Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and intraoperative radiation therapy in the management of gallbladder cancer: a case report.

Gallbladder cancer (GBC) is a rare and highly aggressive malignancy, often characterized by nonspecific clinical presentations and late diagnosis, which contribute to its poor prognosis. It is commonly detected at advanced stages, leading to low survival rates. Surgical resection is the primary treatment, with the extent of surgery depending on the T stage of the cancer. In advanced cases, surgery is only considered if it can potentially be curative. Despite various treatment approaches for advanced GBC, survival outcomes remain poor. In our case series, we introduce a novel treatment approach combining cytoreductive surgery, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Remarkably, we observed a 100% one-year survival rate, with one patient achieving eight years of disease-free survival without recurrence or metastasis. This aggressive treatment strategy did not lead to increased morbidity or mortality, suggesting its safety and feasibility. However, larger-scale studies are required to draw definitive conclusions.

Rare Case of Recurrent Adamantinoma of the Tibia: Limited Efficacy of Pazopanib as a Standalone Treatment.

BACKGROUND Adamantinoma is a rare low-grade malignant bone tumor, usually found in the tibial diaphysis and metaphysis, with histological similarities to mandibular ameloblastoma. The most effective treatment of recurrent adamantinoma is not yet clear. This report is of a 22-year-old woman with recurrent tibial adamantinoma treated with the tyrosine kinase inhibitor pazopanib. CASE REPORT We report the case of a 22-year-old woman who was referred to our center for a suspicious bone lesion in the right tibia. Bone biopsy findings were consistent with an adamantinoma. En bloc resection was completed successfully, with no postoperative complications. Five years later, a positive emission tomography scan revealed mildly increased tracer uptake near the area of the previous lesion and in the right inguinal lymph node. Biopsies of the lesion and inguinal lymph node confirmed recurrence of the adamantinoma. Due to abdominal and pelvic metastasis, the patient underwent surgical debulking, along with an appendectomy, right salpingo-oophorectomy, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Subsequently, the patient was placed on pazopanib for 4 months; however, her tumor continued to worsen after 4 months of chemotherapy. Currently, the patient is receiving gemcitabine and docetaxel as second-line medical therapy. CONCLUSIONS This report showed that pazopanib as standalone treatment does not appear to have promising role on patient outcomes. To the best of our knowledge, this is the second report of pazopanib in the treatment of adamantinoma.

Treatment of recurrent malignant pheochromocytoma with a novel approach: A case report and review of literature.

INTRODUCTION: Pheochromocytomas are rare catecholamine-secreting tumors with a high potential for recurrence post-surgery, necessitating prolonged follow-up. This case highlights the diagnostic and therapeutic challenges in managing recurrent pheochromocytoma. CASE PRESENTATION: A 25-year-old female, with a history of left pheochromocytoma treated with adrenalectomy a decade earlier, presented with a right adrenal mass. Despite controlled hypertension, elevated urine metanephrines suggested recurrence. Imaging showed a right adrenal mass and suspicious left paraaortic lymph nodes, confirming the diagnosis of recurrent malignant pheochromocytoma in the left adrenal bed and right adrenal gland, with metastasis to the paraaortic lymph nodes. The patient underwent right adrenalectomy coupled with cytoreductive surgery (CRS) in the form of excision of left-sided adrenal bed recurrence and left paraaortic lymph node dissection, intraoperative radiation therapy (IORT), and hyperthermic intraperitoneal chemotherapy (HIPEC). On follow-up six years later, the patient remains free from recurrence. DISCUSSION: This case illustrates the importance of continued surveillance in pheochromocytoma patients, even those with a low-risk profile. The recurrence in this case, despite a smaller initial tumor size and no genetic predispositions, underscores the unpredictable nature of pheochromocytomas. The successful management with CRS, IORT, and HIPEC emphasizes the need for a personalized and multifaceted treatment approach. CONCLUSION: Pheochromocytoma patients, including those initially considered low risk, require long-term monitoring due to the risk of recurrence. The utilization of CRS, IORT, and HIPEC in this case was pivotal in managing the recurrent and metastatic malignant disease effectively, demonstrating the significance of a comprehensive, multidisciplinary treatment strategy in such complex cases.

Using machine learning models to predict synchronous genitourinary cancers among gastrointestinal stromal tumor patients.

Objectives: Gastrointestinal stromal tumors (GISTs) can occur synchronously with other neoplasms, including the genitourinary (GU) system. Machine learning (ML) may be a valuable tool in predicting synchronous GU tumors in GIST patients, and thus improving prognosis. This study aims to evaluate the use of ML algorithms to predict synchronous GU tumors among GIST patients in a specialist research center in Saudi Arabia. Materials and Methods: We analyzed data from all patients with histopathologically confirmed GIST at our facility from 2003 to 2020. Patient files were reviewed for the presence of renal cell carcinoma, adrenal tumors, or other GU cancers. Three supervised ML algorithms were used: logistic regression, XGBoost Regressor, and random forests (RFs). A set of variables, including independent attributes, was entered into the models. Results: A total of 170 patients were included in the study, with 58.8% (n = 100) being male. The median age was 57 (range: 9-91) years. The majority of GISTs were gastric (60%, n = 102) with a spindle cell histology. The most common stage at diagnosis was T2 (27.6%, n = 47) and N0 (20%, n = 34). Six patients (3.5%) had synchronous GU tumors. The RF model achieved the highest accuracy with 97.1%. Conclusion: Our study suggests that the RF model is an effective tool for predicting synchronous GU tumors in GIST patients. Larger multicenter studies, utilizing more powerful algorithms such as deep learning and other artificial intelligence subsets, are necessary to further refine and improve these predictions.

Unraveling the epigenetic fabric of type 2 diabetes mellitus: pathogenic mechanisms and therapeutic implications.

Type 2 diabetes mellitus (T2DM) is a rapidly escalating global health concern, with its prevalence projected to increase significantly in the near future. This review delves into the intricate role of epigenetic modifications - including DNA methylation, histone acetylation, and micro-ribonucleic acid (miRNA) expression - in the pathogenesis and progression of T2DM. We critically examine how these epigenetic changes contribute to the onset and exacerbation of T2DM by influencing key pathogenic processes such as obesity, insulin resistance, ß-cell dysfunction, cellular senescence, and mitochondrial dysfunction. Furthermore, we explore the involvement of epigenetic dysregulation in T2DM-associated complications, including diabetic retinopathy, atherosclerosis, neuropathy, and cardiomyopathy. This review highlights recent studies that underscore the diagnostic and therapeutic potential of targeting epigenetic modifications in T2DM. We also provide an overview of the impact of lifestyle factors such as exercise and diet on the epigenetic landscape of T2DM, underscoring their relevance in disease management. Our synthesis of the current literature aims to illuminate the complex epigenetic underpinnings of T2DM, offering insights into novel preventative and therapeutic strategies that could revolutionize its management.

Effectiveness of Dermal Regeneration Templates in Managing Acute Full-thickness and Deep Dermal Burn Injuries: A Comparison with Split-thickness Skin Grafts.

Background: The therapeutic challenge of managing acute full-thickness burns is significantly ameliorated with the introduction of dermal regeneration templates (DRTs). However, an updated synthesis of evidence-based data on the efficacy and safety of different DRTs is required. Methods: This systematic review and meta-analysis conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines aims to evaluate the role of various DRTs in comparison with split-thickness skin grafting in managing acute burn injuries after excision and debridement. A total of 28 randomized clinical trials were assessed, encompassing a wide array of DRTs. Results: The study outcomes pointed to the diverse effectiveness of DRTs, with Integra demonstrating peripheral nerve reinnervation potential and TransCyte promoting rapid re-epithelialization. Some DRTs showed scar formation and skin quality comparable to those of autologous skin grafts. In terms of wound infection, certain treatments, including TransCyte, exhibited a significantly low infection rate. The evaluation of scar quality suggested that various interventions produced acceptable or improved outcomes without hypertrophic scarring. Recovery rates after the interventions displayed a range, with certain treatments showing rapid recovery and satisfactory results. Conclusions: The current systematic review points to the potential benefits of DRTs in managing burn wounds. Further research is necessary to shed light on the long-term impacts of these interventions on wound healing, scar quality, and patient recovery.

The double-edged sword of mesh use in pelvic organ prolapse surgery: a case report.

Introduction: Pelvic organ prolapse (POP) is a prevalent condition among parous women, often warranting surgical intervention. This case accentuates the complications associated with mesh in POP surgeries, iterating the imperative need for an evidence-based approach towards its utilization and exhaustive patient counselling. Case presentation: A 60-year-old female, post-mesh-augmented POP repair, embarked on a 13-year journey characterized by persistent pelvic pain and multiple interventions. Despite undergoing several surgeries across different countries, involving mesh and stone removals, her symptoms, notably pelvic pain and dyspareunia, persisted. Clinical examinations revealed mesh erosion into the perivesical tissue, bladder, and associated stones, which were addressed through multiple interventions, albeit with transient success. Discussion: The complex journey of this patient exemplifies the intricate challenges mesh poses in POP surgeries. While mesh application offers a minimally invasive approach and has proven successful in numerous cases, it simultaneously opens a Pandora's box of potential severe complications, necessitating thorough patient counselling and post-surgery management. Conclusion: The case delineates the challenging path that clinicians and patients tread when navigating through mesh-associated complications post-POP repair. Although mesh has been heralded as a revolutionary approach in POP surgeries, its potential drawbacks necessitate judicious application, ensuring clinicians are well-versed with its associated risks and are adept in managing ensuing complications.

Suspected NUT carcinoma progressing on pembrolizumab, carboplatin, and paclitaxel as first-line treatment: a case report.

Introduction and importance: NUT carcinoma of the thorax is an extremely rare neoplasm characterized by a translocation between the NUT M1 gene and members of the bromodomain genetic family. Due to the rarity of the neoplasm, standardized treatment guidelines have not yet been established. Several chemotherapeutic agents have been used with limited success, due to the rapid development of resistance to treatment. Pembrolizumab, an anti-programmed-death-1 antibody, has become increasingly used in non-small-cell lung carcinomas. Consequently, pembrolizumab may be beneficial in the treatment of NUT carcinoma. Case presentation: In this article, we discuss the case of a 24-year-old man who was referred to our centre due to an incidental mass finding on an unrelated computed tomography scan. Morphological and immunohistochemical characteristics are highly suspicious of NUT carcinoma with bone metastasis. The patient was placed on carboplatin, paclitaxel, and pembrolizumab as first-line therapy. The patient later progressed and began receiving second-line treatment according to Ewing's protocol. 20 months later, the mass continued to grow, and the patient was started on docetaxel and gemcitabine, which was unsuccessful. After discussing with the patient, he decided to stop chemotherapy and begin palliative care. Clinical discussion: NUT carcinoma is an aggressive tumour with poor prognosis. Treatment options are limited and pembrolizumab does not seem to influence the clinical outcome of the neoplasm. Conclusion: Overall, pembrolizumab does not seem to improve the outcomes of NUT carcinoma patients. To the authors' knowledge, this is the second article reporting the effects of pembrolizumab on the progression of NUT carcinoma.

Beyond the curriculum: unveiling medical students' drivers and barriers to research participation at Alfaisal University.

Medical education continually adapts to the needs of future health care professionals, with student motivation in research being a pivotal aspect. This study at Alfaisal University aimed to explore the motivations, benefits, and challenges faced by medical students in extracurricular research activities. Using a mixed-method approach, we combined quantitative surveys with qualitative group interviews. Findings revealed that both extrinsic (e.g., enhancing postgraduate training prospects) and intrinsic (e.g., personal interest and skill refinement) factors significantly motivate students to be involved in research activities. Participants unanimously acknowledged skill enhancement, particularly in literature comprehension, creative ideation, and networking. However, challenges such as conflicts with course scheduling, lack of hands-on experiences, and mentorship issues were identified as potential barriers to research participation. Addressing these barriers and understanding motivations can inform the design of research programs, enhancing the overall student research experience. This study underscores the importance of research in medical education, emphasizing the need for institutions to prioritize addressing challenges and leveraging benefits to prepare medical students for a research-integrated clinical future.NEW & NOTEWORTHY This article examines the motivating factors and obstacles of extracurricular research in Alfaisal University, Saudi Arabia. The study utilizes a mixed methodology of online surveys and in-person group interviews to gain insights from the medical students of the university. We revealed several extrinsic and intrinsic motivators that drove the students; however, there remain several challenges to students during their research journey. Addressing these challenges will help the students obtain a more fruitful, educational research experience.

Exploring Renal Malignancies in Saudi Arabia: Insights from a Tertiary Care Center Study.

This retrospective study aims to describe the characteristics of renal cell carcinoma (RCC) in Saudi Arabia, in terms of epidemiology, clinical presentation, tumor subtype, Fuhrman grade, tumor size and stage, and overall survival. A total of 431 adult patients with a histopathological diagnosis of RCC between 2015 and 2023 were included in the analysis. Most patients (72.4%) had clear cell tumors, followed by chromophobe (15.1%) and papillary (12.5%) subtypes. In males, papillary RCC (85.2%) was more common compared to clear cell (59.8%) and chromophobe (67.7%) subtypes. Significant differences were observed in median body mass index (BMI) across tumor subtypes, and papillary tumor patients exhibited the highest incidence of hematuria (33.3%) compared to other subtypes. The Fuhrman grade also varied significantly among RCC types. Survival times were found to be lower for patients with papillary tumors. No significant difference was observed based on patients' nationality. This study can inform clinical decision-making on patient prognosis and management as well as public health efforts aimed at reducing the alarming rise of RCC incidence.

Beyond the norm: exploring the uncommon squamous cell carcinoma of the prostate using a Saudi tumor registry.

Background: Squamous cell carcinoma (SCC) of the prostate has limited treatment choices and portends a dismal prognosis with an average survival time of ~14-months. This study provides a descriptive overview of SCC of the prostate in Saudi Arabia. Materials and Methods: A retrospective cohort study of patients diagnosed with prostatic SCC between 1 January 2008 and 31 December 2017. Information on demographic and tumor characteristics and the survival of patients was collected from the Saudi Cancer Registry. Survival was depicted through Kaplan-Meier plots. Fisher's exact test was used to assess the association between categorical variables and death, while a Wilcoxon rank sum test was applied for numerical variables. Results: Out of a larger subset of 3607 patients, 16 patients were diagnosed with prostatic SCC, of which half resided in the Central region (50.0%) and most (81.2%) were aged greater than or equal to 60 years. Most patients (62.6%) had poorly differentiated (grade III, 43.8%) lesions, and 50% of cases were metastatic at diagnosis. 62.5% of patients died, all residing in the Eastern and Central regions. Regional extension (75.0%) and distant metastasis (87.5%) were significantly associated with death compared to localized lesions (0.0%) (P=0.022). The 5-year survival rate in our study was 33%. Conclusion: The present study is the first to describe the characteristics of prostatic SCC in Saudi Arabia. Our results are consistent with prior studies showing that prostatic SCC is often high-grade and metastatic at diagnosis, conferring a poor prognosis.

Brain-inhabiting bacteria and neurodegenerative diseases: the "brain microbiome" theory.

Controversies surrounding the validity of the toxic proteinopathy theory of Alzheimer's disease have led the scientific community to seek alternative theories in the pathogenesis of neurodegenerative disorders (ND). Recent studies have provided evidence of a microbiome in the central nervous system. Some have hypothesized that brain-inhabiting organisms induce chronic neuroinflammation, leading to the development of a spectrum of NDs. Bacteria such as Chlamydia pneumoniae, Helicobacter pylori, and Cutibacterium acnes have been found to inhabit the brains of ND patients. Furthermore, several fungi, including Candida and Malassezia species, have been identified in the central nervous system of these patients. However, there remains several limitations to the brain microbiome hypothesis. Varying results across the literature, concerns regarding sample contamination, and the presence of exogenous deoxyribonucleic acids have led to doubts about the hypothesis. These results provide valuable insight into the pathogenesis of NDs. Herein, we provide a review of the evidence for and against the brain microbiome theory and describe the difficulties facing the hypothesis. Additionally, we define possible mechanisms of bacterial invasion of the brain and organism-related neurodegeneration in NDs and the potential therapeutic premises of this theory.

A decade in focus: mixed germ cell tumors with choriocarcinoma components.

Introduction: This 10-year registry review aimed to investigate the clinical behaviour and outcomes of mixed germ cell tumours with choriocarcinoma components, a rare and aggressive subtype of testicular cancer, in Saudi Arabia. The study explores the demographic characteristics of affected patients, tumour profiles, and the mortality rate associated with this malignancy. Methods: Utilizing data from the Saudi Cancer Registry, the authors identified 33 cases of mixed germ cell tumours with choriocarcinoma components among 1001 testicular cancer cases recorded between 2008 and 2017. Demographic information, including age, marital status, region of residency, year of diagnosis, and 10-year survival status, were collected. Tumour factors, such as the basis of diagnosis, origin site, behaviour, grade, extension, and laterality, were also analyzed. Results: The majority of cases (78.8%) occurred in the young age group (18-45 years), and most tumours (97%) originated in normally descended testes. Grade IV (undifferentiated anaplastic) tumours and distant metastasis were present in 45.5% of patients. All cases exhibited malignant tumour behaviour. The overall mortality rate was 15%, with a mean time from diagnosis to death of 7.72 months (range: 0.5-21.5 months). Conclusion: Mixed germ cell tumours with choriocarcinoma components are rare and tend to affect younger populations. These tumours demonstrate aggressive clinical behaviour, with a significant proportion presenting with high-grade lesions and metastasis at diagnosis. The observed mortality rate underscores the poor prognosis associated with this malignancy. Our study provides essential insights into the clinical characteristics of this rare tumour subtype in the Saudi Arabian population, emphasizing the need for further research to identify prognostic factors and optimize management strategies for affected patients.

Neutrophil extracellular traps and long COVID.

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.

Utilization of the emergency department by kidney transplant recipients: a retrospective cohort study from a high-volume transplant center.

This study aims to assess the trends of emergency department (ED) visits among kidney transplant recipients in a high-volume transplant centre. Methods: This retrospective cohort study targeted patients who underwent renal transplantation at a high-volume transplant centre from 2016 to 2020. The main outcomes of the study were ED visits within 30 days, 31-90 days, 91-180 days, and 181-365 days of transplantation. Results: This study included 348 patients. The median (interquartile range) age of patients was 45.0 years (30.8, 58.2). Over half of the patients were male (57.2%). There was a total of 743 ED visits during the first year after discharge. 19% (n=66) were considered high-frequency users. High-volume ED users tended to be admitted more frequently as compared to those with low frequencies of ED visits (65.2% vs. 31.2%, respectively, P<0.001). Conclusion: As evident by the large number of ED visits, suitable coordination of management through the ED remains a pivotal component of post-transplant care. Strategies addressing prevention of complications of surgical procedures or medical care and infection control are aspects with potential for enhancement.

Moyamoya syndrome secondary to mitochondrial disease in a patient with partial trisomy 13q14 and 13q31: A novel case report and literature review.

Moyamoya syndrome (MMS) is a cerebrovascular disease characterized by stenosis of the internal carotid arteries and the formation of an abnormal vascular network at the base of the brain. MMS usually occurs secondary to various conditions, particularly Down syndrome, and sickle cell anemia, and presents with motor deficits, sensory symptoms, recurrent ischemic strokes, hemodynamic transient ischemic attacks, recurrent seizures, and hemorrhage. Trisomy 13 (Patau Syndrome) is a chromosomal abnormality that may be characterized by full or partial trisomy of chromosome 13. Phenotypic features of partial trisomy 13 include leukoencephalopathy, hippocampal hypoplasia, intellectual disability, facial anomalies, and others. Herein, we report a case of a 19-year-old female diagnosed with partial trisomy 13q, characterized by two large duplications in the 13q14 and 13q31 regions, with trisomy-induced bilateral MMS - the first known case to be discussed in literature. Particularly, our patient was identified to have a gain of 22Mb within the 13q14.11q21.31 region - a duplication that has not been described previously. Our patient suffered four strokes between the ages of 5 and 7, later developing intractable seizures, hemiplegia, spasticity in all limbs, global delay, and regression. Despite bilateral encephaloduroarteriosynangiosis and being on several antiepileptic medications, the MMS continued to progress, confounded by the partial trisomy 13. Studies must elucidate the association between mitochondrial damage and MMS, as well as mechanisms of epilepsy associated with chromosomal abnormalities, particularly in the context of underlying mitochondrial diseases.

Xenotransplantation: Current Challenges and Emerging Solutions.

To address the ongoing shortage of organs available for replacement, xenotransplantation of hearts, corneas, skin, and kidneys has been attempted. However, a major obstacle facing xenotransplants is rejection due to a cycle of immune reactions to the graft. Both adaptive and innate immune systems contribute to this cycle, in which natural killer cells, macrophages, and T-cells play a significant role. While advancements in the field of genetic editing can circumvent some of these obstacles, biomarkers to identify and predict xenograft rejection remain to be standardized. Several T-cell markers, such as CD3, CD4, and CD8, are useful in both the diagnosis and prediction of xenograft rejection. Furthermore, an increase in the levels of various circulating DNA markers and microRNAs is also predictive of xenograft rejection. In this review, we summarize recent findings on the advancements in xenotransplantation, with a focus on pig-to-human, the role of immunity in xenograft rejection, and its biomarkers.

Preserving Renal Function without Compromising Oncological Outcomes: A Comparative Study of Partial and Total Nephrectomies in T3 Stage Renal Cell Carcinoma.

The utility of partial nephrectomy (PN) in locally advanced, stage T3 renal cell carcinoma (RCC) is controversial. This retrospective study aimed to review the oncological and functional outcomes of patients with T3a RCC who underwent PN. We included all patients with pT3a stage RCC undergoing either open, laparoscopic, or robotic PN at our center between January 2015 and 2023. A Wilcoxon rank sum test was utilized to compare nephrectomy types (radical nephrectomy [RN] vs PN). Survival analysis was conducted using Kaplan-Meier plots and a log-rank test. P-value < 0.05 indicated statistical significance. There were no significant differences in demographic characteristics between the RN and PN groups, except age (53.0 vs 6.5, respectively; P = 0.012) and body mass index (28.7 vs 34.3, respectively; P = 0.020). Furthermore, there were also no significant differences in the rates of local recurrence (P = 0.597), metastatic progression (P = 0.129), and chemotherapy use (P = 0.367) between nephrectomy types. Patient survival did not differ significantly based on the type of nephrectomy (log-rank P-value = 0.852). Together, our findings indicated that PN and RN yield near-equivalent oncological outcomes in terms of local recurrence, metastasis, and overall survival rates among pT3a RCC patients during a nearly 3-year follow-up period.

Contemporary review on pediatric hypertrophic cardiomyopathy: insights into detection and management.

Hypertrophic cardiomyopathy is the most common genetic cardiac disorder and is defined by the presence of left ventricular (LV) hypertrophy in the absence of a condition capable of producing such a magnitude of hypertrophy. Over the past decade, guidelines on the screening, diagnostic, and management protocols of pediatric primary (i.e., sarcomeric) HCM have undergone significant revisions. Important revisions include changes to the appropriate screening age, the role of cardiac MRI (CMR) in HCM diagnosis, and the introduction of individualized pediatric SCD risk assessment models like HCM Risk-kids and PRIMaCY. This review explores open uncertainties in pediatric HCM that merit further attention, such as the divergent American and European recommendations on CMR use in HCM screening and diagnosis, the need for incorporating key genetic and imaging parameters into HCM-Risk Kids and PRIMaCY, the best method of quantifying myocardial fibrosis and its prognostic utility in SCD prediction for pediatric HCM, devising appropriate genotype- and phenotype-based exercise recommendations, and use of heart failure medications that can reverse cardiac remodeling in pediatric HCM.

Claudins in genitourinary tract neoplasms: mechanisms, prognosis, and therapeutic prospects.

Genitourinary (GU) cancers are among the most prevalent neoplasms in the world, with bladder cancers constituting 3% of global cancer diagnoses. However, several pathogenetic mechanisms remain controversial and unclear. Claudins, for example, have been shown to play a significant role in several cancers of the human body. Their role in GU cancers has not been extensively studied. Aberrant expression of claudins -1, -2, -3, -4, -7, and -11 has been expressed in urothelial cell carcinomas. In prostate cancers, altered levels of claudins -1, -2, -3, -4, and -5 have been reported. Furthermore, the levels of claudins -1, -2, -3, -4, -6, -7, -8, and -10 have been studied in renal cell carcinomas. Specifically, claudins -7 and -8 have proven especially useful in differentiating between chromophobe renal cell carcinomas and oncocytomas. Several of these claudins also correlate with clinicopathologic parameters and prognosis in GU cancers. Although mechanisms underpinning aberrant expression of claudins in GU cancers are unclear, epigenetic changes, tumor necrosis factor-ɑ, and the p63 protein have been implicated. Claudins also provide therapeutic value through tailored immunotherapy via molecular subtyping and providing therapeutic targets, which have shown positive outcomes in preclinical studies. In this review, we aim to summarize the literature describing aberrant expression of claudins in urothelial, prostatic, and renal cell carcinomas. Then, we describe the mechanisms underlying these changes and the therapeutic value of claudins. Understanding the scope of claudins in GU cancers paves the way for several diagnostic, prognostic, and therapeutic innovations.