Abstract Functional outcome after acute ischemic stroke (AIS) varies widely, and existing prognostic scores may not capture complex relationships. We evaluated a diverse set of clinical characteristics and blood biomarkers with multiple machine learning models to predict 3-month functional outcome after AIS, and used explainable artificial intelligence to identify key drivers of performance. Models were trained on 506 patients aged 18–69 years with AIS enrolled at four stroke units in western Sweden. We compared extreme gradient boosting, multilayer perceptron (MLP), and L1- and L2-regularized logistic regression. Feature importance was assessed with Shapley additive global explanations. Of the 506 patients, 105 had an unfavorable outcome (modified Rankin Scale score > 2). All models showed high area under the curve (AUROC, 0.900–0.906). The MLP achieved the highest precision–recall performance (AUPRC, 0.773 ± 0.080) and sensitivity (0.655 ± 0.096), though with lower specificity (0.920 ± 0.035). Stroke severity (NIH Stroke Scale score) was the dominant predictor across models. Among biomarkers, brain-derived tau (BD-tau) was most informative, followed by inflammation-related plasma proteins. In conclusion, machine learning accurately predicted functional outcome after AIS. BD-tau and inflammation-related proteins contributed predictive information above stroke severity, suggesting a potential for blood biomarkers to enhance individualized prognostication after AIS.

Abstract Background and aims Symptomatic carotid stenosis (CS) (≥50%, NASCET) causes a high risk of stroke recurrence, which asymptomatic CS does not. We aimed to identify potential plasma protein biomarkers associated with preoperative ipsilateral ischemic stroke recurrence (PIISR) after presenting event and symptomatic status (SS), using broad proteomic profiling. Methods Prospective cohort study including 168 consecutive participants with CS: 139 symptomatic, of which 18 had a PIISR, and 29 asymptomatic. Relative levels of 5420 plasma proteins were analyzed using Olink Explore HT. Firth logistic regressions were used to estimate OR and 95% CI for proteins and outcomes. Since most PIISR preceded blood sampling (n=15), we adjusted for NfL (neuroaxonal injury biomarker) in multivariable regressions. For SS, multivariate analysis adjusted for CS degree and stroke >6 months before presenting event. Multiple-testing correction used the estimate of the effective multiplicity (Meff), with P 0.05/260=0.0002 considered significant and P<0.001 suggestive. Results Four proteins were suggestively associated with PIISR. For FAM167A and ING2 elevated levels increased the odds of recurrence (OR (95% CI): 5.1 (2.0-14.9) and 3.6 (1.6-9.1), respectively). For NPIPB6 and CA4 elevated levels decreased the odds of recurrence (0.2 (0.1 to 0.6) and 0.3 (0.2 to 0.7), respectively). Five proteins were suggestively associated with SS, one directly, namely ALPK2 (3.1 (1.6-6.8)), and four inversely: CD276 (0.1 (0.03-0.4), ADAMTS8 (0.2 (0.09-0.6)), ENPP1 (0.2 (0.05-0.5)) and GOLGA8F_G (0.4 (0.3-0.7)). Conclusions We identified novel candidate plasma protein biomarkers of CS PIISR and SS. Replication in other stroke cohorts and further investigations into the putative role of these proteins for CS are warranted. Conflict of interest Marie V. Le May: nothing to disclose. Björn Andersson: nothing to disclose. Kara Tai: nothing to disclose. Tara M. Stanne: nothing to disclose. Christina Jern: nothing to disclose. Elias Johansson: nothing to disclose.

INTRODUCTION:Despite modern secondary prevention the risk of recurrent vascular events in ischemic stroke remains substantial, and high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) are associated with vascular recurrence. This study aims to investigate whether other proteins in the inflammatory cascade could serve as better predictive biomarkers. PATIENTS AND METHODS:The discovery cohort comprised 559 ischemic stroke cases from SAHLSIS (age 18-69, median 58 years) with a median follow-up of 14.7 years. Acute-phase plasma levels of 65 inflammation-related proteins were assessed using the Olink Inflammation panel. Replication was sought using 502 cases from SAHLSIS2 (age 18-98, median 68 years) with a median follow-up of 3.6 years. Associations between proteins and recurrent major adverse cardiovascular events (MACE) and recurrent stroke were explored with Cox regression. For MACE in SAHLSIS, exploratory analyses stratified by etiologic subtype were performed. Analyses were adjusted for vascular risk factors and statin status. RESULTS:In SAHLSIS, S100A12 was independently associated with recurrent MACE (adjusted hazard ratio (HR), 1.27 [95% confidence interval 1.10-1.45] per doubling of protein level) and stroke (adjusted HR 1.21 [1.01-1.45]). In SAHLSIS2, the associations for S100A12 replicated (adjusted HR, recurrent MACE 1.25 [1.06-1.48] and stroke 1.35 [1.10-1.66]). Results from the exploratory analyses identified several proteins displaying subtype-specific associations. DISCUSSION:We identified S100A12 as a potential novel blood biomarker of vascular recurrence after ischemic stroke, and the results indicate that there are subtype-specific protein associations to recurrent MACE warranting further investigation.

The prevalence of type 1 diabetes (T1D) is increasing globally and is associated with severe complications, including an increased risk of fractures. This case-control study investigated whether young individuals with well-controlled, long-duration T1D have differences in bone mass and bone biomarkers in comparison with healthy matched controls. Fifty individuals, aged 15.0-17.9 years, with a T1D duration of at least 8 years and (mean ± SD) 10.6 ± 2.1 years were included, hence the participants had diabetes throughout most part of their puberty and growth spurt. The mean HbA1c since diabetes diagnosis was 56 ± 6 mmol/mol (7.3 ± 0.6 %). Bone mass was assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT). Clinical follow-up data were retrieved from the Swedish National Diabetes Registry. The control group comprised 50 healthy matched adolescents, aged 15.1-17.9 years. The groups were well-matched with no significant differences in age, sex, weight, height, body mass index and the self-reported physical activity. Total body less head aBMD and Z-scores were significantly lower in T1D individuals, p < 0.05. Total tibia density and trabecular density, by pQCT, were also lower in the T1D group, p < 0.05. There were no differences between the groups for parathyroid hormone, 25-hydroxyvitamin D, bone-specific alkaline phosphatase (BALP), intact procollagen type I N-propeptide (PINP), sclerostin, bioactive sclerostin and osteoprotegerin. However, individuals with T1D had reduced levels of C-terminal telopeptide of type I collagen (CTX) (p < 0.001) and nuclear factor κB ligand (a.k.a. RANKL) (p = 0.01), indicating altered regulation of osteoclasts. In conclusion, young individuals with well-controlled, long-duration T1D have subnormal bone mass accrual, impaired microstructure at several sites and suppressed RANKL-mediated osteoclastogenesis resulting in reduced bone resorption. Based on these findings, we suggest that bone health should be monitored in pediatric diabetes care to potentially intervene early in life in susceptible individuals to achieve optimal peak bone mass.

INTRODUCTION:Childhood overweight and obesity are emerging global health issues with potential implications for immune function. We aimed to investigate childhood body mass index (BMI) as a risk factor for later inflammatory bowel disease (IBD). METHODS:ABIS (Sweden) and MoBa (Norway) are population-based cohorts following participants prospectively from birth (1997-2009) until 2023. We retrieved anthropometric data at birth, 1, 3, and 7-8 years to examine the association of age-specific standardized BMI percentiles and categories (underweight, normal [reference), overweight, obesity) with later IBD. We also analyzed IBD risk according to BMI trajectories across ages. IBD diagnosis was identified in national health registries. Cohort-specific hazard ratios (aHRs) were adjusted for sociodemographics, parental BMI, IBD, and smoking and pooled using a random-effects model. RESULTS:Overall, among 54 890 children with 803 444 person-years of follow-up, we identified 246 IBD events. Eight-year-olds living with obesity had a 5-fold increased risk of ulcerative colitis (pooled aHR = 5.10; 95% CI , 1.51-17.27), but not a significantly increased risk of Crohn's disease (pooled aHR = 1.38; 95% CI , 0.24-7.98) and IBD overall (pooled aHR = 1.89; 95% CI , 0.71-5.04). Children with overweight or obesity at age 3 had no increased risk of IBD compared to normal-weight children (pooled aHR = 1.15, 95% CI , 0.74-1.77; and 1.05, 95% CI , 0.43-2.58, respectively). Early-life BMI trajectories were not consistently associated with IBD. CONCLUSION:In this Scandinavian birth cohort, 7-8 year-old children with obesity had an increased risk of developing ulcerative colitis later in life. Given the high prevalence of childhood obesity, this observation should be corroborated and possible mechanisms behind the association clarified.

Cutaneous leishmaniasis (CL) is the most prevalent type of leishmaniasis disease and causes skin lesions, mainly ulcers, on exposed parts of the body. The Americas, Mediterranean basin, Middle East, and Central Asia account for approximately 95% of all CL cases. Leishmania (L.) major and L. tropica are the most significant species causing CL. A better understanding of the molecular mechanisms of CL caused by Leishmania parasite species in patients' skin lesions may help inform intervention approaches. Using dual-color reverse transcriptase multiplex ligation-dependent probe amplification (dcRT-MLPA), we evaluated the expression of 144 host immune-related genes in lesions from CL patients infected with two Leishmania species, L. major and L. tropica, in Morocco and Iran, respectively. Distinct gene expression patterns were identified in the lesions of patients infected with L. major and L. tropica. The results revealed that L. tropica-infected patients had rather more significant gene expression than L. major-infected patients relative to healthy volunteers. However, CD14 and IFI6 (interferon alpha inducible protein 6), were two common genes expressed in the lesions of patients infected with L. major and L. tropica. Our analysis revealed that gene expression changes related to the IFN signaling pathway were significant in both lesion groups. This research advances our understanding of the host immune response to zoonotic and anthroponotic leishmaniasis and shows immune transcript signatures in the skin lesions of CL patients infected with L. major and L. tropica. These findings can inform further investigation into the processes underpinning immunity and immunopathology of CL caused by L. major and L. tropica.

Background: Intracerebral hemorrhage (ICH) accounts for 10%-15% of all stroke cases and is associated with a high risk of death and disability. Prior studies in ischemic stroke have demonstrated a less favorable outcome in women compared with men, but there is a paucity of data regarding differences in outcome by sex in ICH. The aim of the present study was to investigate possible sex differences in acute care and the 3-months follow-up of patients with ICH. Methods: Data were collected from the Swedish National Stroke Registry (Riksstroke). Demographic and baseline characteristics were collected, based on in-hospital data and data from 3-months follow-up. Results: Variables of interest were collected from 1,403 patients. Women (45.1%) were significantly older than men, with a mean age ± standard deviation of 77 ± 13years, versus 71 ± 14 years, p < 0.01. On admission, the ICH severity was similar in men and women. There was no significant association between sex and reception of neuroimaging or neurosurgery. Women were less likely to be treated in a stroke unit (80.8% vs. 85.3%, p = 0.03), or discharged to home (51.5% vs. 63.4%, p < 0.01). At 3-months follow-up, there were no sex-related differences regarding dependence, post-ICH self-reported depression, or case fatality. Conclusions: Women were less likely to be treated in a stroke unit, and were less often discharged to home. However, no significant differences in 3-month functional outcome or survival between men and women with ICH were found in this study.

Objectives: Stroke is a major cause of long-term disability and death worldwide. Several studies have shown that women in general have more severe symptoms at arrival to hospital and are less likely to return home and independent living. Our aim with the present study was to update previous results concerning sex differences in baseline characteristics, stroke management, and outcome in a population study from Sahlgrenska University Hospital, Gothenburg, Sweden. Methods: This study included patients with acute ischemic and hemorrhagic stroke in 2014 at Sahlgrenska University Hospital. All data were collected from The Swedish National Stroke Registry (Riksstroke). Results: The study population consisted of 1453 patients, with 46.7% females. Women were 5 years older than men. There was no sex difference in acute stroke severity. Frequency of revascularization was equal between men and women. The stroke mortality rate was the same between the sexes. At 3-months follow-up, women had a worse functional outcome and a higher frequency of depression and post-stroke fatigue. Conclusion: Our results show that there are no sex differences in management of acute stroke. However, the cause of worse functional outcome in women at 3-months follow-up, independent of other risk factors, is not clear and warrants further investigations.

Abstract Aims We investigated the 2 year rate of ischaemic stroke/transient ischaemic attack (IS) in patients with heart failure (HF) who were in sinus rhythm (HF‐SR) and aimed to develop a score for stratifying risk of IS in this population. Methods and results A total of 15 425 patients (mean age 71.5 years, 39% women) with HF‐SR enrolled in the Swedish Heart Failure Register were included; 28 815 age‐matched and sex‐matched controls, without a registered diagnosis of HF, were selected from the Swedish Population Register. The 2 year rate of IS was 3.0% in patients and 1.4% in controls. In the patient group, a risk score including age (1p for 65–74 years; 2p for 75–84 years; 3p for ≥85 years), previous IS (2p), ischaemic heart disease, diabetes, hypertension, kidney dysfunction, and New York Heart Association III/IV class (1p each) was generated. Over a mean follow‐up of 20.1 (SD 7.5) months, the cumulative incidences (per 1000 person‐years) of IS in patients with score 0 to ≥7 were 2.2, 5.3, 8.9, 13.2, 15.7, 20.4, 26.4, and 33.0, with hazard ratios for score 1 to ≥7 (with 0 as reference): 2.4, 4.1, 6.1, 7.2, 9.4, 12.2, and 15.3. The risk score performed modestly (area under the curve 63.7%; P = 0.4711 for lack of fit with a logistic model; P = 0.7062 with Poisson, scaled by deviance). Conclusions In terms of absolute risk, only 27.6% of patients had an annual IS incidence of ≤1%. To which extent this would be amenable to anticoagulant treatment remains conjectural. A score compiling age and specific co‐morbidities identified HF‐SR patients with increased risk of IS with modest discriminative ability.

Objective: Daily subcutaneous self-injection of GH is used worldwide to treat short stature in childhood; longitudinal data on the impact of this regimen on GH-uptake are lacking. Design: Children with/without GH-deficiency participating in clinical trials were followed prospectively ( s 8 times). Blood was sampled pre-GH-injection (dose GH(33)/GH(67) mu g/kg) and either every 30 min thereafter for 24 h (Experimental-setting; 59 GH-curves/15 children); or every 2 h thereafter for 16 h (Clinical-setting; 429 GHcurves/117 children). Pharmacokinetics were estimated by time T-max (h) of maximal GH-concentration (C-max , mU/L) and area under the curve for 16 h (AUC, mU/L * h). Results: In the Clinical-setting, median C-max was 71 mU/L and AUC was 534 mU/L * h, with coefficients of variation for intra-individual variation of 39% and 36%, respectively, and inter-individual variation of 44% and 42%, respectively. 43% of C-max and AUC variability was explained by GH-dose and proxies for injection depth (baseline GH-level, GH(peak) width, BMISDS). In the Experimental- versus Clinical-setting, 85% and 40% of GH-curves, respectively, reached zero-levels within 24 h. A longer duration was found following a more superficial GH-injection. Spontaneous GH-peaks were identified already 6 h after the GH-injection in about half of the curves of both GHD and non-GHD patients. Conclusion: Very broad intra-individual and inter-individual variability was found. A high GH-peak will optimize growth effects; the highest C-max was found after a deep injection of GH at the higher dose and concentration. In as many as 60% of the children, GH remained detectable in serum after 24 h; a constant GH-level will promote IGF-I and metabolic effects.

Objectives: Elevated blood pressure (BP) is common in acute ischemic stroke, but its effect on outcome is not fully understood. We aimed to investigate the association of baseline BP and BP change within the first day after stroke with stroke severity, functional outcome, and mortality. Methods: Patients admitted to hospital with acute ischemic stroke (IS) from 15 February 2005 through 31 May 2009 were consecutively included. Acute stroke severity and functional outcome at three and twelve months were investigated using multivariate regression analysis; the association between BP and all-cause mortality at one, three, and twelve was investigated by Cox proportional hazard regression and Kaplan-Meier survival curves. Results: A total of 799 patients (mean age 78.4 +/- 8.0, 48% men) were included. Higher decreases in systolic and mean arterial blood pressure (Delta SBP and Delta MAP) were associated with decreased 1-month mortality (Delta SBP: hazard ratio, HR: 0.981; 95% CI: 0.968-0.994; p = .005), 3-month mortality (Delta SBP: HR 0.989; 95% CI 0.981 -0.998; p-value .014), and twelve-month mortality (Delta SBP: HR 0.989; 95% CI 0.982 -0.996; p-value-003). Stroke severity was associated with. MAP (B coefficient -. 46, p-value.011). Higher SBP and MAP on admission were associated with better functional outcome at three (SBP: OR 0.987; 95% CI 0.978 -0.997; p-value.008 - MAP: OR 0.985; 95% CI 0.971 -1; p-value.046) and twelve (SBP: OR 0.988; 95% CI 0.979 0.998; p-value-015 - MAP: OR 0.983; 95% CI 0.968 -0.997; p-value.02) months. Conclusion: In this elderly population, higher BP on arrival to the emergency room (ER) and decrease in BP after the patients' arrival to the ward were associated with improved functional outcome and reduced mortality, respectively. These results may reflect a regulatory situation in which elevated initial blood pressure indicates adequate response to cerebral tissue ischemia while subsequent blood pressure decrease instead may be a consequence of partial, successful reperfusion.

OBJECTIVE:Growth hormone (GH) regulates both longitudinal growth and bone acquisition in children, and has profound metabolic effects. The aim was to investigate the association between proteomic biomarkers, body fat, nutrition and bone formation markers, and longitudinal growth in response to GH during the first year of treatment. The degree to which changes in these factors could explain variations in GH-dependent longitudinal growth and bone mineralization was also assessed. METHODS:The individualized GH dose trial included 128 short prepubertal children with either normal (non-GH-deficient) or reduced levels of GH secretion (GH-deficient) (mean age ± SD, 8.6 ± 2.6 years; 90 boys), i.e., with a broad range of GH-secretion and GH-responsiveness, receiving GH treatment (mean 43 μg/kg/day). Blood samples were taken and dual-energy X-ray absorptiometry (DXA) measured at baseline and 1 year of treatment. Step-wise multiple regression models were constructed including three steps with different independent variables added at each step to explain the variance in outcome variables (heightSDS, bone mineral content (BMC) and bone mineral density (BMD). Independent variables included in Step I were previously identified proteomic markers related to GH treatment response, bone formation markers (intact PINP, bone-specific alkaline phosphatase and osteocalcin), variables at treatment start (GH dose mU/kg/day, GH maximum secretion, and difference between child's current and mid-parental heightSDS). Step II explored the added influence of body composition data (body mass index or DXA). Step III explored the added influence of serum nutritional markers and hormones. RESULTS:Step I variables explained 71% of the variation in first year heightSDS gain, median (minimum-maximum) 0.8 (0.24-1.67); and the proportion explained rose to 73% following inclusion of step II variables and 75% following step III. Corresponding values for total body BMC were 58%, 78%, and 80%, respectively. Proportions fell by approximately 20% when BMC was adjusted for height; 33%, 57%, and 57% for steps I, II, and III, respectively. Corresponding values for total body BMD were 29%, 39%, and 45%, respectively. CONCLUSION:For total BMC, as much as 80% of the variation during the first year of GH treatment could be explained by proteomic biomarkers, body fat, nutrition and bone formation markers, whereas for height-adjusted BMC 57% could be explained. The inclusion of information about either body composition (fat/lean mass) or nutritional markers contributed with approximately 20%. The variation in heightSDS gain could be explained to 75%. Hence, information of fat or nutrition markers was needed for explaining the variation in bone acquisition to the same magnitude as explaining the variation in height response.

SummaryObjectivesGrowth hormone (GH) promotes longitudinal growth and bone modelling/remodelling. This study investigated the relationship between levels of bone formation markers and growth during GH treatment in prepubertal children with widely ranging GH secretion levels.MethodsThe study group comprised 113 short prepubertal children (mean age ± SD, 9·37 ± 2·13 years; 99 boys) on GH treatment (33·0 ± 0·06 μg/kg/day) for 1 year. Blood samples were taken at baseline and 1 and 2 weeks, 1 and 3 months, and 1 year after treatment start. Intact amino‐terminal propeptide of type I procollagen (PINP), bone‐specific alkaline phosphatase (BALP) and osteocalcin were measured using an automated IDS‐iSYS immunoassay system.ResultsIntact amino‐terminal propeptide of type I procollagen (PINP), BALP and osteocalcin, increased in the short‐term during GH treatment. PINP after 1 week (P = 0·00077), and BALP and osteocalcin after 1 month (P < 0·0001 and P = 0·0043, respectively). PINP levels at 1 and 3 months correlated positively, and osteocalcin levels at 1 week and percentage change after 1 month correlated negatively, with first year growth response. No significant correlations were found between BALP and first year growth. Multiple regression analysis showed that bone marker levels together with auxological data and insulin‐like growth factor binding protein‐3 explained the variation in first year growth response to 36% at start, 32% after 2 weeks and 48% at 3 months.ConclusionShort‐term increases in levels of the bone formation markers PINP, BALP and osteocalcin showed different temporal patterns, but all correlated with first year growth response during GH treatment. These markers may be a useful addition to existing prediction models for growth response.

BACKGROUND:Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML). METHODS:A total of 20 patients (mean age 76 years) were included within 5-10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed. RESULTS:Patients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann-Whitney test). CONCLUSIONS:Several CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML.

Background/Aim. Relatively few studies have investigated the association of prestroke glycemic control and clinical outcome in acute ischemic stroke (IS) patients, regardless of presence of diabetes mellitus (DM). The aim of this study was to investigate the importance of prestroke glycemic control on survival, stroke severity, and functional outcome of patients with acute IS. Methods. We performed a retrospective survival analysis of 501 patients with IS admitted to Sahlgrenska University Hospital from February 15, 2005, through May 31, 2009. The outcomes of interest were acute and long-term survival; the stroke severity (NIHSS) and the functional outcome, mRS, at 12 months. Results. HbA1c was a good predictor of acute (HR 1.45; CI, 1.09 to 1.93, P = 0.011) and long-term mortality (HR 1.29; CI 1.03 to 1.62; P = 0.029). Furthermore, HbA1c >6% was significantly correlated with acute stroke severity (OR 1.29; CI 1.01 to 1.67; P = 0.042) and predicted worse functional outcome at 12 months (OR 2.68; CI 1.14 to 6.03; P = 0.024). Conclusions. Our study suggests that poor glycemic control (baseline HbA1c) prior to IS is an independent risk factor for poor survival and a marker for increased stroke severity and unfavorable long-term functional outcome.

Background and Purpose— On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke. Methods— We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated ≤24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included. Results— The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0–2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705–1.488). Conclusions— Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01120301.

The process of growth and maturation of long (radius and ulna) and short (metacarpals and phalanges) bones of the hand (enchondroplasia) differs from that of the carpal cuboid bones (chondral osteogenesis). This study aimed to assess the impact of growth hormone (GH) on these two processes of bone maturation. Subjects of the study were 95 prepubertal children: 30 children with GH deficiency and 65 children with idiopathic short stature, aged 7.4 ± 1.9 y (mean ± SD) (trial registration number 98-0198-033). Bone maturation was assessed by the Greulich and Pyle method from X-rays obtained at the start and at 1 and 2 y of GH treatment, separately for carpals, long bones, and short bones, and was expressed as years of delay relative to chronological age. At GH start, the delay in bone maturation in the GH-deficient group was significantly greater for carpals (3.6 ± 1.3 y) than for long (3.0 ± 1.3 y) and short (1.7 ± 1.1 y) bones. The delay was nonsignificantly greater for carpal bones in GH-deficient subjects than in subjects with idiopathic short stature (3.6 ± 1.3 vs. 3.1 ± 1.1 y, respectively) and was normalized after 2 y of GH treatment. The dominant effect of GH was on chondral osteogenesis, with milder effect on enchondroplasia. A distinct delay in carpal and long-bone maturation, which normalizes during 2 y of GH treatment, was typical in GH-deficient children. Therefore, separate carpal bone assessment in bone age reading is needed.

OBJECTIVE:A high-throughput pharmaco-proteomic approach has previously been successfully used to identify lipoprotein biomarkers related to changes in longitudinal growth and bone mass in response to growth hormone (GH) treatment. The aim of this study was to identify protein markers involved in the diverse anabolic and lipolytic remodelling of body composition during GH treatment.DESIGN, PATIENTS AND MEASUREMENTS:The study population consisted of 128 prepubertal children receiving GH treatment. Thirty-nine were short as a result of GH deficiency, and 89 had idiopathic short stature (ISS). Serum protein expression profiles at study start and after 1 year of GH treatment were analysed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Body composition was analysed by dual-energy X-ray absorptiometry (DXA), reliably estimating muscle mass from appendicular (arms and legs) lean soft tissue mass (LST). DXA was also used to estimate appendicular bone mineral content (BMC) and fat mass for the total body.RESULTS:Specific protein expression patterns associated with GH response in different body compartments were identified. Among identified proteins, different isoforms of nutrition markers such as apolipoproteins (Apo) were recognized: Apo C-I, Apo A-II, serum amyloid A4 (SAA4) and transthyretin (TTR). In addition, unidentified peaks were associated with GH effects on specific body compartments.CONCLUSIONS:Our results suggest that unique protein markers are associated with remodelling of different body compartments during GH treatment, which in the future might be useful to optimize GH treatment not only with regard to longitudinal growth.

BACKGROUND:Cerebrovascular lesions are often associated with electrocardiographic (ECG) abnormalities. The main purpose of this work was to investigate the prognostic value of ECG abnormalities and/or elevated cardiac troponin (cTNT) on admission in patients with nontraumatic intracerebral hemorrhage (ICH).METHODS:Ninety-seven consecutive patients with ICH were included. The predictive value of ECG abnormalities and increased TNT on survival were evaluated using Cox proportional hazard model.RESULTS:The most frequently observed ECG abnormalities were the presence of a Q wave (39.6%), followed by prolonged QTc (>0.44 s; 35.4%), which was an independent predictor for long-term mortality (P = 0.019). No difference in QTc was observed between patients with right versus left ICH. Increased cTNT levels at admission had no prognostic value.CONCLUSION:Various ECG changes were common in patients presenting with an ICH, but only prolonged QTc was found to be an independent predictor of poor survival during follow-up after ICH.