Current guidelines for the application of radiofrequency ablation for thyroid nodules: a narrative review.

Background and Objective: Thyroid nodules are frequently incidentally found on physical exam or imaging for an unrelated work-up. Although surgery remains the gold standard for treating symptomatic benign and/or malignant thyroid nodules, radiofrequency ablation (RFA) has emerged as a minimally invasive treatment option for high risk patients and those who decline surgery. The novel application of RFA to treat thyroid disease was originally described for symptomatic, benign thyroid nodules. Since then, several studies have tried to expand its indication to treat primary and recurrent well-differentiated thyroid cancer. The high success rates and the low complication profile, has allowed for quick adoption of RFA as a treatment option for well-selected patients with benign thyroid nodules and locoregional recurrent thyroid malignancy. As such, multidisciplinary guidelines and consensus statements were developed to standardize indications, techniques, outcome measures, and follow-up to ensure the best patient care. This article summarizes the current indications and recommendations to help guide clinicians on how best to effectively and safely utilize RFA to treat thyroid disease. Methods: A PubMed/MEDLINE search between 2000-2022 using a combination of "radiofrequency ablation", "RFA", "thyroid nodule", and "guidelines" was conducted. The inclusion criteria were articles published in English which offered recommendations on RFA use for thyroid nodules. Key Content and Findings: For symptomatic, benign thyroid nodules, RFA is effective at significantly reducing nodule volume. For large nodules, multiple RFA sessions may be needed to achieve clinically significant volume reduction. Patients undergoing RFA for autonomously functioning thyroid nodules may see symptomatic relief but success rates are variable. RFA may serve a curative or palliative role in recurrent well-differentiated thyroid cancers. There is little data describing the use of RFA for primary well-differentiated thyroid cancer >1 cm and the role of RFA for thyroid microcarcinomas remains controversial. Conclusions: RFA is a safe minimally invasive technique and may be considered, in appropriate circumstances, a first-line treatment option for benign thyroid nodules. Practices adopting RFA will likely increase as more clinicians become familiar with this technique, highlighting the importance of developing standardized guidelines.

Beyond the three P's: adrenal involvement in MEN1.

Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients' clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47 ± 11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3-123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional work-up (diagnoses: pheochromocytoma (n = 2), adrenocorticotropic hormone-dependent hypercortisolism (n = 2), hyperandrogenism (n = 1), hyperaldosteronism (n = 1)); surgery was indicated for 5 (83.3%; n = 12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and two with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion's growth rate and size. A baseline hormonal work-up is recommended, and no further biochemical work-up is suggested when the initial assessment shows nonfunctioning lesions.

Mental Health of Children With Special Educational Needs and the Return to In-Person Learning After the COVID-19 Pandemic.

Importance: There is limited evidence on whether the quality of life and behavior of children with special educational needs (SEN) have improved or worsened since schools reopened after COVID-19-related school closures. Objective: To describe the changes in the mental well-being of children and adolescents with SEN during the initial 6 months of resuming in-person learning after COVID-19-related school closures. Design, Setting, and Participants: This repeated cross-sectional study reported data from surveys completed by parents and caregivers of children and adolescents aged 3 to 18 years with SEN studying at special schools in Hong Kong. The first cohort was obtained during COVID-19-related school closure in April 2020 (wave 1) and the second cohort was obtained 6 months after school resumption with data collection between July and October 2021 (wave 2). Data analysis occurred from January to June 2022. Exposure: Diagnosis of a disability or disorder that required school-based special educational programming. Main Outcomes and Measures: Children's emotional and behavioral difficulties (measured with the Strengths and Difficulties Questionnaire [SDQ]), quality of life (measured with the Pediatric Quality of Life Inventory [PedsQL]), lifestyle habits, parental stress, and parental well-being (measured with the PedsQL Family Impact Module) were assessed. Cross-sectional comparisons of well-being between the 2 waves were conducted using analysis of covariance, and multiple regression analysis was performed to identify factors associated with mental health outcomes in wave 2. Results: In wave 1, a total of 456 parents and caregivers of children with SEN (mean [SD] age, 7.44 [3.98] years; 315 boys [69.1%]; 141 girls [30.9%]) responded to the surveys. In wave 2, 519 parents and caregivers of children with SEN (mean [SD] age, 8.16 [4.47] years; 365 boys [70.3%]; 154 girls [29.7%]) responded. After school resumption, preschoolers aged 3 to 5 years with SEN had significantly fewer emotional difficulties (mean [SD] SDQ score, 3.26 [2.39] vs 2.68 [2.03]; standardized mean difference [SMD] = 0.26; 95% CI, 0.07-0.46; Bonferroni-corrected P = .04) and conduct difficulties (mean [SD] SDQ score, 2.88 [1.89] vs 2.41 [1.91]; SMD = 0.25; 95% CI, 0.05-0.44; Bonferroni-corrected P = .01), whereas adolescents had more conduct difficulties (mean [SD] SDQ score, 1.62 [1.50] vs 2.37 [3.02]; SMD = 0.41; 95% CI, 0.13-0.70; Bonferroni-corrected P = .049). The overall quality of life of school-aged children with SEN aged 6 to 11 years worsened after school resumption (mean [SD] PedsQL score, 67.52 [17.45] vs 60.57 [16.52]; SMD = 0.41; 95% CI, 0.19-0.62; Bonferroni-corrected P = .002). Conclusions and Relevance: The findings of this repeated cross-sectional study suggest that preschoolers with SEN had improved emotional and behavioral functioning when school resumed after COVID-19-related closures. School-aged children with SEN, adolescents with SEN, and children with intellectual disabilities were at risk of reduced quality of life, indicating that additional support should be offered to vulnerable groups as they return to schools.

Succinate Dehydrogenase Mutations as Familial Pheochromocytoma Syndromes.

It is recognized that a large portion of pheochromocytoma and paraganglioma cases will have an underlying germline mutation, supporting the recommendation for universal genetic testing in all patients with PPGLs. A mutation in succinate dehydrogenase subunit B is associated with increased rates of developing synchronous and/or metachronous metastatic disease. Patients identified with this mutation require meticulous preoperative evaluation, a personalized surgical plan to minimize the risk of recurrence and tumor spread, and lifelong surveillance.

Primary anastomosis is the preferred surgical approach for proximal intestinal atresia: a retrospective 20-year analysis.

PURPOSE: We aimed to compare the outcomes of primary anastomosis (PA) and enterostomy as treatments for intestinal atresia in neonates to identify the factors influencing the choice of modality. METHODS: We conducted a retrospective single-centre analysis of all neonates with intestinal atresia between 2000 and 2020 and measured the clinical outcomes. We performed logistic regression to identify factors that influenced the choice of surgical approach. RESULTS: Of 62 intestinal atresia neonates, 71% received PA. There were no significant differences in gestation, gender, age at operation, birth weight, or body weight at operation between the PA and enterostomy groups. PA reoperation was not required for 78% of patients, and the PA group had shorter hospital stays. Complications, operative time, duration on parenteral nutrition, time to full enteral feeding were comparable in both groups. Upon multivariate regression analysis, surgeons favoured PA in proximal atresia [Odds ratio (OR) 38.5, 95% Confidence Interval (CI) 2.558-579] while enterostomy in smaller body size [OR 2.75, CI 0.538-14.02] and lower Apgar score [OR 1.1, CI 0.07-17.8]. Subgroup analysis in these patient groups demonstrated comparable outcomes with both surgical approaches. CONCLUSION: Both surgical approaches achieved comparable outcomes, but PA was associated with short hospital stays and the avoidance of stoma-related complications, and reoperation was generally not required. This surgical approach was suitable for patients with proximal atresia, but enterostomy remained a sensible choice for patients with smaller body sizes and lower Apgar scores.

Advances in Endocrine Surgery.

Recent changes in the landscape of endocrine surgery include a shift from total thyroidectomy for almost all patients with papillary thyroid cancer to the incorporation of thyroid lobectomy for well-selected patients with low-risk disease; minimally invasive parathyroidectomy with, and potentially without, intraoperative parathyroid hormone monitoring for patients with well-localized primary hyperparathyroidism; improvement in the management of parathyroid cancer with the incorporation of immune checkpoint blockade and/or targeted therapies; and the incorporation of minimally invasive techniques in the management of patients with benign tumors and selected secondary malignancies of the adrenal gland.

Pheochromocytoma recurrence in hereditary disease: does a cortical-sparing technique increase recurrence rate?

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy is an appealing approach for patients with hereditary pheochromocytoma and lends well to cortex preservation. We sought to examine pheochromocytoma recurrence in patients with hereditary pheochromocytoma in the era of posterior retroperitoneoscopic adrenalectomy and evaluate the predictors of recurrence. METHODS: Patients with hereditary pheochromocytoma who underwent adrenalectomy for pheochromocytoma between 1995 and 2020 with biochemical cure and follow-up >1 year were identified. Recurrence was defined as plasma metanephrines above the upper limit of normal with radiographic evidence of disease in the ipsilateral adrenal bed. RESULTS: Seventy-eight hereditary pheochromocytoma patients (median age = 32.4 years; 60.3% women) underwent 114 adrenalectomies for pheochromocytoma. Of these patients, 40 had multiple endocrine neoplasia type 2A (51.3%), 10 had multiple endocrine neoplasia type B (12.8%), 17 had von Hippel-Lindau disease (21.8%), and 11 had neurofibromatosis type 1 (14.1%). Thirty-eight adrenalectomies (33.3%) were performed before the introduction of posterior retroperitoneoscopic adrenalectomy and 76 (66.7%) after. Cortical-sparing technique was performed in 62 (54.4%) adrenalectomies, with no difference in its use before and after posterior retroperitoneoscopic adrenalectomy introduction (P > .05). During a median follow-up of 80.7 months (interquartile range 43.4-151.2), 12 ipsilateral recurrences (10.5%) were identified. There was no difference in recurrence before and after the introduction of posterior retroperitoneoscopic adrenalectomy or by surgical technique or approach of the entire cohort (P > .05). Recurrence was more common in those with RET M918T mutation (23.5% vs 8.2%; P = .05). Patients with RET M918T mutations had a shorter recurrence-free survival (P = .013). On multivariate analysis, only RET M918T mutation was independently associated with an increased recurrence risk (hazard ratio = 4.30; 95% confidence interval, 1.26-14.66; P = .019). CONCLUSION: The introduction of posterior retroperitoneoscopic adrenalectomy did not influence the recurrence rate after adrenalectomy for hereditary pheochromocytoma patients. Patients with a RET M918T germline mutation are at increased risk for pheochromocytoma recurrence and may benefit from initial total adrenalectomy.

Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism is Associated with Improved Bone Mineral Density Regardless of Postoperative Parathyroid Hormone Levels.

BACKGROUND: Biochemical cure in normocalcemic primary hyperparathyroidism (nPHPT) is defined as parathyroid hormone (PTH) level normalization 6 months after parathyroidectomy. However, recent studies show that a significant number of nPHPT patients have persistent PTH elevation postoperatively. We sought to correlate changes in PTH levels with skeletal outcomes after parathyroidectomy in nPHPT patients. METHODS: Adult patients who underwent parathyroidectomy at a tertiary referral center for sporadic PHPT between 2010 and 2020 were reviewed. Pre- and postoperative (6 months, 18 months, and last follow-up) laboratory and bone mineral densities (BMD) were recorded. Primary outcome was 18-month postoperative BMD change in the lumbar spine (LS), total hip (TH) and femoral neck (FN) in normocalcemic and hypercalcemic PHPT (hPHPT) patients. RESULTS: Of 661 patients included, 68 had nPHPT. nPHPT patients frequently had multigland disease (31% vs. 18%, p = 0.014), more bilateral cervical explorations (22% vs. 13%, p = 0.042), and fewer achieved biochemical cure (76% vs. 95%, p < 0.001) than hPHPT patients. Twenty-eight nPHPT patients had BMD data for comparison. Overall, nPHPT patients had improvement in the LS (1.84%, p = 0.002) and TH (1.64%, p = 0.014). When stratified by postoperative PTH levels, nPHPT patients with persistent PTH elevation had more BMD improvement at the TH than those who normalized PTH (3.73% vs. - 0.83%, p = 0.017). There was no difference in improvement at the LS or FN (p = NS). CONCLUSION: Parathyroidectomy is associated with improved BMD in nPHPT patients with bone disease. Although one in four nPHPT patients had elevated postoperative PTH levels persisting throughout the study, BMD improvement was still seen regardless of postoperative PTH level normalization.

Implementation of a formal sleep center-based screening protocol for primary aldosteronism in patients with obstructive sleep apnea.

BACKGROUND: There is a bidirectional association between primary aldosteronism and obstructive sleep apnea, with evidence suggesting that the treatment of primary aldosteronism can reduce obstructive sleep apnea severity. Current guidelines recommend screening for primary aldosteronism in patients with comorbid hypertension and obstructive sleep apnea, identifying potential candidates for treatment. However, emerging data suggest current screening practices are unsatisfactory. Moreover, data regarding the true incidence of primary aldosteronism among this population are limited. This study aimed to assess the primary aldosteronism screening rate among patients with obstructive sleep apnea and hypertension at our institution and estimate the prevalence of primary aldosteronism among this population. METHODS: Sleep studies conducted at our institution between January and September 2021 were retrospectively reviewed. Adult patients with a sleep study diagnostic of obstructive sleep apnea (respiratory disturbance index ≥5) and a diagnosis of hypertension were included. Patient medical records were reviewed and laboratory data of those with biochemical screening for primary aldosteronism were assessed by an experienced endocrinologist. Screening rates were compared before and after initiation of a screening protocol in accordance with the 2016 Endocrine Society guidelines. RESULTS: A total of 1,005 patients undergoing sleep studies were reviewed; 354 patients had comorbid obstructive sleep apnea and hypertension. Patients were predominantly male (67%), with a mean age of 58 years (standard deviation = 12.9) and mean body mass index of 34 (standard deviation = 8.1). The screening rate for primary aldosteronism among included patients was 19% (n = 67). The screening rate was significantly higher after initiation of a dedicated primary aldosteronism screening protocol (23% vs 12% prior; P = .01). Fourteen screens (21%) were positive for primary aldosteronism, whereas 45 (67%) were negative and 8 (12%) were indeterminate. Four had prior abdominal cross-sectional imaging, with 3 revealing an adrenal adenoma. Compared with patients without primary aldosteronism, patients with positive primary aldosteronism screens were more likely to have a history of hypokalemia (36% vs 4.4%; P = .002). The frequency of hyperlipidemia, diabetes mellitus, and left ventricular hypertrophy did not differ between patients with positive versus negative screens. CONCLUSION: Current screening practices for primary aldosteronism among patients with comorbid obstructive sleep apnea and hypertension are suboptimal. Patients evaluated at sleep centers may represent an optimal population for screening, as the prevalence of primary aldosteronism among this cohort appears high.

COVID-19 vaccination in patients with rheumatic diseases: Vaccination rates, patient perspectives, and side effects.

INTRODUCTION: To investigate the vaccination rate, reported side effects, and patient concerns for COVID-19 vaccination in patients with rheumatic diseases. METHODS: A multicentre cross-sectional study from rheumatology clinics in two major hospitals in Hong Kong was conducted between June 3, 2021 and October 8, 2021. Patient interviews for demographics, clinical characteristics, vaccination status, reported side effects, and factors influencing decisions about vaccination were supplemented with structured questionnaires. RESULTS: Out of 1367 patients, 413 (30.2%) had received COVID-19 vaccination. Side effects were reported in 335 (81.1%) of patients, of which the most common were injection site pain or swelling (66.3%), fatigue (57.1%), fever (19.9%), and headache (19.6%). Multivariate logistic regression models showed that males (odds ratio [OR] = 1.80; p < .001), higher education level (OR = 1.64; p < .001) and healthcare professionals (OR = 4.5; p < .001) were significantly more likely to have received the vaccine. In contrast, patients with hypertension (OR = 0.73; p = .04), systemic lupus erythematous (OR = 0.53; p < .001), stroke (OR = 0.29; p = .01), steroid therapy (OR = 0.59; p = .01), and leflunomide therapy (OR = 0.45; p = .05) were significantly less likely to be vaccinated. Younger age (age, OR = 0.96; p = .003) and messenger RNA (mRNA) vaccines (OR = 4.79; p < .001) were associated with more side effects. There was no difference in risk of side effects between specific rheumatic diseases or drug therapies. CONCLUSION: COVID-19 vaccination is associated with no increased risk of side effects in any particular disease or drug therapy, therefore vaccination should be encouraged in patients with rheumatic disease. In addition, younger age is associated minimally, while mRNA vaccine is associated with increased side effects.

Stones left unturned: Missed opportunities to diagnose primary hyperparathyroidism in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a sequela of primary hyperparathyroidism and an indication for parathyroidectomy. The prevalence of primary hyperparathyroidism in patients with nephrolithiasis is 3% to 5%; however, recent studies suggest that many hypercalcemic patients with nephrolithiasis never undergo workup for primary hyperparathyroidism. Our goal is to evaluate primary hyperparathyroidism screening rates at a tertiary academic health institution and identify opportunities to increase referral rates in patients presenting with nephrolithiasis. METHODS: We retrospectively reviewed 15,725 patients across an academic health system who presented with nephrolithiasis between 2012 and 2020. Calcium levels measured within 6 months of presentation were identified, and those with hypercalcemia (≥10.3 mg/dL) were reviewed if parathyroid hormone levels were measured. Patients with primary hyperparathyroidism were evaluated to see if they were referred to a specialist for treatment. RESULTS: Of 15,725 patients presenting with nephrolithiasis, 12,420 (79%) had calcium levels measured; 630 patients (4.0%) were hypercalcemic, and 207 (33%) had parathyroid hormone levels measured. Patients were more likely to have parathyroid hormone levels sent if they were older, had higher calcium levels, or presented to an outpatient clinic (P = .028, P = .002, P < .001). We identified 89 patients (0.6%) with primary hyperparathyroidism, of which only 35 (39%) were referred for treatment. CONCLUSION: The proportion of patients presenting with nephrolithiasis ultimately diagnosed with primary hyperparathyroidism was significantly lower than others have reported. Additionally, a substantial number of patients with nephrolithiasis did not have calcium and/or parathyroid hormone levels measured. These missed opportunities for diagnosis are critical as early definitive management of primary hyperparathyroidism can prevent recurrent nephrolithiasis and other primary hyperparathyroidism-related end organ effects.

Biodegradation kinetics of ammonium enriched food waste digestate compost with biochar amendment.

High concentration of NH4+-N in food waste digestate (FWD) produced from biological treatment of food waste is considered as a major threat on the composting process resulting in production of immature compost. Hence, a laboratory batch composting study was conducted to examine the feasibility of using biochar as a physical additive to ameliorate the inhibitory effect of NH4+-N and to mitigate the nitrogen loss during FWD composting. FWD was co-composted with tobacco biochar at a dosage of 0%, 2.5%, 5% or 10% (dw) in bench-scale composters with a controlled aeration system. The addition of 10% biochar enhanced the degradation rate resulting in 44% higher carbon decomposition than the control. Besides, 10% biochar amendment reduced NH3 and N loss by 58% and 5%, respectively and significantly reduced NH4+-N content to HKORC limit of < 700 mg/kg dw within 5 days showing the beneficiary impact of biochar addition.

Botulinum toxin treatment for facial palsy: A systematic review.

BACKGROUND: Facial palsy may be complicated by ipsilateral synkinesis or contralateral hyperkinesis. Botulinum toxin is increasingly used in the management of facial palsy; however, the optimum dose, treatment interval, adjunct therapy and performance as compared with alternative treatments have not been well established. This study aimed to systematically review the evidence for the use of botulinum toxin in facial palsy. METHOD: The Cochrane central register of controlled trials (CENTRAL), MEDLINE(R) (1946 to September 2015) and Embase Classic + Embase (1947 to September 2015) were searched for randomised studies using botulinum toxin in facial palsy. RESULTS: Forty-seven studies were identified, and three included. Their physical and patient-reported outcomes are described, and observations and cautions are discussed. DISCUSSION: Facial asymmetry has a strong correlation to subjective domains such as impairment in social interaction and perception of self-image and appearance. Botulinum toxin injections represent a minimally invasive technique that is helpful in restoring facial symmetry at rest and during movement in chronic, and potentially acute, facial palsy. Botulinum toxin in combination with physical therapy may be particularly helpful. Currently, there is a paucity of data; areas for further research are suggested. A strong body of evidence may allow botulinum toxin treatment to be nationally standardised and recommended in the management of facial palsy.

A nacre protein, n16.3, self-assembles to form protein oligomers that dimensionally limit and organize mineral deposits.

The mollusk shell is a complex biological material that integrates mineral phases with organic macromolecular components such as proteins. The role of proteins in the formation of the nacre layer (aragonite mineral phase) is poorly understood, particularly with regard to the organization of mineral deposits within the protein extracellular matrix and the identification of which proteins are responsible for this task. We report new experiments that provide insight into the role of the framework nacre protein, n16.3 (Pinctada fucata), as an organizer or assembler of calcium carbonate mineral clusters. Using a combination of biophysical techniques, we find that recombinant n16.3 (r-n16.3) oligomerizes to form amorphous protein films and particles that possess regions of disorder and mobility. These supramolecular assemblies possess an intrinsically disordered C-terminal region (T64-W98) and reorganize in the presence of Ca(2+) ions to form clustered protein oligomers. This Ca(2+)-induced reorganization leads to alterations in the molecular environments of Trp residues, the majority of which reside in putative aggregation-prone cross-ß strand regions. Potentiometric Ca(2+) titrations reveal that r-n16.3 does not significantly affect the formation of prenucleation clusters in solution, and this suggests a role for this protein in postnucleation mineralization events. This is verified in subsequent in vitro mineralization assays in which r-n16.3 demonstrates its ability to form gel-like protein phases that organize and cluster nanometer-sized single-crystal calcite relative to protein-deficient controls. We conclude that the n16 nacre framework proteome creates a protein gel matrix that organizes and dimensionally limits mineral deposits. This process is highly relevant to the formation of ordered, nanometer-sized nacre tablets in the mollusk shell.