Novel therapeutic perspectives for crescentic glomerulonephritis through targeting parietal epithelial cell activation and proliferation.

INTRODUCTION: Kidney injury is clinically classified as crescentic glomerulonephritis (CrGN) when ≥50% of the glomeruli in a biopsy sample contain crescentic lesions. However, current strategies, such as systemic immunosuppressive therapy and plasmapheresis for CrGN, are partially effective, and these drugs have considerable systemic side effects. Hence, targeted therapy to prevent glomerular crescent formation and expansion remains an unmet clinical need. AREAS COVERED: Hyperproliferative parietal epithelial cells (PECs) are the main constituent cells of the glomerular crescent with cell-tracing evidence. Crescents obstruct the flow of primary urine, pressure the capillaries, and degenerate the affected nephrons. We reviewed the markers of PEC activation and proliferation, potential therapeutic effects of thrombin and thrombin receptor inhibitors, and how podocytes cross-talk with PECs. These experiments may help identify potential early specific targets for the prevention and treatment of glomerular crescentic injury. EXPERT OPINION: Inhibiting PEC activation and proliferation in CrGN can alleviate glomerular crescent progression, which has been supported by preclinical studies with evidence of genetic deletion. Clarifying the outcome of PEC transformation to the podocyte phenotype and suppressing thrombin, thrombin receptors, and PEC hyperproliferation in early therapeutic strategies will be the research goals in the next ten years.

It is clinically classified as crescentic glomerulonephritis (CrGN) when more than 50% of the glomeruli of the kidney in a biopsy sample contain crescentic lesions (crescent shaped injuries). However, current strategies, such as immunosuppressive therapy and plasmapheresis (the removal, treatment and returning of blood) for CrGN, are partially effective, and these drugs have considerable side effects. In order to seek targeted therapy for CrGN, we reviewed the current research evidences. First, the hyperproliferative parietal epithelial cells (PECs) are the main cells within the glomerular crescent seen with cell-tracing evidence. The activated PECs can express specific markers and altered biological characteristics, such as cell growth and multiplication, migration, and extracellular matrix production. CD44, CD74, CD9, and pERK-1/2 are specific markers for PEC activation, and also as the potential therapeutic targets with evidence of gene knockout and inhibitor. Second, during the formation of glomerular crescents, PECs grow and multiply also through cross-talking with podocyte cells by the AngII/SDF-1/CXCR4/ERK1/2, HB-EGF/EGFR/JAK/STAT3, and PDGF/PDGFR signaling pathways, suggesting that the intervention of key molecules in these disease processes may be promising therapeutic targets for CrGN. Third, thrombin and protease-activated receptors (PARs) participate in the excessive proliferation of PEC through activation of the coagulation cascade reaction, PAR-1 and PAR-2. Therefore, anticoagulation therapy, especially inhibition of PAR-1 and PAR-2, is expected to be an effective strategy for the early prevention and treatment of CrGN. The drug vorapaxar selectively antagonizes PAR-1 and is the most promising candidate. These findings will not only improve the outlook for CrGN treatment, but will also help in the treatment of other glomerular diseases with crescentic lesions. [Figure: see text].

Large Contribution of Oral Status for Death Among Modifiable Risk Factors in Older Adults: The Japan Gerontological Evaluation Study (JAGES) Prospective Cohort Study.

BACKGROUND: Oral diseases are preventable and modifiable, but highly prevalent, and cause worse oral status. Particularly, tooth loss has increased in aging societies. However, studies on population-attributable risks of modifiable risk factors for mortality have neglected oral status. This study aimed to investigate the impact of modifiable risk factors on mortality, including oral status. METHODS: This cohort study used the Japan Gerontological Evaluation Study data, including participants aged ≥65 years. The outcome was death between August 2010 and March 2017. We calculated the hazard ratios (HRs) and population attributable fraction (PAF) of modifiable risk factors (oral status, hypertension, depression, heart disease, diabetes, physical activity, smoking status, and alcohol drinking history) for mortality. RESULTS: Analyses included 24 175 men and 27 888 women (mean age: 73.8 [6.0] and 74.2 [6.1], respectively). In men, after adjusting for covariates, having no teeth showed the highest hazard ratio (HR = 1.67, 95% confidence interval [CI] = 1.51-1.86) among the modifiable risk factors, and the PAF for the number of teeth (18.2%) was the second largest following age. In women, having no teeth had the third largest HR (HR = 1.37, 95% CI = 1.19-1.56) following current and former smoking. The PAF for the number of teeth (8.5%) was the sixth largest, which was larger than that of smoking status (4.8%). CONCLUSIONS: In the older population, the HR and PAF of the number of teeth on mortality were sufficiently large compared with other modifiable risk factors, especially in men. Therefore, maintaining good oral status should be included more in global health policies.

Increased numbers of pre-operative circulating monocytes predict risk of developing cardiac surgery-associated acute kidney injury in conditions requiring cardio pulmonary bypass.

BACKGROUND: Evaluating patients' risk for acute kidney injury (AKI) is crucial for positive outcomes following cardiac surgery. Our aims were first to select candidate risk factors from pre- or intra-operative real-world parameters collected from routine medical care and then evaluate potential associations between those parameters and risk of onset of post-operative cardiac surgery-associated AKI (CSA-AKI). METHOD: We conducted two cohort studies in Japan. The first was a single-center prospective cohort study (n = 145) to assess potential association between 115 clinical parameters collected from routine medical care and CSA-AKI (≥ Stage1) risk in the population of patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB). To select candidate risk factors, we employed random forest analysis and applied survival analyses to evaluate association strength. In a second retrospective cohort study, we targeted patients undergoing cardiac surgery with CPB (n = 619) and evaluated potential positive associations between CSA-AKI incidence and risk factors suggested by the first cohort study. RESULTS: Variable selection analysis revealed that parameters in clinical categories such as circulating inflammatory cells, CPB-related parameters, ventilation, or aging were potential CSA-AKI risk factors. Survival analyses revealed that increased counts of pre-operative circulating monocytes and neutrophils were associated with CSA-AKI incidence. Finally, in the second cohort study, we found that increased pre-operative circulating monocyte counts were associated with increased CSA-AKI incidence. CONCLUSIONS: Circulating monocyte counts in the pre-operative state are associated with increased risk of CSA-AKI development. This finding may be useful in stratifying patients for risk of developing CSA-AKI in routine clinical practice.

A Case-Control Study of the APELA Gene and Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy (HDPs) are believed to comprise a group of multifactorial genetic diseases. Recently, it was reported that APELA-knockout mice exhibited HDP-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis. The aim of the present study is to determine the associations between HDPs and single-nucleotide variants or haplotypes in the human APELA gene through a case-control study. The subjects were 196 pregnant women with HDPs and a control group of 254 women without HDPs. Six single-nucleotide variants (rs2068792, rs13120303, rs4541465, rs13152225, rs78639146, and rs67448487) were selected from the APELA gene region. Although there were no significant differences for each single-nucleotide polymorphism in the case-control study, the frequency of the T-A haplotypes rs4541465-rs67448487 was significantly higher in the HDP group, especially in those with gestational hypertension, than in the control group. The results suggest that the APELA gene may be a disease-susceptibility gene for HDP.

Cervical cord injury complicated by acute mesenteric ischemia.

Acute mesenteric ischemia is a rare, life-threatening complication of cervical cord injury. This case report emphasized the importance of prompt diagnosis and treatment of this complication. A 60-year old Japanese man with no co-morbidities was diagnosed as a C2 cervical cord injury and traumatic brain injury after a fall-down trauma. He was admitted to the intensive care unit after cord decompression surgery. Nine days later, he presented tachycardia and hypotension. Ultrasound showed dilated intestines and ascites. Intestinal ischemia was suspected based on the contrast-enhanced computed tomography scan. We performed prompt surgical resection of a broad part of the small intestines. The ischemic region of the intestines was segmental and the cause was attributed to a non-occlusive mechanism. Acute mesenteric ischemia can be fatal and a delay in diagnosis leads to poor outcomes. We focus on predisposing factors in patients with cervical cord injuries and how to prevent this serious diagnosis.

Sympathetic hyperactivity, hypertension, and tachycardia induced by stimulation of the ponto-medullary junction in humans.

OBJECTIVE: The purpose of this study is to investigate changes in autonomic activities and systemic circulation generated by surgical manipulation or electrical stimulation to the human brain stem. METHODS: We constructed a system that simultaneously recorded microsurgical field videos and heart rate variability (HRV) that represent autonomic activities. In 20 brain stem surgeries recorded, HRV features and sites of surgical manipulation were analyzed in 19 hypertensive epochs, defined as the periods with transient increases in the blood pressure. We analyzed the period during electrical stimulation to the ponto-medullary junction, performed for the purpose of monitoring a cranial nerve function. RESULTS: In the hypertensive epoch, HRV analysis showed that sympathetic activity predominated over the parasympathetic activity. The hypertensive epoch was more associated with surgical manipulation of the area in the caudal pons or the rostral medulla oblongata compared to controls. During the period of electrical stimulation, there were significant increases in blood pressures and heart rates, accompanied by sympathetic overdrive. CONCLUSIONS: Our results provide physiological evidence that there is an important autonomic center located adjacent to the ponto-medullary junction. SIGNIFICANCE: A large study would reveal a candidate target of neuromodulation for disorders with autonomic imbalances such as drug-resistant hypertension.

Short-term prediction of preeclampsia using the sFlt-1/PlGF ratio: a subanalysis of pregnant Japanese women from the PROGNOSIS Asia study.

Two prospective multicenter studies demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio cutoff of ≤38 can rule out preeclampsia within 1 week with a negative predictive value (NPV) of 99.3% (PROGNOSIS) and 98.6% (PROGNOSIS Asia). We report a subanalysis of the Japanese cohort from the PROGNOSIS Asia study. Pregnant women with suspected preeclampsia between gestational weeks 18 + 0 days and 36 + 6 days were enrolled at eight Japanese sites. Primary objectives: Assess the performance of the Elecsys® sFlt-1/PlGF ratio cutoff ≤38 to rule out preeclampsia within 1 week and of the cutoff >38 to rule in preeclampsia within 4 weeks. Key secondary objectives: Prediction of maternal and fetal adverse outcomes (MAOs/FAOs) and their relationship with duration of pregnancy. Of 192 women enrolled, 180 (93.8%)/175 (91.1%) were evaluable for primary/combined endpoint analyses. Overall preeclampsia prevalence was 13.3%. A sFlt-1/PlGF ratio of ≤38 provided an NPV of 100% (95% confidence interval [CI], 97.5-100) for ruling out preeclampsia within 1 week, and a ratio of >38 provided a positive predictive value of 32.4% (95% CI, 18.0-49.8) for ruling in preeclampsia within 4 weeks. The area under the curve for the prediction of preeclampsia/maternal/fetal adverse outcomes within 1 week was 94.2% (95% CI, 89.3-97.8). After adjusting for gestational age and final preeclampsia status, Cox regression indicated a 2.8-fold greater risk of imminent delivery for women with a sFlt-1/PlGF ratio >38 versus ≤38. This subanalysis of Japanese women with suspicion of preeclampsia showed high predictive value for a Elecsys sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia.

Economic evaluation of the sFlt-1/PlGF ratio for the short-term prediction of preeclampsia in a Japanese cohort of the PROGNOSIS Asia study.

The PRediction of short-term Outcomes in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) Asia validated the use of the soluble fms-like tyrosine 1/placental growth factor (sFlt-1/PlGF) ratio cutoff value of ≤38 to rule out the occurrence of preeclampsia in the short term in Asian women. We assessed the economic impact of the introduction of the sFlt-1/PlGF ratio test for predicting preeclampsia in Japan using data from the Japanese cohort of PROGNOSIS Asia. The cost analysis was developed with estimates in either a no-test scenario, with clinical decisions based on standard diagnostic procedures alone, or a test scenario, in which the sFlt-1/PlGF ratio test was used in addition to standard diagnostic procedures. For both scenarios, rates of hospitalization and other test characteristics were obtained from the results for the Japanese cohort in PROGNOSIS Asia. The total cost per patient was the main outcome of this cost analysis model. Introduction of the sFlt-1/PlGF ratio test using a cutoff value of 38 resulted in a reduced hospitalization rate compared with the rate in the no-test scenario (14.4% versus 8.7%). The reduction in the rate of hospitalizations led to an estimated 16 373 JPY reduction in healthcare costs per patient. The sFlt-1/PlGF ratio test is likely to reduce the unnecessary hospitalization of women at low risk of developing preeclampsia in the short term while also identifying high-risk individuals requiring appropriate management. Reducing unnecessary hospitalizations would result in significant cost savings in the Japanese healthcare system.

McGRATH MAC video laryngoscope assistance during transesophageal echocardiography may reduce the risk of complications: a manikin study.

BACKGROUND: Although transesophageal echocardiography (TEE) is considered a relatively safe diagnostic monitoring method, blind probe insertion is associated with pharyngeal trauma. Through visual observation of the esophageal inlet with the McGRATH video laryngoscope, it may be possible to insert the TEE probe at an appropriate angle and prevent pharyngeal trauma. We conducted a manikin study to investigate whether the use of the McGRATH video laryngoscope for TEE probe insertion reduced the pressure on the posterior pharyngeal wall. METHODS: Twenty-seven junior (inexperienced group) and 10 senior (experienced group) anesthesiologists participated in this study. The TEE probe was inserted into an airway manikin in a blind fashion (blind group) or under visualization with the McGRATH (McGRATH group) video laryngoscope (three times each). A sealed bag filled with normal saline was placed on the back of the posterior pharyngeal wall of the manikin and connected to a patient monitoring system via a pressure transducer. We measured the internal bag pressure and approximated this value to the pressure on the posterior pharyngeal wall. RESULTS: The pressure on the posterior pharyngeal wall was significantly lower in the McGRATH group than in the blind group (p < 0.001) and was significantly reduced when the McGRATH was employed in both the inexperienced (p < 0.001) and experienced (p < 0.001) groups. CONCLUSIONS: These findings suggest that TEE probe insertion under the assistance of the McGRATH video laryngoscope can reduce the pressure on the posterior pharyngeal wall, regardless of the clinician's experience, and may inform clinical practice with the potential to reduce probe insertion-associated complication rates.

Tracking the evolution of the two successful CC59 methicillin-resistant Staphylococcus aureus clones in Taiwan: the divergence time of the two clades is estimated to be the 1980s.

Clonal complex 59 (CC59) is the dominant community-associated methicillin-resistant Staphylococcus aureus (MRSA) strain in Taiwan and includes the Asian-Pacific clone with Panton-Valentine leukocidin (PVL)-negative/staphylococcal cassette chromosome mec (SCCmec) IVg and the Taiwan clone characterised as PVL-positive/SCCmec V (5C2&5). Nevertheless, data on the evolutionary history of the two dominant CC59 MRSA clones in Taiwan are scarce. In this study, a total of 258 CC59 S. aureus strains from Taiwan were classified by multiple-locus variable-number tandem repeat analysis (MLVA), which revealed two major clusters (MT1 and MT2) with distinct mobile genetic elements (MGEs). However, sequencing and PCR mapping of the ß-lactamase-producing plasmid revealed no difference among all CC59 S. aureus strains. Bayesian evolutionary analysis of 18 of the CC59 S. aureus strains based on core genome alignment revealed two clades: (i) Clade A, which shared the samples with MT1, had the features of mainly harbouring gentamicin-resistant MES6272-2 or MES4578, φSA3 translocation in νSaß and SCCmec IVg; and (ii) Clade B, which shared the samples with MT2, had the features of mainly harbouring streptomycin-resistant MESPM1, PVL phage and SCCmec V (5C2&5). Based on the time-calibrated phylogenetic tree, the estimated time of divergence of the two clades was in the 1980s. These results suggest that the CC59 S. aureus progenitor acquired a ß-lactamase-producing plasmid and then developed the varied genetic backgrounds, which were associated with the acquisition and maintenance of distinct MGEs, leading to differences in antimicrobial susceptibility profiles and molecular virulence determinants.

Evaluation of the risk factors for neurological and neurocognitive impairment after selective cerebral perfusion in thoracic aortic surgery.

PURPOSE: Neurologic complications are seen often after the surgery of the thoracic aorta that uses selective antegrade cerebral perfusion. The objective of this study was to evaluate the impact of atherosclerotic risk factors on neurologic complications in patients who underwent surgery to the thoracic aorta using SCP. METHODS: Data were collected retrospectively on 94 patients who underwent elective ascending aorta/aortic arch replacement. Concomitant procedures were performed as needed. All patients had magnetic resonance imaging (MRI), angiography (MRA) and carotid ultrasound before surgery. Individual cognitive status was measured using four neuropsychological tests before surgery and 7 days after extubation. We compared perioperative factors for risk factors associated with postoperative stroke and postoperative cognitive decline (POCD). RESULTS: 11 patients had strokes after surgery. Operation and extracorporeal circulation times were significantly longer in patients with stroke than those without stroke. Coronary artery disease and SCP time > 150 min were independently associated with postoperative stroke. Of the 83 patients without postoperative stroke, 20 suffered POCD. POCD patients had a significantly higher rate of heterogeneous carotid plaque, and operation time was significant longer in patients with POCD than those without POCD. Independent predictors of POCD were concomitant CABG, heterogeneous carotid plaque, history of cerebrovascular disease and operation time > 450 min. CONCLUSIONS: We found that prolonged SCP time and coronary artery disease increased the risk of postoperative stroke. Heterogeneous carotid plaque, history of cerebrovascular disease, concomitant CABG and prolonged operation time were further significant predictors of POCD.

Effect of scheduled intravenous acetaminophen on postoperative nausea and vomiting in patients undergoing laparoscopic gynecologic surgery.

PURPOSE: The aim of this study was to assess the effect of scheduled intravenous acetaminophen (SIVA) on the incidence of postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecologic surgery (LGS). METHODS: This retrospective observational study identified consecutive patients who underwent LGS at our institution from January to November of 2017 and were managed with either our hospital's old protocol (Group H) or a new protocol using SIVA (Group S). Primary outcomes included the incidences of PONV and the amount of additional antiemetic required in the postoperative period. The secondary outcomes included the pain score on postoperative day 1, the requirement for additional analgesic medications, and the length of hospitalization (LOH). RESULTS: Patients in Group S had significantly lower incidences of PONV from postoperative days 0 to 1 and required significantly less antiemetics or tramadol than those in Group H (P = 0.0085). Patients at a low risk for PONV in Group S had significantly lower incidences of PONV than those in Group H (P = 0.0129). Further, the amount of additional tramadol required was lower in Group S than in Group H (P = 0.0021). CONCLUSION: Introduction of SIVA into the postoperative pain management protocol of LGS may reduce the incidence of PONV and the amount of adjunctive antiemetic medication required from postoperative days 0 to 1. In patients undergoing LGS, PONV prophylaxis using antiemetics should be prescribed depending on PONV risk profile; however, SIVA prophylaxis can be used in all patients regardless of PONV risk profile.

Protein Arginine N-methyltransferases 5 and 7 Promote HIV-1 Production.

Current therapies for human immunodeficiency virus type 1 (HIV-1) do not completely eliminate viral reservoirs in cells, such as macrophages. The HIV-1 accessory protein viral protein R (Vpr) promotes virus production in macrophages, and the maintenance of Vpr is essential for HIV-1 replication in these reservoir cells. We identified two novel Vpr-binding proteins, i.e., protein arginine N-methyltransferases (PRMTs) 5 and 7, using human monocyte-derived macrophages (MDMs). Both proteins found to be important for prevention of Vpr degradation by the proteasome; in the context of PRMT5 and PRMT7 knockdowns, degradation of Vpr could be prevented using a proteasome inhibitor. In MDMs infected with a wild-type strain, knockdown of PRMT5/PRMT7 and low expression of PRMT5 resulted in inefficient virus production like Vpr-deficient strain infections. Thus, our findings suggest that PRMT5 and PRMT7 support HIV-1 replication via maintenance of Vpr protein stability.

N-acetylaspartylglutamate (NAAG) and glutamate carboxypeptidase II: An abundant peptide neurotransmitter-enzyme system with multiple clinical applications.

N-Acetylaspartylglutamate (NAAG) is the third most prevalent neurotransmitter in the mammalian nervous system, yet its therapeutic potential is only now being fully recognized. Drugs that inhibit the inactivation of NAAG by glutamate carboxypeptidase II (GCPII) increase its extracellular concentration and its activation of its receptor, mGluR3. These drugs warrant attention, as they are effective in animal models of several clinical disorders including stroke, traumatic brain injury and schizophrenia. In inflammatory and neuropathic pain studies, GCPII inhibitors moderated both the primary and secondary pain responses when given systemically, locally or in brain regions associated with the pain perception pathway. The finding that GCPII inhibition also moderated the motor and cognitive effects of ethanol intoxication led to the discovery of their procognitive efficacy in long-term memory tests in control mice and in short-term memory in a mouse model of Alzheimer's disease. NAAG and GCPII inhibitors respectively reduce cocaine self-administration and the rewarding effects of a synthetic stimulant. Most recently, GCPII inhibition also has been reported to be efficacious in a model of inflammatory bowel disease. GCPII was first discovered as a protein expressed by and released from metastatic prostate cells where it is known as prostate specific membrane antigen (PSMA). GCPII inhibitors with high affinity for this protein have been developed as prostate imaging and radiochemical therapies for prostate cancer. Taken together, these data militate in favor of the development and application of GCPII inhibitors in more advanced preclinical research as a prelude to clinical trials.

Complete post-operative resolution of "temporary" end-stage kidney disease secondary to aortic dissection without static renal artery obstruction: a case study.

BACKGROUND: Acute kidney injury (AKI), which may progress to end-stage kidney disease (ESKD), is a potential complication of aortic dissection. Notably, in all reported ESKD cases secondary to aortic dissection, imaging evidence of static obstruction of the renal arteries always shows either renal artery stenosis or extension of the dissection into the renal arteries. CASE PRESENTATION: We present the case of a 58-year-old man with hypertension who was diagnosed with a Stanford type B aortic dissection and treated with medications alone because there were no obvious findings indicative of dissection involving the renal arteries. He had AKI, which unexpectedly progressed to ESKD, without any radiological evidence of direct involvement of the renal arteries. Thus, we failed to attribute the ESKD to the dissection and hesitated to perform any surgical intervention. Nevertheless, the patient's hormonal levels, fractional excretion values, ankle brachial indices, and Doppler resistive indices seemed to indirectly suggest kidney malperfusion and implied renal artery hypo-perfusion. However, abdominal computed tomography imaging only revealed progressive thrombotic obstruction of the false lumen and compression of the true lumen in the descending thoracic aorta, despite the absence of anatomical blockage of renal artery perfusion. Later, signs of peripheral malperfusion, such as intermittent claudication, necessitated surgical intervention; a graft replacement of the aorta was performed. Post-operatively, the patient completely recovered after 3 months of haemodialysis, and the markers that had pre-operatively suggested decreased renal bloodstream normalised with recovery of kidney function. CONCLUSIONS: To the best of our knowledge, this is the first report of severe AKI, secondary to aortic dissection, without direct renal artery obstruction, which progressed to "temporary" ESKD and was resolved following surgery. This case suggests that only coarctation above the renal artery branches following an aortic dissection can progress AKI to ESKD, despite the absence of radiological evidence confirming an obvious anatomical blockage. Further, indirect markers suggestive of decreased renal blood flow, such as ankle brachial indices, renal artery resistive indices, urinary excretion fractions, and hormonal changes, are useful for evaluating concomitant AKI and may indicate the need for surgical intervention after a Stanford type B aortic dissection.

Albuminuria, C-reactive protein, and socioeconomic factors are associated with periodontal status in subjects with type 2 diabetes.

Diabetes and periodontitis may increase risk of cardiovascular disease. Whether albuminuria, C-reactive protein (CRP), and socioeconomic factors, known as cardiovascular risks in subjects with poorly controlled diabetes, are independently associated with periodontal status in well-controlled diabetes remains to be elucidated. In 503 subjects with type 2 diabetes, the cross-sectional associations of clinical and socioeconomic factors with periodontal parameters were investigated. Periodontal parameters on all teeth included the probing pocket depth at 6 sites per tooth, bleeding on probing, the plaque score, tooth mobility, and the number of teeth. The subjects had a mean HbA1c value of 6.85% and a median CRP value of 0.06 mg/dL, and 27.9% of the subjects had albuminuria. Albuminuria and CRP values had significant associations with several periodontal parameters, whereas other variables including HbA1c did not. Subjects with albuminuria had significantly higher HbA1c, CRP, and % sites of pocket depth ≥ 4 mm than subjects with normoalbuminuria; additionally, those with high CRP (≥ median) had significantly higher body mass index, HbA1c, % sites of pocket depth ≥ 4 mm, and plaque score than those with low CRP. In multiple linear regression analysis, albuminuria, CRP, education, smoking, and dental attendance exhibited significant associations with periodontal parameters, independent of the effect of age, sex, body mass index, and diabetes therapy. Albuminuria, CRP, education, smoking, and dental attendance were independently associated with periodontal parameters even in subjects with a mean of HbA1c of 6.85%, implying the importance of these factors for the prevention of cardiovascular disease.

Gastric emptying time after breakfast in healthy adult volunteers using ultrasonography.

There is little evidence of gastric excretion after ingestion of solids. We examined gastric emptying times after ingesting normal breakfast in healthy adult volunteer using ultrasonography. Eight adult volunteers fasted for 8 h, and we examined the gastric antral area in the right lateral decubitus position using ultrasonography. Sixteen adult volunteers ingested normal breakfast. We evaluated the gastric antral area in the same manner at two consecutive time points before lunch. Gastric volume was calculated by using an approximation formula based on the antral area. Correlation coefficients between gastric volume and fasting time were calculated. The calculated gastric volume from the gastric antral area after 8 h fasting was 53.1 ml. The gastric volume correlated significantly with fasting time (r = - 0.811, P < 0.001). The time when the attenuation line obtained from two measurements between breakfast to lunch in each subject overlapped the fasting stomach volume (53.1 ml) was taken as gastric empty time. The calculated gastric emptying time was 276.4 ± 58.9 min. This result shows that gastric emptying time was lower than 5 h average after a typical breakfast that contains various food in healthy adult volunteers. However, further research is necessary to establish the clinical safety implications of these findings.

Follow-up Results of HCV GT2 Patients After Sofosbuvir/Ribavirin Therapy: Careful Attention to Occurrence of HCC.

BACKGROUND: We examined treatment the efficacy and data on long-term outcomes in real-world Japanese patients infected with hepatitis C virus (HCV) genotype 2 treated with 12-week sofosbuvir/ribavirin combination therapy. PATIENTS AND METHODS: In a total of 86 patients who were treated with sofosbuvir/ribavirin, sustained virological response (SVR) rates and long-term-outcomes were retrospectively analyzed. RESULTS: The adherence to this combination therapy was 98.8%. The rates of SVR at week 24 (SVR24) achieved with this treatment according to the 'intention-to-treat' and 'per-protocol' analyses were 89.5% and 96.2%, respectively. Two patients who experienced relapse did not have any previously reported resistance-associated substitutions in the HCV non-structural protein 5B (NS5B) polymerase region. We did not observe any patients who experienced late relapse but did observe that 50% and 1.3% of patients with and without a previous history of hepatocellular carcinoma (HCC), respectively, developed HCC after achieving SVR24 (with a mean follow-up period of 2.7±0.8 years). CONCLUSION: Patients with SVR should be carefully followed-up to screen for the occurrence of HCC, although it is infrequent.

Short-Term Prediction of Adverse Outcomes Using the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor) Ratio in Asian Women With Suspected Preeclampsia.

Current diagnostic criteria have limited clinical value for prediction of preeclampsia and fetal adverse outcomes. The prediction of short-term outcome in pregnant women with suspected preeclampsia study in Asia (PROGNOSIS Asia) was a prospective, multicenter study designed to investigate the value of the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio for predicting adverse outcomes in pregnant Asian women with suspected preeclampsia. Seven hundred sixty-four pregnant women at gestational week 20+0 days (18+0 days in Japan) to 36+6 days were enrolled at 25 sites in Asia. The primary objectives were to demonstrate the value of the sFlt-1/PlGF ratio for ruling out preeclampsia within 1 week and ruling in preeclampsia within 4 weeks. The value of the ratio for predicting fetal adverse outcomes was also assessed. Seven hundred patients were evaluable for primary end point analysis. The prevalence of preeclampsia was 14.4%. An sFlt-1/PlGF ratio of ≤38 had a negative predictive value of 98.6% (95% CI, 97.2%-99.4%) for ruling out preeclampsia within 1 week, with 76.5% sensitivity and 82.1% specificity. The positive predictive value of a ratio of >38 for ruling in preeclampsia within 4 weeks was 30.3% (95% CI, 23.0%-38.5%), with 62.0% sensitivity and 83.9% specificity. An sFlt-1/PlGF ratio of ≤38 had a negative predictive value of 98.9% (95% CI, 97.6%-99.6%) for ruling out fetal adverse outcomes within 1 week and a ratio of >38 had a positive predictive value of 53.5% (95% CI, 45.0%-61.8%) for ruling in fetal adverse outcomes within 4 weeks. The sFlt-1/PlGF ratio cutoff of 38 demonstrated clinical value for the short-term prediction of preeclampsia in Asian women with suspected preeclampsia, potentially helping to prevent unnecessary hospitalization and intervention.

Smoking and periodontal microorganisms.

Resolution of dysbiosis following treatment for periodontal disease and tobacco dependence has been reported in longitudinal intervention studies. In the present report, we evaluated the biological findings regarding the effect of smoking on the periodontal microbiome. A standardized electronic search was conducted using MEDLINE; overall, 1099 papers were extracted. Studies that addressed the relationship between tobacco and periodontal pathogens were included. Finally, 42 papers were deemed appropriate for the present review. Functional changes in periodontal pathogens exposed to nicotine and cigarette smoke extract support the clinical findings regarding dysbiosis of the subgingival microbiome. Dysbiosis of the periodontal microbiome was presented in smokers regardless of their periodontal condition (healthy, gingivitis, or periodontitis) and remained significant only in smokers even after the resolution of experimentally-induced gingivitis and following reduction of clinical signs of periodontitis with non-surgical periodontal treatment and over 3 months post-therapy. Based on these findings, smoking cessation in periodontitis patients is beneficial for promoting a health-compatible subgingival microbial community. To maximize the benefits of these interventions in dental settings, further studies on periodontal microbiome are needed to elucidate the impact of tobacco intervention on preventing recurrence of periodontal destruction in the susceptible subjects.