Validity and reliability of the Persian version of Recce stigma scale in people with multiple sclerosis and its impact on quality of life.

BACKGROUND: There is often a fear of social stigma experienced by people with multiple sclerosis (pwMS), which negatively impacts the quality of their lives (QoL). Currently, no Persian-validated questionnaire is available to assess this issue in pwMS. This study aimed to assess the validaty and reliability of the Persian version of Reece Stigma Scale Multiple Sclerosis (RSS-MS) questionnaire for pwMS. METHOD: This cross-sectional was conducted between January and February 2023 in Isfahan, Iran. The demographic and clinical information and the RSS-MS and Multiple Sclerosis Impact Scale-29 (MSIS-29) questionnaires were recorded from pwMS. The content validity index (CVI) and content validity ratio (CVR) have been used to evaluate validity. To identify the factors supporting the MS-related stigma, an exploratory factor analysis (EFA) was conducted. RESULTS: The present study recruited 194 pwMS. Based on factor analysis, only two factors had eigenvalues ≥ 1.0 and exhibited high internal consistency. The Cronbach's α coefficient for internal consistency of the RSS-MS scale was 0.822. More evidence for the construct validity suggested that having higher levels of stigma is significantly correlated with psychological (r = 0.468, p-value < 0.001) and physical dimensions (r = 0.585, p-value < 0.001) of MSIS-29. Expanded Disability Status Scale, disease duration, and treatment duration did not show a significant correlation with stigma (p-value > 0.05). CONCLUSION: This study indicated that the modified version of the RSS-MS scale in the Persian language showed acceptable validity and reliability for evaluating the stigma among Persian pwMS. Furthermore, this study emphasizes the cruciality of monitoring and addressing stigma among pwMS, as it can potentially enhance medical, psychological, physical, and QoL outcomes.

Helicobacter pylori infection and risk of multiple sclerosis: an updated meta-analysis.

Numerous studies have proposed that Helicobacter pylori infection may possess a protective effect in terms of future risk of multiple sclerosis (MS), however is poorly evidenced. We performed a systematic review and meta-analysis to obtain the pooled results regarding the prevalence of H. pylori infection in persons with multiple sclerosis (pwMS) and healthy controls. A comprehensive database search was performed in PubMed, Embase, and medRxiv for all relevant literature published from the inception of the databases until the August 1, 2022. The retrieved articles were first screened by title and abstract, followed by full-text screening based on the pre-established eligibility criteria. The risk of bias was assessed using the ROBINS-I tool. Data on the seroprevalence of H. pylori in pwMS and healthy controls was extracted, and a meta-analysis was performed in Review Manager Version 5.4.1. Sub-group analysis was performed in accordance with the geographical distribution (Eastern and Western countries) and the method of detection of H. pylori infection enzyme-linked-immunoassay (ELISA), Immunofluorescence, Immunochromatography). Furthermore, sensitivity analyses and publication bias were determined. The preliminary database search retrieved a total of 822 studies. Seventeen case-control studies with a total of 2721 pwMS and 2245 controls were included as a final sample size for the meta-analysis. The overall risk of bias was moderate. Overall, the rate of H. pylori infection in pwMS was not significantly different than in healthy controls (OR: 0.79 (95% CI = 0.58-1.08); I2 = 79%, p = 0.14). Subgroup analysis revealed that the rate of H. pylori infection among PwMS was not significant in both Eastern and Western countries (OR: 0.75 (95% CI = 0.52-1.08); I2 = 81%, p = 0.12). In contrast, data revealed that the prevalence of H. pylori infection in pwMS was significantly lower than that of control based on studies utilizing ELISA assays detection (OR: 0.71 (95% CI = 0.50-1.00); I2 = 81%, p = 0.05), while no significant difference was seen on studies using other assays than ELISA (OR: 1.19 (95% CI = 0.81-1.77); I2 = 0%, p = 0.38). Our findings of statistically indifferent prevalence of H. pylori infection as compared between pwMS and healthy controls suggested the absence of protective effect for risk of MS following H. pylori infection.

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.

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.

Endothelium, Platelets, and Coagulation Factors as the Three Vital Components for Diagnosing Bleeding Disorders: A Simplified Perspective with Clinical Relevance.

Bleeding disorders are a major group of hematological disorders, which are highly prevalent in the world. Excessive bleeding can result in serious consequences including hypoperfusion and cardiac arrest. The body has its selfmechanism to control excessive bleeding which is termed hemostasis. Hemostasis is achieved in two major steps, the formation of the primary and secondary hemostatic plugs. Endothelium, platelets, and coagulation factors are three components involved in hemostasis. Endothelium and platelets have a major role in forming the primary hemostatic plug. Consequently, the first step in investigating a bleeding disorder is platelet count. Despite normal platelet count, abnormality in the primary hemostatic plug may arise due to functional defects of the platelets including adhesion, activation, and aggregation. Von Willebrand disease (VWD) is an endothelial defect and the most prevalent inherited defect in coagulation. Abnormalities in the secondary hemostatic plug are largely due to coagulation factor deficiencies, and, to a lesser extent, the presence of inhibitors. Techniques involving viscoelastics have been aiding in rapid diagnosis and are useful in point-of-care testing. This article discusses the investigation of bleeding disorders from the perspective of the endothelium, platelet, and coagulation factor physiology. These three components should be properly investigated to achieve the definitive diagnosis of bleeding disorders.

Hantavirus Infection with Renal Failure and Proteinuria, Colorado, USA, 2019.

In North America, hantaviruses commonly cause hantavirus pulmonary syndrome (HPS). Clinical descriptions of hantavirus-associated renal disease in the Americas are scarce. Herein, we discuss the case of a 61-year-old man whose predominant manifestations were acute kidney injury and proteinuria. Clinical recognition of renal signs in hantavirus infections can reduce risk for death.

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.

Insights into the interplay between Epstein-Barr virus (EBV) and multiple sclerosis (MS): A state-of-the-art review and implications for vaccine development.

Background and Aims: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). MS results from an inflammatory process leading to the loss of neural tissue and increased disability over time. The role of Epstein Barr Virus (EBV), as one of the most common global viruses, in MS development has been the subject of several studies. However, many related questions are still unanswered. This study aimed to review the connection between MS and EBV and provide a quick outline of MS prevention using EBV vaccination. Methods: For this narrative review, an extensive literature search using specific terms was conducted across online databases, including PubMed/Medline, Scopus, Web of Science, and Google Scholar, to identify pertinent studies. Results: Several studies proved that almost 100% of people with MS showed a history of EBV infection, and there was an association between high titers of EBV antibodies and an increased risk of MS development. Various hypotheses are proposed for how EBV may contribute to MS directly and indirectly: (1) Molecular Mimicry, (2) Mistaken Self, (3) Bystander Damage, and (4) Autoreactive B cells infected with EBV. Conclusion: Given the infectious nature of EBV and its ability to elude the immune system, EBV emerges as a strong candidate for being the underlying cause of MS. The development of an EBV vaccine holds promise for preventing MS; however, overcoming the challenge of creating a safe and efficacious vaccine presents a significant obstacle.

Risk of dementia following herpes zoster infection among patients undertreatment versus those not: A systematic review and meta-analysis.

Background and Aims: According to the previous studies, herpes zoster (HZ) has been associated with cognitive function and dementia. There is a hypothesis claiming that dementia risk may be reduced by receiving the antiviral treatment for HZ. The purpose of this systematic review and meta-analysis was to shed light on the association between dementia and HZ in individuals receiving and not receiving antiviral medications. Methods: Studies investigating the association between HZ and dementia were identified through a systematic search in PubMed/MEDLINE, Scopus, Embase, Google Scholar, and Cochrane Library databases from January, 2000 to April, 2022. Data on the risk of dementia in HZ-infected patients under and not under antiviral treatment were extracted. The meta-analysis was conducted using a random-effects model. The modified ROBIN-I tool was used to evaluate the risk of bias assessment. By utilizing the funnel plots, publication bias was investigated. Results: Six cohort studies on 538,531 patients were included. The overall risk of bias assessment was moderate. According to evidence-based cohort studies, there was a significant direct association between HZ and risk of dementia in patients with HZ, who did not receive antiviral treatments (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.03 to 1.28, p = 0.01). On the other hand, there was an inverse relationship between HZ and risk of dementia among patients with HZ, who received antiviral treatments (HR: 0.68, 95% CI: 0.59 to 0.77, p < 0.001). Conclusions: This study demonstrated that antiviral therapies may significantly lower the risk of dementia in patients with HZ. This study also confirmed that patients with HZ, without receiving antiviral therapies, may have an increased risk of developing dementia. Further longitudinal research is warranted in this area.

Exploring the Intricate Interplay Between Obesity and Atrial Fibrillation: Mechanisms, Management, and Clinical Implications.

Atrial fibrillation (AF) stands as a prevalent and escalating cardiac arrhythmia in the United States, with obesity emerging as a prominent modifiable risk factor. This article explores the intricate relationship between obesity and AF, delving into the multifaceted pathophysiological mechanisms linking the 2 conditions. Various factors, such as autonomic dysfunction, left atrial stretch, inflammation, and hormonal imbalances, contribute to the initiation and perpetuation of AF in obese individuals. The Atrial Fibrillation Better Care pathway, emphasizing lifestyle modifications and weight loss strategies, emerges as a practical guideline for managing AF in obesity. This comprehensive review underscores the critical role of obesity as a significant modifiable risk factor for AF, urging a proactive approach to its management. Implementing the Atrial Fibrillation Better Care approach, focusing on encouraging physical activity, promoting healthy dietary habits, and raising awareness about the risks associated with obesity prove essential in preventing and mitigating the burden of AF in the obese population.

Does Caplacizumab for the management of thrombotic thrombocytopenic purpura increase the risk of relapse, exacerbation, and bleeding? An updated systematic review and meta-analysis based on revised criteria by the International Working Group for thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening condition marked by abnormal blood clotting and organ damage. Caplacizumab is a potential treatment for the TTP management. This systematic review and meta-analysis aimed to assess Caplacizumab's effectiveness and safety in the TTP management. A comprehensive database search identified nine studies, including randomized controlled trials and observational studies. Primary outcomes included TTP exacerbation, relapse, and major bleeding. Major bleeding risk was evaluated using updated definitions recommended by the International TTP Working Group in 2021. Revised criteria proposed by the IWG for TTP recurrence were employed for a comprehensive assessment of Caplacizumab's impact on relapse and exacerbation. Analysis revealed Caplacizumab significantly reduced all-cause mortality in TTP patients. Some studies raised concerns about bleeding risk, but overall, it did not significantly differ from standard treatment. Likewise, there was no significant difference in TTP relapse rates between Caplacizumab and standard care. This study supports Caplacizumab as a potential adjunct therapy for TTP. However, careful consideration of its advantages and risks is crucial in clinical practice. Further research is needed to address concerns related to adverse effects like bleeding risk and relapse rates associated with Caplacizumab in the TTP management. The findings emphasize the importance of weighing potential benefits and risks when considering Caplacizumab as an adjunct therapy for TTP.

Safety and efficacy of danazol in immune thrombocytopenia: a systematic review.

Background: The treatment landscape for relapsed or refractory immune thrombocytopenia (ITP) after corticosteroids is complex. Objectives: We aimed to assess the efficacy of danazol in treating ITP and evaluate the safety and adverse events following its administration. Methods: We searched the databases PubMed, EMBASE, and ClinicalTrials.gov for all published studies assessing danazol's efficacy and safety in treating ITP. The retrieved studies were screened by title and abstract, followed by full-text screening based on the eligibility requirements. The quality assessment was performed using a set of questionnaires. The data were extracted on the descriptive characteristics of the studies and participants, drug dosage, efficacy measures, and adverse effects, and the data were synthesized. Results: A total of 17 studies consisting of 901 participants were included. The overall response rate is around 61% in this analysis. Among the participants, 315 (34.9%) were men. The age of participants ranged from 16 to 86 years. Danazol combined with other pharmacologic interventions, including all-trans-retinoic acid or glucocorticoids, generated better results. The most common side effects appear to be liver injury and elevation of liver enzymes, weight gain, oligomenorrhea, amenorrhea, and myalgia. Conclusion: Danazol at low-to-medium doses was well tolerated and succeeded in improving ITP. Danazol therapy may be helpful in the treatment of chronic ITP that is corticosteroid refractory and when corticosteroids or splenectomy (or both) is contraindicated. Danazol can be considered for further research and development in treating primary immune thrombocytopenia.

Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.

INTRODUCTION: Previous studies have reported a decreased risk of dementia with herpes zoster vaccination. Given this background, this systematic review and meta-analysis aimed to investigate the association between herpes zoster vaccination and the risk of dementia. METHODS: We searched five databases until November 2023 for case-control, cross-sectional, or cohort studies investigating the association of herpes zoster vaccination and dementia. Odds ratios and 95% confidence intervals (95% CIs) were pooled in the meta-analysis. Meta-regression, subgroup, and sensitivity analysis were also conducted. RESULTS: We evaluated a total of five studies (one cross-sectional, one case-control, and four cohort studies) that included a total number of 103,615 patients who were vaccinated with herpes zoster vaccine. All the studies were of high quality, ranging from 7 to 9. Due to the high heterogeneity (I2 = 100%, p < .00001) observed in our study, a random effect model was used for the analysis. The pooled odds ratio was 0.84 (95% CI: 0.50, 1.43), p (overall effect) = .53), indicating that herpes zoster vaccination reduces the risk of dementia. CONCLUSION: Herpes zoster vaccination is associated with a reduction of the risk of dementia. More epidemiological studies are needed to confirm the association.

Cardiac complications (arrhythmias and heart failure) in patients with ischemic stroke: A meta-analysis.

BACKGROUND: In patients with ischemic stroke (pwIS), cardiac complications have been observed in observational studies. We conducted a systematic review and meta-analysis to investigate the arrhythmias and heart failure in pwIS. METHODS: Up until September 2023, we searched for case-control, cross-sectional, or cohort studies in 4 databases. For case-control/cross-sectional studies, odds ratios (OR) were determined using a random-effects model meta-analysis, while hazard ratios (HR) were calculated for cohort studies, and 95% confidence intervals (CIs) were pooled in the meta-analysis. RESULTS: In the meta-analysis, we incorporated 5 studies: 2 cohort studies, 2 case-control studies, and 1 cross-sectional study. In all, 81,181 controls and 25,544 pwIS were included in this investigation. The combined OR for case-control studies of arrhythmias was estimated to be 1.86 (95% CI: 0.70-4.94, P = .21), HR for cohort studies of arrhythmias to be 4.2 (95% CI: 1.49-12.01, P < .05), and for cohort studies of heart failure to be 2.9 (95% CI: 2.65-3.18, P < .05), suggesting that pwIS may be more likely to experience cardiac complications. CONCLUSION: Our results revealed that there is a comparatively higher risk of cardiac complications in pwIS; however, more research is needed to evaluate the risk of cardiac complications in pwIS.

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.

Biomarker role of maternal soluble human leukocyte antigen G in pre-eclampsia: A meta-analysis.

INTRODUCTION: Human leukocyte antigen-G (HLA-G) is a non-classical class I HLA molecule shown to regulate the immunomodulation of maternal immune cells to prevent fetal tissue destruction. Low levels of freely circulating maternal soluble HLA-G (sHLA-G) have been observed in pre-eclampsia, however, no pooled evidence exists. This meta-analysis aimed to generate pooled findings on the association of sHLA-G levels with pre-eclampsia and is the first study to perform a trimester-wise comparison of the levels of sHLA-G in preeclamptic cases and normal pregnant controls. METHODS: The databases PubMed, Emba, Web of Science, and Google Scholar through May 31, 2023. Preeclamptic women were defined as cases and normal pregnancies as controls. Data on the level of sHLA-G in cases and controls was extracted and subjected to a meta-analysis using a random-effects model. The pooled effect was expressed in terms of standardized mean difference (SMD). Sensitivity analysis was performed to investigate the effect of the exclusion of each study on the pooled results. Publication bias was assessed statistically. RESULTS: Nine studies with altogether 567 PE cases and 1132 normal pregnancy controls were included in the meta-analysis. The first and third trimester levels of sHLA-G in PE cases were significantly lower than that of normal pregnant controls: (SMD: -0.84 [-1.29; -0.38]; p = .003; I2 = 54%) and (SMD: -0.39 [-0.71; -0.06]; p = .02; I2 = 79%) respectively. Sensitivity analysis revealed significant fluctuations in the pooled findings when few studies were excluded, raising questions on the consistency of results among studies. CONCLUSION: Although we found that first and third-trimester sHLA-G levels in pre-eclampsia are significantly lower, taking into consideration the inconsistent results from the sensitivity analysis, our findings advocate the demand for more studies with larger sample sizes to generate solid ground pooled evidence on the predictive role of sHLA-G in pre-eclampsia.

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.

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.