Characterization of diamond and organic scintillation detectors utilizing radiation sources for continuous plasma operation.

This paper provides a comprehensive study of neutron calibration methodologies, specifically highlighting the capabilities for n-γ discrimination in diamond and EJ-309, and stilbene scintillation detectors. The calibration process detailed in this study includes pulse height analysis and pulse shape discrimination, relying on the analysis of charge deposition resulting from both γ and neutron interactions. Utilizing 60Co and 252Cf radiation sources, the energy spectra of these sources are obtained. The characterized detectors were used in ST40 experiments and allowed acquiring neutron signal during a plasma shot with good agreement among diamond and scintillation detectors. Then, the diamond detector was cross-calibrated against indium activation foils placed at the same location in proximity to the ST40 during plasma shots: both detectors measured a neutron flux of ≈106 cm-2 s-1 at ≈1 m distance from the tokamak center, and the discrepancy between the diamond detector and the activation foils is ≈25%.

Primary urethral carcinoma: Results from a single center experience.

INTRODUCTION AND AIM OF THE STUDY: Primary urethral carcinoma (PUC) is a rare neoplastic disease arising in the urethra, without any evidence of a previous or synchronous carcinoma of the entire urinary tract. Since rare diseases are often incorrectly diagnosed and managed, the aim of this study was to analyze the experience of a single urology center in the treatment of PUC, focusing on neoplasms arising from the male anterior urethra. MATERIALS AND METHODS: Medical records of patients with neoplasms at the level of the penile and bulbar urethra who presented at our tertiary referral center between January 1988 and December 2018 were retrospectively reviewed. Patients with carcinoma of the prostatic urethra were excluded. The diagnosis was obtained with the aid of urethroscopy and lesion biopsy. Local staging was performed by means of contrast-enhanced MRI in selected patients. Staging was achieved by clinical examination, ultrasonography, and CT scan. Radical surgery (radical cystectomy + total penectomy + bilateral inguinal lymphadenectomy) was proposed to patients with ≥T2 tumors or cN+ with a good performance status, proximal tumor and without severe comorbidities. In case of nodal involvement, neoadjuvant chemotherapy was additionally offered. Patients with localized disease (

Primary urethral carcinoma: Results from a single center experience. / Carcinoma uretral primario: resultados de la experiencia de un único centro.

INTRODUCTION AND AIM OF THE STUDY: Primary urethral carcinoma (PUC) is a rare neoplastic disease arising in the urethra, without any evidence of a previous or synchronous carcinoma of the entire urinary tract. Since rare diseases are often incorrectly diagnosed and managed, the aim of this study was to analyze the experience of a single urology center in the treatment of PUC, focusing on neoplasms arising from the male anterior urethra. MATERIALS AND METHODS: Medical records of patients with neoplasms at the level of the penile and bulbar urethra who presented at our tertiary referral center between January 1988 and December 2018 were retrospectively reviewed. Patients with carcinoma of the prostatic urethra were excluded. The diagnosis was obtained with the aid of urethroscopy and lesion biopsy. Local staging was performed by means of contrast-enhanced MRI in selected patients. Staging was achieved by clinical examination, ultrasonography, and CT scan. Radical surgery (radical cystectomy + total penectomy + bilateral inguinal lymphadenectomy) was proposed to patients with ≥T2 tumors or cN + with a good performance status, proximal tumor and without severe comorbidities. In case of nodal involvement, neoadjuvant chemotherapy was additionally offered. Patients with localized disease (

Sporadic non-functioning pancreatic neuroendocrine tumours: multicentre analysis.

BACKGROUND: Outcomes after surgery for sporadic pancreatic neuroendocrine neoplasms (Pan-NENs) were evaluated. METHODS: This multicentre study included patients who underwent radical pancreatic resection for sporadic non-functioning Pan-NENs. In survival analysis, the risk of mortality in this cohort was analysed in relation to that of the matched healthy Italian population. Relative survival (RS) was calculated as the rate between observed and expected survival. Factors related to RS were investigated using multivariable modelling. RESULTS: Among 964 patients who had pancreatic resection for sporadic non-functioning Pan-NENs, the overall RS rate was 91.8 (95 per cent c.i. 81.5 to 96.5) per cent. 2019 WHO grade (hazard ratio (HR) 5.75 (s.e. 4.63); P = 0.030) and European Neuroendocrine Tumour Society (ENETS) TNM stage (6.73 (3.61); P < 0.001) were independent predictors of RS. The probability of a normal lifespan for patients with G1, G2, G3 Pan-NENS, and pancreatic neuroendocrine carcinomas (Pan-NECs) was 96.7, 54.8, 0, and 0 per cent respectively. The probability of a normal lifespan was 99.8, 99.3, 79.8, and 46.8 per cent for those with stage I, II, III, and IV disease respectively. The overall disease-free RS rate was 73.6 (65.2 to 79.5) per cent. 2019 WHO grade (HR 2.10 (0.19); P < 0.001) and ENETS TNM stage (HR 2.50 (0.24); P < 0.001) significantly influenced disease-free RS. The probability of disease-free survival was 93.2, 84.9, 45.2, and 6.8 per cent for patients with stage I, II, III, and IV disease, and 91.9, 45.2, 9.4, and 0.7 per cent for those with G1, G2, G3 Pan-NENS, and Pan-NECs, respectively. CONCLUSION: A surgical approach seems without benefit for Pan-NECs, and unnecessary for small G1 sporadic Pan-NENs. Surgery alone may be insufficient for stage III-IV and G3 Pan-NENs.

Feasibility and relevance of urine culture during stone fragmentation in patients undergoing percutaneous nephrolithotomy and retrograde intrarenal surgery: a prospective study.

PURPOSE: We evaluated if, during lithotripsy, bacteria may be detected in the irrigation fluid of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS). The concordance between urine culture from stone fragmentation (SFUC), bladder (BUC), renal pelvic (RPUC) and stone (SC) was analyzed. We also assessed the correlation between variables and cultures and their association with systemic inflammatory response syndrome (SIRS) and of a positive SC. METHODS: We included 107 patients who underwent PCNL (n = 53) and RIRS (n = 54) from January 2017 to May 2018. Samples for RPUC were obtained by renal catheterization. Stone fragments and irrigation fluid sample were sent for culture. RESULTS: SFUC was positive in 17 (15.9%), BUC in 22 (20.6%), RPUC in 26 (24.3%) and SC in 30 patients (28%). The concordance between SFUC and SC was the highest among all cultures: 94.1%. SFUC and SC grew identical microorganisms in 15/17 (88.2%) patients. Out of 17 (15.9%) patients with SIRS, 8 (7.5%) had sepsis. SFUC had the highest PPV and specificity to detect positive SC and SIRS. Previous urinary tract infection, a preoperative nephrostomy, stone diameter and composition, staghorn calculi, PCNL, positive BUC, RPUC and SFUC were predictors of infected stone. Variables that indicate complex stones, complex PCNL and an infection of the upper tract were associated with SIRS. CONCLUSION: SFUC is technically feasible, easy to retrieve and to analyze. The spectrum of SFUC potential application in clinical practice is when is not possible to perform a SC, e.g. complete dusting or during micro-PCNL.

Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study.

BACKGROUND: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. METHODS: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. RESULTS: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. CONCLUSION: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.

ANTECEDENTES: Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox. RESULTADOS: En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.

Use of an intraoperative wound protector to prevent surgical-site infection after pancreatoduodenectomy: randomized clinical trial.

BACKGROUND: Surgical-site infection (SSI) increases treatment costs, duration of hospital stay and readmission rate after pancreatic surgery. This study aimed to assess whether a wound protector could reduce the risk of superficial incisional SSI after pancreatoduodenectomy. METHODS: This RCT included patients undergoing pancreatoduodenectomy at Verona University Hospital, between 2017 and 2018. The experimental group had a dual-ring wound protector, whereas the control group had standard surgical drapes. The groups were stratified by preoperative biliary stent placement. The primary outcome was the overall rate of superficial SSI. RESULTS: An interim analysis was conducted after 212 patients had been enrolled; 22 patients (10·4 per cent) were excluded owing to inability to complete the pancreatoduodenectomy, or the need for postoperative reintervention. Some 94 patients (49·5 per cent) had a wound protector and 96 (50·5 per cent) had standard drapes. There were no differences between groups in demographics, or in intraoperative findings, pathological data or surgical outcomes. The overall superficial SSI rate was 7·4 per cent, which did not differ between groups (7 per cent in each group; P = 0·585). Subanalysis of patients with a preoperative biliary stent showed a similar outcome (superficial SSI rate 9 versus 8 per cent with wound protector versus surgical drapes respectively; P = 0·536). The trial was stopped prematurely on the grounds of futility. CONCLUSION: Use of a wound protector did not reduce the rate of superficial SSI after pancreatoduodenectomy. Registration number: NCT03820648 (http://www.clinicaltrials.gov).

ANTECEDENTES: La infección de la herida quirúrgica (surgical-site infection, SSI), especialmente de la incisión, aumenta sobremanera los costes del tratamiento, la duración de la estancia y la tasa de reingresos en la cirugía de páncreas. En los últimos años se han introducido los protectores de las heridas (wound protectors, WP) con la intención de reducir la tasa de SSI. Este estudio tuvo como objetivo evaluar si un WP podría reducir la incidencia de la SSI superficial de la incisión (superficial incisional surgical-site infection, SI-SSI) en pacientes sometidos a duodenopancreatectomía cefálica (pancreaticoduodenectomy, PD). MÉTODOS: Ensayo aleatorizado controlado en el que se incluyeron los pacientes a los que se realizó una PD en la Universidad de Verona entre 2017 y 2018. En el grupo experimental se utilizó un WP de doble anillo, mientras que el grupo control se utilizaron tallas quirúrgicas convencionales (standard drape, SD). Los grupos se estratificaron también según la colocación preoperatoria de una prótesis biliar. RESULTADOS: Se incluyeron 212 pacientes, de los que 22 (10%) abandonaron el estudio debido a la imposibilidad de realizar la DP o a la necesidad de una reintervención durante el curso postoperatorio. Los pacientes se dividieron en 94 (49%) en el grupo WP y 96 (51%) en el grupo SD. No se detectaron diferencias entre grupos en cuanto a las variables demográficas y a los resultados intraoperatorios, patológicos o quirúrgicos. La tasa global de SI-SSI fue del 7,4%, que no difirió entre los grupos (WP 7,5% versus SD 7,3%, P = 0,585). Teniendo en cuenta los resultados descritos, se cumplieron los criterios de futilidad del análisis y el ensayo se interrumpió prematuramente. CONCLUSIÓN: En el entorno de un centro de alto volumen, la WP por si sola no redujo la tasa de SI-SSI. Cabría plantear su utilización dentro de un programa multimodal, que debería incluir un replanteamiento interno de la institución encaminado a la reducción de complicaciones infecciosas.

A Brazilian multicentre study evaluating pregnancies induced by cabergoline in patients harboring prolactinomas.

OBJECTIVE: To evaluate the maternal-fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort. METHODS: The prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study, RESULTS: We included 194 women with a mean age of 31 (17-45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases. CONCLUSIONS: Our findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed.

Analysis of the strengths and weaknesses of the programs, policies and practices of infant feeding in ecuador

Adequate nutrition during the first two years is important and ensures an adequate development in the human being. The following research evaluates the Global Strategy for Infant and Young Child Feeding (IYCF) for children under 5 years old, hosted by Ecuador in 2002. The tool applied was established by the Asia Group of The International Baby Food Action Network (IBFAN), which was called the World Breastfeeding Trends Initiative (WBTi). WBTi establishes a framework for assessing the compliance that a country has made in implementing the Global Strategy, helps key stakeholders plan and make decisions at various levels of action, and identifies the strengths and weaknesses of their policies and programs. The tool was applied in 23 key stakeholders from the main cities of the country and from the governmental and private sectors who were working actively for the Nutrition of Ecuadorian children. They were selected on the basis of their position and experience in the program evaluated and their willingness to participate. According to WBTi, Ecuador's level of compliance is Low. Three of the ten indicators that evaluated policies and programs scored critically; likewise, two of the five indicators that evaluated practices were scored with a critical score. The deficiencies in complying with the National Policies, Programs, and Coordination showed an important impact on their overall compliance, which, together with a short duration of breastfeeding and the extensive use of bottle feeding, significantly affect the Infant and Young Child Feeding(AU)

Una correcta nutrición durante los dos primeros años de vida es importante y asegura un adecuado desarrollo en el ser humano. La siguiente investigación evalúo la situación del país y los avances alcanzados en implementar la Estrategia Mundial para la Alimentación de Lactantes y Niños Pequeños (ALNP) (menores de 5 años); acogida por Ecuador en el año 2002. La herramienta fue establecida por el grupo de Asia de la Red Internacional de Grupos Pro-Alimentación Infantil (IBFAN), quien la denominó WBTi -World Breastfeeding Trends Initiative- (por sus siglas en inglés). La WBTi, establece un marco referencial para evaluar el cumplimiento de un país en relación a la implementación de la Estrategia Mundial para la ALNP y ayuda a actores claves a planificar y tomar decisiones en varios niveles de acción, identificando las fortalezas y debilidades de sus políticas y programas orientados a la protección, promoción y apoyo de la Alimentación del Infante. La herramienta se aplicó en 23 actores claves del sector privado y gubernamental, de las principales ciudades del país y quienes trabajaban activamente por la Nutrición de los niños del Ecuador. Los informantes claves, se seleccionaron en base a su cargo y experiencia en el programa evaluado y su voluntad a participar. Acorde a la WBTi, Ecuador tiene un nivel de cumplimiento bajo. Tres de los diez indicadores que evaluaron las políticas y programas de la ALNP obtuvieron un puntaje crítico; por otro lado, dos de los cinco indicadores que evaluaron las prácticas de la ALNP se calificaron con un puntaje crítico. La falla en las Políticas, Programas y Coordinación Nacional mostraron un impacto importante en el cumplimiento global de la Estrategia, las que conjuntamente con una corta duración de la lactancia materna y el amplio uso de la alimentación con biberón afectan de forma importante la alimentación del infante en el Ecuador(AU)

SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis.

The molecular basis of advanced systemic mastocytosis (SM) is not fully understood and despite novel therapies the prognosis remains dismal. Exome sequencing of an index-patient with mast cell leukemia (MCL) uncovered biallelic loss-of-function mutations in the SETD2 histone methyltransferase gene. Copy-neutral loss-of-heterozygosity at 3p21.3 (where SETD2 maps) was subsequently found in SM patients and prompted us to undertake an in-depth analysis of SETD2 copy number, mutation status, transcript expression and methylation levels, as well as functional studies in the HMC-1 cell line and in a validation cohort of 57 additional cases with SM, including MCL, aggressive SM and indolent SM. Reduced or no SETD2 protein expression-and consequently, H3K36 trimethylation-was found in all cases and inversely correlated with disease aggressiveness. Proteasome inhibition rescued SETD2 expression and H3K36 trimethylation and resulted in marked accumulation of ubiquitinated SETD2 in SETD2-deficient patients but not in patients with near-normal SETD2 expression. Bortezomib and, to a lesser extent, AZD1775 alone or in combination with midostaurin induced apoptosis and reduced clonogenic growth of HMC-1 cells and of neoplastic mast cells from advanced SM patients. Our findings may have implications for prognostication of SM patients and for the development of improved treatment approaches in advanced SM.

Measurement of liver and spleen interstitial volume in patients with systemic amyloid light-chain amyloidosis using equilibrium contrast CT.

OBJECTIVES: To investigate equilibrium contrast-enhanced CT (EQ-CT) measurement of extracellular volume fraction (ECV) in patients with systemic amyloid light-chain (AL) amyloidosis, testing the hypothesis that ECV becomes elevated in the liver and spleen and ECV correlates with other estimates of organ amyloid burden. METHODS: 26 patients with AL amyloidosis underwent EQ-CT, and ECV was measured in the liver and spleen. Patients also underwent serum amyloid P (SAP) component scintigraphy with grading of liver and spleen involvement. Mann-Whitney U test was used to test for a difference between patients with amyloid deposition (SAP grade 1-3) and those without (SAP grade 0). Variation in ECV across SAP grades was assessed using the Kruskal-Wallis test and association between ECV and SAP grades with Spearman correlation. RESULTS: Mean ECV in the spleen and liver was significantly greater (p < 0.0005) in amyloidotic organs (SAP grade 1-3) [spleen, liver: 0.430, 0.375] compared with healthy tissues [spleen, liver: 0.304, 0.269]. ECV increased with increasing amyloid burden, showing positive correlation with SAP grade in both the liver (r = 0.758) and spleen (r = 0.867). CONCLUSION: In patients with systemic AL amyloidosis, EQ-CT can demonstrate increased spleen and liver ECV, which is associated with amyloid disease burden.

Lacertus fibrosus augmentation for distal biceps brachii rupture repair: surgical technique.

BACKGROUND: Repair of distal biceps tendon ruptures has become widely accepted. Unfortunately, care of retracted-degenerated injuries remains a challenge for orthopedic surgeons. Complication rates appear to increase when surgery is performed in chronic cases compared to those operated acutely. Multiple techniques for chronic reconstruction with the use of grafts have been described. Recently Morrey, from the Mayo Clinic, proposed a direct anatomic repair of retracted distal biceps tendon ruptures in extreme flexion (60°-90°) to avoid grafting. MATERIALS AND METHODS: The authors propose and describe a new surgical technique using the lacertus fibrosus (LF) as augmentation-elongation for retracted-degenerated distal biceps tendon tears. We present four cases with chronic ruptures with 2-year follow-up. The mean age was 45 years old (33-51), the time of surgery was 13 weeks (4-24) after the trauma, dominant arm was involved in two cases. RESULTS: The mean MEPS was 95/100 at 2-year follow-up. With this technique we increase the length of the tendon up to 2.5 cm. The major complication in our study was transient sensitive radial nerve paresthesia. We did not have any hardware mobilization or muscular herniation. CONCLUSION: With this study we want to present our experience in the treatment of retracted distal biceps tendon tear with lacertus fibrosus augmentation. Our surgical technique is an effective and cheap option for chronic-retracted distal biceps tendon lesions. Recovery time is quicker, and integration is faster due to the use of an autologous vascularized graft. Preoperative ultrasound scan is mandatory in order to evaluate LF integrity, thickness and size.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Myeloid expression of the AP-1 transcription factor JUNB modulates outcomes of type 1 and type 2 parasitic infections.

Activation of macrophages is a key step in the initiation of immune responses, but the transcriptional mechanisms governing macrophage activation during infection are not fully understood. It was recently shown that the AP-1 family transcription factor JUNB positively regulates macrophage activation in response to Toll-like receptor agonists that promote classical or M1 polarization, as well as to the cytokine interleukin-4 (IL-4), which elicits an alternatively activated or M2 phenotype. However, a role for JUNB in macrophage activation has never been demonstrated in vivo. Here, to dissect the role of JUNB in macrophage activation in a physiological setting, mice lacking JUNB specifically in myeloid cells were tested in two infection models: experimental cerebral malaria, which elicits a pathological type 1 immune response, and helminth infection, in which type 2 responses are protective. Myeloid-restricted deletion of Junb reduced type 1 immune activation, which was associated with reduced cerebral pathology and improved survival during infection with Plasmodium berghei. Myeloid JUNB deficiency also compromised type 2 activation during infection with the hookworm Nippostrongylus brasiliensis, leading to diminished cytokine production and eosinophil recruitment and increased parasite burden. These results demonstrate that JUNB in myeloid cells shapes host responses and outcomes during type 1 and type 2 infections.

Proximal humeral fracture fixation: multicenter study with carbon fiber peek plate.

BACKGROUND: Locking plate fixation is a reliable treatment for many displaced proximal humeral fractures. Carbon fiber-reinforced-poly-ether-ether-ketone (CFR-PEEK) plates have recently been introduced as an alternative to traditional metallic plates. METHODS: In a multicenter study involving the Orthopedic Services of 6 Italian hospitals, 182 patients with a proximal humeral fracture were treated with a Diphos H (Lima Corporate, San Daniele del Friuli, Italy) CFR-PEEK plate, 160 of whom were followed clinically and radiographically for 2 years or more. Fractures were classified by Neer's system. The functional results were assessed by Constant and DASH scores. RESULTS: The average time to radiographic healing was 5.6 months in 158 of 160 cases. Mean Constant score was 76, and mean DASH score was 28 at 2 years. There were two nonunions (one septic and one aseptic) and 13 cases of partial (9) or massive (4) humeral head necrosis. In three of the 78 patients treated with the first-generation plates, hardware breakage happened during the operation and the plate was replaced. There was no failure among the cases treated with the thicker second-generation plate. In eight cases, there was a perforation of the humeral head by the cephalic screws. CONCLUSIONS: CFR-PEEK plates proved as reliable as metallic plates in the treatment of proximal humeral fractures. The advantages of these new devices include a better visualization of fracture reduction during intraoperative fluoroscopic assessment and easy hardware removal due to the absence of screw-plate cold fusion.

Oculoleptomeningeal Amyloidosis associated with transthyretin Leu12Pro in an African patient.

Oculoleptomeningeal amyloidosis is a rare manifestation of hereditary transthyretin (TTR) amyloidosis. Here, we present the first case of leptomeningeal amyloidosis associated with the TTR variant Leu12Pro mutation in an African patient. A 43-year-old right-handed Nigerian man was referred to our centre with rapidly progressive neurological decline. He presented initially with weight loss, confusion, fatigue, and urinary and erectile dysfunction. He then suffered recurrent episodes of slurred speech with right-sided weakness. He went on to develop hearing difficulties and painless paraesthesia. Neurological examination revealed horizontal gaze-evoked nystagmus, brisk jaw jerk, increased tone, brisk reflexes throughout and bilateral heel-shin ataxia. Magnetic resonance imaging showed extensive leptomeningeal enhancement. Cerebrospinal fluid analysis showed a raised protein of 6.4 g/dl. Nerve conduction studies showed an axonal neuropathy. Echocardiography was characteristic of cardiac amyloid. TTR gene sequencing showed that he was heterozygous for the leucine 12 proline mutation. Meningeal and brain biopsy confirmed widespread amyloid angiopathy. TTR amyloidosis is a rare cause of leptomeningeal enhancement, but should be considered if there is evidence of peripheral or autonomic neuropathy with cardiac or ocular involvement. The relationship between different TTR mutations and clinical phenotype, disease course, and response to treatment remains unclear.

Reactivity of hypotaurine and cysteine sulfinic acid toward carbonate radical anion and nitrogen dioxide as explored by the peroxidase activity of Cu,Zn superoxide dismutase and by pulse radiolysis.

Hypotaurine and cysteine sulfinic acid are known to be readily oxidized to the respective sulfonates, taurine and cysteic acid, by several oxidative agents that may be present in biological systems. In this work, the relevance of both the carbonate anion and nitrogen dioxide radicals in the oxidation of hypotaurine and cysteine sulfinic acid has been explored by the peroxidase activity of Cu,Zn superoxide dismutase (SOD) and by pulse radiolysis. The extent of sulfinate oxidation induced by the system SOD/H2O2 in the presence of bicarbonate (CO3(•-) generation), or nitrite ((•)NO2 generation) has been evaluated. Hypotaurine is efficiently oxidized by the carbonate radical anion generated by the peroxidase activity of Cu,Zn SOD. Pulse radiolysis studies have shown that the carbonate radical anion reacts with hypotaurine more rapidly (k = 1.1 × 10(9) M(-1)s(-1)) than nitrogen dioxide (k = 1.6 × 10(7) M(-1)s(-1)). Regarding cysteine sulfinic acid, it is less reactive with the carbonate radical anion (k = 5.5 × 10(7) M(-1)s(-1)) than hypotaurine. It has also been observed that the one-electron transfer oxidation of both sulfinates by the radicals is accompanied by the generation of transient sulfonyl radicals (RSO2(•)). Considering that the carbonate radical anion could be formed in vivo at high level from bicarbonate, this radical can be included in the oxidants capable of performing the last metabolic step of taurine biosynthesis. Moreover, the protective effect exerted by hypotaurine and cysteine sulfinate on the carbonate radical anion-mediated tyrosine dimerization indicates that both sulfinates have scavenging activity towards the carbonate radical anion. However, the formation of transient reactive intermediates during sulfinate oxidation by carbonate anion and nitrogen dioxide radical may at the same time promote oxidative reactions.