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Evidence for heterogeneity in response to treatment in mammary tumors of dogs as happens in humans

Vet Res Commun. 2022 May 16. doi: 10.1007/s11259-022-09934-3. Online ahead of print.

ABSTRACT

Tumors are formed by various clones developed over a long time. This gives rise to a heterogeneous nature. This heterogeneity is the hardest challenge in the treatment of cancers because it is the main reason for drug resistance. This is a well-known fact in human cancer. Therefore, we have reasoned that if the tumor heterogeneity in canine mammary gland tumors (CMGTs) could be shown by an ex vivo assay, which will be used first time in veterinary oncology practice, this could be used further in clinics. To achieve this, twenty-six patients were included in the study. Tumor tissues were obtained from animals during routine surgery. Tumor cells were isolated and seeded ex vivo. The cells were exposed to anticancer drugs that are clinically used. Seven days after the treatment, chemosensitivity has luminometrically been assayed by ATP-tumor chemosensitivity assay (ATP-TCA). It has clearly been shown that all the tumor tissues have responded to treatment differently, implying that heterogeneity exists in mammary tumors. There has also been found that there was a weak to moderate statistically significant correlation between tumor size and drug index. However, there has been no correlation between drug index and metastasis to lymph nodes. Hyperplasic areas had relatively higher PCNA values. The results of our study demonstrate the heterogeneity in responses to in vitro drugs. Clinical trials based on test results and follow-up studies with large numbers of animals are needed to prove that such chemotherapeutic activity assessment tests can be clinically useful in predicting drug responses in CMGTs.

PMID:35570257 | DOI:10.1007/s11259-022-09934-3

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Prevalence of non-carious cervical lesions and orthodontic treatment: a retrospective study

Prog Orthod. 2022 May 16;23(1):17. doi: 10.1186/s40510-022-00409-4.

ABSTRACT

BACKGROUND: This study aimed to assess the distribution of non-carious cervical lesions (NCCLs) by tooth type, investigate the prevalence of NCCLs in patients undergoing orthodontic treatment, and identify the possible associated factors.

MATERIAL AND METHODS: A total of 160 patients were enrolled in this retrospective study. Data on the following variables were collected from pre-and post-orthodontic treatment records: age, sex, Angle’s malocclusion, facial pattern, number of activation sessions, compensatory treatment, and retreatment. Frontal, right and left lateral intraoral photographs of each patient were evaluated to identify the presence or absence of NCCLs in each tooth and assess the distribution of NCCLs in the 3840 teeth from the enrolled patients. Furthermore, patients were classified as NCCLs present, irrespective of the number of NCCLs on the teeth or NCCL absent. Bivariate and multivariate Poisson regression analyses with robust variance were used to assess the association between the NCCLs and each independent variable. Prevalence ratio and 95% confidence intervals were calculated and p < 0.05 was considered statistically significant.

RESULTS: The prevalence of NCCLs before and after orthodontic treatment was 22.71% and 30.91%, respectively. Premolars were the most affected teeth, followed by the first molars, canines, and incisors. After statistical analysis, age was found to be the variable factor that influenced the prevalence ratio, with NCCL being the most prevalent when orthodontic treatment was performed in adulthood.

CONCLUSIONS: Premolars were most commonly affected by NCCLs. Furthermore, age seemed to contribute to the increased prevalence of NCCLs in adults undergoing orthodontic treatment.

PMID:35570252 | DOI:10.1186/s40510-022-00409-4

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Benefits and Risks Associated with Low-Dose Aspirin Use for the Primary Prevention of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Control Trials and Trial Sequential Analysis

Am J Cardiovasc Drugs. 2022 May 16. doi: 10.1007/s40256-022-00537-6. Online ahead of print.

ABSTRACT

BACKGROUND: The role of aspirin in cardiovascular primary prevention remains controversial. Moreover, evidence for the potential benefits of aspirin in patients with high cardiovascular risk remains limited.

OBJECTIVE: The aim of this study was to explore the role of low-dose aspirin in primary prevention.

METHODS: The PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized clinical trials (RCTs) from the date of inception to August 2021. The efficacy outcomes were major adverse cardiovascular events (MACE), myocardial infarction (MI), ischemic stroke (IS), all-cause mortality, and cardiovascular mortality, whereas safety outcomes were major bleeding, intracranial hemorrhage, and gastrointestinal (GI) bleeding. Subgroup analyses were based on different cardiovascular risks and diabetes statuses. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using the fixed- and random-effects models, and trial sequential analysis (TSA) was conducted to determine the robustness of the results.

RESULTS: A total of 10 RCTs fulfilled the inclusion criteria. The use of aspirin was associated with a significant reduction in the risk of MACE (RR 0.89, 95% CI 0.84-0.93), MI (RR 0.86, 95% CI 0.78-0.95), and IS (RR 0.84, 95% CI 0.76-0.93); however, aspirin also increased the risk of safety outcomes, i.e. major bleeding (RR 1.42, 95% CI 1.26-1.60), intracranial hemorrhage (RR 1.33, 95% CI 1.11-1.59), and GI bleeding (RR 1.91, 95% CI 1.44-2.54). Subgroup analyses revealed that in the absence of a statistically significant interaction, a trend toward a net benefit of lower incidence of cardiovascular events (number needed to treat of MACE: high risk: 682 vs. low risk: 2191) and lesser risk of bleeding events (number needed to harm of major bleeding: high risk: 983 vs. low risk: 819) was seen in the subgroup of high cardiovascular risk. Meanwhile, the greater MACE reduction was also detected in the high-risk group of diabetes or nondiabetes patients. Furthermore, a post hoc subgroup analysis indicated a significant rate reduction in patients aged ≤ 70 years but not in patients aged > 70 years. TSA confirmed the benefit of aspirin for MACE up to a relative risk reduction of 10%.

CONCLUSION: The current study demonstrated that the cardiovascular benefits of low-dose aspirin were equally balanced by major bleeding events. In addition, the potential beneficial effects might be seen in the population ≤ 70 years of age with high cardiovascular risk and no increased risk of bleeding.

PMID:35570250 | DOI:10.1007/s40256-022-00537-6

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The outcomes of primary pars plana vitrectomy alone as a first surgical procedure in pediatric rhegmatogenous retinal detachment

Int Ophthalmol. 2022 May 16. doi: 10.1007/s10792-022-02346-x. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the characteristics and analyze the results of patients who underwent pars plana vitrectomy (PPV) as the first surgery due to rhegmatogenous retinal detachment (RRD) in pediatric age.

METHODS: The records of pediatric patients who underwent PPV alone due to RRD were reviewed retrospectively. The best corrected visual acuity (BCVA) values were recorded before and after the surgery. Complications during and after the operation, postoperative recurrences were followed-up.

RESULTS: One hundred and six patients included in the study were followed-up for an average of 24.20 ± 11.38 months. The final mean BCVA showed a statistically significant improvement compared to the initial mean BCVA (p < 0.001). During the postoperative follow-up period, recurrent retinal detachment was seen in 31.1% of patients. Anatomical success was achieved at a rate of 68.9% after the first surgery and increased to 95.3% after repeated operations (in 78.3% without any tamponade). Both anatomical and functional success of patients with proliferative vitreoretinopathy (PVR) grade C or worse and patients with macula-off retinal status were poorer (each p value < 0.05). The effect of the etiological factor on anatomical and functional success was not significant (each p value > 0.05).

CONCLUSION: Satisfactory results can be obtained with PPV alone in pediatric RRD. However, it should be noted that postoperative complications and recurrences occur at a high rate and that repeated surgeries are often required. The presence of PVR and macular involvement are seen as negative prognostic factors to the success of surgery.

PMID:35570251 | DOI:10.1007/s10792-022-02346-x

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Real-World Biologic Adherence, Persistence, and Monotherapy Comparisons in US Patients with Psoriasis: Results from IBM MarketScan® Databases

Adv Ther. 2022 May 16. doi: 10.1007/s12325-022-02155-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Limited real-world data are available comparing multiple biologics on their adherence, persistence, and the use of concomitant biologics in the treatment of moderate-to-severe psoriasis in clinical practice. The objective was to compare persistence of and adherence to ixekizumab (IXE) treatment, as monotherapy or with concomitant medication, versus patients receiving other commonly prescribed biologics.

METHODS: Patients who newly initiated IXE, adalimumab (ADA), etanercept (ETN), secukinumab (SEC), or ustekinumab (UST) in IBM MarketScan® databases with diagnosis of psoriasis were identified. Treatment comparisons on medication persistence, adherence, and monotherapy were based on balanced samples after inverse probability of treatment weighting (IPTW).

RESULTS: A higher proportion of patients receiving IXE had had previous biologic therapies (50.3%) versus other biologics (ADA: 9.1%, ETN: 10.9%, SEC: 33.9%, UST: 19.7%). Patients treated with IXE showed statistically (p < 0.001) greater persistence than patients treated with SEC, ADA, UST, or ETN at both 1-year follow-up and up to 3 years of follow-up. Adherence for patients treated with IXE was significantly (p < 0.001) higher compared to ADA, ETN, and UST at both 1-year follow-up and up to 3 years of follow-up. There was no significantly higher adherence in patients treated with IXE compared to those treated with SEC at 1-year follow-up, but IXE had higher adherence than SEC (p < 0.05) at 1-3 year follow-up. IXE showed longer time on monotherapy than ADA (p < 0.001), ETN (p < 0.001), SEC (p < 0.05), and UST (p < 0.001) for both 1-year and 1-3 year follow-up. Sensitivity analyses on persistence, adherence, and monotherapy with further model adjustments after IPTW confirmed the findings.

CONCLUSIONS: Patients treated with IXE were more persistent on and adherent to treatment and remained on monotherapy longer compared to those on all other commonly prescribed biologics combined or with individual biologics.

PMID:35570242 | DOI:10.1007/s12325-022-02155-9

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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