Adolescence is a time of social and cognitive development associated with changes in brain structure and function. These developmental changes may show an altered path in individuals born before 33 weeks' gestation (very preterm; VPT). The cerebellum is affected by VPT birth, but no studies have yet assessed the adolescent development of this structure, or whether developmental changes in cerebellar structure are associated with cognitive and behavioural outcome. We measured cerebellar volumes on structural magnetic resonance images in 65 adolescents who were born before 33 weeks' gestation (VPT) and 34 term-born adolescents (mean age VPT = 15.09, SD = 1.43/mean age term-born = 15.43, SD = 0.56) and again in adulthood (mean age VPT = 18.61, SD = 1.02/mean age term-born = 19.17, SD = 0.95). Participants also underwent neuropsychological tests; the Wechsler Abbreviated Scale of Intelligence and the Controlled Oral Word Association Test and completed the General Health Questionnaire-12. Repeated measures ANOVA showed a main effect of time-point (F = 4.59, df = 1, P = 0.035) and a time-point by group interaction (F = 8.03, df = 1, P = 0.006) on cerebellar growth. By adulthood, cerebellar volumes were 3.11% smaller in the preterm group than they had been in early adolescence (P = 0.000). Cerebellar volume did not change significantly in the control group (P = 0.612). There were significant negative correlations between change in cerebellar volume and GHQ-12 in the VPT group; total score (r = -0.324 P = 0.028) and several subscales; concentration (r = -0.378 P = 0.010), feeling useful (r = -0.311 P = 0.035), decision-making capability (r = -0.348 P = 0.018), overcoming difficulties (r = -0.331 P = 0.025), feeling confident (r = -0.309 P = 0.037) and feeling worthless (r = -0.329 P = 0.026). In the VPT group there were positive correlations between cerebellar volume and full-scale IQ (adolescence; r = 0.471, P = 0.002/adulthood; r = 0.309, P = 0.047), performance IQ (adolescence; r = 0.434, P = 0.004/adulthood; r = 0.345, P = 0.025) and verbal IQ (adolescence; r = 0.401, P = 0.008) which were not maintained after controlling for white matter volume. We have demonstrated a reduction in cerebellar volume between adolescence and young adulthood in VPT individuals, which is correlated with reduced self-reported wellbeing.

Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has been used increasingly as an anticoagulant during continuous renal replacement therapy (CRRT). However, there, are limited data from randomized studies on NM use in patients with a bleeding tendency. This prospective study evaluated the efficacy and safety of NM use during CRRT in patients with acute kidney injury (AKI) patients at high risk of bleeding.Patients with AKI at high risk of bleeding were randomized into the NM and no anticoagulant (NA) groups. The primary outcome was the treatment efficacy represented by the filter lifespan. Several parameters, including safety and patient survival rates at 30 and 90 days, were analyzed as secondary outcomes.Fifty-five patients were included in this study (NM group = 31, NA group = 24). The baseline characteristics did not significantly differ between the groups. The mean filter lifespan was significantly longer in the NM group than in the NA group (31.7 ± 24.1 versus 19.5 ± 14.9 hours; P = 0.035). The most common cause of filter failure was filter clotting, which was significantly more frequent in the NA group than in the NM group (59.6% versus 37.7%, P = 0.024). The Cox proportional hazards model showed a 42.2% longer filter lifespan in the NM group compared with the NA group (hazard ratio, 0.578; 95% confidence interval, 0.362–0.923; P = 0.022). There were no significant differences in the frequencies of transfusions and major bleeding between the groups. Patient survival rates at 30 and 90 days after CRRT initiation were comparable between the groups.Nafamostat mesilate is a safe and effective anticoagulant for CRRT and allows sufficient filter survival without increasing the risk of bleeding in critically ill patients with AKI and bleeding tendencies.

Medium cutoff (MCO) dialyzers help remove larger middle molecules associated with symptoms related to the accumulation of uremic retention solutes. We investigated the effect of an MCO dialyzer on the improvement of quality of life (QOL) in maintenance hemodialysis (HD) patients. Forty-nine HD patients with high-flux dialysis were randomly assigned to either an MCO (Theranova 400, Baxter) or a high-flux (FX CorDiax 80 or 60, Fresenius Medical Care) dialyzer and completed the study. QOL was assessed at baseline and after 12 weeks of treatment using the Kidney Disease Quality of Life Short Form-36, and pruritus was assessed using a questionnaire and visual analog scale. The reduction ratios of middle molecules were also evaluated. Laboratory markers, including serum albumin, did not differ between the two groups after 12 weeks. Removals of kappa and lambda free light chains were greater for MCO dialyzer than high-flux dialyzer. The MCO group had higher scores than the high-flux group in the domains of physical functioning and physical role (75.2 ± 20.8 vs. 59.8 ± 30.1, P = 0.042; 61.5 ± 37.6 vs. 39.0 ± 39.6, P = 0.047, respectively), and the MCO group had lower mean scores for morning pruritus distribution and the frequency of scratching during sleep (1.29 ± 0.46 vs. 1.64 ± 0.64, P = 0.034; 0.25 ± 0.53 vs. 1.00 ± 1.47, P = 0.023, respectively). MCO dialyzers may improve patientreported outcomes, particularly the physical components of QOL and uremic pruritus, in patients with high-flux dialyzers. Patients on maintenance dialysis suffer variable symptoms such as fatigue, generalized weakness, and pruritus. These subjective conditions are assumed to be related to middle molecules that are not cleared by conventional hemodialysis (HD) 1. Middle molecules have molecular weights (MWs) ranging between 500 and 60,000 daltons, and their size is a barrier to removal with dialyzers 2,3. The accumulation of middle molecules is associated with specific complications such as amyloidosis, inflammatory reactions, oxidative stress, and endothelial dysfunction 3-5. Consequently, middle molecules contribute to morbidity and mortality and poor quality of life (QOL) in end-stage renal disease (ESRD) patients 6,7. High-flux dialysis, which has benefits for middle molecule clearance, has not displayed a clear mortality advantage compared with low-flux dialysis; the survival benefits of high-flux dialysis were only observed in patients with hypoalbuminemia and diabetes 8,9. Another dialytic modality, hemodiafiltration (HDF) with increased convection, has a higher efficiency for reducing middle-sized solutes than high-flux dialysis 10,11. Large randomized trials comparing HDF and high-flux dialysis have shown conflicting patient outcome results 12-15 ; however, recent results have consistently shown that HDF with a high convection volume improves patient survival 16-18. Medium cutoff (MCO) dialyzers are characterized by a more even distribution of larger pore sizes and a higher number of pores. MCO dialyzers have a higher permeability and...

The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage; however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI; 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients; 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p < 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75–7.48), p = 0.001; HR = 15.65 (95% CI = 2.43–100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p < 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.

ObjectiveSmoking related cues may elicit smoking urges and psychophysiological responses in subjects with nicotine dependence. This study aimed to investigate the effect of repeated virtual cue exposure therapy using the surround-screen based projection wall system on the psychophysiological responses in nicotine dependence.MethodsThe authors developed 3-dimensional neutral and smoking-related environments using virtual reality (VR) technology. Smoking-related environment was a virtual bar, which comprised both object-related and social situation cues. Ten subjects with nicotine dependence participated in 4-week (one session per week) virtual cue exposure therapy. Psychophysiological responses [electromyography (EMG), skin conductance (SC), and heart rate] and subjective nicotine craving were acquired during each session.ResultsVR nicotine cue elicited greater psychophysiological responses and subjective craving for smoking than did neutral cue, and exposure to social situation cues showed greater psychophysiological responses in SC and EMG than did object-related cues. This responsiveness decreased during the course of repeated therapy.ConclusionThe present study found that both psychophysiological responses and subjective nicotine craving were greater to nicotine cue exposure via projection wall VR system than to neutral cues and that enhanced cue reactivity decreased gradually over the course of repeated exposure therapy. These results suggest that VR cue exposure therapy combined with psychophysiological response monitoring may be an alternative treatment modality for smoking cessation, although the current findings are preliminary.

Patients with advanced chronic kidney disease (CKD) or who are on hemodialysis (HD) could have increased susceptibility to the 2019 coronavirus disease (COVID-19) given their pre-existing comorbidities, older age, compromised immune system, and regular visits to populated outpatient dialysis centers. This study included 14 consecutive patients on HD or with advanced CKD who initiated HD after being diagnosed with laboratory-confirmed COVID-19 from February to April 2020 in hospitals throughout Daegu, South Korea. The included patients, 42.9% of whom were men, had a mean age of 63.5 years. Four patients had a history of contact with a patient suffering from COVID-19. The most common symptom was cough (50.0%), followed by dyspnea (35.7%). The mean time from symptom onset to diagnosis and admission was 2.6 and 3.5 days, respectively. Patients exhibited lymphopenia and elevated inflammatory markers, including C-reactive protein and ferritin. Chest radiography findings showed pulmonary infiltration in 10 patients. All patients underwent regular HD in a negative pressure room and received antiviral agents. Four patients received mechanical ventilation and continuous renal replacement therapy at a median duration of 14.0 and 8.5 days, respectively. One patient underwent extracorporeal membrane oxygenation for three days. Among the 14 patients included, two died due to acute respiratory distress syndrome, nine were discharged from the hospital, and three remained hospitalized. Despite the high-risk conditions associated with worse outcomes, patients on HD did not exhibit extremely poor overall COVID-19 outcomes perhaps due to early diagnosis, prompt hospitalization, and antiviral therapy.

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BackgroundAcute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary exosomes of KTRs.MethodsAmong 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each candidate biomarker by western blot analysis.ResultsA total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed increased expression in STA patients, while 17 proteins were increased in TCMR patients. Among them, we selected five proteins as candidate biomarkers for early diagnosis of TCMR according to significance, degree of quantity variance, and information from the ExoCarta database. We confirmed the proteomic expression levels of five candidate biomarkers by western blot analysis in each patient. Of all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046, respectively).ConclusionsTetraspanin-1 and hemopexin were detected in KTR urine and could act as potential diagnostic proteins for TCMR.