A randomized, open-label, multicenter study of switching to brolucizumab with or without a loading dose for patients with suboptimal anatomically controlled neovascular age-related macular degeneration-the FALCON study.

BACKGROUND: Treatment initiation with brolucizumab, a new potent anti-vascular endothelial growth factor (VEGF) agent, is typically performed with three monthly injections (loading dose) and has been well studied in treatment-naïve patients. However, no clinical data are available yet on whether or not anti-VEGF pretreated patients also benefit from a loading dose. In the clinical setting, different heterogeneous treatment patterns are used as no clinical trial has addressed this so far in a head-to-head comparison. Therefore, the FALCON study is investigating whether patients with unsatisfactory response to previous anti-VEGF treatments benefit from a loading dose at the switch to brolucizumab treatment. METHODS: FALCON is a 52-week, two-arm, randomized, open-label, multicenter, multinational study in patients with residually active neovascular age-related macular degeneration (nAMD) who will be randomized 1:1 and started with brolucizumab 6 mg loading (three monthly loading doses) or brolucizumab 6 mg non-loading (one initial injection) and consecutive treatment every 12 weeks, respectively. The primary objective is to demonstrate non-inferiority of the non-loading vs. loading arm in mean change of best-corrected visual acuity (BCVA) from baseline to the mean value at week 40 to week 52. Secondary objectives include the assessment of anatomical outcomes, treatment intervals, safety and tolerability. RESULTS: FALCON will be the first study to assess treatment initiation with an anti-VEGF agent in a switch situation with or without loading dose in patients with nAMD. CONCLUSIONS: The results will support the optimization of treatment of patients with previous unsatisfactory anti-VEGF response. Therefore, we expect to see an impact on current clinical practice which has been established for more than a decade. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04679935, date of registration-22-Dec 2020; EUDRACT number: 2019-004763-53, date of registration-03 Dec 2019.

Language and executive functioning in young adults with Down syndrome.

BACKGROUND: This study examined the association between executive functioning and language in young adults with Down syndrome (DS). METHOD: Nineteen young adults with DS (aged 19-24 years) completed standardised measures of overall cognition, vocabulary, verbal fluency and executive function skills. RESULTS: Friedman's analysis of variance (χ2 (3) = 28.15, P < .001) and post hoc comparisons indicated that, on average, participants had a significantly lower overall non-verbal than verbal cognitive age equivalent and lower expressive than receptive vocabulary skills. Using Spearman correlations, performance on a verbal measure of cognition inhibition was significantly negatively related to receptive vocabulary (ρ = -.529, adjusted P = .036) and verbal fluency (ρ = -.608, adjusted P = .022). Attention was significantly positively correlated with receptive (ρ = .698, adjusted-p = .005) and expressive (ρ = .542, adjusted P = .027) vocabulary. Verbal working memory was significantly positively associated with receptive vocabulary (ρ = .585, adjusted P = .022) and verbal fluency (ρ = .737, adjusted P = .003). Finally, visuospatial working memory was significantly associated with receptive vocabulary (ρ = .562, adjusted P = .027). CONCLUSIONS: Verbal and non-verbal measures of executive functioning skills had important associations with language ability in young adults with DS. Future translational research is needed to investigate causal pathways underlying these relationships. Research should explore if interventions aimed at increasing executive functioning skills (e.g. attention, inhibition and working memory) have the potential to lead to increases in language for young adults with DS.

Real-world-effectiveness of biological treatment for severe chronic rhinosinusitis with nasal polyps.

BACKGROUND: During the last two years, three different monoclonal antibodies have been approved in many countries for the treatment of patients suffering from severe chronic rhinosinusitis with nasal polyps (CRSwNP). Their efficacy has been demonstrated through large double-blind placebo-controlled clinical studies. Until now, only very limited reports on real-world data regarding this therapy have been published. METHODS: This per protocol analysis included patients with an indication for biological treatment because of uncontrolled CRSwNP, despite long-term nasal steroid treatment, systemic steroid use and/ or endonasal sinus surgery. Baseline data on demographics, medical history and comorbidities, polyp score, quality of life and sense of smell (using Sniffin' Sticks) were assessed and a treatment with either dupilumab or omalizumab was started. The patients were followed up after three and six months. The changes in polyp score, quality-of-life measures and olfaction were noted. RESULTS: 70 consecutive patients were evaluated during the study. Of the patients, 49 were treated with dupilumab and 21 with omalizumab. The polyp score decreased significantly after three and six months, and the quality-of-life parameters and olfaction increased. More than 90% of patients showed a moderate to excellent response to the therapy and there was no difference in the overall response between the two treatments. Olfaction improved in two thirds of the patients, but one third was still anosmic after six months treatment. CONCLUSIONS: This real-world study shows the effectiveness of the monoclonal antibodies dupilumab and omalizumab in the treatment of severe CRSwNP. Nasal polyp scores and quality-of-life parameters as well as measured olfactory function were improved after just three months. The response after guideline-based criteria was insufficient only in 5 patients of this cohort.

Superiority of continuous over intermittent intraoperative nerve monitoring in preventing vocal cord palsy.

BACKGROUND: Continuous intraoperative nerve stimulation (IONM) with uninterrupted monitoring is likely better than intermittent IONM in preventing vocal cord palsy after thyroid surgery. METHODS: This was a comparative study of intermittent versus continuous IONM in patients with benign and malignant thyroid disease treated at a tertiary centre over 10 years. Early postoperative and permanent vocal cord palsy rates were estimated. Multivariable logistic regression analysis was used to quantify the contributions of clinical and histopathological variables to early postoperative and permanent vocal cord palsy. RESULTS: A total of 6029 patients were included, of whom 3139 underwent continuous and 2890 intermittent IONM. Based on nerves at risk (5208 versus 5024 nerves), continuous IONM had a 1·7-fold lower early postoperative vocal cord palsy rate than intermittent monitoring (1·5 versus 2·5 per cent). This translated into a 30-fold lower permanent vocal cord palsy rate (0·02 versus 0·6 per cent). In multivariable logistic regression analysis, continuous IONM independently reduced early postoperative vocal cord palsy 1·8-fold (odds ratio (OR) 0·56) and permanent vocal cord palsy 29·4-fold (OR 0·034) compared with intermittent IONM. One permanent vocal cord palsy per 75·0 early vocal cord palsies was observed with continuous IONM, compared with one per 4·2 after intermittent IONM. Early postoperative vocal cord palsies were 17·9-fold less likely to become permanent with continuous than intermittent IONM. CONCLUSION: Continuous IONM is superior to intermittent IONM in preventing vocal cord palsy.

Cross Disciplinary Role Agreement is Needed When Coordinating Long-Term Opioid Prescribing for Cancer: a Qualitative Study.

BACKGROUND: Cancer pain is highly prevalent and often managed in primary care or by oncology providers in combination with primary care providers. OBJECTIVES: To understand interdisciplinary provider experiences coordinating opioid pain management for patients with chronic cancer-related pain in a large integrated healthcare system. DESIGN: Qualitative research. PARTICIPANTS: We conducted 20 semi-structured interviews with interdisciplinary providers in two large academically affiliated VA Medical Centers and their associated community-based outpatient clinics. Participants included primary care providers (PCPs) and oncology-based personnel (OBPs). APPROACH: We deductively identified 94 examples of care coordination for cancer pain in the 20 interviews. We secondarily used an inductive open coding approach and identified themes through constant comparison coming to research team consensus. RESULTS: Theme 1: PCPs and OBPs generally believed one provider should handle all opioid prescribing for a specific patient, but did not always agree on who that prescriber should be in the context of cancer pain. Theme 2: There are special circumstances where having multiple prescribers is appropriate (e.g., a pain crisis). Theme 3: A collaborative process to opioid cancer pain management would include real-time communication and negotiation between PCPs and oncology around who will handle opioid prescribing. Theme 4: Providers identified multiple barriers in coordinating cancer pain management across disciplines. CONCLUSIONS: Our findings highlight how real-time negotiation about roles in opioid pain management is needed between interdisciplinary clinicians. Lack of cross-disciplinary role agreement may result in delays in clinically appropriate cancer pain management.

Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

Prediction of biochemical cure in patients with medullary thyroid cancer.

BACKGROUND: The impact of number of node metastases versus metastatic lymph node ratio versus AJCC node category on biochemical cure in medullary thyroid cancer (MTC) is not well defined. METHODS: Multivariable logistic regression analysis was used to determine clinical and histopathological variables that contribute to biochemical cure in node-positive MTC. RESULTS: Some 584 of 1026 patients with MTC underwent systematic lymph node dissections for node-positive disease; 27·4 per cent (54 of 197) were biochemically cured after the initial operation and 13·5 per cent (42 of 310 patients) after repeat surgery. Cured patients had significantly less extrathyroid extension (11-14 versus 33·2-55·6 per cent), fewer lymph node metastases (median 2-4 versus 12-16), a lower metastatic lymph node ratio (median 0·05-0·08 versus 0·23-0·28), and were less likely to have AJCC pN1b disease (56-76 versus 89·9-91·6 per cent) and distant metastases (0 versus 28·4-37·1 per cent) than patients who were not cured. Biochemical cure curves advanced steadily up to 7-12 node metastases and a metastatic lymph node ratio of 0·33, eventually levelling off after 16-17 node metastases and metastatic lymph node ratios of 0·45-0·65. In logistic regression analysis, number of lymph node metastases (odds ratio (OR) 17·24 for more than 20 metastases, OR 5·28 for 11-20 metastases, OR 2·22 for 6-10 metastases), preoperative basal serum calcitonin (OR 6·24 for over 1000 pg/ml), reoperation (OR 5·34) and extrathyroid extension (OR 2·42) independently predicted failure to reach biochemical cure. CONCLUSION: Number of lymph node metastases, unlike metastatic lymph node ratio or AJCC node category, determines likelihood of biochemical cure after initial and repeat surgery for node-positive MTC.

ANTECEDENTES: El impacto del número de metástasis ganglionares versus la relación de ganglios linfáticos metastásicos (metastatic lymph node ratio, MLNR) versus el estadio ganglionar según el American Joint Committee on Cancer (AJCC) sobre la curación bioquímica en el cáncer medular de tiroides (medullary thyroid cancer, MTC) no está bien definido. MÉTODOS: Se utilizaron análisis de regresión logística multivariable y análisis estratificados de Kaplan-Meier para determinar las variables clínicas e histopatológicas que contribuyen a la curación bioquímica en el MTC con ganglios positivos. RESULTADOS: En total, 584 de 1.026 pacientes con MTC se sometieron a disecciones sistemáticas de los ganglios linfáticos en caso de enfermedad con ganglios positivos, el 27,4% (54 de 197 pacientes) de los cuales se curaron bioquímicamente después de la cirugía inicial y el 13,5% (42 de 310 pacientes) después de la reintervención quirúrgica. Los pacientes curados tuvieron una extensión extratiroidea significativamente menor (11,1-14% versus 33,2-55,6%), menos metástasis en los ganglios linfáticos (2-4 versus 12-16 metástasis), una MLNR más baja (0,05-0,08 versus 0,23-0,28), una menor frecuencia de estadio ganglionar AJCC pN1b (55,6-76 versus 89,9-91,6%) y no tenían metástasis a distancia (0% versus 28,4-37,1%), Las curvas de tiempo hasta la curación bioquímica avanzaron de manera constante hasta las metástasis de 7 a 12 ganglios y una MLNR de 0,33, y finalmente se nivelaron después de las metástasis de 16 a 17 ganglios y una MLNR de 0,45 a 0,65. En la regresión logística, el número de metástasis en los ganglios linfáticos (razón de oportunidades, odds ratio, OR 17,2 para > 20 metástasis, OR 5,3 para 11-20 metástasis y OR 2,2 para 6-10 metástasis), la calcitonina sérica basal preoperatoria (OR 6,2 para> 1000 pg/mL), la reoperación (OR 5,4) y la extensión extratiroidea (OR 2,4) predijeron de forma independiente el fracaso para alcanzar la curación bioquímica, CONCLUSIÓN: El número de metástasis en los ganglios linfáticos, a diferencia de la MLNR y del estadio ganglionar AJCC, determina la probabilidad de curación bioquímica después de la cirugía inicial y la reintervención para el MTC con ganglios positivos.

Implementing routine communication about costs of cancer treatment: perspectives of providers, patients, and caregivers.

OBJECTIVES: Rising costs in oncology care often impact patients and families directly, making communication about costs and financial impacts of treatment crucial. Cost expenditures could offer opportunities for estimation and prediction, affording personalized conversations about financial impact. We sought to explore providers', patients', and caregivers' preferences towards implementing communication about cost, including when, how, and by whom such information might be provided. METHODS: We conducted semi-structured phone interviews with a diverse population including 12 oncology providers, 12 patients, and 8 patient caregivers (N = 32). The constant comparative method was used to identify mutually agreed upon themes. RESULTS: Participant groups differed in their concerns surrounding cost communication, namely whether they want to receive this information and how such information might impact provider and patient treatment decisions. All participants agreed that oncology providers should not be leading cost conversations. Patients and caregivers identified social workers or financial advisors as most equipped to communicate about cost. Participants emphasized timely cost conversations, ideally around the time of diagnosis. Participants favored various metrics of financial impact beyond overall costs of care including disability, days lost from work, and out-of-pocket expenses. CONCLUSION: Cost transparency should be incorporated into usual care; however, there are several challenges to making cost conversations a part of everyday practice. Patients and family members need resources related to cost to aid in decision-making and those delivering cost information should have competency in oncology, financial advisement, and patient-centered care.

Angiotensin converting enzymes ACE and ACE2 in thyroid cancer progression.

Angiotensin-converting enzymes, ACE and ACE2, play not only a pivotal role in the regulation of blood pressure, but are involved in the processes of pathophysiology, including thyroid dysfunction or progression of several neoplasia such as cancers of skin, lungs, pancreas and leukemia. However, their role in the thyroid carcinogenesis remains unknown. We examined in this study the expression of ACE and ACE2 in thyroid tissues and their possible employment as biomarkers for thyroid cancer progression. Thyroid tissues, including 14 goiters (G), 12 follicular adenomas (FA), 10 follicular thyroid carcinomas (FTC), 14 papillary thyroid carcinomas (PTC) and 11 undifferentiated thyroid carcinomas (UTC), were subjected to RT-PCR and protein analyses with primers or antibodies specific for ACE and ACE2, respectively. FA revealed significantly increased ACE compared to other groups and FTC was significantly higher than UTC. ACE2 was significantly increased in PTC in comparison to G, FA and UTC, and in FTC as compared to G. The ratio ACE/ACE2 decreased, while ACE2/ACE increased with the differentiation grade of thyroid carcinoma. ACE was significantly diminished in individuals older than 50. Both ACEs were significantly diminished in M1 patients, ACE2 additionally in higher tumor masses. ACE and ACE2 are regulated within thyroid benign and malignant tissues. As the transcript ratio between both enzymes correlate proportional with the differentiation status of thyroid cancer, ACE and ACE2 may serve as new markers for thyroid carcinoma.

[TEG-guided treatment of a dabigatran overdose in a patient with acute kidney failure]. / TEG-unterstützte Therapie einer Dabigatranüberdosierung bei einem Patienten mit akutem Nierenversagen.

This article presents the case of a multimorbid male patient with an accidental dabigatran overdose caused by kidney failure in the context of an acute intestinal disorder. After effective initial antagonizing of the dabigatran effect using idarucizumab a dabigatran rebound was detected caused by a single hemodialysis leading to a severe intrapulmonary hemorrhage. As dabigatran plasma level testing was not available and conventional coagulation analysis was out of interpretable range due to the impact of dabigatran, continuous thrombelastography (TEG) was used to detect the effect of dabigatran and monitor the treatment results. The most significant parameter used in the kaolin activated clotting time was the R­time parameter, which was massively prolonged by the interrupted coagulation cascade.

[Disfiguring neurinoma of the nose tip and the columella-rhinosurgical aspects]. / Dysfigurierendes Neurinom der Nasenspitze und der Columella ­ rhinochirurgische Aspekte.

Neurinomas in the nose and the nasal sinuses are rare. In the present work, we present an exceedingly rare case of a disfiguring neurinoma involving the nasal columella. Treatment of choice is complete resection of the tumor. For an optimal view for tumor resection and esthetic and functional reconstruction, we recommend an open surgical approach.

Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer.

BACKGROUND: It remains unclear when postoperative serum calcitonin levels should be measured in patients with medullary thyroid cancer (MTC) and, specifically, whether this decision should be based on the preoperative calcitonin level or nodal status. METHODS: A cohort of patients with previously untreated MTC was studied. Kaplan-Meier analyses, stratified by preoperative calcitonin level, nodal status and number of nodal metastases, were performed to determine time to calcitonin normalization after initial surgery, with statistical analysis by means of the log rank test. RESULTS: Some 213 patients with node-negative and 182 with node-positive MTC were included in the study. Postoperative calcitonin levels normalized in a mean of 3·5 versus 3·7 days respectively among patients with preoperative calcitonin levels of 10-100 pg/ml (P = 0·815); 4·8 versus 5·3 days in those with preoperative calcitonin levels of 100·1-500 pg/ml (P = 0·026); 5·3 versus 9·9 days in patients with preoperative calcitonin levels of 500·1-1000 pg/ml (P = 0·004); and 6·6 versus 57·7 days among those with preoperative calcitonin levels exceeding 1000 pg/ml (P < 0·001). Calcitonin levels normalized in a mean of 4·7 days when nodal metastasis was not present, 5·2 days in those with one to five nodal metastases, 7·0 days in patients with six to ten nodal metastases, and 57·1 days among patients with more than ten nodal metastases. Postoperative calcitonin normalization curves paralleled each other in patients with node-negative MTC, but diverged in those with node-positive disease and with more nodal metastases. CONCLUSION: Calcitonin levels typically normalize within 1 week; and within a fortnight in those with node-positive MTC and preoperative calcitonin levels of 500·1-1000 pg/ml. With node-positive MTC and preoperative calcitonin levels exceeding 1000 pg/ml, and with more than ten nodal metastases, calcitonin normalization takes longer.

A neuromorphic systems approach to in-memory computing with non-ideal memristive devices: from mitigation to exploitation.

Memristive devices represent a promising technology for building neuromorphic electronic systems. In addition to their compactness and non-volatility, they are characterized by their computationally relevant physical properties, such as their state-dependence, non-linear conductance changes, and intrinsic variability in both their switching threshold and conductance values, that make them ideal devices for emulating the bio-physics of real synapses. In this paper we present a spiking neural network architecture that supports the use of memristive devices as synaptic elements and propose mixed-signal analog-digital interfacing circuits that mitigate the effect of variability in their conductance values and exploit their variability in the switching threshold for implementing stochastic learning. The effect of device variability is mitigated using pairs of memristive devices configured in a complementary push-pull mechanism and interfaced to a current-mode normalizer circuit. The stochastic learning mechanism is obtained by mapping the desired change in synaptic weight into a corresponding switching probability that is derived from the intrinsic stochastic behavior of memristive devices. We demonstrate the features of the CMOS circuits and apply the architecture proposed to a standard neural network hand-written digit classification benchmark based on the MNIST data-set. We evaluate the performance of the approach proposed in this benchmark using behavioral-level spiking neural network simulation, showing both the effect of the reduction in conductance variability produced by the current-mode normalizer circuit and the increase in performance as a function of the number of memristive devices used in each synapse.

Using medico-legal claims for quality improvement in maternity care: application and revision of an NHSLA coding taxonomy.

OBJECTIVE: To validate the NHSLA maternity claims taxonomy at the level of a single maternity service and assess its ability to direct quality improvement. DESIGN: Qualitative descriptive study. SETTING: Medico-legal claims between 1 January 2000 and 31 December 2016 from a maternity service in metropolitan Melbourne, Australia. POPULATION: All obstetric claims and incident notifications occurring within the date range were included for analysis. METHODS: De-identified claims and notifications data were derived from the files of the insurer of Victorian public health services. Data included claim date, incident date and summary, and claim cost. All reported issues were coded using the NHSLA taxonomy and the lead issue identified. MAIN OUTCOME MEASURES: Rate of claims and notifications, relative frequency of issues, a revised taxonomy. RESULTS: A combined total of 265 claims and incidents were reported during the 6 years. Of these 59 were excluded, leaving 198 medico-legal events for analysis (1.66 events/1000 births). The costs for all claims was $46.7 million. The most common claim issues were related to management of labour (n = 63, $17.7 million), cardiotocographic interpretation (n = 43, $24.4 million), and stillbirth (n = 35, $656,750). The original NHSLA classification was not sufficiently detailed to inform care improvement programmes. A revised taxonomy and coding flowchart is presented. CONCLUSIONS: Systematic analysis of obstetric medico-legal claims data can potentially be used to inform quality and safety improvement. TWEETABLE ABSTRACT: New taxonomy to target health improvement from maternity claims based on NHSLA Ten Years of Maternity Claims.

Surgical therapy of adrenal tumors: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: Previous guidelines addressing surgery of adrenal tumors required actualization in adaption of developments in the area. The present guideline aims to provide practical and qualified recommendations on an evidence-based level reviewing the prevalent literature for the surgical therapy of adrenal tumors referring to patients of all age groups in operative medicine who require adrenal surgery. It primarily addresses general and visceral surgeons but offers information for all medical doctors related to conservative, ambulatory or inpatient care, rehabilitation, and general practice as well as pediatrics. It extends to interested patients to improve the knowledge and participation in the decision-making process regarding indications and methods of management of adrenal tumors. Furthermore, it provides effective medical options for the surgical treatment of adrenal lesions and balances positive and negative effects. Specific clinical questions addressed refer to indication, diagnostic procedures, effective therapeutic alternatives to surgery, type and extent of surgery, and postoperative management and follow-up regime. METHODS: A PubMed research using specific key words identified literature to be considered and was evaluated for evidence previous to a formal Delphi decision process that finalized consented recommendations in a multidisciplinary setting. RESULTS: Overall, 12 general and 52 specific recommendations regarding surgery for adrenal tumors were generated and complementary comments provided. CONCLUSION: Effective and balanced medical options for the surgical treatment of adrenal tumors are provided on evidence-base. Specific clinical questions regarding indication, diagnostic procedures, alternatives to and type as well as extent of surgery for adrenal tumors including postoperative management are addressed.

Long-term outcome of prophylactic thyroidectomy in children carrying RET germline mutations.

BACKGROUND: A comprehensive assessment has not been undertaken of long-term outcomes in children carrying germline RET mutations and undergoing prophylactic thyroidectomy with the aim of preventing medullary thyroid cancer (MTC). METHODS: A retrospective outcome study (1994-2017) of prophylactic thyroidectomy in children, with and without central node dissection, was performed at a tertiary surgical centre. RESULTS: Some 167 children underwent prophylactic thyroidectomy, 109 without and 58 with concomitant central node dissection. In the highest-risk mutational category, MTC was found in five of six children (83 per cent) aged 3 years or less. In the high-risk category, MTC was present in six of 20 children (30 per cent) aged 3 years or less, 16 of 36 (44 per cent) aged 4-6 years, and 11 of 16 (69 per cent) aged 7-12 years (P = 0·081). In the moderate-risk category, MTC was seen in one of nine children (11 per cent) aged 3 years or less, one of 26 (4 per cent) aged 4-6 years, three of 26 (12 per cent) aged 7-12 years, and seven of 16 (44 per cent) aged 13-18 years (P = 0·006). Postoperative hypoparathyroidism was more frequent in older children (32 per cent in the oldest age group versus 3 per cent in the youngest; P = 0·002), whether or not central node dissection was carried out. Three children developed recurrent laryngeal nerve palsy; all had undergone central node dissection (P = 0·040). All complications resolved within 6 months. Postoperative normalization of calcitonin serum levels was achieved in 114 (99·1 per cent) of 115 children with raised preoperative values. No residual structural disease or recurrence was observed. CONCLUSION: Early prophylactic thyroidectomy is a viable surgical concept in experienced hands, sparing older children the postoperative morbidity associated with delayed neck surgery.

Twenty-year experience of paediatric thyroid surgery using intraoperative nerve monitoring.

BACKGROUND: There are few data on intermittent and continuous intraoperative nerve monitoring (IONM) during thyroidectomy in children. METHODS: All children aged 18 years or younger who had standard thyroid operations using intermittent or continuous IONM between January 1998 and December 2016 were included in the study. The impact of age and type of IONM on basal amplitude, latency and complications after thyroidectomy were assessed. RESULTS: A total of 504 children were included in the study. With continuous IONM, median basal amplitude and latency increased significantly with age, more on the left side (from 199 to 870 µV, and from 3·88 to 5·75 ms) than on the right (from 340 to 778 µV, and from 2·63 to 3·50 ms). Compared with intermittent IONM with needle electrode, continuous IONM with tube electrode resulted in an increase in median basal amplitude in children aged 13-18 years on both sides (from 675 to 778 µV on the right and from 450 to 870 µV on the left), and a decrease in median latency in all children older than 3 years: in children aged 4-6 years, from 4·20 to 3·00 ms on the right and from 6·10 to 4·63 ms on the left; in children aged 7-12 years, from 4·60 to 3·50 ms and from 6·00 to 5·25 ms respectively; and in children aged 13-18 years, from 4·60 to 3·50 ms and from 6·40 to 5·75 ms. Overall, wound infection, but not bleeding/haematoma or vocal fold palsy, affected younger children more: 3 per cent of children aged 3 years or less; 2 per cent of children aged 4-6 years; and 0 per cent of children aged over 6 years (P = 0·031). With continuous IONM, no wound infection, bleeding/haematoma or permanent vocal fold palsy was noted in any age group. CONCLUSION: Continuous IONM measures nerve electrophysiology more accurately than intermittent IONM during thyroidectomy in children.

Risk profile analysis and complications after surgery for autoimmune thyroid disease.

BACKGROUND: Surgical approaches to autoimmune thyroid disease are currently hampered by concerns over postoperative complications. Risk profiles and incidences of postoperative complications have not been investigated systematically, and studies with sufficient power to show valid data have not been performed. METHODS: A prospective multicentre European study was conducted between July 2010 and December 2012. Questionnaires were used to collect data prospectively on patients who had surgery for autoimmune thyroid disease and the findings were compared with those of patients undergoing surgery for multinodular goitre. Logistic regression analysis was used to evaluate risk factors for thyroid surgery-specific complications, transient and permanent recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism. RESULTS: Data were available for 22 011 patients, of whom 18 955 were eligible for analysis (2488 who had surgery for autoimmune thyroid disease and 16 467 for multinodular goitre). Surgery for multinodular goitre and that for autoimmune thyroid disease did not differ significantly with regard to general complications. With regard to thyroid surgery-specific complications, the rate of temporary and permanent vocal cord palsy ranged from 2·7 to 6·7 per cent (P = 0·623) and from 0·0 to 1·4 per cent (P = 0·600) respectively, whereas the range for temporary and permanent hypoparathyroidism was 12·9 to 20·0 per cent (P < 0·001) and 0·0 to 7·0 per cent (P < 0·001) respectively. In logistic regression analysis of transient and permanent vocal cord palsy, autoimmune thyroid disease was not an independent risk factor. Autoimmune thyroid disease, extent of thyroid resection, number of identified parathyroid glands and no autotransplantation were identified as independent risk factors for both transient and permanent hypoparathyroidism. CONCLUSION: Surgery for autoimmune thyroid disease is safe in comparison with surgery for multinodular goitre in terms of general complications and RLN palsy. To avoid the increased risk of postoperative hypoparathyroidism, special attention needs to be paid to the parathyroid glands.

[Ectopic tissue of the thyroid gland and the parathyroid glands]. / Ektopes Gewebe der Schilddrüse und der Nebenschilddrüsen.

Ectopic thyroid tissue results from developmental defects of the early stages of thyroid embryogenesis, in which the median thyroid anlage descends from the floor of the mouth to its final pre-tracheal position. The most common sites of ectopic thyroid tissue are accordingly in the area of the floor of the mouth and in the course of the thyroglossal duct. Rare localizations are intrathoracic (mediastinal, cardiac, pulmonary) and sub-diaphragmatic (including the adrenals, liver, gall bladder, and gastrointestinal tract). The most important differential diagnosis of ectopic thyroid is metastasis of differentiated thyroid carcinoma.By contrast, the term parathyroidectopy is not uniformly defined. Usually, the cervical-central localizations are referred to as "positional variants" (with the exception of the maxillary sinus and high parapharyngeal), whereas the cervical-lateral localizations (carotid sheath, vagus nerve) and those below the brachiocephalic and mediastinal positions (extraligamentary, aortopulmonary window, paravagal) and other rare localizations are classified as "ectopic parathyroid tissue". Parathyroidectomy is very common (in autopsy studies in 28 to 42.8% of all humans). In the context of primary hyperparathyroidism (pHPT), there is a prevalence of 6.3 to 16% of ectopic hyperfunctional parathyroid tissue (predominantly adenomas), which play an important role in the surgical treatment of pHPT.

Evaluation of a novel point-of-care test for active matrix metalloproteinase-8: agreement between qualitative and quantitative measurements and relation to periodontal inflammation.

BACKGROUND AND OBJECTIVES: Severe periodontitis affects about 10% of the world population. In addition, associations between periodontitis and systemic diseases exist. Therefore, the diagnosis should be made quickly and at an early stage. Matrix metalloproteinase-8 (MMP-8) is the most prominent collagenase found in inflamed periodontal tissues. Its active form (aMMP-8) is increasingly used as a diagnostic biomarker. Aim of the present study is to evaluate the diagnostic accuracy of a novel aMMP-8 point-of-care (POC) test in comparison to the standard laboratory test to diagnose the disease rapidly and reliably. MATERIAL AND METHODS: In a prospective, mono-center, double-blinded, case-control study, participants with healthy gums (n = 35), gingivitis (n = 60) and periodontitis (n = 35) were investigated before and after therapy. Beside clinical variables for plaque and inflammation, aMMP-8 concentrations were determined in oral rinsing specimens by the enzyme-linked immunosorbent assay (ELISA) and by POC. Positive and negative percent agreements with their exact one-sided lower 95% confidence limits were calculated. RESULTS: Of 130 participants, 111 finished the study. Overall, positive percent agreements were 75.8% (57.7-88.9) before treatment and 73.7% (56.9-86.6) after treatment. Negative percent agreements were 92.8% (85.7-97.0) before and 93.3% (85.1-97.8) after treatment. Positive test results (POC and ELISA) ranged from 5.7% to 8.6% in healthy patients, 25.0-29.8% in patients with gingivitis and 40.0-48.1% in patients with periodontitis. Patients who had positive aMMP-8 test results (POC) showed higher scores for plaque and inflammation. CONCLUSIONS: The novel POC test to detect aMMP-8 has proved to agree strongly with the standard method, ELISA. The test can be recommended to screen patients at risk for periodontitis in dental offices, at the general practitioner and at specialists for associated diseases.