Fyn and Lyn gene polymorphisms impact the risk of thyroid cancer.

Thyroid cancer is the most common malignancy of the endocrine glands, and during last couple of decades, its incidence has risen alarmingly, across the globe. Etiology of thyroid cancer is still debatable. There are a few worth mentioning risk factors which contribute to initiation of abnormalities in thyroid gland leading to cancer. Genetic instability is major risk factors in thyroid carcinogenesis. Among the genetic factors, the Src family of genes (Src, Yes1, Fyn and Lyn) have been implicated in many cancers but there is little data regarding the association of these (Src, Yes1, Fyn and Lyn) genes with thyroid carcinogenesis. Fyn and Lyn genes of Src family found engaged in proliferation, migration, invasion, angiogenesis, and metastasis in different cancers. This study was planned to examine the effect of Fyn and Lyn SNPs on thyroid cancer risk in Pakistani population in 500 patients and 500 controls. Three polymorphisms of Fyn gene (rs6916861, rs2182644 and rs12910) and three polymorphisms of Lyn gene (rs2668011, rs45587541 and rs45489500) were analyzed using Tetra-primer ARMS-PCR followed by DNA sequencing. SNP rs6916861 of Fyn gene mutant genotype (CC) showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs2182644 of Fyn gene, mutant genotype (AA) indicated statistically significant 17-fold increased risk of thyroid cancer (P < 0.0001). Statistically significant threefold increased risk of thyroid cancer was observed in genotype AC (P < 0.0001) of Fyn gene polymorphism rs12910. In SNP rs2668011 of Lyn gene, TT genotype showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs45587541 of Lyn gene, GA genotypes showed statistically significant 11-fold increased risk in thyroid cancer (P < 0.0001). Haplotype analysis revealed that AAATAG*, AGACAG*, AGCCAA*, AGCCAG*, CAATAG*, CGCCAG* and CGCCGA* haplotypes of Fyn and Lyn polymorphisms are associated with increased thyroid cancer risk. These results showed that genotypes and allele distribution of Fyn and Lyn are significantly linked with increased thyroid cancer risk and could be genetic adjuster for said disease.

Role of Chk1 gene in molecular classification and prognosis of gastric cancer using immunohistochemistry and LORD-Q assay.

Purpose: The aim of the current study was to assess the prognostic value of the Chk1 gene in the DNA damage response pathway in gastric cancer (GC). Methods: Expression levels of the Chk1 were measured in 220 GC tumor tissues and adjacent healthy/noncancerous tissues using real-time PCR and immunohistochemical staining. Genomic instability in GC patients was measured using the long-run real-time PCR technique for DNA-damage quantification assay and comet assay. Results: Significantly downregulated expression of Chk1 was observed at the mRNA level (p < 0.0001) and protein level (p < 0.0001). Significantly increased frequency of lesions/10 kb and comets was observed in tumor tissues compared with control tissues. Conclusion: The data suggest that downregulated expression of Chk1 and positive Heliobacter pylori infection status may have prognostic significance in GC.

Genetic interactions of mitochondrial sirtuins in brain tumorigenesis.

Purpose: The present study was designed to understand the role of expression variations of mitochondrial imported sirtuins in brain tumorigenesis. The expression levels of mitochondrial imported sirtuins were further analyzed for biomarker potential. Methods: Samples from 200 brain tumors and 200 healthy control tissues were used for expression analysis using quantitative PCR and for DNA damage using LORD-Q analysis. Results: Significant deregulation of SIRT3 (p = 0.002), SIRT4 (p = 0.03) and SIRT5 (p = 0.006) was observed in brain tumors versus controls. Co-expression analysis showed a significant correlation between the mitochondrial imported sirtuins versus apoptotic genes. LORD-Q analysis showed a significantly increased frequency of lesions/10 kb of mitochondrial imported sirtuins (p < 0.0001) in brain tumor tissue versus controls. Conclusion: The present study showed a correlation between variations of mitochondrial imported sirtuins and increased brain tumor risk.

Expression deregulation of matrix metalloproteinases and vasoconstriction related genes in Pakistani females with abnormal uterine bleeding.

BACKGROUND: Abnormal uterine bleeding (AUB) is irregular menstrual bleeding which has great impact on female health and life style. Various genetic factors are involved in etiology and pathology of AUB. Present study was designed to explore the association of PTGFR, MMP9, MMP2, TGFB3 and VEGFB with AUB. METHODS: Blood samples of 212 females with AUB were collected along with age-matched healthy control. Expression variation of targeted genes was evaluated using qPCR. Present study cohort was divided into different groups based on demographic parameters and all targeted genes were correlated with study demographics. RESULTS: Expression of targeted genes was significantly (P < 0.001) downregulated in females with AUB compared to control. Reduced (P < 0.01) expression of targeted genes was observed in all age groups (21-30, 31-40, 41-50 year) of AUB patients compared to respective control. Expression of VEGFB increased (P < 0.05) in AUB females with > 9 days bleeding compared to AUB patient had < 9 days bleeding. AUB women with miscarriage history showed upregulation in MMP2, TGFB3 (P < 0.05), and downregulation in MMP9 and VEGFB (P < 0.05) expression compared to AUB group with no miscarriage history. Expression of MMP2 increased (P < 0.05) in AUB females with > 60 kg body weigh compared to AUB patient with < 60 kg weight. CONCLUSION: Present study open a new window for diagnosis of AUB at early stages and suggested a possible involvement of PTGFR, MMP9, MMP2, TGFB3 and VEGFB as candidate biomarkers in AUB.

Morphological and Molecular Characterization of Tylenchorhynchus Clarus Allen, 1955 and T. Zeae Sethi & Swarup, 1968 (Rhabditida: Telotylenchidae) from Iraq.

During a survey on the biodiversity of plant-parasitic nematodes in Misan province (southeast Iraq), Tylenchorhynchus clarus and T. zeae were discovered around the rhizosphere of sugarcane and pumpkin, respectively. The morphological and morphometric data were provided for the recovered species. The morphological characters of both populations are in agreement with the type populations and other populations of them. To the best of our knowledge, this is the first report of these two species from Iraq, and a first report of the association of T. zeae with pumpkin. Molecular phylogenetic analyses of the Iraqi populations of T. clarus and T. zeae using the D2-D3 expansion segments of 28S rDNA and internal transcribed spacer (ITS) rDNA sequences using Bayesian inference (BI), showed they form maximally supported clades with other sequences of both species.

Chromosome 5 harbors two independent deletion hotspots at 5q13 and 5q21 that characterize biologically different subsets of aggressive prostate cancer.

Deletion of chromosome 5q is common in prostate cancer and is linked to aggressive disease. Most previous studies focused on 5q21 where CHD1 is located, but deletion of mapping studies has identified a second deletion hotspot at 5q13. To clarify the prevalence and clinical relevance of 5q13 deletions and to determine the relative importance of 5q13 and 5q21 abnormalities, a tissue microarray containing samples from 12 427 prostate cancers was analyzed by fluorescence in situ hybridization. Deletion of 5q13 and 5q21 was found in 13.5% and 10%, respectively, of 7932 successfully analyzed cancers. Deletion was restricted to 5q13 in 49.4% and to 5q21 in 32.0% of cancers with a 5q deletion. Only 18.6% of 5q-deleted cancers had deletions of both loci. Both 5q13 and 5q21 deletions were significantly linked to advanced tumor stage, high Gleason grade, nodal metastasis and early biochemical recurrence (P < .005 each). Cancers with co-deletion of 5q13 and 5q21 had a worse prognosis than cancers with isolated 5q13 or 5q21 deletion (P = .0080). Comparison with TMPRSS2:ERG fusion status revealed that 5q21 deletions were tightly linked to ERG negativity (P < .0001) while 5q13 deletions were unrelated to the ERG status. In summary, 5q13 deletion and 5q21 deletion are common, but independent genomic alterations with different functional effects lead to aggressive prostate cancer.

Polymorphism in miRNA target sites of CEP-63 and CEP-152 ring complex influences expression of CEP genes and favors tumorigenesis in glioma.

Purpose: The present study was designed to screen the genetic polymorphisms and expression profiling of CEP-152 and CEP-63 genes in brain tumor patients. Methods: The amplification refractory mutation system PCR technique (ARMS-PCR) was used for mutation analysis using 300 blood samples of brain tumor patients and 300 overtly healthy controls. For expression analysis, 150 brain tumor tissue samples along with adjacent uninvolved/normal tissues (controls) were collected. Results: A significantly higher frequency of the mutant genotype of the CEP-152 single nucleotide polymorphism (rs2169757) and CEP-63 single nucleotide polymorphisms (rs9809619 and rs13060247) was observed in patients versus overtly healthy controls. The authors' results showed highly significant deregulation of CEP-152 (p < 0.0001) and CEP-63 (p < 0.0001) in glioma/meningioma tumor tissues versus adjacent normal tissue. Conclusion: The present study showed that variations in CEP-152 and CEP-63 genes were associated with an increased risk of brain tumor.

Lay abstract The purpose of this research was to explore the role of CEP-63 and CEP-152 in brain tumors in the Pakistani population. Loss of function or genetic deletion of these genes results in a mismatch of cell cycle, culminating in a cell phenotype conducive to transformation and tumorigenesis in different regions, including the brain region. Brain tumor is the most common cancer and the second most common cause of cancer death in Asia. The highest incidence rates are observed in Eastern Asia, including Pakistan. The aim of this research was initially to detect genetic variations of CEP-63 and CEP-152 in brain tumor patients. Secondly, expression variation of CEP-63 and CEP-152 was also examined in brain tumor cohort. Results from present study showed the significant involvement of CEP-63 and CEP-152 variations in brain carcinogenesis. Further analysis showed that CEP genes variations may act as predictive or prognostic markers for brain cancer.

Deregulation of mitochondrial sirtuins and OGG1-2a acts as a prognostic and diagnostic biomarker in leukemia.

Purpose: The present study was planned to explore the expression variations of mitochondrial sirtuins and the mitochondrial DNA repair enzyme OGG1-2a in leukemia patients. Oxidative stress and deacetylation levels of leukemia patients were measured in the present study. Methods: A total of 200 leukemia patients along with 200 healthy controls were evaluated using quantitative PCR, 8OXOG assay and deacetylation assay. Results: Significant deregulation of SIRT3 (p < 0.0001), SIRT4 (p < 0.0001), SIRT5 (p < 0.0001), Ki-67 (p < 0.0001) and OGG1-2a (p < 0.0001) was detected in patients versus controls. Survival analysis showed that deregulation of said genes was associated with decreased survival of leukemia patients (SIRT3: p < 0.004; SIRT4: p < 0.0009; SIRT5: p < 0.0001; OGG1-2a: p < 0.03). Receiver operating characteristic curve analysis confirmed the diagnostic values of selected genes in leukemia patients. Levels of 8OXOG adducts were measured, and significantly increased 8OXOG adduct levels were observed in patients versus controls. Conclusion: These data suggest that deregulation of SIRT3, SIRT4, SIRT5 and OGG1-2a acts as a diagnostic and prognostic marker in leukemia.

Lay abstract Leukemia is a type of blood cancer that has shown an increased rate of occurrence worldwide. Studies have shown that environmental and genetic factors are involved in the increased rate of this disease. Of the genetic factors, sirtuins (SIRT3, SIRT4 and SIRT5) and OGG1-2a have not been studied in leukemia. In the present study, the authors aimed to study the genetic/epigenetic changes in these genes in leukemia patients. Results of the present study showed involvement of selected gene variations in the increased rate of leukemia, at least in the Pakistani population.

Association between single nucleotide polymorphisms of DNA damage response pathway genes and increased risk in breast cancer.

Aim: We aimed to evaluate the role of selected single nucleotide polymorphisms of DNA damage response pathway genes in breast cancer (BC). Materials & methods: In present study, 500 BC patients and 500 controls was used to estimate the frequency of single nucleotide polymorphisms of DNA damage response pathway genes. Tetra-amplification refractory mutation system-PCR technique was used for screening of the six selected polymorphisms. Results: Logistic regression analysis showed that heterozygous mutant genotype of rs1800057 (p < 0.0001) and homozygous mutant genotype of rs1801516 (p < 0.0001) was associated with significant increased risk of BC. In the ATR gene, heterozygous mutant genotype of rs2227931 (p < 0.0001) was associated with significant increased risk of BC. However, significant decreased risk of BC was found associated with heterozygous mutant genotype of rs2227928 (p < 0.0002) and homozygous mutant genotype of rs2229032 (p < 0.0001) in patients compared with controls. Conclusion: The present results showed that alteration in DNA damage response pathway gene (ATM & ATR) results in increased BC risk.

Linkage disequilibrium and haplotype analysis of Src and Yes1 genes in thyroid cancer.

Purpose: This study was planned to examine the effects of Src and Yes1 single nucleotide polymorphism (SNPs) on the risk of thyroid cancer in 499 patients and 500 controls. Materials & methods: Three SNPs of Src gene and three SNPs of Yes1 gene were analyzed using Tetra-primer ARMS-PCR followed by sequencing. Results: rs121913314 of Src gene genotype TT showed 32-fold increased risk of thyroid cancer and rs2305994 of Yes1 genotypes TT and CT showed 2.7-fold and 16-fold increased risk in thyroid cancer (p < 0.0001). Haplotype analysis revealed that CATGCC, CATGCT, CATGTC, CATGTT, TATGCC and TATGTTA haplotypes are associated with thyroid cancer risk. Conclusion: Results showed that genotypes and allele distribution of Src and Yes1 genes are significantly linked with increased risk of thyroid cancer.

Trends of utilization of Complete Blood Count parameters for patient management among doctors in Azad Kashmir.

OBJECTIVE: To determine the trends of utilization of CBC parameters in patient management among doctors in different hospitals in Kashmir, Pakistan. METHODD: A self-administered questionnaire-based survey was carried out amongst doctors working in four hospitals of Kashmir i.e. Combined Military Hospital, Muzaffarabad, Combined Military Hospital, Rawalakot, Abbas Institute of Medical Sciences, Muzaffarabad, and District Hospital, Kotli during August to December 2017. RESULTS: Out of 500 physicians, 217 physicians answered the questionnaire, representing a response rate of 43.4%. Only three of the 11 parameters in the CBC report i.e. hemoglobin, white blood cell count and platelets were selected as frequently or always useful by more than 80% of physicians. Rest of the eight parameters of the CBC were found useful by less than 80% of the physicians. Most agreed that the current format of a CBC report gives adequate information. CONCLUSION: The present study concludes that majority of the physicians utilize only three of the basic parameters on the complete blood count. An educational intervention can be planned for the physicians to increase their knowledge about the utility of other parameters.

Repeated anodal trans-spinal direct current stimulation results in long-term reduction of spasticity in mice with spinal cord injury.

KEY POINTS: Spasticity is a disorder of muscle tone that is associated with lesions of the motor system. This condition involves an overactive spinal reflex loop that resists the passive lengthening of muscles. Previously, we established that application of anodal trans-spinal direct current stimulation (a-tsDCS) for short periods of time to anaesthetized mice sustaining a spinal cord injury leads to an instantaneous reduction of spasticity. However, the long-term effects of repeated a-tsDCS and its mechanism of action remained unknown. In the present study, a-tsDCS was performed for 7 days and this was found to cause long-term reduction in spasticity, increased rate-dependent depression in spinal reflexes, and improved ground and skill locomotion. Pharmacological, molecular and cellular evidence further suggest that a novel mechanism involving Na-K-Cl cotransporter isoform 1 mediates the observed long-term effects of repeated a-tsDCS. ABSTRACT: Spasticity can cause pain, fatigue and sleep disturbances; restrict daily activities such as walking, sitting and bathing; and complicate rehabilitation efforts. Thus, spasticity negatively influences an individual's quality of life and novel therapeutic interventions are needed. We previously demonstrated in anaesthetized mice that a short period of trans-spinal subthreshold direct current stimulation (tsDCS) reduces spasticity. In the present study, the long-term effects of repeated tsDCS to attenuate abnormal muscle tone in awake female mice with spinal cord injuries were investigated. A motorized system was used to test velocity-dependent ankle resistance and associated electromyographical activity. Analysis of ground and skill locomotion was also performed, with electrophysiological, molecular and cellular studies being conducted to reveal a potential underlying mechanism of action. A 4 week reduction in spasticity was associated with an increase in rate-dependent depression of spinal reflexes, and ground and skill locomotion were improved following 7 days of anodal-tsDCS (a-tsDCS). Secondary molecular, cellular and pharmacological experiments further demonstrated that the expression of K-Cl co-transporter isoform 2 (KCC2) was not changed in animals with spasticity. However, Na-K-Cl cotransporter isoform 1 (NKCC1) was significantly up-regulated in mice that exhibited spasticity. When mice were treated with a-tsDCS, down regulation of NKCC1 was detected, and this level did not significantly differ from that in the non-injured control mice. Thus, long lasting reduction of spasticity by a-tsDCS via downregulation of NKCC1 may constitute a novel therapy for spasticity following spinal cord injury.

Relationship of single nucleotide polymorphisms and haplotype interaction of mitochondrial unfolded protein response pathway genes with head and neck cancer.

Aim: In this study, we evaluated the effect of selected polymorphisms of mitochondrial unfolded protein response (UPRmt) pathway in 500 head and neck cancer (HNC) patients and 500 healthy controls from Pakistan. Materials & methods: The experiments were conducted using tetra-ARMS PCR followed by DNA sequencing. Results: Multivariate analysis showed that AA genotype of rs3782116 showed fivefold, GG genotype of rs6598072 approximately twofold and CC genotype of rs4946936 and TT genotype of rs12212067 showed twofold increased risk of HNC. Furthermore, haplotype analysis showed that certain haplotypes of UPRmt pathway single nucleotide polymorphisms have significant association with increased HNC risk. Conclusion: These results show that genetic aberrations in UPRmt pathway genes have association with increased HNC risk and can be an indicator of advance clinical outcome especially invasion and metastasis.

The natural history of thoracolumbar kyphosis in achondroplasia.

There are little published data on the natural history and evolution of thoracolumbar kyphotic deformity in achondroplasia. Furthermore, there are few published reports indicating the probability of symptoms and at what kyphotic angle progressive deformity might occur. The lack of knowledge of the fundamental natural history does not allow firm guidelines for the management of this problem. In this respect the role of bracing remains uncertain both in terms of altering the prognosis for further vertebral wedging and overall sagittal profile. This report describes three illustrative cases of thoracolumbar kyphosis (TLK) that occurred in achondroplastic infants. The long-term outcomes are presented to illustrate the diverse clinical behaviour of TLK in this patient group.

Epidemiology of acetabular fractures in Qatar.

OBJECTIVES: This study aimed to review the epidemiological aspects of acetabular fractures treated at Hamad Medical Corporation in Qatar. The study is the first orthopaedic trauma epidemiological study in Qatar and will provide a platform to advance high-level clinical research. METHODS: We obtained data for 103 patients who presented to our level I trauma centre from 2008 to 2010 with a diagnosis of acetabular fracture. Age, sex, the cause of injury, fracture classification, mode of treatment, associated nerve injuries, and other complications were analyzed. RESULTS: The incidence of acetabular fracture was 2/100,000/year. Males (93.2%) predominated. The mean age at injury time was 36 years, and the most common cause of injury was motor vehicle collisions (49.5%). Injuries were mostly primary acetabular fractures (73.6%) in comparison to (26.4%) for associated fractures. Posterior wall fractures were the most common pattern (25.2%). Associated posterior hip dislocation occurred in 21.3% of cases. Data revealed a lower incidence of post-traumatic sciatic nerve palsy (7%) that was present at the time of injury. There were no cases of reported mortality. CONCLUSION: Acetabular fractures are uncommon injuries with motor vehicle collision being the most common cause of injury. Posterior wall fracture was the most frequent pattern, and most of the patients were males. The incidence of post-traumatic sciatic nerve palsy and the proportion of injured women were lower than those reported in literature. Well-trained surgeons and specialized centres for treating these injuries are recommended.

Motivations for (non)participation in population-based health studies among the elderly - comparison of participants and nonparticipants of a prospective study on influenza vaccination.

BACKGROUND: Participation in epidemiological studies has strongly declined in recent years. We examined the reasons for (non)participation in population-based health studies among participants and nonparticipants of a prospective study on influenza vaccination among the elderly. METHODS: Males and females between 65 and 80 years of age (N = 5582) were randomly selected from the residents' registration office in Hannover, Germany, and were invited to participate in a study featuring vaccination with a seasonal adjuvanted influenza vaccine (Fluad™, Novartis) including five follow-up visits (day 0, 1/3, 7, 21, 70 with respect to vaccination). A 24-item nonresponder questionnaire, including 10 items on reasons for participating in a hypothetical health study, was mailed to 1500 randomly selected nonparticipants. The same 10 items were included in the end-of-study questionnaire administered to the participants in the vaccination study (n = 200). Logistic regression analysis with backward elimination was used to identify the reasons most strongly associated with nonparticipation. RESULTS: Five hundred thirty-one (35%) nonparticipants and 200 participants (100%) returned the respective questionnaires. Nonparticipation was associated with a lower interest in obtaining personal health information (OR = 3.32) and a preference for less invasive (OR = 3.01) and less time-demanding (OR = 2.19) studies. Responses to other items, e.g. regarding altruistic motives, monetary compensation, general interest of the study, or study approval through ethics committee and data security authority, did not differ between participants and nonparticipants. CONCLUSIONS: Participation rates in health studies among elderly individuals could potentially be improved by reducing interventions and time demand, for instance by implementing methods of self-sampling and remote data collection. TRIAL REGISTRATION: No. 1100359 (ClinicalTrials.gov, date of registration: 09.02.2015).

Distal junctional kyphosis in patients with Scheuermann's disease: a retrospective radiographic analysis.

PURPOSE: To investigate the relationship between preoperative and postoperative spinopelvic alignment and occurrence of DJK/DJF. STUDY DESIGN/SETTING: This was a retrospective observational cohort study. PATIENT SAMPLE: The sample included 40 patients who underwent posterior correction of SK from January 2006 to December 2014. OUTCOME MEASURES: Correlation analysis between the preoperative and postoperative spinopelvic alignment parameters and development of DJK over the course of the study period were studied. METHODS: Whole spine X-rays obtained before surgery, 3 months after surgery and at the latest follow-up were analyzed. The following parameters were measured: maximum of thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lower instrumented vertebra (LIV) and LIV plumb line. Development of DJK was considered as the primary end point of the study. The patient population was split into a control and DJK group, with 34 patients and 6 patients, respectively. Statistic analysis was performed using unpaired t test for normal contribution and Mann-Whitney test for skew distributed values. The significance level was set to 0.05. RESULTS: DJK occurred in 15% (n = 6) over the study period. There was a significantly lower postoperative TK for the group with DJK (42.4 ± 5.3 vs 49.8 ± 6.7, p = 0.015). LIV plumb line showed higher negative values in the DJK group (-43.6 ± 25.1 vs -2.2 ± 17.8, p = 0.0435). Furthermore, postoperative LL changes were lower for the DJK group (33.84 ± 13.86% vs 31.77 ± 14.05, p < 0.0001.) The age of the patients who developed DJK was also significantly lower than that of the control group (16.8 ± 1.7 vs 19.6 ± 4.9, p = 0.0024.) CONCLUSIONS: SK patients who developed DJK appeared to have a significantly higher degree of TK correction and more negative LIV plumb line. In addition, there may be a higher risk for DJK in patients undergoing corrective surgery at a younger age.

Routine Antenatal Echocardiography in High-Prevalence Areas of Rheumatic Heart Disease: A WHO-Guideline Systematic Review.

Background: Rheumatic Heart Disease (RHD) is the most common cause of valvular heart disease worldwide. Undiagnosed or untreated RHD can complicate pregnancy and lead to poor maternal and fetal outcomes and is a significant factor in non-obstetric morbidity. Echocardiography has an emerging role in screening for RHD. We aimed to critically analyse the evidence on the use of echocardiography for screening pregnant women for RHD in high-prevalence areas. Methods: We searched MEDLINE and Embase to identify the relevant reports. Two independent reviewers assessed the reports against the eligibility criteria in a double-blind process. Results: The searches (date: 4 April 2023) identified 432 records for screening. Ten non-controlled observational studies were identified, five using portable or handheld echocardiography, comprising data from 23,166 women. Prevalence of RHD varied across the studies, ranging from 0.4 to 6.6% (I2, heterogeneity >90%). Other cardiac abnormalities (e.g., congenital heart disease and left ventricular systolic dysfunction) were also detected <1% to 2% of cases. Certainty of evidence was very low. Conclusion: Echocardiography as part of antenatal care in high-prevalence areas may detect RHD or other cardiac abnormalities in asymptomatic pregnant women, potentially reducing the rates of disease progression and adverse labor-associated outcomes. However, this evidence is affected by the low certainty of evidence, and lack of studies comparing echocardiography versus standard antenatal care. Prospective Registration: PROSPERO 2022 July 4; CRD42022344081 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=344081. Research question: 'In areas with a high prevalence of rheumatic heart disease, should handheld echocardiography be added to routine antenatal care?'

p21 Protein Outperforms Clinico-pathological Criteria in Predicting Liver Metastases in Pancreatic Endocrine Tumors.

BACKGROUND/AIM: P21 is a cyclin-dependent kinase inhibitor regulating the cell cycle as a tumor suppressor. Using a p21 immunohistochemistry (IHC) assay, we compared tumor p21 levels with conventional clinico-pathological criteria in primary pancreatic endocrine tumor subsets with and without liver metastases. MATERIALS AND METHODS: Sections from tissue microarray (TMA) including 13 archival metastatic primary and 18 non-metastatic primary pancreatic endocrine carcinomas/tumors (MP-PECAs/NMP-PETs) were stained with a monoclonal anti-p21WAFI,CIP primary antibody. Tumor p21 IHCs were scored as the sum of intensity (0-3) and proportion scores (0-5) (Total Allred score: 0-8), and as p21% labelling index in the tumor. ROC curve analysis was used for most optimal p21 score cut-off (4 or >) and Fisher's exact test was used to compare the association among tumor p21 scores, conventional prognostic criteria, and liver metastases. RESULTS: For PET/PECA patients, mean ages were 55.6 years (27-73) and 49.3 years (28-71), M/F ratios were 7/11 and 7/6. Mean p21 labelling index (%) for MP- PECAs was 24% (range=3-63%) vs. 9% for NMP-PETs (range=1-25%) (p=0.022). The mean p21 index in MP-PECAs was significantly higher (24%) as compared to PIs (7%) (p=0.0047). Using a p21 Allred score of ≥4, high p21 IHC score had strong association with the presence of liver metastases (p-value <0.001). High tumor p21 IHC score had a 93% sensitivity, 68% specificity, 78% predictive accuracy, 66% positive, and 94% negative predictive values. CONCLUSION: In patients with primary PETs, p21 IHC is superior to conventional criteria in predicting presence or absence of liver metastases.