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Objective: To evaluate the association between P1NP and bone strength in postmenopausal women treated with teriparatide. Materials and Methods: This prospective study enrolled 248 postmenopausal women with severe osteoporosis treated with teriparatide. Procollagen type 1 N-terminal propeptide (P1NP) were assessed at baseline, 3, 6, and 12 months. Lumbar spine (LS), femoral neck (FN), and total hip (TH) bone mineral density (BMD) and LS trabecular bone score (TBS) were measured by Dual-energy x-ray absorptiometry at baseline and 12 months. Results: With teriparatide use, P1NP levels increase and peaked at 6 months. Significant increase in LS and hip BMD and LS TBS were also noted. The percentage change or absolute change >10 μg/L in PINP at 3 months was only related to changes in LS BMD at 12 months. With a median baseline P1NP level was 65.5 ng/mL, we found no correlation between P1NP and LS and hip BMD nor LS TBS. There was no association between LS TBS and axial BMD. After treatment, there was also no significance between the changes in TBS and axial BMD. Over the study period, 83.9% of the 248 participants were persistent with teriparatide at 3 months, 77.8% at 6 months, and 67.3% women at 12 months. Conclusion: P1NP levels may provide a signal of osteoporosis risk but is not related to bone strength. Early changes in P1NP may offer information regarding subsequent BMD response so standardized monitoring of P1NP levels at baseline and at 3 months should be considered during osteoporosis therapy. As an additional benefit, serum level monitoring during treatment may also improve medication persistence.

To evaluate the relationship between obstructive sleep apnea (OSA) and diabetic macular edema (DME) and the effect of OSA on refractory DME in patients with type 2 diabetes (T2DM).Retrospective clinical cohort study.A population-based study was conducted at Chang Gung Memorial Hospital from March 1, 2009, to March 1, 2020. Among 14,152 patients who had undergone polysomnography (PSG) and whose data were registered on the sleep center's PSG database, 121 patients (242 eyes) with T2DM were enrolled according to the International Classification of Diseases, Ninth Revision (ICD-9) code 3620 for diabetic retinopathy (DR). Patients with a secondary cause of macular edema and those lacking medical records were excluded. All patients with T2DM enrolled in our study received both optical coherence tomography (OCT) and PSG. The prevalence of severe (apnea-hypopnea index [AHI] ≥30) and nonsevere (AHI30) OSA was compared between patients with and without DME and refractory DME.In total, 102 eyes (54 patients) were divided into groups of 40 eyes with DME or 62 eyes without DME. Severe OSA (odds ratio, 7.36; 95% confidence interval [CI]: 1.32-40.96; P = .023) was significantly associated with DME. Refractory DME was significantly more frequent in patients with severe OSA (27%) than in those with nonsevere OSA (0%; P = .009). Cox proportional hazards regression analysis revealed that OSA (hazard ratio, 2.97; CI, 1.08-8.16; P = .034) independently increased the DME risk after adjustment for age, sex, glycohemoglobin level, hypertension, and hypercholesterolemia.Severe OSA is a risk factor for DME and is associated with having refractory DME.

Background Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole–induced SCAR remains unclear. Objective We aimed to investigate the genetic predisposition of co-trimoxazole–induced SCAR. Methods We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole–induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. Results The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole–induced SCAR (P = 8.2 × 10−9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole–related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole–induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10−21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10−5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole–induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10−23; OR = 40.1). Conclusion This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole–induced SCAR in Asians.

The automated blister epidermal micrograft (ABEM) is a newly introduced surgical transplantation for refractory vitiligo. Comparative analysis of other surgical methods is lacking. We conducted a retrospective study to compare the efficacy, safety, and experience of ABEM with conventional suction blister epidermal graft (SBEG). A total of 118 anatomically based vitiligo lesions from 75 patients were included. The primary outcome was the degree of repigmentation; the patient and operator experience were evaluated. SBEG had a significantly greater incidence of repigmentation (p

Background The declining order of abnormality rates in inner ear test battery of patients with Meniere's disease (MD) is consistent with the decreasing sequence of prevalence of hydrops formation in temporal bone donors of MD. Objective This study investigated inner ear deficits in MD patients with falls, without falls, and after sac operation to compare their inner ear deficits. Methods Twenty MD patients with falls (Group A), 20 MD patients without falls (Group B), and 20 MD patients after sac operation (Group C) were enrolled. All patients underwent an inner ear test battery. Results Group A (with falls) revealed a declining sequence of abnormality rates running from audiometry (92%), cervical vestibular-evoked myogenic potential (cVEMP) test (71%), caloric test (42%) to ocular VEMP (oVEMP) test (38%). In contrast, Group B (without falls) displayed a different declining sequence of abnormality rates running from audiometry, cVEMP test, and oVEMP test to caloric test. Similarly, Group C also displayed the same declining sequence of inner ear deficits to Group A, indicating that Groups A and C may share a similar mechanism. Conclusions Comparing the declining sequence of inner ear deficits in two inner ear disorders may help determine whether both disorders share a similar mechanism.

Endogenous K. pneumoniae endophthalmitis (EKE) has a higher incidence among East Asians, and the most common infectious source of EKE is pyogenic liver abscess (PLA). We investigate the risk factors for poor visual outcomes in patients with PLA-related EKE. The retrospective medical records of 104 patients (120 eyes) diagnosed with PLA-related EKE between 1996 and 2015. In univariate logistic regression analysis, the risk factors for poor visual outcomes were initial visual acuity (VA) worse than counting fingers (CF) (p p = 0.013), hypopyon (p = 0.003), ocular hypertension (p = 0.003), positive intraocular fluids cultures (p p = 0.025), unilateral involvement (p = 0.017), delayed ophthalmologic visit (p = 0.022), initially presented with ocular symptoms ahead of systemic symptoms (p p p = 0.01). The multivariate logistic regression revealed that poor initial VA worse than CF (p = 0.004) and initially presented with ocular symptoms ahead of systemic symptoms (p = 0.007) were the significant independent factors for poor visual outcomes. Early diagnosis and prompt treatment may salvage useful vision in some eyes.

Background Patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have high mortality rates. Disseminated intravascular coagulation has been reported in SJS/TEN patients. The influence of this lethal complication in patients with SJS/TEN is not well known. Objective This study aimed to investigate the risk and outcomes of disseminated intravascular coagulation in patients with SJS/TEN. Methods We analyzed the disseminated intravascular coagulation profiles of patients receiving a diagnosis of SJS/TEN between 2010 and 2019. Results We analyzed 150 patients with SJS/TEN (75 with SJS, 22 with overlapping SJS/TEN, and 53 with TEN) and their complete disseminated intravascular coagulation profiles. Disseminated intravascular coagulation was diagnosed in 32 patients (21.3%), primarily those with TEN. It was significantly associated with systemic complications, including gastrointestinal bleeding, respiratory failure, renal failure, liver failure, infection, and bacteremia. Additionally, SJS/TEN patients with disseminated intravascular coagulation had elevated procalcitonin levels. Among patients with SJS/TEN, disseminated intravascular coagulation was associated with a greater than 10-fold increase in mortality (78.1% vs 7%). Limitations The study limitations include small sample size and a single hospital system. Conclusion Disseminated intravascular coagulation is a potential complication of SJS/TEN and associated with higher mortality. Early recognition and appropriate management of this critical complication are important for patients with SJS/TEN.

To develop a pre-emptive genetic test that comprises multiple predisposing alleles for the prevention of phenytoin-related severe cutaneous adverse reactions (SCARs), three sets of patients with phenytoin-SCAR and drug-tolerant controls from Taiwan, Thailand, and Japan, were enrolled for this study. In addition to cytochrome P450 (CYP)2C9*3, we found that HLA-B*13:01, HLA-B*15:02, and HLA-B*51:01 were significantly associated with phenytoin hypersensitivity with distinct phenotypic specificities. Strikingly, we showed an increase in predictive sensitivity of concurrently testing CYP2C9*3/HLA-B*13:01/HLA-B*15:02/HLA-B*51:01 from 30.5-71.9% for selecting the individuals with the risk of developing phenytoin-SCAR in Taiwanese cohorts, accompanied by a specificity of 77.7% (combined sensitivity, 64.7%; specificity, 71.9% for three Asian populations). Meta-analysis of the four combined risk alleles showed significant associations with phenytoin-SCAR in three Asian populations. In conclusion, combining the assessment of risk alleles of HLA and CYP2C9 potentiated the usefulness of predictive genetic tests to prevent phenytoin hypersensitivity in Asians.

Study design A retrospective study of patients who were hospitalized for infectious spondylodiscitis over a 13-year period. Objective To elucidate the epidemiology and prognostic factors of infectious spondylodiscitis in hemodialysis (HD) patients and to identify the impact of HD on infectious spondylodiscitis. Summary of background data Only a few case studies of infectious spondylodiscitis in HD patients can be found in the literature. Reports of prognostic factors are limited and patients' outcomes have not been well described. Methods The cases of 1402 patients who were hospitalized for infectious spondylodiscitis over a 13-year period were retrospectively reviewed. Of these, 102 patients on maintenance HD were enrolled in this study. Cox proportional hazard model was used to evaluate the risk factors of mortality and recurrence. Results The 102 enrolled patients had an average age 63.3 ± 11.2 years old and male-to-female ratio of 1:1.04. Back pain was present in 75.5% of patients and the most commonly infected site was the lumbosacral spine. Infection associated with vascular access was identified in 31.4% of patients. The prevalence of dialysis via central venous catheters was higher than prevalent HD patients. Methicillin-resistant Staphylococcus aureus was the most common pathogen, followed coagulase-negative staphylococci. The patients' in-hospital survival rate was 82.4%; their vascular access survival rate was 75.5%; their 1-year survival rate was 78.4%, and their 1-year recurrence rate was 20.2%. Congestive heart failure was associated with an increased 1-year mortality. Other variables exhibited no significant relationship with patients' in-hospital mortality, 1-year mortality or recurrence. Conclusion The characteristics and outcomes of infectious spondylodiscitis in HD patients were elucidated. Most of the demographic and clinical variables, evaluated upon admission, did not predict mortality or recurrence. Level of evidence 3.

Background Endophthalmitis is a severe eye infection leading to disabling outcome. Because there were only a few case report illustrating endophthalmitis in chronic dialysis patient, we would like to investigate the epidemiology and clinical features of endophthalmitis in chronic dialysis patient in a tertiary referral center. Methods We searched the health information system in the study hospital with ICD9 encoding endophthalmitis during Jan. 2002 to Dec. 2015. A total of 32 episodes of endophthalmitis occurred in chronic dialysis patients. We performed an 1:2 case-control match on propensity score. The demographic features, clinical manifestation, infection focus and visual outcome were recorded. Results Of the total of 32 patients, 25 were classified as endogenous endophthalmitis and another seven were exogenous. Most patients presented with ophthalmalgia (n = 32, 100%) and periocular swelling (n = 31, 96.8%), whereas half of the patients suffered blurred vision (n = 16, 50%). Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent causative pathogens. Dialysis vascular infection was also a possible unique focus for bacteremia. The visual acuity of the endogenous groups were less likely to improve in the chronic dialysis patients compared with control group. Conclusion This is the first and the largest case series focusing on endophthalmitis in chronic dialysis patients. Our study showed different pathogen spectrum, an unique bacterial origin and worse visual outcome in these group of patients. Prompt referral to ophthalmologists when the patients present with suspicious symptoms (blurred vision, ophthalmalgia and periocular swelling) is crucial.

BACKGROUND: Many techniques have been described to relieve the compression and reduce subluxation of the ulnar nerve following surgery. The subfascial anterior transposition of the ulnar nerve (SfATUN) is one described technique, but involves a long scar, risk of injury to the medial antebrachial cutaneous nerve, and possible nerve ischemia from anterior transposition. We assessed a more refined approach of endoscopy-assisted SfATUN for the treatment of cubital tunnel syndrome.METHODS: A consecutive case series of 21 patients (15 males and 6 females) with evidence of nerve subluxation after ulnar nerve decompression were operated using an endoscopy-assisted SfATUN. Each patient was assessed with pre- and postoperative nerve conduction studies, McGowan grading, and recovery of grip strength.RESULTS: The average age of patients was 54 years (range 23-74 years), and they were followed up for a mean of 9 months (range 3-22 months). Preoperative McGowan grades were eight grade II and 13 grade III. Eighteen of the 21 patients showed improvement, including improvement by two McGowen grades in 8 patients and improvement by one grade in 10 patients. Three grade III patients did not show improvement in grading after surgery. A proportion of 90% of patients showed significant improvements in motor nerve conduction velocity of the ulnar nerve across the elbow (p < 0.001), and all showed some improvement in grip strength (p < 0.001). One patient underwent redo neurolysis.CONCLUSION: A combination of endoscopy-assisted SfATUN allows for decompression transposition and reduced strain on the ulnar nerve through a small scar. This is now our standard approach for cubital tunnel syndrome and the "unstable" nerve.

Aim This study investigated the evolution of vestibular disorders in dizzy older adults from young-old to middle-old to oldest-old individuals, which has been less examined in detail so far. Methods A total of 3714 older patients with vertigo/dizziness in a university hospital were retrospectively reviewed and divided into three groups; namely, the young-old group aged 65-74 years (n = 2307), the middle-old group aged 75-84 years (n = 1176) and the oldest-old group aged ≥85 years (n = 231). All patients underwent an inner ear test battery comprising audiometry, caloric test, cervical and ocular vestibular-evoked myogenic potential tests, and foam posturography. Results The ratios between peripheral and central vestibular disorders ranged from the young-old (60:40%) and middle-old (36:64%) to the oldest-old (25:75%) groups. These results show a decreasing sequence in the prevalence of peripheral vestibular disorders (i.e. benign paroxysmal positional vertigo or Meniere's disease), and an increasing sequence in that of central vestibular disorders (i.e. vertebrobasilar artery insufficiency) from young-old to middle-old to oldest-old patients. Furthermore, the mean Romberg quotients (value from eyes closed divided by that from eyes open) of the sway area on the foam pad were 1.99 ± 0.93, 2.10 ± 1.06 and 2.62 ± 1.78 in the young-old, middle-old and oldest-old groups, respectively, showing a significant difference among them. Conclusions Older patients with central vestibular disorders might be more prone to imbalance and falls than those with peripheral vestibular disorders, partly because patients in the latter group retain other reflex systems; that is, the visuomotor reflex to stabilize the gaze and maintain balance. Hence, adequate vision is important in maintaining balance for older adults with vertigo/dizziness. Geriatr Gerontol Int 2020; 20: 42-46.

Objectives We conducted this retrospective study to elucidate the clinical presentation and outcomes of anal abscess in chronic dialysis patients. Methods We performed a chart review of patients who were hospitalized for anal abscess from Jan. 2002 to Dec. 2015. A total of 3,074 episodes of anal abscess were identified. Of these, 43 chronic dialysis patients with first-time anal abscess were enrolled. Patients were divided into a surgical group and a nonsurgical group according to the treatment received during hospitalization. The baseline characteristics, clinical findings, treatments and outcomes were obtained and analyzed. The endpoints of this study were in-hospital mortality, one-year mortality and one-year recurrence. Results Of the 43 patients, 27 (62.7%) received surgical treatment, and 16 (37.2%) received antibiotic treatment alone. There was no significant difference in age, sex, body mass index, smoking habits, comorbidities, or dialysis characteristics between the two groups. Perianal abscess was the most common type of anal abscess, and 39.5% of patients experienced fistula formation. Most patients had mixed aerobic and anaerobic flora. Our data demonstrate that there was no significant difference in hospital stay, one-year survival or recurrence rate between the surgical group and nonsurgical group. However, there was a trend toward better in-hospital survival in patients who received surgical treatment (p=0.082). Conclusion In chronic dialysis patients with anal abscess, there was no statistically significant difference in clinical presentation and outcomes between the surgical and nonsurgical groups, although the surgical group had a trend of better in-hospital survival.

Reliable prognostic factors that serve as a guide to follow-up of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) have not yet been identified. We sought to investigate the prognostic implications of post-therapy PET in patients with NPC treated with chemoradiotherapy. Patients with locoregionally advanced NPC (stages III and IVa–b) who had completed primary curative treatment for 3 months were eligible. All of the patients underwent 18F-FDG PET and conventional work-up (CWU) for the assessment of treatment response. A total of 165 patients were enrolled. Over a median follow-up of 58 months, 30 patients died and 41 had disease recurrence. The results of the 3-month post-therapy PET and total lesion glycolysis (TLG) of the primary tumor were independent predictors of overall survival. TNM tumor stage, TLG, and post-therapy PET findings were independently associated with disease-free survival (DFS). The results of post-therapy PET were more predictive of DFS than TNM tumor stage (P

Objective:To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai).Methods:We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate ofHLA-B*15:02andHLA-A*31:01of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)–induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database.Results:We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association betweenHLA-B*15:02and OXC-SJS (p= 1.87 × 10−10; odds ratio 27.90; 95% confidence interval [CI] 7.84–99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values ofHLA-B*15:02for OXC-SJS/TEN were 0.73% and 99.97%, respectively.HLA-A*31:01was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p= 0.003; relative risk 0.212; 95% CI 0.077–0.584).Conclusions:Our findings suggest thatHLA-B*15:02is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptiveHLA-B*15:02screening should be evaluated further.

Synthetic mesh kits recently adopted in pelvic reconstructive surgeries have achieved great surgical efficacy, but the effects of transvaginal synthetic mesh procedures on women’s sexual function are still controversial. This study was conducted to demonstrate sexual function in women before and after surgery with transvaginal mesh (TVM) repair for pelvic organ prolapse (POP). A total of 93 sexually active women scheduled for correcting POP with synthetic mesh kits were recruited. In addition to urogynecological history, pelvic examination by the Pelvic Organ Prolapse Quantification system, and urodynamic testing, consenting participants were asked to complete the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) to evaluate sexual function before and after surgery. At the 3-month urodynamic studies, among the 25 patients with coexistent urodynamic stress incontinence (USI) who had undergone a concomitant transobturator suburethral tape procedure (TOT), 1 (4 %) had persistent USI; 8 of 68 (11.8 %) patients with a negative pessary test developed postoperative USI. Six-month prolapse recurrence rates following TVM alone and TVM with concomitant TOT were 9 and 12 %, respectively. The total PISQ-12 score after surgery showed worse results in the TVM alone group but not in the TVM with concomitant TOT group. The individual scores of PISQ-12 after surgery demonstrated prolapse-related items improved in both TVM groups; sexual function worsened in dyspareunia and behavior domains. Our data revealed that transvaginal synthetic mesh procedures for the treatment of POP generated favorable clinical outcomes, but situations might worsen in dyspareunia and behavior domains, thereby invoking a negative emotional reaction during intercourse after surgery.

Intrahepatic metastasis is the primary cause of the high recurrence and poor prognosis of human hepatocellular carcinoma (HCC). However, neither its molecular mechanisms nor markers for its prediction before hepatectomy have been identified. We recently revealed up-regulation of erythroblastic leukemia viral oncogene homolog 3 (ERBB3) in human HCC. Here we examined the clinical and biological significance of ERBB3 in HCC. Up-regulation of ERBB3 in HCC was strongly associated with male gender (P< 0.001), chronic hepatitis B (P = 0.002), microscopic vascular invasion (P = 0.034), early recurrence (P = 0.003), and worse prognosis (P = 0.004). Phosphorylated ERBB3 and its ligands [neuregulins (NRGs)] were detected in both HCC tissues and cells. Phosphorylation of ERBB3 could be induced by conditioned media of HCC cells and abolished by the pretreatment of conditioned media with anti-NRG antibodies or by the silencing of the endogenous NRG expression of the donor HCC cells. Human epidermal growth factor receptor 2 was required for ERBB3 phosphorylation. The downstream phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene homolog pathways were primarily elicited by NRG1/ERBB3 signaling, whereas the mitogen-activated protein kinase/extracellular signal-regulated kinase pathways were elicited by both epidermal growth factor/epidermal growth factor receptor and NRG1/ERBB3 signaling. The activation and silencing of ERBB3-dependent signaling had potent effects on both the migration and invasion of HCC cells, but neither had significant effects on the proliferation of HCC cells, tumor formation, or tumor growth in vitro and in vivo. Conclusion: The constitutive activation of ERBB3-dependent signaling via the NRG1/ERBB3 autocrine loop plays a crucial role in the regulation of cell motility and invasion, which contribute to intrahepatic metastasis and early recurrence of HCC. ERBB3 is a marker for the prediction of intrahepatic metastasis and early recurrence. ERBB3-dependent signaling is a candidate target for the treatment of microscopic vascular invasion and for the prevention of HCC recurrence. (HEPATOLOGY 2011;53:504-516) (This article firstt published online on January 18, 2011; the title has since changed; the correct version appears in print.

Purpose This study evaluated the effects of pain assessment at triage on analgesia provision to pediatric patients with closed long-bone fractures in the emergency department (ED). Methods This was a retrospective cohort study conducted at a university-affiliated teaching hospital. Children who presented to the ED of a teaching hospital with the main diagnosis of a closed fracture of the extremities in 2007 constituted the study cohort. We reviewed the charts and collected the following variables regarding the subjects' ED visits: patient demographics, pain scale reassessment, category of fracture, associated injuries, time from triage to the first administration pain medication, and the route and type of analgesic. The data were divided on the basis of triage in accordance with pain assessment or other triage modifiers. Results In our study, 211 (54.7%) patients enrolled received analgesia. Oral acetaminophen was the most commonly prescribed medication (131 patients, 62.1%), whereas opioids were used in only 24 (11.4%) patients. The average time taken to deliver analgesia to children arriving in our ED was 70 minutes. The logistic regression analysis indicated that enrolled patients triaged based on the pain assessed at triage was not associated with the subsequent provision of analgesia. Analgesia provision was not associated with patients with moderate or severe pain assessed at triage as compared to patients with mild pain. Conclusion The pain management of pediatric patients with closed long-bone fractures in the ED was inadequate and delayed. Moreover, the pain assessment at triage did not predict analgesia provision to these patients.

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01 , we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5–90.3; P = 2.6 × 10 -41 ), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate 2 ) should be cautious and avoid using allopurinol.

Allopurinol, a first-line drug used for treating gout, is increasingly prescribed worldwide to patients with asymptomatic hyperuricemia and comorbid renal or cardiovascular diseases. Nevertheless, allopurinol use has been associated with fatal hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The overall risks of allopurinol use remain unclear.To investigate the incidence of, risk factors for, and mortality associated with allopurinol hypersensitivity in new users of allopurinol.A retrospective nationwide population study was conducted using data from the Taiwan National Health Insurance Research Database, which includes detailed medical records of more than 23 million insured enrollees. Data were collected from January 1, 2005, through December 31, 2011, using the Anatomical Therapeutic Chemical classification system and International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among 1,613,719 patients receiving allopurinol prescriptions, 495,863 were identified as new users.Allopurinol hypersensitivity was identified within 3 months since the first prescription. The period for measuring related hospitalizations was 1 month since the episode, and the period for measuring renal complications or mortality was 2 months since the episode. Poisson regression test and multivariable logistic regression analysis were performed, and P .01 was considered statistically significant.Among the more than 23 million insured enrollees, the annual incidence rates were 4.68 per 1000 new users for allopurinol hypersensitivity, 2.02 per 1000 new users for related hospitalization, and 0.39 per 1000 new users for related mortality. The annual incidence of allopurinol hypersensitivity rose statistically significantly during the study period (P .001). Risk factors for allopurinol hypersensitivity included female sex, age 60 years or older, initial allopurinol dosage exceeding 100 mg/d, renal or cardiovascular comorbidities, and use for treating asymptomatic hyperuricemia. Patients with asymptomatic hyperuricemia and renal or cardiovascular diseases had statistically significantly increased risk of allopurinol hypersensitivity (odds ratio [OR], 1.61; 95% CI, 1.33-1.94; P .001 for renal diseases and OR, 1.52; 95% CI, 1.19-1.93; P .001 for cardiovascular diseases). They also had statistically significantly increased risk of mortality (OR, 5.59; 95% CI, 2.61-11.94; P .001 for renal diseases and OR, 3.57; 95% CI, 2.31-5.51; P .001 for cardiovascular diseases).The use of allopurinol in patients with asymptomatic hyperuricemia accompanied by renal or cardiovascular diseases statistically significantly increased the risk of hypersensitivity reactions. Physicians should be cautious when prescribing allopurinol to high-risk populations and should consider the potential risks of fatal adverse reactions.

ObjectiveAllopurinol, an antihyperuricaemic agent, is one of the common causes of life-threatening severe cutaneous adverse reactions (SCAR), including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The prognostic factors for allopurinol-related SCAR remain unclear. This study aimed to investigate the relationship of dosing, renal function, plasma levels of oxypurinol and granulysin (a cytotoxic protein of SJS/TEN), the disease severity and mortality in allopurinol-SCAR.MethodsWe prospectively enrolled 48 patients with allopurinol-SCAR (26 SJS/TEN and 22 DRESS) and 138 allopurinol-tolerant controls from 2007 to 2012. The human leucocyte antigen (HLA)-B*58:01 status, plasma concentrations of oxypurinol and granulysin were determined.ResultsIn this cohort, HLA-B*58:01 was strongly associated with allopurinol-SCAR (pConclusionsImpaired renal function and increased plasma levels of oxypurinol and granulysin correlated with the poor prognosis of allopurinol-SCAR. Allopurinol prescription is suggested to be avoided in subjects with renal insufficiency and HLA-B*58:01 carriers. An early intervention to increase the clearance of plasma oxypurinol may improve the prognosis of allopurinol-SCAR.

Objective Dyslipidemia with higher inflammatory states, disease activity, and longer disease duration in juvenile idiopathic arthritis (JIA) patients seemed to increase the risks of atherosclerosis. Tumor necrosis factor- α (TNF-α) receptor blocking agent etanercept has been proven to be effective in JIA. However, data about the correlation of anti-inflammatory treatment on lipid profiles and atherogenic index in JIA patients remains limited. This study aimed to investigate the longitudinal changes on lipid profiles and atherogenic index in JIA patients after etanercept treatment. Methods Twenty-three patients diagnosed with JIA (polyarticular type n = 7; oligoarticular type, n = 2; systemic type, n = 10, Enthesitis-related arthritis = 4) received treatment with etanercept during the period 2004–012 in a medical center. We measured their serum lipid profiles at baseline and 2, 4, 6, 12 months later, and determined whether there were differences in complete blood counts, inflammatory mediators, lipid levels and atherogenic indices between patients who had inactive disease (responders) and those who were poor responders (non-responders) to etanercept treatment. Results Analysis of dynamic change in total JIA patients before and after TNF inhibitor therapy showed modest increases in hemoglobin levels (P = 0.02) and decreases in WBC counts, Platelet and CRP levels progressively (p = 0.002, p = 0.006 and p = 0.006, respectively).Twelve of the 23 patients achieved inactive disease status (responders) after 12-months of treatment. In responders, compared to non-responders, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increased significantly (P = 0.007,P = 0.044,P

Objective The objective of this study is to determine the association between the duration of high-altitude (>3000 m) pre-exposure and acute mountain sickness (AMS) incidence. Methods A prospective observational study was conducted on 2 random days each month from April 2007 to March 2008 at Paiyun Lodge (3402 m), Jade Mountain, Taiwan. Demographic data, prior AMS history, symptoms, and scores and the days and times of high-altitude pre-exposure within the preceding 2 months were obtained from lowland ( Results Totally, 1010 questionnaires were analyzed; 106, 76, and 828 trekkers had pre-exposure lasting at least 3 days (group 1), less than 3 days (group 2), and 0 days (group 3), respectively. Acute mountain sickness incidence was significantly higher in groups 2 and 3 than in group 1 (21.70%, 35.53%, 37.08%, respectively; P = .008). Logistic regression analysis indicated a significantly lower AMS risk in group 1 (group 1, P = .004; odds ratio [OR], 0.479; 95% confidence interval [CI], 0.290-0.791; group 2, P = .226; OR, 0.725; 95% CI, 0.430-1.221). In group 1, 28 and 78 trekkers had single and intermittent multiple pre-exposure, respectively. There was no difference in the incidence or severity of AMS symptoms between single and intermittent multiple pre-exposure (AMS, P = .838; headache, P = .891; dizziness or lightheadedness, P = .414; fatigue and/or weakness, P = .957; gastrointestinal symptoms, P = .257; difficulty sleeping, P = .804; AMS score, P = .796). Conclusions High-altitude pre-exposure lasting at least 3 days within the preceding 2 months was associated with a significant lower AMS incidence during a subsequent ascent among Jade Mountain trekkers.

Objective and Background The roles of chronic hepatitis B virus (HBV) co-infection (CI) in carcinogenesis of hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) remained controversial. To gain new insights into this issue, we investigated the postoperative prognostic value of HBVCI in HCV-associated HCC. Methods A study cohort of 115 liver tissues obtained from the noncancerous parts of surgically removed HCV-associated HCCs were subjected to virological analysis in a tertiary care setting. Assayed factors included clinicopathological variables, tissue amounts of viral genomes, genotypic characterization of viruses, as well as the presence of overt (serum HBsAg positive) or occult (serum HBsAg negative but tissue HBV-DNA positive) HBVCI. Cox proportional hazard model was used to estimate postoperative survivals. Results Of the 115 patients, overt and occult HBVCIs were detected in 35 and 16 patients, respectively. Multivariate analysis revealed that tumor size >3 cm (adjusted hazard ratio (AHR), 2.079 [95% confidence interval, 1.149∼3.761]), alpha-fetoprotein >8 ng/mL (AHR, 5.976 [2.007∼17.794]) albumin 50 U/L (AHR,1.086 [1.006∼1.172]), presence of occult HBVCI (AHR, 2.708 [1.317∼5.566]), and absence of overt HBVCI (AHR, 2.216 [1.15∼4.269]) were independently associated with unfavorable disease-free survival. Patients with occult HBVCI had a shorter disease-free (P = 0.002), a shorter overall survival (P = 0.026), a higher bilirubin level (P = 0.003) and a higher prevalence of precore G1896A mutation (P = 0.006) compared with those with overt HBVCI. Conclusion Occult and overt HBVCI served as independent predictors for postoperative survival in HCV-associated HCC.

We describe a case of camptomelic dysplasia identified prenatally with the assistance of three-dimensional ultrasonography. The typical skeletal dysplasia of camptomelic dysplasia – including anterior bowing of the tibia, with skin dimpling over a convex surface at the point of maximal deformity, and talipes equinovarus – was successfully identified using the techniques of surface-rendering, multiplanar displays and rotated volume data. Three-dimensional ultrasonography allows the diagnosis of camptomelic dysplasia , which has a poor prognosis as it is accompanied by respiratory insufficiency and spinal deformities, to be made without delay and provides information supplementary to that provided by two-dimensional ultrasound for early diagnosis of skeletal dysplasia.

Death evasion is crucial for both carcinogenesis and resistance to anticancer therapies. Recently, we identified nucleophosmin (NPM) as a key factor counteracting death stimuli in human hepatocellular carcinoma (HCC) cells. Here we report the identification of a novel NPM-BCL2-associated X protein (BAX) pathway orchestrating death evasion in human HCC cells. Silencing of NPM expression significantly sensitized HCC cells—particularly those bearing inactivated p53 gene (Huh7, Hep3B, and Mahlavu)—to ultraviolet irradiation, mitomycin C, doxorubicin, cisplatin, sorafenib, and lapatinib. This sensitizing effect was not changed further, as p53 expression had been simultaneously silenced. Following cell stress, NPM and BAX were induced and exported out of the nucleoli and nucleus, respectively. BAX was translocated to cytoplasm in cells with relatively high NPM level, or accumulated in the mitochondria in cells with relatively low NPM level and undergoing apoptosis. Subcellular fractionation revealed that silencing of NPM expression greatly enhanced mitochondrial translocation and oligomerization of BAX in Huh7 and Mahlavu cells. In situ proximity ligation assays and reciprocal co-immunoprecipitation revealed a direct interaction between NPM and BAX in the cytoplasm. Silencing of BAX expression abolished the sensitization effect exerted by silencing of NPM in HCC cells. Clinically, up-regulation of NPM was significantly associated with advanced tumor stage and poor prognosis. Conclusion: By directly blockading BAX mitochondrial translocation and activation, NPM helps human HCC cells evade death induction independently of p53-mediated cell death. Silencing of NPM significantly sensitized HCC cells to anticancer therapies. NPM is a potential cotarget in combination with other therapies for HCC, particularly those that harbor inactivated p53 gene. Our findings are of clinical significance because NPM up-regulation and p53 mutations are usually found in advanced human cancers, including HCC. (HEPATOLOGY 2013)

Combined hepatocellular-cholangiocarcinoma (CHC) is a rare liver malignancy. In this study, we compared patient characteristics and outcomes for primary CHC, intrahepatic cholangiocarcinoma (ICC), and hepatocellular carcinoma (HCC).Medical records of patients with tissue-proven CHC (65 cases) treated at the Chang Gung Memorial Hospital between 1991 and 2005 were retrospectively reviewed. These records were compared to records of patients diagnosed with tissue-proven HCC (1985 cases) and ICC (127 cases) during the same period.Hepatitis B and C are major causes of CHC. CHC patients exhibited greater similarity to HCC than to ICC patients with respect to cirrhotic changes, age, and positive serology for hepatitis B surface antigen and anti-hepatitis C antibody. Survival was related to tumor characteristics and intervention therapies, but not to etiologies.The clinical characteristics of CHC are similar to those of HCC, but overall survival is more similar to that of ICC; survival may be related to tumor biology rather than the cause. Multimodal treatment with an initial aggressive therapeutic approach can improve survival.

This study was conducted to investigate the prevalence of and contributing factors to urinary incontinence (UI) in women 5 years after their first birth and to evaluate the associations of UI with delivery mode and quality of life.Between 2005 July and 2006 March, primiparous women who delivered at term in a tertiary hospital were recruited into this cohort study. Immediately postpartum, the women completed a structured urogynecological questionnaire regarding lower urinary tract symptoms. Then the same urogynecological questionnaire, the Incontinence Impact Questionnaire (IIQ-7), and the Urinary Distress Inventory (UDI-6) were mailed to them 5 years later to follow up on UI. Three hundred and twelve women responding to the mailed questionnaires were included in the analyses.The prevalence 5 years after first delivery of stress (SUI) and urge (UUI) UI were 43.6 % and 19.2 %, respectively. Women with UI during their first pregnancy were more likely to develop UI 5 years postpartum than those without it; women who delivered their first child vaginally had a greater incidence of UI than those having cesarean birth; UUI in women following cesarean delivery more negatively impacted emotional health than it did following vaginal birth, whereas the impact of SUI did not significantly differ between delivery groups.UI during the first pregnancy and vaginal delivery in primiparous women may predict an increased risk of having UI 5 years after delivery. UUI adversely affected women's emotional health, especially in those undergoing cesarean section.

Midurethral tapes have shown favorable clinical outcomes for treating stress urinary incontinence (SUI), but the effects of outside-in transobturator midurethral sling procedures (TOT) on women’s sexual function are unclear. We hypothesized that TOT might improve sexual function in women with SUI and therefore conducted this study to investigate sexual function alteration among women who underwent TOT for urodynamic stress incontinence (USI). From November 2009 to October 2010, we recruited 102 women scheduled for correction of USI by TOT procedures in a tertiary hospital. In addition to urogynecologic history, pelvic examination, and urodynamic testing, participants were required to complete three validated questionnaires: Incontinence Impact Questionnaire (IIQ-7), Urogenital Distress Inventory (UDI-6), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Preoperative and postoperative results of these validated questionnaires were evaluated. Eighty-three patients comprising 57 sexually active and 26 sexually inactive patients participated in the 12-month evaluation. Of the 83 patients undergoing TOT, six (7.2 %) had postoperative SUI 12 months postoperatively. Both UDI-6 and IIQ-7 scores were significantly improved postoperatively. The total PISQ-12 score did not change significantly after surgery. Postoperatively, the individual incontinence-related items of the PISQ-12 improved, but climax with intercourse and negative emotional reactions during intercourse worsened (both with p

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug reaction. Although the severity-of-illness score (SCORTEN) has been proposed for toxic epidermal necrolysis (TEN) for 10 years, a prognostic score for DRESS is still lacking. To identify prognostic factors of DRESS patients during hospitalization in one medical health system in Taiwan. We retrospectively reviewed all patients with DRESS diagnosed by dermatologists in Chang Gung Memorial Hospital (CMGH) Health System from 2001 to 2010. To study prognostic factors, we collected data at early disease and maximal disease stages. 91 individuals, including 13 dead patients, were evaluated. Five independent prognostic factors of death were found: heart rate > 90/min, white blood cells >12,000/mm3 and respiratory rate >20/min (at early disease stage), coagulopathy and gastrointestinal bleeding (at maximal disease stage). In addition, systemic inflammatory response syndrome (SIRS) occurred at a much higher percentage among non-survivors throughout hospitalization. We found tachycardia, leukocytosis, tachypnea, coagulopathy, gastrointestinal bleeding and SIRS were associated with a poor outcome in DRESS patients. DRESS patients with persistent SIRS during hospitalization were also associated with a higher mortality risk. Early recognition and prompt intervention in these factors may improve outcome.

Background/PurposeIn 2005, a self-management program, based on the global budget system that met the criteria for reducing Cesarean delivery rates, was introduced to obstetric practices in Taiwan. The purpose of this study was to examine the impact of different national health policies on the Cesarean delivery rate at a tertiary hospital.MethodsWe constructed a Poisson regression model and conducted an interrupted time series analysis to detect the effects of the implementation of each health policy on Cesarean deliveries. We used data collected at two points before the implementation of the global budget system (GBS) policy (in 2001 and 2002), and at two points after the implementation of the hospital-based self-management (HBSM) policy (in 2005 and 2010). All monthly data were collected at these time points.ResultsBetween June 2001 and August 2010, the rate of improvement of vaginal birth after Cesarean section (VBAC) during Period 1 revealed that VBAC may have long-term effects (p

The incidence of chronic lymphocytic leukemia (CLL) in Taiwan is markedly lower than that in Western countries, but we have seen a drastically increasing trend. We explored this distinct incidence trend of CLL for Taiwanese. The epidemiologic data of CLL for Taiwanese and Caucasian Americans during 1986 to 2005 were obtained from the Taiwan National Cancer Registry and Surveillance, Epidemiology, and End Results Program, respectively. The individual effects of time period and birth cohort on the incidence trends were analyzed using an age-period-cohort model. Although there was a weak period effect corresponding to the increased applications of immunophenotyping in 1991 to 1995 in Taiwan, evidences suggested that the age-adjusted incidence rate of CLL for Taiwanese was continuously increasing during the 20-year period while that for Caucasian Americans remained steady. In addition, a much stronger birth-cohort effect was identified for Taiwanese but not for Caucasian Americans. This effect corresponded to the westernization of lifestyle in Taiwan since 1960. We conclude that, in addition to the ethnic difference of incidence, there is distinct increasing incidence trend of CLL in Taiwan. The strong birth-cohort effect underlying this increasing trend indicates that lifestyles and environmental factors may play a role in the development of CLL for Taiwanese.

Acute mountain sickness (AMS) is a pathophysiological symptom complex that occurs in high altitude areas. The AMS prevalence is reportedly 28% on Jade Mountain, the highest mountain (3952 m) in Taiwan. We conducted this study owing to the lack of annual epidemiological data on AMS in Taiwan. Between April 2007 and March 2008, 1066 questionnaires were completed by trekkers visiting Paiyun Lodge on Jade Mountain. Information in the questionnaire included demographic data, mountaineering experience, AMS history, and trekking schedule. Weather data were obtained from the Central Weather Bureau of Taiwan. The Lake Louise AMS score was used to record symptoms and diagnose AMS. The chi-square test or the Student t test was used to evaluate associations between variables and AMS. In our study, the AMS prevalence was 36%. It increased significantly at different rates at different locations on the Jade Mountain trail and varied significantly in different months. Rainy weather tended to slightly increase the incidence of AMS. A lower incidence of AMS was correlated with hig-altitude trekking experience or preexposure (p < 0.05), whereas a higher incidence of AMS was correlated with a prior history of AMS (p < 0.05). The trekkers with AMS were significantly younger, ascended faster from their residence to the entrance or to Paiyun Lodge, and ascended slower from the entrance to the Paiyun Lodge (p < 0.05), but the differences lacked clinical significance. No differences in the incidence of AMS based on blood type, gender, or obesity were observed. The most common symptom among all trekkers was headache, followed by difficulty sleeping, fatigue or weakness, gastrointestinal (GI) symptoms, and dizziness or lightheadedness. In conclusion, the AMS prevalence on Jade Mountain was 36%, varied by month, and correlated with trekking experience, preexposure, and a prior history of AMS. The overall presentation of AMS was similar to that on other major world mountains.

Frequent intrahepatic metastasis causes early tumor recurrence and dismaying prognosis of human hepatocellular carcinoma (HCC). We recently identified overexpression of stathmin1 (STMN1) in human HCC. This study was designed to elucidate the clinical and biological significance of overexpression of STMN1 in HCC. Expression of STMN1 was conducted by quantitative reverse transcription-polymerase chain reaction and immunoblotting assays on 58 pairs of HCC and para-tumor liver tissues from patients with HCC along with normal liver tissues as the controls. Association of STMN1 overexpression with tumor recurrence and prognosis was investigated by Kaplan-Meier cumulative survival and Cox Regression analyses. Roles of STMN1 in cell cycle, cell motility, and invasion were determined by in vitro assays. STMN1 overexpression in hepatoma was strongly associated with local invasion (P = 0.031), early recurrence (P = 0.002), and poor prognosis (P = 0.005), and was an independent indicator for tumor recurrence (P = 0.0045). STMN1 overexpression further identified subgroups of HCC patients with higher tumor recurrence and worse prognosis among HCC patients with early tumor stage (T1) or intermediate histological grades (G2 and G3), both of whom represent the majority of HCC patients receiving primary curative hepatectomy. Silencing STMN1 expression via RNA interference suppressed invasion activity, while ectopic expression of STMN1 enhanced cell invasion and caused polyploidy of cells. In conclusion, STMN1 overexpression could predict early tumor recurrence and poor prognosis, particularly at early stage of hepatoma. Overexpression of STMN1 promoted polyploidy formation, tumor-cell invasion, and intrahepatic metastasis, suggesting that STMN1 can be a target for anti-cancer therapy of human hepatoma.

Stress-induced phosphoprotein 1 (STIP1) has been recently identified as a released biomarker in human ovarian cancer. In addition, STIP1 secreted by human ovarian cancer cells has been shown to promote tumor cell proliferation by binding to ALK2 (activin A receptor, type II-like kinase 2) and activating the SMAD-ID3 signaling pathways. In this study, a total of 330 ovarian cancer tumor samples were evaluated for STIP1 expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. The quantification of immunoreactivity was accomplished by applying an immunohistochemical scoring system (histoscore). Patients with high-level STIP1 expression (histoscore ≥169) had a significantly worse survival (high STIP1, mean survival time = 76 months; low STIP1, mean survival time = 112 months; P

Hemoglobin variability in hemodialysis patients treated with erythropoiesis-stimulating agents has been used to evaluate mortality and comorbidity. Different outcomes have been reported in American and European hemodialysis patients. There are, however, few studies of the effects of hemoglobin variability in peritoneal dialysis patients.We investigated hemoglobin variability in 363 peritoneal dialysis patients over 2 years to evaluate mortality and the association with comorbidity, peritonitis, and hospitalization. The hemoglobin of all patients selected for the study had been monitored for at least 6 months (April 2008 to September 2008). We assessed hemoglobin variability as fluctuations from the target hemoglobin level (11-12.5 g/dL). We defined the following 6 patient groups on the basis of hemoglobin patterns: consistently low (11 g/dL), consistently target range (11-12.5 g/dL), consistently high (12.5 g/dL), low-amplitude fluctuation with low hemoglobin levels, low-amplitude fluctuation with high hemoglobin levels, and high amplitude fluctuation.Only 2% of patients maintained a stable hemoglobin level within the target range and 46.8% of patients exhibited consistently low hemoglobin levels. After 2 years of observation, there was no difference in mortality as assessed by Kaplan-Meier analysis. There were also no differences in peritonitis and hospitalization between the 6 groups. However, the length of hospital stay was longer in the high amplitude fluctuation group (p = 0.008).Hemoglobin variability does not predict mortality in peritoneal dialysis patients.

Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that—in vertebrates—over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations., This research was funded primarily by the European Research Council (ERC) under the European Union’s Horizon 2020 and Seventh Framework Program FP7 research and innovation programs (ERC-AdG-LS8-740041 to J.L.G.-S., ERC-StG-LS2-637591 to M.I., a Marie Sklodowska-Curie Grant (658521) to I.M. and a FP7/2007-2013-ERC-268513 to P.W.H.H.), the Spanish Ministerio de Economía y Competitividad (BFU2016-74961-P to J.L.G.-S., RYC-2016-20089 to I.M., BFU2014-55076-P and BFU2017-89201-P to M.I. and BFU2014-55738-REDT to J.L.G.-S, M.I. and J.R.M.-M), the ‘Centro de Excelencia Severo Ochoa 2013-2017’(SEV-2012-0208), the ‘Unidad de Excelencia María de Maetzu 2017-2021’(MDM-2016-0687), the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program FP7 under REA grant agreement number 607142 (DevCom) to J.L.G.-S., and the CNRS and the ANR (ANR16-CE12-0008-01) to H.E. O.B. was supported by an Australian Research Council Discovery Early Career Researcher Award (DECRA; DE140101962).