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Peripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer

Breast Cancer Res Treat. 2024 Jul 13. doi: 10.1007/s10549-024-07426-3. Online ahead of print.

ABSTRACT

PURPOSE: We evaluated T- and B-cell receptor (TCR and BCR) repertoire diversity and 38 serum cytokines in pre- and post-treatment peripheral blood of 66 patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy plus durvalumab and assessed associations with pathologic response and immune-related adverse events (irAEs) during treatment.

METHODS: Genomic DNA was isolated from buffy coat for TCR and BCR clonotype profiling using the Immunoseq platform and diversity was quantified with Pielou’s evenness index. MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel was used to measure serum cytokine levels, which were compared between groups using moderated t-statistic with Benjamini-Hochberg correction for multiple testing.

RESULTS: TCR and BCR diversity was high (Pielou’s index > 0.75) in all samples. Baseline receptor diversities and change in diversity pre- and post-treatment were not associated with pathologic response or irAE status, except for BCR diversity that was significantly lower post-treatment in patients who developed irAE (unadjusted p = 0.0321). Five cytokines increased after treatment in patients with pathologic complete response (pCR) but decreased in patients with RD, most prominently IL-8. IFNγ, IL-7, and GM-CSF levels were higher in pre-treatment than in post-treatment samples of patients who developed irAEs but were lower in those without irAEs.

CONCLUSION: Baseline peripheral blood cytokine levels may predict irAEs in patients treated with immune checkpoint inhibitors and chemotherapy, and increased post-treatment B-cell clonal expansion might mediate irAEs.

PMID:39002068 | DOI:10.1007/s10549-024-07426-3

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Safety evaluation of outpatient vs inpatient unicompartmental knee arthroplasty: a systematic review and meta-analysis

Arch Orthop Trauma Surg. 2024 Jul 13. doi: 10.1007/s00402-024-05446-8. Online ahead of print.

ABSTRACT

PURPOSE: This systematic review and meta-analysis aimed to evaluate the safety of outpatient and inpatient Unicompartmental Knee Arthroplasty (UKA) based on the incidence of adverse events.

METHOD: A systematic search of the literature was performed in October 2022 on PubMed, Web of Science, Cochrane library, and Embase. The Meta package for R was used to perform the meta-analysis.

RESULT: Five studies with a total of 26,301 patients were included. 5813 patients (22.1%) were treated with outpatient UKA, and 20,488 patients (77.9%) were treated with inpatient UKA. There were no statistically significant differences in the incidence of total complications (RR = 1.36, 95% CI = 0.64-2.89, Z = 0.79, P = 0.43), readmission (RR = 1.02, 95% CI = 0.40-2.60, Z = 0.05, P = 0.96), and venous thrombosis (RR = 1.43, 95% CI = 0.96-2.11, Z = 1.78, P = 0.08). Incidence rates were lower in outpatient UKA regarding urinary tract infection (RR = 1.48, 95% CI = 1.07-2.04, Z = 2.40, P = 0.02), pulmonary embolus (RR = 7.48, 95% CI = 1.80-31.17, Z = 2.76, P < 0.01), and transfusion (RR = 2.77, 95% CI = 1.63-4.71, Z = 3.78, P < 0.01).

CONCLUSION: In summary, outpatient UKA shows lower incidences of hospital-acquired complications such urinary tract infection, pulmonary embolus, and transfusion. It’s worth noting that the incidences of total complications, readmission, and venous thrombosis in outpatient UKA were not higher than the incidences of inpatient UKA, suggestting that outpatient UKA can be considered a safe alternative to inpatient UKA.

PMID:39002050 | DOI:10.1007/s00402-024-05446-8

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Rare tumours of the pancreas: monocentric study

J Cancer Res Clin Oncol. 2024 Jul 13;150(7):349. doi: 10.1007/s00432-024-05884-2.

ABSTRACT

PURPOSE: The biology of rare pancreatic tumours, which differs from that of ductal pancreatic cancer, requires increased attention. Although the majority of rare pancreatic tumours are benign, it is difficult to decide whether an invasive component exists without complete removal of the lesion, despite considerable progress in diagnosis. We are investigating a large cohort of patients with histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas.

METHODS: Here we analyze long-term survival from patients, who underwent resection of histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas. At our department between Jan 1st, 1999, and Dec 31st, 2019. The median follow-up was 61 (range 0-168) month. All statistical analyses were performed using SPSS 26.0 (IBM, Chicago, IL, USA) software.

RESULTS: 46 patients (48%) were followed up for more than 5 years, 18 patients (19%) for more than 10 years. The 5-year and 10-year survival rates for rare non-invasive pancreatic tumours were 72% and 55% respectively. The proportion of rare tumour entities (non-ductal and non-neuroendocrine) increased continuously and statistically significantly (p = 0.004) from 4.2 to 12.3% in our clinic between 1999 and 2019. If there is no invasive growth yet, there is a varying risk of malignant degeneration in the course of the disease. Therefore, the indication for pancreatic resection is still the subject of discussion.

CONCLUSION: The long-term prognosis of rare epithelial pancreatic tumours after R0 resection-even if they are already malignant-is much better than that of ductal pancreatic cancer.

PMID:39002034 | DOI:10.1007/s00432-024-05884-2

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Evaluating the expression pattern of ATXN1 and CDC42EP1 genes and related long noncoding RNAs in oral squamous cell carcinoma

Mol Biol Rep. 2024 Jul 13;51(1):796. doi: 10.1007/s11033-024-09719-8.

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a significant health issue worldwide, and the expression of long non-coding RNAs (lncRNAs) are altered in these malignancies. The present study evaluated the expression level of ATXN1 CDC42EP1 genes and the lncRNAs related to these genes (lnc-ATXN1L, lnc-ATXN1, lnc-ATXN10, and lnc-CDC42EP1) in paraffin blocks of oral and pharyngeal squamous cell carcinoma (SCC) samples from patients referred to Amir Alam Hospital in Tehran, Iran.

METHODS AND RESULTS: This cross-sectional study was conducted on 76 paraffin blocks of oral and pharyngeal squamous cell carcinoma (SCC) samples from patients referred to Amir Alam Hospital in Tehran. The expression levels of ATXN1, CDC42EP1, lnc-ATXN1L, lnc-ATXN1, lnc-ATXN10, and lnc-CDC42EP1 were measured in all samples using a qPCR Master Mix kit. Real-time PCR was used to perform the reactions, and GAPDH was considered the housekeeping gene. Statistical analyses were conducted utilizing the Statistical Package for the Social Sciences (SPSS) version 22.0. The expression of lnc-ATXN1, lnc-ATXN10, and lnc-CDC42EP1 significantly differed between the two groups. All of them were downregulated (p < 0.05), and no significant difference was observed between the SCC samples and the adjacent tissue in other genes (p > 0.05). The expression of genes was not related to age, sex, size, and tumor location (p > 0.05).

CONCLUSIONS: Dysexpression of lnc-ATXN1, lnc-ATXN10, and lnc-CDC42EP1 can be used for diagnosing OSCC.

PMID:39002033 | DOI:10.1007/s11033-024-09719-8

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Genome-wide association study on meningioma risk in Japan: a multicenter prospective study

J Neurooncol. 2024 Jul 13. doi: 10.1007/s11060-024-04727-x. Online ahead of print.

ABSTRACT

PURPOSE: Although meningiomas are the most common primary intracranial tumors, their genetic etiologies have not been fully elucidated. To date, only two genome-wide association studies (GWASs) have focused on European ancestries, despite ethnic differences in the incidence of meningiomas. The aim of this study was to conduct the first GWAS of Japanese patients with meningiomas to identify the SNPs associated with meningioma susceptibility.

METHODS: In this multicenter prospective case-control study, we studied 401 Japanese patients with meningioma admitted in five institutions in Japan, and 50,876 control participants of Japanese ancestry enrolled in Biobank Japan.

RESULTS: The quality control process yielded 536,319 variants and imputation resulted in 8,224,735 variants on the autosomes and 224,820 variants on the X chromosomes. This GWAS eventually revealed no genetic variants with genome-wide significance (P < 5 × 10 – 8) and observed no significant association in the previously reported risk variants rs11012732 and rs2686876 due to low minor allele frequency in the Japanese population.

CONCLUSION: This is the first GWAS of meningiomas in East Asian populations and is expected to contribute to the development of GWAS research for meningiomas.

PMID:39002029 | DOI:10.1007/s11060-024-04727-x

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Stereotactic radiosurgery versus combined stereotactic radiosurgery and bevacizumab for recurrent glioblastoma; a systematic review and meta-analysis of survival

Neurosurg Rev. 2024 Jul 13;47(1):323. doi: 10.1007/s10143-024-02585-9.

ABSTRACT

Recurrent glioblastoma (rGBM) is a brain tumor that is resistant to standard treatments. Although stereotactic radiosurgery (SRS) is a non-invasive radiation technique, it cannot fully prevent tumor recurrence and progression. Bevacizumab blocks tumor blood supply and has been approved for rGBM. However, the best way to combine SRS and bevacizumab is still unclear. We did a systematic review and meta-analysis of studies comparing SRS alone and SRS plus bevacizumab for rGBM. We searched three databases for articles published until June 2023. All statistical analysis was performed by STATA v.17. Our meta-analysis included 20 studies with 926 patients. We found that the combination therapy had a significantly lower rate of overall survival (OS) than SRS alone at 6-month 0.77[95%CI:0.74-0.85] for SRS alone and (100%) for SRS plus bevacizumab. At 1-year OS, 0.39 [95%CI: 0.32-0.47] for SRS alone and 0.61 [95%CI:0.44-0.77] for SRS plus bevacizumab (P-value:0.02). However, this advantage was not seen in the long term (18 months and two years). Additionally, the combination therapy had lower chances of progression-free survival (PFS) than SRS alone at the 6-month and 1-year time points, but the differences were insignificant. Our study indicates that incorporating bevacizumab with SRS may lead to a short-term increase in OS for rGBM patients but not long-term. Additionally, the PFS rate did not show significant improvement in the group receiving combination therapy. Further clinical trials are necessary to validate the enhanced overall survival with combination therapy for rGBM.

PMID:39002028 | DOI:10.1007/s10143-024-02585-9

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Death anxiety among caregivers of patients with advanced cancer: a cross-sectional survey

Support Care Cancer. 2024 Jul 13;32(8):510. doi: 10.1007/s00520-024-08707-9.

ABSTRACT

PURPOSE: This study aimed to investigate death anxiety (DA) in caregivers of patients with advanced cancer and identify associated factors in the context of Chinese culture.

METHODS: Caregivers (N = 588) of advanced cancer patients in a tertiary cancer hospital completed anonymous questionnaire surveys. Measures included the Chinese version of the Templer Death Anxiety Scale (C-T-DAS), the Quality-of-Life Scale, the State-Trait Anxiety Scale, and the Social Support Rating Scale. Data were analyzed in SPSS (IBM Corp, Armonk, NY, USA) using descriptive statistics, Pearson’s correlation test, and linear regression.

RESULTS: Respondents returned 588 (93.03%) of the 632 questionnaires. The total C-T-DAS score was 7.92 ± 2.68 points. The top-scoring dimension was “Stress and pain” (3.19 ± 1.29 points), followed by “Emotion” (2.28 ± 1.31 points) and “Cognition” (1.40 ± 0.94 points). In contrast, the lowest-scoring dimension was “Time” (1.06 ± 0.77 points). Factors associated with DA (R2 = 0.274, F = 13.348, p < 0.001) included quality of life (QoL), trait anxious personality, social support, caregiver length of care, caregiver gender, and patients’ level of activities of daily living (ADL).

CONCLUSIONS: Our results demonstrated high levels of DA in caregivers of patients with advanced cancer. Generally, female caregivers and those with low social support had high DA. Caregivers caring for patients with low ADL levels or with a low QoL and trait anxious personality reported high DA. Certain associated factors help to reduce caregivers DA. Social interventions are recommended to improve the end-of-life transition and trait anxious personality as well as quality of life for caregivers.

PMID:39002026 | DOI:10.1007/s00520-024-08707-9

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Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis

Eur J Clin Pharmacol. 2024 Jul 13. doi: 10.1007/s00228-024-03730-5. Online ahead of print.

ABSTRACT

OBJECTIVE: Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism.

METHODS: We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes.

RESULTS: Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, – 3.72 to – 0.15) and etelcalcetide (- 7.80, – 11.80 to – 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, – 9.73 to – 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, – 6.72 to – 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, – 8.91 to – 2.37), calcitriol (- 9.36, – 14.81 to – 3.92), and paricalcitol (- 9.30, – 13.78 to – 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions.

CONCLUSION: The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

PMID:39002024 | DOI:10.1007/s00228-024-03730-5

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Clinical Features of ACPA-Negative and ACPA-Positive Variants of Rheumatoid Arthritis

Dokl Biochem Biophys. 2024 Jul 13. doi: 10.1134/S1607672924700996. Online ahead of print.

ABSTRACT

The aim of the study was to investigate the features of the clinical picture of the disease in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis.

MATERIALS AND METHODS: : The study included patients with a reliable diagnosis of rheumatoid arthritis (RA) according to the criteria of ACR/EULAR 2010. Depending on the ACPA values, two groups of patients were recruited: ACPA-positive and ACPA-negative, comparable in gender, age, duration of the disease, and therapy. The nature of the onset and course of the disease and the activity of RA were evaluated (according to the DAS28, SDAI, CDAI indices).

RESULTS AND DISCUSSION: : The study involved 79 patients with ACPA-negative variant of RA and 79 ACPA-positive patients. The age of patients (Me [IR] (in years)) with the ACPA(-) variant was 52 [39; 62]; with the ACPA(+) variant, 54 [42; 62]; the duration of the disease (in months) was 59 [23; 122] and 48 [17; 84], respectively. In ACPA(+) patients, a higher disease activity was determined (by the indices DAS 28crp, DAS28esr, SDAI, CDAI), higher values of C-reactive protein and erythrocyte sedimentation rate, and a greater number of painful and swollen joints (p < 0.05). According to the localization of the involved joints, arthritis of the proximal interphalangeal, metacarpal, wrist and shoulder joints was more often determined in ACPA(+) patients. Systemic manifestations of RA at the time of examination and in the anamnesis were statistically significantly more common in ACPA(+) (32.9%) than in ACPA(-) (17.7%) patients. Of the systemic manifestations, rheumatoid nodules were more common in ACPA(+) patients, whereas a tendency to a higher frequency of neuropathy, sclerites, and episcleritis was revealed in ACPA(-) patients.

CONCLUSIONS: . In patients with ACPA(-) subtype, clinical signs of joint damage and the inflammatory component are less pronounced compared to ACPA(+). However, the mixed picture of manifestation, the less “bright” course of the disease, the absence of characteristic immunological biomarkers necessitate long-term and careful monitoring of this group of patients. At the same time, the subjective severity of the disease and dysfunction due to ankylosing joints do not differ from the ACPA(+) variant of RA.

PMID:39002008 | DOI:10.1134/S1607672924700996

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Anti-Carbamylated Protein Antibodies in ACPA-Negative and ACPA-Positive Patients with Rheumatoid Arthritis

Dokl Biochem Biophys. 2024 Jul 13. doi: 10.1134/S1607672924700960. Online ahead of print.

ABSTRACT

The objective of this study was to assess the level of antibodies to carbamylated proteins and analyze the clinical and immunological associations in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis.

MATERIALS AND METHODS: . The study involved 150 patients with a reliable diagnosis of rheumatoid arthritis and 25 patients as healthy controls. Depending on ACPA values, two groups of patients were recruited: ACPA-positive (n = 75) and ACPA-negative (n = 75). RA activity was assessed by the DAS28 index. Determination of antibodies to carbamylated proteins was performed by enzyme-linked immunosorbent assay (BlueGene Biotech, China). Quantitative determination of ACPA in serum was performed by enzyme immunoassay using a commercial reagent kit (AxisShield, UK; upper limit of normal 5.0 U/mL; Orgentec, Germany; upper limit of normal 20.0 U/mL).

RESULTS AND DISCUSSION: . Median anti-CarP in patients with RA was 126.2 [100.83; 157.41] ng/mL and was statistically significantly higher (p < 0.001) than in healthy controls (88.89 [70.53; 107.75] ng/mL). Among all patients with RA, 50 (33.3%) were anti-Carp-positive (22 (29.3%) in the ACPA(+) group and 28 (37.3%) in the ACPA(-) group), and one (2%) volunteer from healthy controls was anti-CarP(+) (p = 0.002). In ROC analysis performed to assess the diagnostic significance of anti-CarP for RA for all patients with RA, the area under the curve was 0.783 ± 0.047 with 95% CI: 0.691-0.874 (p < 0.001), with a cut-off point of 143 ng/mL, specificity 96%, sensitivity 36.7%. In the ACPA(+) RA group, the erosion count was statistically significantly higher (p = 0.044) in anti-CarP(+) patients than in anti-CarP(-) patients. A weak direct correlation between anti-CarP and DAS28 was found in the ACPA(-) RA group.

CONCLUSIONS: . We studied the predictive value of anti-CarP as an auxiliary biomarker in ACPA(+) and ACPA(-) subtypes of RA. ACPA(+) anti-CarP(+) patients have a more “erosive” subtype of the disease than ACPA(+) anti-CarP(-) patients. In ACPA(-) patients, anti-CarP helps to identify a more erosive subtype of the disease, and among ACPA(-) patients it helps to reduce the proportion of seronegative patients. Further studies are required to determine the optimal standards for the laboratory diagnosis of anti-CarP and to clarify the diagnostic potential of these ABs as part of the differential diagnosis of arthritis in other rheumatic diseases.

PMID:39002007 | DOI:10.1134/S1607672924700960