Indirect effects of the COVID-19 pandemic on risk of gestational diabetes and factors contributing to increased risk in a multiethnic population: a retrospective cohort study.

BACKGROUND: The COVID-19 pandemic has had indirect effects on pregnancy outcomes. There is limited data on the impact on gestational diabetes (GDM) in diverse populations and the possible underlying mediators. This study aimed to assess the risk of GDM pre-COVID-19 and in two distinct pandemic exposure periods, and to determine the potential factors contributing to increased risk in a multiethnic population. METHODS: A multicentre, retrospective cohort study was performed of women with singleton pregnancy receiving antenatal care at three hospitals two years pre-COVID-19 (January 2018 - January 2020), first year of COVID-19 with limited pandemic-mitigating restrictions (February 2020 - January 2021) and second year of COVID-19 with stringent restrictions (February 2021 - January 2022). Baseline maternal characteristics and gestational weight gain (GWG) were compared between cohorts. The primary outcome was GDM, assessed using univariate and multivariate generalised estimating equations models. RESULTS: 28,207 pregnancies met the inclusion criteria, 14,663 pregnancies two years pre-COVID-19, 6,890 in COVID-19 Year 1 and 6,654 in COVID-19 Year 2. Maternal age increased across exposure periods (30.7 ± 5.0 years pre-COVID-19 vs 31.0 ± 5.0 years COVID-19 Year 1 vs 31.3 ± 5 years COVID-19 Year 2; p < 0.001). There were increases in pre-pregnancy body mass index (BMI) (25.5 ± 5.7 kg/m2 vs 25.7 ± 5.6 kg/m2 vs 26.1 ± 5.7 kg/m2; p < 0.001), proportion who were obese (17.5% vs 18.1% vs 20.7%; p < 0.001) and proportion with other traditional risk factors for GDM including South Asian ethnicity and prior history of GDM. Rate of GWG and proportion exceeding recommended GWG increased with pandemic exposure (64.3% vs 66.0% vs 66.6%; p = 0.009). GDM diagnosis increased across exposure periods (21.2% vs 22.9% vs 24.8%; p < 0.001). Both pandemic exposure periods were associated with increased risk of GDM on univariate analysis, only COVID-19 Year 2 remaining significantly associated after adjusting for maternal baseline characteristics and GWG (OR 1.17 [1.06, 1.28], p = 0.01). CONCLUSIONS: Diagnosis of GDM increased with pandemic exposure. Progressive sociodemographic changes and greater GWG may have contributed to increased risk. However, exposure to the second year of COVID-19 remained independently associated with GDM after adjusting for shifts in maternal characteristics and GWG.

Clinical and Radiologic Response of Central Giant Cell Granuloma to Denosumab: A 6-Year Prospective Observational Study.

Central giant cell granuloma (CGCG) is a rare lesion of the jaw occurring in young adults and adolescents. Surgery, the traditional mainstay of therapy, is associated with significant morbidity. Denosumab, a humanised monoclonal antibody to RANKL, is effective in a related entity, giant cell tumour of bone (GCTB), but experience in the more indolent CGCG is limited. This prospective observational study of all denosumab-treated CGCG at a tertiary referral centre (2015-2021) aimed to evaluate the safety, efficacy and recurrence risk using denosumab in CGCG at lower-frequency dosing than used for GCTB. All received standardised, time-limited courses of denosumab 120 mg with stepwise increase in dosing interval based on response. They were followed for up to 75 months using a radiation-minimising protocol: 3-monthly clinical, biochemical and radiological assessment (orthopantomograms, cone beam CT). Eight patients, median age 20.5 years [IQR 6], received 13 initial doses [IQR 10] of denosumab 120 mg. Radiologic response was seen after 5.5 doses [IQR 4.5]: ossification in all and size reduction in three. Recurrence occurred in four of seven completing therapy, observed 12 months post-cessation [IQR 6.5]. Larger baseline size, aggressive subtype and fewer than 12 initial doses were more common in the recurrence group. There was no osteonecrosis of the jaw. Hypocalcaemia occurred in one receiving modified dosing. This study represents the largest, most diverse cohort of denosumab-treated CGCG with the longest follow-up in literature. It demonstrates the efficacy of lower-frequency, time-restricted course of denosumab but highlights the risk of recurrence. Long-term follow-up is critical.

Congestive heart failure presence predicts delayed healing of foot ulcers in diabetes: An audit from a multidisciplinary high-risk foot clinic.

AIMS: This retrospective study aimed to investigate both established and less well-explored factors as potential predictive variables for failed and delayed ulcer healing. METHODS: Patients with type 1 or 2 diabetes with foot ulceration presenting consecutively to, and then subsequently managed at, a multidisciplinary, high-risk foot clinic were followed until ulcer healing, amputation or death. Data comprised prospective standardised documentation at each visit and retrospective collection from hospital records, and included patient demographics, comorbidities, laboratory variables, and ulcer infection, depth and area at each presentation. Multiple regression analysis was used to determine independent predictors of failure to heal and delayed healing. RESULTS: Of the 107 consecutive patients studied, 95 (89%) healed overall, 50 (47%) had healed in 12 weeks and the mean healing rate was a 10% decrease in ulcer area per week. Amongst all variables examined, comorbid congestive heart failure (CHF) was the only factor independently predictive of all measured outcomes of failure to heal overall, delayed healing at 12 weeks, and reduced healing rate. Ulcer infection at presentation, longer duration of antibiotic use, and liver enzyme abnormalities of raised ALT and AST:ALT<1 (each suggestive of non-alcoholic fatty liver disease), were also predictive of poor ulcer outcomes. CONCLUSIONS: Comorbid congestive cardiac failure is predictive of delayed foot ulcer healing rate as well as a lower probability of healing overall. Liver enzyme abnormalities also predicted delayed ulcer healing outcomes. The mechanisms underlying these associations with foot ulcer outcomes in diabetes are unclear. Further studies are needed to determine the role of systematic routine documentation of heart failure and its severity, and then targeting of heart failure to potentially aid the management of foot ulcers in diabetes.