Dementia predicted one-year mortality for patients with first hip fracture: a population-based study.

Aims: We aimed to determine the effect of dementia and Parkinson's disease on one, three and 12-month mortality following surgery for fracture of the hip in elderly patients from an Asian population. Patients and Methods: Using a random sample of patients taken from the Taiwan National Health Insurance Research Database, this retrospective cohort study analyzed the data on 6626 elderly patients who sustained a fracture of the hip between 1997 and 2012 who had ICD-9 codes within the general range of hip fracture (820.xx). We used Cox regression to estimate the risk of death associated with dementia, Parkinson's disease or both, adjusting for demographic, clinical, treatment, and provider factors. Results: Among 6626 hip fracture patients, 10.20% had dementia alone, 5.60% had Parkinson's disease alone, and 2.67% had both. Corresponding one-year mortality rates were 15.53%, 11.59%, and 15.82%, compared with 9.22% for those without neurological illness. Adjusted hazard ratio for one-year mortality was 1.45 (95% confidence intervals (CI) 1.17 to 1.79) for those with dementia, and 1.57 (95% CI 1.07 to 2.30) with both dementia and Parkinson's disease versus patients with neither. There was no significant association with death for Parkinson's disease alone. Age, male gender and comorbidities were also associated with a higher risk of mortality. Conclusion: Dementia, with or without Parkinson's disease, is an independent predictor of mortality following surgery for fractures of the hip. Age, male gender and comorbidities also increase the risk of death. Parkinson's disease alone has no significant effect. Cite this article: Bone Joint J 2018;100-B:1220-6.

Effect of high glucose, Porphyromonas gingivalis lipopolysaccharide and advanced glycation end-products on production of interleukin-6/-8 by gingival fibroblasts.

BACKGROUND AND OBJECTIVE: It is known that chronic periodontal infection can magnify the cytokine responses in patients with diabetes. Hyperglycemia increases the proinflammatory status, including the levels of advanced glycation end-products (AGEs), in patients with periodontitis. However, whether AGEs have additional effects on the production of those proinflammatory cytokines in diabetic patients with periodontitis is still unknown. To examine in vitro the effect of hyperglycemia and AGEs on the amounts of interleukin (IL)-6 and IL-8 produced in periodontally infected gingiva, human gingival fibroblasts (HGFs) were stimulated with glucose, AGE-modified bovine serum albumin (AGE-BSA) and Porphyromonas gingivalis LPS in the present study. MATERIAL AND METHODS: Primary culture of HGFs was incubated with various concentrations of AGE-BSA (0, 50, 100 and 200 µg/mL) and LPS (0, 10, 100 or 1000 ng/mL) at two different glucose concentrations - normal glucose (5 mm) and high glucose (25 mm). The amounts of IL-6 and IL-8 produced by HGFs were evaluated using ELISA. Expression of the AGE receptor on HGFs was determined by flow cytometry. RESULTS: High glucose stimulated a significant increase in the production of IL-6 and IL-8 by HGFs compared with normal glucose. This enhanced production of IL-6 and IL-8 could also be observed in the presence of LPS and/or AGE-BSA. When both LPS and AGE-BSA were present, especially at high concentrations (≥ 500 µg/mL of LPS and ≥ 25 µg/mL of AGE-BSA), a synergistic effect on IL-8 production was found in the high-glucose condition. CONCLUSIONS: A synergistic effect of the production of IL-8 could be induced in HGFs with the combination of high glucose, LPS and AGEs.

Home sleep study for patients with myasthenia gravis.

OBJECTIVES: The objective of the study was to examine predictors for sleep-disordered breathing (SDB) in patients with myasthenia gravis (MG) using Watch-PAT. MATERIALS AND METHODS: We prospectively studied 58 consecutive patients with MG without respiratory symptoms for a full-night Watch-PAT with concomitant recording of the MG score and acetylcholine receptor antibody concentration and analyzed potential risk factors of SDB. RESULTS: Twenty-four patients (41%) had definitive SDB, which was mild in 12 patients, moderate in six, and severe in six. Assessing risk factors with multivariate models, we found four significant predictors (BMI, age, male gender, and use of azathioprine); BMI was the most powerful predictor. The severity and prevalence of sleep-disordered breathing had no significant association with MG score, myasthenia stage, or seropositivity of acetylcholine receptor antibody. CONCLUSIONS: The prevalence of SDB in myasthenic patients with mild and moderate weakness was high when using the Watch-PAT. Both myasthenia-specific factors (use of azathioprine) and general predictors in terms of BMI, age, and male gender predisposed the development of SDB in patients with myasthenia gravis. Careful screening of patients with myasthenia gravis at risk of SDB using Watch-PAT might improve the quality of sleep and cardiovascular health through proper treatment of underlying SDB.

Risk of diabetes mellitus among patients with myasthenia gravis.

OBJECTIVES: To determine the risk of diabetes mellitus (DM) in patients with myasthenia gravis (MG) in a large cohort representing 99% of the Taiwan population. METHODS: Data from the Taiwan National Health Insurance Database were used to conduct retrospective cohort analyses. The study cohort comprised 1520 patients with MG who were four-fold frequency matched to those without MG by age and sex, and assigned the same index year. Cox proportional hazard regression analysis was conducted to estimate the risk of DM. RESULTS: The MG cohort had a 1.26-fold increased risk of developing DM compared with the comparison cohort (HR=1.26, 95% CI=1.04-1.53). MG patients without corticosteroids use had no increased risk of developing DM (HR=1.05, 95% CI=0.79-1.40), and MG patients with corticosteroids use had a 1.46-fold increased risk of developing DM (HR=1.46, 95%=1.15-1.86). In addition, patients with MG received aggressive treatment, associated thyroid diseases, and male patients had higher risk of DM. CONCLUSION: This population-based retrospective cohort study demonstrates that MG is associated with a high risk of DM, which might be related to the adverse effect of corticosteroid and aggressive therapy.

The effects of diallyl sulfide upon Porphyromonas gingivalis lipopolysaccharide stimulated proinflammatory cytokine expressions and nuclear factor-kappa B activation in human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Diallyl sulfide (DAS), a flavor compound from garlic, has varied potential therapeutic activities. Periodontitis is a disease that develops because of host-mediated inflammation to periodontal pathogens. In this study, the effects of DAS on the common proinflammatory cytokines and nuclear factor-kappa B (NF-κB) in human gingival fibroblasts (HGFs) being stimulated with lipopolysaccharide from Porphyromonas gingivalis, a potent periodontal pathogen, were evaluated. MATERIAL AND METHODS: Cytotoxicities of DAS and lipopolysaccharide on HGFs were measured with MTS assay. The mRNA and protein expressions of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, from the HGFs treated with lipopolysaccharide with and without DAS were examined with reverse transcription-polymerase chain reaction and immunocytochemistry, respectively. In addition, the activation and nuclear translocation of NF-κB with and without DAS were compared. RESULTS: DAS and lipopolysaccharide treatments within 3 mm and 10 µg/mL, respectively, did not affect the survival rate of HGFs. Lipopolysaccharide (1 µg/mL) significantly increased the mRNA expressions of IL-1ß, IL-6 and TNF-α; however, DAS (1 mm) inhibited these expressions. The protein expressions of TNF-α, IL-1ß, as well as the NF-κB nuclear translocation were increased after lipopolysaccharide treatment, but decreased when there was a DAS pretreatment. CONCLUSION: DAS diminished P. gingivalis lipopolysaccharide-stimulated cytokine expression and NF-κB activation in HGFs; we therefore suggest DAS may be beneficial on periodontal inflammation.

Clinical features of myasthenia gravis patients with autoimmune thyroid disease in Taiwan.

OBJECTIVES: The aim of this study was to analyze the prevalence and clinical features of myasthenia gravis (MG) patients with and without autoimmune thyroid disease (ATD). MATERIALS AND METHODS: Between 1999 and 2009, we reviewed a total of 1482 patients with MG. On the basis of thyroid evaluations, as well as neurological, clinical, and serological findings, the patients were divided into group A (MG patients with ATD) or group B (MG patients without ATD). The patients were categorized as having ocular myasthenia when symptoms restricted to the ocular system were present for 2 years or more. RESULTS: Of the 1482 MG patients, 121 (8.2%) patients were classified into group A. Graves' disease was more predominant (5.7%) than Hashimoto's thyroiditis (1.1%) and antibody-positive thyroid disease (1.4%). MG patients with ATD were predominantly female, were younger at the onset of MG symptoms, had a higher frequency of mild MG (ocular and mild generalized MG) and thymic hyperplasia, and had lower levels of seropositive anti-acetylcholine receptor antibodies. Compared to patients without thyroid eye disease, ATD patients with thyroid eye disease had a higher frequency of ocular MG. CONCLUSIONS: This is the largest review of the clinical features of MG patients with and without ATD to date. We found that compared to ocular MG, mild MG is more commonly associated with ATD. Furthermore, we observed that thymic hyperplasia is more common in MG patients with ATD, while thymoma is more common in MG patients without ATD.

Narrowband ultraviolet B phototherapy for patients with refractory uraemic pruritus: a randomized controlled trial.

BACKGROUND: Pruritus is very common in uraemic patients, but the treatment remains challenging. Studies regarding narrowband ultraviolet B (NB-UVB) phototherapy for uraemic pruritus are rare. OBJECTIVES: To investigate whether or not NB-UVB phototherapy is an effective treatment for uraemic pruritus. METHODS: We conducted a single-blind, randomized, controlled trial for patients with refractory uraemic pruritus. The treatment group received NB-UVB phototherapy three times per week for 6 weeks. The dose of NB-UVB started from 210 mJ cm(-2) and was increased by 10% each time. The control group received time-matched exposures to long-wave UVA radiation. A visual analogue scale (VAS) score was evaluated weekly for pruritus intensity for 12 weeks. The characteristics of pruritus were also assessed by a questionnaire at baseline and after 6 weeks of phototherapy. RESULTS: Both the NB-UVB and control groups had significant and comparable improvement in the pruritus intensity VAS scores during the period of phototherapy and follow-up. Compared with the control group, the NB-UVB group showed a significant improvement in the involved body surface area affected by pruritus (P = 0·006), but not in sleep quality. More detailed regression and estimating analysis revealed that the patients in the NB-UVB group had lower pruritus intensity scores at week 6, week 10 and week 12. This may indicate a beneficial difference at certain time points, but the effect seems marginal. CONCLUSIONS: NB-UVB phototherapy does not show a significant effect in reducing pruritus intensity compared with a control group for refractory uraemic pruritus. Further studies are warranted.

Inhibition of peripheral blood natural killer cell cytotoxicity in patients with myasthenia gravis treated with plasmapheresis.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disorder that may involve natural killer (NK) cells. Although NK cells are part of the innate immune system, they also influence adaptive immune responses. Double-filtration plasmapheresis (DFP) is an effective therapy for MG crisis. Thus, we examined the effects of DFP on the cytotoxicity of NK cells. METHODS: A total of 20 patients with MG and 16 healthy controls were recruited for the study. Ficoll-Paque-isolated peripheral blood mononuclear cells (PBMCs) and K562 cells were used as the effector and target cells, respectively. NK cell cytotoxicity was analyzed using flow cytometry immediately before and after DFP and upon course completion. RESULTS: Double-filtration plasmapheresis treatment decreased significantly the NK cell cytotoxicity in patients with MG, especially in good responders, those who were positive for acetylcholine receptor (AChR) antibodies, and those receiving immunosuppressants. CONCLUSIONS: The decrease in NK cell cytotoxicity after DFP and the decline of AChR antibody titer were observed in good responders indicating that this could benefit patients with MG.

Up-regulation of retinoblastoma protein phosphorylation in gingiva after cyclosporine A treatment: an in vivo and in vitro study.

BACKGROUND AND OBJECTIVE: Cyclosporine A can induce gingival cell proliferation; however, the precise molecular regulation of the proliferation is uncertain. Therefore, this study was carried out to examine, in vivo and in vitro, the expression of genes and proteins associated with gingival cell proliferation after treatment with cyclosporine A. MATERIAL AND METHODS: Forty Sprague Dawley rats with right maxillary posterior edentulous gingivae were assigned to a cyclosporine A group (30 mg/kg daily of cyclosporine A, administered orally) or a control group (administered mineral oil only). The animals were killed 4 wk after treatment. The edentulous gingivae were dissected out and analyzed for the expression of proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (Rb1) mRNA and/or protein, and phosphorylated Rb1 (pRb1), by real-time RT-PCR or immunohistochemistry. In human gingival fibroblast (HGF) cultures, the expression of PCNA, CDK4, cyclin D1 and Rb1 proteins and Rb1 phosphorylation were determined by western blotting after cyclosporine A treatment (0-10(4) ng/mL). RESULTS: Proliferating cell nuclear antigen and cyclin D1 mRNAs (Pcna and Ccnd1, respectively) were expressed more strongly in the gingivae of cyclosporine A-treated animals than in the gingivae of the controls. Immunohistochemical analyses showed that a greater number of gingival cells stained positive for cyclin D1, CDK4 and pRb1 in the cyclosporine A group than in the control group. Increased expression of cyclin D1, CDK4 and PCNA proteins was observed in HGFs after cyclosporine A treatment. The phosphorylation of Rb1 was enhanced in HGFs after treatment with cyclosporine A at concentrations of 10(2)-10(3) ng/mL. CONCLUSION: The increases in cyclin D1, PCNA and CDK4, together with the enhanced phosphorylation of Rb1, suggest that cyclosporine A promotes cell-cycle progression through the G(1)/S transition in the gingiva.

SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda.

BACKGROUND: Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis. OBJECTIVES: To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 (G86R) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index. RESULTS: PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0·5 µg mL(-1) recombinant human SLURP-1 protein. CONCLUSIONS: Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.

Cyclosporine A enhances apoptosis in gingival keratinocytes of rats and in OECM1 cells via the mitochondrial pathway.

BACKGROUND AND OBJECTIVE: We reported previously that cyclosporine A induces a high level of expression of p21 in rat gingival keratinocytes and in OECM1 cells. In this study, the apoptosis of gingival keratinocytes after treatment with cyclosporine A was evaluated using the same models. MATERIAL AND METHODS: Forty Sprague-Dawley rats with right edentulous ridges were assigned into cyclosporine A (30 mg/kg) and control groups. Four weeks later, gingivae were screened for expression of apoptotic genes using microarray analyses and DNA fragmentation. The expression of bcl2-associated X protein (Bax), apoptosis-inducing factor (AIF) and Caspase 3 mRNAs, and the expression of Bax, AIF, Caspase 9 and Fas proteins, were analyzed using the reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. Apoptosis in OECM1 cells (keratinocytes of a gingival carcinoma cell line), after treatment with cyclosporine A, was evaluated by 4',6-diamidino-2-phenylindole (DAPI) staining and flow cytometry, whereas the expression of Bax, AIF, Caspase 3 and 8, Bcl-2 and Fas proteins were examined using western blotting. RESULTS: According to microarray analyses, the expression of certain apoptotic genes was altered in the gingiva of rats who received cyclosporine A, and increased number of DNA fragments were detected. Expression of mRNA or protein for Bax, AIF and Caspase 3 and 9 in the gingivae of rats increased after treatment with cyclosporine A. An increased number of apoptotic bodies and of OECM1 cells in the sub-G1 phase was observed after treatment with cyclosporine A. Increased expression of AIF, Bax and Caspase 3 protein, but not of bcl-2, Caspase 8 or Fas protein, was observed in cells after treatment with cyclosporine A. CONCLUSION: Based on the above findings, we suggest that cyclosporine A might enhance the apoptosis of gingival keratinocytes, mainly via the mitochondrial pathway.

Changes in serum cytokine levels during plasmapheresis in patients with myasthenia gravis.

BACKGROUND: The effect of plasmapheresis on cytokine levels in patients with myasthenia gravis (MG) has not been well established. METHODS: Cytokine levels were measured in 19 patients with MG before and after treatment with one course of double-filtration plasmapheresis (DFP). The control group comprised 6 age- and sex-matched healthy volunteers. RESULTS: At baseline, patients with MG had higher levels of IL-10 than normal controls. The levels of IL-2, IL-4, IL-5, and tumor necrosis factor-alpha were almost undetectable in MG patients. After a single session of DFP treatment, IL-10 levels were significantly increased. After three sessions, IL-10 levels were still higher than those at baseline. Elevated IL-10 level was significantly associated with use of immunosuppressant drugs, thymectomy, and good response to DFP treatment. CONCLUSIONS: Interleukin-10 might play a crucial role in the pathogenesis and perpetuation of MG.

Xanthelasma is not associated with increased risk of carotid atherosclerosis in normolipidaemia.

OBJECTIVES: Extracranial carotid artery (ECCA) atherosclerosis is well known to be associated with cardiovascular diseases. This study aims to investigate the difference of ECCA atherosclerosis between patients with xanthelasma and control subjects in normolipidaemia. METHODS: Carotid atherosclerosis (CA) of 41 (8 males and 33 females) patients with xanthelasma and normolipidaemia, defined as levels of cholesterol below 6.21 mmol/l and triglyceride below 2.26 mmol/l, recruited from Department of Dermatology was compared with that of 85 age- and gender-matched control subjects. The extent and severity of CA were measured by high-resolution B-mode ultrasound and expressed as the mean intima-media thickness (IMT) of the common carotid artery (CCA) and ECCA plaque score. Mixed-effects model and multivariate logistic regression analyses were used to estimate the association between xanthelasma and CA. RESULTS: Patients with xanthelasma showed significantly higher levels of low-density lipoprotein cholesterol (LDL-C) levels and higher body mass index (BMI) compared with the control group. Mixed models identified age, male gender, smoking and subjects of hypertension with medication, but not the presence of xanthelasma, were associated with an increase of CCA IMT. Multivariate logistic regression analysis revealed subjects of male gender, and hypertension with medication, but not the presence of xanthelasma, associated with thicker IMT, defined as IMT >or= 75th percentile, or ECCA plaque score >or= 3. CONCLUSIONS: Normolipidaemia with xanthelasma is not significantly associated with CA, but did relate with adverse cardiovascular profiles, such as higher BMI, waist circumference and LDL-C levels.

Skin and soft tissue infection caused by non-tuberculous mycobacteria.

SETTING: A medical centre in Taipei, Taiwan. OBJECTIVE: To investigate the trend and characteristics of patients with non-tuberculous mycobacteria (NTM) related skin and soft tissue infection. DESIGN: A total of 63 patients with culture-proven diseases were identified from January 1997 to December 2004. The medical records of all patients were reviewed. RESULTS: Twenty-seven patients were infected with rapidly growing mycobacteria (RGM), 19 with Mycobacterium marinum, six with M. avium complex (MAC), five with M. kansasii and six with other species. Most patients presented with a protracted cutaneous lesion without systemic symptoms, and two thirds of the patients had a history of exposure. Seventy-three per cent of the lesions involved the extremities. Underlying illness with suppressed immunity was documented in 30.2% of the patients, and was most prevalent in patients with MAC (100%) and M. kansasii (60%). Of the patients, 62% underwent at least one surgical intervention, and 77.8% received treatment with different antimicrobial combinations. Most patients (86%) recovered completely. Granulomatous inflammation was found in 88.9% of biopsied tissue associated with M. marinum infection, 31.8% with RGM and 25.0% with MAC. CONCLUSION: A combination of surgery and antimicrobials cured most patients with microbiologically proven localised NTM skin and soft tissue infection.

Dopamine-induced apoptosis in human melanocytes involves generation of reactive oxygen species.

BACKGROUND: Previous studies have shown that significant increases in urinary and plasma levels of several monoamines and their metabolites characterize the onset of vitiligo and its progression. Recently, both epidermal keratinocytes and melanocytes were found to have the capacity for the biosynthesis of several catecholamines and serotonin. Some monoamines and their metabolites can induce apoptosis and cytotoxicity in neural cells. However, no previous report has investigated the potential role of these monoamines in inducing apoptosis or cytotoxicity in melanocytes. OBJECTIVES: To study the effects of dopamine (DA), norepinephrine (NE), epinephrine (EP), and serotonin (5-HT) on melanocyte cytotoxicity and apoptosis. METHODS: Primary cultures of normal human melanocytes established from the foreskins of normal individuals were treated with different concentrations of DA, NE, EP and 5-HT for 5 and 7 days. Cell viability was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Melanocyte apoptosis was evaluated by morphological examination and flow cytometric analysis. We also measured the generation of reactive oxygen species (ROS) after DA treatment. RESULTS: Among the four monoamines used in this study, only DA had an effect, dose-dependently decreasing the melanocyte viability at concentrations ranging from 0.01 to 100 micromol L(-1) (0.1 and 1 micromol L(-1), P < 0.05; 10 micromol L(-1), P < 0.01). In addition, DA-induced melanocyte apoptosis was evidenced by the increased percentage of sub-G1 cells from 7.71 +/- 0.28% (control) to 12.22 +/- 1.05% (0.1 micromol L(-1) DA) (P < 0.005), and treatment with the antioxidant N-acetylcysteine (NAC) reversed this apoptotic effect. DA treatment led to the generation of ROS, which could be prevented by pretreatment with NAC. CONCLUSIONS: DA can induce melanocyte apoptosis, which might be related to the generation of ROS. This novel effect might play an important role in the development or progression of vitiligo, which is currently viewed as a disease process closely related to melanocyte apoptosis.

Pitfalls in the differential diagnosis of a pelvic cyst: lessons from a post-menopausal woman with bladder diverticulum.

We present a case of non-obstructive bladder diverticulum in a 75-year-old post-menopausal woman. An ovarian cyst was previously suspected, which resulted in a futile exploratory laparotomy without making any definite diagnosis, 1 year earlier. During this admission, transvaginal ultrasound-guided cyst aspiration was arranged to determine the nature of the presumed 'recurrent' cyst and to relieve the symptoms. Prior to cyst aspiration, up to 700 ml of urine through urinary catheterisation and the gradual disappearance of the 'cyst' alerted us to the possibility of a bladder diverticulum, which was later confirmed by retrograde cystography. This case illustrates the lessons that despite considerable researches having been done on enhancing sonographic accuracy, diagnosis based on imaging alone is likely to be associated with multiple pitfalls. Recognising the common pitfalls and integrating clinical information and alertness with ultrasonic features remains the mainstay of sonographic differential diagnosis.