Spontaneous and serial rupture of both Achilles tendons associated with secondary hyperparathyroidism in a patient receiving long-term hemodialysis

The spontaneous and serial rupture of the bilateral Achilles tendons without history of significant trauma is an uncommon complication in long-term hemodialysis (HD) patients. The majority of these patients have additional predisposing factors, such as previous use of fluoroquinolone antibiotics or corticosteroids. In general, this condition is associated with a coexisting systemic disease, including chronic kidney disease (CKD), secondary hyperparathyroidism, systemic lupus erythematosus (SLE), and diabetes mellitus (DM). Here, we report a 46-year-old man who had been undergoing regular HD for 11 years. He developed a spontaneous and consecutive rupture of both Achilles tendons. Based on previous reports of tendon ruptures in uremic patients and on the patient’s lack of corticosteroid or fluoroquinolone use, we believe that secondary hyperparathyroidism was the predisposing factor in this patient. The mechanism seems to be related to a high parathyroid hormone (PTH) level, which results in osteolytic bone resorption at the tendon insertion site. Treatment and prevention of such tendon ruptures include early surgical repair and control of secondary hyperparathyroidism, by use of vitamin D analogs, and total parathyroidectomy, with or without autotransplantation of a parathyroid gland.     

Elevated frequency and function of regulatory T cells in patients with active chronic hepatitis C

Background

Regulatory T cells (Tregs) play a pivotal role in the persistence of hepatitis C virus infection. The aim of this study was to evaluate the frequency and function of Tregs in patients with chronic hepatitis C (CHC).

Methods

We enrolled 44 CHC patients with elevated alanine aminotransferase (ALT) levels (CH group), 13 CHC patients with persistent normal ALT levels (PNALT group), and 14 age-matched healthy subjects (HS group; controls). Tregs were identified as CD4+, CD25+, and forkhead box P3 (Foxp3)+ T lymphocytes, using three-color fluorescence-activated cell sorting (FACS). The frequency of Tregs was determined by calculating the percentage of CD4+CD25^high T cells among CD4 T cells. CD127 and CD45RA were also analyzed for subsets of Tregs. The levels of serum transforming growth factor (TGF)-β and interleukin (IL)-10 in immunosuppressive assays were detected by enzyme-linked immunosorbent assay (ELISA). The immunosuppressive abilities of Tregs were evaluated by measuring their ability to inhibit the proliferation of effector cells.

Results

Higher proportions of Tregs were found in the CH and PNALT groups compared with the HS group. The populations of CD127 low/negative and CD45RA negative cells were higher in the CH group than in the PNALT group. The expressions of IL-10 and TGF-β in the CH and PNALT groups were significantly higher than those in the HS group. In addition, the immunosuppressive ability of Tregs from the CH group was increased relative to that in the PNALT and the HS group.

Conclusions

CHC patients, irrespective of liver function, had higher frequencies of Tregs than healthy subjects; however, only CHC patients with inflammation showed enhanced immunosuppressive function of Tregs.     

Impact of recurrent lupus nephritis on lupus kidney transplantation

This study was conducted to delineate the frequency of recurrent lupus nephritis in a Chinese kidney transplant cohort and to estimate its impact on long-term transplant outcomes. A total of 32 lupus transplant patients were enrolled in this study, and the medical records were retrospectively reviewed. Patients with unexplained graft abnormalities were subjected to allograft biopsy. Recurrent lupus nephritis was diagnosed by light microscopy, immunofluorescence, and electron microscopy. In addition, to determine the clinical manifestations of recurrent lupus GN in these patients, serum original systemic lupus erythematosus disease activity index (SLEDAI) scores while undergoing allograft biopsy were evaluated. In total, six out of 32 patients (18.8%; mean age, 40.5 ± 9.1 years) were diagnosed as having recurrent lupus nephritis and the mean time at diagnosis was 5.1 ± 4.9 years post-transplantation. According to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 criteria, three of the six cases (50%) were defined as class I, one was class II, one was class IV, and one was class III + V. The graft and patient survival rates of recurrent lupus nephritis (n = 6) were not different from those of patients with other diagnostic entities. Although recurrent lupus nephritis was not uncommon, it did not appear to have a strong negative impact on long-term outcome in Chinese kidney transplant patients. The recurrence was potentially treatable and should not be precluded for receiving transplantation.     

Resistance of Helicobacter pylori strains to antibiotics in Korea with a focus on fluoroquinolone resistance

Background and Aim: New regimens, including those with new fluoroquinolones, have been developed to overcome the antibiotic resistance of Helicobacter pylori. We aimed to assess the antibiotic resistance rates, as well as the molecular mechanisms of fluoroquinolone resistance, of the clinical isolates obtained in Korea. Methods: The minimal inhibitory concentration (MIC) values of ciprofloxacin, amoxicillin, clarithromycin, metronidazole and tetracycline were determined by the agar dilution method for 185 treatment‐naïve Helicobacter pylori isolates. The resistant strains were evaluated for the presence of point mutations in the quinolone resistance‐determining region (QRDR) of the gyrA and gyrB genes by direct nucleotide sequencing. Results: Twenty‐nine (29/185, 15.7%) of the strains were found to be resistant to ciprofloxacin. The resistance rates to amoxicillin, clarithromycin, metronidazole and tetracycline were 2.2% (four of 185), 10.8% (20 of 185), 30.3% (56 of 185) and 0.5% (one of 185), respectively. The most common mutations in the H. pylori gyrA gene were found at codons corresponding to Asp87 (16/29, 55.2%) and Asn91 (10/29, 34.5%). Conclusions: Primary H. pylori resistance to ciprofloxacin occurred at a high frequency. The fluoroquinolone resistance is most likely mediated through amino acid point mutation in the gyrA gene at Asn87 and Asp91.     

A Case of Acute Thrombotic Occlusion of an Anomalous Origin of the Right Coronary Artery From the Left Coronary Sinus: Focus on the Importance of Dual-Source Computed Tomography for Failed Emergency Coronary Angiography

Coronary artery anomalies in patients undergoing coronary angiography are often technically challenging for invasive cardiologists and may delay revascularization time. We report a patient who underwent successful bailout revascularization using dual-source computed tomography after failed emergency angiography. This case emphasizes the utility of dual-source computed tomography, especially in an urgent clinical setting, for allowing interventional cardiologists to rapidly identify and effectively treat the aberrant coronary artery.     

Pilot study on combination of azacitidine and low-dose cytarabine for patients with refractory anemia with excess blast

This study analyzed the outcomes of the combination of azacitidine and low-dose cytarabine in patients newly diagnosed with refractory anemia with excess blast (RAEB). Patients were treated with azacitidine 75 mg/m² for 7 days subcutaneously and cytarabine 20 mg/m² intravenously for 7 days every 28 days. The assigned regimen was repeated for two cycles, then the patients treated with azacytidine alone until progression or allogeneic stem cell transplantation (allo-SCT). Eighteen patients with 5 RAEB-1 and 13 RAEB-2 were enrolled in the current study. After two cycles of the combination therapy, responses were achieved in nine patients (50.0%): four complete response (CR) (22.2%), one partial response (5.6%), two marrow-CR (11.1%), and two hematologic improvement (11.1%). Four patients (22.2%) progressed to acute leukemia during two cycles of the combination therapy. The 1-year overall survival (OS) was 87.5% for the early response group (responses at two cycles) and 0% for the late response group (responses at four cycles, p = 0.042). Plus, the median survival time was 476 days (range, 37–718 days) for the early response group and 221 days (range, 193–249 days) for the late response group. The 1-year OS was 100% for the patients who underwent allo-SCT and 73.4% for those without allo-SCT. In summary, the combination therapy showed promising response rate when compared to treatment with azacitidine alone. However, it was limited in terms of preventing leukemic transformation. Allo-SCT would seem to be the only available treatment that can alter disease progression.     

8-Hydroxydeoxyguanosine: not mere biomarker for oxidative stress, but remedy for oxidative stress-implicated gastrointestinal diseases

Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine (8-OHdG),which can bind to thymidine rather than cytosine,based on which,the level of 8-OHdG is gen-erally regarded as a biomarker of mutagenesis conse-quent to oxidative stress.For example,higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer.However,we have found that exogenous 8-OHdG can paradoxically reduce ROS production,attenuate thenuclear factor-κB signaling pathway,and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1,IL-6,cyclo-oxygenase-2,and induc-ible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1,NOX organizer-1 and NOX activator-1 in vari-ous conditions of inflammation-based gastrointestinal (GI) diseases including gastritis,inflammatory bowel disease,pancreatitis,and even colitis-associated carci-nogenesis.Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases,as well as the pre-vention of inflammation-associated GI cancer.In this editorial review,the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.     

Diffusion-weighted imaging of biliopancreatic disorders: correlation with conventional magnetic resonance imaging

Diffusion-weighted magnetic resonance imaging (DWI) is a well established method for the evaluation of intracranial diseases, such as acute stroke. DWI for extracranial application is more difficult due to physiological motion artifacts and the heterogeneous composition of the organs. However, thanks to the newer technical development of DWI, DWI has become increasingly used over the past few years in extracranial organs including the abdomen and pelvis. Most previous studies of DWI have been limited to the evaluation of diffuse parenchymal abnormalities and focal lesions in abdominal organs, whereas there are few studies about DWI for the evaluation of the biliopancreatic tract. Although further studies are needed to determine its performance in evaluating bile duct, gallbladder and pancreas diseases, DWI has potential in the assessment of the functional information on the biliopancreatic tract concerning the status of tissue cellularity, because increased cellularity is associated with impeded diffusion, as indicated by a reduction in the apparent diffusion coefficient. The detection of malignant lesions and their differentiation from benign tumor-like lesions in the biliopancreatic tract could be improved using DWI in conjunction with findings obtained with conventional magnetic resonance cholagiopancreatography. Additionally, DWI can be useful for the assessment of the biliopancreatic tract in patients with renal impairment because contrast-enhanced computed tomography or magnetic resonance scans should be avoided in these patients.     

Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer

AIM: To investigate M2 isoform of pyruvate kinase (PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS: All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment. Clinical and pathological information were obtained from the medical records. Gene expression microarray data from 60 cancer and 19 non-cancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA. Tissue microarrays were constructed from 368 gastric cancer patients. Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity. Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.RESULTS: PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients (log transformed expression level: 7.6 ± 0.65 vs 6.3 ± 0.51, P < 0.001). Moreover, differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers (log transformed expression level: 7.8 ± 0.70 vs 6.7 ± 0.71, P < 0.001). PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368 (39.1%) human gastric cancer cases. PKM2 expression was not related with stage (P = 0.811), but strongly correlated with gastric cancer differentiation (P < 0.001). Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones. Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells; in contrast, signet-ring cell cancers showed only 17.7% PKM2-positive cells. Importantly, PKM2 expression was correlated with shorter overall survival (P < 0.05) independent of stage only in signet-ring cell cancers.CONCLUSION: PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas. Its function and potential as a prognostic marker should be further verified in gastric cancer.     

Effects of vagus nerve preservation and vagotomy on peptide YY and body weight after subtotal gastrectomy

AIM: To investigate the relationship between the function of vagus nerve and peptide YY_3-36 and ghrelin levels after subtotal gastrectomy.METHODS: We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY_3-36, ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.RESULTS: Vagus nerve preservation group showed less body weight loss and less increase of peptide YY_3-36 compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY_3-36 level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].CONCLUSION: Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY_3-36.