Tag: 12/7/22

Categories : Diseases, Syndromes and ConditionsTags :

Study Uncovers Molecular Pathway for Effect of Stress on Lupus

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A team of researchers have identified a molecular mechanism by which stress affects a neuropsychiatric form of lupus, revealing a potential target for the treatment of the disease. Their findings were published in Annals of the Rheumatic Diseases.

Neuropsychiatric systemic lupus erythromatosus (NPSLE), which affects the central nervous system is one of the most severe forms of lupus, for which there is currently no cure. NPSLE is the least understood yet maybe the most prevalent manifestation of lupus, comprising 14%–80% or more of adult SLE cases and 22%–95% of paediatric cases. It can occur independently of active systemic disease and without serologic activity and is associated with increased morbidity and mortality

The research team, led by Professor Masaaki Murakami at Hokkaido University, focused on a specific type of NPSLE called Neuropsychiatric lupus with diffuse neuropsychological manifestations (dNPSLE). There are believed to be a number of causes for dNPSLE, but little is known about its pathogenesis. The researchers were primarily interested in the effects of stress, as chronic stress is linked to the development of many autoimmune diseases.

The researchers conducted experiments on mice models that exhibit SLE-like symptoms to identify the underlying mechanisms dNPSLE. After subjecting a set of these mice to sleep deprivation stress, they observed that the medial prefrontal cortex (mPFC) of the brain was abnormally activated.

In the mPFC, at least 509 genes’ expressions were significantly affected by sleep deprivation. In particular, there was an upregulation of gene that is required for two interleukins, IL12 and IL23. They further showed that upregulating these two interleukins caused activation of the microglial cells of the mPFC. Blocking IL12 and IL23 pathways in these sleep-deprived mice models inhibited the stress-induced neuropsychiatric symptoms.

Most importantly, they showed that there were elevated levels of IL12 and IL23 in the cerebrospinal fluid of human patients with dNPSLE, which could constitute a diagnostic marker. They also showed that the mPFC in dNPSLE patients is atrophied; together, these observations indicate that the mouse model findings may be applicable to humans.

Summing up, Prof Murakami said: “In revealing the effect of the stress-induced effects on the expression of IL12 and IL23 in dNPSLE, we have identified them as not only a diagnostic marker but also a novel therapeutic target for this disease.”

Source: Hokkaido University

Categories : Obstetrics & GynaecologyTags :

Is Fathers’ Lifestyle a Risk Factor for Partners’ Preeclampsia?

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Photo by Drew Hays on Unsplash

Although various maternal risk factors have been recognised, it is still unclear what causes preeclampsia, and some evidence suggests paternal risk factors such as obesity and cardiovascular disease. New research published in Acta Obstetricia et Gynecologica Scandinavica suggests that fathers’ characteristics and lifestyle however do not in fact play a significant role in their partners’ susceptibility to preeclampsia.

Preeclampsia (PE) is a complex vascular disorder in pregnancy characterized by new-onset hypertension and proteinuria after 20 weeks of gestation or new-onset PE-associated signs in the absence of proteinuria.

In this study, researchers examined questionnaire data from 586 men who had fathered a preeclamptic pregnancy and 660 control men who had fathered a non-preeclamptic pregnancy. Fathers in the former group more often reported preeclampsia in a previously fathered pregnancy, but there were no differences in the socioeconomic background or health history of the preeclamptic and control fathers or their parents.

“Importance of paternal genetic factors has been demonstrated in their partners’ susceptibility to preeclampsia, but the role of paternal phenotype and lifestyle is still not well understood. Both paternal genotype and phenotype need to be addressed in future studies,” said co-author Noora Jaatinen, MD, a University of Turku PhD student.

Source: Wiley

Categories : COVIDTags :

SA Study Finds no Increased Severity in Omicron BA.4 and BA.5 Infections

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South African researchers have found that, compared to Omicron BA.1 and earlier infections, those caused by Omicron BA.4 and BA.5 do not have an increased risk of hospitalisation for severe disease or death.

The study, which appears online in the medRxiv server, aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

In their study, the researchers included public sector patients aged 20 years or older with laboratory-confirmed COVID between 1 and 21 May 2022 (for the BA.4/BA.5 wave) and equivalent prior wave periods. They compared the risk for death and severe hospitalisation/death (all within 21 days of diagnosis), adjusting for for demographics, comorbidities, admission pressure, vaccination and prior infection.

Comparing 3793 patients from the BA.4/BA.5 wave and 190 836 patients from previous waves the risk of severe hospitalisation or death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12). Both Omicron waves had a lower risk of severe outcomes than previous waves. They also found that both prior infection (aHR 0.29) and vaccination (aHR 0.17; 0.40 for boosted vs no vaccine) were protective.

Overall, the researchers found that COVID disease severity was similar for the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to prior infection and vaccination, which were both strongly protective.

Categories : Paediatrics Respiratory DiseasesTags :

Hospital Readmissions for Children with Asthma on The Increase

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Photo by Kelly Sikkema on Unsplash

Hospital readmissions for asthma are increasing among children, likely stemming from COVID lockdowns reducing immunity to common respiratory viruses. These are the findings of a new study published in the Journal of Asthma. The finding highlights the gaps in health care for this most common of chronic paediatric illnesses.

The Australian study, led by the Murdoch Children’s Research Institute, found about one in three children, mostly pre-schoolers, are readmitted to hospital for asthma compared to one in five a decade ago.

Most asthma hospital presentations were preventable, Murdoch Children’s Dr Katherine Chen said, which emphasises the need for a holistic evaluation of each child’s asthma management to prevent future readmissions.

The study involved 767 children, aged three to 18 years, who were admitted to three hospitals in Victoria state between 2017-2018 with a diagnosis of asthma. It found that 34.3% were readmitted to hospital for asthma, with those aged three to five years accounting for 69.2%. Of the 767 participants, 20.6% were readmitted once, and 13.7% had two or more readmissions in 12 months. 

“Our study highlighted gaps in the children’s asthma care,” Dr Chen said. Over a third of children hadn’t had a review of their inhaler technique, and only about a quarter were prescribed a preventer or asked to continue using it.

“Almost three quarters were discharged without a preventer medication, and over 80 per cent did not have a follow-up clinic booked at the hospital, often reserved for children with difficult-to-control asthma. Most families, therefore, need to navigate their child’s asthma follow-up with their GP.”

Recently, said Dr Chen, asthma admissions had spiked due to the rise in respiratory infections and children lacking immunity to common viruses as a result of COVID lockdowns.

Professor Harriet Hiscock at MCRI said that the findings confirmed the important role of GPs in paediatric asthma management and how targeted interventions at each hospital could reduce readmissions.

“Less than 10 per cent were readmitted within 30 days suggesting the importance of ongoing community care and longer-term asthma control,” she said. The need to regularly review overall asthma management, minimise risk factors, arrange follow-up, and support optimum care in the community are key.

“Interactive digital symptom monitoring with specialist nurse support, home-based education and a culturally tailored education program could also help.”

Prof Hiscock said linked datasets were important to objectively measure the burden of asthma cases on health services.

“Our current dataset cannot verify whether the follow-up appointment was attended, whether caregivers had arranged follow-up post-discharge and if the medications were used as prescribed,” she said. “Integrating datasets such as health services and medication use into clinical care will improve the clinician’s understanding of the child’s asthma control and medication adherence and would assist in providing targeted treatments.”

Asthma is the most common chronic paediatric illness in industrialised countries, affecting 8–10% of children.

Source: Murdoch Children’s Research Institute

Categories : Diseases, Syndromes and ConditionsTags :

Low Doses of Benzbromarone may be Better for Gout Treatment

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Doctor shows an X-ray of a foot
Photo by Tima Miroshnichenko on Pexels

A painful inflammatory form of arthritis, gout is characterised by urate crystals accumulating in joints, soft tissue and bones. To decrease blood urate levels in patients and reduce flareups, the standard treatment is xanthine oxidase inhibitors such as febuxostat. But new research published in Arthritis & Rheumatology has found a possible better option in the form of low doses of benzbromarone, a less commonly used drug.

Biochemically, gout is characterised by extracellular fluid urate saturation, which is reflected by hyperuricaemia in the blood, with plasma or serum urate concentrations in excess of 6.8 mg/dL; this is the approximate limit of urate solubility.

Benzbromarone is a uricosuric drug that has been used in the treatment of gout over the last 30 years. It reduces the urate reabsorption, diminishing serum urate levels and therefore preventing gout flares.

In this prospective single-centre, open-labelled trial, 196 men with gout and low urinary excretion of uric acid were randomised to receiving either low-dose benzbromarone (LDBen) or low-dose febuxostat (LDFeb) for 12 weeks.

More participants in the LDBen group achieved the blood urate target of < 6 mg/dL than those in the LDFeb group (61% versus 32%). There was little difference in side effects between the groups.

The authors concluded that, “The results suggest that low dosing of benzbromarone may warrant stronger consideration as a safe and effective therapy to achieve serum urate target in gout.”

Source: Wiley