A case of lung carcinoma with a unique biphasic feature: Implications for histogenesis of "fake mucoepidermoid carcinoma" developing in the peripheral lung.

We present a case of lung carcinoma with a unique biphasic feature. The patient was a 67-year-old male smoker with idiopathic pulmonary fibrosis (IPF). A subpleural tumor in the left lower lobe, embedded in fibrotic tissue, was resected. Histologically, the tumor consisted of major and minor components of mucoepidermoid carcinoma (MEC) and surrounding conventional lepidic adenocarcinoma, respectively. Both components had the same TP53 somatic mutation (p.V157F) but not Mastermind-like 2 (MAML2) gene rearrangement. The two components may have developed from an identical origin. The tumor could be trans-differentiating from lepidic adenocarcinoma to MEC, possibly promoted by IPF-induced tissue damage. The final diagnosis was "adenosquamous carcinoma with mucoepidermoid-like features (that may originate from lepidic adenocarcinoma)." This case has implications for the potential histogenesis of peripheral lung MEC. Over time, the MEC would expand and outgrow the lepidic adenocarcinoma, making it impossible to distinguish between fake and true MEC. The present case suggests that peripheral MEC could differ from proximal MEC in its histogenesis and molecular genetics. Thus, careful examination is necessary to diagnose peripheral lung MEC, particularly in patients with interstitial lung diseases.

Thrombospondin-2 as a Potential Risk Factor in a General Population.

Serum thrombospondin-2 (TSP-2) is a glycoprotein expressed in the extracellular matrix (ECM), which increases during tissue remodeling. It has been shown in recent studies that TSP-2 is a useful predictor of cardiovascular death in patients with heart failure (HF). However, the clinical importance of serum TSP-2 levels in a general population is still unknown. Therefore, we aimed to clarify the association between TSP-2 and clinical risk factors. A periodic epidemiological survey was performed in a community dwelling in the town of Uku, Nagasaki, Japan. A total of 445 residents received a health checkup examination including blood tests such as fasting serum levels of TSP-2. Uni- and multivariate analyses were performed to examine the relationship between TSP-2 and clinical risk factors. All statistical analyses were performed using SAS v9.4 program. The mean ± standard deviation of age was 67.0 ± 9.4 years old. Although serum TSP-2 levels (mean: 20.9 ± 8.5 ng/mL) showed no significant sex difference, they were significantly correlated with the levels of plasma glucose (P < 0.001), insulin (P < 0.01), homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.001), estimated glomerular filtration rate (eGFR) (P < 0.01, inversely), high-sensitivity C-reactive protein (hs-CRP) (P < 0.001), history of atrial fibrillation (P < 0.001), history of cardiovascular diseases (P < 0.001), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (P < 0.001). Moreover, in the multiple stepwise linear regression analysis, the levels of TSP-2 were independently and significantly associated with the history of atrial fibrillation (P < 0.0001), HOMA-IR (P < 0.001), high-sensitivity CRP (P = 0.011), and NT-proBNP (P = 0.043). These results indicated the significant relationship between TSP-2 and clinical risk factors in a general population, suggesting its role as a predictor of heart disease morbidity and mortality.

Serum uric acid is associated with the left ventricular mass index in males of a general population.

The association of serum uric acid (UA) with left ventricular hypertrophy (LVH) remains controversial. We investigated this issue in a general population. Participants consisted of 1,943 subjects (774 males and 1,169 females) aged over 40 years, living in Tanushimaru (a Japanese cohort of the Seven Countries Study). Serum UA and other biochemistry parameters were determined by a standard analytical technique. All individuals underwent anthropometric measurements and 2-dimensional echocardiography. Because serum UA levels are much higher in males than in females, they were analyzed separately. When LV mass index (LVMI) levels were stratified according to tertile as low (≤ 80 cm(2): n = 261), middle (81-103 cm(2): n = 261), and high (≥ 104 cm(2): n = 252) in males, there were significant relationships between LVMI and UA, in addition to age, body mass index, systolic blood pressure, medication for hypertension, triglycerides, and alcohol intake. Multiple stepwise regression analysis revealed LVMI was significantly associated with systolic BP (P < 0.0001), medication for hypertension (P < 0.0001), UA (P = 0.003), BMI (P = 0.019), and alcohol intake (P = 0.038) in males. In females, LVMI was not associated with UA. In a multiple logistic regression analysis, a significantly higher odds ratio of LVH (odds ratio: 1.77, 95%CI: 1.01-3.09, P < 0.05) was observed for males in the highest UA tertile versus the lowest UA tertile after adjustments for confounding factors, but not for females. In this cross-sectional study, there was a clear difference in the relation of UA and LVH between males and females. High serum UA was significantly and independently associated with LVH evaluated by echocardiography in only males of a general population.

Localized anaplastic lymphoma kinase-positive histiocytosis in a cerebellar hemisphere with long-term treatment: illustrative case.

BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive histiocytosis (ALK-H) is an emerging entity in the category of histiocytic neoplasms that was first reported as a multisystemic disease in three infants in 2008. The clinicopathological spectrum of ALK-H has been expanded to include localized disorders in specific organs, but the features of this subtype are not well known. The authors report a case of ALK-H localized in the central nervous system that was difficult to treat and review the relevant literature. OBSERVATIONS: The authors reviewed archival histiocytic tumors at their institute and found a pediatric case of ALK-H localized in a cerebellar hemisphere that had previously been reported as histiocytic sarcoma. Chemotherapy (approximately 1 year), additional surgery, and conventional chemotherapy (approximately 2.5 years) led to clinical remission, and maintenance chemotherapy was continued (approximately 1.5 years). Three years after completing treatment, a high-grade glioma was found in a cerebral hemisphere, and the patient died of the glioma 2 years later. LESSONS: Although the prognosis of ALK-H is generally good according to prior cases, the authors' case required long-term conventional chemotherapy, suggesting the tumor displayed aggressive characteristics. Early administration of ALK inhibitors may be necessary.

Selpercatinib for treating recurrent mixed medullary and follicular cell-derived thyroid carcinoma: a case report.

BACKGROUND: Mixed medullary and follicular cell-derived thyroid carcinoma (MMFCC) is characterized by the coexistence of follicular and C cell-derived tumour cell populations within the same lesion. Due to its rarity, its etiology and clinical course remain unclear, and treatment for advanced or recurrent cases has not been established. CASE PRESENTATION: We report a case of MMFCC treated with selpercatinib. The patient was a 69-year-old male presenting with tumors in the right thyroid lobe and in the upper mediastinum. Fine-needle aspiration (FNA) cytology of the right thyroid lobe tumor revealed a medullary carcinoma; germline RET mutations were not detected. After resection of the right thyroid lobe with central node dissection, rapid intraoperative diagnosis of the mediastinal mass confirmed malignancy, leading to total thyroidectomy with excision of the upper mediastinal tumor. Histologically, the tumor in the right thyroid lobe and the pretracheal lymph node revealed a mixture of medullary and follicular carcinoma components, diagnosed as MMFCC. The mediastinal lymph node exhibited only medullary carcinoma components. At 11 months postoperatively, computed tomography scans showed enlargement of the right supraclavicular and upper mediastinal lymph nodes. FNA cytology of the right supraclavicular lymph node suggested the recurrence of medullary thyroid carcinoma. The gene panel testing (The Oncomine Dx Target Test Multi-CDx system®, Thermo Fisher SCIENTIFIC) of metastatic lymph node revealed RET somatic mutation (M918T). Treatment with selpercatinib was initiated, and both the cervical and mediastinal lymph nodes showed a reduction in size. CONCLUSIONS: We report a rare case of selpercatinib use for MMFCC. Since RET mutations may occur frequently in MMFCC, selpercatinib could be effective in treating MMFCC.

A diagnostically challenging case of inflammatory myofibroblastic tumor primary to the peritoneum.

Introduction: Inflammatory myofibroblastic tumors are difficult to diagnose because of the lack of specific indicators. We describe a diagnostically challenging case of an inflammatory myofibroblastic tumor primary to the peritoneum. Case presentation: The patient was a 25-year-old male who presented at our hospital with lower abdominal pain. Computed tomography revealed a mass lesion 80 mm in diameter just above the bladder. This was suspected to be a bleeding tumor of the urachus. Since malignancy could not be ruled out, surgery was planned. This revealed a fragile tumor arising from the peritoneum. Following its removal, the tumor was diagnosed by histopathological analysis as an inflammatory myofibroblastic tumor. Conclusion: We describe a case of inflammatory myofibroblastic tumor primary to the peritoneum diagnosed by histopathology. Inflammatory myofibroblastic tumor should be considered in the differential diagnosis of abdominal wall and anterior bladder tumors.

Intestinal ultrasound for intestinal Behçet disease reflects endoscopic activity and histopathological findings.

BACKGROUND/AIMS: Intestinal Behçet disease is typically associated with ileocecal punched-out ulcers and significant morbidity and mortality. Intestinal ultrasound is a noninvasive imaging technique for disease monitoring. However, no previous reports have compared intestinal ultrasound with endoscopic ulcer activity or histopathological findings for intestinal Behçet disease. We evaluated the usefulness of intestinal ultrasound for assessing the activity of ileocecal ulcers in intestinal Behçet disease. METHODS: We retrospectively compared intestinal ultrasound findings with 73 corresponding endoscopic images and 6 resected specimens. The intestinal ultrasound findings were assessed for 7 parameters (bowel wall thickness, vascularity [evaluated using the modified Limberg score with color Doppler], bowel wall stratification, white-plaque sign [strong hyperechogenic lines or spots], mesenteric lymphadenopathy, extramural phlegmons, and fistulas), and endoscopic ulcer activity was classified into active, healing, and scar stages. Histopathological findings were evaluated by consensus among experienced pathologists. RESULTS: Bowel wall thickness (P< 0.001), vascularity (P< 0.001), loss of bowel wall stratification (P= 0.015), and white-plague sign (P= 0.013) were significantly exacerbated in the endoscopic active ulcer stage. Receiver operating characteristic curve analysis revealed that a bowel wall thickness of > 5.5 mm (sensitivity 89.7%, specificity 85.3%) was potentially useful for detecting active lesions. When compared with histopathological findings, an increase in bowel wall thickness reflected the ulcer marginal ridge, and the white-plaque sign reflected the ulcer bottom. CONCLUSIONS: Intestinal ultrasound is useful for monitoring intestinal ulcer activity in intestinal Behçet disease.

Intrauterine fetal death due to fetal intracranial hemorrhage associated with maternal vitamin K deficiency: A case report.

Vitamin K deficiency can cause coagulopathy; therefore, supplementation is recommended to prevent intracranial hemorrhage in newborns. Some reports have shown that maternal vitamin K deficiency is associated with intracranial hemorrhage in the fetus. However, no clear guidelines exist for the diagnosis and treatment of maternal vitamin K deficiency to prevent fetal intracranial hemorrhage. We report a case of intrauterine fetal death due to intracranial hemorrhage associated with maternal vitamin K deficiency resulting from hyperemesis gravidarum. In this case, maternal protein induced by vitamin K absence II (PIVKA-II) was high at the time of intrauterine fetal death. Therefore, measuring maternal PIVKA-II levels in high-risk cases may help determine the timing of therapeutic interventions for vitamin K deficiency during pregnancy.

Granulomatous mastitis in a male breast: A case report and review of literature.

Granulomatous mastitis (GM) is a rare disease, particularly among men. Herein, we present a case of GM diagnosed in a 63-year-old male patient who showed reduction in the tumor size during 3 months of observation.

High prevalence of upper lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis in patients with round atelectasis.

BACKGROUND: Upper-lung field pulmonary fibrosis (upper-PF), radiologically consistent with pleuroparenchymal fibroelastosis (PPFE), was reported to develop in patients with a history of asbestos exposure and tuberculous pleurisy, indicating that chronic pleuritis is correlated with upper-PF development. Round atelectasis reportedly emerges after chronic pleuritis. This study aimed to clarify the association between round atelectasis and upper-PF. METHODS: We examined the radiological reports of all consecutive patients with round atelectasis between 2006 and 2018 and investigated the incidence of upper-PF development. RESULTS: Among 85 patients with round atelectasis, 21 patients (24.7%) were confirmed to finally develop upper-PF lesions. Upper-PF was diagnosed after round atelectasis recognition in more than half of the patients (13/21, 61.9%), whereas upper-PF and round atelectasis were simultaneously detected in the remaining 8 patients. At the time of round atelectasis detection, almost all patients (19/21, 90.5%) had diffuse pleural thickening and round atelectasis was commonly observed in non-upper lobes of 19 patients (90.5%). Fourteen patients had round atelectasis in unilateral lung, and the remaining 7 patients had round atelectasis in bilateral lungs. Among all 14 patients with unilateral round atelectasis, upper-PF developed on the same (n = 11) or both sides (n = 3). Thus, upper-PF emerged on the same side where round atelectasis was present (14/14, 100%). The autopsy of one patient revealed a thickened parietal-visceral pleura suggestive of chronic pleuritis. Subpleural fibroelastosis was also observed. CONCLUSIONS: Upper-PF occasionally develops on the same side of round atelectasis. Upper-PF may develop as a sequela of chronic pleuritis.

Serum hepatocyte growth factor and cancer mortality in an apparently healthy Japanese population.

BACKGROUND: In patients with cancer, hepatocyte growth factor (HGF) is elevated and is a predictor of prognosis. We investigated whether serum HGF was a predictive marker for cancer death in a population of community-dwelling Japanese. METHODS: We studied 1492 apparently healthy Japanese adults who underwent health examinations in 1999. Those who reported a history of liver disease or malignancy on a baseline questionnaire were excluded, and plasma HGF was measured in the remaining 1470 participants, who were followed periodically for 10 years. Multivariate proportional hazards regression was used to estimate cancer mortality. RESULTS: A total of 169 participants died during follow-up (61 from cancer, 32 from cerebrocardiovascular disease, and 76 from other diseases). Mean HGF at baseline was significantly higher among decedents than among survivors (0.26 ± 0.11 vs 0.23 ± 0.09 ng/ml, respectively; P < 0.01). The Cox proportional hazards model showed that age, systolic blood pressure, HGF (hazard ratio, 1.27; 95% CI, 1.06-1.52; P = 0.009), albumin level, smoking status, and creatinine were independent predictors of all-cause death. Age, HGF (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = 0.02), and total cholesterol were independent predictive markers for cancer death. CONCLUSIONS: Serum HGF was a predictor of cancer death in an apparently healthy population of community-dwelling Japanese.

Association between physical activity, occupational sitting time and mortality in a general population: An 18-year prospective survey in Tanushimaru, Japan.

AIMS: It is well known that a decline in physical activity is associated with an increase of all-cause death including cardiovascular events and cancer. Few studies have examined the association between occupational sitting time and mortality. Therefore, we investigated this issue in a general population. METHODS: Physical activity and occupational sitting time were measured using the Baecke physical activity questionnaire in 1999. The questionnaire generated indices in three physical activity categories: work, sport and leisure-time. A total physical activity index was calculated by adding these three indices. The Baecke physical activity questionnaire was able to evaluate occupational sitting time. Hazard ratios and 95% confidence intervals (CIs) were calculated using Cox's proportional hazard regression models. RESULTS: We enrolled a total of 1680 participants, who were followed up for 15.9 ± 3.8 years. The final follow-up rate was 93%. During the follow-up period, 397 subjects died. A significant inverse association (p < 0.0001) was found between physical activity and mortality after adjustment for age and sex. Compared with lower levels of physical activity, the adjusted hazard ratio for mortality at higher levels of physical activity was 0.85 (95% CI: 0.78-0.92). Longer occupational sitting time was also significantly associated with higher mortality (p < 0.01). The adjusted hazard ratio for mortality at longer occupational sitting time was 1.16 (95% CI: 1.05-1.27). These findings were observed in males, but not in females. CONCLUSIONS: Our data demonstrated that higher levels of physical activity are associated with a reduced risk of cancer and cardiovascular death. Further, longer occupational sitting time is associated with increased mortality.

Effects of eplerenone on blood pressure and glucose metabolism in Japanese hypertensives with overweight or obesity.

OBJECTIVE: The impact of aldosterone blockade using eplerenone on hypertensives with obesity has not been clarified. We compared the efficacy and safety between eplerenone and trichlormethiazide in hypertensives with overweight or obesity. METHODS: A prospective, randomized, open-labeled, blinded-endpoint design, multicenter trial enrolled 204 hypertension-treated outpatients with obesity [body mass index (BMI) ≥25 kg/m] evaluated by ambulatory blood pressure (BP) measurement. Patients were randomly assigned to receive 50 mg of eplerenone (n = 102) or 1 mg of trichlormethiazide (n = 102), each of which were administered once every morning. Primary efficacy endpoints were systolic and diastolic BPs and biomarkers of glucose metabolism after 6 months of treatment. RESULTS: At baseline, BPs were comparable between the two groups. Systolic/diastolic blood pressure (SBP/DBP) were reduced from 153.9 ±â€Š12.6/84.6 ±â€Š11.8 to 129.8 ±â€Š14.2/73.7 ±â€Š12.2 mm Hg by eplerenone therapy and from 152.2 ±â€Š12.5/85.2 ±â€Š10.9 to 133.8 ±â€Š12.6/76.1 ±â€Š8.6 mm Hg by trichlormethiazide therapy (all; P < .001). The efficacy of SBP reduction after adjustment for age, sex, and BMI was significantly greater in the eplerenone group than the trichlormethiazide (P = .034), although the efficacy of DBP reduction was marginally significant (P = .072). Especially, the efficacy of BP reduction was more effective for aged over 65 years than less than 65 years. However, biomarkers of glucose metabolism were not significantly different between these 2 groups. CONCLUSION: The eplerenone therapy was more effective in BP lowering in hypertensives with overweight or obesity than the trichlormethiazide therapy, especially in the elderly.

Effects of blood pressure lowering in patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis.

The efficacy and safety of blood pressure lowering in patients with heart failure with preserved ejection fraction (HFpEF) remain unknown. We systematically searched PubMed/Medline, ICHUSHI, EMBASE, and the Cochrane Central Library database for randomized controlled trials (RCTs) assessing the efficacy and safety of blood pressure lowering in patients with HFpEF that were published from January 1996 to July 2017. Our study included a total of 10 RCTs involving 13,091 patients with HFpEF that compared all-cause mortality, cardiovascular mortality, heart failure hospitalization, renal dysfunction, and/or hypotension between drug intervention and control groups. Then, we analyzed systolic blood pressure (SBP) before and during trials using the SBP from the RCTs data. SBP decreased in the intervention group (134.7-130.2 mmHg) more than that in the control group (134.4-133.3 mmHg), and heart failure hospitalization was reduced in the intervention group compared to that in the control group [RR 0.89 (0.82-0.97), P = 0.006]. There was no effect of treatment on all-cause mortality, cardiovascular mortality, and hypotension. However, in the studies that compared renal function, SBP decreased in the intervention group (134.3-129.6 mmHg) more than that in the control group (134.0-132.8 mmHg), and the occurrence of renal dysfunction increased in the intervention group compared to that in the control group [RR 1.52 (1.31-1.76), P < 0.00001)]. Blood pressure lowering that achieves SBP levels of ~130 mmHg may be related to the reduction in heart failure hospitalization in patients with HFpEF, but it also possibly leads to an increased risk of renal dysfunction.

Effects of lowering diastolic blood pressure to <80 mmHg on cardiovascular mortality and events in patients with coronary artery disease: a systematic review and meta-analysis.

The target of diastolic blood pressure (DBP) remains controversial in patients with coronary artery disease (CAD). We systematically searched PubMed/Medline and the Cochrane Central database for randomized controlled trials (RCTs) assessing the efficacy and safety of reducing DBP in CAD patients from January 1965 to July 2017. Seven placebo-controlled RCTs enrolling 34,814 CAD patients who achieved DBP <80 mmHg were included in the drug-intervention group. The average achieved blood pressures (BPs) were 126.3/75.1 and 131.5/77.8 mmHg in the drug-intervention and placebo-control groups, respectively. Drug intervention was associated with an 11% reduction in coronary revascularization and a 31% reduction in heart failure. In the drug-intervention group, all-cause death, myocardial infarction, angina pectoris, and stroke were reduced with marginal significance, whereas hypotension was increased by 123%. A meta-analysis of four RCTs, in which the achieved DBP was <75 mmHg, showed that the drug intervention was associated with a 22% reduction in heart failure. These results suggest that reducing DBP to 80 mmHg or less would significantly reduce coronary revascularization and heart failure but at the expense of causing hypotension in CAD patients. Further trials are warranted to prove this issue.

Angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers in hypertensive patients with myocardial infarction or heart failure: a systematic review and meta-analysis.

Angiotensin-converting enzyme inhibitors (ACEIs) are considered primary drugs for the secondary prevention of myocardial infarction (MI), and angiotensin receptor blockers (ARBs) are used when ACEIs cannot be tolerated. However, it is unclear whether ACEIs or ARBs are more appropriate first-line drugs in hypertensive patients with MI or heart failure (HF). The present study aimed to compare the effects of ACEIs and those of ARBs in these patients. Sixty randomized controlled trails (RCTs) that compared the effects of ACEIs and ARBs in patients with MI or HF were extracted by searching PubMed/MEDLINE, Cochrane Database, and the Medical Central Journal database according to the PRISMA guidelines. We finally selected six eligible RCTs and identified three systematic reviews and meta-analyses. The proportion of hypertensive patients ranged from 36 to 69%. Meta-analyses were performed for recurrence or new onset of MI (risk ratio 0.97 [95% confidence interval: 0.88, 1.06]), hospitalization for HF (0.98 [0.84, 1.14]), cardiovascular or total mortality (0.98 [0.91, 1.05]), cardiovascular events or stroke (1.02 [0.94, 1.11]), and adverse events (1.40 [1.11, 1.77]). There were no significant differences between ACEIs and ARBs for all outcomes, except adverse events. Study discontinuation owing to adverse events was significantly more common with ACEIs than with ARBs. Among hypertensive patients with MI or HF, it appears desirable to select the most appropriate drugs, ACEIs or ARBs, in each case by considering the function level, patient background, comorbidity presence, blood pressure target, drug price and other such factors comprehensively in addition to considering tolerability.

Twenty-four-Hour Urinary Potassium Excretion, But Not Sodium Excretion, Is Associated With All-Cause Mortality in a General Population.

BACKGROUND: Few studies have examined the relationship between accurate monitoring of sodium or potassium consumption and mortality. We aimed to investigate the association between 24-hour urinary sodium or potassium excretion and ≈30-year mortality in a Japanese population using 24-hour urine collection. METHODS AND RESULTS: We enrolled a total of 1291 participants, aged 21 to 85 years, who underwent health checkups, including a blood test and 24-hour urine collection. They were followed up for 27.5±9.9 years by December 31, 2015, and the final follow-up rate was 95.8%. Cox proportional hazards regression analysis was used to assess the association between 24-hour urinary sodium or potassium excretion and all-cause mortality. At baseline, the mean 24-hour urinary sodium and potassium excretions were 5.80±2.28 g/d and 1.85±0.82 g/d, respectively. There were 631 deaths during the follow-up. The cumulative survival rate was significantly decreased in the lowest quartile compared with the other higher groups. In the Cox proportional hazard model after adjustment for age and sex, 24-hour urinary potassium excretion, but not sodium excretion, was inversely associated with all-cause mortality. We divided the 24-hour urinary potassium excretion levels into quartiles. After adjustment for confounding factors, the hazard ratio of all-cause mortality in the highest quartile of 24-hour urinary potassium excretion versus the lowest was 0.62 (95% confidence interval, 0.48-0.79; P<0.001). CONCLUSIONS: The 24-hour urinary potassium excretion, but not sodium excretion, was significantly associated with all-cause mortality in the general population.

Impact of cystatin C and microalbuminuria on cognitive impairment in the population of community-dwelling Japanese.

BACKGROUND AND AIMS: Cognitive impairment is an important element affecting our well-being, and as such, early diagnosis is critical today. We investigated whether serum cystatin C and microalbuminuria are associated with cognitive impairment. METHODS: A total of 1943 subjects (774 males, 1169 females, mean age 65.8 years) took part in the investigation, and underwent a health examination in Tanushimaru, Japan, in 2009. The participants' cognitive function was evaluated using of mini-mental state examination (MMSE). We measured the levels of serum cystatin C using latex nephelometric immunoassay. Spot urine samples were used to measure microalbuminuria levels. Multivariate linear regression analyses were used to assess the relationship between MMSE scores and the level of cystatin C or microalbuminuria. All statistical analyses were performed using the SAS system. RESULTS: The mean values of log-transformed serum cystatin C levels and log-transformed microalbuminuria were 0.95 (range 0.41-7.11) mg/L and 10.7 (range 1.1-2600) mg/g·Cr, respectively. The means of MMSE score were 27.7 ± 2.5. In the multivariate linear regression analyses adjusted for age and sex, MMSE was significantly associated with systolic blood pressure (p = 0.024, inversely), cystatin C (p = 0.046, inversely) and microalbuminuria (p = 0.019, inversely), whereas estimated glomerular filtration rate (eGFR) had an insignificant association (p = 0.197). In the multiple stepwise linear regression analysis, age, history of stroke, systolic blood pressure, serum cystatin C were independently associated with MMSE levels. CONCLUSIONS: We demonstrated for the first time that cognitive function was significantly and inversely associated with cystatin C and microalbuminuria, in the relatively younger general population.