Membranoproliferative glomerulonephritis and leukocytoclastic vasculitis without cryoglobulin in chronic hepatitis C virus infection

The etiopathogenesis of extrahepatic manifestations including vasculitis in the context of HCV infection is still unknown. We report a case with lethal extrahepatic manifestations due to chronic hepatitis C virus (HCV) infection. The patient presented leukocytoclastic vasculitis, sensorimotor neuropathy and membranoproliferative glomerulonephritis with positive rheumatoid factor but lacked cryoglobulin. Hypocomplementaemia and deposition of IgM and C3 in the vascular lesion and glomeruli suggested that immune complex disease played a role in the pathogenesis of extrahepatic manifestations independent of cryoglobulin. Although HCV was successfully eliminated by treatment with interferon alpha, she died of cryptococcal infection.     

Impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer: A retrospective study of 50 cases

ObjectiveComputer-aided design and computer-aided manufacturing (CAD/CAM) techniques are increasingly applied to mandibular reconstruction, but the superiority of this method in oral food intake has not been well established. Considering the extent of mandibular defects, this retrospective study was aimed to clarify the impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer.Materials and methodsWe performed a retrospective review of 50 patients who had undergone segmental mandibulectomy with free flap reconstruction for locally advanced oral cancer. The patients’ Functional Oral Intake Scale scores were measured at 3 months after surgery, and possible contributing factors including CAD/CAM mandibular reconstruction and the extent of mandibular defects for oral food intake were subjected to univariate analysis and multivariate logistic regression analysis.ResultsMultivariate logistic regression analysis showed that CAD/CAM mandibular reconstruction was independently associated with good oral intake, whereas both anterior or extensive mandibular resection and glossectomy were also independently associated with poor oral intake after surgery.ConclusionThe present study showed the positive impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer for the first time.     

Descending aorta–external iliac artery bypass for middle aortic syndrome

We encountered a surgical case of middle aortic syndrome (MAS) in a 56-year-old man who had resistant hypertension. Computed tomography showed severe stenosis of the abdominal aorta from below the superior mesenteric artery to above the inferior mesenteric artery. Although bilateral renal artery stenosis was confirmed, renal function was within normal limits. A 10-mm vascular prosthetic graft was used to perform a descending aorta to left external iliac artery bypass. His hypertension was well controlled without medication. This extra-anatomic bypass may be a simple and useful approach for treating MAS if it is not necessary to reconstruct the renal artery or visceral artery.     

Prognostic impact of lipid contents on the target lesion in patients with drug eluting stent implantation

We sought to determine the morphologic predictors of major adverse cardiac events (MACEs) after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES), using integrated backscatter intravascular ultrasound (IB-IVUS). Conventional IVUS and IB-IVUS were performed in 260 consecutive patients who underwent PCI with DES. Three-dimensional analyses were performed to determine plaque volume and the volume of each plaque component (lipid, fibrous, and calcification). Patients were divided into two groups according to the median lipid volume (LV) in the target lesion. MACEs were defined as death, nonfatal myocardial infarction, and any repeat revascularization. The median follow-up interval was 1285 days. MACEs were observed in 64 patients (24.6 %). Patients having a larger LV compared with their counterparts had worse long-term clinical outcomes regarding mortality (3.8 vs. 0 %, P = 0.02) and MACEs (31.5 vs. 17.7 %, P = 0.008) by log-rank test. After adjustment for confounders, large LV (odds ratio 1.95, 95 % confidence interval 1.14–3.33, P = 0.02) was significantly and independently associated with MACEs. The assessment of coronary plaque characteristics in the target lesion may be useful to predict long-term outcome following successful coronary intervention.     

Elevated total iron-binding capacity as a predictor of response to deferasirox therapy in the setting of chronic iron overload

It is difficult to predict the efficacy of deferasirox (DFX) as its pharmacokinetics varies among patients. The area under the curve (AUC) is reportedly useful for determining adequate DFX dosage; however, serum concentration measurements are often challenging. Effective DFX dosage is thus defined by assessing the efficacy of this agent in clinical practice. To analyze a predictive response marker to DFX therapy for use in adjusting the effective dosage during the early treatment phase, we retrospectively evaluated 39 DFX-treated patients. We defined response as a >40 % decrease in serum ferritin concentration from the pretreatment level. A maximum elevation of the total iron-binding capacity (TIBC) correlated with response in a multivariate analysis of iron metabolic markers (R ² = 0.37, p < 0.001). A receiver operating characteristic curve analysis revealed that TIBC elevation had an AUC of 0.85 (p < 0.001) and the optimal cut-off value of TIBC elevation was 150 µg/dl. TIBC elevation of >150 µg/dl is a favorable predictor of effective ferritin reduction in DFX therapy (hazard ratio 29.6, 95 % confidence interval 4.8–183.6; p < 0.001). DFX therapy with TIBC monitoring may enable the determination of the minimum effective DFX dosage.     

Mac-2 binding protein glycosylation isomer as a novel predictive biomarker for patient survival after hepatitis C virus eradication by DAAs

Background

It is crucial to identify risk factors for life prognosis after hepatitis C virus (HCV) eradication among patients with or without a high risk of liver cancer or complications.

Methods

This is a prospective, multicenter and observational study using the database of 1031 patients after HCV eradication by direct-acting antiviral agents (DAAs) to evaluate the development of hepatocellular carcinoma (HCC) and patients’ survival after a sustained virological response (SVR). The Cox proportional hazards regression model was used to estimate hazard ratios associated with HCC development and survival.

Results

AFP at SVR was significantly associated with HCC recurrence in the adjusted model. Liver fibrosis, Mac-2 binding protein glycosylation isomer (M2BPGi) at SVR and smoking status before treatment were positively associated with the development of HCC and M2BPGi was positively associated with HCC recurrence, although not reaching statistical significance. Among patients without a history of HCC, M2BPGi and estimated glomerular filtration rate (eGFR) at SVR were significantly associated with death after viral eradication [M2BPGi (HR 4.07, 95% CI 1.22, 13.57), eGFR (HR 0.97, 95% CI 0.94, 0.99)]. Strikingly, of 16 patients who died, among participants without a history of HCC, only two died of liver cancer associated with HCV, whereas 11 died of non-HCV- related cancer or cardiovascular diseases.

Conclusion

M2BPGi at SVR is a potential predictor for patients’ survival and a candidate biomarker for detecting individuals who are at greater risk of death due to cancer-related and unrelated to HCV, as well as cardiovascular diseases, after viral eradication.

     

Clinical improvements in higher brain function and rapid functional recovery in a case of cerebellar hemorrhage treated by neurocognitive rehabilitation

Cerebellar stroke rarely causes disorders of higher brain function such as cognitive deficits and emotional dysfunction; hence, the prognosis of these patients is uncertain. We report the case of a 34-year-old patient with cerebellar hemorrhage due to arteriovenous malformation causing higher brain dysfunction who was able to return to full-time employment after neurocognitive rehabilitation. Cerebellar stroke caused by nonatherosclerotic diseases or diaschisis may lead to cognitive deficits but these symptoms can be reversed by appropriate therapy. It is important to assess higher brain function in cerebellar stroke patients and to tailor neurocognitive rehabilitation programs appropriately to promote functional recovery.     

Hyperthermia generated with ferucarbotran (Resovist®) in an alternating magnetic field enhances cisplatin-induced apoptosis of cultured human oral cancer cells

Hyperthermia is a promising anti-cancer treatment in which the tissue temperature is increased to 42–45 °C, and which is often used in combination with chemotherapy or radiation therapy. Our aim in the present work was to examine the feasibility of combination therapy for oral cancer with cisplatin and hyperthermia generated with ferucarbotran (Resovist^®; superparamagnetic iron oxide) in an alternating magnetic field (AMF). First, we established that administration of ferucarbotran at the approved dosage for magnetic resonance imaging provides an iron concentration sufficient to increase the temperature to 42.5 °C upon exposure to AMF. Then, we examined the effect of cisplatin combined with ferucarbotran/AMF-induced hyperthermia on cultured human oral cancer cells (HSC-3 and OSC-19). Cisplatin alone induced apoptosis of cancer cells in a dose-dependent manner, as is well known. However, the combination of cisplatin with ferucarbotran/AMF was significantly more effective than cisplatin alone. This result suggests that it might be possible to reduce the clinically effective dosage of cisplatin by administering it in combination with ferucarbotran/AMF-induced hyperthermia, thereby potentially reducing the incidence of serious cisplatin-related side effects. Further work seems justified to evaluate simultaneous thermo-chemotherapy as a new approach to anticancer therapy.