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We evaluated the evolution of thyroid function and autoimmunity among COVID-19 survivors over 6 months in relation to interferon beta-1b treatment and long COVID.We included COVID-19 survivors managed in a major COVID-19 centre between July 2020 and May 2021 who were reassessed three and/or six months after acute COVID-19. Thyroid function tests (TFTs) and anti-thyroid antibody titres were measured at acute COVID-19, 3-month and 6-month.250 COVID-19 survivors were included (mean age 52.7 years, 50.4% men). Persistent thyroid function abnormalities were more likely in those with abnormal TFTs in acute COVID-19 (P 0.001). Among 51 patients with abnormal TFTs in acute COVID-19, 82.4% resolved upon follow-up. Of 199 patients with normal TFTs in acute COVID-19, only 4.5% had incident abnormal TFTs, more likely in interferon-treated patients (P = 0.044) and none clinically overt. Among 129 patients with complete 6-month follow-up for anti-thyroid antibody titres, there was no significant change overall, except for modest increase in anti-thyroid antibody titres among the 84 interferon-treated patients (P 0.05 at both 3 months and 6 months). Long COVID occurred in 19.5% and 10.4% at 3 and 6 months respectively, where TFTs and anti-thyroid antibody titres were not predictive of its occurrence.Over 6 months, most abnormal TFTs in acute COVID-19 resolved, with no significant incident thyroid dysfunction. SARS-CoV-2 infection did not lead to change in thyroid autoimmunity, while interferon treatment was associated with modest increase in anti-thyroid antibody titres. Thyroid function and anti-thyroid antibodies did not play a significant role in long COVID.

Context Reports of thyroid dysfunction following COVID-19 vaccination included cases of relapse of Graves' disease and worsening of pre-existing Graves' disease. Little is known about the thyroid-specific outcomes among patients treated for hyperthyroidism who have received COVID-19 vaccination. Objective Among patients treated for hyperthyroidism, we evaluated factors associated with not receiving the COVID-19 vaccination and whether COVID-19 vaccination was associated with thyroid function instability. Methods We included consecutive patients treated for hyperthyroidism attending the thyroid clinic at a teaching hospital between January and September 2021. They were categorized into vaccinated and unvaccinated groups. The index date was the date of first-dose vaccination for the vaccinated group, and the first date of attendance in the inclusion period for the unvaccinated group. They were followed up until March 2022 or occurrence of thyroid function instability (worsening of thyroid function/increase in antithyroid drug dosage), whichever was earlier. Results A total of 910 patients were included (mean age 51.6 years; 82.1% female). Of these, 86.2% had Graves disease and 67.3% were vaccinated (67.3% BNT162b2; 30.6% CoronaVac; 2.1% heterologous). Abnormal thyroid function and cardiovascular comorbidities were independently associated with unvaccinated status. Upon median follow-up of 5.3 months, thyroid function instability occurred in 15.9% of patients. COVID-19 vaccination did not increase risks of thyroid function instability (hazard ratio 0.78, 95% CI 0.56-1.09, P = .151); this was consistent in Graves disease, both types of vaccines, and regardless of whether baseline thyroid function was normal. Twenty-seven patients overtly thyrotoxic at the time of vaccination received COVID-19 vaccines without triggering a thyroid storm or difficulty in subsequent thyroid function control. Conclusion Among patients treated for hyperthyroidism, abnormal thyroid function was a factor predicting unvaccinated status. Our results should encourage patients treated for hyperthyroidism to receive COVID-19 vaccination to protect themselves from adverse outcomes and potential long-term sequelae of COVID-19.

Background: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients.Methods: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography.Results: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037).Conclusion: Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

Operations are a major precipitating factor for sodium-glucose co-transporter 2 inhibitor (SGLT2i)-associated diabetic ketoacidosis (DKA). This study aimed to investigate the risks of SGLT2i-associated postoperative DKA.We analysed a population-based cohort of patients with type 2 diabetes who underwent operations during 2015-2020. Patients with SGLT2i prescriptions within 6 months before operations were assigned to the SGLT2i group, while others were assigned to the control group. Inverse probability treatment weighting with propensity scores was used to balance the baseline covariates. Postoperative DKA was defined as DKA within 30 days postoperatively.Overall, 147,115 subjects were included (3,419 SGLT2i users; 143,696 controls). Preoperative SGLT2i exposure was associated with increased risks of postoperative DKA (incidence = 6.40/1,000 person-years; incidence rate ratio [IRR] 6.33, 95% confidence interval [CI] 5.57-7.18; p 0.001). Risk factors of SGLT2i-associated postoperative DKA included emergency operation (IRR 24.56, 95% CI 7.42-81.24; p 0.001), preoperative HbA1c ≥8% (IRR 3.10, 95% CI 1.31-7.33; p = 0.010) and insulin use (IRR 2.88, 95% CI 1.27-6.51; p = 0.011). SGLT2i users who developed postoperative DKA had worse outcomes (invasive mechanical ventilation, dialysis, infections/sepsis, intensive care, and length of hospitalization; p 0.05) than those who did not, although SGLT2i users who developed postoperative DKA had better outcomes than non-SGLT2i users who developed postoperative DKA (p 0.05). The risk of postoperative DKA decreased following the implementation of an automatic electronic health record pop-up alert on perioperative precaution regarding SGLT2i (from IRR 4.06 [95% CI 3.41-4.83] to 2.97 [95% CI 2.41-3.65]; p for interaction = 0.020).Preoperative SGLT2i use was associated with increased risks of postoperative DKA in patients with type 2 diabetes. Clinicians could optimize patients' outcomes by appropriate prescription of SGLT2i, while watching out for high-risk features. Implementing automatic electronic health record pop-up alerts may reduce the risk of SGLT2i-associated postoperative DKA.

OBJECTIVE Patients with type 2 diabetes are at higher risk for fracture risk because of attenuated bone turnover and impaired bone microarchitecture. The comparative effect of warfarin over non–vitamin K antagonist oral anticoagulants (NOACs) on incident fractures among patients with type 2 diabetes comorbid with atrial fibrillation (AF) remains to be elucidated. RESEARCH DESIGN AND METHODS This was a retrospective, propensity score–weighted, population-based cohort study of adults with type 2 diabetes and AF who were started on warfarin or NOAC between 2005 and 2019 identified from an electronic database of the Hong Kong Hospital Authority. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, proximal humerus, and wrist). Hazard ratios (HRs) were calculated using Cox proportional hazards regression models. RESULTS A total of 15,770 patients with type 2 diabetes comorbid with AF were included (9,288 on NOAC, 6,482 on warfarin). During a median follow-up of 20 months, 551 patients (3.5%) sustained major osteoporotic fractures (201 [2.2%] in the NOAC group, 350 [5.4%] in the warfarin group). The adjusted cumulative incidence was lower among NOAC users than warfarin users (HR 0.80; 95% CI 0.64, 0.99; P = 0.044). Subgroup analyses showed consistent protective effects against major osteoporotic fractures among NOAC users across sex, age, HbA1c, duration of diabetes, and history of severe hypoglycemia compared with warfarin users. CONCLUSIONS NOAC use was associated with a lower risk of major osteoporotic fractures than warfarin use among patients with type 2 diabetes comorbid with AF. NOAC may be the preferred anticoagulant from the perspective of bone health.

ContextAdipocyte fatty acid-binding protein (AFABP), fibroblast growth factor 21 (FGF21), and pigment epithelium–derived factor (PEDF) are 3 diabetes-related biomarkers whose circulating levels had been shown to associate with nephropathy progression in Chinese patients with type 2 diabetes.ObjectiveHere, we evaluated and compared their prospective associations with the development of sight-threatening DR (STDR), another important diabetic microvascular complication.MethodsBaseline serum AFABP, PEDF, and FGF21 levels were measured in 4760 Chinese individuals with type 2 diabetes and without STDR at baseline. The associations of these biomarkers with incident STDR were analyzed using Cox regression analysis.ResultsAmong these 4760 participants (mean diabetes duration of 11 years and ≥ 50% with nonproliferative DR at baseline), 172 participants developed STDR over a median follow-up of 8.8 years. Participants with incident STDR had comparable baseline serum FGF21 levels but significantly higher baseline serum AFABP and PEDF levels (both P < .001) than those without. However, in multivariable Cox regression analysis, only serum AFABP remained independently associated with incident STDR (hazard ratio 1.28; 95% CI, 1.05-1.55; P = .013). The addition of serum AFABP to a clinical model of conventional STDR risk factors including diabetes duration, glycemic control, albuminuria, and baseline DR status significantly improved the c statistics (P < .001), net reclassification index (P = .0027), and integrated discrimination index (P = .033) in predicting incident STDR among participants without DR or with mild DR at baseline.ConclusionAmong the 3 diabetes-related biomarkers, serum AFABP level appeared to be a more clinically useful biomarker for predicting incident STDR in type 2 diabetes.

BackgroundNon-diabetic overweight/obese metabolic dysfunction-associated fatty liver disease (MAFLD) represents the largest subgroup with heterogeneous liver fibrosis risk. Metabolic dysfunction promotes liver fibrosis. Here, we investigated whether incorporating additional metabolic risk factors into clinical evaluation improved liver fibrosis risk stratification among individuals with non-diabetic overweight/obese MAFLD.Materials and methodsComprehensive metabolic evaluation including 75-gram oral glucose tolerance test was performed in over 1000 participants from the New Hong Kong Cardiovascular Risk Factor Prevalence Study (HK-NCRISPS), a contemporary population-based study of HK Chinese. Hepatic steatosis and fibrosis were evaluated based on controlled attenuation parameter and liver stiffness (LS) measured using vibration-controlled transient elastography, respectively. Clinically significant liver fibrosis was defined as LS ≥8.0 kPa. Our findings were validated in an independent pooled cohort comprising individuals with obesity and/or polycystic ovarian syndrome.ResultsOf the 1020 recruited community-dwelling individuals, 312 (30.6%) had non-diabetic overweight/obese MAFLD. Among them, 6.4% had LS ≥8.0 kPa. In multivariable stepwise logistic regression analysis, abnormal serum aspartate aminotransferase (AST) (OR 7.95, p80%) and negative predictive value (>90%).ConclusionA sequential algorithm incorporating AST and HOMA-IR levels improves fibrosis risk stratification among non-diabetic overweight/obese MAFLD individuals.

Although persistent (≥6 months) postoperative hypoparathyroidism is often believed to be rare after elective total thyroidectomy, we hypothesized a higher incidence in the community and that patients with persistent postoperative hypoparathyroidism may have a higher fracture risk. A population-based analysis was performed using an electronic health database to address these issues.All elective total thyroidectomies performed in 14 major hospitals across the territory over 20 years were analyzed. Persistent postoperative hypoparathyroidism was defined by the requirement of oral calcium and vitamin D shortly postoperatively and continued for ≥6 months. Those with albumin-corrected calcium1.90 mmol/L on ≥1 occasion beyond 1 year postoperation were considered suboptimally controlled. Patients were followed until an index fracture, death, or the time of analysis, whichever was earlier. Multivariable Cox regression analysis was used to identify clinical predictors for fractures.Among 4,123 eligible patients, 460 patients (11.2%) had persistent postoperative hypoparathyroidism. Over a median of 10.3 years, 126 patients suffered from a new fracture (2.77 per 1,000 person-years). There was no difference in fracture events between patients with and without persistent postoperative hypoparathyroidism (P = .761). Subgroup analyses according to the adequacy of persistent postoperative hypoparathyroidism control did not reveal significant differences in fracture events. Age, female, history of fall, and diabetes independently predicted post-thyroidectomy fractures.Persistent postoperative hypoparathyroidism appeared to be a more common complication in the community after elective total thyroidectomy than previously thought. We did not observe a significant difference in fracture risk between patients with and without persistent postoperative hypoparathyroidism. The impact of persistent postoperative hypoparathyroidism control on fracture risk remained to be determined.

Aims Adipocyte fatty acid‐binding protein (AFABP) is associated with cardiovascular diseases in type 2 diabetes. Whether circulating AFABP levels are associated with the risk of heart failure (HF) in type 2 diabetes remains undefined. We investigated the prospective association of circulating AFABP levels with incident HF hospitalization in type 2 diabetes, and its relationship to the use of sodium glucose co‐transporter 2 inhibitors (SGLT2i) which reduce HF risk. Methods and results Baseline serum AFABP level was measured in 3322 Chinese participants without known history of cardiovascular diseases or hospitalization for HF, recruited from the Hong Kong West Diabetes Registry. Its association with incident HF hospitalization was evaluated using multivariable Cox regression analysis. Use of SGLT2i was included as a time‐dependent covariate. Among these 3322 participants (52.9% men; mean age 60.0 ± 12.6), 176 (5.3%) developed HF hospitalization over a median follow‐up of 8 years. Seven hundred and thirty‐one (22%) were started on SGLT2i during the study period (empagliflozin 55.1%, dapagliflozin 44.2%, canagliflozin 0.4%, and ertugliflozin 0.3%). Serum AFABP levels were significantly higher in participants who developed HF hospitalization than those who did not (men: 14.8 vs. 8.3 ng/mL; women: 21.5 vs. 14.6 ng/mL; all: 18.6 vs. 10.9 ng/mL, P

Objective Thyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Methods We conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes. Results One hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19–11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17–0.71; P = .004). Conclusion Thyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.

Purpose Thyroid dysfunction, including thyroiditis, is well recognized in COVID-19 patients. We evaluated thyroid ultrasonographic features among COVID-19 survivors, which are less well known. Methods Adult COVID-19 survivors without known thyroid disorders who attended dedicated COVID-19 clinic underwent thyroid ultrasonography and assessment of thyroid function and autoimmunity. Adults admitted for acute non-thyroidal surgical problems and negative for COVID-19 were recruited as control. SARS-CoV-2 viral load (VL) was presented as the inverse of cycle threshold values from the real-time reverse transcription-polymerase chain reaction of the respiratory specimen on admission. Results In total, 79 COVID-19 patients and 44 non-COVID-19 controls were included. All abnormal thyroid function tests during acute COVID-19 recovered upon follow-up. Thyroid ultrasonography was performed at a median of 67 days after acute COVID-19. The median thyroid volume was 9.73 mL (IQR: 7.87–13.70). In multivariable linear regression, SARS-CoV-2 VL on presentation (standardized beta −0.206, p = 0.042) inversely correlated with thyroid volume, in addition to body mass index at the time of ultrasonography (p

Objective Long COVID (LC) is an emerging global health issue. Fatigue is a common feature. Whether thyroid function and autoimmunity play a role is uncertain. We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC. Methods We included consecutive adults without known thyroid disorder, admitted to a major COVID-19 centre for confirmed COVID-19 from July to December 2020 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured on admission and at follow-up. LC was defined by the presence or persistence of symptoms upon follow-up. Results In total, 204 patients (median age: 55.0 years; 46.6% men) were reassessed at a median of 89 days (IQR: 69–99) after acute COVID-19. Forty-one (20.1%) had LC. Female (adjusted odds ratio [aOR] 2.48, p=0.018) and SARS-CoV-2 PCR cycle threshold value, Long COVID is common among COVID-19 survivors, with female and those with higher viral load in acute COVID-19 particularly vulnerable. Our observation of incident anti-TPO positivity among COVID-19 survivors warrants further follow-up for thyroid dysfunction. Whether anti-TPO plays a protective role in long COVID remains to be elucidated.

Objective: Patients with type 2 diabetes are at higher fracture risk owing to the attenuated bone turnover and impaired bone microarchitecture. The comparative effect of warfarin over non-vitamin K antagonist oral anticoagulants (NOACs) on incident fractures among patients with type 2 diabetes comorbid with atrial fibrillation (AF) remains to be elucidated. Research Design and Methods: This was a retrospective propensity-score weighted population-based cohort study of adults with type 2 diabetes and AF who were started on warfarin or NOAC between 2005 and 2019, identified from the electronic database of the Hong Kong Hospital Authority. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, proximal humerus and wrist). Hazard ratios (HR) were calculated using Cox proportional hazard regression models. Results: 15,770 type 2 diabetes patients comorbid with AF were included (9,288 on NOAC and 6,482 on warfarin). During a median follow-up of 20 months, 551 patients (3.5%) sustained major osteoporotic fractures (201 in NOAC group [2.2%]; 350 in warfarin group [5.4%]). The adjusted cumulative incidence was lower among NOAC users than warfarin users (HR 0.80, 95% CI 0.64-0.99, p=0.044). Subgroup analyses showed consistent protective effects against major osteoporotic fractures among NOAC users across sex, age, HbA1c, duration of diabetes and history of severe hypoglycemia, compared with warfarin users. Conclusions: NOAC use was associated with a lower risk of major osteoporotic fractures than warfarin use, among type 2 diabetes patients comorbid with AF. NOAC may be the preferred anticoagulant from the perspective of bone health.

The coexistence of insulinoma and type 2 diabetes is rare and the diagnostic process is often challenging. Continuous glucose monitoring system devices, which are more readily available nowadays, provide a useful tool for the diagnosis and evaluation of treatment response. Curative surgery is often the mainstay of treatment for insulinoma. Here, we report a Chinese patient with insulinoma diagnosed simultaneously with type 2 diabetes. His insulinoma was managed with endoscopic ultrasound guided-radiofrequency ablation (EUS-RFA) and the patient achieved complete resolution of hypoglycaemic episodes. The case illustrates that while EUS-RFA is an emerging non-invasive treatment modality for pancreatic lesions, limitations exist especially when histological confirmation is essential.

Objective Existing studies reported the potential prognostic role of non‐thyroidal illness syndrome (NTIS), characterized by low triiodothyronine (T3) with normal/low thyroid‐stimulating hormone (TSH), mainly in severe COVID‐19. None considered the significant impact of SARS‐CoV‐2 viral load on adverse outcomes. We aimed to clarify the prognostic role of NTIS among predominantly mild‐to‐moderate COVID‐19 patients. Design A prospective study of COVID‐19 patients. Patients and Measurements Consecutive adults admitted to Queen Mary Hospital for confirmed COVID‐19 from July to December 2020 were prospectively recruited. SARS‐CoV‐2 viral load was represented by cycle threshold (Ct) values from real‐time reverse transcription‐polymerase chain reaction of the respiratory specimen on admission. Serum TSH, free thyroxine and free T3 were measured on admission. The outcome was deterioration in clinical severity, defined as worsening in ≥1 category of clinical severity according to the Chinese National Health Commission guideline. Results We recruited 367 patients. At baseline, 75.2% had mild disease, and 27 patients (7.4%) had NTIS. Fifty‐three patients (14.4%) had clinical deterioration. Patients with NTIS were older, had more comorbidities, worse symptomatology, higher SARS‐CoV‐2 viral loads and worse profiles of inflammatory and tissue injury markers. They were more likely to have clinical deterioration (p 50 years (p = .011) and elevated creatine kinase (p = .017). Conclusions Non‐thyroidal illness syndrome was not uncommon even in mild‐to‐moderate COVID‐19 patients. NTIS on admission could predict clinical deterioration in COVID‐19, independent of SARS‐CoV‐2 viral load, age and markers of inflammation and tissue injury.

ImportanceDiabetes and COVID-19 are both global pandemics, and type 2 diabetes is a common comorbidity in patients with acute COVID-19 and is proven to be a key determinant of COVID-19 prognosis. Molnupiravir and nirmatrelvir-ritonavir are oral antiviral medications recently approved for nonhospitalized patients with mild to moderate COVID-19, following demonstration of their efficacies in reducing adverse outcomes of the disease; it is crucial to clarify whether both oral antiviral medications are efficacious in a population consisting exclusively of patients with type 2 diabetes.ObjectiveTo evaluate the effectiveness of molnupiravir and nirmatrelvir-ritonavir in a contemporary population-based cohort comprising exclusively nonhospitalized patients with type 2 diabetes and SARS-CoV-2 infection.Design, Setting, and ParticipantsThis retrospective cohort study was performed using population-based electronic medical record data for patients in Hong Kong with type 2 diabetes and confirmed SARS-CoV-2 infection between February 26 and October 23, 2022. Each patient was followed up until death, outcome event, crossover of oral antiviral treatment, or end of the observational period (October 30, 2022), whichever came first. Outpatient oral antiviral users were divided into molnupiravir and nirmatrelvir-ritonavir treatment groups, respectively, and nontreated control participants were matched through 1:1 propensity score matching. Data analysis was performed on March 22, 2023.ExposuresMolnupiravir (800 mg twice daily for 5 days) or nirmatrelvir-ritonavir (300 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days, or 150 mg nirmatrelvir and 100 mg ritonavir for patients with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m2).Main Outcomes and MeasuresThe primary outcome was a composite of all-cause mortality and/or hospitalization. The secondary outcome was in-hospital disease progression. Hazard ratios (HRs) were estimated with Cox regression.ResultsThis study identified 22 098 patients with type 2 diabetes and COVID-19. A total of 3390 patients received molnupiravir and 2877 received nirmatrelvir-ritonavir in the community setting. After application of exclusion criteria followed by 1:1 propensity score matching, this study comprised 2 groups. One group included 921 molnupiravir users (487 men [52.9%]), with a mean (SD) age of 76.7 (10.8) years, and 921 control participants (482 men [52.3%]), with a mean (SD) age of 76.6 (11.7) years. The other group included 793 nirmatrelvir-ritonavir users (401 men [50.6%]), with a mean (SD) age of 71.7 (11.5) years, and 793 control participants (395 men [49.8%]), with a mean (SD) age of 71.9 (11.6) years. At a median follow-up of 102 days (IQR, 56-225 days), molnupiravir use was associated with a lower risk of all-cause mortality and/or hospitalization (HR, 0.71 [95% CI, 0.64-0.79]; P P P P = .73) compared with nonuse.Conclusions and RelevanceThese findings suggest that both molnupiravir and nirmatrelvir-ritonavir oral antiviral medications were associated with a lower risk of all-cause mortality and hospitalization among patients with COVID-19 and type 2 diabetes. Further studies in specific populations, such as individuals in residential care homes and individuals with chronic kidney disease, are suggested.

Background Thyroiditis and Graves’ disease have been reported after COVID-19 vaccination. Patients with hypothyroidism due to various etiologies may be at risk of thyroid-specific outcomes. We aimed to evaluate the risks of thyroid-specific outcomes and adverse events after COVID-19 vaccination among patients treated for hypothyroidism. Methods In this population-based cohort from Hong Kong Hospital Authority electronic health records with Department of Health vaccination records linkage, levothyroxine users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine) or CoronaVac (inactivated vaccine) between 23 February and 9 September 2021. Propensity score (PS) weighting with inverse probability of treatment weighting (IPTW) was applied to balance the baseline characteristics among the three groups, which included age, sex, history of COVID-19, health care utilization, comorbidities, baseline thyroid-stimulating hormone (TSH) level (within the 6 months before the index date), and recent use of medications including anti-hypertensive, anti-diabetic and lipid-lowering agents. Study outcomes were dosage reduction or escalation in levothyroxine, emergency department visit, unscheduled hospitalization, adverse events of special interest (AESI) according to World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Results In total, 47,086 levothyroxine users were identified (BNT162b2: n=12,310; CoronaVac: n=11,353; unvaccinated: n=23,423). After PS weighting, all baseline characteristics had standardised differences of less than 0.2, implying a balance of covariates among the three groups. COVID-19 vaccination was not associated with increased risks of levothyroxine dosage reduction (BNT162b2: HR=0.971, 95% CI 0.892–1. 058; CoronaVac: HR=0.968, 95% CI 0.904–1. 037) or escalation (BNT162b2: HR=0.779, 95% CI 0.519–1.169; CoronaVac: HR=0.715, 95% CI 0.481–1. 062). Besides, COVID-19 vaccination was not associated with a higher risk of emergency department visits (BNT162b2: HR=0.944, 95% CI 0.700-1.273; CoronaVac: HR=0.851, 95% CI 0.647-1.120) or unscheduled hospitalization (BNT162b2: HR=0.905, 95% CI 0.539-1.520; CoronaVac: HR=0.735, 95% CI 0.448-1.207). There were two (0. 016%) deaths and six (0. 062%) AESI recorded for BNT162b2 recipients, and one (0. 009%) and three (0. 035%) for CoronaVac recipients, respectively. Sensitivity analyses were performed by stratifying the groups according to age, sex and pre-vaccination thyroid status. The results were largely consistent with the main analysis. Conclusion BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes. Presentation: No date and time listed

Objective: We aimed to characterize SGLT2 inhibitor (SGLT2i) -associated post-operative diabetic ketoacidosis (DKA) in type 2 diabetes patients. Methods: We analyzed a territory-wide cohort of type 2 diabetes patients who underwent operations during 2015-2020. Patients who had SGLT2i prescriptions within 6 months before operations were assigned to SGLT2i group while others to control group. Inverse probability treatment weighting with propensity scores was used to balance the baseline covariates between two groups. Post-operative DKA was defined by DKA within 30 days post-operatively. Results: In total, 151488 type 2 diabetes adults undergoing elective (3260 SGLT2i users; 105540 controls) and emergency operations (1087 SGLT2i users; 416controls) were included. SGLT2i users who underwent emergency operations had higher incidence of post-operative DKA (24.5/1000 person-years) than elective operations (1.0/1000 person-years; p8% (64mmol/mol) and baseline insulin use increased the risk of post-operative DKA. SGLT2i users who developed post-operative DKA had worse outcomes (mechanical ventilation, intensive care and length of hospitalization; p Conclusion: Preoperative SGLT2i use was associated with increased risks of post-operative DKA in type 2 diabetes, higher among patients who underwent emergency operations than elective ones. Clinicians should be vigilant regarding the high-risk group. Effective strategies to mitigate risks of SGLT2i-associated post-operative DKA are urgently needed given the associated morbidities. Disclosure D.T.W.Lui: None. T.Wu: None. X.Liu: None. C.Au: None. C.Lee: None. M.Fung: None. Y.Woo: None. K.C.Tan: None. C.K.Wong: None.

Context There are concerns for COVID-19 vaccination in triggering thyroid autoimmunity and causing thyroid dysfunction. Also, data on the effect of preexisting thyroid autoimmunity on the efficacy of COVID-19 vaccination are limited. Objectives We evaluated the effect of COVID-19 vaccination on thyroid function and antibodies, and the influence of preexisting thyroid autoimmunity on neutralizing antibody (NAb) responses. Methods Adults without a history of COVID-19/thyroid disorders who received the COVID-19 vaccination during June to August 2021 were recruited. All received 2 doses of vaccines. Thyrotropin (TSH), free thyroxine (fT4), free 3,5,3′-triiodothyronine (fT3), antithyroid peroxidase (anti-TPO), and antithyroglobulin (anti-Tg) antibodies were measured at baseline and 8 weeks post vaccination. NAb against SARS-CoV-2 receptor-binding domain was measured. Results A total of 215 individuals were included (129 [60%] BNT162b2; 86 [40%] CoronaVac recipients): mean age 49.6 years, 37.2% men, and 12.1% anti-TPO/Tg positive at baseline. After vaccination, TSH did not change (P = .225), but fT4 slightly increased (from 12.0 ± 1.1 to 12.2 ± 1.2 pmol/L [from 0.93 ± 0.09 to 0.95 ± 0.09 ng/dL], P Conclusion COVID-19 vaccination was associated with a modest increase in antithyroid antibody titers. Anti-TPO increase was greater among BNT162b2 recipients. However, there was no clinically significant thyroid dysfunction post vaccination. NAb responses were not influenced by preexisting thyroid autoimmunity. Our results provide important reassurance for people to receive the COVID-19 vaccination.

Background The relationship between good early control of thyroid hormone levels after thyroidectomy for Graves’ disease (GD) and subsequent risks of mortality and morbidities is not well known. The aim of this study was to examine the association between thyroid hormone levels within a short interval after surgery and long-term mortality and morbidity risks from a population-based database. Methods Patients with GD who underwent complete/total thyroidectomy between 2006 and 2018 were selected from the Hong Kong Hospital Authority clinical management system. All patients were classified into three groups (euthyroidism, hypothyroidism, and hyperthyroidism) according to their thyroid hormone levels at 6, 12, and 24 months after surgery. Cox proportional hazards models were performed to compare the risks of all-cause mortality, cardiovascular disease (CVD), Graves’ ophthalmopathy, and cancer. Results Over a median follow-up of 68 months with 5709 person-years, 949 patients were included for analysis (euthyroidism, n = 540; hypothyroidism, n = 282; and hyperthyroidism, n = 127). The hypothyroidism group had an increased risk of CVD (HR = 4.20, 95 per cent c.i. 2.37 to 7.44, P Conclusions This study showed a higher risk of CVD in postsurgical hypothyroidism and a higher risk of cancer in hyperthyroidism compared with achieving euthyroidism early after thyroidectomy. Patients who were euthyroid at 6 months and 12 months had better outcomes than those achieving euthyroidism only at 6 months or 12 months. Attaining biochemical euthyroidism early after thyroidectomy should become a priority.

Assessing the 6-month efficacy of combined high-intensity focused ultrasound (HIFU) ablation with percutaneous ethanol injection (PEI) in benign thyroid nodules by comparing it with HIFU ablation alone. One hundred and eighty-one (55.2%) patients underwent HIFU alone (group I) while 147 (44.8%) underwent concomitant HIFU and PEI treatment for solid or predominantly solid nodules (group II). Intravenous sedation and analgesia were given before the start of treatment. Extent of nodule shrinkage (by volume reduction ratio (VRR)), pain scores (by 0–10 visual analogue scale) during and after ablation, and rate of vocal cord palsy (VCP), skin burn, and nausea/vomiting were compared between the two groups. The mean amount of ethanol injected in group II was 1.3 ± 0.7 ml. The 3- and 6-month VRR were significantly greater in group II (60.41 ± 20.49% vs. 50.13 ± 21.06%, p = 0.001; and 71.08 ± 21.25% vs. 61.37 ± 22.76%, p = 0.001, respectively), and “on-beam” treatment time was significantly shorter in group II (26.55 min vs. 30.26 min, p = 0.001). Group II patients reported significantly lower pain score during treatment (2.24 ± 3.07 vs. 4.97 ± 3.21, p 0.05). The combined HIFU and PEI approach with improved administration of intravenous sedation and analgesia was associated with a significantly better 6-month efficacy than HIFU alone in benign thyroid nodules without compromising the safety and comfort of patients. • Concomitant HIFU and PEI have a better treatment efficacy than HIFU alone. • Concomitant HIFU and PEI have a comparable safety profile as HIFU alone.

Diabetes is a risk factor for the severity of coronavirus disease 2019 (COVID‐19). Little is known how the COVID‐19 pandemic has disrupted diabetes‐related acute care. We compared hospitalization rates for severe hyperglycemia or hypoglycemia during the COVID‐19 outbreak in Hong Kong (study period: 25 January to 24 April 2020) with those during 25 January to 24 April 2019 (inter‐year control) and 25 October 2019 to 24 January 2020 (intra‐year control), using Poisson regression analysis. Hospitalization rates abruptly decreased after the first confirmed local COVID‐19 case on 23 January 2020, by 27% and 23% compared with the inter‐year and intra‐year control periods, respectively (incidence rate ratio 0.73 and 0.77, P

Objective Since it is unclear whether clinical parameters can independently predict the subsequent treatment response following high intensity focused ultrasound (HIFU) ablation of benign thyroid nodules, we aimed to examine clinical factors that may independently predict 12-month efficacy after HIFU treatment. Methods One hundred and forty patients who had single ablation were categorized into two groups, those with 12-month nodule shrinkage above the median (Group I, n = 70) and with shrinkage below or equal to the median (Group II, n = 70). Baseline characteristics, treatment parameters, percentage change in serum TSH, Free thyroxine (FT4) and thyroglobulin (Tg) from baseline to Day 4 and appearance of microbubbles (hyperechoic marks (HEMs)) during treatment were compared between groups. To determine independent factors, a multivariate analysis was done by logistic regression analysis. Results Baseline characteristics and treatment parameters were comparable between groups. However, on Day-4, group I had significantly lower serum TSH (0.49mIU/L vs. 0.84mIU/L, p = 0.011) and higher FT4 (22.11 pmol/L vs. 18.47 pmol/L, p = 0.008) than group II. The percentage change in TSH, FT4 and Tg were significantly greater in group I (p = 0.002, p = 0.009 and p = 0.001 respectively). The proportion of HEMs observed during treatment was also significantly higher in group I (42.69% vs. 31.72%, p = 0.030). Among the significant factors, the percentage change in FT4 was the only independent factor for 12-month shrinkage (OR = 1.018, 95%CI =1.003–1.032, p = 0.017). Conclusions Percentage change in serum FT4 on post-treatment Day-4 was an independent blood parameter for the subsequent nodule shrinkage at 12 months. This finding could potentially facilitate the decision for earlier retreatment of treated nodules.

Aims We carried out this prospective study of predominantly non-severe COVID-19 patients, to evaluate the influence of glycaemic status on clinical outcomes and neutralising antibody (Nab) responses, potentially relevant to the COVID-19 vaccination programme. Methods We included consecutive adults admitted to Queen Mary Hospital for COVID-19 from July 2020–May 2021. Glycaemic status was defined by admission HbA1c. Clinical deterioration was defined by radiological progression/new oxygen requirement/intensive care requirement/death. COVID-19 survivors had Nab measurements at 1-month, 2-month, 3-month and 6-month post-discharge. Results Among 605 patients (96.9% non-severe COVID-19; 325 normoglycaemia, 185 prediabetes, 95 diabetes), 74(12.2%) had clinical deterioration, more likely with worse glycaemic status and higher HbA1c (p

Objectives There are concerns for COVID-19 vaccination in causing thyroid dysfunction and triggering thyroid autoimmunity. Also, data on the impact of pre-existing thyroid autoimmunity on COVID-19 vaccination efficacy are limited. We evaluated the impact of COVID-19 vaccination on thyroid function and antibodies, and the influence of pre-existing thyroid autoimmunity on neutralizing antibody (NAb) responses. Methods Adults without history of COVID-19 or thyroid disorders who received COVID-19 vaccination between 14 June 2021 and 8 August 2021 at three vaccination centers were recruited. All participants received two doses of vaccines. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies were measured at baseline and 8 weeks after the first dose of vaccination. Post-vaccination NAb against SARS-CoV-2 receptor-binding domain was measured. Results In total, 215 individuals were included (129 BNT162b2 [60%] and 86 CoronaVac [40%] recipients): mean age 49.6 years, 37.2% men, and 12.1% positive for anti-TPO/anti-Tg at baseline. After vaccination, TSH levels did not change (p=0.225), but fT4 slightly increased (from 12. 0±1.1 to 12.2±1.2 pmol/L, p Conclusion COVID-19 vaccination was associated with a modest increase in anti-thyroid antibody titers. Anti-TPO increase was greater among BNT162b2 recipients. However, there was no clinically significant thyroid dysfunction 8 weeks post-vaccination. NAb responses were not influenced by pre-existing thyroid autoimmunity. Our results provided important reassurance to people to proceed to COVID-19 vaccination. Presentation: No date and time listed

BackgroundSome studies have indicated that interferon (IFN) may be valuable in COVID-19. We aimed to evaluate the impact of short-term IFN on incident thyroid dysfunction and autoimmunity among COVID-19 survivors.MethodsWe included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured both on admission and at three months.Results226 patients were included (median age 55.0 years; 49.6% men): 135 were IFN-treated. There tended to be more abnormal TFTs upon reassessment in IFN-treated patients (8.1% vs 2.2%, p=0.080). 179 patients (65.4% IFN-treated) had a complete reassessment of anti-thyroid antibodies. There were significant increases in titres of both anti-thyroid peroxidase antibodies (anti-TPO: baseline 29.21 units [IQR: 14.97 – 67.14] vs reassessment 34.30 units [IQR: 18.82 – 94.65], pvs reassessment 9.14 units [IQR: 6.83 – 17.17], p=0.001) in the IFN-treated group but not IFN-naïve group. IFN treatment (standardised beta 0.245, p=0.001) was independently associated with changes in anti-TPO titre. Of the 143 patients negative for anti-TPO at baseline, 8 became anti-TPO positive upon reassessment (seven IFN-treated; one IFN-naïve). Incident anti-TPO positivity was more likely to be associated with abnormal TFTs upon reassessment (phi 0.188, p=0.025).ConclusionIFN for COVID-19 was associated with modest increases in anti-thyroid antibody titres, and a trend of more incident anti-TPO positivity and abnormal TFTs during convalescence. Our findings suggest that clinicians monitor the thyroid function and anti-thyroid antibodies among IFN-treated COVID-19 survivors, and call for further follow-up studies regarding the clinical significance of these changes.