New MoS2/Tegafur-Containing Pharmaceutical Formulations for Selective LED-Based Skin Cancer Photo-Chemotherapy.

Non-melanoma skin cancer (NMSC) is one of the most common types of cancer worldwide. Despite the low mortality rate, rising incidence and recurrence rates are a burden on healthcare systems. Standard treatments such as chemotherapy, radiotherapy, and surgery are either invasive or toxic to healthy tissues; therefore, new, alternative, selective treatments are needed. In this work, a combined photothermal and chemotherapeutic approach is proposed. MoS2 was used as photothermal agent. It was prepared by a liquid-phase exfoliation and intercalation method using polyvinylpyrrolidone (PVP), followed by recirculation through a custom-built high-power ultrasonication probe. After 6 h of ultrasonication treatment, the average particle size was 165 ± 170 nm. Near-infrared (NIR) irradiation assays (810 nm, 0.1 W/cm2, 30 min, 180 J/cm2) confirmed that MoS2 nanosheets can efficiently convert NIR light into heat and reach 52 °C. The therapeutic doses of MoS2 (125 µg/mL) and Tegafur (50 µg/mL) were optimized and both were simultaneously incorporated into a Carbopol hydrogel. The cells were brought into contact with the hydrogel and irradiated with a custom-built NIR LED system. In HFF-1 cells (normal human fibroblasts), the metabolic activity was 78% (above the 70% toxicity limit-ISO 10993-5:2009(E)), while in A-431 skin cancer cells, it was 28%. In addition, the MoS2 + Tegafur hydrogels led to a 1.9-fold decrease in A-431 cancer cell metabolic activity, 72 h after irradiation, in comparison to MoS2 hydrogels, indicating a combined effect of photothermal and chemotherapy.

EHMT2/G9a and EZH2: Epimarkers in testicular germ cell tumors.

BACKGROUND: Testicular germ cell tumors remain the most frequent solid malignancies in young males. Despite excellent prognosis, the fact that only 60% of patients at diagnosis have elevated serum tumor markers (dependent on stage and histology) and the poor quality of life of patients who develop resistance to chemotherapy cannot be neglected. Consequently, it is mandatory to bring out novel biomarkers. OBJECTIVES: The main goal was to evaluate EZH2 and EHMT2/G9a immunoexpression in a well-characterized patients' cohort of primary and metastatic testicular germ cell tumors, seeking associations with clinicopathological features and discovering differential immunoexpression patterns among specific subtypes. MATERIALS AND METHODS: First, an in silico analysis of the Cancer Genome Atlas database was performed regarding EZH2 and EHMT2/G9a. Then, immunohistochemistry for EZH2 and EHMT2/G9a was carried out in a cohort of testicular germ cell tumor patients, comprising 155 chemo-naïve primary tumors and 11 chemo-treated metastases. Immunoexpression was evaluated using a digital pathology analysis software. RESULTS: Higher EZH2 and EHMT2/G9a expression levels were found in non-seminoma in the in silico analysis, particularly in embryonal carcinoma. Through digital pathology analysis, non-seminomas showed significantly higher EZH2 and EHMT2/G9a immunoexpression, with embryonal carcinoma showing higher expression. Moreover, mixed tumors with 50% or more of embryonal carcinoma component revealed the highest nuclei positivity for both biomarkers. Cisplatin-exposed metastases demonstrated a higher EZH2-positive nuclei and H-score, as well as higher EHMT2/G9a-positive nuclei. DISCUSSION AND CONCLUSION: Overall, our data suggest that EZH2 and EHMT2/G9a might be associated with greater aggressiveness and, eventually, involved in the metastatic setting, paving the way for testing targeted therapies.

New graphene-containing pharmaceutical formulations for infrared lamps-based phototherapy of skin cancer: In vitro validation and ex-vivo human skin permeation.

Basal cell carcinoma (BCC) is the most common form of human cancer, and treatment usually involves surgery, with alternative strategies being needed. We propose the use of carbopol hydrogels (HG) for topical administration of nanographene oxide (GOn) and partially-reduced nanographene oxide (p-rGOn) for photothermal therapy (PTT) of BCC. GOn and p-rGOn incorporated into the HG present lateral sizes ∼200 nm, being stable for 8 months. After 20 min irradiation with an infrared (IR) photothermal therapy lamp (15.70 mW cm-2), GOn-HG increased temperature to 44.7 °C, while p-rGOn-HG reached 47.0 °C. Human skin fibroblasts (HFF-1) cultured with both hydrogels (250 µg mL-1) maintained their morphology and viability. After 20 min IR irradiation, p-rGOn HG (250 µg mL-1) completely eradicated skin cancer cells (A-431). Ex vivo human skin permeability tests showed that the materials can successfully achieve therapeutic concentrations (250 µg mL-1) inside the skin, in 2.0 h for GO HG or 0.5 h for p-rGOn HG.

Pharmaceutical Formulations Containing Graphene and 5-Fluorouracil for Light-Emitting Diode-Based Photochemotherapy of Skin Cancer.

Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide, among which 80% is basal cell carcinoma (BCC). Current therapies' low efficacy, side effects, and high recurrence highlight the need for alternative treatments. In this work, a partially reduced nanographene oxide (p-rGOn) developed in our laboratory was used. It has been achieved through a controlled reduction of nanographene oxide via UV-C irradiation that yields small nanometric particles (below 200 nm) that preserve the original water stability while acquiring high light-to-heat conversion efficiency. The latter is explained by a loss of carbon-oxygen single bonds (C-O) and the re-establishment of sp2 carbon bonds. p-rGOn was incorporated into a Carbopol hydrogel together with the anticancer drug 5-fluorouracil (5-FU) to evaluate a possible combined PTT and chemotherapeutic effect. Carbopol/p-rGOn/5-FU hydrogels were considered noncytotoxic toward normal skin cells (HFF-1). However, when A-431 skin cancer cells were exposed to NIR irradiation for 30 min in the presence of Carbopol/p-rGOn/5-FU hydrogels, almost complete eradication was achieved after 72 h, with a 90% reduction in cell number and 80% cell death of the remaining cells after a single treatment. NIR irradiation was performed with a light-emitting diode (LED) system, developed in our laboratory, which allows adjustment of applied light doses to achieve a safe and selective treatment, instead of the standard laser systems that are associated with damages in the healthy tissues in the tumor surroundings. Those are the first graphene-based materials containing pharmaceutical formulations developed for BCC phototherapy.

Physical activity promotion in the community pharmacy: An opportunity for an expanded role?

BACKGROUND: Physical inactivity is a major risk factor for the development of chronic diseases, and it is increasingly prevalent in the Portuguese population. Pharmacists' role in promoting physical activity (PA) is still not well established, although health promotion is foreseen by law in Portugal. Competing tasks and location where the pharmacy is embedded can hinder this promotion in their daily practice. OBJECTIVE: The aim of this study was to identify the main barriers and facilitators of physical activity promotion (PAP) in Portuguese community pharmacies and explore possible pathways for future implementation of physical activity promotion. METHODS: In-depth, semi-structured interviews were conducted with purposively enrolled community pharmacists. Participant recruitment was aligned with data saturation. Data analysis comprised a mixed model of a deductive theme mapping strategy using the Theoretical Domains Framework (TDF) for the behaviour of promoting physical activity and an inductive approach for any other relevant themes and which might influence PA promotion. RESULTS: Data saturation was reached at eleven interviews. Barriers and facilitators for the behaviour of promoting PA were identified from 11 out of the 14 TDF domains. Following an inductive approach, other emerging codes were clustered in additional seven major themes. Highlighted barriers focused on domains #1 - Knowledge, #10 - Memory, Attention and Decision Processes and #13 - Environmental Context and Resources. Community mapping, establishment of remuneration models and the use of digital technologies were suggested as additional potential contributors to scale up PAP. CONCLUSION: Community pharmacists are well placed inside their communities to serve as a focal point for signposting, engagement with other healthcare professionals and community resources and activities organized by the pharmacy itself. Pharmacists should be supported in being knowledgeable, aware, and available when promoting PA in their daily counseling.

Prevalence of Sleep Disturbances in Latin American Populations and Its Association with Their Socioeconomic Status-A Systematic Review and a Meta-Analysis.

BACKGROUND: The worldwide increase in the prevalence and incidence of sleep disturbances represents a major public health issue. Among multiple determinants affecting sleep health, an individual's socioeconomic status (SES) is the most ignored and underestimated throughout the literature. No systematic review on the relation between SES and sleep health has been previously conducted in Latin America. METHODS: PRISMA guidelines were used. RESULTS: Twenty articles were included in the final sample (all cross-sectional studies), and twelve among them were rated as fair or poor quality. Among these studies, 80.0% (n = 16) were performed in Brazil, 10.0% (n = 2) were performed in Peru, 5.0% (n = 1) were performed in Chile, and 5.0% (n = 1) were multicentric (11 countries). The combined total number of participants was N = 128.455, comprising 3.7% (n = 4693) children, 16.0% (n = 20,586) adolescents, and 80.3% (n = 103,176) adults. The results show the following: (1) The sleep outcomes analyzed were sleep duration, sleep quality/sleep disturbance, insomnia, excessive daytime sleepiness (EDS), obstructive sleep apnea (OSA)/sleep-disordered breathing (SDB) symptoms, and bruxism. (2) The most used determinants were income, education level, employment status/occupation, wealth/assets, and composite indices. (3) Higher SES was associated with shorter sleep duration. (4) Lower SES was associated with a decrease in sleep quality, less frequent snoring, more prevalent EDS, and sleep bruxism. (5) Lower education was associated with insomnia. (6) Higher education was associated with more sleep bruxism. (7) The pooled prevalence using a meta-analysis of the random effects model was 24.73% (95%CI, 19.98-30.19), with high heterogeneity (I2 = 100%). (8) The prevalence of sleep disturbances decreased with high education (OR, 0.83; 95%CI, [0.69-0.99]; I2 = 79%), while it increased with low income (OR, 1.26; 95%CI, [1.12-1.42]; I2 = 59%), unemployment (OR, 2.84; 95%CI, [2.14-3.76]; I2 = 0%), and being a housewife (OR, 1.72; 95%CI, [1.19-2.48]; I2 = 55%). DISCUSSION: This meta-analysis shows that lower SES (education, income, and work) was associated with sleep disturbances in Latin America. Therefore, sleep disturbance management should be addressed with a multidimensional approach, and a significant investment in targeted public health programs to reduce sleep disparities and support research should be made by the government before the situation becomes uncontrollable.

2D Nanomaterials and Their Drug Conjugates for Phototherapy and Magnetic Hyperthermia Therapy of Cancer and Infections.

Photothermal therapy (PTT) and magnetic hyperthermia therapy (MHT) using 2D nanomaterials (2DnMat) have recently emerged as promising alternative treatments for cancer and bacterial infections, both important global health challenges. The present review intends to provide not only a comprehensive overview, but also an integrative approach of the state-of-the-art knowledge on 2DnMat for PTT and MHT of cancer and infections. High surface area, high extinction coefficient in near-infra-red (NIR) region, responsiveness to external stimuli like magnetic fields, and the endless possibilities of surface functionalization, make 2DnMat ideal platforms for PTT and MHT. Most of these materials are biocompatible with mammalian cells, presenting some cytotoxicity against bacteria. However, each material must be comprehensively characterized physiochemically and biologically, since small variations can have significant biological impact. Highly efficient and selective in vitro and in vivo PTTs for the treatment of cancer and infections are reported, using a wide range of 2DnMat concentrations and incubation times. MHT is described to be more effective against bacterial infections than against cancer therapy. Despite the promising results attained, some challenges remain, such as improving 2DnMat conjugation with drugs, understanding their in vivo biodegradation, and refining the evaluation criteria to measure PTT or MHT effects.

Psoas Abscess and Pott's Disease Masked by Concomitant Invasive Staphylococcus aureus Disease: A Case of Misleading Diagnosis.

Psoas abscess is a rare infection classified as primary or secondary depending on the etiology of infection. Staphylococcus aureus is considered the most frequent causative agent. Nevertheless, psoas abscess persistent lack of improvement or any relapse after successful treatment should remind us to exclude other potential diagnoses. Although less frequently, Pott's disease is still one of the predisposing causes, especially in patients with immunocompromised status. This clinical condition has an indolent course and requires a high index of suspicion to avoid severe morbidity. Early recognition and targeted treatment are the principal means of ensuring tuberculosis control. Here we report a very interesting case of a psoas abscess and Pott's disease in a patient suffering from a misleading diagnosis of invasive staphylococcal disease.

Novel Insights on the Role of Epigenetics in Androgen Receptor's Expression in Prostate Cancer.

The androgens/androgen receptor (AR) axis is the main therapeutic target in prostate cancer (PCa). However, while initially responsive, a subset of tumors loses AR expression through mechanisms putatively associated with epigenetic modifications. In this study, we assessed the link between the presence of CpG methylation in the 5'UTR and promoter regions of AR and loss of AR expression. Hence, we characterized and compared the methylation signature at CpG resolution of these regulatory regions in vitro, both at basal levels and following treatment with 5-aza-2-deoxycytidine (DAC) alone, or in combination with Trichostatin A (TSA). Our results showed heterogeneity in the methylation signature of AR negative cell lines and pinpointed the proximal promoter region as the most consistently methylated site in DU-145. Furthermore, this region was extremely resistant to the demethylating effects of DAC and was only significantly demethylated upon concomitant treatment with TSA. Nevertheless, no AR re-expression was detected at the mRNA or protein level. Importantly, after treatment, there was a significant increase in repressive histone marks at AR region 1 in DU-145 cells. Altogether, our data indicate that AR region 1 genomic availability is crucial for AR expression and that the inhibition of histone methyltransferases might hold promise for AR re-expression.

Ageing in the brain: mechanisms and rejuvenating strategies.

Ageing is characterized by the progressive loss of cellular homeostasis, leading to an overall decline of the organism's fitness. In the brain, ageing is highly associated with cognitive decline and neurodegenerative diseases. With the rise in life expectancy, characterizing the brain ageing process becomes fundamental for developing therapeutic interventions against the increased incidence of age-related neurodegenerative diseases and to aim for an increase in human life span and, more importantly, health span. In this review, we start by introducing the molecular/cellular hallmarks associated with brain ageing and their impact on brain cell populations. Subsequently, we assess emerging evidence on how systemic ageing translates into brain ageing. Finally, we revisit the mainstream and the novel rejuvenating strategies, discussing the most successful ones in delaying brain ageing and related diseases.

Association of the Calcification Score of the Abdominal Aorta, Common Iliac, and Renal Arteries with Outcomes in Living Kidney Donors.

BACKGROUND: Vascular calcification is an ever-more-common finding in protocoled pre-transplant imaging in living kidney donors. We intended to explore whether a connection could be found between the Agatston calcification score, prior to kidney donation, and post-donation renal function. METHODS: This is a retrospective analysis of 156 living kidney donors who underwent living donor nephrectomy between January 2010 and December 2016. We quantified the total calcification score (TCaScore) by calculating the Agatston score for each vessel, abdominal aorta, common iliac, and renal arteries. Donors were placed into two different groups based on their TCaScore: <100 TCaScore group and ≥100 TCaScore group. The relationship between TCaScore, 1-year eGFR, proteinuria, and risk of 1 measurement of decreased renal function (eGFR < 60 mL/min/1.73 m2) over 5 years of follow-up was investigated. RESULTS: The ≥100 TCaScore group consisted of 29 (19%) donors, with a median (interquartile range) calcification score of 164 (117-358). This group was significantly older, 56.7 ± 6.9 vs. 45.5 ± 10.6 (p < 0.001), had a higher average BMI (p < 0.019), and had a lower preoperative eGFR (p < 0.014). The 1-year eGFR was similarly diminished, 69.9 ± 15.7 vs. 76.3 ± 15.5 (p < 0.048), while also having an increased risk of decreased renal function during the follow-up, 22% vs. 48% (p < 0.007). CONCLUSIONS: Our study, through univariate analyses, found a relationship between a TCaScore > 100, lower 1-year eGFR, and decreased renal function in 5 years. However, a higher-than-expected vascular calcification should not be an excluding factor in donors, although they may require closer monitoring during follow-up.

From Chronic Alcohol Consumption to Coma: Report of an Uncommon Cause.

Marchiafava-Bignami disease is a rare condition characterized by demyelination of the corpus callosum that can evolve into necrosis. It is associated with thiamine deficiency, chronic alcohol consumption, and less frequently, severe malnutrition. The diagnosis is based on clinical presentation - altered mental state and changes in a neurological examination - and on neuroimaging studies, especially magnetic resonance imaging. Treatment with parenteral thiamine is recommended. The authors present a case of a 50-year-old male, with chronic alcohol abuse and malnutrition, admitted to the hospital with an acute form of the Marchiafava-Bignami disease. An early diagnosis and treatment facilitated neurological and cognitive recovery.

Microvascular Dysfunction Is Associated With Impaired Myocardial Work in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Multimodality Study.

Background Two-dimensional speckle tracking echocardiography has been shown to correlate with microvascular dysfunction, a hallmark of hypertrophic cardiomyopathy (HCM). We hypothesized that there is an association between myocardial work and left ventricular ischemia, with incremental value to global longitudinal strain, in patients with HCM. Methods and Results We performed a prospective assessment of patients with HCM, undergoing 2-dimensional speckle tracking echocardiography and stress perfusion cardiac magnetic resonance. Results were stratified according to obstructive or nonobstructive HCM and the presence of significant replacement fibrosis (late gadolinium enhancement ≥15% of left ventricular mass). Seventy-five patients with HCM (63% men, age 55±15 years) were evaluated, 28% with obstructive HCM (mean gradient 89±60 mm Hg). Perfusion defects were found in 90.7%, involving 22.5±16.9% of left ventricular mass, and 38.7% had late gadolinium enhancement ≥15%. In a multivariable analysis, a lower global work index (r=-0.519, ß-estimate -10.822; P=0.001), lower global work efficiency (r=-0.379, ß-estimate -0.123; P=0.041), and impaired global constructive work (r=-0.532, ß-estimate -13.788; P<0.001) significantly correlated with ischemia. A segmental analysis supported these findings, albeit with lower correlation coefficients. A global work index cutoff ≤1755 mm Hg% was associated with hypoperfusion with a sensitivity of 88% and a specificity of 71%, while the best cutoff for global longitudinal strain (>-15.5%) had a sensitivity of 64% and a specificity of 57%. The association between myocardial work and perfusion defects was significant independently of late gadolinium enhancement ≥15% and obstructive HCM. Conclusions Impaired myocardial work was significantly correlated with the extent of ischemia in cardiac magnetic resonance, independently of the degree of left ventricular hypertrophy or fibrosis, with a higher predictive power than global longitudinal strain.

Bone mineral density progression following long-term simultaneous pancreas-kidney transplantation in type-1 diabetes.

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPKT) has demonstrated favorable impact on the progression of chronic complications in type-1 diabetes (T1D) and terminal chronic kidney disease (CKD). However, some CKD mineral and bone disorders (CKD-MBD) may persist, even after transplantation. There are only a few studies addressing the long-term progression of bone mineral density (BMD) in these patients. Our aim was to assess baseline BMD and long-term progression and consequences in patients with T1D undergoing SPKT. METHODS: A retrospective cohort included patients undergoing SPKT in our tertiary center between 2000 and 2017. BMD progression was assessed on dual X-ray absorptiometry (DXA). Only patients with baseline data and a minimum follow-up of 2 years were included. RESULTS: Seventy-three patients were included, 53.4% male, with a median age at SPKT of 35 years (interquartile range [IQR] 31; 39). At transplantation, the median T-scores for the lumbar spine (LS) and femoral neck (FN) were -1.6 (IQR -2.6; -1.1) and --2.1 (IQR -2.7; -1.6), respectively. Seventy-five percent of patients presented low BMD (osteopenia or osteoporosis) in the LS and 90% in the FN, with 33% osteoporosis in the LS and 36% in the FN. On multivariate analysis, male gender (odds ratio [OR] 10.82, 95% confidence interval (CI) 2.88-40.70) and low body-mass index (BMI) (OR 0.73, 95% CI 0.55-0.97) were significantly associated with lumbar but not femoral osteoporosis. At long-term follow-up, BMD significantly improved in the LS (ΔT-score +0.41, P<0.001) and FN (ΔT-score +0.29, P=0.01), at a median 4 years after SPKT. Twelve (16.4%) and 9 (12.3%) patients showed persistent FN and LS osteoporosis, respectively. Multivariate linear regression showed that high BMI was predictive of improvement in BMD. CONCLUSIONS: This study demonstrated severe skeletal fragility in T1D patients with terminal CKD undergoing SPKT, more than a quarter of whom showed osteoporosis. The significant improvement in BMD may result from metabolic correction by SPKT and from physiological skeleton mineralization, which continues in this age group. BMD progression was positively associated with BMI, due to improved nutritional balance after transplantation.

CT volumetry performs better than nuclear renography in predicting estimated renal function one year after living donation.

The evaluation of split renal function (SRF) is a critical issue in living kidney donations and can be evaluated using nuclear renography (NR) or computerized tomography (CT), with unclear comparative advantages. We conducted this retrospective study in 193 donors to examine the correlation of SRF assessed by NR and CT volumetry and compared their ability to predict remaining donor renal function at 1 year, through multiple approaches. A weak correlation between imaging techniques for evaluating the percentage of the remaining kidney volume was found in the global cohort, with an R2 = 0.15. However, the Bland-Altman plot showed an acceptable agreement (95% of the difference between techniques falling within - 8.51 to 6.11%). The predicted and observed eGFR one year after donation were calculated using the CKD-EPI, and CG/BSA equations. CT volume showed a better correlation than NR for both formulas (adjusted R2 of 0.42. and 0.61 vs 0.37 and 0.61 for CKD-EPI and CG/ BSA equations, respectively). In non-nested modeling tests, CT volumetry was significantly superior to NR for both equations. CT volumetry performed better than NR in predicting the estimated renal function of living donors at 1-year, independently from the eGFR equation.

Chemotherapy-free treatment of recurrent advanced ovarian cancer: myth or reality?

Advanced ovarian cancer remains a leading cause of death from gynecologic malignancy. Surgery and, in most cases, platinum-based chemotherapy with or without maintenance with bevacizumab and/or poly-ADP ribose polymerase inhibitors (PARPi) represent the mainstay of treatment, but the disease typically recurs. The treatment of these patients represents a clinical challenge because sequential chemotherapy regimens are often used, with suboptimal outcomes and cumulative toxicity. Chemotherapy-free regimens, based on combinations of PARPi, vascular endothelial growth factor receptor inhibitors, anti-programmed cell death protein-1/programmed death-ligand 1, and anti-cytotoxic T-lymphocyte-associated protein-4 antibodies, among others, represent a valid option, with manageable toxicity profile and ease of administration. This review addresses this new strategy in the management of recurrent ovarian cancer and discusses its feasibility in the treatment landscape of the disease.

Relapsed Ovarian Cancer Patients with Ascites and/or Pleural Effusion Still Benefit from Treatment: A Real-Life Study.

(1) Background: Relapsed HGSOC with ascites and/or pleural effusion is a poor-prognostic population and poorly represented in clinical studies. We questioned if these patients are worth treating. In other words, if these patients received the most effective treatment, would it change the course of this disease? To our knowledge this is the first real-life study to evaluate this question in this low-survival population. (2) Methods: To tackle this question we performed a retrospective, multi-centric, real-life study, that reviewed relapsed HGSOC patients with ascites and/or pleural effusion. Our rationale was to compare the OS of two groups of patients: responders, i.e., patients who had an imagological response to treatment (complete/partial response/stable disease, RECIST criteria) versus non-responders (no response/progression upon treatment). We evaluated the predictive value of clinical variables that are available in a real-life setting (e.g., staging, chemotherapy, surgery, platinum-sensitivity). Multivariate logistic regression and survival analysis was conducted. A two-step cluster analysis SPSS tool was used for subgroup analysis. Platinum sensitivity/resistance was also analyzed, as well as multivariate and cluster analysis. (3) Results: We included 57 patients, 41.4% first line responders and 59.6% non-responders. The median OS of responders was 23 months versus 8 months in non-responders (p < 0.001). This difference was verified in platinum-sensitive (mOS 28 months vs. 8 months, p < 0.001) and platinum-resistant populations (mOS 16 months vs. 7 months, p < 0.001). Thirty-one patients reached the second line, of which only 10.3% responded to treatment. Three patients out of thirty-one who did not respond in the first line of relapse, responded in the second line. In the second line, the mOS for the responders' group vs. non-responders was 31 months versus 13 months (p = 0.02). The two step cluster analysis tool found two different subgroups with different prognoses based on overall response rate, according to consolidation chemotherapy, neoadjuvant chemotherapy, FIGO staging and surgical treatment. Cluster analysis showed that even patients with standard clinical and treatment variables associated with poor prognosis might achieve treatment response (the opposite being also true). (4) Conclusions: Our data clearly show that relapsed HGSOC patients benefit from treatment. If given an effective treatment upfront, this can lead to a ~3 times increase in mOS for these patients. Moreover, this was irrespective of patient disease and treatment characteristics. Our results highlight the urgent need for a sensitivity test to tailor treatments and improve efficacy rates in a personalized manner.

COVID-19 in kidney transplant recipients: what have we learned one year later? A cohort study from a tertiary center / COVID-19 em receptores de transplante renal: o que aprendemos um ano depois? Um estudo de coorte a partir de um centro terciário

Abstract Introduction: Kidney transplant (KT) recipients have a high risk for adverse outcomes from infections, such as COVID-19. Methods: We have retrospectively reviewed all KT recipients with documented COVID-19 between March 1, 2020, and March 15, 2021, and analyzed patients' characteristics, clinical course, treatment, and outcomes. Results: We identified 123 patients, 72% were male, with a mean age of 54.5±13.0 years. Twenty percent were asymptomatic, 7% had a nosocomial transmission, and 36% of the remainder required hospitalization. Almost all admitted patients received oxygen, 30% required invasive mechanical ventilation (IMV), more than a half had acute kidney injury, with 10% requiring dialysis, and 20% died. Incidence was comparable to that of the Portuguese population, but the mortality rate was almost four times higher (SMR of 3.768 (95% CI:1.723-7.154). Higher body mass index (OR 1.275, P=0.001), lower baseline graft function (OR 0.968, P=0.015), and nosocomial transmission (OR 13.836, P=0.019) were associated with oxygen demand, whereas female gender (OR 3.801, P=0.031) and lower baseline kidney graft function (OR 0.955, P=0.005), but not body mass index, were associated with IMV and/or death. Conclusion: Mortality rate in KT patients was higher than in the general population and lower baseline kidney function was the most consistent marker for adverse outcomes.

Resumo Introdução: Os receptores de transplante renal (TR) apresentam um alto risco para desfechos adversos de infecções, tais como a COVID-19. Métodos: Revisamos retrospectivamente todos os receptores de TR com COVID-19 documentada entre 1º de Março de 2020 e 15 de Março de 2021, e analisamos as características, curso clínico, tratamento e desfechos dos pacientes. Resultados: Identificamos 123 pacientes, 72% do sexo masculino, com uma média de idade de 54,5±13,0 anos. Vinte por cento eram assintomáticos, 7% apresentaram transmissão nosocomial, e 36% do restante necessitaram de internação. Quase todos os pacientes internados receberam oxigênio, 30% necessitaram de ventilação mecânica invasiva (VMI), mais da metade apresentou lesão renal aguda, com 10% necessitando de diálise, e 20% foram a óbito. A incidência foi comparável à da população portuguesa, mas a taxa de mortalidade foi quase quatro vezes superior (TMP de 3,768 (IC 95%: 1,723-7,154). Maior índice de massa corporal (OR 1,275; P=0,001), menor função do enxerto basal (OR 0,968; P=0,015), e transmissão nosocomial (OR 13,836; P=0,019) foram associados à demanda de oxigênio, enquanto sexo feminino (OR 3,801; P=0,031) e menor função do enxerto renal basal (OR 0,955; P=0,005), mas não índice de massa corporal, foram associados à VMI e/ou óbito. Conclusão: A taxa de mortalidade em pacientes com TR foi mais elevada do que na população em geral e a função renal basal mais baixa foi o marcador mais consistente para desfechos adversos.

Case report: Using DNA short tandem repeats to confirm nongestational origin of pulmonary choriocarcinoma.

Gestational trophoblastic neoplasias (GTN) are malignant neoplasms that occur in pregnant or recently pregnant women. Choriocarcinoma (CCA) is a highly aggressive and rare GTN, and cases outside the female genital tract are commonly seen as secondary manifestations of gynecologic disease. In this paper, we describe the case of a 40 years-old female patient with a primary pulmonary CCA who was surgically treated and for whom the confirmation of the primary origin of the tumor was possible using a DNA short tandem repeat genotyping. Distinction between gestational and non-gestational trophoblastic neoplasia is crucial as they require different therapeutic approach and have different prognoses.