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Tumor-associated macrophages of the M1/M2 phenotype are involved in the regulation of malignant biological behavior of breast cancer cells through the EMT pathway

Med Oncol. 2022 May 16;39(5):83. doi: 10.1007/s12032-022-01670-7.

ABSTRACT

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. More and more studies have shown that the tumor immune microenvironment (TME) of TNBC is closely related to its poor prognosis and early metastasis. We try to explain how tumor-associate macrophages (TAMs), an important component of the TME, function in the matrix of TNBC. Therefore, we induced THP-1 cells to become M1-TAMs and M2-TAMs, investigated their influence on breast cancer cells. 82 TNBC paraffin samples were made into tissue microarrays. The expression of macrophages makers were measured by immunohistochemistry. Scratch assay, Transwell assay, CCK-8 cell proliferation assay were performed in the co-culture system of breast cancer cells lines and macrophages to observe the invasion and proliferation ability of breast cancer cell lines. Western Blot (WB) was performed to detect the expression of E-cadherin (CDH1) and N-cadherin (CDH2). M2-TAMs were more numerous than M1-TAMs in the matrix of TNBC cancer nests and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of TNBC cells. M1-TAMs had inhibitory effects. In MCF-7 cells, WB showed a decrease in CDH1 and an increase in CDH2. In MDA-MB-231 cells and BT549 cells, CDH2 expression was reduced and CDH1 expression was increased. All of the above results were statistically significant, p < 0.001. M2-TAMs were more numerous in TNBC and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of breast cancer cells. The mechanism may be related to the epithelial-mesenchymal transition.

PMID:35570226 | DOI:10.1007/s12032-022-01670-7

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Application of different methods used to measure the apparent diffusion coefficient of renal cell carcinoma on the same lesion and its correlation with ISUP nuclear grading

Abdom Radiol (NY). 2022 May 16. doi: 10.1007/s00261-022-03541-1. Online ahead of print.

ABSTRACT

PURPOSE: To determine the most frequently used different apparent diffusion coefficient (ADC) measurement methods in renal cell carcinoma (RCC), and their correlation with the International Society of Urological Pathology (ISUP) histologic grading system.

METHODS: A total of 99 patients who underwent diffusion-weighted imaging and whose pathologic diagnosis of RCC was confirmed were included in the study. As a result of a literature review, region of interest (ROI) selection and measurement methods were determined in five ways. These included a small ROI (ADC1) on the solid part of the lesion showing the most restriction; a large ROI (ADC2) on the solid part of the lesion showing restriction; ROI (ADC3) that covered the lesion in the cross-section with the largest diameter, which was obtained by placing ROIs (ADC4) covering the lesion on all sections of the lesion; three small ROIs (ADC5) on solid parts of the lesion showing the most restriction. Then, ADC measurements were made from the contralateral normal kidney parenchyma. Tumors were pathologically subdivided [71 clear cell RCCs (ccRCC), 17 chromophobe RCCs (chRCC), 11 papillary RCCs (pRCC)], and graded according to the ISUP nuclear grading system (42 high-grade, 57 low-grade). Data were analyzed statistically.

RESULTS: In all measurement methods, ADC values of RCCs were statistically significantly lower than normal kidney ADC values. There were no differences between the ADC3 and ADC4 measurements of RCCs (p = 0.999). There was a statistical difference in other measurement methods (p < 0.001). There were differences between ccRCCs and pRCCs and chRCCs in all measurement methods. In all measurement methods, pRCC and chRCC ADC values ​​were lower than ccRCC ADC values. When ISUP nuclear grading and ADC values ​​were compared, there was a statistically inverse correlation between all ADC measurements. The strongest correlation was found in the ADC1 and ADC5 measurements. When the ADC values ​​of ISUP low and high-grade groups were compared, a significant difference was found in the ADC5 measurement method (p = 0.046).

CONCLUSION: According to the findings of the study, ADC5 is the measurement method that shows the best correlation with the ISUP histologic grading system. Therefore, we think that ADC5 can be the primary measurement method for determining the ADC value of RCCs.

PMID:35570223 | DOI:10.1007/s00261-022-03541-1

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Relationship between SARS-CoV-2 antibody titer and the severity of COVID-19

J Microbiol Immunol Infect. 2022 May 5:S1684-1182(22)00059-7. doi: 10.1016/j.jmii.2022.04.005. Online ahead of print.

ABSTRACT

BACKGROUND: It remains unclear whether high titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies aggravate clinical manifestations in patients or whether severe clinical manifestations result in high antibody titers. Thus, we investigated the cause-effect relationship between SARS-CoV-2 antibody titers and disease severity.

METHODS: We prospectively enrolled patients admitted with the diagnosis of coronavirus disease-19 (COVID-19) from February 2020 to August 2020. We measured SARS-CoV-2 antibody titers, namely anti-receptor-binding domain (RBD) antibody and neutralizing antibody (NAb), from blood samples and calculated the chest radiograph (CXR) scores of the patients to evaluate the severity of COVID-19.

RESULTS: Overall, 40 patients with COVID-19 were enrolled. Pneumonia was observed in more than half of the patients (25/40, 60%). SARS-CoV-2 antibody titers were higher in patients who were aged >60 years (anti-RBD antibodies, P = 0.003 and NAb, P = 0.009), presented with pneumonia (P = 0.006 and 0.007, respectively), and required oxygen therapy (P = 0.003 and 0.004, respectively) than in those who were not. CXR scores peaked (at 15-21 days after the onset of symptoms) statistically significantly earlier than SARS-CoV-2 antibody titers (at 22-30 days for NAb and at 31-70 days for anti-RBD antibody). There was a close correlation between the maximum CXR score and the maximum SAR-CoV-2 antibody titer.

CONCLUSIONS: Based on the comparison of the peak time of SARS-CoV-2 antibody titers with the CXR score after symptom onset, we suggest that severe clinical manifestations result in high titers of SARS-CoV-2 antibodies.

PMID:35570185 | DOI:10.1016/j.jmii.2022.04.005

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Phonatory function and characteristics of voice in recovering COVID-19 survivors

Eur Arch Otorhinolaryngol. 2022 May 15. doi: 10.1007/s00405-022-07419-2. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to evaluate the phonatory function of recovered COVID-19 survivors. The universal outbreak of COVID-19 led to the occurrence of otolaryngological manifestations that raised concerns about the assessment of the phonatory function in recovering patients.

METHODS: This is a prospective, cross-sectional, case-controlled study carried out on 364 laboratory-confirmed non-critical COVID-19 survivors and 100 as healthy controls. The study participants were classified into two groups according to the disease severity. Group1 comprised 212 survivors who recovered from pneumonia and group 2 was made up of 152 survivors of severe pneumonia. All patients were subjected to an auditory perceptual assessment of the voice (APA) and Maximum Phonation Time (MPT) measurements.

RESULTS: Phonasthenic manifestations were significantly more frequent in COVID-19 survivors than in controls (P < 0.000) with a higher percentage recorded among severe pneumonia survivors (87.5%) than among pneumonia survivors (60.8%) with a P value of < 0.01. Dysphonia and excessively soft loudness were significantly more common among survivors than among controls (P < 0.002 and P < 0.000, respectively) with no significant difference between the patient groups. The MPT was significantly shorter among survivors than among controls (P < 0.000). The mean MPT was 15.97 s in the control group, 10.72 s in the pneumonia group, and 8.88 s in the severe pneumonia group, with the differences between the groups being statistically significant (P < 0.000), suggesting a higher impairment of lung volume and phonatory function in severe cases.

CONCLUSIONS: Phonasthenia, dysphonia, and decreased MPT could be otolaryngological manifestations of COVID-19. Laryngeal function assessment should be considered in COVID-19 survivors.

PMID:35570204 | DOI:10.1007/s00405-022-07419-2

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An Example of an Elegant Report on a Complex Issue: Mixity in Bipolar Disorder

Am J Geriatr Psychiatry. 2022 Apr 20:S1064-7481(22)00390-6. doi: 10.1016/j.jagp.2022.04.005. Online ahead of print.

NO ABSTRACT

PMID:35570182 | DOI:10.1016/j.jagp.2022.04.005

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Should we screen for Müllerian anomalies following diagnosis of a congenital renal anomaly?

J Pediatr Urol. 2022 Apr 28:S1477-5131(22)00164-4. doi: 10.1016/j.jpurol.2022.04.017. Online ahead of print.

ABSTRACT

INTRODUCTION: Despite the well-established embryological relationship in the development of renal and Müllerian structures, no clear guidelines exist regarding screening for Müllerian anomalies (MA) in the setting of a renal anomaly (RA). Delayed diagnosis of MA can have significant reproductive consequences.

OBJECTIVE: To investigate the prevalence of coexisting MA in patients with congenital RA.

STUDY DESIGN: This is a retrospective cohort study of females age 12-35 years with a diagnosis of RA, identified by diagnosis codes, who were followed for care between 2013 and 2020. Data were collected on demographics, medical history, clinical presentation, and imaging studies. Descriptive statistics were used to summarize the data. This study was IRB approved.

RESULTS: A total of 465 patients were included in this study, of whom 326 patients (70.3%) had a pelvic evaluation during the study period. Of these 326 patients, 125 (38.3%) were found to have coexistent MA. About one-third of patients who underwent pelvic evaluation due to pain were found to have MA. For 69.6% (87/125) of patients with MA, the RA was diagnosed prior to the MA. The average age at time of RA diagnosis was 6.4 ± 8.8 years and the average age of MA diagnosis was 16.4 ± 6.9 years. Forty-eight (38.4%) patients had obstructive anomalies. Of the Müllerian obstructions, 93.8% were treated with urgent surgery and the remainder started on hormonal suppression. The prevalence of MA was dependent on the RA diagnosis (Figure). Of patients with a solitary kidney, 67.1% were diagnosed with MA. For other parenchymal RA, the prevalence of MA was 20-23%. In patients with solitary kidney, uterus didelphys was the most common MA (52.1%). Thirty percent of patients with a solitary kidney were diagnosed with an obstructive MA.

CONCLUSIONS: In this study, 38% of patients with RA who underwent a pelvic evaluation were found to also have MA. Our study shows the strongest association between MA and solitary kidney, but also emphasizes a significant risk with other RA. Almost 40% of patients with diagnosed MA were found to have an obstruction that required urgent treatment. Delays in diagnosis and treatment of Müllerian obstructions can be detrimental for future reproductive health, due to risk of chronic pain, infertility, infection, and endometriosis. Given the high prevalence of MA in patients with RA, especially those with congenital solitary kidney, routine screening with pelvic ultrasound should be performed around the age of expected menarche.

PMID:35570178 | DOI:10.1016/j.jpurol.2022.04.017

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Influence of intraoperative fluid replacement on ampicillin serum levels and surgical site infections

Surgery. 2022 May 12:S0039-6060(22)00225-2. doi: 10.1016/j.surg.2022.03.041. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical site infections (SSI) occur despite antimicrobial prophylaxis and increase postoperative morbidity and mortality. This could be caused by an intraoperative decrease in antibiotic serum concentrations such as ampicillin after major abdominal surgery due to blood loss and fluid therapy, which possibly promotes SSI. This hypothesis was tested in the present study.

METHODS: This pilot study was performed as a prospective observational trial between March 2018 and May 2019. Ampicillin/sulbactam was administered intravenously during anesthesia induction. Fluid replacement was guided based on hemodynamic variables, including analysis of pulse pressure variation. The primary outcome was ampicillin serum level (ASL), measured after administration and hourly within 4 hours. The incidence of SSI at hospital discharge was the secondary outcome. Linear mixed and logistic regression models were used for statistical analyses.

RESULTS: After screening of 133 adult patients, 129 were enrolled, and 102 completed the study protocol. No correlation was found between the volume of intraoperative fluids and ASL, nor was any association found between ASL and SSI. Based on 5 SSI cases, SSI were associated with higher intraoperative fluid volume. ASL was sufficient to provide intraoperative coverage for all potential bacterial strains.

CONCLUSION: Intraoperative fluid replacement had no effect on ASL up to 4 hours after ampicillin/sulbactam administration. SSI were within an acceptable range, indicating adequate antimicrobial prophylaxis, so intraoperative control of ASL does not seem necessary. In conclusion, contrary to our initial hypothesis, ASL is not influenced by volume turnover or blood loss during major surgery and therefore does not affect SSI.

PMID:35570162 | DOI:10.1016/j.surg.2022.03.041

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Three-Dimensional Virtual Reality Spinal Cord Stimulator Training Improves Trainee Procedural Confidence and Performance

Neuromodulation. 2022 May 12:S1094-7159(22)00631-6. doi: 10.1016/j.neurom.2022.03.005. Online ahead of print.

ABSTRACT

OBJECTIVE: This study evaluates the use of a three-dimensional virtual reality spinal cord stimulator (SCS) training system to enhance trainee confidence and technical proficiency with interlaminar epidural access and SCS placement.

MATERIALS AND METHODS: A total of 14 trainees comprising pain fellows and residents were recruited. Experience and confidence levels were established through pre- and postsurveys. Each trainee performed two sessions placing SCS leads using the training device. In between attempts, a standardized teaching session was performed with the simulator. Performance during each attempt was assessed through objective measures such as needle angle and an evaluation rubric Pain Procedure Rating System (PaPRS). Statistical analysis was performed through paired sample t-test to evaluate a single group between separate trials, whereas unpaired t-test was used to assess the difference between the two groups at baseline or within a single trial.

RESULTS: Participants had statistically significant improvements in their ability to safely access the epidural space (57.1% improving to 100%, p < 0.01) and to effectively drive percutaneous leads to the target level (7.1% improving to 71.4%, p < 0.001). The mean confidence levels improved by 71.4% for interlaminar epidural access (p < 0.001) and 306% for SCS placement (p < 0.001). The mean procedural efficiency (total procedure time) improved by 43.2% (p < 0.001). The PaPRS total score increased by an average of 73.3% (p < 0.001).

CONCLUSIONS: Virtually simulated neuromodulation training is a viable and effective method of augmenting neuromodulation education. Such didactics are options vital for neuromodulation training, given variable exposure during residency and fellowship.

PMID:35570148 | DOI:10.1016/j.neurom.2022.03.005

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Pre-analytical processing protocol of breast biopsies affects multigene panel results

Int J Exp Pathol. 2022 Jun;103(3):112-120. doi: 10.1111/iep.12444.

ABSTRACT

The creation of multigene panels for prognostic and predictive purposes allows a more accurate indication of adjuvant chemotherapy for patients with breast cancer. In a previous study, we reproduced a multigene panel of 21 genes based on the commercial Oncotype-DX method. We submitted 183 embedded specimens obtained from breast surgery on patients with locoregional disease (stages I to III) between 2005 and 2010 performed at the Hospitals of the Medical School of the ABC Foundation. When we analysed the correlations between the score of the multigene panel and the progression-free interval (PFI) in all patients, we did not find a statistically significant association. However, when we selected only the 71 samples that had amplification of at least eight non-housekeeping genes, we observed that those with scores above the 75th percentile had a significantly lower PFI (p = .0054). Samples processed with nonbuffered formaldehyde were associated with a worse quality of extracted RNA (p = .004) and a significantly higher multigene panel score (p = .021). We conclude that variations in the pre-analytical processing of specimens destined for multigene panel amplification can significantly affect the results, with a potential impact on clinical management.

PMID:35569033 | DOI:10.1111/iep.12444

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Difference of income inequalities of denture use by co-payment rates: A JAGES cross-sectional study

Community Dent Oral Epidemiol. 2022 May 15. doi: 10.1111/cdoe.12749. Online ahead of print.

ABSTRACT

OBJECTIVES: Studies suggest that wearing dentures to restore missing teeth can have a positive impact on health status. However, income inequalities in denture wearing exist. The aim of this study was to investigate how differing co-payment rates under the current Japanese Universal Health Insurance Coverage System affect income inequalities in denture non-use among older adults with severe tooth loss.

METHODS: This cross-sectional study used data from the 2019 Japan Gerontological Evaluation Study (JAGES). Self-administered questionnaires were mailed to 345 356 independent people who did not receive long-term care insurance benefits and were aged ≥65 years. The dependent variable was denture non-use, and the independent variable was the equivalent annual household income. The Slope Index of Inequality (SII) and Relative Index of Inequality (RII) were used with regression-based approaches to determine both absolute and relative inequalities in denture non-use by co-payment rates. The covariates were sex, age, years of education, number of teeth and comorbidities.

RESULTS: Of the 240 889 responses received (response rate =69.9%), we analysed 21 594 participants who fulfilled the inclusion criteria. The mean age was 72.8 years (standard deviation =4.1), and 57.6% were men. For 30 per cent, 20 per cent and 10 per cent co-payment rates, the percentages of people who did not use dentures and had severe tooth loss (≤9 teeth) were 18.3%, 13.3%, and 8.5%, respectively. All analyses confirmed significant inequalities in denture non-use. The lower the co-payment rate, the smaller the inequalities. SIIs for each co-payment rate were as follows: 30 per cent =13.35% (95% confidence interval [CI] = 9.61-17.09); 20 per cent =7.85% (95% CI = 4.88-10.81); and 10 per cent =4.85% (95% CI = 2.55-7.16). Inclusion of interaction term between income and co-payment rate significantly lowered the inequalities by co-payment rate in logistic regression analysis and SII. For RII, although the interaction was not statistically significant, a similar trend was observed.

CONCLUSIONS: Income inequalities in denture use existed among older adults with severe tooth loss in Japan, and the inequalities appeared to be greater when the co-payment rate was higher.

PMID:35569009 | DOI:10.1111/cdoe.12749