Adaptation to photoperiod via dynamic neurotransmitter segregation.

Changes in the amount of daylight (photoperiod) alter physiology and behaviour1,2. Adaptive responses to seasonal photoperiods are vital to all organisms-dysregulation associates with disease, including affective disorders3 and metabolic syndromes4. The circadian rhythm circuitry is implicated in such responses5,6, yet little is known about the precise cellular substrates that underlie phase synchronization to photoperiod change. Here we identify a brain circuit and system of axon branch-specific and reversible neurotransmitter deployment that are critical for behavioural and sleep adaptation to photoperiod. A type of neuron called mrEn1-Pet17 in the mouse brainstem median raphe nucleus segregates serotonin from VGLUT3 (also known as SLC17A8, a proxy for glutamate) to different axonal branches that innervate specific brain regions involved in circadian rhythm and sleep-wake timing8,9. This branch-specific neurotransmitter deployment did not distinguish between daylight and dark phase; however, it reorganized with change in photoperiod. Axonal boutons, but not cell soma, changed neurochemical phenotype upon a shift away from equinox light/dark conditions, and these changes were reversed upon return to equinox conditions. When we genetically disabled Vglut3 in mrEn1-Pet1 neurons, sleep-wake periods, voluntary activity and clock gene expression did not synchronize to the new photoperiod or were delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing, we delineated a preoptic area-to-mrEn1Pet1 connection that was responsible for decoding the photoperiodic inputs, driving the neurotransmitter reorganization and promoting behavioural synchronization. Our results reveal a brain circuit and periodic, branch-specific neurotransmitter deployment that regulates organismal adaptation to photoperiod change.

[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation].

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

[Prognostic significance of DEK-NUP214 fusion gene in patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the dynamic change and clinical impact of DEK-NUP214 fusion gene in patients with acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Real-time quantitative polymerase chain reaction (RQ-PCR) and multicolor flow cytometry (FCM) were used to detect DEK-NUP214 gene expression and leukemia-associated immunophenotype (LAIP) in 15 newly diagnosed patients with positive DEK-NUP214 and receiving allo-HSCT from September 2012 to September 2017 at Peking University People's Hospital. The clinical outcome was analyzed using Kaplan-Meier survival curves. The impact of DEK-NUP214 expression was analyzed by log-rank test. Results: The subjects were followed-up with a median period of 657 (62-2 212) days. The median DEK-NUP214 expression level at diagnosis was 488% (274%-1 692%). Thirteen patients achieved complete remission before allo-HSCT. Thirteen patients had a residual DEK-NUP214 expression of 0.38% (0.029%-738.9%) before allo-HSCT. After allo-HSCT, DEK-NUP214 expression in 9/13 patients remained positive, which dropped by around 500 folds (5.7-5 663.0 folds) within a month post-transplant. Five patients died and 2 patients relapsed. The 3-year cumulative incidence of relapse in patients with positive DEK-NUP214 before transplant was 17.5%±11.3% and the 3-year overall survival was 60.5%±13.8%. After allo-HSCT, DEK-NUP214-negative patients had a better outcome. Conclusion: Quantitative monitor of DEK-NUP214 fusion gene could be a sensitive indicator of MRD status after allo-HSCT.

[Negative effects of donor specific anti-HLA antibody on poor hematopoietic recovery in patients with hematological diseases receiving haploidentical stem cell transplantation and rituximab for desensitization].

Objective: To investigate the incidences and risk factors of poor hematopoietic reconstitution (PHR) in patients with hematological diseases who underwent haploidentical allograft and were treated with rituximab for desensitization. Methods: Eight-three donor specific anti-HLA antibody (DSA, 2000 ≤MFI<10 000) positive patients who underwent haploidentical allograft were prospectively enrolled. Rituximab (375 mg/m2) was used for desensitization day-3 of conditioning regimen. Incidence and factors associated with PHR, including primary poor graft function and prolonged thrombocytopenia, were investigated. Results: There were 22 males and 61 females with a median age of 39(range: 1-65) years. Kaplan-Meier analysis showed that the 100 day cumulative incidences of neutrophil and platelet engraftment were 93.0% and 90.7%, respectively. The incidences of PHR were 14.7%. The 3-year relapse rate, non-relapse mortality (NRM) rate, event-free survival (EFS), leukemia-free survival (DFS) and overall survival (OS) were 6.5%, 15.1%, 70.8%, 79.4% and 79.4%, respectively. Patients with DSA MFI<5 000 (group A, n=46) experienced lower PHR (4.4% vs. 27.5%, P=0.003), and higher 3-year EFS (79.5% vs. 59.8%, P=0.020) compared to those with DSA MFI≥5 000 (group B, n=37). Multivariate analysis showed that DSA MFI≥5 000 was correlated with PHR (HR=6.101, P=0.021). PHR was associated with higher NRM (HR=4.110, P=0.026), lower DFS (HR=3.656, P=0.019) and OS (HR=3.656, P=0.019). Conclusion: Our data suggest that high pre-transplant DSA level is a risk factor for PHR in patients with hematological diseases receiving haploidentical allograft and rituximab for desensitization.

Effect of the duration of hospice and palliative care on the quality of dying and death in patients with terminal cancer: A nationwide multicentre study.

Early referral to hospice and palliative care (HPC) has significant benefits, but little is known about the appropriate time for referral. The purpose of this study of terminal cancer patients was to identify the most appropriate time for referral to HPC. Cross-sectional correlation study design was used. Participants were the bereaved relatives, who were the adult primary caregivers of the 1,829 terminal cancer patients who died 2-6 months previously in nationwide centres that provide HPC in Korea. A post-bereavement survey (Good Death Inventory, GDI) of family caregivers was used to assess patients' quality of dying and death. Relative to patients who were in HPC for 3-7 days and HPC for 8-21 days, those in HPC for 22-84 days had significantly higher quality of dying. Propensity score matched comparison between the group hospitalised for 22-84 days (n = 65) and the group hospitalised for 85 days or longer (n = 65) showed no significant differences in all the items on quality of dying and death. Our results suggest that terminal cancer patients who stay in HPC at least for 22 days have improved quality of dying and death.

Reproductive biology of female striped marlin Kajikia audax in the western Pacific Ocean.

Length and mass data for 1260 (536 females, 683 males, 41 sex unknown) striped marlin Kajikia audax were collected at the fish markets of Tungkang, Singkang and Nanfangao from July 2004 to September 2010. Of these samples, 534 gonads (236 females and 298 males) ranging from 95 to 206 cm in eye-to-fork length (LEF ) and 8 to 88 kg in round mass (MR ), were collected. Chi-square tests indicated sex ratios were homogeneous among months in 2004 and 2006-2008, but not in 2005, 2009 and 2010; and there were significant differences in sex ratio by size. The overall sex ratio (RS ) differed significantly from the expected 0·5. Kajikia audax are sexually dimorphic and the proportions of females increased with size between 140 and 210 cm LEF . Reproductive activity was assessed using a gonado-somatic index (IG ), external appearance of the gonads and histological examination and results indicated that the spawning season occurred from April to August with a peak in June to July. Based on histological observations and the distribution of oocyte diameters, K. audax are multiple spawners and their oocytes develop asynchronously. The estimated length-at-50% maturity (LEF50 ) was c. 181 cm (c. 4·8 years of age) for females. The proportion of reproductively active females in the spawning season with ovaries containing postovulatory follicles (0·27) indicated that they spawned every 3·7 days on average. The hydrated oocyte method estimated mean ± S.D. batch fecundity (FB ) to be 4·4 ± 2·02 million eggs; average relative fecundity was 53·6 ± 13·9 oocytes g-1 MR ; and the average annual fecundity was 181·3 ± 48·3 million eggs. The parameters estimated in this study are key information for stock assessments of K. audax in the north-western and central Pacific and will contribute to the conservation, management and sustainable yield of this species.

CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure. T cell homeostasis is critical to determine the potency of the GVT effect. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT. METHODS: In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 152 acute leukemia patients (ALL 83) after related HLA-haplotype- mismatched transplantation. The four SNP genotypes (-1661, -318, CT60 and +49) were determined by TaqMan SNP genotyping assays. RESULTS: ALL recipients of donors with +49 GG showed significantly lower OS (67.7 vs. 90.3 %, P = 0.015) than those with GA+AA. Multivariate analyses showed that +49 GG was an independent risk factor for OS (HR: 0.306, 95 % CI 0.111-0.842, P = 0.022) .23 ALL patients receiving mDLI showed significantly lower OS with +49 GG donor than those with GA+AA (30.0 vs. 83.1 %, P = 0.003). The haplotype analysis revealed only three haplotypes in the donor population -1661/-318/CT60/+49 i.e., ACGG, ACAA and GTGA, the frequencies were 64.1, 19.4 and 16.5 %, respectively. Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcomes as those with +49 GG and +49 GA+AA. CONCLUSION: In summary, the CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival in ALL after allo-HSCT from the related HLA-haplotype-mismatched donor, knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy.

Long-term survival of patients undergoing liver resection for very large hepatocellular carcinomas.

BACKGROUND: This study aimed to assess long-term survival after liver resection for huge hepatocellular carcinoma (HCC). METHODS: Patients with stage I-III HCC who underwent hepatectomy from 2002 to 2010 were identified retrospectively from prospective national databases and followed until December 2012. Patients were assigned into four groups according to tumour size: less than 3·0 cm (small), 3·0-4·9 cm (medium), 5·0-10·0 cm (large) and over 10·0 cm (huge). The primary endpoint was overall survival. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. RESULTS: A total of 11 079 patients with HCC (mean(s.d.) age 59·7 (12·0) years) were eligible for this study. Median follow-up was 72·5 months. Patients with huge HCC had the worst prognosis; overall survival rates for patients with small, medium, large and huge HCC were 72·0, 62·1, 50·8 and 35·0 per cent respectively at 5 years, and 52·6, 41·8, 35·8 and less than 20·0 per cent at 10 years (P < 0·001). Multivariable analysis showed that tumour size affected long-term survival (hazard ratio (HR) 1·31, 1·55 and 2·38 for medium, large and huge HCC respectively versus small HCC). Prognostic factors for huge HCC were surgical margin larger than 0·2 cm (HR 0·70; P = 0·025), poor differentiation (HR 1·34; P = 0·004), multiple tumours (HR 1·64; P < 0·001), vascular invasion (HR 1·52; P = 0·008), cirrhosis (HR 1·37; P = 0·013) and the use of nucleoside analogues (HR 0·69; P = 0·004). CONCLUSION: Huge HCCs have a worse prognosis than smaller HCCs after liver resection. A wide resection margin and antiviral therapy with nucleoside analogues may be associated with favourable long-term survival.

The impact of donor characteristics on the immune cell composition of second allografts in Chinese people.

BACKGROUND: The association of the donor characteristics with the immune cell composition in second allografts remains poorly understood. In this study, we investigated retrospectively the effects of the donor characteristics on the immune cell composition in second allografts. STUDY DESIGN AND METHODS: The immune cell composition in second allografts of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood harvests from 100 healthy donors (male, 47, female, 53; median age, 39 years old) who underwent a second-time donation were correlated with their donor characteristics. RESULTS: The median counts of CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, CD3(+) CD4(-) CD8(-) T cells and monocytes in allografts were 150·17 × 10(6) /kg, 82·57 × 10(6) /kg, 48·02 × 10(6) /kg and 24·97 × 10(6) /kg, respectively. Multivariate analysis showed that the number of lymphocytes and platelets pre-first collection of G-CSF mobilized blood (FM) was strongly associated with the number of total lymphocytes (for lymphocytes, P = 0·003; for platelets, P = 0·012), CD3(+) T cells (for lymphocytes, P = 0·009; for platelets, P = 0·004) and CD3(+) CD4(+) T cells (for lymphocytes, P = 0·035; for platelets, P = 0·004) in the second allograft. The donor's BMI was negatively related to the number of CD3(+) T cells (P = 0·022) and CD3(+) CD4(+) T cells (P = 0·026) in the second allograft. The donor weight was negatively associated with the number of CD3(+) CD4(-) CD8(-) T cells (P = 0·015) in the second allograft, while the pre-FM white blood cell count showed a positive correlation (P = 0·009). CONCLUSION: The results demonstrate the impact of the donor characteristics, including pre-FM platelet count and lymphocyte count, donor BMI and weight, on the immune cell composition in the second allograft.

Association between information provision and decisional conflict in cancer patients.

BACKGROUND: In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). PATIENTS AND METHODS: We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. RESULTS: More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30-0.97] and support (aOR, 0.53; 95% CI 0.33-0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26-0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27-0.77). CONCLUSION: This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.

Increased risk of ischaemic stroke among patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Inflammatory processes including autoimmune diseases which ignite endothelial dysfunction and atherosclerosis may promote development of cardiovascular diseases including ischaemic stroke. This study aimed to evaluate whether multiple sclerosis (MS) increases stroke risk. METHODS: A national insurance claim data set of 22 million enrollees in Taiwan was used to identify 1174 patients with MS and 4696 randomly selected age- and gender-matched controls from 1 January 1997 to 31 December 2010. Both cohorts were followed up until the occurrence of stroke or censor. Relevant covariates, such as age, gender, hypertension, diabetes, hyperlipidaemia, coronary artery disease, congestive heart failure and pregnancy, were included for further survey. The hazard ratio (HR) of stroke was assessed using a Cox proportional hazards regression model. RESULTS: After adjusting for the relevant covariates, the MS cohort had an increased risk of stroke (adjusted HR = 12.1 for 1 year; adjusted HR = 4.69 for 2-5 years) compared with the control cohort within 5 years of follow-up. Amongst participants without comorbidities, the MS cohort was still at a greater stroke risk than the control cohort [HR 4.93, 95% confidence interval (CI) 2.85-8.55]. Moreover, in the population aged ≤40, MS was associated with a significantly increased risk of stroke (HR 12.7, 95% CI 3.44-46.7). CONCLUSIONS: Multiple sclerosis is declared to be associated with an increased risk in developing stroke, which requires closer attention to this group of patients for stroke prevention, especially in the younger population.

Increased risk of ischaemic stroke amongst patients with chronic osteomyelitis: a population-based cohort study in Taiwan.

BACKGROUND AND PURPOSE: Inflammatory processes, which kindle endothelial dysfunction and atherosclerosis, may facilitate the development of cardiovascular disease, including ischaemic stroke. Evident stroke risk factors may not be identified in up to 40% of stroke patients, especially in the younger population. Inflammation remains to be established as a stroke risk factor. In this study, it was assessed whether chronic osteomyelitis (COM), an infectious disease with chronic inflammation, increases stroke risk. METHODS: A national insurance claim data set of 22 million enrollees in Taiwan was used to identify 18 509 patients with COM and 74 034 randomly selected age- and gender-matched controls for a follow-up period of 11 years starting 1 January 2000 and ending 31 December 2010. Stroke risk was analyzed using the Cox proportional hazards regression model. RESULTS: Comorbidities known to increase stroke risk, including hypertension, diabetes, hyperlipidemia, coronary heart disease and peripheral arterial disease, were more frequently noted in the COM group who had significantly greater stroke risk than the control cohort. Comparing only those without comorbidities, COM carried greater stroke risk than the control group [hazard ratio (HR) = 1.40, 95% confidence interval (CI) 1.22-1.62, P < 0.001]. The younger population carried even greater risk (age < 45, HR = 2.73, 95% CI 1.71-4.35; age > 65, HR = 1.16, 95% CI 1.02-1.31). CONCLUSIONS: This is the first report linking COM to an increased risk of developing stroke. Results suggest that COM is a significant stroke risk factor and call for closer attention to this group of patients for more rigorous stroke prevention, especially in the younger age group.

Landing limb posture in volleyball athletes with patellar tendinopathy: a pilot study.

The aims of this pilot study were to investigate how a novel sagittal plane kinematic measurement - the lower extremity contact angle (LECA) - relates to the landing dynamics of elite male volleyball athletes with and without patellar tendinopathy. The LECA was defined as the angle between the ground and the line connecting the center of pressure to the L5S1 marker. 18 athletes (9 with patellar tendinopathy and 9 with asymptomatic tendons) completed simulated spike jumps while instrumented for kinetic and kinematic analysis using a force platform and 3D motion analysis system. The patellar tendinopathic group demonstrated a significantly more acute LECA compared to the asymptomatic group (65.3°±2.2° vs. 69.1°±4.5°) and was the only kinematic or kinetic variable measured to discriminate between the 2 groups. The LECA further demonstrated less variability between trials than sagittal plane hip, knee, and ankle kinematics. Additionally, the LECA's - and not individual joints' - high correlation with the braking impulse ensures its predictive value for landing dynamics (r=- 0.890). The LECA has the potential to be a valuable tool to help assess jumping athletes in both injury prevention screening and as a variable that, if modified, could help alter the maladaptive behavior observed in symptomatic athletes.

HLA and KIR genotyping correlates with relapse after T-cell-replete haploidentical transplantation in chronic myeloid leukaemia patients.

BACKGROUND: Conflicting results have been reported regarding the predicative roles of alloreactive natural killer (NK) cells on the outcomes of transplantation in leukaemia patients. METHODS: We prospectively analysed the human leukocyte antigen (HLA) typing of donor-recipient pairs and the KIR typing of the donors in 97 CML patients to address the predictive roles of NK cells in relapse undergoing T-cell-replete haploidentical transplantation. RESULTS: Patients with class I ligands for the donor-inhibitory KIR gene exhibited decreased molecular and haematologic relapse rates (P=0.003 and P=0.015, respectively). There was a significantly reduced risk of molecular and haematologic relapse in patients with HLA-C1C2 or C2C2 who accepted donors with KIR2DS1 or in patients with HLA-Bw4 who accepted donors with KIR3DS1 ('recipient with relevant KIR ligand for donor-activating KIR', n=25), compared with the remaining transplants (n=72, P=0.009 and P=0.009, respectively). In addition, the presence of class I ligand in the recipients of donor-activating KIR contributed to a decreased relapse rate in patients lacking class I ligand in the recipient of donor-inhibitory KIR (P=0.04 and P=0.03, respectively). CONCLUSIONS: This study suggests that the presence of class I ligands for the donor-activating or donor-inhibitory KIR gene in the recipient might confer some protection against leukaemic relapse in T-cell-replete haploidentical transplantation.

Angle-resolved photoemission spectroscopy of tetragonal CuO: evidence for intralayer coupling between cupratelike sublattices.

We investigate by angle-resolved photoemission the electronic structure of in situ grown tetragonal CuO, a synthetic quasi-two-dimensional edge-sharing cuprate. We show that, in spite of the very different nature of the copper oxide layers, with twice as many Cu in the CuO layers of tetragonal CuO as compared to the CuO(2) layers of the high-T(c) cuprates, the low-energy electronic excitations are surprisingly similar, with a Zhang-Rice singlet dispersing on weakly coupled cupratelike sublattices. This system should thus be considered as a member of the high-T(c) cuprate family, with, however, interesting differences due to the intralayer coupling between the cupratelike sublattices.

Herpes zoster infection associated with acute coronary syndrome: a population-based retrospective cohort study.

BACKGROUND: Vasculopathy in varicella zoster virus (VZV) infection and a proposed association between herpes virus infection and atherosclerosis suggest a possible link between VZV infection and vascular thrombosis. OBJECTIVES: To determine the risk of acute coronary syndrome (ACS) associated with herpes zoster infection. METHODS: We used the Taiwan National Health Insurance Research Database to identify 57,958 patients newly diagnosed with herpes zoster between 1999 and 2010; 231,832 patients without herpes zoster were examined as the control group. Both cohorts were followed up until the end of 2010 to measure the incidence of ACS. Cox proportional-hazards regression and Kaplan-Meier analyses were used to measure the hazard ratios (HR) and the cumulative incidences of ACS, respectively. RESULTS: The incidence of ACS was 1·24-fold higher in the herpes zoster group than in the control group [36·8 vs. 29·6 per 10,000 person-years, 95% confidence interval (CI) 1·16-1·33]. After adjusting for age, sex and comorbidities, the HR of ACS for the herpes zoster group compared with the control group was 1·15 (95% CI 1·07-1·24). Analysis by the time lag (≤ 3 months, ≤ 1 year, > 1 year) showed that the incidence of ACS remained significantly higher in the herpes zoster group than in the control group, with an adjusted HR of 1·10 (95% CI 1·02-1·19) after the 1-year follow-up period. The Kaplan-Meier survival curve showed that the risk of ACS was significantly higher in the herpes zoster group than in the control group (P < 0·001). CONCLUSION: Herpes zoster infection is associated with an increased risk of ACS.

Dehydration is an independent predictor of discharge outcome and admission cost in acute ischaemic stroke.

BACKGROUND AND PURPOSE: Our aim was to investigate the influence of admission dehydration on the discharge outcome in acute ischaemic and hemorrhagic stroke. METHODS: Between January 2009 and December 2011, 4311 ischaemic and 1371 hemorrhagic stroke patients from the stroke registry of Chang Gung healthcare system were analyzed. The eligible patients were identified according to inclusion/exclusion criteria. In total, 2570 acute ischaemic and 573 acute hemorrhagic stroke patients were finally recruited. According to the blood urea nitrogen (BUN) to creatinine (Cr) ratio (BUN/Cr), these patients were divided into dehydrated (BUN/Cr ≥ 15) and non-dehydrated (BUN/Cr < 15) groups. Demographics, admission costs and discharge outcomes including modified Rankin scale (mRS) and Barthel index (BI) were examined. Data were analyzed using multivariate analysis of two-stage least squares including logistic and linear regression. RESULTS: Acute ischaemic stroke with admission dehydration had higher infection rates (P = 0.006), worse discharge BI (62.8 ± 37.4 vs. 73.4 ± 32.4, P < 0.001, adjusted P < 0.001), worse mRS (2.7 ± 1.6 vs. 2.3 ± 1.5, P < 0.001, adjusted P = 0.009) and higher admission costs (2470.8 ± 3160.8 vs. 1901.2 ± 2046.8 US dollars, P < 0.001, adjusted P = 0.013) than those without dehydration. However, acute hemorrhagic stroke with or without admission dehydration showd no difference in admission costs (P = 0.618) and discharge outcomes (BI, P = 0.058; mRS, P = 0.058). CONCLUSION: Admission dehydration is associated with worse discharge outcomes and higher admission costs in acute ischaemic stroke but not in hemorrhagic stroke.

The association between chronic osteomyelitis and increased risk of diabetes mellitus: a population-based cohort study.

Chronic inflammation is a well-known risk factor for type 2 diabetes mellitus (T2DM). The influence of chronic osteomyelitis (COM), an inflammatory disease, on the risk of developing T2DM remains unknown. This study investigated the risk of developing T2DM among COM patients. Using a retrospective cohort study, we identified 20,641 patients with COM and 82,564 age- and sex-matched controls for comparison from the Taiwan National Health Insurance Database (NHIRD) from 1997 to 2010. We followed up the COM cohort and the comparison cohort to compare the incidences of diabetes (ICD-9-CM code 250) until the end of 2010 or until the patients were censored because of death or withdrawal from the insurance program. The diabetes risk was analyzed using the Cox proportional hazards regression model. The incidence of T2DM was 1.6-fold higher in the group of COM patients than in the comparison group (29.1 vs. 18.2 per 10,000 person-years). The COM patients exhibited a higher diabetes risk [adjusted hazard ratio (aHR) = 1.64, 95 % confidence interval (CI) = 1.44-1.87] after controlling for the baseline and comorbidities. Younger and higher income patients exhibited a higher COM-to-reference incidence rate ratio (IRR) for T2DM compared with that of their counterparts. We also observed an increased risk of T2DM in COM patients with comorbidities (aHR = 1.70, 95 % CI = 1.47-1.96) compared with that of their non-COM counterparts. This is the first study to report the association between COM and an increased risk of developing T2DM, particularly among younger and higher income patients.