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Comparison of the Prognostic Outcome between High-Grade Ovarian Sertoli-Leydig Cell Tumors (SLCTs) and Low-Grade SLCTs

Yonsei Med J. 2021 Apr;62(4):366-369. doi: 10.3349/ymj.2021.62.4.366.

ABSTRACT

The purpose of the current study was to compare prognostic outcomes between patients with high-grade ovarian Sertoli-Leydig cell tumors (SLCTs) and those with other low-grade SLCTs. We retrospectively reviewed medical records for 24 patients pathologically diagnosed with SLCTs between 2006 to 2019 at two institutions. The patients were grouped according to pathological grade: SLCT was classified as grade 1, well differentiated; grade 2, intermediated differentiated; or grade 3, poorly differentiated (Meyer’s classification). Statistical analysis was performed to compare survival outcomes according to pathological grade. The median patient age was 42.5 years (range 16-75). Eighteen patients (75%) were International Federation of Gynecology and Obstetrics stage I, and none were diagnosed in stage IV. Nine patients (37.5%) were grade 3, and 15 patients (63.5%) were grades 1-2. When comparing clinical baseline characteristics of the grade 1-2 group with those of the grade 3 group, only serum CA125 level at diagnosis was significantly higher in the grade 3 group (38.34 vs. 382.29, p=0.002). Five patients experienced recurrence of grade 3 disease, while no recurrence was reported in grade 1-2 disease. Four of the five recurrent patients died. In result, grade 3 ovarian SLCT showed significantly poorer prognosis than grade 1-2 disease (overall survival, hazard ratio=14.25, 95% confidence interval=1.881-108.0; log-rank p=0.010). Our findings were consistent with the concept that patients with stage I/grade 1-2 tumors have a good prognosis without adjuvant chemotherapy. Since grade 3 ovarian SLCT appears to be relatively more fatal than grade 1 or 2, patients with grade 3 SLCT might require more aggressive surgical intervention and post-treatment surveillance.

PMID:33779091 | DOI:10.3349/ymj.2021.62.4.366

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Clinical Impact of Natural Killer Group 2D Receptor Expression and That of Its Ligand in Ovarian Carcinomas: A Retrospective Study

Yonsei Med J. 2021 Apr;62(4):288-297. doi: 10.3349/ymj.2021.62.4.288.

ABSTRACT

PURPOSE: Natural killer (NK) cells are innate immune cells with antitumor activity. NKG2D is the most important activating receptor expressed on the NK cell surface; this receptor binds to the ligands MICA/B and ULBPs to activate NK cells. The current study aimed to evaluate the expression of NKG2D by NK cells, and to the evaluate expression of its ligands in ovarian carcinomas; it also examined the clinical relevance of NK receptor/ligand expression by analyzing the relationship between expression, clinicopathological parameters, and prognosis.

MATERIALS AND METHODS: Formalin-fixed paraffin-embedded archival ovarian high-grade serous carcinoma (HGSC, n=79) tissue samples were used for tissue microarray analysis. The expressions of NK cell markers (CD56 and NKG2D) and NKG2D ligands (MICA/B, ULBP1, ULBP3, and ULBP2/5/6) in carcinoma tissues were evaluated by immunohistochemical staining, and the association between these results and clinical prognostic parameters was analyzed statistically.

RESULTS: ULBP1 was highly expressed in 51 cases (64.6%), and ULBP2/5/6 was highly expressed in 56 cases (70.9%) of HGSC. High expression of ULBP1 and ULBP2/5/6 was significantly associated with lower recurrence of HGSC, whereas high expression of ULBP3 was significantly associated with higher recurrence. Multivariate Cox regression analysis revealed that high expression of ULBP1 was associated with increased overall survival and a decreased hazard ratio (0.150, p=0.044), suggesting that it is an independent predictor of better survival.

CONCLUSION: High expression of ULBP1 predicts a better prognosis for HGSC, suggesting that ULBP1 expression could be a novel prognostic indicator in this subset of carcinomas.

PMID:33779082 | DOI:10.3349/ymj.2021.62.4.288

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Ten-Year Trends of Metabolic Syndrome Prevalence and Nutrient Intake among Korean Children and Adolescents: A Population-Based Study

Yonsei Med J. 2021 Apr;62(4):344-351. doi: 10.3349/ymj.2021.62.4.344.

ABSTRACT

PURPOSE: Metabolic syndrome (MetS) comprises a cluster of risk factors for future cardiovascular and metabolic diseases. Only a few recent studies have reported the trend in the prevalence of MetS in youth. This study aimed to analyze trends in the prevalence of MetS and nutrient intake in the last 10 years and investigate the changes in MetS components among Korean children and adolescents.

MATERIALS AND METHODS: We analyzed the data of 9513 children and adolescents aged 10-19 years from the 2008-2017 Korean National Health and Nutrition Examination Surveys. Diagnosis of MetS was based on the International Diabetes Federation (IDF) and modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria.

RESULTS: Based on the IDF criteria, MetS prevalence increased from 1.53% in 2008 to 3.19% in 2017 (p=0.007). Based on the NCEP-ATP III criteria, MetS prevalence increased from 2.18% in 2008 to 3.19% in 2017; however, the increase was not statistically significant. Daily calorie and fat intakes increased significantly during the study period. Among the risk factors that MetS comprises, the prevalence rates of central obesity, low high-density lipoprotein cholesterol levels, and high fasting glucose levels increased significantly.

CONCLUSION: Over the last 10 years, the prevalence of MetS has grown significantly with increasing calorie and fat intake in Korean children and adolescents. Central obesity and high-density lipoprotein cholesterol and fasting glucose levels have worsened. Therefore, active support and close monitoring are required to control MetS and prevent further increase in the prevalence of cardiovascular diseases.

PMID:33779088 | DOI:10.3349/ymj.2021.62.4.344

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Multiplexed measurement of candidate blood protein biomarkers of heart failure

ESC Heart Fail. 2021 Mar 28. doi: 10.1002/ehf2.13320. Online ahead of print.

ABSTRACT

AIMS: There is a critical need for better biomarkers so that heart failure can be diagnosed at an earlier stage and with greater accuracy. The purpose of this study was to design a robust mass spectrometry (MS)-based assay for the simultaneous measurement of a panel of 35 candidate protein biomarkers of heart failure, in blood. The overall aim was to evaluate the potential clinical utility of this biomarker panel for prediction of heart failure in a cohort of 500 patients.

METHODS AND RESULTS: Multiple reaction monitoring (MRM) MS assays were designed with Skyline and Spectrum Mill PeptideSelector software and developed using nanoflow reverse phase C18 chromatographic Chip Cube-based separation, coupled to a 6460 triple quadrupole mass spectrometer. Optimized MRM assays were applied, in a sample-blinded manner, to serum samples from a cohort of 500 patients with heart failure and non-heart failure (non-HF) controls who had cardiovascular risk factors. Both heart failure with reduced ejection fraction (HFrEF) patients and heart failure with preserved ejection fraction (HFpEF) patients were included in the study. Peptides for the Apolipoprotein AI (APOA1) protein were the most significantly differentially expressed between non-HF and heart failure patients (P = 0.013 and P = 0.046). Four proteins were significantly differentially expressed between non-HF and the specific subtypes of HF (HFrEF and HFpEF); Leucine-rich-alpha-2-glycoprotein (LRG1, P < 0.001), zinc-alpha-2-glycoprotein (P = 0.005), serum paraoxanse/arylesterase (P = 0.013), and APOA1 (P = 0.038). A statistical model found that combined measurements of the candidate biomarkers in addition to BNP were capable of correctly predicting heart failure with 83.17% accuracy and an area under the curve (AUC) of 0.90. This was a notable improvement on predictive capacity of BNP measurements alone, which achieved 77.1% accuracy and an AUC of 0.86 (P = 0.005). The protein peptides for LRG1, which contributed most significantly to model performance, were significantly associated with future new onset HF in the non-HF cohort [Peptide 1: odds ratio (OR) 2.345 95% confidence interval (CI) (1.456-3.775) P = 0.000; peptide 2: OR 2.264 95% CI (1.422-3.605), P = 0.001].

CONCLUSIONS: This study has highlighted a number of promising candidate biomarkers for (i) diagnosis of heart failure and subtypes of heart failure and (ii) prediction of future new onset heart failure in patients with cardiovascular risk factors. Furthermore, this study demonstrates that multiplexed measurement of a combined biomarker signature that includes BNP is a more accurate predictor of heart failure than BNP alone.

PMID:33779078 | DOI:10.1002/ehf2.13320

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Exploring patterns of personal alarm system use and impacts on outcomes

Australas J Ageing. 2021 Mar 28. doi: 10.1111/ajag.12941. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the patterns of personal emergency response systems (PERS) use in a statewide cohort of older Australians.

METHODS: PERS data from clients enrolled in the Personal Alarm Victoria program between January 2014 and June 2017 were analysed. Alarm activation reasons were extracted, and a medical record audit was performed for a sub-cohort of patients admitted to a local hospital following an alarm event. Descriptive statistics were used.

RESULTS: There were 42,180 clients enrolled during the study (mean age 80 years, 80% female, 93% living alone). An ambulance attended 44% of the fall-related events and 81% of events coded as unwell. Activation reasons were distributed equally between a fall and feeling unwell, and a repeating pattern of activation reasons was observed. In our sub-cohort (n = 92), the majority of admissions (86%) followed an alarm activation coded as unwell.

CONCLUSION: We demonstrated recurring patterns associated with the reasons for alarm use.

PMID:33779038 | DOI:10.1111/ajag.12941

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Factors predicting positive CT mesenteric angiography results in lower gastrointestinal haemorrhage prior to consideration of intra-arterial angio-embolisation

J Med Imaging Radiat Oncol. 2021 Mar 28. doi: 10.1111/1754-9485.13176. Online ahead of print.

ABSTRACT

INTRODUCTION: Lower gastrointestinal haemorrhage (LGIH) is a challenging phenomenon in a comorbid, elderly population. CT mesenteric angiography (CTMA) allows localisation of the site of haemorrhage, and provides a target for interventional techniques, but the intermittent nature of LGIH makes it challenging to reliably demonstrate extravasation. This study aimed to identify objective factors that may predict scan outcomes.

METHODS: In this retrospective cohort study, all patients undergoing CTMA for LGIH at Monash Health from January 2011 to December 2019 (n = 854) were included. Baseline patient characteristics included age, bowel resection/endoscopic intervention within the past 14 days, known bowel malignancy, anticoagulant/antiplatelet use, duration of symptoms, vital signs, transfusion requirements in the past 24 h and investigation results (recent haemoglobin levels, platelet count, international normalised ratio and creatinine levels). Univariate analysis was performed, and significant factors were entered into a multivariate model.

RESULTS: The final multivariate model was statistically significant (P < 0.001) and consisted of bowel resection/endoscopic intervention within the past 14 days (OR = 2.15), use of antiplatelet agents (OR = 2.03), blood transfusion requirement greater than 3 units per 24 h (OR = 1.79), systolic blood pressure less than 100 mmHg (OR = 1.56) and heart rate greater than 100 beats per minute (OR = 1.52).

CONCLUSION: The factors identified above are objective, independently associated with positive scan outcomes, readily available to radiologists and are useful for more judicious patient selection.

PMID:33779045 | DOI:10.1111/1754-9485.13176

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Disparities in male versus female oncologic outcomes following bladder preservation: A population-based cohort study

Cancer Med. 2021 Mar 28. doi: 10.1002/cam4.3835. Online ahead of print.

ABSTRACT

INTRODUCTION: In surgical series of muscle-invasive bladder cancer (MIBC), women have higher recurrence rates, disease progression, and mortality following radical cystectomy than men. Similar reports of oncologic differences between men and women following trimodality therapy (TMT) are rare. Our hypothesis was that there would be no difference in overall survival (OS) between sexes receiving TMT.

METHODS: We queried the National Cancer Database (NCDB) for patients diagnosed with clinical stage T2-T4aN0 M0 MIBC between 2004-2016. We considered patients to have received TMT if they received 55 Gy in 20 fractions or 59.4-70.2 Gy of radiotherapy with concurrent chemotherapy following a transurethral resection of bladder tumor (TURBT). We used multivariable Cox proportional hazard models to determine whether sex was associated with risk of mortality. In addition to OS, we calculated relative survival (RS) to adjust for the fact that females generally survive longer than males.

RESULTS: Of the patients, 1960 underwent TMT and had survival data. Less than one quarter were female. In the first year following treatment, women had worse OS and RS than men (p = 0.093 and p = 0.030, respectively). However, overall and relative survival differences between sexes were not statistically significantly different in Years 2 and later. Unlike with OS, the RS between sexes remained significant at 9 years; in multivariable analysis based on RS, women were 43% more likely to die than men (p < 0.001).

CONCLUSIONS: Women had a higher initial risk of death than men in the first year following TMT. However, long-term survival between sexes was similar. TMT is an important treatment option in both men and women seeking bladder preservation.

PMID:33779053 | DOI:10.1002/cam4.3835

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Secoisolariciresinol diglucoside induces caspase-3-mediated apoptosis in monolayer and spheroid cultures of human colon carcinoma cells

J Food Biochem. 2021 Mar 29:e13719. doi: 10.1111/jfbc.13719. Online ahead of print.

ABSTRACT

Apoptotic effects of secoisolariciresinol diglucoside (SDG) in 2D and 3D cultures of SW480 cells were investigated. 40-200 μM SDG was used and IC50 values were determined for three different time intervals as 24, 48, or 72 hr for further experiments. BrdU, TUNEL, AIF, and caspase-3 stainings were used. SDG inhibited cell proliferation almost half and half for all time intervals in 2D and 3D cultures and also, induced apoptosis. Apoptotic cell percentages in the control group for 24, 48, and 72 hr were 27.00%, 29.00%, and 28.00%, respectively, while in the SDG treatment group were 59.00%, 61.00%, and 62.00%, respectively. In the spheroid cell culture, apoptotic cell percentages in the control group for 24, 48, and 72 hr were 6.90%, 7.20%, and 7.10%, respectively, while in the SDG treatment group were 19.50%, 19.50%, and 20.70%, respectively. Caspase-3 and AIF antibodies were used to indicate caspase-dependent and -independent apoptotic pathways. Significant increases were seen in both AIF and caspase-3 stainings when compared to the control group but caspase-3 staining results were significantly greater when compared to the AIF staining at all time intervals (p < .05). To prove this, CASP3 gene expression was evaluated by RT-qPCR. Unlike staining results, there was no statistically significant change at 24 hr in 2D and 3D cultures. But, significant upregulation at 48 (2.32-fold in 2D and 2.46-fold in 3D) and 72 hr (5.04-fold in 2D and 6.45-fold in 3D) were seen. PRACTICAL APPLICATIONS: Colon cancer is one of the most prevalent cancer in the developed countries and its etiology is complex. Although the underlying mechanisms are mostly unknown, the link between diet and colon cancer is known and dietary habits can promote cancer or protect against it. In recent years, flaxseed is accepted as a significant functional food ingredient and feeding with it could help in to prevent cancer. Secoisolariciresinol diglucoside is a flaxseed lignan and is metabolized to mammalian lignans by the gut. In the present study, SDG was evaluated for its apoptotic effects in colon carcinoma cell line via monolayer and spheroid cultures using immunohistochemical and gene expression techniques. Findings of this study suggest that SDG may protect against cancers and in particularly against colon cancer and further investigations has to be carried out for detailed underlying mechanisms.

PMID:33778961 | DOI:10.1111/jfbc.13719

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Cesarean delivery rates for overall and multiple pregnancies in Japan: A descriptive study using nationwide health insurance claims data

J Obstet Gynaecol Res. 2021 Mar 28. doi: 10.1111/jog.14772. Online ahead of print.

ABSTRACT

AIM: Due to the lack of national perinatal registries, population-wide descriptive statistics on cesarean deliveries in Japan are unknown. We aim to describe cesarean deliveries for overall and multiple pregnancies using the Japan National Database of health insurance claims.

METHODS: We calculated the national and prefectural cesarean delivery rates for overall and multiple pregnancies in 2014. We described maternal morbidities (e.g., blood transfusion) and the place and type of the institutions providing prenatal and perinatal care.

RESULTS: The national cesarean delivery rates were 18.6% overall and 82.7% for women with multiple pregnancies. Prefectural cesarean delivery rates for overall and multiple pregnancies varied from 12.5% to 24.2% and from 49.2% to 100%, respectively, showing a moderate positive correlation (r = 0.59, p < 0.001). Overall, 1.4% of cesarean patients received an allogeneic blood transfusion, compared to 3.2% for those with multiple pregnancies. In addition, 65.9% of overall cesarean deliveries occurred at hospitals with ≥20 beds, whereas 94.6% of cesarean patients with multiple pregnancies delivered at hospitals. Older patients were more likely to receive their cesarean section at a different institution than their first visit within the same prefecture, but trans-prefectural movement during pregnancy covered by health insurance was most frequent among those in their early thirties: 7.0% overall and 10.7% for multiple pregnancies.

CONCLUSIONS: The overall cesarean delivery rate in Japan was optimal, but the rate was high for multiple pregnancies, with large regional differences. Data on patient movement across institutions and areas would help to improve the perinatal care system.

PMID:33779012 | DOI:10.1111/jog.14772

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Abbreviated Magnetic Resonance Imaging With Breath-Hold Three-Dimensional Magnetic Resonance Cholangiopancreatography: Assessment of Malignant Risk of Pancreatic Intraductal Papillary Mucinous Neoplasm

J Magn Reson Imaging. 2021 Mar 28. doi: 10.1002/jmri.27612. Online ahead of print.

ABSTRACT

BACKGROUND: For surveillance of pancreatic intraductal papillary mucinous neoplasms (IPMNs), magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) is preferred over computed tomography, but the long acquisition time limits its use.

PURPOSE: To investigate the diagnostic performance of abbreviated MRI with breath-hold (BH) three-dimensional MRCP (abbreviated MRI-BH) for malignant risk assessment of pancreatic IPMN.

STUDY TYPE: Retrospective.

POPULATION: Two hundred and thirty-five patients with IPMNs (M:F = 115:120; mean age ± SD, 66 ± 9 years; typical imaging features with ≥2-year stability [N = 172] and histopathologically confirmed [N = 63]).

FIELD STRENGTH/SEQUENCE: 3.0 T/ abbreviated MRI-BH (single-shot fast spin-echo, T1W fat-suppressed gradient-echo sequence, and BH-3D-MRCP).

ASSESSMENT: Abbreviated MRI-BH was reviewed by three reviewers, and its diagnostic performance was assessed using the predetermined scoring system. The diagnostic performance for the mural nodule detection was assessed. Additionally, diagnostic performance of abbreviated MRI was compared with that of full-sequence MRI.

STATISTICAL TESTS: Area under the receiver operating characteristic curve (AUC) with z-test, and linear-weighted kappa values.

RESULTS: Thirty-five patients had malignant IPMN. At a cut-off score ≥3, AUCs of abbreviated MRI-BH for detecting malignant IPMN were 0.959 for reviewer 1, 0.962 for reviewer 2, and 0.956 for reviewer 3. The sensitivity of reviewers 1, 2, and 3 was 97.1% for all, and the specificity was 85.5%, 86.0%, and 85.0%, respectively. Regarding mural nodule detection (N = 22), abbreviated MRI-BH demonstrated a sensitivity of 95.5% and a specificity of 88.3% for reviewer 1, a sensitivity of 86.4% and a specificity of 92.0% for reviewer 2, and a sensitivity of 86.4% and a specificity of 89.2% for reviewer 3. There were no significant differences between AUC of abbreviated MRI-BH and that of full-sequence MRI in the three reviewers (P > 0.05).

DATA CONCLUSION: Abbreviated MRI-BH showed good diagnostic performance for detecting malignant IPMNs by using a predetermined scoring system.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

PMID:33779024 | DOI:10.1002/jmri.27612