Search

Background: Several meta-analyses have identified methodological limitations in female stress urinary incontinence (SUI) trials, precluding the synthesis of primary studies and high-quality evidence.Objectives: Evaluation of outcome measure selection and outcome reporting in randomised controlled trials (RCTs) on surgery for SUI.Search Strategy: Systematic review of RCTs identified from bibliographical databases, including Medline, Cochrane, and EMBASE.Selection Criteria: Randomised controlled trials evaluating the efficacy and safety of surgical interventions for the management of female SUI.Data Collection and Analysis: Two researchers independently assessed the included studies and documented outcomes.Main Results: Overall, 108 studies were identified that included 422 reported outcomes and 119 outcome measures. The three most common outcomes were cure rates (87 studies), quality of life (85 studies), and overactive bladder (78 studies). The median methodological quality rating was 3 (range 0-3) and the outcome reporting quality rating was 3 (range 0-5). Multinomial logistic regression analysis revealed that the methodological quality and use of validated questionnaire were significant predictors of the quality of outcome reporting (β = 0.538, P < 0.001; β = 0.218, P = 0.011, respectively).Conclusions: Outcome reporting in SUI trials is highly variable. Until a core outcome set is developed and implemented, we propose an interim use of three commonly reported outcomes in each domain (treatment success rate - complete cure, partial improvement, or failure of response; urodynamic evaluation outcomes - overactive bladder (OAB), voiding dysfunction, and urodynamic stress incontinence; patient-reported outcomes - quality of life, sexual dysfunction, and patient satisfaction) with the use of validated questionnaires for patient-reported outcomes and subjective success rates. Complications should be also explicitly and comprehensively reported using validated outcome measures.Tweetable Abstract: There is significant variation in outcome reporting in SUI trials. Our systematic review findings aim to form the basis for the development of a core outcome set. [ABSTRACT FROM AUTHOR]

The energy demand in healthcare and hospital premises has distinctive features. Due to specific constraints in terms of service continuity and indoor air quality, the demand is at a large extent constant during the day and throughout the year. Indeed, a healthcare facility must fulfil several different activities. Medical equipment needs electric energy, while the Heating, Ventilation and Air Conditioning systems require thermal energy. It is extremely difficult to define reference characteristics for the energy demand, since the proportions of the different consumptions are strongly connected with the specific activities/services carried out within each structure. The present work aims at analysing the energy demand of a healthcare facility located near Firenze (Italy). The energy demand has been analysed by means of the available documentation to get a basic knowledge of the expected consumption of each component of the facility. These data have been then correlated with information on the actual healthcare activity parameters (e.g. staff in service, medical services) and on weather conditions. As a result, the study led to the definition of the principal energy drivers that characterize the Healthcare Facility. The analysis procedure is thought of general interest for the community working in the field, representing a benchmark for the calibration of energy digital twins and a reference data set useful to carry out building energy efficiency optimization strategies.

Background: Mutations in ANO3 are a rare cause of autosomal dominant isolated or combined dystonia, mainly presenting in adulthood., Cases: We extensively characterize a new, large ANO3 family with six affected carriers. The proband is a young girl who had suffered from tremor and painful dystonic movements in her right arm since the age of 11 years. She later developed a diffuse dystonic tremor and mild extrapyramidal signs (ie, rigidity and hypodiadochokinesis) in her right arm. She also suffered from psychomotor delay and learning difficulties. Repeated structural and functional neuroimaging were unremarkable. A dystonic tremor was also present in her two sisters. Her paternal aunt, father, and a third older sister presented episodic postural tremor in the arms. The father and one sister also presented learning difficulties. The heterozygous p.G6V variant in ANO3 was identified in all affected subjects., Literature Review: Stratification by age at onset divided ANO3 cases into two major groups, where younger patients displayed a more severe phenotype, probably due to variants near the scrambling domain., Conclusions: We describe the phenotype of a new ANO3 family and highlight the need for functional studies to explore the impact of ANO3 variants on its phospholipid scrambling activity., (© 2024 International Parkinson and Movement Disorder Society.)

A passive flexible patch for human skin temperature measurement based on contact sensing and contactless interrogation is presented. The patch acts as an RLC resonant circuit embedding an inductive copper coil for magnetic coupling, a ceramic capacitor as the temperature-sensing element and an additional series inductor. The temperature affects the capacitance of the sensor and consequently the resonant frequency of the RLC circuit. Thanks to the additional inductor, the dependency of the resonant frequency from the bending of the patch has been reduced. Considering a curvature radius of the patch of up to 73 mm, the maximum relative variation in the resonant frequency has been reduced from 812 ppm to 7.5 ppm. The sensor has been contactlessly interrogated by a time-gated technique through an external readout coil electromagnetically coupled to the patch coil. The proposed system has been experimentally tested within the range of 32-46 °C, giving a sensitivity of -619.8 Hz/°C and a resolution of 0.06 °C.

Background: Branched-chain amino acids (BCAAs), including L-leucine (L-Leu), L-isoleucine (L-Ile), L-valine (L-Val), and L-arginine (L-Arg), play a crucial role in mammary gland development, secretion of milk and regulation of the catabolic state and immune response of lactating sows. Furthermore, it has recently been suggested that free amino acids (AAs) can also act as microbial modulators. This study aimed at evaluating whether the supplementation of lactating sows with BCAAs (9, 4.5 and 9 g/d/sow of L-Val, L-Ile and L-Leu, respectively) and/or L-Arg (22.5 g/d/sow), above the estimated nutritional requirement, could influence the physiological and immunological parameters, microbial profile, colostrum and milk composition and performance of sows and their offspring., Results: At d 41, piglets born from the sows supplemented with the AAs were heavier (P = 0.03). The BCAAs increased glucose and prolactin (P < 0.05) in the sows' serum at d 27, tended to increase immunoglobulin A (IgA) and IgM in the colostrum (P = 0.06), increased the IgA (P = 0.004) in the milk at d 20 and tended to increase lymphocyte% in the sows' blood at d 27 (P = 0.07). Furthermore, the BCAAs tended to reduce the Chao1 and Shannon microbial indices (P < 0.10) in the sows' faeces. The BCAA group was discriminated by Prevotellaceae&#95;UCG-004, Erysipelatoclostridiaceae UCG-004, the Rikenellaceae&#95;RC9&#95;gut&#95;group and Treponema berlinense. Arginine reduced piglet mortality pre- (d 7, d 14) and post-weaning (d 41) (P < 0.05). Furthermore, Arg increased the IgM in the sow serum at d 10 (P = 0.05), glucose and prolactin (P < 0.05) in the sow serum at d 27 and the monocyte percentage in the piglet blood at d 27 (P = 0.025) and their jejunal expression of NFKB2 (P = 0.035) while it reduced the expression of GPX-2 (P = 0.024). The faecal microbiota of the sows in Arg group was discriminated by Bacteroidales. The combination of BCAAs and Arg tended to increase spermine at d 27 (P = 0.099), tended to increase the Igs (IgA and IgG, P < 0.10) at d 20 in the milk, favoured the faecal colonisation of Oscillospiraceae UCG-005 and improved piglet growth., Conclusion: Feeding Arg and BCAAs above the estimated requirements for milk production may be a strategy to improve sow productive performance in terms of piglet average daily gain (ADG), immune competence and survivability via modulation of the metabolism, colostrum and milk compositions and intestinal microbiota of the sows. The synergistic effect between these AAs, noticeable by the increase of Igs and spermine in the milk and in the improvement of the performance of the piglets, deserves additional investigation., (© 2023. The Author(s).)

Objectives: There is growing evidence that Parkinson's disease and diabetes are partially related diseases; however, the association between the two, and the impact of specific treatments, are still unclear. We evaluated the effect of T2D and antidiabetic treatment on age at PD onset and on all-cause mortality., Research Design and Methods: The standardized rate of T2D was calculated for PD patients using the direct method and compared with subjects with essential tremor (ET) and the general Italian population. Age at onset and survival were also compared between patients without T2D (PD-noT2D), patients who developed T2D before PD onset (PD-preT2D) and patients who developed T2D after PD onset (PD-postT2D)., Results: We designed a retrospective and prospective study. The T2D standardized ratio of PD (N = 8380) and ET (N = 1032) patients was 3.8% and 6.1%, respectively, while in the Italian general population, the overall prevalence was 5.3%. In PD-preT2D patients, on antidiabetic treatment, the onset of PD was associated with a + 6.2 year delay (p < 0.001) while no difference was observed in PD-postT2D. Occurrence of T2D before PD onset negatively affected prognosis (adjusted hazard ratio = 1.64 [95% CI 1.33-2.02]; p < 0.001), while no effect on survival was found in PD-postT2D subjects (hazard ratio = 0.86, [95% CI 0.53-1.39]; p = 0.54)., Conclusions: T2D, treated with any antidiabetic therapy before PD, is associated with a delay in its onset. Duration of diabetes increases mortality in PD-preT2D, but not in PD-postT2D. These findings prompt further studies on antidiabetic drugs as a potential disease-modifying therapy for PD., (© 2022. The Author(s).)

Equine piroplasmosis (EP) is a vector borne disease caused by apicomplexans protists Babesia caballi (Nuttal et Strickland, 1910) and Theileria equi (Laveran, 1901). Carrier mares may transmit the infection transplacental resulting in neonatal piroplasmosis or abortions. This event has been described for T. equi by several authors over the world, but no evidence for B. caballi has been reported in Europe. In this study, vertical transmission for both parasites in an Italian breed mare has been confirmed using molecular and microscopic tools. Transplacental transmission is an underestimated problem mainly in endemic areas as it not only contributes to the spread and maintenance of the infection, but also produces significant economic losses.

Aim: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy., Methods: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence and only those classified as "critical" were considered in the formulation of recommendations., Results: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists., Conclusion: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of this study was to report the rationale and selection criteria for hemithyroidectomy and ipsilateral central neck dissection in patients with selected papillary thyroid cancer and to report the surgical and oncological outcomes., Design: Single-institution retrospective observational study., Methods: The clinical records of patients with a histopathological diagnosis of low-risk pT1 papillary thyroid cancer who underwent hemithyroidectomy with or without ipsilateral central neck dissection between March 2000 and April 2018 at a tertiary referral center were retrospectively reviewed. Demographic, clinical, and histopathological data were collected., Results: During the study period, 176 patients underwent hemithyroidectomy for PTC. Thirteen patients (13/176, 7.39%) were lost to follow-up and 74 patients (74/163 45.40%) underwent completion thyroidectomy within 1 month because they were classified intermediate ATA initial risk based on definitive pathology. The final study group was composed of 89 patients, who had a median follow-up of 5.3 years. The mean follow-up was 6.3 years (range: 36-207 months). Eighty-four patients (94.38%) did not experience recurrence in the follow-up period. A total of 5/89 patients (5.62%) underwent delayed completion thyroidectomy with or without neck dissection for recurrent malignancy in the residual lobe (3/5) or regional lymph nodes (2/5). The median time from surgery to recurrence was 24.8 months (range: 6-60). The follicular variant was an independent risk factor for recurrence., Conclusions: Hemithyroidectomy with or without prophylactic ipsilateral central neck dissection is a valuable treatment option in selected low-risk papillary thyroid cancers and ensures a low risk of recurrence. Prophylactic ipsilateral central compartment dissection could have a role in improving cancer staging, and accurate ultrasonographic follow-up is essential to identify local recurrence.

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century, prolactinomas represented the paradigm of pituitary tumors for which the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Objective: Thyroid surgery may lead to postoperative complications. The aim of this paper was to determine whether the rate of postoperative hypoparathyroidism (HPT) is influenced by whether surgery is staged., Design: Single-institution retrospective observational study., Methods: The clinical records of 786 patients treated at the Otolaryngology Unit of the Azienda USL-IRCCS di Reggio Emilia between January 1990 and December 2015 were reviewed. Patients were divided into two groups according to the surgical treatment received: group TT (637 patients, 81.04%) underwent single-stage total thyroidectomy; Group cT (149 patients, 18.96%) underwent loboisthmusectomy and delayed completion total thyroidectomy. Transient and permanent HPT, assessed after 6 months of follow-up, were the primary endpoints. Risk factors of postoperative HPT were also analysed as secondary outcomes., Results: Rates of transient HPT in group TT were higher than those observed in group cT, (P = 0.0057). Analysis of risk factors identified sex as an independent risk factor for transient HPT only for group TT (P = 0.0012) and the number of parathyroid glands remaining in situ (PGRIS) as an independent risk factor for transient and permanent HPT for group TT (P < 0.0001 and P = 0.0002, respectively)., Conclusions: This study suggests that the risk of transient postoperative HPT is lower in patients that undergo completion thyroidectomy. Further independent risk factors for postoperative HPT are female sex and PGRIS score. In light of the growing use of conservative surgery for thyroid neoplasms, these findings could help to adequately plan surgery in order to reduce endocrine complications.

Magnesium is an essential nutrient involved in many important processes in living organisms, including protein synthesis, cellular energy production and storage, cell growth and nucleic acid synthesis. In this study, we analysed the effect of magnesium deficiency on the proliferation of SaOS-2 osteosarcoma cells. When quiescent magnesium-starved cells were induced to proliferate by serum addition, the magnesium content was 2-3 times lower in cells maintained in a medium without magnesium compared with cells growing in the presence of the ion. Magnesium depletion inhibited cell cycle progression and caused the inhibition of cell proliferation, which was associated with mTOR hypophosphorylation at Serine 2448. In order to map the intracellular magnesium distribution, an analytical approach using synchrotron-based X-ray techniques was applied. When cell growth was stimulated, magnesium was mainly localized near the plasma membrane in cells maintained in a medium without magnesium. In non-proliferating cells growing in the presence of the ion, high concentration areas inside the cell were observed. These results support the role of magnesium in the control of cell proliferation, suggesting that mTOR may represent an important target for the antiproliferative effect of magnesium. Selective control of magnesium availability could be a useful strategy for inhibiting osteosarcoma cell growth.

Aim: During pregnancy, thyroid homeostasis is physiologically modified, leading to altered levels of thyrotropin (TSH): hence, the adoption of pregnancy-related, population- and method-specific reference ranges is recommended. This monocentric and retrospective study was conducted to establish local pregnancy-related reference intervals for serum TSH in singleton pregnant women using real-life clinical data., Methods: We included women who measured serum TSH during pregnancy at our Laboratory over six years, excluding pregnant women with current or past history of thyroid disease, pituitary or autoimmune diseases, use of medications known to influence thyroid function, multiple and/or pathological pregnancies, BMI >30 Kg/m 2 ., Results: We retrieved a total of 3744 TSH results. Reference limits (90% confidence intervals) for TSH (in mIU/L) are: first trimester 0.09 (0.06-0.12) - 3.16 (3.05-3.29); second trimester 0.25 (0.11-0.30) - 3.55 (3.34-3.73); third trimester 0.42 (0.15-0.48) - 3.93 (3.80-4.08)., Conclusion: In conclusion, real-life clinical data could be used to establish or verify local reference intervals for TSH in pregnant women: this may reduce the risk of misclassification of pregnant women undergoing thyroid function testing.

Background: Scalp Eschar and Neck LymphAdenopathy after Tick bite is a zoonotic non-pathogen-specific disease most commonly due to Rickettsia slovaca and Rickettsia raoultii. Diagnosis is mostly based only on epidemiological and clinical findings, without serological or molecular corroboration. We presented a clinical case in which diagnosis was supported by entomological identification and by R. slovaca DNA amplifications from the tick vector., Case Presentation: A 6-year-old child presented with asthenia, scalp eschar and supraclavicular and lateral-cervical lymphadenopathy. Scalp Eschar and Neck LymphAdenopathy After Tick bite syndrome following a Dermacentor marginatus bite was diagnosed. Serological test on serum revealed an IgG titer of 1:1024 against spotted fever group rickettsiae, polymerase chain reaction assays on tick identified Rickettsia slovaca. Patient was successfully treated with doxycycline for 10 days., Conclusions: A multidisciplinary approach including epidemiological information, clinical evaluations, entomological identification and molecular investigations on tick, enabled proper diagnosis and therapy.

Classification schemes for reporting thyroid cytology of fine needle aspiration (FNA) of thyroid nodules are largely used in clinical practice, but the level of inter-observer agreement among cytopathologists is poorly acknowledged. The present study aimed to explore the inter-observer agreement among the experienced authors of the 2014 Italian Consensus for Classification and Reporting of Thyroid Cytology (ICCRTC). A stratified randomization was performed in order to obtain a sample homogeneously distributed and representative of all ICCRTC classes. Four high-experience raters were randomly selected among the extensors of the Italian consensus. They independently reviewed 60 FNA samples blindly of the initial cytological report and clinical features. Their overall agreement was evaluated according to Fleiss' kappa. The overall inter-observer agreement was moderate (κ 0.46). Specifically, a good agreement was found when the samples were consistent for malignancy (TIR5) or were not adequate for diagnosis (TIR1) (κ 0.67 and κ 0.73, respectively). A moderate agreement was present for suspicious-for-malignant category (TIR4), and a fair agreement was recorded in the two intermediate ones (TIR3A and TIR3B) (κ 0.36 and κ 0.35, respectively). For clinical purposes, the agreement was good (κ 0.74) in differentiating cases with surgical indication (TIR4/TIR5) from those in which surgery is not essential or requires limited extension (TIR3B/TIR3A/TIR2). In conclusion, the present study confirms the reliability of ICCRTC. These data represent a reference for cytopathologists using this system and are useful for the practice of clinicians and surgeons.

Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas. The therapeutic management of acromegaly always requires a personalized strategy. Normal age-matched IGF-I values are the treatment goal. Transsphenoidal surgery by an expert neurosurgeon is the primary treatment modality for most patients, especially if there are neurological complications. In patients with poor clinical conditions or who refuse surgery, primary medical treatment should be offered, firstly with somatostatin analogs (SSAs). In patients who do not reach hormonal targets with first-generation depot SSAs, a second pharmacological option with pasireotide LAR or pegvisomant (alone or combined with SSA) should be offered. Irradiation could be proposed to patients with surgical remnants who would like to be free from long-term medical therapies or those with persistent disease activity or tumor growth despite surgery or medical therapy. Since the therapeutic tools available enable therapeutic targets to be achieved in most cases, the challenge is to focus more on the quality of life., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Acromegaly is a rare disease. Improvements in lifespan in these patients have recently been reported due to transsphenoidal surgery (TSS), advances in medical therapy, and strict criteria for defining disease remission. This document reports the opinions of a group of Italian experts who have gathered together their prolonged clinical experience in the diagnostic and therapeutic challenges of acromegaly patients. Both GH and IGF-I (only IGF-I in those treated with Pegvisomant) are needed in the diagnosis and follow-up. Comorbidities (cardio-cerebrovascular disease, sleep apnea, metabolic derangement, neoplasms, and bone/joint disease) should be specifically addressed. Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Variations in the POLG1 gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma, have recently been associated with Parkinson's disease (PD), especially in patients diagnosed with progressive external ophthalmoplegia (PEO). However, the majority of the studies reporting this association mainly focused on the genetic identification of the variation in POLG1 in PD patient primary cells, and determination of mitochondrial DNA copy number, providing little information about the cellular alterations existing in patient brain cells, in particular dopaminergic neurons. Therefore, through the use of induced pluripotent stem cells (iPSCs), we assessed cellular alterations in novel p.Q811R POLG1 (POLG1 Q811R ) variant midbrain dopaminergic neuron-containing spheroids (MDNS) from a female patient who developed early-onset PD, and compared them to cultures derived from a healthy control of the same gender. Both POLG1 variant and control MDNS contained functional midbrain regionalized TH/FOXA2-positive dopaminergic neurons, capable of releasing dopamine. Western blot analysis identified the presence of high molecular weight oligomeric alpha-synuclein in POLG1 Q811R MDNS compared to control cultures. In order to assess POLG1 Q811R -related cellular alterations within the MDNS, we applied mass-spectrometry based quantitative proteomic analysis. In total, 6749 proteins were identified, with 61 significantly differentially expressed between POLG1 Q811R and control samples. Pro- and anti-inflammatory signaling and pathways involved in energy metabolism were altered. Notably, increased glycolysis in POLG1 Q811R MDNS was suggested by the increase in PFKM and LDHA levels and confirmed using functional analysis of glycolytic rate and oxygen consumption levels. Our results validate the use of iPSCs to assess cellular alterations in relation to PD pathogenesis, in a unique PD patient carrying a novel p.Q811R variation in POLG1, and identify several altered pathways that may be relevant to PD pathogenesis.

Background: Several meta-analyses have identified methodological limitations in female stress urinary incontinence (SUI) trials, precluding the synthesis of primary studies and high-quality evidence., Objectives: Evaluation of outcome measure selection and outcome reporting in randomised controlled trials (RCTs) on surgery for SUI., Search Strategy: Systematic review of RCTs identified from bibliographical databases, including Medline, Cochrane, and EMBASE., Selection Criteria: Randomised controlled trials evaluating the efficacy and safety of surgical interventions for the management of female SUI., Data Collection and Analysis: Two researchers independently assessed the included studies and documented outcomes., Main Results: Overall, 108 studies were identified that included 422 reported outcomes and 119 outcome measures. The three most common outcomes were cure rates (87 studies), quality of life (85 studies), and overactive bladder (78 studies). The median methodological quality rating was 3 (range 0-3) and the outcome reporting quality rating was 3 (range 0-5). Multinomial logistic regression analysis revealed that the methodological quality and use of validated questionnaire were significant predictors of the quality of outcome reporting (β = 0.538, P < 0.001; β = 0.218, P = 0.011, respectively)., Conclusions: Outcome reporting in SUI trials is highly variable. Until a core outcome set is developed and implemented, we propose an interim use of three commonly reported outcomes in each domain (treatment success rate - complete cure, partial improvement, or failure of response; urodynamic evaluation outcomes - overactive bladder (OAB), voiding dysfunction, and urodynamic stress incontinence; patient-reported outcomes - quality of life, sexual dysfunction, and patient satisfaction) with the use of validated questionnaires for patient-reported outcomes and subjective success rates. Complications should be also explicitly and comprehensively reported using validated outcome measures., Tweetable Abstract: There is significant variation in outcome reporting in SUI trials. Our systematic review findings aim to form the basis for the development of a core outcome set., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine expansion in the huntingtin protein. For drug candidates targeting HD, the ability to cross the blood-brain barrier (BBB) and reach the site of action in the central nervous system (CNS) is crucial for achieving pharmacological activity. To assess the permeability of selected compounds across the BBB, we utilized a two-dimensional model composed of primary porcine brain endothelial cells and rat astrocytes. Our objective was to use this in vitro model to rank and prioritize compounds for in vivo pharmacokinetic and brain penetration studies. The model was first characterized using a set of validation markers chosen based on their functional importance at the BBB. It was shown to fulfill the major BBB characteristics, including functional tight junctions, high transendothelial electrical resistance, expression, and activity of influx and efflux transporters. The in vitro permeability of 54 structurally diverse known compounds was determined and shown to have a good correlation with the in situ brain perfusion data in rodents. We used this model to investigate the BBB permeability of a series of new HD compounds from different chemical classes, and we found a good correlation with in vivo brain permeation, demonstrating the usefulness of the in vitro model for optimizing CNS drug properties and for guiding the selection of lead compounds in a drug discovery setting.

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.

Well-established criteria for evaluating the response to treatment and the appropriate followup of individual patients are critical in clinical oncology. The current evidence-based data on these issues in terms of the management of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are unfortunately limited. This document by the Italian Association of Clinical Endocrinologists (AME) on the criteria for the follow-up of GEP-NEN patients is aimed at providing comprehensive recommendations for everyday clinical practice based on both the best available evidence and the combined opinion of an interdisciplinary panel of experts. The initial risk stratification of patients with NENs should be performed according to the grading, staging and functional status of the neoplasm and the presence of an inherited syndrome. The evaluation of response to the initial treatment, and to the subsequent therapies for disease progression or recurrence, should be based on a cost-effective, risk-effective and timely use of the appropriate diagnostic resources. A multidisciplinary evaluation of the response to the treatment is strongly recommended and, at every step in the follow-up, it is mandatory to assess the disease state and the patient performance status, comorbidities, and recent clinical evolution. Local expertise, available technical resources and the patient preferences should always be evaluated while planning the individual clinical management of GEP-NENs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: The risk-benefit ratio of central neck dissection (CND) in patients affected by papillary thyroid carcinoma (PTC) without clinical or ultrasonographic (US) evidence of neck lymph node metastasis (cN0) is currently debated. The aim of this study was to evaluate long-term outcome of CND on locoregional recurrence, distant metastasis, survival, and postoperative complications in a large series of patients with cN0-PTC., Study Design: Observational retrospective controlled study., Methods: Clinical records of patients (n=610) surgically treated for cN0-PTC at the Otolaryngology Unit of the Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, from January 1984 to December 2008, were retrospectively reviewed. Study population was divided into three groups according to surgical treatment: Group A, total thyroidectomy (n=205); Group B, total thyroidectomy and elective ipsilateral CND (n=281); Group C, total thyroidectomy and bilateral CND (n=124)., Results: Of a total of 610 patients, 305 (50%) were classified as low-risk, 278 (45.57%) as intermediate-risk, and 27 (4.43%) as high-risk. Response to initial therapy was excellent in 567 patients (92.95%), acceptable in 21 (3.44%), and incomplete in 22 (3.61%), with no significant differences among groups. Locoregional recurrence was detected in 32 (5.2%) out of 610 patients. Distant metastasis was found in 15 patients (2.5%). Statistical analysis showed no significant differences in the rates of locoregional recurrence (p=0.890) or distant metastasis (p=0.538) among groups. Disease-specific mortality and overall survival did not significantly differ among groups (p=0.248 and 0.223, respectively). Rate of permanent hypoparathyroidism was significantly higher in Group C patients compared to those in Groups A and B., Conclusion: CND does not confer any clear advantage in the treatment of low-risk patients, regardless of surgical procedure. Instead, bilateral CND may be effective in limiting disease relapse and/or progression in patients at higher prognostic risk. Our data indicate that elective CND does not confer any clear advantage in terms of locoregional recurrence and long-term survival, as demonstrated by outcomes of the study Groups, regardless of their different prognostic risk. Elective CND allows a more accurate pathologic staging of central neck lymph nodes, despite its increasing the risk of permanent hypoparathyroidism. Intraoperative pathologic staging is a valuable tool to assess the risk of controlateral lymph node metastasis in the central neck compartment and to limit more aggressive surgery only to cases, otherwise understaged, with lymph node metastasis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled., Methods: The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed., Results: LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy., Conclusion: LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being., Abbreviations: AACE = American Association of Clinical Endocrinologists FT3 = free triiodothyronine FT4 = free thyroxine LT3 = levotriiodothyronine LT4 = levothyroxine MeSH = medicine medical subject headings QoL = quality of life TSH = thyroid-stimulating hormone.

Objective: The objective of this work was to investigate survival, dementia, and genotype-phenotype correlations in patients with Parkinson's disease (PD) with and without mutations on the glucocerebrosidase gene (GBA)., Methods: We included 2,764 unrelated consecutive PD patients: 123 GBA carriers (67 mild-p.N370S and 56 severe mainly p.L444P) and 2,641 noncarriers. Brain perfusion and dopamine transporter imaging was analyzed, including dementia with Lewy Bodies (DLB) as an additional control group., Results: Multivariable analysis adjusted by sex, age at onset, and disease duration attributed to GBA carriers a greater risk for dementia (hazard ratio [HR] = 3.16; p < 0.001) and death (HR = 1.85; p = 0.002) than noncarriers. When dementia was introduced in the model as a time-dependent covariate, the mortality risk remained greater in carriers (HR = 1.65; p = 0.016), suggesting that other clinical features are likely to contribute to reduced survival. At last examination, GBA carriers had worse motor symptoms, particularly nondopaminergic features. Carriers of severe mutations had greater risk for dementia compared to mild mutations (p < 0.001), but similar mortality risk. Consistent with clinical data, GBA carriers showed reduced posterior parietal and occipital cortical synaptic activity and nigrostriatal function than PD noncarriers. Neuroimaging features of carriers of mild mutations overlapped with PD noncarriers, whereas carriers of severe mutations were closer to DLB., Interpretation: Survival is reduced in GBA carriers compared to noncarriers; this seems to be partially independent from the increased risk for early dementia. The risk for dementia is strongly modulated by type of mutation. In the clinical continuum between PD and DLB, patients with GBA mutations seem to localize midway, with carriers of severe mutations closer to DLB than to idiopathic PD. Ann Neurol 2016;80:662-673., (© 2016 American Neurological Association.)

Thyroid fine-needle aspiration (FNA) cytology is the primary tool for the diagnostic evaluation of thyroid nodules. BRAF mutation analysis is employed as an ancillary tool in indeterminate cases, as recommended by the American Thyroid Association management guidelines. Hereby, we report the case of a 73-year-old woman who presented an 8-mm-size, ill-defined, left thyroid nodule. FNA resulted "suspicious for papillary thyroid carcinoma". BRAF mutation status was analyzed, and somatic BRAF (V600E) mutation identified. The patient underwent a total thyroidectomy. At histological examination, the nodule was composed of Langerhans cells, admixed with many eosinophils. A final diagnosis of Langerhans cell histiocytosis of the thyroid was made. Our case emphasizes the critical diagnostic pitfalls due to the use of BRAF (V600E) mutation analysis in thyroid FNA. Notably, BRAF (V600E) mutation is common in melanoma, colorectal carcinoma, lung carcinoma, ovarian carcinoma, brain tumors, hairy cell leukemia, multiple myeloma, and histiocytoses. Therefore, in cases of indeterminate FNA with unclassifiable atypical cells BRAF (V600E) mutated, the possibility of a localization of hystiocytosis or a secondary thyroid malignancy should be taken into account.

Background: The rates of cognitive decline in patients with Parkinson's disease (PD) are higher than in the general population. Age and disease duration have been associated with increasing rates of dementia in PD. However, the role of other factors including gender has been poorly investigated. We investigated the relationship between dementia and gender along with other established risk factors, such as age and disease duration., Methods: We conducted a cross-sectional retrospective study including all consecutive patients diagnosed with idiopathic PD attending a single out-patient tertiary clinic over an 18-year period (1995-2013). Dementia was diagnosed according to DSM-IV criteria., Results: Prevalence of dementia was 11.5% (95%CI, 10.8-12.3) and 13.5% (95%CI, 12.7-14.5) in the whole population (N = 6599) and in those aged ≥60 years (N = 5373), respectively. Age and disease duration were independently associated with dementia, and the latter was associated with dementia up to 84 years of age. Male gender was an independent risk factor. In addition, while the rate of dementia increased in males over all age strata, we found that in females prevalence began to increase steadily after the age of 65 years, reaching male estimates only after 80 years of age. Higher rates in male gender were observed between 60 and 80 years of age., Conclusion: Age and PD duration are confirmed risk factors for dementia. However, disease duration appeared to be a less important factor in cognitive decline in patients aged ≥85 years. As opposed to gender-specific estimates in the general population, male gender is likely associated with higher rates of dementia in PD patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives/hypothesis: The aim of this study was to identify any possible predictive factors of lateral neck recurrence in patients with papillary thyroid carcinoma with no ultrasonographic and/or cytological evidence of lymph node metastasis at time of diagnosis. The influence of lateral neck recurrence on survival was also investigated., Study Design: Observational retrospective study., Methods: Retrospective review of clinical records of 610 patients surgically treated for papillary thyroid carcinoma with clinically negative lymph nodes at the Otolaryngology Unit of the Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, from January 1984 to December 2008., Results: Lateral neck recurrences were ipsilateral to the primary tumor in all cases and were associated with the occurrence of more aggressive histological variants and central neck metastasis. Lateral neck recurrences were more frequently observed in patients with distant metastases and were associated with a reduced disease-specific survival., Conclusion: Lateral neck compartment ipsilateral to the tumor was the most common site of recurrence, with about half of cases appearing in the first 28 months of follow-up. In patients with papillary thyroid carcinoma, detection of lateral neck metastases prior to first surgery is crucial to surgical planning. Aggressive histological variants and postsurgical evidence of lymph node metastasis from papillary thyroid carcinoma in central neck compartment are associated with a higher risk of lateral neck recurrence. In these patients, a closer postsurgical ultrasound surveillance of the lateral neck compartments seems worthwhile., Level of Evidence: 4., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: A very limited number of studies report data on the clinical features of Parkinson's disease (PD) 20 years after onset and beyond., Objective: To characterise PD 20 years after onset, investigating the impact of age at onset and disease duration on the clinical picture and the predictors of outcomes in patients reaching the 20-year time point., Methods: We conducted a retrospective, cross-sectional study and a longitudinal study. All case visits of patients with a disease duration ≥20 years (N=401) were stratified by disease duration (20-22, 23-25, ≥26 years) and by age at onset (cut-off, 50 years). Patients with a disease duration of 20-22 years (N=320) were prospectively followed up for a median of 45 months (IQR 23-89) for the new occurrence of fracture, percutaneous endoscopic gastrostomy, institutionalisation, confinement to a wheelchair or bed and death., Results: Older age at onset and longer disease duration were independently associated with a higher prevalence of major motor and non-motor milestones of disease disability (no interaction observed). In the longitudinal study, the most frequent outcomes were death (N=92), confinement to a wheelchair or bed (N=67) and fracture (N=52). Mortality was associated with the gender: male, older age, dysphagia, orthostatic hypotension, postural instability, fractures and institutionalisation. Fracture was associated with postural instability. Predictors of permanent confinement to a wheelchair or bed were older age, postural instability and institutionalisation. Comorbid dementia at the 20-year examination did not predict any of the outcomes., Conclusions: Age at onset and disease duration are independent determinants of the clinical features of PD beyond 20 years. Non-motor symptoms depend more on age at onset rather than the disease duration itself. Non-levodopa-responsive axial symptoms are the main predictors of all relevant outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)