Lymphoma of the central nervous system originating from the septum pellucidum region: Two case reports with literature review.

RATIONALE: Central nervous system lymphoma (CNSL) originating from the septum pellucidum is exceptionally rare, presenting unique diagnostic and therapeutic complexities. This case report aims to elucidate the diagnostic challenges, treatment strategies, and outcomes of this rare manifestation. By documenting this case, we seek to enhance understanding within the medical community and contribute valuable insights to the management of CNSL, particularly in atypical locations. PATIENT CONCERNS: A 45-year-old female presented with persistent headaches, blurred vision, and motor weakness, prompting a thorough neurological evaluation. Imaging revealed an enhancing mass in the septum pellucidum, leading to the diagnosis of CNSL. The patient's concerns encompassed not only the physical symptoms but also the emotional impact of her diagnosis and treatment journey. DIAGNOSES: Diagnostic confirmation of CNSL involved cerebrospinal fluid analysis and imaging findings, highlighting the challenge of distinguishing lymphoma from other intracranial pathologies. The case underscores the importance of comprehensive diagnostic evaluation in rare CNSL presentations. INTERVENTIONS: Multidisciplinary management included high-dose methotrexate-based chemotherapy and corticosteroids, with consideration for neurosurgical intervention. Psychosocial support and self-care strategies were integrated into the treatment plan to address holistic patient needs. OUTCOMES: Monitoring revealed a positive treatment response, with a reduction observed in the septum pellucidum mass. Regular assessments ensured adherence to interventions and management of treatment-related side effects, contributing to favorable outcomes and improved quality of life for the patient. LESSONS: This case emphasizes the significance of meticulous diagnostic evaluation and personalized treatment approaches in managing rare CNSL presentations. Collaboration among specialists and comprehensive patient support is paramount in optimizing outcomes and addressing the multifaceted challenges posed by CNSL in unique anatomical locations.

Comparative analysis of different therapeutic approaches in the management of protein-energy malnutrition: Case reports from a clinical setting.

BACKGROUND: Severe protein-energy malnutrition (PEM) presents a significant clinical challenge, often compounded by comorbidities such as type 2 diabetes. This case report aims to elucidate the intricacies of managing severe PEM in conjunction with type 2 diabetes, emphasizing the importance of personalized interventions and multidisciplinary collaboration in achieving optimal outcomes. By addressing the unique challenges this complex clinical scenario poses, this report contributes valuable insights to the medical literature and guides clinicians in effectively managing similar cases. METHODS: The patient, pseudonymously identified as Emma Thompson, underwent a comprehensive diagnostic evaluation to assess her symptoms' severity and underlying causes. This included a thorough physical examination, laboratory testing, imaging studies, and collaboration with specialists to formulate a tailored treatment plan. Interventions were meticulously administered, with dosages, strengths, and durations adjusted based on ongoing assessments and patient response. RESULTS: Implementing multidisciplinary therapeutic interventions significantly improved the patient's nutritional status, glycemic control, and overall well-being. Objective measures such as BMI, serum albumin levels, and physical functioning showed marked improvement throughout treatment. Patient-reported outcomes indicated enhanced quality of life, reduced fatigue, and increased energy levels, underscoring the comprehensive success of the integrated therapeutic approach. CONCLUSION: This case report highlights the efficacy of a holistic, patient-centered approach in managing severe PEM and comorbid type 2 diabetes. Optimal outcomes were achieved by addressing the complex interplay of medical conditions through tailored interventions and multidisciplinary collaboration. The lessons from this case underscore the importance of individualized care, ongoing assessment, and long-term follow-up in enhancing patient well-being and guiding future clinical practice.

A rare presentation of Wilson disease with neurological symptoms: Case report and genetic analysis.

RATIONALE: Wilson disease is a rare genetic disorder primarily associated with hepatic symptoms; however, its unique neurological presentation remains a subject of interest in the medical literature. This case report contributes to existing knowledge by highlighting the unusual manifestation of Wilson disease with significant neurological symptoms. PATIENT CONCERNS: The patient, pseudonym John Smith, presented with prominent neurological symptoms, including tremors, dystonia, and psychiatric manifestations. Clinical findings corroborated copper accumulation in the brain, prompting a thorough diagnostic investigation. DIAGNOSES: Genetic analysis revealed two ATP7B mutations, confirming the primary diagnosis of Wilson disease. This case underscores the importance of recognizing atypical neurological presentations in the context of this rare genetic disorder. INTERVENTIONS: Chelation therapy, initiated promptly upon diagnosis, targeted copper overload. The intervention led to notable improvements in neurological symptoms and psychiatric manifestations. The dosage and duration of treatment were adjusted based on regular monitoring. OUTCOMES: Regular follow-up revealed a positive trajectory, with reduced tremors and improved overall well-being. Genetic testing, coupled with clinical assessments, contributed to monitoring treatment efficacy and optimizing therapeutic interventions. LESSONS: The main takeaway lessons from this case include the significance of a comprehensive diagnostic approach, personalized therapeutic interventions, and the imperative to acknowledge the diverse clinical spectrum of Wilson disease. Early recognition and tailored treatment contribute to favorable outcomes in cases with atypical neurological presentations.

Relationship between stress and coronary artery disease: A comprehensive review.

Coronary artery disease (CAD) poses a substantial public health challenge. This review examines the intricate relationship between psychological stress and CAD, drawing from recent research spanning the last 5 to 10 years. The literature review is organized around critical themes. It includes an analysis of genetic loci in CAD susceptibility and underscores the role of green environments in reducing cardiovascular risk. A quantitative analysis presents numerical findings for clarity, while pathophysiological mechanisms are elucidated through informative figures and diagrams. The review engages with controversies and disparities in the literature, offering a balanced perspective. A tabular comparative analysis outlines the strengths and limitations of existing approaches, emphasizing conflicting findings, and environmental factors. The review concludes by distilling key takeaways for healthcare professionals and researchers. Practical implications are explored, and lessons learned from the research process are reflected upon. The conclusion also suggests avenues for further study in understanding stress's impact on CAD.

Two-component nematic superconductivity in 4Hb-TaS2.

Most superconductors have an isotropic, single component order parameter and are well described by the standard (BCS) theory for superconductivity. Unconventional, multiple-component superconductors are exceptionally rare and are much less understood. Here, we combine scanning tunneling microscopy and angle-resolved macroscopic transport for studying the candidate chiral superconductor, 4Hb-TaS2. We reveal quasi-periodic one-dimensional modulations in the tunneling conductance accompanied by two-fold symmetric superconducting critical field. The strong modulation of the in-plane critical field, Hc2, points to a nematic, unconventional order parameter. However, the imaged vortex core is isotropic at low temperatures. We suggest a model that reconciles this apparent discrepancy and takes into account previously observed spontaneous time-reversal symmetry breaking at low temperatures. The model describes a competition between a dominating chiral superconducting order parameter and a nematic one. The latter emerges close to the normal phase. Our results strongly support the existence of two-component superconductivity in 4Hb-TaS2 and can provide valuable insights into other systems with coexistent charge order and superconductivity.

Ethical implications of AI and robotics in healthcare: A review.

Integrating Artificial Intelligence (AI) and robotics in healthcare heralds a new era of medical innovation, promising enhanced diagnostics, streamlined processes, and improved patient care. However, this technological revolution is accompanied by intricate ethical implications that demand meticulous consideration. This article navigates the complex ethical terrain surrounding AI and robotics in healthcare, delving into specific dimensions and providing strategies and best practices for ethical navigation. Privacy and data security are paramount concerns, necessitating robust encryption and anonymization techniques to safeguard patient data. Responsible data handling practices, including decentralized data sharing, are critical to preserve patient privacy. Algorithmic bias poses a significant challenge, demanding diverse datasets and ongoing monitoring to ensure fairness. Transparency and explainability in AI decision-making processes enhance trust and accountability. Clear responsibility frameworks are essential to address the accountability of manufacturers, healthcare institutions, and professionals. Ethical guidelines, regularly updated and accessible to all stakeholders, guide decision-making in this dynamic landscape. Moreover, the societal implications of AI and robotics extend to accessibility, equity, and societal trust. Strategies to bridge the digital divide and ensure equitable access must be prioritized. Global collaboration is pivotal in developing adaptable regulations and addressing legal challenges like liability and intellectual property. Ethics must remain at the forefront in the ever-evolving realm of healthcare technology. By embracing these strategies and best practices, healthcare systems and professionals can harness the potential of AI and robotics, ensuring responsible and ethical integration that benefits patients while upholding the highest ethical standards.

Heart failure and diabetes: Understanding the bidirectional relationship.

Heart failure and diabetes mellitus are 2 common and closely intertwined chronic conditions that often coexist in individuals. The relationship between heart failure and diabetes is bidirectional, meaning that each condition can influence the development and progression of the other. Understanding this complex interplay is crucial for optimizing the management and outcomes of patients with these comorbidities. This review comprehensively analyzed the literature to examine the bidirectional relationship between heart failure and diabetes. We searched various electronic databases and included studies that explored the pathophysiological mechanisms, epidemiology, clinical implications, and therapeutic considerations associated with this relationship. The bidirectional relationship between heart failure and diabetes is multifactorial and involves several interconnected mechanisms. Diabetes is a recognized risk factor for heart failure, increasing the risk of its development and accelerating its progression. On the other hand, heart failure can contribute to the development of insulin resistance and worsen glycemic control in patients with diabetes. Shared risk factors, such as obesity, hypertension, and dyslipidemia, contribute to development of both conditions. Additionally, hyperglycemia, insulin resistance, chronic inflammation, oxidative stress, and mitochondrial dysfunction play significant roles in the pathogenesis of heart failure in individuals with diabetes. The bidirectional relationship between heart failure and diabetes has important clinical implications. Patients with heart failure and diabetes have worse outcomes, including higher hospitalization rates, morbidity, and mortality, than those without diabetes. Optimal management strategies should target both conditions simultaneously, focusing on lifestyle modifications, pharmacotherapy, glycemic control, and cardiovascular risk reduction.

Position statement from the Editors of Anaesthesia and Anaesthesia Reports on best practice in academic medical publishing.

It is essential that academic publishing complies with the highest standards in terms of ethics, research conduct and manuscript preparation. This protects the rights and welfare of research participants, ensures the integrity of study results and aids the communication and dissemination of novel findings into clinical practice. This position statement outlines the current policies and practices of the Editors of Anaesthesia and Anaesthesia Reports in relation to academic medical publishing.

Social media and COVID-19 vaccination hesitancy during pregnancy: a mixed methods analysis.

OBJECTIVE: To evaluate the reasons for COVID-19 vaccine hesitancy during pregnancy. DESIGN: We used regular expressions to identify publicly available social media posts from pregnant people expressing at least one reason for their decision not to accept COVID-19 vaccine. SETTING: Two social media platforms - WhatToExpect and Twitter. SAMPLE: A total of 945 pregnant people in WhatToExpect (1017 posts) and 345 pregnant people in Twitter (435 tweets). METHODS: Two annotators manually coded posts according to the Scientific Advisory Group for Emergencies (SAGE) working group's 3Cs vaccine hesitancy model (confidence, complacency and convenience barriers). Within each 3Cs we created subthemes that emerged from the data. MAIN OUTCOME MEASURES: Subthemes were derived according to the people's posting own words. RESULTS: Safety concerns were most common and largely linked to the perceived speed at which the vaccine was created and the lack of data about its safety in pregnancy. This led to a preference to wait until after the baby was born or to take other precautions instead. Complacency surrounded a belief that they are young and healthy or already had COVID-19. Misinformation led to false safety and efficacy allegations, or even conspiracy theories, and fed into creating confidence and complacency barriers. Convenience barriers (such as availability) were uncommon. CONCLUSION: The information in this study can be used to highlight the questions, fears and hesitations pregnant people have about the COVID-19 vaccine. Highlighting these hesitations can help public health campaigns and improve communication between healthcare professionals and patients.

High-flow nasal oxygen vs. standard oxygen therapy for patients undergoing transcatheter aortic valve replacement with conscious sedation: a randomised controlled trial.

BACKGROUND: Minimally invasive surgery is becoming more common and transfemoral transcatheter aortic valve replacement is offered to older patients with multiple comorbidities. Sternotomy is not required but patients must lie flat and still for up to 2-3 h. This procedure is increasingly being performed under conscious sedation with supplementary oxygen, but hypoxia and agitation are commonly observed. METHODS: In this randomised controlled trial, we hypothesised that high-flow nasal oxygen would provide superior oxygenation as compared with our standard practice, 2 l min-1 oxygen by dry nasal specs. This was administered using the Optiflow THRIVE Nasal High Flow delivery system (Fisher and Paykel, Auckland, New Zealand) at a flow rate of 50 l min-1 and FiO2 0.3. The primary endpoint was the change in arterial partial pressure of oxygen (pO2) during the procedure. Secondary outcomes included the incidence of oxygen desaturation, airway interventions, the number of times the patient reached for the oxygen delivery device, incidence of cerebral desaturation, peri-operative oxygen therapy duration, hospital length of stay and patient satisfaction scores. RESULTS: A total of 72 patients were recruited. There was no difference in change in pO2 from baseline using high-flow compared with standard oxygen therapy: median [IQR] increase from 12.10 (10.05-15.22 [7.2-29.8]) to 13.69 (10.85-18.38 [8.5-32.3]) kPa vs. decrease from 15.45 (12.17-19.33 [9.2-22.8]) to 14.20 (11.80-19.40 [9.7-35.1]) kPa, respectively. The percentage change in pO2 after 30 min was also not significantly different between the two groups (p = 0.171). There was a lower incidence of oxygen desaturation in the high-flow group (p = 0.027). Patients in the high-flow group assigned a significantly higher comfort score to their treatment (p ≤ 0.001). CONCLUSION: This study has demonstrated that high flow, compared with standard oxygen therapy, does not improve arterial oxygenation over the course of the procedure. There are suggestions that it may improve the secondary outcomes studied. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 13,804,861. Registered on 15 April 2019. https://doi.org/10.1186/ISRCTN13804861.

Self-regulation as a resource for coping with developmental challenges during middle childhood and adolescence: the prospective longitudinal PIERYOUTH-study.

BACKGROUND: Self-regulation (SR) as the ability to regulate one's own physical state, emotions, cognitions, and behavior, is considered to play a pivotal role in the concurrent and subsequent mental and physical health of an individual. Although SR skills encompass numerous sub-facets, previous research has often focused on only one or a few of these sub-facets, and only rarely on adolescence. Therefore, little is known about the development of the sub-facets, their interplay, and their specific contributions to future developmental outcomes, particularly in adolescence. To fill these research gaps, this study aims to prospectively examine (1) the development of SR and (2) their influence on adolescent-specific developmental outcomes in a large community sample. METHODS/DESIGN: Based on previously collected data from the Potsdam Intrapersonal Developmental Risk (PIER) study with three measurement points, the present prospective, longitudinal study aims to add a fourth measurement point (PIERYOUTH). We aim to retain at least 1074 participants now between 16 and 23 years of the initially 1657 participants (6-11 years of age at the first measurement point in 2012/2013; 52.2% female). The study will continue to follow a multi-method (questionnaires, physiological assessments, performance-based computer tasks), multi-facet (assessing various domains of SR), and multi-rater (self-, parent-, and teacher-report) approach. In addition, a broad range of adolescent-specific developmental outcomes is considered. In doing so, we will cover the development of SR and relevant outcomes over the period of 10 years. In addition, we intend to conduct a fifth measurement point (given prolonged funding) to investigate development up to young adulthood. DISCUSSION: With its broad and multimethodological approach, PIERYOUTH aims to contribute to a deeper understanding of the development and role of various SR sub-facets from middle childhood to adolescence. The large sample size and low drop-out rates in the first three measurements points form a sound database for our present prospective research. Trial registration German Clinical Trials Register, registration number DRKS00030847.

The association between iron deficiency and outcomes: a secondary analysis of the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial.

In the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial, the use of intravenous iron did not reduce the need for blood transfusion or reduce patient complications or length of hospital stay. As part of the trial protocol, serum was collected at randomisation and on the day of surgery. These samples were analysed in a central laboratory for markers of iron deficiency. We performed a secondary analysis to explore the potential interactions between pre-operative markers of iron deficiency and intervention status on the trial outcome measures. Absolute iron deficiency was defined as ferritin <30 µg.l-1 ; functional iron deficiency as ferritin 30-100 µg.l-1 or transferrin saturation < 20%; and the remainder as non-iron deficient. Interactions were estimated using generalised linear models that included different subgroup indicators of baseline iron status. Co-primary endpoints were blood transfusion or death and number of blood transfusions, from randomisation to 30 days postoperatively. Secondary endpoints included peri-operative change in haemoglobin, postoperative complications and length of hospital stay. Most patients had iron deficiency (369/452 [82%]) at randomisation; one-third had absolute iron deficiency (144/452 [32%]) and half had functional iron deficiency (225/452 [50%]). The change in pre-operative haemoglobin with intravenous iron compared with placebo was greatest in patients with absolute iron deficiency, mean difference 8.9 g.l-1 , 95%CI 5.3-12.5; moderate in functional iron deficiency, mean difference 2.8 g.l-1 , 95%CI -0.1 to 5.7; and with little change seen in those patients who were non-iron deficient. Subgroup analyses did not suggest that intravenous iron compared with placebo reduced the likelihood of death or blood transfusion at 30 days differentially across subgroups according to baseline ferritin (p = 0.33 for interaction), transferrin saturation (p = 0.13) or in combination (p = 0.45), or for the number of blood transfusions (p = 0.06, 0.29, and 0.39, respectively). There was no beneficial effect of the use of intravenous iron compared with placebo, regardless of the metrics to diagnose iron deficiency, on postoperative complications or length of hospital stay.

A PMM2-CDG caused by an A108V mutation associated with a heterozygous 70 kilobases deletion case report.

BACKGROUND: Congenital Disorders of Glycosylation (CDG) are a large group of inborn errors of metabolism with more than 140 different CDG types reported to date (1). The first characterized, PMM2-CDG, with an autosomal recessive transmission, is also the most frequent. The PMM2 gene encodes a phosphomannomutase. Here, a novel genetic variation causing PMM2-CDG is reported.  CASE PRESENTATION: We report the case of a French child, from healthy and unrelated parents, presenting congenital ataxia with hypotonia, hyperlaxity, inverted nipples, as well as altered coagulation parameters and liver function. Transferrin isoelectrofocusing revealed a typical type I CDG profile. Direct Sanger sequencing and quantitative PCR of PMM2 revealed a unique and novel genotype. On one allele, the patient was heterozygote with a known missense variant NM_000303.3(PMM2):c.323C > T, p.Ala108Val in exon 4. On the second allele, whole genome sequencing (WGS) indicated the presence of a novel heterozygous 70 kb deletion. CONCLUSION: We report in the present paper the largest known heterozygous deletion of a PMM2 gene. The observation reveals the impact of a precise diagnostic on genetic counselling: by using WGS, an erroneous conclusion of homozygosity in the case of a relatively rare variant could be avoided, and an index patient with healthy and unrelated parents correctly identified.

The role of parental anxiety symptoms in the treatment of childhood social anxiety disorder.

The study investigated the role of parental anxiety symptoms in treatment outcomes for children with a primary social anxiety disorder compared to children with other primary anxiety disorders. Participants were 152 children between 7 and 18 years and their parents (146 mothers, 123 fathers). Anxiety was assessed pretreatment, posttreatment, and at three months and one year follow ups. There were no baseline differences in parental anxiety symptoms between the two groups. In both groups parental anxiety symptoms decreased from pretreatment to posttreatment, and only mothers' anxiety symptoms decreased further from posttreatment to the one year follow up. Parental anxiety symptoms before the treatment were not related to the being free of all anxiety diagnoses in the children at posttreatment. However, some indications were found for greater improvements during treatment when parents had higher anxiety symptoms before treatment. Changes in parental anxiety symptoms were found to be related to changes in child anxiety symptoms. This was not found for the total clinical severity of all inclusion anxiety disorders. This relation was visible independently in fathers or mothers, or in groups of children with a primary social anxiety disorder or with another primary anxiety disorder. In conclusion, we did not find clear indications that parental anxiety symptoms explain the differences in treatment outcomes for children with a primary social anxiety disorder compared to children with other primary anxiety disorders. More research with larger samples is needed to draw stronger conclusions.

Man vs. machine: A meta-analysis on the added value of human support in text-based internet treatments ("e-therapy") for mental disorders.

Guided internet-based treatment is more efficacious than completely unguided or self-guided internet-based treatment, yet within the spectrum of guidance, little is known about the added value of human support compared to more basic forms of guidance. The primary aims of this meta-analysis were: (1) to examine whether human guidance was more efficacious than technological guidance in text-based internet treatments ("e-therapy") for mental disorders, and (2) whether more intensive human guidance outperformed basic forms of human guidance. PsycINFO, PubMed and Web of Science were systematically searched for randomized controlled trials that directly compared various types and degrees of online guidance. Thirty-one studies, totaling 6215 individuals, met inclusion criteria. Results showed that human guidance was slightly more efficacious than technological guidance, both in terms of symptom reduction (g = 0.11; p < .01) and adherence (0.26 < g < 0.29; p's < 0.01). On the spectrum of human support, results were slightly more favorable for regular guidance compared to optional guidance, but only in terms of adherence (OR = 1.89, g = 0.35; p < .05). Higher qualification of online counselors was not associated with efficacy. These findings extend and refine previous reports on guided and unguided online treatments.

The age-dependent association of risk factors with pancreatic cancer.

BACKGROUND: Pancreatic cancer presents as advanced disease in >80% of patients; yet, appropriate ages to consider prevention and early detection strategies are poorly defined. We investigated age-specific associations and attributable risks of pancreatic cancer for established modifiable and non-modifiable risk factors. PATIENTS AND METHODS: We included 167 483 participants from two prospective US cohort studies with 1190 incident cases of pancreatic cancer during >30 years of follow-up; 5107 pancreatic cancer cases and 8845 control participants of European ancestry from a completed multicenter genome-wide association study (GWAS); and 248 893 pancreatic cancer cases documented in the US Surveillance, Epidemiology, and End Results (SEER) Program. Across different age categories, we investigated cigarette smoking, obesity, diabetes, height, and non-O blood group in the prospective cohorts; weighted polygenic risk score of 22 previously identified single nucleotide polymorphisms in the GWAS; and male sex and black race in the SEER Program. RESULTS: In the prospective cohorts, all five risk factors were more strongly associated with pancreatic cancer risk among younger participants, with associations attenuated among those aged >70 years. The hazard ratios comparing participants with three to five risk factors with those with no risk factors were 9.24 [95% confidence interval (CI) 4.11-20.77] among those aged ≤60 years, 3.00 (95% CI 1.85-4.86) among those aged 61-70 years, and 1.46 (95% CI 1.10-1.94) among those aged >70 years (Pheterogeneity = 3×10-5). These factors together were related to 65.6%, 49.7%, and 17.2% of incident pancreatic cancers in these age groups, respectively. In the GWAS and the SEER Program, the associations with the polygenic risk score, male sex, and black race were all stronger among younger individuals (Pheterogeneity ≤0.01). CONCLUSIONS: Established risk factors are more strongly associated with earlier-onset pancreatic cancer, emphasizing the importance of age at initiation for cancer prevention and control programs targeting this highly lethal malignancy.

Efficacy, safety and quality-of-life data from patients with pre-treated metastatic colorectal cancer receiving trifluridine/tipiracil: results of the TALLISUR trial.

INTRODUCTION: Trifluridine/tipiracil (FTD/TPI) improved both overall and progression-free survival (OS, PFS) of patients with pre-treated metastatic colorectal cancer (mCRC) in the pivotal phase III RECOURSE trial. However, health-related quality of life (HRQoL) was not assessed directly. To this end and to generate post-authorisation data, the TALLISUR trial was conducted. METHODS: In this prospective, multi-centre, Germany-wide, phase IV study, patients with pre-treated mCRC were given the choice to receive either FTD/TPI or best supportive care (BSC). A validated questionnaire, EORTC QLQ-C30, was employed to assess HRQoL. Secondary endpoints included OS, PFS and safety. RESULTS: Of 194 eligible patients, 185 decided to receive FTD/TPI and 9 to receive BSC. The low number of patients in the BSC-arm did not allow statistically meaningful analyses. On the other hand, treatment with FTD/TPI was associated with maintained HRQoL. Median OS was 6.9 months [95% confidence interval (CI) 6.1-8.2 months] and median PFS was 2.5 months (95% CI 2.1-2.9 months). The most frequent treatment-emergent adverse events were neutropenia (27.6%) and anaemia (22.7%). Febrile neutropenia occurred in 1.1%. CONCLUSIONS: Treatment of patients suffering from pre-treated mCRC with FTD/TPI was associated not only with prolonged survival and delayed progression but also with maintained HRQoL.

Subcutaneous injection of an immunologically tolerated protein up to 5 days before skin injuries improves wound healing.

Oral tolerance blocks the development of specific immune responses to proteins ingested by the oral route. One of the first registries of oral tolerance showed that guinea pigs fed corn became refractory to hypersensitivity to corn proteins. Mice fed with chow containing corn are tolerant to zein, and parenteral injection of zein plus adjuvant blocks immunization to unrelated proteins injected concomitantly and reduces unspecific inflammation. Extensive and prolonged inflammatory infiltrate in the wound bed is one of the causes of pathological wound healing. Previous research shows that intraperitoneal injection of zein concomitant with skin injuries reduces the inflammatory infiltrate in the wound bed and improves wound healing. Herein, we tested if one subcutaneous injection of zein before skin injury improves wound healing. We also investigated how long the effects triggered by zein could improve skin wound healing. Mice fed zein received two excisional wounds on the interscapular skin under anesthesia. Zein plus Al(OH)3 was injected at the tail base at 10 min, or 3, 5, or 7 days before skin injuries. Wound healing was analyzed at days 7 and 40 after injury. Our results showed that a zein injection up to 5 days before skin injury reduced the inflammatory infiltrate, increased the number of T-cells in the wound bed, and improved the pattern of collagen deposition in the neodermis. These findings could promote the development of new strategies for the treatment and prevention of pathological healing using proteins normally found in the common diet.