Effect of tonsillectomy combined with steroid pulse therapy upon IgA nephropathy depending on proteinuria status at diagnosis: a nationwide multicenter cohort study in Japan.

BACKGROUND: The effects of tonsillectomy combined with steroid pulse (TSP) therapy for IgA nephropathy (IgAN) are little known. Therefore, we examined the effects of TSP therapy on the kidney outcomes of IgAN in a large, nationwide cohort study in Japan. METHODS: Between 2002 and 2004, 632 IgAN patients with ≥ 0.5 g/day proteinuria at diagnosis were divided into three groups with mild (0.50-0.99 g/day; n = 264), moderate (1.00-1.99 g/day, n = 216), or severe (≥ 2.00 g/day; n = 153). Decline in kidney function and urinary remission were compared among the three groups after TSP therapy, corticosteroid (ST) therapy, or conservative therapy during a mean follow-up of 6.2 ± 3.3 years. 10.6% and 5.9% of patients in the ST and conservative therapy group underwent tonsillectomy. RESULTS: The rate of urinary remission at the final observation was significantly higher in the TSP therapy group than in the ST or conservative therapy groups (mild proteinuria: 64%, 43%, and 41%; moderate proteinuria: 51%, 45%, and 28%; severe proteinuria: 48%, 30%, and 22%, respectively). In contrast, the rate of a 50% increase in serum creatinine was lower in groups TSP therapy, than ST or conservative therapy (mild proteinuria: 2.1%, 10.1% and 16.7%; moderate proteinuria: 4.8%, 8.8% and 27.7%; severe proteinuria: 12.0%, 28.9% and 43.1%, respectively). In multivariate analysis, TSP therapy significantly prevented a 50% increase in serum creatinine levels compared with conservative therapy in groups with moderate and severe proteinuria (hazard ratio, 0.12 and 0.22, respectively). CONCLUSION: TSP significantly increased the rate of proteinuria disappearance and urinary remission in IgAN patients with mild-to-moderate urinary protein levels. It may also reduce the decline in kidney function in patients with moderate-to-severe urinary protein levels.

Analysis of the impact of obesity on the prognosis of IgA nephropathy according to renal function and sex.

BACKGROUND: Few studies have observed the direct effect of obesity on renal prognoses in immunoglobulin A nephropathy (IgAN) or separately evaluated its effects according to sex. We aimed to evaluate the direct and indirect effects of obesity on the renal outcomes of IgAN and observe these effects separately according to renal function and sex. METHODS: We extracted patients with body mass index (BMI) descriptions from a multicenter retrospective cohort analysis in Japan, and excluded those with < 30 days of follow-up, diabetes mellitus, and steroid treatment. Patients were divided into normal (n = 720; 18.5 ≤ BMI < 25) and obese (n = 212; BMI ≥ 25) groups, which were then compared. The endpoints were a 1.5-fold increase in serum creatinine levels and the initiation of renal replacement therapy. RESULTS: The obese group was older, included more males, and was more likely have hypertension, dyslipidemia, proteinuria, tubular atrophy, and lower renal function than the normal group. Patients with an eGFR < 60 mL/min/1.73 m2 had well-matched characteristics between the groups; however, hypertension, low high-density lipoprotein cholesterol, and hypertriglyceridemia were more common in the obese group. Obesity contributed to tubular atrophy, even when adjusted for renal function. In addition, it contributed to proteinuria only in females. However, obesity itself was not a significant prognostic factor. CONCLUSIONS: Although no independent effect on renal prognosis was observed during the study period, the obese group had more risk factors for IgAN progression and obesity contributed to tubular atrophy and female proteinuria. Our results suggest that separately analyzing the prognostic effect of obesity according to sex is important.

Serum IgA/C3 ratio: a useful marker of disease activity in patients with IgA nephropathy.

OBJECTIVE: High serum IgA and low serum C3 levels resulting from lectin and alternative pathway activation might be related to IgA nephropathy (IgAN) progression and exacerbation. This study examined whether the serum IgA/C3 ratio can serve as an IgAN progression marker. METHODS: (1) This nationwide multicenter retrospective study in Japan included 718 patients with biopsy-confirmed IgAN. The patients whose serum creatinine levels at the time of renal biopsy had doubled were defined as having disease progression. (2) Furthermore, to investigate the pathological significance of a reduction in serum IgA/C3 ratio, we reviewed 63 patients whose serum IgA and C3 data at the end of the observation period were obtained. RESULTS: (1) A Kaplan-Meier analysis of the patients with IgAN revealed that the group with a high serum IgA/C3 (≥ 3.3) had a significantly worse renal outcome. In a multivariate analysis of eGFR ≥ 60 mL/min per 1.73m2 at the time of biopsy, poor renal outcome was significantly predicted by a serum IgA/C3 ratio of ≥ 3.3. (2) A 15% reduction in the change of serum IgA/C3 ratio was associated with a significantly higher percentage of complete remission of proteinuria. Among the four groups divided by treatment, both the serum IgA/C3 ratio and proteinuria were reduced only in the tonsillectomy and steroid pulse group. CONCLUSION: The serum IgA/C3 level might reflect the disease activity and be a potent surrogate marker of therapeutic efficacy in patients with IgAN.

Effect of Nonsupplemented Low-Protein Diet on the Initiation of Renal Replacement Therapy in Stage 4 and 5 Chronic Kidney Disease: A Retrospective Multicenter Cohort Study in Japan.

OBJECTIVE: In subjects with chronic kidney disease (CKD), the effect of low-protein diet (LPD) is expected to alleviate uremic symptoms. However, whether LPD is effective in preventing loss of kidney function is controversial. The aim of this study was to evaluate the association between LPD and renal outcomes. METHODS: We conducted a multicenter cohort study of 325 patients who suffered CKD stage 4 and 5 with eGFR ≥10 mL/min/1.73 m,2 between January 2008 and December 2014. The primary diseases of the patients were chronic glomerulonephritis (47.7%), nephrosclerosis (16.9%), diabetic nephropathy (26.2%), and others (9.2%). The patients were divided into four groups, based on the mean protein intake (PI)/day, group 1 (n = 76): PI < 0.5 g/kg ideal body weight/day, group 2 (n = 56): 0.5 ≤ PI < 0.6 g/kg/day, group 3 (n = 110): 0.6 ≤ PI < 0.8 g/kg/day, group 4 (n = 83): PI ≥ 0.8 g/kg/day. Dietary supplementation with essential amino acids and ketoanalogues was not used. The outcome measure was occurrence of renal replacement therapy (RRT) (hemodialysis, peritoneal dialysis, renal transplantation (excluding preemptive transplantation)) and all-cause mortality until December 2018. Cox regression models were used to examine whether LPD was associated with the risk of outcomes. RESULTS: During a mean follow-up of 4.1 ± 2.2 years. Thirty-three patients (10.2%) died of all causes, 163 patients (50.2%) needed to start RRT, and 6 patients (1.8%) received a renal transplant. LPD therapy of 0.5 g/kg/day or less was significantly related to a lower risk of RRT and all-cause mortality [Hazard ratio = 0.656; 95% confidence interval, 0.438 to 0.984, P = .042]. CONCLUSIONS: These results suggest that non-supplemented LPD therapy of 0.5 g/kg/day or less may prolong the initiation of RRT in stage 4 and 5 CKD patients.

Prognostic factors of IgA nephropathy presenting with mild proteinuria at the time of diagnosis (a multicenter cohort study).

BACKGROUND: Clinical factors affecting renal prognosis in patients with immunoglobulin A nephropathy (IgAN) and low urinary protein excretion (U-Prot) remain unclear. This study evaluated such factors in patients with clinical grade I (CG-I) IgAN with U-Prot < 0.5 g/day. METHODS: This secondary analysis of a previous retrospective study included 394 patients with CG-I IgAN. The primary outcome was the first occurrence of a 1.5-fold increase in serum creatinine levels from baseline. Factors related to renal prognosis were examined using univariate and multivariate Cox regression analyses. CG-I was divided into C-Grade Ia (CG-Ia) (n = 330) with baseline eGFR ≥ 60 ml/min/1.73 m2, and C-Grade Ib (CG-Ib) (n = 64) with baseline eGFR < 60 ml/min/1.73 m2. Outcome incidence was compared between conservative and aggressive therapy (corticosteroids and/or tonsillectomy) groups. RESULTS: Overall outcome incidence was significantly higher in CG-Ib than in CG-Ia; the cumulative incidence was significantly higher in CG-Ib (hazard ratio, 9.67; 95% confidence interval, 2.90-32.23). Older age, higher IgA levels, eGFR < 60 mL/min/1.73 m2, lower eGFR at baseline were independent prognostic factors for CG-I. Older age, lower eGFR, higher IgA levels at baseline, and U-Prot remission at 1-year post-diagnosis were independent prognostic factors for CG-Ib. Aggressive therapy tended to suppress the cumulative outcome incidence compared with conservative therapy in CG-Ib (p = 0.087). CONCLUSION: An eGFR < 60 mL/min/1.73 m2 is a significant predictor of renal prognosis in patients with IgAN and U-Prot < 0.5 g/day.

Laparoscopic Esophagogastric Anastomosis With Stapled Pseudo-Fornix for Reflux Esophagitis Prevention After Proximal Gastrectomy.

Laparoscopic esophagogastric anastomosis is not commonly performed after proximal gastrectomy (PG) because of its technical complexity and the lack of a gold standard for reconstruction. We describe a simple and convenient technique of laparoscopic esophagogastrostomy with stapled pseudo-fornix for reflux esophagitis (RE) prevention after PG. Laparoscopic PG (LPG) was performed in four patients with gastric cancer in the upper third of the stomach, and the remnant stomach was prepared for reconstruction. After making a small hole on the anterior wall of the remnant stomach 45 mm distal to the proximal stump and on the dorsal side of the esophageal stump, a 45 mm no-knife linear stapler was applied. To create a "pseudo-fornix," a common lumen was made by cutting the center of the four staple rows at a length of 15 mm. The entry hole was closed using the laparoscopic hand-sewn suturing technique. The mean operation time was 240 min, with an estimated blood loss of <10 ml. No intraoperative complications or conversion to open surgery were observed. One patient developed stenosis of the esophagogastrostomy successfully treated by endoscopic balloon dilatation. Endoscopic surveillance three months after surgery revealed no incidence of RE in any of the patients. Laparoscopic esophagogastric anastomosis with stapled pseudo-fornix is convenient and beneficial in preventing RE after PG and should be considered the treatment of choice for reconstruction after LPG in selected patients with proximal gastric cancer.

Decreased peripheral perfusion measured by perfusion index is a novel indicator for cardiovascular death in patients with type 2 diabetes and established cardiovascular disease.

Cardiovascular disease (CVD) is still the major cause of mortality in patients with type 2 diabetes. Despite of recent therapies, mortality and resources spent on healthcare due to CVD is still important problem. Thus, appropriate markers are needed to predict poor outcomes. Therefore, we investigated the role of peripheral perfusion as an indicator for cardiovascular death in patients with type 2 diabetes and established CVD. This retrospective cohort study included 1080 patients with type 2 diabetes and history of CVD recruited from the outpatient clinic at Matsushita Memorial Hospital in Osaka, Japan. Peripheral perfusion is assessed using the perfusion index (PI), which represents the level of circulation through peripheral tissues. The median age and PI values were 74 years (range: 67-79 years) and 2.6% (range: 1.1-4.3%), respectively. During follow-up duration, 60 patients died due to CVD. The adjusted Cox regression analysis demonstrated that the risk of developing cardiovascular death was higher in the first quartile (Hazard ratio, 6.23; 95% CI, 2.28 to 22.12) or second quartile (Hazard ratio, 3.04; 95% CI, 1.46 to 6.85) of PI than that in the highest quartile (fourth quartile) of PI. PI (per 1% decrease) was associated with the development of cardiovascular death (Hazard ratio, 1.39; 95% CI, 1.16 to 1.68). PI could be a novel indicator of cardiovascular death in patients with type 2 diabetes and established CVD.

Impact of the number of steroid pulses in tonsillectomy combined with steroid pulse therapy: a nationwide retrospective study in Japan.

BACKGROUND: Steroid pulse therapy with tonsillectomy is known as a major treatment for IgA nephropathy (IgAN). However, its protocol was different among institutions and the effects of varying the number of steroid pulses remain unclear. METHODS: From a total of 1,174 IgAN patients in a multicenter retrospective cohort analysis in Japan, 195 patients were treated by tonsillectomy combined with corticosteroid. They were divided into four groups based on the number of administered steroid pulses from 0 to three (TSP0-3), and remission of urinary abnormalities and renal survival until 1.5-fold increase in serum creatinine level from baseline were analyzed among the four groups and between TSP1 and TSP3. RESULTS: Among the four groups, renal function was relatively good when the estimated glomerular filtration rate was approximately 80-90 mL/min/1.73m2 and proteinuria was relatively mild (< 1.0 g/gCre). The ratio of patients who developed renal dysfunction was < 5% in all groups, and the cumulative renal survival rate by Kaplan-Meier analysis was similar among groups (log-rank test, p = 0.37), despite varying clinical backgrounds and treatments. After adjustment of the background variables between TSP1 and TSP3, the remission rates of urinary abnormalities were similar and the renal survival rate also remained similar (66.8 vs. 85.4%, p = 0.45). CONCLUSIONS: In patients with mild proteinuria and good renal function, the number of steroid pulses did not affect the renal outcome in steroid pulse therapy with tonsillectomy. The adaptation and protocols, such as the number of steroid pulses, should be determined for each IgAN patient's background.

A Case of Endovascular Treatment for In-Hospital Stroke with COVID-19 under Protected Code Stroke.

Objective: Coronavirus disease 2019 (COVID-19) is characterized by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and presents with respiratory symptoms. Overall, 5.7% of COVID-19 patients with severe respiratory status have been reported to develop acute cerebrovascular diseases (CVDs), and 41.3% of COVID-19 cases were considered nosocomial infections. Therefore, Protected Code Stroke, which is a guideline for acute stroke management that takes into account the safety of healthcare workers, has been developed. We created an operational manual for COVID-19 in the endovascular treatment center of our hospital and report our experience treating acute stroke in a COVID-19 patient. Case Presentation: A 67-year-old man presented with a 5-day history of fever. Chest CT showed ground glass opacity (GGO) on admission, and the polymerase chain reaction (PCR) test for COVID-19 was positive. Dysarthria, right-sided hemiparesis, and aphasia were discovered on the morning of the third day after hospitalization. MRI showed an acute ischemic stroke at the left corona radiata and occlusion of the left middle cerebral artery (MCA). Progression of right-sided hemiparesis and exacerbation of respiratory status developed after the MRI. Tracheal intubation was performed, and the patient was treated with intravenous alteplase and mechanical thrombectomy (MT). Recanalization of blood flow was not obtained, and the neurological deficits remained. Conclusion: MT was performed for large-vessel occlusion (LVO) in a COVID-19 patient during the COVID-19 pandemic. Safety for healthcare workers and appropriate rapid treatment for acute stroke patients are both vital in the current environment.

[A Case of Pancreatic Adenocarcinoma with Inferior Vena Cava Invasion].

A 66-year-old Japanese woman was admitted to our hospital for jaundice. Abdominal computed tomography(CT) showed dilatation of the intra- and extra-hepatic bile duct, and a hypovascular lesion measuring 30mm in diameter in the head of the pancreas. This tumor was in contact with the(superior mesenteric vein: SMV)and(inferior vena cava: IVC), but there were no obvious signs of invasion. Upper gastrointestinal endoscopy showed obstruction of the duodenum. We chose to perform an upfront surgery, considering the patient's general condition being stable and the difficulties associated with endoscopic biliary drainage. During surgery, stiff attachment between the tumor and IVC was identified and wedge resection of the IVC wall was performed. SMV resection and end-to-end reconstruction were also carried out. Pathological studies of the surgical specimen revealed direct invasion by the pancreatic adenocarcinoma into the adventitia of the IVC. The postoperative course was uneventful, and the patient was discharged from the hospital on the 27th postoperative day; she underwent adjuvant chemotherapy(S-1 100mg/day)and is still alive without tumor recurrence, 21 months after surgery. Cases of resected pancreatic adenocarcinoma directly invading the IVC are rare. In this case, pancreaticoduodenectomy along with wedge resection of the IVC wall could safely be performed, and no complications were observed. There is a need for further accumulation of similar cases.

Peripheral perfusion, measured by perfusion index, is a novel indicator for renal events in patients with type 2 diabetes mellitus.

Diabetic kidney disease (DKD) is one of the leading causes of end stage renal disease. Despite recent therapies, mortality due to DKD and resources spent on healthcare are important problems. Thus, appropriate markers are needed to predict renal outcomes. Therefore, we investigated the role of peripheral perfusion as an indicator for renal events in patients with type 2 diabetes mellitus. This retrospective cohort study included 566 patients who were admitted to Matsushita Memorial Hospital in Osaka, Japan for type 2 diabetes mellitus. Peripheral perfusion was assessed using perfusion index (PI), which represents the level of circulation through peripheral tissues and was measured on each toe using a Masimo SET Radical-7 (Masimo Corporation, Irvine, CA, USA) instrument. The duration of follow up was 3.0 years. The median age of patients was 70 years (IQR range: 61-77 years) and median PI value was 2.9% (IQR range: 1.8-4.8%). Multiple logistic regression analyses showed that PI (per 1% increase) was associated with an odds ratio of composite of end-stage renal disease (ESRD) and/or doubling of serum creatinine level; n = 40 (odds ratio 0.823 [95% CI: 0.680-0.970]), and composite of ESRD, doubling of serum creatinine level, and renal death and/or cardiovascular death; n = 44 (odds ratio 0.803 [95% CI: 0.665-0.944]). The factors which were statistically significant in univariate analysis and those known to be related factors for renal event were considered simultaneously as independent variables for multiple logistic regression analysis. PI can be a novel indicator for renal events in patients with type 2 diabetes mellitus.

Decreased microcirculatory function measured by perfusion index is predictive of cardiovascular death.

BACKGROUND: The importance of microcirculation for adverse outcomes in the early phase of critical illnesses has been reported. Microcirculatory function is assessed using the perfusion index (PI), which represents the level of circulation through peripheral tissues. We investigated the correlation between PI and cardiovascular death to explore whether it can serve as a predictor of cardiovascular death. METHODS AND RESULTS: This retrospective study included 2171 patients admitted to Matsushita Memorial Hospital in Osaka, Japan, for medical treatment. We measured PI for all patients. To examine the effects of PI on cardiovascular death, a Cox proportional hazard model was used. The median age and PI values were 72 years (range 63-79 years) and 2.7% (range 1.4-4.6%), respectively. During the 3927.7 person-years follow-up period, a total of 54 patients died due to cardiovascular disease. PI was positively correlated with BMI (P < 0.0001) and total cholesterol levels (P = 0.004). PI was negatively correlated with age (P < 0.0001), heart rate (P < 0.0001), and creatinine levels (P < 0.0001). Adjusted Cox regression analyses demonstrated that PI was associated with an increased hazard of cardiovascular death (hazard ratio 0.84; 95% CI; range 0.72-0.99). In addition, compared with patients with a high PI (> 3.7%), those with a low PI (≤ 2.0%) had a significantly increased risk of cardiovascular death. This low PI group had a hazard ratio of 3.49 (95% CI 1.73-7.82). CONCLUSIONS: The PI is a valuable predictor for cardiovascular death in a clinical setting.

Universal Equation of State Describes Osmotic Pressure throughout Gelation Process.

The equation of state of the osmotic pressure for linear-polymer solutions in good solvents is universally described by a scaling function. We experimentally measure the osmotic pressure of the gelation process via osmotic deswelling. We find that the same scaling function for linear-polymer solutions also describes the osmotic pressure throughout the gelation process involving both the sol and gel states. Furthermore, we reveal that the osmotic pressure of polymer gels is universally governed by the semidilute scaling law of linear-polymer solutions.

Decreased microcirculatory function measured by perfusion index is a novel indicator of diabetic kidney disease in patients with type 2 diabetes.

AIMS/INTRODUCTION: Diabetic kidney disease has been considered as an important risk factor of cardiovascular disease. Chronic hypoxia is considered to be the main cause of renal injury. Diminished microcirculatory blood flow could be associated with hypoxia in the kidney. Whether diminished microcirculation is associated with diabetic kidney disease has not yet been reported. Here, we investigated the correlation between microcirculatory function and diabetic kidney disease in patients with type 2 diabetes. MATERIALS AND METHODS: Our cross-sectional study included 574 patients who were admitted to Matsushita Memorial Hospital in Moriguchi, Japan, for type 2 diabetes. Microcirculatory function was assessed using the perfusion index (PI), which represents the level of circulation through peripheral tissues. We measured the PI for all patients. RESULTS: The median age and PI values were 70 years (range 60-77 years) and 2.8% (range 1.6-4.8%). Multiple regression analyses showed that the PI independently correlated with the logarithm of urinary albumin excretion (P = 0.009) and estimated glomerular filtration rate (P = 0.005), respectively. Multiple logistic regression analyses showed that patients with systolic blood pressure (SBP) greater than the median and PI less than or equal to the median (high-low group) had a significantly increased odds of albuminuria compared with those with SBP less than or equal to the median and PI greater than the median (low-high group), and patients with SBP greater than the median and PI less than or equal to the median (high-low group) had a significantly increased odds of estimated glomerular filtration rate <60 mL/min per 1.73 m2 compared with those with SBP less than or equal to the median and PI greater than the median (low-high group) or SBP greater than the median and PI greater than the median (high-high group). CONCLUSIONS: PI could be a novel indicator of diabetic kidney disease in patients with type 2 diabetes.

Pulsed Terahertz Radiation for Sensitive Quantification of Carbonate Minerals.

Quantification of natural carbonate minerals, namely, aragonite, high- and low-Mg calcite, and dolomite provides essential information about biomineralization, carbon cycling on Earth, and the evolution of ocean chemistry, and is also useful in many other scientific, pharmaceutical, and industrial fields. However, X-ray diffractometer has previously been the only practical tool to identify and quantify carbonate minerals, including calcium carbonate (CaCO3) polymorphs. We propose new fingerprint terahertz (THz) absorption and reflective index spectra in the 1-6 THz range that probe the lattice phonon modes and can be used for sensitive quantification of these four carbonate minerals, including polymorphs. In THz time-domain spectroscopy with our unique attenuated total reflection system, high- and low-Mg calcite and aragonite show different absorbance and reflective index amplitudes at 3.32 THz, which corresponds to the transverse optic mode. Dolomite shows a distinct absorbance peak and reflective index at 4.82 THz because its space group (R3̅) is different from that of calcite (R3̅c). THz absorbance and reflective index curves of the mixed carbonate materials, which typically occur in natural environments, correspond well to the curves calculated from the results of single-mineral samples (R 2 > 0.98). Remarkably, the absorbance and reflective index can quantify small fractions (<1%) of low-Mg calcite in an aragonite matrix with high linearity (R 2 = 0.99). Our findings provide a new method for screening low-Mg calcite diagenetic overprints on primary aragonitic skeletons such as corals, which is crucial for climate reconstructions using the isotopic analyses because a 1% overprint can cause estimated temperature deviations of ∼1 °C. THz spectra of carbonate minerals offer not only a new high-sensitivity quantification tool for interdisciplinary fields, but also safer light-source handling than X-ray diffractometer.

Association Between Tonsillectomy and Outcomes in Patients With Immunoglobulin A Nephropathy.

Importance: Immunoglobulin A nephropathy is a major cause of end-stage renal disease worldwide; previous methods of medical management, including use of renin-angiotensin system inhibitors and corticosteroids, remain unproven in clinical trials. Objective: To investigate the possible association between tonsillectomy and outcomes in patients with IgA nephropathy. Design, Setting, and Participants: This cohort study included 1065 patients with IgA nephropathy enrolled between 2002 and 2004 and divided into 2 groups, those who underwent tonsillectomy and those who did not. Initial treatments (renin-angiotensin system inhibitors or corticosteroids) within 1 year after renal biopsy were also evaluated. A 1:1 propensity score matching was performed to account for between-group differences and 153 matched pairs were obtained. Follow-up concluded January 31, 2014. Analysis was conducted between September 11, 2017, and July 31, 2018. Exposure: Tonsillectomy. Main Outcomes and Measures: The primary outcome was the first occurrence of a 1.5-fold increase in serum creatinine level from baseline or dialysis initiation. Secondary outcomes included additional therapy with renin-angiotensin system inhibitors or corticosteroids initiated 1 year after renal biopsy and adverse events. Results: In 1065 patients (49.8% women; median [interquartile range] age, 35 [25-52] years), the mean (SD) estimated glomerular filtration rate was 76.6 (28.9) mL/min/1.73 m2 and the median (interquartile range) proteinuria was 0.68 (0.29-1.30) g per day. In all, 252 patients (23.7%) underwent tonsillectomy within 1 year after renal biopsy and 813 patients (76.3%) did not undergo tonsillectomy. The primary outcome was reached by 129 patients (12.1%) during a median (interquartile range) follow-up of 5.8 (1.9-8.5) years. In matching analysis, tonsillectomy was associated with primary outcome reduction (hazard ratio, 0.34; 95% CI, 0.13-0.77; P = .009). In subgroup analyses, benefit associated with tonsillectomy was not modified by baseline characteristic differences. Those undergoing tonsillectomy required fewer additional therapies 1 year following renal biopsy (adjusted hazard ratio, 0.37; 95% CI, 0.20-0.63; P < .001) without increased risks for adverse events, except transient tonsillectomy-related complications. Conclusions and Relevance: This study found that tonsillectomy was associated with a lower risk of renal outcomes in patients with IgA nephropathy. The potential role of tonsillectomy should be considered for preventing end-stage renal disease in patients with IgA nephropathy.

[Hepatic and Pancreatic Metastases of a Rectal Gastrointestinal Stromal Tumor in a Patient with Long-Term Survival following Combined Therapy-ACase Report].

A 68-year-old woman underwent Miles' surgery with a diagnosis of a rectalgastrointestinalstromaltumor (GIST)in 2004. In 2005 and 2006, she developed liver metastases that were surgically removed, but once again in June 2006, she presented with liver metastasis, and imatinib therapy(400mg/day)was administered. In October 2016, she was diagnosed with progression of liver metastasis, and a tumor in the pancreatic body was identified on a CT scan. The patient was referred to our institution for treatment. We performed right hepatectomy and distalpancreatectomy in January 2017. Immunohistochemically, the recurrent tumor was positive for c-kit and CD34, and the diagnosis of GIST was confirmed. The pathological diagno- sis was a high-risk GIST showing 43mitoses per 50 high-power fields. Imatinib therapy(400mg/day)was administered after surgery. She is currently alive without recurrence.

Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104 [OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial.

BACKGROUND: Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is standard care for stage II gastric cancer. Whether the duration of S-1 could be shortened to 6 months (corresponding to four courses) without worsening survival is unclear. The aim of this study was to investigate the non-inferiority of four courses of S-1 compared with eight courses of S-1 for patients with stage II gastric cancer. METHODS: We did a phase 3, open-label, randomised controlled, non-inferiority trial at 59 hospitals in Japan. Patients aged 20-80 years with stage II adenocarcinoma of the stomach were randomly assigned (1:1) to eight courses or four courses of S-1. Randomisation was done by the Japan Clinical Oncology Group Data Center website, using a minimisation method with a random component using institution, stage (IIA vs IIB), age (<70 years vs ≥70 years), and mode of operation (open gastrectomy with bursectomy vs open gastrectomy without bursectomy vs laparoscopic gastrectomy) as adjustment factors. One course was 80 mg/day per m2 of S-1 administered for 4 weeks followed by a rest for 2 weeks. The primary endpoint was relapse-free survival, analysed by intention to treat, with a non-inferiority margin for the hazard ratio (HR) set at 1·37. This study is registered at UMIN-Clinical Trial Registry, number UMIN000007306. FINDINGS: Between Feb 16, 2012, and March 19, 2017, 590 patients were enrolled (295 per group). 528 (89%) patients were analysed at the first planned interim analysis in March, 2017, at which time the point estimate of HR for the four-course group compared with the eight-course group was 2·52 (95% CI 1·11-5·77), which exceeded 1·37 and met the prespecified criteria for early termination. Predictive probability for showing non-inferiority at the final analysis was calculated to be 2·9%. The study was stopped for futility. Updated 3-year relapse-free survival analysed in May, 2017, was 93·1% (95% CI 87·8-96·1) for the eight-course group and 89·8% (84·2-93·5) for the four-course group (HR 1·84, 95% CI 0·93-3·63). The most common grade 3-4 adverse event was neutropenia, observed in 46 (16%) patients in the eight-course group and 51 (17%) patients in the four-course group. INTERPRETATION: S-1 for 1 year should remain as standard adjuvant chemotherapy for stage II gastric cancer. FUNDING: Japan Agency for Medical Research and Development; the Ministry of Health, Labour and Welfare of Japan; the National Cancer Center Research and Development Fund, Japan.

The perfusion index is a useful screening tool for peripheral artery disease.

The number of people with peripheral artery disease (PAD) has been increasing globally; therefore, it is important to explore more options to screen patients who are at a risk of developing PAD. The perfusion index (PI) represents the degree of circulation through the peripheral tissues and is measured noninvasively. We investigated the correlation between the PI and ankle-brachial index (ABI) to explore whether the PI could be used a screening tool for PAD. This cross-sectional study included 390 patients. We measured the ABI and PI for all patients. The median ABI value was 1.06 (0.92-1.13); the PI was 1.7% (0.9-3.5). The PI was higher in men than in women (P < 0.0001). The PI was positively correlated with the estimated glomerular filtration rate and ABI in both men and women. The sensitivity and specificity of the PI to predict PAD (ABI ≤0.9) were 90.0% and 80.3%, respectively, and the cutoff PI value was 1.5% in men. The sensitivity and specificity of the PI to predict PAD were 82.1% and 79.2%, respectively, and the cutoff PI value was 1.1% in women. PI could be a reliable screening tool for diagnosing PAD because it does not restrict the patient's mobility, can be completed in a short time period, and is associated with reduced costs.

A grading system that predicts the risk of dialysis induction in IgA nephropathy patients based on the combination of the clinical and histological severity.

Histological classification is essential in the clinical management of immunoglobulin A nephropathy (IgAN). However, there are limitations in predicting the prognosis of IgAN based on histological information alone, which suggests the need for better prognostic models. Therefore, we defined a prognostic model by combining the grade of clinical severity with the histological grading system by the following processes. We included 270 patients and explored the clinical variables associated with progression to end-stage renal disease (ESRD). Then, we created a predictive clinical grading system and defined the risk grades for dialysis induction by a combination of the clinical grade (CG) and the histological grade (HG). A logistic regression analysis revealed that the 24-h urinary protein excretion (UPE) and the estimated glomerular filtration rate (eGFR) were significant independent variables. We selected UPE of 0.5 g/day and eGFR of 60 ml/min/1.73 m2 as the threshold values for the classification of CG. The risk of progression to ESRD of patients with CG II and III was significantly higher than that of patients with CG I. The patients were then re-classified into nine compartments based on the combination of CG and HG. Furthermore, the nine compartments were grouped into four risk groups. The risk of ESRD in the moderate, high, and super-high-risk groups was significantly higher than that in the low-risk group. Herein, we are giving a detailed description of our grading system for IgA nephropathy that predicted the risk of dialysis based on the combination of CG and HG.