Management of low-risk papillary thyroid cancer. Minimally-invasive treatments dictate a further paradigm shift?

BACKGROUND: Current management options for PTMC include lobo-isthmectomy and active surveillance (AS). Recently, ultrasound-guided minimally invasive procedures (MITs) are offered as a nonsurgical therapy for PTMC because they do not require hospitalization and general anaesthesia, and do not result in loss of thyroid function or cosmetic damage. MITs are reported to consistently provide, mostly in large retrospective series of patients, a rapid, safe, and cost-effective way to eradicate low-risk thyroid malignancies. However, conclusive data from well-conducted prospective studies on the histologically-proven completeness of tumor ablation and the long-term clinical advantages versus AS are still lacking. OBJECTIVES: This study aimed to evaluate the efficacy and safety of ultrasound-guided minimally invasive treatments (MITs) for PTMC in comparison to traditional surgical methods and active surveillance, and to assess their role in current clinical practice. METHODS: A structured literature review was conducted using keywords related to PTMC, MIT, and comparative techniques. Studies were evaluated based on treatment modality, patient selection, follow-up duration, complication rates, and clinical outcomes. RESULTS: MITs have shown promising results in the management of PTMC. These treatments offer several advantages over surgery, such as reduced use of surgical resources, lower costs, minimal work disruption, and fewer major complications. However, there are still limitations, including the need for long-term surveillance and the potential risk of incomplete tumor ablation. CONCLUSIONS: MITs represent a promising non-surgical option for managing low-risk PTMC, especially for patients ineligible for or refusing surgery. Despite favorable outcomes, more robust prospective data are needed to confirm their long-term benefits and completeness of tumor ablation. Interdisciplinary discussions and thorough patient education on the advantages and limitations of MITs are crucial for informed decision-making.

Probing gaps in educational outcomes within the U.S.: A dual moderation multiple mediator latent growth model.

Racial/ethnic disparities in math achievement are especially troubling because math proficiency predicts long-term educational outcomes, but the mechanisms underlying these disparities remain unclear. Previous research has demonstrated that across diverse samples, both within and outside the United States, the relation between students' academic aspirations and later postsecondary attainment is mediated by initial levels of math ability and by growth in that ability across time. The key issue examined in this investigation is the extent to which students' underestimation or overestimation of their math ability (i.e., calibration bias) moderates those mediated effects and whether this moderation varies as a function of race/ethnicity. Using data from two longitudinal national surveys (i.e., NELS:88 and HSLS:09), these hypotheses were tested in samples of East Asian American, Mexican American, and Non-Hispanic White American high school students. In both studies and in all groups, the model explained large portions of the variance in postsecondary attainment. In East Asian Americans and non-Hispanic White Americans, calibration bias moderated the effect mediated by 9th grade math achievement. The strength of this effect was greatest at high levels of underconfidence and steadily weakened as self-confidence grew, suggesting that some degree of underconfidence may be achievement-promoting. Indeed, in the East Asian American sample, this effect became negative at high levels of overconfidence (i.e., academic aspirations actually predicted the lowest postsecondary attainment levels). Educational implications of these findings are discussed and possible reasons for the failure to find moderation effects in the Mexican American sample are explored.

Impacto pronóstico de la utilización intensiva de tecnologías complementarias intraoperatorias en gliomas cerebrales. Revisión de la literatura y presentación de 1 caso

Introducción: El manejo de los gliomas cerebrales durante las últimas cuatro décadas ha sufrido cambios relevantes en su estudio y tratamiento. Dentro de estos cambios se encuentra el desarrollo de técnicas imagenológicas, neurofisiológicas e histopatológicas. El presente trabajo intenta estimar el impacto que la utilización de dichas tecnologías ha tenido sobre el pronóstico de los pacientes. Material y método: Revisión exhaustiva de la literatura en medios digitales e impresos abarcando mayormente publicaciones y comunicaciones desde la década de 1980 hasta el presente. Se expone 1 caso sometido recientemente a cirugía por los autores en el que se utilizaron varias de estas herramientas, presentando el análisis que se llevó a cabo en la planificación quirúrgica. Resultados: La literatura muestra mejorías consistentes pero discretas en el pronóstico asociado al uso de tecnologías complementarias intraoperatorias en gliomas cerebrales, relacionadas a la ayuda que prestarían en la extensión de la resección tumoral y en la preservación funcional. Conclusiones: La utilización intensiva de las tecnologías complementarias descritas parece recomendable si la planificación quirúrgica anticipa beneficios fundados en cuanto a morbi-mortalidad para un paciente en particular. Se debe ser cauto en anticipar y generalizar el impacto pronóstico global que puedan tener, beneficio que es consistente en la literatura pero que en estos momentos parece modesto en términos generales en especial para gliomas de alto grado.

Introduction: The management of cerebral gliomas during the last four decades has undergone relevant changes in terms of its study and treatment. Among these changes is the development of imaging, neurophysiological and histopathological techniques. The present study attempts to estimate the impact that the use of these technologies has had on the prognosis of patients. Material and Method: Comprehensive review of the literature in digital and print media covering mostly publications and communications from the 1980s to the present. 1 case recently submitted to surgery by the authors in which several of these tools were used is exposed, presenting the analysis that was carried out in the surgical planning. Results: The literature shows consistent but discrete improvements in the prognosis associated with the use of intraoperative complementary technologies in cerebral gliomas, related to the help they would provide in the extension of tumor resection and functional preservation. Conclusions: The intensive use of the complementary technologies described seems advisable if surgical planning anticipates well-founded benefits in terms of morbidity and mortality for a particular patient. Caution should be exercised in anticipating and generalizing the global prognostic impact they may have, a benefit that is consistent in the literature but currently seems modest in general terms especially for high grade gliomas.

Estimate of the rate of unreported COVID-19 cases during the first outbreak in Rio de Janeiro.

In this work we fit an epidemiological model SEIAQR (Susceptible - Exposed - Infectious - Asymptomatic - Quarantined - Removed) to the data of the first COVID-19 outbreak in Rio de Janeiro, Brazil. Particular emphasis is given to the unreported rate, that is, the proportion of infected individuals that is not detected by the health system. The evaluation of the parameters of the model is based on a combination of error-weighted least squares method and appropriate B-splines. The structural and practical identifiability is analyzed to support the feasibility and robustness of the parameters' estimation. We use the Bootstrap method to quantify the uncertainty of the estimates. For the outbreak of March-July 2020 in Rio de Janeiro, we estimate about 90% of unreported cases, with a 95% confidence interval (85%, 93%).

A model for COVID-19 with isolation, quarantine and testing as control measures.

In this article we propose a compartmental model for the dynamics of Coronavirus Disease 2019 (COVID-19). We take into account the presence of asymptomatic infections and the main policies that have been adopted so far to contain the epidemic: social distancing, isolation of a portion of the population, quarantine for confirmed cases and testing. We refer to quarantine as strict isolation, and it is applied to confirmed infected cases. In the proposed model, the proportion of people in isolation, the level of contact reduction and the testing rate are control parameters that can vary in time, representing policies that evolve in different stages. We obtain an explicit expression for the basic reproduction number R0 in terms of the parameters of the disease and of the control policies. In this way we can quantify the effect that isolation and testing have in the evolution of the epidemic. We present a series of simulations to illustrate different realistic scenarios. From the expression of R0 and the simulations we conclude that isolation (social distancing) and testing among asymptomatic cases are fundamental actions to control the epidemic, and the stricter these measures are and the sooner they are implemented, the more effective they are in flattening the curve of infections. Additionally, we show that people that remain in isolation significantly reduce their probability of contagion, so risk groups should be recommended to maintain a low contact rate during the course of the epidemic.

Technical validation of a new microfluidic device for enrichment of CTCs from large volumes of blood by using buffy coats to mimic diagnostic leukapheresis products.

Diagnostic leukapheresis (DLA) enables to sample larger blood volumes and increases the detection of circulating tumor cells (CTC) significantly. Nevertheless, the high excess of white blood cells (WBC) of DLA products remains a major challenge for further downstream CTC enrichment and detection. To address this problem, we tested the performance of two label-free CTC technologies for processing DLA products. For the testing purposes, we established ficollized buffy coats (BC) with a WBC composition similar to patient-derived DLA products. The mimicking-DLA samples (with up to 400 × 106 WBCs) were spiked with three different tumor cell lines and processed with two versions of a spiral microfluidic chip for label-free CTC enrichment: the commercially available ClearCell FR1 biochip and a customized DLA biochip based on a similar enrichment principle, but designed for higher throughput of cells. While the samples processed with FR1 chip displayed with increasing cell load significantly higher WBC backgrounds and decreasing cell recovery, the recovery rates of the customized DLA chip were stable, even if challenged with up to 400 × 106 WBCs (corresponding to around 120 mL peripheral blood or 10% of a DLA product). These results indicate that the further up-scalable DLA biochip has potential to process complete DLA products from 2.5 L of peripheral blood in an affordable way to enable high-volume CTC-based liquid biopsies.

Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies.

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. METHODS: Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field. OBJECTIVE: The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.

Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis.

Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density. Several drugs with different efficacy and safety profiles are available. The long-term therapeutic strategy should be planned, and the initial treatment should be selected according to the individual site-specific fracture risk and the need to give the maximal protection when the fracture risk is highest (i.e. in the late life). The present consensus focused on the strategies for the treatment of postmenopausal osteoporosis taking into consideration all the drugs available for this purpose. A short revision of the literature about treatment of secondary osteoporosis due both to androgen deprivation therapy for prostate cancer and to aromatase inhibitors for breast cancer was also performed. Also premenopausal females and males with osteoporosis are frequently seen in endocrine settings. Finally particular attention was paid to the tailoring of treatment as well as to its duration.

Laser ablation and 131-iodine: a 24-month pilot study of combined treatment for large toxic nodular goiter.

CONTEXT: It is normally recognized that the preferred treatment in large toxic thyroid nodules should be thyroidectomy. OBJECTIVE: The aim of the study was to assess the efficacy of combined laser ablation treatment (LAT) and radioiodine 131 (131I) treatment of large thyroid toxic nodules with respect to rapidity of control of local symptoms, of hyperthyroidism, and of reduction of administered 131I activity in patients at refusal or with contraindications to surgery. DESIGN AND SETTING: We conducted a pilot study at a single center specializing in thyroid care. PATIENTS: Fifteen patients were treated with LAT, followed by 131I (group A), and a series of matched consecutive patients were treated by 131I only (group B). INTERVENTION(S): Laser energy was delivered with an output power of 3 W (1800 J per fiber per treatment) through two 75-mm, 21-gauge spinal needles. Radioiodine activity was calculated to deliver 200 Gy to the hyperfunctioning nodule. MAIN OUTCOME MEASURE(S): Thyroid function, thyroid peroxidase antibody, thyroglobulin antibody, ultrasound, and local symptoms were measured at baseline and up to 24 months. RESULTS: Nodule volume reduction at 24 months was: 71.3 ± 13.4 vs 47.4 ± 5.5%, group A (LAT+131I) vs group B (131I), respectively; P < .001). In group A (LAT+131I), a reduction in radioiodine-administered activity was obtained (-21.1 ± 8.1%). Local symptom score demonstrated a more rapid reduction in group A (LAT+131I). In three cases, no 131I treatment was needed after LAT. CONCLUSIONS: In this pilot study, combined LAT/131I treatment induced faster and greater improvement of local and systemic symptoms compared to 131I only. This approach seems a possible alternative to thyroidectomy in patients at refusal of surgery.

Cancer recurrence in papillary thyroid microcarcinoma: a multivariate analysis on 231 patients with a 12-year follow-up.

AIM: Papillary thyroid microcarcinoma (PMC) is considered a common disease with a good prognosis and low rate of recurrence but the extension of initial surgical treatment and the need of completion thyroidectomy are still controversial. Aim of this study is the assessment of the prognostic factors that are predictive of cancer recurrence on a large controlled series of patients with a prolonged follow-up. METHODS: A total of 231 patients with PMC were followed up for a median period of 12 years (range 5-35 years). The patients included 54 males and 177 females, with a mean age at the time of first diagnosis of 45.7±12.7 years. RESULTS: At presentation 158 patients had no metastases, whereas 73 had lymph node metastases and 1 had bone metastases. Surgery included 177 total thyroidectomies and 54 lobectomies. Eighty-four patients underwent lymph node dissection, and 131 patients were treated with radioiodine therapy. The disease recurred in 15 patients (6.5%): 5 cases of local recurrence, all of which in the contralateral lobe after lobectomy, 13 cases of lymph-node metastases, and 2 cases of lung metastases. Multivariate analysis showed that two parameters were predictive for local recurrence: age <45 years (P=0.05; RR: 6.9; 95% CI: 1.59-29.9) and evidence of lymph-node metastases at presentation (P=0.03; RR: 3.24; 95% CI: 1.17-8.55) CONCLUSION: Total or near-total thyroidectomy seems to reduce the risk of local recurrences in non-incidental PMC. Prophylactic dissection of central compartment nodes in the absence of clinically evident metastases seems not to change the risk of recurrence. In incidental PTMC without multifocality, extracapsular extension or histologically-proven lymph node metastases, lobectomy is associated with a very low risk of recurrence. Follow-up with neck ultrasonography seems advisable at yearly intervals, as recurrences may present from less than one year until several years after thyroidectomy. Radioiodine ablation of thyroid remnants should be considered only in young patients in presence of multifocal tumors, histologically-proven metastatic lymph nodes to the significantly higher risk of recurrence.

No thyroid abnormalities in patients submitted to cardiac catheterization in the first eighteen months of life.

BACKGROUND: No data are available about the risk of thyroid disturbance after exposure to low-dose radiation due to the use of cardiac catheterization in the first years of life. AIM: To determine the risk of functional and morphological thyroid abnormalities in a homogeneous cohort of patients who underwent diagnostic low-dose radiation for heart catheterization during the first 18 months of life. SUBJECTS AND METHODS: Fifty-five patients, submitted to cardiac catheterization during the first 18 months of life, underwent evaluation of the thyroid function and structure after a median period of 13 yr since the first radiation exposure. Sixty-eight unexposed controls matched for age and sex, underwent the same protocol. Twenty-two patients were then re-evaluated after a median period of 22 yr. RESULTS: Thyroid function resulted normal in both patients and controls. The prevalence of small thyroid nodules and inhomogeneous structures in ultrasound study was not augmented in irradiated patients compared to controls. No thyroid tumors or reduced thyroid volume were observed. CONCLUSIONS: Neither functional nor morphological disorders of the thyroid gland were demonstrated after a period up to 24 yr in patients exposed to diagnostic ionizing radiation for cardiac catheterization during the first 18 months of life.

Lack of association between IL-1ß, TNF-α, and IL-10 gene polymorphisms and sporadic Parkinson's disease in an Italian cohort.

OBJECTIVE: There is increasing evidence suggesting that neuroinflammation and microglia activation may play important roles in the pathway leading to neuronal cell death in Parkinson's disease (PD). Chronic activation of microglia may cause neuronal damage through the release of potentially cytotoxic molecules, such as pro-inflammatory cytokines. Different functional promoter polymorphisms within genes coding pro- or anti-inflammatory cytokines involved in the immune reactions in the brain might influence the risk of developing PD or the age of disease onset. AIM: To investigate the interleukin (IL)-1ß-511, tumor necrosis factor alpha (TNF-α)-308, and interleukin (IL)-10-1082 gene polymorphisms as susceptibility factors for PD. METHODS: We analyzed genotype and allele distributions of these polymorphisms in 146 Italian patients with PD and 156 healthy controls. RESULTS: None of the polymorphisms we investigated was found to be associated with PD or with age of disease onset. No significant differences between patients with PD and controls were found as regards the concomitant presence of variant alleles in the three polymorphisms studied. We found that only the combined genotype TNF-α-308GG/IL-1ß-511T+ is associated with a decreased risk of PD. CONCLUSION: Our results indicate that the cytokine gene polymorphisms we investigated are not related to the development of PD in the Italian population; further studies are warranted to clarify the role of the TNF-α-308GG/IL-1ß-511T+ combined genotype.

Low-activity (2.0 GBq; 54 mCi) radioiodine post-surgical remnant ablation in thyroid cancer: comparison between hormone withdrawal and use of rhTSH in low-risk patients.

OBJECTIVE: (a) To compare the efficacy of low-activity (2 GBq; 54 mCi) (131)I ablation using l-thyroxine withdrawal or rhTSH stimulation, and (b) to assess the influence of thyroid remnants volume on the ablation rate. DESIGN: Patients underwent neck ultrasound, (131)I neck scintigraphy and radioiodine uptake. Post-therapy whole body scan (WBS) was acquired after 4-6 days. Ablation was assessed after 6-12 months by WBS, Tg and TgAb following l-thyroxine withdrawal. METHODS: Group A: preparation by L-T(4) withdrawal (37 days); 21 patients received (131)I (2.02+/-0.22 GBq; 54.6+/-5.9 mCi) and on the day of treatment, TSH, Tg, TgAb were measured; Group B: stimulation by rhTSH; 21 patients received (131)I (1.97+/-0.18 GBq; 53.2+/-4.9 mCi) 24 h after the second injection of rhTSH (0.9 mg) and TSH, Tg and TgAb were measured after 2 days. RESULTS: At follow-up, 90.0% of patients from group A and 85.0% of patients from group B had Tg levels <1 ng/ml; no uptake was observed in 95.2% and in 90.5% of patients from group A or B respectively, with no statistical differences for both ablation criteria. Before (131)I treatment, small thyroid remnants (<1 ml) were detected by US in <25% of all patients. CONCLUSIONS: The use of rhTSH for the preparation of low-risk patients to ablation therapy with low activities of (131)I (2 GBq; 54 mCi) is safe and effective and avoids hypothyroidism. The presence of thyroid remnants smaller than 1 ml at US evaluation had no effect on the ablation rate.

[Autonomic neuropathy in a diabetic population. Validity of cardiovascular tests and correlations with the complications]. / Neuropatia autonomica in una popolazione diabetica. Validità dei test cardiovascolari e correlazione con le complicanze.

The disfunction of the autonomic system nervous is a frequent finding in diabetes mellitus. Among objective tests proposed for its diagnosis, those assessing cardiovascular reflexes (cardiovascular tests: CVTs) explore the autonomic functionality by means of a group of standardized manoeuvres of relatively easy execution that study the baroreceptorial reflex arc. In our study, CVTs were performed in a population of 207 diabetic patients with no symptoms of autonomic neuropathy. A computerized automatic system (Cardionomic) was utilized. CTVs included: Deep Breathing, Lying to Standing, Valsalva Manoeuvre, Orthostatic Hypotension, Standing to Lying and Cough Test. Diabetic patients were broken down in groups according to: a) age, b) HbA1c levels, c) disease duration. We have then compared the presence of diabetic complications between the group of diabetics positive for cardiovascular disautonomia (CVD+) with another group of diabetics who were negative for cardiovascular disautonomia (DCV-). Our results show a remarkable correlation between autonomic neuropathy and patients age, HbA1c levels and disease duration. Also they show a strong positive correlation between CDV+ and the severity of arteriopathy. We conclude that autonomic neuropathy may play an important role in the pathogenesis of diabetic arteriopathy.

Thyroid tissue: US-guided percutaneous interstitial laser ablation-a feasibility study.

PURPOSE: To evaluate percutaneous interstitial laser photocoagulation (ILP) as a palliative treatment of recurrent thyroid carcinoma untreatable with surgery or radioiodine administration. MATERIALS AND METHODS: By using 18 resected thyroid glands, the volume and histologic pattern of ILP-induced thyroid damage were assessed. In vivo treatment feasibility was evaluated by using a low-energy laser in two volunteers before thyroidectomy for huge autonomously functioning nodules. With ultrasonographic (US) monitoring, a 21-gauge spinal needle was inserted into the thyroid nodules. A 300-microm quartz fiberoptic guide was inserted through the needle lumen, and the fiber tip was placed in direct contact with the tissue. Laser irradiation was performed with a 1.064-nm Nd:YAG laser in surgically resected glands, which were treated with 2, 3, 5, or 7 W. RESULTS: Tissue ablation was well-defined histologically, and its area was related to laser irradiation parameters (range, 0-26 mm). No correlation was found between US images and the actual extent of laser-induced lesions. Large colloid or fluid collections did not permit regular heat diffusion within the tissue. In vivo low-energy ILP was performed without technical difficulties or complications. CONCLUSION: ILP induces well-defined tissue ablation correlated with energy parameters in thyroid glands devoid of cystic areas. ILP could be a therapeutic tool for highly selected problems in thyroid tumor treatment.

Changes in concanavalin A-reactive proteins in neurological disorders.

Changes of glycosylation of cerebrospinal fluid proteins such as alpha2-macroglobulin, and prostaglandin D synthase were studied by lectin blotting, using concanavalinA, in multiple sclerosis (n = 42) and neuropathies (n = 20) in comparison to neurological controls (n = 22). The concanavalinA-reactivity of alpha2-macroglobulin, which was increased in the neuropathies but not in multiple sclerosis compared to controls, correlated with the total concanavalinA-reactivity in controls and neuropathies but not in multiple sclerosis, indicating that the protein could be abnormally glycosylated in the latter disease. Although the concentration and the concanavalinA-reactivity of prostaglandin D synthase were not significantly different in the three groups, the two parameters correlated only in neuropathies but not in controls or multiple sclerosis, probably due to the high heterogeneity of the protein. These changes deserve to be studied in further detail in view of their potential clinical applications.