Cardiovascular Implications of Gynecological Disorders: Bridging the Gap Between Gynecology and Cardiology.

Gynecological disorders such as endometriosis, polycystic ovary syndrome, and gynecological cancers are increasingly recognized as potential risk factors for cardiovascular disease (CVD). Endometriosis, a chronic inflammatory condition, exhibits shared pathogenic mechanisms with CVD, including endothelial dysfunction and an atherogenic lipid profile. Emerging evidence suggests a link between endometriosis and an elevated risk of cardiovascular events such as myocardial infarction, ischemic heart disease, and hypertension. Polycystic ovary syndrome, characterized by hormonal imbalances and metabolic derangements, is associated with an increased risk of hypertension, myocardial infarction, and structural cardiac abnormalities, even after controlling for obesity. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, are also associated with an increased burden of cardiovascular comorbidities and mortality. Cancer treatments, including chemotherapy and radiation therapy, can further contribute to cardiovascular toxicity. Understanding the interplay between gynecological disorders and CVD is crucial for identifying high-risk individuals, implementing preventive strategies, and providing comprehensive care. A multidisciplinary approach involving gynecologists, cardiologists, and other specialists is essential for optimizing the management of these complex conditions and improving overall patient outcomes.

Neurological efficacy and safety of mesenchymal stem cells (MSCs) therapy in people with multiple sclerosis (pwMS): An updated systematic review and meta-analysis.

BACKGROUND: Current therapeutic strategies for multiple sclerosis (MS) aim to suppress the immune response and reduce relapse rates. As alternative treatments, mesenchymal stem cells (MSCs) are being explored. MSCs show promise in repairing nerve tissue and reducing autoimmune responses in people with MS (pwMS). OBJECTIVE: This review delves into the literature on the efficacy and safety of MSC therapy for pwMS. METHODS: A comprehensive search strategy was employed to identify relevant articles from five databases until January 2024. The inclusion criteria encompassed interventional studies. Efficacy and safety data concerning MSC therapy in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) groups were extracted and analyzed. RESULTS: A comprehensive analysis encompassing 30 studies revealed that individuals who underwent intrathecal (IT) protocol-based transplantation of MSCs experienced a noteworthy improvement in their expanded disability status scale (EDSS) compared to the placebo group. Weighted mean difference (WMD) was -0.28; 95 % CI -0.53 to -0.03, I2 = 0 %, p-value = 0.028); however, the intravenous (IV) group did not show significant changes in EDSS scores. The annualized relapse rate (ARR) did not significantly decrease among pwMS (WMD = -0.34; 95 % CI -1.05 to 0.38, I2 = 98 %, p-value = 0.357). Favorable results were observed in magnetic resonance imaging (MRI), with only 19.11 % of pwMS showing contrast-enhanced lesions (CEL) in the short term and no long-term MRI activity. The most common complications in both short-term and long-term follow-ups were infection, back pain, and gastrointestinal symptoms. CONCLUSIONS: The study highlights the safety potential of MSC therapy for pwMS. While MRI-based neural regeneration shows significant treatment potential, the effectiveness of MSC therapy remains uncertain due to study limitations and ineffective outcome measures. Further research is needed to establish efficacy and optimize evaluation methods for MSC therapy on pwMS.

Intravenous Iron Therapy in Heart Failure Patients With Iron Deficiency: Benefits, Safety, and Guidelines.

Iron deficiency is a common comorbidity in heart failure (HF) patients, with up to 50% of ambulatory patients with HF affected. Intravenous (IV) iron therapy has emerged as a promising treatment approach for HF patients with concomitant iron deficiency. This review summarizes the current literature on the use of IV iron therapy in HF patients, focusing on its benefits in improving quality of life, and exercise capacity, and reducing HF hospitalizations. However, concerns about the long-term cardiotoxic effects of IV iron, including the risk of iron overload, are also addressed. The review highlights the importance of a balanced approach to iron replacement and provides an overview of the 2022 American College of Cardiology/American Heart Association guidelines, which recommend IV iron therapy for eligible patients. Additionally, the review underscores the need for further research, particularly in HF patients with preserved ejection fraction and acute HF. While IV iron therapy shows promise, questions about its safety and specific formulations remain to be fully addressed.

Oral SERD, a Novel Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer.

Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease. ESR1 mutations have been identified as a common mechanism of endocrine therapy resistance in ER+ breast cancer. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has shown some activity against ESR1 mutant tumors. However, due to its poor bioavailability and need for intramuscular injection, it may not be the optimal therapy for patients. Second-generation SERDs were developed to overcome these limitations. These newer drugs have improved oral bioavailability and pharmacokinetics, making them more convenient and effective for patients. Several oral SERDs are now in phase III trials for early and advanced ER+ breast cancer. This review summarizes the background of oral SERD development, the current status, and future perspectives.

Opportunities and Challenges for a Histology-Agnostic Utilization of Trastuzumab Deruxtecan.

PURPOSE OF REVIEW: This review delves into the prospects and challenges offered by a potential pan-histological utilization of trastuzumab deruxtecan (T-DXd) in patients with advanced solid tumors. RECENT FINDINGS: The HER2-targeted antibody-drug conjugate (ADC) T-DXd has shown broad activity across cancer types, with current indications for patients with biomarker-selected breast, gastric, and non-small-cell lung cancer and relevant activity observed in multiple histology-specific trials. Moreover, two recently reported phase 2 trials (DESTINY-Pantumor02 and HERALD) have supported the potential for a pan-cancer utilization of this ADC in patients with advanced cancers expressing HER2 or with HER2 amplifications. By improving the delivery of cytotoxic chemotherapy, ADCs have allowed for meaningful clinical advantages in broad populations of cancer patients, often leading to survival advantages over conventional chemotherapy. Notably, the broad spectrum of activity of certain ADCs has led to the hypothesis of a histology-agnostic utilization based on detecting specific biomarkers, similar to what is already established for certain targeted treatments and immunotherapy. To date, T-DXd has shown the broadest activity across cancer types, with current approvals in breast, gastric, and lung cancer, and relevant antitumor activity observed in a multiplicity of additional cancer types. The optimization of the drug dose, identification of predictive biomarkers, and clarification of mechanisms of resistance will be critical steps in view of a pan-histological expansion in the use of T-DXd.

Anterior Cruciate Ligament Tear Using Magnetic Resonance Imaging among Patients Undergoing Arthroscopy in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Magnetic Resonance Imaging is the preferred imaging modality in patients having anterior cruciate ligament tears. The aim of this study was to find out the prevalence of anterior cruciate ligament tears using magnetic resonance imaging among patients undergoing arthroscopy in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted in the Department of Orthopaedics and Traumatology of a tertiary care centre. Data from 17 November 2017 to 17 October 2022 were collected between 26 December 2022 and 30 December 2022 from the hospital records. Ethical approval was obtained from Institutinal Review Committee of the same institute (Reference number: 233/22). All patients with a knee injury who received arthroscopy were included in the study. Magnetic resonance imaging reports, arthroscopic findings and relevant data of each case were retrieved from the medical case records of patients. Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results: Among patients with arthroscopy confirmed anterior cruciate ligament tear, 138 (91.39%) (86.92 to 95.86, 95% Confidence Interval) had anterior cruciate ligament tear diagnosed with magnetic resonance imaging. The mean age of the patients who had anterior cruciate ligament tear in the magnetic resonance imaging was 32.35±11.31 years. Out of them, 87 (63%) were males and 51 (37%) were females. The mean duration of the injury was 11.60±18.47 months. Conclusions: The prevalence of anterior cruciate ligament tear using magnetic resonance imaging among patients undergoing arthroscopy in tertiary care centres was similar when compared to other similar studies when conducted in similar settings. Keywords: anterior cruciate ligament tears; arthroscopy; cross-sectional studies; MRI.

Vascular therapy for Duchenne muscular dystrophy (DMD).

Duchenne muscular dystrophy (DMD) is a progressive disease characterized by the wasting of the muscles that eventually lead to difficulty moving and, ultimately, premature death from heart and respiratory complications. DMD deficiency is caused by mutations in the gene encoding dystrophin, which prevents skeletal muscle, cardiac muscle, and other cells from producing the functional protein. Located on the cytoplasmic face of the plasma membrane of muscle fibers, dystrophin serves as a component of the dystrophin glycoprotein complex (DGC), mechanically reinforces the sarcolemma, and stabilizes the DGC, preventing it from contraction-mediated muscle degradation. In DMD muscle, dystrophin deficiency leads to progressive fibrosis, myofiber damage, chronic inflammation, and dysfunction of the mitochondria and muscle stem cells. Currently, DMD is incurable, and treatment involves the administration of glucocorticoids in order to delay disease progression. In the presence of developmental delay, proximal weakness, and elevated serum creatine kinase levels, a definitive diagnosis can usually be made after an extensive review of the patient's history and physical examination, as well as confirmation through muscle biopsy or genetic testing. Current standards of care include the use of corticosteroids to prolong ambulation and delay the onset of secondary complications, including respiratory muscle and cardiac functions. However, different studies have been carried out to show the relationship between vascular density and impaired angiogenesis in the pathogenesis of DMD. Several recent studies on DMD management are vascular targeted and focused on ischemia as a culprit for the pathogenesis of DMD. This review critically discusses approaches-such as modulation of nitric oxide (NO) or vascular endothelial growth factor (VEGF)-related pathways-to attenuate the dystrophic phenotype and enhance angiogenesis.

Pulmonary artery sarcoma masquerading as pulmonary embolism: an under-recognised entity.

Pulmonary artery sarcoma is a rare disease with only a handful of cases reported. It is histologically classified as leiomyosarcoma, spindle cell sarcoma, fibrous histiocytoma or undifferentiated sarcoma. The disease is mostly misdiagnosed as pulmonary thromboembolism and carries a grim prognosis with an average survival of only a few months. Misdiagnosis often results in patients being treated inappropriately and diagnosed in later stages of the disease. This delay in diagnosis can be associated with significant mortality in the setting of an already poor prognosis. Early aggressive surgery targeting complete surgical resection is the standard treatment. Chemotherapy and radiation therapy have been tried with variable outcomes. Given the aggressive nature of pulmonary artery sarcoma, regular post-surgery follow-up is indicated.

Teenager with acute psychosis due to non-paraneoplastic anti-N-methyl-d-aspartate receptor encephalitis with a successful recovery: A case report.

Introduction: Anti NMDAR encephalitis is a neuropsychiatric syndromic disease caused by an immunological response. Acute behavioral changes, psychosis, and catatonia are common clinical manifestations, are seizures, amnesia, speech difficulties, dyskinesia, and autonomic dysregulation. Case presentation: We discuss the case of a 14-year-old girl who had psychotic symptoms and tested positive for anti-NMDAR antibodies. Discussion: Patients present with psychiatric symptoms such as delusions, hallucinations, agitation, changes in speech mania, disorganized thinking, catatonia, insomnia, and often seizures. Anti-NMDAR encephalitis should be suspected in teenage patient with acute psychotic symptoms and seizure episodes. A multidisciplinary treatment strategy is required. Conclusion: The delayed treatment can lead to complications and delayed recovery complicating the disease process so multidisciplinary approach of treatment is necessary.

Cardiovascular disease risk factors distribution and clustering across different geographic levels in Nepal.

BACKGROUND: In an effort to reduce the burgeoning problem of cardiovascular diseases (CVD), it is imperative to understand the variation of risk factors across different geographic regions. This study aims to shed light on examining the leading risk factors of CVD and it's clustering across Nepal. METHODS: Data from a nationally representative survey were analyzed to estimate the distribution of four major risk factors (high blood pressure, overweight, obesity, and smoking) of cardiovascular diseases. Similarly, this study also assessed the intra-cluster correlation coefficients (ICCs) of CVD risk factors at the household, community (urban/rural), district, and province level. RESULTS: This study included 14 418 adult population with age of 15 years and above of which 41.7% were male and 58.3% were female. Higher prevalence of all four CVD risk factors was found in the richest quintile, people living in hilly region, most noticeably among residents of metropolitan city and in Gandaki, Bagmati, and Province 1. The ICC decreased as the socio-geographic clustering units decreased in size from province, district, and household level clustering. The ICC was highest at province level for "province 1" for raised blood pressure than other provinces. CONCLUSIONS: Risk factors of CVD in Nepal are concentrated prominent in highly urbanized areas and ICC is low as the level of geography decreased from province, district, and household. The findings can be applied in directing prevention activities at different levels to mitigate the higher burden of risk factors of CVD in Nepal.

Undiagnosed Case of Klippel-Trenaunnay Syndrome Presenting as Extensive Heterotrophic Ossification and Flexion Deformity of Right Lower Limb Requiring Amputation : A Case Report.

Klippel-Trenaunnay Syndrome is a rare disease characterized by a clinical triad of capillary malformation, soft tissue and bony hypertrophy, and atypical varicosity. This syndrome ranges from asymptomatic disease to life-threatening bleeding, embolism, and deformities. Management includes early diagnosis, prevention, and treatment of complications. We present a case of a 43-year-old male presenting with pain, swelling and deformity of the right leg for 30 years. On examination, diffusely enlarged tender right limb with several dark patchy discolorations, multiple tortuous vessels were found. Right leg X-ray showed heterotrophic ossification and distortion of ankle joint. Due to chronic severe pain, recurrent infection, contracture and flexion deformity of right leg, the patient underwent above knee amputation. This case focuses on the variable presentation and multiple problems faced by patients with Klippel-Trenaununay Syndrome as they get diagnosed late and shows the importance of high index of suspicion for early diagnosis and prevention of complications.