Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. METHODS: To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. RESULTS: Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. CONCLUSIONS: Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840.

A relook into the association of the estrogen receptor [alpha] gene (PvuII, XbaI) and adolescent idiopathic scoliosis: a study of 540 Chinese cases.

STUDY DESIGN: A genetic association study of estrogen receptor-[alpha] gene (ESR1) with adolescent idiopathic scoliosis (AIS) in Chinese. OBJECTIVES: To investigate whether: 1) PvuII and XbaI polymorphisms in ESR1 are predisposition factor for AIS and 2) these polymorphisms correlate with the severity of curvature in AIS. SUMMARY OF BACKGROUND DATA: A common single nucleotide polymorphism (SNP) in ESR1 (XbaI) was found to be associated with curve severity in Japanese AIS patients recently. The role of ESR1 as a predisposition gene using a case-control design in other ethnic groups is required to confirm the previous associations. METHODS: A total of 540 Chinese AIS girls with Cobb angle above 20 degrees were recruited as cases together with 260 healthy controls. The effect of ESR1 SNPs on severity of scoliosis was analyzed in a subgroup of AIS patients (n = 364) followed up until skeletal maturity with the maximum Cobb angle recorded. Two SNPs in ESR1 were genotyped by PCR-restriction fragment length polymorphism in all subjects. RESULTS: The allelic frequency of X allele was 23% in both case and control groups. The P allele was found at allelic frequency of 40% and 36% in the case and control groups, respectively. No association between the two ESR1 SNPs and the occurrence of AIS by both genotype and haplotype analysis could be established, suggesting that both SNPs were not predisposition alleles for AIS. AIS patients with different genotypes showed no difference in the maximum Cobb angle. No association was found between the genotype and anthropometric measurements in AIS patients. CONCLUSION: The previously reported association with curve severity could not be replicated in our large series of Chinese AIS patients. The current study also did not show any association of the 2 SNPs with increased risk of having AIS.

Generalized osteopenia in adolescent idiopathic scoliosis--association with abnormal pubertal growth, bone turnover, and calcium intake?

STUDY DESIGN: A cross-sectional study in girls with adolescent idiopathic scoliosis (AIS) and healthy counterparts of similar age. OBJECTIVES: To study the association of bone mass with anthropometric parameters, bone turnover, and calcium intake in 621 girls with AIS, aged 11-6-years, and compare the results with 300 healthy girls of similar age. SUMMARY OF BACKGROUND DATA: Generalized low bone mass has been documented in AIS, yet the cause of low bone mineral density in AIS is unknown. METHODS: Corrected height and arm span, bone mineral density and bone mineral content of proximal femur, lumbar spine, and distal tibia, and bone turnover markers (bone alkaline phosphatase [bALP] and deoxypyridinoline) were evaluated. RESULTS: From age 13 years and older, the AIS group had longer anthropometric parameters (P < 0.05), generalized lower bone mass (P < 0.035), and 38.6% higher in bALP (P < 0.004) when compared with controls. A stronger inverse correlation between bALP and bone mass was noted in the AIS group. The bALP was positively correlated with bone area of tibia (P = 0.013) in the AIS group only. Deoxypyridonine of the AIS group was not different from the controls until age 15 years. The mean calcium intake of the AIS group was very low (only 361 mg/day), and calcium intake was significantly associated with bone mass in the AIS group. Low bone mass in AIS could be explained by faster anthropometric bone growth, higher bone turnover, and lower calcium intake in multiple regression analysis. CONCLUSIONS: Results from the current study showed that an abnormally faster growth rate and higher bone turnover in the patient with AIS might lead to increased bone dimensions. Calcium intake in patients with AIS was very low and likely to be insufficient for normal bone mineralization. Therefore, low bone mass in AIS may result from abnormal bone mineralization qualitatively and quantitatively and, thus, fails to catch up with increased bone growth during the peripubertal period.