Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review.

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications.

Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study.

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate.

Shear wave elastography of the brachioradialis spastic muscle and its correlations with biceps brachialis and clinical scales.

BACKGROUND: Shear wave elastography technique estimates biological tissue shear elastic modulus (µ[kPa]), which can be used as an objective, muscle-specific indicator of stiffness increase caused by spasticity. We measured both the brachioradialis and biceps brachialis µ in hemiparetic post-stroke patients (n = 11). The spastic arm was compared with the supposedly non-affected contralateral limb and correlated with Fugl-Meyer Assessment and Modified Ashworth Scales. METHODS: Shear elastic modulus was estimated using an Aixplorer V.9 ultrasound device with the elbow at full extension. Average shear elastic modulus t-test, effect sizes, correlation matrix, spider plots and factor analysis were used to check for differences between spastic and nonspastic sides and explore relationships among the variables. FINDINGS: Spastic brachioradialis µ (22.54 ± 11.59 kPa) and biceps brachialis (26.86 ± 12.07 kPa) were significantly greater than the non-spastic counterparts (13.13 ± 2.81 kPa, p = 0.031, ηp2 = 0.3846 for brachioradialis and 15.25 ± 5.00 kPa, p = 0.007, ηp2 = 0.5345 for biceps brachialis). Significant correlations were observed between the spastic brachioradialis and biceps µ and Modified Ashworth Scales, but no correlation with Fugl-Meyer Assessment. INTERPRETATION: Elastography can provide muscle-specific shear elastic modulus estimations of spastic brachioradialis and biceps brachialis, which are distinct from the nonspastic side. In some patients, there was no clear correspondence of the Fugl-Meyer Assessment functional scale with Modified Ashworth Scales and µ, suggesting that spasticity is not the only determinant of arm function. Additionally, shear wave elastography of brachioradialis and biceps brachialis muscles may guide the spasticity treatment, for instance, selecting the preferable candidate for botulinum toxin therapy.

Undernutrition and short duration of breastfeeding association with child development: a population-based study

Abstract Objective: To explore the relationship of undernutrition and the short duration of breastfeeding with child development of children 0-66 months of age residing in Ceará, Brazil. Methods: The authors of the present study utilized population-based data from children enrolled in the Study on Maternal and Child Health in Ceará, Brazi (PESMIC). Children's development was assessed with the Ages and Stages Questionnaire third version, validated in Brazil. Undernutrition was accessed through anthropometric measures obtained by trained staff. Breastfeeding information was obtained through the mothers' report and confirmed in the child's governmental booklet. The authors used logistic regressions adjusted for sample clusters used in PESMIC design in a theoretical model for known determinants of child development following the World Health Organization nurturing framework. Results: A total of 3,566 children were enrolled in the sixth PESMIC study and had their development assessed. The authors found that 8.2%, 3.0%, 2.1%, and 3.6% of children were stunted, underweight, or wasted, at the time of the interview, respectively. All studied factors were associated with a higher prevalence of child development impairment in at least one of the assessed domains. Underweight was the factor with the strongest effect, with an adjusted odds ratio (AOR) of 4,14 (2,26-7,58), p < 0.001. Breastfeeding for up to two months compared to more than six months (AOR2,08 (1,38-3,12)) was also associated. Conclusions: The authors found that undernutrition and short duration of breastfeeding are associated with development outcomes among Brazilian children. As a result, integrated nutritional programs may improve child development outcomes.

Fatores associados ao desenvolvimento infantil em crianças brasileiras: linha de base da avaliação do impacto do Programa Criança Feliz / Factors associated infant development in Brazilian children: baseline of the impact assessment of the Happy Child Program / Factores asociados al desarrollo infantil en niños brasileños: base de referencia para la evaluación del impacto del Programa Niño Feliz

Resumo: O objetivo deste artigo foi avaliar os fatores socioeconômicos, familiares e individuais associados ao desenvolvimento infantil no primeiro ano de vida, entre famílias em vulnerabilidade social. Trata-se de uma análise transversal, com dados da linha de base de um ensaio randomizado. O estudo incluiu 3.242 crianças < 12 meses de idade, residentes em 30 municípios de cinco regiões do Brasil. A escolha de estados e municípios foi intencional, tendo como base a implementação do Programa Criança Feliz. A amostra foi selecionada a partir de crianças elegíveis para o Programa Criança Feliz, cujo objetivo é promover a estimulação e o desenvolvimento infantil. O Ages and Stages Questionnaire (ASQ) foi utilizado para avaliação do desenvolvimento infantil. Um modelo de análise multinível em três níveis (estado, município e indivíduos), usando teste de Wald para heterogeneidade e tendência linear, estimou a média do ASQ-3 e intervalo de 95% de confiança (IC95%). Análises foram ajustadas para potenciais confundidores. Foram analisadas informações de 3.061 (94,4%) crianças com dados disponíveis para ASQ-3. Escores de desenvolvimento infantil (total e em todos os domínios) foram cerca de 12% menores em crianças nascidas pré-termo e com restrição do crescimento intrauterino (pequenas para idade gestacional). Observou-se menores escores em filhos de mães com baixa escolaridade, com sintomas de depressão, com duas ou mais crianças menores de sete anos residindo no domicílio e que não relataram autopercepção de apoio/ajuda durante a gestação. Conclui-se que características potencialmente modificáveis (escolaridade, depressão materna e prematuridade/restrição do crescimento intrauterino) apresentaram maior impacto na redução do escore de desenvolvimento em todos os domínios avaliados.

Abstract: The study aimed to assess socioeconomic, family, and individual factors associated with infant development (i.e., in the first year of life) among families with social vulnerability. This was a cross-sectional analysis of baseline data from a randomized trial. The study included 3,242 children < 12 months of age living in 30 municipalities from five regions of Brazil. The choice of states and municipalities was intentional, based on the implementation of the Brazilian Happy Child Program. The sample was selected among eligible children for the Brazilian Happy Child Program, and the objective was the promotion of infant development. The Ages and Stages Questionnaire (ASQ) was used to assess infant development. A three-level analytical model (state, municipality, and individuals), using the Wald test for heterogeneity and linear trend, estimated the mean ASQ-3 and 95% confidence interval (95%CI). The analyses were adjusted for potential confounders. Information was analyzed for 3,061 (94.4%) children with available data for ASQ-3. Infant development scores (total and in all the domains) were some 12% lower in preterm children and those with intrauterine growth restriction (small for gestational age). Lower scores were seen in children of mothers with low schooling, depressive symptoms, two or more children under seven years of age living in the household, and who did not report self-perceived support or help during the pregnancy. In conclusion, potentially modifiable characteristics (schooling, maternal depression, and prematurity/intrauterine growth restriction) showed greater impact on reducing the infant development score in all the target domains.

Resumen: El objetivo fue evaluar los factores socioeconómicos, familiares e individuales, asociados al desarrollo infantil en el primer año de vida, entre familias con vulnerabilidad social. Se trata de un análisis transversal, con datos de la base de referencia de un ensayo aleatorio. El estudio incluyó a 3.242 niños < 12 meses de edad, residentes en 30 municipios de cinco regiones de Brasil. La elección de estados y municipios fue intencional, considerando como base la implementación del Programa Niño Feliz. La muestra se seleccionó a partir de niños elegibles para el Programa Niño Feliz, cuyo objetivo es promover la estimulación y el desarrollo infantil. Se utilizó el Ages and Stages Questionnaire (ASQ) para la evaluación del desarrollo infantil. Un modelo de análisis multinivel en tres niveles (estado, municipio e individuos), usando el test de Wald para la heterogeneidad y tendencia lineal, estimó la media del ASQ-3 y el intervalo de 95% de confianza (IC95%). Los análisis se ajustaron para potenciales factores de confusión. Se analizó información de 3.061 (94,4%) niños con datos disponibles para ASQ-3. Las puntuaciones de desarrollo infantil (total y en todos los dominios) fueron cerca de un 12% menores en niños nacidos pretérmino y con restricción del crecimiento intrauterino (pequeños para la edad gestacional). Se observaron menores puntuaciones en hijos de madres con baja escolaridad, con síntomas de depresión, con dos o más niños menores de siete años residiendo en el domicilio y que no informaron autopercepción de apoyo/ayuda durante la gestación. Se concluye que las características potencialmente modificables (escolaridad, depresión materna y prematuridad/restricción del crecimiento intrauterino) presentaron un mayor impacto en la reducción de la puntuación de desarrollo en todos los dominios evaluados.

Maternal and neonatal factors associated with child development in Ceará, Brazil: a population-based study.

BACKGROUND: The first 1000 days of life are a critical period when the foundations of child development and growth are established. Few studies in Latin America have examined the relationship of birth outcomes and neonatal care factors with development outcomes in young children. We aimed to assess the association between pregnancy and neonatal factors with children's developmental scores in a cross-sectional, population-based study of children in Ceará, Brazil. METHODS: Population-based, cross-sectional study of children aged 0-66 months (0-5.5 years) living in Ceará, Brazil. We examined the relationship of pregnancy (iron and folic acid supplementation, smoking and alcohol consumption) and neonatal (low birth weight (LBW) gestational age, neonatal care interventions, and breastfeeding in the first hour) factors with child development. Children's development was assessed with the Ages and Stages Questionnaire (ASQ-BR). We used multivariate generalized linear models that accounted for clustering sampling to evaluate the relationship of pregnancy and neonatal factors with development domain scores. FINDINGS: A total of 3566 children were enrolled. Among pregnancy factors, children whose mothers did not receive folic acid supplementation during pregnancy had lower fine motor and problem-solving scores (p-values< 0.05). As for neonatal factors, LBW was associated with 0.14 standard deviations (SD) lower (CI 95% -0.26, - 0.02) communication, 0.24 SD lower (95% CI: - 0.44, - 0.04) fine motor and 0.31 SD lower (CI 95% -0.45, - 0.16) problem-solving domain scores as compared to non-LBW children (p values < 0.05). In terms of care, newborns that required resuscitation, antibiotics for infection, or extended in-patient stay after birth had lower development scores in selected domains. Further, not initiating breastfeeding within the first hour after birth was associated with lower gross motor and person-social development scores (p-values < 0.05). CONCLUSION: Pregnancy and neonatal care factors were associated with later child development outcomes. Infants at increased risk of suboptimal development, like LBW or newborns requiring extended in-patient care, may represent groups to target for supplemental intervention. Further, early integrated interventions to prevent adverse pregnancy and newborn outcomes may improve child development outcomes.

Post-partum depression: a cross-sectional study of women enrolled in a conditional cash transfer program in 30 Brazilian cities.

OBJECTIVE: Investigate factors associated with symptoms of postpartum depression in mothers from families in social vulnerability. METHODS: Information was used from the baseline of a randomized trial to assess a child development program that enrolled 3,242 children < 12 months of age from beneficiary families of the Bolsa Família Program residing in 30 municipalities (counties) in six states of Brazil. The Edinburgh Postnatal Depression Scale (EPDS) was applied to the mothers, and depression was defined as score ≥10. Information on the mother (schooling, age, parity, marital status, skin color, smoking, number of prenatal appointments, and planning of the pregnancy), family (paternal schooling, household crowding, support from the child's father and the family during the pregnancy, and number of children under 7 years living in the household), and infant (sex, gestational age, birthweight, Apgar score, and child's age at the time of the interview) was collected. Prevalence rates for depressive symptoms were calculated with crude and adjusted odds ratios (OR) and 95% confidence intervals (95%CI), using hierarchical logistic regression, in a multilevel model. RESULTS: The analysis included 3,174 mothers with information on EPDS. The interviews were conducted on average 7.9 months (standard deviation= 2.9) after childbirth. Overall prevalence of depressive symptoms was 26.5% (25.0-28.1%). In the adjusted analysis, higher parity was associated with higher odds of postpartum depression (p <0.001). Women with ≥3 previous deliveries showed an odds 84% higher of presenting depressive symptoms (OR= 1.84; 1.43-2.35) than primiparae. Higher maternal and paternal schooling, presence of husband or partner, and having received support from the child's father and the family during the pregnancy were protective factors against postpartum depression. CONCLUSION: The study showed high prevalence of postpartum depressive symptoms. Promotion of parental education, alongside with the promotion of support to the woman during pregnancy by the child's father and by the family, as well as family planning leading to birth spacing are measures that may help to prevent postpartum depressive symptoms.

Radio-induced esophageal motility disorders: An unrecognized diagnosis.

PURPOSE: Esophageal motility disorders (EMD) after cervical or thoracic radiation therapy (RT) may represent a late impairment and appear under-diagnosed. This study aimed to assess the prevalence of EMD, diagnosed by high-resolution esophageal manometry (HREM) after cervical or thoracic RT. In this retrospective, single-centre study, all patients whom received cervical or thoracic RT and underwent HREM were eligible. MATERIAL AND METHODS: Oncologic data were collected: site of neoplasia, type of cancer, oncologic management (surgery and chemotherapy). EMD were classified according to the new Chicago Classification. RESULTS: Twenty patients (14 females), of mean age 62.33±11.14 years were included. Breast cancer was the most represented indication for RT (40%). Other cancers were lung tumor, head and neck tumors and Hogdkin's lymphoma. Dysphagia was the most frequent symptom justifying HREM (70%). Patients received a mean of 51±19.27 Gy, 70% of them (14/20) had radiation therapy concomitantly with chemotherapy. The delay between last radiation therapy session and HERM was 10.68±12.42 years. Twelve (60%) patients had an abnormal pattern at on HERM. Among them, 3 patients (15%) presented with a major motility disorder. The most frequent motility disorder was ineffective esophageal motility in 8 (40%) patients, 1 (5%) patient presented with type II achalasia. CONCLUSION: EMD should be suspected in patients with a history of cervical or thoracic RT in case of upper GI symptoms with normal endoscopy. In these particular patients, a manometric diagnosis that can explain their symptoms is of particular importance to limit anxiety linked to unexplained troubles.

Development of a hyperimmune equine serum therapy for COVID-19 in Argentina

The disease named COVID-19, caused by the SARS-CoV-2 coronavirus, is currently generating a global pandemic. Vaccine development is no doubt the best long-term immunological approach, but in the current epidemiologic and health emergency there is a need for rapid and effective solutions. Convalescent plasma is the only antibody-based therapy available for COVID-19 patients to date. Equine polyclonal antibodies (EpAbs) put forward a sound alternative. The new generation of processed and purified EpAbs containing highly purified F(ab’)2 fragments demonstrated to be safe and well tolerated. EpAbs are easy to manufacture allowing a fast development and scaling up for a treatment. Based on these ideas, we present a new therapeutic product obtained after immunization of horses with the receptor-binding domain of the viral Spike glycoprotein. Our product shows around 50 times more potency in in vitro seroneutralization assays than the average of convalescent plasma. This result may allow us to test the safety and efficacy of this product in a phase 2/3 clinical trial to be conducted in July 2020 in the metropolitan area of Buenos Aires, Argentina.

La enfermedad denominada COVID-19 es causada por el coronavirus SARS-CoV-2 y es actualmente considerada una pandemia a nivel global. El desarrollo de vacunas es sin duda la mejor estrategia a largo plazo, pero debido a la emergencia sanitaria, existe una necesidad urgente de encontrar soluciones rápidas y efectivas para el tratamiento de la enfermedad. Hasta la fecha, el uso de plasma de convalecientes es la única inmunoterapia disponible para pacientes hospitalizados con COVID-19. El uso de anticuerpos policlonales equinos (EpAbs) es otra alternativa terapéutica interesante. La nueva generación de EpAbs incluyen el procesamiento y purificación de los mismos y la obtención de fragmentos F(ab’)2 con alta pureza y un excelente perfil de seguridad en humanos. Los EpAbs son fáciles de producir, lo cual permite el desarrollo rápido y la elaboración a gran escala de un producto terapéutico. En este trabajo mostramos el desarrollo de un suero terapéutico obtenido luego de la inmunización de caballos utilizando el receptor-binding domain de la glicoproteína Spike del virus. Nuestro producto mostró ser alrededor de 50 veces más potente en ensayos de seroneutralización in vitro que el promedio de los plasmas de convalecientes. Estos resultados nos permitirían testear la seguridad y eficacia de nuestro producto en ensayos clínicos de fase 2/3 a realizarse a partir de julio de 2020 en la zona metropolitana de Buenos Aires, Argentina.

Inmunoensayo multiplex para el diagnóstico simultáneo de diabetes mellitus autoinmune y enfermedad celíaca / Multiplex immunoassay for simultaneous diagnostic of autoimmune diabetes mellitus and celiac disease

Introducción: la diabetes mellitus autoinmune (DMA) y la enfermedad celíaca (EC) son enfermedades crónicas, poligénicas y multifactoriales vinculadas con la disfunción del sistema inmune. Dado que es frecuente que un mismo paciente presente ambas patologías, la detección simultánea de los marcadores de autoinmunidad de DMA y EC sería una estrategia racional para mejorar el diagnóstico. Objetivos: desarrollar un inmunoensayo basado en citometría de flujo (FloCMIA multiplex) para la detección simultánea y discriminativa de marcadores de DMA (GADA e IA-2A) y de EC (tTgA). Materiales y métodos: las muestras analizadas consistieron en sueros provenientes de 35 individuos controles normales y 21 pacientes con diabetes mellitus tipo 1 (DM1). Se empleó un modelo de "doble paratope" incubando los sueros con una mezcla de microesferas de diferente fluorescencia interna, cada una adsorbida con un autoantígeno: TrxGAD, TrxIA-2 o H6-tTg, y una mezcla de dichos autoantígenos biotinilados. Los inmunocomplejos se detectaron con estreptavidina-ficoeritrina y se adquirió en un citómetro de flujo. Resultados: FloCMIA multiplex detectó GADA en el 76,2% de los pacientes e IA-2A en el 52,38% (sensibilidad analítica: 88,24 y 56,25% respectivamente,y especificidad: 85,71%) y tTgA en el 42,86% (sensibilidad analítica: 50,0%, y especificidad: 80,0%). Estos resultados se contrastaron con el ensayo de unión de radioligando para GADA e IA-2A y se detectaron 80,95 y 76,19% de los sueros respectivamente (especificidad: 100%), y con un ELISA para tTgA se detectó un 38,1% (especificidad: 97,1%). Conclusiones: FloCMIA multiplex permitió detectar y discriminar GADA, IA-2A y/o tTgA, -en un único acto analítico- en sueros de pacientes con DMA y/o EC. El novedoso inmunoensayo desarrollado simplifica el screening de la población a gran escala

Introduction: autoimmune diabetes mellitus (ADM) and celiac disease (CD) are chronic, polygenic and multifactorial diseases associated with immune system dysfunction. As it is frequent that a patient presents both pathologies, the simultaneous detection of autoimmunity markers of ADM and CD would be a rational strategy to improve the diagnosis. Objectives: to develop an immunoassay based on Flow Cytometry (FloCMIA multiplex) for the simultaneous and discriminative detection of markers for ADM (GADA and IA-2A) and CD (tTgA). Materials and methods: thirty five serum samples of control individuals and 21 type 1 diabetes mellitus (T1DM) patients were assayed. A "double bridge" model was used for the assay, incubating the serum samples with a mixture of microspheres containing different amount of internal fluorescence, each one adsorbed with an autoantigen: TrxGAD, TrxIA-2 or H6-tTg, and a mixture of the same biotinilated autoantigens. The immunocomplexes were detected using streptavidinphycoerytrin and then acquired in a flow cytometer. Results: FloCMIA multiplex detected GADA in 76.2% of the patients; IA-2A in 52.38% (analytical sensitivity: 88.24% and 56.25% respectively, and specificity: 85.71%) and tTgA in 42.86% (analytical sensitivity: 50.0%, and specificity: 80.0%). These results were compared with the radioligand binding assay for GADA and IA-2A, detecting 80.95% and 76.19% of the serum samples respectively (100% specificity), and with an ELISA for tTgA detecting 38.1% (97.1% specificity). Conclusions: FloCMIA multiplex allowed detecting and discriminating GADA, IA-2A and/or tTgA, -in a single assay- in serum samples of ADM and/or CD. The novel developed immunoassay simplifies the screening of the large scale population

Instant messenger smartphone application for endosonographer/cytopathologist real-time interaction at a distance in EUS-FNA for solid pancreatic lesions.

Background and study aims Telecytopathology (TCP) may allow proper and timely evaluation of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens. The aim of this study was to evaluate the feasibility of TC through a multiplatform instant messenger smartphone application to evaluate specimens of EUS-FNA of pancreatic solid lesions. Patients and methods Twenty-three patients (14 male/9 female; median age: 56 yr.; age range: 33 - 86) with a solid pancreatic lesion were included. Exclusion criteria were as follows: age < 18 yr and predominantly cystic lesions. During each EUS-FNA, after each pass, the aspirated material was spread over a glass slide and was stained by the endoscopist. The glass slide was then reviewed on a microscope with a smartphone fitted in, and the most representative fields were captured and sent to the cytopathologist using WhatsApp Messenger. Results In initial evaluation using TCP rapid on-site evaluation (ROSE), adequate cellularity of the glass slide was detected in 16 of 23 patients (69.6 %). An initial diagnosis of malignancy (positive or suspicious) was possible in 14 of 23 patients (60.8 %). Conclusion The current study demonstrated the feasibility of a low-cost, Internet-based, telecytopathology system using WhatsApp Messenger to provide ROSE of EUS-FNA slides in patients with solid pancreatic lesions.

[Identification of neurodegenerative diseases in administrative databases in France: A systematic review of the literature]. / Identification des maladies neurodégénératives dans les bases de données médicoadministratives en France : revue systématique de la littérature.

BACKGROUND: Given the health, social and economic burden of neurodegenerative diseases (ND), the development of epidemiologic studies is required. Administrative databases, such as the French national health insurance database (SNIIRAM) could represent an opportunity for researchers. ND could be presumed from drug reimbursement data, hospital stays or registration of a chronic condition. The aim of this study was to describe, in French administrative databases, algorithms used to identify Alzheimer's disease and associated disorders (ADAD), Parkinson's disease and associated disorders (PDAD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). METHODS: A systematic literature review was performed in Medline and gray literature through December 31th, 2015. French studies focusing on ADAD, PDAD, MS or ALS as a primary health outcome, conducted among one of the SNIIRAM data sources (outpatient reimbursements, chronic condition registration, hospital discharge) were included. RESULTS: Thirty-four studies were included (ADAD, n=18, PDAD, n=9, MS, n=4, ALS, n=3), leading to 36 algorithms. For each studied ND, there was an important variability in the algorithms, concerning (i) the type of criteria used (administrative database versus multi-source systems); (ii) the number of criteria used; (iii) the definition used for each criteria. The extent and level of drug exposure highly varied. Identification through hospitalizations showed variations in terms of type of stay (short stay, long-term stay, psychiatric ward…), extent of diagnosis codes used, diagnosis type (principal, related, associated diagnosis) and period used. A validation study was conducted for 2 out of 36 algorithms (PDAD), and criteria completeness was estimated for 3 algorithms (MS, ALS). CONCLUSION: Despite the increase in ND identification among French administrative databases, few algorithms have been validated. Validation studies should be encouraged.

General antibiotic exposure is associated with increased risk of developing chronic rhinosinusitis.

OBJECTIVE: Antibiotic use and chronic rhinosinusitis (CRS) have been independently associated with microbiome diversity depletion and opportunistic infections. This study was undertaken to investigate whether antibiotic use may be an unrecognized risk factor for developing CRS. STUDY DESIGN: Case-control study of 1,162 patients referred to a tertiary sinus center for a range of sinonasal disorders. METHODS: Patients diagnosed with CRS according to established consensus criteria (n = 410) were assigned to the case group (273 without nasal polyps [CRSsNP], 137 with nasal polyps [CRSwNP]). Patients with all other diagnoses (n = 752) were assigned to the control group. Chronic rhinosinusitis disease severity was determined using a validated quality of life (QOL) instrument. The class, diagnosis, and timing of previous nonsinusitis-related antibiotic exposures were recorded. Results were validated using a randomized administrative data review of 452 (38.9%) of patient charts. The odds ratio of developing CRS following antibiotic exposure were calculated, as well as the impact of antibiotic use on the subsequent QOL. RESULTS: Antibiotic use significantly increased the odds of developing CRSsNP (odds ratio: 2.21, 95% confidence interval, 1.66-2.93, P < 0.0001) as compared to nonusers. Antibiotic exposure was significantly associated with worse CRS QOL scores (P = 0.0009) over at least the subsequent 2 years. These findings were confirmed by the administrative data review. CONCLUSION: Use of antibiotics more than doubles the odds of developing CRSsNP and is associated with a worse QOL for at least 2 years following exposure. These findings expose an unrecognized and concerning consequence of general antibiotic use. LEVEL OF EVIDENCE: 3b. Laryngoscope, 2016 127:296-302, 2017.

Effects of bark flour of Passiflora edulis on food intake, body weight and behavioral response of rats

ABSTRACT Effects of treatment with the bark flour of Passiflora edulis Sims, Passifloraceae, were evaluated. Adult male Wistar rats were treated for 30 days (130 mg/kg, p.o.) with the albedo flour, flavedo and full bark of P. edulis, corresponding to albedo associated with flavedo. Behavioral response observed after treatment with bark flour P. edulis showed sedative effects by the reduction of exploratory activity and increased duration of immobility in the open field test for the group of animals that received the albedo flour associated with the flavedo. Sedative effects were observed in the absence of motor incoordination or muscle relaxation. Food intake of experimental animals was not changed, but the weight gain was decreased both in animals that received only albedo flour, and in those who received the full bark flour. The full bark flour of Passiflora showed sedative effects, without anxiolytic effect detectable and muscle relaxation or motor incoordination, and reduces body weight gain.

Impact of endoscopic dacryocystorhinostomy on sinonasal quality of life.

BACKGROUND: Dacryocystorhinostomy (DCR) is the criterion standard of surgical treatment for complete nasolacrimal obstruction and dacryocystitis. There has been an expansion in the indication of the endonasal DCR (eDCR), but the impact of surgical manipulating an otherwise healthy nasal mucosa on postoperative sinonasal quality of life remains unknown. The purpose of this study was to determine whether patients who underwent eDCR experienced any decrement in sinonasal quality of life. METHODS: A retrospective chart review of 44 patients who underwent eDCR between June 2012 and May 2015. The primary outcome was the total and nasal-specific domain 1 scores of the disease specific validated Sino-Nasal Outcomes Test 22. Preoperative scores were compared with the postoperative scores on days 0-30, 30-90, and 90-180 visits. A subgroup analysis of patients without nasal symptoms who underwent concomitant nasal surgical procedures was also performed. RESULTS: A statistically significant increase was observed between the preoperative score and the first postoperative score (days 0-30) in both total (7.5 [0-44] to 24 [0-51], median [interquartile range]) and domain 1 (2.5 [0-11] to 9 [0-18]) scores (p = 0.0066 and p = 0.0001, respectively). In contrast, there was no statistically significant difference between the pre- and postoperative scores on days 30-90 or 90-180. Similar results were observed in the subgroup analysis. CONCLUSION: Analysis of our findings indicated that, in general, eDCR was well tolerated by patients and nasal symptom scores returned to baseline values within 30-90 days of surgery. The concomitant performance of septoplasty in the setting of asymptomatic septal deviation did not confer any long-term improvement in symptoms of nasal obstruction.

The impact of comorbidity on health-related quality of life in elderly patients with chronic myeloid leukemia.

The primary objective of this study was to investigate whether the presence of comorbidities was associated with a lower health-related quality of life (HRQOL) in elderly patients with chronic myeloid leukemia (CML). A sample of 174 CML patients aged 60 years or above was analyzed. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). A number of pre-selected sociodemographic and disease-related factors were considered as potential confounding factors for the association between comorbidity and HRQOL. Mean age of the 174 patients analyzed was 70 years (range 60-87 years) and 55 % were male. Overall, 111 patients (64 %) reported at least one comorbidity. Analysis stratified by age group category showed a greater proportion of patients with comorbidities in the older sub-group population (≥70 years) compared to younger patients (60 to 69 years). Differences in HRQOL outcomes between patients with no comorbidity at all and those with two or more comorbid conditions were at least twice the magnitude of a clinically meaningful difference in all the physical and mental health scales of the SF-36. In multivariate analysis, after adjusting for key confounding factors, the following scales were significantly lower in those with comorbidity: general health (p < 0.001), bodily pain (p < 0.001), physical functioning (p = 0.002), and vitality (p = 0.002). Assessing comorbidity in elderly patients with CML is important to facilitate identification of those most in need of HRQOL improvements.

Lobular capillary hemangioma formation: An unusual complication of submucous resection with power instrumentation of the inferior turbinate.

Submucous resection with powered instrumentation (SRPI) is an effective surgical method to achieve inferior turbinate (IT) reduction with minimal morbidity. We describe a series of two cases of capillary hemangioma (pyogenic granuloma) that developed in the posterior third of the IT as a late complication after SRPI.

Seizure frequency reduction after posteromedial hypothalamus deep brain stimulation in drug-resistant epilepsy associated with intractable aggressive behavior.

OBJECTIVES: The aim of this study was to analyze the impact of deep brain stimulation (DBS) of the posteromedial hypothalamus (pHyp) on seizure frequency in patients with drug-resistant epilepsy (DRE) associated with intractable aggressive behavior (IAB). METHODS: Data were collected retrospectively from nine patients, who received bilateral stereotactic pHyp-DBS for the treatment of medically intractable aggressive behavior, focusing on five patients who also had DRE. All patients were treated at the Colombian Center and Foundation of Epilepsy and Neurological Diseases-FIRE (Chapter of the International Bureau for Epilepsy), in Cartagena de Indias, Colombia from 2010 to 2014. Each case was evaluated previously by the institutional ethical committee, assessing the impact of aggressive behavior on the patient's family and social life, the humanitarian aspects of preserving the safety and physical integrity of caregivers, and the need to prevent self-harm. Epilepsy improvement was measured by a monthly seizure reduction percentage, comparing preoperative state and outcome. Additional response to epilepsy was defined by reduction of the antiepileptic drugs (AEDs). Aggressive behavior response was measured using the Overt Aggression Scale (OAS). RESULTS: All the patients with DRE associated with IAB presented a significant decrease of the rate of epileptic seizures after up to 4 years follow-up, achieving a general 89.6% average seizure reduction from the state before the surgery. Aggressiveness was significantly controlled, with evident improvement in the OAS, enhancing the quality of life of patients and families. SIGNIFICANCE: In well-selected patients, DBS of the pHyp seems to be a safe and effective procedure for treatment of DRE associated with refractory aggressive behavior. Larger and prospective series are needed to define the pHyp as a target for DRE in different contexts.

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents.

Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson's disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group received continuous HFS of the ipsilateral STN starting a week prior to intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated group did not receive STN-HFS but only dopaminergic grafts. A control group was neither lesioned nor transplanted. Over the following 7 weeks, the animals were probed on a series of behavioral tasks to evaluate possible graft and/or stimulation-induced functional effects. Behavioral and histological data suggest that STN-HFS significantly increased graft cell survival, graft-host integration, and functional recovery. These findings might open an unexplored road toward combining neuromodulative and neuroregenerative strategies to treat severe neurologic conditions.

Frame-based stereotactic neurosurgery in children under the age of seven: Freiburg University's experience from 99 consecutive cases.

INTRODUCTION: Stereotactic frame-based procedures proved to be precise, safe and are of widespread use among adult patients. Regarding pediatric patients few data is available, therefore the use of the stereotactic frame remains controversial in this population. This motivated us to report our experience in stereotactic procedures in the youngest patients and review the literature concerning this subject. METHODS: All frame-based procedures performed in patients younger than seven years in the University of Freiburg during the last 10 years were retrospectively analyzed and discussed under the light of the current literature. RESULTS: The studied population was composed of 72 patients under the age of seven (mean 3.4±2.1 years-old), in whom 99 stereotactic procedures were performed. Brain tumor was present in 60 patients, hydrocephalus in five, cystic lesions in three, intracranial abscess in three and epilepsy in one patient. Stereotactic surgery was performed in 36 cases for brachytherapy, in 29 for biopsy, in 20 cases for cyst puncture, in eight for stereotactically guided endoscopic ventriculostomy, in five for catheter placement and in one case for depth electrode insertion. The overall complication rate was 5%. There were three cases of pin penetration through the skull, one case of frame dislocation after extensive cyst drainage and two skull fractures. Neurologic deficit related to frame fixation was observed in none of the cases. In disagreement with other authors, no case of pin related infection, air embolism, hematoma or CSF leak was observed. CONCLUSION: Frame-based stereotactic neurosurgery is a safe technique also in the youngest patients. Rather than the simple use of torque-limiting devices training and experience in the manual adjustment of the stereotactic frame in children have been proven to be crucial factors that contribute to reducing pin related complications.