Dangerous Variation or Patient-Centered Care? Palliative Care and Pain Providers' Comfort, Experiences, and Approaches when Treating Cancer Pain With Coexisting Aberrant Behaviors.

BACKGROUND: Patients with cancer-related pain are at high risk for aberrant drug use behaviors (ADB), including self-escalation, diversion and concurrent illicit substance or opioid misuse; however, limited evidence is available to guide opioid prescribing for patients with life-limiting illness and concurrent or suspected ADB. We sought to characterize how specialists evaluate for and manage these high-risk behaviors in patients with cancer-related pain. METHODS: We conducted telephonic semi-structured interviews with palliative care and pain medicine providers. Participants discussed their own comfort and experience level with identifying and managing ADB in patients with life-limiting illness. They were subsequently presented with a series of standardized scenarios and asked to describe their concerns and management strategies. RESULTS: 95 interdisciplinary pain and palliative care specialists were contacted; 37 agreed to participate (38.9%). Analysis of interview contents revealed several central themes: (1) widespread discomfort and anxiety regarding safe and compassionate opioid prescribing for high-risk patients, (2) belief that widely used risk-mitigation tools such as opioid contracts and urine drug screens provided inadequate support for decision-making, and (3) lack of institutional and organizational support and guidance for safe prescribing strategies. Most clinicians reported self-education regarding addiction and alternative prescribing/pain management strategies. Providers varied widely in their willingness to discontinue opioid prescribing in a patient with aberrant behavior and pain associated with life-limiting illness. CONCLUSION: Providers caring for patients demonstrating ADB and cancer-related pain struggle to balance safe prescribing with symptom management. Increased guidance is needed regarding opioid prescribing, monitoring, and discontinuation in high-risk patients.

Photonics-powered augmented reality skin electronics for proactive healthcare: multifaceted opportunities.

Rapid technological advancements have created opportunities for new solutions in various industries, including healthcare. One exciting new direction in this field of innovation is the combination of skin-based technologies and augmented reality (AR). These dermatological devices allow for the continuous and non-invasive measurement of vital signs and biomarkers, enabling the real-time diagnosis of anomalies, which have applications in telemedicine, oncology, dermatology, and early diagnostics. Despite its many potential benefits, there is a substantial information vacuum regarding using flexible photonics in conjunction with augmented reality for medical purposes. This review explores the current state of dermal augmented reality and flexible optics in skin-conforming sensing platforms by examining the obstacles faced thus far, including technical hurdles, demanding clinical validation standards, and problems with user acceptance. Our main areas of interest are skills, chiroptical properties, and health platform applications, such as optogenetic pixels, spectroscopic imagers, and optical biosensors. My skin-enhanced spherical dichroism and powerful spherically polarized light enable thorough physical inspection with these augmented reality devices: diabetic tracking, skin cancer diagnosis, and cardiovascular illness: preventative medicine, namely blood pressure screening. We demonstrate how to accomplish early prevention using case studies and emergency detection. Finally, it addresses real-world obstacles that hinder fully realizing these materials' extraordinary potential in advancing proactive and preventative personalized medicine, including technical constraints, clinical validation gaps, and barriers to widespread adoption.

Assessing the frequency and types of errors involved in the use of a modified intravenous N-acetylcysteine protocol for acetaminophen overdose.

BACKGROUND: Acetaminophen overdose is a leading cause of acute liver failure in developing countries. N-acetylcysteine (NAC) is a highly effective antidote for acetaminophen hepatotoxicity, typically initiated in the emergency department. Due to a known high rate of errors with the standard three-bag IV NAC protocol, in 2019, the Ontario Poison Center changed to a modified 3% IV NAC one-bag protocol. This study was undertaken to determine the frequency and types of errors associated with the use of this protocol. METHODS: Data were gathered via chart review of Ontario Poison Centre electronic medical record cases identified as receiving IV NAC for acetaminophen overdose between August 1 and September 30, 2022. 218 total charts were identified, and 188 were deemed eligible based on inclusion and exclusion criteria. RESULTS: Errors were identified in 25% of charts, consisting of dosing errors in 11.7%, stopping errors in 9.0%, initiation errors in 3.7%, and interruptions in therapy in 3.2%. Dosing errors were the most common type of error (44.4%), with overdoses occurring three times more than underdoses. Errors were identified at 39% of geographic locations in the charts reviewed, with similar frequency in Ontario, Manitoba, and Nunavut. Clinical outcomes were similar in charts with and without errors. INTERPRETATION: The rate of errors identified with this 3% IV NAC one-bag protocol is lower than reported for the standard three-bag protocol, but remains high due to dosing errors. Previously reported issues with prolonged interruptions in therapy with the standard three-bag protocol were low with the current 3% one-bag protocol. Although severe outcomes are rare, IV NAC overdose can be fatal. Identifying local factors in emergency departments that can contribute to administration errors (i.e., dose calculation, pump programming issues) can enhance the safety of this important antidote.

RéSUMé: CONTEXTE: La surdose d'acétaminophène est l'une des principales causes d'insuffisance hépatique aiguë dans les pays en développement. La N-acétylcystéine (NAC) est un antidote très efficace contre l'hépatotoxicité de l'acétaminophène, généralement initiée au service des urgences. En raison d'un taux élevé connu d'erreurs avec le protocole NAC standard à 3 sacs IV, en 2019, le Centre antipoison de l'Ontario a adopté un protocole NAC à 1 sac IV modifié à 3 %. Cette étude a été entreprise pour déterminer la fréquence et les types d'erreurs associées à l'utilisation de ce protocole. MéTHODES: Les données ont été recueillies au moyen d'un examen des dossiers médicaux électroniques du Centre antipoison de l'Ontario qui ont reçu une dose IV de NAC pour une surdose d'acétaminophène entre le 1 août et le 30 septembre 2022. 218 cartes au total ont été identifiées, et 188 ont été jugées admissibles en fonction de critères d'inclusion et d'exclusion. RéSULTATS: Des erreurs ont été relevées dans 25 % des dossiers, soit des erreurs de dosage dans 11,7 %, des erreurs d'arrêt dans 9,0 %, des erreurs d'initiation dans 3,7 % et des interruptions du traitement dans 3,2 %. Les erreurs de dosage étaient le type d'erreur le plus courant (44,4 %), les surdoses étant trois fois plus fréquentes que les sous-doses. Des erreurs ont été relevées à 39 % des emplacements géographiques dans les cartes examinées, avec une fréquence similaire en Ontario, au Manitoba et au Nunavut. Les résultats cliniques étaient similaires dans les tableaux avec et sans erreurs. INTERPRéTATION: Le taux d'erreurs identifiées avec ce protocole à un sac NAC IV à 3 % est inférieur à celui du protocole standard à 3 sacs, mais reste élevé en raison d'erreurs de dosage. Les problèmes précédemment rapportés avec les interruptions prolongées du traitement avec le protocole standard à 3 sacs étaient faibles avec le protocole actuel à 3% à un sac. Bien que les résultats graves soient rares, une surdose de NAC IV peut être fatale. L'identification de facteurs locaux dans les services d'urgence qui peuvent contribuer aux erreurs d'administration (c.-à-d. le calcul de la dose, les problèmes de programmation de la pompe) peut améliorer l'innocuité de cet antidote important.

Single-Dose enoxaparin for portomesenteric venous thrombosis prophylaxis after sleeve gastrectomy.

Introduction: Portomesenteric venous thrombosis (PMVT) may complicate sleeve gastrectomy. We believe that single dose of enoxaparin postoperatively can reduce the risk of PMVT. Objective: The objective was to study the outcomes of enoxaparin single dose compared to other perioperative prophylactic doses in preventing PMVT. Methods: Participants included 590 patients who underwent laparoscopic sleeve gastrectomy (LSG). These retrospective cohort data were collected from patient medical charts after bariatric surgery. Patients were followed up in the close postoperative period and at 1, 3, 6, 12, and 18 months. Descriptive statistical analysis was carried out. The objective was to estimate the incidence of PMVT with postoperative single 40 mg subcutaneous enoxaparin prophylactic regimen. Results: From January 2017 to December 2021, 590 patients with obesity underwent LSG. Five patients developed PMVT with an estimate incidence of 0.85%. Three patients had unexplained tachycardia and three patients had postoperative bleeding. Conclusions: Single-dose enoxaparin 40 mg is an effective thrombosis prophylaxis without increasing risk of bleeding.

Résumé Introduction: La thrombose veineuse portomésentérique (TVPM) peut compliquer la gastrectomie en manchon. Nous pensons qu'une dose unique d'énoxaparine en postopératoire peut réduire le risque de PMVT. Objectif: L'objectif était d'étudier les résultats de la dose unique d'énoxaparine par rapport à d'autres doses prophylactiques périopératoires dans la prévention de la PMVT. Méthodes: Les participants comprenaient 590 patients ayant subi une gastrectomie laparoscopique en manchon (LSG). Ces données de cohorte rétrospectives ont été collectées à partir des dossiers médicaux des patients après une chirurgie bariatrique. Les patients ont été suivis dans la période postopératoire étroite et à 1, 3, 6, 12 et 18 mois. Une analyse statistique descriptive a été réalisée. L'objectif était d'estimer l'incidence de la PMVT avec un régime prophylactique postopératoire unique d'énoxaparine sous-cutanée de 40 mg. Résultats: De janvier 2017 à décembre 2021, 590 patients obèses ont subi une LSG. Cinq patients ont développé une PMVT avec une incidence estimée à 0,85 %. Trois patients présentaient une tachycardie inexpliquée et trois patients présentaient des hémorragies postopératoires. Conclusions: Une dose unique d'énoxaparine de 40 mg est une prophylaxie efficace contre la thrombose sans augmenter le risque de saignement. Mots-clés: Énoxaparine, gastrectomie laparoscopique en manchon, thrombose veineuse portomésentérique prophylaxie, thromboembolie veineuse.

Histone demethylase KDM5 regulates cardiomyocyte maturation by promoting fatty acid oxidation, oxidative phosphorylation, and myofibrillar organization.

AIMS: Human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a platform to identify and characterize factors that regulate the maturation of CMs. The transition from an immature foetal to an adult CM state entails coordinated regulation of the expression of genes involved in myofibril formation and oxidative phosphorylation (OXPHOS) among others. Lysine demethylase 5 (KDM5) specifically demethylates H3K4me1/2/3 and has emerged as potential regulators of expression of genes involved in cardiac development and mitochondrial function. The purpose of this study is to determine the role of KDM5 in iPSC-CM maturation. METHODS AND RESULTS: KDM5A, B, and C proteins were mainly expressed in the early post-natal stages, and their expressions were progressively downregulated in the post-natal CMs and were absent in adult hearts and CMs. In contrast, KDM5 proteins were persistently expressed in the iPSC-CMs up to 60 days after the induction of myogenic differentiation, consistent with the immaturity of these cells. Inhibition of KDM5 by KDM5-C70 -a pan-KDM5 inhibitor, induced differential expression of 2372 genes, including upregulation of genes involved in fatty acid oxidation (FAO), OXPHOS, and myogenesis in the iPSC-CMs. Likewise, genome-wide profiling of H3K4me3 binding sites by the cleavage under targets and release using nuclease assay showed enriched of the H3K4me3 peaks at the promoter regions of genes encoding FAO, OXPHOS, and sarcomere proteins. Consistent with the chromatin and gene expression data, KDM5 inhibition increased the expression of multiple sarcomere proteins and enhanced myofibrillar organization. Furthermore, inhibition of KDM5 increased H3K4me3 deposits at the promoter region of the ESRRA gene and increased its RNA and protein levels. Knockdown of ESRRA in KDM5-C70-treated iPSC-CM suppressed expression of a subset of the KDM5 targets. In conjunction with changes in gene expression, KDM5 inhibition increased oxygen consumption rate and contractility in iPSC-CMs. CONCLUSION: KDM5 inhibition enhances maturation of iPSC-CMs by epigenetically upregulating the expressions of OXPHOS, FAO, and sarcomere genes and enhancing myofibril organization and mitochondrial function.

Direct immunofluorescence on formalin-fixed, paraffin-embedded versus fresh frozen human renal biopsies: a comparative study.

BACKGROUND: The data referring to the value of direct immunofluorescence on formalin-fixed, paraffin-embedded tissue (IF-Paraffin) in the diagnosis of renal diseases is controversial. The aim of this study was to investigate whether renal biopsies evaluated by routine immunofluorescence on frozen tissue (IF-Frozen) would yield adequate findings to confirm diagnoses when the IF-Paraffin technique was applied. METHODS: To show immunoglobulins, complement components, and light chains, 55 native renal biopsies were subjected to IF-Paraffin and IF-Frozen staining techniques. The intensity of the staining was compared, and the sensitivity and specificity were calculated. RESULTS: The IF-Paraffin technique showed a sensitivity of 89%, 81%, 86%, 30%, 71%, 60%, and 77% for IgG, IgM, IgA, C1q, C3, κ, and λ, respectively, whereas specificity was 91%, 100%, 100%, 96%, 94%, 98%, and 100%. It showed diagnostic findings in 87% of cases. Compared to cases that had both IF-Paraffin and IF-Frozen staining techniques, 43 of 55 showed either equal intensity for the diagnostic immunoglobulin/complement or a little difference. CONCLUSIONS: Direct immunofluorescence on formalin-fixed, paraffin-embedded sections cannot replace immunofluorescence on frozen sections in the assessment of renal biopsies, but may be a "salvage technique" when frozen tissue is insufficient or unavailable and must be interpreted with great caution.

Community cervical cancer screening and precancer risk in women living with HIV in Jos Nigeria.

BACKGROUND: High HIV prevalence, and lack of organized screening for the indigent population receiving care and treatment within HIV clinics in low-resource settings increases cervical cancer incidence. We sought to determine predictors of cervical precancer in women living with HIV and receiving cervical cancer screening in Jos, Nigeria. METHODS: A cross-sectional study of women living with HIV and receiving care and treatment in adult HIV/AIDS clinics in Jos-Metropolis, Nigeria between June 2020 and April 2023. Ethical approvals were obtained from the ethics committee in Jos, Nigeria and Northwestern University IRB, USA. Informed consent was obtained from eligible participants, and data on socio-demographics, cancer risk factors, and cytology reports were collected. The outcome variables were cervical precancer lesions. The independent variables were prior Pap smear status, socio-demographics, income, educational, and other reproductive health factors. Descriptive statistics was done to obtain means ± sd, frequencies, and percentages for the variables. Univariate and bivariate analyses were done to determine predictors of cervical dysplasia. Analyses were performed using R software. RESULTS: Of 957 women screened, 570 were living with HIV and 566 women had cytology report and were included in the final analysis. The mean age was 45.08 ± 8.89 years and 81.6% had no prior evidence of Pap test (under-screened). Prevalence of cervical dysplasia was 24% (mild and severe dysplasia were 12.9% and 11.1%, respectively). Age above 45 years (aOR = 3.48, p = 0.009), postmenopausal status (aOR = 7.69, p = 0.000), and women with no history of prior IUCD use (aOR = 5.94, p = 0.0001), were predictors for severe dysplasia. Women who had history of STI (aOR = 0.17, p = 0.000), prior use of IUCD (aOR = 0.32, p = 0.004), prior use of condom (aOR = 2.50, p = 0.003) and had co-morbidities (aOR = 0.46, p = 0.009) were more likely to have had a Pap test in the past. CONCLUSIONS: The majority of indigent women receiving care at HIV clinics had their first Pap test screening, and lack of organized screening among older and post-menopausal women with HIV, puts women at a higher risk of developing severe cervical precancer lesions.

Epidemiology and survival outcomes of HIV-associated cervical cancer in Nigeria.

INTRODUCTION: Invasive cervical cancer (ICC) is an HIV-associated cancer that is preventable and precancerous stages including early ICC stages could be detected through screening offering opportunities for treatment and cure. The high incidence in women living with HIV and late presentation often at advanced stages of ICC with limited treatment facilities often result in early mortality. We sought to compare the epidemiologic characteristics and survival differences in HIV status of ICC patients in Nigeria. METHODS: We conducted a cohort study at two federal academic hospital-based research sites in Jos University Teaching Hospital, and Lagos University Teaching Hospital Nigeria, between March 2018 and September 2022. We enrolled women with histologically confirmed ICC with known HIV status, and FIGO staging as part of the United States of America's National Institutes of Health/National Cancer Institute funded project titled 'Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria'. The primary outcome was all-cause mortality with assessment of overall survival (OS) and time to death after ICC diagnosis. OS distribution was estimated using the method of Kaplan-Meier and compared between groups using the log-rank test. RESULTS: A total of 239 women with confirmed ICC were enrolled and included in this analysis, of whom 192 (80.3%) were HIV-negative (HIV-/ICC +), and 47 (19.7%) were HIV-positive (HIV +/ICC +). The HIV +/ICC + patients were younger with median age 46 (IQR: 40-51) years compared to 57 (IQR: 45-66) among HIV-/ICC + (P < 0.001). Squamous cell carcinoma was the commonest histopathologic variant in 80.4% of ICC diagnosis, moderately differentiated tumor grade in 68.1% in both groups. HIV +/ICC + diagnosis was at FIGO advanced stages in 64.9% compared to 47.9% in HIV-/ICC +. The HIV-/ICC + women had better OS compared to HIV +/ICC + participants (p = 0.018), with 12-month OS 84.1% (95%CI 75-90%) and 67.6% (95%CI 42-84%) respectively. CONCLUSION: ICC is diagnosed at a relatively young age in women living with HIV, with a significantly lower overall survival probability compared to women without HIV. The trend of presentation and diagnosis at advanced stages in women living with HIV could partly explain the differences in overall survival.

Epidemiology and Survival outcomes of HIV-associated cervical cancer in Nigeria.

Introduction: Invasive cervical cancer (ICC) is an HIV-associated cancer that is preventable and precancerous stages including early ICC stages could be detected through screening offering opportunities for treatment and cure. The high incidence in women living with HIV and late presentation often at advanced stages of ICC with limited treatment facilities often result in early mortality. We sought to compare the epidemiologic characteristics and survival differences in HIV status of ICC patients in Nigeria. Methods: We conducted a cohort study at two federal academic hospital-based research sites in Jos University Teaching Hospital, and Lagos University Teaching Hospital Nigeria, between March 2018 and September 2022. We enrolled women with histologically confirmed ICC with known HIV status, and FIGO staging as part of the United States of America's National Institutes of Health/National Cancer Institute funded project titled 'Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria'. The primary outcome was all-cause mortality with assessment of overall survival (OS) and time to death after ICC diagnosis. OS distribution was estimated using the method of Kaplan-Meier and compared between groups using the log-rank test. Results: A total of 239 women with confirmed ICC were enrolled and included in this analysis, of whom 192 (80.3%) were HIV-negative (HIV-/ICC+), and 47 (19.7%) were HIV-positive (HIV+/ICC+). The HIV+/ICC) patients were younger with median age 46 (IQR: 40-51) years compared to 57 (IQR: 45-66) among HIV-/ICC+) (P<0.001. Squamous cell carcinoma was the commonest histopathologic variant in 80.4% of ICC diagnosis, moderately differentiated tumor grade in 68.1% in both groups. HIV+/ICC+ diagnosis was at FIGO advanced stages in 64.9% compared to 47.9% in HIV-/ICC+. The HIV-/ICC+ women had better OS compared to HIV+/ICC+ participants (p=0.018), with 12-month OS 84.1% (95%CI: 75% - 90%) and 67.6% (95%CI: 42%-84%) respectively. Conclusion: ICC is diagnosed at a relatively young age in women living with HIV, with a significantly lower overall survival probability compared to women without HIV. The trend of presentation and diagnosis at advanced stages in women living with HIV could partly explain the differences in overall survival.

Genetic inactivation of ß-catenin is salubrious, whereas its activation is deleterious in desmoplakin cardiomyopathy.

AIMS: Mutations in the DSP gene encoding desmoplakin, a constituent of the desmosomes at the intercalated discs (IDs), cause a phenotype that spans arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy. It is typically characterized by biventricular enlargement and dysfunction, myocardial fibrosis, cell death, and arrhythmias. The canonical wingless-related integration (cWNT)/ß-catenin pathway is implicated in the pathogenesis of ACM. The ß-catenin is an indispensable co-transcriptional regulator of the cWNT pathway and a member of the IDs. We genetically inactivated or activated ß-catenin to determine its role in the pathogenesis of desmoplakin cardiomyopathy. METHODS AND RESULTS: The Dsp gene was conditionally deleted in the 2-week-old post-natal cardiac myocytes using tamoxifen-inducible MerCreMer mice (Myh6-McmTam:DspF/F). The cWNT/ß-catenin pathway was markedly dysregulated in the Myh6-McmTam:DspF/F cardiac myocytes, as indicated by a concomitant increase in the expression of cWNT/ß-catenin target genes, isoforms of its key co-effectors, and the inhibitors of the pathway. The ß-catenin was inactivated or activated upon inducible deletion of its transcriptional or degron domain, respectively, in the Myh6-McmTam:DspF/F cardiac myocytes. Genetic inactivation of ß-catenin in the Myh6-McmTam:DspF/F mice prolonged survival, improved cardiac function, reduced cardiac arrhythmias, and attenuated myocardial fibrosis, and cell death caused by apoptosis, necroptosis, and pyroptosis, i.e. PANoptosis. In contrast, activation of ß-catenin had the opposite effects. The deleterious and the salubrious effects were independent of changes in the expression levels of the cWNT target genes and were associated with changes in several molecular and biological pathways, including cell death programmes. CONCLUSION: The cWNT/ß-catenin was markedly dysregulated in the cardiac myocytes in a mouse model of desmoplakin cardiomyopathy. Inactivation of ß-catenin attenuated, whereas its activation aggravated the phenotype, through multiple molecular pathways, independent of the cWNT transcriptional activity. Thus, suppression but not activation of ß-catenin might be beneficial in desmoplakin cardiomyopathy.

Carotid Body Tumor: A Case Report of a Rare Neuroendocrine Neoplasm.

Carotid body tumors are rare neuroendocrine tumors originating from paraganglionic cells in the carotid body. Although these tumors are typically slow-growing and benign, their location and vascularity present unique challenges in management. Here, we present a case study of a 58-year-old male who presented with a painless, gradually enlarging neck mass over a six-month period. Physical examination revealed a non-tender, pulsatile mass measuring approximately 3 cm in the left carotid triangle. Imaging studies, including ultrasound and contrast-enhanced computed tomography, confirmed the presence of a well-defined, hypoechoic mass at the left carotid bifurcation, displacing adjacent vessels. A multidisciplinary team planned surgical resection, guided by imaging, resulting in the successful removal of the tumor. Histopathological examination confirmed the diagnosis of a carotid body tumor. This case report underscores the significance of accurate diagnosis, a multidisciplinary approach, and advanced imaging techniques in managing carotid body tumors. Surgical resection, guided by imaging, aims to achieve complete excision while preserving vital structures. Long-term follow-up is crucial to detect potential recurrence or progression early.

Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria.

BACKGROUND: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). METHODS: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. RESULTS: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43-58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. CONCLUSION: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

Epidemiology and incidence of oral squamous cell carcinoma in the Iraqi population over 5 years (2014-2018).

Background: Oral squamous cell carcinoma is one of the most common and life-threatening neoplasms worldwide, and is responsible for approximately 90% of all oral malignancies. Aim: This study was aimed at providing updated information on oral squamous cell carcinoma in all Iraqi governorates for the 5-year period from 2014 to 2018, including the annual incidence and demographic variables. Materials and Methods: The total number of oral squamous cell carcinoma cases in Iraq, along with associated demographic information (age, sex, and site), for the 5-year period from 2014 to 2018 was obtained. The statistical analysis consisted of descriptive analysis, including frequency, percentage, and mean ± standard deviation. A χ 2 test was performed to compare frequencies between male and female patients, among age groups, and among different OSCC sites. The χ 2 test was also used to assess the association of each OSCC site with age and sex. The significance threshold was set at p < 0.05, and the confidence interval was set at 95%. The incidence rate of oral squamous cell carcinoma for each year was calculated by dividing the number of OSCC cases per year by the population of Iraq, then multiplying the result by 100,000. Results: A total of 722 cases were recorded. Statistically, oral squamous cell carcinoma was found to be more prevalent in males and individuals over 40 years of age. The tongue was the most common site of occurrence. Lip squamous cell carcinoma cases were high in males. The incidence rate of oral squamous cell carcinoma was estimated to be 0.4 per 100,000 people. Conclusion: Males and older people are at relatively higher risk of developing oral cancer. The tongue is the most affected site, but any site in the oral cavity may be involved. Further exploration of the causes of oral malignancy in Iraq is necessary to improve prevention strategies.

Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance.

Insulin resistance (IR) during obesity is linked to adipose tissue macrophage (ATM)-driven inflammation of adipose tissue. Whether anti-inflammatory glucocorticoids (GCs) at physiological levels modulate IR is unclear. Here, we report that deletion of the GC receptor (GR) in myeloid cells, including macrophages in mice, aggravates obesity-related IR by enhancing adipose tissue inflammation due to decreased anti-inflammatory ATM leading to exaggerated adipose tissue lipolysis and severe hepatic steatosis. In contrast, GR deletion in Kupffer cells alone does not alter IR. Co-culture experiments show that the absence of GR in macrophages directly causes reduced phospho-AKT and glucose uptake in adipocytes, suggesting an important function of GR in ATM. GR-deficient macrophages are refractory to alternative ATM-inducing IL-4 signaling, due to reduced STAT6 chromatin loading and diminished anti-inflammatory enhancer activation. We demonstrate that GR has an important function in macrophages during obesity by limiting adipose tissue inflammation and lipolysis to promote insulin sensitivity.

Meeting report - Desmosome dysfunction and disease: Alpine desmosome disease meeting.

Desmosome diseases are caused by dysfunction of desmosomes, which anchor intermediate filaments (IFs) at sites of cell-cell adhesion. For many decades, the focus of attention has been on the role of actin filament-associated adherens junctions in development and disease, especially cancer. However, interference with the function of desmosomes, their molecular constituents or their attachments to IFs has now emerged as a major contributor to a variety of diseases affecting different tissues and organs including skin, heart and the digestive tract. The first Alpine desmosome disease meeting (ADDM) held in Grainau, Germany, in October 2022 brought together international researchers from the basic sciences with clinical experts from diverse fields to share and discuss their ideas and concepts on desmosome function and dysfunction in the different cell types involved in desmosome diseases. Besides the prototypic desmosomal diseases pemphigus and arrhythmogenic cardiomyopathy, the role of desmosome dysfunction in inflammatory bowel diseases and eosinophilic esophagitis was discussed.

Endovascular Repair of an Ascending Aorta Dissection After Self-expanding TAVR by Suprasternal Approach.

Management of rare ascending aortic complications after transcatheter aortic valve replacement (TAVR) remains a poorly defined area of knowledge. Furthermore, because most patients undergoing TAVR are at intermediate to high surgical risk, the treatment of such complications often requires endovascular approaches. Herein, we present a novel technique of endovascular ascending aorta stent graft delivery from the innominate artery for the treatment of a type A aortic dissection after self-expandable TAVR implantation, specifically addressing the landing of the aortic stent within the crown of the TAVR valve.

Double dartos flap layer in tubularized incised plate urethroplasty to prevent urethrocutaneous fistula in uncircumcised patients with distal hypospadias.

Urethrocutaneous fistula may complicate hypospadias repair. We noticed that double-layered preputial dartos flaps added to tubularized incised plate urethroplasty can reduce the risk of urethrocutaneous fistula. The aim of this study was to compare the outcomes of tubularized incised plate urethroplasty with double-layered preputial dartos flaps to with single-layered local fascial flaps in preventing urethrocutaneous fistula. A retrospective cohort study was conducted between January 2017 and December 2020 at Jordan University Hospital (Amman, Jordan). Boys who were aged between 6 months and 5 years, diagnosed with distal hypospadias, and not circumcised were included. The primary outcome was the occurrence of urethrocutaneous fistula in patients who underwent tubularized incised plate urethroplasty with a double-layered fascial flap. The results showed a total of 163 boys with distal hypospadias; among them, 116 patients underwent tubularized incised plate urethroplasty with a single-layered fascial flap, and 47 underwent tubularized incised plate urethroplasty with a double-layered fascial flap. The development of urethrocutaneous fistula was higher in the group receiving tubularized incised plate urethroplasty with a single-layered fascial flap than in the group receiving tubularized incised plate urethroplasty with a double-layered fascial flap after 1 month, 6 months, and 12 months (6.9% vs 0, 10.3% vs 0, and 5.2% vs 0, respectively), and the difference after 6 months was statistically significant (P = 0.02).

Delayed-enhancement cardiac magnetic resonance imaging detects disease progression in patients with mitral valve disease and atrial fibrillation.

Objectives: The mechanism by which mitral valve (MV) disease leads to atrial fibrillation (AF) remains poorly understood. Delayed-enhancement cardiac magnetic resonance imaging (DE-MRI) has been used to assess left atrial (LA) fibrosis in patients with lone AF before catheter ablation; however, few studies have used DE-MRI to assess MV-induced LA fibrosis in patients with or without AF undergoing MV surgery. Methods: Between March 2018 and September 2022, 38 subjects were enrolled; 15 age-matched controls, 14 patients with lone mitral regurgitation (MR), and 9 patients with MR and AF (MR + AF). Indexed LA volume, total LA wall, and regional LA posterior wall (LAPW) enhancement were defined by the DE-MRI. One-way analysis of variance was performed. Results: LA volume and LA enhancement were associated (r = 0.451, P = .004). LA volume differed significantly between controls (37.1 ± 10.6 mL) and patients with lone MR (71.0 ± 35.9, P = .020 and controls and patients with MR + AF (99.3 ± 47.4, P < .001). The difference in LA enhancement was significant between MR + AF (16.7 ± 9.6%) versus controls (8.3 ± 3.9%, P = .006) and MR + AF versus lone MR (8.0 ± 4.8%, P = .004). Similarly, the was significantly more LAPW enhancement in the MR + AF (17.5 ± 8.7%) versus control (9.2 ± 5.1%, P = .011) and MR + AF versus lone MR (9.8 ± 6.0%, P = .020). Conclusions: Patients with MR + AF had significantly more total and LAPW fibrosis compared with both controls and lone MR. Volume and delayed enhancement were associated, but there was no difference between MR and MR + AF.

Cystadenocarcinoma of the gallbladder: A case report.

Introduction and importance: Cystadenoma and cystadenocarcinoma of the biliary duct remain a rare diagnosis, the localization is intrahepatic in 97% of the cases and extrahepatic in 3%of them [1]. Cystadenocarcinoma of the gallbladder is the rarest localization, it's usually diagnosed late because of the poor symptoms and the nonspecific lesions in the different imaging.Only hundreds of cases have been reported for cystadenocarcinoma of the gallbladder.This case report has been reported in line with the SCARE Criteria. Case presentation: We present a 70-year-old woman, with no family or personal history, who was complaining of pain in the right hypochondrium and an altered general well-being, with no other clinical abnormalities.The imaging including abdominal sonography, CT scan, and MRI concluded at a budding lesion formed in the gallbladder wall which measured 65 × 15mm.Cancer of the gallbladder was suspected and the patient was operated. A resection of segment s4b and 5 of the liver was performed with lymphadenectomy. The post-operative clinical course was uneventful.The diagnosis of cystadenocarcinoma of the gallbladder was confirmed on an anatomopathological exam of the specimen. Conclusion: Cystadenocarcinoma is a rare diagnosis.There are no specific symptoms or lesions at the imaging.The confirmation is obtained on an anatomopathological study of the specimen.