Common and Distinct Clinical Features in Adult Patients with Anti-Aminoacyl-tRNA Synthetase Antibodies: Heterogeneity within the Syndrome

Objective

To identify similarities and differences in the clinical features of adult Japanese patients with individual anti-aminoacyl-tRNA synthetase antibodies (anti-ARS Abs).

Methods

This was a retrospective analysis of 166 adult Japanese patients with anti-ARS Abs detected by immunoprecipitation assays. These patients had visited Kanazawa University Hospital or collaborating medical centers from 2003 to 2009.

Results

Anti-ARS Ab specificity included anti-Jo-1 (36%), anti-EJ (23%), anti-PL-7 (18%), anti-PL-12 (11%), anti-KS (8%), and anti-OJ (5%). These anti-ARS Abs were mutually exclusive, except for one serum Ab that had both anti-PL-7 and PL-12 reactivity. Myositis was closely associated with anti-Jo-1, anti-EJ, and anti-PL-7, while interstitial lung disease (ILD) was correlated with all 6 anti-ARS Abs. Dermatomyositis (DM)-specific skin manifestations (heliotrope rash and Gottron’s sign) were frequently observed in patients with anti-Jo-1, anti-EJ, anti-PL-7, and anti-PL-12. Therefore, most clinical diagnoses were polymyositis or DM for anti-Jo-1, anti-EJ, and anti-PL-7; clinically amyopathic DM or ILD for anti-PL-12; and ILD for anti-KS and anti-OJ. Patients with anti-Jo-1, anti-EJ, and anti-PL-7 developed myositis later if they had ILD alone at the time of disease onset, and most patients with anti-ARS Abs eventually developed ILD if they did not have ILD at disease onset.

Conclusion

Patients with anti-ARS Abs are relatively homogeneous. However, the distribution and timing of myositis, ILD, and rashes differ among patients with individual anti-ARS Abs. Thus, identification of individual anti-ARS Abs is beneficial to define this rather homogeneous subset and to predict clinical outcomes within the “anti-synthetase syndrome.”     

Thrombophilia Associated with Anti-DFS70 Autoantibodies

Context

Anti-DFS70 antibodies are the most frequent antinuclear antibodies (ANA) found in healthy individuals. We assessed the clinical significance of the presence of anti-DFS70 antibodies.

Methods

We defined a group of patients (n = 421) with anti-DFS70 antibodies and a group of patients (n = 63) with a history of idiopathic arterial and/or venous thrombotic disease and/or obstetric complication (i.e. ≥3 miscarriages, fetal death or premature birth with eclampsia). Anti-DFS70 antibodies prevalence was also assessed in a cohort of 300 healthy blood donors.

Results

The prevalence of thrombotic disease and/or obstetric complication in the 421 patients with anti-DFS70 antibodies was 13.1% (n = 55) and the prevalence of connective tissue disease was 19% (n = 80). Among the 63 patients with a history of thrombosis and/or obstetric complications, 7 (11.1%) had anti-DFS70 antibodies and among the latter, 5 had no common thrombophilic factor. In contrast, the prevalence of anti-DFS70 antibodies was of 3.0% (9 out of 300) in healthy donors. Finally, the Activated Partial Thromboplastin Time (aPTT) ratio of patients with a history of thrombosis and anti-DFS70 antibodies was lower than the aPTT ratio of other patients, suggesting that thrombotic patients with anti-DFS70 antibodies may have a hypercoagulable state.

Conclusion

We described here for the first time an immune procoagulant state involving anti-DFS70 antibodies.     

Novel Humoral Prognostic Markers in Small-Cell Lung Carcinoma: A Prospective Study

Purpose

Favourable small cell lung carcinoma (SCLC) survival outcomes have been reported in patients with paraneoplastic neurological disorders (PNDs) associated with neuronal antibodies (Neur-Abs), but the presence of a PND might have expedited diagnosis. Our aim was to establish whether neuronal antibodies, independent of clinical neurological features, correlate with SCLC survival.

Experimental Design

262 consecutive SCLC patients were examined: of these, 24 with neurological disease were excluded from this study. The remaining 238 were tested for a broad array of Neur-Abs at the time of cancer diagnosis; survival time was established from follow-up clinical data.

Results

Median survival of the non-PND cohort (n = 238) was 9.5 months. 103 patients (43%) had one or more antigen-defined Neur-Abs. We found significantly longer median survival in 23 patients (10%) with HuD/anti-neuronal nuclear antibody type 1 (ANNA-1, 13.0 months P = 0.037), but not with any of the other antigen-defined antibodies, including the PND-related SOX2 (n = 56, 24%). An additional 28 patients (12%) had uncharacterised anti-neuronal nuclear antibodies (ANNA-U); their median survival time was longer still (15.0 months, P = 0.0048), contrasting with the survival time in patients with non-neuronal anti-nuclear antibodies (detected using HEp-2 cells, n = 23 (10%), 9.25 months). In multivariate analyses, both ANNA-1 and ANNA-U independently reduced the mortality hazard by a ratio of 0.532 (P = 0.01) and 0.430 (P<0.001) respectively.

Conclusions

ANNAs, including the newly described ANNA-U, may be key components of the SCLC immunome and have a potential role in predicting SCLC survival; screening for them could add prognostic value that is similar in magnitude to that of limited staging at diagnosis.     

The Potential for a Blood Test for Scabies

Background

Scabies afflicts millions of people worldwide, but it is very difficult to diagnose by the usual skin scrape test, and a presumptive diagnosis is often made based on clinical signs such as rash and intense itch. A sensitive and specific blood test to detect scabies would allow a physician to quickly make a correct diagnosis.

Objective

Our objective was to profile the mite-specific antibodies present in the sera of patients with ordinary scabies.

Methods

Sera of 91 patients were screened for Ig, IgD, IgE, IgG and IgM antibodies to S. scabiei, as well as to the house dust mites Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei.

Results

45%, 27% and 2.2% of the patients had measurable amounts of mixed Ig, IgG and IgE that recognized scabies mite antigens. However, 73.6% of the scabies patients had serum IgM that recognized scabies proteins, and all except two of them also had IgM that recognized all of the three species of dust mites. No patient had serum antibody exclusively reactive to scabies mite antigens.

Conclusions

Co-sensitization or cross-reactivity between antigens from scabies and house dust mites confounds developing a blood test for scabies.     

Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population

Background/Aims

Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti-gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies.

Methodology/Principal Findings

Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for HLA-A, B, DRB1, and DQB1 loci. Anti-gAChR antibodies in the sera form AIH patients were measured using the luciferase immunoprecipitation system, and examined allelic association in patients with or without anti-gAChR antibodies.

Methodology/ Methods

We detected anti-α3 or -β4 gAChR antibodies in 11.5% (30/260) of patients with AIH. Among AIH patients there was no significant association between HLA-A, B DQB1 alleles and the positivity for anti-gAChR antibodies. Whereas the HLA-DRB1*0403 allele showed a significantly increased frequency in AIH patients with anti-gAChR antibodies compared with those without anti-gAChR antibodies.

Conclusions/Significance

The frequency of the HLA-DRB1*0403 allele differed among Japanese patients with AIH according to the presence or absence of anti-gAChR antibodies. Our findings suggest that particular HLA class II molecules might control the development of anti-gAChR antibodies in the autoimmune response to gAChR.     

Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy

Background

Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC.

Methods

Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS).

Results

41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib.

Conclusions

The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients.

Trial Registration

ClinicalTrials.gov NCT02430974     

Ambient Fine Particulate Matter Suppresses In Vivo Proliferation of Bone Marrow Stem Cells through Reactive Oxygen Species Formation

Aims

Some environmental insults, such as fine particulate matter (PM) exposure, significantly impair the function of stem cells. However, it is unknown if PM exposure could affect the population of bone marrow stem cells (BMSCs). The present study was to investigate the effects of PM on BMSCs population and related mechanism(s).

Main Metheods

PM was intranasally distilled into male C57BL/6 mice for one month. Flow cytometry with antibodies for BMSCs, Annexin V and BrdU ware used to determine the number of BMSCs and the levels of their apoptosis and proliferation in vivo. Phosphorylated Akt (P-Akt) level was determined in the BM cells with western blotting. Intracellular reactive oxygen species (ROS) formation was quantified using flow cytometry analysis. To determine the role of PM-induced ROS in BMSCs population, proliferation, and apotosis, experiments were repeated using N-acetylcysteine (NAC)-treated wild type mice or a triple transgenic mouse line with overexpression of antioxidant network (AON) composed of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase-1 with decreased in vivo ROS production.

Key Findings

PM treatment significantly reduced BMSCs population in association with increased ROS formation, decreased P-Akt level, and inhibition of proliferation of BMSCs without induction of apoptosis. NAC treatment or AON overexpression with reduced ROS formation effectively prevented PM-induced reduction of BMSCs population and proliferation with partial recovery of P-Akt level.

Significance

PM exposure significantly decreased the population of BMSCs due to diminished proliferation via ROS-mediated mechanism (could be partially via inhibition of Akt signaling).     

Experience Sampling-Based Personalized Feedback and Positive Affect: A Randomized Controlled Trial in Depressed Patients

Objectives

Positive affect (PA) plays a crucial role in the development, course, and recovery of depression. Recently, we showed that a therapeutic application of the experience sampling method (ESM), consisting of feedback focusing on PA in daily life, was associated with a decrease in depressive symptoms. The present study investigated whether the experience of PA increased during the course of this intervention.

Design

Multicentre parallel randomized controlled trial. An electronic random sequence generator was used to allocate treatments.

Settings

University, two local mental health care institutions, one local hospital.

Participants

102 pharmacologically treated outpatients with a DSM-IV diagnosis of major depressive disorder, randomized over three treatment arms.

Intervention

Six weeks of ESM self-monitoring combined with weekly PA-focused feedback sessions (experimental group); six weeks of ESM self-monitoring combined with six weekly sessions without feedback (pseudo-experimental group); or treatment as usual (control group).

Main outcome

The interaction between treatment allocation and time in predicting positive and negative affect (NA) was investigated in multilevel regression models.

Results

102 patients were randomized (mean age 48.0, SD 10.2) of which 81 finished the entire study protocol. All 102 patients were included in the analyses. The experimental group did not show a significant larger increase in momentary PA during or shortly after the intervention compared to the pseudo-experimental or control groups (χ² (2) =0.33, p=.846). The pseudo-experimental group showed a larger decrease in NA compared to the control group (χ² (1) =6.29, p=.012).

Conclusion

PA-focused feedback did not significantly impact daily life PA during or shortly after the intervention. As the previously reported reduction in depressive symptoms associated with the feedback unveiled itself only after weeks, it is conceivable that the effects on daily life PA also evolve slowly and therefore were not captured by the experience sampling procedure immediately after treatment.

Trial Registration

Trialregister.nl/trialreg/index.asp. NTR1974     

Assessment of a Standardized Pre-Operative Telephone Checklist Designed to Avoid Late Cancellation of Ambulatory Surgery: The AMBUPROG Multicenter Randomized Controlled Trial

Objectives

To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial).

Design

Multicenter, two-arm, parallel-group, open-label randomized controlled trial.

Setting

11 university hospital ambulatory surgery units in Paris, France.

Participants

Patients scheduled for ambulatory surgery and able to be reached by telephone.

Intervention

A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults), was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone.

Main Outcome Measures

Rate of cancellation on the day of surgery or the day before.

Results

The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6%) vs. 113 (5.8%), adjusted odds ratio [95% confidence interval] = 0.91 [0.65–1.29], (p = 0.57)). Checklist administration revealed that 355 patients (28.0%) had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0%) still had questions concerning the fasting state.

Conclusions

A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01732159","term_id":"NCT01732159"}}NCT01732159     

Identification of Bacteriology and Risk Factor Analysis of Asymptomatic Bacterial Colonization in Pacemaker Replacement Patients

Background

Recent researches revealed that asymptomatic bacterial colonization on PMs might be ubiquitous and increase the risk of clinical PM infection. Early diagnosis of patients with asymptomatic bacterial colonization could provide opportunity for targeted preventive measures.

Objective

The present study explores the incidence of bacterial colonization of generator pockets in pacemaker replacement patients without signs of infection, and to analyze risk factors for asymptomatic bacterial colonization.

Methods

From June 2011 to December 2013, 118 patients underwent pacemaker replacement or upgrade. Identification of bacteria was carried out by bacterial culture and 16S rRNA sequencing. Clinical risk characteristics were analyzed.

Results

The total bacterial positive rate was 37.3% (44 cases), and the coagulase-negative Staphylococcus aureus detection rate was the highest. Twenty two (18.6%) patients had positive bacterial culture results, of which 50% had coagulase-negative staphylococcus. The bacterial DNA detection rate was 36.4 % (43 cases). Positive bacterial DNA results from pocket tissues and the surface of the devices were 22.0% and 29.7%, respectively. During follow-up (median, 27.0 months), three patients (6.8%, 3/44) became symptomatic with the same genus of microorganism, S. aureus (n=2) and S. epidermidis (n=1). Multivariable logistic regression analysis showed that history of bacterial infection, use of antibiotics, application of antiplatelet drugs, replacement frequency were independent risk factors for asymptomatic bacterial colonization.

Conclusion

There was a high incidence of asymptomatic bacterial colonization in pacemaker patients with independent risk factors. Bacterial culture combined genetic testing could improve the detection rate.     

Efficacy of a Community-Based Physical Activity Program KM2H2 for Stroke and Heart Attack Prevention among Senior Hypertensive Patients: A Cluster Randomized Controlled Phase-II Trial

Objective

To evaluate the efficacy of the program Keep Moving toward Healthy Heart and Healthy Brain (KM2H²) in encouraging physical activities for the prevention of heart attack and stroke among hypertensive patients enrolled in the Community-Based Hypertension Control Program (CBHCP).

Design

Cluster randomized controlled trial with three waves of longitudinal assessments at baseline, 3 and 6 months post intervention.

Setting

Community-based and patient-centered self-care for behavioral intervention in urban settings of China.

Participants

A total of 450 participants diagnosed with hypertension from 12 community health centers in Wuhan, China were recruited, and were randomly assigned by center to receive either KM2H² plus standard CBHCP care (6 centers and 232 patients) or the standard care only (6 centers and 218 patients).

Intervention

KM2H² is a behavioral intervention guided by the Transtheoretical Model, the Model of Personalized Medicine and Social Capital Theory. It consists of six intervention sessions and two booster sessions engineered in a progressive manner. The purpose is to motivate and maintain physical activities for the prevention of heart attack and stroke.

Outcome Measures

Heart attack and stroke (clinically diagnosed, primary outcome), blood pressure (measured, secondary outcome), and physical activity (self-report, tertiary outcome) were assessed at the individual level during the baseline, 3- and 6-month post-intervention.

Results

Relative to the standard care, receiving KM2H² was associated with significant reductions in the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs. 9.90%, p<0.05), and moderate reduction in blood pressure (-3.72mmHg in DBP and -2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95% CI: 0.04, 0.85) post-intervention, respectively.

Conclusion

The program KM2H² is efficacious to reduce the risk of heart attack and stroke among senior patients who are on anti-hypertensive medication. Findings of this study provide solid data supporting a formal phase-III trial to establish the effectiveness of KM2H² for use in community settings for prevention.

Trial Registration

ISRCTN Register ISRCTN12608966     

Adjunctive Aripiprazole Treatment for Risperidone-Induced Hyperprolactinemia: An 8-Week Randomized,Open-Label,Comparative Clinical Trial

Objective

The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia.

Methods

One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8.

Results

One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups.

Conclusions

Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia.

Trial Registration

chictr.org ChiCTR-IOR-15006278     

Post-Tooth Extraction Bacteraemia: A Randomized Clinical Trial on the Efficacy of Chlorhexidine Prophylaxis

Objectives

To investigate the development of post-extraction bacteraemia (PEB) after the prophylactic use of chlorhexidine (CHX).

Patients and Methods

A total of 201 patients who underwent a tooth extraction were randomly distributed into four groups: 52 received no prophylaxis (CONTROL), 50 did a mouthwash with 0.2% CHX before the tooth extraction (CHX-MW), 51 did a mouthwash with 0.2% CHX and a subgingival irrigation with 1% CHX (CHX-MW/SUB_IR) and 48 did a mouthwash with 0.2% CHX and a continuous supragingival irrigation with 1% CHX (CHX-MW/SUPRA_IR). Peripheral venous blood samples were collected at baseline, 30 seconds after performing the mouthwash and the subgingival or supragingival irrigation, and at 30 seconds and 15 minutes after completion of the tooth extraction. Blood samples were analysed applying conventional microbiological cultures under aerobic and anaerobic conditions performing bacterial identification of the isolates.

Results

The prevalences of PEB in the CONTROL, CHX-MW, CHX-MW/SUB_IR and CHX-MWSUPRA_IR groups were 52%, 50%, 55% and 50%, respectively, at 30 seconds and 23%, 4%, 10% and 27%, respectively, at 15 minutes. The prevalence of PEB at 15 minutes was significantly higher in the CONTROL group than in the CHX-MW group (23% versus 4%; p = 0.005). At the same time, no differences were found between CONTROL group and CHX-MW/SUB_IR or CHX-MW/SUPRA_IR groups. Streptococci (mostly viridans group streptococci) were the most frequently identified bacteria (69–79%).

Conclusions

Performing a 0.2% CHX mouthwash significantly reduces the duration of PEB. Subgingival irrigation with 1% CHX didn’t increase the efficacy of the mouthwash while supragingival irrigation even decreased this efficacy, probably due to the influence of these maneuvers on the onset of bacteraemia.

Clinical Relevance

These results confirm the suitability of performing a mouthwash with 0.2% CHX before tooth extractions in order to reduce the duration of PEB. This practice should perhaps be extended to all dental manipulations.

Trial Registration

Clinicaltrials.gov NCT02150031     

The Rate of Helicobacter pylori Seropositivity in a Group of Korean Patients with HLA-B27-Associated Acute Anterior Uveitis

Purpose

To investigate an association between Helicobacter pylori seropositivity and HLA-B27-positive acute anterior uveitis (AAU) in Korean patients.

Methods

Retrospective analysis was performed with data from 106 patients previously diagnosed with AAU without clinical evidence of spondyloarthropathy. Serum immunoglobulin G antibodies to H. pylori were measured by enzyme-linked immunosorbent assay, and HLA typing was performed using polymerase chain reaction of DNA amplification. We included 72 non-uveitis patients and 35 age- and sex-matched healthy controls in the study.

Results

Of the 106 patients with AAU, 41 (38.7%) were HLA-B27-positive, and 45 (42.5%) were seropositive for H. pylori. Patients with HLA-B27-positive AAU had a significantly lower prevalence of H. pylori seropositivity compared to those with HLA-B27-negative AAU and healthy controls (24.4% vs. 53.8%, p = 0.003; 24.4% vs. 57.1%, p = 0.004, respectively). In the non-uveitis group, however, HLA-B27-positive patients exhibited similar H. pylori seropositivity prevalence to HLA-B27-negative patients and healthy controls (45.5% vs. 55.7%, p = 0.529; 45.5% vs. 57.1%, p = 0.497, respectively). In multivariate analysis, a low prevalence of H. pylori seropositivity was significantly associated with HLA-B27-positive AAU (odds ratio = 0.340, 95% confidence interval 0.135–0.855, p = 0.022).

Conclusions

Our results suggest an inverse association between H. pylori seropositivity and HLA-B27-positive AAU. Further investigation of this association is needed, given the low prevalence of H. pylori seropositivity observed in patients with HLA-B27-positive AAU.     

Impact of Somatic Mutations in the D-Loop of Mitochondrial DNA on the Survival of Oral Squamous Cell Carcinoma Patients

Objectives

The aim of this study was to investigate somatic mutations in the D-loop of mitochondrial DNA (mtDNA) and their impact on survival in oral squamous cell carcinoma patients.

Materials and Methods

Surgical specimen confirmed by pathological examination and corresponding non-cancerous tissues were collected from 120 oral squamous cell carcinoma patients. The sequence in the D-loop of mtDNA from non-cancerous tissues was compared with that from paired cancer samples and any sequence differences were recognized as somatic mutations.

Results

Somatic mutations in the D-loop of mtDNA were identified in 75 (62.5%) oral squamous cell carcinoma patients and most of them occurred in the poly-C tract. Although there were no significant differences in demographic and tumor-related features between participants with and without somatic mutation, the mutation group had a better survival rate (5 year disease-specific survival rate: 64.0% vs. 43.0%, P = 0.0266).

Conclusion

Somatic mutation in D-loop of mtDNA was associated with a better survival in oral squamous cell carcinoma patients.     

The Influence of Phacoemulsification on Surgical Outcomes of Trabeculectomy with Mitomycin-C for Uveitic Glaucoma

Purpose

To evaluate the influence of phacoemulsification after trabeculectomy on the postoperative intraocular pressure (IOP) in eyes with uveitic glaucoma (UG).

Setting

Kumamoto University Hospital, Kumamoto, Japan.

Design

A retrospective cohort study.

Methods

The medical records of patients with UG who had trabeculectomy with mitomycin-C (MMC) were reviewed. Complete and qualified surgical failures were defined by an IOP of ≥21 mmHg (condition A), ≥18 mmHg (condition B), or ≥15 mmHg (condition C) without and with glaucoma eye drops, respectively. Kaplan-Meier survival analysis, generalized by the Wilcoxon test, and the Cox proportional hazards model analysis were conducted. Post-trabeculectomy phacoemulsification was treated as a time-dependent variable. In 24 (30%) of the included 80 eyes, phacoemulsification was included, and they were divided into two groups: groups I (8 eyes with phacoemulsification within 1 year after trabeculectomy) and group II (16 eyes after 1 year following trabeculectomy).

Results

Multivariable Cox proportional hazards model analysis showed post-trabeculectomy phacoemulsification was a significant factor in both complete success and qualified success based upon condition C (P = 0.0432 and P = 0.0488, respectively), but not for the other conditions. Kaplan–Meier survival analyses indicated significant differences in success probabilities between groups I and group II for complete success and qualified success based upon condition C (P = 0.020 and P = 0.013, respectively). There was also a significant difference for qualified success based upon condition B (P = 0.034), while there was no significant difference for the other conditions.

Conclusion

Post-trabeculectomy phacoemulsification, especially within 1 year, can cause poor prognosis of IOP control of UG eyes after trabeculectomy with MMC.     

Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis?

Purpose/Objectives

Treatment of the primary tumor reportedly improves survival in several types of metastatic cancer. We herein evaluated the efficacy and toxicity of radiotherapy for the primary tumor in prostate cancer with metastasis.

Materials/Methods

The study cohort included 140 men with metastatic prostate cancer at initial diagnosis. Metastatic sites were divided into 4 groups as follows: solitary bone, 2–4 bones, ≥5 bones, and visceral organs. Patient, tumor, and treatment characteristics, and clinical outcomes were compared between patients treated with (prostate radiotherapy [PRT] group) or without radiotherapy to the primary tumor.

Results

Patients in PRT group presented with a statistically significantly younger age (p = .02), whereas other characteristics showed no significant difference. Overall survival (OS) and biochemical failure-free survival (BCFFS) were improved in PRT patients (3-year OS: 69% vs. 43%, p = 0.004; 3-year BCFFS: 52% vs. 16%, p = 0.002). Multivariate analysis identified PRT as a significant predictor of both OS (hazard ratio [HR] = 0.43, p = 0.015). None of the 38 PRT patients experienced severe (grade ≥3) genitourinary or gastrointestinal toxicity.

Conclusions

Our data suggest that radiotherapy to the primary tumor was associated with improved OS and BCFFS in metastatic prostate cancer. The results of this study warrant prospective controlled clinical trials of this approach in stage IV prostate cancer patients with limited extent of bone metastasis and good performance status.     

Clinical Effect of Antioxidant Glasses Containing Extracts of Medicinal Plants in Patients with Dry Eye Disease: A Multi-Center,Prospective, Randomized,Double-Blind,Placebo-Controlled Trial

Purpose

To investigate the clinical efficacy and safety of wearable antioxidant glasses containing extracts of medicinal plants in patients with mild dry eye disease (DED).

Methods

Fifty patients with mild DED were randomly assigned to wear either extracts of antioxidant medicinal plants containing (N = 25) or placebo glasses (N = 25). Patients wore the glasses for 15 min three times daily. The ocular surface disease index (OSDI) score, tear film break up time (BUT), and Schirmer’s test were evaluated and compared within the group and between the groups at baseline, 4 weeks, and 8 weeks after treatment.

Results

OSDI score and tear film BUT were significantly improved in the treatment group at 4 and 8 weeks after wearing glasses (all P < 0.001). Compared to the placebo group, the OSDI scores were significantly lower in the treatment group at 8 weeks (P = 0.007). The results of the Schirmer’s test showed significant improvement in the treatment group at 4 weeks (P = 0.035), however there were no significant differences between the other groups or within the groups. No adverse events were reported during the study.

Conclusions

Antioxidant glasses containing extracts of medicinal plants were effective in improving in DED both subjectively and objectively. Wearing antioxidants glasses might be a safe and adjunctive therapeutic option for DED.

Trial Registration

ISRCTN registry 71217488     

Anti-MJ/NXP-2 autoantibody specificity in a cohort of adult Italian patients with polymyositis/dermatomyositis

Introduction

Autoantibodies in patients with polymyositis/dermatomyositis (PM/DM) are associated with unique subsets, clinical course and outcome. Anti-MJ antibodies, which recognize the nuclear protein NXP-2/MORC3, are reported in ~25% of juvenile DM. Prevalence and clinical significance of anti-MJ antibodies in adult Italian PM/DM patients were studied.

Methods

Sera from 58 consecutive adult Italian PM/DM patients were analyzed by immunoprecipitation of ³⁵S-labeled K562 cells extract, ELISA (anti-MJ, Jo-1), Western blot and indirect immunofluorescence. Clinical associations were analyzed using information from medical charts.

Results

Anti-MJ antibodies were the most prevalent specificity (17%) found mainly in DM (30%, 8 cases) vs 8% of PM (2 cases, P = 0.02). Comparing 10 anti-MJ (+) vs 48 anti-MJ (-) cases, DM was more common (P = 0.03), and age at onset was younger in anti-MJ (+) (P = 0.0006). In anti-MJ (+), heliotrope rash (P = 0.01) and calcinosis (P = 0.09) were more frequent. None of them had heart or lung involvement, or malignancy. Myopathy in anti-MJ (+) patients responded well to therapy and none of them had elevated CPK at last visit (0% vs 25% in anti-MJ (-)). Only 60% of anti-MJ (+) showed immunofluorescent nuclear dots staining, despite PML localization of NXP-2/MORC3.

Conclusions

Anti-MJ antibodies are the most frequent specificity in our cohort of adult Italian PM/DM. Anti-MJ (+) were associated with young onset DM, calcinosis, no internal organ involvement and good response of myopathy to therapy. Anti-MJ reported in juvenile DM is also found in adult PM/DM, and could be a new useful biomarker.     

Impact of Pacemaker Lead Characteristics on Pacemaker Related Infection and Heart Perforation: A Nationwide Population-Based Cohort Study

Background

Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications.

Methods and Results

Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07–0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08–0.83; P = 0.023).

Conclusions

There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.