Abildgaardklinge1383

The study aimed to define the clinical, biochemical and genetic features of adult patients with osteopenia/osteoporosis and/or bone fragility and low serum alkaline phosphatase (sALP).

Twenty-two patients with at least two sALP values below the reference range were retrospectively enrolled after exclusion of secondary causes. Data about clinical features, mineral and bone markers, serum pyridoxal-5'-phosphate (PLP), urine phosphoethanolamine (PEA), lumbar and femur bone densitometry, and column X-ray were collected. Peripheral blood DNA of each participant was analyzed to detect ALPL gene anomalies.

Pathogenic ALPL variants (pALPL) occurred in 23% and benign variants in 36% of patients (bALPL), while nine patients harbored wild-type alleles (wtALPL). Fragility fractures and dental anomalies were more frequent in patients harboring pALPL and bALPL than in wtALPL patients. Of note, wtALPL patients comprised women treated with tamoxifen for hormone-sensitive breast cancer. Mineral and bone markers were simple clinical and biochemical features is predictive of ALPL anomalies, and, therefore, they should be carefully identified. Tamoxifen emerged as a hypophosphatasemic drug.Atopic dermatitis (AD) is a common inflammatory dermatologic disease clinically characterized by intense itch, recurrent eczematous lesions, and a chronic or relapsing disease course. Mild-to-moderate AD can be controlled by using moisturizers and topical immunomodulators such as topical corticosteroids and calcineurin inhibitors. If topical therapies fail, phototherapy and systemic immunosuppressant therapies, such as ciclosporin, methotrexate, and azathioprine, can be considered. However, relapse and side effects could still occur. The pathogenesis of AD involves epidermal barrier dysfunction, skin microbiome abnormalities, and cutaneous inflammation. Inflammatory mediators, such as interleukin (IL)-4, IL-13, IL-31, IL-33, IL-17, IL-23, and thymic stromal lymphopoietin, are involved in AD development. Therefore, a series of biological agents targeting these cytokines are promising approaches for treating AD. Dupilumab is the first biological agent approved for the treatment of AD in patients aged 6 years and older in the United States. Tralokinumab, lebrikizumab, and nemolizumab have also been confirmed to have significant efficacy against AD in phase III or IIb clinical trials. Also, fezakinumab was effective in severe AD patients in a phase IIa trial. However, phase II trials of ustekinumab, tezepelumab, etokimab, secukinumab, and omalizumab have failed to meet their primary endpoints. Phase II trials of GBR 830 and KHK 4083 are ongoing. In general, further studies are needed to explore new therapeutic targets and improve the efficacy of biological agents.Carpal tunnel syndrome (CTS), compression of the median nerve lying deep under the flexor retinaculum, is the most common entrapment neuropathy of the upper limb. After a failure of conservative treatments, such as non-steroidal anti-inflammatory drugs (NSAIDs) and splinting, interventional techniques are required. Hydrodissection is an injection technique that separates the nerve from the surrounding tissue. Although this technique is gaining ground in modern medicine, the state-of-the-art literature is lacking a clear protocol or approach for hydrodissection for CTS. In this article, we describe a safe, minimally invasive, effective, and easy-to-use ultrasound-guided hydrodissection technique for CTS.

Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE).

A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Picrotoxin antagonist Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores).

Median time from admission to LUS examination was 4 days (IQR 2, 8). The median number of B-lines was 12 (IQR 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score HR = 9.79, 95% CI (1.87, 51.35), and LUS-score HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses.

In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating. CLINICALTRIALS.

NCT04377035.

NCT04377035.

Ion channels have been proposed as therapeutic targets for different types of malignancies. One of the most studied ion channels in cancer is the voltage-gated potassium channel ether-à-go-go 1 or Kv10.1. Various studies have shown that Kv10.1 expression induces the proliferation of several cancer cell lines and in vivo tumor models, while blocking or silencing inhibits proliferation. Kv10.1 is a promising target for drug discovery modulators that could be used in cancer treatment. This work aimed to screen for new Kv10.1 channel modulators using a thallium influx-based assay.

Pharmacological effects of small molecules on Kv10.1 channel activity were studied using a thallium-based fluorescent assay and patch-clamp electrophysiological recordings, both performed in HEK293 stably expressing the human Kv10.1 potassium channel.

In thallium-sensitive fluorescent assays, we found that the small molecules loperamide and amitriptyline exert a potent inhibition on the activity of the oncogenic potassium channel Kv10.