Development and validation study of compact biophotonic platform for detection of serum biomarkers.

The application of advances in personalized medicine requires the support of in vitro diagnostic techniques aimed at the accurate, fast, sensitive, and precise determination of selected biomarkers. Herein, a novel optical centrifugal microfluidic device is developed for clinical analysis and point-of-care diagnostics. Based on compact disc technology, the integrated biophotonic system enables multiple immunoassays in miniaturized mode. The disposable microfluidic discs are made in cyclic olefin copolymer (COP), containing arrays of immobilized probes. In the developed approach, up to six patient samples can each be tested simultaneously. A portable instrument (<2 kg) controls the assay and the high-sensitive reproducible optical detection in transmission mode. Also, the instrument incorporates specific functionalities for personalized telemedicine. The device (analytical method, disc platform, reader, and software) has been validated to diagnose IgE-mediated drug allergies, such as amoxicillin and penicillin G. The total and specific IgE to ß-lactam antibiotics were determined in human serum from patients (25 µL). The excellent analytical performances (detection limit 0.24 ng/mL, standard deviation 7-20 %) demonstrated that the developed system could have the potential for a broader impact beyond the allergy field, as it applies to other IVD tests.

Systematic Cholecystectomy During Cytoreductive Surgery Plus HIPEC: A Critical Analysis of an Empirical Tradition.

BACKGROUND: Some procedures performed during cytoreductive surgery (CRS) and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) are based on empirical data. One of these procedures is systematic cholecystectomy. This study aimed to perform a critical analysis of the need for systematic cholecystectomy during CRS+HIPEC of patients with peritoneal carcinomatosis using long-term follow-up data. METHODS: Patients with peritoneal surface malignancies who were candidates for CRS+HIPEC and underwent surgery between January 2008 and December 2022 were analyzed. For patients with gallbladder involvement due to the disease or for patients whose preoperative study showed the presence of cholelithiasis, cholecystectomy was performed as part of the surgery, which was avoided for the remaining patients. All postoperative adverse events that occurred in the first 90 days were recorded, and clinical records focused on the development of biliary pathology during the follow-up period were studied. RESULTS: The results from a consecutive series of 443 patients with peritoneal surface malignancies who underwent surgery between January 2008 and December 2022 were analyzed. The average age of the cohort was 50 years. The median follow-up period for the cohort was 41 months (range, 12-180 months), with a disease-free survival of 17 months. For 373 of the patients, CRS+HIPEC was completed without an associated cholecystectomy, and in 16 of them, the appearance of cholelithiasis was detected during the follow-up period. Only two patients in the series showed complications derived from gallstones and required a delayed cholecystectomy. CONCLUSIONS: Although cholecystectomy is a safe procedure in the context of CRS+HIPEC, it is not risk free, and its routine performance may be unnecessary.

Identifying the ideal weekly training load for in-game performance in an elite Brazilian soccer team.

Introduction: The purpose of this study was to investigate the ideal training load to be applied during periods of fixture congestion to ensure an adequate dose-response effect for performance maintenance. Methods: Match performance data and corresponding pre-match training load sessions (both N = 498 match performance cases and training-block session cases) were collected (with the catapult system, VECTOR7) from 36 male professional soccer players (23.5 ± 5.2 years; 178 ± 4 cm; 75.5 ± 6.0 kg) belonging to the Brazilian First Division team during the 2022 season. The following data were collected in match and training sessions: jump, acceleration, deceleration, and change of direction (COD); running distance producing metabolic power at different intensities (>20, >20-35, >35-45, >45-55, and >55 W kg-1), total distance (m), relative distance (m/min), running distance at different speeds (>20, >25, and >30 km/h), number of sprints (running >25 km/h), and maximum speed (km/h). Mixed linear model (MLM), decision tree regression (DTR), and cluster K means model (SPSS v.26) approach were performed to identify the most critical variables (and their respective load) in the training sessions that could explain the athlete's match performance. Results: MLM and DTR regression show that training load significantly affects game performance in a specific way. According to the present data, an interference phenomenon can occur when a high load of two different skills (running in a straight line vs COD, deceleration, and jumping) is applied in the same training block of the week. The cluster approach, followed by a chi-squared test, identified significant associations between training load and athlete match performance in a dose-dependent manner. Discussion: The high load values described here have a beneficial effect on match performance, despite the interference between stimuli discussed above. We present a positive training load from a congested season from the Brazilian First Division team. The study suggests that an interference effect occurs when high physical training loads are applied to different specific physical skills throughout the season.

Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA).

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.

Standardizing Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer Treatment: Navigating Complexities and Charting the Path Forward.

The incorporation of hyperthermic intraperitoneal chemotherapy (HIPEC) into the treatment landscape for ovarian cancer has invoked a spectrum of emotions, ranging from enthusiastic anticipation to cautious skepticism [...].

Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study.

BACKGROUND AIMS: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a highly challenging disease to treat. Systemic chimeric antigen receptor (CAR) T cells have shown impressive efficacy in hematologic malignancies but have been less effective in solid tumors. We explored whether intraperitoneal (i.p.) administration of CAR T cells could provide an effective and robust route of treatment for PC from CRC. METHODS: We generated second-generation carcinoembryonic antigen (CEA)-specific CAR T cells. Various animal models of PC with i.p. and extraperitoneal metastasis were treated by i.p. or intravenous (i.v.) administration of CEA CAR T cells. RESULTS: Intraperitoneally administered CAR T cells exhibited superior anti-tumor activity compared with systemic i.v. cell infusion in an animal model of PC. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong anti-tumor activity in an animal model of PC with metastasis in i.p. or extraperitoneal organs. Moreover, compared with systemic delivery, i.p. transfer of CAR T cells provided increased anti-tumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after i.p. administration of our newly constructed prostate stem cell antigen-directed CAR T cells. CONCLUSIONS: Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.

POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1.

The small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial-mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1-SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1-SUMO1. POTEE activates Rac1 in the invadopodium by recruiting TRIO-GEF (triple functional domain protein), and it induces tumor cell proliferation and metastasis in vitro and in vivo. We found that the co-localization of POTEE with Rac1 is correlated with more aggressive breast cancer subtypes. Given its role in tumor dissemination, the leading cause of cancer-related deaths, POTEE could represent a potential therapeutic target for these types of cancer.

Water-assisted synthesis of stable and multicolored CsPbX3@SiO2 core-shell nanoparticles as fluorescent probes for biosensing.

Colloidal lead halide perovskite nanocrystals are highly luminescent materials with great promise as fluorescent probes in biosensing as long as their intrinsic instability in aqueous media is effectively addressed. In this study, we successfully prepared stable and multicolored CsPbX3@SiO2 (X = Cl/Br, Br and I) core-shell nanoparticles through a simple method based on the water-induced transformation of Cs4PbX6 into CsPbX3, combined with sol-gel procedures. We observed that the concentration of the Cs4PbX6 precursor plays a crucial role in the formation of isolated nanospheres with uniform silica coating and in controlling the number of core-free particles. Furthermore, our research expands this approach to other halide compositions, resulting in multicolored core-shell nanoparticles with emission wavelengths ranging from 490 to 700 nm, average sizes below 30 nm, and photoluminescence quantum yields close to 60%. Unlike in previous reports, the silica coating boosts the photoluminescence quantum yields compared to uncoated counterparts and provides increased structural stability for more than four days. Moreover, a controlled thermal treatment confers water stability to the as-synthesized nanoparticles. To establish the feasibility of the developed materials as fluorescent probes, we successfully demonstrated their specific recognition of a humanized antibody (omalizumab) used in treating patients with severe allergic asthma. This work paves the way to develop in vitro tests using CsPbX3@SiO2 core-shell nanoparticles as fluorogenic probes.

A systematic review of reminder and guidance systems for Alzheimer's Disease and Related Dementias patients: context, barriers and facilitators.

Purpose. To present the latest available research assessing the actual impact of reminder and guidance technologies for daily activities in Alzheimer's Disease and Related Dementia's patients, outlining design implications for these technologies.Materials and methods. The search was conducted in the ACM Digital Library, IEEExplore, ScienceDirect, PubMed, Cochrane Library, Sage Journal, ResearchGate, and SemanticScholar. An iteratively-developed Boolean search string was built including up to 18 AND/OR terms across Four categories (Memory Aids, Technology, Daily Activities, Memory Impairment). We qualitatively analyzed the findings and discussions of the findings reported in 40 studies in our corpus to determine common barriers to, and facilitators of, effective intervention implementation and adoption.Results. Forty studies fulfilled the inclusion and exclusion criteria. In existing studies, individuals with Alzheimer's Disease and Related Dementias understand the usefulness of different functions that can be provided within an app to assist with everyday tasks. There was a high level of heterogeneity regarding the studies' location, duration, and evaluation methodology.Conclusions. There is a need for assistive reminder and guidance technologies to be tailored towards autonomy, identity and personalization. Future work should include motivating features to aid during mood changes and feelings of insecurity.IMPLICATIONS FOR REHABILITATIONIn existing studies, older adults with cognitive impairment understand the usefulness of different functions that can be provided within an app to assist with everyday tasks.There is a high level of heterogeneity regarding the studies' location, duration, and evaluation methodology.There is ample need for these reminder technologies to be tailored towards autonomy, identity and personalization.Future work should include motivating features to aid during mood changes and feelings of insecurity.

Relación entre la discapacidad en locomoción y en comunicación y la escolaridad en pacientes con parálisis cerebral / Relationship between locomotion and communication incapacities and scholarship in patients with cerebral palsy

RESUMEN Objetivo : Identificar la relación entre la severidad de la discapacidad en locomoción y en comunicación y la escolaridad en pacientes con parálisis cerebral. Material y métodos : Estudio transversal y retrospectivo en 316 pacientes con parálisis cerebral entre los 3 y 12 años, atendidos entre julio del 2016 y junio del 2017 en el Instituto Nacional de Rehabilitación "Dra. Adriana Rebaza Flores" AMISTAD PERU-JAPÓN, Lima-Perú. Resultados : La edad promedio fue 6 años (rango de 3 a 12 años), 57% del sexo masculino. La parálisis cerebral espástica representó el 69,7% seguida por la discinética en 20,9%. El 69,6% estaba escolarizado y más del 50% presentó discapacidad severa en locomoción y comunicación. Se encontró una relación inversa entre la severidad de la discapacidad en locomoción y en comunicación y la escolaridad. Conclusiones : Los niños con parálisis cerebral que presentan una mayor severidad de la discapacidad en locomoción y comunicación, tienen una menor asistencia a la escuela.

SUMMARY Objective : to evaluate the relationship between severity of locomotion and communication incapacities and scholarship in patients with brain palsy. Methods : cross-sectional study carried out in 316 patients from 3-12 years of age with cerebral palsy attended from July 2016 and June 2017 at the Instituto Nacional de Rehabilitación "Dra. Adriana Rebaza Flores" AMISTAD PERU-JAPÓN, Lima-Peru. Results : mean age was 6 years (range 3-12); 57% were males. Spastic cerebral palsy was found in 69.7% followed by dyskinetic cerebral palsy in 20%; 69.6% were in the school and more than 50% of them had severe locomotion and communications incapacities. An inverse relationship was found between severity of locomotion and communications incapacities and scholarship. Conclusions : Children with cerebral palsy who have locomotion and communications incapacities tended to have less school attendance.

Low-dose prophylaxis protocol for heterotopic ossification after hip preservation surgery in a sport participants cohort.

BACKGROUND: Heterotopic ossification (HO) is a well-known complication of arthroscopic and open surgical treatment of femoroacetabular impingement (FAI). Incidence of heterotopic ossification has been reported in the literature between 0% and 44% after hip arthroscopy and between 18.2% and 25% after anterior mini-open surgery. Currently, pharmacological prophylaxis with NSAIDs and selective COX-2 inhibitors are commonly used and their effectiveness is well documented in literature. HYPOTHESIS: We hypothesized that the low-dose prophylaxis protocol with selective cox-2 inhibitors decreases the risk of heterotopic ossification in open or arthroscopic hip preservation surgery in athletes. METHODS: This study is an analysis of prospectively gathered data on 98 sport participant patients who underwent arthroscopic or anterior mini-open treatment for FAI between April 2008 and April 2018. All the patients received postoperative oral prophylaxis with 60 mg etoricoxib once daily for two weeks. Post-operative X-rays were performed at 1, 3, and 12 months after surgery and reviewed by two orthopedic surgeons blinded to the type and side of surgery. HO were graded according to the Brooker classification. Descriptive statistics was used to analyze demographic data. Bivariate analysis was performed to analyze the association of HO with each of the following variables: type of surgery, physical activity, time of evolution of symptoms, age at surgery, and sex. Finally, a regression model analysis was performed to determine the presence of confounding effects between variables. RESULTS: The study cohort was composed of 54 patients in the arthroscopic treatment group and 44 patients in the anterior mini-open group. HO was identified in 6 (13.6%) patients in the mini-open group. No HO was identified in the arthroscopic group. In the bivariate analysis, "type of surgery" was the only variable that showed a statistically significant association with HO (p = 0.007). CONCLUSION: Results of this study suggest that anterior mini-open treatment was characterized by a higher risk of HO development compared to hip arthroscopy for femoroacetabular impingement treatment regardless of pharmacological prophylaxis. The treatment regimen of 60 mg etoricoxib daily for two weeks was an effective prophylaxis for HO formation in sport participant patients compared with data available in the literature.

Correlation between MOVA3D, a Monocular Movement Analysis System, and Qualisys Track Manager (QTM) during Lower Limb Movements in Healthy Adults: A Preliminary Study.

New technologies based on virtual reality and augmented reality offer promising perspectives in an attempt to increase the assessment of human kinematics. The aim of this work was to develop a markerless 3D motion analysis capture system (MOVA3D) and to test it versus Qualisys Track Manager (QTM). A digital camera was used to capture the data, and proprietary software capable of automatically inferring the joint centers in 3D and performing the angular kinematic calculations of interest was developed for such analysis. In the experiment, 10 subjects (22 to 50 years old), 5 men and 5 women, with a body mass index between 18.5 and 29.9 kg/m2, performed squatting, hip flexion, and abduction movements, and both systems measured the hip abduction/adduction angle and hip flexion/extension, simultaneously. The mean value of the difference between the QTM system and the MOVA3D system for all frames for each joint angle was analyzed with Pearson's correlation coefficient (r). The MOVA3D system reached good (above 0.75) or excellent (above 0.90) correlations in 6 out of 8 variables. The average error remained below 12° in only 20 out of 24 variables analyzed. The MOVA3D system is therefore promising for use in telerehabilitation or other applications where this level of error is acceptable. Future studies should continue to validate the MOVA3D as updated versions of their software are developed.

Standardizing In Vitro ß-Lactam Antibiotic Allergy Testing with Synthetic IgE.

The global prevalence of ß-lactam allergy poses a major challenge in administering first-line antibiotics, such as penicillins, to a significant portion of the population. The lack of ß-lactam IgE antibody pools with defined selectivity hampers the standardization and validation of in vitro assays for ß-lactam allergy testing. To address this limitation, this study introduces a synthetic IgE specific to ß-lactam antibiotics as a valuable tool for drug allergy research and diagnostic tests. Using phage display technology, we constructed a library of human single-chain antibody fragments (scFv) to target the primary determinant of amoxicillin, a widely used ß-lactam antibiotic. Subsequently, we produced a complete human synthetic IgE molecule using the highly efficient baculovirus expression vector system. This synthetic IgE molecule served as a standard in an in vitro chemiluminescence immunoassay for ß-lactam antibiotic allergy testing. Our results demonstrated a detection limit of 0.05 IU/mL (0.63 pM), excellent specificity (100%), and a four-fold higher clinical sensitivity (73%) compared to the in vitro reference assay when testing a cohort of 150 serum samples. These findings have significant implications for reliable interlaboratory comparison studies, accurate labeling of allergic patients, and combating the global public health threat of antimicrobial resistance. Furthermore, by serving as a valuable trueness control material, the synthetic IgE facilitates the standardization of diagnostic tests for ß-lactam allergy and demonstrates the potential of utilizing this synthetic strategy as a promising approach for generating reference materials in drug allergy research and diagnostics.

HIPEC in Ovarian Cancer Is the Future and Always Will Be? Results from a Spanish Multicentric Survey.

Ovarian cancer is the leading cause of death due to gynecological tumors in the female population. Despite optimal first-line treatment, including cytoreduction and platinum-based systemic chemotherapy, recurrences are frequent. The use of hyperthermic intraperitoneal chemotherapy (HIPEC) has been criticized, especially because of the lack of randomized controlled trials (RCTs) with convincing results to support the use of HIPEC in patients with ovarian cancer with peritoneal dissemination. In 2018, the clinical trial published by Van Driel et al. reported improved outcomes in favor of HIPEC treatment with cisplatin. In this study, we conducted a national survey within the Spanish group of peritoneal surgical oncology (Grupo Español de Cirugía Oncológica Peritoneal, GECOP) to explore the impact of the results of this RCT on clinical practice. A total of 33 groups completed the survey. Routine clinical practice was not changed in 28 of the 33 groups (85%) based on the results of the Van Driel trial. Despite the results of this RCT, most groups considered that more RCTs are needed and that, in the future, HIPEC may become the standard of care. In conclusion, the results from RCTs evaluating HIPEC treatment in patients with ovarian cancer has not been transferred to clinical practice.

Treatment of Peritoneal Surface Malignancies by Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Spain: Results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP).

INTRODUCTION: Treatment of Peritoneal Surface Malignancies (PSM) with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved results never seen before in these patients, which classically have a poor prognosis. The possibility of conducting clinical trials in these diseases is complicated, since some of them are rare, so the analysis of large databases provides very valuable scientific information. The aim of this study is to analyze the global results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP), whose objective is to register all patients scheduled for HIPEC nationwide. METHODS: This is a retrospective analysis of the data recorded in the REGECOP from 36 Spanish hospitals from 2001 to 2021. There were 4159 surgical interventions in 3980 patients. RESULTS: 66% are women and 34% are men with a median age of 59 years (range 17-86). 41.5% of the patients were treated for Peritoneal Metastases (PM) of colorectal cancer (CRC); 32.4% were women with ovarian cancer (OC) with PM; 12.8% were treated for pseudomyxoma peritonei (PMP); 6.2% had PM from gastric cancer (GC); 4.9% had PM of non-conventional origin; and, finally, 2.1% of cases were patients diagnosed with peritoneal mesothelioma. The median Peritoneal Cancer Index (PCI) was 9 (0-39), and complete cytoreduction was achieved in 81.7% of the procedures. Severe morbidity (Dindo-Clavien grade III-IV) was observed in 17.7% of surgeries, with 2.1% mortality. Median hospital stay was 11 days (0-259). Median overall survival (OS) was 41 months for CRC patients, 55 months for women with OC, was not reached in PMP patients, was 14 months for GC patients, and 66 months in mesothelioma patients. CONCLUSIONS: large databases provide extremely useful data. CRS with HIPEC in referral centers is a safe treatment with encouraging oncologic results in PSM.