Utility of plasma D-dimer for diagnosis of venous thromboembolism after hepatectomy

BACKGROUND Venous thromboembolism(VTE)is a potentially fatal complication of hepatectomy.The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative bleeding.Therefore,we hypothesized that monitoring plasma D-dimer could be useful in the early diagnosis of VTE after hepatectomy.AIM To evaluate the utility of monitoring plasma D-dimer levels in the early diagnosis of VTE after hepatectomy.METHODS The medical records of patients who underwent hepatectomy at our institution between January 2017 and December 2020 were retrospectively analyzed.Patients were divided into two groups according to whether or not they developed VTE after hepatectomy,as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower extremities.Clinicopathological factors,including demographic data and perioperative D-dimer values,were compared between the two groups.Receiver operating characteristic curve analysis was performed to determine the D-dimer cutoff value.Univariate and multivariate analyses were performed using logistic regression analysis to identify significant predictors.RESULTS In total,234 patients who underwent hepatectomy were,of whom(5.6%)were diagnosed with VTE following hepatectomy.A comparison between the two groups showed significant differences in operative time(529 vs 403 min,P=0.0274)and blood loss(530 vs 138 mL,P=0.0067).The D-dimer levels on postoperative days(POD)1,3,5,7 were significantly higher in the VTE group than in the non-VTE group.In the multivariate analysis,intraoperative blood loss of>275 mL[odds ratio(OR)=5.32,95%confidence interval(CI):1.05-27.0,P=0.044]and plasma D-dimer levels on POD 5≥21μg/mL(OR=10.1,95%CI:2.04-50.1,P=0.0046)were independent risk factors for VTE after hepatectomy.CONCLUSION Monitoring of plasma D-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the postoperative period.

Treatment of portosystemic shunt-borne hepatic encephalopathy in a 97-year-old woman using balloon-occluded retrograde transvenous obliteration:A case report

BACKGROUND Hyperammonemia and hepatic encephalopathy are common in patients with portosystemic shunts.Surgical shunt occlusion has been standard treatment,although recently the less invasive balloon-occluded retrograde transvenous obliteration(B-RTO)has gained increasing attention.Thus far,there have been no reports on the treatment of portosystemic shunts with B-RTO in patients aged over 90 years.In this study,we present a case of hepatic encephalopathy caused by shunting of the left common iliac and inferior mesenteric veins,successfully treated with B-RTO.CASE SUMMARY A 97-year-old woman with no history of liver disease was admitted to our hospital because of disturbance of consciousness.She had no jaundice,spider angioma,palmar erythema,hepatosplenomegaly,or asterixis.Her blood tests showed hyperammonemia,and abdominal contrast-enhanced computed tomography revealed a portosystemic shunt running between the left common iliac vein and the inferior mesenteric vein.She was diagnosed with hepatic encephalopathy secondary to a portosystemic shunt.The patient did not improve with conservative treatment:Lactulose,rifaximin,and a low-protein diet.B-RTO was performed,which resulted in shunt closure and improvement in hyperammonemia and disturbance of consciousness.Moreover,there was no abdominal pain or elevated levels of liver enzymes due to complications.The patient was discharged without further consciousness disturbance.CONCLUSION Portosystemic shunt-borne hepatic encephalopathy must be considered in the differential diagnosis for consciousness disturbance,including abnormal behavior and speech.

Traditional Chinese medicine for promoting mental health of patients with COVID-19:a scoping review

Objective:This study aimed to systematically review and depict the current studies of traditional Chinese medicine for the mental health of patients with coronavirus disease 2019(COVID-19).Methods:A scoping review was conducted by searching PubMed,Web of Science,CNKI,Wanfang database,VIP database,and SinoMed,with the retrieval time being from the establishment of the database to April 18,2022.The basic information of the included studies,objective,design,types of patients,interventions,outcomes,etc.,was reviewed and summarized narratively.Methodological quality was assessed using the Cochrane Risk of Bias assessment tool,the methodological index for nonrandomized studies or the Newcastle-Ottawa scale.Results:We identified 30 traditional Chinese medicine(TCM)studies from six databases.Among them,finished randomized controlled trials(n=16)accounted for most of the studies,followed by single-arm studies(n=9).In terms of study theme,20 studies defined the mental health of patients with COVID-19 as the research theme.Psychological assessment was included in the inclusion criteria(performed before participation)of nine studies,whereas the other studies only mentioned the mental outcomes.TCM interventions included TCM exercises(Yijinjing,Baduanjin,Liuzijue,Taichi),acupoint stimulation(auricular and body points),moxibustion,decoction,or granules based on TCM syndrome differentiation,decoction,or granules with fixed formulae(Baidu Jieduan granules,Xuanfei Baidu decoction,and Qingfei Paidu decoction),Chinese patent medicine(Jinhua Qinggan granules),TCM psychological therapy(TCM ideological therapy,TCM five-tone therapy,and TCM psychological sand table),and TCM nursing(dialectical care,dialectical diet,and psychological counseling).Anxiety and depression were the main outcomes evaluated in regard to mental health in patients with COVID-19.The limitations of methodological quality were predominantly from follow-up,blinding,and registration.Positive results were reported by 27 studies(90%,n=30).Conclusion:We summarized the existing literature about the impact of TCM on mental health in patients with COVID-19.The number of studies evaluating the impact of TCM on mental health is encouraging,but overall methodological quality was low.Several TCM interventions warrant further evaluation,particularly among populations outside of China,for the purpose of establishing supporting evidence.More importantly,research with stronger methodological quality needs to be developed.

Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination:A case report and review of literature

BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

Short-and long-term outcome of interferon therapy for chronic hepatitis B infection

Hepatitis B virus(HBV) infection is a serious clinical problem worldwide. Conventional interferon(IFN)-α has been approved for the treatment of chronic hepatitis B(CHB). Short-term studies have demonstrated that IFN-based therapy is moderately effective in inducing the loss of hepatitis e antigen(HBeAg) or seroconversion(30%-40%) in HBeAg-positive patients and also produces sustained HBV DNA suppression(20%-30%) in HBeAg-negative patients. Many studies have reported a correlation between the HBV genotype and response to IFN treatment. The highest response rate to IFN treatment was found in patients infected with HBV genotype A, followed by HBV genotypes B, C, and D. The long-term effect of IFN-α on CHB has not yet been elucidated. The ability of IFN-α treatment to prevent new cirrhosis, complications associated with cirrhosis, and development of hepatocellular carcinoma(HCC) is controversial. The beneficial effect of IFN-α treatment in reducing the development of HCC has mainly been observed in treatment responders who already have cirrhosis. These inconsistent findings may be attributed to the inevitable limitations of comparisons across studies, including differences in the baseline characteristics of the study and the moderate suppression of HBV replication by IFN-α relative to nucleoside/nucleos(t)ide analogs.

Clinical outcomes of ampullary neoplasms in resected margin positive or uncertain cases after endoscopic papillectomy

BACKGROUND Endoscopic papillectomy(EP) for benign ampullary neoplasms could be a lessinvasive alternative to pancreatoduodenectomy(PD). There are some problems and limitations with EP. The post-EP resection margins of ampullary tumors are often positive or uncertain because of the burning effect of EP. The clinical outcomes of resected margin positive or uncertain cases after EP remain unknown.AIM To investigate the clinical outcomes of resected margin positive or uncertain cases after EP.METHODS Between January 2007 and October 2018, all patients with ampullary tumors who underwent EP at Kobe University Hospital were included in this study. The indications for EP were as follows: adenoma, as determined by preoperative endoscopic biopsy, without bile/pancreatic duct extension, according to endoscopic ultrasound or intraductal ultrasound. The clinical outcomes of resected margin positive or uncertain cases after EP were retrospectively investigated.RESULTS Of the 45 patients, 29 were male, and 16 were female. The mean age of the patients was 65 years old. Forty-one patients(89.5%) underwent en bloc resection,and 4 patients(10.5%) underwent piecemeal resection. After EP, 33 tumors were histopathologically diagnosed as adenoma, and 12 were diagnosed as adenocarcinoma. The resected margins were positive or uncertain in 24 patients(53.3%). Of these cases, 15 and 9 were diagnosed as adenoma and adenocarcinoma, respectively. Follow-up observation was selected for all adenomas and 5 adenocarcinomas. In the remaining 4 adenocarcinoma cases,additional PD was performed. Additional PD was performed in 4 cases, and residual carcinoma was found after the additional PD in 1 of these cases. In the follow-up period, local tumor recurrence was detected in 3 cases. Two of these cases involved primary EP-diagnosed adenoma. The recurrent tumors were also adenomas detected by biopsy. The remaining case involved primary EPdiagnosed adenocarcinoma. The recurrent tumor was also an adenocarcinoma.All of the recurrent tumors were successfully treated with argon plasma coagulation(APC). There was no local or lymph node recurrence after the APC.The post-APC follow-up periods lasted for 57.1 to 133.8 mo. No ampullary tumor-related deaths occurred in all patients.CONCLUSION Resected margin positive or uncertain cases after EP could be managed by endoscopic treatment including APC, even in cases of adenocarcinoma. EP could become an effective less-invasive first-line treatment for early stage ampullary tumors.

Comparison of DWI and PET/CT in evaluation of lymph node metastasis in uterine cancer

AIM: To investigate diffusion-weighted imaging (DWI) and positron emission tomography and computed tomography (PET/CT) with Ⅳ contrast for the preoperative evaluation of pelvic lymph node (LN) metastasis in uterine cancer. METHODS: Twenty-five patients with endometrial or cervical cancer who underwent both DWI and PET/CT before pelvic lymphadenectomy were included in this study. For area specific analysis, LNs were divided into eight regions: both common iliac, external iliac, internal iliac areas, and obturator areas. The classification for malignancy on DWI was a focally abnormal signal intensity in a location that corresponded to the LN chains on the T1WI and T2WI. The criterion for malignancy on PET/CT images was increased tracer uptake by the LN.RESULTS: A total of 36 pathologically positive LN areas were found in 9 patients. With DWI, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detecting metastatic LNs on an LN area-by-area analysis were 83.3%, 51.2%, 27.3%, 93.3% and 57.0%, respectively, while the corresponding values for PET/CT were 38.9%, 96.3%, 70.0%, 87.8% and 86.0%. Differences in sensitivity, specificity and accuracy were significant (P < 0.0005). CONCLUSION: DWI showed higher sensitivity and lower specificity than PET/CT. Neither DWI nor PET/CT were sufficiently accurate to replace lymphadenectomy.

Maintenance for healed erosive esophagitis:PhaseⅢcomparison of vonoprazan with lansoprazole

AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg(n = 201), vonoprazan 10 mg(n = 202), or vonoprazan 20 mg(n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events(AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen Ⅰ/Ⅱ levels, and gastric mucosa histopathology results.RESULTS Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg(P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg(5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan(P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSION Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.

Long-term outcome of percutaneous ethanol injection therapy for minimum-sized hepatocellular carcinoma

AIM: To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma (HCC) treated with percutaneous ethanol injection (PEI). METHODS: PEI was applied to 42 lesions in 31 patients (23 male and eight female) with HCC < 15 mm in diameter, over the past 15 years. RESULTS: Overall survival rate was 74.1% at 3 years, 49.9% at 5 years, 27.2% at 7 years and 14.5% at 10 years. These results are superior to, or at least the same as those for hepatic resection and radiofrequency ablation. Survival was affected only by liver function, but not by sex, age, etiology of Hepatitis B virus or Hepatitis C virus, α-fetoprotein levels, arterial and portal blood flow, histological characteristics, and tumor multiplicity or size. Patients in Child-Pugh class A and B had 5-, 7- and 10-years survival rates of 76.0%, 42.2% and 15.8%, and 17.1%, 8.6% and 0%, respectively (P = 0.025). CONCLUSION: Treatment with PEI is best indicated for patients with HCC < 15 mm in Child-Pugh class A.

Impact of hepatitis C virus heterogeneity on interferon sensitivity:An overview

Hepatitis C virus(HCV)is a major cause of liver disease worldwide.HCV is able to evade host defense mechanisms,including both innate and acquired immune responses,to establish persistent infection,which results in a broad spectrum of pathogenicity,such as lipid and glucose metabolism disorders and hepatocellular carcinoma development.The HCV genome is characterized by a high degree of genetic diversity,which can be associated with viral sensitivity or resistance(reflected by different virological responses)to interferon(IFN)-based therapy.In this regard,it is of importance to note that polymorphisms in certain HCV genomic regions have shown a close correlation with treatment outcome.In particular,among the HCV proteins,the core and nonstructural proteins(NS)5A have been extensively studied for their correlation with responses to IFN-based treatment.This review aims to cover updated information on the impact of major HCV genetic factors,including HCV genotype,mutations in amino acids 70 and91 of the core protein and sequence heterogeneity in the IFN sensitivity-determining region and IFN/ribavirin resistance-determining region of NS5A,on virological responses to IFN-based therapy.

Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller than 2 cm

AIM:To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma(HCC)smaller than 2 cm.METHODS:Nodules smaller than 2 cm(n=34)revealed by ultrasonography(US)in 29 patients with liver cirrhosis were analyzed.Histological diagnosis of HCC was performed by ultrasonographic guidance:moderately-differentiated HCC(n=24);well-differentiated HCC(n=10).The patterns disclosed by the four imaging modalities defined the conclusive diagnosis of HCC:(1)contrast-enhanced computed tomography(CECT),hypervascularity in the arterial phase and washout in the equilibrium phase;(2)Sonazoid contrast-enhanced US(CEUS),hypervascularity in the early vascular phase and defect in the Kupffer phase;(3)gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid(Gd-EOBDTPA)-enhanced magnetic resonance imaging(MRI),hypervascularity in the arterial phase and/or defect in the hepatobiliary phase;and(4)CT arterioportal angiography:hypervascularity by CT during arteriography and/ or perfusion defect by CT during arterial portography.RESULTS:Overall,the sensitivity of diagnosing HCC smaller than 2 cm was 52.9%(18/34)(95%CI:35.170.2)by CECT;67.6%(23/34)(95%CI:49.5-82.6)by Sonazoid CEUS;76.5%(26/34)(95%CI:58.8-89.3) by Gd-EOB-DTPA MRI;and 88.2%(30/34)(95%CI: 72.5-96.7)by CT arterioportal angiography.The diagnostic sensitivity of detecting moderately-differentiated HCC by CECT,Sonazoid CEUS,Gd-EOB-DTPA MRI and CT arterioportal angiography was 62.5%(15/24)(95%CI: 40.6-81.2),79.2%(19/24)(95%CI:57.8-92.9),75.0% (18/24)(95%CI:53.3-90.2)and 95.8%(23/24)(95% CI:78.9-99.9),respectively.A significant difference(P< 0.05)was observed between CECT and CT arterioportal angiography in all nodules.There was no difference between Sonazoid CEUS,Gd-EOB-DTPA MRI,and CT arterioportal angiography.The combined sensitivity of Sonazoid CEUS and Gd-EOB-DTPA MRI was 94.1%(32/34).CONCLUSION:Changing the main diagnostic modality for HCC smaller than 2 cm from CT arterioportal angiography to Sonazoid CEUS and Gd-EOB-DTPA MRI is recommended.

Narrow-band imaging observation of colorectal lesions using NICE classification to avoid discarding significant lesions

AIM: To assess the risk of failing to detect diminutive and small colorectal cancers with the "resect and discard" policy.METHODS: Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancersand their endoscopic features were assessed. RESULTS: In total, we found 681 cases of diminutive(1-5 mm) lesions in 402 patients and 197 cases of small(6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal(SM) scanty invasive carcinomas, 1 and 1 were SM deeply invasive carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically.CONCLUSION: The risk of failing to detect diminutive and small colorectal invasive cancer with the "resect and discard" strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy.

Gastric plexiform fibromyxoma resected by endoscopic submucosal dissection after observation of chronological changes:A case report

A 66-year-old man was diagnosed with a gastric submucosal tumor. Endoscopic ultrasound(EUS) revealed an iso/hypoechoic mass in the third layer. No malignant cells were detected in a histological examination. Yearly follow-up endoscopy and EUS showed the slow growth of the tumor. Endoscopic submucosal dissection(ESD) was performed and a glistening tumor was resected. The lesion showed a multinodular plexiform growth pattern consisting of spindle cells with an abundant fibromyxoid stroma that was rich in small vessels. The tumor was diagnosed as plexiform fibromyxoma(PF) by immunohistochemistry. Although difficulties are associated with reaching a diagnosis preoperatively, chronological changes on EUS may contribute to the diagnosis of PF. ESD may also be useful in the diagnosis and treatment of PF.

Erythropoietin gene transfer into rat testes by in vivo electropo-ration may reduce the risk of germ cell loss caused by cryptorchidism

Aim： To investigate the effects of rat Erythropoietin （Epo） on spermatogenesis by transferring rat Epo gene into cryptorchid testes by means of in vivo electroporation. Methods： Sprague-Dawley rats with surgically-induced unilateral cryptorchidism were divided into three groups： the first group was given intratesticular injections of pCAGGS-Epo （pCAGGS-Epo group）, the second group was given intratesticular injections of pCAGGS （pCAGGS group）, and the third group were given intratesticular injections of phosphate-buffered saline （PBS group）. At the same time, square electric pulses of 30 V were applied six times with a time constant of 100 ms. One or two weeks after injection, each testis was weighed and the ratio of the total number of germ cells to that of Sertoli cells （G/S ratio） was calculated to evaluate the impairment of spermatogenesis. Ten testes taken from each of the three groups were examined at each time point. Results： The testicular weight after the injection of pCAGGS-Epo or pCAGGS control plasmid was （0.85 ± 0.08） g and （0.83 ± 0.03） g, respectively, at week 1 （P = 0.788） and （0.62 ± 0.06） g and （0.52 ± 0.02） g, respectively, at week 2 （P = 0.047）. At week 1, spermatids and sperm were more abundant in testes with pCAGGS-Epo than those in the control testes. At week 2, spermatids and sperm were hardly detected in either group. The G/S ratio was 23.27 ± 6.80 vs. 18.63 ± 5.30 at week 1 （P = 0.0078） and 7.16 ± 3.06 vs. 6.05 ± 1.58 at week 2 （P = 0.1471）, respectively. Conclusion： The transfer of Epo to rat testes by in vivo electroporation may reduce the risk of the germ cell loss caused by cryptorchidism.

Impact of formal training in endoscopic submucosal dissection for early gastrointestinal cancer: A systematic review and a meta-analysis

AIM: To summarize the clinical impact of a formal training for the effectiveness and safety of endoscopic submucosal dissection for gastrointestinal cancer.METHODS: We searched databases including PubM ed, EMBASE and the Cochrane Library and Science citation Index updated to August 2014 to include eligible articles. In the Meta-analysis, the main outcome measurements were en bloc resection rate, local recurrence rate(R0) and the incidence of procedure-related complications(perforation, bleeding). RESULTS: En bloc resection was high for both, dissecting stomach tumors with an overall percentage of 93.2%(95%CI: 90.5-95.8) and dissecting colorectal tumors with an overall percentage of 89.4%(95%CI: 85.1-93.7). Although the number of studies reporting R0 resection(the dissected specimen was revealed free of tumor in both vertical and lateral margins) was small, the overall estimates for R0 resection were 81.4%(95%CI: 72-90.8) for stomach and 85.9%(95%CI: 77.5-95.5) for colorectal tumors, respectively. The analysis showed that the percentage of immediate perforation and bleeding were very low; 4.96(95%CI: 3.6-6.3) and 1.4%(95%CI: 0.8-1.9) for colorectal tumors and 3.1%(95%CI: 2.0-4.1) and 4.8%(95%CI: 2.8-6.7) for stomach tumors, respectively. CONCLUSION: In order to obtain the same rate of success of the analyzed studies it is a necessity to create training centers in the western countries during the "several years" of gastroenterology residence first only to teach EGC diagnose and second only to train endoscopic submucosal dissection.

Successful treatment of warfarin-induced skin necrosis using oral rivaroxaban: A case report

BACKGROUND Heparin is commonly recommended for warfarin-induced skin necrosis;however, there is currently no established therapy for this disease. We present a serious case of warfarin-induced skin necrosis that was successfully treated with oral rivaroxaban, a factor Xa inhibitor.CASE SUMMARY A 48-year-old woman was admitted to the hospital for cellulitis of the right lower extremity. After antibiotic treatment, she developed pain and swelling of the left lower extremity, and deep vein thrombosis of both lower extremities was diagnosed. She was treated with a continuous heparin injection;subsequently,oral warfarin was concomitantly administered. Heparin was terminated after the therapeutic range was reached. On the following day, the patient had swelling and pain in the left lower extremity. In addition to decrease in protein S activity due to systemic lupus erythematosus, warfarin also reduced protein C activity,resulting in further hypercoagulation and skin necrosis. Warfarin was discontinued, and continuous heparin injection was resumed. Although the patient had to undergo amputation of the distal end of her left foot, continuous heparin injection was switched to oral rivaroxaban, and she was eventually discharged from the hospital in remission.CONCLUSION Administration of direct oral anticoagulants instead of warfarin is important in patients with decreased protein S and C activity.

Suppression of fibrosis in human pterygium fibroblasts by butyrate and phenylbutyrate

AIM：To evaluate the antifibrogenic effects of butyrate or phenylbutyrate,a chemical derivative of butyrate,in human pterygium fibroblasts.METHODS：Human pterygium fibroblasts obtained from patient pterygium tissue were treated with butyrate or phenylbutyrate for 48h.Expression ofα-smooth muscle actin,collagen I,collagen III and matrix metalloproteinase-1m RNA was measured by quantitative real-time reverse transcription polymerase chain reaction,and acetylated histone was evaluated by Western blotting.RESULTS：Butyrate inhibitedα-smooth muscle actin,type III collagen and matrix metalloproteinase-1 expressions,and phenylbutyrate inhibited types I and III collagen and matrix metalloproteinase-1 expressions without changing cell viability as well as both of these increased histone acetylation.These results suggested that butyrate and phenylbutyrate suppress fibrosis through a mechanism involving histone deacetylase inhibitor.CONCLUSION：This indicates that butyrate or phenylbutyrate have antifibrogenic effects in human pterygium fibroblasts and could be novel types of prophylactic and/or therapeutic drugs for pterygium,especially phenylbutyrate,which does not have the unpleasant smell associated with butyrate.

Impact of penile rehabilitation with low-dose vardenafil on recovery of erectile function in Japanese men following nerve-sparing radical prostatectomy

Erectile dysfunction （ED） is a major complication after radical prostatectomy （RP）; however, debatecontinues regarding the efficacy of penile rehabilitation in the recovery of the postoperative erectile function （EF）. This study includeda total of 103 consecutive sexually active Japanese men with localized prostate cancer undergoing nerve-sparing RP, and analyzed the postoperative EF, focusing on the significance of penile rehabilitation. In this series, 24 and 79 patients underwent bilateral and unilateral nerve-sparing RPs, respectively, and 10 or 20 mg of vardenafil was administered to 35 patients at least once weekly, who agreed to undergo penile rehabilitation. Twelve months after RP, 48 （46.6%） of the 103 patients were judged to have recovered EF sufficient for sexual intercourse without any assistance. The proportion of patients who recovered EF in those undergoing penile rehabilitation （60.0%） was significantly greater than that in those without penile rehabilitation （38.2%）. Of several parameters examined, the preoperative International Index of Erectile Function-5 （IIEF-5） score and nerve-sparing procedure were significantly associated with the postoperative EF recovery rates in patients with and without management by penile rehabilitation, respectively. Furthermore, univariate analysis identified the preoperative IIEF-5 score, nerve-sparing procedure and penile rehabilitation as significant predictors of EF recovery, among which the preoperative IIEF-5 score and nerve-sparing procedure appeared to be independently associated with EF recovery. Considering these findings, despite the lack of independent significance, penile rehabilitation with low-dose vardenafil could exert a beneficial effect on EF recovery in Japanese men following nerve-sparing RP.

Magnetic resonance angiography for the primary diagnosis of pulmonary embolism: A review from the international workshop for pulmonary functional imaging

Pulmonary contrast enhanced magnetic resonance angiography(CE-MRA) is useful for the primary diagnosis of pulmonary embolism(PE). Many sites have chosen not to use CE-MRA as a first line of diagnostic tool for PE because of the speed and higher efficacy of computerized tomographic angiography(CTA). In this review, we discuss the strengths and weaknesses of CEMRA and the appropriate imaging scenarios for the primary diagnosis of PE derived from our unique multiinstitutional experience in this area. The optimal patient for this test has a low to intermediate suspicion for PE based on clinical decision rules. Patients in extremis are not candidates for this test. Younger women(< 35 years of age) and patients with iodinated contrast allergies are best served by using this modality We discuss the history of the use of this test, recent technical innovations, artifacts, direct and indirect findings for PE, ancillary findings, and the effectiveness(patient outcomes) of CE-MRA for the exclusion of PE. Current outcomes data shows that CE-MRA and NM V/Q scans are effective alternative tests to CTA for the primary diagnosis of PE.

Roles of the two distinct proteasome pathways in hepatitis C virus infection

Hepatitis C virus(HCV) infection often causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The development of a HCV cell culture system enabled us to investigate its whole HCV life cycle and develop a better understanding of the pathogenesis of this virus. Post-translational modification plays a crucial role in HCV replication and in the maturation of viral particles. There is growing evidence also suggesting that the ubiquitin-proteasome pathway and the ubiquitin-independent proteasome pathway are involved in the stability control of HCV proteins. Many viruses are known to manipulate the proteasome pathways to modulate the cell cycle, inhibit apoptosis, evade the immune system, and activate cell signaling, thereby contributing to persistent infection and viral carcinogenesis. The identification of functional interactions between HCV and the proteasome pathways will therefore shed new light on the life cycle and pathogenesis of HCV. This review summarizes the current knowledge on the involvement of the ubiquitin-dependent and-independent proteasome pathways in HCV infection and discusses the roles of these two distinct mechanisms in HCV pathogenesis.