Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Analysis of Urinary Oligosaccharides and Glycoamino Acids for the Diagnosis of Mucopolysaccharidosis and Glycoproteinosis.

BACKGROUND: Mucopolysaccharidosis (MPS) and glycoproteinosis are 2 groups of heterogenous lysosomal storage disorders (LSDs) caused by defective degradation of glycosaminoglycans (GAGs) and glycoproteins, respectively. Oligosaccharides and glycoamino acids have been recognized as biomarkers for MPS and glycoproteinosis. Given that both groups of LSDs have overlapping clinical features, a multiplexed assay capable of unambiguous subtyping is desired for accurate diagnosis, and potentially for severity stratification and treatment monitoring. METHODS: Urinary oligosaccharides were derivatized with 3-methyl-1-phenyl-2-pyrazoline-5-one (PMP) and analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) together with the underivatized glycoamino acids. Novel biomarkers were identified with a semi-targeted approach with precursor mass scanning, the fragmentation pattern (if applicable), and the biochemical basis of the condition. RESULTS: A UPLC-MS/MS analysis with improved chromatographic separation was developed. Novel biomarkers for MPS-IIIA, IIIB, IIIC, and VII were identified and validated. A total of 28 oligosaccharides, 2 glycoamino acids, and 2 ratios were selected as key diagnostic biomarkers. Validation studies including linearity, lower limit of quantitation (LLOQ), and precision were carried out with the assay performance meeting the required criteria. Age-specific reference ranges were collected. In the 76 untreated patients, unambiguous diagnosis was achieved with 100% sensitivity and specificity. Additionally, the levels of disease-specific biomarkers were substantially reduced in the treated patients. CONCLUSIONS: A multiplexed UPLC-MS/MS assay for urinary oligosaccharides and glycoamino acids measurement was developed and validated. The assay is suitable for the accurate diagnosis and subtyping of MPS and glycoproteinosis, and potentially for severity stratification and monitoring response to treatment.

Influence of colour background on anti-viral activity against viral haemorrhagic septicaemia virus in zebrafish regulated by circadian rhythm signalling pathway.

The influence of colour background on the regulation of behavioural and physiological responses in zebrafish is widely recognized. However, its specific effect on virus infection in zebrafish remains unclear. This study aimed to explore the susceptibility of zebrafish to viral haemorrhagic septicaemia virus (VHSV) infection in relation to background colour, investigate the underlying mechanisms, and elucidate the involvement of key molecules, using proteomic and gene expression analyses. The results revealed that zebrafish housed in a blue tank exhibited higher survival rates and considerably reduced VHSV replication compared to those housed in a yellow tank. Further, up-regulation of apolipoprotein 1 (APOA1) was identified as a crucial shared mechanism associated with survival in zebrafish exposed to VHSV infection and reared in a blue background. The mRNA expression level of bmal1a, a core gene involved in the circadian rhythm, was consistently downregulated in fish from the blue tank compared to fish from the yellow tank, regardless of infection status. Subsequently, zebrafish in the blue tank were exposed to daylight conditions to stimulate per2 and pgc1a expression, aiming to investigate their potential impact on VHSV infection. The validity of these interconnected events, triggered by background colour, involving APOA1 up-regulation, circadian rhythm modulation, and antiviral responses, was confirmed by treatments with hesperetin and cyclosporine A, an activator and inhibitor of apoa1 respectively. Our findings revealed the influence of background colour on the apoa1 expression level, thus establishing the involvement of a novel network through circadian rhythm signalling.

Survival Prediction Model for Patients with Hepatocellular Carcinoma and Extrahepatic Metastasis Based on XGBoost Algorithm.

Purpose: Accurate estimation of survival is of utmost importance in patients with hepatocellular carcinoma (HCC) and extrahepatic metastasis. This study aimed to develop a survival prediction model using real-world data. Patients and Methods: A total of 993 patients with treatment-naïve HCC and extrahepatic metastasis were included from 13 Korean hospitals between 2013 and 2018. Patients were randomly divided into a training set (70.0%) and a test set (30.0%). The eXtreme Gradient Boosting (XGBoost) algorithm was applied to predict survival at 3, 6, and 12 months. Results: The mean age of the patients was 60.8 ± 12.3 years, and 85.4% were male. During the study period, 96.1% died, and median survival duration was 4.0 months. In multivariate analysis, Child-Pugh class, number and size of tumors, presence of vascular or bile duct invasion, lung or bone metastasis, serum AFP, and primary anti-HCC treatment were associated with survival. We constructed a model for survival prediction based on the relevant variables, which is available online (https://metastatic-hcc.onrender.com/form). Our model demonstrated high performance, with areas under the receiver operating characteristic curves of 0.778, 0.794, and 0.784 at 3, 6, and 12 months, respectively. Feature importance analysis indicated that the primary anti-HCC treatment had the highest importance. Conclusion: We developed a model to predict the survival of patients with HCC and extrahepatic metastasis, which demonstrated good discriminative ability. Our model would be helpful for personalized treatment and for improving the prognosis.

A Real-World Comparative Study of Microwave and Radiofrequency Ablation in Treatment-Naïve and Recurrent Hepatocellular Carcinoma.

The efficacy and safety of microwave ablation (MWA) compared to radiofrequency ablation (RFA) for patients with treatment-naïve and recurrent hepatocellular carcinoma (HCC) has not been clarified in Korea. There were 150 HCC patients (100 in the RFA group and 50 in the MWA group) enrolled in our study. The primary outcome was one- and two-year disease-free survival (DFS). Secondary outcomes were complete response (CR) rate, two-year survival rate, risk factors for DFS and complication rate. Treatment outcomes were also assessed using propensity-score matching (PSM). The MWA group had better one- and two-year DFS than the RFA group (p = 0.035 and p = 0.032, respectively), whereas the CR rate, two-year survival rate, and complication rate were similar between the two groups with fewer major complications in the MWA group (p = 0.043). Patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. MWA was also an independent factor for favorable one- and two-year DFS. Finally, the MWA group still showed better one- and two-year DFS than the RFA group after PSM. In conclusion, MWA could be an alternative treatment to RFA especially in patients with a high risk of recurrence, perivascular tumors, and small tumor size.

Epidemiological and Clinical History of Viral Hepatitis in Korea.

Viral hepatitis is the most important cause of acute and chronic liver disease in Korea. Particularly, hepatitis B virus (HBV) is the leading cause of liver-related mortality. Because of the nationwide vaccinations in the 1980s, hepatitis B surface antigen positive rates substantially decreased from 8% to 3%. Moreover, the introduction of potent nucleoside or nucleotide analogs led to the effective treatment of patients who had already been infected by HBV. The remaining issue has been to develop novel drugs that can cure HBV infection. Hepatitis C virus (HCV), on the other hand, is a hepatotropic virus that is parenterally transmitted. In Korea, the prevalence of HCV is estimated to be approximately 1%. Although no effective vaccine for HCV has been developed yet, highly effective and safe direct-acting antiviral therapy, which has a short treatment duration of 8 - 12 weeks, has made HCV eradication possible globally. Currently, the unsolved issue regarding HCV management is low disease awareness among patients and health care providers. Therefore, nationwide testing for anti-HCV would be a solution to identify patients infected with HCV but with no symptoms. Lastly, the Hepatitis A virus (HAV) is orally transmitted and results in acute hepatitis. In Korea, the young adult population is a high-risk group since this group is not vaccinated against HAV. More active vaccination and improved hygiene would be necessary to prevent HAV infection.

Radiofrequency Ablation of Hepatocellular Carcinoma (≤ 5 cm) with Saline-Perfused Electrodes: Factors Affecting Local Tumor Progression.

Purpose: We aimed to assess local tumor progression (LTP) rate and associated prognostic factors in 92 patients who underwent radiofrequency ablation (RFA) using saline-perfused electrodes to treat hepatocellular carcinoma (HCC) (≤ 5 cm). Materials and Methods: Total 92 patients with 148 HCCs were treated with RFA using salineperfused electrodes, from 2009 to 2015. We retrospectively evaluated technical success, technique efficacy, and LTP rates. Potential prognostic factors for LTP were perivascular tumor, subphrenic tumor, artificial ascites, tumor size (≥ 2 cm), and previous treatment of transarterial chemoembolization. Analysis was performed by lesion, rather than by person. Results: During follow-up period from 1 to 97.4 months, total cumulative LTP rates were 7.9%, 11.4%, and 14.6% at 1, 3, and 5 years, respectively. These values were significantly higher in the perivascular (35.1%; p = 0.009) and subphrenic group (38.9%; p = 0.002) at 5-year. We did not observe any significant difference in LTP according to other prognostic factors (p > 0.05). Conclusion: RFA with saline-perfused electrode is a safe and effective treatment modality for HCC (≤ 5 cm), with lower LTP rates. Nevertheless, perivascular and subphrenic HCCs demonstrated higher LTP rate than other sites. It is imperative to note that perivascular and subphrenic location of HCC are associated with a high risk of local recurrence, despite the use of salineperfused electrodes.

Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea.

BACKGROUND: A real-life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice. METHODS: We analyzed 590 consecutively enrolled patients with CHC-1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance-associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen. RESULTS: The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was "indeterminate." Overall, 518 patients were treated with a 24-week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV-"indeterminate" patients was not difference 95.0% in the RAV-negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC. CONCLUSIONS: Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC-1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.

Two-Stage Total Knee Arthroplasty for Prosthetic Joint Infection.

PURPOSE: This retrospective review was conducted to identify prognostic factors for two-stage reimplantation for infected total knee arthroplasty (TKA) and the rate of reinfection following revision TKA. MATERIALS AND METHODS: Out of 88 patients diagnosed with post-TKA infection between 1998 and 2011, 76 underwent two-stage reimplantation and were reviewed in this study. The 76 patients were divided into two groups-those who experienced reinfection and those who did not. Comorbidities, culture results, and inflammation indices were analyzed and compared between the two groups. RESULTS: Of the 76 patients who underwent a two-stage reimplantation, 18 (23.7%) experienced reinfection. Patients with more than three comorbidities had significantly higher reinfection rates than those with less than three comorbidities (47.1% vs. 4.8%, p=0.032). The reinfection rate between the culture positive prosthetic joint infection group and the culture negative prosthetic joint infection group was not significantly different (p=0.056). Inflammation indices (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) showed a statistically significant difference between patients with reinfection and those without reinfection at 4 weeks after the first-stage surgery. CONCLUSIONS: Reimplantation must be carefully performed when the risk of reinfection is high, particularly in patients with more than three systemic or local comorbidities and higher inflammation indices (ESR and CRP) prior to revision TKA.

Acute pancreatitis secondary to ciprofloxacin therapy in patients with infectious colitis.

BACKGROUND/AIMS: Ciprofloxacin is considered to be a safe and effective treatment for acute infectious colitis. However, this drug may cause drug-induced pancreatitis, albeit rarely. METHODS: From March 2007 to February 2012, we studied 227 patients who were hospitalized for infectious colitis at St. Mary's Hospital. All of the patients received ciprofloxacin therapy for the treatment of infectious colitis. We observed a few cases of rare adverse events, including ciprofloxacin-induced acute pancreatitis diagnosed based on the Naranjo algorithm. RESULTS: During ciprofloxacin therapy, seven of 227 patients (3.1%) developed rare pancreatitis as defined by the Naranjo algorithm; pancreatic enzyme activity was sporadically elevated with ciprofloxacin use. After ciprofloxacin administration, the average interval until the development of pancreatitis was 5.5 days (range, 4 to 7 days). On abdominal computed tomography, pancreatic swelling and homogenous enhancement was noted in three of seven patients. Complicating acute pancreatitis was gradually but completely resolved after cessation of ciprofloxacin administration. The mean recovery time was 11.3 days (range, 8 to 15 days). CONCLUSIONS: We observed that ciprofloxacin-induced pancreatitis may occur with an incidence of approximately 3%. Ciprofloxacin-induced pancreatitis presents a short latency, suggesting an idiosyncratic hypersensitivity reaction. Practitioners should be aware that drug-induced pancreatitis can occur during ciprofloxacin therapy.

Effect of microbubble contrast agent during high intensity focused ultrasound ablation on rabbit liver in vivo.

OBJECTIVE: To evaluate the effect of a microbubble contrast agent (SonoVue) during HIFU ablation of a rabbit liver. MATERIALS AND METHODS: HIFU ablations (intensity of 400W/cm(2) for 4s, six times, with a 5s interval between exposures) were performed upon 16 in vivo rabbit livers before and after intravenous injection of a microbubble contrast agent (0.8ml). A Wilcoxon signed rank test was used to compare mean ablation volume and time required to tissue ablation on real-time US. Shape of ablation and pattern of coagulative necrosis were analyzed by Fisher's exact test. RESULTS: The volume of coagulative necrosis was significantly larger in the combination microbubble and HIFU group than in the HIFU alone group (P<0.05). Also, time to reach ablation was shorter in the combination microbubble and HIFU group than in the HIFU alone group (P<0.05). When analyzing the shape of tissue ablation, a pyramidal shape was more prevalently in the HIFU alone group compared to the combination microbubble and HIFU group (P<0.05). Following an analysis of the pattern of coagulative necrosis, non-cavitary necrosis was found in ten and cavitary necrosis in six of the samples in the combination microbubble and HIFU group. Conversely, non-cavitary necrosis occurred in all 16 samples in the HIFU alone group (P<0.05). CONCLUSION: HIFU of in vivo rabbit livers with a microbubble contrast agent produced larger zones of ablation and more cavitary tissue necrosis than without the use of a microbubble contrast agent. Microbubble contrast agents may be useful in tissue ablation by enhancing the treatment effect of HIFU.

Long-term outcome of high-intensity focused ultrasound in advanced pancreatic cancer.

OBJECTIVES: The aim of this study was to evaluate safety and efficacy of high-intensity focused ultrasound (HIFU) for advanced pancreatic cancer (PC). METHODS: Patients with PC TNM stage III or IV were included. Magnetic resonance imaging was performed 2 weeks before and after the HIFU. The ablating tumor volume was calculated by ratio of the nonperfused necrotic area of the planned area on contrast-enhanced T1-weighted image on post-HIFU magnetic resonance imaging. The ablation results were stratified into 4 ranges: 100% to 90% unenhanced area of targeting area, 90% to 50%, within 50%, and no change. RESULTS: High-intensity focused ultrasound treatment was performed without severe adverse event in 46 patients, 49 times (male-female = 25:21; mean age, 60.7 ± 10.0; TNM stage 3-stage 4 = 18:28). Average size of the PC lesion was 4.2 ± 1.4 cm (1.6-9.3 cm). After HIFU treatment, ablating tumor volume was as follows: 90% to 100% in 38 lesions, 90% to 50% in 8, and within 50% in 3. Overall median survival (S1) from initial PC diagnosis was 12.4 months. Overall survival (S2) rates at 6, 12, and 18 months from HIFU were 52.2%, 30.4%, and 21.79%, respectively, with a median survival of 7.0 months CONCLUSIONS: High-intensity focused ultrasound is safe and effective, which induced excellent local tumor control in most patients with advanced PC.

Oltipraz therapy in patients with liver fibrosis or cirrhosis: a randomized, double-blind, placebo-controlled phase II trial.

OBJECTIVES: Oltipraz, a cancer chemopreventive agent, has an anticirrhotic effect in animals. A phase II trial was designed to investigate the preliminary efficacy of oltipraz therapy in liver fibrosis or cirrhosis. METHOD: Of 83 patients who were randomized to receive placebo, oltipraz 60 mg bid or oltipraz 90 mg qd for 24 weeks, 68 completed the study without any major protocol violation. Pre- and post-treatment liver biopsies, and blood fibrosis markers were assessed. KEY FINDINGS: Twenty-four weeks of oltipraz treatment showed no significant differences in the proportions of patients showing an improvement in histological outcomes, including Ishak fibrosis score. In the oltipraz 60 mg bid group, there was a trend of decreases in hepatic collagen area and plasma transforming growth factor-ß1 (TGF-ß1, a blood fibrosis marker) levels from baseline to week 24. In the per-protocol population (n = 68), decreases in plasma TGF-ß1 correlated with those in the Ishak fibrosis score, suggesting that circulating TGF-ß1 serves a possible indicator for fibrosis treatment. CONCLUSIONS: No significant differences in liver histological outcomes were seen among the three treatment groups in this 24-week pilot study. Our finding indicates an association between TGF-ß1 repression and improvement in the histological index of fibrosis.

High-intensity focused ultrasound ablation in hepatic and pancreatic cancer: complications.

PURPOSE: To evaluate the complications of high-intensity focused ultrasound (HIFU) in patients with hepatic and pancreatic cancer. MATERIALS AND METHODS: From January 2006 to December 2008, 133 sessions of HIFU treatment were performed in 114 consecutive patients with primary hepatic tumor (n = 57), hepatic metastasis (n = 22), and pancreatic cancer (n = 35) under general anesthesia. The extracorporeal, ultrasound-guided Model-JC system (HAIFU, Chongqing, China) was used. Artificial pleural effusion was created to obtain an adequate sonographic window for ablating hepatic dome masses in 53 patients. We reviewed medical records and imaging findings before, during, and after HIFU. RESULTS: All patients had skin redness, edema, and pain in the treatment regions. All hepatic tumor patients had necrosis of the ribs along the main ultrasound beam path that did not require further treatment. Major complications included biliary obstruction, symptomatic pleural effusion, pneumothorax and fistula formation between an abdominal wall abscess and the ablated hepatic tumor. In 35 pancreatic cancer patients, major complications included third-degree burns and fistula formation between the tumor and duodenum. Delayed complications in hepatic tumor patients included a diaphragmatic rupture and rib fractures along the ultrasound pathway. CONCLUSION: The complications of HIFU develop mainly around the targeted lesions or along the ultrasound beam pathway. It is essential to have awareness of the possible complications related to HIFU and its imaging features for to avoiding serious complications.

Clevudine-induced viral response, associated with continued reduction of HBsAg titer, was durable after the withdrawal of therapy.

BACKGROUND: This study was conducted to evaluate the durability of clevudine-induced viral response after the withdrawal of treatment. METHODS: Patients who showed a complete response [alanine aminotransferase (ALT) normalization and hepatitis B virus (HBV) DNA <4,700 copies/mL for hepatitis B envelope antigen (HBeAg)-negative patients; ALT normalization, HBV DNA <4,700 copies/mL, and HBeAg seroconversion for HBeAg-positive patients] in the previous clevudine phase III trials were followed for an additional 96 weeks without any treatment for hepatitis B. RESULTS: Of the 63 patients in the study cohort, 73% and 35% of the patients had HBV DNA <141,500 and <4,700 copies/mL, respectively, and 75% of the patients had normal ALT at the end of follow-up. HBeAg seroconversion was maintained in 81% of the patients and hepatitis B surface antigen (HBsAg) loss occurred in 3 patients. Continued HBsAg titer decrease (-0.5 log IU/mL) was observed in the sustained viral responders, suggesting the reduction of covalently closed circular DNA in hepatocytes. CONCLUSIONS: The clevudine-induced viral response was durable in the majority of patients for 2 years after the withdrawal of treatment.

Sustained low hepatitis B viral load predicts good outcome after curative resection in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Little is known about the role of hepatitis B virus (HBV) factors in the long-term prognosis of hepatocellular carcinoma (HCC) after resection. The objective of the present study was to identify the changing patterns of HBV levels and its effect on outcome after resection. METHODS: This study recruited 188 patients with HBV-related HCC who underwent curative resection. Among the 188 patients, 115 were alive without recurrence at 12 months, and had serial measurements of viral levels. RESULTS: The mean age was 53 years and the mean follow-up period was 48.5 months. With multivariate analysis, tumor size > 5 cm (P = 0.047), Child-Pugh class B (P = 0.017), vascular invasion (P = 0.028), and HBV DNA > 10(4) copies/mL at the time of resection (P = 0.003) were independently predictive of HCC recurrence for the entire population. For the 115 patients with serial measurements of viral levels, tumor size > 5 cm, HBV DNA > 10(4) copies/mL at resection, and the absence of sustained HBV DNA level < 10(4) copies/mL, the presence of cirrhosis, and elevated aminotransferase levels (> 40 IU/L) were marginally or significantly associated with HCC recurrence and overall survival. However, on multivariate analysis, sustained HBV DNA level < 10(4) copies/mL was the only factor for both low recurrence (P = 0.002; odds ratio [OR] 3.13; 95% confidence interval [CI] 1.55-6.35) and longer survival (P = 0.002; OR 3.76; 95% CI 1.61-8.78). CONCLUSIONS: A high HBV replication state is among the most important predictors of adverse outcome after resection of HBV-related HCC. The sustained suppression of HBV below 10(4) copies/mL is a strong protective factor for long-term recurrence-free and overall survival.

A case of spontaneous regression of advanced gastric cancer.

An 84 yr-old male with a history of nausea and vomiting for 3 weeks was admitted to our hospital. Esopahgogastroduodenoscopy showed the diffuse infiltrative type of gastric cancer encircling from the cardia to the lower body. On abdominal computerized tomography, the gastric wall was diffusely thickened with overlying mucosal enhancement without lymph node involvement. Histologic examination revealed poorly differentiated adenocarcinoma. So surgical resection was planned. However, patient refused all medical care, and then he was discharged. He lived without any medical support and then he revisited our hospital and showed relieved symptoms on the follow-up exam. On esophagogastroduodenoscopy, the gastric mucosa of the body looked normal without any dysplastic change. Abdominal CT revealed a decreased thickening of the gastric wall of the body. The histology from the endoscopic forceps biopsy showed no evidence of malignancy. The patient is alive without any sign of tumor recurrence after 14 months.

[Remission of ulcerative colitis after appendectomy: a case report].

The inverse correlation of appendectomy and ulcerative colitis is well known, but the effect of appendectomy on the clinical course of ulcerative colitis remains unclear. Although the majority of opinions were negative for the therapeutic advantage of appendectomy in patients with ulcerative colitis, advocates for positive effect of appendectomy have been proposed in a few case reports and a prospective study from Western countries. We herein report a case of ulcerative colitis who experienced clinical remission after appendectomy for acute appendicitis. The patient was 35 year old male and had been managed with immunosuppressant before appendectomy. The very acute change in clinical course and a long period of remission after appendectomy highly suggest the therapeutic effect of appendectomy for ulcerative colitis.

Vascular injury associated with blunt trauma without dislocation of the knee.

Failure to recognize popliteal artery injury and restore vessel continuity of flow after blunt trauma is a major cause of lower extremity amputation and morbidity. A high index of suspicion and early recognition of the injury are paramount for limb salvage. We experienced a rare case of poplitial artery occlusion with the presence of arterial pulses due to collateral circulation after blunt trauma. Expeditious revascularization was achieved by using posterior approach, allowing two surgical teams to work simultaneously. This case illustrates that, even in the absence of knee dislocation, surgeons must always consider the possibility of a popliteal artery damage whenever a blunt trauma near the knee.

Revision total knee arthroplasty with a cemented posterior stabilized, condylar constrained or fully constrained prosthesis: a minimum 2-year follow-up analysis.

BACKGROUND: The clinical and radiological outcomes of revision total knee arthroplasty with a cemented posterior stabilized (PS), condylar constrained knee (CCK) or a fully constrained rotating hinge knee (RHK) prosthesis were evaluated. METHODS: This study reviewed the clinical and radiological results of 36 revision total knee arthroplasties with a cemented PS, CCK, and RHK prosthesis in 8, 25, and 13 cases, respectively, performed between 1998 and 2006. The mean follow-up period was 30 months (range, 24 to 100 months). The reason for the revision was aseptic loosening of one or both components in 15, an infected total knee in 18 and a periprosthetic fracture in 3 knees. The average age of the patients at the time of the revision was 65 years (range, 58 to 83 years). The original diagnosis for all primary total knee arthroplasties was osteoarthritis except for one case of a Charcot joint. All revision prostheses were fixed with cement. The bone deficiencies were grafted with a cancellous allograft in the contained defect and cortical allograft fixed with a plate and screws in the noncontained defect. A medial gastrocnemius flap was needed to cover the wound dehiscence in 6 of the 18 infected cases. RESULTS: The mean Knee Society knee score improved from 28 (range, 5 to 43) to 83 (range, 55 to 94), (p < 0.001) and the mean Knee Society function score improved from 42 (range, 10 to 66) to 82 (range, 60 to 95), (p < 0.001) at the final follow-up. Good or excellent outcomes were obtained in 82% of knees. There were 5 complications (an extensor mechanism rupture in 3 and recurrence of infection in 2 cases). Three cases of an extensor mechanism defect (two ruptures of ligamentum patellae and one patellectomy) were managed by the RHK prosthesis to provide locking stability in the heel strike and push off phases, and two cases of recurrent infection used an antibiotic impregnated cement spacer. The radiological tibiofemoral alignment improved from 1.7 degrees varus to 3.0 degrees valgus in average. Radiolucent lines were observed in 18% of the knees without progressive osteolysis. CONCLUSIONS: Revision total knee requires a more constrained prosthesis than primary total knee arthroplasty because of the ligamentous instability and bony defect. This short to midterm follow-up analysis demonstrated that a well planned and precisely executed revision can reduce pain and improve the knee function significantly. Infected cases showed as good a result as those with aseptic loosening through the use of antibiotics-impregnated cement beads and proper soft tissue coverage with a medial gastrocnemius flap.

Antiapoptotic effects of anthocyanins on rotator cuff tenofibroblasts.

Degeneration of the rotator cuff tendon, which involves apoptosis of the tenofibroblasts, is one of the most common shoulder problems that can lead eventually to a full-thickness rotator cuff tendon tear. The current authors evaluated both the ability of anthocyanins, which are powerful antioxidants, to reduce apoptosis in oxidation-stressed rotator cuff tenofibroblasts, and the molecular mechanism for this antiapoptotic action. Anthocyanins demonstrated a dose-dependent ability to inhibit H(2)O(2)-induced apoptosis in cultured tenofibroblasts, as assessed by MTT assay and FACS analysis. H(2)O(2) increased the phosphorylation of extracellular regulated kinase1/2 (ERK1/2) and of c-Jun N-terminal kinase (JNK) and the production of reactive oxygen species (ROS). In contrast, treatment with anthocyanins decreased this activation of ERK1/2 and JNK, as confirmed by Western blot analysis, and reduced the production of ROS, as verified by fluorescent microscopic and FACS analyses. These findings suggest that anthocyanins, by suppressing JNK, ERK1/2, and intracellular ROS production, have a concentration-dependent antiapoptotic effect on rotator cuff tenofibroblasts exposed to an oxidative stressor, and may have therapeutic potential.