Risk Factors of Outcomes of COVID-19 Patients in Korea: Focus on Early Symptoms.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the globe, and it is important to determine the risk factors of death in the general population. Our study aimed to determine the risk factors of death and severe illness requiring supplemental oxygen therapy based on the demographic and clinical characteristics of COVID-19 patients in Korea. METHODS: In this study, we used data provided by the Korea Disease Control and Prevention Agency (KDCA) and analyzed a total of 5,068 patients with COVID-19, excluding 19 pregnant women and 544 individuals with missing data. We performed logistic regression analysis to determine the impact of early symptoms on survival and severe disease. Logistic regression models included sex, age, number of comorbidities, symptoms on admission, blood pressure, heart rate, and body temperature as explanatory variables, and death and oxygen therapy as outcome variables. RESULTS: Logistic regression analyses revealed that the male sex, older age (≥ 60 years), higher number of comorbidities, presence of symptoms on admission, heart rate ≥ 120 bpm, and body temperature ≥ 37.5°C presented with higher risk of in-hospital death and oxygen therapy requirement. Conversely, rhinorrhea and headache were associated with a low risk of death and oxygen therapy requirement. The findings showed that cough, sputum, and fever were the most common symptoms on admission, while 25.3% of patients with COVID-19 were asymptomatic. CONCLUSION: COVID-19 patients with high-risk early symptoms on admission, such as dyspnea and altered mental status, and those without low-risk symptoms of rhinorrhea and headache should be included in priority treatment groups.

Determinants Used to Justify the Strength of Recommendations among Korean Clinical Practice Guidelines.

BACKGROUND: A standardized systematic approach to grade evidence and the strength of recommendations is important for guideline users to minimize bias and help interpret the most suitable decisions at the point of care. The study aims to identify and classify determinants used to make judgement for the strength of recommendations among 56 Korean clinical practice guidelines (CPGs), and explore strong recommendations based on low quality of evidence. METHODS: Determinants used in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach among 34 CPGs which have reported both strength of recommendations and level of evidence were reviewed. RESULTS: Five of 34 CPGs (14.7%) considered quality of evidence, benefits and harms, patients' values and preferences, and costs. And 24 of 34 CPGs (70.6%) considered both magnitude of effect and feasibility as additional determinants. Judgement table was not widely provided for use to translate evidence into recommendations. Eighty-two of 121 recommendations (67.8%, ranged 20.0% to 100.0%) among 11 CPGs using the same judgement scheme showed 'strong' strength of recommendations based on low or very low quality of evidence. Among 5 paradigmatic situations that justify strong recommendations based on low or very low evidence, situation classified as 'potential equivalence, one option clearly less risky or costly' was 87.8% for 82 strong recommendations. Situation classified as 'uncertain benefit, certain harm' was 4.9%. CONCLUSION: There is a need to introduce and systematize an evidence-based grading system. Using judgement table to justify the strength of recommendations and applying the 5 paradigmatic situations mentioned above is also recommended in the near future.

Methodological Quality Appraisal of 27 Korean Guidelines Using a Scoring Guide Based on the AGREE II Instrument and a Web-based Evaluation.

This study evaluated the methodological quality of CPGs using the Korean AGREE II scoring guide and a web-based appraisal system and was conducted by qualified appraisers. A total of 27 Korean CPGs were assessed under 6 domains and 23 items on the AGREE II instrument using the Korean scoring guide. The domain scores of the 27 guidelines were as following: the mean domain score was 82.7% (median 84.7%, ranging from 55.6% to 97.2%) for domain 1 (scope and purpose); 53.4% (median 56.9%, ranging from 11.1% to 95.8%) for domain 2 (stakeholder involvement); 63.0% (median 71.4%, ranging from 13.5% to 90.6%) for domain 3 (rigor of development); 88.9% (median 91.7%, ranging from 58.3% to 100.0%) for domain 4 (clarity of presentation); 30.1% (median 27.1%, ranging from 3.1% to 67.7%) for domain 5 (applicability); and 50.2% (median 58.3%, ranging from 0.0% to 93.8%) for domain 6 (editorial independence). Three domains including scope and purpose, rigor of development, and clarity of presentation were rated at more than 60% of the scaled domain score. Three domains including stakeholder involvement, applicability, and editorial independence were rated at less than 60% of the scaled domain score. Finally, of the 27 guidelines, 18 (66.7%) were rated at more than 60% of the scaled domain score for rigor of development and were categorized as high-quality guidelines.

Development of Quality Management Systems for Clinical Practice Guidelines in Korea.

This study introduces the Clinical practice guidelines (CPGs) appraisal system by the Korean Academy of Medical Sciences (KAMS). Quality management policies for CPGs vary among different countries, which have their own cultures and health care systems. However, supporting developers in guideline development and appraisals using standardized tools are common practices. KAMS, an organization representing the various medical societies of Korea, has been striving to establish a quality management system for CPGs, and has established a CPGs quality management system that reflects the characteristics of the Korean healthcare environment and the needs of its users. KAMS created a foundation for the development of CPGs, set up an independent appraisal organization, enacted regulations related to the appraisals, and trained appraisers. These efforts could enhance the ability of each individual medical society to develop CPGs, to increase the quality of the CPGs, and to ultimately improve the quality of the information available to decision-makers.

Comparison of postoperative estimated glomerular filtration rate between kidney donors and radical nephrectomy patients, and risk factors for postoperative chronic kidney disease.

OBJECTIVES: To compare post-nephrectomy renal function between kidney donors and renal cell carcinoma patients, to evaluate trends in recovery, and to identify factors relevant to renal failure. METHODS: Patients who had radical or donor nephrectomy from four different institutions between 2003 and 2012 were reviewed. Propensity score matching was carried out and 79 patients were selected for each group. The estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula preoperatively and postoperatively at 1, 3, 6, 12, 24 and 36 months. Mean estimated glomerular filtration rate was compared, and the difference between preoperative values and each preceding date was calculated. A multivariate logistic regression was used to determine independent factors for a decrease in estimated glomerular filtration rate to <60 mL/min/1.73 m(2) . RESULTS: The donor nephrectomy group showed a trend of improved estimated glomerular filtration rate recovery at 24 months and 36 months compared with the radical nephrectomy group, which was statistically significant (P = 0.028, P = 0.012). Multivariate logistic regression showed that renal cell carcinoma (odds ratio 4.605, 95% confidence interval 1.626-13.040, P = 0.004), a baseline estimated glomerular filtration rate lower than 110 (odds ratio 4.477, 95% confidence interval 1.360-14.742, P = 0.014) and age older than 40 years (odds ratio 21.616, 95% confidence interval 2.761-169.222, P = 0.003) were predictive factors for a decrease in renal function. CONCLUSIONS: Renal cell carcinoma is an independent risk factor for chronic kidney disease after nephrectomy. In addition, age older than 40 years and a baseline estimated glomerular filtration rate of 110 mL/min/1.73 m(2) or less seem to represent risk factors associated with chronic kidney disease after nephrectomy.

23-Hydroxytormentic acid and niga-ichgoside f1 isolated from Rubus coreanus attenuate cisplatin-induced cytotoxicity by reducing oxidative stress in renal epithelial LLC-PK1 cells.

The unripe fruits of Rubus coreanus (Rosaceae) are used in traditional Chinese medicine to relieve kidney dysfunction. In the present study, we evaluated the protective effects of the triterpenoid glycoside niga-ichigoside F1 (NIF1) and of its aglycone 23-hydroxytormentic acid (23-HTA) isolated from the unripe fruits of Rubus coreanus (Rosaceae) against cisplatin-induced cytotoxicity in renal epithelial LLC-PK1 cells. Pretreating LLC-PK1 cells with 23-HTA or NIF1 was found to prevent cisplatin-induced cytotoxicity and apoptosis. In addition, 23-HTA or NIF1 pretreatment significantly improved the changes associated with cisplatin toxicity by increasing levels of glutathione (GSH) and decreasing levels of malondialdehyde (MDA) and reactive oxygen species (ROS). The activity of antioxidant enzymes including catalase (CAT) and superoxide dismutase (SOD) was significantly lower in cisplatin-treated LL-PK1 cells, and 23-HTA or NIF1 treatment notably increased the these enzyme activity and protein and mRNA levels of CAT and manganese SOD (MnSOD). Moreover, cisplatin caused a significant decrease in nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and pretreatment with 23-HTA or NIF1 significantly suppressed the cisplatin-induced translocation of Nrf2 in LLC-PK1 cells. Taken together, these results suggest that 23-HTA ameliorates cisplatin-induced toxicity via modulation of antioxidant enzymes through activation of Nrf2 in LLC-PK1 cells.

Association of IL10, IL10RA, and IL10RB polymorphisms with benign prostate hyperplasia in Korean population.

Cytokines such as interleukin 10 (IL10) may play an important role in the process of inflammation. The aim of this study was to analyze the association between IL10, IL10RA and IL10RB single nucleotide polymorphisms (SNPs), and benign prostate hyperplasia (BPH) in Korean population. All patients with BPH were divided into two groups according to international prostate symptom score (IPSS), prostate specific antigen (PSA) level, Q(max), and prostate volume. We selected two IL10 SNPs (rs1518111 and rs1554286), three IL10RA SNPs (rs2256111, rs4252243, and rs2228054), and two IL10RB SNPs (rs999788 and rs2834167). Genotypes of seven SNPs were determined through direct sequencing. The G/G genotype of IL10RB polymorphism (rs2834167) was associated with a high PSA level compared with the A/G + A/A genotypes (P = 0.009). Of IL10 SNP, the A/A genotype of rs1518111 and T/T genotype of rs1554286 were associated with small prostate volume, respectively (P = 0.011, P = 0.014). Moreover, the T/T genotype of IL10RB polymorphism (rs999788) was associated with high prostatic volume compared with the T/C + C/C genotypes (P = 0.033). The linkage disequilibrium (LD) blocks were formed in IL10 and IL10RA. However, haplotypes in the LD block were not associated with BPH. It is concluded that there is a strong association between the IL10 and IL10RB SNPs, and BPH in Korean population.

Epigenetic inactivation of HOXA5 and MSH2 gene in clear cell renal cell carcinoma.

The high-throughput method using microarray is an easy and fast way to analyze the methylation status of hundreds of preselected genes and to screen them for signatures in methylation. The aim of our study is to detect hypermethylated genes and to analyze the association between methylation status and clinicopathological parameters of clear cell renal cell carcinoma. The genetic substrate included 62 cancer tissues and 62 matched adjacent normal kidney tissues. We adapted the GoldenGate genotyping assay to determine the methylation state of 1505 specific CpG sites in 807 genes. We identified two genes (HOXA5 and MSH2) with ß-value differences of more than 0.3 between cancer and normal tissues. The high methylation group in HOXA5 had high Fuhrman's nuclear grade (P= 0.041). Other data in HOXA5 and MSH2 were not significant with methylation status (P > 0.05). Survival curve of the high methylation group in HOXA5 was slightly lower than that of the low methylation group. However, the statistical significances of overall survival in HOXA5 and MSH2 were low (P > 0.05). We report the hypermethylation of two genes in clear cell renal cell carcinoma. The data we obtained could provide the basis for a diagnostic test pathological assessment, or prognosis in clear cell renal cell carcinoma.

Vasectomy is not a simple procedure: subtotal testicular infarction.

A 32-year-old man presented with severe scrotal pain after vasectomy. Scrotal ultrasound showed the presence of enlargement and decreased echogenicity of more than the upper two-thirds of the right testis. After orchiectomy, scrotal pain disappeared. This is the first report of simple orchiectomy after subtotal testicular infarction due to a suture tie of vasectomy. During vasectomy, it is important to dissect the bare vas to minimize vascular injury.

Life-threatening complications associated with the tyrosine kinase inhibitor sunitinib malate.

Adverse events associated with sunitinib, such as cardiac toxicities, renal damage, and hemostatic complications, are well known. The authors report 3 cases in which patients experienced severe life-threatening complications after commencing sunitinib treatment. One patient developed heart failure with dilation of the left ventricle and decrease in the ejection fraction after one cycle of sunitinib and required treatment with an angiotensin-converting enzyme inhibitor, loop diuretics, and dobutamine. Another patient developed coronary artery stenosis after one cycle of sunitinib and was managed through percutaneous coronary intervention. Although follow-on coronary angiography revealed normal findings after 6 further cycles of sunitinib, this patient eventually expired due to multi-organ failure. The third patient had chronic renal failure before sunitinib treatment and required hemodialysis due to acute-on-chronic renal failure after commencing sunitinib treatment.

Neuroanatomical study of periprostatic nerve distributions using human cadaver prostate.

We investigated the distribution and navigation of periprostatic nerve fibers and constructed a 3-dimensional model of nerve distribution. A total of 5 cadaver specimens were serially sectioned in a transverse direction with 0.5 cm intervals. Hematoxylineosin staining and immunohistochemical staining were then performed on whole-mount sections. Three representative slides from the base, mid-part, and apex of each prostate were subsequently divided into 4 sectors: two lateral, one ventral, and one dorsal (rectal) part. The number of nerve fibers, the distance from nerve fiber to prostate capsule, and the nerve fiber diameters were analyzed on each sector from the representative slides by microscopy. Periprostatic nerve fibers revealed a relatively even distribution in both lateral and dorsal parts of the prostate. There was no difference in the distances from the prostate capsule to nerve fibers. Nerve fibers in the ventral area were also thinner as compared to other areas. In conclusion, periprostatic nerve fibers were observed to be distributed evenly in the periprostatic area, with the exception of the ventral area. As the number of nerve fibers on the ventral part is fewer in comparison, an excessive high up incision is insignificant during the nerve-sparing radical prostatectomy.

Effect of dominant hemispheric stroke on detrusor function in patients with lower urinary tract symptoms.

OBJECTIVES: To determine the effect of unilateral hemispheric lesion on voiding dysfunction by comparing urodynamic parameters in dominant, non-dominant and bilateral hemispheric stroke patients. METHODS: We retrospectively reviewed the medical records of patients from a magnetic resonance imaging and urodynamic study. We identified 69 cases among 192 stroke patients who had undergone urodynamic study due to lower urinary tract symptoms from June 2003 to December 2008. RESULTS: Among the analyzed variables in the urodynamic study, total bladder capacity, voided volume, postvoid residual urine volume, maximum flow rate, average flow rate, detrusor pressure at the maximum flow rate, and bladder compliance did not show statistically significant differences among dominant, non-dominant and bilateral hemispheric stroke patients groups (P > 0.05). The dominant hemispheric stroke group had detrusor overactivity in 64.2% of cases and detrusor underactivity in 35.8%; the non-dominant hemispheric stroke group had detrusor overactivity in 66.7% of cases and detrusor underactivity in 33.3%; and the bilateral stroke group had detrusor overactivity in 60.0% of cases and detrusor underactivity in 40.0% (P = 0.946). CONCLUSION: Urodynamic findings cannot be characterized by the laterality of the unilateral hemispheric ischemic lesion. There are no significant differences in lower urinary tract symptoms between dominant, non-dominant and bilateral hemispheric ischemic stroke patients.

Dystrophic calcification and stone formation on the entire bladder neck after potassium-titanyl phosphate laser vaporization for the prostate: a case report.

Dystrophic calcification can be defined as a calcification that occurs in degenerated or necrotic tissue. It is associated with multiple clinical conditions, such as collagen vascular diseases. It involves the deposition of calcium in soft tissues despite no generalized disturbance in the calcium or phosphorus metabolism, and this is often seen at sites of previous inflammation or damage. Potassium-titanyl phosphate (KTP) laser vaporization of the prostate is safe and relatively bloodless procedure that results in a shorter catheterization, immediate symptomatic improvement, and less severe postoperative irritative symptoms. However, longer follow-up studies or reports about complications are lacking. Here in we report a case of dystrophic calcification and stone formation on the entire bladder neck after performing KTP laser vaporization of benign prostate hyperplasia. That was treated by lithotripsy and transurethral resection.

Acute pyelonephritis: clinical characteristics and the role of the surgical treatment.

The epidemiology of acute pyelonephritis (APN) has changed with time. Therefore we investigated the current clinical characteristics of APN and the significance of proper surgical management for treatment of 1,026 APN patients in South Korea for the past 5 yr. The male-to-female ratio was about 1:8. The peak ages of female patients were 20s (21.3%) and over 60s (23.7%), while that of male was over 60s (38.1%). The occurrence of sepsis was 10.1%. Complicated APN patients were 35.4%. Ninety-four patients (9.2%) needed urological procedures. The duration of the flank pain and of the costovertebral angle tenderness in complicated APN patients was statistically significantly longer than that with simple APN patients (4.3 vs. 3.4 days, 4.4 vs. 4.0 days). If flank pain and costovertebral angle tenderness sustain over 4 days, proper radiologic studies should be performed immediately with the consideration of surgical procedure. Also the resistance to antibiotics was increasing. As the sensitivities to ampicillin (27.2%) and trimethoprim/sulfamethoxazole (44.7%) of Escherichia coli and Klebsiella pneumoniae were very low, it is necessary to take the careful choice of antibiotics into consideration.

Villous adenoma of the urinary bladder.

Villous adenomas arising in the urinary tract are an uncommon occurrence. They have been identified in the urachus, urethra, prostate, and throughout the bladder. Villous adenomas arising in the bladder are rare tumors that have been described as isolated cases and a few case series. We report a new case of a large villous adenoma arising in the bladder that was treated by transurethral resection.

Treatment of infected urachal cysts.

The urachus is a fibrous cord that arises from the anterior bladder wall and extends cranially to the umbilicus. Traditionally, infection has been treated using a two-stage procedure that includes an initial incision and drainage which is then followed by elective excision. More recently, it has been suggested that a single-stage excision with improved antibiotics is a safe option. Thus, we intended to compare the effects of the two-stage procedure and the single-stage excision. We performed a retrospective review on nine patients treated between May 1990 and September 2005. The methods used in diagnosis were ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and cystoscopy. The study group was comprised of three males and six females with a mean age of 28.2 years (with a range from three to 71 years). Symptoms consisted of abdominal pain, abdominal mass, fever, and dysuria. The primary incision and drainage followed by a urachal remnant excision with a bladder cuff excision (two-stage procedure) was performed in four patients. The mean postoperative hospitalization lasted 5.8 days (with a range of three to seven days), and there were no reported complications. A primary excision of the infected urachal cyst and bladder cuff (single-stage excision) was performed in the other five patients. These patients had a mean postoperative hospitalization time of 9.2 days (with a range of four to 15 days), and complications included an enterocutaneous fistula, which required additional operative treatment. The best method of treating an infected urachal cyst remains a matter of debate. However, based on our results, the two-stage procedure is associated with a shorter hospital stay and no complications. Thus, when infection is extensive and severe, we suggest that the two-stage procedure offers a more effective treatment option.

Prognostic value of ERG, PTEN, CRISP3 and SPINK1 in predicting biochemical recurrence in prostate cancer.

The established prognostic factors associated with prostatic adenocarcinoma are the Gleason score, pathological T staging and serum prostatic-specific antigen (PSA) level. However, these prognostic factors alone are not sufficient for predicting prognostic characteristics, including early stage or advanced prostate cancer, presence of metastasis or disease-related mortality. The purpose of the present study was to simultaneously evaluate the prognostic value and associations of four biomarkers, namely, transcriptional regulator ERG (ERG), phosphatase and tensin homolog (PTEN), cysteine-rich secretory protein 3 (CRISP3) and serine protease inhibitor Kazal type I (SPINK1), and to conduct risk stratification of prostate cancer for use in patient management. A total of 68 formalin-fixed, paraffin-embedded, prostate cancer samples from radical prostatectomies were obtained in the Kyung Hee University Hospital (Seoul, Korea) and were studied immunohistochemically for ERG, PTEN, CRISP3 and SPINK1 to determine the proportion and intensity of staining. SPINK1 expression was mutually exclusive of ERG expression (P=0.001). The loss of PTEN and high CRISP3 expression are unfavorable indicators for prostate cancer, as PTEN loss was associated with shorter biochemical recurrence (BCR) (P=0.039), and high CRISP3 expression was associated with increased BCR (P<0.001) and cancer-related mortalities (P=0.011). Using the combination of low PTEN and high CRISP3 expression enables attention to be focused on patients who exhibit a poor prognosis. Subgrouping of patients, into high-risk and low-risk categories, was correlated with BCR-free survival in prostate cancer upon multivariate analysis (P=0.030). Overall, low PTEN and high CRISP3 expression significantly characterize the subgroups of prostate cancer that have a poor prognosis for BCR.

Salvage helical tomotherapy for prostate cancer recurrence following definitive external beam radiotherapy: A case report.

Salvage prostatectomy for recurrent prostate cancer after external beam radiotherapy (EBRT) has resulted in positive outcomes; however, it is technically challenging and is associated with a number of risks. When a patient exhibits recurrent prostate cancer following definitive EBRT and presents with comorbidities meaning that they cannot receive a prostatectomy, it is difficult to treat due to the numerous limitations of current salvage therapies. In the present study, two cases of salvage reirradiation using helical tomotherapy for locally recurrent prostate cancer following definitive EBRT are presented. The two patients received EBRT without severe complications. Local recurrence was confirmed by serum levels of prostate-specific antigen, repeat prostate biopsy, prostate magnetic resonance imaging and a bone scan. Salvage reirradiation using helical tomotherapy was performed and resulted in promising outcomes without any complications. In conclusion, helical tomotherapy can be a safe and effective salvage treatment modality for locally recurrent prostate cancer following definitive EBRT.