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The alcohol biomarker phosphatidylethanol (PEth) – recommendations for use and interpretation of test results

Lakartidningen. 2023 Jun 12;120:23029.

ABSTRACT

Phosphatidylethanol (PEth) is a group of phospholipids that are formed in blood from the corresponding phosphatidylcholines in the presence of ethanol by action of phospholipase D. Since PEth formation requires ethanol, it is used as a specific alcohol biomarker. Use of PEth measurement in whole blood as an alcohol biomarker has risen sharply in recent years, increasing the demand for knowledge about how it should be utilized and test results evaluated. In Sweden, the use since 2013 of harmonized LC-MS analytical methods targeting the main form PEth 16:0/18:1, and confirmation of comparable test results between laboratories in the Equalis (Uppsala, Sweden) external quality control program (CV <15%), has enabled use of common decision limits. A measurable PEth result confirms ethanol exposure, but due to interindividual variations in test response to a given dose and elimination half-life during abstinence, it is not possible to indicate the exact amount or time of alcohol intake. However, a PEth level above 0.30 µmol/L (~210 µg/L) is a strong indicator of harmful drinking, while a test result below 0.05 µmol/L (~35 µg/L) excludes harmful drinking but does not confirm complete abstinence. According to current test statistics from two Swedish hospital laboratories, each performing > 60 000 routine PEth measurements annually, ~45-50% of the values were < 0.05 µmol/L, ~23-24% between 0.05-0.30 µmol/L, ~16-19% between 0.30-1.0 µmol/L, and ~10-12% > 1.0 µmol/L. Some PEth results even exceeded 10 µmol/L.

PMID:37306004

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Income disparities between adult childhood cancer survivors and their peers-A register-based cohort study from the SALiCCS research programme

Cancer Med. 2023 Jun 12. doi: 10.1002/cam4.6218. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood cancer survivors face various adverse consequences. This Nordic register-based cohort study aimed to assess whether survivors of childhood cancer are more likely to have low income than their peers.

METHODS: We identified 17,392 childhood cancer survivors diagnosed at ages 0 to 19 between 1971 and 2009 with 83,221 age-, sex-, and country-matched population comparisons. Annual disposable income at ages 20 to 50 years was retrieved from statistical offices (for 1990-2017) and categorized into low income and middle/high income. The number of transitions between income categories were assessed using binomial regression analyses.

RESULTS: The prevalence of annual low income among childhood cancer survivors was 18.1% and 15.6% among population comparisons (risk ratio [RR] 1.17; 95% confidence interval [CI] 1.16-1.18). Compared to population comparisons, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to transition from low to middle/high income and 12% (10%-15%) more likely to transition from middle/high to low income during follow-up. Among those initially in the low income category, survivors were 7% (95% CI 3%-11%) more likely to remain in the low income category. If the initial category was middle/high income, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to remain in the middle/high income and 45% (37%-53%) more likely to transition to the low income category permanently.

CONCLUSIONS: Childhood cancer survivors are at higher risk for low income in adulthood than their peers. These disparities might be reduced by continued career counseling along with support in managing within the social security system.

PMID:37305982 | DOI:10.1002/cam4.6218

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The clinical characteristics of Parkinson’s disease patients with concomitant periodic limb movements in sleep

Zhonghua Yi Xue Za Zhi. 2023 Jun 20;103(23):1793-1796. doi: 10.3760/cma.j.cn112137-20230227-00291.

ABSTRACT

The current study aimed to investigate the clinical characteristics of Parkinson’s disease (PD) patients with concomitant periodic limb movements in sleep (PLMS). The clinical data of 36 PD patients who underwent polysomnography (PSG) in Beijing Tiantan Hospital from October 2018 to July 2022 were collected. Unified Parkinson’s Disease Rating Scale 3.0 and Hoehn & Yahr (H-Y) stage were used to evaluate the disease severity. Patients were divided into two groups: the PLMS+group periodic limb movements in sleep index [(PLMSI)≥15 times/h] and the PLMS-group (PLMSI<15 times/h), using the PLMSI 15 times/h as the cut-off value. The clinical characteristics between the two groups were compared. There were 15 patients (42%) in the PLMS+group and 21 patients (58%) in the PLMS-group, among which 12 patients (12/15) in the PLMS+group and 9 patients (42.9%) in the PLMS-group had rapid eye movement sleep behavior disorder (RBD). The rate of RBD in PLMS+group was higher than that in PLMS-group (P<0.05). There was statistically significant difference in the blood folate level between the PLMS-group and PLMS+group [6.20 (5.14, 11.70) ng/ml vs 4.41 (3.07, 5.64) ng/ml] (P<0.01). Folate deficiency was more common in the PLMS+group, while no statistically significant differences were found in homocysteine and ferritin levels (both P>0.05). Four patients in the PLMS+group had falling experience, while 14.3% (3/21) patients in the PLMS-group had falling experience. Patients in the PLMS+group were more likely to fall. The PLMS+group had higher arousal index according to PSG [PLMS-group: 11.90 (9.10, 15.80) times/h; PLMS+group: 21.50 (19.35, 29.90) times/h] (P<0.05). No statistically significant differences in other sleep parameters were detected between the two groups (all P>0.05). Meanwhile, the apnea-hypopnea index (AHI) in both groups was higher than normal (<5 times/h), of which the PLMS-group was 9.80 (4.70, 22.20) times/h and the PLMS+group was 8.20 (1.70, 11.15) times/h, indicating that PD patients were more likely to experience sleep apnea and hypopnea. PD patients with PLMS had lower folate level, higher risk for falls, higher sleep arousal index, more sleep fragmentation, and higher prevalence of RBD.

PMID:37305940 | DOI:10.3760/cma.j.cn112137-20230227-00291

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Comparison of intraoperative neurophysiological monitoring between patients with arthrogryposis multiplex congenita and adolescent idiopathic scoliosis

Zhonghua Yi Xue Za Zhi. 2023 Jun 20;103(23):1774-1780. doi: 10.3760/cma.j.cn112137-20221215-02661.

ABSTRACT

Objective: To compare the intraoperative neurophysiological monitoring (IONM) results between patients with arthrogryposis multiplex congenita (AMC) and adolescent idiopathic scoliosis (AIS) and to analyze the influence of congenital spinal deformity on IONM in AMC patients, thus to evaluate the efficiency of IONM in AMC patients. Methods: A cross-sectional study. The clinical data of 19 AMC patients underwent correction surgery from July 2013 to January 2022 in Nanjing Drum Tower Hospital were retrospectively reviewed. There were 13 males and 6 females with a mean age of (15.2±5.6) years, and the average Cobb angle of main curve was 60.8°±27.7°. And 57 female AIS patients of similar age and curve type with the AMC patients during the same period were selected as the control group, with an average age of (14.6±4.4) years and a mean Cobb angle of 55.2°±14.2°. The latency and amplitude of samatosensory evoked potentials (SSEPs) and transcranial electric motor evoked potentials (TCeMEPs) were compared between the two groups. The difference in IONM data between AMC patients with and without congenital spinal deformity was also evaluated. Results: The success rates of SSEPs and TCeMEPs were 100% and 14/19 for AMC patients, 100% and 100% for AIS patients. The SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency, TCeMEPs-amplitude showed no significant difference between AMC patients and AIS patients (P>0.05 for all). The side-difference of TCeMEPs-amplitude showed an increasing trend in AMC patients when compared with that in AIS patients, but there was no statistical difference between the two groups [(147.0±185.6) μV vs (68.1±311.4) μV, P=0.198]. The SSEPs-amplitude value was (1.4±1.1) μV on concave side in AMC patients with congenital spinal deformity, and it was (2.6±1.2) μV on concave side in AMC patients without congenital spinal deformity (P=0.041). The SSEPs-amplitude value was (1.4±0.8) μV on convex side in AMC patients with congenital spinal deformity, and it was (2.6±1.3) μV on convex side in AMC patients without congenital spinal deformity (P=0.028). Conclusions: The values of SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency and TCeMEPs-amplitude are similar in AMC and AIS patients. The SSEPs-amplitude of AMC patients with congenital spinal deformity is lower than that of AMC patients without congenital spinal deformity.

PMID:37305937 | DOI:10.3760/cma.j.cn112137-20221215-02661

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Efficacy of intravenous thrombolysis with tenecteplase in treating the branch atheromatous disease

Zhonghua Yi Xue Za Zhi. 2023 Jun 20;103(23):1753-1758. doi: 10.3760/cma.j.cn112137-20230217-00226.

ABSTRACT

Objective: To explore the efficacy of intravenous thrombolysis with tenecteplase (TNK) in the treatment of branch atheromatous disease (BAD). Methods: A total of 148 BAD patients hospitalized in the stroke center of Zhengzhou People’s Hospital from January 2020 to March 2023 were retrospectively included. According to whether TNK was used for treatment, the patients were divided into the TNK group (52 cases) and the control group (96 cases). The propensity score matching (PSM) method was used to eliminate baseline differences between the two groups, and 46 pairs were successfully matched. Early neurological deterioration (END) was defined as an increase in the national Institutes of Health Stroke Scale (NIHSS) scores within 7 days of stroke≥2. The 90-day modified Rankin Scale (mRS) was used to compare the long-term efficacy between the two groups. A binary logistic regression model was used to analyze the influencing factors of clinical outcomes in patients with BAD. Results: Among the 92 patients, 62 were males and 30 were females, with an average age of (61.0±9.5) years. After PSM, there were statistically significant differences in NIHSS score at discharge [2 (0, 4) vs 4 (3, 8)] and length of hospital stay [9 (6, 13) d vs 11 (9, 14) d] (both P<0.05) between the two groups. The proportion of mRS 0-2 in TNK group was higher than that in the control group [82.6%(38/46) vs 60.8%(28/46)], while the proportion of END and mRS≥4 was lower than that in the control group [10.8%(5/46) vs 30.4%(14/46); 8.7%(4/46) vs 26.0%(12/46)], with statistically significant differences (P<0.05). The 90-day mortality in the control group was 2.2% (1/46), while no death was detected in the TNK group. Conclusion: Intravenous thrombolysis therapy with TNK can not only increase the proportion of 90-day mRS 0-2 in BAD patients, but also reduce the incidence of END.

PMID:37305934 | DOI:10.3760/cma.j.cn112137-20230217-00226

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Clinical and biological features and prognosis of patients with leukemic non-nodal mantle cell lymphoma

Zhonghua Yi Xue Za Zhi. 2023 Jun 20;103(23):1746-1752. doi: 10.3760/cma.j.cn112137-20220928-02043.

ABSTRACT

Objective: To investigate the clinical, biological and prognostic characteristics of leukemic non-nodal mantle cell lymphoma (nnMCL). Methods: The clinical data of 14 patients with nnMCL and 238 patients with classical mantle cell lymphoma (cMCL) in Blood Diseases Hospital, Chinese Academy of Medical Sciences from November 2000 to October 2020 were retrospectively analyzed. Among the 14 patients with nnMCL, there were 9 males and 5 females, with the age [M (Q1, Q3)] of 57.5 (52.3, 67.0) years. Among the 238 patients with cMCL, there were 187 males and 51 females, with the age of 58.0 (51.0, 65.3) years. The clinical and biological characteristics of the two groups were recorded and compared. Follow-up and efficacy evaluation were conducted by re-examination during hospital stay and telephone follow-up and so on. Results: The proportion of CD200 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [14.6% (19/130)] (P=0.001). The proportion of CD23 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [13.5% (23/171)] (P<0.001). The proportion of CD5 expression in nnMCL patients was 10/14, which was lower than that in cMCL patients [97.4% (184/189)] (P=0.001). The proportion of CD38 expression in nnMCL patients was 4/14, which was lower than that in cMCL patients [69.6% (112/161)] (P=0.005). The expression proportion of sex-determining region of Y chromosome-related high-mobility-group box 11 (SOX11) in nnMCL patients was 1/5, which was lower than that in cMCL patients [77.9% (60/77)] (P=0.014). The proportion of immunoglobulin heavy chain variable region (IGHV) mutations in nnMCL patients was 11/11, which was higher than that in cMCL patients [26.0% (13/50)] (P<0.001). As of April 11, 2021, the follow-up time for nnMCL and cMCL patients was 31 (8-89) months and 48 (0-195) months, respectively. Among the 14 nnMCL patients, 6 patients were still under observation, and 8 patients were treated. The overall response rate (ORR) was 8/8, including 4 patients with complete remission and 4 patients with partial response. The median overall survival and median progression-free survival were not reached in nnMCL patients. In the cMCL group, 50.0% (112/224) patients achieved a complete response, 24.6% (55/224) patients achieved a partial response, and ORR was 74.6% (167/224). There was no statistically significant difference in ORR between the two groups (P=0.205). Conclusions: nnMCL patients have an indolent progression, with higher expression rates of CD23 and CD200 and lower expression rates of SOX11, CD5 and CD38. Most patients have IGHV mutations, with a relatively good prognosis, and”watch and wait”approach is an optional treatment.

PMID:37305933 | DOI:10.3760/cma.j.cn112137-20220928-02043

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Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis

Cancer Med. 2023 Jun 12. doi: 10.1002/cam4.6220. Online ahead of print.

ABSTRACT

BACKGROUND: The associations of adiposity with aggressive prostate cancer risk are unclear. Using two-sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer.

METHODS: We examined the association of these genetically predicted adiposity-related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases).

RESULTS: In inverse-variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61-1.19), 0.80 (0.53-1.23) and 0.97 (0.88-1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer.

CONCLUSIONS: We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies.

PMID:37305903 | DOI:10.1002/cam4.6220

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Treatment of Piperacillin-Tazobactam-Nonsusceptible/Ceftriaxone-Susceptible Infections With Carbapenem Versus Carbapenem-Sparing Antimicrobials

Open Forum Infect Dis. 2023 Jun 8;10(6):ofad262. doi: 10.1093/ofid/ofad262. eCollection 2023 Jun.

ABSTRACT

BACKGROUND: Escherichia coli and Klebsiella pneumoniae with a piperacillin-tazobactam-nonsusceptible/ceftriaxone-susceptible (TZP-NS/CRO-S) phenotype have been increasingly identified, with limited available literature evaluating treatment strategies.

METHODS: This was a retrospective study of noncritically ill adults hospitalized between 2013 and 2021 and treated at least 48 hours for TZP-NS/CRO-S E coli or K pneumoniae infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy.

RESULTS: Of 1062 patients screened, 200 were included (CG, n = 51; CSG, n = 149). Baseline characteristics, including Charlson Comorbidity Index (CCI; median [interquartile range], 6 [3-9] vs 6 [4-9]; P = .704), were similar between groups, except for more immunocompromised CG patients (29% vs 11%, P = .001). The most common infection sources were urinary (31% vs 57%, P = .002) and bloodstream (18% vs 17%, P = .887). Eighty-eight percent of the CG received meropenem, while 58% of the CSG received ceftriaxone as targeted therapy. There was no statistical difference in the primary endpoint between overall groups (27% vs 17%, P = .123), nor when stratified by infection source. More patients in the CSG switched to oral therapy (15 [29%] vs 100 [67%], P < .001). In multivariate analysis, CCI was an independent predictor of the primary outcome (odds ratio [OR], 1.199 [95% confidence interval, 1.074-1.340]; P = .001), while treatment with carbapenem-sparing therapy was not.

CONCLUSIONS: Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort.

PMID:37305841 | PMC:PMC10249260 | DOI:10.1093/ofid/ofad262

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Protective effect of IAXO-102 on renal ischemia-reperfusion injury in rats

J Med Life. 2023 Apr;16(4):623-630. doi: 10.25122/jml-2022-0280.

ABSTRACT

Ischemia/reperfusion injury (IRI) is a common cause of kidney damage, characterized by oxidative stress and inflammation. In this study, we investigated the potential protective effects of IAXO-102, a chemical compound, on experimentally induced IRI in male rats. The bilateral renal IRI model was used, with 24 adult male rats randomly divided into four groups (N=6): sham group (laparotomy without IRI induction), control group (laparotomy plus bilateral IRI for 30 minutes followed by 2 hours of reperfusion), vehicle group (same as control but pre-injected with the vehicle), and treatment group (similar to control but pre-injected with IAXO-102). We measured several biomarkers involved in IRI pathophysiology using enzyme-linked immunosorbent assay (ELISA), including High mobility group box1 (HMGB1), nuclear factor kappa b-p65 (NF-κB p65), interleukin beta-1 (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 8-isoprostane, Bcl-2 associated X protein (BAX), heat shock protein 27 (HSP27), and Bcl-2. Statistical analysis was performed using one-way ANOVA and Tukey post hoc tests. Our results showed that IAXO-102 significantly improved kidney function, reduced histological alterations, and decreased the inflammatory response (IL-1, IL-6, and TNF) caused by IRI. IAXO-102 also decreased apoptosis by reducing pro-apoptotic Bax and increasing anti-apoptotic Bcl-2 without impacting HSP27. In conclusion, our findings suggest that IAXO-102 had a significant protective effect against IRI damage in the kidneys.

PMID:37305825 | PMC:PMC10251395 | DOI:10.25122/jml-2022-0280

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Assessment of tumor microenvironment expression and clinical significance of immune inhibitory molecule CTLA-4, ligand B7-1, and tumor-infiltrating regulatory cells in Hodgkin lymphoma

J Med Life. 2023 Apr;16(4):599-609. doi: 10.25122/jml-2023-0019.

ABSTRACT

Classical Hodgkin lymphoma represents a paradigm of tumor cell-microenvironment interactions as the neoplastic Hodgkin Reed-Sternberg (HRS) cells typically constitute less than 1% of the total tumor volume. CTLA-4, a member of the CD28/B7 immunoglobulin superfamily, and CD28 and their ligands B7-1 and B7-2 are critically important for the initial activation of naive T cells. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of the HL microenvironment. The study included 50 histopathological confirmed cases of Hodgkin lymphoma. IHC staining for CTLA-4 and B7-1 was performed on archival paraffin-embedded biopsy. SPSS version 17 was used for statistical analysis. CTLA-4 IHC expression in HRS cells was negative in all cases, while in immune cells, CTLA-4 expression was observed in 45 (90%) cases. CD80 expression was present in all cases, both in HRS and immune cells. There was a significant association between HRS cell percentage and IPS score (p-value=0.001). Mean survival duration was longer in <50% immune cells compared to >50% groups, with an overall mean survival of 67.633 months. Considering the CTLA4 expression in immune cells within the microenvironment and the availability of targeted drugs like Iplimumab, which act through CTLA4 blockade, it may be appropriate to use this as targeted therapy in HL cases, particularly in those with refractory disease who are unable to achieve cure prior to ASCT.

PMID:37305822 | PMC:PMC10251379 | DOI:10.25122/jml-2023-0019