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Radiation Oncology (London, England) Jun 2024Radiation-induced fibrosis (RIF) is an important late complication of radiation therapy, and the resulting damaging effects of RIF can significantly impact...
BACKGROUND
Radiation-induced fibrosis (RIF) is an important late complication of radiation therapy, and the resulting damaging effects of RIF can significantly impact reconstructive outcomes. There is currently a paucity of effective treatment options available, likely due to the continuing knowledge gap surrounding the cellular mechanisms involved. In this study, detailed analyses of irradiated and non-irradiated human skin samples were performed incorporating histological and single-cell transcriptional analysis to identify novel features guiding development of skin fibrosis following radiation injury.
METHODS
Paired irradiated and contralateral non-irradiated skin samples were obtained from six female patients undergoing post-oncologic breast reconstruction. Skin samples underwent histological evaluation, immunohistochemistry, and biomechanical testing. Single-cell RNA sequencing was performed using the 10X single cell platform. Cells were separated into clusters using Seurat in R. The SingleR classifier was applied to ascribe cell type identities to each cluster. Differentially expressed genes characteristic to each cluster were then determined using non-parametric testing.
RESULTS
Comparing irradiated and non-irradiated skin, epidermal atrophy, dermal thickening, and evidence of thick, disorganized collagen deposition within the extracellular matrix of irradiated skin were readily appreciated on histology. These histologic features were associated with stiffness that was higher in irradiated skin. Single-cell RNA sequencing revealed six predominant cell types. Focusing on fibroblasts/stromal lineage cells, five distinct transcriptional clusters (Clusters 0-4) were identified. Interestingly, while all clusters were noted to express Cav1, Cluster 2 was the only one to also express Cav2. Immunohistochemistry demonstrated increased expression of Cav2 in irradiated skin, whereas Cav1 was more readily identified in non-irradiated skin, suggesting Cav1 and Cav2 may act antagonistically to modulate fibrotic cellular responses.
CONCLUSION
In response to radiation therapy, specific changes to fibroblast subpopulations and enhanced Cav2 expression may contribute to fibrosis. Altogether, this study introduces a novel pathway of caveolin involvement which may contribute to fibrotic development following radiation injury.
Topics: Humans; Female; Single-Cell Analysis; Fibroblasts; Caveolin 1; Skin; Breast Neoplasms; Caveolin 2; Radiation Injuries; Fibrosis; Middle Aged
PubMed: 38926892
DOI: 10.1186/s13014-024-02472-z -
Critical Care (London, England) Jun 2024Health-related quality of life (HRQoL) is one of the most important outcome variables for assessing the effectiveness of intensive care, together with mortality and... (Review)
Review
BACKGROUND
Health-related quality of life (HRQoL) is one of the most important outcome variables for assessing the effectiveness of intensive care, together with mortality and survival, where comorbidity is suggested to have high impact. However, studies are lacking that examine to what extent HRQoL is affected after a general ICU period, beyond that of the effects that may be claimed to be due to comorbidities.
DESIGN
Purpose-specific literature review including literature searches in PubMed, Cinahl, Scopus, and Cochrane library between 2010 and 2021.
MEASUREMENTS AND RESULTS
This Purpose-specific, i.e., task focused review examines HRQoL (assessed by either SF-36 or EQ-5D, > 30 days after leaving the hospital) in adult patients (≥ 18 years) having an ICU length of stay > 24 h. Further, the HRQoL comparisons were adjusted for age or comorbidity. A total of 11 publications were found. A majority comprised observational, prospective cohort studies, except three that were either case-control, cross-sectional comparison, or retrospective cohort studies. A total of 18,566 critically ill patients were included, and the response rate ranged from 16 to 94%. In all studies, a recurrent relevant finding was that HRQoL after ICU care was affected by pre-ICU comorbidities. In three studies (n = 3), which included a comorbidity adjusted control group, there were no effect of the critical care period itself on the registered HRQoL after the critical care period.
CONCLUSION
Health-Related Quality of Life (HRQoL) in former ICU patients appears to be primarily influenced by comorbidity. A notable limitation in this field of research is the high heterogeneity observed in the studies reviewed, particularly in terms of the HRQoL measurement tool employed, the duration of follow-up, the methodology for comorbidity assessment, and the adjustments for age and sex. Despite these variations and the limited number of studies in the review, the findings suggest a minimal HRQoL impact beyond the effects of comorbidity. Given the significant dearth of comprehensive studies in this domain, there is an escalating call for more thorough and detailed research endeavours.
Topics: Humans; Quality of Life; Comorbidity; Survivors; Critical Care; Critical Illness; Intensive Care Units
PubMed: 38926875
DOI: 10.1186/s13054-024-04997-x -
World Journal of Surgical Oncology Jun 2024The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the...
INTRODUCTION
The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction.
METHODS
The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison.
RESULTS
Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively).
CONCLUSION
The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.
Topics: Humans; Retrospective Studies; Female; Male; Middle Aged; Survival Rate; Prognosis; Aged; Hyperthermia, Induced; Hyperthermic Intraperitoneal Chemotherapy; Follow-Up Studies; Adult; Cytoreduction Surgical Procedures; Combined Modality Therapy; Peritoneal Neoplasms; Urinary Tract; Urologic Surgical Procedures; Plastic Surgery Procedures; Postoperative Complications
PubMed: 38926860
DOI: 10.1186/s12957-024-03457-8 -
Journal of Vascular Surgery. Venous and... Jun 2024Vascularized lymph node transfer (VLNT) has become an important surgical technique in the treatment of lymphedema. Considering the different available regions available...
OBJECTIVE
Vascularized lymph node transfer (VLNT) has become an important surgical technique in the treatment of lymphedema. Considering the different available regions available for flap harvest, we aimed to analyze different donor sites for VLNT with respect to donor-site morbidity, impact on limb volume and patient-reported outcome measurements (PROMs).
METHODS
A single-center prospective study on all patients receiving VLNT at the Department of Plastic Surgery and Hand Surgery of the University Hospital Zurich between September 2016 and 2023 was conducted. Lymph nodes were harvested either from the omentum (GE-VLNT), the lateral thoracic wall (LTW) or the superficial inguinal region (SI-VLNT). Volume measurements and PROMs were assessed preoperatively and at different postoperative intervals.
RESULTS
Overall, 70 patients with upper limb lymphedema (21%) or lower limb lymphedema (79%) with different lymphedema stages were included. 49 patients received GE-VLNT, followed by LTW-VLNT (n = 16) and SI-VLNT (n = 5). Lymph node harvest from the superficial inguinal region was associated with a significantly higher frequency of seroma development. Average percentage volume loss related in comparison to the preoperative volume of the affected limb was 9% after GE-VLNT, 10% after LTW-VLNT and 5% after SI-VLNT without a significant difference between the groups. PROMs revealed significant improvements for physical functioning, symptoms and psychological well-being, with no difference between VLNT techniques.
CONCLUSIONS
VLNT leads to a significant improvement of quality of life and can effectively reduce limb volume, regardless of the selection of donor-site. GE-VLNT has become our flap of choice due to its low donor-site morbidity and its properties that allow a double transplantation while avoiding a second donor-site.
PubMed: 38925528
DOI: 10.1016/j.jvsv.2024.101934 -
Journal of Plastic, Reconstructive &... Jun 2024In an era where globalization and social media significantly reshape beauty standards, it is imperative to delve into the subjectivity of beauty and attractiveness. The...
BACKGROUND
In an era where globalization and social media significantly reshape beauty standards, it is imperative to delve into the subjectivity of beauty and attractiveness. The lips, a key element in facial aesthetics, contribute significantly to the perception of attractiveness, and also have a profound impact on an individual's self-esteem.
OBJECTIVE
To analyze the influence of ethnicity on the aesthetic preferences for lip characteristics, among male and female faces.
MATERIALS AND METHODS
This study encompassed a sample of 231 study participants (153 women and 78 men) with an average age of 23.2 ± 2.8 years, representing ethnicities such as African, Caucasian, Middle Eastern, and South Asian. Participants were asked to rate a series of images showcasing various lip variants, providing insights into their aesthetic preferences.
RESULTS
Demographic analysis revealed gender and ethnic variations in aesthetic preferences for all the investigated lip parameters. Women were 2.42 times more likely than men to prefer no Cupid's indentation on a female model (p = 0.0019).
CONCLUSIONS
The study underscores the importance of understanding cultural influences on beauty standards and challenges the notion of a universal beauty ideal. The evolving role of social media trends, such as Cupid's bow indentation elimination, raises questions about the dynamic nature of aesthetic preferences among different ethnicities.
PubMed: 38924896
DOI: 10.1016/j.bjps.2024.06.013 -
Skin Research and Technology : Official... Jul 2024Skin cutaneous melanoma (SKCM) is an aggressive form of malignant melanoma with poor prognosis and high mortality rates. Disulfidptosis is a newly discovered cell death...
BACKGROUND
Skin cutaneous melanoma (SKCM) is an aggressive form of malignant melanoma with poor prognosis and high mortality rates. Disulfidptosis is a newly discovered cell death regulatory mechanism caused by the abnormal accumulation of disulfides. This unique pathway is guiding significant new research to understand cancer progression for targeted treatment. However, the correlation between disulfidptosis with long non-coding RNAs (lncRNAs) in SKCM remains unknown at present.
METHODS
The Cancer Genome Atlas database furnished lncRNA expression data and clinical information for SKCM patients. Pearson correlation and Cox regression analyses identified disulfidptosis-related lncRNAs associated with SKCM prognosis. ROC curves and a nomogram validated the model. TME, immune infiltration, GSEA analysis, immune checkpoint gene expression profiling, and drug sensitivity were assessed in high and low-risk groups. Consistent clustering categorized SKCM patients for personalized clinical treatment guidance.
RESULTS
A total of twelve disulfidptosis-related lncRNAs were identified for the development of prognosis prediction models. The area under the curve (AUC) values of the ROC curve and the nomogram provided reliable discrimination to evaluate the prognostic potential for SKCM patients. The TME played a crucial role in tumorigenesis, progression and prognosis, and the risk scores were closely related to immune cell infiltration. Meanwhile, the combination of chemotherapy, targeted therapy, and immunotherapy was recommended for low-risk patients based on drug sensitivity and immune efficacy analyses.
CONCLUSION
We identified a risk model of twelve disulfidptosis-related lncRNAs that could be used to predict the prognosis of SKCM patients and help guide immunotherapy and chemotherapy for personalized treatment plans.
Topics: Humans; RNA, Long Noncoding; Melanoma; Skin Neoplasms; Prognosis; Tumor Microenvironment; Male; Female; Middle Aged; Nomograms; Melanoma, Cutaneous Malignant; Biomarkers, Tumor; ROC Curve
PubMed: 38924611
DOI: 10.1111/srt.13814 -
PLoS Pathogens Jun 2024AXL+ Siglec-6+ dendritic cells (ASDC) are novel myeloid DCs which can be subdivided into CD11c+ and CD123+ expressing subsets. We showed for the first time that these...
AXL+ Siglec-6+ dendritic cells (ASDC) are novel myeloid DCs which can be subdivided into CD11c+ and CD123+ expressing subsets. We showed for the first time that these two ASDC subsets are present in inflamed human anogenital tissues where HIV transmission occurs. Their presence in inflamed tissues was supported by single cell RNA analysis of public databases of such tissues including psoriasis diseased skin and colorectal cancer. Almost all previous studies have examined ASDCs as a combined population. Our data revealed that the two ASDC subsets differ markedly in their functions when compared with each other and to pDCs. Relative to their cell functions, both subsets of blood ASDCs but not pDCs expressed co-stimulatory and maturation markers which were more prevalent on CD11c+ ASDCs, thus inducing more T cell proliferation and activation than their CD123+ counterparts. There was also a significant polarisation of naïve T cells by both ASDC subsets toward Th2, Th9, Th22, Th17 and Treg but less toward a Th1 phenotype. Furthermore, we investigated the expression of chemokine receptors that facilitate ASDCs and pDCs migration from blood to inflamed tissues, their HIV binding receptors, and their interactions with HIV and CD4 T cells. For HIV infection, within 2 hours of HIV exposure, CD11c+ ASDCs showed a trend in more viral transfer to T cells than CD123+ ASDCs and pDCs for first phase transfer. However, for second phase transfer, CD123+ ASDCs showed a trend in transferring more HIV than CD11c+ ASDCs and there was no viral transfer from pDCs. As anogenital inflammation is a prerequisite for HIV transmission, strategies to inhibit ASDC recruitment into inflamed tissues and their ability to transmit HIV to CD4 T cells should be considered.
PubMed: 38924030
DOI: 10.1371/journal.ppat.1012351 -
International Wound Journal Jul 2024Cultured epidermal autograft, JACE®, was introduced into the Japanese national health insurance system in 2009 and has been used in more than 1000 cases of extensive...
Cultured epidermal autograft, JACE®, was introduced into the Japanese national health insurance system in 2009 and has been used in more than 1000 cases of extensive burns. The aim of this study was to investigate whether the use of JACE® contributes to survival rate in extensive burns. In this study, 119 cases were selected from 3990 cases in Tokyo Burn Unit Association registry data from 2009 to 2023, excluding cases with less than 40% total body surface area, cases of deaths within 4 weeks and cases with unknown length of hospital stay. In total, 25 patients treated with JACE® were selected and matched with another 25 patients who did not receive JACE® using propensity score matching. The results showed that patients treated with JACE® had a significantly higher survival rate than did those who were not treated with JACE® at all time points between 6 and 9 weeks post-injury. In addition, there was no significant difference in length of hospital stay between the groups. These results suggest that the use of JACE® in patients with extensive burns contributes to patient survival and does not prolong hospital stay.
Topics: Humans; Burns; Male; Female; Registries; Propensity Score; Middle Aged; Adult; Skin Transplantation; Aged; Tokyo; Survival Rate; Young Adult; Length of Stay; Autografts; Retrospective Studies; Transplantation, Autologous; Adolescent; Treatment Outcome
PubMed: 38923296
DOI: 10.1111/iwj.14952 -
JAMA Network Open Jun 2024Opioid medications are commonly prescribed for the management of acute postoperative pain. In light of increasing awareness of the potential risks of opioid prescribing,...
IMPORTANCE
Opioid medications are commonly prescribed for the management of acute postoperative pain. In light of increasing awareness of the potential risks of opioid prescribing, data are needed to define the procedures and populations for which most opioid prescribing occurs.
OBJECTIVE
To identify the surgical procedures accounting for the highest proportion of opioids dispensed to adults after surgery in the United States.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional analysis of the 2020-2021 Merative MarketScan Commercial and Multi-State Databases, which capture medical and pharmacy claims for 23 million and 14 million annual privately insured patients and Medicaid beneficiaries, respectively, included surgical procedures for individuals aged 18 to 64 years with a discharge date between December 1, 2020, and November 30, 2021. Procedures were identified using a novel crosswalk between 3664 Current Procedural Terminology codes and 1082 procedure types. Data analysis was conducted from November to December 2023.
MAIN OUTCOMES AND MEASURES
The total amount of opioids dispensed within 3 days of discharge from surgery across all procedures in the sample, as measured in morphine milligram equivalents (MMEs), was calculated. The primary outcome was the proportion of total MMEs attributable to each procedure type, calculated separately among procedures for individuals aged 18 to 44 years and those aged 45 to 64 years.
RESULTS
Among 1 040 934 surgical procedures performed (mean [SD] age of patients, 45.5 [13.3] years; 663 609 [63.7%] female patients), 457 016 (43.9%) occurred among individuals aged 18 to 44 years and 583 918 (56.1%) among individuals aged 45 to 64 years. Opioid prescriptions were dispensed for 503 058 procedures (48.3%). Among individuals aged 18 to 44 years, cesarean delivery accounted for the highest proportion of total MMEs dispensed after surgery (19.4% [11 418 658 of 58 825 364 MMEs]). Among individuals aged 45 to 64 years, 4 of the top 5 procedures were common orthopedic procedures (eg, arthroplasty of knee, 9.7% of total MMEs [5 885 305 of 60 591 564 MMEs]; arthroscopy of knee, 6.5% [3 912 616 MMEs]).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of the distribution of postoperative opioid prescribing in the United States, a small number of common procedures accounted for a large proportion of MMEs dispensed after surgery. These findings suggest that the optimal design and targeting of surgical opioid stewardship initiatives in adults undergoing surgery should focus on the procedures that account for the most opioid dispensed following surgery over the life span, such as childbirth and orthopedic procedures. Going forward, systems that provide periodic surveillance of opioid prescribing and associated harms can direct quality improvement initiatives to reduce opioid-related morbidity and mortality.
Topics: Humans; Analgesics, Opioid; Adult; Female; Middle Aged; Male; Cross-Sectional Studies; Pain, Postoperative; Practice Patterns, Physicians'; Patient Discharge; United States; Adolescent; Young Adult; Drug Prescriptions; Surgical Procedures, Operative
PubMed: 38922619
DOI: 10.1001/jamanetworkopen.2024.17651 -
Journal of Patient-reported Outcomes Jun 2024Breast cancer-related lymphedema (BRCL) is one of the most common causes of upper extremity (UE) lymphedema in developed nations and substantially impacts health-related...
BACKGROUND
Breast cancer-related lymphedema (BRCL) is one of the most common causes of upper extremity (UE) lymphedema in developed nations and substantially impacts health-related quality of life. To advance our understanding of the epidemiology and treatment of BRCL, rigorously developed and validated patient-reported outcome measures (PROMs) are needed. This study aimed to demonstrate the iterative content validity of a modular UE lymphedema-specific PROM called the LYMPH-Q UE module.
METHODS
A multi-step iterative qualitative approach was used. Semi-structured interview data from in-depth qualitative interviews with adult women (18 years and older) with BCRL were used to develop the first set of the LYMPH-Q UE scales. The content validity of these scales was demonstrated with patient and clinician feedback. Over the course of cognitive debriefing interviews, additional concepts of lymphedema worry and impact on work were identified as missing from the LYMPH-Q UE module. Subsequently, two new qualitative studies (a focus group and in-depth concept elicitation interviews with patients) were conducted, and two new scales were developed to measure lymphedema worry and impact on work life and their content validity was demonstrated.
RESULTS
Qualitative data from in-depth and cognitive interviews with 15 (age 40-74 years) and 16 (age 38-74 years) women with BRCL, respectively, and feedback from 12 clinical experts, were used to develop and demonstrate the content validity of six LYMPH-Q UE scales measuring symptoms, function, appearance, psychological, information, and arm sleeve. Additionally, data from in-depth interviews with 12 (age 35-72 years) women with UE lymphedema and four focus groups (n = 16 women; age 35-74 years) was used to develop and assess the content validity of two new LYMPH-Q UE scales measuring lymphedema worry and impact on work life. The content validity of the previously established six scales was also demonstrated in these subsequent qualitative studies.
CONCLUSION
The LYMPH-Q UE is a modular PROM developed using international guidelines for PROM development and can be used in clinical practice, research, and quality improvement to enhance patient-centered shared decision-making. This study's innovative and iterative approach to content validation demonstrates that the LYMPH-Q UE is a comprehensive measure that includes important concepts relevant to patients with UE lymphedema.
Topics: Humans; Female; Patient Reported Outcome Measures; Middle Aged; Quality of Life; Qualitative Research; Upper Extremity; Aged; Interviews as Topic; Adult; Reproducibility of Results; Lymphedema; Breast Cancer Lymphedema; Focus Groups; Breast Neoplasms; Psychometrics
PubMed: 38922461
DOI: 10.1186/s41687-024-00701-3