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Elevated T-cell Exhaustion and Urinary Tumor DNA Levels Are Associated with Bacillus Calmette-Guérin Failure in Patients with Non-muscle-invasive Bladder Cancer

Eur Urol. 2022 Oct 6:S0302-2838(22)02636-7. doi: 10.1016/j.eururo.2022.09.008. Online ahead of print.

ABSTRACT

BACKGROUND: The functional status of immune cells in the tumor microenvironment and tumor characteristics may explain bacillus Calmette-Guérin (BCG) failure in high-risk non-muscle-invasive bladder cancer (NMIBC).

OBJECTIVE: To characterize molecular correlates of post-BCG high-grade (HG) recurrence using multiomics analysis.

DESIGN, SETTING, AND PARTICIPANTS: Patients with BCG-treated NMIBC (n = 156) were included in the study. Metachronous tumors were analyzed using RNA sequencing (n = 170) and whole-exome sequencing (n = 195). Urine samples were analyzed for immuno-oncology-related proteins (n = 190) and tumor-derived DNA (tdDNA; n = 187).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was post-BCG HG recurrence. Cox regression and Wilcoxon rank-sum, t, and Fisher’s exact tests were used for analyses.

RESULTS AND LIMITATIONS: BCG induced activation of the immune system regardless of clinical response; however, immunoinhibitory proteins were observed in the urine of patients with post-BCG HG recurrence (CD70, PD1, CD5). Post-BCG HG recurrence was associated with post-BCG T-cell exhaustion (p = 0.002). Pre-BCG tumors from patients with post-BCG T-cell exhaustion had high expression of genes related to cell division and immune function. A high predicted post-BCG exhaustion score for pre-BCG tumors was associated with worse post-BCG HG recurrence-free survival (HGRFS; p = 0.002). This was validated in independent cohorts. Pre-BCG class 2a and 2b tumors (UROMOL2021 scheme) were associated with worse post-BCG HGRFS (p = 0.015). Post-BCG exhaustion was observed in patients with high pre-BCG neoantigen load (p = 0.017) and MUC4 mutations (p = 0.002). Finally, the absence of post-BCG tdDNA clearance identified patients at high risk of recurrence (p = 0.018). The retrospective design and partial overlap for analyses are study limitations.

CONCLUSIONS: Post-BCG HG recurrence may be caused by T-cell exhaustion. Tumor subtype and pre-BCG tumor characteristics may identify patients at high risk of post-BCG HG recurrence. Urinary measurements have potential for real-time assessment of treatment response.

PATIENT SUMMARY: A dysfunctional immune response to bacillus Calmette-Guérin (BCG) therapy may explain high-grade recurrences of bladder cancer.

PMID:36210217 | DOI:10.1016/j.eururo.2022.09.008

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A review of open pelvic fractures with concurrent genitourinary injuries

Eur J Orthop Surg Traumatol. 2022 Oct 9. doi: 10.1007/s00590-022-03388-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Open pelvic fractures (OPFs) are uncommon but potentially lethal traumatic injuries. Often caused by high energy blunt trauma, they can cause severe injury to abdominal and pelvic structures. We sought to conduct a review of the literature in order to ascertain the rates of genitourinary injury and vaginal laceration after OPF and the rates of resulting infection and mortality.

METHODS: A review of PubMed was conducted to identify studies reporting the rates of genitourinary injury from OPF. Study characteristics, patient characteristics, and outcomes were collected. The data were pooled, and descriptive statistics were obtained.

RESULTS: Eight studies encompassing 343 patients were included. Average age was 35.1 years (10-85.9), 28% were female, and the average Injury Severity Score was 26.5 (4-75). 95.5% of patients had a blunt mechanism of injury. Motor vehicle collision (23.9%), motorcycle accident (19.7%), and pedestrian struck (19.3%) were the most common etiologies. Overall mortality and infection rates were 31.2% and 18.7%, respectively. 19.7% of patients suffered an injury to the genitourinary system, and 32.4% of females sustained a vaginal laceration.

DISCUSSION: OPFs have the potential for extremely high morbidity and mortality. While much research has been done to prevent early mortality from hemorrhage, there is comparatively little research into late mortality stemming from infection and sepsis. Intravenous antibiotics are the mainstay of treatment, and local antibiotics usage has been encouraged. In patients with a vaginal laceration, it is important to provide antibiotic coverage for vaginal flora.

PMID:36209481 | DOI:10.1007/s00590-022-03388-8

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Holistic sleep improvement strategies for frontline nurses served during a public health emergency (COVID-19) in Wuhan, China: A quasi-experimental study

Nurs Open. 2022 Oct 9. doi: 10.1002/nop2.1397. Online ahead of print.

ABSTRACT

AIM: To examine effects of holistic sleep improvement strategies on frontline nurses who served in Wuhan, China, during a public health emergency (COVID-19).

DESIGN: A pre-post-test design with single group was conducted with a convenience sample applied the Transparent Reporting of Evaluations with Non-randomized Designs statement.

METHODS: Fifty-two nurses were recruited from a COVID-19 designated hospital, receiving holistic sleep improvement intervention, which concentrated on scientific human resource management, comfortable sleep environment establishment, self-relaxation and self-adjustment training and humanistic care. Data was collected at baseline and 4-week follow-up post intervention using self-reported questionnaires.

RESULTS: The total score of Pittsburgh Sleep Quality Index scale was 8.69 ± 4.346 at baseline. After 4 weeks of follow-up, the score statistically significantly decreased to 7.48 ± 3.691. Subjective sleep quality (p = .016), sleep efficiency (p = .015), sleep disturbances (p = .007) were statistically significantly improved after the intervention, while there were no statistically significant differences in sleep latency (p = .205), sleep duration (p = .375), sleep medication (p = .723) or daytime dysfunction (p = .747).

PMID:36209473 | DOI:10.1002/nop2.1397

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Intravenous Amino Acids may Mediate the Adverse Effect of Early Parenteral Nutrition on Mortality in Critically Ill Patients Requiring Mechanical Ventilation: A Post Hoc Analysis of the NEED trial

JPEN J Parenter Enteral Nutr. 2022 Oct 9. doi: 10.1002/jpen.2455. Online ahead of print.

ABSTRACT

BACKGROUND: There is controversy regarding the optimal timing of initiating PN in critically ill patients. We aimed to evaluate the association between early PN and clinical outcomes and explore the mediation effects of different macronutrients in a cohort of mechanically ventilated patients.

METHODS: This is a post-hoc analysis of the NEED trial aiming to investigate the effect of implementing an evidence-based feeding guideline in newly-admitted critically ill patients. All eligible patients were divided into those who received early PN within the first three days of enrollment (Early PN) or those who did not (Non-early PN). Propensity score matching (PSM) with a one-to-one nearest neighbor-matching algorithm was applied to control potential confounders. Mediation analysis was used to test the indirect effect of different macronutrients from PN on the relationship between early PN and 28-day mortality.

RESULTS: The PSM created 370 matched pairs out of 1154 patients that met the eligibility criteria. Compared with non-early PN, patients receiving early PN had significantly higher 28-day mortality (19.7% versus 12.4%; hazard ratio = 1.904, 95% confidence interval [CI]: 1.063-3.410, P = 0.03). Mediation analysis showed that amino acids from early PN mediated 65% (mediation effect = 0.07, 95% CI: 0.02-0.13, P = 0.01) of the detrimental effect of early PN on the 28-day mortality.

CONCLUSIONS: Early PN is associated with increased 28-day mortality in critically ill patients requiring invasive mechanical ventilation. The detrimental effect may be mediated by intravenous amino acids from early PN. This article is protected by copyright. All rights reserved.

PMID:36209461 | DOI:10.1002/jpen.2455

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Congenital granular cell epulis: 24 new cases with more differences than similarities to granular cell tumor

Ultrastruct Pathol. 2022 Jul 4;46(4):388-400. doi: 10.1080/01913123.2022.2107750.

ABSTRACT

Congenital granular cell epulis (CGCE) is a rare tumor of gingiva that is exclusive to newborns, has marked female predominance, and is rarely associated with other abnormalities. Although benign in behavior, CGCE can be lethal by obstruction of respiration and/or deglutition and can require a multidisciplinary team of specialist at birth for survival of an otherwise normal infant. Histologically, CGCE resembles granular cell tumor (GCT), but unlike GCT, which is Schwannian-derived, derivation of CGCE remains an enigma, largely because of its low prevalence. This study presents 24 new cases of CGCE, the largest series since the original description 150 years ago and permits detailed study of homogeneity of cases diagnosed as CGCE as well as detailed comparisons of CGCE with GCT by clinical, morphological, immunohistochemical, and ultrastructural studies. The data show homogeneity within the CGCE cases, more differences than similarities between CGCE and GCT, and no immunohistochemical staining for common placental proteins/hormones in CGCE. The findings support a primitive mesenchymal cell origin, and a progressive degenerative process in CGCE, rather than neoplasia. Prenatal detection of this lesion is important to facilitate adequate preparations for support of these infants during labor and delivery.

PMID:36209431 | DOI:10.1080/01913123.2022.2107750

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A group theoretic approach to model comparison with simplicial representations

J Math Biol. 2022 Oct 9;85(5):48. doi: 10.1007/s00285-022-01807-2.

ABSTRACT

The complexity of biological systems, and the increasingly large amount of associated experimental data, necessitates that we develop mathematical models to further our understanding of these systems. Because biological systems are generally not well understood, most mathematical models of these systems are based on experimental data, resulting in a seemingly heterogeneous collection of models that ostensibly represent the same system. To understand the system we therefore need to understand how the different models are related to each other, with a view to obtaining a unified mathematical description. This goal is complicated by the fact that a number of distinct mathematical formalisms may be employed to represent the same system, making direct comparison of the models very difficult. A methodology for comparing mathematical models based on their underlying conceptual structure is therefore required. In previous work we developed an appropriate framework for model comparison where we represent models, specifically the conceptual structure of the models, as labelled simplicial complexes and compare them with the two general methodologies of comparison by distance and comparison by equivalence. In this article we continue the development of our model comparison methodology in two directions. First, we present a rigorous and automatable methodology for the core process of comparison by equivalence, namely determining the vertices in a simplicial representation, corresponding to model components, that are conceptually related and the identification of these vertices via simplicial operations. Our methodology is based on considerations of vertex symmetry in the simplicial representation, for which we develop the required mathematical theory of group actions on simplicial complexes. This methodology greatly simplifies and expedites the process of determining model equivalence. Second, we provide an alternative mathematical framework for our model-comparison methodology by representing models as groups, which allows for the direct application of group-theoretic techniques within our model-comparison methodology.

PMID:36209430 | DOI:10.1007/s00285-022-01807-2

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Az egészségügyi szakdolgozók létszámváltozása az európai egészségügyi rendszerekben 2000 és 2018 között

Orv Hetil. 2022 Oct 9;163(41):1639-1648. doi: 10.1556/650.2022.32580. Print 2022 Oct 9.

ABSTRACT

INTRODUCTION: Ensuring the supply of healthcare professionals is an important health policy issue nowadays.

OBJECTIVE: The aim of our research is to provide a comprehensive picture of the health workforce situation in the European OECD countries.

DATA AND METHODS: Indicators analyzed regarding the numbers of practising midwives, nurses, physiotherapists and total hospital beds were derived from the “OECD Health Statistics 2021” database for the period 2000-2018. 24 European OECD countries were grouped according to the type of healthcare system and geographical location. Data were subsequently compared by parametric and nonparametric tests, focusing especially on years 2000, 2010, 2018.

RESULTS: Between 2000 and 2018, there was a 14% increase in the average number of midwives, a 30% increase in the average number of nurses, and a 41% increase in the average number of physiotherapists per 100,000 population in the OECD countries examined. Per 100 hospital beds, the average number of midwives increased by 72%, the number of nurses by 86%, and the number of physiotherapists by 97%. Significant results for all three years analyzed were obtained in the number of physiotherapists per 100 hospital beds (p = 0.014; p<0.001; p = 0.002) when comparing the Western and Eastern European countries examined. As for the healthcare systems, significant results were obtained only in the number of nurses per 100 hospital beds for the year 2010 (p = 0.048).

CONCLUSION: Among healthcare professional groups, the number of physiotherapists increased the most in Europe. The numbers of healthcare professionals per 100 beds are significantly higher in Western European countries analyzed compared to Eastern European countries. Orv Hetil. 2022; 163(41): 1639-1648.

PMID:36209424 | DOI:10.1556/650.2022.32580

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NetTDP: permutation-based true discovery proportions for differential co-expression network analysis

Brief Bioinform. 2022 Oct 8:bbac417. doi: 10.1093/bib/bbac417. Online ahead of print.

ABSTRACT

Existing methods for differential network analysis could only infer whether two networks of interest have differences between two groups of samples, but could not quantify and localize network differences. In this work, a novel method, permutation-based Network True Discovery Proportions (NetTDP), is proposed to quantify the number of edges (correlations) or nodes (genes) for which the co-expression networks are different. In the NetTDP method, we propose an edge-level statistic and a node-level statistic, and detect true discoveries of edges and nodes in the sense of differential co-expression network, respectively, by the permutation-based sumSome method. Furthermore, the NetTDP method could further localize the differences by inferring the TDPs for edge or gene subsets of interest, which can be selected post hoc. Our NetTDP method allows inference on data-driven modules or biology-driven gene sets, and remains valid even when these sub-networks are optimized using the same data. Experimental results on both simulation data sets and five real data sets show the effectiveness of the proposed method in inferring the quantification and localization of differential co-expression networks. The R code is available at https://github.com/LiminLi-xjtu/NetTDP.

PMID:36209415 | DOI:10.1093/bib/bbac417

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Depression among caregivers of cancer patients: Updated systematic review and meta-analysis

Psychooncology. 2022 Oct 9. doi: 10.1002/pon.6045. Online ahead of print.

ABSTRACT

BACKGROUND: It is imperative to provide care for patients with terminal illnesses such as cancer, though it demands time, financial resources and other unmet needs. Subsequently, caregivers might be exposed to psychological stress and other mental health problems. Previous meta-analysis finding shows caregivers of cancer patient suffer from depression. During the past four years, there has been a considerable increase in the number of newly studies, and we therefore intended to update this finding and provide current global prevalence of depression among caregivers of Cancer patients.

METHODS: We searched PubMed, SCOPUS, CINAHIL, Embase, and PsychINFO to identify peer-reviewed studies which reported the prevalence of depression among caregivers of cancer patients using pre-defined eligibility criteria. Studies were pooled to estimate the global prevalence of depression using a random-effect meta-analysis model. Heterogeneity was assessed using Cochran’s Q and I2 – statistics. Funnel plot asymmetry and Egger’s regression tests were used to check for publication bias.

RESULT: Our search identified 4375 studies, of which 35 studies with 11,396 participants were included in the meta-analysis. In the current review, the pooled prevalence of depression among caregivers of Cancer patients was 42.08% (95% CI: 34.71-49.45). The pooled prevalence of depression was higher in the studies that used cross-sectional data (42%, 95% CI: 31-52) than longitudinal data (34%, 95%CI: 18-50). We also observed a higher rate of depression among female caregivers when compared to their male counterparts (57.6%) (95% CI: 29.5-81.5).

CONCLUSION: Globally, around two in five cancer patient caregivers screened positive for depression, which needs due attention. Routine screening of depressive symptoms and providing psychosocial support for caregivers is crucial. This article is protected by copyright. All rights reserved.

PMID:36209385 | DOI:10.1002/pon.6045

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Comparative Study Between Topical Application Of Triamcinolone Acetonide After Fractional Carbon Dioxide Laser Versus Micro-needling In Treatment Of Resistant Alopecia Areata

Dermatol Ther. 2022 Oct 9:e15913. doi: 10.1111/dth.15913. Online ahead of print.

ABSTRACT

BACKGROUND: Alopecia areata (AA) is a disease that affects the psychological well-being of the affected individuals. Laser-assisted drug delivery and micro needling are promising methods for the treatment of different dermatological diseases.

AIM: The aim of the study was to compare the efficacy of topical application of triamcinolone acetonide after fractional carbon dioxide laser versus micro-needling in the treatment of resistant alopecia areata from a clinical and dermoscopic perspective.

PATIENTS AND METHODS: Thirty patients were randomly divided into two groups of 15 patients each: the Laser group received fractional CO2 laser treatment followed by topical application of triamcinolone acetonide, and the Micro-needling group received dermapen treatment followed by topical application of triamcinolone acetonide.

RESULTS: In our study, we found no statistically significant difference between the studied groups before and after treatment, except for black dot, which is higher in the microneedling group than in the laser group (46.7% versus 13.3%). There is a statistically significant difference between the studied groups in terms of treatment response at the first follow-up, with 13.3% of the laser group seeing terminal hair regrowth compared to 0 in the microneedling group after 12 weeks. Regarding the degree of improvement, there was no statistically significant difference between the laser group and the microneedling group.

CONCLUSION: The use of fractional CO2 laser and microneedling for transepidermal drug delivery (TED) allowed for more uniform drug distribution. There was no significant difference between the two treatment methods in terms of their high effectiveness in the treatment of resistant alopecia areata. This article is protected by copyright. All rights reserved.

PMID:36209381 | DOI:10.1111/dth.15913