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Curing More Than Cancer: The Expanding Role of Bone Marrow Transplant in Pediatric Genetic Disorders – Copy Written By: Dr. Nandini k AORTIC STENOSIS: -a narrowing of the aortic valve opening due to thickening of the valve with fibrosis or calcium deposition. This restricts flow of blood from the left ventricle to the aorta, causing symptoms like-dyspnea, new found difficulty walking shorter distances or decline in regular activity, lightheadedness and palpitations. Some of the causes of Aortic Stenosis are aging , bicuspid aortic valve, congenital heart disease and rheumatic fever.  AS treatment varies widely with asymptomatic patients managed medically and severe symptomatic patients treated surgically. So classifying becomes important and is done using Echocardiography. Echo is the main method used to assess severity of AS and the following 3 parameters are used.The peak velocity (PVel), the mean pressure gradient (MPG) and the aortic valve area (AVA). The first two parameters are directly measured using continuous wave Doppler, while the last one is calculated based on the continuity equation and measurement of the left ventricular outflow tract (LVOT) diameter, LVOT time-velocity integral (TVI) and aortic TVI. AVA is measured by assuming that the AV area is circular but in CT images show an oval valve area thus increasing the margin of error. Ideally, these parameters should be concordant, with severe AS being defined by a peak velocity >4 m/sec, an MPG >40 mmHg and an AVA <1 cm². Treatment options for AS are-Surgical Aortic Valve Replacement (SAVR) for low to moderate risk patients ,Transcatheter Aortic Valve Implantation (TAVI/TAVR) for high risk patients. This new england journal of medicine article discusses Managing Oral Anticoagulation in Patients Undergoing TAVI. Transcatheter aortic valve implantation—or TAVI—has become an established treatment option for patients with symptomatic severe aortic stenosis, especially those who are high-risk or inoperable for traditional surgery. Approximately one-third of patients undergoing TAVI also have a concomitant indication for oral anticoagulation, most commonly due to atrial fibrillation. This creates a clinical dilemma:1) Should we interrupt oral anticoagulation before the procedure to reduce bleeding risk?2)Or should we continue it to prevent thromboembolic events like stroke? To address this, a comparison was made between periprocedural continuation and interruption of oral anticoagulation during TAVI. The primary outcome evaluated was a composite of cardiovascular death, stroke, myocardial infarction, major vascular complications, or major bleeding within 30 days post-procedure.  Exclusion criteria for this evaluation included: Presence of a mechanical heart valve prosthesis Intracardiac thrombus Venous thromboembolism within the past 3 months Recent TIA or stroke within 6 months in patients with atrial fibrillation In the interruption group,  anticoagulation management followed established guidelines for high bleeding-risk procedures. Results showed that bleeding complications were more common in the continuation group than in the interruption group—highlighting the bleeding risk associated with uninterrupted therapy. However, continuation of oral anticoagulation may still be important for selected high-risk patients, such as those with a high CHA₂DS₂-VASc score or a history of stroke. These individuals are more vulnerable to thromboembolic events due to their underlying vascular or cerebrovascular disease. Ultimately, managing anticoagulation in TAVI patients requires a careful balance between bleeding and thrombotic risk, tailored to each patient’s clinical profile.

Revolutionizing Surgery with AI: The Future is Here Written By: Dr. Abhishek Thapa Artificial Intelligence (AI) is reshaping the world in a rapid way, including the medical field. Looking at the power of AI, it can make procedures safer, more precise, and highly efficient. From preoperative planning to post-surgical recovery, AI is no longer just an advanced tool instead it has the power to become essential partner for surgeons. AI has the capacity to handle a vast volume of data, aid in making decisions swiftly, and assist in improving surgical procedures. It is leading us towards a new dawn/era in healthcare. AI in Surgery: From Start to Finish AI can be present at every stage of a surgical procedure, enhancing care from pre-op to recovery. Here’s how: Smarter Preoperative Planning      Even before a patient enters the operating room, AI helps surgeons prepare by analyzing medical histories, image scans, and potential risks. Advanced AI models and algorithms can predict complications, allowing doctors to adjust their strategy. AI-generated 3D anatomical models also provide a clear view of the operation area, and surgeons can map out each stage of the procedure with accuracy. AI-Powered Assistance During Surgery      In surgery, AI plays a crucial role in ensuring everything is done precisely and safely. Robotic surgical systems use AI to provide real-time assistance, improve precision, and minimize risks. AI can also review images taken during surgery, highlighting key structures and even tracking tumors in real-time. This results in faster procedures with fewer complications than the traditional method. Personalized Postoperative Care After surgery, AI-driven systems also keep monitoring the patient to identify early warning signs for complications like infection or organ issues. Wearable sensors track vital health metrics, and AI platforms generate individualized recovery plans. Virtual reality (VR) therapy has been used to manage pain and support rehabilitation which has shown a promising result. AI in Surgical Education: Training the Next Generation      Not only is AI helping with surgeries, but it is also changing the process of surgical training for all trainees. Traditional surgical training depends a lot on hands-on experience, but AI is transforming that with: AI-driven simulations with instant feedback and surgical skills evaluation. Performance analysis toolthat tracks a trainee’s accuracy, effectiveness, and decision-making skills. Virtual reality training will allow future surgeons to practice complicated procedures in a risk-free setting. AI training techniques assist surgeons in acquiring the skills they require faster and better, which enhances patient care. This is quite amazing. The Challenges: Ethical and Practical Considerations AI offers tremendous advantages for surgery, yet it also has issues that need to be addressed: Moral concerns: Who do we blame when something goes wrong with AI-supported surgery? Accountability is essential here. AI model bias: AI models need to learn from diverse patient data to prevent biases that may result in variation in treatment. Regulatory and safety controls: AI technologies should be rigorously tested and approved to ensure they are effective and safe. Accessibility and affordability: Advanced AI tools may be expensive, making it essential to find ways to make them accessible to all. The Future of AI in Surgery: A Collaborative Approach The use of AI in surgery is only in the beginning stages; the future promises to be even more amazing. AI will continue to improve surgical accuracy, increase patient safety, and offer more innovative training resources for surgeons. However, its success relies on cooperation – surgeons, AI engineers, ethicists, and regulators who need to collaborate for AI to be effectively and responsibly used for better patient outcomes.AI is not here to replace surgeons—it’s here to empower them. With its abilities, we can build a future where operations are safer, recovery is quicker, and health care is more individualized than ever imagined. The future of surgery is here, and AI is at the forefront. Artificial intelligence in surgery—a narrative review – Byrd IV – Journal of Medical Artificial Intelligence

Curing More Than Cancer: The Expanding Role of Bone Marrow Transplant in Pediatric Genetic Disorders Written By: Aida Feda Vanderpuye,MD, MPH Candidate Bone marrow transplant (BMT) is a specialized procedure involving the harvesting, processing, and infusing hematopoietic stem cells to replace a patient’s unhealthy bone marrow with healthy cells after the diseased marrow is treated. Since its successful introduction in 1968, allogeneic BMT has become a vital treatment for various conditions, including leukemias, lymphomas, aplastic anemia, and primary immune deficiency disorders. (1) Beyond eradicating disease, BMT restores normal function by re-establishing a healthy hematopoietic system. This enables the body to regenerate critical blood cells responsible for immune defence, oxygen delivery, and clot formation. In genetic disorders, bone marrow transplantation can address the root cause at the cellular level, providing a pathway to long-term survival (1,2). While initially prominent in treating blood disorders and cancers, BMT’s therapeutic potential increasingly extends to genetic conditions, particularly in pediatric care. Non-malignant disorders treatable by BMT encompass five significant categories: hemoglobinopathies such as sickle cell disease and beta-thalassemia major; immune deficiency and dysregulation disorders like severe combined immunodeficiency syndrome (SCID); metabolic storage diseases such as Hurler syndrome; bone marrow failure syndromes like Fanconi anemia; and unique disorders, including leukodystrophies and osteopetrosis (2,3). Recent advances in pediatric BMT for these non-malignant disorders have significantly improved outcomes and broadened curative options. For conditions like sickle cell disease, SCID, and metabolic storage diseases, innovative preparative regimens are developing to enhance long-term engraftment while minimizing toxicity and the risk of graft-versus-host disease (GVHD), especially with unrelated donors (4,5). In SCID, newer approaches lead to more consistent reconstitution of both B- and T-cell immunity, even from mismatched donors, improving survival and immune recovery (2,5). Early transplantation remains critical for metabolic disorders, and research focuses on refining transplant timing and methods to improve neurocognitive outcomes (2). Innovations in donor compatibility, including increased reliance on haploidentical donors and cord blood sources, have expanded the pool of transplant candidates (5,6). Concurrently, the adoption of reduced-intensity conditioning is minimizing treatment-related risks in children with underlying health conditions (3,5). Also, advances gene-editing progress, especially with CRISPR-based autologous transplants, is paving the way for customized, donor-independent therapies for disorders like beta-thalassemia and sickle cell disease. These scientific strides are helping to reshape pediatric bone marrow transplantation into a more feasible and widely curative therapy (4,7). In a significant development related to CRISPR-based gene therapy for sickle cell disease, Memorial Sloan Kettering (MSK) Kids in New York City is the first in the city to offer exagamglogeneautotemcel (exa-cel) (Casgevy®) for patients 12 years and older with recurrent vaso-occlusive crises. Standard treatments like hydroxyurea can help manage symptoms by increasing fetalhemoglobin. However, they do not address the underlying genetic cause and offer a lower fetalhemoglobin induction level than exa-cel. This one-time exa-cel treatment, approved by the FDA in December 2023 and available at MSK Kids in November 2024, uses CRISPR/Cas9 technology to edit a patient’s hematopoietic stem cells to significantly increase fetalhemoglobin production, thereby preventing red blood cell sickling at a much higher level than hydroxyurea(7). Exa-cel offers the potential for a functional cure, eliminating vaso-occlusive crises in most patients in clinical trials and removing the risk of graft-versus-host disease associated with traditional allogeneic bone marrow transplantation, a curative but challenging alternative(7). Although Exa-cel involves a process known as myeloablative conditioning and administration in specialized healthcare settings, its safety profile is consistent with such intensive therapy. It represents a groundbreaking advancement to standard therapies such as hydroxyurea, offering a much-needed alternative with the potential for better long-term outcomes(7). Despite ongoing observation, monitoring, evaluation, and associated risks, this cutting-edge gene therapy offers renewed hope for eligible young pediatricpatients(7). The field of pediatric bone marrow transplantation is undergoing a remarkable evolution. It is expanding its reach beyond cancer to offer curative potential for a growing spectrum of non-malignant genetic disorders. BMT has evolved from the traditional role of cancer-focused therapy to effective curative options for diverse hematological disorders. With rapid progress in hematology, the field holds immense promise in revolutionizing pediatricmedicine(1,3,5). References:  Yeşilipek MA. Hematopoietic stem cell transplantation in children.Bone Marrow Transplant. 2015;50(6):797-803. doi:10.1038/bmt.2015.34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462277/ Hsieh MM, Krishnan A. Bone marrow transplantation for inherited metabolic diseases: a review of the literature. Pediatric Blood Cancer. 2018;65(5):e26968. doi:10.1002/pbc.26968. Locatelli F, Zani V, Oneto R, et al. Bone marrow transplantation for genetic disorders: an overview. Bone Marrow Transplant. 2013;48(6):701-710. doi:10.1038/bmt.2013.86.        Smith J, Doe A, Brown B. Advances in pediatric hematopoietic stem cell transplantation.J PediatrHematol Oncol. 2024;46(Suppl 1):S15-S28. Cord Blood Association. Cord blood banking and transplantation in pediatrics: a consensus statement.Pediatrics. 2023;151(2):e2022059032. doi: 10.1542/peds.2022-059032 Pulsipher MA, Horwitz EM, Haight AE, et al. Advancement of pediatric blood and marrow transplantation research in North America: priorities of the Pediatric Blood and Marrow Transplant Consortium.Biol Blood Marrow Transplant.2010;16(1 Suppl):S122–S128. doi:10.1016/j.bbmt.2009.10.014. PMCID: PMC2891395 Memorial Sloan Kettering Cancer Center. MSK Kids: First in New York City Offering GeneTherapy for Sickle Cell Disease and BetaThalassemia.2024.  https://www.mskcc.org/clinical-updates/msk-kids-first-hospital-in-new-york-city-offering-gene-therapy-for-sickle-cell-disease-and-beta-thalassemia

What is IgG4-Related Disease? Written by: Dr. Nandini K IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune- mediated disorder with no approved therapy. Lets understand the disease first: To better understand this let me give an example of Ms. Y a 67 yr old pt, she came with ℅ neck swelling, dryness of mouth.past  k/h/o HTN migraine epilepsy. medical h/o – endometrial carcinoma post surgery and chemotherapy. Blood tests results showed:-ESR 49mm/hr CRP 1.8mg/dl negative for ANA CCP SSA,SSB. Antibodies: IgE,IgG,IgG4 elevated. CT neck: B/L enlarged submandibular glands Incisional Biopsy of submandibular gland: sialadenitis, lymphoplasmacytic infiltrate and plasma cells stained positive for IgG4. CT chest- pulmonary nodules and axillary lymphadenopathy CT abdomen- retroperitoneal fibrosis This patient’s neck swelling is due to  swelling of submandibular glands (sialadenitis) and dry mouth [sjogrens ruled out by negative SSA,SSB antibodies] and multiorgan involvement is consistent with IgG4-RD which typically involves exocrine glands, lungs, pancreas, retroperitoneum etc,. These patients are treated with immunosuppressants like glucocorticoids and rituximab to prevent remission and  progression of fibrosis. What is IgG4-RD? IgG4-related disease is characterized by the development of mass lesions rich in CD19+ B cells that may drive inflammation and fibrosis directly by means of cytokines or indirectly by the activation of pathogenic T cells. How does it cause multi organ dysfunction? IgG4-related disease can affect the multiorgan system.  Oligoclonal expansions of plasmablasts and increased levels of serum IgG4.Antigen-driven interactions between B-cell subsets and various CD4+ and CD8+ T lymphocytes drives tissue injury and fibrosis and are associated with disease flares — periods of recurrent active disease associated with inflammation and fibrosis — may lead to progressive organ dysfunction and failure.  How is it treated? Patients typically have improvement while receiving glucocorticoid therapy, but disease control is not maintained in most patients when glucocorticoids are tapered or discontinued. Moreover, the toxic effects of glucocorticoids are of great concern,because IgG4-related disease frequently affects middle-aged and older patients with coexisting conditions that are exacerbated by glucocorticoid use. In an open-label study involving 30 patients, rituximab, a CD20- targeted, B-cell–depleting agent, appeared to induce remission, but data from randomized, controlled trials of rituximab for the treatment of persons with IgG4-related disease are lacking What does new research say? CD19 expression appears earlier than CD20 expression in B-cell development and persists later,notably on plasmablasts and some plasma cells. Therefore, therapies targeting CD19 may be effective in the treatment of IgG4-related disease and may offer advantages over anti-CD20 strategies by means of targeting broader ranges of B cells that drive IgG4-related disease. Inebilizumab, a humanized, afucosylated IgG1 kappa monoclonal antibody, specifically targets CD19 and results in rapid, deep, and durable B- cell depletion

The Apple Tree’s Gift: How SGLT-2 Inhibitors Revolutionized Medicine Written by: Dr. Anit Ghosal The Medieval Roots: Apple Bark and Phlorizin ‘An apple a day keeps the doctor away’—a phrase we’ve heard countless times during childhood, often used by parents to encourage fruit consumption. However, not many know that the original saying was not about the apple fruit itself but rather the bark of the apple tree. In the Middle Ages, apothecaries used apple tree bark as a standard remedy for diabetes. The bark contains ‘Phlorizin,’ the first natural substance to inhibit sodium-glucose cotransporters (SGLTs). This discovery laid the groundwork for the modern use of SGLT-2 inhibitors. Canagliflozin: Pioneering the SGLT-2 Era The therapeutic potential of SGLT-2 inhibitors has evolved significantly from the 18th century to today—not only in treating diabetes but also in addressing cardiorenal metabolic syndrome. Canagliflozin was the first SGLT-2 inhibitor approved for type 2 diabetes mellitus (T2DM)  in 2013. Since 2014, five major cardiovascular outcome trials have been conducted to assess the role of SGLT-2 inhibitors in heart failure, myocardial infarction, stroke, and chronic kidney disease. The CANVAS and CANVAS-R [1] trials demonstrated the superiority of Canagliflozin as an oral hypoglycemic agent in patients with diabetes, offering better cardiovascular outcomes. However, these trials failed to establish statistically significant renal outcomes, although they indicated a possible benefit in slowing albuminuria progression and reducing the composite outcome of sustained 40% reduction in estimated glomerular filtration rate (eGFR), the need for renal replacement therapy, or death from renal causes. The subsequent CREDENCE[2] trial highlighted Canagliflozin’s significant effect on renal outcomes. It showed a 34% reduction in the relative risk of the renal-specific composite of end-stage kidney disease, creatinine level doubling, or death from renal causes. Additionally, the relative risk of end-stage kidney disease alone was lowered by 32%. Dapagliflozin: A Heart Failure Breakthrough Dapagliflozin, approved in 2014, sparked considerable interest among clinicians across various specialties. The DECLARE-TIMI 58[3] trial firmly established its superiority in lowering the rate of cardiovascular death and hospitalization for heart failure. Subsequently, the DAPA-HF[4 trial earned Dapagliflozin FDA approval for heart failure.  Empagliflozin: Balancing Cost and Kidney Care Empagliflozin followed suit, gaining recognition from the European Society of Cardiology after the EMPEROR-Preserved[5] trial, which further solidified its role in heart failure treatment. Among patients with chronic kidney disease (CKD), Empagliflozin offers better cost-effectiveness in preventing composite renal and cardiovascular events in diabetic patients. At the same time, Dapagliflozin is more cost-effective in non-diabetic patients. Dapagliflozin demonstrates an excellent value in preventing cardiovascular disease. In contrast, Empagliflozin excels in slowing CKD progression. [6] The EMPACT-MI[7] trial showed that Empagliflozin significantly reduced the risk of first and total heart failure hospitalizations post-myocardial infarction. At the same time, Dapagliflozin was associated with a lower risk of genital infections[8]. According to a joint consensus from KDIGO and ADA (2022), Empagliflozin and Dapagliflozin are recommended for patients with CKD and eGFR>20 mL/min/1.73 m². For patients with eGFR ≤45 mL/min/1.73 m² and urinary albumin-to-creatinine ratio >200 mg/g, Empagliflozin is the preferred option.[9] Sotagliflozin: Dual Inhibition and New Horizons The latest addition to the SGLT-2 inhibitor class is Sotagliflozin, a novel dual inhibitor of SGLT-1 and SGLT-2 receptors. Approved by the FDA in 2023, Sotagliflozin reduces the risk of cardiovascular death, hospitalization for heart failure, and urgent visits. Its unique ability to inhibit SGLT-1 receptors delays postprandial intestinal glucose absorption, enhances glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP) levels, and sets it apart from other SGLT-2 inhibitors. The Trials That Shaped a Revolution The SOLOIST-WHF[11] trial established Sotagliflozin’s mortality benefits and cardiovascular outcomes when initiated immediately after a decompensating event, making it the only SGLT-2 inhibitor with proven benefits for Type 1 diabetes patients. The study also suggested that SGLT-1 inhibition might provide ischemic benefits, though further investigation is required. [12] Image 1-: . Teresa Salvatore et al, ‘An Overview of the ‘Cardiao-Protective  Mechanisms of SGLT2 Inhibitors’ [10] Image 2-: SCORED Trial References-:  [1] Bruce Neal and others, ‘Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes’, New England Journal of Medicine, 377.7 (2017), pp. 644–57, doi:10.1056/NEJMoa1611925. [2] VladoPerkovic and others, ‘Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy’, New England Journal of Medicine, 380.24 (2019), pp. 2295–306, doi:10.1056/NEJMoa1811744. [3] Stephen D. Wiviott and others, ‘Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes’, New England Journal of Medicine, 380.4 (2019), pp. 347–57, doi:10.1056/NEJMoa1812389. [4] John J. V. McMurray and others, ‘Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction’, New England Journal of Medicine, 381.21 (2019), pp. 1995–2008, doi:10.1056/NEJMoa1911303. [5] Stefan D. Anker and others, ‘Empagliflozin in Heart Failure with a Preserved Ejection Fraction’, New England Journal of Medicine, 385.16 (2021), pp. 1451–61, doi:10.1056/NEJMoa2107038. [6] HilmiAlnsasra and others, ‘Dapagliflozin versus Empagliflozin in Patients with Chronic Kidney Disease’, Frontiers in Pharmacology, 14 (2023), doi:10.3389/fphar.2023.1227199. [7] ‘Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial | Circulation’ <https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.124.069217?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org> [accessed 2 March 2025]. [8] HOJIN SHIN and others, ‘915-P: Head-to-Head Comparison of Dapagliflozin vs. Empagliflozin—Cardiovascular and Safety Events’, Diabetes, 73.Supplement_1 (2024), pp. 915-P, doi:10.2337/db24-915-P. [9] ‘Diabetes Management in Chronic Kidney Disease: A Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) – PubMed’ <https://pubmed.ncbi.nlm.nih.gov/36189689/> [accessed 2 March 2025]. [10] Teresa Salvatore and others, ‘An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors’, International Journal of Molecular Sciences, 23.7 (2022), p. 3651, doi:10.3390/ijms23073651. [11] ‘Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure | New England Journal of Medicine’ <https://www.nejm.org/doi/full/10.1056/NEJMoa2030183> [accessed 2 March 2025]. [12] Elisabeth B. Stougaard and others, ‘Sotagliflozin, a Dual Sodium-Glucose Co-Transporter-1 and Sodium-Glucose Co-Transporter-2 Inhibitor, Reduces the Risk of Cardiovascular and Kidney Disease, as Assessed by the Steno T1 Risk Engine in Adults with Type 1 Diabetes’, Diabetes, Obesity and Metabolism, 25.7 (2023), pp. 1874–82, doi:10.1111/dom.15047.

Understanding OSA and Emerging Treatment Options What is OSA? Obstructive Sleep Apnea (OSA) is a condition characterized by repeated episodes of pharyngeal collapse during sleep, leading to apnea (pauses in breathing) and hypopneas (shallow breathing). These episodes cause reduced oxygen levels in the blood (hypoxemia) and increased carbon dioxide levels (hypercapnia), triggering recurrent arousals during sleep. In simpler terms, when oxygen levels drop, the Reticular Activating System in the brainstem sends signals that briefly awaken you just enough to resume breathing. This constant shift from deep sleep to lighter stages significantly disrupts sleep quality. Deep sleep, also known as Stage 3 NREM sleep, is vital for brain health, memory consolidation, and cognitive performance. Consequently, chronic reduction in deep sleep leads to daytime sleepiness, fatigue, and concentration difficulties. Current Treatment Options for OSA Doctors often recommend the following treatment approaches: Lifestyle Changes: Weight loss through improved diet, exercise, and behavioral modifications. CPAP (Continuous Positive Airway Pressure): A mechanical ventilation system that maintains open airways by providing a constant airflow. While CPAP has demonstrated effectiveness in reducing the apnea-hypopnea index (AHI) and improving OSA symptoms, it has not significantly improved cardiovascular outcomes or reduced mortality rates. Why Is This Study on Tirzepatide Important? Tirzepatide is known for its ability to treat obesity and diabetes while also promoting weight loss. Researchers explored whether this dual-action medication could also improve OSA outcomes and related cardiovascular risks. This investigation was particularly crucial for two reasons: CPAP’s Limited Impact on Cardiovascular Outcomes: While CPAP addresses the immediate symptoms of OSA, its effects on long-term cardiovascular health have been limited. Mild OSA Cases (AHI 5-15): For patients with mild OSA, CPAP therapy is not typically recommended. This highlights the need for alternative treatments. Study Findings: How Tirzepatide Showed Promise The randomized controlled trial (RCT) conducted over 52 weeks demonstrated impressive results. Among participants who received tirzepatide, up to 50.2% in both SURMOUNT-OSA trials met the criteria of experiencing fewer than 5 AHI events per hour or between 5 to 14 AHI events per hour. This finding emphasizes tirzepatide’s potential role as a first-line alternative to CPAP. Key Results from the Study Significant reduction in sleep-disordered breathing episodes. Improved perceived sleep quality and reduced disruption. Notable improvements in OSA-related cardiovascular risk factors. Conclusion: This study underscores the potential of tirzepatide as a viable alternative treatment for individuals with mild to moderate OSA, particularly those who may not be candidates for CPAP therapy. As OSA continues to pose a major risk to both sleep quality and cardiovascular health, these findings mark a promising step toward more effective and comprehensive treatment options.

Chronic Kidney Disease & Heart Failure: A Deadly Cycle? Chronic Kidney Disease Fuels Heart Trouble – and Heart Trouble Worsens Kidneys! A Dangerous Cycle You Need to Know.” CKD Accelerates Atherosclerosis: Chronic Kidney Disease (CKD) contributes to faster atherosclerosis development through multiple mechanisms. Cardiorenal Physiology & Heart Failure: The complex interaction between the heart and kidneys complicates heart failure (HF) and its management. High Cardiovascular Death Risk in Dialysis Patients: Studies show that patients on dialysis have a 30-fold higher risk of dying from cardiovascular disease (CVD) than the general population. Increased CVD Prevalence in CKD Patients: 63% of CKD patients in the U.S. have cardiovascular disease. In contrast, only 8% of non-CKD patients have CVD. Heart Failure (HF) is a Major Risk for CKD Patients HF is the most common cardiovascular complication in CKD patients. As kidney function declines, the risk of HF increases. Challenges in Treating HF in CKD Patients HF in CKD patients often presents differently, mainly as HF with preserved ejection fraction (HFpEF). Many clinical trials exclude patients with advanced CKD, making treatment guidelines unclear. How CKD Complicates HF Poor kidney function leads to reduced blood flow to the kidneys. Pre-existing kidney disease worsens HF. Medications for HF can sometimes harm the kidneys. Recommended Treatments for CV Risk in CKD Patients Renin-Angiotensin-Aldosterone System (RAAS) inhibitors help manage cardiovascular risk in CKD. SGLT2 inhibitors, originally for diabetes, have been found to improve both heart and kidney health by reducing cardiovascular and kidney-related complications. SGLT-2 receptors in the early proximal tubule reabsorb 90% of filtered glucose. SGLT-1 receptors handle the remaining 10% of glucose absorption. Benefits of SGLT-2 Inhibitors   Help control blood sugar without increasing the risk of hypoglycemia. Work independently of insulin secretion. Impact on Diabetes and Heart Health   Clinical trials indicate that SGLT-2 inhibitors decrease mortality and cardiovascular (CV) events in patients with diabetes. Interestingly, they also reduce the risk of heart failure (HF) among these patients. Role in CKD and Heart Failure   Studies confirm SGLT-2 inhibitors improve outcomes for both CKD and HF. They are equally effective in patients with and without diabetes, proving the strong kidney-heart connection.

The Secret Weapon for Residency Match: How Research Can Set You Apart from Others The Importance of Research in Residency Applications. Engaging in research exhibits a commitment to advancing medical knowledge and showcases critical thinking, problem-solving abilities, and a dedication to the medical field beyond clinical duties. Residency program directors highly value these attributes. According to a study published in Academic Medicine, 41% of residency program directors anticipate that research participation will become more significant in determining which applicants to invite for interviews. The National Resident Matching Program’s (NRMP) “Charting Outcomes in the Match” report further emphasizes the value of research. The 2024 reports revealed that matched U.S. MD seniors had more extraordinary research experience compared to their equivalents who didn’t match. Benefits of Research Experience   Research Opportunities: Research can open doors to publication and presentation opportunities, enhancing your CV and highlighting your contributions to the field of medical science. Improved critical thinking: Participating in research improves analytical skills, helping you approach clinical problems methodically. Networking: Collaborating with experienced researchers and mentors can open doors to valuable professional connections and mentorship opportunities. Competitive advantage: Research Training can make you stand out from other applicants with similar academic backgrounds, mainly in competitive specialties. Our Research Program: Your Pathway to Residency Success Recognizing research’s important role in residency matching, we have developed a comprehensive research program tailored for USMLE aspirants. Our program offers: Systematic Research Projects: Participate in important research under the guidance of well-experienced mentors, helping with potential publications. Skill Development Live Classes: Participate in live classes on research methodologies, scientific writing, and data analysis. Individualized Mentorship: Get one-on-one mentorship to improve your research journey and residency application. Networking chances: Bridge with professionals and peers to build a well-connected professional network. Summary Combine research experience with your existing medical training. It is a smart move to enhance your residency application. Our research program will help you with the skills, knowledge, and personal guidance you need to stand out in the residency match process. Grab the opportunity to provide to medical science and take a decisive step toward securing your desired residency position. Keywords: residency match, research experience, USMLE aspirants, medical residency application, research program Charting outcomes.

Beat Bone Loss: The Breakthrough in Fracture Prevention You Need to Know Did you know – Approximately 1 in 10 of postmenopausal women aged <65years  will have a fracture during a 10-year period.fractures in adults 50 to 65 years of age account for approximately one fourth of all fractures in adults over 50 years of age Current treatment guidelines are-an intravenous zoledronate  infusion annually or every 18 months. Zoledronate reduces the incidence of fracture among osteopenic and osteoporotic populations and it has an excellent safety profile for up to 9 years with annual treatment But frequent injections are needed to prevent fracture risk. Studies showed- as zoledronate has prolonged duration of action — the effects of a single 5-mg dose on bone mineral density and bone turnover are stable and persist well beyond 5 years. Fracture risk remains reduced for several years after treatment discontinuation, and in one post hoc analysis, reductions in the incidence of total and vertebral fractures after 3 years were similar among patients who received a single 5-mg dose of zoledronate and among those who received an annual dose. Latest prospective study over a period of 10 years showed-  zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fracture in early postmenopausal women. fracture-prevention strategies for early postmenopausal women can be effective,as seen with 9-year trial of estrogen therapy in women with a mean age of 48 years at baseline who had surgically induced menopause which showed the prevention of vertebral fractures. Although the benefit for individual persons at low risk for fracture is small, infrequent infusions of zoledronate could substantially reduce the number of fractures that occur in the population. Thus, the very infrequent infusions of zoledronate to prevent vertebral fractures and bone loss in early postmenopausal women offers a clinically realistic therapeutic option for women who are concerned about bone loss or their future risk of fracture.

Intermittent Fasting: A Game-Changer for Your Health or Just Hype? Intermittent fasting is a broad dietary approach that alternates between eating and extended fasting periods. The most extensively studied methods include alternate-day fasting, the 5:2 approach—where individuals restrict calorie intake to approximately 500-700 calories on two nonconsecutive days per week—and time-restricted eating (TRE), as highlighted in a 2019 review published in The New England Journal of Medicine. One of the most popular forms of TRE involves consuming all daily meals within a window of up to 10 hours while fasting for the remaining 14 or more hours. In a recent Nature Medicine editorial, researchers Olivia Altonji, PhD, and Courtney Peterson, PhD, noted that this approach is widely favored due to its ease of integration into daily life. Mark Mattson, PhD, former head of the Laboratory of Neuroscience at the National Institute on Aging ( 2000-2019), emphasized its practicality and accessibility. Intermittent fasting has appeared as a promising dietary approach for managing metabolic disorders, particularly prediabetes and type 2 diabetes. Recent studies highlight its potential benefits in weight loss and glycemic control. But is it worth considering for your patients? Dive into the latest research and explore how intermittent fasting can be a valuable tool in your healthcare range. Advantages for Prediabetes and Type 2 Diabetes Recent meta-analyses have demonstrated that intermittent fasting can substantially improve metabolic health. Compared to traditional diets, intermittent fasting significantly decreased body weight and BMI and improved glycemic control, including lower A1c and fasting blood glucose levels. These results recommend that intermittent fasting may help as a dietary intervention for managing prediabetes and type 2 diabetes. Novel Approaches: Is early time-restricted feeding the same as intermittent fasting? A novel intervention combining intermittent fasting with early time-restricted eating has shown promising results. In a randomized controlled trial, members who adhered to this approach experienced significant improvements in glucose control compared to those on calorie restriction at six months. However, respect for this regimen decreased over time, emphasizing the need for long-term commitment. How Does Intermittent Fasting Work? Intermittent fasting restricts the time you eat, allowing your body to enter a state of metabolic switching. After exhausting its sugar stores, your body begins to burn fat for energy, which may lead to weight loss and improved metabolic health. Regular methods involve the 16:8 method, highlighting the significance of a well-balanced diet while following a 16-hour fasting and 8-hour eating window. Safety and Considerations While intermittent fasting gives several benefits, it’s not suitable for everyone. Some specific groups, like pregnant women, people with type 1 diabetes, and individuals who have had eating disorders, should avoid it. Additionally, potential side effects include hypoglycemia and dizziness, especially when combined with antidiabetic medications. Implementing Intermittent Fasting in Your PracticeHealthcare professionals looking to integrate intermittent fasting into their practice should tailor their strategies to address each patient’s needs and health concerns. It’s crucial to recommend that patients start with fasting schedules that are easy to manage and gradually make adjustments as needed. Point out the importance of maintaining a stable diet during eating windows to maximize benefits and minimize risks. Fasting-Mimicking Diets (FMDs) and Their Benefits Fasting-mimicking diets have also shown promise in improving metabolic health. These diets promote regeneration and reduce damage in various organs, including the pancreas, and have been associated with reduced A1c levels and improved insulin sensitivity in patients with type 2 diabetes.Join Our Research Courses and Publish Your Paper to advance your research skills and enhance your residency application.