Pub Date : 2025-11-01DOI: 10.1016/j.disamonth.2025.102013
Nalla Jaipal Reddy MD , Neo Zhong Yi Benjamin MBBS , Pannala Harsha Reddy MBBS , Andy Thai MD , Hamza Muntasir Al Rawashdeh MBBS , Chiranjeevee Saravanan MBBS , Priyadarshi Prajjwal MBBS , Yogesh Tekuru MBBS, MPH , Pugazhendi Inban MD , Jobby John MBBS
Background
The ketogenic diet, known for its anti-inflammatory and neuroprotective effects, has gained attention as a potential therapeutic approach for modulating inflammation and improving clinical outcomes in Multiple Sclerosis patients.
Objectives
To systematically evaluate and synthesize clinical and preclinical evidence on the ketogenic diet's role in modulating inflammation in Multiple Sclerosis patients and quantitatively assess its effects on inflammation.
Results
The meta-analysis revealed significant effects of the KD on inflammatory markers in MS patients. At 3 months, Leptin levels decreased significantly (mean difference: -2.63 ng/mL, 95 % CI: -3.03 to -2.24, p < 0.00001), and Adiponectin levels increased (mean difference: -1.78 mcg/mL, 95 % CI: -2.26 to -1.29, p < 0.00001). At 6 months, Leptin again decreased (mean difference: -2.18 ng/mL, 95 % CI: -2.92 to -1.43, p < 0.00001), and Adiponectin increased (mean difference: -1.65 mcg/mL, 95 % CI: -1.93 to -1.36, p < 0.00001). However, Neurofilament Light Chain (NfL) showed no significant change (mean difference: -0.10, 95 % CI: -0.61 to 0.40, p > 0.05), suggesting stable neurodegeneration biomarkers. The overall results suggest that the ketogenic diet reduces Leptin, increases Adiponectin, but does not worsen neurodegeneration, highlighting its anti-inflammatory effects.
Conclusion
The ketogenic diet shows promise in improving inflammation, fatigue, depression, and quality of life in MS patients. While neurodegenerative biomarkers like NfL remain stable, deeper ketosis may enhance neuroprotection. Further long-term studies are needed to confirm these effects.
{"title":"The role and benefits of ketogenic diet in modulating inflammation in multiple sclerosis: A systematic review and meta-analysis","authors":"Nalla Jaipal Reddy MD , Neo Zhong Yi Benjamin MBBS , Pannala Harsha Reddy MBBS , Andy Thai MD , Hamza Muntasir Al Rawashdeh MBBS , Chiranjeevee Saravanan MBBS , Priyadarshi Prajjwal MBBS , Yogesh Tekuru MBBS, MPH , Pugazhendi Inban MD , Jobby John MBBS","doi":"10.1016/j.disamonth.2025.102013","DOIUrl":"10.1016/j.disamonth.2025.102013","url":null,"abstract":"<div><h3>Background</h3><div>The ketogenic diet, known for its anti-inflammatory and neuroprotective effects, has gained attention as a potential therapeutic approach for modulating inflammation and improving clinical outcomes in Multiple Sclerosis patients.</div></div><div><h3>Objectives</h3><div>To systematically evaluate and synthesize clinical and preclinical evidence on the ketogenic diet's role in modulating inflammation in Multiple Sclerosis patients and quantitatively assess its effects on inflammation.</div></div><div><h3>Results</h3><div>The meta-analysis revealed significant effects of the KD on inflammatory markers in MS patients. At 3 months, Leptin levels decreased significantly (mean difference: -2.63 ng/mL, 95 % CI: -3.03 to -2.24, <em>p</em> < 0.00001), and Adiponectin levels increased (mean difference: -1.78 mcg/mL, 95 % CI: -2.26 to -1.29, <em>p</em> < 0.00001). At 6 months, Leptin again decreased (mean difference: -2.18 ng/mL, 95 % CI: -2.92 to -1.43, <em>p</em> < 0.00001), and Adiponectin increased (mean difference: -1.65 mcg/mL, 95 % CI: -1.93 to -1.36, <em>p</em> < 0.00001). However, Neurofilament Light Chain (NfL) showed no significant change (mean difference: -0.10, 95 % CI: -0.61 to 0.40, <em>p</em> > 0.05), suggesting stable neurodegeneration biomarkers. The overall results suggest that the ketogenic diet reduces Leptin, increases Adiponectin, but does not worsen neurodegeneration, highlighting its anti-inflammatory effects.</div></div><div><h3>Conclusion</h3><div>The ketogenic diet shows promise in improving inflammation, fatigue, depression, and quality of life in MS patients. While neurodegenerative biomarkers like NfL remain stable, deeper ketosis may enhance neuroprotection. Further long-term studies are needed to confirm these effects.</div></div>","PeriodicalId":51017,"journal":{"name":"Dm Disease-A-Month","volume":"71 11","pages":"Article 102013"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Multiple sclerosis (MS) is a chronic neurodegenerative and autoimmune disease characterized by CNS inflammation and demyelination. Although current disease-modifying therapies (DMTs) can reduce peripheral immune responses, their impact on CNS-compartmentalized inflammation remains limited. Bruton Tyrosine Kinase inhibitors (BTKis) have emerged as promising oral agents targeting both B cells and microglia.
Objective
To evaluate the safety profiles and effectiveness of two BTK inhibitors- Tolebrutinib and Evobrutinib in the management of relapsing multiple sclerosis.
Methods
A literature search was conducted using PubMed, Embase, and Scopus for randomized controlled trials published between 2020 and 2024. Studies comparing Evobrutinib and Tolebrutinib in MS patients were screened and evaluated based on predetermined inclusion and exclusion criteria. Four relevant RCTs were matched and examined in more detail.
Results
On MRI, both BTK inhibitors showed decreases in gadolinium-enhancing lesions; Tolebrutinib demonstrated dose-dependent efficacy in reducing new Gd-enhancing lesions and T2 lesion counts, with optimal effects at 60 mg daily. Evobrutinib showed dose-dependent decreases in serum neurofilament light (NfL) levels and relapse rates, with twice-daily dosing providing greater BTK inhibition and clinical benefit. Nasopharyngitis, temporary increases in liver enzymes, and mild gastrointestinal symptoms were among the frequent side effects for both agents. The included studies did not report any direct clinical comparisons of CNS penetration or microglial modulation.
Conclusion
With good safety and efficacy profiles in treating relapsing multiple sclerosis, both of the BTKis (Evobrutinib and Tolebrutinib) show promise. Both have promise as oral treatments of the future, but Tolebrutinib might have better effects on the central nervous system. To confirm long-term results and determine their role in progressive MS, more phase III trials are necessary.
{"title":"Multiple sclerosis updates and the safety and efficacy of Bruton tyrosine kinase inhibitors in it: A systematic review","authors":"Priyadarshi Prajjwal MBBS , Prachi Vikrambhai Patel MBBS , Zeel Vishnubhai Patel MBBS , Pugazhendi Inban MD , Divyakshi Patel MBBS , Priya Mahato MBBS , Laiba Shamim MBBS , Nathan Joseph Silva Godinho MD , Yogesh Tekuru MBBS, MPH","doi":"10.1016/j.disamonth.2025.102012","DOIUrl":"10.1016/j.disamonth.2025.102012","url":null,"abstract":"<div><h3>Background</h3><div>Multiple sclerosis (MS) is a chronic neurodegenerative and autoimmune disease characterized by CNS inflammation and demyelination. Although current disease-modifying therapies (DMTs) can reduce peripheral immune responses, their impact on CNS-compartmentalized inflammation remains limited. Bruton Tyrosine Kinase inhibitors (BTKis) have emerged as promising oral agents targeting both B cells and microglia.</div></div><div><h3>Objective</h3><div>To evaluate the safety profiles and effectiveness of two BTK inhibitors- Tolebrutinib and Evobrutinib in the management of relapsing multiple sclerosis.</div></div><div><h3>Methods</h3><div>A literature search was conducted using PubMed, Embase, and Scopus for randomized controlled trials published between 2020 and 2024. Studies comparing Evobrutinib and Tolebrutinib in MS patients were screened and evaluated based on predetermined inclusion and exclusion criteria. Four relevant RCTs were matched and examined in more detail.</div></div><div><h3>Results</h3><div>On MRI, both BTK inhibitors showed decreases in gadolinium-enhancing lesions; Tolebrutinib demonstrated dose-dependent efficacy in reducing new Gd-enhancing lesions and T2 lesion counts, with optimal effects at 60 mg daily. Evobrutinib showed dose-dependent decreases in serum neurofilament light (NfL) levels and relapse rates, with twice-daily dosing providing greater BTK inhibition and clinical benefit. Nasopharyngitis, temporary increases in liver enzymes, and mild gastrointestinal symptoms were among the frequent side effects for both agents. The included studies did not report any direct clinical comparisons of CNS penetration or microglial modulation.</div></div><div><h3>Conclusion</h3><div>With good safety and efficacy profiles in treating relapsing multiple sclerosis, both of the BTKis (Evobrutinib and Tolebrutinib) show promise. Both have promise as oral treatments of the future, but Tolebrutinib might have better effects on the central nervous system. To confirm long-term results and determine their role in progressive MS, more phase III trials are necessary.</div></div>","PeriodicalId":51017,"journal":{"name":"Dm Disease-A-Month","volume":"71 11","pages":"Article 102012"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.disamonth.2025.102011
{"title":"Foreword: Role of Bruton tyrosine kinase inhibitors and ketogenic diet for inflammatory modulation in multiple sclerosis","authors":"","doi":"10.1016/j.disamonth.2025.102011","DOIUrl":"10.1016/j.disamonth.2025.102011","url":null,"abstract":"","PeriodicalId":51017,"journal":{"name":"Dm Disease-A-Month","volume":"71 11","pages":"Article 102011"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Takotsubo cardiomyopathy (TTC) is an acute, reversible cardiac syndrome triggered by physical or emotional stress, involving complex multi-system interactions, with unclear mechanisms and variable prognosis across patient subgroups.
Objectives
To synthesize current evidence on comorbidities, biomarkers, genetic predispositions, prognostic factors, and management strategies in TTC, highlighting clinical implications and research gaps for improved diagnosis, prevention, and patient outcomes.
Methods
A systematic review was conducted on studies published between January 2015 and July 2025. Search was performed across Embase, PubMed, Web of Science, Scopus and Google Scholar using predefined MeSH terms and keywords. Twenty-five studies were included in this review. Quality assessment was conducted using the Newcastle-Ottawa Scale.
Results
TTC was associated with psychiatric disorders, malignancies, endocrine and inflammatory conditions, and neurological insults. Apical ballooning morphology predicted worse outcomes. Biomarkers (NT-proBNP/TnI) and echocardiography improved diagnostic accuracy. Adrenergic receptor polymorphisms (GRK5 L41Q, α2CDel322–325) increased susceptibility in select populations, though genetic findings were inconsistent. Psychological support and beta-blockers improved recovery, while machine learning models enhanced prognostic prediction. ICU-based early echocardiographic screening identified high-risk patients. Multi-disciplinary approaches integrating cardiovascular, psychological, and genetic considerations yielded better patient outcomes. Evidence was limited by heterogeneity, small genetic cohorts, and inconsistent follow-up durations, highlighting the need for standardized diagnostic criteria and prospective, multicenter studies.
Conclusion
TTC is a multifactorial syndrome requiring integrated diagnostic, therapeutic, and preventive strategies. Early detection, comorbidity management, and personalized care improve prognosis. Standardized research is needed to refine understanding and optimize management.
背景：Takotsubo心肌病（TTC）是一种由身体或情绪应激引发的急性、可逆性心脏综合征，涉及复杂的多系统相互作用，机制不明确，不同患者亚组预后不同。目的：综合目前TTC的合并症、生物标志物、遗传易感性、预后因素和管理策略的证据，突出临床意义和研究差距，以改善诊断、预防和患者预后。方法：对2015年1月至2025年7月发表的研究进行系统综述。使用预定义的MeSH术语和关键词在Embase、PubMed、Web of Science、Scopus和b谷歌Scholar上进行搜索。本综述纳入了25项研究。使用纽卡斯尔-渥太华量表进行质量评估。结果：TTC与精神疾病、恶性肿瘤、内分泌和炎症以及神经损伤有关。顶端球囊形态预示较差的预后。生物标志物（NT-proBNP/TnI）和超声心动图提高了诊断的准确性。肾上腺素能受体多态性（GRK5 L41Q, α2CDel322-325）增加了特定人群的易感性，尽管遗传结果不一致。心理支持和β受体阻滞剂改善了康复，而机器学习模型增强了预后预测。基于icu的早期超声心动图筛查确定高危患者。综合心血管、心理和遗传因素的多学科方法产生了更好的患者预后。证据受到异质性、小遗传队列和不一致的随访时间的限制，强调需要标准化的诊断标准和前瞻性的多中心研究。结论：TTC是一种多因素综合征，需要综合诊断、治疗和预防策略。早期发现、合并症管理和个性化护理可改善预后。需要标准化的研究来完善认识和优化管理。
{"title":"Takotsubo cardiomyopathy: Advances in pathophysiology, diagnostic biomarkers, genetic insights, multisystemic involvement, treatment updates & multidisciplinary interventions","authors":"Pugazhendi Inban MD , Andy Thai MD , Rushin S. Parekh MBBS , Dastan Kudaiarov MD , Khyati Thalamanchi MBBS , Jobby John MBBS , Renu Sharma MBBS , Prasanna Sakthi Aravazhi MBBS","doi":"10.1016/j.disamonth.2025.102029","DOIUrl":"10.1016/j.disamonth.2025.102029","url":null,"abstract":"<div><h3>Background</h3><div>Takotsubo cardiomyopathy (TTC) is an acute, reversible cardiac syndrome triggered by physical or emotional stress, involving complex multi-system interactions, with unclear mechanisms and variable prognosis across patient subgroups.</div></div><div><h3>Objectives</h3><div>To synthesize current evidence on comorbidities, biomarkers, genetic predispositions, prognostic factors, and management strategies in TTC, highlighting clinical implications and research gaps for improved diagnosis, prevention, and patient outcomes.</div></div><div><h3>Methods</h3><div>A systematic review was conducted on studies published between January 2015 and July 2025. Search was performed across Embase, PubMed, Web of Science, Scopus and Google Scholar using predefined MeSH terms and keywords. Twenty-five studies were included in this review. Quality assessment was conducted using the Newcastle-Ottawa Scale.</div></div><div><h3>Results</h3><div>TTC was associated with psychiatric disorders, malignancies, endocrine and inflammatory conditions, and neurological insults. Apical ballooning morphology predicted worse outcomes. Biomarkers (NT-proBNP/TnI) and echocardiography improved diagnostic accuracy. Adrenergic receptor polymorphisms (GRK5 L41Q, α2CDel322–325) increased susceptibility in select populations, though genetic findings were inconsistent. Psychological support and beta-blockers improved recovery, while machine learning models enhanced prognostic prediction. ICU-based early echocardiographic screening identified high-risk patients. Multi-disciplinary approaches integrating cardiovascular, psychological, and genetic considerations yielded better patient outcomes. Evidence was limited by heterogeneity, small genetic cohorts, and inconsistent follow-up durations, highlighting the need for standardized diagnostic criteria and prospective, multicenter studies.</div></div><div><h3>Conclusion</h3><div>TTC is a multifactorial syndrome requiring integrated diagnostic, therapeutic, and preventive strategies. Early detection, comorbidity management, and personalized care improve prognosis. Standardized research is needed to refine understanding and optimize management.</div></div>","PeriodicalId":51017,"journal":{"name":"Dm Disease-A-Month","volume":"72 2","pages":"Article 102029"},"PeriodicalIF":4.3,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.disamonth.2025.101982
Jerrold B. Leikin MD FACP, FACEP, FAACT, FACMT, FACOEM, FASAM
{"title":"Foreword for Schizophrenia and psychosis in children and adolescents: An inspiring journey of scientific progress and the rich influences of history and religion","authors":"Jerrold B. Leikin MD FACP, FACEP, FAACT, FACMT, FACOEM, FASAM","doi":"10.1016/j.disamonth.2025.101982","DOIUrl":"10.1016/j.disamonth.2025.101982","url":null,"abstract":"","PeriodicalId":51017,"journal":{"name":"Dm Disease-A-Month","volume":"71 10","pages":"Article 101982"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号