional study was conducted among 2933 adults (859 dyslipidemia patients and 2074 healthy control individuals) from April to December 2021 to investigate the association between 331 selected SNPs with dyslipidemia and increased susceptibility risks of CVD, NAFLD and/or T2DM, and covariates. RESULTS: The genotypic frequencies of six SNPs were found to be significantly different in dyslipidemia patients subjects compared to the control group among males and females. In males, three SNPs were found to be significant, the rs11172113 in over-dominant model, the rs646776 in recessive and over-dominant models, and the rs1111875 in dominant model. On the other hand, two SNPs were found to be significant in females, including rs2954029 in recessive model, and rs1801251 in dominant and recessive models. The rs17514846 SNP was found for dominant and over-dominant models among males and only the dominant model for females. We found that the six SNPs linked to gender type had an influence in relation to disease susceptibility. When controlling for the four covariates (gender, obesity, hypertension, and diabetes), the difference between dyslipidemia and the control group remained significant for the six variants. Finally, males were three times more likely to have dyslipidemia in comparison with females, hypertension was two times more likely to be present in the dyslipidemia group, and diabetes was six times more likely to be in the dyslipidemia group. CONCLUSION: The current investigation provides evidence of association for a common SNP to coronary heart disease and suggests a sex-dependent effect and encourage potential therapeutic applications.

Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies.

ABSTRACTSmall molecule therapy is a critical component of targeted anticancer treatment, with tyrosine kinase inhibitors (TKIs) being the first compounds to treat the clonal Chronic Myelogenous Leukaemia (CML) translocation t (9;22) (q34; q11) effectively since 2001. TKIs, such as imatinib, have improved the 10-year survival rate of CML patients to 80%. They bind the BCR::ABL1 kinase and inhibit downstream signaling pathways. However, therapy failure may be seen in 20-25% of CML patients due to intolerance or inadequacy related to BCR::ABL1 dependent or independent mechanisms. This review aimed to summarize current treatment options involving TKIs, resistance mechanisms and the prospective approaches to overcome TKI resistance. We highlight BCR::ABL1-dependent mechanisms of TKI resistance by reviewing clinically-documented BCR::ABL1 mutations and their consequences for TKI binding. In addition, we summarize BCR::ABL1 independent pathways, including the relevance of drug efflux, dysregulation of microRNA, and the involvement of alternative signaling pathways. We also discuss future approaches, such as gene-editing techniques in the context of CML, as potential therapeutic strategies.

Prevalence, predictors, and outcomes of major congenital anomalies: A population-based register study.

Congenital anomalies (CAs) are a leading cause of morbidity and mortality in early life. We aimed to assess the incidence, risk factors, and outcomes of major CAs in the State of Qatar. A population-based retrospective data analysis of registry data retrieved from the Perinatal Neonatal Outcomes Research Study in the Arabian Gulf (PEARL-Peristat Study) between April 2017 and March 2018. The sample included 25,204 newborn records, which were audited between April 2017 and March 2018, of which 25,073 live births were identified and included in the study. Maternal risk factors and neonatal outcomes were assessed for association with specific CAs, including chromosomal/genetic, central nervous system (CNS), cardiovascular system (CVS), facial, renal, multiple congenital anomalies (MCAs) using univariate and multivariate analyses. The incidence of any CA among live births was 1.3% (n = 332). The most common CAs were CVS (n = 117; 35%), MCAs (n = 69, 21%), chromosomal/genetic (51; 15%), renal (n = 39; 12%), CNS (n = 20; 6%), facial (14, 4%), and other (GIT, Resp, Urogenital, Skeletal) (n = 22, 7%) anomalies. Multivariable regression analysis showed that multiple pregnancies, parity ≥ 1, maternal BMI, and demographic factors (mother's age and ethnicity, and infant's gender) were associated with various specific CAs. In-hospital mortality rate due to CAs was estimated to be 15.4%. CAs were significantly associated with high rates of caesarean deliveries (aOR 1.51; 95% CI 1.04-2.19), Apgar < 7 at 1 min (aOR 5.44; 95% CI 3.10-9.55), Apgar < 7 at 5 min (aOR 17.26; 95% CI 6.31-47.18), in-hospital mortality (aOR 76.16; 37.96-152.8), admission to neonatal intensive care unit (NICU) or perinatal death of neonate in labor room (LR)/operation theatre (OT) (aOR 34.03; 95% CI 20.51-56.46), prematurity (aOR 4.17; 95% CI 2.75-6.32), and low birth weight (aOR 5.88; 95% CI 3.92-8.82) before and after adjustment for the significant risk factors. This is the first study to assess the incidence, maternal risk factors, and neonatal outcomes associated with CAs in the state of Qatar. Therefore, a specialized congenital anomaly data registry is needed to identify risk factors and outcomes. In addition, counselling of mothers and their families may help to identify specific needs for pregnant women and their babies.

Maternal risk factors of COVID-19-affected pregnancies: A comparative analysis of symptomatic and asymptomatic COVID-19 from the Q-PRECIOUS registry.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has had consequences on the pregnant population, as disease severity is associated with the quality of maternal health and pregnancy complications, increasing maternal and neonatal morbidity. Worldwide descriptive data help describe risk factors that could predict symptomatic and severe COVID-19 in pregnancy. OBJECTIVES: To describe demographic features and risk factors of pregnant women with COVID-19 in Qatar and compare symptomatic versus asymptomatic disease. STUDY DESIGN AND METHODOLOGY: Clinical characteristics and risk factors of pregnant women with COVID-19 in Qatar from March 2020 to March 2021 was retrospectively reviewed, comparing the cohort with the general pregnant population. Crude and adjusted odds ratios (aORs) were computed, comparing symptomatic versus asymptomatic infection. RESULTS: Of the 500 women, 347 reported at least one symptom at diagnosis (347/500; 69.4%). The majority fell in the 30-39 years age group (241/500; 48%), with more than half in the obese body mass index (BMI) category. The cohort was 66% (332/500) Qatari women, compared with the 26% expected in the population (26.4% vs 66.4% p < 0.001). Compared with the 2019 national statistics, the number of women was higher in the >40 years age group (5% vs 7.6%, p = 0.027) and grand multiparous group (5.4% vs 13.6%, p < 0.001). The symptom most commonly reported by the symptomatic group was cough (276/500; 55%), followed by fever, fatigue, and myalgia. In the adjusted analysis, the symptomatic group had 2.7 times higher odds of being asthmatic (OR = 2.67, 95% CI 1.1-6.7, p = 0.037). Women aged >40 years had 6.6 times higher odds of symptomatic disease (aOR = 6.6, 95% CI 1.08-39.73, p = 0.041). A history of contact with a patient with symptomatic COVID and earlier gestational age at diagnosis increased the odds (aOR = 2.06, 95% CI 1.2-3.54, p = 0.009; aOR = 0.73 95% CI 0.57-0.96; p = 0.017). CONCLUSIONS: This study cohort included significantly more Qatari women, older women, grand multiparous women, a higher proportion with pre-existing and gestational diabetes, and higher BMI than national data. In addition, contact to a patient with symptomatic disease, history of asthma, older age, and earlier gestational age at diagnosis were significantly associated with symptomatic disease.

Impact of the fear of Covid-19 infection on intent to breastfeed; a cross sectional survey of a perinatal population in Qatar.

OBJECTIVES: Infection control measures during the Covid-19 pandemic have focused on limiting physical contact and decontamination by observing cleaning and hygiene rituals. Breastfeeding requires close physical contact and observance of hygienic measures like handwashing. Worries around contamination increase during the perinatal period and can be expressed as increase in obsessive compulsive symptoms. These symptoms have shown to impact breastfeeding rates. This study attempts to explore any relationship between the Covid-19 pandemic and perinatal obsessive-compulsive symptomatology and whether the Covid-19 pandemic has any impact on intent to breastfeed. METHODS: A cross sectional survey of perinatal women attending largest maternity centre in Qatar was carried out during the months of October to December 2020. Socio-demographic information, intent to breastfeed and information around obsessive compulsive thoughts around Covid-19 pandemic were collected using validated tools. RESULTS: 15.7% respondents report intent to not breastfeed. 21.4% respondents reported obsessive-compulsive symptoms. 77.3% respondents believed the biggest source of infection was from others while as only 12% of the respondents believed that the source of infection was through breastfeeding and 15.7% believed the vertical transmission as the main source of risk of transmission. CONCLUSIONS: The rates of Obsessive-compulsive symptoms were increased and the rates of intent to breastfeed were decreased when compared with pre pandemic rates. The obsessive-compulsive symptoms and the intent to not breastfeed were significantly associated with fear of infection to the new-born. Obsessive-compulsive symptoms were not significantly correlated with intent to breastfeed and can be seen as adaptive strategies utilized by women to continue breastfeeding in the context of fear of infection.

Incidence, risk factors, and feto-maternal outcomes of inappropriate birth weight for gestational age among singleton live births in Qatar: A population-based study.

BACKGROUND: Abnormal fetal growth can be associated with factors during pregnancy and at postpartum. OBJECTIVE: In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes associated with small-for-gestational age (SGA) and large-for-gestational age (LGA) infants. METHODS: We performed a population-based retrospective study on 14,641 singleton live births registered in the PEARL-Peristat Study between April 2017 and March 2018 in Qatar. We estimated the incidence and examined the risk factors and outcomes using univariate and multivariate analysis. RESULTS: SGA and LGA incidence rates were 6.0% and 15.6%, respectively. In-hospital mortality among SGA and LGA infants was 2.5% and 0.3%, respectively, while for NICU admission or death in labor room and operation theatre was 28.9% and 14.9% respectively. Preterm babies were more likely to be born SGA (aRR, 2.31; 95% CI, 1.45-3.57) but male infants (aRR, 0.57; 95% CI, 0.4-0.81), those born to parous (aRR 0.66; 95% CI, 0.45-0.93), or overweight (aRR, 0.64; 95% CI, 0.42-0.97) mothers were less likely to be born SGA. On the other hand, males (aRR, 1.82; 95% CI, 1.49-2.19), infants born to parous mothers (aRR 2.16; 95% CI, 1.63-2.82), or to mothers with gestational diabetes mellitus (aRR 1.36; 95% CI, 1.11-1.66), or pre-gestational diabetes mellitus (aRR 2.58; 95% CI, 1.8-3.47) were significantly more likely to be LGA. SGA infants were at high risk of in-hospital mortality (aRR, 226.56; 95% CI, 3.47-318.22), neonatal intensive care unit admission or death in labor room or operation theatre (aRR, 2.14 (1.36-3.22). CONCLUSION: Monitoring should be coordinated to alleviate the risks of inappropriate fetal growth and the associated adverse consequences.

Incidence, Risk Factors, and Outcomes of Preterm and Early Term Births: A Population-Based Register Study.

Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar. We examined 15,865 singleton live births using 12-month retrospective registry data from the PEARL-Peristat Study. PTB and ETB incidence rates were 8.8% and 33.7%, respectively. PTB and ETB in-hospital mortality rates were 16.9% and 0.2%, respectively. Advanced maternal age, pre-gestational diabetes mellitus (PGDM), assisted pregnancies, and preterm history independently predicted both PTB and ETB, whereas chromosomal and congenital abnormalities were found to be independent predictors of PTB but not ETB. All groups of PTB and ETB were significantly associated with low birth weight (LBW), large for gestational age (LGA) births, caesarean delivery, and neonatal intensive care unit (NICU)/or death of neonate in labor room (LR)/operation theatre (OT). On the other hand, all or some groups of PTB were significantly associated with small for gestational age (SGA) births, Apgar < 7 at 1 and 5 min and in-hospital mortality. The findings of this study may serve as a basis for taking better clinical decisions with accurate assessment of risk factors, complications, and predictions of PTB and ETB.