Urinary biomarkers of kidney tubule injury, risk of acute kidney injury, and mortality in patients with acute ischaemic stroke treated at a stroke care unit.

BACKGROUND AND PURPOSE: Urinary liver-type fatty-acid binding protein (L-FABP), which is a biomarker of kidney tubule injury, has been studied extensively and established as a risk marker of acute kidney injury (AKI). The aim of this study was to investigate whether kidney tubule injury is associated with the development of AKI and mortality in patients with acute ischaemic stroke. METHODS: Acute ischaemic stroke patients hospitalized in the stroke care unit (SCU) within 24 h after symptom onset were prospectively investigated. AKI was defined on the basis of Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Baseline urinary L-FABP was measured on admission. We evaluated the associations among urinary L-FABP, incidence of AKI, and 90-day mortality adjusted for renal function, albuminuria and other potentially predictive variables, using multivariable analysis. RESULTS: In total, 527 acute ischaemic stroke patients (342 men, median age 74 years) were enrolled in the study. Twenty-seven patients (5.1%) experienced AKI within 7 days of admission. In the univariate analysis, high urinary L-FABP level had positive associations with AKI [53.8 µg/g creatinine (Cr) vs. 3.9 µg/g Cr; P < 0.001] and 90-day mortality (15.5 µg/g Cr vs. 4.0 µg/g Cr; P < 0.001). In the multivariate analysis, elevated urinary L-FABP level (per 10-µg/g Cr increase) was independently associated with AKI (odds ratio 1.225, 95% confidence interval (CI) 1.083-1.454; P = 0.003) and 90-day mortality (hazard ratio 1.091, 95% CI 1.045-1.138; P < 0.001). CONCLUSION: Urinary biomarkers of kidney tubule injury are independently associated with the development of AKI and 90-day mortality in patients with acute ischaemic stroke treated at the SCU.

Does preoperative enteral nutrition reduce the incidence of surgical complications in patients with Crohn's disease? A case-matched study.

AIM: Currently, the notion that preoperative optimization with enteral nutrition (EN) reduces the incidence of complication after surgery in Crohn's disease (CD) patients is being debated. This case-matched study was to evaluate the impact of preoperative EN on surgical outcomes in patients with CD. METHOD: Twenty-four patients received EN therapy with an elemental diet (1800-2400 kcal/day) for at least 2 weeks before the planned surgery (EN group). A further 24 patients who underwent surgery without receiving preoperative EN or parenteral nutrition formed a control group based on four matched criteria: age (≤/>40 years), the use of preoperative medications (corticosteroids/azathioprine/biologics), disease behaviour (inflammatory/stricturing/penetrating) and main surgical procedure (ileal resection/ileocolonic resection/colectomy). The incidence of complications observed within 30 days after surgery was compared between the two groups. Septic complications were defined as anastomotic leak, intra-abdominal abscess, entero-cutaneous fistula or wound infection. RESULTS: In the EN group, the median serum albumin level significantly increased, while C-reactive protein (CRP) significantly decreased during the preoperative EN (albumin, from 3.0 mg/dl to 3.1 mg/dl, P = 0.04; CRP, from 3.05 mg/dl to 2.52 mg/dl, P = 0.02). The incidence of postoperative septic complications was significantly lower in the EN group compared with the control group (4% vs 25%, P = 0.04). The occurrence rate of overall complications was lower in the EN group (21% vs 29%, P = 0.51), but not statistically significant. CONCLUSION: In patients with CD, preoperative optimization with EN reduced the overall rate of postoperative complications and significantly decreased postoperative septic complications.

The relationship between stroke severity and prior direct oral anticoagulant therapy in patients with acute ischaemic stroke and non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: Anticoagulant treatment with a vitamin K antagonist (VKA) has been reported to reduce stroke severity when patients with atrial fibrillation (AF) suffer acute ischaemic stroke (AIS). Direct oral anticoagulant (DOAC) therapy also has the potential to reduce the initial severity of AIS. However, the effect of DOAC therapy on the severity of AIS is not well known. The aim of the present study was to investigate the effect of DOACs on initial stroke severity in patients with AIS and non-valvular AF. METHODS: From March 2011 to July 2016, consecutive patients with AIS having non-valvular AF were recruited. The effects of prior DOAC treatment on severity were assessed by multivariate logistic regression analyses. RESULTS: A total of 484 patients [208 women; median age 79 (interquartile range, 71-85) years; National Institutes of Health Stroke Scale (NIHSS) score 9 (interquartile range, 3-20)] were enrolled. Of these, 352 (73%) were on no anticoagulant medication, 54 (11%) were undertreated with a VKA, 35 (7%) were sufficiently treated (admission prothrombin time-international normalized ratio: ≥2.0 for patients <70 years old and ≥1.6 for ≥70 years old) with a VKA and 43 (9%) were on a DOAC. The initial NIHSS score (median 10 in patients with no anticoagulation, 13 in undertreated VKA, 7 in sufficient VKA and 6 in DOAC, P = 0.018) was different among the groups. Multivariate analysis showed that DOAC was independently and negatively associated with severe (initial NIHSS score ≥ 10) stroke (odds ratio, 0.39; P = 0.041), compared with no anticoagulant therapy. CONCLUSIONS: Direct oral anticoagulant treatment prior to the event should reduce initial stroke severity in patients with AIS and non-valvular AF.

Tacrolimus vs. anti-tumour necrosis factor agents for moderately to severely active ulcerative colitis: a retrospective observational study.

BACKGROUND: There have been no comparative studies of tacrolimus vs. anti-tumour necrosis factor (anti-TNF) agents to determine which treatment is safer or more effective in refractory ulcerative colitis (UC). AIM: To compare short-term safety and efficacy of tacrolimus vs. anti-TNF agents for active UC. METHODS: One hundred patients with moderate-to-severe active UC were studied. Fifty patients were treated with oral tacrolimus (TAC group). The other 50 patients were treated with anti-TNF agents (anti-TNF group): 40 with infliximab and 10 with adalimumab. Primary endpoints were clinical response and remission rates, colectomy rate, and the incidence of adverse events during 12 weeks. RESULTS: The incidence of adverse events was 12% in the TAC vs. 18% in the anti-TNF groups (P = 0.58). At week 12, clinical remission rate was 40% in the TAC vs. 28% in the anti-TNF groups (P = 0.29). Clinical response (including remission) rate was 62% in the TAC vs. 64% in the anti-TNF groups (P > 0.99). Five patients (10%) in the TAC and 8 (16%) in the anti-TNF groups required colectomy (P = 0.55). In a subgroup analysis restricted to severely active UC, the response rate was 50% in the TAC vs. 25% in the anti-TNF groups (P = 0.24). In severely active UC, the response rate tended to be higher in patients treated with tacrolimus, albeit not statistically significant. CONCLUSIONS: Both tacrolimus and anti-TNF agents appeared to be safe and effective in the management of moderate-to-severe active UC. However, randomised controlled trials are warranted to confirm the results obtained in this study.

Consecutive monitoring of faecal calprotectin during mesalazine suppository therapy for active rectal inflammation in ulcerative colitis.

BACKGROUND: No studies have monitored the levels of faecal calprotectin (FC) during mesalazine suppository therapy for proctitis in ulcerative colitis (UC). AIMS: To evaluate the value of consecutive monitoring of FC in patients with UC during mesalazine suppository therapy. METHODS: One hundred and sixty patients with active inflammation limited to the rectum were treated with mesalazine 1 g suppository once daily for 8 weeks. Patients who achieved clinical remission were advised to maintain the treatment, and were followed up for further 40 weeks. FC levels were measured every 8 weeks during the study. RESULTS: At week 8, 118 patients (74%) went into clinical remission, of whom 88 achieved endoscopic healing. The median FC level significantly decreased in patients with clinical and endoscopic remission (both P < 0.0001), while it did not change significantly in those without remission. Eighty (68%) of the 118 patients with remission continued the treatment. Twenty-four patients (30%) relapsed during the 40-week follow-up. In patients with clinical relapse, the median FC level elevated already 8 weeks before the diagnosis of relapse. In contrast, in patients who maintained remission it remained at a low level and did not significantly change during the follow-up. Elevated FC level (≥55 µg/g) was useful for the early diagnosis of relapse (88% sensitivity and 80% specificity). CONCLUSIONS: Faecal calprotectin may represent a useful biomarker for the assessment of disease activity in UC patients treated with mesalazine suppositories. Serial monitoring of faecal calprotectin appears to be valuable for the prediction and early diagnosis of relapse during maintenance therapy.

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study.

BACKGROUND: A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety. RESULTS: Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75-1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81-1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. CONCLUSION: Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. CLINICAL TRIAL IDENTIFIER: UMIN000002557.

Methotrexate-related lymphoproliferative disorder arising in the gingiva of a patient with rheumatoid arthritis.

Methotrexate (MTX) is the primary drug used in the management of rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. MTX is a strong immunosuppressive agent and has been reported to cause iatrogenic immunodeficiency-associated lymphoproliferative disorders (LPDs). Stomatitis caused by MTX-related cytotoxicity may occur, but gingival MTX-related LPDs are rare. In this article we present a case of gingival MTX-related LPD in a 60-year-old male with RA. The local findings of the gingival ulceration and alveolar bone exposure were similar to those of bisphosphonate-related osteonecrosis of the jaw. However, he had never received bisphosphonate therapy. The biopsy specimen of the gingival lesion was diagnosed as diffuse large B-cell lymphoma with Epstein-Barr virus positivity. Immediate withdrawal of MTX resulted in marked remission of the LPD.

Elevated glucose level adversely affects infarct volume growth and neurological deterioration in non-diabetic stroke patients, but not diabetic stroke patients.

BACKGROUND AND PURPOSE: Hyperglycemia is recognized as a common occurrence associated with a high risk of poor outcome in ischaemic stroke patients. However, little is known about the association between elevated glucose level, growth of infarct volume and neurological deterioration in ischaemic stroke patients without diabetes. The present study aimed to clarify this issue in acute ischaemic stroke patients with arterial occlusion. METHODS: We studied 375 acute ischaemic stroke patients with arterial occlusion within 24 h of onset. Diabetes was diagnosed in patients with a known history of diabetes or HbA1c value ≥ 6.5%. Infarct volume was measured on admission and at follow-up within 48 h using diffusion-weighted imaging. Neurological deterioration was defined as an increase of ≥ 4 points in National Institutes of Health Stroke Scale score within 7 days of stroke onset. We examined the relationship between glucose level on admission, infarct volume growth and neurological deterioration in three categories (all patients, non-diabetes and diabetes) using multivariate modeling. RESULTS: Diabetes was present in 104 patients (27.7%). Multivariate regression analysis showed that elevated glucose level was independently associated with infarct volume growth in all patients (P = 0.034) and non-diabetes (P = 0.002), but not in diabetes (P = 0.871). Moreover, elevated glucose level was independently associated with neurological deterioration in all patients [odds ratio (OR), 1.010; 95% confidence interval (CI), 1.004-1.017; P = 0.002] and non-diabetes (OR, 1.014; 95% CI, 1.002-1.026; P = 0.022), but not diabetes (OR, 1.006; 95% CI, 0.998-1.014; P = 0.151). CONCLUSIONS: Glucose level appears to influence infarct volume growth and neurological deterioration, particularly in non-diabetic patients with ischaemic stroke.

Admission hyperglycemia causes infarct volume expansion in patients with ICA or MCA occlusion: association of collateral grade on conventional angiography.

BACKGROUND AND PURPOSE: Hyperglycemia (HG) is associated with infarct volume expansion in acute ischaemic stroke patients. However, collateral circulation can sustain the ischaemic penumbra and limit the growth of infarct volume. The aim of this study was to determine whether the association between HG and infarct volume expansion is dependent on collateral circulation. METHODS: We performed a retrospective analysis of 93 acute ischaemic stroke patients with internal carotid artery or middle cerebral artery occlusion within 24 h of onset were retrospectively studied. HG was diagnosed in patients with an admitting blood glucose value ≥140 mg/dl. Angiographic collateral grade 0-1 was designated as poor collateral circulation and grade 2-4 as good collateral circulation. Infarct volume was measured at admission and at again within 7 days using diffusion-weighted magnetic resonance images. RESULTS: Among 34 patients with poor collateral grade, the change in infarct volume was significantly greater in the HG group than in the non-HG group (106.0 ml vs. 22.7 ml, P = 0.002). Among the 59 patients with good collateral circulation, the change in infarct volume was greater in the HG group than in the non-HG group (53.3 ml vs. 10.9 ml, P = 0.047). Multiple regression analysis indicated that admission HG (P = 0.004), baseline National Institutes of Health Stroke Scale score (P = 0.018), and poor collateral circulation (P = 0.040) were independently associated with infarct volume expansion. CONCLUSIONS: Infarct volume expansion was greater in individuals with HG on admission regardless of collateral circulation status.

[Peripheral intrapulmonary lipoma: report of a case].

A 62-year-old woman who had undergone a left mastectomy for a breast cancer consulted us for an abnormal chest shadow. Chest computed tomography showed a well-defined nodule of 1 cm diameter periphery in lower lobe of the right lung. The differential diagnosis included benign lung tumors, such as intrapulmonary lymph nodes, granuloma etc. However, because of her past history we needed to consider metastasis. To make diagnosis, a wedge resection of the pulmonary nodule was performed. The tumor was diagnosed as a lipoma. No malignant cells were seen. Although peripheral intrapulmonary lipoma is very rare, it should be kept in mind in the differential diagnosis of an intrapulmonary nodule.

The oro-ileal transit of cellulose.

The effects of cellulose and the interindividual variations on the transit time in the small intestine remain unclear, but no previous study has to date taken these factors into sufficient consideration. We assessed the oro-ileal transit time and the recovery percentage of cellulose in the terminal ileum looking at interindividual variations. Seven healthy males received 100 mL of a dietary fiber-free basal diet with 5 g cellulose and 5 g of polyethylene glycol 4000. The ileal contents were aspirated every 30 min via an experimental tube placed in the terminal ileum to assess the oro-ileal transit time and the recovery percentage of cellulose. The mean percentage (with standard deviation) of the amounts of cellulose collected in the terminal ileum was 98.4%+/- 16.5% (ranging from 67.4% to 114.5%) with a coefficient variation of 16.8%. The average times (in hours) taken for 20%, 40%, 60%, and 80% of cellulose to reach the terminal ileum were 5.5 +/- 1.1, 6.7 +/- 0.7, 8.5 +/- 1.3, and 8.8 +/- 1.2, respectively, with large interindividual variations. In conclusion, the averaged recovery percentage of cellulose in the terminal ileum was approximately 100%, in accordance with the present generally accepted definition of dietary fiber. However, there were large interindividual variations in the oro-ileal transit time and the percentage of cellulose recovered.

Unsuspected small ameloblastoma in the alveolar bone: a collaborative study of 14 cases with discussion of their cellular sources.

BACKGROUND: Intraosseous ameloblastoma (IA) is the quintessence of epithelial odontogenic tumor and histologically and behaviorally defined as an undoubted neoplastic process. Current information must lead to the consensus that IA arises from the embryologic inclusions of odontogenic epithelium within the jawbone. Nevertheless, clinically oriented evidence is limited to this day. METHODS: The clinical and radiographic features, behavior, and pathology of 14 cases of small IA confined to the alveolar region were systematically examined. RESULTS: Six cases were a chance finding. There was no gender predilection and half of the lesions clustered in middle age (>40 years). The posterior region of the mandible (n = 7) and the anterior segment of the maxilla (n = 4) were favored. Five radiographic characteristics were recognized: interradicular (n = 5) and periradicular (n = 3), and periapical, residual and pericoronal (n = 2 each). They showed solid (n = 12) or unicystic (n = 2) growth pattern and 12 lesions were divided into seven follicular, three desmoplastic, and two plexiform subtypes. The main location of tumor was microscopically traceable in six cases; three interradicular type outside the periodontal ligament space and two periradicular and one periapical variants inside. CONCLUSION: By in-depth evaluation of the spatial relationship between tumor and its surrounding structure, the alveolar process, periodontal ligament space, and pericoronal area are all the likely starting points of IA. This report re-awakens the oral pathologist to the histogenetic significance of incipient IA as the only available human specimen for reappraisal of their origin.