Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1), an extracellular matrix glycoprotein, has been implicated in the pathogenesis of several disorders including cancer. However, little is known about the expression and significance of SPARCL1 in human breast cancer. The aim of this study was to determine the expression pattern and clinicopathological significance of SPARCL1 in a Chinese breast cancer cohort. mRNA and protein expression of SPARCL1 in human breast cancer cell lines and breast cancer tissues was detected using the reverse transcription-polymerase chain reaction, real-time quantitative PCR, and Western blotting, respectively. Immunostaining of SPARCL1 in 282 Chinese breast cancer samples was examined and associations with clinicopathological parameters were analyzed. Compared to the positive expression in immortalized human breast epithelial cells, SPARCL1 was nearly absent in human breast cancer cell lines. Similarly, a significantly reduced expression of SPARCL1 was observed in human breast cancer tissues compared to that in normal breast epithelial tissues, for both mRNA and protein levels (P < 0.001). Immunohistochemical analysis showed that strong cytoplasmic immunostaining of SPARCL1 was observed in almost all normal breast samples (43/45) while moderate and strong immunostaining of SPARCL1 was only detected in 191 of 282 (67.7%) breast cancer cases. Moreover, down-regulation of SPARCL1 was significantly correlated with lymphatic metastasis (P = 0.020) and poor grade (P = 0.044). In conclusion, SPARCL1 may be involved in the breast tumorigenesis and serve as a promising target for therapy of breast cancer.
De La Garza Ramos, Rafael;Echt, Murray;Benton, Joshua A.;Gelfand, Yaroslav;Longo, Michael;Yanamadala, Vijay;Yassari, Reza
Journal of Korean Neurosurgical Society
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v.63
no.6
/
pp.777-783
/
2020
Objective : To compare the accuracy and breach rates of freehand (FH) versus navigated (NV) pedicle screws in the thoracic and lumbar spine in patients with metastatic spinal tumors. Methods : A retrospective review of adult patients who underwent pedicle screw fixation in the thoracic or lumbar spine for metastatic spinal tumors between 2012 and 2018 was conducted. Breaches were assessed based on the Gertzbein and Robbins classification and only screws placed >4 mm outside of the pedicle wall (lateral or medial) were considered breached. Results : A total of 62 patients received 547 pedicle screws (average 8 per patient) - 34 patients received 298 pedicle screws in the FH group and 28 patients received 249 screws in the NV group. There were 40/547 breaches, corresponding to a breach and accuracy rate of 7.3% and 92.7%, respectively. The breach rate was 9.7% in the FH group and 4.4% in the NV group (chi-squared test, p=0.017); this corresponded to an accuracy rate of 90.3% and 95.6%, respectively. Only one patient from the overall cohort (in the FH group) required revision surgery due to a medial breach abutting the spinal cord (1.6% of all patients; 2.9% of FH patients); no patient suffered organ, vessel, or neurological injury from screw breaches. Conclusion : Navigated pedicle screw placement in patients with metastatic spinal tumors has a significantly higher radiographic accuracy compared to the FH technique. However, the revision surgery was low and no patient suffered from clinically-relevant breach. Navigation also offers the advantage of real-time localization of spinal tumors and aids in targeting and resection of these lesions.
Kim, Chungsoo;Lee, Jimin;Park, Rae Woong;Lee, Sukhyang
Korean Journal of Clinical Pharmacy
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v.29
no.4
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pp.254-266
/
2019
Background: Patients with cardiovascular risks are recommended to use statins and antiplatelet agents to prevent major cerebro-cardiovascular events (MACCE). Antiplatelet agents also possess anti-inflammatory and antioxidant effects, in addition to their inhibitory activity on platelets. The differences in clinical outcomes in ischemic heart disease (IHD) based on the type of antiplatelet therapy combined with statin treatment were investigated in this study. Methods: We conducted a retrospective cohort study using electronic medical records of IHD patients from January 2010 to December 2014 at Ajou University Hospital. Patients on combination therapy of antiplatelet drugs and statins were grouped based on antiplatelet drug types: clopidogrel, cilostazol, or sarpogrelate. Propensity score matching was applied to balance the baseline of the groups of clopidogrel vs. cilostazol and the groups of clopidogrel vs. sarpogrelate. The incidence and risk of MACCE as primary outcomes were assessed between the groups of antiplatelet drugs. Results: Among the approximately 128,500 patients with IHD, 1,049 patients had taken a combination therapy of statin and antiplatelet agents. The cohorts of patients administered clopidogrel, cilostazol, or sarpogrelate were 906, 79, and 64, respectively. The incidence of MACCE was not significantly different among the cohorts (p=0.58), and there were no differences between clopidogrel vs. cilostazol (p=0.72) or clopidogrel vs. sarpogrelate (p=1.00) after propensity score matching. Conclusion: There was no difference in the incidence of MACCE based on the type of antiplatelet drug (clopidogrel, cilostazol, or sarpogrelate) in combination with a statin in patients with IHD.
Community-acquired pneumonia (CAP) is a major risk factor of mortality in chronic obstructive pulmonary disease (COPD). Streptococcus pneumoniae (colloquially known as pneumococcus) is one of important pathogens of CAP in patients with COPD. Preventive interventions for pneumonia include pneumococcal and influenza vaccinations. A prospective, cohort study has been performed to investigate the protective effects of pneumococcal and influenza vaccinations on the severity of community-acquired pneumonia requring hospital admission in patients with COPD. Seven university-affiliated hospitals in Korea have participated in the study. The aim of this study was to construct an online registration system for the multi-institutional researchers that facilitates efficient collection and management of COPD patient data. This study has presented three basic strategies-accurate data input, convenient data completion, and real-time data management-to supplement the demerits of existing offline clinical study. The proposed online registration system has already been applied to a multi-institutional clinical study and was acknowledged for its high performance.
Globally researchers at medical institutions are actively sharing COHORT data of patients to develop vaccines and treatments to overcome the COVID-19 crisis. OMOP-CDM, a common data model that efficiently shares medical data research independently operated by individual medical institutions has patient personal information (e.g. PII, PHI). Although PII and PHI are managed and shared indistinguishably through de-identification or anonymization in medical institutions they could not be guaranteed at 100% by complete de-identification and anonymization. For this reason the security of the OMOP-CDM database is important but there is no detailed and specific OMOP-CDM security inspection tool so risk mitigation measures are being taken with a general security inspection tool. This study intends to study and present a model for implementing a tool to check the security vulnerability of OMOP-CDM by analyzing the security guidelines for the US database and security controls of the personal information protection of the NIST. Additionally it intends to verify the implementation feasibility by real field demonstration in an actual 3 hospitals environment. As a result of checking the security status of the test server and the CDM database of the three hospitals in operation, most of the database audit and encryption functions were found to be insufficient. Based on these inspection results it was applied to the optimization study of the complex and time-consuming CDM CSF developed in the "Development of Security Framework Required for CDM-based Distributed Research" task of the Korea Health Industry Promotion Agency. According to several recent newspaper articles, Ramsomware attacks on financially large hospitals are intensifying. Organizations that are currently operating or will operate CDM databases need to install database audits(proofing) and encryption (data protection) that are not provided by the OMOP-CDM database template to prevent attackers from compromising.
Communications for Statistical Applications and Methods
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v.29
no.4
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pp.421-439
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2022
Phase I dose-finding trials are essential in drug development. By finding the maximum tolerated dose (MTD) of a new drug or treatment, a Phase I trial establishes the recommended doses for later-phase testing. The primary toxicity endpoint of interest is often a binary variable, which describes an event of a patient who experiences dose-limiting toxicity. However, there is a growing interest in dose-finding studies regarding non-binary outcomes, defined by either the weighted sum of rates of various toxicity grades or a continuous outcome. Although several novel methods have been proposed in the literature, accessible software is still lacking to implement these methods. This study introduces a newly developed R package, UnifiedDoseFinding, which implements three phase I dose-finding methods with non-binary outcomes (Quasi- and Robust Quasi-CRM designs by Yuan et al. (2007) and Pan et al. (2014), gBOIN design by Mu et al. (2019), and by a method by Ivanova and Kim (2009)). For each of the methods, UnifiedDoseFinding provides corresponding functions that begin with next that determines the dose for the next cohort of patients, select, which selects the MTD defined by the non-binary toxicity endpoint when the trial is completed, and get oc, which obtains the operating characteristics. Three real examples are provided to help practitioners use these methods. The R package UnifiedDoseFinding, which is accessible in R CRAN, provides a user-friendly tool to facilitate the implementation of innovative dose-finding studies with nonbinary outcomes.
Didan Ariadapa Rahadi;Elfira Yusri;Syandrez Prima Putra;Rima Semiarty;Dian Pertiwi;Cimi Ilmiawati
Journal of Preventive Medicine and Public Health
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v.56
no.3
/
pp.221-230
/
2023
Objectives: The second wave of coronavirus disease 2019 (COVID-19) cases in Indonesia, during which the Delta variant predominated, took place after a vaccination program had been initiated in the country. This study was conducted to assess the impact of COVID-19 vaccination on unfavorable clinical outcomes including hospitalization, severe COVID-19, intensive care unit (ICU) admission, and death using a real-world model. Methods: This single-center retrospective cohort study involved patients with COVID-19 aged ≥18 years who presented to the COVID-19 emergency room at a secondary referral teaching hospital between June 1, 2021 and August 31, 2021. We used a binary logistic regression model to assess the effect of COVID-19 vaccination on unfavorable clinical outcomes, with age, sex, and comorbidities as confounding variables. Results: A total of 716 patients were included, 32.1% of whom were vaccinated. The elderly participants (≥65 years) had the lowest vaccine coverage among age groups. Vaccination had an effectiveness of 50% (95% confidence interval [CI], 25 to 66) for preventing hospitalization, 97% (95% CI, 77 to 99) for preventing severe COVID-19, 95% (95% CI, 56 to 99) for preventing ICU admission, and 90% (95% CI, 22 to 99) for preventing death. Interestingly, patients with type 2 diabetes had a 2-fold to 4-fold elevated risk of unfavorable outcomes. Conclusions: Among adults, COVID-19 vaccination has a moderate preventive impact on hospitalization but a high preventive impact on severe COVID-19, ICU admission, and death. The authors suggest that relevant parties increase COVID-19 vaccination coverage, especially in the elderly population.
Background: Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. Methods: The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. Results: The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). Conclusion: A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.
The single nucleotide polymorphism (SNP) rs1053004 in Signal transducer and activator of transcription 3 (STAT3) was recently reported to be associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in a Chinese cohort. This study was aimed at investigating whether the SNP might also contribute to HCC susceptibility in the Thai population. Study subjects were enrolled and divided into 3 groups including CHB-related HCC (n=211), CHB without HCC (n=233) and healthy controls (n=206). The SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Data analysis revealed that the distribution of different genotypes was in Hardy-Weinberg equilibrium (P>0.05). The frequencies of allele T (major allele) in HCC patients, CHB patients and healthy controls were 51.4%, 58.6% and 61.4%, respectively, whereas the frequencies of C allele (minor allele) were 48.6%, 41.4% and 38.6%. The C allele frequency was higher in HCC when compared with CHB patients (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.02-1.74, P=0.032). The genotype of SNP rs1053004 (CC versus TT+TC) was significantly associated with an increased risk when compared with CHB patients (OR=1.83, 95% CI=1.13-2.99, P=0.015). In addition, we observed a similar trend of association when comparing HCC patients with healthy controls (OR=1.77, 95% CI=1.07-2.93, P=0.025) and all controls (OR=1.81, 95% CI=1.19-2.74, P=0.005). These findings suggest that the SNP rs1053004 in STAT3 might contribute to HCC susceptibility and could be used as a genetic marker for HCC in the Thai population.
Background: The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21may have an important relationship with tumor cell sensitivity to EGFR-TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC). Materials and Methods: The presence of mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and targeted therapy were assessed by electrochemical luminescence. Results: The mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy, chemotherapy and targeted treatment, serum CEA levels were abnormally high in 54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR mutation rate was 18.8%, while with 5~19 ng/mL and ${\geq}20ng/mL$, the rates were 36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being 20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level ${\geq}50ng/mL$, the EGFR mutation rate was only 20.0%, approximately the same as in cases with the CEA level<5 ng/mL. Conclusions: There is a positive correlation between serum CEA expression level and EGFR mutation status in NSCLC patients, namely the EGFR mutation-positive rate increases as the serum CEA expression level rises within a certain range (${\geq}20ng/mL$, especially 20~49 ng/mL). If patient samples are not suitable for EGFR mutation testing, or cannot be obtained at all, testing serum CEA levels might be a simple and easy screening method. Hence, for the NSCLC patients with high serum CEA level (${\geq}20ng/mL$, especially 20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve better clinical efficacy and quality of life.
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