Long-term results of intraoperative multicatheter breast implant (IOMBI) for accelerated partial breast irradiation (APBI) on early breast cancer patients.

BACKGROUND AND PURPOSE: Multicatheter breast brachytherapy is a standard technique for accelerated partial breast irradiation (APBI) in early breast cancer patients. Intraoperative multicatheter breast implant (IOMBI) followed by perioperative high-dose-rate brachytherapy (PHDRBT) offers a novel and advantageous approach. We present long-term oncological, toxicity, and cosmesis outcomes for a well-experienced single institution. MATERIALS AND METHODS: Eligible women aged ≥ 40 years with clinically and radiologically confirmed unifocal invasive or in situ ≤ 3 cm breast tumors underwent IOMBI during breast-conserving surgery. Patients meeting APBI criteria by definitive pathologic results received 3.4 Gy × 10fx with PHDRBT. Patients not suitable for APBI received PHDRBT-boost followed by WBRT. RESULTS: A total of 171 patients underwent IOMBI during BCS, 120 patients (70.1 %) were suitable for APBI and 51 (29.8 %) for anticipated PHDRBT-boost. The median age was 61 years (range: 40-78), the median tumor size was 1.1 cm (range: 0.2-3.5), with a histological diagnosis of invasive ductal carcinoma in 78.9 % and ductal in situ in 21.1 %. A median of 9 catheters (range: 4-14) were used. For APBI, the median CTV and V100 were 40.8 cc (range: 8.6-99) and 35.4 cc (range: 7.2-94). The median of healthy breast tissue irradiated represents 7.2 % (range: 2.3-28 %) and the median local treatment duration was 10 days (range: 7-16). With a median follow-up of 8.8 years (range: 0.3-16.25), the 8-year local, locoregional, and distant control rates were 99 %, 98.1 %, and 100 %. G1-G2 late-toxicity rate was 53.4 %. Long-term cosmetic evaluation was excellent-good in 90.8 %. CONCLUSION: IOMBI&PHDRBT program reports excellent long-term oncological outcomes, with a reduction from unnecessary irradiation exposure which translates into low long-term toxicity and good cosmesis outcomes, especially on well-selected APBI patients.

Automated Computer-Assisted Medical Decision-Making System Based on Morphological Shape and Skin Thickness Analysis for Asymmetry Detection in Mammographic Images.

Breast cancer is a significant health concern for women, emphasizing the need for early detection. This research focuses on developing a computer system for asymmetry detection in mammographic images, employing two critical approaches: Dynamic Time Warping (DTW) for shape analysis and the Growing Seed Region (GSR) method for breast skin segmentation. The methodology involves processing mammograms in DICOM format. In the morphological study, a centroid-based mask is computed using extracted images from DICOM files. Distances between the centroid and the breast perimeter are then calculated to assess similarity through Dynamic Time Warping analysis. For skin thickness asymmetry identification, a seed is initially set on skin pixels and expanded based on intensity and depth similarities. The DTW analysis achieves an accuracy of 83%, correctly identifying 23 possible asymmetry cases out of 20 ground truth cases. The GRS method is validated using Average Symmetric Surface Distance and Relative Volumetric metrics, yielding similarities of 90.47% and 66.66%, respectively, for asymmetry cases compared to 182 ground truth segmented images, successfully identifying 35 patients with potential skin asymmetry. Additionally, a Graphical User Interface is designed to facilitate the insertion of DICOM files and provide visual representations of asymmetrical findings for validation and accessibility by physicians.

Unmet healthcare needs among the population aged 50+ and their association with health outcomes during the COVID-19 pandemic.

The COVID-19 pandemic led to unprecedented levels of subjective unmet healthcare needs (SUN). This study investigates the association between SUN in 2020 and three health outcomes in 2021-mortality, cancer, and self-assessed health (SAH), among adults aged 50 years and older, using data from the regular administration of the Survey of Health, Ageing and Retirement in Europe and from the two special waves administered in 2020 and 2021 regarding COVID-19. Three types of SUN were surveyed: care foregone due to fear of contracting COVID-19, pre-scheduled care postponed, and inability to get medical appointments or treatments demanded. We resort on the relative risk and the logistic specification to investigate the association between SUN and health outcomes. To avoid simultaneity, 1-year lagged SUN variables are used. We found a negative association between SUN and mortality. This result differs from the (scarce) previous evidence, suggesting that health systems prioritised life-threatening conditions, in the pandemic context. In line with previous studies, we obtained a positive association between SUN and worse health, in the case of cancer, though it is statistically significant only for the global measure of SUN (any reason). The higher chances of reporting cancer among those exposed to SUN might mean delayed cancer diagnosis, confirming that healthcare foregone was truly needed for a timely diagnosis. The association between SUN and poor or fair SAH is positive but not statistically significant, for the period analysed.

Radiocirugía estereotáxica por gamma knife en un paciente con cavernoma cerebral y síndrome de Evans

El cavernoma cerebral es una malformación vascular de diagnóstico infrecuente. Se define como una malformación a nivel de la vasculatura microcerebral que, dependiendo a la ubicación y si existe la posibilidad de ruptura, conlleva a una emergencia que puede terminar en la muerte del paciente. En esta oportunidad se reporta el caso de un paciente con cavernoma cerebral asociado al síndrome de Evans. Se decide manejo quirúrgico de la lesión por aumento de intensidad de cefalea e intolerancia oral. Dada la coexistencia del Síndrome de Evans y la alta tasa de morbimortalidad es que se decide manejo quirúrgico mediante radiocirugía estereotáxica con gamma knife. El uso de dosis de margen bajo para tratamiento con gamma knife para uso en cavernomas cerebrales produce un manejo controlado para sintomatología de convulsiones y mejor expectativa de calidad de vida.

Cerebral cavernoma is an infrequently diagnosed vascular malformation. It is defined as a malformation at the level of the microcerebral vasculature that, depending on the location and if there is a possibility of rupture, leads to an emergency that can end in the death of the patient. On this occasion, we report a case of a patient with cerebral cavernoma associated with Evans syndrome. Surgical management of the lesion was decided due to increased intensity of headache and oral intolerance. Given the coexistence of Evans Syndrome and the high rate of morbidity and mortality, surgical management was decided by stereotaxic radiosurgery with a gamma knife. The use of low-margin doses for treatment with gamma knife for use in brain cavernomas produces controlled management for seizure symptoms and better quality of life expectancy.

Treatment-refractory heart failure as a manifestation of aortic arch atresia.

BACKGROUND: Distal segment atresia (isthmus) is an extremely rare anatomical variant of obstructive aortic arch anomalies. CASE REPORT: We present the case of a newborn who, at 48 hours of life, presented a clinical picture of heart failure. The initial echocardiogram showed a congenital interrupted aortic arch type A, patent ductus arteriosus, and ventricular septal defect. Prostaglandins were initially indicated. Subsequently, a second echocardiogram showed the absence of ductus arteriosus; the CT angiography study confirmed this finding and revealed blood flow to the descending aorta through small intercostal blood vessels. The possibility of atresia of the distal segment (isthmus) of the aortic arch was considered and confirmed at the time of surgery. CONCLUSIONS: Aortic atresia should be considered a diagnostic possibility in the presence of type A interrupted aortic arch since the hemodynamic behavior between them is similar. Surgical medical treatment should be individualized since this condition is frequently an emergency in the neonatal period. However, this is not always the case, as other cases have been reported in schoolchildren and adults.

INTRODUCCIÓN: La atresia de segmento distal (istmo) de arco aórtico es una variante anatómica extremadamente rara de las anomalías obstructivas del arco aórtico. CASO CLÍNICO: Se presenta el caso de un recién nacido que a las 48 horas de vida presentó un cuadro clínico de insuficiencia cardiaca. El estudio de ecocardiograma inicial mostró una anomalía congénita de interrupción de arco aórtico tipo A, conducto arterioso y comunicación interventricular. De inicio se indicaron prostaglandinas. Posteriormente, el segundo ecocardiograma mostró la ausencia del conducto arterioso; el estudio de angiotomografía confirmó este hallazgo y también reveló flujo sanguíneo hacia aorta descendente a través de pequeños vasos sanguíneos intercostales. Se consideró la posibilidad de atresia del segmento distal (istmo) de arco aórtico y se confirmó al momento del acto quirúrgico. CONCLUSIONES: La atresia aórtica debe ser considerada como posibilidad diagnóstica en presencia de interrupción de arco aórtico tipo A, ya que el comportamiento hemodinámico entre ellos es similar. El tratamiento médico quirúrgico debe individualizarse, ya que es frecuente que sea una urgencia en el periodo neonatal. Sin embargo, no sucede así siempre, ya que se han reportado casos en escolares y adultos.

Sedation versus General Anesthesia for Tracheal Intubation in Children with Difficult Airways: A Cohort Study from the Pediatric Difficult Intubation Registry.

BACKGROUND: Sedated and awake tracheal intubation approaches are considered safest in adults with difficult airways, but little is known about the outcomes of sedated intubations in children. The primary aim of this study was to compare the first-attempt success rate of tracheal intubation during sedated tracheal intubation versus tracheal intubation under general anesthesia. The hypothesis was that sedated intubation would be associated with a lower first-attempt success rate and more complications than general anesthesia. METHODS: This study used data from an international observational registry, the Pediatric Difficult Intubation Registry, which prospectively collects data about tracheal intubation in children with difficult airways. The use of sedation versus general anesthesia for tracheal intubation were compared. The primary outcome was the first-attempt success of tracheal intubation. Secondary outcomes included the number of intubation attempts and nonsevere and severe complications. Propensity score matching was used with a matching ratio up to 1:15 to reduce bias due to measured confounders. RESULTS: Between 2017 and 2020, 34 hospitals submitted 1,839 anticipated difficult airway cases that met inclusion criteria for the study. Of these, 75 patients received sedation, and 1,764 patients received general anesthesia. Propensity score matching resulted in 58 patients in the sedation group and 522 patients in the general anesthesia group. The rate of first-attempt success of tracheal intubation was 28 of 58 (48.3%) in the sedation group and 250 of 522 (47.9%) in the general anesthesia group (odds ratio, 1.06; 95% CI, 0.60 to 1.87; P = 0.846). The median number of intubations attempts was 2 (interquartile range, 1 to 3) in the sedation group and 2 (interquartile range, 1, 2) in the general anesthesia group. The general anesthesia group had 6 of 522 (1.1%) intubation failures versus 0 of 58 in the sedation group. However, 16 of 58 (27.6%) sedation cases had to be converted to general anesthesia for successful tracheal intubation. Complications were similar between the groups, and the rate of severe complications was low. CONCLUSIONS: Sedation and general anesthesia had a similar rate of first-attempt success of tracheal intubation in children with difficult airways; however, 27.6% of the sedation cases needed to be converted to general anesthesia to complete tracheal intubation. Complications overall were similar between the groups, and the rate of severe complications was low.

Treatment-refractory heart failure as a manifestation of aortic arch atresia / Falla cardiaca refractaria a tratamiento como manifestación de atresia de arco aórtico

Abstract Background: Distal segment atresia (isthmus) is an extremely rare anatomical variant of obstructive aortic arch anomalies. Case report: We present the case of a newborn who, at 48 hours of life, presented a clinical picture of heart failure. The initial echocardiogram showed a congenital interrupted aortic arch type A, patent ductus arteriosus, and ventricular septal defect. Prostaglandins were initially indicated. Subsequently, a second echocardiogram showed the absence of ductus arteriosus; the CT angiography study confirmed this finding and revealed blood flow to the descending aorta through small intercostal blood vessels. The possibility of atresia of the distal segment (isthmus) of the aortic arch was considered and confirmed at the time of surgery. Conclusions: Aortic atresia should be considered a diagnostic possibility in the presence of type A interrupted aortic arch since the hemodynamic behavior between them is similar. Surgical medical treatment should be individualized since this condition is frequently an emergency in the neonatal period. However, this is not always the case, as other cases have been reported in schoolchildren and adults.

Resumen Introducción: La atresia de segmento distal (istmo) de arco aórtico es una variante anatómica extremadamente rara de las anomalías obstructivas del arco aórtico. Caso clínico: Se presenta el caso de un recién nacido que a las 48 horas de vida presentó un cuadro clínico de insuficiencia cardiaca. El estudio de ecocardiograma inicial mostró una anomalía congénita de interrupción de arco aórtico tipo A, conducto arterioso y comunicación interventricular. De inicio se indicaron prostaglandinas. Posteriormente, el segundo ecocardiograma mostró la ausencia del conducto arterioso; el estudio de angiotomografía confirmó este hallazgo y también reveló flujo sanguíneo hacia aorta descendente a través de pequeños vasos sanguíneos intercostales. Se consideró la posibilidad de atresia del segmento distal (istmo) de arco aórtico y se confirmó al momento del acto quirúrgico. Conclusiones: La atresia aórtica debe ser considerada como posibilidad diagnóstica en presencia de interrupción de arco aórtico tipo A, ya que el comportamiento hemodinámico entre ellos es similar. El tratamiento médico quirúrgico debe individualizarse, ya que es frecuente que sea una urgencia en el periodo neonatal. Sin embargo, no sucede así siempre, ya que se han reportado casos en escolares y adultos.

Recognition of Cell Wall Mannosylated Components as a Conserved Feature for Fungal Entrance, Adaptation and Survival Within Trophozoites of Acanthamoeba castellanii and Murine Macrophages.

Acanthamoeba castellanii (Ac) is a species of free-living amoebae (FLAs) that has been widely applied as a model for the study of host-parasite interactions and characterization of environmental symbionts. The sharing of niches between Ac and potential pathogens, such as fungi, favors associations between these organisms. Through predatory behavior, Ac enhances fungal survival, dissemination, and virulence in their intracellular milieu, training these pathogens and granting subsequent success in events of infections to more evolved hosts. In recent studies, our group characterized the amoeboid mannose binding proteins (MBPs) as one of the main fungal recognition pathways. Similarly, mannose-binding lectins play a key role in activating antifungal responses by immune cells. Even in the face of similarities, the distinct impacts and degrees of affinity of fungal recognition for mannose receptors in amoeboid and animal hosts are poorly understood. In this work, we have identified high-affinity ligands for mannosylated fungal cell wall residues expressed on the surface of amoebas and macrophages and determined the relative importance of these pathways in the antifungal responses comparing both phagocytic models. Mannose-purified surface proteins (MPPs) from both phagocytes showed binding to isolated mannose/mannans and mannosylated fungal cell wall targets. Although macrophage MPPs had more intense binding when compared to the amoeba receptors, the inhibition of this pathway affects fungal internalization and survival in both phagocytes. Mass spectrometry identified several MPPs in both models, and in silico alignment showed highly conserved regions between spotted amoeboid receptors (MBP and MBP1) and immune receptors (Mrc1 and Mrc2) and potential molecular mimicry, pointing to a possible convergent evolution of pathogen recognition mechanisms.

Four-fraction ultra-accelerated minimal breast irradiation in early breast cancer: The initial feasibility results of an institutional experience.

PURPOSE: To evaluate the feasibility, early toxicity, and clinical outcomes of early-breast cancer patients in a single-arm, phase I/II study of an ultra-accelerated, four-fraction schedule of minimal breast irradiation (4f-AMBI) using a multicatheter, minimally-invasive, intraoperative tumor bed implant (MITBI) during breast-conserving surgery (BCS). METHODS AND MATERIALS: Eligible women aged >40 years with clinically and radiologically confirmed, unifocal invasive or in situ ≤3 cm tumors were considered as potential candidates for MITBI during BCS. After the pathology report, patients who met APBI criteria received ultra-accelerated four-fractions irradiation (6.2 Gy BID x 4fx over 2 days) with perioperative HDR-brachytherapy (PHDRBT). Early complications, toxicity, clinical outcomes, and cosmetic results were analyzed. RESULTS: Of 89 patients initially implanted, 60(67.4%) were definitively included in the 4f-AMBI-protocol. The median age was 64.4 years; the median CTV was 32.1 cc (6.9-75.4 cc), and the external-V100 was 43.1 cc (12.87-107 cc), representing 5% of the breast tissue irradiated with a median CTV D90 of 6.2 Gy (5.6-6.28 Gy). The entire local treatment (BCS&MITBI-4f-AMBI) was completed at a median of 8 days (4-10 days). The rate of early complications was 11%. There were no major complications. Acute skin-subcutaneous G1 toxicity was reported in 11.7%, and late G1 toxicity on 36.7%. After a median follow-up of 27 months (11-51 months), the local, elsewhere, locoregional and distant-control rates were 100%, 98.3%, 100%, and 100% respectively. The early-cosmetic evaluation was excellent-good in 94.5% of patients evaluated. CONCLUSIONS: Ultra-accelerated, four-fraction, minimal breast irradiation (4f-AMBI) using a minimally-invasive tumor bed implant procedure is safe, dosimetrically feasible, and shows small irradiated volumes. This program provides low toxicity rates and excellent short-term clinical and cosmesis outcomes.

Dose volume histogram constraints in patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative HDR brachytherapy.

BACKGROUND: Wound healing complications (WHC), osteoradionecrosis (ORN), and nerve damage (ND) are common adverse effects in adult patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative high dose rate brachytherapy (PHDRB) alone or combined with external beam radiotherapy (EBRT). RATIONALE: Analysis of the treatment factors contributing to these complications can potentially minimize their occurrence and severity. PATIENTS: A total of 169 patients enrolled in two parallel prospective studies were included in this analysis. Previously Unirradiated cases (Group 1; n = 139) were treated with surgical resection, 16-24 Gy of PHDRB and 45 Gy of EBRT. Adjuvant chemotherapy was given to selected patients with high-grade tumors. Previously irradiated cases (Group 2; n = 30) were treated with surgical resection and 32-40 Gy of PHDRB without further EBRT. METHODS: Patient factors, tumor factors, surgical factors, PHDRB factors and EBRT factors were analyzed using Cox univariate and multivariate analysis. RESULTS: In Previously Unirradiated cases, WHC, ORN and ND occurred in 38.8%, 5.0% and 19.4%. Multivariate analysis indicated that WHC increased with CTV size (p = 0.02) and CTV2cm3 Physical dose (p = 0.02). ORN increased with Bone2cm3 EQD2 ≥ 67 Gy(p = 0.01) and ND was more frequent in patients with TV100DVH-based dose (tissue volume encompassed by the 100% isodose) ≥ 84 Gy (p < 0.01). In Previously Irradiated cases, WHC, ORN and ND occurred in 63.3%, 3.3% and 23.3%. Multivariate analysis showed that WHC was more frequent in patients with Skin2cm3Lifetime EQD2 ≥ 84 Gy (p = 0.01) and ND was more frequent after CTVD90 Physical Doses ≥ 40 Gy (p < 0.01). CONCLUSIONS: WHC in Previously Unirradiated patients can be minimized by using a more conservative CTV definition together with a meticulous implant technique and planning aimed to minimize hyperdose CTV2cm3 areas. In Previously Irradiated patients WHC may be mimimized considering Lifetime EQD2 Skin2cm3 doses. ORN can be reduced by using the Bone2cm3 EQD2 constraint. ND occurs more frequently in patients with large tumors receiving high treated volume doses, but no specific constraints can be recommended due to the lack of peripheral nerve definition during brachytherapy planning.

Estrategias de consolidación de vínculos en contexto de intervenciones en salud intercultural en América Latina: una revisión sistemática / Link consolidation strategies in the context of intercultural health interventions in Latin America: a systematic review / Estratégias de consolidação de vínculos no contexto das intervenções interculturais em saúde na América Latina: uma revisão sistemática

OBJETIVO: Describir las estrategias de consolidación de los vínculos en el contexto de las intervenciones de salud orientadas a la salud intercultural en América Latina. METODOLOGÍA: Revisión sistemática cualitativa, utilizando el flujograma prisma para selección de artículos. Las bases de datos revisadas fueron: SciELO, PubMed (MEDLINE), Redalyc y Scopus. Los criterios de inclusión fueron artículos originales y/o revisión, con metodología cualitativa y cuantitativa descriptiva, que no tuvieran más de 10 años desde su publicación, basados en países pertenecientes a América Latina y cuyo idioma sea español, portugués y/o inglés. La calidad metodológica se evaluó mediante la guía de lectura crítica de CASPe. Se analizaron un total de 19 estudios publicados entre el periodo 2014-2021. RESULTADOS: La consolidación de vínculos se logra a través de la participación activa de integrantes de las comunidades en el diseño de las intervenciones en salud. La preparación de los profesionales es clave, considerando el desarrollo de la competencia intercultural como una piedra angular. Adicionalmente, las políticas públicas en salud permean en la ejecución de los programas e intervenciones en salud intercultural. CONCLUSIÓN: La construcción de vínculos y de relaciones sólidas y de confianza toman tiempo, y es necesario que haya suficiente co-diseño y un proceso participativo para establecer la relación entre equipo de salud y comunidades. Es necesario reconocer el contexto epistemológico y cosmológico que impulsa la salud y el bienestar en las comunidades nativas.

OBJECTIVE: Describe the strategies for consolidating links in the context of health programs/interventions aimed at intercultural health in Latin America. METHODOLOGY: Qualitative systematic review, using the prism flowchart for article selection. The databases reviewed were: SciELO, PubMed (MEDLINE), Redalyc,andScopus.The inclusion criteria were original articles and/or reviews, with descriptive qualitative and quantitative methodology, whichwere not more than 10 years old from their publication, based on countries belonging to Latin America and whose language is Spanish, Portuguese,and/or English. The methodological quality was evaluated using the CASPe critical reading guide. A total of 19 studies published between the 2014-2021 period were analyzed. RESULTS: The consolidation of links isachieved through the active participation of community members in the design of health disturbances. The preparation of professionals is key, considering the development of intercultural competence as a cornerstone. Additionally, public health policies permeate the execution of intercultural health programs and interventions.CONCLUSIONS: Building bonds and solid, trusting relationships take time, and there needs to be sufficient co-design and a participatory process to establish the relationship between the health team and the communities. It is necessary to recognize the epistemological and cosmological context that drives health and well-being in native communities

OBJETIVO: Descrever as estratégias de consolidação de vínculos no contexto das intervenções de saúde orientado à saúde intercultural na América Latina. METODOLOGIA: Revisão sistemática qualitativa, utilizando o fluxograma prisma para seleção dos artigos. Os bancosde dados usadas são:SciELO, PubMed (MEDLINE), Redalyc eScopus. Os critérios de inclusão foram artigos originais e/ou revisões, com metodologia qualitativa e quantitativa descritiva, com até 10 anos de sua publicação, baseados em países pertencentes à América Latina e cujo idioma seja espanhol, português e/ou inglês. A qualidade metodológica foi avaliada por meio do guia de leitura crítica CASPe.Foram analisados 19 estudos publicados entre o período 2014-2021. RESULTADOS: A consolidação dos vínculos é alcançada por meio da participação ativa dos membros da comunidade no desenho das intervenções de saúde. A preparação dos profissionais é fundamental, tendo como pilar fundamental o desenvolvimento da competência intercultural. Além disso, as políticas públicas de saúde permeiam a execução de programas e intervenções de saúde intercultural. CONCLUSÃO: A construção de vínculos e relações sólidas e de confiança leva tempo, e é preciso haver co-design suficiente e um processo participativo para estabelecer a relação entre a equipe de saúde e as comunidades. É necessário reconhecer o contexto epistemológico e cosmológico que impulsiona a saúde e o bem-estar nas comunidades nativas

Local Preirradiation of Infarcted Cardiac Tissue Substantially Enhances Cell Engraftment.

The success of cell therapy for the treatment of myocardial infarction depends on finding novel approaches that can substantially implement the engraftment of the transplanted cells. In order to enhance cell engraftment, most studies have focused on the pretreatment of transplantable cells. Here we have considered an alternative approach that involves the preconditioning of infarcted heart tissue to reduce endogenous cell activity and thus provide an advantage to our exogenous cells. This treatment is routinely used in other tissues such as bone marrow and skeletal muscle to improve cell engraftment, but it has never been taken in cardiac tissue. To avoid long-term cardiotoxicity induced by full heart irradiation we developed a rat model of a catheter-based heart irradiation system to locally impact a delimited region of the infarcted cardiac tissue. As proof of concept, we transferred ZsGreen+ iPSCs in the infarcted heart, due to their ease of use and detection. We found a very significant increase in cell engraftment in preirradiated rats. In this study, we demonstrate for the first time that preconditioning the infarcted cardiac tissue with local irradiation can substantially enhance cell engraftment.

The Prevalence of Difficult Airway in Children With Beckwith-Wiedemann Syndrome: A Retrospective Cohort Study.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is the most common congenital overgrowth disorder with an incidence of approximately 1 in 10,000 live births. The condition is characterized by lateralized overgrowth, abdominal wall defects, macroglossia, and predisposition to malignancy. Historically, children with BWS have been presumed to have difficult airways; however, most of the evidence to support this has been anecdotal and derived from case reports. Our study aimed to determine the prevalence of difficult airway in patients with BWS. We hypothesized that most patients with BWS would not have difficult airways. METHODS: We retrospectively reviewed the electronic medical records of patients enrolled in our institution's BWS registry. Patients with a molecular diagnosis of BWS who were anesthetized between January 2012 and July 2019 were included for analysis. The primary outcome was the presence of difficult airway, defined as difficult facemask ventilation, difficult intubation, or both. We defined difficult intubation as the need for 3 or more tracheal intubation attempts and the need for advanced airway techniques (nondirect laryngoscopy) to perform tracheal intubation or a Cormack and Lehane grade ≥3 during direct laryngoscopy. Secondary objectives were to define predictors of difficult intubation and difficult facemask ventilation, and the prevalence of adverse airway events. Generalized linear mixed-effect models were used to account for multiple anesthesia events per patient. RESULTS: Of 201 BWS patients enrolled in the registry, 60% (n = 122) had one or more documented anesthetics, for a total of 310 anesthetics. A preexisting airway was present in 22 anesthetics. The prevalence of difficult airway was 5.3% (95% confidence interval [CI], 3.0-9.3; 18 of 288) of the cases. The prevalence of difficult intubation was 5.2% (95% CI, 2.9-9.4; 12 of 226). The prevalence of difficult facemask ventilation was 2.9% (95% CI, 1.4-6.2; 12 of 277), and facemask ventilation was not attempted in 42 anesthetics. Age <1 year, macroglossia, lower weight, endocrine comorbidities, plastics/craniofacial surgery, tongue reduction surgery, and obstructive sleep apnea were associated with difficult airways in cases without a preexisting airway. About 83.8% (95% CI, 77.6-88.5) of the cases were intubated with a single attempt. Hypoxemia was the most common adverse event. CONCLUSIONS: The prevalence of difficult tracheal intubation and difficult facemask ventilation in children with BWS was 5.2% and 2.9%, respectively. We identified factors associated with difficult airway, which included age <1 year, macroglossia, endocrine abnormalities, plastics/craniofacial surgery, tongue reduction surgery, and obstructive sleep apnea. Clinicians should anticipate difficult airways in patients with these factors.

The Role of IgM Antibodies in T Cell Lymphoma Protection in a Novel Model Resembling Anaplastic Large Cell Lymphoma.

MRL/lpr mice typically succumb to immune complex-mediated nephritis within the first year of life. However, MRL/lpr mice that only secrete IgM Abs because of activation-induced deaminase deficiency (AID-/-MRL/lpr mice) experienced a dramatic increase in survival. Further crossing of these mice to those incapable of making secretory IgM (µS mice) generated mice lacking any secreted Abs but with normal B cell receptors. Both strains revealed no kidney pathology, yet Ab-deficient mice still experienced high mortality. In this article, we report Ab-deficient MRL/lpr mice progressed to high-grade T cell lymphoma that can be reversed with injection of autoreactive IgM Abs or following adoptive transfer of IgM-secreting MRL/lpr B cells. Anti-nuclear Abs, particularly anti-dsDNA IgM Abs, exhibited tumor-killing activities against a murine T cell lymphoma cell line. Passive transfers of autoreactive IgM Abs into p53-deficient mice increased survival by delaying onset of T cell lymphoma. The lymphoma originated from a double-negative aberrant T cell population seen in MRL/lpr mice and most closely resembled human anaplastic large cell lymphoma. Combined, these results strongly implicate autoreactive IgM Abs in protection against T cell lymphoma.

Comprehensive Quantitative Proteome Analysis of Aedes aegypti Identifies Proteins and Pathways Involved in Wolbachia pipientis and Zika Virus Interference Phenomenon.

Zika virus (ZIKV) is a global public health emergency due to its association with microcephaly, Guillain-Barré syndrome, neuropathy, and myelitis in children and adults. A total of 87 countries have had evidence of autochthonous mosquito-borne transmission of ZIKV, distributed across four continents, and no antivirus therapy or vaccines are available. Therefore, several strategies have been developed to target the main mosquito vector, Aedes aegypti, to reduce the burden of different arboviruses. Among such strategies, the use of the maternally-inherited endosymbiont Wolbachia pipientis has been applied successfully to reduce virus susceptibility and decrease transmission. However, the mechanisms by which Wolbachia orchestrate resistance to ZIKV infection remain to be elucidated. In this study, we apply isobaric labeling quantitative mass spectrometry (MS)-based proteomics to quantify proteins and identify pathways altered during ZIKV infection; Wolbachia infection; co-infection with Wolbachia/ZIKV in the A. aegypti heads and salivary glands. We show that Wolbachia regulates proteins involved in reactive oxygen species production, regulates humoral immune response, and antioxidant production. The reduction of ZIKV polyprotein in the presence of Wolbachia in mosquitoes was determined by MS and corroborates the idea that Wolbachia helps to block ZIKV infections in A. aegypti. The present study offers a rich resource of data that may help to elucidate mechanisms by which Wolbachia orchestrate resistance to ZIKV infection in A. aegypti, and represents a step further on the development of new targeted methods to detect and quantify ZIKV and Wolbachia directly in complex tissues.

Pandemia do coronavírus e impactos na saúde mental: uma revisão integrativa da literatura / Coronavirus pandemic and impacts on mental health: an integrative literature review

Em cenários de pandemia, como a COVID-19, a ruptura da cadeia de infecção é fundamental para a proteção da saúde da população. Este processo pode ser atingido mediante a adoção de medidas de restrição do contato humano, como isolamento, quarentena e distanciamento social. Embora fundamentadas em achados científicos e necessárias para conter o avanço da COVID-19, as medidas de isolamento social pode gerar impactos à saúde mental da população. Nesse sentido, a presente pesquisa visa avaliar a produção científica a respeito dos impactos da quarentena decorrente da COVID-19 na saúde mental. Trata-se de uma revisão integrativa da literatura científica, realizada por meio da exploração nas bases de dados PubMed e Biblioteca Virtual em Saúde (BVS), no período de março de 2020. Nessas bases de dados, foram utilizadas as palavraschave: COVID-19 and psychological consequences, COVID-19 and psychological impact of quarantine, obteve-se 10 artigos, dos quais 4 artigos, foram incluídos na análise após a exclusão de artigos duplicados e revisões de literatura, sendo 3 da PubMed e 1 da BVS. Os resultados sugerem alta frequência de relatos de reações e sintomas possivelmente associados a transtornos mentais, tais como queixas de ansiedade, depressão, insônia, estresse, pânico, solidão, angústia, obsessão e compulsão entre outros. Ficou evidente que grupos de risco como idosos e pessoas com doenças crônicas apresentaram maior probabilidade para o desenvolvimento de transtornos mentais. Ademais, análises dos impactos do coronavírus na dimensão psicológica podem corroborar para construção de intervenções pautadas na promoção, prevenção e tratamento em saúde mental.

In pandemic scenarios, such as COVID-19, the disruption of the infection chain is fundamental for the protection of the population's health. This process can be achieved through the adoption of measures to restrict human contacts, such as isolation, quarantine, and social distance. Although based on scientific findings and necessary to contain the advancement of COVID-19, social isolation measures can have an impact on the population's mental health. In this sense, this research aims to evaluate scientific production regarding the impacts of the quarantine resulting from COVID-19 on mental health. It is an integrative review of the scientific literature, carried out through the exploration in the PubMed and Virtual Health Library (BVS) databases, in March 2020. In these databases, the keywords were used: COVID -19 and psychological consequences, COVID-19 and psychological impact of quarantine, 10 articles were obtained, of which 4 articles were included in the analysis after excluding duplicate articles and literature reviews, 3 from PubMed and 1 from the BVS. The results suggest a high frequency of reports of reactions and symptoms possibly associated with mental disorders, such as complaints of anxiety, depression, insomnia, stress, panic, loneliness, anguish, obsession, and compulsion, among others. It was evident that risk groups such as the elderly and people with chronic diseases were more likely to develop mental disorders. In addition, analyzes of the impact of coronavirus on the psychological dimension can support the construction of interventions based on promotion, prevention, and treatment in mental health.

A Qualitative Assessment of Factors That Children, Parents, and Clinicians Prioritize in the Setting of Elective Anesthesia and Surgery.

BACKGROUND: Assessing the postoperative recovery of pediatric patients is challenging as there is no validated comprehensive patient-centered recovery assessment tool for this population. A qualitative investigative approach with in-depth stakeholder interviews can provide insight into the recovery process and inform the development of a comprehensive patient-centered postoperative assessment tool for children. METHODS: We conducted open-ended, semistructured interviews with children 6-12 years old undergoing elective surgery (n = 35), their parents (n = 37), and clinicians (n = 23) who commonly care for this population (nurses, anesthesiologists, and surgeons). A codebook was developed and analyzed using NVivo 12 Plus. The codebook was iteratively developed using a qualitative content analysis approach with modifications made throughout to refine codes. We report the results of this thematic analysis of patient, parent, and clinician transcripts. RESULTS: Postoperative recovery priorities/concerns overlapped and also diverged across the 3 groups. Topics prioritized by children included mobility and self-care, as well as access to a strong social support network following surgery. The majority of children reported feeling anxious about the surgery and separating from their parents, as well as sadness about their inability to participate in activities while recovering. Although children highly valued familial support during recovery, there was variable awareness of the impact of surgery on family members and support network. In contrast, parents focused on the importance of clear and open communication among themselves and the health care team and being equipped with appropriate knowledge and resources on discharge. The immediate repercussions of the child's surgery, such as pain, confusion, and nausea, appeared to be a primary focus of both parents and clinicians when describing recovery. Clinicians had a comprehensive awareness of the possible psychological impacts of surgery in children, while parents reported varying degrees of awareness or concern regarding longer-term or more latent impacts of surgery and anesthesia (eg, anxiety and depression). Prior experience with pediatric surgery emerged as a distinguishing characteristic for parents and clinicians as parents without prior experience expressed less understanding of or comfort with managing a child's recovery following surgery. CONCLUSIONS: A patient-centered qualitative investigative approach yielded insights regarding the importance of various aspects of recovery in pediatric patients, their parents, and members of the health care team. Specifically, this investigation highlighted the importance of clear communication providing anticipatory guidance for families presenting for elective surgery in an effort to optimize patient recovery. This information will be used in the development of a patient-centered recovery assessment tool.

Dose volume histogram constraints in patients with head and neck cancer treated with surgery and adjuvant HDR brachytherapy: A proposal of the head and neck and skin GEC ESTRO Working group.

BACKGROUND: The Head and Neck and Skin (HNS) Working group of the GEC-ESTRO acknowledges the lack of widely accepted Dose Volume Histogram (DVH) constraints in adjuvant head and neck brachytherapy and issues recommendations to minimize mandibular Osteoradionecrosis (ORN) and Soft Tissue Necrosis (STN). METHODS: A total of 227 patients with the diagnosis of head and neck cancer treated with surgery and adjuvant HDR brachytherapy alone or combined with other treatment modalities during the period 2000-2018 were analyzed. RESULTS: STN was observed in 28 out of 227 cases (12.3%) with an average time to appearance of 4.0 months. In previously unirradiated cases, there was a positive correlation between CTV size and STN (p = 0.017) and a trend towards significance between Total EQD2-DVH TV100 dose and STN (p = 0.06). The risk of STN in the absence of both factors (i.e, CTV < 15 cm3 and Total EQD2-DVH TV100 dose < 87 Gy) was 2%, with one factor present 15.7% and with both factors 66.7% (p = 0.001). ORN was observed in 13 out of 227 cases (5.7%) with an average time to appearance of 26.2 months. In unirradiated cases, ORN correlated with Total Physical Dose to Mandible2cm3 (p = 0.027). Patients receiving Total Physical Doses greater than 61 Gy had a 20-fold increased risk of ORN. CONCLUSIONS: In Unirradiated patients the panel recommends to avoid implantation of postoperative CTVs exceeding 15 cm3 at Total EQD2-DVH TV100 doses in excess of 87 Gy as well as to limit the irradiation of the Mandible2cm3 to 61 Gy. In previously irradiated patients the panel cannot make a recommendation based on the available results.

Identification and recombinant expression of an antimicrobial peptide (cecropin B-like) from soybean pest Anticarsia gemmatalis

Insects can be found in numerous diverse environments, being exposed to pathogenic organisms like fungi and bacteria. Once these pathogens cross insect physical barriers, the innate immune system operates through cellular and humoral responses. Antimicrobial peptides are small molecules produced by immune signaling cascades that develop an important and generalist role in insect defenses against a variety of microorganisms. In the present work, a cecropin B-like peptide (AgCecropB) sequence was identified in the velvetbean caterpillar Anticarsia gemmatalis and cloned in a bacterial plasmid vector for further heterologous expression and antimicrobial tests. Methods AgCecropB sequence (without the signal peptide) was cloned in the plasmid vector pET-M30-MBP and expressed in the Escherichia coli BL21(DE3) expression host. Expression was induced with IPTG and a recombinant peptide was purified using two affinity chromatography steps with Histrap column. The purified peptide was submitted to high-resolution mass spectrometry (HRMS) and structural analyses. Antimicrobial tests were performed using gram-positive (Bacillus thuringiensis) and gram-negative (Burkholderia kururiensis and E. coli) bacteria. Results AgCecropB was expressed in E. coli BL21 (DE3) at 28°C with IPTG 0.5 mM. The recombinant peptide was purified and enriched after purification steps. HRMS confirmed AgCrecropB molecular mass (4.6 kDa) and circular dichroism assay showed α-helix structure in the presence of SDS. AgCrecropB inhibited almost 50% of gram-positive B. thuringiensis bacteria growth. Conclusions The first cecropin B-like peptide was described in A. gemmatalis and a recombinant peptide was expressed using a bacterial platform. Data confirmed tertiary structure as predicted for the cecropin peptide family. AgCecropB was capable to inhibit B. thuringiensis growth in vitro.(AU)