SEOM-GEICO clinical guideline on epithelial ovarian cancer (2023).

In recent years, the incorporation of new strategies to the therapeutic armamentarium has completely changed the outcomes of epithelial ovarian cancer (EOC). The identification of new predictive and prognostic biomarkers has also enabled the selection of those patients more likely to respond to targeted agents. Nevertheless, EOC is still a highly lethal disease and resistance to many of these new agents is common. The objective of this guideline is to summarize the most relevant strategies to manage EOC, to help the clinician throughout the challenging diagnostic and therapeutic processes and to provide evidence-based recommendations.

Influence of educational level on the prevalence of risk behaviors during the perinatal period. / Influencia del nivel de estudios en la prevalencia de conductas de riesgo durante el periodo perinatal.

The objective of this work was to assess changes during pregnancy and after childbirth in diet, consumption of tobacco, electronic cigarettes, cannabis, alcohol use and exposure to environmental tobacco smoke depending on the mother's educational level.A cross-sectional study was carried out whose target population was 18,822 Galician women aged 18-49 who gave birth between September 2015 and August 2016, and their 19,204 live-born children. A descriptive analysis was performed, and the prevalence of different behaviors was estimated at three time points - pre-pregnancy, pregnancy and after childbirth - depending on the mother's educational level. Percentages of change were calculated.Information was obtained from 6,436 women. Regardless of the educational level, during pregnancy there was an improvement in the different lifestyles. In the first months after childbirth, lifestyles worsened, except for exposure to environmental tobacco smoke and the use of electronic cigarettes. Most of the risk behaviors showed a gradient depending on the educational level; thus, the lower the educational level, the higher the prevalence of risk behaviors.In general, during pregnancy all women adopted healthier lifestyles that they abandoned in the months following childbirth. Women with a lower level of education showed a higher prevalence of risk behaviors, both in the period prior to pregnancy, as well as during pregnancy and after childbirth.

El objetivo de este trabajo fue valorar cambios durante el embarazo y tras el parto en la dieta, consumo de tabaco, cigarrillos electrónicos, alcohol, cannabis y exposición al humo ambiental de tabaco en función del nivel de estudios de la madre. Para ello, se llevó a cabo un estudio transversal cuya población objetivo fueron 18.822 mujeres gallegas de 18-49 años que dieron a luz entre septiembre 2015 y agosto 2016, y sus 19.204 hijos/as nacidos vivos. Se realizó un análisis descriptivo y se estimó la prevalencia de diferentes conductas en tres momentos temporales ­pre-embarazo, embarazo y tras el parto­ en función del nivel de estudios de la madre. Se calcularon los porcentajes de cambio. Se obtuvo información de 6.436 mujeres. Con independencia del nivel de estudios, durante el embarazo se produce una mejora en los diferentes estilos de vida. En los primeros meses tras el parto los estilos de vida empeoran, con excepción de la exposición al humo ambiental de tabaco y el consumo de cigarrillos electrónicos. La mayoría de las conductas de riesgo muestran un gradiente dependiente del nivel educativo; así, a menor nivel educativo, mayor es la prevalencia de conductas de riesgo. En general, durante el embarazo todas las mujeres adoptan estilos de vida más saludables que abandonan en los meses siguientes al parto. Las mujeres con menor nivel de estudios muestran una mayor prevalencia de conductas de riesgo, tanto en el periodo previo al embarazo, como en el embarazo y tras el parto.

Evolution of Medical Students' Interest in Orthopaedic Surgery Careers from Matriculation to Graduation.

Introduction: Little is known about risk factors for changes in students' interest in orthopaedics during medical school. We aimed to identify variables associated with diminished (vs. sustained) and emerging (vs. no) plans to become board certified in orthopaedic surgery. Methods: We conducted a retrospective national-cohort study of students who matriculated in US MD-granting medical schools in academic years 1993 to 1994 through 2000 to 2001. The outcome measure was the evolution of students' board-certification plans in orthopaedic surgery from matriculation to graduation using responses on the Association of American Medical Colleges' Matriculating Student Questionnaire and Graduation Questionnaire. Covariates included demographic, attitudinal, experiential, and career intention variables. Results: Of 53,560 graduates with complete data, 2,765 students reported diminished interest in becoming board certified in orthopaedics, 1,345 reported emerging interest, and 1,327 reported sustained interest. In multivariable logistic regression models, students who were female (adjusted odds ratio [aOR] 1.83, 95% confidence interval [CI] 1.43-2.34), Asian (aOR 1.46, 95% CI 1.18-1.82), reported greater importance of social responsibility (aOR 1.16, 95% CI 1.02-1.33) and prestige (aOR 1.20, 95% CI 1.10-1.30) in choosing a medicine career, and planned full-time university faculty careers (aOR 1.58, 95% CI 1.33-1.89) at graduation were independently more likely to have diminished (vs. sustained) interest. Students who participated in research and/or authorship electives (aOR 3.50, 95% CI 3.00-4.07) and who attended private institutions (aOR 1.23, 95% CI 1.10-1.39) were more likely to have emerging (vs. no) interest. Conclusions: Twice as many students lost interest than gained interest in orthopaedics during medical school, and the cohort of students interested in orthopaedics became less diverse over the course of medical school. Several risk factors amenable to change were identified. Interventions that target these risk factors are warranted to increase the diversity of the orthopaedic surgery workforce.

[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

INTRODUCTION: malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. OBJECTIVE: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. METHODS: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. RESULTS: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. CONCLUSIONS: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Tolerability of the niraparib individualized starting dose in the PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib first-line maintenance therapy.

PURPOSE: To explore safety and tolerability parameters for the niraparib individualized starting dose (ISD) in patients with newly diagnosed advanced ovarian cancer that responded to platinum-based chemotherapy who participated in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016). METHODS: The PRIMA protocol was amended so newly enrolled patients received an ISD based on baseline body weight/platelet count. In this ad hoc analysis, the timing, duration, and resolution of the first occurrence of common any-grade hematologic (thrombocytopenia, anemia, neutropenia) and nonhematologic (nausea, asthenia/fatigue, constipation, insomnia, hypertension) treatment-emergent adverse events (TEAEs) were evaluated by treatment arm in the ISD safety population (data cutoff, November 17, 2021; median follow-up, 3.5 years). RESULTS: Of 733 randomized patients, 255 were enrolled after the ISD protocol amendment and received ≥ 1 dose of study treatment (niraparib, 169; placebo, 86). In the niraparib arm, median times to first events were 22.0-35.0 days for hematologic TEAEs and 7.0-56.0 days for nonhematologic TEAEs. First events resolved in ≥ 89.8% of patients for hematologic TEAEs; for nonhematologic TEAEs, resolution rates ranged from 55.3% (insomnia) to 86.0% (nausea). Median durations of first hematologic TEAEs were ≤ 16.0 days, but for first nonhematologic TEAEs ranged from 18.0 days (nausea) to 134.0 days (insomnia). CONCLUSION: The niraparib ISD was generally well tolerated and TEAEs were manageable. Common hematologic and nonhematologic TEAEs occurred early and first events of hematologic TEAEs had a short duration (≈ 2 weeks) and a high resolution rate. These findings support close monitoring immediately following niraparib initiation and may help inform patient expectations for niraparib safety.

Impact of the use of small-area models on estimation of attributable mortality at a regional level.

The objective of this study is to assess the impact of applying prevalences derived from a small-area model at a regional level on smoking-attributable mortality (SAM). A prevalence-dependent method was used to estimate SAM. Prevalences of tobacco use were derived from a small-area model. SAM and population attributable fraction (PAF) estimates were compared against those calculated by pooling data from three national health surveys conducted in Spain (2011-2014-2017). We calculated the relative changes between the two estimates and assessed the width of the 95% CI of the PAF. Applying surveys-based prevalences, tobacco use was estimated to cause 53 825 (95% CI: 53 182-54 342) deaths in Spain in 2017, a figure 3.8% lower obtained with the small-area model prevalences. The lowest relative change was observed in the Castile-La Mancha region (1.1%) and the highest in Navarre (14.1%). The median relative change between regions was higher for women (26.1%), population aged ≥65 years (6.6%), and cardiometabolic diseases (9.0%). The differences between PAF by cause of death were never greater than 2%. Overall, the differences between estimates of SAM, PAF, and confidence interval width are small when using prevalences from both sources. Having these data available by region will allow decision-makers to implement smoking control measures based on more accurate data.

Glucose metabolism outcomes after pituitary surgery in patients with acromegaly.

AIM: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. METHODS: A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. RESULTS: A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had diabetes mellitus (DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9) [51.9 mmol/mol (IQR 46.4-62.8)]. In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), arthropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-I levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of DM. At the last follow-up visit after surgery, 21.1% of the DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). CONCLUSION: Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.

Time Dependence Between Tobacco Consumption and Lung Cancer Mortality in Spain.

OBJECTIVES: Lung cancer is the leading cause of cancer death and the second most common cancer in both sexes worldwide, with tobacco being its main risk factor. The aim of this study is to establish the temporal relationship between smoking prevalence and lung cancer mortality in Spain. METHODS: To model the time dependence between smoking prevalence and lung cancer mortality, a distributed lag non-linear model was applied adjusting for sex, age, year of mortality and population at risk. Smoking prevalence data from 1991-2020 were used. Considering a maximum lag of 25 years, mortality data from 2016-2020 were included. The effect of prevalence on mortality for each lag is presented in terms of relative risk (RR). To identify the lag at which smoking prevalence has the greatest effect on mortality, the RR of the different lags were compared. RESULTS: The optimal lag observed between smoking prevalence and lung cancer mortality in Spain was 15 years. The maximum RR was 2.9 (95%CI: 2.0-4.3) for a prevalence of 71% and a 15-year lag. The RR was 1.8 for a prevalence of 33%, an approximate median value between 1991-2020, and a 15-year lag. CONCLUSIONS: In Spain, lung cancer mortality is affected by smoking prevalence 15 years prior. Knowing the evolution of the smoking prevalence series in a country and establishing a lag time is essential to predict how lung cancer incidence and mortality will evolve.

Reduction in Hippocampal Amyloid-ß Peptide (Aß) Content during Glycine-Proline-Glutamate (Gly-Pro-Glu) Co-Administration Is Associated with Changes in Inflammation and Insulin-like Growth Factor (IGF)-I Signaling.

Alzheimer's disease (AD) is characterized by the deposition in the brain of senile plaques composed of amyloid-ß peptides (Aßs) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE), has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aß levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aß25-35 for 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aß-degrading enzymes associated with these GPE-related effects. GPE prevented the Aß-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1, and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme, was also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aß insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aß levels through modulation of levels and/or activity of Aß proteases.

Orthopaedic Surgery Attrition Before Board Certification: A National-Cohort Study of US MD Graduates in Orthopaedic Surgery Residency Programs.

Introduction: Little is known about attrition before American Board of Orthopaedic Surgery (ABOS) board certification for orthopaedic residents training in Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedics programs. This national-cohort study examined orthopaedic surgery attrition, associated risk factors, and specialties pursued by residents who left orthopaedics. Methods: From August 2022 through July 2023, we analyzed deidentified, individual-level data from the Association of American Medical Colleges for 129,860 US MD-granting medical-school matriculants in academic years 1993 to 1994 through 2000 to 2001. Graduates with records of training ≥1 year in orthopaedic surgery during GME and of board certification as of May 2020 were included. Retention was defined as being ABOS-certified; attrition was defined as being certified by another specialty board and not ABOS. We identified variables independently associated with attrition from orthopaedics using multivariable logistic regression analysis and reported adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Of 4,319 US medical-school graduates from 1997 to 2009 with ≥1 year of orthopaedic surgery GME, 4,085 (94.6%) obtained ABOS board certification (retention) and 234 did not (attrition). Women (OR 2.8, 95% CI 2.0-3.9), first-generation college graduates (OR 1.6, 95% CI 1.1-2.2), Asians (OR 1.9, 95% CI 1.4-2.7), and residents who placed greater importance on innovation/research in choosing medicine as a career (OR 1.4, 95% CI 1.1-1.7) and completed ≥1 year of research during GME (OR 2.4, 95% CI 1.7-3.5) were more likely to leave orthopaedics. Overall, 121 trainees who left orthopaedics selected surgical specialties for board certification, most commonly plastic surgery (n = 66) and general surgery (n = 45). Conclusions: The increased risk of attrition among women, Asians, first-generation college graduates, and trainees endorsing higher importance of innovation/research in choosing medicine and participating in research during GME raises concerns about the potential loss of underrepresented groups among orthopaedic surgeons and surgeon-scientists. Efforts to mitigate attrition among residents in high-risk groups are warranted.

Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Late metastases: a rare cause of diarrhea.

We present the case of a 64-year-old female with personal history of breast carcinoma diagnosed in 2011, treated and discharged from the Oncology service after 10 years disease-free who, 21 years after the diagnosis, undergoes a colonoscopy with biopsy sampling due to a 2-year period of diarrhea and weight loss, which histological study show infiltration of the large intestine's by breast carcinoma. Due to the usual lymphatic widespread, metastases of breast cancer in the gastrointestinal tract are extremely rare with nonspecific symptoms, long latency periods and poor prognosis.

Intracranial thrombus composition is associated with occlusion location and endovascular treatment outcomes: results from ITACAT multicenter study.

BACKGROUND: The impact of thrombolytics directed towards different thrombus components regarding site of occlusion in combination with mechanical thrombectomy (MT) to achieve endovascular complete recanalization is unclear. METHODS: Retrospective analysis of a prospective database in two stroke centers. Intracranial thrombi retrieved by MT were analyzed using hematoxylin-eosin staining for fibrin and red blood cell proportions, and CD61 immunostaining for platelets proportion in thrombus (PLTPT) assessment. Thrombi composition, baseline variables, etiology, treatment features and occlusion location were analyzed. RESULTS: Overall, 221 patients completed the per protocol analysis and 110 cases achieved a final expanded Thrombolysis in Cerebral Infarction (eTICI) 3 (49%) of which 70 were MT (32%) by first pass effect (FPE). Thrombi from medium distal vessel occlusions had higher PLTPT compared with thrombi from proximal large vessel occlusions (68% vs 61%, P=0.026). In particular, middle cerebral artery M2-M3 segment thrombi had the highest PLTPT (70%), and basilar artery thrombi the lowest PLTPT (41%). After logistic regression analysis adjusted for occlusion location and intravenous fibrinolysis, lower baseline National Institutes of Health Stroke Scale score (adjusted OR (aOR) 0.95, 95% CI 0.913 to 0.998) and PLTPT (aOR 0.97, 95% CI 0.963 to 0.993) were independently associated with FPE. Fewer MT passes (aOR 0.67, 95% CI 0.538 to 0.842) and platelet poor thrombus (<62% PLTPT; aOR 2.39, 95% CI 1.288 to 4.440) were independently associated with final eTICI 3. CONCLUSIONS: Occlusion location might be a surrogate parameter for thrombus composition. Platelet poor clots and fewer MT passes were independently associated with complete endovascular recanalization. Clinical trials testing the benefits of combining selective intra-arterial platelet antagonists with MT to improve endovascular outcomes are warranted.

Femtosecond-Assisted Mushroom Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to describe our technique for performing femtosecond laser (FSL)-assisted mushroom configuration in deep anterior lamellar keratoplasty (DALK). METHODS: We describe our surgical technique for a mushroom-configuration DALK using a femtosecond laser (FSL) both to prepare the graft and to perform a precut of the recipient cornea, as well as the steps for the dissection of the recipient cornea and for donor cornea implantation. Moreover, we show the parameters of energy and spot separation and the external and internal diameters as well as the thickness of the external and internal keratotomy. RESULTS: We performed a retrospective case series study of 20 patients with a mean follow-up of 4.36 ± 2.54 years. The indication for surgery was leukoma in 15 cases (75%), keratoconus in 4 cases (20%), and stromal corneal dystrophy in 1 case (5%). Four cases had to be converted to penetrating keratoplasty. The overall results were as follows: The mean preoperative corrected distance visual acuity increased from 0.11 ± 0.09 (0.01-0.30) to 0.78 ± 0.22 (0.30-1.0) with spectacles and to 0.92 ± 0.13 (0.5-1.0) with a gas permeable contact lens. The mean final cylinder was 3.90 ± 1.86 (1.25-7.0). The mean endothelial cell count at 6 months was 2033.83 ± 570.53 cells/mm2 (930-3207), and the mean final spherical equivalent was -4.67 ± 2.91 (-0.25 to -9.00). CONCLUSIONS: FSL-assisted technology is useful to achieve a predictable and safe procedure when using mushroom configuration to perform DALK. Our conversion rate from DALK to penetrating keratoplasty was similar to or even lower than that reported in the literature. In the successful DALK cases, the visual and refractive results were similar to those reported in other studies using FSL-assisted DALK (with a standard or mushroom configuration).

EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells.

DNA replication faces challenges from DNA lesions originated from endogenous or exogenous sources of stress, leading to the accumulation of single-stranded DNA (ssDNA) that triggers the activation of the ATR checkpoint response. To complete genome replication in the presence of damaged DNA, cells employ DNA damage tolerance mechanisms that operate not only at stalled replication forks but also at ssDNA gaps originated by repriming of DNA synthesis downstream of lesions. Here, we demonstrate that human cells accumulate post-replicative ssDNA gaps following replicative stress induction. These gaps, initiated by PrimPol repriming and expanded by the long-range resection factors EXO1 and DNA2, constitute the principal origin of the ssDNA signal responsible for ATR activation upon replication stress, in contrast to stalled forks. Strikingly, the loss of EXO1 or DNA2 results in synthetic lethality when combined with BRCA1 deficiency, but not BRCA2. This phenomenon aligns with the observation that BRCA1 alone contributes to the expansion of ssDNA gaps. Remarkably, BRCA1-deficient cells become addicted to the overexpression of EXO1, DNA2 or BLM. This dependence on long-range resection unveils a new vulnerability of BRCA1-mutant tumors, shedding light on potential therapeutic targets for these cancers.

Biodegradable Biocomposite of Starch Films Cross-Linked with Polyethylene Glycol Diglycidyl Ether and Reinforced by Microfibrillated Cellulose.

Biopolymers are biodegradable and renewable and can significantly reduce environmental impacts. For this reason, biocomposites based on a plasticized starch and cross-linker matrix and with a microfibrillated OCC cardboard cellulose reinforcement were developed. Biocomposites were prepared by suspension casting with varied amounts of microfibrillated cellulose: 0, 4, 8, and 12 wt%. Polyethylene glycol diglycidyl ether (PEGDE) was used as a cross-linking, water-soluble, and non-toxic agent. Microfibrillated cellulose (MFC) from OCC cardboard showed appropriate properties and potential for good performance as a reinforcement. In general, microfiber incorporation and matrix cross-linking increased crystallization, reduced water adsorption, and improved the physical and tensile properties of the plasticized starch. Biocomposites cross-linked with PEGDE and reinforced with 12 wt% MFC showed the best properties. The chemical and structural changes induced by the cross-linking of starch chains and MFC reinforcement were confirmed by FTIR, NMR, and XRD. Biodegradation higher than 80% was achieved for most biocomposites in 15 days of laboratory compost.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Experimental Study of a Sequential Membrane Process of Ultrafiltration and Nanofiltration for Efficient Polyphenol Extraction from Wine Lees.

The wine industry is a sector of great importance in the Spanish economy, contributing substantial annual revenues. However, one challenge facing the industry is the amount of waste generated, reaching millions of tons annually. These residues consist of organic matter of industrial interest, such as polyphenols. These substances are characterised by their excellent antioxidant properties, making them ideal for use in the food, cosmetic, and pharmaceutical industries. Modern techniques, such as membrane technology, are explored for their extraction based on separating compounds according to size. This work studies a sequential filtration process using ultrafiltration (UF) and nanofiltration (NF) membranes at different operating conditions (2 bar and 9.5 bar for UF and NF, respectively, at 20 °C) to extract polyphenols from wine lees. The results show a total polyphenols rejection rate for each process of 54% for UF and 90% for NF. Pore blocking models have been studied for the UF process and an intermediate pore blocking of the membrane upon wine lees filtration has been identified. A mathematical model that justifies the behavior of a polymeric NF membrane with the filtration of pre-treated vinasse residues has been validated. This study shows a viable process for extracting polyphenols from wine lees with sequential membrane technology.

From the gut to the brain: the long journey of phenolic compounds with neurocognitive effects.

The human gut microbiota is a complex community of micro-organisms that play a crucial role in maintaining overall health. Recent research has shown that gut microbes also have a profound impact on brain function and cognition, leading to the concept of the gut-brain axis. One way in which the gut microbiota can influence the brain is through the bioconversion of polyphenols to other bioactive molecules. Phenolic compounds are a group of natural plant metabolites widely available in the human diet, which have anti-inflammatory and other positive effects on health. Recent studies have also suggested that some gut microbiota-derived phenolic metabolites may have neurocognitive effects, such as improving memory and cognitive function. The specific mechanisms involved are still being studied, but it is believed that phenolic metabolites may modulate neurotransmitter signaling, reduce inflammation, and enhance neural plasticity. Therefore, to exert a protective effect on neurocognition, dietary polyphenols or their metabolites must reach the brain, or act indirectly by producing an increase in bioactive molecules such as neurotransmitters. Once ingested, phenolic compounds are subjected to various processes (eg, metabolization by gut microbiota, absorption, distribution) before they cross the blood-brain barrier, perhaps the most challenging stage of their trajectory. Understanding the role of phenolic compounds in the gut-brain axis has important implications for the development of new therapeutic strategies for neurological and psychiatric disorders. By targeting the gut microbiota and its production of phenolic metabolites, it may be possible to improve brain function and prevent cognitive decline. In this article, the current state of knowledge on the endogenous generation of phenolic metabolites by the gut microbiota and how these compounds can reach the brain and exert neurocognitive effects was reviewed.

Dose-Related Side Effects of Intravitreal Injections of Humanized Anti-Vascular Endothelial Growth Factor in Rats: Glial Cell Reactivity and Retinal Ganglion Cell Loss.

Purpose: In a previous study, we documented that the Intravitreal injections (IVIs) of bevacizumab in rats caused a retinal inflammatory response. We now study whether the IVI of other humanized anti-VEGF: ranibizumab and aflibercept also cause an inflammatory reaction in the rat retina and if it depends on the dose administered. Finally, we study whether this reaction affects retinal ganglion cell (RGC) survival. Methods: Albino Sprague-Dawley rats received a single IVI of 5 µL of PBS or ranibizumab or aflibercept at the concentration used in clinical practice (10 µg/µL or 40 µg/µL) or at a lower concentration (0.38 µg/µL and 1.5 µg/µL) calculated to obtain within the rat eye the same concentration as in the human eye in clinical practice. Others received a single 5 µL IVI of a polyclonal goat anti-rat VEGF (0.015 µg/µL) or of vehicle (PBS). Animals were processed 7 days or 1 month later. Retinal whole mounts were immunolabeled for the detection of microglial, macroglial, RGCs, and intrinsically photosensitive RGCs (ipRGCs). Fluorescence and confocal microscopy were used to examine retinal changes, and RGCs and ipRGCs were quantified automatically or semiautomatically, respectively. Results: All the injected substances including the PBS induced detectable side effects, namely, retinal microglial cell activation and retinal astrocyte hypertrophy. However, there was a greater microglial and macroglial response when the higher concentrations of ranibizumab and aflibercept were injected than when PBS, the antibody anti-rat VEGF and the lower concentrations of ranibizumab or aflibercept were injected. The higher concentration of ranibizumab and aflibercept resulted also in significant RGC death, but did not cause appreciable ipRGC death. Conclusions: The IVI of all the substances had some retinal inflammatory effects. The IVI of humanized anti-VEGF to rats at high doses cause important side effects: severe inflammation and RGC death, but not ipRGC death.