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Biomedicines Jun 2024Mesenchymal stromal/stem cells (MSCs) play a critical role in wound healing. Corlicyte is an MSC product derived from allogeneic umbilical cord tissue donated under an...
BACKGROUND
Mesenchymal stromal/stem cells (MSCs) play a critical role in wound healing. Corlicyte is an MSC product derived from allogeneic umbilical cord tissue donated under an institutional review board-approved protocol and processed in accordance with section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act. This open-label phase 1 trial was performed under a United States Food and Drug Administration Investigational New Drug Application to establish the safety and tolerability of Corlicyte in patients with diabetes and chronic diabetic foot ulcer (DFU).
METHODS
Escalating doses were applied topically twice a week for up to 8 weeks after ulcer debridement, wound photography, and measurement. Subjects were followed for 4 weeks after the treatment phase. Adverse events were assessed at every visit.
RESULTS
Nine subjects in 2 dosing cohorts completed the trial. No subjects experienced a serious adverse reaction to Corlicyte or the development of anti-human leukocyte antigen (HLA) antibodies. Sixty percentage of subjects in the lower dose cohort experienced ulcer closure by Day 70 of follow-up, while the mean ulcer size was reduced by 54-67% in the other subjects.
CONCLUSIONS
Topical administration of Corlicyte, a novel biologic therapy consisting of allogeneic umbilical cord lining MSCs, appeared safe and tolerable and resulted in a significant decrease in ulcer area, demonstrating its potential as a therapy for healing of chronic DFU.
PubMed: 38927582
DOI: 10.3390/biomedicines12061375 -
Biomedicines Jun 2024the COVID-19 pandemic has brought to light the intricate interplay between viral infections and preexisting health conditions. In the field of kidney diseases, patients...
INTRODUCTION
the COVID-19 pandemic has brought to light the intricate interplay between viral infections and preexisting health conditions. In the field of kidney diseases, patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Chronic Kidney Disease (CKD) face unique challenges when exposed to the SARS-CoV-2 virus. This study aims to evaluate whether SARS-CoV-2 virus infection impacts renal function differently in patients suffering from ADPKD and CKD when compared to patients suffering only from CKD.
MATERIALS AND METHODS
clinical data from 103 patients were collected and retrospectively analyzed. We compared the renal function of ADPKD and CKD patients at two distinct time points: before COVID-19 infection (T0) and 1 year after the infection (T1). We studied also a subpopulation of 37 patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min and affected by ADPKD and CKD.
RESULTS
clinical data were obtained from 59 (57.3%) ADPKD patients and 44 (42.7%) CKD patients. At T1, ADPKD patients had significantly higher serum creatinine levels compared to CKD patients, and a significantly lower eGFR was observed only in ADPKD patients with eGFR < 60 mL/min compared to CKD patients ( < 0.01, < 0.05; respectively). Following COVID-19 infection, ADPKD-CKD patients exhibited significantly higher variation in both median serum creatinine ( < 0.001) and median eGFR ( < 0.001) compared to CKD patients.
CONCLUSION
the interplay between COVID-19 and kidney disease is complex. In CKD patients, the relationship between COVID-19 and kidney disease progression is more established, while limited studies exist on the specific impact of COVID-19 on ADPKD patients. Current evidence does not suggest that ADPKD patients are at a higher risk of SARS-CoV-2 infection; however, in our study we showed a significant worsening of the renal function among ADPKD patients, particularly those with an eGFR < 60 mL/min, in comparison to patients with only CKD after a one-year follow-up from COVID-19 infection.
PubMed: 38927508
DOI: 10.3390/biomedicines12061301 -
Biomedicines May 2024Critical-size bone defects necessitate bone void fillers that should be integrated well and be easily vascularized. One viable option is to use a biocompatible synthetic...
Critical-size bone defects necessitate bone void fillers that should be integrated well and be easily vascularized. One viable option is to use a biocompatible synthetic polymer and sonocoat it with zinc oxide (ZnO) nanoparticles (NPs). However, the ideal NP concentration and size must be assessed because a high dose of ZnO NPs may be toxic. Electrospun PDLLA/PLGA scaffolds were produced with different concentrations (0.5 or 1.0 s of sonocoating) and sizes of ZnO NPs (25 nm and 70 nm). They were characterized by SEM, EDX, ICP-OES, and the water contact angle. Vascularization and integration into the surrounding tissue were assessed with the CAM assay in the living chicken embryo. SEM, EDX, and ICP-OES confirmed the presence of ZnO NPs on polymer fibers. Sonocoated ZnO NPs lowered the WCA compared with the control. Smaller NPs were more pro-angiogenic exhibiting a higher vessel density than the larger NPs. At a lower concentration, less but larger vessels were visible in an environment with a lower cell density. Hence, the favored combination of smaller ZnO NPs at a lower concentration sonocoated on PDLLA/PLGA electrospun meshes leads to an advanced state of tissue integration and vascularization, providing a valuable synthetic bone graft to be used in clinics in the future.
PubMed: 38927362
DOI: 10.3390/biomedicines12061155 -
Antibiotics (Basel, Switzerland) Jun 2024Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phenotypic colistin resistance is highly associated with...
Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phenotypic colistin resistance is highly associated with plasmid-mediated mobile colistin resistance () genes. -bearing have been detected in many countries, with the emergence of colistin-resistant pathogens a global concern. This study assessed the distribution of , , , , and genes with phenotypic colistin resistance in isolates from diarrheal infants and children in Bangladesh. Bacteria were identified using the API-20E biochemical panel and 16s rDNA gene sequencing. Polymerase chain reactions detected gene variants in the isolates. Their susceptibilities to colistin were determined by agar dilution and E-test by minimal inhibitory concentration (MIC) measurements. Over 31.6% (71/225) of isolates showed colistin resistance according to agar dilution assessment (MIC > 2 μg/mL). Overall, 15.5% of isolates carried genes (7, ; 17, ; 13, and , with co-occurrence occurring in two isolates). Clinical breakout MIC values (≥4 μg/mL) were associated with 91.3% of -positive isolates. The -positive pathogens included twenty spp., five , five spp., two , and three . The -genes appeared to be significantly associated with phenotypic colistin resistance phenomena ( = 0.000), with 100% colistin-resistant isolates showing MDR phenomena. The age and sex of patients showed no significant association with detected variants. Overall, -associated colistin-resistant bacteria have emerged in Bangladesh, which warrants further research to determine their spread and instigate activities to reduce resistance.
PubMed: 38927200
DOI: 10.3390/antibiotics13060534 -
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 -
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 -
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