Categories
Nevin Manimala Statistics

Role for G-CSF in neutrophilic extramedullary myelopoiesis in a murine model of systemic juvenile idiopathic arthritis

Arthritis Rheumatol. 2022 Mar 3. doi: 10.1002/art.42104. Online ahead of print.

ABSTRACT

OBJECTIVES: Systemic juvenile idiopathic arthritis (sJIA) is a systemic inflammatory disease of childhood-onset. sJIA is associated with neutrophilia, including immature granulocytes, potentially driven by the growth factor granulocyte-colony stimulating factor (G-CSF). This study aimed to unravel the role of G-CSF in the pathology of sJIA.

METHODS: Injection of complete Freund’s adjuvant (CFA) in BALB/c mice induces mild inflammation and neutrophilia in wild-type (WT) mice and a more pronounced disease, reminiscent to patients, in interferon-γ (IFN-γ) knock-out (KO) mice. Extramedullary myelopoiesis was studied in CFA-immunised mice by single-cell RNA-sequencing and the effect of G-CSFR-blockage on neutrophil development and sJIA pathology was evaluated. Additionally, in patients, plasma G-CSF-levels were measured.

RESULTS: Both in sJIA patients and in a corresponding mouse model, plasma levels of G-CSF are increased. Using the model, we demonstrate that G-CSF is responsible for the observed neutrophilia and extramedullary myelopoiesis and the induction of immature neutrophils and myeloid-derived suppressor-like cells. Administration of a G-CSF-receptor antagonising antibody blocked the maturation and differentiation of neutrophils in CFA-immunised mice. In IFN-γ KO mice, treatment was associated with almost complete inhibition of arthritis due to its reduced neutrophilia and osteoclast formation. Disease symptoms were ameliorated although slight increases in IL-6, TNF-α and IL-17 were detected upon G-CSFR inhibition in the IFN-γ KO mice, associated with mild increases in weight loss, tail damage and immature RBCs.

CONCLUSION: We described the role of G-CSF in a sJIA-like mouse model and point towards an important role for G-CSF-induced myelopoiesis and neutrophilia, regulating the development of arthritis.

PMID:35243819 | DOI:10.1002/art.42104

Categories
Nevin Manimala Statistics

Prognostic significance of albumin-bilirubin score in patients with unresectable hepatocellular carcinoma undergoing combined immunotherapy and radiotherapy

J Med Imaging Radiat Oncol. 2022 Mar 3. doi: 10.1111/1754-9485.13398. Online ahead of print.

ABSTRACT

INTRODUCTION: We aimed to explore the prognostic value of albumin-bilirubin (ALBI) scores in unresectable hepatocellular carcinoma (HCC) treated with combined immune checkpoint inhibitors (ICIs) and radiotherapy (RT).

METHODS: Patients with unresectable HCC receiving combined ICI and RT (July 2018 to February 2021) were retrospectively enrolled and analysed. Cox regression modelling was implemented to identify prognostic factors. Survival analysis was performed using the Kaplan-Meier method. Survival was compared using log-rank tests.

RESULTS: A total of 38 patients were enrolled. The median follow-up was 16.5 months (range: 6.7-29.9). The objective response rate (ORR) was 28.9%, including complete response in three (7.9%) patients. The median progression-free survival (PFS) was 5.6 months (95% confidence interval (CI): 3.2-8.0), and the median overall survival (OS) was 12.9 months (95% CI: 8.3-17.6). In the multivariate Cox regression analysis, ALBI score and age were identified as independent prognostic factors for PFS and OS. Patients with grade 1 ALBI scores who were ≥53 years of age (the low-risk group) had statistically significantly higher ORRs (50.0% vs. 13.6%) and prolonged median PFS (15.3 vs. 2.7 months) and OS (not reached vs. 10.1 months). Grade 3 haematological toxicities and/or liver function abnormalities occurred in 15 (39.5%) patients; treatment was not interrupted. No grade 4 or higher side effects were observed.

CONCLUSION: Combined ICI and RT is an effective modality for treating unresectable HCC with moderate side effects. ALBI scores merits consideration when applying this combined treatment modality. These results should be validated within large cohort studies.

PMID:35243796 | DOI:10.1111/1754-9485.13398

Categories
Nevin Manimala Statistics

Pairwise association of key lifestyle factors and risk of colorectal cancer: a prospective pooled multicohort study

Cancer Rep (Hoboken). 2022 Mar 3:e1612. doi: 10.1002/cnr2.1612. Online ahead of print.

ABSTRACT

BACKGROUND: Several lifestyle factors are associated with an increased risk of colorectal cancer (CRC). Although lifestyle factors co-occur, in most previous studies these factors have been studied focusing upon a single risk factor or assuming independent effects between risk factors.

AIM: To examine the pairwise effects and interactions of smoking, alcohol consumption, physical inactivity, and body mass index (BMI) with risk of subsequent colorectal cancer (CRC).

METHODS AND RESULTS: We used METCA cohort data (pooled data from seven population-based Finnish health behavior survey studies during years 1972-2015) consisting of 171 063 women and men. Participants’ smoking, alcohol consumption, physical inactivity and BMI measures were gathered, and participants were categorized into those exposed and those not exposed. The incidence of CRC was modeled by Poisson regression with main and interaction effects of key lifestyle factors. The cohort members were followed-up through register linkage to the Finnish Cancer Registry for first primary CRC case until the end of 2015. Follow-up time was 1715, 690 person years. The highest pairwise CRC risk was among male smokers who had overweight (BMI ≥ 25 kg/m2 ) (HR 1.75, 95% CI 1.36-2.26) and women who had overweight and consumed alcohol (HR 1.45, 95% CI 1.14-1.85). Overall, among men the association of lifestyle factors and CRC risk was stronger than among women. In men, both having overweight and being a smoker combined with any other adverse lifestyle factor increased CRC risk. Among women, elevated CRC risks were observed for those who were physically inactive and who consumed alcohol or had overweight. No statistically significant interactions were detected between pairs of lifestyle factors.

CONCLUSIONS: This study strengthens the evidence of overweight, smoking, and alcohol consumption as CRC risk factors. Substantial protective benefits in CRC risk can be achieved by preventing smoking, maintaining BMI to <25 kg/m2 and not consuming alcohol.

PMID:35243812 | DOI:10.1002/cnr2.1612

Categories
Nevin Manimala Statistics

Paediatric trauma imaging in a regional Queensland hospital: Do we need clearer guidance?

Emerg Med Australas. 2022 Mar 3. doi: 10.1111/1742-6723.13954. Online ahead of print.

ABSTRACT

OBJECTIVE: Paediatric trauma is a major cause of morbidity and mortality in those aged 0-14. Anatomical and physiological differences require a specialised approach to paediatric trauma care. Medical imaging, particularly computed tomography (CT) scans, requires specific consideration because of the consequences of radiation exposure in the paediatric population. The present study compares current practice of CT scan ordering in paediatric trauma patients at a regional Australian hospital against consensus guidelines published in the UK.

METHODS: A retrospective audit of paediatric trauma CT scans referred from the ED from May 2017 to May 2018 was completed. Details relating to CT scan ordering were reviewed and compliance with the Royal College of Radiologists Paediatric trauma protocols, was determined. Descriptive statistics and χ2 tests comparing those that met and did not meet guidelines were performed.

RESULTS: A total of 71 CT scans were included with an overall compliance rate of 56.3%. Specific regional compliance was lowest with CT neck at 14%. Patients where a trauma call was initiated were more likely to receive a full body (pan) scan rather than region specific imaging. Compliance improved when paediatric team involvement was documented.

CONCLUSIONS: Evidence-based guidelines for CT imaging in paediatric trauma are essential to reduce unnecessary radiation exposure for children. The present study has demonstrated that current practice has the potential to be improved and that decisions should involve a multidisciplinary team.

PMID:35243766 | DOI:10.1111/1742-6723.13954

Categories
Nevin Manimala Statistics

A systematic review of inequalities in the uptake of, adherence to, and effectiveness of behavioral weight management interventions in adults

Obes Rev. 2022 Mar 3:e13438. doi: 10.1111/obr.13438. Online ahead of print.

ABSTRACT

The extent to which behavioral weight management interventions affect health inequalities is uncertain, as is whether trials of these interventions directly consider inequalities. We conducted a systematic review, synthesizing evidence on how different aspects of inequality impact uptake, adherence, and effectiveness in trials of behavioral weight management interventions. We included (cluster-) randomized controlled trials of primary care-applicable behavioral weight management interventions in adults with overweight or obesity published prior to March 2020. Data about trial uptake, intervention adherence, attrition, and weight change by PROGRESS-Plus criteria (place of residence, race/ethnicity, occupation, gender, religion, education, socioeconomic status, social capital, plus other discriminating factors) were extracted. Data were synthesized narratively and summarized in harvest plots. We identified 91 behavioral weight loss interventions and 12 behavioral weight loss maintenance interventions. Fifty-six of the 103 trials considered inequalities in relation to at least one of intervention or trial uptake (n = 15), intervention adherence (n = 15), trial attrition (n = 32), or weight outcome (n = 34). Most trials found no inequalities gradient. If a gradient was observed for trial uptake, intervention adherence, and trial attrition, those considered “more advantaged” did best. Alternative methods of data synthesis that enable data to be pooled and increase statistical power may enhance understanding of inequalities in behavioral weight management interventions.

PMID:35243743 | DOI:10.1111/obr.13438

Categories
Nevin Manimala Statistics

Morphology Analysis of Unlabeled Red Blood Cells based on Quantitative Differential Phase Contrast Microscopy

Cytometry A. 2022 Mar 3. doi: 10.1002/cyto.a.24546. Online ahead of print.

ABSTRACT

The current classical blood smear technique to observe the morphology of single red blood cells (RBCs) for classification is a laborious and error-prone process. To objectively evaluate the morphology of blood cells, we established a method of computational imaging based on a programmable light emitting diode (LED) array. By using quantitative differential phase contrast (qDPC), we characterized the morphology of unlabeled RBCs as well as blood smears. By focusing on comparing the difference of imaging between unlabeled RBCs and stained RBCs under multi-mode microscopic imaging technology, we demonstrated that qDPC could clearly differentiate discocytes and spherocytes in both unlabeled RBCs and blood smears. The phase map provided by QPI further enhanced the classification accuracy. According to statistical analysis from morphological indexes, the qDPC imaging has a significantly improvement in non-circularity, texture inhomogeneity and equivalent diameters of cells. Thus, this method has a significant superiority in the capability to analyze the morphology of RBCs and could be applied to clinical assays for determining morphological, functional, and structural deterioration of RBCs.

PMID:35243761 | DOI:10.1002/cyto.a.24546

Categories
Nevin Manimala Statistics

Submandibular gland transfer for the prevention of radiation-induced xerostomia in oropharyngeal cancer: Dosimetric impact in the intensity modulated radiotherapy era

Head Neck. 2022 Mar 4. doi: 10.1002/hed.27021. Online ahead of print.

ABSTRACT

BACKGROUND: Submandibular gland (SMG) transfer decreased radiation-associated xerostomia in the 2/3-dimensional radiotherapy era. We evaluated the dosimetric implications of SMG transfer on modern intensity modulated radiotherapy (IMRT) plans.

METHODS: Eighteen oropharynx cancer patients underwent SMG transfer followed by IMRT; reoptimized plans using the baseline SMG location were generated. Mean salivary gland, oral cavity, and larynx doses were compared between clinical plans and reoptimized plans.

RESULTS: No statistically significant difference in mean SMG dose (27.53 Gy vs. 29.61 Gy) or total salivary gland dose (26.12 Gy vs. 26.41 Gy) was observed with or without SMG transfer (all p > 0.05). Mean oral cavity and larynx doses were not statistically different. Neither tumor site, target volume crossing midline, stage, nor salivary gland volumes were associated with mean doses.

CONCLUSIONS: Salivary gland doses were similar with or without SMG transfer. IMRT likely decreases the benefit of SMG transfer on the risk of radiation-associated xerostomia.

PMID:35243719 | DOI:10.1002/hed.27021

Categories
Nevin Manimala Statistics

Blood long non-coding RNA intersectin 1-2 is highly expressed and links with increased Th17 cells, inflammation, multiple organ dysfunction, and mortality risk in sepsis patients

J Clin Lab Anal. 2022 Mar 4:e24330. doi: 10.1002/jcla.24330. Online ahead of print.

ABSTRACT

BACKGROUND: Long non-coding RNA intersectin 1-2 (lnc-ITSN1-2) exacerbates inflammation and promotes T-helper (Th) cell differentiation, also serves as a biomarker in critical illness diseases. However, its clinical role in sepsis remains obscure. Hence, the study aimed to explore the relationship of lnc-ITSN1-2 with Th cells, inflammation, disease severity, multiple organ dysfunction, and mortality risk in sepsis.

METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 95 sepsis patients and 50 health controls, followed by lnc-ITSN1-2 evaluation using RT-qPCR. PBMC Th1, Th17 cells and their secreted cytokines in serum were detected by flow cytometry and ELISA, respectively.

RESULTS: Lnc-ITSN1-2 in sepsis patients was higher than it in health controls (Z = -7.328, p < 0.001). Lnc-ITSN1-2 correlated with increased interferon-gamma (p = 0.009), Th17 cells (p = 0.022), and interleukin-17A (p = 0.006), but not Th1 cells (p = 0.169) in sepsis patients. Moreover, lnc-ITSN1-2 had a positive connection with C-reactive protein (p = 0.001), acute pathologic and chronic health evaluation (APACHE) II (p = 0.024), and sequential organ failure assessment (SOFA) scores (p = 0.022). Regarding SOFA subscales, lnc-ITSN1-2 linked with elevated respiratory system score (p = 0.005), cardiovascular system score (p = 0.007), and renal system score (p = 0.004) but no other subscales. Besides, lnc-ITSN1-2 had an increasing trend, but no statistical difference, in septic deaths compared to survivors (Z = -1.852, p = 0.064).

CONCLUSION: Lnc-ITSN1-2 reflects sepsis progression and unfavorable prognosis to some extent, which may serve as a potential biomarker to improve the management of sepsis patients.

PMID:35243686 | DOI:10.1002/jcla.24330

Categories
Nevin Manimala Statistics

Effectiveness and safety of carboxytocin versus oxytocin in preventing postpartum hemorrhage: A systematic review and meta-analysis

J Obstet Gynaecol Res. 2022 Mar 3. doi: 10.1111/jog.15174. Online ahead of print.

ABSTRACT

OBJECTIVE: This study compared the effectiveness and safety of carbetocin and oxytocin in preventing postpartum hemorrhage (PPH).

METHODS: A systematic literature search was performed on PubMed, Embase, and the Cochrane Library for relevant studies published up to February 2019. Next, two independent reviewers screened the studies according to the selection criteria as well as the strategies recommended by the Cochrane Collaboration. Data were then extracted and evaluated. All statistical analyses were performed using RevMan 5.1.

RESULTS: A total of 24 studies involving 37 383 patients were included for analysis. For cesarean section patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contraction (odds ratio [OR] = 0.48, 95% confidence interval [CI] [0.35, 0.65], p < 0.00001), PPH (OR = 0.70, 95% CI [0.51, 0.95], p = 0.02), blood loss (mean [MD] = -64.36, 95% CI [-107.78, -20.93], p = 0.004), and transfusion (OR = 0.59, 95% CI [0.42, 0.82], p = 0.002), and there was no significant difference in severe PPH (OR = 0.84, 95% CI [0.66, 1.090], p = 0.19). For vaginal delivery patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contractions (OR = 0.48, 95% CI [0.25, 0.93], p = 0.03), PPH (OR = 0.28, 95% CI [0.09, 0.91], p = 0.03), and blood loss (MD = -63.52, 95% CI [-113.43, -13.60], p = 0.01), and there were no significant differences in severe PPH (OR = 0.82, 95% CI [0.40, 1.69], p = 0.59) and transfusion (OR = 0.60, 95% CI [0.22, 1.61], p = 0.31). With regard to safety, for cesarean section patients, carbetocin was superior to oxytocin in reduction of the incidence of headache (OR = 0.72, [0.55, 0.95], p = 0.02), and there were no significant differences in nausea, vomiting, abdominal pain, flushing, tremors, itching, dizziness, and fever. For vaginal delivery patients, there were no significant differences in nausea, vomiting, headache, abdominal pain, flushing, tremors, itching, dizziness, and fever between the two drugs.

CONCLUSION: For patients undergoing cesarean section and vaginal delivery, carbetocin was superior to oxytocin in effectiveness and similar in safety. Therefore, carbetocin is expected to be an alternative uterine contraction agent for preventing PPH.

PMID:35243717 | DOI:10.1111/jog.15174

Categories
Nevin Manimala Statistics

The effect of bolus size on masticatory parameters at swallowing threshold in children using a hard, solid, artificial test food

J Texture Stud. 2022 Mar 3. doi: 10.1111/jtxs.12671. Online ahead of print.

ABSTRACT

The effect of different bolus sizes on food breakdown has been studied in adults, but not in children. The objective of this study was to study median particle size (MPS) and other parameters of masticatory function at swallowing threshold (ST) in 8-10-year-old-children with two different bolus sizes. A randomized cross-over trial was undertaken in 89 eight to ten-year-old children. The study was performed with informed consent and ethical approval. The artificial test food used was made of a condensation silicone (Optosil Comfort®) following a standardized protocol. Two bolus sizes (three or four quarters of a 20 mm diameter, 5 mm thick tablet) were randomized to avoid an order effect and performed in different sessions. Variables were: MPS (X50 ) at ST, number of cycles until ST, sequence and cycle duration as well as cycles/g. Comparisons were performed with paired-T and Wilcoxon-tests, regressions and correlations were run. Cutoff for statistical significance was .05. Statistically significant differences were found for all variables; X50 (2.5±.8 vs 2.8±.7mm, p<.001), cycles until ST (38 vs 40, p=.022), sequence (25 vs 27 seconds, p=.003) and cycle duration (650 vs 683 ms, p=.015) and cycles/g (27 vs 21 cycles/gram, p<.001), three or four quarters respectively. In conclusion, in children, as in adults, chewing on a bigger bolus size leads to a larger MPS (X50 ) at ST. When chewing on a larger bolus the number of cycles increases, but not enough to swallow the same particle size since the number of cycles/g is less with a bigger bolus size.

PMID:35243636 | DOI:10.1111/jtxs.12671