Efficacy and safety of burosumab compared with conventional therapy in patients with X-linked hypophosphatemia: A systematic review.

Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.

Private Equity Acquisition in Ophthalmology and Optometry: A Time Series Analysis of the Pre-COVID, COVID Pre-Vaccine, and COVID Post-Vaccine Eras

ObjectiveTo identify temporal and geographic trends in private equity (PE) backed acquisitions of ophthalmology and optometry practices in the United States from 2012 to 2021. DesignCross-sectional time series analysis using acquisition data from 10/21/2019 to 9/1/2021 compared to previously published data from 1/1/2012-10/20/2019. Acquisition data was compiled from 6 financial databases, 5 industry news outlets, and publicly available press releases. Linear regression models were used to compare rates of acquisition. Subjects245 PE acquisitions of ophthalmology and optometry practices in the United States between 10/21/2019 and 9/1/2021. MeasuresNumber of total acquisitions, practice type, locations, provider details, and geographic footprint. Results245 practices associated with 614 clinical locations and 948 ophthalmologists or optometrists were acquired by 30 PE-backed platform companies. 18 of 30 platform companies were new compared to our prior study. Of these acquisitions from 10/21/2019 - 9/1/2021, 127, 29, and 89 were comprehensive, retina, and optometry practices, respectively. From 2012 to 2021, monthly acquisitions increased by 0.947 acquisitions per year (p<0.001*). Texas, Florida, Michigan, and New Jersey were the states with the greatest number of PE acquisitions with 55, 48, 29, 28 clinic acquisitions, respectively. Average monthly PE acquisitions were 5.71 per month from 1/1/2019 - 2/29/2020 (pre-COVID), 5.30 per month 3/1/2020-12/31/2020 (COVID pre-vaccine, p=0.8072), and were 8.78/month 1/1/2021-9/1/2021 (COVID post-vaccine, p=0.1971). ConclusionPE acquisitions increased from 2012-2021 as companies continue to utilize both regionally focused and multi-state models of add-on acquisitions.

Unique challenges and outcomes of young women with breast cancers from a tertiary care cancer centre in India.

BACKGROUND: Young (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying. METHODS: The YBC treated with a curative intent between 2015 and 2016 at our institute were analysed. RESULTS: There were 1228 patients with a median age of 36 (12-40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) -III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0-131) months, 5-year overall and disease-free survival was 79.6% (76.8-82.5) and 59.1% (55.8-62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8-90.6), 77.3% (73.4-81.2), 69.7% (52.5-86.9) and disease-free survival was 94% (85.9-100), 65.9% (60.3-71.5), 55% (50.5-59.5), and 29.6% (14-45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6-86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients. CONCLUSION: More than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus.

Dual inhibition of COVID-19 spike glycoprotein and main protease 3CLpro by Withanone from Withania somnifera / 中草药·英文版

Objective: To identify the safe and effective natural inhibitors of spike glycoprotein and main protease 3CLpro using potential natural antiviral compounds which are studied under various animal models and viral cell lines. Methods: First, compounds were retrieved from the PubChem database and predicted for their druggability using the MolSoft web server, and compounds having drug-like property were predicted for major adverse drug reactions like cardiotoxicity, hepatotoxicity, arrhythmia, myocardial infarction, and nephrotoxicity using ADVERpred. Docking of nontoxic antiviral compounds with spike glycoprotein and main protease 3CLpro was performed using AutoDock vina by PyRx 0.8 version. The stability of compound-protein interactions was checked by molecular dynamic (MD) simulation using Schrodinger Desmond software. Results: Based on the druggable and nontoxic profile, nine compounds were selected. Among them, Withanone from Withania somnifera showed the highest binding affinity and best fit at active sites 1 of spike glycoprotein (glycosylation site) and main protease 3CLpro via interacting with active site amino acid residues before and after MD simulation at 50 ns. Withanone, which may reduce the glycosylation of SARS-CoV-2 via interacting with Asn343 and inhibit viral replication. Conclusion: The current study reports Withanone as a non-toxic antiviral against SARS-CoV-2 and serve as a potential lead hit for further experimental validation.

N-heterocyclic carbene-metal complexes as bio-organometallic antimicrobial and anticancer drugs, an update (2015-2020).

N-heterocyclic carbenes (NHCs) are organic compounds that typically mimic the chemical properties of phosphines. NHCs have made a significant impact on the field of coordination and organometallic chemistry because they are easy to prepare and handle and because of their versatility and stability. Importantly, the physicochemical properties of NHCs can be easily fine-tuned by simple variation of substituents on the nitrogen atoms. Over the past few years, various NHC-metal complexes have been extensively used as metal-based drug candidates and catalysts (homogeneous or heterogeneous) for various applications. To help assist future work with these compounds, this review provides a thorough review on the latest information involving some biomedical applications of NHC-metal complexes. Specifically, this article focuses on recent advances in the design, synthesis, characterization and biomedical applications (e.g., antimicrobial and anticancer activity) of various NHC-metal complexes (metal: silver, gold, palladium, rhodium, ruthenium, iridium and platinum) covering work published from 2015 to 2020. It is hoped that the promising discoveries to date will help accelerate studies on the encouraging potential of NHC-metal complexes as a class of effective therapeutic agents.

Validity of the vertical tube-shift method in determining the relationship between the mandibular third molar roots and the inferior alveolar nerve canal

OBJECTIVES: To assess the validity of the vertical tube-shift method using intraoral periapical radiography (IOPAR) for determining the relationship between the mandibular third molar roots and the inferior alveolar nerve (IAN) canal in comparison with cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Fifty impacted mandibular third molars were analyzed using the IOPAR vertical tube-shift method and CBCT. The relationship of the IAN canal to the impacted mandibular third molar was recorded as buccal, lingual or in line with the apex and was compared with CBCT findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the vertical tube-shift method in depicting the relationship (buccal/lingual/in line with the apex) of the IAN canal to the third molar root apex was calculated. RESULTS: The sensitivity and specificity PPV and NPV of the IOPAR vertical tube-shift technique was found to be highest for a lingual relationship (100%) followed by buccal (94.4%, 92.3%, 97.1%, and 85.7%) and in line with the apex relationship (88.9%, 95.0%, 80.0%, and 97.4%) of the IAN canal with the third molar root apex, respectively. A statistically significant association was observed between the IOPAR vertical tube-shift method and the CBCT with a P-value <0.01. CONCLUSION: The vertical tube-shift method can be used as an effective diagnostic tool in assessing the relationship of the IAN canal to the third molar root apex with high sensitivity, specificity, PPV, and NPV.