The Two-Year Results of Using Radiofrequency Ablation as a Novel Treatment for Persistent or Relapsed Graves' Disease: A Prospective Study.

Objectives: Graves' disease (GD) is the most common cause of hyperthyroidism. Antithyroid drugs (ATDs) are the first-line treatment, but when discontinued, >50% of patients experience relapses. Conventional definitive treatment options include surgery and radioiodine therapy (RAI), each with its own disadvantages. Radiofrequency ablation (RFA) achieved promising short-term remission rates in a previous pilot study. The current study reports our experience of using RFA to treat relapsed GD in the largest cohort of patients with a longer follow-up period. Methods: This single-arm prospective study recruited consecutive patients aged ≥18 with persistent/relapsed GD requiring ATD from two tertiary endocrine surgery centers. Those with compressive goiter, suspected thyroid malignancy, moderate-to-severe Graves' ophthalmopathy, preference for surgery/RAI, or pregnancy were excluded. Eligible patients received ultrasound-guided RFA to the entire bulk of the thyroid gland. ATDs were discontinued afterward, and thyroid function tests were monitored bimonthly. The primary outcome was the disease remission rate at 24 months follow-up after single-session RFA, defined as being biochemically euthyroid or hypothyroid without ATD. Secondary outcomes were complication rates. Results: Of the 100 patients considered, 30 (30.0%) patients were eligible and received RFA. Most were female patients (93.3%). The median total thyroid volume was 23 mL (15.9-34.5). All completed 24 months follow-up. After single-session RFA, disease remission rates were 60.0% at 12 months and 56.7% at 24 months. Among the 13 patients with relapse after RFA, 9 (69%) required a lower ATD dose than before RFA; 2 received surgery without complications. Total thyroid volume was the only significant factor associated with relapse after RFA (odds ratio 1.054, confidence interval 1.012-1.099, p = 0.012). At 24 months, RFA led to disease remission in 100% of the 9 patients with a total thyroid volume <20 mL and 35% of patients with a total thyroid volume ≥20 mL (p = 0.007). There was no vocal cord palsy, skin burn, hematoma, or thyroid storm after RFA. Conclusions: In a highly selected group of patients with relapsed GD and predominantly small thyroid glands, single-session RFA may achieve disease remission. Smaller total thyroid volume may be a favorable factor associated with disease remission after RFA. The results of this study need to be confirmed with a long-term clinical trial. Clinical Trial Registration: This study is registered at www.clinicaltrial.gov with identifier NCT06418919.

Long-term kidney outcomes in patients with permanent hypoparathyroidism after total thyroidectomy for benign disease: A population-based study.

BACKGROUND: Permanent hypoparathyroidism is a significant complication after total thyroidectomy. This study aimed to evaluate the long-term impact of postoperative permanent hypoparathyroidism on kidney outcomes. METHODS: Data of patients undergoing total thyroidectomy from 1999 to 2014 were retrieved. The estimated glomerular filtration rate was determined from serum creatinine results. Permanent hypoparathyroidism was defined as requiring oral calcium and vitamin D supplements postoperatively for at least 6 months. The primary outcome was a sustained decline in the estimated glomerular filtration rate from baseline by ≥50%. Secondary outcomes were end-stage kidney disease (a composite of sustained estimated glomerular filtration rate <15 mL/min/1.73 m2, need for dialysis, and kidney transplantation) and rate of estimated glomerular filtration rate decline. Patients with and without permanent hypoparathyroidism were compared. Multivariable Cox regression analysis was performed to identify independent risk factors for sustained estimated glomerular filtration rate decline by ≥50%. RESULTS: In total, 3,245 patients were eligible for analysis; 418 patients (12.9%) had permanent hypoparathyroidism. Upon median follow-up of 11.6 years, more patients with permanent hypoparathyroidism had a sustained decline in estimated glomerular filtration rate from baseline by ≥50% compared to those without (15.6% vs 6.9%, P < .001). Similar findings were obtained on Kaplan-Meier analysis (P < .001). Permanent hypoparathyroidism was an independent risk factor for sustained estimated glomerular filtration rate decline by ≥50% (adjusted hazard ratio 2.77, P < .001). Other risk factors included age, preoperative estimated glomerular filtration rate <60 mL/min/1.73m2, and diabetes mellitus. Patients with permanent hypoparathyroidism had a more rapid estimated glomerular filtration rate decline (-1.60 vs -0.70 mL/min/1.73 m2/year, difference -0.91 mL/min/1.73m2/year, P < .001). CONCLUSION: Patients with postsurgical permanent hypoparathyroidism were at greater risk of renal impairment. Further research is warranted to improve the identification and preservation of parathyroid glands during thyroidectomy to minimize patient morbidity.

Optimal timing of a colonoscopy screening schedule depends on adenoma detection, adenoma risk, adherence to screening and the screening objective: A microsimulation study.

Colonoscopy-based screening provides protection against colorectal cancer (CRC), but the optimal starting age and time intervals of screening colonoscopies are unknown. We aimed to determine an optimal screening schedule for the US population and its dependencies on the objective of screening (life years gained or incidence, mortality, or cost reduction) and the setting in which screening is performed. We used our established open-source microsimulation model CMOST to calculate optimized colonoscopy schedules with one, two, three or four screening colonoscopies between 20 and 90 years of age. A single screening colonoscopy was most effective in reducing life years lost from CRC when performed at 55 years of age. Two, three and four screening colonoscopy schedules saved a maximum number of life years when performed between 49-64 years; 44-69 years; and 40-72 years; respectively. However, for maximum incidence and mortality reduction, screening colonoscopies needed to be scheduled 4-8 years later in life. The optimum was also influenced by adenoma detection efficiency with lower values for these parameters favoring a later starting age of screening. Low adherence to screening consistently favored a later start and an earlier end of screening. In a personalized approach, optimal screening would start earlier for high-risk patients and later for low-risk individuals. In conclusion, our microsimulation-based approach supports colonoscopy screening schedule between 45 and 75 years of age but the precise timing depends on the objective of screening, as well as assumptions regarding individual CRC risk, efficiency of adenoma detection during colonoscopy and adherence to screening.

A comparison of cardiovascular disease, cancer, mortality, and Graves' ophthalmopathy following treatment for hyperthyroidism: A Bayesian network meta-analysis.

OBJECTIVES: This network meta-analysis aimed to evaluate the association of anti-thyroid drugs (ATD), radioactive iodine (RAI), and thyroidectomy with subsequent outcomes in patients with newly-diagnosed hyperthyroidism. METHODS: The Ovid Medline, Ovid Embase, and Cochrane Library databases were searched for observational studies and randomized controlled trials. Included studies were published on or before 1st May 2022 involving at least two of the treatments among ATD, RAI, and thyroidectomy for hyperthyroidism. Pairwise comparisons and Bayesian network meta-analysis were used to estimate hazard ratios (HRs) and their credible interval (CrI) of outcomes, including cardiovascular disease (CVD), cancer, overall mortality, and Graves' ophthalmopathy (GO). RESULTS: A total of 22 cohort studies with 131,297 hyperthyroidism patients were included. Thyroidectomy was associated with lower risks of mortality and GO than ATD (HR = 0.54, 95% CrI: 0.31, 0.96; HR = 0.31, 95% CrI: 0.12, 0.64) and RAI (HR = 0.62, 95% CrI: 0.41, 0.95; HR = 0.18, 95% CrI: 0.07, 0.35). RAI had a higher risk of GO (HR = 1.70, 95% CrI: 1.02, 2.99) than ATD treatment. CONCLUSIONS: This Bayesian network meta-analysis indicated that thyroidectomy was associated with lower risks of mortality and GO in newly-diagnosed hyperthyroid patients compared to ATD and RAI. Relative to ATD, RAI therapy increased the risk of GO.

General Principles for the Safe Performance, Training, and Adoption of Ablation Techniques for Benign Thyroid Nodules: An American Thyroid Association Statement.

Background: The primary goal of this interdisciplinary consensus statement is to provide a framework for the safe adoption and implementation of ablation technologies for benign thyroid nodules. Summary: This consensus statement is organized around three key themes: (1) safety of ablation techniques and their implementation, (2) optimal skillset criteria for proceduralists performing ablative procedures, and (3) defining expectations of success for this treatment option given its unique risks and benefits. Ablation safety considerations in pre-procedural, peri-procedural, and post-procedural settings are discussed, including clinical factors related to patient selection and counseling, anesthetic and technical considerations to optimize patient safety, peri-procedural risk mitigation strategies, post-procedural complication management, and safe follow-up practices. Prior training, knowledge, and steps that should be considered by any physician who desires to incorporate thyroid nodule ablation into their practice are defined and discussed. Examples of successful clinical practice implementation models of this emerging technology are provided. Conclusions: Thyroid ablative procedures provide valid alternative treatment strategies to conventional surgical management for a subset of patients with symptomatic benign thyroid nodules. Careful patient and nodule selection are critical to the success of these procedures as is extensive pre-procedural patient counseling. Although these emerging technologies hold great promise, they are not without risk and require the development of a unique skillset and environment for optimal, safe performance and consistent outcomes.

Because I'm happy - positive affect and its predictive value for future disease activity in patients with inflammatory bowel diseases: a retrospective cohort study.

Background: While the detrimental impact of negative emotions on the clinical course of inflammatory bowel disease (IBD) and quality of life has been extensively investigated, evidence for a potential impact of positive emotions is scarce. Objectives: We aim to analyse contributing factors of positive affect and their predictive value for disease course in IBD patients. Design: In this retrospective cohort study, epidemiological, psychosocial and IBD disease characteristics of Swiss IBD cohort study patients were analysed longitudinally. Methods: Epidemiological, psychosocial and disease characteristics were extracted from the database of the Swiss IBD cohort study. Participants' positive emotions were assessed cross-sectionally with the seven-item Marburg questionnaire (range 1-6) addressing positive affect in different aspects of daily life. Predictors of positive emotions were identified by linear regression. The quantitative longitudinal impact of positive emotions on the further disease course was analysed using a multivariable Cox proportional hazards model. Results: Among 702 IBD patients, those reporting more positive emotions were found to have significantly less intense medical treatment, less pain and fewer depressive symptoms (p < 0.05). A higher percentage of variability in positive emotions was explained by pain (36%) and depressive symptoms (13%) than by epidemiological characteristics (0.3%), or characteristics of IBD and its treatment (2.4%). Patients with higher levels of positive emotions (score > 3.5) experienced longer flare-free survival, also after adjusting for confounders (adjusted hazard ratio: 0.39, p < 0.05). Conclusions: The absence of pain and depressive symptoms were the strongest drivers for high positive affect. Higher scores of positive affect were associated with longer disease-free survival in IBD patients.

A Prospective Study Evaluating the Feasibility and Accuracy of Post-operative Laryngeal Ultrasonography (LUSG) in Assessment of Vocal Cord Function After Esophagectomy.

BACKGROUND: Vocal cord paresis (VCP) is a serious complication after esophagectomy. Conventional diagnosis of VCP relies on flexible laryngoscopy (FL), which is invasive. Laryngeal ultrasonography (LUSG) is non-invasive and convenient. It has provided accurate VC evaluation after thyroidectomy but it is unclear if it is just as accurate following esophagectomy. This prospective study evaluated the feasibility and accuracy of LUSG in VC assessment on day-1 after esophagectomy. METHODS: Consecutive patients from a tertiary teaching hospital who underwent elective esophagectomy were prospectively recruited. All received pre-operative FL, and post-operative LUSG and FL on Day-1, each performed by a blinded, independent assessor. The primary outcomes were feasibility and accuracy of LUSG in the diagnosis of VCP on Day-1 post-esophagectomy. The accuracy of voice assessment (VA) was analyzed. RESULTS: Twenty-six patients were eligible for analysis. The median age was 70 years (66-73). Majority were male (84.6%). Twenty-five (96.2%) received three-phase esophagectomy. Twenty-four (96%) had same-stage anastomosis at the neck. Three (11.5%) developed temporary and one (3.8%) developed permanent unilateral VCP. Overall VC visualization rate by LUSG was 100%; sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy of LUSG were 75.0%, 100%, 100%, 98.0%, 98.1% respectively, and superior to VA. Combining LUSG with VA findings could pick up all VCPs i.e. improved sensitivity and NPV to 100%. CONCLUSION: LUSG is a highly feasible, accurate and non-invasive method to evaluate VC function early after esophagectomy. Post-operative FL may be avoided in patients with both normal LUSG and voice.

Psychometric properties of EQ-5D-5L for use in patients with Graves' disease.

BACKGROUND: The EQ-5D-5 L is a commonly used generic measure of health. This study aimed to evaluate the psychometric properties of the EQ-5D-5 L in patients with Graves' disease (GD). METHODS: A prospective cohort of patients with GD recruited at three public hospitals in Hong Kong completed the EQ-5D-5 L and ThyPRO-39 questionnaires at baseline, 1-month, and 6-month follow-ups. Convergent validity was tested by examining the Spearman correlation between EQ-5D-5 L and ThyPRO-39 scores at baseline. 1-month test-retest reliability was assessed by Intraclass Correlation Coefficient (ICC), Gwet's Agreement Coefficient 2 (AC2), and percentage agreement. Responsiveness of EQ-5D-5 L index and EQ-VAS scores was assessed using effect size statistics (standardized effect size [SES] and standardized response mean [SRM]). RESULTS: Of 125 recruited patients, 101 (80.8%) and 100 (80.0%) patients were followed up at 1- and 6-month, respectively. For convergent validity, there was a moderate negative correlation between EQ-5D-5 L index or EQ-VAS score and ThyPRO-39 overall QoL-impact score (-0.350, -0.451), between EQ-VAS score and composite score (-0.483), and strong negative correlation between EQ-5D-5 L index score and composite score (-0.567). The Gwet's AC2 and percentage agreement were the highest in self-care (0.964 and 0.967), followed by mobility (0.952 and 0.962), usual activities (0.934 and 0.948), pain/discomfort (0.801 and 0.887), and anxiety/depression (0.788 and 0.882). The ICC for the EQ-5D-5 L index and the EQ-VAS was 0.707 and 0.700. For patients who reported having 'worsened' health at 6-month follow-up, the SES and SRM were - 0.66 and - 0.42 for EQ-5D-5 L index and - 1.15 and - 1.00 for EQ-VAS, respectively. CONCLUSIONS: The EQ-5D-5 L demonstrated convergent validity, test-retest reliability, and responsiveness to worsened health status among patients with GD.

Discharge of postoperative patients with an opioid prescription is associated with increased persistent opioid use, healthcare expenditures and mortality: a retrospective cohort study.

BACKGROUND: The risk factors for persistent opioid use after surgical discharge and the association between opioid prescription at discharge and postoperative emergency department visits, readmission, and mortality are unclear. METHODS: This population-based retrospective cohort study involved opioid-naive patients who underwent surgical procedures from January 1, 2000 to November 30, 2020. The data source was Hong Kong Hospital Authority Clinical Management System electronic health record. The primary outcome was the incidence of new persistent opioid use. Other study outcomes included 30-day emergency department visits, 30-day readmission, and 30-day all-cause mortality. Multivariable logistic regression models were used to estimate the association between opioid prescription at discharge and persistent opioid use, emergency department visits, readmission, and all-cause mortality. RESULTS: Over a median follow-up of 1 month with 36 104 person-years, 438 128 patients (opioid prescription: 32 932, no opioid prescription: 405 196) who underwent surgical procedures were analysed, of whom 15 112 (3.45%) had persistent opioid use after discharge. Prescribing opioids on discharge was associated with increased risks of developing persistent opioid use (odds ratio [OR]: 2.30, 95% confidence interval [CI]: 2.19-2.40, P<0.001), 30-day emergency department visits (OR: 1.28, 95% CI: 1.23-1.33, P<0.001), 30-day readmission (OR: 1.17, 95% CI: 1.13-1.20, P<0.001), and 30-day all-cause mortality (OR: 1.68, 95% CI: 1.53-1.86, P<0.001). CONCLUSIONS: In this large cohort of patients undergoing surgery, an opioid prescription on discharge was associated with a higher chance of persistent opioid use and increased risks of postoperative emergency department visits, readmission, and mortality. Minimising opioid prescriptions on discharge could improve perioperative patient outcomes.

Clinical Outcomes for Previously Treated Patients with Advanced Gastric or Gastroesophageal Junction Cancer: A Systematic Literature Review and Meta-Analysis.

PURPOSE: Although second-line treatments improve survival compared to best supportive care in patients with advanced gastric cancer with disease progression on first-line therapy, prognosis remains poor. A systematic review and meta-analysis were conducted to quantify the efficacy of second-or-later line systemic therapies in this target population. METHODS: A systematic literature review (January 1, 2000 to July 6, 2021) of Embase, MEDLINE, and CENTRAL with additional searches of 2019-2021 annual ASCO and ESMO conferences was conducted to identify studies in the target population. A random-effects meta-analysis was performed among studies involving chemotherapies and targeted therapies relevant in treatment guidelines and HTA activities. Outcomes of interest were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) presented as Kaplan-Meier data. Randomized controlled trials reporting any of the outcomes of interest were included. For OS and PFS, individual patient-level data were reconstructed from published Kaplan-Meier curves. RESULTS: Forty-four trials were eligible for the analysis. Pooled ORR (42 trials; 77 treatment arms; 7256 participants) was 15.0% (95% confidence interval (CI) 12.7-17.5%). Median OS from the pooled analysis (34 trials; 64 treatment arms; 60,350 person-months) was 7.9 months (95% CI 7.4-8.5). Median PFS from the pooled analysis (32 trials; 61 treatment arms; 28,860 person-months) was 3.5 months (95% CI 3.2-3.7). CONCLUSION: Our study confirms poor prognosis among patients with advanced gastric cancer, following disease progression on first-line therapy. Despite the approved, recommended, and experimental systemic treatments available, there is still an unmet need for novel interventions for this indication.

Pre-operative Cinacalcet Administration Reduces Immediate Post-operative Hypocalcemia Following Total Parathyroidectomy in Severe Renal Hyperparathyroidism.

BACKGROUND: In severe renal hyperparathyroidism (RHPT), whether administrating Cinacalcet before total parathyroidectomy can reduce post-operative hypocalcemia remains unclear. We compared post-operative calcium kinetics between those who took Cinacalcet before surgery (Group I) and those who did not (Group II). METHODS: Patients with severe RHPT (defined by PTH ≥ 100 pmol/L) who underwent total parathyroidectomy between 2012 and 2022 were analyzed. Standardized peri-operative protocol of calcium and vitamin D supplementation was followed. Blood tests were performed twice daily in the immediate post-operative period. Severe hypocalcemia was defined as serum albumin-adjusted calcium < 2.00 mmol/L. RESULTS: Among 159 patients who underwent parathyroidectomy, 82 patients were eligible for analysis (Group I, n = 27; Group II, n = 55). Demographics and PTH levels before Cinacalcet administration were comparable (Group I: 169 ± 49 pmol/L vs Group II: 154 ± 45, p = 0.209). Group I had significantly lower pre-operative PTH (77 ± 60 pmol/L vs 154 ± 45, p < 0.001), higher post-operative calcium (p < 0.05), and lower rate of severe hypocalcemia (33.3% vs 60.0%, p = 0.023). Longer duration of Cinacalcet use correlated with higher post-operative calcium levels (p < 0.05). Cinacalcet use for > 1 year resulted in fewer severe post-operative hypocalcemia than non-users (p = 0.022, OR 0.242, 95% CI 0.068-0.859). Higher pre-operative ALP independently correlated with severe post-operative hypocalcemia (OR 3.01, 95% CI 1.17-7.77, p = 0.022). CONCLUSION: In severe RHPT, Cinacalcet led to significant drop in pre-operative PTH, higher post-operative calcium levels, and less frequent severe hypocalcemia. Longer duration of Cinacalcet use correlated with higher post-operative calcium levels, and the use of Cinacalcet for > 1 year reduced severe post-operative hypocalcemia.

Efficacy of single-session radiofrequency ablation (RFA) in rendering euthyroidism for persistent/relapsed Graves' disease, a pilot study.

OBJECTIVES: Graves' disease (GD) is the most common cause of hyperthyroidism. Antithyroid drug (ATD) is often the first-line treatment but > 50% patients suffer a relapse when ATD is discontinued. Surgery or radioiodine remains the current options of definitive treatment in these patients. This pilot study examined the short-term efficacy of single-session thyroid radiofrequency ablation (RFA) as a novel definitive treatment for persistent/relapsed GD. METHODS: Consecutive patients with persistent/relapsed GD requiring ATD were considered. Those with a clear surgical indication, either thyroid lobe volume ≥ 20 mL; those who were pregnant or lactating; and those who had any severe medical conditions that would pose extra treatment risks were excluded. Eligible patients received ultrasound-guided RFA of the entire bulk of thyroid gland. Thyroid function tests were monitored bi-monthly. The primary outcome was disease remission rate, defined as a state of biochemical euthyroidism or hypothyroidism without ATD. Secondary outcomes were complication rates. RESULTS: Of the 68 patients considered, 15 (22.1%) patients were eligible. Most were females (93.3%). The median age was 37 (IQR 31-48) years old. The disease remission rates were 79.0% at 6 months and 73.3% at 12 months. Among the 4 patients who relapsed after RFA, three required less ATD dose than before RFA. RFA was well-tolerated in the ambulatory setting. There were no vocal cord palsy, skin burn, hematoma, or thyroid storm after RFA. CONCLUSIONS: In well-selected patients, single-session RFA of the thyroid gland may be a potential treatment for patients with persistent/relapsed GD. It is a safe and well-tolerated ambulatory procedure. KEY POINTS: • Radiofrequency ablation of the thyroid gland is an efficacious treatment for persistent/relapsed Graves' disease in well-selected patients. • Radiofrequency ablation of the thyroid gland for the treatment of persistent/relapsed Graves' disease is a safe and well-tolerated ambulatory procedure. • Radiofrequency ablation of the thyroid gland may be a potential alternative treatment for well-selected patients with persistent/relapsed GD who do not wish to undergo either thyroidectomy or radioactive iodine or continue antithyroid drugs.

Thyroid cancer.

The past 5-10 years have brought in a new era in the care of patients with thyroid cancer, with the introduction of transformative diagnostic and management options. Several international ultrasound-based thyroid nodule risk stratification systems have been developed with the goal of reducing unnecessary biopsies. Less invasive alternatives to surgery for low-risk thyroid cancer, such as active surveillance and minimally invasive interventions, are being explored. New systemic therapies are now available for patients with advanced thyroid cancer. However, in the setting of these advances, disparities exist in the diagnosis and management of thyroid cancer. As new management options are becoming available for thyroid cancer, it is essential to support population-based studies and randomised clinical trials that will inform evidence-based clinical practice guidelines on the management of thyroid cancer, and to include diverse patient populations in research to better understand and subsequently address existing barriers to equitable thyroid cancer care.

Parathyroidectomy versus oral cinacalcet on cardiovascular parameters in peritoneal dialysis patients with advanced secondary hyperparathyroidism (PROCEED): a randomized trial.

BACKGROUND: This trial aimed to evaluate oral cinacalcet versus total parathyroidectomy (PTx) with forearm autografting on cardiovascular surrogate outcomes and health-related quality of life (HRQOL) measures in dialysis patients with advanced secondary hyperparathyroidism (SHPT). DESIGN: In this pilot prospective randomized trial conducted in two university-affiliated hospitals, 65 adult peritoneal dialysis patients with advanced SHPT were randomized to receive either oral cinacalcet or PTx. Primary endpoints were changes in left ventricular (LV) mass index by cardiac magnetic resonance imaging and coronary artery calcium scores (CACS) over 12 months. Secondary endpoints included changes in heart valves calcium scores, aortic stiffness, biochemical parameters of chronic kidney disease-mineral bone disease (CKD-MBD) and HRQOL measures over 12 months. RESULTS: Changes in LV mass index, CACS, heart valves calcium score, aortic pulse wave velocity and HRQOL did not differ between groups or within groups, despite significant reductions in plasma calcium, phosphorus and intact parathyroid hormone in both groups. Cinacalcet-treated patients experienced more cardiovascular-related hospitalizations than those who underwent PTx (P = .008) but the difference became insignificant after adjusting for baseline difference in heart failure (P = .43). With the same monitoring frequency, cinacalcet-treated patients had fewer hospitalizations due to hypercalcemia (1.8%) than patients who underwent PTx (16.7%) (P = .005). No significant changes were observed in HRQOL measures in either group. CONCLUSIONS: Both cinacalcet and PTx effectively improved various biochemical abnormalities of CKD-MBD and stabilized but did not reduce LV mass, coronary artery and heart valves calcification, or arterial stiffness, or improve patient-centered HRQOL measures in PD patients with advanced SHPT. Cinacalcet may be used in place of PTx for treating advanced SHPT. Long-term and powered studies are required to evaluate PTx versus cinacalcet on hard cardiovascular outcomes in dialysis patients. Trial registration: ClinicalTrials.gov identifier: NCT01447368.

A prospective follow-up of thyroid volume and thyroiditis features on ultrasonography among survivors of predominantly mild to moderate COVID-19.

Background: We previously showed that higher SARS-CoV-2 viral load correlated with smaller thyroid volumes among COVID-19 survivors at 2 months after acute COVID-19. Our current follow-up study evaluated the evolution of thyroid volumes and thyroiditis features within the same group of patients 6 months later. Methods: Adult COVID-19 survivors who underwent thyroid ultrasonography 2 months after infection (USG1) were recruited for follow-up USG 6 months later (USG2). The primary outcome was the change in thyroid volume. We also reassessed thyroiditis features on USG, thyroid function and anti-thyroid antibodies. Results: Fifty-four patients were recruited (mean age 48.1 years; 63% men). The mean thyroid volume increased from USG1 to USG2 (11.9 ± 4.8 to 14.5 ± 6.2 mL, p < 0.001). Thirty-two patients (59.3%) had significant increase in thyroid volume by ≥15%, and they had a median increase of +33.3% (IQR: +20.0% to +45.0%). Multivariable logistic regression analysis showed that only higher baseline SARS-CoV-2 viral load independently correlated with significant thyroid volume increase on USG2 (p = 0.022). Among the seven patients with thyroiditis features on USG1, six (85.7%) had the features resolved on USG2. None had new thyroiditis features on USG2. All abnormal thyroid function during acute COVID-19 resolved upon USG1 and USG2. Conclusion: Most COVID-19 survivors had an increase in thyroid volume from early convalescent phase to later convalescent phase. This increase correlated with high initial SARS-CoV-2 viral load. Together with the resolution of thyroiditis features, these may suggest a transient direct atrophic effect of SARS-CoV-2 on the thyroid gland with subsequent recovery of thyroid volume and thyroiditis features.

Value assignment and uncertainty evaluation for anion and single-element reference solutions incorporating historical information.

The National Institute of Standards and Technology, which is the national metrology institute of the USA, assigns certified values to the mass fractions of individual elements in single-element solutions, and to the mass fractions of anions in anion solutions, based on gravimetric preparations and instrumental methods of analysis. The instrumental method currently is high-performance inductively coupled plasma optical emission spectroscopy for the single-element solutions, and ion chromatography for the anion solutions. The uncertainty associated with each certified value comprises method-specific components, a component reflecting potential long-term instability that may affect the certified mass fraction during the useful lifetime of the solutions, and a component from between-method differences. Lately, the latter has been evaluated based only on the measurement results for the reference material being certified. The new procedure described in this contribution blends historical information about between-method differences for similar solutions produced previously, with the between-method difference observed when a new material is characterized. This blending procedure is justified because, with only rare exceptions, the same preparation and measurement methods have been used historically: in the course of almost 40 years for the preparation methods, and of 20 years for the instrumental methods. Also, the certified values of mass fraction, and the associated uncertainties, have been very similar, and the chemistry of the solutions also is closely comparable within each series of materials. If the new procedure will be applied to future SRM lots of single-element or anion solutions routinely, then it is expected that it will yield relative expanded uncertainties that are about 20 % smaller than the procedure for uncertainty evaluation currently in use, and that it will do so for the large majority of the solutions. However, more consequential than any reduction in uncertainty, is the improvement in the quality of the uncertainty evaluations that derives from incorporating the rich historical information about between-method differences and about the stability of the solutions over their expected lifetimes. The particular values listed for several existing SRMs are given merely as retrospective illustrations of the application of the new method, not to suggest that the certified values or their associated uncertainties should be revised.

Clinical outcomes of chemotherapy-based therapies for previously treated advanced colorectal cancer: a systematic literature review and meta-analysis.

PURPOSE: The purpose of this study was to evaluate clinical outcomes of standard therapies in previously treated, advanced colorectal cancer (CRC) patients. METHODS: A systematic literature review was conducted in Embase, MEDLINE, and CENTRAL databases (January 2000-July 2021), annual oncology conferences (2019-2021), and clinicaltrials.gov to identify studies evaluating the use of licensed interventions in second-line or later settings. The primary outcome of interest was objective response rate (ORR) and secondary outcomes included progression-free survival (PFS) and overall survival (OS). ORR was pooled using the Freeman-Tukey double arcsine transformation. For survival outcomes, published Kaplan-Meier curves for OS and PFS were digitized to re-construct individual patient-level data and pooled following the methodology described by Combescure et al. (2014). RESULTS: Twenty-three trials evaluating standard chemotherapies with or without targeted therapies across 4,791 advanced CRC patients contributed to our meta-analysis. In the second-line setting, the random effects pooled estimate of ORR was 22.4% (95% confidence interval (CI): 18.0, 27.1), median PFS was 7.0 months (95% CI: 6.4, 7.4), and median OS was 14.9 months (95% CI: 13.6, 16.1). In the third-line or later setting, the random effects pooled estimate of ORR was 1.7% (95% CI: 0.8, 2.7), median PFS was 2.3 months (95% CI: 2.0, 2.8), and median OS was 8.2 months (95% CI: 7.1, 9.1). CONCLUSION: Standard treatments have limited efficacy in the second-line or later setting with worsening outcomes in later lines. Given the global burden of CRC, further research into novel and emerging therapeutic options following treatment failure is needed.

A Population-Based Study of SGLT2 Inhibitor-Associated Postoperative Diabetic Ketoacidosis in Patients with Type 2 Diabetes.

INTRODUCTION AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.