Complete Response With Trametinib in Advanced Low-Grade Serous Ovarian Carcinoma: A Case Report.

Low-grade serous ovarian carcinoma (LGSOC) is an uncommon subtype of ovarian cancer, and it is usually associated with reduced sensitivity to chemotherapy and worse outcomes. We present a case involving a 45-year-old female patient diagnosed with stage III-C low-grade serous ovarian carcinoma (LGSOC) in 2013. She achieved a complete response for 29 months after undergoing platinum-based chemotherapy and interval cytoreduction. However, in 2016, both local and distant relapses were observed. As there was no benefit from hormonal therapy and the patient refused chemotherapy, bevacizumab was initiated, resulting in disease stabilization for 30 months. At disease progression, trametinib was proposed, and the patient experienced an ongoing sustained complete response for over 36 months. To the best of our knowledge, this is the first report, outside of a clinical trial, regarding a complete response with single agent MEK inhibitor therapy in a patient with recurrent LGSOC, with unknown BRAF V600E mutation. We present the following case in accordance with the CAse REports (CARE) checklist.

Comparing Prognosis for BRCA1, BRCA2, and Non-BRCA Breast Cancer.

BACKGROUND: Germline pathogenic variants (PV) in BRCA1 and BRCA2 genes, which account for 20% of familial breast cancer (BC) cases, are highly penetrant and are associated with Hereditary Breast/Ovarian Cancer Syndrome. Previous studies, mostly including higher numbers of BRCA1 BC patients, yielded conflicting results regarding BRCA1/2 BC outcomes. In the Portuguese population, BRCA2 BC is diagnosed more frequently than BRCA1 BC. We aimed to compare clinicopathological characteristics and prognosis between BC patients with BRCA1 and BRCA2 mutations and a control group without germline PV (BRCA-wt). Furthermore, we explored the frequency and outcomes of risk-reducing surgeries in BRCA-mutated patients. METHODS: Prospective follow-up was proposed for patients with a diagnosed BRCA1/2 PV. For this study, a matched control group (by age at diagnosis, by decade, and by stage at diagnosis) included BC patients without germline PV. We compared overall survival (OS) and invasive disease-free survival (iDFS) within the three groups, and the use of risk-reducing surgeries among the BRCA cohort. RESULTS: For a mean follow-up time of 113.0 months, BRCA-wt patients showed longer time to recurrence (p = 0.002) and longer OS (p < 0.001). Among patients with BRCA mutations, no statistical differences were found, although patients with BRCA2 BC had longer iDFS and OS. Uptake of risk-reducing surgeries (contralateral prophylactic mastectomy and salpingo-oophorectomy) were negative predictors of invasive disease and death, respectively. CONCLUSIONS: Testing positive for a BRCA PV is associated with a higher risk of relapse and death in patients with BC in the Portuguese population. Risk-reducing mastectomy and salpingo-oophorectomy were associated with lower incidence of relapse and longer median iDFS and OS, respectively.

Accuracy of intrapartum cardiotocography in identifying acidemia at birth by umbilical cord blood gasometry in high-risk pregnancies.

OBJECTIVE: The aim of this study was to evaluate the accuracy of intrapartum cardiotocography in identifying acidemia at birth by umbilical cord blood gasometry in high-risk pregnancies. METHODS: This was a retrospective cohort study of singleton high-risk parturients using intrapartum cardiotocography categories I, II, and III. The presence of fetal acidemia at birth was identified by the analysis of umbilical cord arterial blood pH (<7.1). Associations between variables were determined using the chi-square test and Kruskal-Wallis tests. RESULTS: We included 105 cases of cardiotocography category I, 20 cases of cardiotocography category II, and 10 cases of cardiotocography category III. cardiotocography category III had a higher prevalence of cesarean sections compared to cardiotocography category I (90.0 vs. 42.9%, p<0.006). Venous pH was higher in patients with cardiotocography category I compared to cardiotocography category III (7.32 vs. 7.23, p=0.036). Prevalence of neonatal intensive care unit (NICU) admission was lower in neonates of patients with cardiotocography category I compared to cardiotocography category III (3.8 vs. 30.0%, p=0.014). Prevalence of composite adverse outcomes was lower in neonates of patients with cardiotocography category I compared to cardiotocography category II (9.5 vs. 30.0%, p=0.022) and cardiotocography category III (9.5 vs. 60.0%, p=0.0004). cardiotocography categories II and III had low sensitivity (0.05 and 0.00, respectively) and high negative predictive value (NPV) (0.84 and 0.91, respectively) for identifying fetal acidemia at birth. The three categories of intrapartum cardiotocography showed high specificities (96.0, 99.0, and 99.0%, respectively). CONCLUSION: All three categories of intrapartum cardiotocography showed low sensitivity and high specificity for identifying acidemia at birth.

Ectopic Cushing's Syndrome Secondary to Acinic Cell Carcinoma of the Parotid Gland: A Case Report.

We present a case report of a patient with a rare high-grade transformation of an acinic cell carcinoma (ACC) of the parotid gland, who developed Cushing's syndrome (CS) as a result of ectopic secretion of adrenocorticotropic hormone by the tumour. The hypercortisolism was successfully treated with metyrapone, and the ACC was treated with local radiotherapy and a combined six cycles of gemcitabine and cisplatin, having achieved a partial response to the tumour. A multidisciplinary approach and combined medical treatment with radiotherapy and were essential for disease control and CS management. ACC should be considered in the differential diagnosis of ectopic CS.

Accuracy of intrapartum cardiotocography in identifying fetal acidemia by umbilical cord blood analysis in low-risk pregnancies.

OBJECTIVE: The aim of this study was to evaluate the accuracy of intrapartum cardiotocography in identifying fetal acidemia by umbilical cord blood analysis in low-risk pregnancies. METHODS: This is a retrospective cohort study of low-risk singleton pregnancies in labor after performing intrapartum cardiotocography categories I, II, and III. The presence of fetal acidemia at birth was identified by analyzing the pH of umbilical cord arterial blood (pH<7.1). RESULTS: No significant effect of the cardiotocography category on the arterial (p=0.543) and venous (p=0.770) pH of umbilical cord blood was observed. No significant association was observed between the cardiotocography category and the presence of fetal acidemia (p=0.706), 1-min Apgar score <7 (p=0.260), hospitalization in the neonatal intensive care unit (p=0.605), newborn death within the first 48 h, need for neonatal resuscitation (p=0.637), and adverse perinatal outcomes (p=0.373). Sensitivities of 62, 31, and 6.0%; positive predictive values of 11.0, 16.0, and 10.0%; and negative predictive values of 85, 89.0, and 87.0% were observed for cardiotocography categories I, II, and III, respectively. CONCLUSION: The three categories of intrapartum cardiotocography presented low sensitivities and high negative predictive values to identify fetal acidemia at birth in low-risk pregnancies.

Accuracy of intrapartum cardiotocography in identifying acidemia at birth by umbilical cord blood gasometry in high-risk pregnancies

SUMMARY OBJECTIVE: The aim of this study was to evaluate the accuracy of intrapartum cardiotocography in identifying acidemia at birth by umbilical cord blood gasometry in high-risk pregnancies. METHODS: This was a retrospective cohort study of singleton high-risk parturients using intrapartum cardiotocography categories I, II, and III. The presence of fetal acidemia at birth was identified by the analysis of umbilical cord arterial blood pH (<7.1). Associations between variables were determined using the chi-square test and Kruskal-Wallis tests. RESULTS: We included 105 cases of cardiotocography category I, 20 cases of cardiotocography category II, and 10 cases of cardiotocography category III. cardiotocography category III had a higher prevalence of cesarean sections compared to cardiotocography category I (90.0 vs. 42.9%, p<0.006). Venous pH was higher in patients with cardiotocography category I compared to cardiotocography category III (7.32 vs. 7.23, p=0.036). Prevalence of neonatal intensive care unit (NICU) admission was lower in neonates of patients with cardiotocography category I compared to cardiotocography category III (3.8 vs. 30.0%, p=0.014). Prevalence of composite adverse outcomes was lower in neonates of patients with cardiotocography category I compared to cardiotocography category II (9.5 vs. 30.0%, p=0.022) and cardiotocography category III (9.5 vs. 60.0%, p=0.0004). cardiotocography categories II and III had low sensitivity (0.05 and 0.00, respectively) and high negative predictive value (NPV) (0.84 and 0.91, respectively) for identifying fetal acidemia at birth. The three categories of intrapartum cardiotocography showed high specificities (96.0, 99.0, and 99.0%, respectively). CONCLUSION: All three categories of intrapartum cardiotocography showed low sensitivity and high specificity for identifying acidemia at birth.

Accuracy of intrapartum cardiotocography in identifying fetal acidemia by umbilical cord blood analysis in low-risk pregnancies

SUMMARY OBJECTIVE: The aim of this study was to evaluate the accuracy of intrapartum cardiotocography in identifying fetal acidemia by umbilical cord blood analysis in low-risk pregnancies. METHODS: This is a retrospective cohort study of low-risk singleton pregnancies in labor after performing intrapartum cardiotocography categories I, II, and III. The presence of fetal acidemia at birth was identified by analyzing the pH of umbilical cord arterial blood (pH<7.1). RESULTS: No significant effect of the cardiotocography category on the arterial (p=0.543) and venous (p=0.770) pH of umbilical cord blood was observed. No significant association was observed between the cardiotocography category and the presence of fetal acidemia (p=0.706), 1-min Apgar score <7 (p=0.260), hospitalization in the neonatal intensive care unit (p=0.605), newborn death within the first 48 h, need for neonatal resuscitation (p=0.637), and adverse perinatal outcomes (p=0.373). Sensitivities of 62, 31, and 6.0%; positive predictive values of 11.0, 16.0, and 10.0%; and negative predictive values of 85, 89.0, and 87.0% were observed for cardiotocography categories I, II, and III, respectively. CONCLUSION: The three categories of intrapartum cardiotocography presented low sensitivities and high negative predictive values to identify fetal acidemia at birth in low-risk pregnancies.

Experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária / Experience in managing action research on hepatitis C survey in the prison community

Resumo Objetivou-se relatar a experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária no Triângulo Mineiro, Minas Gerais. A proposta foi desenvolvida entre março de 2019 e março de 2020, alcançando 240 pessoas, com o intuito de conter a disseminação do agravo por meio de inquérito, testagem e acompanhamento dos casos positivos. Adotou-se ação intersetorial, com articulação entre universidades, sociedade médica, hospital de ensino e Secretaria de Estado de Justiça e Segurança Pública. As estratégias para o gerenciamento da pesquisa-ação foram: cenários e atores do estudo, registro e formalização da atividade, aplicação dos testes e manejo dos internos reagentes. Dificuldades foram identificadas quanto à acomodação de rotinas entre equipe de pesquisadores e funcionamento próprio da penitenciária, o que exigiu treinamento ostensivo entre as partes e articulações gerenciais. Considera-se que o relato, quando destaca as estratégias adotadas para a condução da pesquisa, colabora para a organização de investigações futuras que visem acessar essa população ainda invisibilizada.

Abstract We aimed to report the experience in managing action research on hepatitis C investigation in the prison community in the Triângulo Mineiro region, Minas Gerais, Brazil. The proposal was developed from March 2019 to March 2020, reaching 240 people to contain the spread of the disease through a survey, testing, and monitoring of positive cases. We adopted intersectoral action with articulation between Universities, Medical Society, Teaching Hospital, and State Secretariat for Justice and Public Security. Strategies for the management of action research are described: study settings and stakeholders, registration and formalization of the activity, application of tests, and management of reagent inmates. We identified difficulties regarding the accommodation of routines among the research team and the proper functioning of the penitentiary, which required extensive training between the parties and managerial articulations. We consider that the report collaborates with the organization of future research aimed at accessing this still invisible population, the prison community when it highlights the strategies adopted to conduct the research.

Experience in managing action research on hepatitis C survey in the prison community. / Experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária.

We aimed to report the experience in managing action research on hepatitis C investigation in the prison community in the Triângulo Mineiro region, Minas Gerais, Brazil. The proposal was developed from March 2019 to March 2020, reaching 240 people to contain the spread of the disease through a survey, testing, and monitoring of positive cases. We adopted intersectoral action with articulation between Universities, Medical Society, Teaching Hospital, and State Secretariat for Justice and Public Security. Strategies for the management of action research are described: study settings and stakeholders, registration and formalization of the activity, application of tests, and management of reagent inmates. We identified difficulties regarding the accommodation of routines among the research team and the proper functioning of the penitentiary, which required extensive training between the parties and managerial articulations. We consider that the report collaborates with the organization of future research aimed at accessing this still invisible population, the prison community when it highlights the strategies adopted to conduct the research.

Objetivou-se relatar a experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária no Triângulo Mineiro, Minas Gerais. A proposta foi desenvolvida entre março de 2019 e março de 2020, alcançando 240 pessoas, com o intuito de conter a disseminação do agravo por meio de inquérito, testagem e acompanhamento dos casos positivos. Adotou-se ação intersetorial, com articulação entre universidades, sociedade médica, hospital de ensino e Secretaria de Estado de Justiça e Segurança Pública. As estratégias para o gerenciamento da pesquisa-ação foram: cenários e atores do estudo, registro e formalização da atividade, aplicação dos testes e manejo dos internos reagentes. Dificuldades foram identificadas quanto à acomodação de rotinas entre equipe de pesquisadores e funcionamento próprio da penitenciária, o que exigiu treinamento ostensivo entre as partes e articulações gerenciais. Considera-se que o relato, quando destaca as estratégias adotadas para a condução da pesquisa, colabora para a organização de investigações futuras que visem acessar essa população ainda invisibilizada.

OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized clinical trial.

BACKGROUND AND PURPOSE: In breast cancer (BC) patients, the involvement of four or more lymph nodes (LN) is an indication of regional irradiation. The optimal treatment strategy remains unclear when fewer nodes are involved and lymphadenectomy is not performed. We designed a clinical trial to show the non-inferiority of Incidental (INC) compared to intentional (INT) irradiation of axillary nodes in patients with early-stage BC and low burden LN involvement. MATERIALS AND METHODS: BC patients, cN0 (n = 487) undergoing breast conservation surgery and sentinel node biopsy, with total tumor load assessed by OSNA (One-Step Nucleic Acid Amplification) of 250-15,000 copies mRNA CK19/µL in sentinel LN were randomized to receive INC or INT nodal irradiation. The primary endpoint was 5-year disease-free survival (DFS). Secondary endpoints were locoregional recurrence (LRR), distant recurrence (DR), and acute and chronic toxicity (CT). RESULTS: Five-years DFS were 93.7% (INC) and 93.8% (INT) (difference 0.1% [one-sided 95% CI < 5.7%]; non-inferiority p = 0.075). Cumulative Incidences of LRR were 3.5% (INC) and 3.4% (INT) (difference of 0.1% [<4.8%]; p = 0.021), and 5% (INC) and 3.5% (INT) (difference 1.4% [<6.0%]; non-inferiority p = 0.101) for DR. CT was more Incident with INT (26.9%) than with INC (19.2%), though the difference was not statistically significant (HR 1.39 [95% CI: 0.92, 2.10]; p = 0.11). CONCLUSION: Intentional does not outperform incidental irradiation by more than 5.7% in terms of 5-year DFS, 4.8% for LRR, and 6% for DR. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02335957.

Humoral Immune Response of SARS-CoV-2-Infected Patients with Cancer: Influencing Factors and Mechanisms.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with cancer show worse outcomes compared with patients without cancer. The humoral immune response (HIR) of patients with cancer against SARS-CoV-2 is not well characterized. To better understand it, we conducted a serological study of hospitalized patients with cancer infected with SARS-CoV-2. MATERIALS AND METHODS: This was a unicentric, retrospective study enrolling adult patients with SARS-CoV-2 admitted to a central hospital from March 15 to June 17, 2020, whose serum samples were quantified for anti-SARS-CoV-2 receptor-binding domain or spike protein IgM, IgG, and IgA antibodies. The aims of the study were to assess the HIR to SARS-CoV-2; correlate it with different cancer types, stages, and treatments; clarify the interplay between the HIR and clinical outcomes of patients with cancer; and compare the HIR of SARS-CoV-2-infected patients with and without cancer. RESULTS: We included 72 SARS-CoV-2-positive subjects (19 with cancer, 53 controls). About 90% of controls revealed a robust serological response. Among patients with cancer, a strong response was verified in 57.9%, with 42.1% showing a persistently weak response. Treatment with chemotherapy within 14 days before positivity was the only factor statistically shown to be associated with persistently weak serological responses among patients with cancer. No significant differences in outcomes were observed between patients with strong and weak responses. All IgG, IgM, IgA, and total Ig antibody titers were significantly lower in patients with cancer compared with those without. CONCLUSION: A significant portion of patients with cancer develop a proper HIR. Recent chemotherapy treatment may be associated with weak serological responses among patients with cancer. Patients with cancer have a weaker SARS-CoV-2 antibody response compared with those without cancer. IMPLICATIONS FOR PRACTICE: These results place the spotlight on patients with cancer, particularly those actively treated with chemotherapy. These patients may potentially be more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, so it is important to provide oncologists further theoretical support (with concrete examples and respective mechanistic correlations) for the decision of starting, maintaining, or stopping antineoplastic treatments (particularly chemotherapy) not only on noninfected but also on infected patients with cancer in accordance with cancer type, stage and prognosis, treatment agents, treatment setting, and SARS-CoV-2 infection risks.

The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients.

BACKGROUND: Controversies exist about the effect of renin-angiotensin system inhibitors (RASi) on coronavirus disease 2019 (COVID-19) outcome. The inhospital use of RASi and its effect on inflammatory sate are still poorly studied during the COVID-19 pandemic. OBJECTIVES: We aimed to compare the impact of previous and inhospital RASi exposure on the outcome and inflammatory response of COVID-19 patients. METHODS: Single-centre, ambispective analysis of hospitalized adult COVID-19 patients at Hospital de Santa Maria, Lisbon, between March and August 2020 was performed. We excluded asymptomatic patients and those admitted due to another disease. The primary outcome was inhospital all-cause mortality. Illness severity was assessed based on the development of acute respiratory distress syndrome/acute lung injury (ARDS/ALI), intensive care unit (ICU) admission, and need for invasive mechanical ventilation (IMV). We used C-reactive protein (CRP), ferritin, and interleukin 6 (IL-6) as surrogate markers of the inflammatory response. RESULTS: From a total of 432 patients, 279 were selected, among whom 133 (47.7%) were receiving a RASi. Chronic treatment with RASi was not associated with the risk of death (OR 1.24, 95% CI 0.66-2.31, p=0.500), ARDS/ALI development (OR 1.12, 95% CI 0.67-1.86, p=0.676), ICU admission (OR 1.11, 95% CI 0.67-1.84, p = 0.686), and IMV need (OR 1.03, 95% CI 0.58-1.84, p=0.917) in a univariable and multivariable analysis. Inhospital RASi withdrawing was associated with the risk of death (OR 4.38, 95% CI 1.11-17.21, p=0.035) and ARDS/ALI development (OR 4.33, 95% CI 1.49-12.6, p=0.007), the latter remaining significant after adjustment. Previous exposure to RASi was associated with lower CRP levels at admission (p=0.018). IL-6 levels were significantly higher in those patients whose RASi were stopped (p=0.024). CONCLUSION: Previous and inhospital exposure to RASi was not associated with mortality nor severity of COVID-19. This study supports current guidance on RASi management during the COVID-19 pandemic.

Sweet Taste Dysgeusia in a Patient with Indapamide-Related Hyponatremia: Case Report and Review of the Literature.

Sweet taste dysgeusia is a rare symptom where patients experience all food as having a sweet taste. While its cause is still unknown, it has been increasingly reported in the setting of lung cancer and syndrome of inappropriate secretion of antidiuretic hormone-related hyponatremia. In this case report, we present what we believe to be the first case of sweet taste dysgeusia in a non-cancer context. We will briefly review and summarize all published cases describing this symptom and also reflect upon the nature of this condition focusing on the role of serum sodium levels in sweet taste receptor modulation.

Malabsorption Syndrome due to Intestinal Amyloidosis as Presentation of Renal Cell Carcinoma.

Renal cell carcinoma accounts for approximately 3% of adult malignancies. Designated in the literature as "the great masquerader," the great diversity of clinical manifestations is associated with the several paraneoplastic syndromes that potentially accompany it. Paraneoplastic amyloidosis is described in about 3-8% of cases, only exceptionally as an initial manifestation, with uncommon gastrointestinal involvement. A rare case of malabsorption by intestinal amyloidosis is presented as initial manifestation of renal cell carcinoma, emphasizing the need for early recognition of these paraneoplastic conditions.

Acalculous Acute Pancreatitis in a COVID-19 Patient.

Coronavirus disease 2019 (COVID-19) is a multisystemic condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with manifestations ranging from mild upper respiratory symptoms to cytokine storm causing acute respiratory distress syndrome. Pancreatic exocrine tissue and endocrine islets both express angiotensin-converting enzyme 2 (ACE2), the proven receptor for SARS-CoV-2 cell internalization. An increase in pancreatic enzymes has been increasingly recognized in patients with COVID-19, but little is known about the real prevalence of acute pancreatitis in this population. We report a case of acute acalculous pancreatitis in a COVID-19 patient. LEARNING POINTS: Acute pancreatitis may be a manifestation of SARS-CoV-2 infection.Future studies must address the real impact of pancreatic involvement in COVID-19 patients.

T cells in mesenteric and subcutaneous adipose tissue of Holstein-Friesian cows.

The importance of immune cells present in the adipose tissue to metabolic homeostasis has been increasingly recognized. Nevertheless, in bovines few studies have so far addressed the immune cell populations resident in this tissue. Here we developed an eight-colour flow cytometry panel to address T cell populations present in bovine adipose tissue. Our results showed that γδ T cells, CD4+ and CD8+ CD3+ non-γδ T cells, as well as NK cells, are present in the mesenteric and subcutaneous adipose tissue of Holstein-Friesian cows. The frequency of both γδ T cells and CD8+ non-γδ T cells was found higher in mesenteric than in subcutaneous adipose tissue. The majority of T cells in adipose tissue presented a CD45RO+CD62L- phenotype, characteristic of effector memory cells, and the frequency of these cellular populations was higher than in the blood. The ratio of CD4+ T cells over CD8+ T cells was similar between subcutaneous and mesenteric adipose tissue but different from the one found in blood. Overall, our results highlight particular phenotypic characteristics of bovine adipose tissue T cell populations.