Surgical itinerary in parathyroid hyperfunction: 63 cases operated on

Universitatea de Medicină și Farmacie ”Gr. T. Popa”, Iași, Clinica IV-a Chirurgie, Clinica V-a Pediatrie, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Introducere: Multiplele aspecte etiopatogenice și anatomo-clinice ale hiperparatiroidismului (HP): pri-mar (HPP), renal (HPR), familial, din NEM etc. constituie o patologie care realizează o continuă provocare. În afara fenotipului și simptomatologiei polimorfe, a noilor achiziții diagnostice și terapeutice, frapează contrastul dintre incidența/prevalența sindromului în creștere în tările dezvoltate – mai ales pe seama observațiilor asimptomatice - și seriile limitate numeric sau cazurile izolate cu manifestări “istorice”, publicate în literatura națiunilor “în tranziție” sau subdezvoltate. Material și metoda: Din 1986 în clinica noastră au fost operate 63 observații de HP: 20 HPP – adenoame =17, carcinoame=2, paratiromatoza=1 și 43 HPR – HP secundar (HPS)=23 și tertiar=20. Am înregistrat 44 femei și 19 bărbati (raport 2,3/1) cu limite de vârstă 15 – 67 (medie 47) ani. Diagnosticul și indicația chirurgicală au fost stabilite clinic prin prezența suferinței renale – urolitiaza multipla sau recidivata în HPP – insuficiența renală cronică în regim de hemodializa în HPR, sindrom osos manifest – osteoporoza, dureri osoase, chisturi și fracturi, manifestări neuromusculare, psihonevrotice, digestive și cardiovasculare în ambele varietăți. Datele de laborator au obiectivat valori anormale ale calciului seric total și ionizat, fosforului și fosfatazei alcaline și în special ale iPTH iar explorarile localizatoare au inclus ultrasonografia – mai puțin concludentă în leziunile multiglandulare și mai recent scintigrafia cu 99mTc-tetrophosmin. Rezultate: Toate cazurile au fost operate practicându-se exereza simplă în 17 adenoame și “în bloc” cu lobul tiroidian ipsilateral în două cancere (unul fiind o recidivă la 4 ani după indepărtarea unui adenom), într-un adenom chistic intratiroidian ca și în cazul de paratiromatoza (de asemenea recidiva după exere-za extra muros a unui adenom). În observațiile de HPR au fost executate 24 paratiroidectomii subtotale (în 20 observatii reușindu-se exereza standard a 3 si ½ glande, în rest indepartandu-se 3 sau doar 2 paratiroide) si respectiv 19 paratiroidectomii totale (6 cu autotransplant glandular și 13 simple). Din considerente tactice sau pentru leziuni asociate explorarea/exereza chirurgicală a fost extinsă la tiroida (29 cazuri) sau timus (20 cazuri). Examenul anatomopatologic a precizat diagnosticul final în toate obser-vațiile. Rezultatele imediate și în timp au fost bune în special în HPP. Nu au fost hipocalcemii persistente chiar în cazul paratiroidectomiilor extinse dar am notat o paralizie recurentială, un hematom al lojei și recidiva în două cazuri de autotransplant antibrahial ca și cea a unui cancer la 4 ani după extirparea unui adenom (leziune noua ?). Concluzii: Paratiroidectomia – cu rafinamentele sale recente: minim invazivă, endoscopică sau asistată robotic – este singurul tratament eficace și definitiv în HPP și constituie o terapie simptomatică impor- tantă, deși suboptimal, în cazurile de HPR (a căror tratament ideal este transplantul renal). Exerezele paratiroidiene trebuie practicate doar de specialiști antrenați în această chirurgie.Background: Hyperparathyroidism (HP) is a constantly evolving entity with multiple clinical varieties i.e.: primary (HPP), renal (HPR), familial, in MEN etc., proteiform phenotype and symptomatology, continous modernizing diagnosis and therapeutic methods and striking differences in epidemiology between developed nations and the 3rd world’s or “in transition” countries. Material and methods: The study population comprised 63 patients with HP operated on from 1986 in our clinic. There were 20 cases with PHP (17 adenomas, 2 carcinomas and one parathyromatosis) and 43 cases with RHP (23 secondary and 20 tertiary). The series included 44 women and 19 men (ratio 2,3/1), aged 15-67 (range 47) years. As a rule the documentation of signs and symptoms as well as recording of the surgical indications were consistently thorough. The presence of multiple and recurrent urolithiasis in HPP and renal failure on hemodialysis in HPR as well as bone, muscular, neuropsychiatric, digestive and cardiovascular manifestation in both syndromes are constantly described. Laboratory data indicated abnormally levels of serum calcium, phosphorus, alkaline phosphatase but especially of the iPTH. Localisation procedures included ultrasonography less valuable for multiglandular lesions and recently 99mTc-tetrophosmin scan. Results: All the cases were operated on: 17 simple exeresis for adenomas and 4 “en bloc” resections to-gether with the thyroid lobe for two carcinomas, intrathyroid cystic adenoma and parathyromatosis one case each. In HPR 20 patients underwent standard subtotal parathyroidectomy (3 and ½ glands) but in 3 cases only 3 or even 2 glands were founded and 19 total parathyroidectomy respectively (6 with auto- transplantation). Thyroid (n=29) and thymus (20) resections were practiced for associated lesions or tac- tical reasons. Pathology established the final diagnosis. Immediate and late results were good especially in HPP. Persistent hypocalcemia was not encountered even in extended resections but we avow a cervi-cal hematoma,a recurrent laryngeal nerve palsy, two antibrahial recurrences and a carcinoma developed four years after resection of an adenoma (new lesion ?). Conclusions: Parathyroidectomy with its recent refinements in minimally invasive, endoscopic, video- and robotic techniques constitutes the gold standard therapy for HPP and still remains the only permanently effective method offering an improved quality of life in HPR. These operations must be done by high-specialised surgeons

Choledocoscopy in the surgery of mechanical jaundice

Universitatea de medicina si farmacie “Gr. T. Popa”, Iasi, clinica a IV-a chirurgie, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Scopul lucrării: Diversitatea etiopatogenică a icterului mecanic justifică explorarea coledocoscopică, necesară unui diagnostic de certitudine. Material şi metodă: Între anii 2002 - 2011 am utilizat coledocoscopul flexibil la 58 de pacienți internați cu icter mecanic. La 21 (36,2 %) dintre aceştia icterul s-au dovedit a fi de etiologie neoplazică: 5 (8,6 %) cazuri cu ampulom vaterian (care au beneficiat de duodenopancreatectomie cefalică), 14 (24,1 %) cazuri cu neoplasm al capului de pancreas şi două (3.4 %) cazuri cu colangiocarcinom). Ceilalți 37 (63,8 %) de pacienți au avut o etiologie litiazică, la care coledocolitotomia asistată coledocoscopic şi asociată colecistectomiei a permis vindecarea. Rezultate. Discuții: Dintre pacienții cu suspiciune de icter mecanic neoplazic, în două (3,4 %) cazuri a fost necesară coledocoscopia care a certificat diagnosticul de colangiocarcinom atât prin aspectul imagistic, dar mai ales datorită posibilității prelevării biopsiei şi examenului histopatologic. În explorarea icterului mecanic. cu etiologie litiazică examenul coledocoscopic permite vizualizarea calculilor în 16 (27,5 %) cazuri la care celelalte explorări imagistice erau neconcludente. În toate cazurile controlul coledocoscopic a certificat absența calculilor în calea biliarặ principalặ la finalul intervenției, oferind astfel siguranță privind acuratețea actului chirurgical. Concluzii: Coledocoscopia aduce siguranță în chirurgia căii biliare principale atât în ceea ce priveşte diagnosticul, permițând vizualizarea şi prelevarea biopsiei în leziunile tumorale ale căii biliare principale cât şi în tratamentul litiazei biliare, oferind posibilitatea controlului imediat (intraoperator) al căii biliare principale după coledocolitotomie.Abstract. Background. The diverse etiology of mechanical jaundice requires a choledocoscopy to allow a correct diagnosis. Methods: Between 2002 and 2011, we used flexible choledocoscope, in 58 patients with mechanical jaundice admitted in our clinic. 21 (36, 2 %) cases proved to be of neoplastic etiology: 5 (8, 6%) cases diagnosed with vaterian ampuloma (treated by cephalic duodenopancreatectomy), 14 (24, 1 %) cases with pancreatic head cancer and two (3, 4 %) cases with cholangiocarcinoma. The remaining 37 (63, 8 %) cases were caused by lithiasis, treated by choledocolhitotomy associated with choledocoscopy and cholecystectomy. Results. Discussion: Among patients with suspected neoplastic mechanical jaundice, in two (3.4 %) cases choledocoscopy was necessary, in order to sustained the diagnosis of colangiocarcinoma, by macroscopically appearance, and also by the biopsy sampling and histological examination. In mechanical jaundice of lithiasis etiology, the choledocoscopy permitted the visualization of stones in 16 (27, 5%) cases in which, other imagistic investigations were inconclusive. In all cases choledocoscopic control certified the absence of gallstones in the bile duct at the end of the surgical procedure, and thereby provides safety of the surgical act. Conclusions: Choledocoscopy adds certainty in the main bile duct surgery both in terms of correct diagnosis, allowing visualization and biopsy sampling of the main bile duct in tumor lesions and in treatment of gallstone disease, allowing immediate control of the main bile duct after choledocolithotomy

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

SARS-CoV-2 transmission risk from asymptomatic carriers: Results from a mass screening programme in Luxembourg.

BACKGROUND: To accompany the lifting of COVID-19 lockdown measures, Luxembourg implemented a mass screening (MS) programme. The first phase coincided with an early summer epidemic wave in 2020. METHODS: rRT-PCR-based screening for SARS-CoV-2 was performed by pooling of samples. The infrastructure allowed the testing of the entire resident and cross-border worker populations. The strategy relied on social connectivity within different activity sectors. Invitation frequencies were tactically increased in sectors and regions with higher prevalence. The results were analysed alongside contact tracing data. FINDINGS: The voluntary programme covered 49% of the resident and 22% of the cross-border worker populations. It identified 850 index cases with an additional 249 cases from contact tracing. Over-representation was observed in the services, hospitality and construction sectors alongside regional differences. Asymptomatic cases had a significant but lower secondary attack rate when compared to symptomatic individuals. Based on simulations using an agent-based SEIR model, the total number of expected cases would have been 42·9% (90% CI [-0·3, 96·7]) higher without MS. Mandatory participation would have resulted in a further difference of 39·7% [19·6, 59·2]. INTERPRETATION: Strategic and tactical MS allows the suppression of epidemic dynamics. Asymptomatic carriers represent a significant risk for transmission. Containment of future outbreaks will depend on early testing in sectors and regions. Higher participation rates must be assured through targeted incentivisation and recurrent invitation. FUNDING: This project was funded by the Luxembourg Ministries of Higher Education and Research, and Health

A clinical and cost effectiveness trial of a parent group intervention to manage challenging restricted and repetitive behaviours in young children with autism spectrum disorder: study protocol for a randomized controlled trial

Background Restricted and repetitive behaviours vary greatly across the autism spectrum, and although not all are problematic some can cause distress and interfere with learning and social opportunities. We have, alongside parents, developed a parent group based intervention for families of young children with autism, which aims to offer support to parents and carers; helping them to recognise, understand and learn how to respond to their child’s challenging restricted repetitive behaviours. Methods The study is a clinical and cost-effectiveness, multi-site randomised controlled trial of the Managing Repetitive Behaviours (MRB) parent group intervention versus a psychoeducation parent group Learning About Autism (LAA) (n = 250; 125 intervention/125 psychoeducation; ~ 83/site) for parents of young children aged 3–9 years 11 months with a diagnosis of autism. All analyses will be done under intention-to-treat principle. The primary outcome at 24 weeks will use generalised estimating equation (GEE) to compare proportion of children with improved RRB between the MRB group and the LAA group. The GEE model will account for the clustering of children by parent groups using exchangeable working correlation. All secondary outcomes will be analysed in a similar way using appropriate distribution and link function. The economic evaluation will be conducted from the perspective of both NHS costs and family access to local community services. A ‘within trial’ cost-effectiveness analysis with results reported as the incremental cost per additional child achieving at least the target improvement in CGI-I scale at 24 weeks. Discussion This is an efficacy trial to investigate the clinical and cost-effectiveness of a parent group based intervention designed to help parents understand and manage their child’s challenging RRB. If found to be effective, this intervention has the potential to improve the well-being of children and their families, reduce parental stress, greatly enhance community participation and potential for learning, and improve longer-term outcomes. Trial registration Trial ID: ISRCTN15550611 Date registered: 07/08/2018. Sponsor and Monitor: Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust R&D Manager Lyndsey Dixon, Address: St Nicholas Hospital, Jubliee Road, Gosforth, Newcastle upon Tyne NE3 3XT, [email protected], Tel: 0191 246 722

Brief Report: Testing the Psychometric Properties of the Spence Children’s Anxiety Scale (SCAS) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) in Autism Spectrum Disorder

Anxiety is a prevalent and impairing co-morbidity among individuals with autism spectrum disorder (ASD), yet assessment measures, including screening tools, are seldom validated with autism samples. We explored the psychometric properties of the child and parent reports of the Spence Children’s Anxiety Scale (SCAS) and the Screen for Anxiety Related Disorder-71 (SCARED-71) with 49 males with ASD (10–16 years, 63% co-occurring anxiety). Both measures had excellent internal consistency and fair-good parent–child agreement. The SCAS has a higher proportion of items evaluating observable behaviors. Predictive power of the measures did not differ. Higher cut-points in the parent reports (SCARED only) and lower cut-points in the child reports may enhance prediction in this sample. Choice of measure and cut-points should be considered alongside intended purpose

Elevated visual dependency in young adults after chemotherapy in childhood

Chemotherapy in childhood can result in long-term neurophysiological side-effects, which could extend to visual processing, specifically the degree to which a person relies on vision to determine vertical and horizontal (visual dependency). We investigated whether adults treated with chemotherapy in childhood experience elevated visual dependency compared to controls and whether any difference is associated with the age at which subjects were treated. Visual dependency was measured in 23 subjects (mean age 25.3 years) treated in childhood with chemotherapy (CTS) for malignant, solid, non-CNS tumors. We also stratified CTS into two groups: those treated before 12 years of age and those treated from 12 years of age and older. Results were compared to 25 healthy, age-matched controls. The subjective visual horizontal (SVH) and vertical (SVV) orientations was recorded by having subjects position an illuminated rod to their perceived horizontal and vertical with and without a surrounding frame tilted clockwise and counter-clockwise 20° from vertical. There was no significant difference in rod accuracy between any CTS groups and controls without a frame. However, when assessing visual dependency using a frame, CTS in general (p = 0.006) and especially CTS treated before 12 years of age (p = 0.001) tilted the rod significantly further in the direction of the frame compared to controls. Our findings suggest that chemotherapy treatment before 12 years of age is associated with elevated visual dependency compared to controls, implying a visual bias during spatial activities. Clinicians should be aware of symptoms such as visual vertigo in adults treated with chemotherapy in childhood

Comparisons of the factor structure and measurement invariance of the Spence children’s anxiety scale - parent version in children with autism spectrum disorder and typically developing anxious children

The Spence Children’s Anxiety Scale - Parent version (SCAS-P) is often used to assess anxiety in children with autism spectrum disorder (ASD), however, little is known about the validity of the tool in this population. The aim of this study was to determine whether the SCAS-P has the same factorial validity in a sample of young people with ASD (n=285), compared to a sample of typically developing young people with anxiety disorders (n=224). Poor model fit with all of the six hypothesised models precluded invariance testing. Exploratory factor analysis indicated that different anxiety phenomenology characterises the two samples. The findings suggest that cross-group comparisons between ASD and anxious samples based on the SCAS-P scores may not always be appropriat

Tumor-Associated Macrophages (TAMs) Form an Interconnected Cellular Supportive Network in Anaplastic Thyroid Carcinoma

BACKGROUND: A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC. METHODOLOGY/PRINCIPAL FINDINGS: Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a "microglia-like" appearance on these cells which we termed "Ramified TAMs" (RTAMs). In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells. CONCLUSION: ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic functions which remain to be determined

Variability in school closure decisions in response to 2009 H1N1: a qualitative systems improvement analysis

<p>Abstract</p> <p>Background</p> <p>School closure was employed as a non-pharmaceutical intervention against pandemic 2009 H1N1, particularly during the first wave. More than 700 schools in the United States were closed. However, closure decisions reflected significant variation in rationales, decision triggers, and authority for closure. This variability presents the opportunity for improved efficiency and decision-making.</p> <p>Methods</p> <p>We identified media reports relating to school closure as a response to 2009 H1N1 by monitoring high-profile sources and searching Lexis-Nexis and Google news alerts, and reviewed reports for key themes. News stories were supplemented by observing conference calls and meetings with health department and school officials, and by discussions with decision-makers and community members.</p> <p>Results</p> <p>There was significant variation in the stated goal of closure decision, including limiting community spread of the virus, protecting particularly vulnerable students, and responding to staff shortages or student absenteeism. Because the goal of closure is relevant to its timing, nature, and duration, unclear rationales for closure can challenge its effectiveness. There was also significant variation in the decision-making authority to close schools in different jurisdictions, which, in some instances, was reflected in open disagreement between school and public health officials. Finally, decision-makers did not appear to expect the level of scientific uncertainty encountered early in the pandemic, and they often expressed significant frustration over changing CDC guidance.</p> <p>Conclusions</p> <p>The use of school closure as a public health response to epidemic disease can be improved by ensuring that officials clarify the goals of closure and tailor closure decisions to those goals. Additionally, authority to close schools should be clarified in advance, and decision-makers should expect to encounter uncertainty disease emergencies unfold and plan accordingly.</p