Integration of network-based approaches for assessing variations in metabolic profiles of alkalized and non-alkalized commercial cocoa powders.

Cocoa can undergo an alkalization process to enhance its color and solubility. It reduces astringency and alters its composition, particularly in the phenolic compound content, which is related to cocoa health benefits. This study aimed to investigate the impact of alkalization on the composition of seven commercial cocoa powders. A liquid chromatography-based metabolomic approach was employed to assess the metabolic differences between alkalized and non-alkalized cocoa powders. Supervised orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify the most discriminating variables between groups. A feature-based molecular network (FBMN) was used to explore the chemical space. Three hundred forty-seven metabolites were obtained as the most discriminant, among which 60 were tentatively annotated. Phenolic compounds, lysophosphatidylethanolamines, amino acids, and their derivatives were significantly reduced in alkalized cocoas. In contrast, fatty acids and their derivatives significantly increased with alkalization. Despite the variability among commercial cocoas, chemometrics allowed the elucidation of alterations induced specifically by alkalization in their composition.

Modulation of the Hyperglycemia Condition in Diabetic Lab Rats with Extracts of the Creole Jamaica Flower (Hibiscus sabdariffa L.) from the Morelia Region (Mexico).

Extracts from Jamaica flowers (Hibiscus sabdariffa) from Morelia (Mexico) were evaluated as antidiabetic ingredients in a diabetic rat lab model for 80 days at doses of 200, 400, and 600 mg extract/kg rat weight. The hydroalcoholic extract (water:ethanol 80:20 (v/v) at 50 °C) showed a TPC value of 403.28 ± 7.71 mg GAE/g extract, and an antioxidant activity of 0.219 ± 0.00003 mmol Trolox/g (ABTS) and 0.134 ± 0.00001 mmol Trolox/g (DPPH). The extract allowed reducing the diabetic glucose plasma levels under fasting conditions in a dose-dependent manner by 35.2%, 41.63%, and 50.1%. Additionally, the highest dose of the extract (600 mg/kg) slightly reduced the short-term postprandial glucose response while improving the long-term response, reducing hyperglycemia by 45.1%. The same dose also improved lipid metabolism by reducing total cholesterol, triglycerides, VLDL, and LDL, while the HDL level increased. The improvement in glucose and lipid management in the treated groups also led to reduced levels of glycosylated hemoglobin, as well as lower insulin resistance (TyG index), compared to the diabetic control group. The results of this study suggest that extracts from Hibiscus sabdariffa (Morelia) can be used as potential functional ingredients or nutraceuticals for managing the diabetic condition.

Rituximab-induced cystoid macular edema in a patient with systemic lupus erythematosus: A case report and literature review.

Cystoid macular edema (CME) is considered a rare adverse effect of rituximab use, with only a limited number of cases published in the literature. Although its etiopathogenesis is still unknown, its mechanism seems to be related to a transient elevation of cytokines after rituximab infusion resulting in an increased permeability of retinal vessels. We report the first case of rituximab-induced CME in a patient with systemic lupus erythematosus (SLE), where rituximab was used to treat hematological complications. A month after the 2nd infusion, the patient developed blurred vision and decreased visual acuity in the right eye. An optic coherence tomography (OCT) was performed, being diagnosed with CME. Rituximab was then discontinued, exhibiting a complete resolution of the condition within 4 weeks. The aim of our work is to report the first case in a patient with SLE and also carry out a brief review of the subject comparing it to all previously published cases.

Economic impact of immunoglobulin replacement therapy in secondary immunodeficiency to hematological cancer: a single center observational study.

This is the first report of the health economic benefits derived from preventing infections through Immunoglobulin Replacement Therapy (IgRT) in patients with secondary immunodeficiency due to hematological malignancies. We conducted a retrospective population-based cohort study using patient medical history and pharmacy data from the Hospital Clínico San Carlos for 21 patients between 2011 and 2020. The pharmacoeconomic impact of using prophylactic IgRT was assessed by comparing characteristics of the SID patients 1 year before and after initiating IgRT measured by direct medical and tangible indirect costs. Results indicate a marked reduction in hospitalization days following IgRT initiation, decreasing from an average of 13.9 to 6.1 days per patient, with the elimination of ICU admissions. While emergency department visits decreased significantly, the number of routine consultations remained unchanged. Notably, absenteeism from work dropped substantially. The financial analysis revealed significant reductions in medication use and fewer ancillary tests, resulting in considerable cost savings. Specifically, total expenditure dropped from €405,088.18 pre-IgRT to €295,804.42 post-IgRT-including the cost of IgRT itself at €156,309.60. Overall, the annual savings amounted to €109,283.84, validating the cost-effectiveness of IgRT in managing SID in patients with hematological cancers.

Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy - A comprehensive review.

Cancer incidences are rising each year. In 2020, approximately 20 million new cancer cases and 10 million cancer-related deaths were recorded. The World Health Organization (WHO) predicts that by 2024 the incidence of cancer will increase to 30.2 million individuals annually. Considering the invasive characteristics of its diagnostic procedures and therapeutic methods side effects, scientists are searching for different solutions, including using plant-derived bioactive compounds, that could reduce the probability of cancer occurrence and make its treatment more comfortable. In this regard, oridonin (ORI), an ent-kaurane diterpenoid, naturally found in the leaves of Rabdosia rubescens species, has been found to have antitumor, antiangiogenesis, antiasthmatic, antiinflammatory, and apoptosis induction properties. Extensive research has been performed on ORI to find various mechanisms involved in its anticancer activities. This review article provides an overview of ORI's effectiveness on murine and human cancer populations from 1976 to 2022 and provides insight into the future application of ORI in different cancer therapies.

Post- versus intra-operative implant for breast cancer interstitial brachytherapy: How to choose?

Purpose: Breast brachytherapy (BB) represents an important radiation therapy modality in modern breast cancer treatments. Currently, BB is mainly used for accelerated partial breast irradiation (APBI), local boost after whole breast radiation therapy (WBRT), and as salvage re-irradiation after second lumpectomy (APBrl). Two multi-catheter interstitial brachytherapy (MIB) techniques can be offered: intra-operative (IOB) and post-operative (POB) brachytherapy. The aim of this article was to summarize current available data on these two different brachytherapy approaches for breast cancer. Material and methods: A literature search was performed, and different experiences published by BB expert teams were analyzed and compared. These two different brachytherapy approaches for breast cancer have also been presented and discussed during meetings of the GEC-ESTRO BCWG. In addition, expert recommendations were defined. Results: A comprehensive description and practical comparison of both the techniques, i.e., IOB and POB, considering the latest available published data were presented. Different technical, logistic, and clinical aspects of both the methods were thoroughly examined and analyzed. This detailed comparison of the two breast brachytherapy techniques was supported by scientific data from extensive experience of experts, facilitating an objective analysis that, to our knowledge, has not been previously published. Conclusions: Based on the comprehensive analysis of both the brachytherapy techniques available, this article serves as a valuable resource to guide breast teams in selecting the optimal BB technique (POB or IOB), considering hospital environment, multi-disciplinary collaboration, and patient logistics.

Long-term results of intraoperative multicatheter breast implant (IOMBI) for accelerated partial breast irradiation (APBI) on early breast cancer patients.

BACKGROUND AND PURPOSE: Multicatheter breast brachytherapy is a standard technique for accelerated partial breast irradiation (APBI) in early breast cancer patients. Intraoperative multicatheter breast implant (IOMBI) followed by perioperative high-dose-rate brachytherapy (PHDRBT) offers a novel and advantageous approach. We present long-term oncological, toxicity, and cosmesis outcomes for a well-experienced single institution. MATERIALS AND METHODS: Eligible women aged ≥ 40 years with clinically and radiologically confirmed unifocal invasive or in situ ≤ 3 cm breast tumors underwent IOMBI during breast-conserving surgery. Patients meeting APBI criteria by definitive pathologic results received 3.4 Gy × 10fx with PHDRBT. Patients not suitable for APBI received PHDRBT-boost followed by WBRT. RESULTS: A total of 171 patients underwent IOMBI during BCS, 120 patients (70.1 %) were suitable for APBI and 51 (29.8 %) for anticipated PHDRBT-boost. The median age was 61 years (range: 40-78), the median tumor size was 1.1 cm (range: 0.2-3.5), with a histological diagnosis of invasive ductal carcinoma in 78.9 % and ductal in situ in 21.1 %. A median of 9 catheters (range: 4-14) were used. For APBI, the median CTV and V100 were 40.8 cc (range: 8.6-99) and 35.4 cc (range: 7.2-94). The median of healthy breast tissue irradiated represents 7.2 % (range: 2.3-28 %) and the median local treatment duration was 10 days (range: 7-16). With a median follow-up of 8.8 years (range: 0.3-16.25), the 8-year local, locoregional, and distant control rates were 99 %, 98.1 %, and 100 %. G1-G2 late-toxicity rate was 53.4 %. Long-term cosmetic evaluation was excellent-good in 90.8 %. CONCLUSION: IOMBI&PHDRBT program reports excellent long-term oncological outcomes, with a reduction from unnecessary irradiation exposure which translates into low long-term toxicity and good cosmesis outcomes, especially on well-selected APBI patients.

Very accelerated partial breast irradiation in 1 or 2 days: Late toxicity and early oncological outcome of the GEC-ESTRO VAPBI cohort.

PURPOSE: To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer. MATERIALS: Methods: In this retrospective, observational, international multicenter study (HDH F20220713143949), patients with low-risk breast cancer underwent lumpectomy + vAPBI (high-dose rate multicatheter interstitial brachytherapy-MIBT). VAPBI was performed with 4(4x6.2 Gy/2d), 3(3x7.45 Gy/2d) or 1 fraction (1x16Gy or 1x18Gy/1d). Primary endpoint was late toxicity. Secondary endpoints were cumulative incidence of breast cancer local relapse (LR) and distant metastatic relapse (DMR) and specific (SS) and overall (OS) survivals. Prognostic factors for late toxicity were analyzed. RESULTS: From 01/2012 to 06/2022, 516 pts with early breast cancer were enrolled. Median follow-up was 44 months [95 %CI 39-46]. Median age was 71 years [40-100]. Median tumor size was 12 mm [1-35]. VAPBI delivered 1, 3 and 4 fractions for 205pts (39.7 %), 167pts (32.4 %) and 144pts (28 %) respectively. 221 late toxicity events were observed in 168pts (32.6 %) (Fibrosis, dyschromia, pain and telangiectasia). Grade 2 and 3 late toxicities were observed in 7.2 and 0.6 % respectively (no G4) with no difference between 1 and ≥ 2 treatment days. CTV > 50 cc (p = 0.007) and V150 > 40 % (p = 0.027) were prognostic factors for G ≥ 2 late toxicity. Four-year cumulative incidence rates of LR and DMR were 2 % [95 %CI 0-3] and 1 % [95 %CI 0-2] respectively. CONCLUSIONS: VAPBI based on 1 or ≥ 2 days of MIBT represents an attractive de-escalation of irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows encouraging local control. Longer follow-up is warranted in order to confirm these preliminary results.

Lymphoid interstitial pneumonia in a patient with systemic lupus erythematosus: Case report and literature review.

Lymphoid interstitial pneumonia (LIP) is a rare form of interstitial pulmonary disease, which has been described in association with a wide range of autoimmune disorders. Although the association of this entity with Sjogren's syndrome is well known, only a few cases are reported in relation to systemic lupus erythematosus (SLE). The aim of this paper is to review the cases reported in literature to date, as well as to describe the characteristics of these patients including the new case presented herein. We will be focusing on the case of a 36-year-old female patient diagnosed with SLE on hydroxychloroquine treatment who develops pleuritic chest pain and progressive dyspnea after 3 years of follow-up. The chest CT scan showed pleural thickening and both multiple and bilateral micronodules. A lung biopsy was also performed, revealing an infiltration of lymphocytes, plasma cells, and histiocytes in the alveolar septa suggestive of LIP. After conducting a review of the literature, we identified seven other cases describing SLE in association with LIP. The majority of them were young women, and LIP tends to appear early in the course of the disease, even as a form of initial presentation in some cases. Symptoms included cough, dyspnea, and pleuritic pain, with the exception of one case which was asymptomatic. It is noteworthy that half of the patients were positive for anti-SSA/anti-SSB autoantibodies, and some of them also met criteria for Sjogren's syndrome. Treatment with steroids and other immunosuppressive agents improved symptoms in all of them.

Green hospital pharmacy: A sustainable approach to the medication use process in a tertiary hospital. / [Artículo traducido] Farmacia hospitalaria ecológica: un enfoque sostenible del proceso de utilización de medicamentos en un hospital de tercer nivel.

BACKGROUND: Sustainable management of healthcare waste has a positive impact on the global environment. In order to reduce it, the sustainable practice of the pharmacotherapeutic process in all its stages is essential. OBJECTIVE: To analyse the sustainability strategies proposed by the pharmacy service to reduce drug waste derived from the pharmacotherapeutic process. SECONDARY OBJECTIVES: To analyse the stage of the pharmacotherapeutic process and the number and type of drugs involved. METHODS: The study was carried out in a tertiary-level hospital. To coordinate the proposals, a referent pharmacist from every pharmacy department area was selected. Four stages of the process were evaluated (management, validation, dispensing and compounding), patients concerned were classified as outpatients or inpatients, and drugs potentially involved were analysed by the administration route: Into oral or parenteral. RESULTS: Twenty eight ideas were proposed, which could affect more than 1200 drugs. 39.3% would affect the validation process, 17.9% the procurement management, 17.9% dispensing, and 7.1% the compounding. Implementation feasibility and acceptability of these proposals were evaluated. Those with the greatest potential were: Limiting the duration of treatments when possible, favouring the implementation of computer prescription order entry, favouring the use of the oral route over the parenteral route, and implementing computers in the preparation areas to avoid the use of paper guides. DISCUSION: In our study, many ideas have been proposed by hospital pharmacists to improve the sustainability of the medication use process. When assessing these proposals by impact and feasibility, according to our results, shorten as much as possible the duration of treatments, computerization of the medication use process, and oral administration over intravenous should be prioritized in order to reduce environmental impact.

Retinal hemorrhages due to intracranial hypertension, is it possible to differentiate them from those associated with abuse?

BACKGROUND: Retinal hemorrhages (RHs) are suggestive of abusive head trauma (AHT). Even so, controversy persists about other possible causes, a fact that hinders the diagnosis of abuse. OBJECTIVE: To determine the prevalence and patterns of RHs associated with increased intracranial pressure (ICP) in young children. PARTICIPANTS AND METHODS: Prospective, single center study of children aged 29 days-3 years undergoing a lumbar puncture with opening pressure (OP) measured during routine clinical care in the emergency department, over a 4-year period. Children with known causes of RHs were excluded. All the children underwent a detailed ophthalmological examination within 72 h of admission. For children with RHs, an in-depth investigation was carried out to rule out AHT. RESULTS: Thirty-four patients were included: 20(58.8 %) were boys, median age 11.7 months (range 1-33 months). Overall, 29(85.3 %) had clinical findings of increased ICP. The duration of symptoms was ≤4 days in all patients except one, in whom it was 1.5 months. The median OP was 27cmH2O (range 20-60cmH2O). One of the children was found to have RHs, with evaluation resulting in a diagnosis of AHT. No RHs were found in any of the others studied. Using the Wilson method, we can be confident to an upper limit of 95 % that the probability of RHs occurring secondary to increased ICP alone is at most 0.1. CONCLUSIONS: RHs were not detected in patients with isolated nontraumatic increased ICP, measured via OP and diagnosed in the ED. Therefore, if RHs are detected, investigation into the possibility of AHT is warranted.

A Comprehensive Review of the Effect of Honey on Human Health.

Honey is a nutritious, healthy, and natural food, to which antioxidant, anti-inflammatory, and antimicrobial properties have been attributed, mainly due to its content of phenolic compounds. The aim of this review is to analyze the available evidence of the effect of honey on humans. Forty-eight clinical trials published between 1985 and 2022 were analyzed, with a total of 3655 subjects. More beneficial effects of honey intake than no or negative effects on different cardiovascular and metabolic risk factors, glucose tolerance, mucositis caused by chemo-radiotherapy, cough in children and wound healing, among others have been observed. Although the number of studies conducted to date is limited and the different investigations are not standardized, beneficial effects of honey intake have been observed, especially when its intake replaces the intake of other sweeteners. In addition, honey could be a safe adjuvant to be administered alongside drugs used for certain diseases.

How Healthy Is It to Fortify Cocoa-Based Products with Cocoa Flavanols? A Comprehensive Review.

(1) Background: Cocoa's healthy benefits may be attributed to the potent antioxidant activity of cocoa polyphenols, mainly flavanols, which have been characterised as existing in a high concentration in cocoa. However, the phenolic composition of cocoa and cocoa-derived products is highly variable, and manufacturing processes might significantly reduce their phenolic content. For that reason, the full characterisation of cocoa and cocoa-derived products before evaluating their bioactivity is crucial. The aim of this review is to analyse the available evidence on the effect of flavanol-fortified cocoa-derived products on human health. (2) Methods: Forty-eight clinical trials focused on the health effect of consuming flavanol-fortified drinks, bars and chocolate have been reviewed, with a total of 1523 subjects. (3) Results: Although studies differ widely in methodology, dosage, duration, and target population, beneficial effects of flavanol-rich cocoa consumption have been observed at doses ranging from 45.3 mg/d to 1078 mg/d, especially on cardiovascular health and cognitive function. (4) Conclusions: Considering the high consumption and acceptability of cocoa and cocoa-derived products, the fortification of cocoa products as well as other highly consumed foods with cocoa flavanols could be an effective strategy for health promotion.

Regulatory aspects of a nanomaterial for imaging therapeutic cells.

The ability to track therapeutic cells upon administration to the patient is of interest to both regulators and developers of cell therapy. The European Commission Horizon2020 project nTRACK from 2017-2022 aimed to develop a multi-modal nano-imaging agent to track therapeutic cells during development of a cell therapy. As part of this project, we investigated the regulatory pathway involved for such a product if marketed as a stand-alone product. An important regulatory hurdle appeared to be the appropriate regulatory classification of the nTRACK nano-imaging agent, as neither the definition for medicinal product nor the definition for medical device appeared to be a good fit for the purpose of the product and we were confronted with diverging views of competent authorities on the classification. As a consequence, the information requirements to fulfill before conducting a First in Human trial are not evident and can only be decided upon by closely collaborating and communicating with the relevant authorities throughout the development of the product. Moreover, standard test methods for demonstrating the quality and safety of a medicinal product or medical device are not always suitable for nanomaterials such as the nTRACK nano-imaging agent. Regulatory agility is therefore a great need to prevent delay of promising medical innovations, although regulatory guidance on these products will likely improve with more experience. In this article, we outline the lessons learnt related to the regulatory process of the nTRACK nano-imaging agent for tracking therapeutic cells and offer recommendations to both regulators and developers of similar products.

Added Sugar Consumption in Spanish Children (7-12 y) and Nutrient Density of Foods Contributing to Such Consumption: An Observational Study.

BACKGROUND: Diets rich in free sugars are associated with an increased risk of obesity. The aim of the present study is to estimate the intake of added sugars in the population of Spanish children and analyze the quality of the foods that contribute to this intake. METHODS: An observational study was conducted to collect self-reported information on weekly food consumption in 1775 Spanish children (7-12 years). Nutrient contents were obtained from different databases. Two nutritional density indices were constructed taking into account all nutrients provided and compared with two previously described indices. RESULTS: The average consumption of added sugars in Spanish children was 55.7 ± 1.0 g/day. The products that most contributed to added sugar intake were biscuits (13.3%), cocoa powder (11.1%), sweetened yogurts (9.9%), and dairy desserts (8.6%). Among these, dairy products had considerable nutritional value. Parents' perception of nutritional value was not aligned with the actual nutritional value. CONCLUSION: The consumption of added sugars was higher than recommended. Public awareness efforts should focus on: (1) the reduction of consumption of low-nutritional quality products containing high amounts of added sugars; (2) the industrial reformulation of most consumed products to reduce sugar content and increase valuable nutrients; and (3) nutritional education.

A relevant number of patients do not increase their engagement in physical, social and leisure activities at the medium-term after total knee arthroplasty: a prospective cohort study.

PURPOSE: The purpose of this study was to investigate the changes in engagement in physical, leisure and social activities in older adults following primary TKA. METHODS: A prospective study of 106 patients with a mean age of 72.6 (SD 7.4) years undergoing primary TKA was performed. Physical, social and leisure activities performed by the patients preoperatively and postoperatively at 3-year were recorded. Activities were selected according to the age, and grouped as passive, moderate and high intensity. The energy spent in each activity was expressed in Metabolic Equivalent of Task (MET) units. Charlson Comorbidity Index, Mini-mental test and Western Ontario and McMaster Universities (WOMAC) scores were also used. Multivariate analysis was used to identify predictors of active patients. RESULTS: Mean WOMAC significantly improved from preoperative (34.8, SD 11.8) to final follow-up (74.4, SD 11.1) (p = 0.001), and the mean energy spent increased from 10.7 (SD 13.6) to 28.2 (SD 16.2) MET-hour weekly (p = 0.001) with a decrease in the passive activities and increase in the moderate activities. However, the participation in high-intensity activities according to age was negligible. Only 65 (61.3%) patients were considered active postoperatively (weekly spending ≥ 40 MET), although the WOMAC scores were not significantly different between active and sedentary patients. Active patients compared with sedentary patients had a significant increase in engagement in physical, social and leisure activities, and a decrease in passive activities. Female gender (p = 0.037), less preoperatively participation in passive activities (p = 0.042), and greater participation in social activities (p = 0.027) were significant predictors of active patients at the final follow-up. CONCLUSION: Overall, most patients increased their activity level postoperatively. However, 38.6% of patients had no increased engagement in moderate physical, social or leisure activities at the medium-term despite improvements in pain and function provided by TKA. LEVEL OF EVIDENCE: II.

Synergy of carbohydrate and caffeine ingestion on physical performance and metabolic responses to exercise: A systematic review with meta-analysis.

Carbohydrates (CHO) and caffeine (CAF) are two ergogenic aids commonly used among athletes to enhance performance. However, there is some controversy as to whether the concurrent intake of both supplements might result in an additive and synergistic improvement in exercise performance. The aim of this systematic review and meta-analysis was to determine the effect of adding CAF to a protocol of CHO ingestion, compared with the intake of each ergogenic aid alone and with placebo, on exercise performance and metabolic responses in healthy young physically active adults. This study was conducted according to PRISMA 2020 guidelines. The PubMed, Web of Science, Medline Complete, CINAHL, SPORTDiscus and CENTRAL databases were searched including randomized controlled trials (RCT) that were at least single blind. The risk of bias assessment was performed using the Cochrane Risk-of-Bias tool 2. Meta-analysis were performed on performance variables and rating of perceived exertion (RPE) using the random-effects model. Thirteen RCT with 128 participants (117 men and 11 women) were included in this study. The ingestion of CAF and CHO reduced sprint time during repeated sprint protocols in comparison with CHO isolated ingestion (SMD: -0.45; 95% CI: -0.85, -0.05) while there was a tendency for a reduction in the time employed during time trials (SMD: -0.36; 95% CI: -0.77, 0.05). The RPE tended to be lower with CAF and CHO compared with CHO isolated ingestion during steady-state exercise (SMD: -0.43; 95% CI: -0.91, 0.05) with no differences between conditions in performance trials (SMD: -0.05, 95% CI: -0.39, 0.29). Although most of the studies showed higher values of blood glucose when CHO was co-ingested with CAF compared with PLA, only two studies observed higher values with CHO and CAF co-ingestion with respect to the isolated intake of CHO. One study observed greater fat oxidation and lower glycogen use when CAF was added to CHO. In terms of cortisol levels, one study showed an increase in cortisol levels when CAF was co-ingested with CHO compared with PLA. In summary, concurrent CHO and CAF intake may produce an additive ergogenic effect respect of the isolated ingestion of CHO. This additive effect was present when CHO was provided by a 6-9% of CHO solution (maltodextrin/dextrin + fructose) and CAF is administered in a dose of 4-6.5 mg/kg.

Combined Immune Defect in B-Cell Lymphoproliferative Disorders Is Associated with Severe Infection and Cancer Progression.

B cell chronic lymphoproliferative diseases (B-CLPD) are associated with secondary antibody deficiency and other innate and adaptive immune defects, whose impact on infectious risk has not been systematically addressed. We performed an immunological analysis of a cohort of 83 B-CLPD patients with recurrent and/or severe infections to ascertain the clinical relevance of the immune deficiency expression. B-cell defects were present in all patients. Patients with combined immune defect had a 3.69-fold higher risk for severe infection (p = 0.001) than those with predominantly antibody defect. Interestingly, by Kaplan-Meier analysis, combined immune defect showed an earlier progression of cancer with a hazard ratio of 3.21, than predominantly antibody defect (p = 0.005). When B-CLPD were classified in low-degree, high-degree, and plasma cell dyscrasias, risk of severe disease and cancer progression significantly diverged in combined immune defect, compared with predominantly antibody defect (p = 0.001). Remarkably, an underlying primary immunodeficiency (PID) was suspected in 12 patients (14%), due to prior history of infections, autoimmune and granulomatous conditions, atypical or variegated course and compatible biological data. This first proposed SID classification might have relevant clinical implications, in terms of predicting severe infections and cancer progression, and might be applied to different B-CLPD entities.

Food made us human: Recent genetic variability and its relevance to the current distribution of macronutrients.

Numerous dietary strategies are currently used for the prevention of metabolic diseases and for weight loss. Some of the strategies that are used do not have an appropriate physiological-nutritional basis and do not take into account the genetic changes that have occurred recently. Thus, in certain cases, they can be harmful to human health. This review aims to explain the genetic mutations that have occurred during human evolution from the first hominids to Homo sapiens and to explain how they have influenced the way we feed ourselves. Some mutations favored brain development and others are related to the digestion of nutrients such as lactose and starch. The influence of the domestication of food and the practice of cooking on human nutrition is also explained. In addition, this review intends to justify the current recommendations on the caloric distribution of macronutrients based on the important influence of genetic changes and adaptations that have occurred in our species.

Four-fraction ultra-accelerated minimal breast irradiation in early breast cancer: The initial feasibility results of an institutional experience.

PURPOSE: To evaluate the feasibility, early toxicity, and clinical outcomes of early-breast cancer patients in a single-arm, phase I/II study of an ultra-accelerated, four-fraction schedule of minimal breast irradiation (4f-AMBI) using a multicatheter, minimally-invasive, intraoperative tumor bed implant (MITBI) during breast-conserving surgery (BCS). METHODS AND MATERIALS: Eligible women aged >40 years with clinically and radiologically confirmed, unifocal invasive or in situ ≤3 cm tumors were considered as potential candidates for MITBI during BCS. After the pathology report, patients who met APBI criteria received ultra-accelerated four-fractions irradiation (6.2 Gy BID x 4fx over 2 days) with perioperative HDR-brachytherapy (PHDRBT). Early complications, toxicity, clinical outcomes, and cosmetic results were analyzed. RESULTS: Of 89 patients initially implanted, 60(67.4%) were definitively included in the 4f-AMBI-protocol. The median age was 64.4 years; the median CTV was 32.1 cc (6.9-75.4 cc), and the external-V100 was 43.1 cc (12.87-107 cc), representing 5% of the breast tissue irradiated with a median CTV D90 of 6.2 Gy (5.6-6.28 Gy). The entire local treatment (BCS&MITBI-4f-AMBI) was completed at a median of 8 days (4-10 days). The rate of early complications was 11%. There were no major complications. Acute skin-subcutaneous G1 toxicity was reported in 11.7%, and late G1 toxicity on 36.7%. After a median follow-up of 27 months (11-51 months), the local, elsewhere, locoregional and distant-control rates were 100%, 98.3%, 100%, and 100% respectively. The early-cosmetic evaluation was excellent-good in 94.5% of patients evaluated. CONCLUSIONS: Ultra-accelerated, four-fraction, minimal breast irradiation (4f-AMBI) using a minimally-invasive tumor bed implant procedure is safe, dosimetrically feasible, and shows small irradiated volumes. This program provides low toxicity rates and excellent short-term clinical and cosmesis outcomes.