Case report: Treatment with Phesgo® in a patient receiving hemodialysis.

Introduction: Patients with metastatic HER2-positive breast cancer have multiple therapeutic options. However, most are not studied in the renal replacement therapy (RRT) setting. Case report: We report the use of Phesgo® (subcutaneous fixed-dose combination of trastuzumab and pertuzumab) combined with exemestane as a first-line treatment of metastatic HER2-positive breast cancer in a hemodialysis patient with multiple comorbidities. Partial response was attained, with disease progression after 8 months without evidence of significant toxicity. Discussions: This case report is, to our knowledge, the first published case documenting the use of Phesgo® in a hemodialysis patient. No new safety signs were seen, and activity was documented, adding support to the use of this drug combination in such a patient population.

Study design for DESTINY-Breast Respond HER2-low Europe: T-DXd in patients with HER2-low advanced breast cancer.

Trastuzumab deruxtecan (T-DXd) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). Results on T-DXd treatment in HER2-low mBC have so far been limited to clinical trials. DESTINY-Breast Respond HER2-low Europe (NCT05945732) is a multi-center, multi-country, observational, prospective, non-interventional study planning to enroll 1350 patients from 216 sites receiving T-DXd or conventional chemotherapy as their routine clinical care for advanced stage breast cancer in 12 European countries. This non-interventional study will provide real-world insight into T-DXd treatment for HER2-low mBC with data on effectiveness, safety and tolerability, patient-reported outcomes, treatment patterns, geriatric health status and HER2 testing. This will be beneficial for improving guidance to maximize patient treatment benefit.

Trastuzumab deruxtecan (T-DXd; Enhertu^®) is a medicine approved to treat cancers that produce a protein called HER2 on the surface of cancer cells. T-DXd works by targeting the HER2 protein to deliver chemotherapy directly to cancer cells. Until recently, breast cancers were classified as HER2-positive (high level of HER2 protein on cancer cells) or HER2-negative (very low level/no HER2 protein on cancer cells). T-DXd was approved for treating patients with HER2-positive advanced breast cancer in Europe in 2022. In 2023 the DESTINY-Breast04 clinical trial showed that T-DXd was more effective than current standard chemotherapies, when treating advanced breast cancer patients with low levels of the HER2 protein (historically classified as HER2-negative cancer). This trial led to the approval of T-DXd for treating advanced HER2-low breast cancer, providing a new treatment option for 50­60% of breast cancer patients. More information is needed about T-DXd treatment in the real world (for patients treated in the hospital, rather than in a clinical trial). This article describes the purpose and design of the DESTINY-Breast Respond HER2-low Europe study, which will collect and report more information about how effective T-DXd treatment is in the real world. This is a large study aiming to include 1350 eligible patients from 12 countries across Europe. Patients will report their experience of side effects (such as nausea and vomiting) to improve management of T-DXd treatment and maximize patient benefit. The study will also examine how elderly patients respond to T-DXd treatment, and how HER2 levels are being tested. Clinical Trial Registration: ICH CGP: NCT05945732, registered on 6 July 2023 (ClinicalTrials.gov).

Epidemiology, Management, and Survival Outcomes of Germ Cell Cancer in Southern Portugal: A Population-Based Study (2008-2012).

INTRODUCTION: Building on previous suboptimal survival results, we aimed to perform a study of the epidemiological status, management, and outcomes of germ cell tumors (GCT) in the Portuguese population. MATERIALS AND METHODS: Retrospective populational study of GCT cases diagnosed between 2008 and 2012 in southern Portugal. Joinpoint regression was used to compute average annual percentage change (AAPC) in incidence rate. ESMO/EAU guidelines served as references to evaluate compliance. Association between compliance with guidelines and hospital GCT case load was performed by generalized estimating equation. Survival was calculated by Kaplan-Meier and prognostic factors by Cox models. RESULTS: The study included 401 GCT male cases. The AAPC was 5.4% (IC 95% 3.3-7.4, P < .001) from 1999 (an earlier cohort published) to 2012. The median time to diagnosis was 63 days (Q25 = 33 days; Q75 = 114 days; IQR = 81 days). For stage II/III the median time to start chemotherapy was 34 days (Q25 = 22 days; Q75 = 56 days; IQR = 22 days). In 86% cases there was noncompliance with guidelines for the orchiectomy report, 6% for staging, 38% for tumor markers evaluation, 20% for treatment and 25% for chemotherapy dose intensity. The 5-year overall survival was 93.8% (95% CI, 91.3%-96.4%). Hospitals that managed ≤ 3 GCT cases/ year had higher odds for noncompliance with guidelines of blood markers, treatment and dose intensity. None of GCT healthcare access and management factors studied were associated with prognosis. CONCLUSIONS: The burden of GCT is rising in Portugal. Although survival has improved, efforts must be made to nationally enhance training and expertise in GCT and support region adapted models of centralization of care.

Loss of RAS Mutations in Liquid Biopsies of Patients With Multi-Treated Metastatic Colorectal Cancer.

BACKGROUND: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC). METHODS: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment. RESULTS: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients. CONCLUSIONS: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease.

A Rare Case of Isolated Prostate Recurrence From Testicular Seminoma.

We report the case of a 32-year-old male diagnosed with a left-sided testicular seminoma treated with radical inguinal orchiectomy and staged as pT1bN0M0S0 (rete testis invasion) - stage IA. Adjuvant treatment options were discussed, and active surveillance was chosen. Two years later, he presented with urinary retention alternating with pollakiuria, a feeling of incomplete bladder emptying, dyspareunia, and anejaculation. A rectal examination documented an enlarged, nodular, painful prostate. Blood and urine analyses, including serum tumor markers, were unremarkable. Pelvic magnetic resonance (MR) documented a central, nodular, solid, hypermetabolic, prostatic tumor with a size of 40x50x25 mm, invasion of the right seminal vesicle, right anterolateral wall of the rectum, and postero-inferior bladder wall, and an absent lymph node and visceral disease. A transrectal ultrasound-guided (TRUS) biopsy documented prostatic metastasis of the seminoma. The patient was treated with four cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (ChT) with a complete (clinical, radiologic, metabolic, and pathological) response. After five years of follow-up, he remains asymptomatic without a recurrence of the disease.

Characterization of Functional Coatings on Cork Stoppers with Laser-Induced Breakdown Spectroscopy Imaging.

Evaluating the efficiency of surface treatments is a problem of paramount importance for the cork stopper industry. Generically, these treatments create coatings that aim to enhance the impermeability and lubrification of cork stoppers. Yet, current methods of surface analysis are typically time-consuming, destructive, have poor representativity or rely on indirect approaches. In this work, the use of a laser-induced breakdown spectroscopy (LIBS) imaging solution is explored for evaluating the presence of coating along the cylindrical surface and in depth. To test it, several cork stoppers with different shaped areas of untreated surface were analyzed by LIBS, making a rectangular grid of spots with multiple shots per spot, to try to identify the correspondent shape. Results show that this technique can detect the untreated area along with other features, such as leakage and holes, allowing for a high success rate of identification and for its performance at different depths, paving the way for future industry-grade quality control solutions with more complex surface analysis.

Comparative study using propensity score matching analysis in patients undergoing surgery for colorectal cancer with or without multimodal prehabilitation.

INTRODUCTION: The complication rate after major abdominal surgery is from 35 to 50%. The multimodal prehabilitation covers all the pre-operative problems to guarantee a faster recovery and reduce the rate of morbidity and mortality after a colorectal procedure. METHODS: Observational study, in patients with CRC who underwent surgical treatment between November 2020 and September 2022. The data of the patients were placed in 2 groups: prehabilitation group (PPH) and no prehabilitation group (NPPH). Demographic data, type of cancer, operative data, and postoperative data were collected. Characteristics between the groups were compared after a propensity score matching (PSM) analysis for the detection of differences. RESULTS: After the PSM analysis, 46 patients were in PPH, and 63 patients were in NPPH. There was no significant difference in postoperative complications (p = 0.192). The median of comprehensive complication index (CCI) was 0 (p = 0.552). Patients in the NPPH had more hospital readmissions (p = 0.273) and more emergency room visits (p = 0.092). Multivariate log binomial regression adjusted for complications showed that pre-habilitation reduces the risk of a pos-operative complication (OR: 0.659, 95%CI, 0.434-1.00, p = 0.019). CONCLUSIONS: The postoperative complication rate and LOS were similar between patients who receive operative multimodal prehabilitation for CRC surgery and those who did not. Prehabilitation was associated with reduced risk of postoperative complication after multivariate log binomial regression adjusted for complications. Patients who underwent prehabilitation had a slightly lower tendency for postoperative ER visits and hospital readmissions.

Structural modification of naturally occurring phenolics as a strategy for developing cytotoxic molecules towards cancer cells.

Natural products belonging to different chemical classes have been established as a promising source of novel anticancer drugs. Several low-molecular-weight compounds from the classes of monoterpenes, phenylpropanoids, and flavonoids were shown to possess anticancer activities in previous studies. In this work, over 20 semisynthetic derivatives of molecules belonging to these classes, namely thymol, eugenol, and 6-hydroxyflavanone were synthesized and tested for their cytotoxicity against two human cancer cell lines, namely AGS cells (gastric adenocarcinoma) and A549 cells (human lung carcinoma). An initial screening based on viability assessment was performed to identify the most cytotoxic compounds at 100 µM. The results evidenced that two 6-hydroxyflavanone derivatives were the most cytotoxic among the compounds tested, being selected for further studies. These derivatives displayed enhanced toxicity when compared with their natural counterparts. Moreover, the lactate dehydrogenase (LDH) assay showed that the loss of cell viability was not accompanied by a loss of membrane integrity, thus ruling out a necrotic process. Morphological studies with AGS cells demonstrated chromatin condensation compatible with apoptosis, confirmed by the activation of caspase 3/7. Furthermore, a viability assay on a noncancer human embryonic lung fibroblast cell line (MRC-5) confirmed that these two derivatives possess selective anticancer activity.

Brewer's Spent Grain, Coffee Grounds, Burdock, and Willow-Four Examples of Biowaste and Biomass Valorization through Advanced Green Extraction Technologies.

This paper explores the transformation of biowastes from food industry and agriculture into high-value products through four examples. The objective is to provide insight into the principles of green transition and a circular economy. The first two case studies focus on the waste generated from the production of widely consumed food items, such as beer and coffee, while the other two examine the potential of underutilized plants, such as burdock and willow, as sources of valuable compounds. Phenolic compounds are the main target in the case of brewer's spent grain, with p-coumaric acid and ferulic acid being the most common. Lipids are a possible target in the case of spent coffee grounds with palmitic (C16:0) and linoleic (C18:2) acid being the major fatty acids among those recovered. In the case of burdock, different targets are reported based on which part of the plant is used. Extracts rich in linoleic and oleic acids are expected from the seeds, while the roots extracts are rich in sugars, phenolic acids such as chlorogenic, caffeic, o-coumaric, syringic, cinnamic, gentisitic, etc. acids, and, interestingly, the high-value compound epicatechin gallate. Willow is well known for being rich in salicin, but picein, (+)-catechin, triandrin, glucose, and fructose are also obtained from the extracts. The study thoroughly analyzes different extraction methods, with a particular emphasis on cutting-edge green technologies. The goal is to promote the sustainable utilization of biowaste and support the green transition to a more environmentally conscious economy.

Sustainable Transformation of Two Algal Species of Different Genera to High-Value Chemicals and Bioproducts.

This study investigates the potential of two algae species from different genera, namely the recently isolated Scenedesmus obliquus BGP and Porphyridium cruentum, from the perspective of their integral sustainable transformation to valuable substances. Conventional Soxhlet and environmentally friendly supercritical fluid extraction were applied to recover oils from the species. The extracts were characterized through analytical techniques, such as GC-Fid and LC-MS/MS, which allowed their qualitative and quantitative differentiation. Thus, P. cruentum oils contained up to 43% C20:4 and C20:5 fatty acids, while those of S. obliquus BGP had only residual amounts. The LC-MS/MS analysis of phenolic compounds in the S. obliquus BGP and P. cruentum extracts showed higher content of 3-OH-4-methoxybenzoic acid and kaempferol 3-O-glycoside in the former and higher amounts of ferulic acid in the latter. Total phenolic content and antioxidant activity of the oils were also determined and compared. The compositional analysis of the oil extracts revealed significant differences and varying potentialities based on their genera and method of extraction. To the best of our knowledge our work is unique in providing such detailed information about the transformation prospects of the two algae species to high-value chemicals and bioproducts.

Assessment of Gnaphalium viscosum (Kunth) Valorization Prospects: Sustainable Recovery of Antioxidants by Different Techniques.

This work investigates the prospects for exploitation of Gnaphalium viscosum (Kunth) abundant but with limited applications till present biomass. The feasibility of traditional techniques (two-phase solvent, and the benchmark Soxhlet extraction) and supercritical extraction without/with a cosolvent at T = 40-60 °C and p = 30-50 MPa was examined to explore the possibility of recovering phytochemicals from G. viscosum leaves, flowers and stems. The efficiency of the techniques was assessed and compared based on yield, influence of solvents used, total phenolic content and antioxidant activity of the extracts. Phenolics of different complexities were identified and quantified by applying LC (LC-MS/MS, and LC-HRAM), while the fatty acid profile was determined by GC-FID. The results of this extensive study demonstrated the huge valorization potential and prospects of G. viscosum, since highly potent antioxidants such as kaempferol, kaempferol-3-O-ß-d-glucoside (astragalin), and chlorogenic acid were ascertained in considerable amounts. Furthermore, for the first time, the presence of leontopodic acid, a greatly substituted derivative of glucaric acid, was detected in the species.

Analysis of Nerve Endings in the Superior Labrum-Biceps Complex by Fluorescence Immunohistochemistry and Confocal Laser Microscopy.

Objectives The capsuloligamentous structures of the shoulder work as static stabilizers, together with the biceps and rotator cuff muscles, increasing the contact surface of the glenoid cavity. Free nerve endings and mechanoreceptors have been identified in the shoulder; however, there are a few studies that describe the presence of these nerves in the biceps' insertion. The present study aimed to describe the morphology and distribution of nerve endings using immunofluorescence with protein gene product 9.5 (PGP 9.5) and confocal microscopy. Methods Six labrum-biceps complexes from six fresh-frozen cadavers were studied. The specimens were coronally cut and prepared using the immunofluorescence technique. In both hematoxylin and eosin (H&E) and immunofluorescence, the organization of the connective tissue with parallel collagen fibers was described. Results In the H&E study, vascular structures and some nerve structures were visualized, which were identified by the elongated presence of the nerve cell. All specimens analyzed with immunofluorescence and confocal microscopy demonstrated poor occurrence of morphotypes of sensory corpuscles and free nerve endings. We identified free nerve endings located in the labrum and in the bicipital insertion, and sparse nerve endings along the tendon. Corpuscular endings with fusiform, cuneiform, and oval aspect were identified in the tendon. Conclusion These findings support the hypothesis that the generation of pain in the superior labral tear from Anterior to posterior (SLAP) lesions derives from the more proximal part of the long biceps cord and even more from the upper labrum. Future quantitative studies with a larger number of specimens may provide more information on these sensory systems.

Analysis of Nerve Endings in the Superior Labrum-Biceps Complex by Fluorescence Immunohistochemistry and Confocal Laser Microscopy / Análise de terminações nervosas no complexo labrum-bíceps superior usando imunohistoquímica de fluorescência e microscopia a laser confocal

Abstract Objectives The capsuloligamentous structures of the shoulder work as static stabilizers, together with the biceps and rotator cuff muscles, increasing the contact surface of the glenoid cavity. Free nerve endings and mechanoreceptors have been identified in the shoulder; however, there are a few studies that describe the presence of these nerves in the biceps' insertion. The present study aimed to describe the morphology and distribution of nerve endings using immunofluorescence with protein gene product 9.5 (PGP 9.5) and confocal microscopy. Methods Six labrum-biceps complexes from six fresh-frozen cadavers were studied. The specimens were coronally cut and prepared using the immunofluorescence technique. In both hematoxylin and eosin (H&E) and immunofluorescence, the organization of the connective tissue with parallel collagen fibers was described. Results In the H&E study, vascular structures and some nerve structures were visualized, which were identified by the elongated presence of the nerve cell. All specimens analyzed with immunofluorescence and confocal microscopy demonstrated poor occurrence of morphotypes of sensory corpuscles and free nerve endings. We identified free nerve endings located in the labrum and in the bicipital insertion, and sparse nerve endings along the tendon. Corpuscular endings with fusiform, cuneiform, and oval aspect were identified in the tendon. Conclusion These findings support the hypothesis that the generation of pain in the superior labral tear from Anterior to posterior (SLAP) lesions derives from the more proximal part of the long biceps cord and even more from the upper labrum. Future quantitative studies with a larger number of specimens may provide more information on these sensory systems.

Resumo Objetivos As estruturas capsulo-ligamentares do ombro funcionam como estabilizadores estáticos, juntamente com os músculos do bíceps e do manguito rotador, aumentando a superfície de contato da cavidade glenoide. Terminações nervosas livres e mecanorreceptores foram identificados no ombro; no entanto, existem alguns estudos que descrevem a presença desses nervos na inserção do bíceps. Este estudo teve como objetivo descrever a morfologia e distribuição de terminações nervosas utilizando imunofluorescência com protein gene product 9.5 (PGP 9.5) e microscopia confocal. Métodos Foram estudados seis complexos labrum-bíceps de seis cadáveres congelados frescos. Os espécimes foram cortados coronalmente e preparados pelo método de imunofluorescência. Tanto em hematoxilina e eosina (H&E) quanto em imunofluorescência, foi descrita a organização do tecido conjuntivo com fibras paralelas de colágeno. Resultados No estudo de H&E, foram visualizadas estruturas vasculares e algumas estruturas nervosas, que foram identificadas pela presença alongada da célula nervosa. Todas as amostras analisadas com imunofluorescência e microscopia confocal demonstraram baixa ocorrência de morfotipos de corpúsculos sensoriais e terminações nervosas livres. Identificamos terminações nervosas livres localizadas no labrum, inserção bicipital e terminações nervosas esparsas ao longo do tendão. Terminais corpusculares com aspecto fusiforme, cuneiforme e oval foram identificados no tendão. Conclusão Esses achados corroboram a hipótese de que a geração de dor nas lesões labrais superiores de anterior a posterior (SLAP, na sigla em inglês) deriva da parte mais proximal do cabo longo do bíceps e ainda mais do labrum superior. Estudos quantitativos futuros com um número maior de espécimes podem fornecer mais informações sobre esses sistemas sensoriais.

Lymph node yield in the pathological staging of resected nonmetastatic colon cancer: The more the better?

INTRODUCTION: Guidelines recommend regional lymphadenectomy with a lymph node yield (LNY) of at least 12 lymph nodes (LN) for adequate colon cancer (CC) staging. LNY ≥22LN may improve survival, especially in right-sided CC [Lee et al., Surg Oncol, 27(3), 2018]. This multicentric retrospective cohort study evaluated the impact of LNY and tumor laterality on CC staging and survival. MATERIALS AND METHODS: Patients with stage I-III CC that underwent surgery from 2012 to 2018 were grouped according to LNY: <22 and ≥ 22. Primary outcomes were LN positivity (N+ rate) and disease-free survival (DFS). Overall survival (OS) was the secondary outcome. Exploratory analyses were performed for laterality and stage. RESULTS: We included 795 patients (417 < 22LN, 378 ≥ 22LN); 53% had left-sided CC and 29%/37%/38% had stage I/II/III tumors. There was no association between LNY ≥22LN and N+ rate after adjustment for grade, T stage, lymphovascular invasion (LVI) and perineural invasion; a trend for a higher N+ rate in left-sided CC was identified (interaction p = 0.033). With a median follow-up of 63.6 months for DFS and 73.2 months for OS, 254 patients (31.9%) relapsed and 207 (26.0%) died. In multivariate analysis adjusted for age, ASA score, laparoscopic approach, T/N stage, mucinous histology, LVI and adjuvant chemotherapy, LNY ≥22LN was significantly associated with both DFS (HR 0.75, p = 0.031) and OS (HR 0.71, p = 0.025). Restricted cubic spline analysis showed a more significant benefit for right-sided CC. CONCLUSION: LNY ≥22LN was associated with longer DFS and OS in patients with operable CC, especially for right-sided CC.

EPIDEMIOLOGY, CLASSIFICATION, AND TREATMENT OF BILATERAL FRACTURES OF THE DISTAL RADIUS.

Objective: To study epidemiology, fracture pattern, associated injuries, and treatment of individuals with bilateral distal radius fracture, in a tertiary hospital. Methods: Retrospective cross-sectional study developed based on patients with bilateral distal radius fracture from January 2012 to November 2017. Demographic data, trauma mechanism, radiological patterns, degree of deviation, associated injuries, classification of fractures according to the Association of Osteosynthesis (AO), the Salter-Harris (SH) and Frykman scales, and type of treatment used in each case. Results: 13 cases were included in the trial, 10 adults and three children. In infants, the mean age was 9.6 years (7-11 years), and low-energy trauma was described in all these cases. In total, 66.6% of the children presented the SHII classification . In adult patients, the mean age observed was 43.5 years (27-56 years), with high-energy trauma reported in four (40%) cases. The AO 23C.3 and 23B.2 classifications were the most prevalent in adults. Conclusion: In adult individuals, there was a higher incidence of open fractures, wrist joint involvement, ulna fracture, and concomitant injuries, with high-energy trauma observed only in this group, corresponding to half of the cases. Level of Evidence IV, Case Series.

Objetivo: Estudar epidemiologia, padrão de fraturas, lesões associadas, e tratamento dos indivíduos com fratura de rádio distal bilateral, em um hospital terciário. Métodos: Estudo transversal retrospectivo desenvolvido a partir de pacientes com fratura de rádio distal bilateral no período entre janeiro de 2012 e novembro de 2017. Foram analisados dados demográficos, mecanismo de trauma, padrões radiológicos, grau de desvio, lesões associadas, classificação das fraturas de acordo com AO, Salter Harris (SH) e Frykman, e tipo de tratamento empregado em cada caso. Resultados: 13 casos foram incluídos no ensaio, sendo 10 adultos e três crianças. Nos infantes, a média de idade foi de 9,6 anos (7-11 anos), e o trauma de baixa energia esteve descrito na totalidade destes casos. A classificação SHII esteve presente em 66,6% das crianças. Nos pacientes adultos, a média de idade observada foi de 43,5 anos (27-56 anos), com o mecanismo de trauma de alta energia relatado em quatro (40%) casos. A classificação AO 23C.3 e 23B.2 foram as mais prevalentes nos adultos. Conclusão: Em indivíduos esqueleticamente maduros, observou-se maior incidência de fraturas expostas, acometimento articular do punho, fratura de ulna e lesões concomitantes, sendo o trauma de alta energia observado apenas neste grupo, correspondendo a metade dos casos. Nível de Evidência IV, Série de Casos.

SARS-CoV-2 Antibody Seroprevalence in Patients With Cancer on Systemic Antineoplastic Treatment in the First Wave of the COVID-19 Pandemic in Portugal.

At the time of the first wave of the COVID-19 pandemic, patients with cancer were considered to be at high risk of serious illness and had a higher exposure risk since they needed frequent and nondeferrable hospital visits. Serological tests were not routinely used, and seroprevalence in this population was unknown. A single-center, cross-sectional study was developed to determine the seroprevalence of anti-SARS-CoV-2 antibodies (Abs) in patients with cancer undergoing systemic antineoplastic treatment. One hundred patients were consecutively recruited in a two-week period (6th-20th May 2020), and serum samples were tested for the presence of immunoglobulin M (IgM) and immunoglobulin G (IgG) Abs directed against both spike (S) and nucleocapsid (N) SARS-CoV-2 proteins in two distinct time points (at recruitment and 4-8 weeks later). IgG-positive results were subject to confirmation, in the same serum sample, using two distinct assays. At the time of the first study visit, no patient had a previously confirmed diagnosis of COVID-19, one reported previous contact with a COVID-19 patient, and all had a baseline SARS-CoV-2-negative RT-PCR. Two patients tested positive for SARS-CoV-2 IgG in the first study visit, which was not confirmed in either of the two confirmatory assays. Seventy-two patients were tested at the second study visit, all with negative IgG tests. IgM was persistently positive at both study visits in one patient and was positive in another patient at the second study visit, both with negative RT-PCR and serum IgG. No patient tested positive for RT-PCR within the study timeframe. No evidence of prior or acute SARS-CoV-2 infection was documented in this cohort of patients with cancer undergoing systemic treatment, and no additional exposure risk was documented compared to general population seroprevalence studies. The study was inconclusive regarding the role of SARS-CoV-2 serology in patients with cancer in the early phase of the pandemic. This study did show that, with adherence to recommended preventive measures, it was safe to maintain systemic cancer therapy.

Lewy body dementia is associated with an increased risk of atrial fibrillation: A case-control study.

BACKGROUND: Lewy bodies are a hallmark of Dementia with Lewy Bodies. They can also be found in the sinoatrial node and may be associated with heart disease. OBJECTIVES: We aimed to investigate a possible association between Lewy Body dementia and atrial fibrillation. METHODS: We performed a case-control study based on our centre's cohort of degenerative dementia (Dementia with Lewy Bodies and Alzheimer's disease) patients. The possible association between Lewy Body dementia and atrial fibrillation was studied through a binomial logistic regression, which adjusted for comorbidity data. RESULTS: We included 461 patients. 45 of the 398 (11.3%) with Alzheimer's disease and 14 of the 63 with Dementia with Lewy Bodies (22.2%) had atrial fibrillation. Heart failure (OR = 3.345, 95%CI = [1.618, 6.916], p = 0.001), hypertension (OR = 2.547, 95%CI = [1,137, 5.703], p = 0.023), stroke (OR = 2.274, 95%CI = [1.013, 5.103], p = 0.046) and Dementia with Lewy Bodies (OR = 2.536, 95%CI = [1.105, 5.822], p = 0.028) were associated with atrial fibrillation. CONCLUSIONS: We found an association between Dementia with Lewy bodies and Atrial Fibrillation.

Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer.

PURPOSE: Despite extensive genomic and transcriptomic profiling, it remains unknown how signaling pathways are differentially activated and how tumors are differentially sensitized to certain perturbations. Here, we aim to characterize AKT signaling activity and its association with other genomic or IHC-based PI3K/AKT pathway biomarkers as well as the clinical activity of ipatasertib (AKT inhibitor) in the FAIRLANE trial. EXPERIMENTAL DESIGN: In FAIRLANE, 151 patients with early triple-negative breast cancer (TNBC) were randomized 1:1 to receive paclitaxel with ipatasertib or placebo for 12 weeks prior to surgery. Adding ipatasertib did not increase pathologic complete response rate and numerically improved overall response rate by MRI. We used reverse-phase protein microarrays (RPPA) to examine the total level and/or phosphorylation states of over 100 proteins in various signaling or cell processes including PI3K/AKT and mTOR signaling. One hundred and twenty-five baseline and 127 on-treatment samples were evaluable by RPPA, with 110 paired samples at both time points. RESULTS: Tumors with genomic/protein alterations in PIK3CA/AKT1/PTEN were associated with higher levels of AKT phosphorylation. In addition, phosphorylated AKT (pAKT) levels exhibited a significant association with enriched clinical benefit of ipatasertib, and identified patients who received benefit in the absence of PIK3CA/AKT1/PTEN alterations. Ipatasertib treatment led to a downregulation of AKT/mTORC1 signaling, which was more pronounced among the tumors with PIK3CA/AKT1/PTEN alterations or among the responders to the treatment. CONCLUSIONS: We showed that the high baseline pAKT levels are associated with the alterations of PI3K/AKT pathway components and enriched benefit of ipatasertib in TNBC.

Epidemiology, classification, and treatment of bilateral fractures of the distal radius / Epidemiologia, classificação e tratamento de fraturas bilaterais do raio distal

ABSTRACT Objective: To study epidemiology, fracture pattern, associated injuries, and treatment of individuals with bilateral distal radius fracture, in a tertiary hospital. Methods: Retrospective cross-sectional study developed based on patients with bilateral distal radius fracture from January 2012 to November 2017. Demographic data, trauma mechanism, radiological patterns, degree of deviation, associated injuries, classification of fractures according to the Association of Osteosynthesis (AO), the Salter-Harris (SH) and Frykman scales, and type of treatment used in each case. Results: 13 cases were included in the trial, 10 adults and three children. In infants, the mean age was 9.6 years (7-11 years), and low-energy trauma was described in all these cases. In total, 66.6% of the children presented the SHII classification . In adult patients, the mean age observed was 43.5 years (27-56 years), with high-energy trauma reported in four (40%) cases. The AO 23C.3 and 23B.2 classifications were the most prevalent in adults. Conclusion: In adult individuals, there was a higher incidence of open fractures, wrist joint involvement, ulna fracture, and concomitant injuries, with high-energy trauma observed only in this group, corresponding to half of the cases. Level of Evidence IV, Case Series.

RESUMO Objetivo: Estudar epidemiologia, padrão de fraturas, lesões associadas, e tratamento dos indivíduos com fratura de rádio distal bilateral, em um hospital terciário. Métodos: Estudo transversal retrospectivo desenvolvido a partir de pacientes com fratura de rádio distal bilateral no período entre janeiro de 2012 e novembro de 2017. Foram analisados dados demográficos, mecanismo de trauma, padrões radiológicos, grau de desvio, lesões associadas, classificação das fraturas de acordo com AO, Salter Harris (SH) e Frykman, e tipo de tratamento empregado em cada caso. Resultados: 13 casos foram incluídos no ensaio, sendo 10 adultos e três crianças. Nos infantes, a média de idade foi de 9,6 anos (7-11 anos), e o trauma de baixa energia esteve descrito na totalidade destes casos. A classificação SHII esteve presente em 66,6% das crianças. Nos pacientes adultos, a média de idade observada foi de 43,5 anos (27-56 anos), com o mecanismo de trauma de alta energia relatado em quatro (40%) casos. A classificação AO 23C.3 e 23B.2 foram as mais prevalentes nos adultos. Conclusão: Em indivíduos esqueleticamente maduros, observou-se maior incidência de fraturas expostas, acometimento articular do punho, fratura de ulna e lesões concomitantes, sendo o trauma de alta energia observado apenas neste grupo, correspondendo a metade dos casos. Nível de Evidência IV, Série de Casos.

Microwave-Assisted Extraction of Phenolic Compounds from Spent Coffee Grounds. Process Optimization Applying Design of Experiments.

In this study, sustainable technology microwave-assisted extraction (MAE) in association with green solvents was applied to recover phenolic compounds from spent coffee grounds (SCGs). A design of experiments (DOE) was used for process optimization. Initially, a 24-1 two level Fractional Factorial Design was used and ratios "solvent to solute" and "ethanol to water" were identified as the significant experimental factors. Consequently, Central Composite Design (CCD) was applied to analyze the effects of the significant variables on the response yield, total polyphenols content (TPC), and antioxidant activity (AA) by the DPPH assay method, and quadratic surfaces to optimize those responses were generated. The values of the significant factors of 16.7 (solvent/solute) and 68.9% (ethanol/water) were optimized simultaneously the yield (%) at 6.98 ± 0.27, TPC (mg GAE/g) at 117.7 ± 6.1, and AA (µmol TE/g) at 143.8 ± 8.6 and were in excellent agreement with those predicted from the CCD model. The variations of the compositions of the lipids, caffeine, pentacyclic diterpenes, and FAME as a function of the dominant factor % ethanol in the solvent mixture were analyzed by applying NMR and GC-FID, and the results obtained confirmed their determinative significance.