Analyzing Neoadjuvant Chemotherapy Effects in HER2-Low Breast Cancer: Real World Data.

PURPOSE: Neoadjuvant chemotherapy (NAC) can be used as upfront therapy in aggressive breast cancer (BC). human epidermal growth factor receptor 2 (HER2)-low BC, defined as tumors scoring +1 or +2 on immunohistochemistry without HER2 gene amplification by in situ hybridization, lacks information on real-world data (RWD) outcomes, especially in the NAC setting. This subgroup, which does not reach the HER2 positive criteria due to its lower receptor expression, represents a distinct clinical category potentially requiring tailored therapeutic approaches. STUDY OBJECTIVE:  The objective of this study is to characterize patients with BC with HER2-low status who received NAC in a Brazilian public reference center for female tumors and key outcomes such as pathological complete response (pCR), overall survival (OS), and metastasis-free survival (MFS). METHODS: A retrospective cohort study based on a large BC database from a reference cancer center in Brazil. Patients with BC that received NAC, diagnosed between 2011 and 2020, were included if they presented HER2-low status (defined as tumors scoring +1 or +2 on immunohistochemistry without HER2 gene amplification by in situ hybridization) and had complete data on outcomes. Clinical and demographic data were collected, such as age, menopausal status, Ki-67, hormone receptor expression and others. Key outcomes from the study comprised pCR (defined as ypT0/TIs/ypN0), overall survival, and metastasis-free survival (MFS). Survival analyses were conducted through the semiparametric Kaplan-Meier method to assess OS and MFS by pCR status, considering BC diagnosis as the index date. RESULTS: Overall, 297 patients were eligible and 141 were included in the study after matching the HER2-low definition. The pCR was seen in 18 out of 141 patients (12.7%). The median overall survival was 8.2 years, and the median MFS was 2.7 years. The OS of pCR was 83.4% and non-pCR was 58.1%; the DFS of pCR was 55.5% and non-pCR 40.6%. CONCLUSION: This study gives updated insights on pCR, OS, and MFS in women with HER2-low BC exposed to NAC.

Acute post-orchiectomy pain does not reduce alpha rams' interest in feed resources.

Sheep pain is an animal welfare issue monitored based on behavioral responses, including appetite. Dominant (alpha) males have priority for accessing limited feed resources, however, the effects of pain on feed interest in members of a group with defined social hierarchy are unknown. Our objective was to investigate effects of acute post-orchiectomy pain on alpha rams' interest in accessing a limited feed resource. Eighteen rams were randomly housed in pens of 3 rams. After acclimation, the first 5-d (consecutive) battery of a behavior test was performed. In this test, 180 g of the regular diet concentrate was placed in a portable trough in the center of the pen; this feed was supplemental to the diet and represented a limited, albeit strongly preferable feed resource. Rams were filmed for 5 min after the feed introduction. Hierarchical levels (alpha, beta, and gamma) were defined based on the social hierarchical index according to higher initiator and lower receptor agonistic behaviors from the social network analyses. After 15 d, a second 5-d behavioral test battery was repeated. On the following day, alpha rams were castrated. Flunixin meglumine was given immediately before surgery and a final behavioral test was performed 8 h post-orchiectomy, concurrent with an expected peak in postoperative pain. For all recordings, the latency, frequency, and duration of time that each ram had its mouth inside the feed trough were recorded, and the Unesp-Botucatu sheep acute pain scale pain scale (USAPS) was applied. The social hierarchical index was highest in alpha rams, followed by beta and gamma. The pain scores were statistically equivalent across the 11 evaluation days for beta and gamma rams, whereas there was an increase in the final evaluation for alpha. There was no difference in latency, frequency, and duration between alpha, beta, and gamma rams across evaluations. We concluded that acute post-orchiectomy pain did not decrease alpha rams' interest in accessing limited feed. Routine feeding offers a valuable chance to detect pain-related behavior using the USAPS in rams. However, dominance may confound appetite-related behaviors in assessing acute pain, as alpha rams' interest in limited feed remained unaffected by the pain.

Incidence and reasons for discontinuation of first-line therapy in patients with multiple myeloma: results from a historical cohort, Brazil 2009-2020.

Multiple myeloma (MM) is an incurable hematological cancer requiring multiple lines of anti-myeloma regimens to promote disease remission and increase patient survival. The study assessed the incidence and reasons for discontinuation of first-line therapy in outpatients who started MM therapy in Belo Horizonte, Brazil from 2009 to 2020. A historical cohort study in which patients were followed from treatment initiation until discontinuation of first-line therapy. Discontinuation of first-line therapy was characterized as (i) discontinuation followed by a second-line therapy, and (ii) discontinuation that prevented patients from receiving a subsequent line of treatment. Non-parametric competing risk analysis with a 95% confidence interval estimated the cumulative incidences of discontinuation followed by a second-line therapy. The probability of discontinuation was compared according to selected variables using the Gray's test at a significance level of 5%. Approximately half of the participants (n = 260) were female and younger than 65 years. Discontinuation of first-line therapy followed by a second-line therapy accounted for 50.4% of the patients and occurred up to 30th month. The main reason for discontinuation not qualifying patients for receiving second-line therapy was to achieve a response to treatment. The maximum times for discontinuation not followed by a second-line therapy ranged from 12 to 20 months due to deaths or response to treatment. The probability of receiving second-line therapy was higher among patients initiating therapy in 2009-2014 and those not undergoing transplantation. In conclusion, discontinuation of first-line therapy followed by second-line treatment occurred as likely as the discontinuation not followed by a subsequent line.

Real-world evidence of neoadjuvant chemotherapy for breast cancer treatment in a Brazilian multicenter cohort: Correlation of pathological complete response with overall survival.

OBJECTIVES: We aimed to evaluate the pCR rate in patients receiving NAC for the treatment of breast cancer (BC) in a multicenter cohort in Brazil. Additionally, we aimed to use RWD to assess the impact of pCR on OS and DFS. METHODS: This was a retrospective, multicenter cohort study that included female patients over 18 years of age who were diagnosed with nonmetastatic breast cancer and received NAC. OS and DFS at five years were estimated by the Kaplan‒Meier method. Additionally, we conducted a multivariate analysis to identify factors that were significantly associated with pCR and OS. RESULTS: From 2011 to 2020, 1891 patients were included in the study, and 421 (22,3%) achieved pCR (ypT0 ypN0). Considering the presence of residual DCIS, pCR was achieved in 467 patients (23,5%). The pCR rate varied between the subtypes: HER-2+ (p = 0,016) and clinical stage IIIA and IIIB (p < 0,001). Among HER-2+ patients, those who received trastuzumab had a significantly higher pCR rate than those who did not receive trastuzumab (p < 0.0001). Similarly, patients with TNBC who received treatment with platinum-based regimens also showed higher pCR rates (p < 0.0001). OS was grouped according to pCR status, and the OS rate was 88,3% in the pCR group and 58.1% in the non-pCR group (p < 0.0001). The five-year DFS was 92.2% in the pCR group and 64.3% in the non-pCR group (p < 0.0001). CONCLUSION: The pCR rate and its prognostic value varied across BC subtypes. In our study, pCR could be used as a surrogate of favorable clinical outcome, as it was associated with higher OS and DFS rates.

Connecting Implementation Science, Community-Engaged Research, and Health Promotion to Address Cancer Inequities in Massachusetts: The UMB/DF-HCC U54 Outreach Core.

The Outreach Core of the U54 Partnership between the Dana-Farber/Harvard Cancer Center and the University of Massachusetts Boston created a new model for addressing cancer inequities that integrates implementation science, community-engaged research, and health promotion. Key elements of the approach include engaging a Community Advisory Board, supporting students from underrepresented minority backgrounds to conduct health promotion and community-engaged research, increasing the delivery of evidence-based cancer prevention programs to underserved communities (directly and by training local organizations), supporting research-practice partnerships, and disseminating findings. Our model highlights the need for long-term investments to connect underserved communities with evidence-based cancer prevention.

Exploring attitudes of adolescents and caregivers towards community-based delivery of the HPV vaccine: a qualitative study.

BACKGROUND: Human Papillomavirus (HPV) vaccination among adolescents is an important strategy to prevent cervical and other cancers in adulthood. However, uptake remains far below the Healthy People 2020 targets for the US. Given the barriers to population-level vaccination policies and challenges to incorporating additional action items during clinical visits, we sought to explore alternative delivery mechanisms, specifically delivery of the vaccine in community settings. METHODS: We conducted six focus groups (three with adolescents aged 11-14 who had not received the HPV vaccine and three with caregivers of adolescents meeting those criteria) from Black, Latino, and Brazilian communities in Massachusetts. We utilized a framework analysis approach that involved a multi-stage coding process employing both prefigured and emergent codes. Initial interpretations were refined through consultation with an advisory board. RESULTS: Adolescents and caregivers expressed a range of concerns about the HPV vaccine and also described interest in learning more about the vaccine, emphasizing the importance of a relationship with a trusted provider as a facilitator of vaccine acceptance. Regarding community-based delivery of the vaccine, reactions were mainly negative. However, adolescents and caregivers noted that receiving information in community settings that could seed a conversation with a trusted provider would be welcome. Interestingly, the notion of a trusted provider seemed to extend broadly to practitioners linked to the trusted main provider. CONCLUSIONS: The study highlights an opportunity for increasing HPV vaccination among some racial and ethnic minority populations by leveraging trusted community organizations to provide information and seed conversations with a potentially broad group of trusted providers. A task-shifting approach, or reliance on staff with fewer formal credentials, may offer opportunities to support vaccination in resource-constrained settings.

Hepatotoxicidade induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada / Azathioprine-induced hepatotoxicity in a Vogt-Koyanagi-Harada syndrome patient

Este relato teve como objetivo apresentar um caso de hepatotoxicidade colestática induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada. À admissão, apresentava icterícia +3/+4, acolia fecal e colúria, além de aumento de marcadores hepáticos, sendo compatível com síndrome colestática, cuja etiologia foi confirmada após exclusão de outras causas possíveis e retirada da azatioprina. A paciente evoluiu, após 1 semana de retirada do fármaco, com diurese livre de coloração menos escura e evacuação presente, sem acolia. Além disso, houve melhora nos exames que precederam a alta hospitalar

This report aimed at presenting a case of azathioprine-induced cholestatic hepatotoxicity in a patient with Vogt-Koyanagi-Harada syndrome. On admission, she presented with jaundice +3/+4, acholic feces, and choluria, as well as increased hepatic markers, all consistent with cholestatic syndrome, the etiology of which was confirmed after other possible causes were ruled out and azathioprine was discontinued. After 1 week of the drug discontinuation, the patient progressed with free diuresis of lighter color and defecation, with no acholia. In addition, tests performed before discharge were improved.

Artrite reumatoide do tipo EORA com trombocitose significativa: relato de caso / Elderly-onset rheumatoid arthritis with significant thrombocytosis: a case report

Este relato teve como objetivo apresentar um caso de elderly onset rheumatoid arthritis associada à trombocitose reacional significativa. À admissão, o paciente apresentava quadro de poliartrite de pequenas e grandes articulações associado à rigidez matinal. Após exames solicitados, evidenciaram-se trombocitose de 1.697.000 cel./mm³ e anticorpos antipeptídeos citrulinados positivos, sendo diagnosticado com artrite reumatoide do tipo elderly onset rheumatoid arthritis.

This report aimed at presenting a case of elderly-onset rheumatoid arthritis associated with significant reactive thrombocytosis. On admission, the patient presented polyarthritis of small and large joints associated with morning stiffness. After the performance of the requested tests, thrombocytosis of 1,697,000 cells/mm3 and positive anti-CCP were evidenced, and the patient was diagnosed with elderly-onset rheumatoid arthritis.

Clinical Presentation and Response to Therapy in Children with Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis occurs predominantly in adult males. Herein, we compare the clinical presentation and the response to antimony therapy of CL in children versus adults. Participants included 571 patients with CL; of these, 129 were children (age ≤ 12 years). Cure was defined as the complete healing of ulcer in the absence of raised borders at day 90 after initiation of therapy. Failure was defined by the presence of an active ulcer or a scar with elevated borders at day 90. In comparison with adults, children had shorter duration of illness, more lesions in the head, and smaller ulcers. Risk factors for therapeutic failure were younger age, shorter duration of disease, higher number of lesions, and larger size of the biggest ulcer. When age was categorized in ≤ 12-year-olds (children versus adults), it predicted therapeutic failure with statistical significance at day 60 but not at day 90. In conclusion, our data indicate that there are significant differences in the clinical presentation of CL between children and adults. Physicians caring for children with CL should be aware that lesions may take longer to heal and remain alert for the possibility of higher odds of therapeutic failure in this group.

The benefits of a public pharmacist service in chronic hepattis C treatment: The real-life results of sofosbuvir-based therapy.

BACKGROUND: In Brazil, the sofosbuvir-based therapy was introduced in the public health system (SUS) in 2015 to treat Chronic Hepatitis C (CHC). This drug and other direct-acting antiviral agents (DAAs) represent a major advance in the HCV-infection treatment due to their high effectiveness and tolerability. However, the drug safety profile is limited by significant drug interactions and its use is restricted for their high cost. Pharmacists have the opportunity to improve patient care by monitoring the therapy, recommending strategies to guarantee treatment adherence, effectiveness and safety, preventing complications of the disease, and drug-related problems, thus reducing the cost for patients and payers. OBJECTIVE: This study aimed to assess the results of the one of the first patient group treated with sofosbuvir in Brazil and their opinions about the benefits of clinical pharmacist services in the achievement of the cure for CHC and in the management of their therapy difficulties. METHODS: This cohort study (November 2015-January 2017) enrolled 240 patients followed up by the clinical pharmacists at the University Pharmacy (UPh) of the Federal University of Santa Catarina, Brazil, during the CHC treatment. The therapeutic schemes used were sofosbuvir + daclatasvir or + simeprevir associated or not with ribavirin. At the end of the therapy, the patients provided qualitative feedback about the clinical pharmacist services. RESULTS: The study demonstrated high levels of treatment adherence (99.2% of completion rates) and effectiveness rates (Sustained Virological Response rates) (92.1%). Patients reported high levels of satisfaction with the care provided on account of the good rapport built with their pharmacist, the counseling and education on HCV-infection and on sofosbuvir-based therapy utilization, motivation for adherence, and convenient access to the pharmacist. CONCLUSIONS: The clinical pharmacist services provided by the UPh was beneficial to patients treated for CHC with the sofosbuvir-based therapy.

Autocuidado do paciente renal com a fístula arteriovenosa / Autocuidado del paciente renal con la fístula de arteriovenosa

Objetivo: Avaliar atividades de autocuidado com a fístula arteriovenosa em renais crônicos. Metodologia: Estudo descritivo, transversal, com abordagem quantitativa, realizado com 60 pacientes em unidade de diálise no Nordeste Brasileiro, de setembro a outubro de 2018. Os dados foram coletados por meio de entrevistas e analisados através de estatística descritiva. O estudo foi aprovado pelo Comitê de Ética e Pesquisa (Parecer nº 233.953/13). Resultados: Os cuidados realizados frequentemente foram: não permitir a verificação da pressão arterial (71,7%), administração de medicamentos e a coleta de sangue no membro da fístula (71,6%), realizar higiene do membro da fistula (68,4%) e evitar carregar peso (68,3%). Os cuidados menos referidos foram: colocar compressa morna no dia anterior à hemodiálise (30,0%) e fazer exercícios de preensão com bola de borracha (15%). Conclusão: O conhecimento dos pacientes quanto às atividades de autocuidado com a fístula arteriovenosa foi considerado insuficiente, ao evidenciar maior preocupação ante a possibilidade de procedimentos clínicos realizados no braço da fístula, seguidos da higiene e sobrecarga no membro. Estes dados reforçam a importância do planejamento das atividades educativas de forma criativa e permanente pelos profissionais de saúde direcionadas para este público e que poderão auxiliar o enfermeiro na priorização das ações. (AU)

Objetivo: Evaluar actividades de autocuidado con fístula arteriovenosa en renales crónicos. Metodología: Un estudio descriptivo, transversal con un enfoque cuantitativo, realizado con 60 pacientes en una unidad de diálisis en el noreste de Brasil, de septiembre a octubre de 2018. Los datos fueron recolectados por médio de entrevistas y analizados mediante estadística descriptiva. El estudio fue aprobado por el Comité de Ética e Investigación (Opinión nº 233.953/13). Resultados: Los cuidados más frecuentes fueron: no permitir la verificación de la presión arterial (71,7%), la administración de medicamentos y la recolección de sangre en la extremidad de la fístula (71,6%), realizar la higiene de la extremidad de la fístula (68.4%) y evitar cargar peso (68.3%). Los cuidados menos informadas fueron: poner una compresa tibia el día anterior a la hemodiálisis (30.0%) y hacer ejercicios de agarre con pelota de goma (15%). Conclusión: El conocimiento de los pacientes renales crónicos con respecto a las actividades de auto cuidado con fístula arteriovenosa fue insuficiente, y se identificó la actividades más y menos conocida entre los pacientes. Estos datos refuerzan la importancia de las actividades educativas planificadas por profesionales de la salud dirigidas a este público y pueden ayudar a las enfermeras a planificar estas acciones. (AU)

Objective: To evaluate self care activities with arteriovenous fistula in chronic renal patients. Methodology: A descriptive, cross-sectional study with a quantitative approach, conducted with 60 patients in a dialysis unit in Northeast Brazil, from September to October 2018. Data were collected through interviews and analyzed using descriptive statistics. The study was approved by the Ethics and Research Committee (Opinion nº 233.953/13). Results: The most frequent cares were: not allowing blood pressure verification (71.7%) and medication administration and blood collection in the fistula limb (71.6%), perform fistula limb hygiene with water and antiseptic soap (68.4%) and avoid carrying weight (68.3%). The least reported cares were: putting warm compress on the day before hemodialysis (30.0%) and do pressure exercise with rubber ball (15%). Conclusion: The knowledge of chronic renal patients regarding self care activities with arteriovenous fistula was insufficient, and the most and least known care among patients was identified. These data reinforce the importance of educational activities planned by health professionals aimed at this audience and can assist nurses in planning these actions. (AU)

Hearing Rehabilitation through Bone-Conducted Sound Stimulation: Preliminary Results

Abstract Introduction The bone-anchored hearing aid (BAHA) is a bone conduction system that transmits the sound directly to the inner ear by surpassing the skin impedance and the subcutaneous tissue. It is indicated for patients with mixed, conductive and unilateral sensorineural hearing loss who did not benefit from conventional hearing aids (HAs). Although the benefits from BAHA are well demonstrated internationally, this field still lacks studies in Brazil. Objective To assess the auditory rehabilitation process in BAHA users through audiological, speech perception and tinnitus aspects. Methods Individuals with hearing loss were assessed before and after the implantation. The participants were subjected to pure tone audiometry in free field, functional gain audiometry, speech perception tests, tinnitus handicap inventory (THI) in open format, and to the visual analog scale (VAS). Results It was found that the participants benefited from the use of BAHA. The difference in the performance of the participants before and after the BAHA surgery was significant in terms of hearing acuity. There was no statistically significant difference in the speech perception tests. The tinnitus assessment showed that 80% of the participants scored slight tinnitus severity in THI after using a BAHA. Eighty percent of the participants classified their tinnitus as absent tomild in the VAS after the surgery. Conclusion Based on the results of the current study, we can conclude that the participants improved both the auditory perception and the tinnitus handicap. (AU)

Hearing Rehabilitation through Bone-Conducted Sound Stimulation: Preliminary Results.

Introduction The bone-anchored hearing aid (BAHA) is a bone conduction system that transmits the sound directly to the inner ear by surpassing the skin impedance and the subcutaneous tissue. It is indicated for patients with mixed, conductive and unilateral sensorineural hearing loss who did not benefit from conventional hearing aids (HAs). Although the benefits from BAHA are well demonstrated internationally, this field still lacks studies in Brazil. Objective To assess the auditory rehabilitation process in BAHA users through audiological, speech perception and tinnitus aspects. Methods Individuals with hearing loss were assessed before and after the implantation. The participants were subjected to pure tone audiometry in free field, functional gain audiometry, speech perception tests, tinnitus handicap inventory (THI) in open format, and to the visual analog scale (VAS). Results It was found that the participants benefited from the use of BAHA. The difference in the performance of the participants before and after the BAHA surgery was significant in terms of hearing acuity. There was no statistically significant difference in the speech perception tests. The tinnitus assessment showed that 80% of the participants scored slight tinnitus severity in THI after using a BAHA. Eighty percent of the participants classified their tinnitus as absent to mild in the VAS after the surgery. Conclusion Based on the results of the current study, we can conclude that the participants improved both the auditory perception and the tinnitus handicap.

Photodynamic Therapy Mediated by 5-aminolevulinic Acid Promotes the Upregulation and Modifies the Intracellular Expression of Surveillance Proteins in Oral Squamous Cell Carcinoma.

Expression of proteins related to cell surveillance has been described in tumors presenting resistance to photodynamic therapy (PDT). The aim of this study was to verify whether there was upregulation of proteins related to resistance in oral squamous cell carcinoma (OSCC) after PDT. OSCC was chemically induced in rats and treated after one cycle of PDT mediated by 5-aminolevulinic acid (5-ALA-PDT). Immunolabeling of p-NFκB, Bcl-2, survivin, iNOS, p-Akt, p-mTOR and cyclin D1 was performed after the treatment. There was increased expression of Bcl-2 (P = 0.008), iNOS (P = 0.020), p-Akt (P = 0.020) and p-mTOR (P = 0.010) by surviving neoplastic cells after PDT when compared to the control. In conclusion, after one cycle of 5-ALA-mediated PDT, Bcl-2, p-Akt, p-mTOR and iNOS were upregulated in neoplastic cells of OSCC, suggesting an activation of antiapoptosis and cell proliferation pathways. This fact must be considered in the establishment of PDT protocols for OSCC treatment, mainly those in which PDT will be combined with chemotherapy drugs targeted at the studied proteins.

Paracoccidioidomicose na gestação: relato de caso / Paracoccidioidomycosis in pregnancy: case report

Introdução: a paracoccidioidomicose (PCM) é uma micose sistêmica causada pelo fungo Paracoccidioides brasiliensis. O Brasil é considerado país endêmico da doença, que afeta principalmente trabalhadores rurais adultos, do sexo masculino, em contato constante com a vegetação e solo. Objetivo: relatar o caso clínico de uma paciente gestante de 23 anos, apresentando linfadenomegalia em região cervical, supraclavicular e axilar de origem desconhecida, moradora de área urbana em Juiz de Fora - MG e seguimento de diagnóstico e tratamento durante período de internação em unidade hospitalar. Relato de caso: as informações foram obtidas por meio de revisão do prontuário a partir da assinatura do Termo de Consentimento Livre e Esclarecido, entrevista com a paciente, registro fotográfico dos métodos diagnósticos aos quais a paciente foi submetida e revisão da literatura; realizada biópsia do linfonodo acometido, obtendo o laudo histopatológico de Paracoccidioidomicose. Terapêutica medicamentosa específica foi administrada em regime hospitalar e o quadro sintomático da paciente prosseguiu com involução. Apaciente segue em acompanhamento em pré-natal na unidade, não observando, até o momento, repercussões materno-fetais ao uso da Anfotericina B, prosseguindo assim, com involução do quadro. Conclusão: verificou-se que a Paracoccidioidomicose na gravidez deve ser abordada clinicamente de forma atenta e enérgica tendo em vista minimizar ou tornar nulas as repercussões materno-fetais graves

Introduction: paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis. Brazil is considered endemic to this disease, affecting mainly adult rural male workers in constant contact with vegetation and soil. Objective: to report the clinical case of a 23-year-old pregnant woman, showing lymphadenomegaly in the cervical, supraclavicular and axillary spots, living in an urban area. Case report: the information was obtained by reviewing the medical files after the Free Informed Consent was signed, interviewing the patient along with pictures of the diagnostic methods the patient was submitted and literature review; a biopsy of the affected lymph node obtained the histopathological report of Paracoccidioidomycosis. Specific drug therapy was started on an in-patient basis, and the patient's clinical picture proceeded with involution. The follow up has been made on out-patient prenatal care, and has not observed, until now, maternal-fetal repercussions on the use of Amphotericin B, followed by clinical signs involution. Conclusion: It has been observed that paracoccidioidomycosis in pregnancy should be approached more aggressively in order to minimize or render serious maternal-fetal repercussions void.

Hepatitis C in Brazil: lessons learned with boceprevir and telaprevir.

In 2012, the first-generation protease inhibitors telaprevir (TVR) and boceprevir (BOC) were introduced in the Brazilian health system for treatment of chronic hepatitis C, after their approval by the National Committee for Health Technology Incorporation (CONITEC). However, these medicines were discontinued in 2015. The short period of use in therapy and their high cost require a discussion about the consequences for patients and for the health system of the early incorporation of new therapies. The article presents a qualitative analysis of the incorporation process of both medications in Brazil and the results of a multicenter study that included patients treated with BOC or TVR between January 2011 and December 2015 in five Brazilian cities. The study included 855 patients (BOC: n=247) and (TVR: n=608). The document analysis showed that CONITEC's decision to incorporate BOC and TVR was based on results of phase III clinical trials that compared sustained virologic response (SVR) rates of patients treated with BOC and TVR with rates of those that received placebo. However, these studies included a low percentage of cirrhotic patients. The SVR rates observed in this multicenter study were worse than clinical trials pointed out (BOC: 45.6%; TVR: 51.8%), but similar to those achieved with previously adopted therapies. The discontinuation rate due to adverse events was (BOC: 15.4%; TVR: 12.7%). Based on these unsatisfactory results, the study brings a discussion that goes beyond the therapy outcomes, exploring the incorporation of these high-cost medicines and the related decision-making process, contributing to future decisions in medicine policies and in the treatment of chronic hepatitis C.

Quality Assessment of Prognostic Studies Using Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma.

Cancer stem cells (CSC) have been investigated as prognostic markers in oral squamous cell carcinoma (OSCC). However, an assessment of the reporting quality of these studies has not been performed yet. The aim of this study was to describe the reporting quality of prognostic studies involving CSCs and OSCC, focusing mainly on the immunohistochemical reproducibility. By means a systematic review, 34 articles were selected. Analyses of both general reporting quality and immunohistochemistry technique were performed by using checklists for multiple aspects related to study reproducibility. A total of 21 different CSC markers were cited in the selected studies, evaluated by means of a wide range of antibodies, most of them (40.3%) without clone description. Discrepancies in intracellular immunolabeling were noted for some markers. The mean global score for general quality assessment revealed limits in the quality of the articles. The main problems were related to lack of report on OSCC characteristics and treatment, sample size rationale, and sensitivity analysis or internal validation of the markers. Although there was a high frequency of studies having "good or very good" score for immunohistochemistry reproducibility, the frequency of articles with "poor or very poor" score for individual items was expressive, mainly for description of immunolabeling analysis (38.2% of the studies were poorly described). In conclusion, although there is a significant range of CSC markers with promising results for prognosis of OSCC, the inadequate reporting of important sections in the published studies, including immunohistochemistry technique, may limit the quality of the investigation.

Resistance of oral cancer cells to 5-ALA-mediated photodynamic therapy.

Photodynamic therapy (PDT) has been indicated for oral squamous cell carcinoma (OSCC) at early stages. Chemo and radio-resistance are frequently observed in OSCC, but it is unknown whether this tumor can develop resistance to PDT. It was investigated the process of acquiring resistance to multiple cycles of PDT by using OSCC cells. We also analyzed the expression of anti-apoptotic proteins and those related to Akt/mTOR pathway. Sub-lethal doses of PDT were applied, consisting of a constant concentration of 5-aminolevulinic acid (5-ALA) (1 mM, 4-h incubation) and increasing irradiation dose with LED (from 5.86 to 10.54 J/cm2 ). Cell viability, migration capacity, intracellular expression of protoporphyrin IX (PpIX), mitochondrial density, and pro-survival proteins were investigated in PDT-resistant cells. Six OSCC cell generations resistant to PDT were isolated. The resistant cells exhibited a survival phenotype characterized by a reduction in the expression of endogenous PpIX, increase in mitochondrial density, increase in migration capacity, and up-regulation of p-NFκB, p-survivin, iNOS, p-Akt Ser473 , cyclin D1, p-mTOR Ser2481 , and p-mTOR Ser2448 . OSCC cells are able to survive doses of 5-ALA-PDT by reducing PpIX synthesis and activating signaling pathways related to the inhibition of apoptosis and improvement of cell proliferation. Further studies are necessary to confirm whether this PDT-resistance phenotype can be clinically present, mainly in OSCC showing clinical recurrences after exposure to different PDT protocols.

Frequency and risk factors for the birth of small-for-gestational-age newborns in a public maternity hospital.

OBJECTIVE:: To determine the frequency and risk factors of small-for-gestational-age newborns in a high-risk maternity. METHODS:: This is an observational, cross-sectional, and case-control study, conducted in a public tertiary care maternity hospital. Data from 998 newborns and their mothers were collected through interviews and review of medical records and prenatal care cards. Some placentas underwent histopathological analysis. The variables of small-for-gestational-age and non-small-for-gestational-age newborns and of their mothers were statistically compared by means of Student's t test, Fisher's exact test, and odds ratio. The significance level used was 0.050. RESULTS:: There was a 17.9% frequency of small-for-gestational-age newborns. The statistically significant factors associated with the birth of these babies were female sex (p=0.012); positive history of another small-for-gestational-age child (p=0.006); inadequate prenatal care (p=0.019); smoking (p=0.003); hypertensive disorders of pregnancy (p=0.007); placental bleeding (p=0.009) and infarction (p=0.001). CONCLUSION:: In the population studied, the frequency of small-for-gestational-age newborns was high and associated with sex, inappropriate prenatal care, presence of maternal diseases and addictions, and placental abnormalities. OBJETIVO:: Determinar a frequência e os fatores de risco de recém-nascidos pequenos para idade gestacional em uma maternidade de alto risco. MÉTODOS:: Trata-se de um estudo observacional, transversal e caso-controle, realizado em maternidade pública de nível terciário. Foram levantados dados de 998 recém-nascidos e de suas respectivas mães por meio de entrevista e análise de prontuários e de cartões do pré-natal. Algumas placentas foram submetidas à análise anatomopatológica. As variáveis dos recém-nascidos pequenos e não pequenos para idade gestacional e de suas respectivas mães foram comparadas estatisticamente pelo teste paramétrico t de Student, pelo teste exato de Fisher e por odds ratio. O nível de significância adotado foi de 0,050. RESULTADOS:: A frequência de recém-nascidos pequenos para idade gestacional foi de 17,9%. Os fatores com significado estatístico associados ao nascimento desses bebês foram sexo feminino (p=0,012); história positiva para filho anterior pequeno para idade gestacional (p=0,006); realização de pré-natal inadequado (p=0,019); tabagismo (p=0,003); doença hipertensiva específica da gestação (p=0,007); hemorragia (p=0,009) e infarto (p=0,001) placentários. CONCLUSÃO:: Na população estudada, a frequência de recém-nascidos pequenos para idade gestacional foi elevada e relacionada ao sexo, à inadequação do pré-natal, à presença de doenças e vícios maternos e às alterações placentárias.

Frequency and risk factors for the birth of small-for-gestational-age newborns in a public maternity hospital / Frequência e fatores de risco para o nascimento de recém-nascidos pequenos para idade gestacional em maternidade pública

ABSTRACT Objective: To determine the frequency and risk factors of small-for-gestational-age newborns in a high-risk maternity. Methods: This is an observational, cross-sectional, and case-control study, conducted in a public tertiary care maternity hospital. Data from 998 newborns and their mothers were collected through interviews and review of medical records and prenatal care cards. Some placentas underwent histopathological analysis. The variables of small-for-gestational-age and non-small-for-gestational-age newborns and of their mothers were statistically compared by means of Student's t test, Fisher's exact test, and odds ratio. The significance level used was 0.050. Results: There was a 17.9% frequency of small-for-gestational-age newborns. The statistically significant factors associated with the birth of these babies were female sex (p=0.012); positive history of another small-for-gestational-age child (p=0.006); inadequate prenatal care (p=0.019); smoking (p=0.003); hypertensive disorders of pregnancy (p=0.007); placental bleeding (p=0.009) and infarction (p=0.001). Conclusion: In the population studied, the frequency of small-for-gestational-age newborns was high and associated with sex, inappropriate prenatal care, presence of maternal diseases and addictions, and placental abnormalities.

RESUMO Objetivo: Determinar a frequência e os fatores de risco de recém-nascidos pequenos para idade gestacional em uma maternidade de alto risco. Métodos: Trata-se de um estudo observacional, transversal e caso-controle, realizado em maternidade pública de nível terciário. Foram levantados dados de 998 recém-nascidos e de suas respectivas mães por meio de entrevista e análise de prontuários e de cartões do pré-natal. Algumas placentas foram submetidas à análise anatomopatológica. As variáveis dos recém-nascidos pequenos e não pequenos para idade gestacional e de suas respectivas mães foram comparadas estatisticamente pelo teste paramétrico t de Student, pelo teste exato de Fisher e por odds ratio. O nível de significância adotado foi de 0,050. Resultados: A frequência de recém-nascidos pequenos para idade gestacional foi de 17,9%. Os fatores com significado estatístico associados ao nascimento desses bebês foram sexo feminino (p=0,012); história positiva para filho anterior pequeno para idade gestacional (p=0,006); realização de pré-natal inadequado (p=0,019); tabagismo (p=0,003); doença hipertensiva específica da gestação (p=0,007); hemorragia (p=0,009) e infarto (p=0,001) placentários. Conclusão: Na população estudada, a frequência de recém-nascidos pequenos para idade gestacional foi elevada e relacionada ao sexo, à inadequação do pré-natal, à presença de doenças e vícios maternos e às alterações placentárias.