Associations of free, bioavailable and total 25-hydroxyvitamin D with neonatal birth anthropometry and calcium homoeostasis in mother-child pairs in a sunny Mediterranean region.

Sufficient vitamin D status is crucial for successful pregnancy and fetal development. The assessment of 25-hydroxyvitamin D (25(OH)D) concentrations is commonly used to evaluate vitamin D status. Our objective was to examine the interrelated biodynamics of maternal and neonatal total, free and bioavailable 25(OH)D in maternal-neonatal dyads at birth and their associations with homeostasis and neonatal birth anthropometry. We analysed a cohort of seventy full-term mother-child pairs. We found positive associations between all neonatal measures of vitamin D status. Maternal forms exhibited a similar pattern of association, except for the bioavailable maternal form. In multivariate analysis, both total and free maternal 25(OH)D concentrations were correlated with all neonatal forms (neonatal total 25(OH)D: 1·29 (95 % CI, 1·12, 1·46) for maternal total 25(OH)D, 10·89 (8·16, 13·63) for maternal free 25(OH)D), (neonatal free 25(OH)D: 0·15 for maternal total 25(OH)D, 1·28 (95 % CI, 0·89, 1·68) for maternal free 25(OH)D) and (0·13 (95 % CI, 0·10, 0·16), 1·06 (95 % CI, 0·68, 1·43) for maternal free 25(OH)D), respectively, with the exclusion of the bioavailable maternal form. We observed no significant interactions within or between groups regarding maternal and neonatal vitamin D parameters and maternal calcium and parathyroid hormone concentrations, and neonatal birth anthropometry. Our study indicates that bioavailable maternal and neonatal 25(OH)D have no significant effects on vitamin D equilibrium, Ca homeostasis and neonatal anthropometry at birth. However, we observed an interaction between maternal and neonatal total and free 25(OH)D concentrations at the maternal-neonatal interface, with no associations observed with other calciotropic or anthropometric outcomes.

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.

Deciphering the role of claudins in lung cancer.

Lung cancer remains a major global health challenge, characterized by aggressive malignancy and poor prognostic outcomes. This review article focuses on the pivotal role of claudins, a family of tight junction proteins, in the pathophysiology of lung cancer. Claudins are integral to maintaining epithelial barrier function and cellular polarity, yet they are intricately involved in the progression and metastasis of lung cancer. The aberrant expression of claudins has been observed across various histological subtypes of lung cancer, indicating their potential as diagnostic and prognostic biomarkers. Specifically, claudins such as claudin-1, -2, -3, -4, and -7 exhibit diverse expression patterns that correlate with tumor aggressiveness, patient survival rates, and response to therapies. Inflammation and cytokine modulation significantly influence claudin expression, affecting tumor microenvironment dynamics and cancer progression. This review also highlights the therapeutic implications of targeting claudins, particularly in cases resistant to conventional treatments. Recent advances in this area suggest that claudin-modulating agents may enhance the efficacy of existing therapies and offer new avenues for targeted interventions. By integrating the latest research, this article aims to provide a comprehensive understanding of claudin's roles in lung cancer and encourages further clinical trials to explore claudin-targeting therapies. This could pave the way for more effective management strategies, improving outcomes for lung cancer patients.

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.

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.

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.

Unveiling the Web: Exploring the Multifaceted Role of Neutrophil Extracellular Traps in Ocular Health and Disease.

Neutrophil extracellular traps (NETs) play an essential role in antimicrobial defense. However, NETs have also been shown to promote and mediate a wide spectrum of diseases, including cancer, diabetes mellitus, cardiovascular diseases, and ocular diseases. Data regarding NETs in ocular diseases remain limited. In physiological conditions, NETs protect the eye from debris and cleave proinflammatory cytokines, including several interleukins. On the other hand, NETs play a role in corneal diseases, such as dry eye disease and ocular graft-versus-host disease, where they promote acinar atrophy and delayed wound healing. Additionally, NET levels positively correlate with increased severity of uveitis. NETs have also been described in the context of diabetic retinopathy. Although increased NET biomarkers are associated with an increased risk of the disease, NETs also assist in the elimination of pathological blood vessels and the regeneration of normal vessels. Targeting NET pathways for the treatment of ocular diseases has shown promising outcomes; however, more studies are still needed in this regard. In this article, we summarize the literature on the protective roles of NETs in the eye. Then, we describe their pathogenetic effects in ocular diseases, including those of the cornea, uvea, and retinal blood vessels. Finally, we describe the therapeutic implications of targeting NETs in such conditions.

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.

Associations between total, free and bioavailable 25-hydroxyvitamin D forms with adiponectin and irisin in maternal-neonatal pairs at birth from Greece.

Background: Apart from the well-established skeletal effects, vitamin D has been explored as a secretagogue influencing various adipokines, including adiponectin and irisin. Recent evidence suggests that specific forms of 25-Hydroxyvitamin D (25(OHD), such as free and bioavailable 25(OH)D, may provide more accurate measurements of vitamin D status. The relationship between vitamin D status and serum irisin and adiponectin concentrations remains largely unexplored, particularly during pregnancy. Methods: We analyzed data from 67 healthy maternal-neonatal pairs from Northern Greece at birth. Biochemical and hormonal tests were conducted on each maternal-neonatal pair. The vitamin D forms were estimated using validated mathematical models. Subsequently, regression analyses were conducted to determine the association between the vitamin D forms and adipokine levels. Results: Bioavailable maternal 25(OH)D was inversely associated with neonatal irisin concentrations [ß=-73.46 (-140.573 to -6.341), p=0.034]. No other associations were observed between maternal vitamin D status and neonatal adipokine concentrations. Conclusion: In conclusion, maternal bioavailable vitamin D concentrations are inversely associated with neonatal serum irisin concentrations, warranting further studies to evaluate the underlying mechanisms for this finding.

Assessing the prevalence of generalized anxiety disorder in a multicultural medical education setting in Saudi Arabia during the COVID-19 pandemic.

Introduction: Mental health among medical students is an area that has been increasingly garnering world-wide attention. Yet, despite this increased attention, research related to anxiety disorders in Saudi Arabia remain limited. This study aims to address this gap by assessing the prevalence of generalized anxiety disorder (GAD) as well as explore its association with students' sociodemographic factors and academic performance among medical students in a Saudi Arabian institute that has a diverse, multicultural student body. Methods: The study takes place in a unique educational environment: a privately funded institute in Riyadh, the capital of Saudi Arabia, with 32% of its student body comprising international students from over 40 countries, during the COVID-19 pandemic. The study deploys the use of a survey that was sent to the students at this institute via their institutional emails. A survey containing 33 items assessing demographics, GAD using GAD-7 questionnaire, stress-relief measures, online learning experience during the pandemic, mental disorders, anxiety associated with the pandemic, two open-ended questions, and one item assessing sleep difficulty. Results: The results of the survey showed that a significant majority of the responders' scores in the GAD-7 assessment were in the range of moderate to severe anxiety. The results also suggest that low cGPA and the first academic years are significantly associated with higher GAD-7 scores. Students found severe time constraints, difficult educational content, and lack of psychological support to be major sources of stress. Furthermore, students suggested providing an in-house psychologist, personalized feedback, and guidance on study tactics as methods to reduce anxiety. Conclusion: These findings, among others, suggest a need for further studies and research in this field to uncover broader patterns and inform targeted mental health support strategies.

Trends in genitourinary cancer mortality in the United States: analysis of the CDC-WONDER database 1999-2020.

Introduction: Sociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States. Methods: Mortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban-rural status, and geographic region using a significance level of p < 0.05. Results: Overall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3-4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West. Discussion: Significant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.

Expression of Claudins in Preneoplastic Conditions of the Gastrointestinal Tract: A Review.

Premalignant lesions of the gastrointestinal tract are a group of disorders which act as the harbinger of malignant tumors. They are the ground-zero of neoplastic transformation, and their identification and management offer patients the best opportunity of blocking the progress of cancer. However, diagnoses of some of these conditions are hard to make, and their clinical importance is difficult to assess. Recent reports indicated that several claudin proteins have altered expressions in many cancers, including esophageal, gastric, colon, liver, and pancreatic cancers. The early identification of the aberrant expression of these proteins could lead to the early diagnosis and management of gastrointestinal tumors. Specifically, claudins -1, -2, -3, -4, and -18 are frequently overexpressed in gastrointestinal preneoplastic lesions. These altered expressions have shown clinical value in several tumors, providing diagnostic and prognostic information. In this article, we review the literature on the aberrant expression of claudins in preneoplastic lesions of the gastrointestinal tract. Additionally, we summarize their diagnostic and prognostic implications.

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.

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.

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.

A Young Patient with Undiagnosed Polycythemia-Paraganglioma Syndrome: A Case Report.

BACKGROUND Erythrocytosis results from primary or secondary causes and is characterized by an increased red blood cell count. Secondary erythrocytosis is a result of an underlying cause outside the bone marrow and is often mediated by erythropoietin. Paragangliomas are rare tumors characterized by increased release of catecholamines with symptoms such as hypertension, hematuria, headache, sweating, and post-micturition syncope. Polycythemia-paraganglioma syndrome (PPS) is exceedingly rare, and reports in the literature are limited. CASE REPORT A 14-year-old female patient presented to our clinic with sweating, palpitations, and palmar erythema. The patient's history was significant for uninvestigated hypertension diagnosed at the age of 9. There was no history of smoking or illicit drug use. Blood investigations revealed an elevated hemoglobin level of 18.5 g/dL and a hematocrit of 57.5%. Whole-genome sequencing found no mutations, excluding polycythemia vera from the differential diagnosis. Computed tomography (CT) revealed 2 lesions compatible with urinary bladder paragangliomas and retroperitoneal lesions, likely representing metastatic lymphadenopathy. Whole-body gallium-68 DOTATATE PET/CT scan demonstrated significant tracer uptake within the necrotic retroperitoneal lymph nodes. However, evaluation of the bladder lesion was limited due to physiological urinary excretion of the tracer. A 24-hour urine collection demonstrated high normetanephrine levels of 24 µmol/L. These findings confirmed the diagnosis of PPS. CONCLUSIONS PPS is largely associated with HIF2A mutations. This article describes the case of a young PPS patient and highlights the importance of considering neoplasms in the differential diagnosis of hypertension in young patients. Further, it is crucial to conduct clinical investigations on young hypertensive patients to exclude underlying causes such as renal diseases, coarctation of the aorta, and neuroendocrine disorders.

Aberrant Expression of Claudins in Head and Neck Carcinomas and Their Prognostic and Therapeutic Value: A Narrative Review.

Head and neck carcinomas have been associated with poor prognosis. Recent studies have highlighted the role of claudins' expression in tumors throughout the body, and their prognostic and therapeutic role. Understanding the role of claudins and how their expression affects the progression of carcinomas in the head and neck region may allow for advances in the prognosis and management of this type of cancer. Several studies have highlighted the aberrant expression of the proteins in carcinomas in this region. Specifically, the overexpression of claudin-1 and downregulation of claudins-4, -7, and -17 have been linked with poor survival in oral squamous cell carcinoma patients. In laryngeal squamous cell carcinoma, increased levels of claudins-1 and reduced levels of claudins-3, -8, and -11 have been linked with poor outcomes. Targeting these proteins has shown promising outcomes as therapeutic in preclinical studies. However, studies remain extremely limited in nasal and hypopharyngeal carcinomas. In this review, we survey the available literature describing the aberrant expression of various claudins in carcinomas in this region, while highlighting their potential prognostic and therapeutic value. Then, we describe some molecular mechanisms involved in the aberrant expression of claudins and how they can be utilized as therapeutic targets.

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.

Gemcitabine-Induced Myositis in a Luminal B Breast Cancer patient: A Case Report.

Human epidermal growth factor receptor-positive breast cancer is an aggressive cancer which represents approximately a quarter of all breast cancers worldwide. Recent advances have led to the development of targeted therapies, such as trastuzumab (H), which have significantly improved prognosis. Such therapies are currently used alongside other chemotherapeutic agents, such as paclitaxel (P) and gemcitabine (G). The most common side effects of PGH combination therapy include thrombocytopenia and anemias. However, there have been no previous reports of myositis resulting from this combination. We report the case of a 54-year-old metastatic breast cancer patient on PGH therapy who developed muscle weakness. The patient was initially treated with trastuzumab, pertuzumab, and paclitaxel. However, pertuzumab was changed to gemcitabine due to severe diarrhea. After the fourth cycle of PGH, the patient presented with muscle weakness and creatine kinase levels of up to 6755 U/L. Magnetic resonance imaging of the femur and pelvis revealed diffuse bilateral myositis, suggesting a diagnosis of gemcitabine-induced myositis. The patient was placed on intravenous fluids and corticosteroids, which resolved her condition. To our knowledge, this is the first report of gemcitabine-induced myositis in a breast cancer patient. Further studies are needed to determine the underlying mechanisms of gemcitabine-induced myositis and develop preventative measures.

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.