Shrunken pore syndrome (SPS) is defined as cystatin C-based-eGFR (eGFRcys)/creatinine-based-eGFR (eGFRcreat) <0.6 or 0.7 and is associated with an increased cardiovascular risk. SPS has been described in children, but no link to increased morbi-mortality was demonstrated.
Study the prevalence of SPS in a pediatric population using several glomerular filtration rate (GFR) estimating formulas and measured GFR and evaluate the potential link with cardiovascular risk.
In 307 renal risk pediatric patients, we studied prevalence of SPS either with CKiDU25creat and cyst or with FAScreat and cyst and EKFCcreat. The characteristics of patients with SPS (defined with Full-age spectrum equation (FAS) and/or European Kidney Function Consortium equation (EKFC)) were compared.
The prevalence of SPS varies widely depending on the threshold and the formulas used. Higher C-reactive protein (CRP) and phosphate levels and smaller size are observed in children with SPS defined with FAS and/or EKFC and might be associated with long-term increased cardiovascular risk. Further studies in wider general pediatric populations are warranted.
Rapidly advancing evidence documents that a broad array of synthetic chemicals found ubiquitously in the environment contribute to disease and disability across the lifespan. Although the early literature focused on early life exposures, endocrine-disrupting chemicals (EDCs) are now understood to contribute substantially to chronic disease in adulthood, especially metabolic, cardiovascular, and reproductive consequences as well as endocrine cancers. The contribution to mortality is substantial, with over 90,000 deaths annually and at least $39 billion/year in lost economic productivity in the United States (US) due to exposure to certain phthalates that are used as plasticizers in food packaging. Importantly, exposures are disproportionately high in low-income and minoritized populations, driving disparities in these conditions. Though non-Hispanic Blacks and Mexican Americans comprise 12.6% and 13.5% of the US population, they bear 16.5% and 14.6% of the disease burden due to EDCs, respectively. Many of these exposures can be modified through safe and simple behavioral changes supported by proactive government action to both limit known hazardous exposures and to proactively screen new industrial chemicals prior to their use. Routine healthcare maintenance should include guidance to reduce EDC exposures, and a recent report by the Institute of Medicine suggests that testing be conducted, particularly in populations heavily exposed to perfluoroalkyl substances—chemicals used in nonstick coatings as well as oil- and water-resistant clothing.
Autonomic dysfunction is a clinical hallmark of infection caused by SARS-CoV-2, but the underlying mechanisms are unknown. The vagus nerve inflammatory reflex is an important, well-characterized mechanism for the reflexive suppression of cytokine storm, and its experimental or clinical impairment facilitates the onset and progression of hyperinflammation. Recent pathological evidence from COVID-19 victims reveals viral infection and inflammation in the vagus nerve and associated nuclei in the medulla oblongata. Although it has been suggested that vagus nerve inflammation in these patients mediates dysregulated respiration, whether it also contributes to dysfunction of the vagus nerve inflammatory reflex has not been addressed. Because lethality and tissue injury in acute COVID-19 are characterized by cytokine storm, it is plausible to consider evidence that impairment of the inflammatory reflex may contribute to overproduction of cytokines and resultant hyperinflammatory pathogenesis. Accordingly, here the authors discuss the inflammatory reflex, the consequences of its dysfunction in COVID-19, and whether there are opportunities for therapeutic intervention.
Autoimmune hemolytic anemia (AIHA) may be associated with transfusion reactions and risk of alloimmunization.
To evaluate the transfusion policy and rate of alloimmunization and its clinical significance in AIHA.
Data from 305 AIHA patients followed at a reference hematologic Center in Milan, Italy from 1997 to 2022 were retrospectively/prospectively collected (NCT05931718).
Overall, 33% patients required transfusions with a response rate of 83% and eight transfusion reactions (7%), none hemolytic. Alloantibodies were detected in 19% of patients, being associated with higher transfusion burden (p = 0.01), lower Hb increase post-transfusion (p = 0.05), and transfusion reactions (p = 0.04). Along decades, the rate of RBC transfusions decreased from 53% to 20% and that of alloimmunization dropped from 30% to 6% likely due to the adoption of prestorage leukoreduction, the use of more restrictive Hb thresholds, and the implementation of molecular typing.
Severe symptomatic AIHA may be safely transfused provided appropriate matching of patients and donors.
The objective of this study is to better characterize the features and outcomes of a large population of patients with mixed connective tissue disease (MCTD).
We performed an observational retrospective multicenter cohort study in France. Patients who fulfilled at least one diagnostic criterion set for MCTD and none of the criteria for other differentiated CTD (dCTD) were included.
Three hundred and thirty patients (88% females, median [interquartile range] age of 35 years [26–45]) were included. The diagnostic criteria of Sharp or Kasukawa were met by 97.3% and 93.3% of patients, respectively. None met other classification criteria without fulfilling Sharp or Kasukawa criteria. After a median follow-up of 8 (3–14) years, 149 (45.2%) patients achieved remission, 92 (27.9%) had interstitial lung disease, 25 (7.6%) had pulmonary hypertension, and 18 (5.6%) died. Eighty-five (25.8%) patients progressed to a dCTD, mainly systemic sclerosis (15.8%) or systemic lupus erythematosus (10.6%). Median duration between diagnosis and progression to a dCTD was 5 (2–11) years. The presence at MCTD diagnosis of an abnormal pattern on nailfold capillaroscopy (odds ratio [OR] = 2.44, 95% confidence interval [95%CI] [1.11–5.58]) and parotid swelling (OR = 3.86, 95%CI [1.31–11.4]) were statistically associated with progression to a dCTD. Patients who did not progress to a dCTD were more likely to achieve remission at the last follow-up (51.8% vs. 25.9%).
This study shows that MCTD is a distinct entity that can be classified using either Kasukawa or Sharp criteria, and that only 25.8% of patients progress to a dCTD during follow-up.
Choline acetyltransferase (ChAT) is required for the biosynthesis of acetylcholine, the molecular mediator that inhibits cytokine production in the cholinergic anti-inflammatory pathway of the vagus nerve inflammatory reflex. Abundant work has established the biology of cytoplasmic ChAT in neurons, but much less is known about the potential presence and function of ChAT in the extracellular milieu.
We evaluated the hypothesis that extracellular ChAT activity responds to inflammation and serves to inhibit cytokine release and attenuate inflammation.
After developing novel methods for quantification of ChAT activity in plasma, we determined whether ChAT activity changes in response to inflammatory challenges.
Active ChAT circulates within the plasma compartment of mice and responds to immunological perturbations. Following the administration of bacterial endotoxin, plasma ChAT activity increases for 12–48 h, a time period that coincides with declining tumor necrosis factor (TNF) levels. Further, a direct activation of the cholinergic anti-inflammatory pathway by vagus nerve stimulation significantly increases plasma ChAT activity, whereas the administration of bioactive recombinant ChAT (r-ChAT) inhibits endotoxin-stimulated TNF production and anti-ChAT antibodies exacerbate endotoxin-induced TNF levels, results of which suggest that ChAT activity regulates endogenous TNF production. Administration of r-ChAT significantly attenuates pro-inflammatory cytokine production and disease activity in the dextran sodium sulfate preclinical model of inflammatory bowel disease. Finally, plasma ChAT levels are also elevated in humans with sepsis, with the highest levels observed in a patient who succumbed to infection.
As a group, these results support further investigation of ChAT as a counter-regulator of inflammation and potential therapeutic agent.
Autoimmune thyroid disease (AITD) and rheumatoid arthritis (RA) share a genetic background, and the prevalence of AITD in RA patients is increased. Whereas immunomodulatory treatments are used in RA, they are rarely used in AITD.
We hypothesized that disease-modifying antirheumatic drugs (DMARDs) as used in RA might lower the risk of incident AITD.
A nationwide cohort study including 13,731 patients with new-onset RA from the Swedish Rheumatology Quality Register 2006–2018 and 63,201 matched general population comparators linked to national registers to identify AITD. We estimated relative risks (hazard ratios) of AITD after RA diagnosis in RA patients compared to the general population, and in relation to DMARD treatment, using Cox regression.
Following RA diagnosis, 321 (2.3%) of the RA patients and 1838 (2.9%) of the population comparators developed AITD, corresponding to an incidence of 3.7 versus 4.6 per 1000 person-years, hazard ratio, 0.81; 95% CI, 0.72–0.91. The decreased risk of incident AITD among RA patients compared to the general population was most pronounced among biologic DMARD (bDMARD) treated patients, with a hazard ratio of 0.54; 95% CI, 0.39–0.76. Among RA patients, subgrouped by bDMARD use, TNF-inhibitors were associated with the most pronounced decrease, hazard ratio, 0.67; 95% CI, 0.47–0.96.
In contrast to the increased prevalence of AITD in RA patients at diagnosis, our results indicate that the risk of AITD decreases following RA diagnosis. This decrease is especially pronounced in RA patients treated with bDMARDs. These findings support the hypothesis that DMARDs might have a preventive effect on AITD.
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