Exploring perceptions of inpatient hospital attire in children with cancer.

BACKGROUND: Attire bolsters identity, self-expression, and comfort. Hospital gowns are known to be distressing in adults. Attitudes of children with cancer toward hospital attire remain uninvestigated and may be a modifiable factor in overall well-being. METHODS: A 39-item mixed methods survey evaluated perceptions of patient attire in children with cancer. Children aged 7-18 years were recruited at an academic medical center. Data analysis included simple statistics and thematic analysis. RESULTS: Forty children with cancer receiving oncologic care participated. Participants' mean age was 12.4 (SD = 3.0, range = 7-17) years, and 25 (62%) were male. Quantitative data revealed 81% of participants preferred their own attire when admitted to the hospital, feeling more comfortable in such when well (91%) or sick (75%). They did not feel like they "must" wear a gown when admitted (60%) and did not want to be asked about preferred inpatient attire (63%). Thematic analysis revealed that children had strong negative views of gowns and preferred to wear their own attire in the hospital, which provided physical and emotional comfort. Children worried wearing their own clothing could impede their care. CONCLUSION: Children with cancer prefer wearing their own clothes in the hospital for physical and emotional comfort. They are willing to wear gowns for ease of care; however, they do not want to arbitrate when they need to make that choice. Providers may ease distress by considering a child's own clothes as default hospital attire with instructions for when a gown is necessary for good clinical care.

Molecular Basis and Diagnostic Approach to Isolated and Syndromic Lateralized Overgrowth in Childhood.

OBJECTIVE: To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to classify it by molecular genetics. and STUDY DESIGN: We categorized 186 retrospective cases of LO diagnosed between 2003 and 2023 into suspected Beckwith-Wiedemann spectrum (BWSp), PIK3CA-Related Overgrowth Spectrum (PROS), vascular overgrowth (VO) , or isolated (ILO), based on initial clinical assessments, to determine the appropriate first-tier molecular tests and tissue for analysis. Patients underwent testing for 11p15 epigenetic abnormalities or somatic variants in genes related to PI3K/AKT/mTOR, vascular proliferation, and RAS-MAPK cascades using blood or skin DNA. For cases with negative initial tests, a sequential cascade molecular approach was employed to improve diagnostic yield. RESULTS: This approach led to a molecular diagnosis in 54% of cases, 89% of cases consistent with initial clinical suspicions and 11% reclassified. BWSp was the most common cause, with 43% of cases exhibiting 11p15 abnormalities. PROS had the highest confirmation rate, with 74% of clinically diagnosed patients showing a PIK3CA variant. VO demonstrated significant clinical overlap with other syndromes. Molecular diagnosis of ILO proved challenging, with only 21% of cases classifiable into a specific condition. CONCLUSION: Despite, LO is underdiagnosed from a molecular viewpoint and to date has had no diagnostic guidelines, which would be crucial for addressing potential cancer predisposition, enabling precision medicine treatments, or guiding management. This study sheds light on the molecular etiology of LO, highlighting the importance of tailored diagnostic approach and of selecting appropriate testing to achieve the highest diagnostic yield.

A Novel Splice Donor Site Mutation Leading to Inherited Type I Protein S Deficiency.

Inherited Protein S (PS) deficiency is an autosomal dominant thrombotic disorder. We encountered a case of inherited type I PS deficiency following a close examination for recurrent pregnancy loss and identified the mutation responsible; a novel splice donor site mutation in intron 13 of the PROS1 gene appeared to have caused a frameshift with premature termination at amino acid +551. These results will contribute to the creation of an accurate database and define the molecular basis for PS deficiency.

Patient reported outcomes following MR-guided radiotherapy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: This systematic review provides an overview of literature on the impact of MR-guided radiotherapy (MRgRT) on patient reported outcomes (PROs) in patients with prostate cancer (PC). METHODS: A systematic search was performed in October 2023 in PubMed, EMBASE and Cochrane Library. The PICOS framework (i.e., patient, intervention, comparison, outcome, study design) was used to determine eligibility criteria. Included were studies assessing PROs following MRgRT for PC with sample size >10. Methodological quality was assessed using the ROBINS-I and RoB 2. Relevant mean differences (MD) compared to pre-RT were interpreted using minimal important differences (MID). Meta-analyses were performed using random-effects models. Between-study heterogeneity was assessed using the I2-statistic. RESULTS: Eleven observational studies and one randomized controlled trial (n=897) were included. Nine studies included patients with primary PC with MRgRT as first-line treatment (n=813) and three with MRgRT as second-line treatment (n=84). Substantial risk of bias was found in five studies. EORTC QLQ-C30 and EORTC QLQ-PR25 scores were pooled from three studies, and EPIC-26 scores from four studies. Relevant MDs for the urinary domain were found with the EPIC-26 (MD-10.0 [95%CI -12.0 - -8.1]; I20%) and the EORTC QLQ-PR25 (MD8.6 [95%CI -4.7-22.0]; I297%), both at end-RT to one month follow-up. Relevant MDs for the bowel domain were found with the EPIC-26 (MD-4.7 [95%CI -9.2 - -0.2]; I282%), at end-RT or one month follow-up, but not with the EORTC QLQ-PR25. For both domains, no relevant MDs were found after three months of follow-up. No relevant MDs were found in the general QoL domains of the EORTC QLQ-C30. CONCLUSION: MRgRT for PC results in a temporarily worsening of patient-reported urinary and bowel symptoms during the first month after treatment compared to pre-RT, resolving at 3 months. No clinically relevant changes were found for general QoL domains. These results provide important information for patient counseling and can serve as a benchmark for future studies.

Georg Schmorl Prize of the German Spine Society (DWG) 2023: the influence of sarcopenia and paraspinal muscle composition on patient-reported outcomes: a prospective investigation of lumbar spinal fusion patients with 12-month follow-up.

PURPOSE: This study aimed to investigate the impact of sarcopenia and lumbar paraspinal muscle composition (PMC) on patient-reported outcomes (PROs) after lumbar fusion surgery with 12-month follow-up (12 M-FU). METHODS: A prospective investigation of patients undergoing elective lumbar fusion was conducted. Preoperative MRI-based evaluation of the cross-sectional area (CSA), the functional CSA (fCSA), and the fat infiltration(FI) of the posterior paraspinal muscles (PPM) and the psoas muscle at level L3 was performed. Sarcopenia was defined by the psoas muscle index (PMI) at L3 (CSAPsoas [cm2]/(patients' height [m])2). PROs included Oswestry Disability Index (ODI), 12-item Short Form Healthy Survey with Physical (PCS-12) and Mental Component Scores (MCS-12) and Numerical Rating Scale back and leg (NRS-L) pain before surgery and 12 months postoperatively. Univariate and multivariable regression determined associations among sarcopenia, PMC and PROs. RESULTS: 135 patients (52.6% female, 62.1 years, BMI 29.1 kg/m2) were analyzed. The univariate analysis demonstrated that a higher FI (PPM) was associated with worse ODI outcomes at 12 M-FU in males. Sarcopenia (PMI) and higher FI (PPM) were associated with worse ODI and MCS-12 at 12 M-FU in females. Sarcopenia and higher FI of the PPM are associated with worse PCS-12 and more leg pain in females. In the multivariable analysis, a higher preoperative FI of the PPM (ß = 0.442; p = 0.012) and lower FI of the psoas (ß = -0.439; p = 0.029) were associated with a worse ODI at 12 M-FU after adjusting for covariates. CONCLUSIONS: Preoperative FI of the psoas and the PPM are associated with worse ODI outcomes one year after lumbar fusion. Sarcopenia is associated with worse ODI, PCS-12 and NRS-L in females, but not males. Considering sex differences, PMI and FI of the PPM might be used to counsel patients on their expectations for health-related quality of life after lumbar fusion.

Advanced photocatalysis as a viable and sustainable wastewater treatment process: A comprehensive review.

In our era, water pollution not only poses a serious threat to human, animal, and biotic life but also causes serious damage to infrastructure and the ecosystem. A set of physical, chemical, and biological technologies have been exploited to decontaminate and/or disinfect water pollutants, toxins, microbes, and contaminants, but none of these could be ranked as sustainable and scalable wastewater technology. The photocatalytic process can harmonize the sunlight to degrade certain toxins, chemicals, microbes, and antibiotics, present in water. For example, transition metal oxides (ZnO, SnO2, TiO2, etc.), when integrated into an organic framework of graphene or nitrides, can bring about more than 90% removal of dyes, microbial load, pesticides, and antibiotics. Similarly, a modified network of graphitic carbon nitride can completely decontaminate petrochemicals. The present review will primarily highlight the mechanistic aspects for the removal and/or degradation of highly concerned contaminants, factors affecting photocatalysis, engineering designs of photoreactors, and pros and cons of various wastewater treatment technologies already in practice. The photocatalytic reactor can be a more viable and sustainable wastewater treatment opportunity. We hope the researcher will find a handful of information regarding the advanced oxidation process accomplished via photocatalysis and the benefits associated with the photocatalytic-type degradation of water pollutants and contaminants.

Atypical Presentation and Evolution of Necrotizing Enterocolitis as a PIK3CA Pathological Variant.

Activating mutation of PIK3CA is linked with cases of overgrowth syndromes and belongs to the PIK3CA-related overgrowth spectrum (PROS). Mutations in this gene are associated with vascular malformations, brain abnormalities, and an increased risk for certain tumors. We report the case of a newborn girl, preterm at 34 weeks of gestation, referred to our center for atypical necrotizing enterocolitis (NEC). At laparotomy, the appearance of the intestinal tract was described as puffy, cauliflower-like with a dark purplish coloration. Subsequently, the colostomy was described as having a consistent proliferative appearance. Medical treatment with sirolimus resulted in minimal improvement. There are no reported cases in the literature of association between NEC and PIK3CA mutation. It is possible that PIK3CA mutation, including the related vascular anomalies, plays a role in the pathogenesis of NEC with this condition.

Impact of Electronic Patient-Reported Outcomes on Unplanned Consultations and Hospitalizations in Patients With Cancer Undergoing Systemic Therapy: Results of a Patient-Reported Outcome Study Compared With Matched Retrospective Data.

BACKGROUND: The evaluation of electronic patient-reported outcomes (ePROs) is increasingly being used in clinical studies of patients with cancer and enables structured and standardized data collection in patients' everyday lives. So far, few studies or analyses have focused on the medical benefit of ePROs for patients. OBJECTIVE: The current exploratory analysis aimed to obtain an initial indication of whether the use of the Consilium Care app (recently renamed medidux; mobile Health AG) for structured and regular self-assessment of side effects by ePROs had a recognizable effect on incidences of unplanned consultations and hospitalizations of patients with cancer compared to a control group in a real-world care setting without app use. To analyze this, the incidences of unplanned consultations and hospitalizations of patients with cancer using the Consilium Care app that were recorded by the treating physicians as part of the patient reported outcome (PRO) study were compared retrospectively to corresponding data from a comparable population of patients with cancer collected at 2 Swiss oncology centers during standard-of-care treatment. METHODS: Patients with cancer in the PRO study (178 included in this analysis) receiving systemic therapy in a neoadjuvant or noncurative setting performed a self-assessment of side effects via the Consilium Care app over an observational period of 90 days. In this period, unplanned (emergency) consultations and hospitalizations were documented by the participating physicians. The incidence of these events was compared with retrospective data obtained from 2 Swiss tumor centers for a matched cohort of patients with cancer. RESULTS: Both patient groups were comparable in terms of age and gender ratio, as well as the distribution of cancer entities and Joint Committee on Cancer stages. In total, 139 patients from each group were treated with chemotherapy and 39 with other therapies. Looking at all patients, no significant difference in events per patient was found between the Consilium group and the control group (odds ratio 0.742, 90% CI 0.455-1.206). However, a multivariate regression model revealed that the interaction term between the Consilium group and the factor "chemotherapy" was significant at the 5% level (P=.048). This motivated a corresponding subgroup analysis that indicated a relevant reduction of the risk for the intervention group in the subgroup of patients who underwent chemotherapy. The corresponding odds ratio of 0.53, 90% CI 0.288-0.957 is equivalent to a halving of the risk for patients in the Consilium group and suggests a clinically relevant effect that is significant at a 2-sided 10% level (P=.08, Fisher exact test). CONCLUSIONS: A comparison of unplanned consultations and hospitalizations from the PRO study with retrospective data from a comparable cohort of patients with cancer suggests a positive effect of regular app-based ePROs for patients receiving chemotherapy. These data are to be verified in the ongoing randomized PRO2 study (registered on ClinicalTrials.gov; NCT05425550). TRIAL REGISTRATION: ClinicalTrials.gov NCT03578731; https://www.clinicaltrials.gov/ct2/show/NCT03578731. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/29271.

Patient-reported outcomes with selpercatinib treatment in patients with RET-driven cancers in the phase I/II LIBRETTO-001 trial.

BACKGROUND: This post-hoc retrospective study describes long-term patient-reported outcomes (PROs) for REarranged during Transfection (RET)-altered non-small-cell lung cancer (NSCLC), medullary thyroid cancer (MTC), non-MTC thyroid cancer (TC), and tumor agnostic (TA) patients (Data cut-off: January 2023) from the LIBRETTO-001 trial. PATIENTS AND METHODS: Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). Patients with MTC also completed a modified version of the Systemic Therapy-Induced Diarrhea Assessment Tool (mSTIDAT). The proportion of patients with improved, stable, or worsened status after baseline was reported. PROs were summarized at 3 years (cycle 37) post-baseline for the NSCLC and MTC cohorts, and at 2 years (cycle 25) post-baseline for the TC and TA cohorts. Time-to-event outcomes (time to first improvement or worsening and duration of improvement) were reported. RESULTS: The baseline assessment was completed by 200 (63.3%), 209 (70.8%), 50 (76.9%), and 38 (73.1%) patients in the NSCLC, MTC, TC, and TA cohorts, respectively. The total compliance rate was 80%, 82%, 70%, and 85%, respectively. Approximately 75% (NSCLC), 81% (MTC), 75% (TC), and 40% (TA) of patients across all cohorts reported improved or stable QLQ-C30 scores at year 3 (NSCLC and MTC) or year 2 (TC and TA) with continuous selpercatinib use. Across cohorts, the median time to first improvement ranged from 2.0 to 19.4 months, the median duration of improvement ranged from 1.9 to 28.2 months, and the median time to first worsening ranged from 5.6 to 44.2 months. The total compliance rate for the mSTIDAT was 83.7% and the proportion of patients with MTC who reported diarrhea on the mSTIDAT was reduced from 80.8% at baseline to 35.6% at year 3. CONCLUSIONS: A majority of patients with RET-driven cancers improved or remained stable on most QLQ-C30 domains, demonstrating favorable health-related quality of life as measured by the QLQ-C30 during long-term treatment with selpercatinib.

Oncoplastic breast-conserving surgery (OBCS) vs. mastectomy with reconstruction: a comparison of outcomes in an underserved population.

Background: Oncoplastic breast-conserving surgery (OBCS) has demonstrated superior cosmetic outcomes to traditional breast-conserving surgery (BCS) while maintaining oncologic safety. While prior studies have compared OBCS to mastectomy, there is a scarcity of literature on the impact of social determinants of health on outcomes. Furthermore, although traditionally tumors larger than 5 cm and multifocal disease were treated with mastectomy, the literature has now shown OBCS to be safe in treating such disease. As a result, patients with large or multifocal tumors could be eligible for both mastectomy and OBCS, which prompts the need for comparison between the two. Thus, the aim of our study was to compare OBCS and mastectomy with reconstruction using BREAST-Q and oncologic outcome measures, as well as stratify these outcomes based on race, ethnicity, and body mass index (BMI). Methods: A retrospective chart review was performed for 57 patients treated with OBCS and 204 patients treated with mastectomy with reconstruction from 2015 to 2021. Variables including age, race, ethnicity, BMI, insurance status, surgery type, pathology, recurrence, and complications were recorded. Patient-reported outcomes (PROs) were recorded using BREAST-Q pre- and post-operatively. Results: Despite having a higher BMI (P<0.001), OBCS yielded higher "satisfaction with breast" and "satisfaction with outcome" than mastectomy (P=0.02 and P=0.02, respectively). When stratified by race, there were no statistical differences in the PROs between the two surgeries for Hispanic nor African American patients. OBCS had a significantly lower rate of infection and fewer additional surgeries than mastectomy (P=0.004 and P<0.001, respectively). There were no differences in positive margin rate or recurrence rate between the groups. Conclusions: In our study, OBCS yielded better PROs than mastectomy while maintaining oncologic safety and resulting in fewer surgeries and complications. These excellent outcomes in a majority non-Caucasian cohort support the utilization of OBCS for underserved, minority populations. Larger studies evaluating PROs in diverse and uninsured groups are needed to reinforce these conclusions.

Duodenal mucosa of untreated celiac disease patients has altered expression of the GAS6 and PROS1 and the negative regulator tyrosine kinase TAM receptors subfamily.

Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

Patient-reported outcomes in randomized clinical trials of systemic therapy for advanced soft tissue sarcomas in adults: A systematic review.

BACKGROUND: This systematic review evaluates reporting of patient-reported outcomes (PROs) within randomized clinical trials (RCTs) for advanced soft tissue sarcoma (STS) patients. METHODS: A systematic literature search from January 2000 - August 2022 was conducted for phase II/III RCTs evaluating systemic treatments in adult patients with advanced STS. Quality of PRO reporting was assessed using the CONSORT PRO extension. RESULTS: Out of 7294 abstracts, 59 articles were included; comprising 43 RCTs. Only 15 RCTs (35%) included PROs, none as primary endpoints. Only 10 of these RCTs reported PROs, either in the primary (6/10) or secondary publication (1/10) or in both (3/10), with a median time interval of 23 months. The median CONSORT PRO adherence score was 5.5/14, with higher scores in publications focusing exclusively on PROs. CONCLUSION: These results highlight the need for improved and more consistent PRO reporting to inform patient care in the setting of advanced STS.

Perspective of Health Care Professionals and Cancer Survivors on the Usage of Technology in Consultations.

This study explored the integration of technology in healthcare consultations between healthcare professionals (HCPs) and cancer survivors. The research aimed to understand how technological tools influence the dynamics and environment of cancer survivor rehabilitation consultations. The study used Actor-Network Theory (ANT) to analyze the effects of new technological actors in consultations and Invisible Work Theory to uncover hidden workflows associated with technology implementation. The study combined observations and in-depth interviews with HCPs and cancer survivors conducted in March to May 2022, and a follow-up group interview in November 2023. The study revealed that technology's presence notably impacts the relationship between HCPs and cancer survivors, with HCPs expressing concerns that technology disrupts the consultation and challenges the relation. Over time, HCPs gradually began to use laptops during consultations to varying degrees, although the resistance to fully embracing technology persisted. This resistance is attributed to perceived pressure from management and a mismatch with established practices. The findings address the challenges in digital literacy and confidence among HCPs to facilitate the effective incorporation of technology and enhance the patient-clinician relationship. This research contributes to a deeper understanding of the interplay between digital health tools and patient-clinician relationships, highlighting the complexities and opportunities in digitizing healthcare consultations.

PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis.

BACKGROUND: Diabetic foot ulcers (DFUs) pose a serious long-term threat because of elevated mortality and disability risks. Research on its biomarkers is still, however, very limited. In this paper, we have effectively identified biomarkers linked with macrophage excretion in diabetic foot ulcers through the application of bioinformatics and machine learning methodologies. These findings were subsequently validated using external datasets and animal experiments. Such discoveries are anticipated to offer novel insights and approaches for the early diagnosis and treatment of DFU. METHODS: In this work, we used the Gene Expression Omnibus (GEO) database's datasets GSE68183 and GSE80178 as the training dataset to build a gene model using machine learning methods. After that, we used the training and validation sets to validate the model (GSE134431). On the model genes, we performed enrichment analysis using both gene set variant analysis (GSVA) and gene set enrichment analysis (GSEA). Additionally, the model genes were subjected to immunological association and immune function analyses. RESULTS: In this study, PROS1 was identified as a potential key target associated with macrophage efflux in DFU by machine learning and bioinformatics approaches. Subsequently, the key biomarker status of PROS1 in DFU was also confirmed by external datasets. In addition, PROS1 also plays a key role in macrophage exudation in DFU. This gene may be associated with macrophage M1, CD4 memory T cells, naïve B cells, and macrophage M2, and affects IL-17, Rap1, hedgehog, and JAK-STAT signaling pathways. CONCLUSIONS: PROS1 was identified and validated as a biomarker for DFU. This finding has the potential to provide a target for macrophage clearance of DFU.

Perspective: How can risks to patients be limited during spine surgeons' learning curves?

Background: Learning curves (LC) are typically defined by the number of different spinal procedures surgeons must perform before becoming "proficient," as demonstrated by reductions in operative times, estimated blood loss (EBL), length of hospital stay (LOS), adverse events (AE), fewer conversions to open procedures, along with improved outcomes. Reviewing 12 studies revealed LC varied widely from 10-44 cases for open vs. minimally invasive (MI) lumbar diskectomy, laminectomy, transforaminal lumbar interbody fusion (TLIF), anterior lumbar interbody fusion (ALIF), and oblique/extreme lateral interbody fusions (OLIF/XLIF). We asked whether the risks of harm occurring during these LC could be limited if surgeons routinely utilized in-person/intraoperative mentoring (i.e., via industry, academia, or well-trained colleagues). Methods: We evaluated LC for multiple lumbar operations in 12 studies. Results: These studies revealed no LC for open vs. MI lumbar diskectomy. LC required 29 cases for MI laminectomy, 10-44 cases for MI TLIF, 24-30 cases for MI OLIF, and 30 cases for XLIF. Additionally, the LC for MI ALIF was 30 cases; one study showed that 32% of major vascular injuries occurred in the first 25 vs. 0% for the next 25 cases. Shouldn't the risks of harm to patients occurring during these LC be limited if surgeons routinely utilized in-person/intraoperative mentoring? Conclusions: Twelve studies showed that the LC for at different MI lumbar spine operations varied markedly (i.e., 10-44 cases). Wouldn't and shouldn't spine surgeons avail themselves of routine in-person/intraoperative mentoring to limit patients' risks of injury during their respective LC for these varied spine procedures ?

Health-related quality of life and associated risk factors in patients with Multiple Osteochondromas: a cross-sectional study.

PURPOSE: To evaluate the health-related quality of life and associated risk factors for Multiple Osteochondromas patients. METHODS: A cross-sectional, observational study was conducted from May to December 2022 during the routine visit to the referral center for rare skeletal disorders. All patients with Multiple Osteochondromas aged ≥ 3 years were included. EuroQol 5-dimension questionnaires, and demographic, clinical, and surgical history data were collected. Descriptive statistics, Fisher's exact test, One-sample t-test, Spearman's correlation, and multiple linear and logistic regression were performed to analyze the data. Results are reported following STROBE guidelines. RESULTS: A total of 128 patients were included in the study, with a mean age of 14 [SD, 10] years. The mean EQ-5D Index Value was 0.863 [SD, 0.200] and the EQ-VAS was 84 [SD, 19] with a positive correlation between two scores [r = 0.541, p < 0.001]. Patients frequently referred problems in pain/discomfort [78.8%], anxiety/depression [50%], and usual activities [38.8%] dimensions. Increasing age was the common risk factor for health-related quality of life [p < 0.000], as well as Index Value and VAS scores were significantly lower in surgical patients [p = 0.001 and p < 0.001, respectively]. CONCLUSION: Increasing age and surgical procedures were found highly associated with reduced health-related quality of life in Multiple Osteochondromas patients. Our findings provide relevant information to support the establishment of patient-centered healthcare pathways and pave the way for further research into medical and non-medical therapeutic strategies for these patients.

N-acetylcysteine Treatment in Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis/Pre-COPD: Distinct Meta-analyses.

INTRODUCTION: N-acetylcysteine (NAC) is a mucolytic agent with antioxidant properties. Oxidative stress is a key pathogenic mechanism in chronic respiratory conditions such as COPD and chronic bronchitis (CB). In these meta-analyses we investigated the efficacy of NAC in subjects with COPD or CB, the latter being a potential pre-COPD condition (CB/pre-COPD). METHODS: The meta-analyses were conducted according to PRISMA guidelines. Exacerbations were assessed using total number of exacerbations. Improvement in patients' respiratory symptoms and/or patients quality of life (QoL) were measured by validated tools or assessed at the end of the study. RESULTS: Twenty studies were included, of which seven evaluated NAC in patients with symptoms of CB/pre-COPD as entry criterion. NAC treated patients showed a significant reduction of the incidence of exacerbations as compared to placebo both in COPD (IRR=0.76; 95% confidence interval (CI) 0.59-0.99) and CB/pre-COPD (IRR=0.81; 95% CI 0.69-0.95). Sensitivity analyses in studies with duration higher than 5 months, confirmed the overall results. CB/pre-COPD patients treated with NAC were significantly more likely to experience an improvement in symptoms and/or QoL compared to placebo (odds ratio (OR)=3.47; 95% CI 1.92-6.26). A similar trend was observed in the few COPD studies evaluable. Sensitivity analyses showed a significant association of NAC with improvement in symptoms and/or QoL both in CB/pre-COPD and COPD patients. CONCLUSIONS: These findings provide novel data of NAC on the improvement in symptoms and QoL in addition to prevention of exacerbations in COPD and CB/pre-COPD. PROSPERO registry no. CRD42023468154.

Characteristics and patient-reported outcomes of long-term lung cancer survivors.

Background: Due to advances in screening and treatment of lung cancer, there has been increased interest in long-term lung cancer survivors (LTLCS). The aim of this study was to evaluate the prevalence of LTLCS, their characteristics and patient-reported outcomes (PROs) of LTLCS. Methods: Cross-sectional study that included patients diagnosed with primary lung cancer between Jan 2012 and Dec 2016 whose overall survival (OS) was greater than 5 years. A self-administered questionnaire was applied, including European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), Patient Health Questionnaire-4 (PHQ-4) and two open questions regarding quality of life (QoL) and suggestions for improvements. Factors potentially related to QoL were analysed. Results: Of 767 lung cancer patients, 158 (20.6%) were LTLCS and LTLCS' proportion increased yearly. Most patients were male (70.9%) with median age of 65 [interquartile range (IQR), 56-71] years. Fifty-seven percent had adenocarcinoma, 66.2% were diagnosed at early stages but 8.9% were at stage IV. During follow-up, 77.1% quitted smoking, 31.8% had disease progression/relapse and 15.2% developed other tumours. Of all living LTLCS, 100 (85%) patients answered the PROs questionnaire. The median Global Health score was 66.67 (IQR, 50-83), social functioning had the best score and emotional functioning the worst. Pain and fatigue were the symptoms with the worst impact on QoL. PHQ-4 identified mental distress in 36% and patients with a lower QoL were more likely to present anxiety (35.3% vs. 9.4%, P=0.007) or depression (27.9% vs. 3%, P=0.006). In the open questions, patients reported pain (17%), lack of familiar/financial support (16%), dyspnoea (14%), depression (8%), concern for the future (8%) and limitations performing daily activities (8%) as the aspects with most impact in QoL. The most suggested measures were improvement of care provided by health institutions (25%) and better social support (16%). Conclusions: Prevalence of LTLCS is increasing and survivors may experience a high prevalence of anxiety and depression as well as a high disease burden affecting QoL. Therefore, it's important to provide multidisciplinary continuous patient-centred care and a careful follow-up for all lung cancer patients, including LTLCS.

Structural and Dynamic Analyses of Pathogenic Variants in PIK3R1 Reveal a Shared Mechanism Associated among Cancer, Undergrowth, and Overgrowth Syndromes.

The PI3K enzymes modify phospholipids to regulate cell growth and differentiation. Somatic variants in PI3K are recurrent in cancer and drive a proliferative phenotype. Somatic mosaicism of PIK3R1 and PIK3CA are associated with vascular anomalies and overgrowth syndromes. Germline PIK3R1 variants are associated with varying phenotypes, including immunodeficiency or facial dysmorphism with growth delay, lipoatrophy, and insulin resistance associated with SHORT syndrome. There has been limited study of the molecular mechanism to unify our understanding of how variants in PIK3R1 drive both undergrowth and overgrowth phenotypes. Thus, we compiled genomic variants from cancer and rare vascular anomalies and sought to interpret their effects using an unbiased physics-based simulation approach for the protein complex. We applied molecular dynamics simulations to mechanistically understand how genetic variants affect PIK3R1 and its interactions with PIK3CA. Notably, iSH2 genetic variants associated with undergrowth destabilize molecular interactions with the PIK3CA receptor binding domain in simulations, which is expected to decrease activity. On the other hand, overgrowth and cancer variants lead to loss of inhibitory interactions in simulations, which is expected to increase activity. We find that all disease variants display dysfunctions on either structural characteristics or intermolecular interaction energy. Thus, this comprehensive characterization of novel mosaic somatic variants associated with two opposing phenotypes has mechanistic importance and biomedical relevance and may aid in future therapeutic developments.