A single-center review of pre-exposure prophylaxis with tixagevimab–cilgavimab in solid organ transplant recipients

Background

Coronavirus disease 2019 (COVID-19) continues to negatively impact solid organ transplant recipients (SOTr). Data on the use of tixagevimab–cilgavimab (tix-cil) in vaccinated SOTr during circulation of Omicron and its subvariants are limited. Therefore, this single-center review was conducted to evaluate tix-cil efficacy in multiple organ transplant groups during a study period where Omicron B.1.1.529, BA.2.12.1, and BA.5 predominated.

Methods

In this single-center retrospective study, we evaluated the incidence of COVID-19 infection in adult SOTr who did or did not receive pre-exposure prophylaxis (PrEP) with tix-cil. SOTr were included if they were at least 18 years of age and met emergency use authorization criteria for tix-cil use. The primary outcome analyzed was the incidence of COVID-19 infection.

Results

Ninety SOTr met inclusion criteria and comprised of two groups, tix-cil PrEP (n = 45) and no tix-cil PrEP (n = 45). Of SOTr who received tix-cil PrEP, three (6.7%) developed COVID-19 infection, compared to eight (17.8%) in the no tix-cil PrEP group (p = .20). Of the 11 SOTr diagnosed with COVID-19, 15 (82.2%) were fully vaccinated against COVID-19 prior to transplantation. Moreover, 18.2% and 81.8% of the COVID-19 cases observed were asymptomatic and mild-to-moderate, respectively.

Discussion

Our study results, which included months when BA.5 was in increased circulation, suggest no significant difference in COVID-19 infection with or without use of tix-cil PrEP in our solid organ transplant groups. As the COVID-19 pandemic continues to evolve, clinical utility of tix-cil should be evaluated against new, emerging strains.

     

Bioevaluation of synthetic pyridones as dual inhibitors of α-amylase and α-glucosidase enzymes and potential antioxidants

Herein, a library of novel pyridone derivatives 1–34 was designed, synthesized, and evaluated for α-amylase and α-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1–34 were synthesized via a one-pot multi-component reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1–34 were structurally characterized by different spectroscopic techniques. Most of the tested compounds showed more promising inhibition potential than the standard acarbose (IC₅₀ = 14.87 ± 0.16 µM) but compounds 13 and 12 were found to be the most potent compounds with IC₅₀ values of 9.20 ± 0.14 µM and 3.05 ± 0.18 µM against α-amylase and α-glucosidase enzymes, respectively. Compounds 1–34 also displayed moderate antioxidant potential in the range of IC₅₀ = 96.50 ± 0.45 to 189.98 ± 1.00 µM in comparison to the control butylated hydroxytoluene (BHT) (IC₅₀ = 66.50 ± 0.36 µM), in DPPH radical scavenging activities. Additionally, all synthetic derivatives were subjected to a molecular docking study to investigate the interaction details of compounds 1–34 (ligands) with the active site of enzymes (receptors). These results indicate that the newly synthesized pyridone class may serve as promising lead candidates for controlling diabetes mellitus and as antioxidants.     

Expanding on the phenotypic spectrum of Woodhouse-Sakati syndrome due to founder pathogenic variant in DCAF17: Report of 58 additional patients from Qatar and literature review

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive neuroendocrine and ectodermal disorder caused by variants in the DCAF17 gene. In Qatar, the c.436delC variant has been reported as a possible founder pathogenic variant with striking phenotypic heterogeneity. In this retrospective study, we report on the clinical and molecular characteristics of additional 58 additional Qatari patients with WSS and compare them to international counterparts' findings. A total of 58 patients with WSS from 32 consanguineous families were identified. Ectodermal and endocrine (primary hypogonadism) manifestations were the most common presentations (100%), followed by diabetes mellitus (46%) and hypothyroidism (36%). Neurological manifestations were overlapping among patients with intellectual disability (ID) being the most common (75%), followed by sensorineural hearing loss (43%) and both ID and aggressive behavior (10%). Distinctive facial features were noted in all patients and extrapyramidal manifestations were uncommon (8.6%). This study is the largest to date on Qatari patients with WSS and highlights the high incidence and clinical heterogeneity of WSS in Qatar due to a founder variant c.436delC in the DCAF17 gene. Early suspicion of WSS among Qatari patients with hypogonadism and ID, even in the absence of other manifestations, would shorten the diagnostic odyssey, guide early and appropriate management, and avoid potential complications.     

Detection of a new deleterious SGCE gene variant in Moroccan family with inherited myoclonus–dystonia

Myoclonus–dystonia (M‐D) is a pleiotropic neuropsychiatric disorder with autosomal dominant mode of inheritance with variable severity and incomplete penetrance. Pathogenic variants in ξ‐sarcoglycan gene SGCE are the most frequently known genetic cause of M‐D with maternal imprinting, and in most cases, a symptomatic individual inherits the pathogenic variant from his or her father. This work reported a missense mutation c.662G> T inherited in the M‐D Moroccan family described for the first time, which is deleterious based on protein modeling analysis.     

Impact of postmenopausal osteoporosis on the lives of Omani women and the use of cultural and religious practises to relieve pain: A hermeneutic phenomenological study

Introduction

Osteoporosis is a significant clinical and public health concern worldwide. Despite the impact of this condition on women's lives, most studies have focused on its clinical manifestations, drug efficacy, and medical treatment. Furthermore, most studies have been conducted in the West. This study aimed to uncover the personal experiences of postmenopausal Omani women living with osteoporosis.

Methods

In this interpretive phenomenological study, a purposive sample of 15 postmenopausal Omani women with osteoporosis was recruited from primary and secondary care facilities in Muscat, Oman. Semi-structured one-to-one interviews were conducted via Zoom and telephone because of coronavirus disease 2019 restrictions. The interviews were audio-recorded, and the Ajjawi and Higgs framework was used to analyse the data thematically.

Results

The following key themes were constructed from the interviews: the impact of osteoporosis on religious practices, cultural and social life, and financial status, and the benefits derived from religious and cultural practices and rituals, including Muslim prayer, recitation of Quranic verses, and herbal remedies to cope with osteoporosis-related pain and suffering.

Conclusion

Osteoporosis and fragility fractures have a significant impact on the religious, cultural, and financial lives of postmenopausal Omani women with osteoporosis. Muslim prayers, recitation of Quranic verses, and herbal remedies are coping strategies for pain in this population.

Patient or Public Contribution

Postmenopausal Omani women with osteoporosis participated in this study through interviews and contributed their lived experiences. Orthopaedic doctors helped recruit patients with postmenopausal osteoporosis.