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Incidence, Risk Factors, Characteristics, and Outcome of Chronic Graft Versus Host Disease in Children Undergoing Haploidentical Peripheral Blood Stem Cell Transplant With Post-Transplant Cyclophosphamide

J Pediatr Hematol Oncol. 2023 Nov 20. doi: 10.1097/MPH.0000000000002786. Online ahead of print.

ABSTRACT

AIM: Chronic graft versus host disease (cGVHD) is a major cause of morbidity postallogeneic peripheral blood stem cell transplant (PBSCT). There is paucity of literature describing incidence, risk factors, characteristics, and outcome of cGVHD in children undergoing haploidentical PBSCT with post-transplant cyclophosphamide (PTCy). Here, we describe our experience from our center regarding the same.

METHODS: All children who underwent haploidentical PBSCT with PTCy between January 2016 and December 2021 at our center and survived beyond day+100 post-transplant were included in this retrospective study. Conditioning regimens used were: Thiotepa-Fludarabine-Cyclophosphamide with 2 Gy single fraction total body irradiation, Thiotepa-Busulfan-Fludarabine, Fludarabine-total body irradiation and Fludarabine-Melphalan. Peripheral blood was used as stem cell source in all patients. GVHD prophylaxis was PTCy 50 mg/kg on day +3 and +4, Mycophenolate mofetil and Calcineurin inhibitors. Clinical and laboratory data was electronically retrieved and analyzed based on National Institute of Health Consensus Criteria-2014 at regular intervals. Impact of various patient, donor, and transplant-related factors on development of cGVHD were analyzed. Incidence of relapse, event free survival (EFS) and overall survival (OS) were calculated and compared between cGVHD and no cGVHD groups. Patients with rejection were excluded from risk factor analysis for cGVHD but were considered for survival analysis.

RESULTS: Fifty-one children included in this study. Median age of transplant of our cohort was 7.5 years with male:female=1.6:1. Eight patients had rejection with autologous recovery. History of acute GVHD (aGVHD) was present in 15/51 (Grade III to IV in 7/51). cGVHD developed in 19/51 patients (mild-9/51, moderate-6/51, and severe-4/51). Skin was the most common organ involved (100%) followed by gastrointestinal tract (47.4%), liver (36.8%), eyes (21%), lungs (21%), mouth (15.7%), and joints (5.2%). Advanced donor age (>30 y) and previous aGVHD were found to be significantly associated with increased risk of developing cGVHD. At last follow-up, complete response and partial response of cGVHD was seen in 6/19 and 4/19 patients, respectively. Overall mortality was 15/51 (cause of mortality was relapse of cancer 8/15, cGVHD-3/15, other 4/15). EFS and OS of full cohort was 55% and 70.6%, respectively. Compared with patients without cGVHD, patients with cGVHD demonstrated a lower relapse (18.2% vs. 40%, P=0.2333), higher EFS (68.4% vs. 53.1%, P=0.283), and higher OS (73.7% vs. 68.8%, P=0.708).

CONCLUSION: Incidence of cGVHD was high in children undergoing haploidentical PBSCT with PTCy. Other than PBSC graft source; donor age and previous aGVHD were the risks factors for development of cGVHD. Patients with cGVHD had lower incidence of relapse translating into better survival but this difference was not statistically significant.

PMID:37983773 | DOI:10.1097/MPH.0000000000002786

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Surgical quality determines the long-term survival superiority of right over left thoracic esophagectomy for localized esophageal squamous cell carcinoma patients: a real-world multicenter study

Int J Surg. 2023 Nov 17. doi: 10.1097/JS9.0000000000000897. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the long-term overall survival (OS) of right versus left thoracic esophagectomy, and to evaluate whether surgical quality impacts comparison result.

BACKGROUND: Controversy regarding the optimal thoracic esophagectomy approach persists for esophageal squamous cell carcinoma (ESCC). No study has assessed the effect of surgical quality in comparison between right and left approaches.

METHODS: We consecutively recruited 5556 operable ESCC patients from two high-volume centers in China, of whom 2220 and 3336 received right and left thoracic esophagectomy, respectively. Cumulative sum was used to evaluate the learning curve for operation time of right approach, as the indicator of surgical proficiency.

RESULTS: With a median follow-up of 83.1 months, right approach, harvesting more lymph nodes, tended to have a better OS than left approach (Mean: 23.8 vs. 16.7 nodes; adjusted HR=0.93, 95% CI: 0.85-1.02). Subset analysis by the extent of lymphadenectomy demonstrated that right approach with adequate lymphadenectomy (≥ 15 nodes) resulted in statistically significant OS benefit compared with left approach (adjusted HR=0.86, 95% CI: 0.77-0.95), but not with limited lymphadenectomy. Subset analysis by surgical proficiency showed that proficient right approach conferred a better OS than left approach (adjusted HR=0.75, 95% CI: 0.64-0.88), but improficient right approach did not have such survival advantage.

CONCLUSIONS: Surgical quality plays a crucial role in survival comparison between surgical procedures. Right thoracic esophagectomy performed with adequate lymphadenectomy and surgical proficiency, conferring more favorable survival than left approach, should be recommended as the preferred surgical procedure for localized ESCC.

PMID:37983771 | DOI:10.1097/JS9.0000000000000897

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Differential efficacy of segmentectomy and wedge resection in sublobar resection compared to lobectomy for solid-dominant stage IA lung cancer: a systematic review and meta-analysis

Int J Surg. 2023 Nov 17. doi: 10.1097/JS9.0000000000000896. Online ahead of print.

ABSTRACT

BACKGROUND: Currently, the impact of sublobar resection versus lobectomy on the prognosis of solid-dominant stage IA lung cancer is contradictory in different studies, which requires further exploration.

METHODS: We analyzed 26 studies, including one randomized controlled trial and retrospective cohort studies. Pooled hazard ratios (HR) and 95% confidence intervals (CI) were calculated using fixed-effects or random-effects models based on heterogeneity levels.

RESULTS: The analysis included 12667 patients, with 3488 undergoing sublobar resections and 9179 receiving lobectomies. The overall analysis revealed no statistically significant difference in overall survival (OS) (HR=1.28, 95% CI: 0.98-1.69) between sublobar resection and lobectomy, but lobectomy was associated with better recurrence-free survival (RFS) (HR=1.39, 95% CI: 1.10-1.75). Subgroup analyses revealed that, for tumors with a diameter ≤2 cm, sublobar resection versus lobectomy showed no significant difference in OS but sublobar resection had lower RFS. For 2-3 cm tumors, both OS and RFS were significantly lower in the sublobar resection group. When consolidation-to-tumor ratio (CTR) ranged from 0.5 to <1, OS didn’t differ significantly, but RFS was significantly lower in sublobar resection. Lung cancers with CTR=1 showed significantly lower OS and RFS in the sublobar resection group. Segmentectomy provided similar OS and RFS compared to lobectomy, while wedge resection had a detrimental effect on patient prognosis. However, wedge resection may have provided comparable outcomes for patients aged 75 years or older.

CONCLUSION: Our findings suggest that segmentectomy and lobectomy yield similar oncological outcomes. However, compared to lobectomy, wedge resection is associated with a poorer prognosis. Nevertheless, for elderly patients, wedge resection is also a reasonable surgical option.

PMID:37983767 | DOI:10.1097/JS9.0000000000000896

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Low-value home-based nursing care: A national survey study

J Adv Nurs. 2023 Nov 20. doi: 10.1111/jan.15970. Online ahead of print.

ABSTRACT

AIMS: To explore potential areas of low-value home-based nursing care practices, their prevalence and related influencing factors of nurses and nursing assistants working in home-based nursing care.

DESIGN: A quantitative, cross-sectional design.

METHODS: An online survey with questions containing scaled frequencies on five-point Likert scales and open questions on possible related influencing factors of low-value nursing care. The data collection took place from February to April 2022. Descriptive statistics and linear regression were used to summarize and analyse the results.

RESULTS: A nationwide sample of 776 certified nursing assistants, registered nurses and nurse practitioners responded to the survey. The top five most delivered low-value care practices reported were: (1) ‘washing the client with water and soap by default’, (2) ‘application of zinc cream, powders or pastes when treating intertrigo’, (3) ‘washing the client from head to toe daily’, (4) ‘re-use of a urinary catheter bag after removal/disconnection’ and (5) ‘bladder irrigation to prevent clogging of urinary tract catheter’. The top five related influencing factors reported were: (1) ‘a (general) practitioner advices/prescribes it’, (2) ‘written in the client’s care plan’, (3) ‘client asks for it’, (4) ‘wanting to offer the client something’ and (5) ‘it is always done like this in the team’. Higher educational levels and an age above 40 years were associated with a lower provision of low-value care.

CONCLUSION: According to registered nurses and certified nursing assistants, a number of low-value nursing practices occurred frequently in home-based nursing care and they experienced multiple factors that influence the provision of low-value care such as (lack of) clinical autonomy and handling clients’ requests, preferences and demands. The results can be used to serve as a starting point for a multifaceted de-implementation strategy.

REPORTING METHOD: STROBE checklist for cross-sectional studies.

PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nursing care is increasingly shifting towards the home environment. Not all nursing care that is provided is effective or efficient and this type of care can therefore be considered of low-value. Reducing low-value care and increasing appropriate care will free up time, improve quality of care, work satisfaction, patient safety and contribute to a more sustainable healthcare system.

PMID:37983754 | DOI:10.1111/jan.15970

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Stepwise Functionalization of Pillar[5]arene-Containing [2]Rotaxane with Pentafluorophenyl Ester Stoppers

Chemistry. 2023 Nov 20:e202303501. doi: 10.1002/chem.202303501. Online ahead of print.

ABSTRACT

Detailed investigations on the stepwise bis-functionalization of a pillar[5]arene-containing rotaxane building block have been carried out. Upon a first stopper exchange, the pillar[5]arene moiety of the mono-acylated product is preferentially located close to its reactive pentafluorophenyl ester stopper, thus limiting the accessibility of the reactive carbonyl group by the nucleophilic reagents. Selective mono-functionalization is thus very efficient. Introduction of a second stopper is then possible to generate dissymmetrical rotaxanes with different amide stoppers. Moreover, when dethreading is possible upon the second acylation, the pillar[5]arene plays the role of a protecting group allowing the synthesis of dissymmetrical axles particularly difficult to prepare under statistical conditions. Finally, detailed conformational analysis of the rotaxanes revealed that the position of the pillar[5]arene moiety on its axle subunit is mainly governed by polar interactions in nonpolar organic solvents while solvophobic effects are playing a major role in polar solvents.

PMID:37983752 | DOI:10.1002/chem.202303501

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Variability analysis of LC-MS experimental factors and their impact on machine learning

Gigascience. 2022 Dec 28;12:giad096. doi: 10.1093/gigascience/giad096.

ABSTRACT

BACKGROUND: Machine learning (ML) technologies, especially deep learning (DL), have gained increasing attention in predictive mass spectrometry (MS) for enhancing the data-processing pipeline from raw data analysis to end-user predictions and rescoring. ML models need large-scale datasets for training and repurposing, which can be obtained from a range of public data repositories. However, applying ML to public MS datasets on larger scales is challenging, as they vary widely in terms of data acquisition methods, biological systems, and experimental designs.

RESULTS: We aim to facilitate ML efforts in MS data by conducting a systematic analysis of the potential sources of variability in public MS repositories. We also examine how these factors affect ML performance and perform a comprehensive transfer learning to evaluate the benefits of current best practice methods in the field for transfer learning.

CONCLUSIONS: Our findings show significantly higher levels of homogeneity within a project than between projects, which indicates that it is important to construct datasets most closely resembling future test cases, as transferability is severely limited for unseen datasets. We also found that transfer learning, although it did increase model performance, did not increase model performance compared to a non-pretrained model.

PMID:37983748 | DOI:10.1093/gigascience/giad096

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A Historic Cohort Analysis of Radiographic and Serologic Findings in Patients With Scleroderma and Interstitial Lung Disease

J Clin Rheumatol. 2023 Nov 20. doi: 10.1097/RHU.0000000000002042. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVE: Few studies have investigated associations between rheumatologic serology patterns and different interstitial lung disease (ILD) patterns.

METHODS: We present novel findings of a historic cohort study (n = 454) with data collected from 2011 to 2021 within our hospital system. In this institutional review board-approved study, data regarding rheumatologic serologies and ILD patterns were noted based on chart review in patients with scleroderma. The Kruskal-Wallis rank sum and χ2 tests were used for statistical analysis.

RESULTS: Results showed a statistically significant association between anti-U1 snRNP with lymphoid interstitial pneumonia, which has not been previously described.

CONCLUSIONS: We demonstrated novel serologic associations with ILD patterns, which have important clinical implications. More robust and high-powered studies are needed to elucidate the role of serologic testing and their association with ILD phenotypes.

PMID:37983683 | DOI:10.1097/RHU.0000000000002042

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Preliminary evaluation of wound healing potential of Leonurus japonicus Houtt. extracts

Chem Biodivers. 2023 Nov 20:e202301243. doi: 10.1002/cbdv.202301243. Online ahead of print.

ABSTRACT

Leounurs japonicus Houtt. is a medicinal plant popular in Brazil as “rubim”, used in local folk medicine for several applications as an anti-inflammatory, antioxidant, analgesic, and antimicrobial phytomedicine. The traditional use for wound healing is related; however, few studies have evaluated the wound healing activity. Thus, this study aimed to analyze the popular indication of the hydroalcoholic and aqueous extracts of L. japonicus aerial parts in a rat wound healing model. The initial chemical characterization was performed using flavonoid quantification and complemented with mass spectroscopy/chemometrics analysis. The wound’s lesion contraction and tissue regeneration (histological study stained with hematoxylin-eosin and picrosirius) were determined. Hydroalcoholic and aqueous extracts presented high flavonoid content, and mass spectrometry analysis of the extracts demonstrated the presence of compounds with a mass between 100-650, reinforcing the presence of polyphenolic constituents. The extracts of L. japonicus improve various wound healing phases, like inflammatory modulation, wound contraction, and collagen synthesis, resulting in faster healing in rats. These effects could be related to the extracts’ polyphenolic compounds.

PMID:37983672 | DOI:10.1002/cbdv.202301243

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Analytic and Clinical Validity of Myositis-Specific Antibodies by Line-Blot Immunoassay Is Essential

J Clin Rheumatol. 2023 Nov 20. doi: 10.1097/RHU.0000000000002043. Online ahead of print.

ABSTRACT

OBJECTIVES: This study assessed the concordance between line blot (LB) and immunoprecipitation (IP) assays for detecting myositis-specific antibodies (MSAs) in idiopathic inflammatory myopathies (IIMs) and their association with IIM subtypes.

METHODS: One hundred patients with IIM were enrolled, and MSA was detected using LB and IP. The IIM subtypes, including immune-mediated necrotizing myopathy-like, anti-tRNA synthetase syndrome-like, and clinically amyopathic dermatomyositis-like, were clinically diagnosed. The validity and reliability of the LB compared with the IP were evaluated. Optimal cutoff levels for LB were determined using various statistical methods including Cohen κ, Gwet’s AC, diagnostic odds ratios, and receiver operating characteristic analysis.

RESULTS: Line blot exhibited lower specificity and accuracy than IP in predicting IIM subtypes. Some MSAs performed better at higher LB cutoff values. Anti-signal recognition particle antibodies showed poor performance in predicting the immune-mediated necrotizing myopathy-like subtype using LB. Raising the cutoffs improved the reliability of anti-threonyl-tRNA synthetase and anti-signal recognition particle antibodies. Anti-histidyl-tRNA synthetase antibodies performed well at lower positivity, whereas diagnostic odds ratios increased for anti-transcription intermediary factor 1γ and anti-nuclear matrix protein 2 with higher cutoffs.

CONCLUSIONS: Inconsistencies between LB and IP have been observed in patients with IIM. Individual optimal cutoffs for MSA by LB correlating with IP were determined. Rheumatologists should consider the differences between LB and IP results when classifying IIM subtypes.

PMID:37983669 | DOI:10.1097/RHU.0000000000002043

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Male reproductive hormone disorders among copper smelter workers

Toxicol Ind Health. 2023 Nov 20:7482337231215864. doi: 10.1177/07482337231215864. Online ahead of print.

ABSTRACT

Male workers in copper smelting are exposed to copper, lead, and arsenic. This study aimed to assess the effects of combined exposure to these metals on male reproductive hormone levels and assesses malondialdehyde (MDA) as an oxidative stress parameter. The study was conducted on 40 copper smelter workers compared with 40 non-exposed workers. Laboratory investigations included levels of serum copper, blood lead, serum arsenic, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and MDA. Levels of copper, arsenic, lead, FSH, and LH were significantly increased compared to controls. However, a statistically significant decrease in the mean value of testosterone was found among exposed workers. Positive correlations between serum copper and both serum FSH and MDA levels were statistically significant as were correlations between serum arsenic and MDA levels. Testosterone levels showed significant negative correlations with both copper and arsenic among exposed workers. A linear regression model of copper, arsenic, and lead levels as independent variables with FSH, LH, and testosterone as dependent variables revealed a significant negative association between serum copper and testosterone levels. The current study concluded that combined exposure to copper, arsenic, and lead in secondary copper smelters had a negative impact on male reproductive hormone levels that may be mediated by oxidative stress.

PMID:37983667 | DOI:10.1177/07482337231215864