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Background: Controversy exists with the presence of alterations in descending pain inhibition mechanisms in patients with non‐specific neck pain (NSNP). The aim of the present study was to evaluate the status of conditioned pain modulation CPM, remote pressure pain thresholds (PPT), and psychological factors in a specific subgroup of patients with NSNP such as young adult students. In addition, possible associations between CPM, psychological factors, and pain characteristics were analyzed. Methods: Thirty students with recurrent or chronic NSNP and 30 pain‐free students were included in this cross‐sectional study. The following measures were assessed: CPM, remote PPT, psychological factors (depression, anxiety, pain catastrophizing, and kinesiophobia), pain characteristics (duration, intensity, severity of chronic pain, interference with daily life), and central sensitization inventory (CSI). Results: No significant differences were found in the efficacy of CPM between students with chronic or recurrent NSNP and pain‐free students (β coefficient = −0.67; 95% CI = −1.54, 0.20). However, students with pain showed a significantly higher remote PPT (mean difference = −1.94; 95% CI = −2.71, −1.18). and a greater presence of anxious (mean difference = 6; 95% CI = 2, 9) and depressive symptoms (mean difference = 8.57; 95% CI = 3.97, 13.16). In addition, significant moderate or strong correlations were found between CPM and pain intensity (partial r = 0.41), pain catastrophizing and mean pain intensity (r = 0.37), grade (r = 0.50), and interference of pain (r = 0.57), kinesiophobia and disability (r = 0.38), and depression and CSI (r = 0.39). Conclusions: Young adult students with chronic or recurrent NSNP present remote hyperalgesia and symptoms of depression and anxiety but not dysfunctional CPM. [ABSTRACT FROM AUTHOR]

Simple Summary: Survivors of childhood brain tumors, because of the treatments they have undergone, have a greater risk of dying earlier from cardiovascular causes compared to the general population. The objective of this study was to evaluate differences between cardiovascular risk biomarkers and cardiopulmonary exercise test (CPET) results from childhood brain tumor survivors and healthy controls. We found worse CPET performance in survivors associated with higher endothelin-1 values compared to controls. Correlation analysis showed an inverse relationship between CPET results and leptin, emphasizing the role of radiotherapy as a possible cause in the genesis of a greater cardiovascular risk in survivors of childhood brain tumors. In recent decades, the improvement of treatments and the adoption of therapeutic protocols of international cooperation has led to an improvement in the survival of children affected by brain tumors. However, in parallel with the increase in survival, long-term side effects related to treatments have been observed over time, including the activation of chronic inflammatory processes and metabolic alterations, which can facilitate the onset of metabolic syndrome and increased cardiovascular risk. The aim of this study was to find possible statistically significant differences in the serum concentrations of early biomarkers of metabolic syndrome and in the results of cardiopulmonary exercise testing between survivors of childhood brain tumors and healthy controls. This is a prospective and observational study conducted on a group of 14 male patients who survived childhood brain tumors compared with the same number of healthy controls. The concentrations of early metabolic syndrome biomarkers [adiponectin, leptin, TNF-α, IL-1, IL-6, IL-10, endothelin-1, apolipoprotein B, and lipoprotein (a)] were measured and a cardiopulmonary exercise test (CPET) was performed. Results: Childhood brain tumor survivors performed worse on average than controls on the CPET. Furthermore, they showed higher endothelin-1 values than controls (p = 0.025). The CPET results showed an inverse correlation with leptin. The differences found highlight the greater cardiovascular risk of brain tumor survivors, and radiotherapy could be implicated in the genesis of this greater cardiovascular risk. [ABSTRACT FROM AUTHOR]

Introduction: Frailty is widely acknowledged as influencing health outcomes among critically ill old patients. Yet, the traditional understanding of its impact has predominantly been through frequentist statistics. We endeavored to explore this association using Bayesian statistics aiming to provide a more nuanced understanding of this multifaceted relationship. Methods: Our analysis incorporated a cohort of 10,363 older (median age 82 years) patients from three international prospective studies, with 30-day all-cause mortality as the primary outcome. We defined frailty as Clinical Frailty Scale ≥ 5. A hierarchical Bayesian logistic regression model was employed, adjusting for covariables, using a range of priors. An international steering committee of registry members reached a consensus on a minimal clinically important difference (MCID). Results: In our study, the 30-day mortality was 43%, with rates of 38% in non-frail and 51% in frail groups. Post-adjustment, the median odds ratio (OR) for frailty was 1.60 (95% CI 1.45–1.76). Frailty was invariably linked to adverse outcomes (OR > 1) with 100% probability and had a 90% chance of exceeding the minimal clinically important difference (MCID) (OR > 1.5). For the Clinical Frailty Scale (CFS) as a continuous variable, the median OR was 1.19 (1.16–1.22), with over 99% probability of the effect being more significant than 1.5 times the MCID. Frailty remained outside the region of practical equivalence (ROPE) in all analyses, underscoring its clinical importance regardless of how it is measured. Conclusions: This research demonstrates the significant impact of frailty on short-term mortality in critically ill elderly patients, particularly when the Clinical Frailty Scale (CFS) is used as a continuous measure. This approach, which views frailty as a spectrum, enables more effective, personalized care for this vulnerable group. Significantly, frailty was consistently outside the region of practical equivalence (ROPE) in our analysis, highlighting its clinical importance. [ABSTRACT FROM AUTHOR]

Sexual dysfunction (SD) is a common symptom for many with multiple sclerosis (MS). However, most studies researching this topic have predominantly White samples. While this matches epidemiological estimates, research has shown that those of other ethnic groups, such as African Americans/Blacks and Hispanics/Latinos, tend to exhibit more symptomology. This study aimed to determine if this greater symptomology in other ethnic groups with MS holds for SD. Study participants were recruited from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Participants completed the MSISQ-19 and the PDDS and provided demographic information. Study participants were 5445 respondents (Mage = 51 years, SD = 9.56, 75% female, 93% White). White, African American/Black, and Hispanic/Latino groups were compared on sexual dysfunction. Linear mixed effects modeling revealed that the MSISQ-19 subscale scores were significantly different for the African American/Black group (t = − 2.48, p < 0.013) and all female participants (t = − 2.58, p < 0.010). African American/Black participants had the least amount of primary SD (M = 10.56, 95% CI [9.09, 12.03]). African American/Black participants had the highest amount of secondary SD (M = 18.62, 95% CI [17.15, 20.09]), though the result was not statistically significant. Additionally, African American/Black females scored higher in all subscale scores when compared to African American/Black males, with a 3-point and 2-point difference in primary and tertiary symptoms. Our study has highlighted the importance of clinicians assessing for SD within their patients and to consider potential differences in symptom presentations of racial groups. [ABSTRACT FROM AUTHOR]

Objectives The main aim was to determine the effects of percutaneous electrical nerve stimulation (PENS) and transcutaneous electrical nerve stimulation (TENS) on endogenous pain mechanisms in patients with musculoskeletal pain. Design A systematic review and meta-analysis. Methods The search was conducted on March 1, 2022, in the EMBASE, CINAHL, PubMed, PEDro, Cochrane Library, Web of Science, Medline, and SCOPUS databases. Randomized controlled trials comparing the use of transcutaneous or percutaneous electrostimulation with a placebo, control group, or standard treatment in patients with musculoskeletal pain were included. Outcome measurements were quantitative sensory testing somatosensory variables like pressure pain threshold (PPT), conditioned pain modulation, and temporal summation of pain. The pooled data were evaluated in Review Manager 5.4. Results Twenty-four randomized controlled trials (n = 24) were included in the qualitative analysis and 23 in the meta-analysis. The immediate effects of PENS and TENS on local PPTs were significant, with a moderate effect size (standardized mean difference [SMD] 0.53; 95% confidence interval [CI]: 0.34 to 0.72; P  < 0.00001). When only studies with a lower risk of bias were analyzed, the heterogeneity decreased from I 2 = 58% (P  < 0.00001) to I 2 = 15% (P  = 0.01), and a decrease in the overall effect was observed (SMD 0.33; 95% CI: 0.7 to 0.58). The short-term effects on local PPTs were not significant when compared with the control group (P  = 0.13). The mid-term effects on local PPTs were significant, showing a large effect size (SMD 0.55; 95% CI: 0.9 to 1.00; P  = 0.02). The immediate effects on conditioned pain modulation were significant, with a large effect size (SMD 0.94; 95% CI: 0.48 to 1.41; P  < 0.0001). Conclusion PENS and TENS have a mild–moderate immediate effect on local mechanical hyperalgesia in patients with musculoskeletal pain. It appears that these effects are not sustained over time. Analyses suggest an effect on central pain mechanisms producing a moderate increase in remote PPT, an increase in conditioned pain modulation, but further studies are needed to draw clearer conclusions. [ABSTRACT FROM AUTHOR]

Objective: Early COVID‐19 eating disorders (EDs) research used regionally restricted samples with little sociodemographic diversity. The present study aimed to address these research gaps by examining whether pandemic‐related changes in ED symptoms and mental healthcare prevalence differed for historically marginalized groups within a national sample of US college students. Method: Participants included 242,906 US college students (Mage = 23.45, SD = 7.04; MBMI = 25.28, SD = 5.91) who completed the repeated cross‐sectional multi‐institute Healthy Minds Study between January 2019 and May 2021. Moderated logistic regressions examined whether pandemic‐related changes in individuals' likelihoods of exhibiting current probable ED, reporting lifetime ED diagnoses, and—among individuals with current probable ED—mental healthcare engagement differed for diverse gender, sexual, and racial/ethnic identity groups, and by body mass index (BMI) and financial stress. Results: There were increases of 5% and 12% in individuals' likelihoods of exhibiting current probable ED and symptomatic individuals' mental healthcare engagement, respectively, pre‐ to post‐COVID‐19 onset, but no pandemic‐related changes in lifetime ED diagnosis prevalence. There were also important variations in these time‐trends for different marginalized groups. For example, individuals identifying as genderqueer/gender nonconforming and lesbian exhibited increasing ED symptoms pre‐ to post‐COVID‐19 onset, and individuals with current probable ED and higher BMIs were increasingly likely to receive mental healthcare. Associations between financial stress, and the ED and mental healthcare outcomes did not change over time. Discussion: These findings provide insight into groups of US college students that experienced disproportionate ED burden during the pandemic at the population level, and directions for research and interventions that warrant consideration. [ABSTRACT FROM AUTHOR]

In this study, the effect of a remotely supervised, home-based, family-centered individualized rehabilitation program of motor activities for individuals with Rett syndrome (RTT) was evaluated. Thirteen participants with classic genetically confirmed RTT followed by a three-month program of motor activities at home. A total of 47 rehabilitative goals were set. Goals achievement, motor function, and parental satisfaction were evaluated. Each program was carried out by the participant's parents and remotely supervised via Skype calls, twice by a therapist experienced in RTT rehabilitation. Thirty-seven (78.7%) rehabilitative goals were achieved or overachieved. Ten participants (76.9%) significantly increased their gross motor functional level with a medium size effect (0.604). Parental reports of the involved families suggest, on average, a high level of usefulness of the program (4.4/5), adherence to the program (4.4/5), and general satisfaction (4.5/5). Our findings strongly support the implementation of such programs for this population. As these programs were remotely supervised, they can be implemented when the children are away from referenced facilities for long durations, such as during long holidays or a Covid-19 type lockdown. A remote supervised motor activity program carried out by the primary caregiver supports motor functioning in RTT. Therapists should consider family members' motivation to carry out the activities and integrate them into the family's daily routine. The program should be flexible to adapt to any sudden change in medical and environmental conditions, functional ability, and family members' motivational levels. [ABSTRACT FROM AUTHOR]

This retrospective cohort study investigates risks of hospitalised fall or hip fractures in working age adults receiving mental health care in South London. Patients aged 18 to 64, who received a first mental illness diagnosis between 2008 and 2016 were included. Primary outcome was hospitalised falls, secondary outcome was hip fractures. Age- and gender-standardised incidence rates and incidence rate ratios (IRRs) compared to local general population were calculated. Multivariate Cox proportionate hazard models were used to investigate which mental health diagnoses were most at risk. In 50,885 patients incidence rates were 8.3 and 0.8 per 1,000 person-years for falls and hip fractures respectively. Comparing mental health patients to the general population, age-and-gender-adjusted IRR for falls was 3.6 (95% CI: 3.3–4.0) and for hip fractures 7.5 (95% CI: 5.2–10.4). The falls IRR was highest for borderline personality and bipolar disorder and lowest for schizophreniform and anxiety disorder. After adjusting for multiple confounders in the sample of mental health service users, borderline personality disorder yielded a higher and anxiety disorder a lower falls risk. Working age adults using mental health services have almost four times the incidence of hospitalised falls compared to general population. Targeted interventions are warranted. • Falls/hip fractures were more frequent in mental health patients than controls. • Borderline personality disorder had the highest incidence of hospitalised falls. • Anxiety disorder had the lowest incidence of falls, similar to controls. • Borderline personality disorder had a higher falls risk than other conditions. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the current standard of therapy in several cancer types. Patients (pts) with lung cancer display higher response rates to CT when given after ICIs. Although ICIs have failed to demonstrate antitumour activity in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), little is known about CT effect after ICIs. We aimed to assess whether sequential ICIs followed by CT may be an alternative therapeutic approach in a population of pts with mCRC. We retrospectively assessed CT after ICI (CAICI) failure in pts with mCRC. The ICI regimen consisted of anti-PD(L)1 alone or in combination. The primary end-point was objective response rate. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Between 2014 and 2018, 29 pts with mCRC received CAICI (MSS tumours, 27 pts [86%]). The median number of previous lines was 4 (range, 2–7). Regimens included TAS-102 (n = 14), FOLFIRI (irinotecan, leucovorin, and fluorouracil; n = 6) or FOLFOX (oxaliplatin, leucovorin, and fluorouracil; n = 4), regorafenib (n = 3) and carboplatin (1 pt with BRCA mutation). Partial response and stable disease were observed in 4 (19%) and 9 (43%) pts, respectively (disease control rate, 62%). The median PFS and OS were 3.8 months (95% confidence interval [CI] = 1.5–5.4) and 8.0 months (95% CI = 4.2–14.0), respectively. ICIs administered before CT might enhance cytotoxic effects even in pts with immunorefractory MSS mCRC. The results of this small cohort need to be validated in independent prospective cohorts. The role of ICIs as modifiers of both tumour cells and microenvironment in mCRC deserves further research. • Chemotherapy (CT) beyond immunotherapy was assessed in patients with metastatic colorectal cancer (mCRC). • Immunotherapy followed by CT provides tumour control in mCRC. • Immunorefractory mCRC could benefit from sequential immunotherapy and CT. • Immunotherapy-induced delayed effects might enhance chemotherapy in mCRC. [ABSTRACT FROM AUTHOR]

Background: Pulmonary vein isolation is the cornerstone of catheter ablation in patients with atrial fibrillation (AF). However, with advanced left atrial (LA) structural changes, additional targeted catheter ablation of low‐voltage zones (LVZs) has produced favorable results. Therefore, with the advent of single‐shot techniques, it would be helpful to predict the presence of LVZs before an ablation procedure. Objective: We hypothesized that computed tomography (CT)‐derived left atrial volume index (LAVI), in combination with other objective parameters, could be used to develop a score able to predict the presence of LVZs. Methods: In a large cohort of patients undergoing their first AF ablations, comprehensive echocardiographic evaluations and cardiac CT were performed. During the electrophysiological studies, LA geometry and electroanatomic voltage maps were created. LVZs were defined as areas ≥1 cm2 with bipolar peak‐to‐peak voltage amplitudes ≤0.5 mV. Results: In a derivation cohort of 374 patients, predictors of LVZs were identified by regression analysis and used to build the Zentralklinik Bad Berka and University of L'Aquila (ZAQ) score (age ≥65 years; female sex; and CT‐LAVI ≥57 mL/m2). The ZAQ score of 2 points accurately identified the presence and the extent of LVZs (area under the curve [AUC], 0.809; 95% confidence interval [CI], 0.758‐0.861; P <.001 and 3 [interquartile range, IQR, 1.5‐4.5] vs 7 cm2 [IQR 4‐9]; P =.001). In a validation cohort of 103 patients, the predictive value of the score was confirmed (AUC, 0.793; 95% CI, 0.709‐0.878; P <.001 and 4 [IQR, 2‐7] vs 11.5 cm2 [IQR, 8‐16.5]; P =.001). Conclusions: The ZAQ score identifies LVZs and may be useful for planning the ablation strategy ahead of time. [ABSTRACT FROM AUTHOR]

Background: Translation of findings from randomised controlled trials (RCT), the foundation of evidence‐based medicine, into clinical practice requires an understanding of relationships between patient characteristics, treatment practices and outcomes. We propose a novel technique, External Validity Analysis (EVA), to evaluate applicability of findings from a large RCT, comparing baseline characteristics, interventions and outcomes between the RCT and a large clinical database. Aim: To perform EVA of the findings of a randomised controlled trial (ESTHER‐1) to a population in an Australian clinic setting. To demonstrate this method, we evaluated the discordance in first cycle follicle‐stimulating hormone (FSH) exposure and outcomes between the two populations, to inform clinical practice. Materials and Methods: In this retrospective, descriptive analysis, we compared practices and outcomes between the follitropin alfa 'conventional' dosing arm of the ESTHER‐1 trial and a selected comparable clinic subpopulation of patients who underwent controlled ovarian stimulation using FSH. Results: Mean FSH exposure was 34% higher in the clinic subpopulation than in the trial subpopulation, resulting in higher average ovarian response without improving the likelihood of clinical pregnancy or live birth. Conclusions: EVA allowed for the comparison of a trial population with a selected clinic population with similar characteristics. With respect to FSH consumption, this analysis revealed higher exposure to FSH in the clinic setting without a corresponding benefit. The comparison reveals population differences as well as the potential to improve clinical outcomes through a reappraisal of current practices and objectives in gonadotropin dose selection. [ABSTRACT FROM AUTHOR]

Objective: Early initiation of renal replacement therapy (RRT) effect on survival and renal recovery of critically ill patients is still uncertain. We aimed to systematically review current evidence comparing outcomes of early versus late initiation of RRT in critically ill patients. Methods: We searched the Medline (via Pubmed), LILACS, Science Direct, and CENTRAL databases from inception until November 2016 for randomized clinical trials (RCTs) or observational studies comparing early versus late initiation of RRT in critically ill patients. The primary outcome was mortality. Duration of mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and renal function recovery were secondary outcomes. Meta-analysis and trial sequential analysis (TSA) were used for the primary outcome. Results: Sixty-two studies were retrieved and analyzed, including 11 RCTs. There was no difference in mortality between early and late initiation of RRT among RCTs (odds ratio [OR] = 0.78; 95% confidence interval [CI]: 0.52-1.19; I 2 = 63.1%). Trial sequential analysis of mortality across all RCTs achieved futility boundaries at both 1% and 5% type I error rates, although a subgroup analysis of studies including only acute kidney injury patients was not conclusive. There was also no difference in time on mechanical ventilation, ICU and hospital LOS, or renal recovery among studies. Early initiation of RRT was associated with reduced mortality among prospective (OR = 0.69; 95% CI: 0.49-0.96; I 2 = 85.9%) and retrospective (OR = 0.61; 95% CI: 0.41-0.92; I 2 = 90.9%) observational studies, both with substantial heterogeneity. However, subgroup analysis excluding low-quality observational studies did not achieve statistical significance. Conclusion: Pooled analysis of randomized trials indicates early initiation of RRT is not associated with lower mortality rates. The potential benefit of reduced mortality associated with early initiation of RRT was limited to low-quality observational studies. [ABSTRACT FROM AUTHOR]

In a previous effort we showed that compared with immigrants who are permanent residents, undocumented immigrants are more likely to binge drink, but less likely to drink while impaired (DWI) partly due to their limited amount of driving. This report examines a related risk: riding with an impaired driver (RWI). Data came from an ongoing longitudinal sample of Latino immigrants to Miami-Dade County, FL. Descriptive analyses and regression techniques were applied. While DWI rates among Latino immigrants is heavily limited by their access to a car, RWI rates were not restricted by driving limitations, nor related to participants' legal immigration status (LIS). RWI rates were linked only to heavy drinking. Because it is not affected by driving limitations, RWI for these Latino immigrants is perhaps a more immediate risk than DWI. Addressing RWI among Latino immigrants should be a priority for traffic safety to Miami/Dade country. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of exposure to pesticides on the central auditory functions (CAF) of Brazilian tobacco growers.Design: This was a cross-sectional study carried out between 2010 and 2012. Participants were evaluated with two behavioural procedures to investigate CAF, the random gap detection test (RGDT) and the dichotic digit test in Portuguese (DDT).Study sample: A total of 22 growers exposed to pesticides (study group) and 21 subjects who were not exposed to pesticides (control group) were selected.Results: No significant differences between groups were observed for pure-tone thresholds. A significant association between pesticide exposure and the results for RGDT and DDT was found. Significant differences between pesticide-exposed and nonexposed subjects were found for RGDT frequency average and DDT binaural average, when including age and hearing level as covariates. Age was significantly associated with RGDT frequency average, DDT left ear score, DDT binaural average and DDT right ear advantage. Hearing levels were not significantly associated with any of the test scores. The relative risk of failing the DDT and RGDT for the study group was 1.88 (95% CI: 1.10–3.20) and 1.74 (95% CI: 1.06–2.86), respectively, as compared with the control group.Conclusions: The results showed that tobacco growers exposed to pesticides exhibited signs of central auditory dysfunction characterised by decrements in temporal processing and binaural integration processes/abilities. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Environmental cadmium (Cd) exposure is associated with type 2 diabetes. However, the association of Cd and gestational diabetes mellitus (GDM) is unknown. OBJECTIVES: We examined the association between body burden of Cd and GDM risk. METHODS: We used 140 GDM cases and 481 randomly selected noncase subcohort members from the Omega Study to conduct a case-cohort study. Creatinine (Cr)--corrected Cd in early pregnancy urine (U-Cd) was measured by inductively coupled plasma mass spectrometry. Tertiles (< 0.29; 0.29--0.42; > 0.43 μg/g Cr) were defined using the subcohort's U-Cd distribution. GDM was diagnosed using the 2004 American Diabetes Association guidelines. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: GDM cases had higher geometric mean U-Cd (0.39 μg/g Cr; 95% CI: 0.37, 0.41) than noncases (0.31 μg/g Cr; 95% CI: 0.29, 0.33). Odds ratios for GDM increased with increasing U-Cd tertile (OR = 1.64; 95% CI: 0.88, 3.05 for middle vs. low tertile; OR = 2.07; 95% CI: 1.15, 3.73 for high vs. low tertile; p-trend = 0.015). Overweight/obesity (body mass index ≥ 25 kg/m²) did not modify the association between U-Cd and GDM (p = 0.26). CONCLUSIONS: Our findings suggest that body burden of Cd increases risk of GDM in a dose-dependent manner. Improved understanding of environmental factors influencing GDM may facilitate early identification of women at high risk of GDM. [ABSTRACT FROM AUTHOR]

Simple Summary: Early prediction of response to cancer therapies is critical for treatment personalisation. In patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiation therapy (nCRT), delta radiomics applied to mesorectal features could potentially lead to the development of predictive models of treatment response. Pre- and post-treatment MRIs of patients treated at a single institution were analysed. Radiomic features of the mesorectum and GTV were extracted and predictive models of pathological complete response (pCR) and two-year disease-free survival (2yDFS) were developed. In 203 patients with LARC, a total of 565 variables were evaluated; the best performing 2yDFS prediction model was based on one GTV and two mesorectal features with an AUC of 0.79 in the training set and 0.70 in the validation set. The mesorectum may contain important radiomics information for predicting response to nCRT treatment in LARC patients. Background: The aim of this study is to evaluate the delta radiomics approach based on mesorectal radiomic features to develop a model for predicting pathological complete response (pCR) and 2-year disease-free survival (2yDFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (nCRT). Methods: Pre- and post-nCRT MRIs of LARC patients treated at a single institution from May 2008 to November 2016 were retrospectively collected. Radiomic features were extracted from the GTV and mesorectum. The Wilcoxon–Mann–Whitney test and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the features in predicting pCR and 2yDFS. Results: Out of 203 LARC patients, a total of 565 variables were evaluated. The best performing pCR prediction model was based on two GTV features with an AUC of 0.80 in the training set and 0.69 in the validation set. The best performing 2yDFS prediction model was based on one GTV and two mesorectal features with an AUC of 0.79 in the training set and 0.70 in the validation set. Conclusions: The results of this study suggest a possible role for delta radiomics based on mesorectal features in the prediction of 2yDFS in patients with LARC. [ABSTRACT FROM AUTHOR]

Context: Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. Objective: To assess holistic life-span health and healthrelated quality-of-life (HRQL) among current and former National Collegiate Athletic Association student–athletes (SAs). Design: Cross-sectional study. Setting: A large Division I university. Patients or Other Participants: Population-based sample of 496 university students and alumni (age 17-84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. Main Outcome Measure(s): Participants completed anonymous, self-report questionnaires. We measured the Short- Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. Results: Older alumni (age 43+years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P= .04; Cohen d =0.69; probability of clinically important difference [pCID]=77%; treatment odds ratio [OR]=14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P , .001; d=1.05; pCID=85%; OR=5.8, 95% CI = 2.0, 16) and current students (P , .001; d = 2.25; pCID .99.5%; OR=7.1, 95% CI=3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P=.006; d=-0.52; pCID= 40%) and mental component HRQL (P=.008; d =0.50; pCID= 48%) versus NAs but similar psychosocial treatment odds (OR= 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs. No differences were observed between SAs and NAs in physical component HRQL. Conclusions: The SAs demonstrated significant, clinically meaningful evidence of greater joint health concerns later in life, comparable cardiopulmonary health, and differences in life-span psychosocial health and HRQL profiles compared with NAs. These data provide timely evidence regarding a compelling public issue and highlight the need for further study of life-spanhealth among modern athletes. [ABSTRACT FROM AUTHOR]

Objective: Middle ear cholesteatoma may lead to the erosion of the bony structures of the temporal bone, possibly causing intra- and extracranial complications. Surgical treatment is mandatory, and due to possible residual/recurrent disease, the use of reliable diagnostic methods is essential. Our study aimed to evaluate the reliability of non-EPI DW-MRI for the follow-up of cholesteatoma after surgery. Methods: In a study group including 53 consecutive patients who underwent surgery for cholesteatoma at a tertiary university hospital, an imaging protocol was applied, including non-echo planar diffusion-weighted imaging magnetic resonance (MR) at 1 month after surgery and then at 6 and 12 months after surgery. Based on the combination of preoperative assessment and intraoperative findings, the study group was divided into 3 subgroups: petrous bone (PB) cholesteatoma, complicated cholesteatoma and uncomplicated cholesteatoma. PB cholesteatoma patients were treated by a subtotal petrosectomy, whereas complicated and uncomplicated cholesteatoma patients were treated either by a canal wall up procedure or a retrograde (inside-out) canal wall down technique with bone obliteration technique (BOT). Results: The results show that patients who had positive findings on non-EPI DW-MRI scans 1 month after surgery consequently underwent revision surgery during which residual cholesteatoma was noted. All the patients who displayed negative findings on non-EPI DWI-MRI scan at 1 month after surgery did not show the presence of a lesion at the 6- and 12-month evaluations. The 6 patients who displayed residual cholesteatoma at the 1-month follow-up presented dehiscence/exposure of the facial nerve canal at the primary surgery, mostly at the level of the labyrinthine segment. Conclusion: Non-EPI DW-MRI is a useful and reliable tool for follow-up cholesteatoma surgery, and when applied early, as was done in the protocol proposed in the present study, this tool may be used to detect the presence of residual cholesteatoma in some patients, prompting the planning of early revision surgery. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the feasibility of an online self-sampling pilot intervention for HIV testing addressed to gay, bisexual, and other men who have sex with men (GBMSM) and trans women (TW) users of dating apps in Spain. The website https://www.testate.org/ was designed to offer self-sampling kits for HIV testing and online consultation of the results. It was advertised on gay dating apps. Participants requested the delivery of a saliva self-sampling kit by mail and a postage-paid envelope to send the sample to the reference laboratory. An anonymous acceptability survey was conducted. The cascade of care was estimated. From November 2018 to December 2021, 4623 individual users ordered self-sampling kits, 3097 returned an oral fluid sample to the reference laboratory (67.5% return rate). 87 reactive results were detected. 76 were confirmed to be HIV-positive, we estimated an HIV prevalence of 2.45% (95% CI 1.9–3.0%). 100% of those referred to specialized care are in treatment. 45.8% of participants took more than one test. 23 incident cases were detected among repeat testers, of which 20 were confirmed. The estimated incidence was 1.00 confirmed case per 100 individual-years of follow-up. 98.01% of participants would recommend it to a friend. The most identified advantages were convenience and privacy. We demonstrated that the online offer of oral self-sampling kits for HIV detection and reporting results online among GBMSM and TW users of dating apps is feasible. The intervention counted with a high acceptability and high efficacy (in terms of reactivity, confirmation and linkage to care rates). [ABSTRACT FROM AUTHOR]

Objective The objective was to assess the effectiveness of neural mobilization (NM) techniques in the management of musculoskeletal neck disorders with nerve-related symptoms (MND-NRS). Methods We conducted a systematic review with meta-analysis, using pain intensity, disability, perceived function, cervical range of motion, and mechanosensitivity as the main outcome measures. Results The systematic review included 22 studies (n  = 978). More favorable outcomes were observed for NM on pain intensity compared with control interventions (standardized mean differences (SMDs) −0.92; 95% CI −1.66−0.18), but not compared with other treatments (OTs) (SMD 1.06; 95% CI −0.02 to 2.15). Regarding neck pain intensity, no significant differences were found in favor of NM compared with OTs (SMD 0.37; 95% CI −0.35 to 1.1). However, between-treatment differences were found in favor of OT on arm-pain intensity (SMD 0.57; 95% CI 0.08–1.05). In addition, the grouped MA did not show statistically significant differences between NM and OT outcomes on the cervical range of motion (SMD 0.16; 95% CI −0.06 to 0.38). However, compared with no intervention, NM was associated with significantly improved outcomes in cervical rotation (SMD 0.91; 95% CI 0.61–1.22). Similar results were found regarding disability (SMD −0.08; 95% CI −0.36−0.20, and SMD −1.44; 95% CI −2.28−0.6, respectively). Finally, NM was associated with more favorable outcomes on mechanosensitivity compared with OT (SMD 0.79; 95% CI 0.15–1.42) and greater improvements in function compared with no intervention (SMD 0.89; 95% CI 0.16–1.62). Conclusions NM appeared to be effective to improve overall pain intensity when embedded in a physiotherapy treatment in the management of MND-NRS. When compared with no intervention, it was effective to improve neck rotation, disability, and function. However, it was not superior to other types of treatments in improving overall pain intensity, neck pain intensity, arm pain intensity, cervical range of motion and disability, except for mechanosensitivity. [ABSTRACT FROM AUTHOR]

Objectives To assess the efficacy of the novel anti-IL-23 monoclonal antibody guselkumab in a real-life observational cohort of patients with early PsA. Methods We conducted an observational study on patients with early PsA followed by the joint dermatology-rheumatology clinics of two Italian centres starting therapy with guselkumab for severe skin involvement. Each patient was evaluated at baseline and every 24 weeks for one year, recording Disease Activity Index for PsA (DAPSA), PASI, VAS Pain, VAS Prutitus, Patient's Global Assessment (PtGA) and assessing DAPSA response. Results Twenty-four patients were recruited (16 women). The mean duration of skin disease was 12.5 years (CI 8; 17), but all patients had a shorter articular disease duration, 21.29 months (CI 15.9; 26.68). At baseline, all patients displayed a moderate cutaneous disease with a mean PASI of 15.2 (CI 11.7–18.6) and high disease activity, characterized by mean DAPSA of 26.84 (CI 22.49–31.19). An inflammatory low back pain was reported by five patients (20%) with a mean BASDAI 5.1 (CI 4,38–5,85) at baseline. The majority of guselkumab-treated patients (n  = 18; 75%) reached DAPSA remission or DAPSA low disease activity after six months. Seventeen out of 24 patients completed 12 months of treatment, 11 of them (65%) in low disease activity, six (35%) in remission. All patients with axial disease reported improvement of inflammatory low back pain at week 24 with a mean BASDAI 2.98 (CI 2,18– 3,77). No significant side effects were reported. Conclusions Real-life data on a cohort of early PsA patients confirm the efficacy and safety of guselkumab on peripheral and axial manifestations. [ABSTRACT FROM AUTHOR]

This study investigated the effects of 7 days of 600 mg/day anthocyanin-rich blackcurrant extract intake on small intestinal permeability, enterocyte damage, microbial translocation, and inflammation following exertional heat stress. Twelve recreationally active men (maximal aerobic capacity = 55.6 ± 6.0 ml·kg−1·min−1) ran (70% VO2max) for 60 min in an environmental chamber (34 °C, 40% relative humidity) on two occasions (placebo/blackcurrant, randomized double-blind crossover). Permeability was assessed from a 4-hr urinary excretion of lactulose and rhamnose and expressed as a ratio of lactulose/rhamnose. Venous blood samples were taken at rest and 20, 60, and 240 min after exercise to measure enterocyte damage (intestinal fatty acid-binding protein); microbial translocation (soluble CD14, lipopolysaccharide-binding protein); and interleukins 6, interleukins 10, and interleukins 1 receptor antagonist. Exercise increased rectal temperature (by ∼2.8 °C) and heart rate (by ∼123 beats/min) in each condition. Blackcurrant supplementation led to a ∼12% reduction in lactulose/rhamnose ratio (p <.0034) and enterocyte damage (∼40% reduction in intestinal fatty acid-binding protein area under the curve; p <.0001) relative to placebo. No between-condition differences were observed immediately after exercise for lipopolysaccharide-binding protein (mean, 95% confidence interval [CI]; +80%, 95% CI [+61%, +99%]); soluble CD14 (+37%, 95% CI [+22%, +51%]); interleukins 6 (+494%, 95% CI [+394%, +690%]); interleukins 10 (+288%, 95% CI [+105%, +470%]); or interleukins 1 receptor antagonist (+47%, 95% CI [+13%, +80%]; all time main effects). No between-condition differences for these markers were observed after 60 or 240 min of recovery. Blackcurrant extract preserves the GI barrier; however, at subclinical levels, this had no effect on microbial translocation and downstream inflammatory processes. [ABSTRACT FROM AUTHOR]

Background: Data characterizing individuals with a stoma in Portugal is limited. Establishing epi- demiological estimates can enhance understanding of this population and facilitate the adaptation of healthcare models. Objectives: To estimate the prevalence and incidence of individuals in Portugal who have undergone intestinal or urinary ostomy in 2021. Methodology: Observational, longitudinal, and retrospective study using a stoma appliance dispensing database. Results: In 2021, an estimated 22,045 individuals had at least one stoma, with 19,793 [95%CI:19,599;19,994] having an intestinal/urinary stoma. Most of these individuals were men (61.4%) with a mean age of 70.5 years and resided in the inland region of Portugal. Colostomy was the most prevalent type of intestinal/urinary stoma (48.8%). The estimated incidence of new cases was 6,622, of which 5,834 [95%CI:5,680;5,984] were intestinal/urinary stomas. Conclusion: These results characterize the profile of individuals with intestinal and urinary stomas in Portugal. They may be useful in adjusting prevention and health monitoring programs for this population and allocating specialized resources. [ABSTRACT FROM AUTHOR]

Objective: The aim of this umbrella review with meta-meta-analysis was to assess the effectiveness of orthopedic manual therapy in isolation on pain sensitization in patients with chronic musculoskeletal pain. Design: A systematic search was performed in different databases including systematic reviews with or without meta-analysis. The outcome measures included were pressure pain threshold, temporal summation, and conditioned pain modulation. The results of the different reviews were statistically synthesized through a random-effect meta-analysis, of all standardized mean differences and the corresponding 95% confidence interval reported by each study. Results: For mechanical hyperalgesia, the meta-meta-analysis of three meta-analyses revealed a statistically significant small-moderate effect of orthopedic manual therapy, with no evidence of heterogeneity and moderate-quality evidence. In terms of temporal summation, one meta-analysis revealed a statistically significant small effect of orthopedic manual therapy intervention, with moderate heterogeneity and low quality of evidence. Finally, one review without meta-analysis found that orthopedic manual therapy improved endogenous analgesia with low-quality evidence. Conclusion: Orthopedic manual therapy in isolation improved mechanical hyperalgesia with moderate-quality evidence, as well as temporal summation and conditioned pain modulation with low-quality evidence. However, its effects are limited only to immediate and short-term. [ABSTRACT FROM AUTHOR]

Background: Two‐dimensional speckle tracking evaluation (2D‐STE) is a useful tool to evaluate the complexity of atrial function by the analysis of the different phases of atrial deformation and by the combination with Doppler measurements of diastolic function. Aim of the study: To evaluate the role of the left atrial (LA) strain parameters to predict worsening chronic heart failure (CHF). Methods: We enrolled outpatients affected by CHF referred to our heart failure unit. Each patient underwent a medical visit, an electrocardiogram (ECG), and an echocardiographic examination. LA function was assessed by 2D‐STE. The three phases of LA strain, that is, the reservoir (LAr), the conduit (LAcd), and the contraction (LAct)—were evaluated. Moreover, the ratio between E and LAr (E/LAr) and those between LAr and septal (LAr/Ees), lateral (LAr/Eel), and septal‐lateral (LAr/Eem) E/e' were measured. During follow‐up, the events related to worsening of heart failure were evaluated. Results: Two hundred eleven patients were enrolled. During a mean follow‐up of 14 ± 7 months, 37 patients showed at least one event related to heart failure worsening. At univariate Cox regression analysis, LAr, LAcd, LAct, E/LAr, LAr/Ees, LAr/Eel, and LAr/Eem were all associated with events related to heart failure worsening, but at multivariate regression analyses, only LAr (Hazard Ratio, HR:.95; 95% Confidence Interval, CI:.92–.99; p:.031), LAct (HR: 1.06; 95% CI: 1.01–1.12; p:.027), E/LAr (HR: 1.10; 95%CI: 1.0–1.16; p <.001), LAr/Ees (HR:.57; 95% CI:.37–.87; p:.010), and LAr/Eem (HR:.71; 95% CI:.53–.96; p:.026) remained significantly associated with the events. Finally, in a predictive model including the other relevant echocardiographic parameters LAr < 18%, LAct > −10.0%, LAr/Ees < 1.28, and E/LAr > 3.70 were associated with a statistically significant overall net reclassification improvement. Conclusions: In CHF patients, the measure of the LA reservoir and contraction by 2D‐STE is independently associated with heart failure worsening, but the accuracy in predicting the events is even greater when the reservoir is combined with the Doppler measures of diastolic function. [ABSTRACT FROM AUTHOR]

Introduction: Breastfeeding has significant health benefits for infants and birthing persons, including reduced risk of chronic disease. The American Academy of Pediatrics recommends exclusively breastfeeding infants for 6 months and recently extended its recommendation for continuing to breastfeed with supplementation of solid foods from one to two years. Studies consistently identify lower breastfeeding rates among US infants, with regional and demographic variability. We examined breastfeeding in birthing person-infant pairs among healthy, term pregnancies enrolled in the New Hampshire Birth Cohort Study between 2010 and 2017 (n = 1176). Methods: Birthing persons 18–45 years old were enrolled during prenatal care visits at ~ 24–28 weeks gestation and have been followed since enrollment. Breastfeeding status was obtained from postpartum questionnaires. Birthing person and infant health and sociodemographic information was abstracted from medical records and prenatal and postpartum questionnaires. We evaluated the effects of birthing person age, education, relationship status, pre-pregnancy body mass index, gestational weight gain (GWG), smoking and parity, and infant sex, ponderal index, gestational age and delivery mode on breastfeeding initiation and duration using modified Poisson and multivariable linear regression. Results: Among healthy, term pregnancies, 96% of infants were breastfed at least once. Only 29% and 28% were exclusively breastfed at 6-months or received any breastmilk at 12-months, respectively. Higher birthing person age, education, and parity, being married, excessive GWG, and older gestational age at delivery were associated with better breastfeeding outcomes. Smoking, obesity, and cesarean delivery were negatively associated with breastfeeding outcomes. Conclusions: Given the public health importance of breastfeeding for infants and birthing persons, interventions are needed to support birthing persons to extend their breastfeeding duration. Significance: What is already known? The benefits of breastfeeding to child and birthing person health are well-documented, however, rates of breastfeeding initiation and duration continue to fall short of health-based guidelines. Regional differences exist and certain rural New England states tend to have amongst the highest breastfeeding rates in the US. What this study adds? This study of n = 1176 birthing persons-infant pairs enrolled in the New Hampshire Birth Cohort Study, a rural, general population pregnancy cohort, suggests that factors influencing breastfeeding outcomes align closely with studies conducted in urban settings and using nationally-representative surveys. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from epidemiological studies evaluating these associations are inconsistent. OBJECTIVES: We estimated the associations of pregnancy PFAS concentrations with child body mass index (BMI) z-scores and risk of overweight/ obesity in eight U.S. cohorts. METHODS: We used data from 1,391 mother–child pairs who enrolled in eight Environmental influences on Child Health Outcomes (ECHO) cohorts (enrolled: 1999–2019). We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between the ages of 2 and 5 y and calculated age- and sex-specific BMI 풵-scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI 풵-scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and Bayesian approaches for mixtures. We explored whether child sex modified these associations. RESULTS: We observed a pattern of subtle positive associations of PFAS concentrations in pregnancy with BMI 풵-scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI 풵-scores (β=0.07; 95% CI: 0.01, 0.12). Each doubling in perfluroundecanoic acid [relative risk (RR)=1.10; 95% CI: 1.04, 1.16] and 푁-methyl perfluorooctane sulfonamido acetic acid (RR=1.06; 95% CI: 1.00, 1.12) was associated with increased risk of overweight/obesity, with some evidence of a monotonic dose–response relation. We observed weaker and more imprecise associations of the PFAS mixture with BMI or risk of overweight/obesity. Associations did not differ by child sex. DISCUSSION: In eight U.S.-based prospective cohorts, gestational exposure to higher levels of PFAS were associated with slightly higher childhood BMI 풵-score and risk of overweight or obesity. Future studies should examine associations of gestational exposure to PFAS with adiposity and related cardiometabolic consequences in older children. [ABSTRACT FROM AUTHOR]

Background: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. Methods: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. Results: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22). Conclusions: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation. [ABSTRACT FROM AUTHOR]

Simple Summary: The Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/(leukocytes − neutrophils) and lactate dehydrogenase (LDH) and is correlated with outcomes in patients with non-small-cell lung cancer treated with anti PD-(L)1 but has not been validated in an older cohort of patients. LIPI is associated with poorer overall survival in older patients. LIPI is a simple and accessible worldwide tool that could serve as a prognostic factor and can be useful in identifying patients who will not benefit from such treatment. Immunotherapy with immune checkpoint blockers (ICB) represents a valid therapeutic option in older patients for several solid cancer types. However, most of the data concerning efficacy and adverse events of ICB available are derived from younger and fitter patients. Reliable biomarkers are needed to better select the population that will benefit from ICB especially in older patients who may be at a higher risk of developing immune-related adverse events (irAEs) with a greater impact on their quality of life. The Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/[leukocytes − neutrophils]) and lactate dehydrogenase (LDH) and is correlated with outcomes in patients treated with ICB in non-small-cell lung cancer. We aimed to assess the impact of LIPI in ICB outcomes in a dedicated cohort of older patients. The primary objective was to study the prognostic role of LIPI score in patients aged 70 years or above in a real-life population treated with anti-programmed death-(ligand)1 (anti PD-(L)1). dNLR and LDH were collected in a prospective cohort of patients aged 70 years or above treated with PD-(L)1 inhibitors with metastatic disease between June 2014 and October 2017 at Gustave Roussy. LIPI categorizes the population into three different prognostic groups: good (dNLR ≤ 3 and LDH ≤ ULN—upper normal limit), intermediate (dNLR > 3 or LDH > ULN), and poor (dNLR > 3 and LDH > ULN). Anti PD-(L)1 benefit was analyzed according to overall survival (OS), progression free survival (PFS), and overall response rate (ORR) using RECIST v1.1. criteria. In the 191 older patients treated, most of them (95%) were ICB-naïve, and 160 (84%) had an ECOG performance status of 0–1 with a median age at ICB treatment of 77 (range, 70–93). The most common tumor types were melanoma (66%) and non-small-cell lung cancer (15%). The median follow-up duration was 18.8 months (95% CI 14.7–24.2). LIPI classified the population into three different groups: 38 (23%) patients had a good LIPI score, 84 (51%) had an intermediate LIPI score, and 43 (26%) had a poor LIPI score. The median OS was 20.7 months [95% CI, 12.6–not reached] compared to 11.2 months [95% CI, 8.41–22.2] and 4.7 months [95% CI, 2.2–11.3] in patients with a good, intermediate, and poor LIPI score, respectively (p = 0.0003). The median PFS was 9.2 months [95% CI, 6.2–18.1] in the good LIPI group, 7.2 months [95% CI, 5.4–13] in the intermediate LIPI group, and 3.9 months [95% CI, 2.3–8.2] in the poor LIPI group (p = 0.09). The rate of early death (OS < 3 months) was 37% in the poor LIPI group compared to 5% in the good LIPI group (<0.001). Poor LIPI score was associated with a poorer outcome in older patients treated with anti PD-(L)1. LIPI is a simple and accessible worldwide tool that can serve as a prognostic factor and can be useful for stratification benefit from ICB. [ABSTRACT FROM AUTHOR]

This study used longitudinal prospective data from a representative Canada-wide survey to assess the impact of childhood family experience on well-being during adolescence. First, we constructed family composition profiles to capture the number and type of changes in family structure that occurred in our sample over a 12-year period. Then, we examined links between initial family status, family composition profiles, timing of parental separation, and later behavioral outcomes during adolescence. Marital status at birth, as well as 2 different family transition profiles, were linked to externalized problems during adolescence. Timing of the first family transition suppressed the effect of family transition profiles on adolescent behavioral outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) reduce blood concentrations of thyroid hormones in laboratory animals, but it is unclear whether PBDEs disrupt thyroid hormones in pregnant women or newborn infants. OBJECTIVES: We investigated the relationship between maternal PBDE levels and thyroid hormone concentrations in maternal and cord sera. METHODS: We used data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort of 389 pregnant women in Cincinnati, Ohio, who were enrolled from 2003 through 2006 and delivered singleton infants. Maternal serum PBDE concentrations were measured at enrollment (16 ±3 weeks of gestation). Thyroid hormone concentrations were measured in maternal serum at enrollment (n = 187) and in cord serum samples (n = 256). RESULTS: Median maternal serum concentrations of BDEs 28 and 47 were 1.0 and 19.1 ng/g lipid, respectively. A 10-fold increase in BDEs 28 and 47 concentrations was associated with a 0.85-μg/dL [95% confidence interval (CI): 0.05, 1.64] and 0.82-μg/dL (95% CI: 0.12, 1.51) increase in maternal total thyroxine concentrations (TT4), respectively. Both congeners were also positively associated with maternal free thyroxine (FT4). We also observed positive associations between BDE-47 and maternal total and free triiodothyronine (TT3 and FT3). A 10-fold increase in BDE-28 was associated with elevated FT3 concentrations (β = 0.14 pg/mL; 95% CI: 0.02, 0.26). In contrast, maternal PBDE levels were not associated with thyroid hormone concentrations in cord serum. CONCLUSIONS: These findings suggest that maternal PBDE exposure, particularly BDEs 28 and 47, are associated with maternal concentrations of T4 and T3 during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. Methods: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. Results: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22). Conclusions: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation. [ABSTRACT FROM AUTHOR]

The article presents a study on the impact of autologous priming on blood conservation in patients after cardiac surgery. Topics include the need for alternative perfusion techniques to lower hemodilution, the effectiveness of a protocol of retrograde autologous prime (RAP) and venous antegrade prime (VAP), and the increase in postoperative hematocrits. It also discusses the use of a retrospective review to examine patients' data on their surgeries.

Introduction: A sedentary lifestyle in adolescents contributes to the occurrence of different diseases, making it relevant to investigate associated factors. Objective: To analyze the association between sedentary lifestyle and socioeconomic status in adolescents from public schools. Materials and Methods: Cross-sectional study, carried out with 347 adolescents enrolled in public high schools in the city of Divinópolis, Minas Gerais. Data collection took place in 2017. Sedentary lifestyle was assessed using the International Physical Activity Questionnaire and socioeconomic status using the criteria of the Brazilian Association of Research Companies. Descriptive and analytical statistics were performed using a multivariate logistic regression model. Results: 347 adolescents participated in the investigation. The mean age of the group was 16.4 ± 1.0 years. Individuals characterized as sedentary constituted 38.9% of the sample, of which 66.7% were female. Having a higher socioeconomic level decreases the probability of being sedentary (OR=0.235; 95%IC: 0,069-0,803; p=0.021), just as being a student in public schools in the southwest region increases this chance (OR=2,68; 95%IC:1,370-5,239; p=0,04). Discussion: The reasons why socioeconomic conditions can influence a sedentary lifestyle are varied. The absence of public spaces can contribute to the increase in sedentary lifestyles in adolescents with lower socioeconomic status. Conclusion: This investigation highlights the importance of public investments in policies to encourage the practice of physical activity for adolescents, especially for females and lower socioeconomic status. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to explore how a nutritional intervention that improves the biochemical and functional profile of dysphagic older people impacts on nursing workload and costs for nursing homes. Background: Dysphagic institutionalized older people particularly at risk of malnutrition require more intensive support from nursing staff and higher costs for nursing homes. Method: This is an open pre–post longitudinal multicentre quasi‐experimental study without a control group. Results: There is a significant reduction in the number of enemas (from 3.51 to 1.11 enemas), with an average nursing workload reduction from 52 to 16 min per patient every month. Each nurse also spent 20 h less per patient every month spoon‐feeding. This resulted in nursing staff cost savings. Conclusions: The nutritional intervention led to a significantly better quality of life for the patients manifested through increased independence and social engagement. This reduced workload for nursing staff and costs for nursing home administrators. Implications for Nursing Management: Sensitive, targeted nutritional interventions have the potential to improve nursing home residents' quality of life and enable a more efficient use of resources. This study revealed reduced workload and cost savings due to less time spent administering enemas and spoon‐feeding, in addition to reduced malnutritional consequences. [ABSTRACT FROM AUTHOR]

Sarcoid-like granulomatosis (SLG) reaction caused by immunotherapy remains poorly understood. This study aims to investigate the outcome of patients with cancer and SLG associated with immunotherapy. Between April 2016 and June 2020, 434 patients with immunological adverse events were screened from the ImmunoTOX assessment board of Gustave Roussy, an academic cancer centre in France. Among them, 28 patients had SLG associated with immunotherapy (SLG cohort) and 406 patients had other immunological adverse events (control cohort). Clinical characteristics and outcome of patients were compared from SLG and control cohort. The SLG cohort consisted of 28 patients, 14 women and 14 men, with the median (range) age of 56.5 (28.7–75.3) years. Patients in the SLG cohort with sarcoidosis were asymptomatic (only radiographical finding) in 13 (46.4%) cases; otherwise, the most frequent symptoms were dyspnoea in 8 (28.6%) patients and cough in 5 (17.8%) patients. The computerised tomography scan found sarcoidosis localisations in mediastinal or peri-hilar thoracic lymph nodes in 26 (92.9%) patients, and lung parenchymal involvement was found in 14 (50.0%) patients. The radiographic Scadding stages for sarcoidosis classification were distributed in stages 0, I, II, III and IV in 2 patients (7.1%), 13 patients (46.4%), 11 patients (39.3%), 1 patient (3.6%) and 1 patient (3.6%), respectively. Compared with patients with other immunological toxicities (cohort control), patients with sarcoidosis presented most frequently with melanoma (75.0% versus 21.9% of patients; p < 0.001) and more often received combined therapies of anti–programmed cell death 1 plus anti–cytotoxic T-lymphocyte antigen 4 protein (46.4% versus 12.6% of patients; p = 0.002). Patients with sarcoidosis had an improved overall survival (OS); the median OS was not reached in the SLG cohort and 40.4 months in the control cohort, hazard ratio = 0.232 (95% confidence interval: 0.086–0.630) (p = 0.002). Sarcoidosis-like reactions in patients receiving immunotherapy were reported as non-severe immunological reactions in most cases and were correlated with improved OS. SLG should not be misdiagnosed as tumour progression in patients receiving immunotherapy treatment for cancer. • Sarcoidosis associated with immunotherapy correlated with improved overall survival. • Sarcoidosis associated with anticancer immunotherapy was generally of mild severity. • Sarcoidosis seems more related to the combination of anti–programmed cell death 1 plus anti–cytotoxic T-lymphocyte antigen 4 protein. [ABSTRACT FROM AUTHOR]

This study sought to compare point-of-care ultrasound (POCUS) and conventional X-rays for detecting fractures in children. This was a prospective, non-randomized, convenience-sample study conducted in five medical centers. It evaluated pediatric patients with trauma. POCUS and X-ray examination results were treated as dichotomous variables with fracture either present or absent. Descriptive statistics were calculated in addition to prevalence, sensitivity, specificity, positive predictive value and negative predictive value, including 95% confidence intervals (CIs). The Cohen κ coefficient was determined as a measurement of the level of agreement. A total of 554 examinations were performed with POCUS and X-ray. On physical examination, swelling, localized hematoma and functional limitation were found in 66.73%, 33.78% and 53.74% of participants, respectively. The most-studied areas were limbs and hands/feet (58.19% and 38.27%), whereas the thorax was less represented (3.54%). Sensitivity of POCUS was 91.67% (95% CI, 76.41-97.82%) for high-skill providers and 71.50 % (95% CI, 64.75-77.43%) for standard-skill providers. Specificity was 88.89% (95% CI, 73.00-96.34%) and 82.91% (95% CI, 77.82-87.06%) for high- and standard-skill providers, respectively. Positive predictive value was 89.19% (95% CI, 73.64-96.48%) and 75.90% (95% CI, 69.16-81.59%) for high- and standard-skill providers, respectively. Negative predictive value was 91.43% (95% CI, 75.81-97.76%) and 79.44% (95% CI, 74.21-83.87%) for high- and standard-skill providers, respectively. The Cohen κ coefficient showed very good agreement (0.81) for high-skill providers, but moderate agreement (0.54) for standard-skill providers. We noted good diagnostic accuracy of POCUS in evaluating fracture, with excellent sensitivity, specificity, and positive and negative predictive value for high-skill providers. [ABSTRACT FROM AUTHOR]

Background Plumb line distances (PDs) are widely used in conservative clinical practice to evaluate the sagittal shape of the spine. Objective The objective was to assess the normative values of PDs in a large, healthy population in an age range representative of the adolescent population with spinal deformities, and to correlate it with x-ray measurements. Design This was a cross-sectional study. Methods Participants were 584 healthy individuals (341 females) with x-rays showing no spine deformities. The whole sample (OVERALL) was divided into 5 groups: 6 to 9 years old (n = 106); >10 years, Risser 0 with triradiate cartilage open (n = 129) or closed (n = 104); Risser 1 to 2 (n = 126); and Risser 3 to 5 (n = 119). PDs were taken by maintaining a tangent to the thoracic kyphosis apex at C7, T12, L3, and S2. Sagittal index (C7 + L3), and sagittal and coronal balances (C7 related to S2) were calculated. Results In OVERALL, PDs at C7, T12, L3, and S2 were 39.9 ± 16.7, 21.4 ± 15.3, 39.9 ± 15, 20.6 ± 17.0 mm, respectively. Sagittal index was 79.8 ± 26.8, sagittal balance was 19.3 ± 17 mm anterior to S2 plumb line; 13.5% had a coronal imbalance of 11.4 ± 5.4 mm to the right and 24.7% of 13.2 ± 6.0 mm to the left. C7 and L3 PDs, sagittal index, and sagittal balance were significantly lower in ages 6 to 9 compared to older patients in Risser 1 to 2 group. C7 and S2 PDs and sagittal index were significantly larger in males. Sagittal index correlated with thoracic kyphosis Cobb degrees (r = 0.47). Limitations The participants were not randomly chosen from the general population; and they had an x-ray because of spine pathology suspicion. Conclusions This study shows normative data to be used in clinical practice. Sagittal spinopelvic alignment has gained more and more importance in the last decades because of its high correlation to Health-Related Quality of Life scores in adults. 1 [ABSTRACT FROM AUTHOR]

Background: The normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of 'relative hypoxia' which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients. Methods: In this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO2) ≤0.5 and PaO2/FiO2 ≥ 200 mmHg underwent a 2-hour exposure to hyperoxia (FiO2 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24 h and 48 h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2 h of hyperoxia (t1) and 2 h after returning to their baseline FiO2 (t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test. Results: EPO increased within 48 h in patients exposed to hyperoxia from 16.1 [7.4-20.2] to 22.9 [14.1-37.2] IU/L (p = 0.022). Serum ROS transiently increased at t1, and glutathione increased at t2. Early reductions in microvascular density and perfusion were seen during hyperoxia (perfused small vessel density: 85% [95% confidence interval 79-90] of baseline). The response after 2 h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO2. Conclusions: A two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48 h. Adequately controlled studies are needed to confirm the effect of short-term hyperoxia on erythropoiesis. Trial registration: ClinicalTrials.gov (www.clinicaltrials.gov), NCT02481843, registered 15th June 2015, retrospectively registered [ABSTRACT FROM AUTHOR]

Objective: Topoisomerase 1 (topo-1) is an important target for the treatment of metastatic colorectal cancer (CRC). The aim of the present study was to evaluate the correlation between topo-1 single-nucleotide polymorphisms (SNPs) and clinical outcome in metastatic CRC (mCRC) patients. Methods: With the use of specific software (PROMO 3.0), we performed an in silico analysis of topo-1 promoter SNPs; the rs6072249 and rs34282819 SNPs were included in the study. DNA was extracted from 105 mCRC patients treated with FOLFIRI ± bevacizumab in the first line. SNP genotyping was performed by real-time PCR. Genotypes were correlated with clinical parameters (objective response rate, progression-free survival, and overall survival). Results: No single genotype was significantly associated with clinical variables. The G allelic variant of rs6072249 topo-1 SNP is responsible for GC factor and X-box-binding protein transcription factor binding. The same allelic variant showed a nonsignificant trend toward a shorter progression-free survival (GG, 7.5 months; other genotypes, 9.3 months; HR 1.823, 95% CI 0.8904-3.734; p = 0.1). Conclusion: Further analyses are needed to confirm that the topo-1 SNP rs6072249 and transcription factor interaction could be a part of tools to predict clinical outcome in mCRC patients treated with irinotecan-based regimens. [ABSTRACT FROM AUTHOR]

Aims and objectives To confirm the accuracy of the EASI system compared to the standard 12-lead electrocardiogram, which is the gold standard, in monitoring the two major parameters used in the Coronary Care Units to detect myocardial ischaemia: ST-segment and J-point. Background Continuous electrocardiograph monitoring is used in the Coronary Care Units to detect cardiac conduction abnormalities and to show the morphology of electrocardiographic waves and tracts. Its accuracy is essential for efficient nursing vigilance, particularly for monitoring the ST segment and the J-point, in which alterations may indicate the onset of myocardial ischaemia. Design An observational study was conducted. Methods The enrolled patients ( n = 253) simultaneously underwent standard electrocardiogram (10 electrodes) and EASI electrocardiogram (five electrodes). Data were collected by the Coronary Care Units nurses. Tests to compare differences in means and medians between the two sets of measurements were performed, and the Bland-Altman plots were used to illustrate their agreement. Results All 6·072 electrocardiographic leads (3·036 standard and 3·036 EASI) were recorded and analysed. Between the two measurement methods, very small statistically significant differences were found in some leads which are not clinically relevant for both the ST-segment or the J-point. Conclusions This study confirms that the accuracy of the EASI 12-leadelectrocardiogram, compared to the standard 12-leadelectrocardiogram, which is the gold standard, is acceptable for clinical practice to monitor the two major parameters used in the Coronary Care Units for detecting myocardial ischaemia: ST-segment and J-point. Relevance to clinical practice The EASI system ensures: (1) ease of use and comfort for patients admitted to Coronary Care Units because it only requires five electrodes; (2) increased efficacy of nursing vigilance in the early detection of changes in ST-segment and J- point measurements. [ABSTRACT FROM AUTHOR]

Aim No epidemiological data on halitosis are available from Italy. Thus, the aim of this population-based cross-sectional study was to estimate the prevalence of halitosis in an urban adult population from North Italy and to explore related oral risk indicators. Materials and Methods The survey used a two-stage probability sampling method to collect a representative sample of inhabitants, aged between 20 and 75 years, in the city of Turin. Seven hundred and forty-four adults were clinically examined (47% of sampled subjects) for oral malodor and periodontal conditions. Using a standardized questionnaire social, health and halitosis-related parameters were collected. Logistic models with interaction terms between tongue coating scores (TCS) and periodontal status were used to explore halitosis risk indicators. Results The prevalence estimate of halitosis according to the organoleptic assessment was 53.51% (95% CI: 48.55-58.50). A statistically significant correlation was found between organoleptic and gas chromatography measurements ( p < 0.0001). Stronger associations between halitosis and periodontitis were observed in people having higher TCS: adjusted odds ratio considering low and high TCS in individuals with severe periodontitis were 2.95 and 20.77 ( p ≤ 0.003). Conclusions Due to the high prevalence of halitosis in the Turin population, its diagnosis and management should be incorporated in comprehensive dental care. [ABSTRACT FROM AUTHOR]

Objectives: Female gender has been shown to negatively affect the outcomes of surgical bypass for peripheral arterial disease (PAD). We examined gender-related disparities in outcomes of endovascular PAD procedures in a large population-based study. Methods: We used discharge data from California hospitals to identify patients who had PAD interventions during 2005 to 2009. Logistic regression was used for 12-month reintervention, and Cox proportional hazard regression was used for amputation-free survival comparisons. Results: A total of 25 635 patients had endovascular procedures (11 389 [44.4%] women). Women were more likely than men (34.5% vs 30.1%, P < .0001) to have critical limb ischemia (CLI). Twelve-month reintervention rate in women was similar to men. Amputation-free survival was better among women than men (hazard ratio 0.84, 95% confidence interval [CI] 0.76-0.93, P = .0006). Conclusion: Despite presenting more frequently with CLI, women had better amputation-free survival than men following endovascular procedures. Future research should determine whether findings favor one type of PAD treatment modality over another for women. [ABSTRACT FROM AUTHOR]

Although transcatheter aortic valve replacement (TAVR) has expanded the proportion of patients with aortic stenosis (AS) who are candidates for valve replacement, some patients remain untreated, and their outcomes are not clear. We evaluated 172 consecutive patients with severe symptomatic AS referred for TAVR who declined (n = 55) or were not candidates for (n = 117) intervention. We examined clinical and echocardiographic variables associated with mortality. There were 77 deaths, and mean follow-up was 17.9 ± 10.9 months for survivors. Mortality rate at 1 and 2 years was 39.2% and 52.6%, respectively. There was a significant difference in mortality rate between patients who declined the procedure and those who were not candidates (p = 0.001), with 1-year mortality rates of 20.6% and 48.4%, respectively. On multivariate analysis, 4 variables were independently associated with all-cause mortality: New York Heart Association Class IV heart failure (hazard ratio [HR] 2.6, 95% confidence interval [CI] 1.6 to 4.2, p <0.001), glomerular filtration rate <48 ml/min (HR 2.1, 95% CI 1.3 to 3.4, p = 0.002), albumin <3.9 g/dl (HR 1.9, 95% CI 1.2 to 3.1, p = 0.007), and ejection fraction <50% (HR 1.9, 95% CI 1.4 to 3.0, p = 0.01). In this new era with expanded treatment options, patients with severe symptomatic AS who remain untreated after referral for TAVR experience a mortality rate of 39% at 1 year. The presence of advanced heart failure, renal dysfunction, low albumin, and/or left ventricular dysfunction identifies patients at higher risk of mortality. [ABSTRACT FROM AUTHOR]

Aim There is a paucity of up-to-date data regarding prevalence and risk indicators of periodontitis in Italy. Therefore, the aim of this study was to evaluate the prevalence of periodontitis and its risk indicators among adults from an urban area in North Italy. Material and Methods This cross-sectional survey used a stratified two-stage probability sampling method to draw a representative sample of the adult population of the city of Turin. About 1600 individuals, 20-75 years old, were randomly selected and 736 subjects agreed to participate (47% of the sampled subjects). Clinical parameters were assessed using a full-mouth protocol. Logistic models were applied to assess associations between periodontitis and its putative risk indicators. Age was included as restricted cubic spline. Results Based on CDC/ AAP case definition, the prevalence estimates of severe and moderate periodontitis were 34.94% (95% CI: 31.23-38.74) and 40.78% (95% CI: 36.89-44.79). The probability of periodontitis increased in smokers (adjusted OR 2.06, 95% IC: 1.26-3.37, p = 0.004) and with age but leveled off in the 50+ year-old group ( p < 0.001). Conclusion Periodontitis was highly prevalent in the Turin population. The present data will enable development of appropriate public health programs and allocation of resources. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the prevalence of dental pain during pregnancy and its association with sociodemographic factors and oral health conditions among 315 pregnant women in South Brazil. Participants were interviewed to obtain sociodemographic data, such as age, educational level, employment status, family income, and marital and parity status. Medical and dental histories were also collected, including the occurrence of dental pain and the use of dental services during pregnancy. Clinical examinations were performed to assess the presence of visible plaque and gingival bleeding and to calculate the decayed, missing, and filled teeth index. Means and standard deviations of continuous variables and frequencies and percentages of categorical variables were calculated. Independent variables were included in a multivariate logistic regression analysis. A total of 173 (54.9 %) pregnant women reported dental pain during pregnancy. After adjustment of the analysis, caries activity remained the main determinant of dental pain (odds ratio 3.33, 95 % CI 1.67-6.65). The prevalence of dental pain during pregnancy was high and the presence of caries activity was a determinant of dental pain. Moreover, access to oral health care was low, despite pregnant women's increased need for dental assistance. [ABSTRACT FROM AUTHOR]

Simple Summary: Deficient Mismatch Repair (dMMR) is an oncogenic path accounting for around 15% of cancers. It is considered as the first predictive marker of efficacy for immune checkpoint inhibitors (ICI). However, around 39% of cases are refractory and additional biomarkers are needed. The Lung Immune Prognostic Index (LIPI) is a score reflecting the host inflammation, based on lactate deshydrogenase level, and derived neutrophils to leucocytes ratio. We aimed to assess the LIPI as a prognostic factor for ICI efficacy in patients with dMMR tumors. We found that patients with a Poor LIPI were more likely to experience disease progression, fast progression (death within the first 3 months of ICI), and have shorter overall and progression free survivals. This score is a low-cost, simple, and accessible prognostic tool in dMMR that merits further investigation in prospective studies. Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p < 0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46–8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, the introduction of immunotherapy radically changed the therapeutic algorithm of non-small-cell lung cancer as an upfront or secondary strategy. Unfortunately, the small amount of patient benefits from immune-checkpoint inhibitors (ICI) and the prognostic role of concomitant treatments are a burning open issue. The use of steroids was associated with poor outcomes during ICI. We investigated the impact of intercurrent steroids, according to clinical indication, which is actually unclear. Interestingly, the use of intercurrent steroids given for cancer-unrelated symptoms has no survival impact on our study cohort. Background: Baseline steroids before ICI have been associated with poor outcomes, particularly when introduced due to cancer symptoms. Methods: Retrospective analysis of advanced NSCLC patients treated with ICI. We collected the use of intercurrent steroids (≥10 mg of prednisone-equivalent) within the first eight weeks of ICI. We correlated steroid use with patient outcomes according to the indications. Results: 413 patients received ICI, 299 were steroids-naïve at baseline. A total of 49 patients received intercurrent steroids (16%), of whom 38 for cancer-related symptoms and 11 for other indications, such as immune-related events. Overall, median (m) progression-free survival (PFS) was 1.9 months (mo.) [95% CI, 1.8-2.4] and overall survival (OS) 10 mo. [95% CI, 8.1–12.9]. Intercurrent steroids under ICI correlated with a shorter PFS/OS (1.3 and 2.3 mo. respectively, both p < 0.0001). Intercurrent steroids for cancer-related symptoms correlated with poorest mPFS [1.1 mo.; 95% CI, 0.9–1.5] and mOS [1.9 mo.; 95%CI, 1.5–2.4; p < 0.0001)]. No mOS and mPFS differences were found between cancer-unrelated-steroid group and no-steroid group. Steroid use for cancer-related symptoms was an independent prognostic factor for poor PFS [HR 2.64; 95% CI, 1.2–5.6] and OS [HR 4.53; 95% CI, 1.8–11.1], both p < 0.0001. Conclusion: Intercurrent steroids during ICI had no detrimental prognostic impact if the indication was unrelated to cancer symptoms. [ABSTRACT FROM AUTHOR]

The ICARUS trial is a phase II, open label, multicenter, single arm study conducted to investigate the efficacy, safety, and tolerability of a rechallenge treatment with the first-generation tyrosine kinase inhibitor (TKI) gefitinib in advanced non-small-cell lung cancer (NSCLC) patients carrying activating mutations of the epidermal growth factor receptor (EGFR). The ICARUS trial enrolled 61 patients who were rechallenged with gefitinib at progression after second-line chemotherapy. Serum-derived circulating cell-free DNA (cfDNA) collected before the rechallenge from a cohort of 29 patients, was retrospectively analyzed for the EGFR exon 19 deletions and for the p.L858R and p.T790M single nucleotide variants (SNV). The analysis of cfDNA detected the same EGFR activating mutation reported in the tumor tissue in 20/29 patients, with a sensitivity of 69%. Moreover, a p.T790M variant was found in 14/29 patients (48.3%). The median progression-free survival (PFS) was 2.7 months for p.T790M positive patients (CI 95% 1.4–3.1 months) versus 3.5 months for the p.T790M negative patients (CI 95% 1.6–5.3 months), resulting in a statistically significant difference (Long rank test p = 0.0180). These findings confirmed the role of the p.T790M mutation in the resistance to first-generation TKIs. More importantly, our data suggest that TKI rechallenge should be guided by biomarker testing. [ABSTRACT FROM AUTHOR]