Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS)

Background@#The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. @*Methods@#The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. @*Results@#The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. @*Conclusions@#The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS)

Background@#The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. @*Methods@#The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. @*Results@#The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. @*Conclusions@#The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

The Colonoscopic Characteristics and Clinical Manifestations Associated with Lower Gastrointestinal Tract Bleeding in Patients with Chronic Kidney Disease / 대한내과학회지

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have a high risk of gastrointestinal tract bleeding because of platelet dysfunction attributable to uremia, a poor blood supply, and frequent use of anticoagulant agents. We describe the colonoscopic characteristics of lower gastrointestinal tract bleeding (LGIB) in patients with CKD. METHODS: A total of 230 hospitalized patients with CKD who underwent colonoscopy because of suspected LGIB between January 2003 and August 2016 were reviewed retrospectively. We categorized CKD into five stages according to the estimated glomerular filtration rate and compared the colonoscopic findings and clinical manifestations among these five subgroups. RESULTS: Of the 230 patients with CKD suspected of LGIB, 73 (31.7%, 103 cases) were colonoscopically confirmed to exhibit LGIB. Their mean age was 65.7 ± 12.8 years, and 52.1% were female (n = 38). The most common causes of LGIB were hemorrhoidal bleeding (32 cases, 43.8%), followed by bleeding of colorectal ulcers (21 cases, 28.8%), diverticular bleeding (12 cases, 16.4%), colitis-related bleeding (12 cases, 16.4%), and angiodysplastic bleeding (12 cases, 16.4%). As the CKD stage progressed, the incidence of LGIB increased (p = 0.043). On multivariate logistic regression analysis, LGIB was more common in CKD patients with hemorrhoids (odds ratio [OR]: 4.349, 95% confidence interval [CI]: 2.043–9.256, p < 0.001) or colorectal ulcers (OR: 20.001, 95% CI: 4.780–83.686, p ℃ 0.001) and in those on hemodialysis (OR: 6.863, 95% CI: 1.140–41.308, p = 0.035). CONCLUSIONS: In CKD patients, the risk of LGIB is significantly increased by hemorrhoids, colorectal ulcers, and a positive hemodialysis status.

The Colonoscopic Characteristics and Clinical Manifestations Associated with Lower Gastrointestinal Tract Bleeding in Patients with Chronic Kidney Disease / 대한내과학회지

BACKGROUND/AIMS@#Patients with chronic kidney disease (CKD) have a high risk of gastrointestinal tract bleeding because of platelet dysfunction attributable to uremia, a poor blood supply, and frequent use of anticoagulant agents. We describe the colonoscopic characteristics of lower gastrointestinal tract bleeding (LGIB) in patients with CKD.@*METHODS@#A total of 230 hospitalized patients with CKD who underwent colonoscopy because of suspected LGIB between January 2003 and August 2016 were reviewed retrospectively. We categorized CKD into five stages according to the estimated glomerular filtration rate and compared the colonoscopic findings and clinical manifestations among these five subgroups.@*RESULTS@#Of the 230 patients with CKD suspected of LGIB, 73 (31.7%, 103 cases) were colonoscopically confirmed to exhibit LGIB. Their mean age was 65.7 ± 12.8 years, and 52.1% were female (n = 38). The most common causes of LGIB were hemorrhoidal bleeding (32 cases, 43.8%), followed by bleeding of colorectal ulcers (21 cases, 28.8%), diverticular bleeding (12 cases, 16.4%), colitis-related bleeding (12 cases, 16.4%), and angiodysplastic bleeding (12 cases, 16.4%). As the CKD stage progressed, the incidence of LGIB increased (p = 0.043). On multivariate logistic regression analysis, LGIB was more common in CKD patients with hemorrhoids (odds ratio [OR]: 4.349, 95% confidence interval [CI]: 2.043–9.256, p < 0.001) or colorectal ulcers (OR: 20.001, 95% CI: 4.780–83.686, p ℃ 0.001) and in those on hemodialysis (OR: 6.863, 95% CI: 1.140–41.308, p = 0.035).@*CONCLUSIONS@#In CKD patients, the risk of LGIB is significantly increased by hemorrhoids, colorectal ulcers, and a positive hemodialysis status.

Prognostic Factors for Node-Negative Advanced Gastric Cancer after Curative Gastrectomy

PURPOSE: Lymph node (LN) metastasis is the best prognostic indicator in non-distant metastatic advanced gastric cancer. This study aimed to assess the prognostic value of various clinicopathologic factors in node-negative advanced gastric cancer. MATERIALS AND METHODS: We retrospectively analyzed the clinical records of 254 patients with primary node-negative stage T2~4 gastric cancer. These patients were selected from a pool of 1,890 patients who underwent radical resection at Memorial Jin-Pok Kim Korea Gastric Cancer Center, Inje University Seoul Paik Hospital between 1998 and 2008. RESULTS: Of the 254 patients, 128 patients (50.4%), 88 patients (34.6%), 37 patients (14.6%), and 1 patient (0.4%) had T2, T3, T4a, and T4b tumors, respectively. In a univariate analysis, operation type, T-stage, venous invasion, tumor size, and less than 15 LNs significantly correlated with tumor recurrence and cumulative overall survival. In a multivariate logistic regression analysis, tumor size, venous invasion, and less than 15 LNs significantly and independently correlated with recurrence. In a multivariate Cox proportional hazards analysis, tumor size (hazard ratio [HR]: 2.926; 95% confidence interval [CI]: 1.173~7.300; P=0.021), venous invasion (HR: 3.985; 95% CI: 1.401~11.338; P=0.010), and less than 15 LNs (HR: 0.092; 95% CI: 0.029~0.290; P<0.001) significantly correlated with overall survival. CONCLUSIONS: Node-negative gastric cancers recurred in 8.3% of the patients in our study. Tumor size, venous invasion, and less than 15 LNs reliably predicted recurrence as well as survival. Aggressive postoperative treatments and timely follow-ups should be considered in cases with these characteristics.

A Case of Bad Prognosis for Membranous Nephropathy in a Patient with Mixed Connective Tissue Disease

Incidence of renal involvement in mixed connective tissue disease (MCTD) is low. In the presence of glomerulonephritis, membranous nephropathy (MN) in MCTD is common. A 47-year-old woman presented with hypothyroidism. She developed Raynaud's phenomenon, arthralgia, and incomplete lupus erythematosus, diagnosed with MCTD. One year after then, the patient developed persistent proteinuria (1+) without hematuria. Following diagnosis with MCTD, her renal function began to deteriorate. The renal biopsy showed late stage MN. For the treatment of MN with mild proteinuria and MCTD, we prescribed an angiotensin II receptor blocker and 7.5 mg of methotrexate per week and 300 mg of hydroxychloroquine daily. The patient had a reduced estimated glomerular filtration rate of 55% for the subsequent eight years. The MN in MCTD is known to show good renal prognosis. Here, we report on a rare case of MN in MCTD in Korea with a bad prognosis.

Estimation of Daily Salt Intake through a 24-Hour Urine Collection in Pohang, Korea

There is an established relationship between a high salt diet and public health problems, especially hypertension and cardiovascular disease. We estimated daily salt intake in a group of adults and assessed its association with related variables in Pohang, Korea. We conducted a cross-sectional survey in 2013 with 242 adults. Urine was collected for 24 hr to estimate daily salt intake, and questionnaires about salt preference were administered. The mean daily salt intake was 9.9+/-4.6 g. There was no difference in salt intake between high systolic blood pressure (SBP) participants and normal SBP participants (10.5+/-4.7 g/d vs. 9.6+/-4.3 g/d, P=0.339), but high diastolic blood pressure (DBP) participants reported more salt intake than normal DBP participants (10.4+/-4.9 g/d vs. 9.7+/-4.1 g/d, P=0.049). Salt intake and body mass index demonstrated a positive correlation (P=0.001). A preference for Korean soup or stew was associated with high salt intake (P=0.038). Dietary salt intake in Korean adults is still higher than the recommendation from the World Health Organization. More efforts should be made to reduce the salt consumption of Korean adults.

A Case of High dose Colchicine with No Efficacy in a Patient with Chronic Kidney Disease Taking Rifampicin

A 54-year-old male on chronic hemodialysis, who was taking rifampicin for tuberculous lymphadenitis, was admitted for an acute gout attack. After administrating 3.6 mg of colchicine for 2 days, symptoms began to alleviate. Despite the relatively high dosage in this end-stage renal disease patient, there were no adverse effects, such as diarrhea, vomiting, or myopathy. After 1 and 6 hours of 0.6 mg colchicine administration, serum colchicine was 1.3930 ng/mL and 0.2464 ng/mL, respectively. These values were lower than the mean concentrations in 13 other patients with chronic kidney disease (CKD) after the same time intervals (4.34+/-0.56 ng/mL and 1.49+/-0.15 ng/mL, respectively). As rifampicin is an inducer of cytochrome P450 3A4, metabolism of colchicine had increased. When taking colchicine and rifampicin simultaneously, a higher colchicine dose may be needed for the treatment of acute gout in patients with CKD.

Estimating 24-Hour Urine Sodium Level with Spot Urine Sodium and Creatinine

The 24-hr urine sodium excretion level was estimated based on the spot urine sodium, and the efficacy of the formula was validated to determine the status of low salt intake or =100 mEq/day using the estimated amount> or =100 mEq/day was 84.3%, 87.6%, and 84.8%, respectively. In conclusion, the three equations used to estimate the 24-hr urine sodium content were useful to determine the status of low salt intake.

Estimated 24-Hour Urine Sodium Excretion Is Correlated with Blood Pressure in Korean Population: 2009-2011 Korean National Health and Nutritional Examination Survey

No large-scale studies have investigated the association between salt intake and hypertension in Korean population. To investigate the relationship of blood pressure to salt consumption, we analyzed data from 19,476 participants in the 2009-2011 Korean National Health and Nutritional Examination Survey (KNHANES). Urinary sodium excretion over 24-hr (24HUNa) was estimated from spot urine tests using Tanaka's equation. The study subjects were stratified into hypertensive and normotensive groups. Hypertensive participants (n=6,552, 33.6%) had higher estimated 24HUNa, 150.4+/-38.8 mEq/day, than normotensive participants, 140.5+/-34.6 mEq/day (P<0.001). The association between 24HUNa and blood pressure outcomes was not affected by adjustment for other risk factors for hypertension (odds ratio 0.001; 95% confidence interval 0.001-0.003; P<0.001). Increases in 24HUNa of 100 mEq/day were associated with a 6.1+/-0.3/2.9+/-0.2 mmHg increase in systolic/diastolic blood pressure in all participants. This effect was stronger in hypertensive participants (increase of 8.1+/-0.5/3.4+/-0.3 mmHg per 100 mEq/day) and smaller in normotensive participants (2.9+/-0.3/1.3+/-0.2 mmHg). These results support recommendations for low salt intake in Korean population to prevent and control adverse blood pressure levels.

Analysis of Correlation between 24-Hour Urinary Sodium and the Degree of Blood Pressure Control in Patients with Chronic Kidney Disease and Non-Chronic Kidney Disease

We investigated the association between 24-hr urinary sodium (24UNA) and adequacy of blood pressure (BP) control in patients with chronic kidney disease (CKD) and nonCKD. All data were collected retrospectively by accessing the electrical medical records in patients with 24-hr urine collection and serum creatinine. Enrolled 400 subjects were subgrouped by the amount of 24UNA, or CKD stage. The appropriate BP was defined as BP or =90 mEq/day was 2.441 (1.249-4.772, P=0.009) higher than that of 24UNA <90 mEq/day among participants with proteinuria. There was difference in the amount of 24UNA between CKD and non-CKD except each stage of CKD group. In conclusion, salt intake estimated by 24-hr urine sodium excretion is a risk factor to achieve appropriate BP control.

Estimated Amount of 24-Hour Urine Sodium Excretion Is Positively Correlated with Stomach and Breast Cancer Prevalence in Korea

Stomach cancer is one of the most common cancers in Korea. The aim of this study was to identify the association between the prevalence of cancer, particularly stomach cancer, and the amount of 24-hr urine sodium excretion estimated from spot urine specimens. The study included 19,083 subjects who took part in the Korean National Health and Nutritional Examination Survey between 2009 and 2011. The total amount of urine sodium excreted in a 24-hr period was estimated by using two equations based on the values for spot urine sodium and creatinine. In subjects who had an estimated 24-hr urine sodium excretion of more than two standard deviations above the mean (group 2), the prevalence of stomach cancer was higher than in subjects with lower 24-hr sodium excretion (group 1). By using the Tanaka equation to estimate it, the prevalence of stomach cancer was 0.6% (114/18,331) in group 1, whereas it was 1.6% (9/568) in group 2 (P=0.006). By using the Korean equation, the prevalence was 0.6% (115/18,392) in group 1, and 1.6% in group 2 (8/507) (P=0.010). By using the Tanaka equation, breast cancer in women is more prevalent in group 2 (1.9%, 6/324) than group 1 (0.8%, 78/9,985, P=0.039). Higher salt intake, as defined by the estimated amount of 24-hr urine sodium excretion, is positively correlated with a higher prevalence of stomach or breast cancer in the Korean population.

Higher Prevalence of Klebsiella pneumoniae Extended-Spectrum beta-Lactamase in Patients on Renal Replacement Therapy

The prevalence of antibiotic resistance is higher in patients undergoing renal replacement therapy (RRT) than in patients who did not undergo RRT. We investigated the presence of KP (Klebsiella pneumoniae) in patients who underwent RRT. All data were collected retrospectively by accessing patient medical records from 2004 to 2011 for the culture results of all patients who were positive for KP. We grouped the patients by the presence of extended-spectrum beta-lactamase (ESBL) into a KP ESBL(-) group (KP[-]) and a KP ESBL(+) group (KP[+]). In total, 292 patients (23.1%) were in the KP(+) group, and 974 patients (76.9%) were in the KP(-) group. A greater percentage of KP(+) was found in patients who underwent RRT (7.5%) than in patients who did not undergo RRT (3.2%) (OR, 2.479; 95% CI,1.412-4.352). A Cox's hazard proportional model analysis was performed, and for patients with pneumonia, the risk of KP(+) was 0.663 times higher in patients who had lower albumin levels, 2.796 times higher in patients who had an inserted Levin tube, and 4.551 times higher in patients who underwent RRT. In conclusion, RRT can be a risk factor for KP(+) in patients with pneumonia.

How Long Should We Monitor the Patient for Bleeding after Percutaneous Renal Biopsy? / 대한신장학회지

PURPOSE: Percutaneous renal biopsy (PRB) may become complicated by serious bleeding. Overnight observation after renal biopsy is a standard safety strategy. Although it was recently reported that outpatient observation is safe, appropriate observation time after the renal biopsy is still in debate. We evaluated prospectively the incidence, onset time and risk factors of hemorrhagic complications to determine the optimal duration of observation after PRB. METHODS: We enrolled 100 patients who underwent renal biopsy from October 2009 to April 2010 using the standard strategy. The biopsy was performed by two experienced nephrologists using 16-gauge spring-loaded biopsy gun under real-time ultrasound guidance. Serial color Doppler ultrasound was done immediately, 8 hours, 24 hours and 1 week after the PRB. RESULTS: The 32 patients experienced hemorrhagic complications (32.0%, 10 with gross hematuria, 26 with hematoma, and 4 with both), and 1 major complication occurred 3 days after PRB. Baseline serum creatinine of the patient with the major complication was 6.0 mg/dL. Serum creatinine and BMI were higher in complication group (p<0.05). Number of needle passes, blood pressure, and degree of edema and proteinuria were not related to the complication. In multivariate analysis, serum creatinine was the only significant risk factor of complication (p=0.007). Hemorrhagic complications developed in 9 patients (28.1%) between 8 and 24 hours after PRB, all of which were minor. CONCLUSION: The 8 hours' observation time after renal biopsy may be deemed appropriate for stable patients with normal creatinine.

Clinical Characteristics and Adherence of Patients Who Were Prescribed Home Oxygen Therapy Due to Chronic Respiratory Failure in One University Hospital: Survey after National Health Insurance Coverage / 결핵및호흡기질환

BACKGROUND: Despite the benefits of home oxygen therapy in patients suffering chronic respiratory failure, previous reports in Korea revealed lower compliance to oxygen therapy and a shorter time for oxygen use than expected. However, these papers were published before oxygen therapy was covered by the national insurance system. Therefore, this study examined whether there were some changes in compliance, using time and other clinical features of home oxygen therapy after insurance coverage. METHODS: This study reviewed the medical records of patients prescribed home oxygen therapy in our hospital from November 1, 2006 to September 31, 2008. The patients were interviewed either in person or by telephone to obtain information related to oxygen therapy. RESULTS: During study period, a total 105 patients started home oxygen therapy. The mean age was 69 and 60 (57%) were male. The mean oxygen partial pressure in the arterial blood was 54.5 mmHg and oxygen saturation was 86.3%. Primary diseases that caused hypoxemia were COPD (n=64), lung cancer (n=14), Tb destroyed lung (n=12) and others. After oxygen therapy, more than 50% of patients experienced relief of their subjective dyspnea. The mean daily use of oxygen was 9.8+/-7.3 hours and oxygen was not used during activity outside of their home (mean time, 5.4+/-3.7 hours). Twenty four patients (36%) stopped using oxygen voluntarily 7+/-4.7 months after being prescribed oxygen and showed a less severe pulmonary and right heart function. The causes of stopping were subjective symptom relief (n=11), inconvenience (n=6) and others (7). CONCLUSION: The prescription of home oxygen has increased since national insurance started to cover home oxygen therapy. However, the mean time for using oxygen is still shorter than expected. During activity of outside their home, patients could not use oxygen due to the absence of portable oxygen. Overall, continuous education to change the misunderstandings about oxygen therapy, more economic support from national insurance and coverage for portable oxygen are needed to extend the oxygen use time and maintain oxygen usage.

Congenital Cystic Adenomatoid Malformation of Lung in Adults: Clinical, Pathologic and Radiologic Evaluation of Six Patients / 결핵및호흡기질환

BACKGROUND: Congenital cystic adenomatoid malformation of the lung (CCAM) is a rare congenital developmental anomaly of the lower respiratory tract. Most cases are diagnosed within the first 2 years of life, so adult presentation of CCAM is rare. We describe here six adult cases of CCAM and the patients underwent surgical resection, and all these patients were seen during a five and a half year period. The purpose of this study was to analyze the clinical, radiological and histological characteristics of adult patients with CCAM. METHODS: Through medical records analysis, we retrospectively reviewed the clinical characteristics, the chest pictures (X-ray and CT) and the histological characteristics. RESULTS: Four patients were women and the mean age at diagnosis was 23.5 years (range: 18~39 years). The major clinical presentations were lower respiratory tract infection, hemoptysis and pneumothorax. According to the chest CT scan, 5 patients had multiseptated cystic lesions with air fluid levels and one patient had multiple cavitary lesions with air fluid levels, and these lesions were surrounded by poorly defined opacities at the right upper lobe. All the patients were treated with surgical resection. 5 patients underwent open lobectomy and one patient underwent VATS lobectomy. On the pathological examination, 3 were found to be CCAM type I and 3 patients were CCAM type II, according to Stocker's classification. There was no associated malignancy on the histological studies of the surgical specimens. CONCLUSION: As CCAM can cause various respiratory complications and malignant changes, and the risks associated with surgery are extremely low, those patients who are suspected of having or who are diagnosed with CCAM should go through surgical treatment for making the correct diagnosis and administering appropriate treatment.

A Case of Tuberculous Pleural Effusion Developed after Percutaneous Needle Biopsy of a Solitary Pulmonary Nodule / 결핵및호흡기질환

A tuberculous pleural effusion may be a sequel to a primary infection or represent the reactivation of pulmonary tuberculosis. It is believed to result from a rupture of a subpleural caseous focus in the lung into the pleural space. It appears that delayed hypersensitivity plays a large role in the pathogenesis of a tuberculous pleural effusion. We encountered a 52 years old man with pleural effusion that developed several days after a CT guided percutaneous needle biopsy of a solitary pulmonary nodule. He was diagnosed with TB pleurisy. It is believed that his pleural effusion probably developed due to exposure of the parenchymal tuberculous focus into the pleural space during the percutaneous needle biopsy. This case might suggest one of the possible pathogeneses of tuberculous pleural effusion.

Comparison of oral N-acetylcysteine(NAC) and prehydration for preventing contrast-induced nephropathy in patients with renal dysfunction / 대한내과학회지

BACKGROUND: Contrast induced nephropathy (CIN) is an important cause of acute renal failure in patients with renal dysfunction. We investigated whether oral NAC alone was sufficient to prevent CIN to the same extent as hydration in patients with renal dysfunction, and whether these treatments resulted in diffierences in the urinary excretion of nitric oxide, a vasodilator. METHODS: A total of 27 patients with renal dysfunction, who underwent radiographic examination with nonionic and low osmolar contrast, were randomly assigned to receive either NAC (600 mg orally twice daily; N=11) or 0.45% saline hydration (1 mL/kg/Hr; N=16) 12 hours prior to and 12 hours after the contrast procedure. We measured serum creatinine (sCr), fractional excretion of sodium (FENa), creatinine clearance (CCr), and urinary nitrite before and after contrast administration. RESULTS: The mean volume of contrast used was similar in the two groups (100.9+/-54.8 mL vs 114.7+/-38 mL; p=0.43), as was baseline sCr in the two groups (2.31+/-1.59 mg/dL vs 2.18+/-1.41 mg/dL; p=0.98). Treatment did not significantly affect the incidence of CIN, with 18.2% and 12.5% in the NAC group and hydration group, respectively (p=1.0). The urinary nitrite/creatinine ratio (micro mol/mg) was 1.26+/-0.57 and 1.43+/-0.64 at baseline and 48 hours after contrast exposure in the NAC group, respectively, and 0.80+/-0.40 and 1.18+/-0.60 in the hydration group, respectively, which were not significantly different. FENa increased significantly after contrast exposure in the NAC group compared with hydration group (p=0.04) CONCLUSIONS: NAC alone may prevent CIN. When bolus hydration is contraindicated in patients with renal dysfunction, administration of NAC alone may be sufficient.