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Abstract Context The efficacy and safety of testosterone replacement therapy (TRT) in hypogonadal men remain incompletely understood. Objective To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to determine the effects of TRT on patient important outcomes and adverse events in hypogonadal men. Data Sources We searched Ovid Medline, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus, from inception to 2 March 2017. Study Selection Randomized clinical trials assessing the efficacy and adverse events of TRT of at least 12 weeks compared with placebo in adult men with hypogonadism, defined by morning total testosterone ≤300 ng/dL and at least one symptom or sign of hypogonadism. Data Extraction Reviewers working independently and in duplicate assessed the quality of RCTs and collected data on patient characteristics, interventions, and outcomes. Results We found four RCTs (including 1779 patients) at low risk of bias. Compared with placebo, TRT was associated with a small but significant increase in sexual desire or libido [standardized mean difference (SMD): 0.17; 95% confidence interval (CI), 0.01, 0.34; n = 1383], erectile function (SMD: 0.16; 95% CI, 0.06, 0.27; n = 1344), and sexual satisfaction (SMD: 0.16; 95% CI, 0.01, 0.31; n = 676) but had no effect on energy or mood. TRT was associated with an increased risk of developing erythrocytosis (relative risk: 8.14; 95% CI, 1.87, 35.40; n = 1579) compared with placebo but had no significant effect on lower urinary tract symptoms. Conclusion In hypogonadal men, TRT improves sexual desire, erectile function and sexual satisfaction; however, it increases the risk of erythrocytosis. This study shows that in hypogonadal men, testosterone replacement therapy improves sexual desire, erectile function, and sexual satisfaction; however, it increases the risk of erythrocytosis.

Background In recent years management practices in relation to low-risk papillary microcarcinoma (PMC) have been evolving with increased awareness of the potential overdiagnosis and overtreatment of PMCs, and guidelines recommendations for non-surgical management options such as active surveillance. This study aimed to develop an in-depth understanding of patients’ experiences of the communication of their PMC diagnosis, their treatment preferences and decision making. Methods Semi-structured qualitative interviews with 25 patients diagnosed pre-operatively with PMC < 1 year since their diagnosis and treatment. Interviews were conducted between September 2015 and July 2016 and were audio-recorded and transcribed verbatim. Framework analysis method was used to analyse the data. Results The diagnosis and treatment experience of PMC patients varied widely. The majority of patients were asymptomatic, and their PMC was initially detected via an imaging test requested for a reason unrelated to a thyroid disorder or symptom. Clinicians generally described PMC to patients as being a “small” or “slow-growing” cancer, and there was little evidence that clinicians had discussions about the possibility of overdiagnosis or overtreatment. Overall, surgery was the only option discussed and offered to patients. Patients preference for treatment was largely based on eliminating the possibility of the cancer spreading (thyroidectomy) or not wanting to be on thyroid replacement medication for the rest of their life (hemi-thyroidectomy). Many patients reported emotional and physical side-effects associated with their diagnosis and treatment, however patients generally indicated that active surveillance is not something they would have been interested in if it was offered to them. Conclusions Evidence continues to emerge that many patients with PMCs may be overdiagnosed, and management guidelines are recommending more conservative management options for these patients. As a result, shared decision making around treatment options is vital so that patients are fully aware of the meaning of their diagnosis and their management options including active surveillance. Importantly, interventions to reduce unnecessary diagnoses of PMC are critically needed.

Purpose Identify factors that can be used to assess the appropriateness of a thyroid biopsy and propose a pathway to define inappropriate thyroid biopsies in practice. Methods We identified factors utilized in clinical guidelines and existing literature to determine the clinical indications for a thyroid biopsy. Subsequently, we assembled a multidisciplinary panel of experts, including patients, clinicians, researchers, and quality experts, to integrate these factors and develop a pathway for assessing the appropriateness of thyroid biopsies. Results Through literature review and stakeholder engagement, we identified multiple factors to determine if a thyroid biopsy is necessary: ultrasound risk assessment, presence of compressive symptoms and/or clinical suspicion of high-risk thyroid cancer, life expectancy, comorbidity burden, surgical risk, personal risk factors for thyroid cancer, thyroid function levels, local resources and medical expertise and patient values and preferences. We proposed a multiple-tier classification for the appropriateness of thyroid biopsy that begins with ultrasound findings (e.g., size, thyroid cancer risk) and encompasses the evaluation of additional patient-specific factors. Conclusion Assessment of the appropriateness of a thyroid biopsy is possible. Although, thyroid nodule ultrasound risk assessment is a pivotal factor for this assessment, additional factors should be considered (e.g., life expectancy, personal risk factors for thyroid cancer, patient preferences). Yet, additional efforts are needed to operationalize the objective implementation of these factors in clinical practice.

Optical communications providing huge capacity and low latency remain vulnerable to a range of attacks. In consequence, encryption at the optical layer is needed to ensure secure data transmission. In our previous work, we proposed LightPath SECurity (LPSec), a secure cryptographic solution for optical transmission that leverages stream ciphers and Diffie–Hellman (DH) key exchange for high-speed optical encryption. Still, LPSec faces limitations related to key generation and key distribution. To address these limitations, in this paper, we rely on Quantum Random Number Generators (QRNG) and Quantum Key Distribution (QKD) networks. Specifically, we focus on three meaningful scenarios: In Scenario A, the two optical transponders (Tp) involved in the optical transmission are within the security perimeter of the QKD network. In Scenario B, only one Tp is within the QKD network, so keys are retrieved from a QRNG and distributed using LPSec. Finally, Scenario C extends Scenario B by employing Post-Quantum Cryptography (PQC) by implementing a Key Encapsulation Mechanism (KEM) to secure key exchanges. The scenarios are analyzed based on their security, efficiency, and applicability, demonstrating the potential of quantum-enhanced LPSec to provide secure, low-latency encryption for current optical communications. The experimental assessment, conducted on the Madrid Quantum Infrastructure, validates the feasibility of the proposed solutions.

Despite the increase in thyroid cancer incidence among adolescents and young adults (AYAs), this group has received limited attention. We reviewed the epidemiology and challenges of thyroid cancer care among AYAs, and proposed a research agenda to improve their care. Thyroid cancer is the most common cancer in American adults 16-33 years of age. AYAs with thyroid cancer face challenges including overdiagnosis reduced healthcare access and inconsistent care. Successful treatment of these patients results in additional challenges due to ongoing side effects of treatment as well as lasting impacts on their quality of life. These challenges should fuel a collaborative research agenda aimed at improving the quality of care for AYAs with thyroid cancer across the spectrum of diagnosis, treatment and survivorship.

PurposeUnderstanding the method of thyroid cancer detection has potential implications on interpreting incidence rates, the diagnosis and management of thyroid cancer. We conducted a systematic review of studies reporting methods of thyroid cancer detection to estimate the frequency of incidentally found cancers and classify triggers of incidental thyroid cancer diagnosis.MethodsWe searched multiple bibliographic databases from inception to June 2020. A pair of reviewers, working independently and in duplicate selected studies for inclusion, extracted data, and evaluated each trial’s risk of bias. Studies enrolling patients older than 18 years with thyroid cancer confirmed histologically were included.ResultsIn total, 17 cohorts and 1 cross-sectional study, conducted between 1991 and 2018, enrolling 4668 patients with thyroid cancer were included: 88% had papillary thyroid cancer and 23% had papillary thyroid microcarcinoma. The proportion of patients with non-incidental and incidental thyroid cancer was similar: 49% [95% confidence interval (CI): 40–58%]. Subgroup analysis showed that most patients with incidental thyroid cancers had tumor size <10 mm (76%; 95% CI: 56–92%), age >45 (61%; 95% CI: 56–67%), and were detected through imaging (35%; 95% CI: 26–45%), of which ultrasound was the most common modality (27%; 95% CI: 14–43%). The heterogeneity for all the effect sizes was large and significant.ConclusionsAbout half of thyroid cancers were found incidentally through the use of imaging studies, in particular neck ultrasound. These incidentally found cancers were mostly small papillary thyroid cancer. These results highlight opportunities for interventions aimed at reducing drivers of overdiagnosis.

The digital extraction of detailed neuronal morphologies from microscopy data is an essential step in the study of neurons. Ever since Cajal’s work, the acquisition and analysis of neuron anatomy has yielded invaluable insight into the nervous system, which has led to our present understanding of many structural and functional aspects of the brain and the nervous system, well beyond the anatomical perspective. Obtaining detailed anatomical data, though, is not a simple task. Despite recent progress, acquiring neuron details still involves using labor-intensive, error prone methods that facilitate the introduction of inaccuracies and mistakes. In consequence, getting reliable morphological tracings usually needs the completion of post-processing steps that require user intervention to ensure the extracted data accuracy. Within this framework, this paper presents NeuroEditor, a new software tool for visualization, editing and correction of previously reconstructed neuronal tracings. This tool has been developed specifically for alleviating the burden associated with the acquisition of detailed morphologies. NeuroEditor offers a set of algorithms that can automatically detect the presence of potential errors in tracings. The tool facilitates users to explore an error with a simple mouse click so that it can be corrected manually or, where applicable, automatically. In some cases, this tool can also propose a set of actions to automatically correct a particular type of error. Additionally, this tool allows users to visualize and compare the original and modified tracings, also providing a 3D mesh that approximates the neuronal membrane. The approximation of this mesh is computed and recomputed on-the-fly, reflecting any instantaneous changes during the tracing process. Moreover, NeuroEditor can be easily extended by users, who can program their own algorithms in Python and run them within the tool. Last, this paper includes an example showing how users can easily define a customized workflow by applying a sequence of editing operations. The edited morphology can then be stored, together with the corresponding 3D mesh that approximates the neuronal membrane.

Background Initiation of Glucagon-Like Peptide-1 receptor agonists (GLP-1RA) in patients with type 2 diabetes (T2D) treated with levothyroxine may decrease the required levothyroxine dose due to weight loss or enhance levothyroxine absorption through delayed gastric emptying. These changes may cause thyroid hormone over-replacement and increased risk of atrial fibrillation/flutter (AF/Aflutter) and stroke. Our study aims to investigate the impact of GLP-1RA initiation on risks of AF/Aflutter and stroke in patients with T2D treated with levothyroxine, compared to sodium-glucose cotransporter 2 (SGLT2) inhibitors. Methods Leveraging the target trial emulation framework, we conducted a retrospective study using observational data to emulate a new user, active comparator trial examining the effects of initiating GLP-1RA (exposure group) versus SGLT2 inhibitors (control group), with random treatment assignment emulated by propensity score matching with 1:1 ratio. We used a 15% nationally representative sample of U.S. Medicare beneficiaries to identify participants > 65 years, continuously on stable dose of levothyroxine for ≥ 6 months before the index date (i.e., GLP-1RA or SGLT2 inhibitor initiation), with continuous Medicare enrollment, without malignant cancer or palliative care during 1 year before the index date. The primary outcome was AF/Aflutter, and secondary outcome was stroke, including ischemic stroke or transient ischemic attack. We assessed the per-protocol effects of GLP-1RA vs. SGLT2 inhibitors using inverse-probability-censoring weighted Cox proportional hazards models. Results After matching, the study cohort included 2,384 participants in both GLP-1RA and SGLT2 groups with mean age (SD): 73.3 (5.9) vs. 73.2 (5.8), and 71.5% and 71.8% of female. The median follow-up time was 1.05 years. Compared to SGLT2 inhibitors, initiation of GLP-1RA was associated with higher risk of AF/Aflutter (HR: 1.46; 95% CI: 1.28–1.67), while no statistically significant difference was observed between the two groups for stroke (HR: 1.17; 95% CI: 0.98–1.39). Sensitivity analyses showed consistent results, including restricting outcomes to inpatient visits, conducting an intention-to-treat analysis, applying a prevalent new user design, and substituting SGLT2 inhibitors with dipeptidyl peptidase-4 (DPP4) inhibitors as the active comparator. Conclusions In patients with T2D historically treated with stable doses of levothyroxine, GLP-1RA initiation was associated with a higher risk of AF/Aflutter. Further research is warranted to investigate the potential roles of weight loss, TSH fluctuations, and levothyroxine dose adjustment after GLP-1RA in mediating the cardiovascular risk.

Background In contrast to the rapid increase in thyroid cancer incidence, the mortality has remained low and stable over the last decades. In Ecuador, however, thyroid cancer mortality has increased. The objective of this study is to determine possible drivers of high rates of thyroid cancer mortality, through a cross-sectional analysis of all patients attending a thyroid cancer referral center in Ecuador. Methods From June 2014 to December 2017, a cross-sectional study was conducted at the Hospital de Especialidades Eugenio Espejo, a regional reference public hospital for endocrine neoplasia in adults in Quito, Ecuador. We identified the mechanism of detection, histopathology and treatment modalities from a patient interview and review of clinical records. Results Among 452 patients, 74.8% were young adults and 94.2% (426) were female. 13.7% had a family history of thyroid cancer, and patients’ median tumor size was 2 cm. The incidental finding was 54.2% whereas 45.8% was non-incidental. Thyroid cancer histology reported that 93.3% had papillary thyroid cancer (PTC), 2.7% follicular, 1.5% Hurtle cells, 1.6% medullary, 0.7% poor differentiated, and 0.2% anaplastic carcinoma. The mean MACIS (metastasis, age, completeness, invasion, and size) score was 4.95 (CI 4.15–5.95) with 76.2% of the thyroid cancer patients having MACIS score less than or equal to 6. The very low and low risk of recurrence was 18.1% (79) and 62% (271) respectively. An analysis of 319 patients with non-metastatic thyroid cancer showed that 10.7% (34) of patients had surgical complications. Moreover, around 62.5% (80 from 128 patients with thyroglobulin laboratory results) of TC patients had a stimulated-thyroglobulin value equal or higher than 2 ng/ml. Overall, a poor surgical outcome was present in 35.1% (112) patients. Out of 436 patients with differentiated thyroid carcinoma, 86% (375) received radioactive iodine. Conclusion Thyroid cancer histological characteristics and method of diagnosis are like those described in other reports without any evidence of the high frequency of aggressive thyroid cancer histology. However, we observed evidence of overtreatment and poor surgical outcomes that demand additional studies to understand their association with thyroid cancer mortality in Ecuador.