Kidney Function Decline Identified as Key Mortality Risk Marker in Transthyretin Amyloid Cardiomyopathy: JAMA

UK: A recent retrospective cohort study has highlighted the critical role of kidney function in patients diagnosed with transthyretin amyloid cardiomyopathy (ATTR-CM). The findings, published in JAMA Cardiology, revealed that a decline in kidney function is not only common among these patients but also serves as a significant predictor of mortality, even after accounting for other well-established markers of disease progression.

“Declining estimated glomerular filtration rate (eGFR) serves as a standalone indicator of ATTR-CM disease progression, offering valuable insights for optimizing treatment strategies in clinical practice,” the researchers wrote.

ATTR-CM, a rare and progressive condition characterized by the deposition of amyloid fibrils in the heart, has traditionally been evaluated primarily through cardiac-specific parameters. Chronic kidney dysfunction is linked to poorer outcomes, yet the impact of changes in kidney function over time on prognosis remains unclear. To clarify the same, Adam Ioannou, National Amyloidosis Centre, Royal Free Hospital, University College London, London, United Kingdom, and colleagues aimed to evaluate the prognostic significance of a reduction in eGFR within a large cohort of patients with ATTR-CM.

For this purpose, the researchers conducted a retrospective, observational, single-center cohort study of patients diagnosed with ATTR-CM at the National Amyloidosis Centre (NAC) in the UK. The study included individuals who had a baseline eGFR assessment and a follow-up assessment at one year, spanning from January 2000 to April 2024, with data analyzed in June 2024.

The primary outcome was the association between a decline in kidney function, defined as a decrease in eGFR greater than 20%, and the risk of all-cause mortality.

Key Findings:

  1. Cohort Characteristics:
    • Among 2001 patients, the mean age was 75.5 years, with 13.1% females.
  2. Kidney Function Decline:
    • The median change in eGFR was −5 mL/min/1.73 m².
    • 24.0% (481 patients) experienced a decline in kidney function (defined as eGFR decrease >20%).
  3. Genotype and Cardiac Phenotype:
    • Patients with kidney function decline more frequently had the p.(V142I) genotype (20.6% vs. 13.3%).
    • They exhibited more severe cardiac involvement at baseline, indicated by:
      • Higher median NT-proBNP levels (2949 pg/mL versus 2309 pg/mL).
      • Higher median troponin T levels (0.060 ng/mL versus 0.052 ng/mL).
  4. Baseline Kidney Function:
    • The baseline eGFR of those with and without kidney function decline was similar (63 versus 61 mL/min/1.73 m²).
  5. Mortality Risk:
    • The decline in kidney function was associated with a 1.7-fold increased risk of mortality (HR, 1.71).
    • This risk was consistent across the following:
      • Genotypes:
        • Wild type: HR, 1.64.
        • p.(V142I): HR, 1.70.
        • Non-p. (V142I): HR, 1.51.
      • NAC disease stages:
        • Stage 1: HR, 1.69.
        • Stage 2: HR, 1.69.
        • Stage 3: HR, 1.61.
  6. Independent Association with Mortality:
    • After adjusting for increases in NT-proBNP and outpatient diuretic intensification, the decline in kidney function remained an independent predictor of mortality (HR, 1.48).

In the large cohort of patients with ATTR-CM, a decline in kidney function was a common occurrence and consistently linked to an increased risk of mortality, even after accounting for established markers of cardiac disease progression. Incorporating kidney function decline as an endpoint in contemporary trials could help identify clinically significant and potentially modifiable events earlier in the disease course.

“Combining kidney function decline with established markers such as NT-proBNP progression and outpatient diuretic intensification offers a straightforward and universally applicable model. This approach integrates multiple aspects of the cardiorenal axis into a single scoring system, enabling better identification of patients with rapid ATTR-CM progression who face the highest mortality risk,” the researchers concluded.

Reference:

Ioannou A, Razvi Y, Porcari A, et al. Kidney Outcomes in Transthyretin Amyloid Cardiomyopathy. JAMA Cardiol. Published online November 17, 2024. doi:10.1001/jamacardio.2024.4578

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Melatonin Supplementation Shows Promise for Managing Diabetic CKD: A New Randomized Trial Investigates Its Effects

Iran: A new study published in the BMC journal Trials is exploring the potential benefits of melatonin supplementation for patients with diabetic chronic kidney disease (CKD). The double-blind, randomized controlled trial aims to investigate the effects of melatonin on key metabolic parameters, oxidative stress, and inflammatory biomarkers, which are often elevated in individuals suffering from diabetes and kidney disease.

Diabetic CKD is a serious and growing health issue characterized by a decline in kidney function due to the damaging effects of diabetes. It is often associated with increased oxidative stress, inflammation, and disruptions in lipid metabolism, all of which exacerbate the disease progression. Current treatment options primarily focus on managing blood sugar levels and slowing kidney function decline, but additional therapies are needed to address the broader metabolic disturbances seen in these patients.

Melatonin, a hormone naturally produced by the pineal gland, is best known for regulating sleep-wake cycles. However, emerging research suggests melatonin may also have potent antioxidant and anti-inflammatory properties. Given these potential benefits, Hossein Imani, Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran, and colleagues hypothesize that melatonin supplementation could help mitigate the metabolic and oxidative dysfunctions associated with diabetic CKD.

For this purpose, the researchers are conducting a double-blind, randomized, placebo-controlled clinical study to investigate the effects of melatonin supplementation in diabetic patients with chronic kidney disease (CKD). Laboratory assessments will be used to diagnose diabetic CKD in the participants. Forty-eight eligible diabetic patients with CKD will be selected and randomly assigned to receive either 5 mg melatonin tablets or an identical placebo twice daily for 10 weeks. Throughout the study, participants will be asked to maintain their usual diet and physical activity levels.

The study’s primary outcome is to evaluate changes in oxidative stress and inflammatory biomarkers. Secondary outcomes include assessing changes in lipid profiles, renal function indicators, fasting blood sugar levels, serum insulin levels, and systolic and diastolic blood pressure (SBP and DBP). Other secondary measures will include serum phosphorus concentration, sleep quality, body weight, body mass index (BMI), and waist circumference (WC).

Statistical analysis will be performed using SPSS software (version 25) to determine the significance of the results.

The researchers note that diabetic kidney disease, a leading cause of end-stage renal disease (ESRD), progresses more rapidly in diabetic patients compared to non-diabetic CKD. Preventing progression to ESRD can improve a patient’s quality of life. Melatonin, a natural antioxidant, has shown promise in protecting against various pathophysiological conditions by scavenging free radicals and modulating apoptosis.

“Animal studies suggest melatonin can reduce oxidative stress, inflammation, and lipid peroxidation in the kidneys, improving metabolic parameters and kidney function. Despite numerous experimental studies, clinical trials on melatonin’s efficacy in DKD patients are limited, highlighting the need for further human studies to explore its potential benefits,” they concluded.

Reference:

Sadeghi, S., Hakemi, M.S., Pourrezagholie, F. et al. Effects of melatonin supplementation on metabolic parameters, oxidative stress, and inflammatory biomarkers in diabetic patients with chronic kidney disease: study protocol for a double-blind, randomized controlled trial. Trials 25, 757 (2024). https://doi.org/10.1186/s13063-024-08584-x

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Systemic inflammation may play role in association between skin disease severity and CVD in psoriasis: JAMA

Sweden: A recent study has shed light on the intricate relationship between psoriasis, systemic inflammation, and cardiovascular disease (CVD), highlighting the interconnected nature of these health issues. Psoriasis, a chronic inflammatory skin condition, has long been recognized for its impact on skin health, but this research underscores its broader implications, particularly concerning cardiovascular risks.

The study, published in JAMA Dermatology, revealed that psoriasis severity, measured by the Psoriasis Area and Severity Index (PASI), was linked to systemic inflammation. Additionally, PASI and systemic inflammation, assessed through GlycA levels, were connected to CVD, with systemic inflammation potentially mediating the relationship between PASI and CVD.

Psoriasis is linked to an elevated risk of cardiovascular disease, though the precise mechanisms driving this connection remain uncertain. Understanding these pathways could aid in developing targeted treatments and provide insight into how peripheral inflammation, like psoriatic skin lesions, contributes to CVD. With this in mind, Axel Svedbom, Dermatology and Venereology Clinic, Karolinska University Hospital, Stockholm, Sweden, and colleagues aimed to investigate whether systemic inflammation mediates the relationship between psoriasis severity and CVD.

For this purpose, the researchers analyzed data from two cohorts: the PACI (2013–2022) in Maryland and the SPC (2000–2005) in Sweden. PACI included patients with prevalent psoriasis referred by dermatologists, while SPC included incident psoriasis cases from various practices. Psoriasis severity was assessed using PASI, and systemic inflammation was measured via GlycA, a glycan biomarker of acute-phase proteins.

Mediation analysis examined associations between PASI, systemic inflammation, and outcomes like noncalcified coronary burden (NCB) and cardiovascular events. Data analysis from October 2023 to January 2024 explored how systemic inflammation might mediate the link between psoriasis severity and cardiovascular risk.

Based on the study, the researchers reported the following findings:

  • Of 260 eligible patients in the PACI cohort, 62.3% were male, with a median age of 51.
  • Of 509 eligible patients in the SPC cohort, 46.6% were male, with a median age of 43.
  • PASI was associated with GlycA levels and cardiovascular disease in both studies.
  • GlycA levels were independently associated with CVD.
  • The direct effect of PASI on noncalcified coronary burden (NCB) was 0.94.
  • The indirect effect of PASI on NCB via GlycA was 0.19.
  • The odds ratio for the direct effect of PASI on cardiovascular events was 1.23.
  • The odds ratio for the indirect effect of PASI on cardiovascular events via GlycA was 1.16.

“The findings indicate that systemic inflammation, assessed through GlycA levels, may mediate the relationship between psoriasis severity, measured by PASI scores, and cardiovascular disease in individuals with psoriasis. Further research could investigate whether managing skin disease severity helps reduce subclinical atherosclerosis and the risk of cardiovascular events,” the researchers concluded.

Reference:

Svedbom A, Mallbris L, González-Cantero Á, et al. Skin Inflammation, Systemic Inflammation, and Cardiovascular Disease in Psoriasis. JAMA Dermatol. Published online November 20, 2024. doi:10.1001/jamadermatol.2024.4433

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Semaglutide associated with Nonarteritic Anterior Ischemic Optic Neuropathy: JAMA

Nonarteritic anterior ischemic optic neuropathy (NAION) is
the second most common form of optic neuropathy and a significant cause of
blindness among adults. Authors’ anecdotal clinical experience motivated them
to study whether semaglutide is associated with an increased risk of developing
NAION.

Semaglutide (Ozempic; Novo Nordisk) was approved by the US
Food and Drug Administration (FDA) in December 2017 to treat type 2 diabetes
(T2D) and in December 2022 to treat obesity (typically at higher doses, as
Wegovy [Novo Nordisk]). Weekly new-to-brand prescriptions in the United States
of these and other glucagon-like peptide receptor agonist (GLP-1 RA) drugs increased
by approximately 60% from 2021 to 2023.

In major medical centers, neuro-ophthalmologists are most
likely to evaluate suspected cases of NAION. This study was designed to
capitalize on this expertise by characterizing the risk of NAION among
individuals using semaglutide within a neuro-ophthalmology practice at a single
academic center.

In a retrospective matched cohort study using data from a
centralized data registry of patients evaluated by neuro-ophthalmologists at 1
academic institution from December 1, 2017, through November 30, 2023, a search
for International Statistical Classification of Diseases and Related Health
Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text
search yielded 16 827 patients with no history of NAION. Propensity matching
was used to assess whether prescribed semaglutide was associated with NAION in
patients with type 2 diabetes (T2D) or overweight/obesity, in each case
accounting for covarying factors (sex, age, systemic hypertension, T2D,
obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease)
and contraindications for use of semaglutide. The cumulative incidence of NAION
was determined with the Kaplan-Meier method and a Cox proportional hazards
regression model adjusted for potential confounding comorbidities. Data were
analyzed from December 1, 2017, through November 30, 2023.

Among 16 827 patients, 710 had T2D (194 prescribed
semaglutide; 516 prescribed non–GLP-1 RA antidiabetic medications; median [IQR]
age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361
prescribed semaglutide; 618 prescribed non–GLP-1 RA weight-loss medications;
median [IQR] age, 47 [32-59] years; 708 [72%] female).

In the population with T2D, 17 NAION events occurred in
patients prescribed semaglutide vs 6 in the non–GLP-1 RA antidiabetes cohort.

The cumulative incidence of NAION for the semaglutide and
non–GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95%
CI, 0%-3.5%), respectively.

A Cox proportional hazards regression model showed higher
risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95%
CI, 1.62-11.29); P < .001).

In the population of patients who were overweight or obese,
20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the
non–GLP-1 RA cohort.

The cumulative incidence of NAION for the semaglutide vs
non–GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95%
CI, 0%-1.8%), respectively.

A Cox proportional hazards regression model showed a higher
risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI,
2.21-26.36; P < .001).

This study is the first to report an association between
semaglutide and NAION, although the design of study did not enable query into a
causal relationship between the two. The best approaches to confirm, refute, or
refine findings would be to conduct a much larger, retrospective, multicenter
population-based cohort study; a prospective, randomized clinical study; or a
postmarket analysis of all GLP-1 RA drugs. A risk inherent in larger studies,
however, is the standard use of ICD-10 diagnostic codes given that there is no
ICD-10 code for NAION. The most specific code relevant to NAION is the broader
category of ischemic optic neuropathy. SThe manual review of records for this
study revealed that 40% of cases coded as ischemic optic neuropathy were not
actually NAION but rather arteritic ischemic optic neuropathy from giant cell
arteritis (which is commonly managed by neuro-ophthalmologists) or other forms of
ischemic or nonischemic optic neuropathies.Manual review is not practical for
extremely large databases, and the lack of a specific ICD-10 code for NAION (as
identified by Hamedani et al31) would be a severe hindrance for any large
study. Emerging algorithms would improve the accuracy of diagnostic coding in
larger studies but would not attain the precision of a manual review and might
not provide sufficient accuracy to establish a statistical association between
use of a drug and occurrence of a relatively uncommon disorder like NAION.

Source: Jimena Tatiana Hathaway, MD, MPH; Madhura P. Shah,
BS; David B. Hathaway, MD; JAMA Ophthalmol.
doi:10.1001/jamaophthalmol.2024.2296

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Risk of internal bleeding doubles among patients receiving anticoagulants and NSAID painkillers: Study

“For people taking blood thinners for blood clots in their legs or lungs, our research highlights the importance of being cautious when considering NSAIDs for pain or inflammation. We recommend that patients consult their doctor before taking NSAIDs along with a blood thinner.”

In an accompanying editorial [2] Professor Robert F Storey from the University of Sheffield, UK, said: “Oral anticoagulants (OACs), including vitamin K antagonists (VKAs) such as warfarin and the direct-acting oral anticoagulants (DOACs) apixaban, dabigatran, edoxaban, and rivaroxaban, are central to the treatment and prevention of a range of thrombotic conditions, including venous thromboembolism (VTE), a term encompassing deep vein thrombosis and pulmonary embolism.

“All currently available OACs increase the risk of bleeding. In the management of VTE, a significant proportion of patients are recommended long-term OAC, meaning that cumulative risk can be considerable. OAC-related bleeding can range from events that are usually termed trivial, for example superficial bruising or gum bleeding, through to major bleeding, associated with significant disability or even death.

“NSAIDs are very commonly used for their analgesic, antipyretic, and anti-inflammatory properties. Making up 8% of prescriptions worldwide, but also available without prescription, they are consumed in huge quantities every year.

“It seems clear that avoiding NSAIDs in combination with OAC is the safest strategy to avoid excess bleeding risk. However, if this is not possible, what mitigation can be put in place? NSAID prescription should obviously be at the lowest dose and for the shortest time possible, but choice of agent and route may also be important.

“An episode of VTE mandates initiation of anticoagulation, usually an OAC, in all but the rarest of circumstances. However, when doing so, physicians must consider the full context of a patient’s bleeding risk factors, including NSAID use. It is important to appropriately counsel the patient, consider alternatives to NSAIDs, including non-pharmacological therapies, and pursue all possible mitigation strategies to reduce the chance of an adverse outcome.”

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Nonguided implant placement approach okay for placement of One-piece mini-implants to support mandibular overdenture: Study

Nonguided implant placement approach okay for placement of One-piece mini-implants to support mandibular overdenture suggests a study published in the Clinical Oral Implants Research.

A study was done to assess the relative position of mini-implants to retain a mandibular overdenture, according to the surgical protocol, technical and anatomical factors.Mandibular cone-beam computed tomography (CBCT) scans were analyzed for 73 patients who received four one-piece titanium-zirconium mini-implants. Drilling was performed using a 1.6 mm needle drill and a 2.2 mm Pilot Drill, according to the bone density with a surgical stent. Post-insertion CBCT images in DICOM format were analyzed using the E-Vol-DX software with BAR filters. Divergence angle between implants and between implants and the overdenture path of insertion was measured using CliniView 10.2.6 software. Results: Divergence between implants ranged from 0° to 22.3° (mean = 4.2; SD = 3.7) in the lateral and from 0° to 26.2° (mean = 5.3; SD = 4.1) in the frontal projections (p < .001). Only 1 (0.2%) and 3 (0.7%) of the measurements were higher than 20° in the lateral and frontal views, respectively. The mean angulations between the implant and the path of insertion for the overdenture were 9.3° (SD = 7.5) and 4.0° (SD = 2.9) for the lateral and frontal views, respectively (p < .001). Regression analyses showed a significant association between the divergence of implants and the frontal view projection (p < .001), greater distance between the paired implants (p = .017), the flapped surgical protocol (p = .002), higher final insertion torque (p = .011), and deeper preparation with the needle drill (p < .001). The mini-implants were placed with low divergence angles and satisfactory parallelism. Factors including shorter distances between the implants, higher density bone, and a flapless surgical approach all contributed positively to improved parallelism of the mini-implants.

Reference:

Leles, C. R., de Oliveira Moura-Neto, L., Silva, J. R., Nascimento, L. N., Curado, T. F. F., Costa, N. L., Schimmel, M., & McKenna, G. (2024). A cross-sectional CBCT assessment of the relative position of one-piece titanium-zirconium mini-implants placed for mandibular overdentures using non-guided surgery. Clinical Oral Implants Research, 00, 1–10. https://doi.org/10.1111/clr.14335

Keywords:

Nonguided, implant, placement, approach, okay, placement, One-piece, mini-implants, support, mandibular, overdenture, study, Clinical Oral Implants Research, Leles, C. R., de Oliveira Moura-Neto, L., Silva, J. R., Nascimento, L. N., Curado, T. F. F., Costa, N. L., Schimmel, M., & McKenna, G.

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Gujarat Junior Doctors on Strike demanding stipend hike, Pending Arrears

Bhuj: The resident doctors at Gujarat Adani Institute of Medical Sciences (GAIMS) and GK General Hospital, Bhuj, have been on strike for the last four days over their demands for payment of the pending arrears and an increase in their monthly stipends.

These doctors have urged the authorities for an immediate increment of stipends for junior and intern doctors, in line with Gujarat government guidelines. Further, they have also requested the release of arrears along with the November stipend for all the affected doctors, effective from April 2024.

In every three years, the stipend for the MBBS interns and resident doctors is revised and increased. According to this rule, the doctors should have been given a stipend hike from April. However, this time, they have been given increments from October, sources at the Institute informed Medical Dialogues.

Writing to the authorities, the doctors referred to the NMC notification dated 6th September, 2023 (Post Graduate Medical Education Board – PGMEB, Clause 5.5), which mentions that “The post-graduate students undergoing post-graduate degree/Diploma/Super-Speciality course in all institutions shall be paid stipend at par with the stipend being paid to post-graduate students of State Government medical institutions in the State/Union Territory where the institution is located.”

Also Read: Gujarat: Thousands of Resident Doctors Cease Work demanding stipend hike

They also relied on NMC UG Medical Education Board Directive dated 22nd April 2021 (Draft Regulations for CRMI 2021). Clause 6.3 of the said Regulations states that ‘All Interns shall be paid a stipend as fixed by appropriate fee fixation authority applicable to the institution/university/state.”

Further, the doctors pointed out that a Gujarat Government directive clearly outlines that the stipend structure for State Government medical institutions shall serve as a benchmark for other institutions in the State, including private entities.

While this is the 4th day of strike, sources at the institute informed Medical Dialogues that the students are yet to receive any positive response from the Adani management. Today, the representatives from the medical college also went to discuss the issue with the Health Secretary. 

Meanwhile, the Federation of Resident Doctors Association (FORDA) has extended its support to the protesting medicos at GAIMS, Bhuj. Raising the issue, the association wrote in its X (formerly Twitter handle), “A clear defiance of the #Gujarat state MER & #NMC guidelines- @AdaniOnline owned #GAIMS not giving revised stipend & arrears to its Resident doctors. Is money a problem at @AdaniFoundation? Very strange! You can’t flourish if you treat your own like that!”

The National Secretary of FORDA India, Dr. Meet Gohnia, wrote in an X post, “Resident & Intern Doctors of GAIMS, Bhuj are on indefinite strike from last 3 days regarding non payment of revised stipend & arrears as per rules of Government of Gujarat. Stipend as per government rule is right of Doctors & Management should fulfill this. Request to @NMC_BHARAT @CMOGuj to look into this matter. We stand with Resident & Intern Doctors of GAIMS.”

The Resident Doctors’ Association (RDA) at PGIMS, Rohtak has also extended its support to the GAIMS medicos. It wrote, “@CMOGuj #nmc should to do right by the students We stand with @FordaIndia and residents of #GAIMS for their determination to raise voice!!!!”

Also Read: Rajasthan: 7000 resident doctors strike for stipend increase, bond policy changes, workplace safety

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First new treatment for asthma attacks in 50 years

An injection given during some asthma and COPD attacks is more effective than the current treatment of steroid tablets, reducing the need for further treatment by 30%. The findings, published in The Lancet Respiratory Medicine, could be “game-changing” for millions of people with asthma and COPD around the world, scientists say.

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Certain hormone replacement therapy tablets linked to increased heart disease and blood clot risk

Certain hormone replacement therapy (HRT) tablets containing both estrogen and progestogen are associated with a higher risk of heart disease and rare but serious blood clots known as venous thromboembolism (VTE) in women around the age of menopause, finds a study from Sweden published in The BMJ today.

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Talk therapy and rehabilitation may improve long COVID symptoms, but effects are modest

Cognitive behavioral therapy (CBT) and a program of physical and mental rehabilitation probably improve symptoms of long COVID, but the effects are modest, finds a review of the latest evidence published in The BMJ.

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