Emerging biomarkers and molecular targets for precision medicine in cervical cancer.

Cervical cancer remains a significant global health burden, necessitating innovative approaches for improved diagnostics and personalized treatment strategies. Precision medicine has emerged as a promising paradigm, leveraging biomarkers and molecular targets to tailor therapy to individual patients. This review explores the landscape of emerging biomarkers and molecular targets in cervical cancer, highlighting their potential implications for precision medicine. By integrating these biomarkers into comprehensive diagnostic algorithms, clinicians can identify high-risk patients at an earlier stage, enabling timely intervention and improved patient outcomes. Furthermore, the identification of specific molecular targets has paved the way for the development of targeted therapies aimed at disrupting key pathways implicated in cervical carcinogenesis. In conclusion, the evolving landscape of biomarkers and molecular targets presents exciting opportunities for advancing precision medicine in cervical cancer. By harnessing these insights, clinicians can optimize treatment selection, enhance patient outcomes, and ultimately transform the management of this devastating disease.

Should an Incidental Meckel Diverticulum Be Resected? A Systematic Review.

Background: Meckel Diverticulum [MD), a common congenital anomaly of the gastrointestinal tract, poses a dilemma when incidentally encountered during surgery. Despite historical descriptions and known complications of symptomatic MD, the decision to resect an incidental MD (IMD) lacks clear guidelines. This study aims to assess whether resecting IMDs is justified by synthesizing evidence from studies published between 2000 and 2023. Factors influencing this decision, such as demographic risks, surgical advancements and complications, are systematically examined. Methods and Material: Following the PRISMA 2020 guidelines, this review incorporates 42 eligible studies with data on outcomes of asymptomatic MD management. Studies, both favoring and opposing resection, were analyzed. Results: Considering complications, malignancy potential, and operative safety, the risk-benefit analysis presents a nuanced picture. Some authors propose conditional resection based on specific criteria, emphasizing patient-specific factors. Of 2934 cases analyzed for short- and long-term complications, the morbidity rate was 5.69%. Of 571 cases where mortality data were available, all 5 fatalities were attributed to the primary disease rather than IMD resection. Conclusion: The sporadic, unpredictable presentation of IMD and the variability of both the primary disease and the patient make formulation of definitive guidelines challenging. The non-uniformity of complications reporting underscores the need for standardized categorization. While the balance of evidence leans towards resection of IMDs, this study acknowledges the individualized nature of this decision. Increased safety in surgery and anesthesia, along with better understanding and management of complications favor a judicious preference for resection, while taking into account patient characteristics and the primary disease.

Knowledge, attitude, and practices about breast cancer among women in a high-altitude sub-Himalayan region: Are we reaching the unreached?

Background: Breast cancer awareness and early detection are critical for reducing the global burden of the disease. This study assessed breast cancer awareness among women in a high-altitude sub-Himalayan region of North India. Materials and Methods: A cross-sectional survey was conducted among women attending the gynecology outpatient clinic in a district hospital. A structured questionnaire was used to collect data on breast cancer knowledge, attitudes, and practices. Participants received posttest health education and counseling on breast cancer prevention strategies. Result: The study included 188 participants with a mean age of 31.0 ± 8.8 years. The findings revealed inadequate knowledge about breast cancer among a significant portion of the cohort. Misconceptions about risk factors, such as breastfeeding, oral contraceptive use, and past wrongdoings, were observed. Only half of the participants believed early-stage breast cancer could be effectively treated. Limited awareness of screening methods, including self-breast examination and mammography, was noted. Barriers to breast self-examination (BSE) included considering it unnecessary and lacking knowledge about its execution. Conclusion: This study highlights insufficient breast cancer awareness in the high-altitude sub-Himalayan region. Targeted interventions, including health campaigns and electronic media, should be prioritized to improve knowledge and promote early detection practices.

Validation of Left Atrial Volume Correction for Single Plane Method on Four-Chamber Cine Cardiac MRI.

BACKGROUND: Left atrial (LA) assessment is an important marker of adverse cardiovascular outcomes. Cardiovascular magnetic resonance (CMR) accurately quantifies LA volume and function based on biplane long-axis imaging. We aimed to validate single-plane-derived LA indices against the biplane method to simplify the post-processing of cine CMR. METHODS: In this study, 100 patients from Leeds Teaching Hospitals were used as the derivation cohort. Bias correction for the single plane method was applied and subsequently validated in 79 subjects. RESULTS: There were significant differences between the biplane and single plane mean LA maximum and minimum volumes and LA ejection fraction (EF) (all p < 0.01). After correcting for biases in the validation cohort, significant correlations in all LA indices were observed (0.89 to 0.98). The area under the curve (AUC) for the single plane to predict biplane cutoffs of LA maximum volume ≥ 112 mL was 0.97, LA minimum volume ≥ 44 mL was 0.99, LA stroke volume (SV) ≤ 21 mL was 1, and LA EF ≤ 46% was 1, (all p < 0.001). CONCLUSIONS: LA volumetric and functional assessment by the single plane method has a systematic bias compared to the biplane method. After bias correction, single plane LA volume and function are comparable to the biplane method.

A systematic review of artificial intelligence tools for chronic pulmonary embolism on CT pulmonary angiography.

Background: Chronic pulmonary embolism (PE) may result in pulmonary hypertension (CTEPH). Automated CT pulmonary angiography (CTPA) interpretation using artificial intelligence (AI) tools has the potential for improving diagnostic accuracy, reducing delays to diagnosis and yielding novel information of clinical value in CTEPH. This systematic review aimed to identify and appraise existing studies presenting AI tools for CTPA in the context of chronic PE and CTEPH. Methods: MEDLINE and EMBASE databases were searched on 11 September 2023. Journal publications presenting AI tools for CTPA in patients with chronic PE or CTEPH were eligible for inclusion. Information about model design, training and testing was extracted. Study quality was assessed using compliance with the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Results: Five studies were eligible for inclusion, all of which presented deep learning AI models to evaluate PE. First study evaluated the lung parenchymal changes in chronic PE and two studies used an AI model to classify PE, with none directly assessing the pulmonary arteries. In addition, a separate study developed a CNN tool to distinguish chronic PE using 2D maximum intensity projection reconstructions. While another study assessed a novel automated approach to quantify hypoperfusion to help in the severity assessment of CTEPH. While descriptions of model design and training were reliable, descriptions of the datasets used in training and testing were more inconsistent. Conclusion: In contrast to AI tools for evaluation of acute PE, there has been limited investigation of AI-based approaches to characterising chronic PE and CTEPH on CTPA. Existing studies are limited by inconsistent reporting of the data used to train and test their models. This systematic review highlights an area of potential expansion for the field of AI in medical image interpretation.There is limited knowledge of A systematic review of artificial intelligence tools for chronic pulmonary embolism in CT. This systematic review provides an assessment on research that examined deep learning algorithms in detecting CTEPH on CTPA images, the number of studies assessing the utility of deep learning on CTPA in CTEPH was unclear and should be highlighted.

Rectovaginal Fistulas Not Involving the Rectovaginal Septum Should Be Treated Like Anal Fistulas: A New Concept and Proposal for a Reclassification of Rectovaginal Fistulas.

Background: Many rectovaginal fistulas(RVF), especially low RVF, do not involve/penetrate the RV-septum, but due to lack of proper nomenclature, such fistulas are also managed like RVF (undertaking repair of RV-septum) and inadvertently lead to the formation of a high RVF (involving RV-septum) in many cases. Therefore, REctovaginal Fistulas, Not Involving the Rectovaginal Septum, should be Treated like Anal fistulas(RENISTA) to prevent any risk of injury to the RV septum. This concept(RENISTA) was tested in this study. Methods: RVFs not involving RV-septum were managed like anal fistulas, and the RV-septum was not cut/incised. MRI, objective incontinence scoring, and anal manometry were done preoperatively and postoperatively. High RVF (involving RV-septum) were excluded. Results: Twenty-seven patients with low RVF (not involving RV-septum) were operated like anal fistula[age:35.2±9.2 years, median follow-up-15 months (3-36 months)]. 19/27 were low fistula[<1/3 external anal sphincter(EAS) involved] and fistulotomy was performed, whereas 8/27 were high fistula (>1/3 EAS involved) and underwent a sphincter-sparing procedure. Three patients were excluded. The fistula healed well in 22/24 (91.7%) patients and did not heal in 2/24 (8.3%). The healing was confirmed on MRI, and there was no significant change in mean incontinence scores and anal pressures on tonometry. RV-septum injury did not occur in any patient. Conclusions: RVF not involving RV-septum were managed like anal fistulas with a high cure rate and no significant change in continence. RV-septum injury or formation of RVF with septum involvement did not occur in any patient. The RENISTA concept was validated in the present study. A new classification was developed to prevent any inadvertent injury to the RV-septum.

Characterisation of the octogenarians presenting to the diagnostic heart failure clinic: SHEAF registry.

INTRODUCTION: Heart failure (HF) incidence is increasing in older adults with high hospitalisation and mortality rates. Treatment is complicated by side effects and comorbidities. We investigated the clinical characteristics of octogenarians presenting to the HF clinic. METHODS: Data were collected on octogenarians (80-89 years) referred to the HF clinic in two periods. The data included demographics, HF phenotype, comorbidities, symptoms and treatment. We investigate the temporal changes in clinical characteristics using χ2 test. We aimed to determine the clinical characteristics which were associated with optimisation of HF pharmacological intervention in the clinic, conducting multivariate regression analysis. Statistical significance is determined at p<0.05. RESULTS: Data were collected in April 2012 to January 2014 and in June 2021 to December 2022. In this cross-sectional study of temporal data, 571 octogenarians were referred to the clinic in the latter period, in whom the prevalence of HF was 68.48% (391 patients). HF with preserved ejection fraction (HFpEF) was the most common phenotype and increased significantly compared with the first period (46.3% and 29.2%, p<0.001). Frailty, chronic kidney disease and ischaemic heart disease increased significantly versus the first period (p<0.001). During the second period, and following the consultation, of the patients with HF with reduced ejection fraction (HFrEF), 86.4% and 82.7% were on a beta blocker and on an ACE inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, respectively. Clinical characteristics associated with further optimisations of HF pharmacological therapy in the HF clinic were: New York Heart Association (NYHA) functional class III and the presence of HFrEF phenotype CONCLUSIONS: With a prevalence of HF at 68% among the octogenarians referred to the HF clinic, HFpEF incidence is rising. The decision to optimise HF pharmacological treatment in octogenarians is driven by NYHA functional class III and the presence of HFrEF phenotype.

Outcome of lung transplantation in patients with pulmonary alveolar microlithiasis in the era of COVID-19 infection.

Lung transplant recipients are at higher risk of developing COVID-19 infection compared to other solid organ transplants. The risk further increases in the unvaccinated patients. We present a case of a 43-year-old male who underwent bilateral sequential lung transplantation for pulmonary alveolar microlithiasis (PAM) and had an uneventful recovery. However, two years post-transplantation, the patient developed chronic lung allograft dysfunction (CLAD) with bronchiolitis obliterans syndrome and two episodes of COVID-19 infection. During the second episode of COVID-19 infection, the patient developed sepsis and multi-organ dysfunction ultimately resulting in death. Our case report highlights the increased susceptibility of PAM patients' post-lung transplant to COVID-19 infection. Continuous follow-up of PAM patients' post-lung transplantation is necessary to prevent unfavorable outcomes.

Noninvasive Techniques for Tracking Biological Aging of the Cardiovascular System: JACC Family Series.

Population aging is one of the most important demographic transformations of our time. Increasing the "health span"-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.

The development and evaluation of a vaccination pathway for children with intellectual and developmental disability and needle fear.

This qualitative study describes the development and evaluation of a clinical pathway to facilitate the implementation of catch-up vaccinations for children with significant needle fear, particularly in children with developmental disabilities. The Specialist Immunization Team, based at a tertiary level teaching children's hospital, participated in process mapping activities using Motivational Interviewing (MI) techniques and reflective discussions. Team members developed a clinical pathway by incorporating parental feedback from semistructured interviews and clinical expertise from within the team, facilitated by colleagues from the Child Development Unit. A process map was developed that included process strengths and touch points with an action plan that was discussed and agreed upon. A repeat process mapping activity was conducted 16 months later. Reports from parental feedback included: positive, efficient, and successful experiences of having their child undergo catch-up vaccinations. The experience empowered families for further procedures. Team members reported improvements in triaging appropriate children for the pathway, and an increase in confidence to interact and manage behaviors of children with significant anxiety and challenging behaviors. They also reported an increase in successful vaccinations with improved clinical judgment of facilitating the sedation pathway. This study demonstrates that using group facilitation using motivational interviewing in reflective discussions and process mapping utilizing parent and staff feedback in service improvement activities results in efficient and successful service delivery with improved patient outcomes.

Access to child developmental assessment services in culturally and linguistically diverse metropolitan Sydney: a retrospective cohort analysis.

BACKGROUND: Despite the increasing prevalence of neurodevelopmental disorders (NDD), data regarding access to child development services have remained limited globally. Long wait times are a major barrier to developmental assessments, impacting on care and outcomes. The aim is to retrospectively analyse the demographic profile and prioritisation of patients seen at a child developmental assessment service (CDAS) in a vulnerable region of Sydney, and explore factors affecting wait times. METHODS: Data was collated and analysed for 2354 patients from 2018 to 2022. Socio-Economic Indexes for Areas (SEIFA) were collated from the Australian Bureau of Statistics. Descriptive statistics were used for demographic data and various statistical methods were used to analyse the relationships and impact of factors likely to affect wait lists. RESULTS: The median age was 51 months (IQR41-61) and males comprised 73.7% of the cohort. 64% of children were from culturally and linguistically diverse backgrounds (CALD) and 47% lived in the most disadvantaged suburbs. The median wait time was 302.5 days (IQR175-379) and 70% of children were seen within 12 months. CALD patients and children over 5-years had shorter wait times. Most children with Global Developmental Delay (GDD) were from the lowest four SEIFA deciles and waited longer for an appointment. 42.6% were seen within the priority allocated time or sooner. Children with ASD and/or severe GDD were prioritised to be seen earlier. Overall, the study could not demonstrate any difference in the wait times according to the prioritisation groups. CONCLUSION: This study provides insights into the profile, prioritisation processes and wait lists of children seen by CDAS in South Western Sydney with high rates of social vulnerability and presents an argument to discuss benchmarking targets with service providers. It identifies the need to prioritise children living in suburbs with socioeconomic disadvantage and refine prioritisation and data collection processes to improve wait times.

Validation of 2D flow MRI for helical and vortical flows.

PURPOSE: The main objective of this study was to develop two-dimensional (2D) phase contrast (PC) methods to quantify the helicity and vorticity of blood flow in the aortic root. METHODS: This proof-of-concept study used four-dimensional (4D) flow cardiovascular MR (4D flow CMR) data of five healthy controls, five patients with heart failure with preserved ejection fraction and five patients with aortic stenosis (AS). A PC through-plane generated by 4D flow data was treated as a 2D PC plane and compared with the original 4D flow. Visual assessment of flow vectors was used to assess helicity and vorticity. We quantified flow displacement (FD), systolic flow reversal ratio (sFRR) and rotational angle (RA) using 2D PC. RESULTS: For visual vortex flow presence near the inner curvature of the ascending aortic root on 4D flow CMR, sFRR demonstrated an area under the curve (AUC) of 0.955, p<0.001. A threshold of >8% for sFRR had a sensitivity of 82% and specificity of 100% for visual vortex presence. In addition, the average late systolic FD, a marker of flow eccentricity, also demonstrated an AUC of 0.909, p<0.001 for visual vortex flow. Manual systolic rotational flow angle change (ΔsRA) demonstrated excellent association with semiautomated ΔsRA (r=0.99, 95% CI 0.9907 to 0.999, p<0.001). In reproducibility testing, average systolic FD (FDsavg) showed a minimal bias at 1.28% with a high intraclass correlation coefficient (ICC=0.92). Similarly, sFRR had a minimal bias of 1.14% with an ICC of 0.96. ΔsRA demonstrated an acceptable bias of 5.72°-and an ICC of 0.99. CONCLUSION: 2D PC flow imaging can possibly quantify blood flow helicity (ΔRA) and vorticity (FRR). These imaging biomarkers of flow helicity and vorticity demonstrate high reproducibility for clinical adoption. TRIALS REGISTRATION NUMBER: NCT05114785.

Transanal opening of the intersphincteric space (TROPIS): a novel procedure on the horizon to effectively manage high complex anal fistulas.

Anal fistulas, especially complex and high fistulas, are difficult to manage. The transanal opening of the intersphincteric space (TROPIS) procedure was first described in 2017, and a high success rate of over 90% was reported in high complex fistulas. Since then, more studies and even a meta-analysis have corroborated the high efficacy of this procedure in high fistulas. Conventionally, the main focus was to close the internal (primary) opening for the fistula to heal. However, most complex fistulas have a component of the fistula tract in the intersphincteric plane. This component is like an abscess (sepsis) in a closed space (2 muscle layers). It is a well-known fact that in the presence of sepsis, healing by secondary intention leads to better results than attempting to heal by primary intention. Therefore, TROPIS is the first procedure in which, instead of closing the internal opening, the opening is widened by laying open the fistula tract in the intersphincteric plane so that healing can occur by secondary intention. Although the drainage of high intersphincteric abscesses through the transanal route was described 5 decades ago, the routine utilization of TROPIS for the definitive management of high complex fistulas was first described in 2017. The external anal sphincter (EAS) is completely spared in TROPIS, as the fistula tract on either side of the EAS is managed separately-inner (medial) to the EAS by laying open the intersphincteric space and outer (lateral) to the EAS by curettage or excision.

Absorbable antibiotic beads for treatment of LVAD driveline infections.

BACKGOUND: Infections of the left ventricular assist device (LVAD) driveline are a dreaded complication that results in high mortality and morbidity. METHOD: We retrospectively reviewed five consecutive patients with severe continuous-flow LVAD (HVAD, Heartmate 2, and Heartmate 3) driveline infection. These infections, which developed on an average of 960.4 ± 843.9 days after LVAD placement, were refractory to systemic antibiotics and local wound care. All were treated with extensive surgical debridement, local installation of absorbable antibiotic-loaded calcium sulfate beads (vancomycin and tobramycin), primary wound closure, and 6 weeks of systemic antibiotics after surgery. RESULTS: Four patients had resolution of DLI, and one had a recurrent infection at another part of the driveline 7 months after the complete resolution of the previous site. This patient was successfully treated with debridement and bead placements. Three patients still have their LVADs, while two received orthotopic heart transplants. At the time of the transplant, there was no evidence of gross infection of the LVAD drivelines or pumps. At the average follow-up time of 425.8 ± 151 days, no patients have an active infection. CONCLUSION: Treatment of LVAD driveline infection with absorbable antibiotic beads with primary wound closure is a viable option and merits further investigation.

4D Flow Cardiac MR in Primary Mitral Regurgitation.

BACKGROUND: Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established. PURPOSE: To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation. STUDY TYPE: Prospective, single-center, two arm, interventional vs. nonintervention observational study. POPULATION: Forty-four patients (male N = 30; median age 68 [59-75]) with at least moderate primary mitral regurgitation; either awaiting mitral valve surgery (repair [MVr], replacement [MVR]) or undergoing "watchful waiting" (WW). FIELD STRENGTH/SEQUENCE: 5 T/Balanced steady-state free precession (bSSFP) sequence/Phase contrast imaging/Multishot echo-planar imaging pulse sequence (five shots). ASSESSMENT: Patients underwent transthoracic echocardiography (TTE), phase-contrast MR (PMRI), 4DF-MR and 6-minute walk test (6MWT) at baseline, and a follow-up PMRI and 6MWT at 6 months. MR-Rvol was quantified by PMRI, 4DF-MR, and TTE by one observer. The pre-operative MR-Rvol was correlated with the post-operative decrease in the LV end-diastolic volume index (LVEDVi). STATISTICAL TESTS: Included Student t-test/Mann-Whitney test/Fisher's exact test, Bland-Altman plots, linear regression analysis and receiver operating characteristic curves. Statistical significance was defined as P < 0.05. RESULTS: While Bland-Altman plots demonstrated similar bias between all the modalities, the limits of agreement were narrower between 4DF-MR and PMRI (bias 15; limits of agreement -36 mL to 65 mL), than between 4DF-MR and TTE (bias -8; limits of agreement -106 mL to 90 mL) and PMRI and TTE (bias -23; limits of agreement -105 mL to 59 mL). Linear regression analysis demonstrated a significant association between the MR-Rvol and the post-operative decrease in the LVEDVi, when the MR-Rvol was quantified by PMRI and 4DF-MR, but not by TTE (P = 0.73). 4DF-MR demonstrated the best diagnostic performance for reduction in the post-operative LVEDVi with the largest area under the curve (4DF-MR 0.83; vs. PMRI 0.78; and TTE 0.51; P = 0.89). DATA CONCLUSION: This study demonstrates the potential clinical utility of 4DF-MR in the assessment of primary mitral regurgitation. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

Garg incontinence scores: New scoring system on the horizon to evaluate fecal incontinence. Will it make a difference?

The main aim of this opinion review is to comment on the recent article published by Garg et al in the World Journal of Gastroenterology 2023; 29: 4593-4603. The authors in the published article developed a new scoring system, Garg incontinence scores (GIS), for fecal incontinence (FI). FI is a chronic debilitating disease that has a severe negative impact on the quality of life of the patients. Rome IV criteria define FI as multiple episodes of solid or liquid stool passed into the clothes at least twice a month. The associated social stigmatization often leads to significant under-reporting of the condition, which further impairs management. An important point is that the complexity and vagueness of the disease make it difficult for the patients to properly define and report the magnitude of the problem to their physicians. Due to this, the management becomes even more difficult. This issue is resolved up to a considerable extent by a scoring questionnaire. There were several scoring systems in use for the last three decades. The prominent of them were the Cleveland Clinic scoring system or the Wexner scoring system, St. Marks Hospital or Vaizey's scores, and the FI severity index. However, there were several shortcomings in these scoring systems. In the opinion review, we tried to analyze the strength of GIS and compare it to the existing scoring systems. The main pitfalls in the existing scoring systems were that most of them gave equal weightage to different types of FI (solid, liquid, flatus, etc.), were not comprehensive, and took only the surgeon's perception of FI into view. In GIS, almost all shortcomings of previous scoring systems had been addressed: different weights were assigned to different types of FI by a robust statistical methodology; the scoring system was made comprehensive by including all types of FI that were previously omitted (urge, stress and mucus FI) and gave priority to patients' rather than the physicians' perceptions while developing the scoring system. Due to this, GIS indeed looked like a paradigm shift in the evaluation of FI. However, it is too early to conclude this, as GIS needs to be validated for accuracy and simplicity in future studies.