Study identifies high BP and triglycerides as risk factors for IgA nephropathy

China: A recent Mendelian randomization (MR) study published in Frontiers in Medicine has shed light on the causal effect of high blood pressure (BP) and triglyceride (TG) on IgA nephropathy.

The study revealed high BP and triglyceride as risk factors causally connected with immunoglobulin A nephropathy (IgAN), of which high BP was strongly related to IgAN onset.

Results from previous research indicate that both TG and high BP have strong correlations with IgAN. However, there is no clarity if there is a direct causal effect of triglycerides and high blood pressure on IgAN.

High blood pressure and hyperlipidemia are common complications of renal dysfunction in IgAN. Although its exact cause is unknown, recent research indicates that high BP and triglycerides may play a causal role in IgAN.

Against the above background, Yijun Yan, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, and colleagues aimed to explore the causalities between HBP and TG, and IgAN based on MR analysis.

For this purpose, the researchers sourced from genome-wide association study (GWAS) summary data of IgAN (GCST90018866) and two exposure factors, TG (ukb-d-30870_raw) and HBP (ukb-a-437), from the GWAS Catalog and Integrative Epidemiology Unit (IEU) OpenGWAS databases, respectively.

Five methods were utilized to perform MR analysis after taking out single nucleotide polymorphisms (SNPs) as instrumental variables, including MR-Egger, weighted mode, weighted median, simple mode, and inverse variance weighted (IVW), followed by the sensitivity analysis containing the heterogeneity, horizontal pleiotropy test, and leave-one-out (LOO) analysis. Finally, the researchers performed the enrichment analysis and interaction network construction of genes corresponding to SNPs of high BP and TG.

The study led to the following findings:

  • The univariate MR results revealed that high BP and TG regarded as risk factors were causally related to IgAN based on random-effect IVM method, of which TG had a weaker impact.
  • The reliability of these univariate MR results was certified by the sensitivity analysis, in which there was no horizontal pleiotropy and exaggerated influence of each SNP.
  • High BP was markedly causally related to IgAN with the help of multivariate MR analysis, rather than TG. Therefore, when HBP and TG occur simultaneously, HBP is a direct influencing factor on IgAN.
  • A total of 208 and 153 genes separately corresponding to SNPs of TG and HBP were included in enrichment analysis, and thereinto, genes relevant to TG were mainly enriched in lipid homeostasis and cholesterol metabolism, while genes concerned with HBP played their roles in the regulation of cell growth, aldosterone synthesis and secretion and so forth.

In conclusion, the results showed a causal effect of triglyceride and high BP on IgAN, both of them are risk factors, and HBP is the direct influencing factor of IgAN.

“Since the sample data used in this study originated in East Asia and Europe, the causality currently applies only to these regions. Enrichment analysis of genes corresponding to SNPs of TG and high BP might spark interest in further molecular biological mechanism investigation in IgAN,” the researchers wrote.

Reference:

Yang, Y., Li, Y., Feng, X., Ding, C., Zhang, J., & Liu, Z. (2024). The causal effect of triglyceride and high blood pressure on IgA nephropathy: A Mendelian randomization study. Frontiers in Medicine, 11, 1338462. https://doi.org/10.3389/fmed.2024.1338462

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Early intervention after first seizure prevents long-term epilepsy and associated cognitive deficits: Study

Only a very small percentage of neurons show changes after an epileptic seizure in mice, but these alterations can be permanent and trigger future seizures that can affect the whole brain and lead to impaired cognition, like memory and learning, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The researchers identified an experimental treatment that, if provided within the first 48 hours after the first seizure, can prevent these long-term changes. The findings, which were published recently in The Journal of Clinical Investigation, suggest a promising target for developing treatments for epilepsy and preventing downstream effects of seizures.

Epilepsy is characterized by excessive activity of brain cells-neurons-which generate seizures. Research is increasingly showing that the development of epilepsy involves changes of synapses, which are structures that connect one neuron to another. While an estimated 3.4 million people in the United States live with some form of epilepsy, it is still unknown what causes it, and there is no cure. Further, half of individuals with epilepsy experience cognitive impairment, such as problems with memory, or with emotional regulation, but it remains unclear why or how epilepsy changes brain cells to cause this. What’s more, epilepsy is common in children with autism and individuals with dementia.

“It is clear that there is some connection between an epileptic brain, impaired memory and trouble controlling emotions and how we act on those feelings, but we don’t understand the underlying mechanisms,” said Frances E. Jensen, MD, chair of the Department of Neurology, and senior author of the study. “Existing treatments for epilepsy only help manage seizures. This research gives us a promising starting point for developing therapies that prevent them from happening.”

In this study, the researchers used a method that “tagged” neurons in the hippocampus-an area commonly affected by epilepsy, and critical for memory-of mice that were activated by epileptic activity. The researchers were able to monitor those activated neurons over time and observe how they responded to subsequent seizures. They found that only about twenty percent of neurons in the hippocampus were activated by seizures. Over time, the overactivity of these neurons diminished their ability to make connections with other neurons, called synapses, which is necessary for learning.

“The overactive neurons lose their ability to build the strong synapses necessary for learning, which may explain why some people with epilepsy have trouble with learning and with memory,” said Jensen. “If we can stop these neurons from undergoing changes after being activated by seizures, our hope is that we can also prevent not only the progression of epilepsy, but also avoid these cognitive deficits individuals experience long-term.”

To see if they could prevent neurons from becoming permanently epileptic, the researchers used an experimental glutamate receptor-blocker, called IEM-1460, which has been shown to reduce neuron hyperexcitability in models of mice with epilepsy. They found when they treated mice with this blocker in the first 48 hours after their very first seizure the neurons did not become permanently activated, and the subjects did not experience future seizures or the associated effects, like impaired cognition and trouble learning.

“Now that we have identified the subgroup of neurons that are impacted by epilepsy, we can investigate what makes these cells vulnerable to becoming epileptic, and whether that is something we can develop a therapy to stop,” said Jensen. “We are also eager to determine whether there is a glutamate receptor-blocker that works similarly to IEM-1460 in humans, which could be given to people after their first seizure, and prevent the lifelong struggles associated with epilepsy.”

Reference:

Bo Xing, Aaron J. Barbour, Joseph Vithayathil, Xiaofan Li, Sierra Dutko, Jessica Fawcett-Patel, Eunjoo Lancaster, Delia M. Talos, and Frances E. Jensen, Reversible synaptic adaptations in a subpopulation of murine hippocampal neurons following early-life seizures, Journal of Clinical Investigation, DOI:10.1172/JCI175167.

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SGLT2 inhibitors clinically beneficial in patients with gout, suggests review

USA: Sodium-glucose cotransporter type 2 (SGLT2) inhibitors may provide improved outcomes in treating gout and its common comorbidities, a recent review has shown. SGLT2 inhibitors are a popular drug class in the management of cardiometabolic and diabetic conditions.

The review, published in Nature Reviews Rheumatology, suggested that the mechanism of SGLT2 inhibition in patients with arthritic disease could provide anti-inflammatory benefits while reducing the risk of renal and cardiovascular outcomes in such patients—as the drug class is already indicated to treat.

Chio Yokose, Massachusetts General Hospital, Boston, MA, USA, and colleagues described the characteristics of gout and its most common comorbidities.

They noted that gout is the most common form of inflammatory arthritis worldwide, which is characterized by painful recurrent flares of inflammatory arthritis and is associated with a transiently increased risk of adverse cardiovascular events. Furthermore, gout is associated with various cardiometabolic–renal comorbidities such as chronic kidney disease (CKD), type 2 diabetes, and cardiovascular disease (CVD). These comorbidities, potentially combined with gout flare-related inflammation, contribute to persistent premature mortality in gout, independently of traditional cardiovascular risk factors and serum urate concentrations.

The researchers add, “Although better implementation of standard goud care could improve gout outcomes, there is a need for deliberate efforts to address the CV risk in gout patients to reduce mortality.”

SGLT2 inhibitors are approved for multiple indications owing to their ability to lower the risk of hospitalizations for heart failure and CKD, all-cause, and cardiovascular death, making them an attractive treatment option for gout. These medications have been also shown to reduce serum urate concentrations, the causal culprit in gout risk, and are linked with a reduced risk of incident and recurrent gout, potentially due to their anti-inflammatory effects. Thus, SGLT2 inhibition could simultaneously address both gout symptoms and its comorbidities.

According to the authors, this is not the first analysis to consider a potential role in gout management for the SGLT2 inhibitor class.

A study presented during the European Congress on Rheumatology (EULAR) 2023 meeting in May 2023 showed initiating an SGLT2 inhibitor significantly lowered the risk of incident gout among at-risk patients with type 2 diabetes, compared to other drug classes, including GLP-1 receptor agonists (HR, 0.39), DPP-4 inhibitors (hazard ratio [HR], 0.54), and sulfonylurea (HR, 0.61).

These promising clinical data come with the disclosure that researchers are still seeking to understand the anti-gout and urate-lowering properties of SGLT2 inhibitors, Yokose, and colleagues noted. They suggested such mechanisms may be due to enhanced uricosuria and anti-inflammatory pathways in SGLT2 inhibition.

“Although additional research is needed to determine SGLT2 inhibitors’ role in gout management, available evidence indicates that these drugs have the potential to improve outcomes among gout patients,” the researchers concluded.

Reference:

Yokose, C., McCormick, N., Abhishek, A., Dalbeth, N., Pascart, T., Lioté, F., Gaffo, A., FitzGerald, J., Terkeltaub, R., Sise, M. E., Januzzi, J. L., Wexler, D. J., & Choi, H. K. (2024). The clinical benefits of sodium–glucose cotransporter type 2 inhibitors in people with gout. Nature Reviews Rheumatology, 20(4), 216-231. https://doi.org/10.1038/s41584-024-01092-x

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FDA clears rapid PCR test for sore throat and respiratory infections

The US Food and Drug Administration has granted 510(k) clearance to bioMerieux for a rapid respiratory/sore throat panel. The test will help clinicians make more informed decisions about antibiotic prescribing.

The new PCR test is capable of detecting upto 15 most common bacteria, viruses, and viral subtypes that cause respiratory or sore throat infections in about 15 minutes from samples taken from nasopharyngeal and throat swabs.

The COVID-19 pandemic has demonstrated the need for healthcare professionals to have diagnostic tests available as close as possible to the patient, providing actionable results quickly. A fast and innovative syndromic testing range, BIOFIRE  SPOTFIRE  perfectly matches these new medical needs worldwide.

The BIOFIRE  SPOTFIRE  R/ST Panel is a unique multiplex PCR1 test capable of detecting and identifying nucleic acids from up to 15 of the most common bacteria, viruses, and viral subtypes responsible for respiratory or sore throat infections in about 15 minutes. Samples can be taken from a nasopharyngeal swab when a respiratory tract infection is suspected, or from a throat swab in case of a pharyngitis syndrome.

“To prescribe or not to prescribe antimicrobials is the age-old question for outpatient upper respiratory infections. The flexibility of this syndromic panel allows healthcare professionals to test for multiple pathogens with overlapping signs and symptoms, ultimately allowing the diagnostic to drive informed decision-making during the outpatient visit. These results further empower the advancement of antimicrobial stewardship and modernize patient care.” declared Dr Charles K. Cooper, Executive Vice-President, Chief Medical Officer, bioMérieux

The BIOFIRE SPOTFIRE R/ST Panel is the third panel to receive FDA clearance for use on the BIOFIRE® SPOTFIRE® System. The two other panels available for use on this system are the BIOFIRE  SPOTFIRE  Respiratory (R) Panel and BIOFIRE® SPOTFIRE® Respiratory (R) Panel Mini, detecting 15 and 5 of the most common respiratory pathogens respectively.

A CLIA-waiver allows the BIOFIRE  SPOTFIRE  System and its so-authorized panels to be used by non-lab professionals and in any clinical setting where patients seek care including an urgent care, physician office, local pharmacy, student health clinic, or an emergency department.

“Receiving FDA clearance for the BIOFIRE  SPOTFIRE  R/ST Panel, just one year after the successful launch of the BIOFIRE  SPOTFIRE  solution, marks another milestone in our mission to move testing closer to the patient,” said Jennifer Zinn, Executive Vice President, Clinical Operations, bioMérieux. “With our innovative approach, we are committed to enhancing patient care by providing healthcare professionals with the tools they need to deliver expedited and effective diagnoses. Together, we are revolutionizing the landscape of healthcare, one diagnosis at a time.”

The BIOFIRE  SPOTFIRE  R/ST Panel is currently CE-marked under IVDD (In Vitro Diagnostic Directive) and has been submitted for CE-marking under IVDR (In Vitro Diagnostic Regulation).

bioMérieux will also submit the BIOFIRE  SPOTFIRE  Respiratory / Sore Throat (R/ST) Panel Mini to the FDA for review for a 510(k) clearance. This panel is intended to detect and identify nucleic acids from 5 of the most common viral and bacterial causes of respiratory tract infections from either a nasopharyngeal or throat swab respectively. The BIOFIRE  SPOTFIRE  R/ST Panel Mini is not yet available for sale.

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Prices Of Essential Medicines To Rise Slightly From April 1

New Delhi: A slight hike in the price of essential medicines, such as painkillers, antibiotics, and anti-infectives, is set to take place on April 1st, in line with the change observed in the Wholesale Price Index (WPI) between 2022 and 2023.

Through a recent notification, the National Pharmaceutical Pricing Authority (NPPA) has declared to permit the pharmaceutical sector to increase the Maximum Retail Price (MRP) of scheduled formulations by approximately 0.00551% at the start of the fiscal year 2024-25, considering the change observed in the Wholesale Price Index (WPI) between 2022 and 2023.

As a consequence, beginning on April 1, there may be a slight spike in the cost of essential medicines such as painkillers, antibiotics, and others.

The notice stated,

‘Based on the Wholesale Price Index (WPI) data provided by the office of the Economic Advisor, Department of Industry and Internal Trade Ministry of Commerce and Industry, the annual change in WPI works out as (+) 0.00551% during the calendar year 2023 over the corresponding period in 2022.”

In continuation, it is worth notifying that in accordance with Paragraph 16(2) of the Drug Price Control Order (DPCO) 2013, the manufacturers may increase the maximum retail price (MRP) of scheduled formulations once a year, in the month of April, on the basis of the wholesale price index with respect to previous calendar year and no prior approval of the Government in this regard shall be required.

Therefore in light of the above, the notice further added,

“As per provisions of Paragraph 16(2) of Drug Price Control order (DPCO) 2013, the manufacturers may increase the Maximum Retail Price (MRP) of scheduled formulations on the basis of this WPI and no prior approval of the government in this regard shall be required.”

The previous year, the Medical Dialogues Team reported that based on the Wholesale Price Index (WPI) data provided by the Office of the Economic Advisor, Department of Industry and Internal Trade, Ministry of Commerce and Industry, the annual change in the WPI worked out as 12.1218% during the calendar year 2022 over the corresponding period in 2021.

To view the official notice, click the link below:

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Hair-straightening products linked to acute kidney failure risk: Research

In the pursuit of beauty, there can be unexpected risks. Recent research has uncovered a concerning connection between hair-straightening products and kidney health. French researchers have unveiled a disturbing link between these popular cosmetic items and acute kidney failure, shedding light on a potentially overlooked health hazard. Their findings, published in The New England Journal of Medicine, reveal a troubling association between glyoxylic acid—a common ingredient in these products—and the formation of calcium oxalate crystals within the kidneys.

Lead researcher Dr. Emmanuel Letavernier of Tenon Hospital in Paris, France, expressed alarm at the rapid onset of severe kidney failure observed in animal models within a mere 24 hours of exposure to the suspect straightening cream. These findings have prompted urgent calls to action, with researchers urging the removal of products containing glyoxylic acid from the market and notifying relevant regulatory agencies.

Reference: Kidney Injury and Hair-Straightening Products Containing Glyoxylic Acid,The New England Journal of Medicine, DOI: 10.1056/NEJMc2400528

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Nations fail to reach pandemic accord: talks to resume April

Two years of talks aimed at striking a landmark global agreement on handling future pandemics failed to seal a deal in time on Thursday, and will restart next month for one final push.

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Calls for ‘smartphone free’ childhood grow in UK

It is the question many adults dread being asked by their children: when can I have a smartphone? But as fears grow about the impact of the gadgets on young minds, some UK parents are fighting back.

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Do sweeteners increase your appetite? New evidence from randomized controlled trial says no

Replacing sugar with artificial and natural sweeteners in foods does not make people hungrier—and also helps to reduce blood sugar levels, a new study has found.

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Women with obesity do not need to gain weight during pregnancy, new study suggests

The guidelines for weight gain during pregnancy in obese women have long been questioned. New research from Karolinska Institutet supports the idea of lowering or removing the current recommendation of a weight gain of at least 5 kg. The results are published in The Lancet.

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