Osteoporosis in the at‐risk asthmatic

The effect of inhaled glucocorticosteroids (ICS) on bone metabolism and subsequent osteoporosis is controversial. Explanations for this controversy include various study designs, duration of use, outcome measures, and population demographics of research studies with intranasal or inhalational ICS. Patients with poorly controlled asthma are at greatest risk of osteoporosis because they are commonly treated with intermittent or continuous systemic corticosteroids (SCS) or high‐dose ICS. A 45‐year‐old Caucasian woman presents with moderate‐to‐severe asthma with frequent albuterol use and nighttime awakenings at least once weekly. She is on fluticasone/salmeterol 500/50 μg one inhalation twice daily and montelukast 10 mg/day. She requires prednisone 15 mg three times per day for 5 days up to three times a year. Is this patient at greater risk of osteopenia, characterized by a T‐score between ?1.0 and ?2.5, and subsequent osteoporosis and an increased risk of fractures? If she has osteopenia, should she be treated with a bisphosphonate? The risk of osteoporosis and fracture increases significantly with frequent administration of SCS, and patients on such medications should undergo preventative measures and treatment. This study discuses factors that contribute to an increased risk of osteoporosis/osteopenia in patients with asthma and suggests recommendations based on the current literature.     

Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease

Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress β-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated β-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute–specific mouse models showed diminished β-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma’s AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/β-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models.     

Differences in t cell receptor restriction fragment length polymorphisms in patients with rheumatoid arthritis

Objective. The purpose of this study was to determine whether a T cell receptor (TCR) polymorphism, either by itself or in combination with particular HLA polymorphism, leads to susceptibility to rheumatoid arthritis (RA). Methods. Eight restriction fragment length polymorphisms (RFLPs) detected with TCR gene segments were investigated in 46 individuals with RA and were compared with data from normal control subjects. Results. A statistically significant difference in the genotype frequencies of a Taq I RFLP detected with the TCRα constant region (C_α) gene was noted. In addition, when the DR4+ subpopulations were examined, the allelic frequency of a 2-kb Bam HI fragment detected with a V_β8 gene was increased in the samples from RA patients (P < 0.0086). Conclusion. The results of this study suggest that germline differences in the TCR repertoire may be associated with RA, and that there is a contributory effect of DR4+ haplotypes with certain TCR haplotypes in susceptibility to RA.     

Ongoing rabies outbreak in dogs of unprecedented scale and human cases in Nelson Mandela Bay Municipality,South Africa,up to 13 February 2022

More than 430 cases of rabies have been confirmed in dogs in the Nelson Mandela Bay Metropolitan Municipality of South Africa since July 2021. We describe the ongoing outbreak, its geographical spread and six related human deaths that have occurred. Further investigation of the outbreak and vaccination of the dog population is required. Raising awareness among healthcare providers, the public, and among international travellers planning to visit the region, is key for action to protect human and animal health.     

An emergency physician's guide to prosthetic heart valves: valve-related complications

Serious valve-related complications that occur in patients with prosthetic valves have been discussed. The emergency physician's role primarily is to recognize the high probability that one of these serious complications exists and hospitalize the patient so that rapid definitive diagnoses and therapeutic decisions are not delayed.