Ketamine subcutaneous continuous infusion for depressive symptoms at home: A case report beyond pain use.

OBJECTIVES: Ketamine has been widely used in refractory pain as an opioid adjuvant. Evidence suggests that ketamine can also have an essential role in easing depressive symptoms. Its rapid onset of action makes it a valuable choice in palliative care. METHODS: We present a case of a 70-year-old man with stage IV renal carcinoma and bone metastasis. The main symptoms included neuropathic pain, depression, and a persistent and severe desire for death. RESULTS: We started continuous subcutaneous infusion with morphine 30 mg and ketamine 100 mg/day. The dose of ketamine was incremented to the maximum of 250 mg/day. During the 28-day treatment, we observed an overall improvement in neuropathic pain, depressive symptoms, and other end-of-life psychological aspects of distress. Only minor psychological side effects were identified, which were controlled by using midazolam in the continuous subcutaneous infusion. SIGNIFICANCE OF RESULTS: Some studies have already demonstrated the benefits of ketamine use in alleviating depression, using parental infusion or oral formulas, which are administered in hospice care. Our report enhances the benefit of the subcutaneous route for palliative patients cared for at home.

The impact of pre-, pro- and synbiotics supplementation in colorectal cancer treatment: a systematic review.

Introduction: The effectiveness of the supplementation of prebiotics, probiotics and synbiotics as a therapeutic approach in colorectal cancer (CRC) remains unclear. The aim of this systematic review is to critically examine the current scientific evidence on the impact of modulating the microbiota, through the use of prebiotics, probiotics and synbiotics, in patients diagnosed with CRC undergoing treatment, to determine the potential therapeutic use of this approach. Methods: This systematic review was made according to the PRISMA 2020 guidelines. Inclusion criteria were randomized controlled trials (RCT) comparing the impact of pre-, pro-, or synbiotic supplementation with placebo or standard care in patients with CRC undergoing treatment. Exclusion criteria were non-human studies, non-RCTs, and studies in languages other than English or Portuguese. Six databases were consulted, namely, Cochrane Library, Pubmed, Scopus, Cinahl, MedicLatina and Web of Science until May of 2023. RAYYAN software was used to manage the search results and risk of bias was assessed according to the guidelines of the Cochrane Collaboration using the Rob 2.0 tool. Results: Twenty-four RCTs met the inclusion criteria and were included in this review. Administration of pre-, pro-, or synbiotics improved surgical outcomes such as the incidence of infectious and non-infectious postoperative complications, return to normal gut function, hospital length of stay, and antibiotic usage. The supplementation of these microorganisms also alleviated some symptoms from chemotherapy and radiotherapy, mainly diarrhea. Evidence on the best approach in terms of types of strains, dosage and duration of intervention is still scarce. Conclusions: Pre-, pro-, and synbiotics supplementation appears to be a beneficial therapeutic approach in CRC treatment to improve surgical outcomes and to alleviate side-effects such as treatment toxicity. More RCTs with larger sample sizes and less heterogeneity are needed to confirm these potential benefits and to determine the best strains, dosage, and duration of administration in each situation. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023413958.

Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle.

Foot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzootic areas, underscoring the need to develop new fast-acting therapies for FMD control during outbreaks. Interferons (IFNs) are among the immune system's first line of defense against viral infections. Bovine type III IFN delivered by a replication defective adenovirus (Ad) vector has effectively blocked FMD in cattle. However, the limited duration of protection-usually only 1-3 days post-treatment (dpt)-diminishes its utility as a field therapeutic. Here, we test whether polyethylene glycosylation (PEGylation) of recombinant bovine IFNλ3 (PEGboIFNλ3) can extend the duration of IFN-induced prevention of FMDV infection in both vaccinated and unvaccinated cattle. We treated groups of heifers with PEGboIFNλ3 alone or in combination with an adenovirus-based FMD O1Manisa vaccine (Adt-O1M) at either 3 or 5 days prior to challenge with homologous wild type FMDV. We found that pre-treatment with PEGboIFNλ3 was highly effective at preventing clinical FMD when administered at either time point, with or without co-administration of Adt-O1M vaccine. PEGboIFNλ3 protein was detectable systemically for >10 days and antiviral activity for 4 days following administration. Furthermore, in combination with Adt-O1M vaccine, we observed a strong induction of FMDV-specific IFNγ+ T cell response, demonstrating its adjuvanticity when co-administered with a vaccine. Our results demonstrate the promise of this modified IFN as a pre-exposure prophylactic therapy for use in emergency outbreak scenarios.

Mitochondrial Dysfunction in Advanced Maternal Aged Cumulus Cells: A Possible Link to ATP Synthase Impairment?

Age-related changes in the mitochondrial status of human cumulus cells (hCCs) impact oocyte quality; however, the relationship between hCC mitochondrial (dys)function and reproductive aging remains poorly understood. This study aimed to establish the interplay between hCC mitochondrial dysfunction and women's reproductive potential. In this investigation, 266 women were enrolled and categorized into two groups based on their age: a young group (<35 years old) and an advanced maternal age (AMA) group (≥35 years old). Comprehensive analysis of reproductive outcomes was conducted in our population. Various mitochondrial-related parameters were analyzed across distinct subsets. Specifically, mitochondrial membrane potential (∆Ψm) and mitochondrial mass were examined in 53 samples, mtDNA content in 25 samples, protein levels in 23 samples, bioenergetic profiles using an XF24 Extracellular Flux Analyzer in 6 samples, and levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in 39 and 43 samples, respectively. In our study, the reproductive potential of AMA women sharply decreased, as expected. Additionally, an impairment in the mitochondrial function of hCCs in older women was observed; however, no differences were found in terms of mitochondrial content. Regarding oxidative phosphorylation, metabolic profiling of hCCs from AMA women indicated a decrease in respiratory capacity, which was correlated with an age-dependent decrease in the ATP synthase (ATP5A1) protein level. However, intracellular ROS and ATP levels did not differ between groups. In conclusion, our study indicates that age-related dysfunction in hCCs is associated with impaired mitochondrial function, and, although further studies are required, ATP synthase could be relevant in this impairment.

Chronic gastric volvulus with diaphragmatic eventration: Case presentation.

INTRODUCTION AND IMPORTANCE: Gastric volvulus is a rare clinical entity which occurs due to the rotation of the stomach and can have life-threatening complications. This condition can have an acute or chronic presentation and its symptoms will vary according to the degree of obstruction and rapidity of onset. CASE PRESENTATION: We report a case of a 84-year-old male with history of frequent periods of constipation and lack of appetite who presented to the emergency room with left-sided abdominal pain and distension and persistent nausea, without the ability to vomit. Abdominal radiograph, computed tomography scan of the abdomen, contrast-enhanced examination and upper endoscopy were consistent with a gastric volvulus secondary to diaphragmatic eventration. The patient's symptoms resolved after nasogastric tube placement and fluid resuscitation. However, he was proposed to a laparoscopic anterior gastropexy to prevent symptom recurrence. He remains asymptomatic after 3 years of follow-up. CLINICAL DISCUSSION: The diagnosis of gastric volvulus is based mainly on clinical presentation and abdominal imaging. The main principles of surgical intervention include stomach decompression with volvulus reduction, followed by gastropexy and correction of any predisposing intra-abdominal factors. CONCLUSION: Definitive treatment of both acute and chronic gastric volvulus includes a surgical approach. Laparoscopic anterior gastropexy has been found to be a viable alternative in these patients.

Randomized crossover clinical trial of a Mindfulness-based intervention for nurse leaders: A pilot study / Ensayo clínico aleatorizado cruzado de una intervención basada en mindfulness con enfermeros líderes: estudio piloto / Ensaio clínico randomizado cruzado de uma intervenção baseada em mindfulness em enfermeiros líderes: estudo-piloto

Objective: to analyze the effects of a Mindfulness-based intervention on nurse leaders' emotional intelligence and resilience. Method: a pilot study of a randomized crossover clinical trial. The sample (n=32) was randomized into Group A (n=18) and Group B (n=14) and evaluated at the pre-test, post-test and follow-up moments. The outcomes were assessed using the Emotional Intelligence Measure, the Connor-Davidson Resilience Questionnaire and the Five Facet Mindfulness Questionnaire, and analyzed using Generalized Linear Mixed Models. Results: a total of 32 nurses with a mean age of 42.6 years old were evaluated. The analyses showed significant interactions between the effects of the group x moment factors on the Self-motivation (p=0.005), Sociability (p<0.001), Self-control (p=0.013), and Total (p=0.002) emotional intelligence skill scores; as well as on the Observe (p=0.042), Describe (p=0.008), Non-judgment (p<0.001), Act with awareness (p=0.004) and Total (p<0.001) mindfulness facets. Post-test: there was a statistically significant increase in the Sociability (p=0.009) and Self-control (p=0.015) emotional intelligence skills; as well as in the Non-judgment (p=0.022) and Total (p=0.002) mindfulness facets. Follow-up: a significant increase was observed in the Non-judgment (p=0.024) and Total (p=0.026) mindfulness facets. The "resilience" variable did not present statistical significance in the "group x moment" factor, both in the post-test and during follow-up. Conclusion: the Mindfulness-based intervention used proved to be effective in increasing nurse leaders' emotional intelligence and dispositional mindfulness skills. Brazilian Registry of Clinical Trials (RBR-3c62gy), registered on March 4 th , 2020, updated on September 16 th , 2022.

Objetivo: analizar los efectos de una intervención basada en mindfulness sobre la inteligencia emocional y la resiliencia de enfermeros líderes. Método: estudio piloto de un ensayo clínico aleatorizado cruzado. Muestra (n=32) aleatorizada en el grupo A (n=18) y grupo B (n=14), se los evaluó en el pretest, postest y seguimiento. Los resultados fueron evaluados mediante la Medida de Inteligencia Emocional, el Cuestionario de Resiliencia de Connor-Davidson y el Cuestionario Mindfulness de Cinco Facetas, y analizados por el Generalized Linear Mixed Models . Resultados: fueron evaluadas 32 enfermeras con una edad promedio de 42,6 años. Los análisis mostraron interacciones significativas de los efectos de los factores grupo vs. momento en los puntajes de las habilidades de automotivación (p=0,005), sociabilidad (p<0,001), autocontrol (p=0,013) y total (p=0,002) de inteligencia emocional; de las facetas observar (p=0,042), describir (p=0,008), no juzgar (p<0,001), actuar con conciencia (p=0,004) y total (p<0,001) de mindfulness. Postest: hubo un aumento estadísticamente significativo de las habilidades de sociabilidad (p=0,009) y autocontrol (p=0,015) de inteligencia emocional; de las facetas no juzgar (p=0,022) y total (p=0,002) de mindfulness . Seguimiento: se observó un aumento significativo en las facetas no juzgar (p=0,024) y total (p=0,026) de mindfulness . La variable resiliencia no presentó significación estadística en el factor grupo vs. momento en el postest y seguimiento. Conclusión: la intervención basada en mindfulness utilizada demostró ser eficaz para aumentar la inteligencia emocional y las habilidades de mindfulness disposicional de los enfermeros líderes. Registro Brasileño de Ensayos Clínicos (RBR-3c62gy), registrado el 4 de marzo de 2020, actualizado el 16 de septiembre de 2022.

Objetivo: analisar os efeitos de uma intervenção baseada em mindfulness na inteligência emocional e resiliência de enfermeiros líderes. Método: estudo-piloto de ensaio clínico randomizado cruzado. Amostra (n=32) randomizada em grupo A (n=18) e grupo B (n=14), avaliados nos momentos pré-teste, pós-teste e seguimento. Os desfechos foram avaliados pela Medida de Inteligência Emocional, pelo Questionário de Resiliência Connor-Davidson e pelo Questionário das Cinco Facetas de Mindfulness , e analisados pelo Generalized Linear Mixed Model . Resultados: foram avaliadas 32 enfermeiras com idade média de 42,6 anos. As análises mostraram interações significativas dos efeitos dos fatores Grupo x Momento nos escores das habilidades de automotivação (p=0,005), sociabilidade (p<0,001), autocontrole (p=0,013) e total (p=0,002) de inteligência emocional; das facetas observar (p=0,042), descrever (p=0,008), não julgar (p<0,001), agir com consciência (p=0,004) e total (p<0,001) de mindfulness . Pós-teste: houve aumento estatisticamente significante das habilidades de sociabilidade (p=0,009) e autocontrole (p=0,015) de inteligência emocional; das facetas não julgar (p=0,022) e total (p=0,002) de mindfulness . Seguimento: observou-se aumento significativo das facetas não julgar (p=0,024) e total (p=0,026) de mindfulness . A variável resiliência não apresentou significância estatística no fator Grupo x Momento, no pós-teste e seguimento. Conclusão: a intervenção baseada em mindfulness utilizada mostrou-se efetiva no aumento das habilidades de inteligência emocional e mindfulness disposicional de enfermeiros líderes. Registro Brasileiro de Ensaios Clínicos (RBR-3c62gy), registrado em 04 de março de 2020, atualizado em 16 de setembro de 2022.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil.

This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Bioelectrical Impedance Analysis (BIA) for the Assessment of Body Composition in Oncology: A Scoping Review.

Bioelectrical Impedance Analysis (BIA) is a reliable, non-invasive, objective, and cost-effective body composition assessment method, with high reproducibility. This scoping review aims to evaluate the current scientific and clinical evidence on BIA for body composition assessment in oncology patients, under active treatment. Literature search was conducted through MEDLINE, CINAHL, Scopus and Web of Science databases, following PRISMA-ScR Guidelines. Inclusion criteria comprised studies reporting the use of BIA for body composition evaluation in adults with cancer diagnosis. Studies including non-cancer pathology or only assessing nutritional status were excluded. This scoping review comprised a total of 36 studies: 25 were original studies including 18 prospective studies, six cross-sectional studies and one retrospective study and 11 were systematic reviews. Population size for the included original articles ranged from 18 to 1217 participants, comprising a total of 3015 patients with cancer with a mean baseline Body Mass Index (BMI) ranging from 20.3 to 30.0 kg/m2 and mean age ranging between 47 and 70 years. Review articles included a total of 273 studies, with a total of 78,350 participants. The current review considered studies reporting patients with head and neck cancer (HNC) (n = 8), breast cancer (BC) (n = 4), esophageal cancer (EC) (n = 2), liver cancer (n = 2), pancreatic cancer (PC) (n = 3), gastric cancer (GC) (n = 3), colorectal cancer (CRC) (n = 8), lung cancer (LC) (n = 1), skin cancer (SK) (n = 1) and multiple cancer types (n = 6). BIA is a suitable and valid method for the assessment of body composition in oncology. BIA-derived measures have shown good potential and relevant clinical value in preoperative risk evaluation, in the reduction of postoperative complications and hospital stay and as an important prognostic indicator in persons with cancer. Future research on the diagnostic value and clinical applications of BIA and BIA-derived phase angle (PhA) should be conducted in order to predict its impact on patient survival and other clinical outcomes.

Recent insights explaining susceptibility to endometriosis-From genetics to environment.

Endometriosis is a disease with a heterogeneous pathogenesis, explained by multiple theories, and also with a polymorphic presentation. The purpose of this literature review is to systematize the genetic, inflammatory, and environmental factors related to the pathophysiology of endometriosis. Current evidence suggests that endometriosis is a complex inherited genetic condition, in which the genes that determine susceptibility to the disease interact with the environment to develop different phenotypes. Genetic variants associated with risk of endometriosis have been identified in several genome-wide association studies, in addition to a group of genes related to the pathophysiology of endometriosis, namely the estrogen, progesterone and androgen receptors and the cytochrome P450 gene, as well as the p53 gene. The role of inflammation is controversial; however, it is an essential process, both in the initiation and perpetuation of the disease, in and outside the pelvis. Alterations in reactive oxygen species pathways that consequently determine oxidative stress are typical in the inflammatory environment of endometriosis. The role of environmental factors is a relatively new and broad-spectrum topic, with inconsistent evidence. Multiple factors have been studied such as endocrine-disrupting chemicals, metals, intrauterine exposure to diethylstilbesterol and lifestyle risk factors. In conclusion, endometriosis remains a mysterious condition, with multifactorial factors involved in its pathophysiology. The progress that has been made in the genetic predisposition to endometriosis may allow the establishment of new therapeutic targets. On the other hand, understanding the role of the environment in this disease may allow preventive intervention, minimizing its incidence and/or severity. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology Reproductive System Diseases > Environmental Factors Reproductive System Diseases > Genetics/Genomics/Epigenetics.

Low responders may benefit from undergoing ovarian stimulation with a long GnRH agonist protocol with corifollitropin alfa followed by hMG.

OBJECTIVE: To evaluate the outcomes of a long GnRH agonist protocol with corifollitropin alfa followed by hMG in low responders. METHODS: Retrospective cohort study. Patients with a suboptimal previous ovarian response (<9 oocytes) and a normal ovarian reserve (Poseidon groups 1 and 2) were classified in 1) Group 1 (n=88), submitted to a second cycle with a GnRH antagonist protocol using rFSH/hMG; 2) Group 2 (n=66), submitted to a long GnRH agonist protocol with corifollitropin alfa followed by hMG (named as simplified long protocol). Clinical outcomes were compared between groups and between the first/second cycle of each group. RESULTS: Clinical outcomes were similar between groups. There were no differences in the number of oocytes [7(5-11.75) versus 7(5-10), p=0.802], clinical pregnancy (19.3% versus 18.2%, p=0.858) and live birth rates (18.2% versus 15.2%, p=0.619). However, baseline characteristics were different, decoding a poor prognosis among women in group 2. Both groups (1 and 2) had significantly higher number of oocytes, pregnancy, and live birth rates in the second cycle. In group 2, there was a higher rate of embryo transfer (56.1% versus 27.3%, p<0.001). In group 1, despite the similar rate of embryo transfer, there was a higher positive hCG (23.9% versus 8.0%, p=0.004). CONCLUSIONS: Both simplified long protocol and GnRH antagonist protocol are suitable for low responders. The best second cycle clinical outcomes experienced in a population with worse prognosis (group 2) suggests that the simplified long protocol may be a better option, although prospective well-conducted studies must explore this hypothesis.

Fungating Breast Wound: A Rare Manifestation of Primary Breast Leiomyosarcoma.

Leiomyosarcomas are the least frequent primary breast sarcomas, making it an extraordinarily rare malignancy. The clinical manifestation of this entity as a fungating breast wound is, on its own, highly unusual in developed nations, mainly due to the improvement of worldwide screening programs and easier access to health care. Management of this breast wound remains challenging, and an accurate histopathological diagnosis is essential for a proper treatment plan. Thus, we present this rare case of metastatic breast leiomyosarcoma to contribute to the scarce literature regarding this disease.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil

Abstract This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Mutation of FMDV Lpro H138 residue drives viral attenuation in cell culture and in vivo in swine.

The foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) is a papain like protease that cleaves the viral polyprotein and several host factors affecting host cell translation and induction of innate immunity. Introduction of Lpro mutations ablating catalytic activity is not tolerated by the virus, however, complete coding sequence deletion or introduction of targeted amino acid substitutions can render viable progeny. In proof-of-concept studies, we have previously identified and characterized FMDV Lpro mutants that are attenuated in cell culture and in animals, while retaining their capacity for inducing a strong adaptive immunity. By using molecular modeling, we have now identified a His residue (H138), that resides outside the substrate binding and catalytic domain, and is highly conserved across serotypes. Mutation of H138 renders possible FMDV variants of reduced virulence in vitro and in vivo. Kinetics studies showed that FMDV A12-LH138L mutant replicates similarly to FMDV A12-wild type (WT) virus in cells that do not offer immune selective pressure, but attenuation is observed upon infection of primary or low passage porcine epithelial cells. Western blot analysis on protein extracts from these cells, revealed that while processing of translation initiation factor eIF-4G was slightly delayed, no degradation of innate sensors or effector molecules such as NF-κB or G3BP2 was observed, and higher levels of interferon (IFN) and IFN-stimulated genes (ISGs) were induced after infection with A12-LH138L as compared to WT FMDV. Consistent with the results in porcine cells, inoculation of swine with this mutant resulted in a mild, or in some cases, no clinical disease but induction of a strong serological adaptive immune response. These results further support previous evidence that Lpro is a reliable target to derive numerous viable FMDV strains that alone or in combination could be exploited for the development of novel FMD vaccine platforms.

Efficacy of different neoadjuvant treatment regimens in BRCA-mutated triple negative breast cancer: a systematic review and meta-analysis.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer strongly associated with BRCA mutation. Standard neoadjuvant chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is still a matter of discussion. Other agents, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and anti-vascular endothelial growth factor (VEGF) antibodies were evaluated in the neoadjuvant setting. This systematic review and meta-analysis intend to evaluate the impact of neoadjuvant treatments in pCR rates in TNBC gBRCA mutation, beyond traditional standard chemotherapy. METHODS: PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase and key oncological meetings for trials were searched for studies reporting neoadjuvant chemo-immunotherapy in BRCA positive TNBC. RESULTS: Out of 1238 records reviewed, thirty-one trials were included, resulting in a total 619 BRCA-mutated TNBC patients. In BRCA mutated TNBC patients who received cisplatin in monotherapy the proportion of patients who achieved pCR was 0.53 (95%CI [0.30, 0.76]), and when treatment combined standard chemotherapy and platin derivatives the proportion of pCR increased to 0.62 (95% CI [0.48, 0.76]). The group of patients treated with platin derivatives, anthracyclines ± taxanes achieved the highest proportion of pCR, 0.66. Patients treated with PARPi alone show a pCR proportion of 0.55 (95% CI [0.30, 0.81]); and when standard chemotherapy and platin derivatives were combined with PARPi the proportion of pCR did not vary. CONCLUSIONS: Patients with BRCA mutated TNBC treated with cisplatin in monotherapy demonstrate inferior proportion in the pCR achievement when compared with standard chemotherapy plus platin derivates. The best pCR was achieved with platin derivates in association with anthracyclines ± taxanes. No difference in pCR was found between PARPi alone vs PARPi with standard chemotherapy.

Invasive Lobular Carcinoma Arising in Ectopic Breast Tissue: A Case Report.

Incomplete regression of the embryonic mammary line occurs in 0.3-6% of the population. Ectopic breast tissue is mostly asymptomatic and can undergo malignant transformation. Ectopic breast cancer accounts for 0.2-0.6% of all breast cancers. Screening breast examinations can miss these lesions due to their location making the diagnosis more challenging. We describe a case of a primary invasive lobular carcinoma in an ectopic breast on the left axilla detected in a 49-year-old woman. Firstly diagnosed as a sebaceous cyst, the lesion was excised under local anesthesia. Histopathology showed breast tissue widely infiltrated by an invasive carcinoma. Excision of the remnant tissue with axillary lymph node dissection was performed. Ectopic breast carcinoma is a rare diagnosis and there is a general lack of awareness. The presence of an abnormal mass along the mammary ridge should raise clinicians' attention. Management of primary ectopic breast carcinoma should be based on a multidisciplinary approach under the same principles as breast cancer. Furthermore, it does not appear to bring a worse prognosis when diagnosed at similar disease stages.

Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs.

Under experimental conditions, pigs infected with Ebola Virus (EBOV) develop disease and can readily transmit the virus to non-human primates or pigs. In the event of accidental or intentional EBOV infection of domestic pigs, complex and time-consuming safe depopulation and carcass disposal are expected. Delaying or preventing transmission through a reduction in viral shedding is an absolute necessity to limit the spread of the virus. In this study, we tested whether porcine interferon-α or λ3 (porIFNα or porIFNλ3) delivered by a replication-defective human type 5 adenovirus vector (Ad5-porIFNα or Ad5-porIFNλ3) could limit EBOV replication and shedding in domestic pigs. Our results show that pigs pre-treated with Ad5-porIFNα did not develop measurable clinical signs, did not shed virus RNA, and displayed strongly reduced viral RNA load in tissues. A microarray analysis of peripheral blood mononuclear cells indicated that Ad5-porIFNα treatment led to clear upregulation in immune and inflammatory responses probably involved in protection against disease. Our results indicate that administration of Ad5-porIFNα can potentially be used to limit the spread of EBOV in pigs.

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments.

After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs' biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs' properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.

Identificação de alterações auditivas em crianças pré-escolares / Identification of hearing disorders in preschool children / Identificación de trastornos auditivos en niños en edad preescolar

Programas de saúde auditiva estão voltados predominantemente para crianças entre 0 e 3 anos de idade ou para os maiores de 7. As crianças entre estas duas faixas etárias não estão em nenhum destes programas, porém é neste grupo que mais ocorrem problemas de orelha média, e, é, neste grupo, possível detectar as perdas auditivas mínimas, leves ou unilaterais que não foram identificadas nos programas de triagem auditiva neonatal. Objetivo: Identificar alterações auditivas em crianças pré-escolares por meio de um programa de triagem auditiva. Método: Trata-se de estudo descritivo, transversal e observacional realizado em duas escolas municipais do município de Mauá. A amostra foi composta por crianças de cinco e seis anos de idade. O programa de triagem auditiva foi composto: a. otoscopia; b. timpanometria, e c. registro das emissões otoacústicas transiente (EOAT) e produto de distorção (EOAPD). Em vista da pandemia iniciada em março de 2020, não foi possível avaliar as crianças de três e quatro anos. Resultados: 28,44% (n= 31) de crianças falharam na otoscopia. Das 78 (71,55%) crianças que passaram na otoscopia, 30,8% falharam na timpanometria; 16,7% nas Emissões Otoacústicas Produto de Distorção (DPOAE) e 19,2% nas Emissões Otoacústicas por estímulo Transiente (TPOAE); 30,76% (n= 24) das crianças falharam em pelo menos um dos três procedimentos. Conclusão: foram identificadas 30,76% de crianças com risco de alteração auditiva que devem ser encaminhadas para avaliação médica e audiológica.

Hearing health programs are predominantly aimed at children between 0 and 3 years of age or those older than 7. Children between these two age groups are not in any of these programs, but it is in this group that the most middle ear problems occur, and, it is in this group, possible to detect minimal, mild, or unilateral hearing loss that was not identified in neonatal hearing screening programs. Objective: To identify hearing alterations in preschool children through a hearing screening program. Method: This is a descriptive, cross-sectional, and observational study conducted in two municipal schools in the municipality of Mauá. The sample consisted of children aged five and six years. The hearing screening program was composed of a. otoscopy; b. tympanometry and, c. recording of transient otoacoustic emissions (TOAE) and distortion product (DPOAE). In view of the pandemic that began in March 2020, it was not possible to evaluate the three and four-year-old children. Results: 28.44% (n= 31) of the children failed otoscopy. Of the 78 (71.55%) children who underwent otoscopy, 30.8% failed tympanometry: 16.7% in Distortion Product Otoacoustic Emissions (DPOAE) and 19.2% in Transient Stimulus Otoacoustic Emissions (TPOAE); 30.76% (n= 24) of the children failed at least one of the three procedures. Conclusion: 30.76% of children at risk of hearing impairment were identified and should be referred for medical and audiological evaluation.

Los programas de salud auditiva están dirigidos principalmente a niños entre 0 y 3 años o mayores de 7 años. Los niños entre estos dos grupos de edad no están en ninguno de estos programas, pero es en este grupo que ocurren la mayoría de los problemas del oído medio, y, es en este grupo, posible detectar la pérdida de audición mínima, leve o unilateral que no se identificó en los programas de cribado auditivo neonatal. Objetivo: Identificar las alteraciones auditivas en niños en edad preescolar a través de un programa de detección auditiva. Método: Se trata de un estudio descriptivo, transversal y observacional realizado en dos colegios municipales del municipio de Mauá. La muestra estuvo constituida por niños de cinco y seis años y sus padres/tutores. El programa de detección de audición estuvo compuesto por: a. Cuestionario para padres/tutores sobre la historia de la salud auditiva de los niños; b. otoscopia; c. timpanometria y, d. Registro de emisiones otoacústicas transitorias (EOT) y producto de distorsión (DPOAE). Ante la pandemia que comenzó en marzo de 2020, no fue posible realizar los reexámenes ni evaluar a los niños de tres y cuatro años. Resultados: 28,44% (n= 31) de los niños no pasaron la otoscopia. De los 78 (71,55%) niños que se sometieron a otoscopia, 30,8% fallaron la timpanometria; 16,7% en emisiones otoacústicas de productos de distorsión (DPOAE) y 19,2% en emisiones otoacústicas de estímulo transitorio (TPOAE); 30,76% (n= 24) de los niños fallaron por lo menos uno de los tres procedimientos. Conclusión: 30,76% de los niños con riesgo de deficiencia auditiva fueron identificados y deben ser referidos para evaluación médica y audiológica.

Fertility preservation in women with haematological malignancies.

The incidence of haematological malignancies is increasing in women of childbearing age. Survival rates accompany this increase, making it essential to assess the impact of treatments on their future quality of life, evaluate the impact of each treatment on ovarian reserve and define the fertility preservation techniques used by women with haematologic malignancies. A retrospective study was conducted after data collection from 61 women diagnosed with haematological malignancies and followed-up in a fertility preservation centre between January 2008 and June 2019. Cancer treatments caused a decrease in ovarian reserve, demonstrated by an increase in FSH levels and a decrease in AMH levels. When assessing which treatments have the greatest impact on AMH levels, we found that the BEACOPP regimen, and the agents vincristine, etoposide, procarbazine, prednisone and the haematopoietic stem cell transplantation were mainly responsible. Regarding pregnancy after oncological treatments, of the eleven women who became pregnant, ten did so spontaneously. This study reinforces the importance of referring patients to a fertility preservation consultation before starting oncological treatment, as most of them opt to preserve fertility. This work also helps to clarify the impact of each chemotherapeutic agent on the ovarian reserve.