Fractures and other chest wall abnormalities after thoracotomy for esophageal cancer: A retrospective cohort study.

BACKGROUND: Chest pain following a thoracotomy for esophageal cancer is frequently reported but poorly understood. This study aimed to (1) determine the prevalence of thoracotomy-related thoracic fractures on postoperative imaging and (2) compare complications, long-term pain, and quality of life in patients with versus without these fractures. METHODS: This retrospective cohort study enrolled patients with esophageal cancer who underwent a thoracotomy between 2010 and 2020 with pre- and postoperative CTs (<1 and/or >6 months). Disease-free patients were invited for questionnaires on pain and quality of life. RESULTS: Of a total of 366 patients, thoracotomy-related rib fractures were seen in 144 (39%) and thoracic transverse process fractures in 4 (2%) patients. Patients with thoracic fractures more often developed complications (89% vs. 74%, p = 0.002), especially pneumonia (51% vs. 39%, p = 0.032). Questionnaires were completed by 77 after a median of 41 (P25 -P75 28-91) months. Long-term pain was frequently (63%) reported but was not associated with thoracic fractures (p = 0.637), and neither were quality of life scores. CONCLUSIONS: Thoracic fractures are prevalent in patients following a thoracotomy for esophageal cancer. These thoracic fractures were associated with an increased risk of postoperative complications, especially pneumonia, but an association with long-term pain or reduced quality of life was not confirmed.

Rib Fixation for Multiple Rib Fractures: Healthcare Professionals Perceived Barriers and Facilitators to Clinical Implementation.

BACKGROUND: Surgical stabilization of rib fractures (SSRF) is associated with improved respiratory symptoms and shorter intensive care admission in patients with flail chest. For multiple rib fractures, the benefit of SSRF remains a topic of debate. This study investigated barriers and facilitators of healthcare professionals to SSRF as treatment for multiple traumatic rib fractures. METHODS: Dutch healthcare professionals were asked to complete an adapted version of the Measurement Instrument for Determinants of Innovations questionnaire to identify barriers and facilitators of SSRF. If ≥ 20% of participants responded negatively, the item was considered a barrier, and if ≥ 80% responded positively, the item was considered a facilitator. RESULTS: Sixty-one healthcare professionals participated; 32 surgeons, 19 non-surgical physicians, and 10 residents. The median experience was 10 years (P25-P75 4-12). Sixteen barriers and two facilitators for SSRF in multiple rib fractures were identified. Barriers included lack of knowledge, experience, evidence on (cost-)effectiveness, and the implication of more operations and higher medical costs. Facilitators were the assumption that SSRF alleviates respiratory problems and the feeling that surgeons are supported by colleagues for SSRF. Non-surgeons and residents reported more and several different barriers than surgeons (surgeons: 14; non-surgical physicians: 20; residents: 21; p < 0.001). CONCLUSION: For adequate implementation of SSRF in patients with multiple rib fractures, implementation strategies should address the identified barriers. Especially, improved clinical experience and scientific knowledge of healthcare professionals, and high-level evidence on the (cost-) effectiveness of SSRF potentially increase its use and acceptance.

Safety and Performance of Narhinel 0.9% Sodium Chloride Monodose and Otrisal 0.74% Sodium Chloride Monodose Nasal Saline Solutions and Nasal Aspirators in Real-World Settings: Postmarket Clinical Follow-up Study Results.

Background: Blocked or stuffy nose is a common and bothersome symptom of colds, particularly for young children who are unable to clear their noses on their own. Nasal saline solutions and nasal aspirators are designed to gently cleanse and remove blocking nasal secretions. Objective: To assess the safety and performance of 2 monodose isotonic saline solutions (Narhinel 0.9% and Otrisal 0.74% sodium chloride; GSK Consumer Healthcare SARL, a Haleon company, Nyon, Switzerland) and 2 nasal aspirators with disposable hard- and soft-nozzle refills used as a standalone or combination treatment. Methods: We conducted 2 observational, online questionnaire-based, postmarket clinical follow-up studies in Europeans who had used any of the devices ≥1 time in the past 6 months. Coprimary objectives were to confirm the safety and performance of the saline solutions (Narhinel and Otrisal, Study 1) and nasal aspirators (with hard- and soft-nozzle refills, Study 2). Safety was assessed via the proportion of patients reporting adverse events and/or device malfunctions while using the devices within the previous 6 months, and performance was assessed by satisfaction rated on a 5-point scale, with "satisfied" and "very satisfied" being the highest performance ratings. Results: A total of 1136 (Study 1) and 1237 (Study 2) questionnaires were initiated by volunteer participants. Less than 2% of participants reported adverse events for any evaluated product in the previous 6 months. Most participants were "satisfied" or "very satisfied" with the devices for their intended use, with 78% to 91% of participants in the Narhinel arm, 73%-94% in the Otrisal arm, 71% to 95% in the soft-nozzle arm, and 71% to 80% in the hard-nozzle arm giving these ratings. Conclusions: These data support the safety and performance of 2 monodose saline solutions (Narhinel and Otrisal) for nasal cleansing, nasal moisturization, and/or loosening nasal secretions, and of nasal aspirators (with hard- and soft-nozzle refills) for clearing a blocked nose and removing nasal secretions.

Susceptibility of Domestic Swine to Experimental Infection with Severe Acute Respiratory Syndrome Coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease, has been shown to infect several species. The role of domestic livestock and associated risks for humans in close contact with food production animals remains unknown for many species. Determining the susceptibility of pigs to SARS-CoV-2 is critical to a One Health approach to manage potential risk for zoonotic transmission. We found that pigs are susceptible to SARS-CoV-2 after oronasal inoculation. Among 16 animals, we detected viral RNA in group oral fluids and in nasal wash from 2 pigs, but live virus was isolated from only 1 pig. Antibodies also were detected in only 2 animals at 11 and 13 days postinoculation but were detected in oral fluid samples at 6 days postinoculation, indicating antibody secretion. These data highlight the need for additional livestock assessment to determine the potential role of domestic animals in the SARS-CoV-2 pandemic.

A systematic review of the use of the Satiety Quotient.

The satiating efficiency of food has been increasingly quantified using the Satiety Quotient (SQ). The SQ integrates both the energy content of food ingested during a meal and the associated change in appetite sensations. This systematic review examines the available evidence regarding its methodological use and clinical utility. A literature search was conducted in six databases considering studies from 1900 to April 2020 that used SQ in adults, adolescents and children. All study designs were included. From the initial 495 references found, fifty-two were included. Of the studies included, thirty-three were acute studies (twenty-nine in adults and four in adolescents) and nineteen were longitudinal studies in adults. A high methodological heterogeneity in the application of the SQ was observed between studies. Five main utilisations of the SQ were identified: its association with (i) energy intake; (ii) anthropometric variables; (iii) energy expenditure/physical activity; (iv) sleep quality and quantity and (v) to classify individuals by their satiety responsiveness (i.e. low and high satiety phenotypes). Altogether, the studies suggest the SQ as an interesting clinical tool regarding the satiety responsiveness to a meal and its changes in responses to weight loss in adults. The SQ might be a reliable clinical indicator in adults when it comes to both obesity prevention and treatment. There is a need for more standardised use of the SQ in addition to further studies to investigate its validity in different contexts and populations, especially among children and adolescents.

Squamous cell carcinoma of the breast, are there two entities with distinct prognosis? A series of 39 patients.

PURPOSE: Squamous cell carcinoma (SCC) of the breast is a rare entity of breast cancer, with a very poor prognosis, and whose pathophysiology is still unwell established. Therapeutic management is very heterogeneous due to its incomplete understanding. Nevertheless, it seems that two histological entities can be distinguished: pure SCC close to the cutaneous origin, and metaplastic squamous breast cancer (MSBC). The aim of this study is therefore to assess the difference in survival according to the histological type (SCC or MSBC) and to describe the demographic, clinical, and therapeutic characteristics of the two underlying populations. METHODS: Our data came from a monocentric retrospective series of 39 patients treated between 1985 and 2018 at the Gustave Roussy Institute (France) for a breast SCC. RESULTS: Of the 39 patients included, 64% had MSBC and 36% had a pure form. The overall and recurrence-free survival at 3 years [CI 95%] was 72.3% [56.9%; 87.0%] and 67.2% [51.2%; 83.2%], respectively. The overall 3-year survival of patients with MSBC was significantly lower than that with pure SCC: HR [CI 95%] 9.5 [1.2; 73.1], p = 0.008. The 3-year recurrence-free survival of patients with MSBC was also poorer: HR [CI 95%] 11.9 [1.6; 90.7], p = 0.002. Patients with MSBC also tended to be younger, have a large lesion size, and be more metastatic. CONCLUSION: The histological nature of SCC seems to bring fundamental new elements to the therapeutic management as it impacts recurrence and survival. It should therefore be better characterized at diagnosis in order to possibly adapt treatments.

Satiety responsiveness but not food reward is modified in response to an acute bout of low versus high intensity exercise in healthy adults.

To compare the effect of iso-caloric low and high intensity exercises on Satiety Quotient and Food Reward in response to a fixed meal in healthy young adults. Anthropometric measurements, body composition (BIA), aerobic capacity (VO2 max) and food preferences were assessed in 19 healthy normal-weight young adults (21 ±â€¯0.5 years old, 10 men). They randomly completed 3 experimental sessions: i) control session without exercise (CON); ii) High Intensity exercise session (HIE); iii) Low intensity exercise session (LIE). Thirty minutes after exercise or rest, then received a fixed lunch. Food reward (Leeds Food Preference Questionnaire) was assessed before and after the meal. Appetite sensations were assessed at regular intervals, SQ was calculated from the lunch meal and self-reported food intake was collected for the rest of the day. Mean body weight was 66.7 ±â€¯9.2 kg, body mass index was 22.3 ±â€¯2.9 kg/m2 and FM% was 18.7 ±â€¯6.8%. Appetite feelings did not differ between conditions and were not affected by exercise. SQ for satiety was not different between conditions. SQ hunger on CON was significantly higher than on LIE and HIE (p ≤ 0.05) with no difference between exercise conditions. SQ for desire to eat was significantly higher on CON versus HIE (p ≤ 0.01) with no differences between CON and LIE and between exercise sessions. SQ PFC was significantly lower on HIE compared with CON (p = 0.02) with no differences between LIE and CON and between LIE and HIE. Food reward was not significantly different between the three condition as well as self-reported total food and macronutrient intake for the rest of the days. Acute exercise, depending on its intensity, might affect the satiating response to food intake in healthy adults, without altering food reward.

Effect of exercise-meal timing on energy intake, appetite and food reward in adolescents with obesity: The TIMEX study.

The present study manipulated the delay between exercise and test meal to investigate its effect on energy intake, appetite sensations and food reward in adolescents with obesity. Fifteen adolescents with obesity randomly completed 3 experimental sessions: i) rest without exercise (CON); ii) 30 min of exercise 180 min before lunch (EX-180); iii) 30 min of exercise 60 min before lunch (EX-60). Ad libitum energy intake was assessed at lunch and dinner, and food reward (LFPQ) assessed before and after lunch. Appetite sensations were assessed at regular intervals. Absolute energy intake was not different between conditions despite a 14.4% lower intake in EX-60 relative to CON. Lunch relative energy intake (REI: energy intake - exercise-induced energy expenditure) was higher in CON compared with EX-60 (p < 0.001). Lunch fat intake was lower in EX-60 compared with CON (p = 0.01) and EX-180(p = 0.02). Pre-lunch hunger in CON was lower than EX-180 (p = 0.02). Pre-lunch prospective food consumption and desire to eat were lower in CON compared with both exercise conditions (p = 0.001). A significant condition effect was found for explicit liking for high-fat relative to low-fat foods before lunch (p = 0.03) with EX-60 being significantly lower than EX-180 (p = 0.001). The nutritional and food reward adaptations to exercise might be dependent on the timing of exercise, which is of importance to optimize its effect on energy balance in adolescents with obesity. CLINICAL TRIAL REFERENCE: NCT03807609.

[What support for vulnerable people during confinement?] / Quel accompagnement pour les personnes vulnérables en contexte de confinement ?

What are the ethical issues in connection with the support of the most vulnerable people in a context of health crisis, forcing them to be confined? Because the concept of vulnerability is broad and complex, the "Espace éthique PACA-Corse" (PACA-Corsica Ethical Structure) has taken a particular interest in the care of children with disabilities, children entrusted to child welfare services and people with psychiatric disorders. Confinement has led to a reorganisation of the access to healthcare services and medico-social support, possibly revealing or aggravating some situations of vulnerability, or even pushing aside certain people. Those most isolated or at risk of abuse may have experienced a double confinement. How to identify and respond to the needs of people already in vulnerable situations before confinement, who, isolated in the epidemic context, have seen their vulnerabilities increase? While new ways of working have been introduced in times of containment, some were interesting, others have shown their limits. The challenge was to find the right measure to address the specificity of each situation, to activate care networks in an effective and supportive manner, despite limited resources and the emergency context. The difficulty was to make protocols and care values coexist, acting in a reactive and creative way. While revealing vulnerabilities, this period has required both humility toward uncertainty and a duty of responsibility to care for those most in need.

Optimal timing of exercise for influencing energy intake in children during school lunch.

INTRODUCTION: Laboratory studies have shown that exercise can reduce energy intake, with a benefit to moderate-to-vigorous physical activity (MVPA) in individuals. The aim of the current study was to identify the impact of MVPA before lunch on ad libitum energy intake in very young children in a natural setting. METHODS: Three conditions were tested on three occasions, each using a counterbalance testing sequence as follows: A) Meal_MVPA: Meal at the beginning of the lunch period followed by a 40-min MVPA (reference condition); B) LPA_meal: 40 min of light intensity exercise session followed by lunch; C) MVPA_meal: MVPA followed by lunch. Children were instructed to eat their ad libitum lunch box (7-9 items) to reach 4/5 on the satiety visual analogue scale. RESULTS: 21 participants [8 boys and 13 girls; 80% normal weight; mean age: 5.6 (standard deviation: 0.5) years] participated in the study. Energy intake was significantly greater in the LPA_Meal condition [509 kcal (95% confidence interval: 448-570)] than in Meal_MVPA [442 kcal (380-504)] (p = 0.011) and MVPA_Meal [432 kcal (371-494)] (p < 0.001) conditions (p < 0.05). The energy from lipids was significantly greater in the LPA_Meal [154 kcal (130-177)] than in Meal_MVPA conditions [120 kcal (97-144)] (p = 0.016). CONCLUSION: The current study may indicate that it is possible for young school children to benefit from anorexigenic exercise in real-life settings. In addition, it was possible to delay mealtime without increasing energy intake when MVPA was provided during the delay period. Finally, the introduction of MVPA prevented an increase in lipid consumption observed for LPA.

Mechanical efficiency in children with different body weight: a longitudinal assessment of the quality cohort.

Net mechanical efficiency (MEnet), which reflects the body's ability to transfer energy above resting levels in external work, is similar in young children regardless of their body weights. However, it is unclear whether MEnet remains stable during growth and maturation. We sought to determine whether net mechanical efficiency (MEnet) changes over a period of 3 years in children and to identify the factors associated with possible changes. A total of 169 children participating in the QUALITY (Quebec Adipose and Lifestyle InvesTigation in Youth) cohort completed an incremental cycling test, resulting in the same maximal power output during both visits. For MEnet, resting energy consumption was subtracted from total energy consumption at each exercise stage. Physical activity was measured using an accelerometer worn for 7 days. Participants were measured at year one and again two years later. MEnet did not differ across the visits at the 25, 50 and 75 watt stages. However, the participants exhibited lower MEnet values at follow-up for the 100 and 125 W stages (23(3) vs. 20(1)%; 25(4) vs. 20(2)%; p<0.01). Declines in MEnet correlated positively with declines in moderate-to-vigorous physical activity levels (r=0.78, p<0.05). The declines in moderate-to-vigorous physical activity levels across the visits were identified as significant predictors of MEnet changes at 100 and 125 W over 3 years, accounting for 22% of the relationship. In children, MEnet, determined at high exercise intensity, decreases within a period of three years, and the decrement appeared to be related to moderate-to-vigorous physical activity.

Acute post-exercise energy and macronutrient intake in lean and obese youth: a systematic review and meta-analysis.

AIM: This review aims to determine if acute exercise affects subsequent energy and macronutrients intake in obese and non-obese children and adolescents. METHODS: Databases were searched between January 2015 and December 2015 for studies reporting energy and/or macronutrients intake immediately after an acute exercise and control condition, in children and adolescents. From the initial 118 references found, 14 were included for subsequent analysis after screening representing 31 acute exercise conditions that varied in intensity, duration and modality. RESULTS: One study found increased energy intake after exercise, seven decreased and 23 revealed no change. The meta-analysis revealed a significant effect of acute exercise on intake in obese but not in lean youth by a mean difference of -0.430 (95% confidence interval=-0.703 to -0.157, P=0.002) displaying low heterogeneity (I2=0.000; Q=5.875; df=9, P=0.752). The analysis showed that intense exercise only reduces intake in obese children (no intensity effect in lean). Unchanged macronutrients intake was reported in nine studies as opposed to three which found modified lipids, protein and/or carbohydrate intake. CONCLUSION: Although acute exercise does not affect energy intake in lean, it appears to reduced food intake in obese youth when intense, without altering the macronutrients composition of the meal.

[Tutors of resiliency of children and adolescents living in camps in Port-au-Prince and surrounding cities]. / Les tuteurs de résilience des enfants et adolescents vivant dans des camps à Port-au-Prince et dans les villes avoisinantes.

OBJECTIVES: In the context of sustainable reconstruction of Haiti following the earthquake of January 12, 2010, this research analyses the processes of resilience and creators of young and adolescent Haitians. In particular, it examines the role of family, school, care institutions, beliefs, association networks, the state and the international community in the development of these processes. These strata are considered as human resources that may assist in the living of difficult experiences, and reconstruction-shoring research mainly aims to identify guardians' resilience among young and adolescent Haitians living in camps in Port-au-Prince and the other most affected cities after the nearby earthquake. METHODOLOGY: From a questionnaire developed jointly with the University Lumière Lyon 2 (CRPPC) Editec and the State University of Haiti (UEH) in the context of research, individual interviews were conducted with a sample of n=1475 children and adolescents, 782 girls and 693 boys, 19% of whom were under the age of 6 years, 52% aged 6 to 15 years and 29% aged 15 to 20 years. This allowed the collection of their perception and representation of different elements, which serve as scaffolding to cope with the post-traumatic situation they experienced and to analyse and establish the correlation links between the tutors identified. Among the young people in the sample, 97% are mostly educated, and they remain in three cities that have been particularly affected by the earthquake: the capital Port-au-Prince, Leogane a commune of Port-au-Prince located in the department of the West, and Jacmel a commune of Haiti and head of the department of the South East. We enjoyed the perception and representation of children and adolescents on several potential guardians' resilience: family, school, health care institutions, places of worship, social and community networks, government and international organizations. RESULTS: Some data concluded that tutors can actually be correlated and identified by sex and level of development topics. Analyses revealed that the majority of children had not lost their parents and said they feel safe with their families. Academic performance tended mostly to increase after the earthquake, young people perceived care as accessible and available, and the majority claim to be Protestant. They certify that they have many friends and have ties in the community and feel safe in the streets. The data show a positive dominance of religious practice and sense of trust in institutions of care on the part of girls while the boys claim to have more confidence in the State. The school performance is more important to those aged between 6-15 years, while the older ones practice less religion and rely less on the State and international organizations. These results suggest the importance of institutions such as the family, places of worship, educational institutions, health centres, community, etc.

Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines. PATIENTS AND METHODS: A total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs. RESULTS: TIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P < 0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95 P = 0.003; HR 0.89, 95% CI 0.81-0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95% CI 0.18-1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95% CI 0.20-1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2-, HER2+, ER-/HER2-). CONCLUSIONS: We confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL should not be used as a parameter to select patients for anthracyclines chemotherapy.

Independent associations between child and parent perceived neighborhood safety, child screen time, physical activity and BMI: a structural equation modeling approach.

OBJECTIVE: The main objective of this study was to investigate whether children's perceptions of neighborhood safety are associated with their weight status and weight-related behaviors, independently of their parents' perceptions. METHODS: Data were from the baseline wave (collected in 2005-2008) of the Quebec Adipose and Lifestyle Investigation in Youth (QUALITY), an ongoing prospective study of 630 children aged 8-10 years (from Quebec, Canada) at risk of obesity. Weight and height were measured, and World Health Organization age- and sex-specific body mass index (BMI) z-scores were computed. Physical activity was measured by accelerometry, and time spent watching television, playing computer and video games during week and weekend days was self-reported. Structural equation modeling was used to simultaneously estimate the associations between parent and child perceived safety, with children's BMI z-score, physical activity and screen time. RESULTS: The results suggest that, when parent perceived safety was at the mean, children who perceived their neighborhood as being safest had nearly an additional 70 daily activity counts per minute (representing an ~10% increase in overall physical activity level) compared with children who perceived it as being least safe. Among children who perceived a mean level of safety, those whose parents perceived their neighborhood as being safest spent approximately an hour less per day in front of screens compared with those whose parents perceived their neighborhood as being least safe. Parent and child perceptions of safety both indirectly contribute to children's weight status by differentially impacting weight-related behaviors. CONCLUSION: Findings indicate that targeting both parent and child perceived neighborhood safety could bolster efforts to promote healthy weight and weight-related behaviors among children.

X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome.

Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects.

Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study.

BACKGROUND: There is a need to develop surrogates for treatment efficacy in the neoadjuvant setting to speed-up drug development and stratify patients according to outcome. Preclinical studies showed that chemotherapy induces an antitumor immune response. In order to develop new surrogates for drug efficacy, we assessed the prognostic value of tumor-infiltrating lymphocytes (TIL) on residual disease after neoadjuvant chemotherapy (NACT) in patients with triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Three hundred four TNBC patients with residual disease after NACT were retrospectively identified in three different hospitals. Hematoxylin and eosin-stained slides from surgical postchemotherapy specimens were evaluated for intratumoral (It-TIL) and stromal (Str-TIL) TIL. Cases were classified as High-TIL if It-TIL and/or Str-TIL >60%. RESULTS: TIL were assessable for 278 cases. Continuous It-TIL and Str-TIL variables were strong prognostic factors in the multivariate model, both for metastasis-free [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.77-0.96, P = 0.01 and HR 0.85, 95% CI 0.75-0.98, P = 0.02 for Str-TIL and It-TIL, respectively] and overall survival (HR 0.86, 95% CI 0.77-0.97, P = 0.01 and HR 0.86, 95% CI 0.75-0.99, P = 0.03 for Str-TIL and It-TIL, respectively). The 5-year overall survival rate was 91% (95% CI 68% to 97%) for High-TIL patients (n = 27) and 55% (95% CI 48% to 61%) for Low-TIL patients (HR 0.19, 95% CI 0.06-0.61, log-rank P = 0.0017). The major prognostic impact of TIL was seen for patients with large tumor burden following NACT (residual tumor >2 cm and/or node metastasis). In all but one High-TIL case, It-TIL and Str-TIL values were lower on the prechemotherapy sample. CONCLUSIONS: The presence of TIL in residual disease after NACT is associated with better prognosis in TNBC patients. This parameter may represent a new surrogate of drug efficacy to test investigational agents in the neoadjuvant setting and a new prognostic marker to select patients at high risk of relapse.

Induction of mesenchymal stem cell differentiation and cartilage formation by cross-linker-free collagen microspheres.

Because of poor self-healing ability, joint cartilage can undergo irreversible degradation in the course of various diseases or after injury. A promising approach for cartilage engineering consists of using of mesenchymal stem cells (MSC) and a differentiation factor combined with an injectable carrier biomaterial. We describe here a novel synthesis route for native collagen microspheres that does not involve the use of potentially toxic crosslinking agents. An emulsion was formed between a type I collagen solution and perfluorinated oil, stabilised by a biocompatible triblock perfluorinated copolymer surfactant. Spherical microparticles of fibrillar collagen were formed through a sol-gel transition induced by ammonia vapours. Electron microscopy observations showed that these self-cross-linked microspheres were constituted by a gel of striated collagen fibrils. Microspheres that were loaded with transforming growth factor beta (TGF-ß)3 progressively released this differentiation factor over a four weeks period. Human MSC rapidly adhered to TGF-ß3-loaded microspheres and, after 21 d of culture, exhibited typical chondrocyte morphology and produced an uncalcified matrix made of the predominant cartilage components, aggrecan and type II collagen, but devoid of the hypertrophic marker type X collagen. Subcutaneous co-injection of MSC and TGF-ß3-loaded microspheres in mice consistently led to the formation of a cartilage-like tissue, which was however hypertrophic, calcified and vascularised. In conclusion, we developed cross-linker free collagen microspheres that allowed chondrogenic differentiation of MSC in vitro and in vivo.

A real-world study of quality of life following treatment with xylometazoline hydrochloride in individuals with common cold.

BACKGROUND: The common cold is a frequent, acute, and mild upper respiratory human disease. Nasal congestion has been considered the most bothersome symptom in the common cold, impacting quality of life (QoL). Topical decongestants containing steroids benefit QoL in allergic rhinitis, but no published research has assessed the impact of topical decongestants on QoL in the common cold. OBJECTIVE: To evaluate the effects of xylometazoline hydrochloride 0.1% (Otrivin, GSK Consumer Healthcare SARL, Switzerland) for up to 7 days on QoL in participants with nasal congestion associated with the common cold. DESIGN: This was a decentralized, longitudinal, open-label study. METHODS: The study enrolled 136 participants (⩾18 years) with early symptoms of the common cold, of which 102 were included in the modified intention-to-treat (mITT) population. Within 24 h of study product receipt, participants confirmed a 'plugged nose' and ⩾1 other common cold symptom. Primary endpoints were Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) total score, total and individual symptom scores, and total QoL score. Secondary endpoints were additional QoL scores. Exploratory and post hoc analyses included median days to resolution for each QoL factor and analyses of five QoL categories. RESULTS: Consistent improvements in symptoms and QoL were seen in the mITT population. From day 1, improvements were seen in the 'plugged nose' symptom (p = 0.0023), WURSS-21 total QoL score, and all individual QoL scores (p < 0.0001 for all). After the last dose needed, significant improvements were seen in sleep quality (73%), vitality (76%), physical activity (71%), social activity (80%), and sensation (81%). No serious or unexpected adverse events were reported. CONCLUSION: This study is the first to demonstrate in a real-life setting that treating nasal congestion in adults with xylometazoline hydrochloride 0.1% during the common cold positively impacts QoL factors relevant to daily living [Otrivin: Quality of Life (QoL) Impact in a Real-World Setting; https://clinicaltrials.gov/study/NCT05556148].

Impact of xylometazoline hydrochloride 0.1% on quality of life in people with blocked nose associated with the common coldThe common cold is a widespread, mild respiratory illness for which a hallmark symptom is a blocked or stuffy nose, which makes breathing and sleeping difficult. This study focused on how a nasal spray called Otrivin (containing xylometazoline hydrochloride 0.1%) impacts the quality of life (QoL) of people suffering from nasal congestion due to the common cold.Participants answered a questionnaire called the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), which helped understand how people experience respiratory symptoms and how different aspects of QoL were impacted. Participants also responded to eight additional QoL questions not covered in the WURSS-21.The results showed that from the first day of using the nasal spray, participants experienced significant relief from the blocked nose symptom and reported an overall improvement in their QoL and well-being, such as in sleep quality, energy levels, senses, and physical and social activities.In conclusion, this real-world study demonstrated that using xylometazoline hydrochloride 0.1% nasal spray during the common cold can significantly improve nasal congestion and various aspects of a person's daily life. These findings provide valuable evidence for using this nasal spray to relieve symptoms and enhance the overall well-being of individuals with the common cold.