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The coronavirus disease 2019 (COVID-19) that can cause extreme acute respiratory syndrome has posed a catastrophic threat to public health. The vaccines had indeed restored optimism and, after more than two years of battling the pandemic, there is renewed hope for the transition to endemicity. At the start of vaccination efforts, when supply shortages of vaccines were inevitable, every nation determined the high-risk population groups to be given priority for the COVID-19 vaccines. In this paper, the characteristics of the initial COVID-19 vaccine recipients in Malaysia are described. In line with the policies of many other countries, Malaysia firstly inoculated frontline healthcare workers, and subsequently the list of front liners grew to include defense and security personnel and those involved in the provision of essential services. People with disabilities or those with special needs and several underlying medical conditions that increased their risk of developing severe COVID-related illnesses were included in the priority categories. These included patients with severe lung disease, chronic heart disease, chronic kidney disease, chronic liver disease, neurological disease, diabetes mellitus and obesity in adults, splenic dysfunction, and severe mental illness. With little information and under circumstances of great uncertainty, the Health Ministry of a middle-income country had developed a vaccination priority-list based on the disease's epidemiology and clinical data, vaccine type, operational considerations, and risk evaluation. Early evidence was presented and suggested that the full vaccination with any of the three predominant vaccines (AZD1222, BNT162b2, and CoronaVac) in the country had been highly effective in preventing COVID-19 infections, COVID-19-related ICU admissions, and death. As many SARS-CoV-2 variants of concern (VoC), such as the Omicron BA.2/4/5, are emerging, future vaccination strategies may necessitate the need to change the immunogen of the vaccine, as well as considerations for when to give high-risk groups booster injections. These considerations are valuable for future planning by policymakers and healthcare providers to make vaccination policy and decisions, especially for the inclusion of the COVID-19 vaccines into national immunization programs. [ABSTRACT FROM AUTHOR]

The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. Here, we examined how putamen volume, neuronal density, and mood-modulated functional activity relate to family history and prospective course of depression. The study includes 115 second- and third-generation offspring at high or low risk for depression based on the presence or absence of major depressive disorder in the first generation. Offspring were followed longitudinally using semistructured clinical interviews blinded to their familial risk; putamen structure, neuronal integrity, and functional activation were indexed by structural magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (N -acetylaspartate/creatine ratio), and functional MRI activity modulated by valence and arousal components of a mood induction task, respectively. After adjusting for covariates, the high-risk individuals had lower putamen volume (standardized betas, β- left = −0.17, β- right = −0.15, p s =.002), N -acetylaspartate/creatine ratio (β- left = −0.40, β- right = −0.37, p s <.0001), and activation modulated by valence (β- left = −0.22, β- right = −0.27, p s <.05) than low-risk individuals. Volume differences were greater at younger ages, and N -acetylaspartate/creatine ratio differences were greater at older ages. Lower putamen volume also predicted major depressive disorder episodes up to 8 years after the scan (β- left = −0.72, p =.013; β- right = −0.83, p =.037). Magnetic resonance spectroscopy and task functional MRI measures were modestly correlated (0.27 ≤ r ≤ 0.33). Findings demonstrate abnormalities in putamen structure and function in individuals at high risk for major depressive disorder. Future studies should focus on this region as a potential biomarker for depressive illness, noting meanwhile that differences attributable to family history may peak at different ages based on which MRI modality is being used to assay them. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the frequency of Human Papillomavirus (HPV) genotypes in wastewater of Salto city, Uruguay, in order to obtain a general overview of the circulating genotypes in their population. HPV was detected in 34% (32/93) of the wastewater samples collected and analyzed during 2020/21 in Salto city, Uruguay. Thirty-three genotypes were observed, of which 16 presented read abundance higher than 1%, including both high-risk (HR) and low-risk (LR) genotypes. HR genotypes 31, 16, 58, 52, 33 and 59 were detected representing 40% (163,220 reads) of the total read abundance, with genotypes 31 (64,365), 16 (39,337) and 58 (36,332) being the most abundant. LR genotypes 72, 6, 11 and 40 were also detected in a high frequency, accounting for 37% (148,359) of the HPV reads. This study highlights the high frequency of HR genotypes of HPV, circulating in the population of Salto city which is a burden in public health mainly due to the devastating impact of cervical cancer in women. [ABSTRACT FROM AUTHOR]

To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC). We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors. Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology. Observation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research. • Some subgroups of high-intermediate-risk and high-risk endometrial cancer (EC) represent <1% of all ECs. • Three-year cause-specific survival after observation or brachytherapy only is higher than 85% in 15 of the 16 subgroups. • Observation or brachytherapy may be adequate in stage I endometrioid ECs without grade 3 or lymphovascular space invasion. • Non-endometrioid ECs without myometrial invasion have a good prognosis with only observation or vaginal brachytherapy. [ABSTRACT FROM AUTHOR]

The proclivity of certain pre-malignant and pre-invasive breast lesions to progress while others do not continues to perplex clinicians. Clinicians remain at a crossroads with effectively managing the high-risk patient subpopulation owing to the paucity of biomarkers that can adequately risk-stratify and inform clinical decisions that circumvent unnecessary administration of cytotoxic and invasive treatments. The immune system mounts the most important line of defense against tumorigenesis and progression. Unfortunately, this defense declines or "ages" over time—a phenomenon known as immunosenescence. This results in "inflamm-aging" or the excessive infiltration of pro-inflammatory chemokines, which alters the leukocyte composition of the tissue microenvironment, and concomitant immunoediting of these leukocytes to diminish their antitumor immune functions. Collectively, these effects can foster the sequelae of neoplastic transformation and progression. The erythrocyte cell antigen, Duffy antigen receptor for chemokines(DARC/ACKR1), binds and internalizes chemokines to maintain homeostatic levels and modulate leukocyte trafficking. A negative DARC status is highly prevalent among subpopulations of West African genetic ancestry, who are at higher risk of developing breast cancer and disease progression at a younger age. However, the role of DARC in accelerated inflamm-aging and malignant transformation remains underexplored. Herein, we review compelling evidence suggesting that DARC may be protective against inflamm-aging and, therefore, reduce the risk of a high-risk lesion progressing to malignancy. We also discuss evidence supporting that immunotherapeutic intervention—based on DARC status—among high-risk subpopulations may evade malignant transformation and progression. A closer look into this unique role of DARC could glean deeper insight into the immune response profile of individual high-risk patients and their predisposition to progress as well as guide the administration of more "cyto-friendly" immunotherapeutic intervention to potentially "turn back the clock" on inflamm-aging-mediated oncogenesis and progression. [ABSTRACT FROM AUTHOR]

Background: Most of the extraintestinal human infections worldwide are caused by specific extraintestinal pathogenic Escherichia coli (ExPEC) lineages, which also present a zoonotic character. One of these lineages belongs to ST38, a high-risk globally disseminated ExPEC. To get insights on the aspects of the global ST38 epidemiology and evolution as a multidrug-resistant and pathogenic lineage concerning the three axes of the One Health concept (humans, animals, and natural environments), this study performed a global phylogenomic analysis on ST38 genomes. Methods: A phylogenetic reconstruction based on 376 ST38 genomes recovered from environments, humans, livestock, and wild and domestic animals in all continents throughout three decades was performed. The global information concerning the ST38 resistome and virulome was also approached by in silico analyses. Results: In general, the phylogenomic analyses corroborated the zoonotic character of the ExPEC ST38, since clonal strains were recovered from both animal and human sources distributed worldwide. Moreover, our findings revealed that, independent of host sources and geographic origin, the genomes were distributed in two major clades (Clades 1 and 2). However, the ST38 accessory genome was not strictly associated with clades and sub-clades, as found for the type 2 T3SS ETT2 that was evenly distributed throughout Clades 1 and 2. Of note was the presence of the Yersinia pestis-like high-pathogenicity island (HPI) exclusively in the major Clade 2, in which prevails most of the genomes from human origin recovered worldwide (2000 to 2020). Conclusions: This evidence corroborates the HPI association with successful E. coli ST38 establishment in human infections. [ABSTRACT FROM AUTHOR]

Abstract Background High-risk pregnancies require increased health and care resources to reduce the severe perinatal consequences. The adoption of a health-promoting lifestyle and social determinants is an important strategy for achieving the desired outcomes of pregnancy. This study aimed to compare intermediate determinants of social health in low and high-risk pregnant women. Methods This unmatched case-control study was performed with a ratio of 1: 2 and 300 pregnant women including 200 healthy and 100 pregnant women with gestational hypertension were included using the available sampling technique. Data were collected using socio-demographic and obstetrics, Health-promoting behaviors, Self-efficacy, Perceived stress, and Social support questionnaires by the self-report method. Results There was no significant difference in the demographic characteristics between the two groups, except for the spouse's education status. The total score of health-promoting behaviors and social support in the healthy group was significantly higher than women with gestational hypertension. However, the perceived stress in women with gestational hypertension was significantly higher than in the healthy group. In the multivariate analysis, those women with high stress [AOR 1.13, 95% CI (1.08–1.18)] and whose Spouse’s Educational status was low [AOR 4.94, 95% CI (1.54–15.81)] had higher odds of gestational hypertension than women who haven’t respectively. The development of gestational hypertension was decreased by increasing the score of social support [AOR 0.96, 95% CI (0.93–0.98)]. The results showed that the two variables of social support (β=0.331) and self-efficacy (β=0.215) have the greatest impact on the score of health-promotion behaviors, respectively. Based on regression analysis, 21.2% of the health-promotion behaviors changes could be explained by three independent variables. Conclusion Women with gestational hypertension have unhealthier lifestyles. Having a high level of stress is a risk factor for gestational hypertension but Social support has a protective effect on it. Recognizing the risk factors of gestational hypertension could help the determination of high-risk cases and it is important to pay attention to women's psychosocial to create appropriate sources of social support and provide the necessary action to reduce stress.

Minimally invasive surgery may not be an appropriate surgical approach in intermediate- and high-risk endometrial carcinoma, even though adjuvant therapy is given. The objective of this study was to evaluate the results of open surgery including lymphadenectomy without adjuvant therapy in patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma. Two hundred fifty-six patients with uterine-confined endometrioid endometrial carcinoma were treated with open surgery, including pelvic with or without para-aortic lymphadenectomy. Of the 81 patients with uterine-confined intermediate- or high-risk disease, 77 were treated with systematic lymphadenectomy without adjuvant therapy. Seven patients developed recurrence, comprising 5.5% (3/55) and 18.2% (4/22) of the intermediate- and high-risk patients, respectively. The time to recurrence was 1–66 months. The sites of recurrence were the vaginal apex (n = 2), lung (n = 2), vaginal sidewall (n = 1), pelvic lymph nodes (n = 1), and para-aortic to supraclavicular nodes (n = 1). Of these, five patients were alive without disease after salvage treatment, but two understaged high-risk patients died of disease. The five-year disease-specific survival rates of intermediate- and high-risk patients were 100% and 90%, respectively. The present study indicated that patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma had excellent survival when treated with open surgery, including lymphadenectomy alone. The safety of omitting adjuvant therapy should be evaluated in prospective randomized trials comparing open surgery with minimally invasive surgery.

Although treatment of multiple myeloma has changed dramatically over time, there is still a subpopulation of patients who do not respond to treatments and are labeled as high risk. A combination of serum and genomic markers can be used to identify and stratify these patients according to associations with outcome. The most common method of identifying the genomic markers of high-risk multiple myeloma is using fluorescence in situ hybridization using probes to identify IgH translocations or copy number changes including the t(4;14), t(14;16), t(14;20), gain 1q, and del(17p). However, as research studies utilize newer technologies, such as whole genome sequencing, more high-risk factors are being identified including mutations of TP53, DIS3, BRAF, and complex structural events. Integration of comprehensive genomic studies into clinical trials will aid in defining the genomic high-risk landscape of multiple myeloma, which in turn can be transferred to individual patient diagnostics and treatment management.

Abstract Background The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors. Methods We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or

Abstract Background Valproate is a teratogenic drug that should be avoided during the preconception period and pregnancy. The aim was to explore general practitioners’ (GPs) prescription patterns over time, describe trends, and explore inter-practice variation within primary care. Methods We identified women of childbearing age (12–46 years old) in the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network. We performed repeated cross-sectional analyses from 2004 to 2018 to determine rates of prescription and a retrospective cohort estimated the prevalence of use of valproate during pregnancy. Results In 2004, 0.31% (95% Confidence Interval (95%CI):0.18 to 0.44%) women were prescribed valproate, decreasing to 0.16% (95%CI:0.07 to 0.24%) by 2018. Among women with epilepsy, the rate fell from 15.2% (95%CI:14.4 to 16.0%) to 8.8% (95% CI:8.2 to 9.7%) over the same period. In 2018, almost two thirds (62.2%) of women who were prescribed valproate had epilepsy only, whereas bipolar disorder and migraine accounted for 15.8% and 7.4% respectively. Contraceptive prescriptions did not increase over time, and only in 2018 was there greater odds of being prescribed contraception (OR 1.41, 95%CI:1.08 to 1.45). Just under a fifth (19.7%) of women were prescribed valproate during their pregnancy; two out of three of these pregnancies were preceded by folic acid prescription (5 mg). While some practices reduced their rate of valproate prescription, others did not. Conclusions Regulatory guidelines have changed GPs' prescription patterns in women of childbearing potential for valproate but not for contraception. Further research is needed to identify the barriers of GPs and women of childbearing potential to undertaking contraception.

BackgroundFetal specialists support standardizing the practice of offering women palliative care for life limiting fetal diagnoses. However, there is little data available regarding what fetal specialists do in practice. Since 2003, our center has kept a database of all women referred for fetal complications.MethodsRetrospective electronic chart review of pregnant women between 2006 and 2012 using UCSD's Fetal Care and Genetics Center referral database. Objectives were to determine: (I) how many high risk pregnancies referred to the University of California San Diego Medical Center (UCSD) over a 6-year period have potentially life limiting fetal diagnoses; (II) pregnancy outcome; and (III) referral rate to perinatal palliative care.ResultsBetween July 2006 and July 2012, 1,144 women were referred to UCSD's Fetal Care and Genetics Center, a tertiary care center. Of that cohort, 332 women (29%) were diagnosed prenatally with a potentially life limiting fetal diagnosis. Most women were Hispanic or Latino, married, and had previous children. The median gestation at confirmed diagnosis was 19 weeks. Trisomy 13, Trisomy 18, and anencephaly comprised 21% of cases. The pregnancy outcome was determined in 95% cases: 56% therapeutic abortion, 16% intrauterine fetal demise, and 23% live birth. Only 11% of cases were referred to perinatal palliative care.ConclusionsThe vast majority of women with potentially life limiting fetal diagnoses are not referred to perinatal palliative care. Evaluation of how to integrate palliative care into high-risk obstetrics is needed.

Analysis of high-risk HPV status on formalin-fixed paraffin-embedded (FFPE) tissue material is valuable for cervical-, head and neck-, anogenital- and other types of cancer, but commercial HPV assays have been developed specifically for cervix swab cells. We evaluated the BD Onclarity™ HPV Assay for the detection of high-risk HPV on an assortment of relevant FFPE tissues with known HPV status. Detection of high-risk HPV types using the BD Onclarity™ HPV Assay in FFPE specimens was easy and accurate.

Human cytomegalovirus (HCMV) is a herpesvirus that infects between 40% and 95% of the population worldwide, usually without symptoms. The host immune response keeps the virus in a latent stage, although HCMV can reactivate in an inflammatory context, which could result in sequential lytic/latent viral cycles during the lifetime and thereby participate in HCMV genomic diversity in humans. The high level of HCMV intra-host genomic variability could participate in the oncomodulatory role of HCMV where the virus will favor the development and spread of cancerous cells. Recently, an oncogenic role of HCMV has been highlighted in which the virus will directly transform primary cells; such HCMV strains are named high-risk (HR) HCMV strains. In light of these new findings, this review defines the criteria that characterize HR-HCMV strains and their molecular as well as the phenotypic impact on the infected cell and its tumor microenvironment. [ABSTRACT FROM AUTHOR]

Learning objectives: After completing this activity, practitioners will be better able to: • Discuss the association between brain alterations and vulnerability or resilience to MDD in people with familial risk • Define how structural and functional brain alterations associated with vulnerability or resilience could lead to a better understanding of the pathophysiology of MDD Aim: Familial history is associated with an increased risk for major depressive disorder (MDD). Despite the increased risk, some members of the familial high-risk population remain healthy, that is, resilient. Defining the structural and functional brain alterations associated with vulnerability or resilience could lead to a better understanding of the pathophysiology of MDD. This study aimed to review the current literature and discuss the association between brain alterations and vulnerability or resilience to MDD in people with familial risk. Methods: A literature search on MRI studies investigating structural and functional alterations in populations at familial risk for MDD was performed using the PubMed and SCOPUS databases. The search was conducted through June 13, 2022. Results: We reviewed and summarized the data of 72 articles (25 structural MRI, 35 functional MRI, 10 resting-state fMRI, one structural/functional MRI combined, and one structural/functional/resting-state fMRI combined). These findings suggested that resilience in high-risk individuals is related to the amygdala structure, frontal lobe activity, and functional connectivity between the amygdala and multiple frontal regions. Conclusion: Resilient and vulnerable individuals exhibit structural and functional differences in multiple frontal and limbic regions. However, further systematic longitudinal research incorporating environmental factors is required to validate the current findings. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Applied Ecology / Yingyong Shengtai Xuebao is the property of Chinese Journal of Applied Ecology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Identifying the prevalence and management of patients at high-risk for breast cancer can improve resource utilization and provide individualized screening strategies.Objective: The purpose of this study was to identify the prevalence of high-risk patients in our institution who presented for screening mammography and to understand how they utilized downstream resources offered to them.Materials and Methods: This single institution retrospective study utilized the Tyrer-Cuzick risk assessment model to provide lifetime risk of breast cancer of patients presenting for screening mammography over a one-year period. Their subsequent management and resource utilization were collated.Results: High-risk patients comprised 7.7% (701/9061) of our screening population. Of those high-risk women offered a Breast Center (BC) consultation, 75.2% (276/367) participated in the consultation, with 51.1% (141/276) of those patients completing MRI for supplemental screening. Risk reducing medication was adopted by 7.6% (6/79) of those offered. Of patients offered a genetics consultation, 66.3% (53/80) participated in the consultation, and 50.0% (40/80) completed genetic testing.Conclusions: Identifying and understanding high-risk patient cohorts, whether locally or in a population-based context, is important for individualized patient care and practice efficiency. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Ciencias Médicas de Pinar del Río is the property of Editorial Ciencias Medicas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To identify clinical and central features that differentiate ADHD youth with and without familial risk for bipolar I disorder (BD). Methods: Psychostimulant-free ADHD youth (10–18 years) with and without a first-degree relative with BD and healthy controls were enrolled. Bilateral ventrolateral prefrontal cortex (VLPFC) proton magnetic resonance spectroscopy (1H MRS) scans and a range of symptom ratings were performed. Results: A total of n = 145 youth were enrolled. ADHD youth with a family history of BD exhibited greater manic and depressive symptom severity, ADHD hyperactivity/impulsive symptom severity, and higher parent-reported ratings of dysregulation compared with ADHD youth without a BD family history. Although VLPFC metabolite levels did not differ across groups, choline levels in the left VLPFC correlated with different symptom ratings. Conclusion: Symptom profiles including more severe mood and externalizing symptoms, but not VLPFC neurochemistry, differentiate psychostimulant-free ADHD youth with and without a family history of BD. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple Myeloma (MM) is considered an incurable chronic disease, which prognosis depends on the presence of different genomic alterations. To accomplish a complete molecular diagnosis in a single essay, we have designed and validated a capture-based NGS approach to reliably identify pathogenic mutations (SNVs and indels), genomic alterations (CNVs and chromosomic translocations), and IGH rearrangements. We have observed a good correlation of the results obtained using our capture panel with data obtained by both FISH and WES techniques. In this study, the molecular classification performed using our approach was significantly associated with the stratification and outcome of MM patients. Additionally, this panel has been proven to detect specific IGH rearrangements that could be used as biomarkers in patient follow-ups through minimal residual disease (MRD) assays. In conclusion, we think that MM patients could benefit from the use of this capture-based NGS approach with a more accurate, single-essay molecular diagnosis. Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival (p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes (p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients. [ABSTRACT FROM AUTHOR]

NOTCH1 is a cell surface receptor that releases its intracellular domain as transcription factor upon activation. With the advent of next-generation sequencing, the NOTCH1 gene was found recurrently mutated in chronic lymphocytic leukaemia (CLL). Here, virtually all NOTCH1 mutations affect the protein's PEST-domain and impair inactivation and degradation of the released transcription factor, thus increasing NOTCH1 signalling strength. Besides sequence alterations directly affecting the NOTCH1 gene, multiple other genomic and non-genomic alterations have by now been identified in CLL cells that could promote an abnormally strong NOTCH1 signalling strength. This renders NOTCH1 one of the key signalling pathways in CLL pathophysiology. The frequency of genomic alterations affecting NOTCH1 signalling is rising over the CLL disease course culminating in the observation that besides TP53 loss, 8q gain and CDKN2A/B loss, NOTCH1 mutation is a hallmark genomic alteration associated with transformation of CLL into an aggressive lymphoma (Richter transformation). Both findings associate deregulated NOTCH1 signalling with the development of high-risk CLL. This narrative review provides data on the role of NOTCH1 mutation for CLL development and progression, discusses the impact of NOTCH1 mutation on treatment response, gives insight into potential modes of NOTCH1 pathway activation and regulation, summarises alterations that have been discussed to contribute to a de-regulation of NOTCH1 signalling in CLL cells and provides a perspective on how to assess NOTCH1 signalling in CLL samples. [ABSTRACT FROM AUTHOR]

Patients with high-risk prostate cancer (PCa) experience heterogeneous oncological outcomes. In this study, we assessed the patients who underwent an RP procedure because of high-risk prostate cancer in subgroups formed according to D'Amico criteria and analyzed the effects of these criteria on biochemical recurrence (BCR) after RP. We retrospectively identified high-risk non-metastatic PCa patients who underwent RP between 2006 and 2020 in our hospital. Groups were formed as follows: group 1 consisted of those with an ISUP grade 4 − 5 biopsy, group 2 consisted of those with a clinical stage T2c, group 3 consisted of those with a tPSA level ≥ 20 ng/ml, and group 4 consisted of those with locally advanced disease. Survival analyses were made by Kaplan–Meier test and Log Rank test. A P value <0.05 was accepted as statistically significant. Of all patients, 61.8% were cured by only RP and 38.2% had recurrences. Rates of BCR were significantly different among groups (P = 0.003). In group 1, group 2, group 3, and group 4, BCR rates were 30.8%, 13%, 40.8%, and 70.6%, respectively. Mean BCR-free survival was 82.47 ± 11.64 months. In group 2, BCR-free survival was higher than that in group 3 and group 4 (P1 = 0.020 and P2 = 0.001) and in group 1, BCR-free survival was higher than that in group 4 (P = 0.016). There was no significant difference between group 3 and 4 (P > 0.05). Despite the developments in the imaging technology, an elevated tPSA level remains to be an important predictor for BCR-free survival. [ABSTRACT FROM AUTHOR]

Ischemic stroke is by far the most common type of cerebrovascular event and remains a major cause of death and disability globally. Despite advancements in acute stroke care, primary prevention is still the most cost-effective approach in reducing the burden of ischemic stroke. The two main strategies for primary stroke prevention include population-wide versus high-risk group interventions. Interventions such as increasing access to primary care, regulation of salt and sugar contents in processed foods, public education, and campaigns to control cerebrovascular risk factors are examples of population-wide interventions. High-risk group interventions, on the other hand, focus on recognition of individuals at risk and aim to modify risk factors in a timely and multifaceted manner. This article provides an overview on conventional modifiable risk factors for ischemic stroke and highlights the emerging risk factors and approaches for high-risk group identification and treatment. [ABSTRACT FROM AUTHOR]

Background: Oesophageal replacement by colonic interposition remains a major challenge due to its complexity and high incidence of complications; here we applied the two-stage operation strategy to oesophageal replacement by colonic interposition in high-risk oesophageal cancer patients following gastrectomy.Methods: We performed a retrospective analysis on the data of patients with a history of distal gastrectomy who underwent one-stage and two-stage oesophageal replacement by colonic interposition from February 2012 to February 2020, and explored the relationship between the staging strategy and postoperative outcomes.Results: The clinical data of 93 patients were collected and analysed. There were no significant differences in the patients' characteristics between the two groups (all p > 0.05), except for comorbidities and Charlson Comorbidity Index (all p < 0.05). The Clavien-Dindo score between the two groups was also not significantly different (p > 0.05). The logistic regression models revealed that patients who had received preoperative therapy had a higher Clavien-Dindo score (p < 0.05), but the stage strategy did not (p > 0.05).Conclusions: The two-stage operation is feasible in high-risk patients who need to undergo colonic interposition for oesophageal replacement. At the same time, it lowers the technical threshold of colonic interposition for oesophageal replacement, increasing this surgical technique's acceptability. [ABSTRACT FROM AUTHOR]

Objectives: investigate whether prenatal characteristics were associated with dietary pattern of pregnant women. Methods: we studied 200 high-risk pregnant women in Fortaleza, Ceará. The identification of dietary patterns was performed through principal component analysis with the orthogonal Varimax rotation. Poisson regression was used to estimate prevalence ratios (PR) and respective confidence intervals (CI95%). Results: three major dietary patterns were identified: 'common Brazilian', 'healthy' and 'energydense'. After adjustments conducted with multivariate analysis, pregnant women who had not received dietary guidance in prenatal consultations (34%) were less likely to adhere to the 'healthy' pattern (PR = 0,81; CI95%= 0,67-0,95). Pregnant women who attended an appropriate number of consultations (= 6 consultations) (41%) showed greater adherence to the 'healthy' pattern (PR = 1,15; CI95%= 1,01-1,32) and lower adherence to the 'energy-dense' pattern (PR = 0,85; CI95%= 0,74-0,99). Conclusion:it was observed that the high-risk pregnant women who attended an adequate number of consultations during the prenatal care had a higher chance to adhere to the 'healthy' pattern and a lower chance to adhere to the 'energy-dense' pattern. Not receiving guidelines on prenatal nutrition was inversely associated with the healthy pattern. Thus, the importance of high-risk pregnant women undergoing an appropriate prenatal care is reinforced. [ABSTRACT FROM AUTHOR]

Keywords: CABG; CVVH; fluid management; high-risk; ultrafiltration EN CABG CVVH fluid management high-risk ultrafiltration 2951 2957 7 09/06/22 20221001 NES 221001 INTRODUCTION Coronary artery bypass grafting (CABG) surgery for coronary artery disease (CAD) remains the most common cardiac surgery performed in the USA and Canada.1-4 The increased age of patients along with risk factors for CAD (i.e., hypertension [HTN], diabetes mellitus [DM], obesity, and chronic kidney disease [CKD]) increase the perioperative risk for acute kidney injury (AKI) and subsequent fluid overloaded (FO) states. Two of these four patients (Patients #1 and #11) met the CVVH requirements (Table 3) and were initiated on CVVH in the postoperative period (before UF therapy) (Table 4) due to postoperative shock states and anuria. CVVH is the preferred choice over conventional HD for postoperative cardiac surgery patients due to improved hemodynamic tolerance.14 Adult cardiac surgery patients mostly present acutely after many years of chronic medical conditions and modifiable risk factors, including HTN, DM, obesity, hyperlipidemia, physical inactivity, and smoking. Four of the UF patients received postoperative new onset CVVH and UF therapy and 10 of the UF patients received only postoperative UF therapy (no CVVH). [Extracted from the article]

Background: How to implement robotic-assisted PCI safely and when to escalate to more complex cases has not been previously described. We sought to evaluate clinical outcomes in patients undergoing robotic-assisted PCI in the first year of a newly established robotic-assisted PCI program.Methods: All patients who underwent robotic-assisted PCI in the first 12 months at a single academic center were included in the study. Lesion complexity was characterized as "PRECISE-like", "CORA-PCI-like", or "CORA-PCI excluded" based on established criteria. The primary outcome was clinical success, defined as <30% residual stenosis after stenting with a final TIMI flow grade 2-3 and no procedural complications. Secondary outcomes included robotic success, defined as clinical success with robotic completion, unintentional manual conversion rate, procedure time, and procedural complications.Results: Of the 57 consecutive lesions treated, 12 (22.6%) had a PRECISE-like lesion complexity while 32 (56.1%) had a CORA- PCI-like, and 13 (22.8%) a CORA-PCI excluded lesion complexity. There was no significant difference in clinical success (100.0% vs. 96.7% vs. 100.0%, p = 1.00) among the groups but robotic success was numerically lower as complexity increased (100.0% vs. 80.0% vs. 72.7%, p = 0.15), with an increased frequency of manual conversion. There was no significant difference in procedural complication rates among the groups. The robotic completion rate improved during the study period.Conclusion: Robotic-assisted PCI, can be safely implemented in a moderate-sized academic center, with a rapid escalation in patient and lesion complexity. [ABSTRACT FROM AUTHOR]

Background: Human papillomaviruses (HPVs) are non-enveloped, double-stranded DNA viruses and most women in the world are probably infected with at least one type of the virus during their sexual life. Oncogenic HPVs are predominantly sexually-transmitted pathogens and several high-risk types are associated with nearly all cases of cervical cancer worldwide. In view of paucity of data on the prevalence and distribution of various high risk HPV subtypes, this study was carried out to provide evidence based local data for cervical cancer preventive programs within this region. Methodology: This was a descriptive cross-sectional study involving 145 consenting women living in Ugbegun rural community of Edo central senatorial district, Edo State, Nigeria. Informed consent of each participant was obtained and socio-demographic information collected through interviewer-administered collection tool. Cervical swab sample was collected using the female cervical cell collection kit for HPV DNA testing. HPV DNA was detected by the Hybribio 21 HPV Geno array test kit which uses polymerase chain reaction (PCR) amplification and flow through hybridization assay. Summary statistics were presented as mean, standard deviation, median, frequency and proportions as appropriate using the Statistical Package for the Social Sciences (SPSS) version 22.0. Association of sociodemographic characteristics of the women with HPV prevalence was done using the 't' test, with p value less than 0.5 considered statistical significance. Results: Twenty four of the 145 women tested positive, giving HPV prevalence of 16.6%. Six HPV serotypes were detected; types 16, 18, 35, 45, 52 and 58. HPV types 16 and 18 were most frequent, contributing 54.2%, and coinfection occurred in 29.2%. HPV-positive women had significantly higher mean number of life time sexual partners (p=0.046) and mean parity (p=0.0001) compared to HPV-negative women. The mean age of the women (p=0.710), mean age at menarche (p=0.570) and mean age at coitarche (p=0.940) were not significantly associated with prevalence of HPV Conclusion: This study showed predominance of oncogenic cervical HPV types 16 and 18 within this sub region of rural Nigeria. Strengthening reproductive and sexual education in both males and females with focus on HPV vaccination, delaying sexual activities and reduction in number of child birth are strategies which could prevent high risk HPV infection and cervical cancer in rural communities. [ABSTRACT FROM AUTHOR]

to identify the obstetric practices used in labor and delivery in parturients classified as high risk was the objective of the present study. Method: quantitative study. The population consisted of postpartum women classified as high risk. Data collection took place from October 2016 to August 2017. SPSS® 20.0 was used. The study was approved with opinion number 1,757,596 Results: 319 women were analyzed. The prevailing profile was white women (58.7%), aged between 20 and 35 years (70.7%). Most underwent prenatal care (99.3%) and were primiparous (40.4%). The most frequent pathologies were hypertension (50.0%) and diseases associated with metabolism (22.3%). About the monitoring of labor, 83.3% of auscultation of the fetal heartbeat. Cesarean section prevailed among 60.8% of women. Regarding non-pharmacological methods for pain relief, the most used were: hot spray bath (37.9%), perineal exercise ball (25.0) Conclusion: all obstetric practices, in addition to ensuring a safe evolution, provide an experience positive about childbirth, even if the classification is high risk. [ABSTRACT FROM AUTHOR]

In pregnancy, the attachment relationship between a mother and her baby begins to develop and women are more motivated and willing to make changes to become more engaged and responsive mothers and have better relationships with their children. A transgenerational framework has proposed that dysfunctional relationship patterns are often repeated across generations and this has broadened the understanding of early difficulties in parenting. Despite this there has been little research specifically examining high-risk perinatal women and how their interactions with their infants are related to attachment or relational outcomes. This pilot study aims to evaluate, and to explore the acceptability and feasibility, of participating in the Supporting Transitions, Attachment and Relationships (STAR Mums) program, a psychodynamic attachment-based group intervention, for pregnant women with risk factors for attachment difficulties. The STAR Mums program aims to intervene during pregnancy to assist women with risk factors in the transition to parenthood with the desired outcome to improve the quality of mother-infant emotional interactions, regulation and the attachment relationship. This is a mixed-methods design study incorporating both qualitative and quantitative assessments of five groups of five first-time mothers over a 12-month period. This paper outlines the STAR Mums intervention and protocol for assessing acceptability and feasibility. The STAR Mums program takes a preventative approach and supports early intervention for parents at risk of attachment difficulties with their infants. The results of this study will inform revisions to the current treatment manual and a larger-scale program evaluation to further examine the efficacy of this intervention. [ABSTRACT FROM AUTHOR]

Objectives: The current best practice implementation project aimed to improve the quality of continuity of care and emotional well-being in women with high-risk pregnancies. Introduction: Perinatal mental health disorders, such as perinatal depression and anxiety, are considered major health issues and are associated with poor maternal and neonatal outcomes. Women with high-risk pregnancies are considered a group of women with a substantial vulnerability and the value of continuity of care is vital in this group. Methods: The current project used the pre–post implementation clinical audit following the JBI Evidence Implementation framework. A baseline audit and a follow-up audit were conducted involving 120 high-risk pregnant women in a hospital's obstetric unit. An intervention was performed establishing a midwife consultation and a referral circuit for the different healthcare professionals. A screening was performed through several validated questionnaires. Results: To reflect the continuum of care, three topics were selected, including antenatal psychosocial assessment, intrapartum care and postpartum depression assessment, with a total of 10 criteria. The baseline audit results showed 0% compliance in all the criteria since the proposed standards of care did not exist before the audit. After the implementation of the strategies, the compliance achieved 100% in all audit criteria. A multidisciplinary hospital guideline was established for standardized care and mental well-being care for high-risk pregnant women. Conclusion: Follow-up in the mental health of pregnant women is insufficient. Improving emotional well-being in pregnancy should be a target of clinical practice. More national and international guidelines to assess mental well-being during pregnancy and the postpartum period should be developed. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to examine whether elective inclusion of the posterolateral supraclavicular node (SCL) region to the standard medial SCL target volume improves SCL control and survival outcomes in patients with high-risk node-positive breast cancer undergoing regional nodal irradiation (RNI).Methods and Materials: We retrospectively reviewed 544 consecutive women with high-risk breast cancer treated with postoperative chest wall/breast and RNI in our center from January 2015 to December 2016. High-risk features were defined as clinical or pathologic stage N2-3b disease. Patients were classified into the medial SCL irradiation (M-SCLI) group and the entire SCL irradiation (E-SCLI) group, which included both the medial and the posterolateral SCL region. SCL recurrence (SCLR), disease-free survival (DFS), and overall survival (OS) were estimated and compared. Propensity-score matching (PSM) and multivariate cox regression were used for analysis.Results: The median follow-up time was 64.2 months. Before PSM, there was no significant difference in the cumulative incidence of SCLR between the 2 groups, with 5-year rates of 2.0% in the M-SCLI group and 0.6% in the E-SCLI group (P = .1). After PSM, there was also no significant difference in the cumulative incidence of SCLR (2.1% vs 0.5%; P = .2). Only 2 patients had recurrence in the posterolateral SCL region, with 1 patient in each group. Similarly, there was no significant difference in DFS and OS between the M-SCLI and E-SCLI group both before PSM (5-year rates of 78.5% vs 78.8%, P = .8; 92.2% vs 90.0%, P = .2) and after PSM (76.7% vs 77.2%, P = .8; 91.5% vs 88.4%, P = .1). Multivariate analysis demonstrated that E-SCLI was not independently prognostic for DFS and OS.Conclusions: E-SCLI does not appear to be associated with improved SCL control and survival outcomes in high-risk node-positive breast cancer. These data do not support the routine use of E-SCLI in N2-3b disease. We initiated a multicenter randomized controlled phase 3 study comparing M-SCLI and E-SCLI to further validate these results. [ABSTRACT FROM AUTHOR]

Objectives: To determine the incidence and types of inborn errors of metabolism (IEMs) in high-risk children using mass spectrometry techniques. Methods: Children considered high-risk for IEM were screened for metabolic diseases during a 3-y period. Dried blood spots and urine samples were analyzed by tandem mass spectrometry (LC–MS/MS) and gas chromatograph–mass spectrometry (GCMS). Samples with abnormal amino acids were confirmed by high-performance liquid chromatography (HPLC). Results: Eight hundred and twenty-two suspected cases were evaluated; of which, 87 possible cases of IEMs were identified. Homocystinuria (n = 51) was the most common IEM detected followed by biotinidase deficiency (n = 7), glutaric aciduria type 1 (n = 7), and carnitine uptake defect (n = 6). Overall, there were 45 (51.7%) cases of organic acidemia, 31 cases (35.6%) of amino acid defect, 9 (10.3%) cases of fatty-acid oxidation disorders, and 2 (2.3%) cases of probable mitochondrial disorder. Conclusion: IEMs are common in India, with a hospital-based incidence of 1 in approximately 6642 among high-risk children. Screening of high-risk children by mass spectrometry techniques is a valuable strategy for early diagnosis of IEMs where universal newborn screening is not yet available. [ABSTRACT FROM AUTHOR]

Background: This investigation explored the clinical features, pathological outcomes, and biochemical recurrence (BCR) duration among high-risk prostate cancer (HRPC) patients who have undergone neoadjuvant therapy (NAT) in combination with radical prostatectomy (RP) and pelvic lymph node dissection (PLND). Additionally, we identified prognostic indicators that discern pathological complete response (pCR) or minimal residual disease (MRD) and BCR., Methods: In total, we examined 76 HRPC patients, who received NAT with either androgen deprivation therapy (ADT) plus apalutamide or ADT plus abiraterone, with subsequent RP and PLND. We conducted a genetic evaluation of patients receiving neoadjuvant apalutamide. Additionally, patient pathological outcomes, circulating prostate-specific antigen (PSA) response rates, and BCR duration were analyzed. Lastly, we employed uni- and multivariate analyses to screen for prognostic factors that govern pCR or MRD and BCR duration., Results: Patient median age and median PSA at presentation were 69 years (IQR: 66-73), and 47.6 ng/mL (IQR: 24.1-105.75), respectively. We observed marked changes in pCR or MRD rates between the two cohorts. In particular, the ADT plus apalutamide cohort (51.5%) exhibited enhanced rates relative to the ADT plus abiraterone cohort (25.6%) (p = 0.03). The median BCR duration was substantially prolonged among neoadjuvant apalutamide cohort relative to the neoadjuvant abiraterone cohort (261 days vs. 76 days, p = 0.04). Using multivariate analysis, we revealed that the postintervention pre-RP PSA content (≤ 0.1 ng/mL vs. > 0.1 ng/mL) remained a substantial stand-alone indicator of pCR or MRD (odds ratio: 10.712, 95% CI: 2.725-42.105, p < 0.001). Furthermore, supplemental analyses revealed that the ADT plus apalutamide cohort exhibited an augmented serum response rate, which, in turn, reduced the post-intervention pre-RP PSA content. Based on our genetic profiling of the neoadjuvant apalutamide cohort demonstrated high-frequency deleterious changes in the AR axis (30.3%), followed by TP53 mutations (15.15%). Patients with defective AR axis experienced a remarkably shorter median BCR duration relative to patients with other or no genetic alterations (52.5 days vs. 286 and 336 days, respectively, p < 0.0001). Furthermore, using multivariate analysis, we demonstrated that achieving pCR or MRD (hazard ratio [HR]: 0.170, 95% CI: 0.061-0.477, p < 0.001) and presence of defective AR signaling (HR: 11.193, 95% CI: 3.499-35.806, p < 0.001) were strong stand-alone indicators of BCR., Conclusions: Herein, we demonstrated the superior performance of ADT plus apalutamide in achieving pCR or MRD and in extending BCR duration among HRPC patients. Post-intervention pre-RP PSA content as well as genetic shifts, especially in the AR axis, are critical indicators of patient pathological and clinical outcomes. These findings highlight the significance of genetic testing and PSA content monitoring in treating HRPC patients., (© 2024 Wiley Periodicals LLC.)

Purpose: Approximately 25% to 50% of patients with high-risk localized prostate cancer experience biochemical recurrence (BCR) within 2 years of radical prostatectomy. The Apa-RP study (NCT04523207) investigated whether adjuvant apalutamide plus androgen deprivation therapy (ADT) in high-risk patients who have undergone radical prostatectomy improved BCR-free survival., Materials and Methods: Apa-RP was a multicenter, open-label, single-arm, phase 2 study conducted in community urology practices in the US. High-risk patients who had radical prostatectomy received 12 cycles of apalutamide (240 mg daily; 28-day cycles) plus ADT. The primary end point was BCR-free survival. Secondary end points included testosterone recovery (≥150 ng/dL) and safety., Results: One hundred eight patients were enrolled; median age was 66.0 years (range 46.0-77.0 years). Median preoperative PSA and baseline testosterone were 7.6 ng/mL (range 2.2-62.7 ng/mL) and 340.0 ng/dL (range 43.0-939.0 ng/dL), respectively. The BCR-free rate at 24 months (12 months after completion of planned therapy) was 100% (90% CI 93-100). Serum testosterone recovery rate (≥50 and ≥150 ng/dL) 12 months after treatment completion was 96% (95% CI 88-98) and 77% (95% CI 66-85), respectively. Overall, 107 (99%) patients experienced treatment-emergent adverse events, with 24 (22%) experiencing grade 3 to 4 events., Conclusions: In Apa-RP, BCR-free survival was 100% with 77% of patients having testosterone recovery (≥150 ng/dL) within 12 months of actual treatment completion and a manageable safety profile. These results provide proof of concept that treatment intensification with 12 cycles of apalutamide plus ADT could become an option for patients with high-risk localized prostate cancer who have undergone radical prostatectomy., Trial Registration: ClinicalTrials.gov Identifier: NCT04523207.

Purpose: Until March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) without additional hormone therapy (HT) at our institution. In this study, we aimed to evaluate long-term outcomes of this treatment., Materials and Methods: Patients with prostate cancer who received HDR-BT and EBRT between April 1997 and March 2021 and who were followed up for at least 6 months were included in the study. High-risk groups were classified into five levels according to the National Comprehensive Cancer Network guidelines. The EBRT and HDR-BT doses were 39-45 Gy/13-25 fractions. and 16.5-22 Gy/2-4 fractions, respectively. None of the patients received HT during initial treatment. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. Biochemical failure was also determined., Results: Seventy-two patients were enrolled in the study, with a median follow-up of 91.9 months. The median age and initial prostate-specific antigen (iPSA) level were 71 years and 10.95 ng/mL, respectively. The median biologically effective dose for HDR-BT plus EBRT was 270.3 Gy. The 5- and 7-year bFFF, CSS, and OS rates were 85.2 and 74.2%, 100 and 100%, and 95.7 and 91.9%, respectively. Only the iPSA ≤ 20 group was associated with the higher bFFF rate. The 7-year bFFF rates in the groups with iPSA ≤ 20 and iPSA > 20 were 86.6 and 48.6%, respectively., Conclusion: HDR-BT plus EBRT without HT might be an alternative treatment option for patients with high-risk localized prostate cancer and iPSA levels ≤ 20. Further studies are required to validate the efficacy of this treatment strategy., (© 2024. The Author(s).)

Background: Multiple preoperative calculators are available online to predict preoperative mortality risk for noncardiac surgical patients. However, it is currently unknown how these risk calculators perform across different raters. The current study investigated the interrater reliability of three preoperative mortality risk calculators in an elective high-risk noncardiac surgical patient population to evaluate if these calculators can be safely used for identification of high-risk noncardiac surgical patients for a preoperative multidisciplinary team discussion., Methods: Five anesthesiologists assessed the preoperative mortality risk of 34 high-risk patients using the preoperative score to calculate postoperative mortality risks (POSPOM), the American College of Surgeons surgical risk calculator (SRC), and the surgical outcome risk tool (SORT). In total, 170 calculations per calculator were gathered., Results: Interrater reliability was poor for SORT (ICC (C.I. 95%) = 0.46 (0.30-0.63)) and moderate for SRC (ICC = 0.65 (0.51-0.78)) and POSPOM (ICC = 0.63 (0.49-0.77). The absolute range of calculated mortality risk was 0.2-72% for POSPOM, 0-36% for SRC, and 0.4-17% for SORT. The coefficient of variation increased in higher risk classes for POSPOM and SORT. The extended Bland-Altman limits of agreement suggested that all raters contributed to the variation in calculated risks., Conclusion: The current results indicate that the preoperative risk calculators POSPOM, SRC, and SORT exhibit poor to moderate interrater reliability. These calculators are not sufficiently accurate for clinical identification and preoperative counseling of high-risk surgical patients. Clinicians should be trained in using mortality risk calculators. Also, clinicians should be cautious when using predicted mortality estimates from these calculators to identify high-risk noncardiac surgical patients for elective surgery., (© 2024. The Author(s).)

Background: Primary adjunctive therapy with corticosteroids have been shown to reduce coronary artery abnormalities in high-risk Kawasaki Disease (KD) patients in Japan (RAISE study). We evaluated their effect on outcomes in North American patients with high-risk KD., Methods: We performed a single-center retrospective review of high-risk KD patients between 2010 - 2023. From 2017-2023, adjunctive corticosteroids in a modified RAISE regimen (mRAISE) were given to high-risk patients as primary adjunctive therapy with intravenous gammaglobulin (IVIG) and aspirin. We compared CA outcomes in these patients and those presenting from 2010-2016, when mRAISE therapy was not administered., Results: A total of 221 high-risk KD patients were treated at our institution between 2010-2023. Among these, 83 received the mRAISE regimen and 138 did not (no corticosteroid, n=82, corticosteroid in a non-mRAISE regimen, n=56). There were no significant differences in coronary artery outcomes in the mRAISE and non-mRAISE groups. Patients receiving the mRAISE regimen were significantly less likely to receive more than one dose of IVIG when compared to those who did not receive this regimen (11% vs 33%, p<0.001)., Conclusion: Use of adjunctive primary therapy with corticosteroids in a mRAISE regimen in high-risk KD patients resulted in significantly decreased IVIG retreatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Problem: Monochorionic-diamniotic (MCDA) twin pregnancies are high-risk, requiring specialized monitoring and procedures to screen for and treat potential complications., Aim: This study examined decisions to use social media among those who have experienced MCDA pregnancies and how these groups influenced treatment and management decisions for these rare, complicated pregnancies., Methods: An online mixed-methods, retrospective survey, was completed in 2021 by 624 participants who experienced MCDA pregnancies within 5 years of the study; participants were recruited from online MCDA pregnancy groups on Facebook and Twitter. Data was analyzed using descriptive statistics and thematic analysis., Findings: Sixty-nine percent of participants used social media to communicate during their MCDA pregnancies, an 18 increase from before pregnancy, and most (74.2 %) used online support groups during pregnancy. Thematic analysis revealed participants used social media primarily to find others with similar experiences, learn more about MCDA pregnancies, and obtain guidance. Most would also recommend joining social media during a similar pregnancy. Nearly half indicated that social media influenced MCDA pregnancy management and treatment decisions - like decisions regarding birth plans, providers, and MCDA-related complications. Several participants cautioned that support groups can be triggering when negative stories are shared., Conclusion: Social media can provide information, support, and improve advocacy for those experiencing MCDA pregnancies. Providers may consider online groups as another source of support for pregnant people and be prepared to address questions that may arise. This study also reveals opportunities for increased and/or improved patient educational materials and patient-provider communication related to MCDA pregnancies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Given the strong association between high-risk HPV genotypes, such as HPV 16 and 18, and cervical cancer, this study aimed to compare the distribution of common HPV genotypes in the southwest Iranian population with those included in the available vaccines., Methods: Based on the sample quality, DNA was extracted from the biological samples of 8036 individuals included in the study using three different methods (automated instrument, column, and precipitation), and a total of 21 different HPV genotypes were detected using real-time PCR., Results: The majority of participants were women (> 99%), with a positive rate of HPV infection of 29.9%, in which high-risk genotypes were dominant in 84.9% cases. The highest rate of HPV infections was observed in the age ≤ 30 years (35.9%). HPV 6 and 16 were the most frequent low- and high-risk genotypes, respectively. Multi HPV infections were observed in 35% of positive samples and the highest cross infections were observed between HPV6 and 16. Co-infection with HPV 16 and 18 was observed in 21 positive samples (1%). Although vaccination is essential to reduce the outcome of HPV infections, such as cervical cancer, other frequently occurring high-risk genotypes are not included in the 9-valent vaccine., Conclusion: Since the association between cervical cancer and other high-risk HPV types rather than 16 and 18 has been less studied, investigating their pathogenicity in cervical cancer is recommended. Furthermore, the new generation of HPV vaccines should contain other frequently occurring high-risk genotypes beyond those currently covered in approved vaccines., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Inter-atrial septum (IAS) stenting in duct-dependent congenital heart disease patient has shown to be an effective way to maintain inter-atrial blood flow, however it is still considered a high risk procedure and inter-atrial septum stenting remains a low-frequency procedure., Method: A single-center observational cohort study was carried out at the National Cardiovascular Center Harapan Kita (NCCHK) between April 2019 and April 2023. This study included duct-dependent congenital heart disease patients. The extracted data were baseline characteristics, clinical findings, complications, and outcomes of the patients., Result: Eleven patients with duct-dependent physiology were intervened with inter-atrial septum stenting. The patients were 4 females and 7 males with the median age of implantation being 150 days (range 11-703 days) and the median weight being 3.9 (range 2.8-9) kg, with 2 patients weighing less than 3 kg. The average stent diameter was 8.50 (2.03) mm with an average length of 24.45 (7.94) mm. Non-restrictive atrial flow was successfully achieved in 90.90% of the procedures, corresponding to 10 patients., Conclusion: Inter-atrial septum stenting in duct-dependent congenital heart disease patients produces reliable patency with a very good intra-procedural success rate., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: Estimate patient counts, treatment patterns and outcomes of a subset of patients with early breast cancer (EBC) presenting with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive features, who are at high-risk of recurrence, in Taiwan. Materials & methods: Data from Taiwan's National Health Insurance Research Database and Taiwan Cancer Registry from 1 January 2011 to 31 December 2020 were analyzed. Results: There were 4500 patients with high-risk EBC (10.4% of all patients with EBC) from 2012 to 2018, with an annual average incidence of 643 that increased over time. Five-year progression was 24.8% in patients with high-risk EBC and 8-year survival was low (69.6%). Conclusion: Patients with hormone receptor positive, human epidermal growth factor receptor 2 negative, node positive high-risk EBC clinical features are an increasing high-risk subset of all patients with EBC.

Background: For women at increased risk of breast cancer, the National Comprehensive Cancer Network (NCCN) guidelines recommend clinical encounters every 6-12 months. While screening mammography has corresponded with a relative risk reduction in breast cancer mortality of approximately 20%, evidence validating clinical breast examination (CBE) as an efficacious screening modality is deficient. Our study aimed to assess the conventional merit of regular CBE for breast cancer detection among individuals at increased risk of breast cancer development., Methods: Women > 18 years with documented high-risk encounters at Corewell Health West from 1 January 2018 to 31 December 22 were retrospectively reviewed. High-risk criteria included genetic predisposition, 5-year (> 1.7%) or lifetime (> 20%) Tyrer-Cuzick and/or Gail Model risk estimations, thoracic radiotherapy before age 30 years, lobular carcinoma in-situ, or atypical hyperplasia. Patients with a history of breast cancer or bilateral prophylactic mastectomy prior to 2018 were excluded., Results: Of the 9171 cumulative high-risk encounters among 2493 women, only one breast cancer was detected by CBE. CBE resulted in 1 (0.04%) cancer diagnosis compared with 30 (1.2%) detected on screening imaging and 10 (0.4%) self-reported. Of the 30 image-detected cancers, 28 (93.3%) had no detectable clinical findings at the time of preoperative consultation. Self-reported and CBE-detected cancers were more likely to be of higher clinical stage compared with imaging-detected malignancies., Conclusions: The role of routine CBE as a cancer detection modality in the high-risk patient population appears to be limited. Telemedicine can be offered to individuals who have completed screening imaging but are unable to commit and/or are inconvenienced by in-person high-risk breast cancer assessments., (© 2024. Society of Surgical Oncology.)