Welcome to the FIFTH Edition of The Clinical Chronicle!

From groundbreaking trials reshaping cardiovascular and stroke care to the game changing role of AI in medicine, we’re diving into the innovations defining tomorrow’s practice. With cancer rates rising in younger adults, new FDA safety warnings, and seismic shifts in healthcare policy, the landscape is evolving fast.

Stay sharp. Stay ahead. This is the future of medicine.

SCORED Trial: Sotagliflozin Shows Independent Reductions in Heart Attack and Stroke Risk

A Prespecified Secondary Analysis Reveals Significant Cardiovascular Benefits in High-Risk Patients with Type 2 Diabetes and CKD

A groundbreaking analysis from the SCORED trial reveals that sotagliflozin (Inpefa), the first dual SGLT1/2 inhibitor, significantly lowers the risk of both stroke and myocardial infarction (MI) in high-risk patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).

Among 10,584 patients studied, sotagliflozin led to a 23% reduction in major adverse cardiovascular events (MACE), with a 32% lower risk of MI and a 34% lower risk of stroke. This translates to 1.2 strokes and 0.7 heart attacks avoided per 100 patients over two years.

Key Findings:

• MACE reduction: 4.8 events per 100 person-years with sotagliflozin vs. 6.3 with placebo (HR 0.77, P=0.0020).

• Myocardial infarction risk: 1.8 vs. 2.7 per 100 person-years (HR 0.68, P=0.0041).

• Stroke risk: 1.2 vs. 1.8 per 100 person-years (HR 0.66, P=0.012).

Experts from Mount Sinai emphasized that "Sotagliflozin is the first SGLT inhibitor to demonstrate a significant reduction in both MI and stroke," setting it apart from traditional SGLT2 inhibitors. This dual blockade of SGLT1 (found in the gut, kidney, heart, and brain) and SGLT2 (found in the kidney) may be the key to its unique cardiovascular benefits.

Sotagliflozin is now making waves in cardiovascular risk reduction for patients with diabetes and CKD. With its dual mechanism, this therapy could reshape the future of diabetes management and cardiovascular protection.

Source: THELANCET

SGLT2 Inhibitors & GLP-1 Agonists: A Potential Advantage in COPD Management

New Data Suggest Lower Risk of Exacerbations in Patients with Type 2 Diabetes and COPD

A propensity-matched cohort study published in JAMA suggests that SGLT2 inhibitors and GLP-1 receptor agonists may reduce COPD exacerbations in adults with type 2 diabetes. Compared to DPP-4 inhibitors, these medications were associated with a 14-19% lower risk of moderate or severe COPD exacerbations.

The study analyzed U.S. insurance claims data, identifying adults over 40 with type 2 diabetes and active COPD. SGLT2 inhibitors and GLP-1 receptor agonists showed similar benefits, with no significant difference between them. However, DPP-4 inhibitor users were older, had more advanced COPD, and were more likely to be frail, raising concerns about residual confounding despite propensity matching.

While these findings highlight an intriguing potential benefit of SGLT2 inhibitors and GLP-1 receptor agonists, researchers caution that observational studies cannot fully replace randomized clinical trials (RCTs). Further research is needed before these medications can be routinely recommended for COPD management.

Source: JAMA

HOPE Trial: Alteplase Shows Promise for Late-Window Stroke Patients

Thrombolysis Up to 24 Hours May Benefit Non-Thrombectomy Candidates.

New findings from the HOPE trial suggest that IV alteplase may improve functional outcomes in stroke patients treated 4.5 to 24 hours after symptom onset, particularly for those without access to endovascular thrombectomy (EVT). The study, presented at the International Stroke Conference, found that patients receiving alteplase had a better overall functional recovery compared to standard care.

However, the treatment carried a higher risk of symptomatic intracranial hemorrhage (3.8% vs. 0.5%), though 90-day mortality rates were identical between groups (10.8%).

HOPE builds on previous research, including TRACE-III, which demonstrated benefits of late-window thrombolysis with tenecteplase. Unlike the unsuccessful TIMELESS trial, which included a high proportion of EVT-treated patients, HOPE focused on patients with salvageable brain tissue and medium-to-distal vessel occlusions, making its findings more applicable to real-world practice.

While subgroup analysis suggested greater benefit in M2 occlusions and intracranial atherosclerosis-related strokes, these findings remain exploratory. Further research is needed to refine patient selection for late thrombolysis, but HOPE strengthens the case for extending IV thrombolysis beyond traditional time limits for select stroke patients.

Source: THEHEART.ORG

AI: Shaping the Future of Medicine

Enhancing Physician Expertise, Not Replacing It

The AMA champions augmented intelligence (AI) is a concept that highlights AI’s role in assisting, rather than replacing, human decision-making in medicine. As AI adoption in healthcare accelerates, its ethical deployment remains critical to ensuring transparency, equity, and physician oversight.

Physician sentiment toward AI is evolving. A 2024 AMA survey found that 66% of physicians now use AI tools, up from 38% in 2023, with 68% recognizing its advantages in clinical practice. However, challenges remain, including data privacy, liability concerns, and the need for evidence-based implementation.

AI’s potential extends beyond diagnostics, aiding in administrative efficiency, personalized treatment planning, and remote patient monitoring. As AI integration deepens, ensuring robust governance, cybersecurity, and responsible deployment will be essential in maximizing its benefits while minimizing risks.

Physicians and healthcare leaders must stay engaged in shaping AI’s role in medicine one that empowers clinicians, enhances care delivery, and ultimately improves patient outcomes.

Source: AMA

Patisiran(Onpattro) Shows Sustained Benefit in hereditary transthyretin amyloidosis(hATTR) Polyneuropathy

A Landmark 5-Year Study on RNAi Therapy

The longest study to date on patisiran (Onpattro) confirms its sustained benefit for hereditary transthyretin amyloidosis (hATTR) with polyneuropathy. Findings from a global open-label extension (OLE) of the APOLLO and Phase II trials reveal that patisiran stabilizes polyneuropathy and improves key clinical measures over five years.

Of 138 patients who completed the study, polyneuropathy disability remained stable in 55.5% and improved in 9.5%. Neuropathy Impairment Scores (NIS) increased by an average of 10.9 points, significantly lower than the 25.4-point worsening seen in the placebo group during the parent trial. Nutritional status, quality of life, and functional measures also improved.

Patisiran, an RNA interference (RNAi) therapeutic, targets transthyretin (TTR) mRNA, preventing the production of misfolded proteins that drive amyloid deposits. Despite its benefit in hATTR polyneuropathy, the FDA declined to expand its indication for ATTR cardiomyopathy in 2023.

Patients treated earlier in the APOLLO study had higher survival rates, with mortality rates per 100 patient-years of 3.3 compared to 12.8 in the placebo-first group. However, 22.3% of patients discontinued due to adverse events, most commonly infusion-related reactions.

Although limited by its open-label design and potential selection bias, this study reinforces the importance of early intervention in hATTR and highlights the long-term potential of RNAi therapeutics in medicine.

Source: JAMA

Cancer in 2025: A Rising Burden for Younger Adults and Women

Over 2 Million Diagnoses Expected, With Shifting Trends in Incidence

The American Cancer Society projects over 2 million new cancer cases and 618,000 deaths in the U.S. in 2025. While overall cancer mortality has declined 34% since 1991, thanks to reduced smoking, early detection, and better treatments, incidence rates are rising among younger adults and women.

For the first time, women under 65 have a higher lung cancer risk than men, despite historically lower smoking rates. Nonsmokers now account for a substantial proportion of lung cancer cases, making it a growing area of concern. Meanwhile, prostate, lung, and colorectal cancers will remain the most common in men, while breast, lung, and colorectal cancers will dominate in women.

Cancer incidence has increased in women ages 50 to 64, surpassing men in this age group. Younger women (under 50) now face an 82% higher incidence rate than males their age, largely driven by breast cancer and thyroid cancer.

Although cancer remains more common in older adults, its proportion in those under 50 has risen. The share of diagnoses in adults 65 and older has dropped from 61% to 59%, despite their growing population. Pancreatic cancer incidence and mortality continue to climb, making it the third leading cause of cancer-related deaths, with potential for further rise.

Cervical cancer rates in women ages 30 to 44 have increased, reversing a long-standing decline. However, young women vaccinated against HPV (ages 20-24) saw a 6% drop, reinforcing the vaccine’s impact in preventing disease.

With shifting trends and rising incidence in younger populations, early detection, prevention, and targeted interventions are more critical than ever.

Source: American Cancer Society

DOACs vs. Warfarin: A Safer, More Effective Choice for Afib in Valvular Heart Disease

New Study Strengthens Case for Direct Oral Anticoagulants

For patients with atrial fibrillation (AF) and valvular heart disease (VHD) excluding those with mechanical heart valves, direct oral anticoagulants (DOACs) outperformed warfarin in reducing the risks of stroke, systemic embolism, and bleeding, according to a recent study in The Journal of the American Heart Association.

In a large, real-world analysis of over 80,000 patients, treatment with rivaroxaban (Xarelto) and apixaban (Eliquis) significantly lowered the risk of stroke or embolism (HR 0.70), while all DOACs, including dabigatran (Pradaxa) and edoxaban (Savaysa), reduced bleeding risks (HR 0.72) compared to warfarin. The study excluded patients with mechanical heart valves and moderate to severe mitral stenosis, who remain advised to stay on warfarin based on existing guidelines.

This study reinforces the growing safety and efficacy data supporting DOACs for AF patients with a range of VHDs, including mitral regurgitation, aortic stenosis, tricuspid regurgitation, and bioprosthetic valves. Given that one-third of AF patients have some form of VHD, this shift in anticoagulation strategy could have a broad impact on clinical decision-making.

While the findings suggest a strong case for preferring DOACs over warfarin in eligible patients, further trials are needed to confirm these benefits across all types of VHD. As anticoagulation options evolve, personalized treatment decisions remain key in optimizing stroke prevention and bleeding risk.

Source: JAHA

Egg Allergy No Longer a Barrier to Vaccination

New Evidence Confirms Safety Across All Vaccines

Concerns about egg allergy and vaccines are officially a thing of the past. While some vaccines contain trace amounts of egg protein, new research confirms that none pose a risk to egg-allergic individuals, including those with a history of anaphylaxis.

For years, guidelines have advised that influenza vaccines can be given without regard to egg allergy, and now, the same applies to the yellow fever vaccine. In the largest study to date, 171 children with egg allergy including 24% with a history of anaphylaxis received the yellow fever vaccine without any allergic reactions, even after skin testing.

As a result, screening for egg allergy is no longer necessary before administering any vaccine. While vaccine providers should always be prepared for rare allergic reactions, no special precautions are required for egg-allergic recipients. This shift simplifies vaccination protocols, ensuring broader and safer access for all patients.

Source: UPTODATE

Study Links Lithium to Thyroid and Kidney Dysfunction

Lithium in Bipolar Disorder: Weighing the Risks

Lithium remains a first-line treatment for bipolar disorder, but new research highlights potential risks for thyroid and kidney dysfunction. A large retrospective cohort study from Hong Kong found that lithium use doubled the risk of hypothyroidism and increased the likelihood of chronic kidney disease (CKD) stage 3 or higher compared with non-lithium treatments.

The risks were dose-dependent, with higher serum lithium levels tied to increased dysfunction:

• Hypothyroidism risk increased at levels above 0.50 mEq/L

• Hyperthyroidism risk rose at levels above 0.50 mEq/L

• CKD stage 3 or higher was more likely at levels above 0.58 mEq/L

Interestingly, these thresholds fall within or even below the recommended therapeutic range for lithium maintenance, raising questions about optimal dosing for long-term treatment. However, no increased risk was observed for severe kidney disease, including end-stage renal failure.

While lithium is effective in preventing mood episode recurrence and reducing suicide risk, clinicians must balance these benefits against potential complications. The findings reinforce the importance of regular thyroid and kidney function monitoring to detect and manage issues early. Given that discontinuing lithium may increase the risk of relapse and hospitalization, treatment decisions should be tailored to each patient’s history and long-term needs.

Source: JAMA

FDA Issues Boxed Warning for Glatiramer Acetate Over Anaphylaxis Risk

The FDA has added a boxed warning to glatiramer acetate (Copaxone, Glatopa), a widely used multiple sclerosis (MS) treatment, due to rare but serious cases of anaphylaxis. This severe allergic reaction can occur at any time, from the first dose to years into treatment.

Between 1996 and 2024, 82 reported cases of anaphylaxis were linked to glatiramer acetate, with a median onset of 5 months after starting the drug. Six patients died, and over half required hospitalization, including intensive care in some cases. Symptoms typically appear within an hour of injection and may include wheezing, swelling of the face or throat, and hives, rapidly progressing to severe rash, shock, or respiratory failure.

Patients are advised to seek immediate emergency care if symptoms occur. The updated prescribing information reinforces the importance of early recognition and treatment with epinephrine. With more than 3 million patient-years of postmarket exposure, these cases remain rare, but healthcare providers should remain vigilant.

Source: FDA

Optimizing Ulcerative Colitis Treatment: Best Options After Anti-TNF Failure

Recent studies presented at the Crohn’s and Colitis Congress compared the effectiveness of ustekinumab (Stelara), vedolizumab (Entyvio), and Janus kinase (JAK) inhibitors in patients with ulcerative colitis who failed anti-TNF therapy.

A meta-analysis found no significant differences between ustekinumab and vedolizumab in terms of hospitalization rates, corticosteroid-free remission, or the need for surgical intervention. Researchers emphasized the need for further studies to determine predictive factors that could guide treatment selection.

Another study comparing JAK inhibitors to vedolizumab found similar clinical outcomes, with no major differences in steroid-free remission rates or overall clinical remission. This suggests JAK inhibitors could be as effective as vedolizumab for patients needing an alternative after anti-TNF failure.

However, when JAK inhibitors were compared to ustekinumab, they showed a higher likelihood of achieving endoscopic remission. This finding indicates that JAK inhibitors may be a superior option for some patients, offering better mucosal healing outcomes. Importantly, the incidence of adverse events did not differ significantly between the two treatment groups.

These findings highlight the expanding treatment landscape for ulcerative colitis, reinforcing the importance of personalized therapy selection based on patient response and clinical goals.

Source: Crohn's and Colitis Congress 2025

US Health Care Spending: Key Insights from a Decade of Data

Type 2 Diabetes Tops Spending, While County-Level Variations Reveal Inequities and Opportunities for Reform

A comprehensive study analyzing US health care spending from 2010 to 2019 has uncovered significant variations across health conditions, types of care, and counties. The research, which examined over 40 billion insurance claims and nearly 1 billion facility records, found that type 2 diabetes accounted for the highest spending at 143.9billion,followedbymusculoskeletaldisorders(143.9billion,followedbymusculoskeletaldisorders(108.6 billion), oral disorders (93billion),andischemicheartdisease(93billion),andischemicheartdisease(80.7 billion).

Key Findings:

• Ambulatory care represented the largest share of spending at 42.2%, while hospital inpatient care and prescribed retail pharmaceuticals accounted for 23.8% and 13.7%, respectively.

• At the county level, per capita spending ranged from 3,410 in ClarkCounty,Idaho,to 13,332 in Nassau County, New York, highlighting stark geographic disparities.

• Utilization rates (e.g., visits, admissions, prescriptions) drove more variation in spending across counties than differences in price or intensity of care.

Implications for Policy and Practice:
The study underscores the need to address unexplained variations in spending, particularly for high-cost conditions like type 2 diabetes. Policymakers can leverage these findings to:

• Target inefficiencies in care delivery.

• Improve access to primary and preventive care, reducing reliance on costly emergency services.

• Emulate best practices from low-spending, high-performing regions to optimize health outcomes and control costs.

Challenges and Limitations:
While the study provides unprecedented granularity, it excludes spending on durable medical equipment, Veterans Affairs, and other payers. Additionally, data sparsity and reliance on claims-based estimates may affect precision.

Conclusion:
This groundbreaking dataset offers a roadmap for reducing health care costs and improving equity across the US. By understanding local variations in spending and utilization, stakeholders can design targeted interventions to enhance care quality and affordability.

Source: JAMA

The Impact of Abortion Bans: Rising Birth Rates and Infant Mortality

Studies Reveal Disproportionate Impact on Marginalized Groups

After Roe v. Wade was overturned, states with strict abortion bans saw a rise in birth rates and infant mortality, according to two JAMA studies. The most affected were Black individuals, Medicaid recipients, and those without college degrees.

One study, led by Suzanne Bell, PhD, MPH, of Johns Hopkins, found that in 14 states with 6-week or complete bans, birth rates increased by 22,180 excess births beyond expected levels. Unmarried women, those under 35, and racially minoritized groups saw the largest spikes.

A second study, led by Alison Gemmill, PhD, reported 478 excess infant deaths in these states. The infant mortality rate rose 5.6% overall, with Black infants facing a nearly 11% higher increase.

This comes amid widespread obstetric unit closures, leaving expectant mothers with fewer resources. Bell noted that many were likely forced to carry unwanted or high-risk pregnancies, leading to adverse outcomes.

Texas, an early adopter of a 6-week ban, heavily influenced these results, with past research linking its policy to worsening maternal health. Experts stress the need for paid parental leave, Medicaid expansion, and better childcare access to mitigate harm.

While data alone may not change policy, researchers say these findings should drive discussions on maternal and infant health in the post-Roe era. More studies are needed to assess the long-term effects of these bans.

Source: JAMA

Upcoming Events & Deadlines

1. Society of Hospital Medicine (SHM): 22nd - 25th April, 2025

2. ACP 2025: April 3-5 New Orleans, LA

3. Chest 2025 submission deadline: Feb 26 2025

4. ACC 2025: March 29–31, 2025 in Chicago, IL

5. DDW 2025: May 3 - 6 San Diego, CA