Continuous positive airway pressure treatment reduces renal tubular damage in patients with obstructive sleep apnea: A retrospective single-center cohort study.

BACKGROUND: Chronic intermittent hypoxia (IH) plays a significant role in the pathogenesis of obstructive sleep apnea (OSA) comorbidities. The prevalence of chronic kidney disease is higher in patients with OSA than the general population, and renal function decline is well correlated with renal tubular injury. However, little is known about the impact of OSA-induced chronic IH on the renal tubules. METHODS: We conducted a retrospective survey of clinical records performing multiple regression analysis and cluster analysis with particular attention to the 3% oxygen desaturation index (ODI) and urinary N-acetyl-ß-d-glucosaminidase (NAG). RESULTS: In patients with suspicion of OSA, urinary NAG creatinine ratio (UNCR) was elevated as their 3% ODI increased (n = 197, p < 0.001), and the elevated UNCR decreased following CPAP treatment in patients with OSA (n = 46, p = 0.014). Multiple regression analysis showed that 3% ODI was associated with UNCR. Cluster analysis identified three clusters of patients with OSA, including two younger age clusters, one of which was characterized by high BMI, high 3% ODI, and high prevalence of major comorbidities. In a comparative analysis of younger age cases (age ≤ 55, n = 82), the UNCR level was higher in patients with severe 3% ODI (3% ODI > 40 events/h, n = 24) (p = 0.014). CONCLUSIONS: Our results indicate that even at younger ages, OSA patients with severe chronic IH and major comorbidities are susceptible to renal tubular damage. Early treatment with CPAP may attenuate renal tubular injury and progression toward end-stage renal disease.

Long-term clinical clerkship improves medical students' attitudes toward team collaboration.

Objectives: To examine the related factors associated with medical students' attitudes toward team collaboration. Methods: This cross-sectional study targeted medical students, residents, and doctors. A survey was conducted from 2016 to 2017 using the Japanese version of the Jefferson Scale of Attitudes Toward Interprofessional Collaboration (JeffSATIC-J), which evaluated "working relationship" and "accountability." We analyzed 2409 questionnaire responses with JeffSATIC-J items and the gender item. Analysis of variance was used for factors associated with the JeffSATIC-J score and Spearman's rank correlation coefficient for the relationship between educational intervention and the JeffSATIC-J score. Results: First-year students' scores were the highest (F(2, 2045) = 13.42 to 18.87, p < .001), and female students' scores were significantly higher than those of male students (F(1, 2045) = 21.16 to 31.10, p < .001). For residents' scores, the institution was not a significant variable. Female "accountability" scores were significantly higher than those of males (F (1,108) = 4.95, p = .03). Gender was not a significant variable for doctors' scores. Sixth-year students' scores were significantly correlated with the length of clinical clerkship (r(5)=.78 to .96, p<.05), with the exception of females' "working relationship" scores. The medical school with the highest JeffSATIC-J scores had the longest clinical clerkship in the community. Conclusions: These results indicate that long-term clinical clerkship in the community at higher grades is important in improving medical students' attitudes toward team collaboration. A qualitative study is required to confirm our findings.

Reading on a smartphone affects sigh generation, brain activity, and comprehension.

Electronic devices have become an indispensable part of our daily lives, while their negative aspects have been reported. One disadvantage is that reading comprehension is reduced when reading from an electronic device; the cause of this deficit in performance is unclear. In this study, we investigated the cause for comprehension decline when reading on a smartphone by simultaneously measuring respiration and brain activity during reading in 34 healthy individuals. We found that, compared to reading on a paper medium, reading on a smartphone elicits fewer sighs, promotes brain overactivity in the prefrontal cortex, and results in reduced comprehension. Furthermore, reading on a smartphone affected sigh frequency but not normal breathing, suggesting that normal breathing and sigh generation are mediated by pathways differentially influenced by the visual environment. A path analysis suggests that the interactive relationship between sigh inhibition and overactivity in the prefrontal cortex causes comprehension decline. These findings provide new insight into the respiration-mediated mechanisms of cognitive function.

Long-term clinical course of immunotactoid glomerulopathy complicated with diffuse large B-cell lymphoma.

We report a case of immunotactoid glomerulopathy (ITG) complicated with diffuse large B-cell lymphoma (DLBCL). A 68-year-old woman presented with leg edema and was diagnosed with nephrotic syndrome (NS). Renal biopsy revealed ITG. We treated the patient with prednisolone (20 mg/day) and she achieved complete remission of NS. Steroids were gradually reduced. After 1 year, the patient presented with a breast mass determined on biopsy to be DLBCL. She underwent six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. Follow-up revealed complete remission of both DLBCL and ITG. NS recurred after 5 years and she was simultaneously diagnosed with recurrence of DLBCL in bone marrow. She underwent four cycles of R-EPOCH (rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin) therapy and entered remission for DLBCL. NS improved, but the treatment did not lead to remission. After 2 additional years, NS and DLBCL recurred again. She was administered rituximab and NS improved, although proteinuria tended to increase thereafter. One year later, we started prednisolone (10 mg/day), and proteinuria tended to decrease. She is currently undergoing outpatient follow-up. This case suggests that ITG with MGUS should be treated with the possibility of developing malignant hematological disease during the course.

Optogenetic activation of DRN 5-HT neurons induced active wakefulness, not quiet wakefulness.

There has been a long-standing controversy regarding the physiological role of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) in sleep/wake architecture. Some studies have reported that 5-HT acts as a sleep-promoting agent, but several studies have suggested that DRN 5-HT neurons function predominantly to promote wakefulness and inhibit rapid eye movement (REM) sleep. Furthermore, recent studies have reported that there is a clear neurobiological difference between a waking state that includes alertness and active exploration (i.e., active wakefulness) and a waking state that is devoid of locomotion (i.e., quiet wakefulness). These states have also been shown to differ clinically in terms of memory consolidation. However, the effects of 5-HT neurons on the regulation of these two different waking states have not been fully elucidated. In the present study, we attempted to examine the physiological role of DRN 5-HT neurons in various sleep/wake states using optogenetic methods that allowed manipulation of cell-type specific neuronal activation with high temporal and anatomical precision. We crossed TPH2-tTA and TetO-ChR2(C128S) mice to obtain mice with channelrhodopsin-2 (ChR2) [C128S]-expressing central 5-HT neurons, and we activated DRN-5HT neurons or medullary 5-HT neurons. Optogenetic activation of DRN 5-HT neurons caused rapid transition from non-REM sleep to active wakefulness, not quiet wakefulness, whereas activation of medullary 5-HT neurons did not appear to affect sleep/wake states or locomotor activity. Our results may shed light on the physiological role of DRN 5-HT neurons in sleep/wake architecture and encourage further investigations of the cortical functional connectivity involved in sleep/wake state regulation.

Histological Transformation to Large Cell Neuroendocrine Carcinoma from Lung Adenocarcinoma Harboring an EGFR Mutation: An Autopsy Case Report.

We herein report a 58-year-old Japanese woman who survived 14 years after surgery for lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) exon 19 deletion. She developed recurrence, for which she underwent multimodal therapy, including EGFR-tyrosine kinase inhibitor (TKI) administration. She ultimately died from a rapidly progressive right lung tumor that was resistant to EGFR-TKI. According to the autopsy findings, she had combined large-cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the right lung, which retained an EGFR exon 19 deletion in both components. Therefore, the histological transformation to LCNEC can be a mechanism of acquired EGFR-TKI resistance.

The Future of Pharmaceutical Education Based on Our Experience of Medical Education.

We have experienced a series of big revolutions in medical education in Japan. In undergraduate courses, common guidelines had been established for medical education (the model core-curriculum of medical education). Then, from 2005, a standard achievement testing system [objective structured clinical examination (OSCE) and computer based testing (CBT)] was begun, and clinical clerkships were accordingly promoted. In post-graduate courses, a new clinical resident training system was initiated in 2004, and there are currently approximately 40000 clinical instructors nationwide. Accreditation of Japanese medical schools based on global standards for quality improvement has just begun. Almost the same process has taken effect in the field of pharmaceutical education (PE), such as the preparation of guidelines for PE and clinical training, a shift to a six-year course, and the establishment of an accreditation organization. The educational guidelines were revised in 2013 to provide better clinical training. Both of these educational revolutions aim at providing the proper education to train healthcare professionals committed to practicing "patient-centered medicine" and to becoming lifelong learners. To educate such professionals naturally includes improving their communicative competency, and cultivating their professionalism along with their acquisition of scientific and medical knowledge, based on both quantitative and qualitative study. The Society for Medical Education has begun a new "Medical education specialist (MES) training system" responding to the need of MES in every medical school and training hospital. A new PE specialist educational system can be expected soon, as well.

Evaluation of validity of the urine dipstick test for identification of reduced glomerular filtration rate in Japanese male workers aged 40 years and over.

OBJECTIVES: We evaluated the validity of the urine dipstick test for identifying reduced glomerular filtration rate (GFR) in male workers. METHODS: This study was conducted in male workers aged ≥ 40 yr. Reduced GFR was categorized as either estimated GFR (eGFR) < 60 ml/min/1.73 m(2) (eGFR <60) or eGFR < 50 ml/min/1.73 m(2) (eGFR < 50). Four sets of criteria were used to evaluate the GFR on the basis of proteinuria excretion, as measured using the urine dipstick test. Receiver operating characteristic curves were created based on the sensitivity and specificity and used to calculate the area under the curve (AUC) and the 95% confidence intervals (CI). RESULTS: A total of 5,799 workers were included in this study. Use of an abnormal proteinuria criterion of 1+-3+ and a reduced GFR criterion of eGFR < 60 resulted in a sensitivity and specificity of 7.8% and 97.4%, respectively, while a reduced GFR criterion of eGFR < 50 resulted in a sensitivity and specificity of 37.8% and 97.4%, respectively. The AUC was 0.52 (95% CI, 0.48-0.55) for eGFR < 60 and 0.70 (95% CI, 0.59-0.80) for eGFR < 50. CONCLUSIONS: In this study, 92.2% of participants with an eGFR < 60 and 62.2% of participants with an eGFR < 50 were overlooked in the urine dipstick test. These results suggest that the urine dipstick test only is not sufficient enough to identify reduced GFR and that both a urine dipstick test and other measures of GFR are required to reliably identify reduced GFR.

Fatigue in Japanese people with multiple sclerosis.

The aim of this study was to obtain descriptions of the experiences of fatigue of people with multiple sclerosis, including experiences related to their interpersonal relations and social life. We used a qualitative, exploratory, and descriptive design and conducted semistructured interviews with nine participants. Seven concepts emerged from the data analysis: "fatigue as an individualized and novel sensation", "self-analysis of the factors that are associated with fatigue", "effects of fatigue on living and the self", "unique measures for handling fatigue", "insufficient coping", "living with fatigue", and "the assumption of a lack of common understanding of fatigue." Based on these findings, fatigue was found to affect the lifestyle of people with MS and their ability to be true to themself. As a result, the participants devised their own way of coping with fatigue. However, the coping measures also created other dilemmas, which led to isolation. Nevertheless, the participants made efforts to live with fatigue on their own terms.

Having one kidney does not accelerate the rate of development of diabetic nephropathy lesions in type 1 diabetic patients.

OBJECTIVE: Reduced nephron number is hypothesized to be a risk factor for chronic kidney disease and hypertension. Whether reduced nephron number accelerates the early stages of diabetic nephropathy is unknown. This study investigated whether the rate of development of diabetic nephropathy lesions was different in type 1 diabetic patients with a single (transplanted) kidney compared with patients with two (native) kidneys. RESEARCH DESIGN AND METHODS: Three groups of volunteers were studied: 28 type 1 diabetic kidney transplant recipients with 8-20 years of good graft function, 39 two-kidney patients with duration of type 1 diabetes matched to the time since transplant in the one-kidney group, and 30 age-matched normal control subjects. Electron microscopic morphometry was used to estimate glomerular structural parameters on 3.0 +/- 1.4 glomeruli per biopsy. RESULTS: In the one- versus two-kidney diabetic subject groups, respectively, serum creatinine (means +/- SD 1.3 +/- 0.4 vs. 0.9 +/- 0.2 mg/dl; P < 0.001), systolic blood pressure (133 +/- 13 vs. 122 +/- 11 mmHg; P < 0.001), and albumin excretion rate (median [range] 32.1 microg/min [2-622] vs. 6.8 microg/min [2-1,495]; P = 0.006) were higher. There were no differences in the one- versus two-kidney diabetic subject groups, respectively, in glomerular basement membrane width (median [range] 511 nm [308-745] vs. 473 nm [331-814]), mesangial fractional volume (mean +/- SD 0.30 +/- 0.06 vs. 0.27 +/- 0.07), mesangial matrix fractional volume (0.16 +/- 0.05 vs. 0.16 +/- 0.06), and mesangial matrix fractional volume per total mesangium (0.61 +/- 0.07 vs. 0.64 +/- 0.09). However, these glomerular structural parameters were statistically significantly higher in both diabetic subject groups compared with normal control subjects. Results were similar when patients receiving ACE inhibitors were excluded from the analyses. CONCLUSIONS: Reduced nephron number is not associated with accelerated development of diabetic glomerulopathy lesions in type 1 diabetic patients.

[Successful treatment with micafungin (MCFG) of severe peritonitis due to Candida parapsilosis with chronic renal failure patient on hemodialysis].

A 49 year-old woman with chronic renal failure (CRF) on continuous ambulatory peritoneal dialysis (CAPD) because of Goodpasture Syndrome was admitted to our hospital since she had a high fever and severe abdominal pain. A diagnosis of peritonitis was made from the physical examination and laboratory findings. The peritonitis was refractory to conventional antibiotics therapy. Candida parapsilosis was detected from dialysite. The peritonitis was aggravated although the antibiotic was changed to an antifungal agent (fluconazole 400mg/day). Fluconazole was replaced to micafungin (MCFG) and the catheter for CAPD was removed. The fungal peritonitis improved dramatically and beta-D glucan was decreased from 104 to 12.6 (pg/ml). No adverse effect was observed after using MCFG. It has been known that fungal peritonitis of CRF patients is refractory to treatment and the mortality rate is high. To our best knowledge, there is no report that MCFG was used for CRF patients with fungal peritonitis. However, we used MCFG safely and effectively for CRF patients. Therefore, it is suggested that MCFG is a new effective and safe antifungal agent for Candida parapsilosis peritonitis with CRF.

Regular hemodialysis reverses gastric mucosal atrophy of patients with chronic renal failure.

BACKGROUND/AIMS: Gastric mucosa of patients with chronic renal failure on regular hemodialysis is known to retain fundic glands relatively intact, but no evidence for regeneration of fundic glands by hemodialysis has been provided to date. This study was performed to investigate endoscopically and histopathologically if hemodialysis to treat renal failure would regenerate the background gastric mucosa and to elucidate factors associated with the mucosal regeneration. METHODOLOGY: First, the relationship between duration of hemodialysis and the degree of atrophy of the background gastric mucosa was investigated in patients with chronic renal failure treated and not treated by hemodialysis. Treated patients were further divided into long-term group treated for 4 years or longer and short-term group treated for shorter than 4 years. The degree of atrophy of gastric mucosa was evaluated by hematoxylin-eosin staining, PAS-alucian blue staining and immunohistochemical staining to detect Ki-67 expression using biopsy specimens obtained from gastric mucosa. The labeling index is the proportion of positively labeled cells with respect to the total number of cells. The proliferative index was calculated by multiplying the labeling index and the proliferative zone (length of the area between the uppermost and lowest labeled cells). Serum gastrin, glucagon and cholecystokinin were assayed as well as urine epidermal growth factor to elucidate factors associated with regeneration of gastric mucosa. Helicobacter pylori infection was examined by ELISA. RESULTS: In the long-term group, the degree of atrophy of gastric mucosa was endoscopically evaluated to be C1 type. In both of the two hemodialysis groups, endoscopically identified fundic gland region was histologically confirmed to be fundic glands by both hematoxylin-eosin staining and PAS-alucian blue staining. Epithelial cell proliferative index was significantly higher in long-term and short-term hemodialysis group than non-hemodialysis group (P=0.0001). No significant difference in serum gastrin, glucagon and cholecystokinin as well as urine epidermal growth factor was detectable among the three groups. Most patients of both hemodialysis groups were H. pylori-negative. CONCLUSIONS: A possibility of regeneration of the background gastric mucosa in proportion to the duration of hemodialysis was suggested on the basis of histopathological evidence. The observed regeneration of gastric mucosa was ascribable to elimination of factors associated with atrophy of gastric mucosa including H. pylori by hemodialysis.

[Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy].

We report a case of methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis treated with antibiotic therapy. A 67-year-old man was admitted to our hospital because of proteinuria, hematuria, purpura, and high fever one month after a graft replacement of an abdominal aortic aneurysm. MRSA was detected in specimens of his blood, sputum, and joint fluid. Before his operation, he had shown no renal abnormalities. He presented with a rapid deterioration of renal function following MRSA infection. Maximum level of proteinuria was 1.5 g/day, serum creatinine (Cr) was 3.5 mg/dl, and blood urea nitrogen was 57 mg/dl. Renal biopsy revealed necrotizing crescentic glomerulonephritis. Immunofluorescence examination showed IgA and C3 deposits. Clinical and pathological examinations showed the typical features of MRSA-associated glomerulonephritis. Vancomycin and fosfomycin were administered intravenously. The serum level of C-reactive protein fell from 22.0 mg/dl to 0.1 mg/dl. Proteinuria also decreased and the patient's renal function improved in parallel with the decreased activity of MRSA infection. After three months of antibiotic treatment, proteinuria was negative and the level of serum Cr had dropped to 0.9 mg/dl. These findings suggest that antibiotic treatment can lead to complete remission of MRSA-associated glomerulonephritis.

Urinary albumin as an indicator of diabetic nephropathy lesions in Japanese type 2 diabetic patients.

UNLABELLED: Caucasian type 2 diabetic patients with microalbuminuria (MA) or overt nephropathy (ON) show greater heterogeneity of renal lesions than type 1 diabetic patients. We examined whether a similar situation exists in 30 Japanese type 2 diabetic patients [21 male, age 48 +/- (SD) 8 years, known duration 11 +/- (SD) 8 years] without definable renal disease other than diabetic nephropathy. Six patients were normoalbuminuric (NA), 11 MA, and 13 had ON. Normal controls were 9 age-matched Japanese living-related renal transplant donors. Electron microscopic morphometry was performed on renal biopsy specimens and related to renal function. Glomerular basement membrane width and mesangial fractional volume [Vv(Mes/glom)] were increased in all type 2 diabetic patients groups (NA, MA, ON) as compared with normal controls. The Vv(Mes/glom) correlated directly with urinary albumin/creatinine. However, Vv(Mes/glom) as well as glomerular basement membrane width overlapped among the three functional categories (NA, MA, ON) and normal controls. IN CONCLUSION: (1) similar to Caucasian type 2 diabetic patients, Japanese type 2 diabetic patients have greater heterogeneity of renal structure than Caucasian type 1 diabetic patients, and (2) urinary albumin is not a reliable indicator of underlying renal structure in Japanese type 2 diabetic patients.