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Extranodal presentation in limited stage diffuse large B-cell lymphoma as a prognostic marker in three SWOG trials S0014, S0313 and S1001

Haematologica. 2022 Jul 14. doi: 10.3324/haematol.2022.281004. Online ahead of print.

ABSTRACT

Not available.

PMID:35833300 | DOI:10.3324/haematol.2022.281004

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Improved outcomes with 7+3 induction chemotherapy for acute myeloid leukemia over the past four decades: analysis of SWOG trial data

Haematologica. 2022 Jul 14. doi: 10.3324/haematol.2022.280765. Online ahead of print.

ABSTRACT

We have previously shown that complete response (CR) rates and overall survival (OS) of patients with acute myeloid leukemia (AML) have improved since the 1980s. However, we have not previously evaluated how the length of first CR (CR1) has changed over this time period. To address this, we analyzed 1,247 patients age 65 or younger randomized to 7+3 arms from 5 SWOG studies: S8600 (n=530), S9031 (n=98), S9333 (n=57), S0106 (n=301), S1203 (n=261). We evaluated length of CR1 and survival after relapse from CR1 over the 4 decades these studies represent. Both length of CR1 and survival after relapse from CR1 have improved over the last four decades. The relative benefit associated with CR1 and the relative detriment associated with relapse have decreased over this period; while achieving CR1 and relapse from CR1 still have strong prognostic associations with outcomes, the magnitude of the association has decreased over time. Possible explanations for these patterns include higher CR rates with salvage therapies after relapse, more frequent use of hematopoietic cell transplant, and better supportive care.

PMID:35833298 | DOI:10.3324/haematol.2022.280765

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Does slow release oral morphine have impact on craving and impulsivity in heroin dependent individuals?

Int Clin Psychopharmacol. 2022 Jul 14. doi: 10.1097/YIC.0000000000000418. Online ahead of print.

ABSTRACT

Craving and impulsivity are addiction components which explain why heroin-dependant individuals (HDI), continue using heroin despite not wanting to do so. Opioid maintenance treatment (OMT), such as slow-release oral morphine (SROM), is the most effective treatment for opioid dependence. However, the impact of SROM on craving and impulsivity remains unclear. In this observational study, 23 HDI receiving SROM, their usual OMT, took part in the experiment. Each of the participants filled in the perceived level of craving with a visual analog scale. Their impulsivity was assessed via three laboratory tasks, the stop-signal reaction time, the Balloon Analogue Risk Task and delay discounting. Each evaluation was performed before and after SROM administration. Craving was significantly reduced after administration of SROM (difference 2.83; P = 0.0010), whereas there were no significant differences in performance in the three laboratory tasks. In the long term, we observed an improvement on delay discounting correlated with the duration and dosage of SROM. The acute impact of SROM appears to significantly reduce craving, without impacting impulsivity. Observation of the correlation between delay discounting and the duration and dosage of OMT is of great interest and should be studied further.

PMID:35833289 | DOI:10.1097/YIC.0000000000000418

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Effect of pediatric ventilation weaning technique on work of breathing

Respir Res. 2022 Jul 13;23(1):184. doi: 10.1186/s12931-022-02106-6.

ABSTRACT

BACKGROUND: Ventilator liberation is one of the most challenging aspects in patients with respiratory failure. Most patients are weaned through a transition from full to partial respiratory support, whereas some advocate using a continuous spontaneous ventilation (CSV). However, there is little scientific evidence supporting the practice of pediatric ventilator liberation, including the timing of onset of and the approach to weaning mode. We sought to explore differences in patient effort between a pressure controlled continuous mode of ventilation (PC-CMV) [in this cohort PC assist/control (PC-A/C)] with a reduced ventilator rate and CSV, and to study changes in patient effort with decreasing PS.

METHODS: In this prospective physiology cross-over study, we randomized children < 5 years to first PC-A/C with a 25% reduction in ventilator rate, or CSV (continuous positive airway pressure [CPAP] + PS). Patients were then crossed over to the other arm. Patient effort was measured by calculating inspiratory work of breathing (WOB) using the Campbell diagram (WOBCampbell), and by pressure-rate-product (PRP) and pressure-time-product (PTP). Respiratory inductance plethysmography (RIP) was used to calculate the phase angle. Measurements were obtained at baseline, during PC-A/C and CPAP + PS, and during decreasing set PS (maximum -6 cmH2O).

RESULTS: Thirty-six subjects with a median age of 4.4 (IQR 1.5-11.9) months and median ventilation time of 4.9 (IQR 3.4-7.0) days were included. Nearly all patients (94.4%) were admitted with primary respiratory failure. WOBCampbell during baseline [0.67 (IQR 0.38-1.07) Joules/L] did not differ between CSV [0.49 (IQR 0.17-0.83) Joules/L] or PC-A/C [0.47 (IQR 0.17-1.15) Joules/L]. Neither PRP, PTP, ∆Pes nor phase angle was different between the two ventilator modes. Reducing pressure support resulted in a statistically significant increase in patient effort, albeit that these differences were clinically negligible.

CONCLUSIONS: Patient effort during pediatric ventilation liberation was not increased when patients were in a CSV mode of ventilation compared to a ventilator mode with a ventilator back-up rate. Reducing the level of PS did not lead to clinically relevant increases in patient effort. These data may aid in a better approach to pediatric ventilation liberation. Trial registration clinicaltrials.gov NCT05254691. Registered 24 February 2022.

PMID:35831900 | DOI:10.1186/s12931-022-02106-6

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Reference values of impulse oscillometry (IOS) for healthy Chinese children aged 4-17 years

Respir Res. 2022 Jul 12;23(1):182. doi: 10.1186/s12931-022-02080-z.

ABSTRACT

OBJECTIVE: To establish the predicted value of pulmonary function determined by impulse oscillometry (IOS) in children (4-17 years old) in China.

METHODS: A total of 6270 healthy children aged 4-17 years in China were included. The Master Screen IOS pulmonary function device (Jaeger Co, Germany) was used to detect the respiratory impedance (Zrs), resonant frequency (Fres), respiratory system resistance (Rrs) and respiratory system reactance (Xrs) at various oscillation frequencies, and the indices above were analysed. Stepwise multivariate regression was used to establish the regression equation of related parameters of IOS in different sexes, ages, height, and weight.

RESULTS: The differences in the main IOS parameters between different age stages were statistically significant regardless of sex (P < 0.05). The stepwise multivariate regression analysis showed that IOS parameters were related to height, age, and weight, and most IOS parameters were most closely related to height (the absolute value of the regression coefficient was the largest). With increasing age and height, the values of Z5, R5, R20, R5-R20, and Fres decreased, while the value of X5 increased. Through height, age, and weight, we obtained the normal predicted values equation of children’s IOS parameters. Compared with the other reference equations, our reference equation is more suitable for Chinese children.

CONCLUSIONS: The study revealed the reference values of IOS parameters in healthy Chinese children. In the evaluation of results for lung function measurements, this predicted value equation is more consistent with the characteristics of Chinese children than other reference equations.

CLINICAL TRIAL: ChiCTR: 1800019029.

PMID:35831898 | DOI:10.1186/s12931-022-02080-z

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Staff and patient experience of the implementation and delivery of a virtual health care home monitoring service for COVID-19 in Melbourne, Australia

BMC Health Serv Res. 2022 Jul 13;22(1):911. doi: 10.1186/s12913-022-08173-1.

ABSTRACT

BACKGROUND: Provision of virtual health care (VHC) home monitoring for patients who are experiencing mild to moderate COVID-19 illness is emerging as a central strategy for reducing pressure on acute health systems. Understanding the enablers and challenges in implementation and delivery of these programs is important for future implementation and re-design. The aim of this study was to explore the perspectives of staff involved with the implementation and delivery, and the experience of patients managed by, a VHC monitoring service in Melbourne, Australia during the COVID-19 pandemic.

METHODS: A descriptive qualitative approach informed by naturalist inquiry was used. Staff interviews were analysed using the Consolidated Framework for Implementation Research (CFIR). Patient experience was captured using a survey and descriptive statistics were used to describe categorical responses while content analysis was used to analyse free text responses as they related to the CFIR. Finally, data from the interviews and patient experience were triangulated to see if patient experience validated data from staff interviews.

RESULTS: All 15 staff were interviewed, and 271 patients were surveyed (42%). A total of four final overarching themes emerged: service implementation enablers, service delivery benefits for patients, fragmentation of care, and workforce strengths. 19 subthemes aligned with 18 CFIR constructs from staff and patient data.

CONCLUSION: Rapid implementation was enabled through shared resources, dividing implementation tasks between senior personnel, engaging furloughed healthcare staff in design and delivery, and having a flexible approach that allowed for ongoing improvements. Benefits for patients included early identification of COVID-19 deterioration, as well as provision of accurate and trustworthy information to isolate safely at home. The main challenges were the multiple agencies involved in patient monitoring, which may be addressed in the future by attributing responsibility for monitoring to a single agency.

PMID:35831887 | DOI:10.1186/s12913-022-08173-1

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Protocol for a systematic review and meta-analysis of the diagnostic accuracy of artificial intelligence for grading of ophthalmology imaging modalities

Diagn Progn Res. 2022 Jul 14;6(1):15. doi: 10.1186/s41512-022-00127-9.

ABSTRACT

BACKGROUND: With the rise of artificial intelligence (AI) in ophthalmology, the need to define its diagnostic accuracy is increasingly important. The review aims to elucidate the diagnostic accuracy of AI algorithms in screening for all ophthalmic conditions in patient care settings that involve digital imaging modalities, using the reference standard of human graders.

METHODS: This is a systematic review and meta-analysis. A literature search will be conducted on Ovid MEDLINE, Ovid EMBASE, and Wiley Cochrane CENTRAL from January 1, 2000, to December 20, 2021. Studies will be selected via screening the titles and abstracts, followed by full-text screening. Articles that compare the results of AI-graded ophthalmic images with results from human graders as a reference standard will be included; articles that do not will be excluded. The systematic review software DistillerSR will be used to automate part of the screening process as an adjunct to human reviewers. After the full-text screening, data will be extracted from each study via the categories of study characteristics, patient information, AI methods, intervention, and outcomes. Risk of bias will be scored using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) by two trained independent reviewers. Disagreements at any step will be addressed by a third adjudicator. The study results will include summary receiver operating characteristic (sROC) curve plots as well as pooled sensitivity and specificity of artificial intelligence for detection of any ophthalmic conditions based on imaging modalities compared to the reference standard. Statistics will be calculated in the R statistical software.

DISCUSSION: This study will provide novel insights into the diagnostic accuracy of AI in new domains of ophthalmology that have not been previously studied. The protocol also outlines the use of an AI-based software to assist in article screening, which may serve as a reference for improving the efficiency and accuracy of future large systematic reviews.

TRIAL REGISTRATION: PROSPERO, CRD42021274441.

PMID:35831880 | DOI:10.1186/s41512-022-00127-9

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Improvement in insulin sensitivity and prevention of high fat diet-induced liver pathology using a CXCR2 antagonist

Cardiovasc Diabetol. 2022 Jul 12;21(1):130. doi: 10.1186/s12933-022-01564-y.

ABSTRACT

BACKGROUND: Liver pathology (LP) characteristic of non-alcoholic fatty acid disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is a prevalent co-morbidity of type 2 diabetes (T2D). Accumulating evidence indicates that neutrophils driving insulin resistance (IR), including hepatic IR, precipitate T2D-associated NAFLD/NASH. We hypothesized that targeting neutrophil accumulation into insulin-sensitive tissues in mice using a CXCR2 antagonist under T2D-precipitating high fat diet (HFD) could improve insulin sensitivity and prevent the progression towards liver pathology reminiscent of NAFLD/NASH.

METHODS: Mice were age-matched and on standard rodent chow prior to 1:1 randomization into control and HFD formulated with the CXCR2 antagonist AZD5069 or with biologically inactive substitute. They were monitored for metabolic changes including insulin sensitivity using the hyperinsulinemic-euglycemic clamp and hepatic histopathologic evaluation in H&E-stained sections as well as via immunofluorescence microscopy of liver sections for leukocyte markers, collagen 1A1 formation, α-smooth muscle actin (SMA), and galectin-3 expression, for 16 weeks. Statistical tests used to determine significant differences among study groups and outcomes include Student’s t-test, one-way ANOVA, repeated measures two-way ANOVA, and Fisher’s exact test, depending on the analytical question.

RESULTS: Compared to mice on HFD, mice in the AZD5069-formulated HFD exhibited improved insulin sensitivity, a modest reduction in weight gain, and a significant improvement in LP and markers related to NAFLD/NASH. Mice in the AZD5069-formulated HFD also exhibited reduced neutrophil accumulation into the liver at the end of the 16 week study period.

CONCLUSIONS: These results show, for the first time, the effectiveness of a selective CXCR2 antagonist to improve insulin sensitivity, concomitantly preventing the progression towards LP characteristic of NAFLD/NASH. This represents a novel approach to target IR and developing LP under T2D-susceptible conditions using a single agent. Furthermore, our data extend the growing evidence in support of neutrophils as a leukocyte population that imprints and maintains a chronic inflammatory state in the progression of dysregulated metabolism in liver-specific co-morbid conditions.

PMID:35831885 | DOI:10.1186/s12933-022-01564-y

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circCYP24A1 promotes Docetaxel resistance in prostate Cancer by Upregulating ALDH1A3

Biomark Res. 2022 Jul 13;10(1):48. doi: 10.1186/s40364-022-00393-1.

ABSTRACT

BACKGROUND: Docetaxel (DTX) is the most widely prescribed first-line chemotherapy for advanced prostate cancer (PCa). Unfortunately, DTX resistance invariably emerges, leading to worse prognosis of PCa. Growing evidence has shown that circRNAs had complex spatiotemporal specificity during the tumor development and oncogenesis. This study was designed to investigate the biological functions and possible molecular mechanisms of circRNAs in DTX resistance of PCa.

METHODS: circRNAs in established DTX-resistant DU145 cell line were identified by RNA sequencing. Biological function of circCYP24A1 was verified in vitro and in vivo. The potential role of circCYP24A1 in the development of DTX-resistant PCa was investigated via dual-luciferase reporter assays, RIP assays and RNA pull-down assays. Univariate and multivariate logistic regression analyses was used to predict DTX-chemotherapy response based on patients’ clinical and biological information.

RESULTS: CircCYP24A1 was identified to be upregulated in DTX-resistant DU145 cells. Upregulated circCYP24A1 was found to suppress the DTX chemosensitivity in vitro and in vivo. Furthermore, we found that circCYP24A1 promoted DTX resistance in PCa via regulating ALDH1A3 expression by sponging miR-1301-3p and activating PI3K/AKT/mTOR signaling pathway. Statistical analyses elucidated that circCYP24A1 was an independent risk factor to predict DTX response (OR = 0.165; 95% CI: 0.038-0.723; P = 0.017).

CONCLUSIONS: This study demonstrated that circCYP24A played an essential role in DTX resistance in PCa, suggesting that circCYP24A1 could be a promising biomarker to predict DTX response and a potential therapeutic target in PCa patients resistant to DTX chemotherapy.

PMID:35831872 | DOI:10.1186/s40364-022-00393-1

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Remineralization and protection from demineralization: effects of a hydroxyapatite-containing, a fluoride-containing and a fluoride- and hydroxyapatite-free toothpaste on human enamel in vitro

Head Face Med. 2022 Jul 13;18(1):26. doi: 10.1186/s13005-022-00330-5.

ABSTRACT

BACKGROUND: The aim was to evaluate the remineralization potential as well as the extent of protection against renewed demineralization of enamel by hydroxyapatite-containing toothpaste (Karex) in comparison to fluoride-containing (Elmex) and fluoride- and hydroxyapatite-free toothpaste (Ajona) as control.

METHODS: Fifty-seven enamel samples were obtained from 19 human teeth. Five demarcated surfaces were created on each tooth (S0-S4). Four of the surfaces (S1-S4) were exposed to lactic acid (pH 3) for 8 h (demineralization). S0 was left untreated as control. S1 was solely treated with acid. After demineralization, S2 was exposed to Karex for 2 min, of which 15 s were brushing. S3 was treated with Elmex and S4 with Ajona, accordingly. Then, the samples were evaluated using a scanning electron microscope and ImageJ image analysis software to determine the percentage of demineralization. Afterwards, S2-S4 were again exposed to lactic acid for 2 h, and subjected to pixel analysis another time. Data were statistically analysed using ANOVA with post-hoc Scheffé test and the Kurskal-Wallis test.

RESULTS: The surfaces treated with Elmex showed the lowest percentage of demineralization (mean 5.01 ± 0.98%) (p < 0.01). Thus, Elmex remineralized more effectively compared to Ajona (8.89 ± 1.41%) and Karex (9.85 ± 1.63%) (p < 0.01). Furthermore, Elmex showed the lowest percentage of demineralized enamel after new demineralization (median 6.29%), followed by Ajona (11.92%) and Karex (13.46%) (p < 0.001).

CONCLUSION: In terms of remineralization and protection against renewed demineralization, a hydroxyapatite-containing toothpaste (Karex) appears to be inferior to a fluoride-containing toothpaste (Elmex) and a fluoride- and hydroxyapatite-free toothpaste (Ajona). Hence, the recommendation to use Karex to protect against demineralization should be critically questioned.

PMID:35831871 | DOI:10.1186/s13005-022-00330-5