Impact of telemedical management on hospitalization and mortality in heart failure patients with diabetes: a post-hoc subgroup analysis of the TIM-HF2 trial.

BACKGROUND: The TIM-HF2 study demonstrated that remote patient management (RPM) in a well-defined heart failure (HF) population reduced the percentage of days lost due to unplanned cardiovascular hospital admissions or all-cause death during 1-year follow-up (hazard ratio 0.80) and all-cause mortality alone (HR 0.70). Higher rates of hospital admissions and mortality have been reported in HF patients with diabetes compared with HF patients without diabetes. Therefore, in a post-hoc analysis of the TIM-HF2 study, we investigated the efficacy of RPM in HF patients with diabetes. METHODS: TIM-HF2 study was a randomized, controlled, unmasked (concealed randomization), multicentre trial, performed in Germany between August 2013 and May 2018. HF-Patients in NYHA class II/III who had a HF-related hospital admission within the previous 12 months, irrespective of left ventricular ejection fraction, and were randomized to usual care with or without added RPM and followed for 1 year. The primary endpoint was days lost due to unplanned cardiovascular hospitalization or due to death of any cause. This post-hoc analysis included 707 HF patients with diabetes. RESULTS: In HF patients with diabetes, RPM reduced the percentage of days lost due to cardiovascular hospitalization or death compared with usual care (HR 0.66, 95% CI 0.48-0.90), and the rate of all-cause mortality alone (HR 0.52, 95% CI 0.32-0.85). RPM was also associated with an improvement in quality of life (mean difference in change in global score of Minnesota Living with Heart Failure Questionnaire score (MLHFQ): - 3.4, 95% CI - 6.2 to - 0.6). CONCLUSION: These results support the use of RPM in HF patients with diabetes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01878630.

Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial.

BACKGROUND: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. METHODS: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. RESULTS: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. CONCLUSIONS: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. CLINICAL TRIAL REGISTRATION: NCT03021525.

Distinct clonal lineages and within-host diversification shape invasive Staphylococcus epidermidis populations.

S. epidermidis is a substantial component of the human skin microbiota, but also one of the major causes of nosocomial infection in the context of implanted medical devices. We here aimed to advance the understanding of S. epidermidis genotypes and phenotypes conducive to infection establishment. Furthermore, we investigate the adaptation of individual clonal lines to the infection lifestyle based on the detailed analysis of individual S. epidermidis populations of 23 patients suffering from prosthetic joint infection. Analysis of invasive and colonizing S. epidermidis provided evidence that invasive S. epidermidis are characterized by infection-supporting phenotypes (e.g. increased biofilm formation, growth in nutrient poor media and antibiotic resistance), as well as specific genetic traits. The discriminating gene loci were almost exclusively assigned to the mobilome. Here, in addition to IS256 and SCCmec, chromosomally integrated phages was identified for the first time. These phenotypic and genotypic features were more likely present in isolates belonging to sequence type (ST) 2. By comparing seven patient-matched nasal and invasive S. epidermidis isolates belonging to identical genetic lineages, infection-associated phenotypic and genotypic changes were documented. Besides increased biofilm production, the invasive isolates were characterized by better growth in nutrient-poor media and reduced hemolysis. By examining several colonies grown in parallel from each infection, evidence for genetic within-host population heterogeneity was obtained. Importantly, subpopulations carrying IS insertions in agrC, mutations in the acetate kinase (AckA) and deletions in the SCCmec element emerged in several infections. In summary, these results shed light on the multifactorial processes of infection adaptation and demonstrate how S. epidermidis is able to flexibly repurpose and edit factors important for colonization to facilitate survival in hostile infection environments.

Developmental dynamics of homoarginine, ADMA and SDMA plasma levels from birth to adolescence.

Guanidino compounds such as dimethylarginines (SDMA, ADMA) and L-homoarginine ((L-)hArg) can interfere with bioavailability and function of the main NO-donor L-arginine (L-Arg). High ADMA and SDMA but low L-hArg concentrations have been associated with cardio- and cerebrovascular events and mortality in adults. The role of guanidino compounds in paediatric patients remains less clear. We, therefore, compared guanidino compound levels in plasma samples of 57 individuals with chronic kidney disease (CKD) and 141 individuals without CKD from the age of 0 to 17 years, including patients with different comorbidities by correlation and regression analyses. We found highest hArg, SDMA and ADMA concentrations in neonates (Kruskal-Wallis, p < 0.001 for all). From the age of 1 year on, hArg levels increased, whereas SDMA und ADMA levels further decreased in children. SDMA and ADMA are higher in children with CKD independent of GFR (mean factor 1.92 and 1.38, respectively, p < 0.001 for both), and SDMA is strongly correlated with creatinine concentration in children with CKD (Spearman's rho 0.74, p < 0.001). We provide guanidino compound levels in a large sample covering all paediatric age groups for the first time. Our data can be used to assess the role of guanidino compounds such as hArg in disease states, i.e. cerebro- and cardiovascular disorders in childhood and adolescence.

Disentangling pharmacological and expectation effects in antidepressant discontinuation among patients with fully remitted major depressive disorder: study protocol of a randomized, open-hidden discontinuation trial.

BACKGROUND: Antidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence. METHODS: To disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be manipulated by varying verbal instructions using an open-hidden paradigm. Within the open trial arms, participants will receive full information about treatment, i.e., high expectation. Within the hidden trial arms, participants will be informed about a 50% chance of discontinuing versus remaining on their antidepressant, i.e., moderate expectation. A total of N = 196 participants will be randomly assigned to either of the four experimental groups: open discontinuation (OD; n = 49), hidden discontinuation (HD; n = 49), open continuation (OC; n = 49), or hidden continuation (HC; n = 49). Discontinuation symptom load during the 13-week experimental phase will be our primary outcome measure. Secondary outcome measures include discontinuation symptom load during the subsequent 39-week clinical observation phase, recurrence during the 13-week experimental period, recurrence over the course of the complete 52-week trial evaluated in a time-to-event analysis, and stress, anxiety, and participants' attentional and emotional processing at 13 weeks post-baseline. Blood and saliva samples will be taken as objective markers of antidepressant blood serum level and stress. Optional rsfMRI measurements will be scheduled. DISCUSSION: Until today, no study has explored the interplay of pharmacological effects and patients' expectations during antidepressant discontinuation. Disentangling their effects has important implications for understanding mechanisms underlying adverse discontinuation symptoms. Results can inform strategies to manage discontinuation symptoms and optimize expectations in order to help patients and physicians discontinue antidepressants more safely and effectively. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05191277), January 13, 2022.

Combined Short-Pulse and Directional Deep Brain Stimulation of the Thalamic Ventral Intermediate Area for Essential Tremor.

OBJECTIVE: Novel deep brain stimulation (DBS) systems allow directional and short-pulse stimulation to potentially improve symptoms and reduce side effects. The aim of this study was to investigate the effect of short-pulse and directional stimulation, in addition to a combination of both, in the ventral intermediate thalamus (VIM)/posterior subthalamic area (PSA) on tremor and stimulation-induced side effects in patients with essential tremor. MATERIALS AND METHODS: We recruited 11 patients with essential tremor and VIM/PSA-DBS. Tremor severity (Fahn-Tolosa-Marin), ataxia (International Cooperative Ataxia Rating Scale), and paresthesia (visual analog scale) were assessed with conventional omnidirectional and directional stimulation with pulse width of 60 µs and 30 µs. RESULTS: All stimulation conditions reduced tremor. The best directional stimulation with 60 µs reduced more tremor than did most other stimulation settings. The best directional stimulation, regardless of pulse width, effectively reduced stimulation-induced ataxia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. All new stimulation modes reduced occurrence of paresthesia, but only the best directional stimulation with 30 µs attenuated paresthesia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. The best directional stimulation with 30 µs reduced tremor, ataxia, and paresthesia compared with conventional stimulation in most patients. Correlation analyses indicated that more anterior stimulation sites are associated with stronger ataxia reduction with directional 30 µs than with conventional 60 µs stimulation. CONCLUSION: Directional and short-pulse stimulation, and a combination of both, revealed beneficial effects on stimulation-induced adverse effects.

Diabetes, Glycated Hemoglobin (HbA1c), and Neuroaxonal Damage in Parkinson's Disease (MARK-PD Study).

BACKGROUND: Diabetes is associated with incidence and prevalence of Parkinson's disease (PD). Furthermore, glycated hemoglobin (HbA1c) levels have been linked with motor function and progression. OBJECTIVES: We evaluated the relationship between prevalent diabetes and HbA1c levels with serum neurofilament light chain (NfL) levels as marker of neuroaxonal damage. METHODS: NfL concentrations were analyzed with Simoa in serum of 195 PD patients with available HbA1c values. Motor (MDS-UPDRS III, Hoehn & Yahr [H&Y]) and cognitive (Montreal Cognitive Assessment [MoCA]) function was assessed and vascular comorbidities were documented from medical records. RESULTS: PD patients with prevalent diabetes had higher serum NfL levels and lower MoCA scores independent of age, body mass index (BMI), and vascular risk factors. Furthermore, diabetes was associated with higher H&Y stages in unadjusted and age/BMI-adjusted models. Higher HbA1c levels were associated with increased NfL in unadjusted and age/BMI-adjusted models. CONCLUSIONS: In PD patients, diabetes and high HbA1c are associated with increased neuroaxonal damage and cognitive impairment. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Serum neurofilament light chain and postural instability/gait difficulty (PIGD) subtypes of Parkinson's disease in the MARK-PD study.

The PIGD (postural instability / gait difficulty) subtype of Parkinson´s disease (PD) is associated with faster cognitive and motor decline. So far, there are no quantifiable biomarkers to aid clinical subtyping. Neurofilament light chain (NfL) is a highly specific marker of neuro-axonal damage and can be assessed in blood. Here, we investigated if serum NfL concentrations are associated with PIGD subtype and PIGD scores in PD patients at advanced disease stages. Furthermore, we evaluated if serum NfL is associated with motor and cognitive function assessed with MDS-UPDRS part III and Montreal cognitive assessment (MoCA). Serum NfL levels were analyzed with Single Molecule Assays (Simoa) in blood of 223 PD patients from the bioMARKers in Parkinson's Disease (MARK-PD) study. Serum NfL concentrations were higher in PIGD patients independent of age, sex and disease duration. In linear regression analysis, serum NfL levels were associated with MoCA, MDS-UPDRS III and PIGD scores in unadjusted models, but remained significant after adjustment only with PIGD scores. In conclusion, increased serum NfL levels were associated with PIGD subtype and PIGD scores in patients with advanced PD.

Ten Years of Improving Acute Stroke Management in a Metropolitan Area: A Population-Based Quantification of Quality Indicators.

BACKGROUND AND PURPOSE: Rapid access to acute stroke treatment improves clinical outcomes in patients with ischemic stroke. We aimed to shorten the time to admission and to acute stroke treatment for patients with acute stroke in the Hamburg metropolitan area by collaborative multilevel measures involving all hospitals with stroke units, the Emergency Medical Services (EMS), and health-care authorities. METHODS: In 2007, an area-wide stroke care quality project was initiated. The project included mandatory admission of all stroke patients in Hamburg exclusively to hospitals with stroke units, harmonized acute treatment algorithms among all hospitals, repeated training of the EMS staff, a multimedia educational campaign, and a mandatory stroke care quality monitoring system based on structured data assessment and quality indicators for procedural measures. We analyzed data of all patients with acute stroke who received inhospital treatment in the city of Hamburg during the evaluation period from the quality assurance database data and evaluated trends of key quality indicators over time. RESULTS: From 2007 to 2016, a total of 83,395 patients with acute stroke were registered. During this period, the proportion of patients admitted within ≤3 h from symptom onset increased over time from 27.8% in 2007 to 35.2% in 2016 (p < 0.001). The proportion of patients who received rapid thrombolysis (within ≤30 min after admission) increased from 7.7 to 54.1% (p < 0.001). CONCLUSIONS: Collaborative stroke care quality projects are suitable and effective to improve acute stroke care.

Validation of the German eHealth impact questionnaire for online health information users affected by multiple sclerosis.

BACKGROUND: Persons with multiple sclerosis (MS) are confronted by an overwhelming amount of online health information, which can be valuable but also vary in quality and aim. Therefore, it is of great importance for developers and providers of eHealth information to understand its impact on the users. The eHealth Impact Questionnaire (eHIQ) has been developed in the United Kingdom to measure the potential effects of health and experimental information websites. This contains user's general attitudes towards using the internet to gain health information and attitudes towards a specific health related website. The self-complete questionnaire is divided into two independently administered and scored parts: the 11-item eHIQ part 1 and the 26-item eHIQ part 2. This study aimed to validate the psychometric properties of the German version of the eHealth Impact Questionnaire (eHIQ-G). METHODS: 162 people with multiple sclerosis browsed one of two possible websites containing information on MS and completed an online survey. Internal consistency was assessed by Cronbach's alpha and structural validity by Confirmatory Factor Analysis. Construct validity was examined by assessing correlations with the reference instruments eHealth Literacy Questionnaire and the General Self-Efficacy Scale measuring related, but dissimilar constructs. Moreover, we investigated the mean difference of the eHIQ-G score between the two websites. Data were analyzed using SPSS and AMOS software. RESULTS: The eHIQ-G subscales showed high internal consistency with Cronbach's alpha from 0.833 to 0.885. The 2-factor model of eHIQ part 1 achieved acceptable levels of goodness-of-fit indices, whereas the fit for the 3-factor model of eHIQ part 2 was poor and likewise for the alternative modified models. The correlations with the reference instruments were 0.08-0.62 and as expected. Older age was related with lower eHIQ part 1 score, whereas no significant effect was found for education on eHIQ part 1. Although not significant, the website 'AMSEL' reached higher mean scores on eHIQ part 2. CONCLUSIONS: The eHIQ-G has good internal consistency, and sufficient structural and construct validity. This instrument will facilitate the measurement of the potential impact of eHealth tools.

Mandibular condyle morphology among patients with mucopolysaccharidosis: An observational study of panoramic radiographs.

BACKGROUND: Mucopolysaccharidoses (MPS) are a group of rare metabolic diseases characterized by a wide spectrum of symptoms including progressive condylar resorption. AIM: The aim of this study was to quantify the severity of condylar involvement in MPS I individuals in comparison with a group of non-MPS individuals and to describe how condylar changes may vary among the different types of MPS. DESIGN: Fifty panoramic radiographs of MPS patients (13.4 ± 6.2 years) with MPS I (n = 14), MPS II (n = 2), MPS IV (n = 8) and MPS VI (n = 2) were compared with forty panoramic radiographs of non-MPS individuals. The severity of condylar resorption was evaluated using a qualitative score (grades 0-3) and using the ratio of condylar height to ramus height (CH: RH). RESULTS: All MPS I and VI individuals showed pronounced bilateral degenerative condylar resorption. In contrast, individuals with MPS II and IV exhibited heterogeneous findings. The quantification of condylar height to ramus height revealed that CH: RH was significantly decreased in MPS I as compared to that of non-MPS individuals (P < .001). In contrast, the CH: RH ratios of MPS II and IV showed great variability. CONCLUSION: Mucopolysaccharidoses subtypes differ with regard to the severity of condylar resorption.

Sphingosine-1-Phosphate, Motor Severity, and Progression in Parkinson's Disease (MARK-PD).

BACKGROUND: Treatment with sphingosine-1-phosphate (S1P) agonists confers neuroprotective effects in animal models of Parkinson's disease (PD). OBJECTIVES: We assessed the association of serum S1P levels with motor and cognitive symptoms in patients with PD. METHODS: S1P concentrations were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in serum of 196 PD patients and in 196 age- and sex-matched controls. Motor (Unified Parkinson's disease rating scale III [UPDRS III], Hoehn and Yahr) and cognitive (Montreal Cognitive Assessment [MoCA]) function were assessed at baseline. Follow-up data was available from 64 patients (median [interquartile range], 513 [381-677] days). RESULTS: S1P levels were lower in PD patients compared with controls, that is 1.75 (1.38-2.07) and 1.90 (1.59-2.18) µmol/L, respectively (P = 0.001). In PD patients, lower S1P concentrations were associated with higher UPDRS III scores and Hoehn and Yahr stage. In the follow-up cohort, S1P concentrations below the median were associated with faster motor decline (hazard ratio: 4.78 [95% CI, 1.98, 11.50]), but not with cognitive worsening. CONCLUSIONS: Our observations reveal an association of S1P with PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Trimethyllysine, vascular risk factors and outcome in acute ischemic stroke (MARK-STROKE).

Trimethyllysine (TML) is involved in the generation of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO) by gut microbiota. In clinical studies, elevated TML levels predicted major adverse cardiovascular events (MACE) in patients with acute or stable coronary artery disease (CAD). In contrast to cardiovascular patients, the role of TML in patients with acute cerebral ischemia is unknown. Here, we evaluated circulating TML levels in 374 stroke patients from the prospective biomarkers in stroke (MARK-STROKE) study. Compared with 167 matched healthy controls, acute ischemic stroke patients had lower median TML plasma concentrations, i.e. 0.71 vs. 0.47 µmol/L (p < 0.001) and this difference persisted after adjusting for age and sex. TML plasma concentrations were associated with age, serum creatinine, glucose, cholesterol and lysine. Patients with prevalent arterial hypertension, atrial fibrillation or a history of myocardial infarction had increased TML levels, but this observation was not independent of age, sex and GFR. In 274 patients, follow-up data were available. During a median follow-up of 284 [25th-75th percentile: 198, 431] days, TML was not associated with incident MACE (stroke, myocardial infarction, death). In summary, our data suggests a different role of TML in acute ischemic stroke compared with CAD patients.

The ability of the eating assessment tool-10 to detect penetration and aspiration in Parkinson's disease.

PURPOSE: Dysphagia is common in patients with Parkinson's disease (PD) and often leads to pneumonia, malnutrition, and reduced quality of life. This study investigates the ability of the Eating Assessment Tool-10 (EAT-10), an established, easy self-administered screening tool, to detect aspiration in PD patients. This study aims to validate the ability of the EAT-10 to detect FEES-proven aspiration in patients with PD. METHODS: In a controlled prospective cross-sectional study, a total of 50 PD patients completed the EAT-10 and, subsequently, were examined by Flexible Endoscopic Evaluation of Swallowing (FEES) to determine the swallowing status. The results were rated through the Penetration-Aspiration Scale (PAS) and data were analyzed retrospectively. RESULTS: PAS and EAT-10 did not correlate significantly. Selected items of the EAT-10 could not predict aspiration or residues. 19 (38%) out of 50 patients with either penetration or aspiration were not detected by the EAT-10. The diagnostic accuracy was established at only a sufficient level (AUC 0.65). An optimal cut-off value of ≥ 6 presented a sensitivity of 58% and specificity of 82%. CONCLUSIONS: The EAT-10 is not suited for the detection of penetration and aspiration in PD patients. Therefore, it cannot be used as a screening method in this patient population. There is still a need for a valid, simple, and efficient screening tool to assist physicians in their daily diagnostics and to avoid clinical complications.

Low homoarginine/SDMA ratio is associated with poor short- and long-term outcome after stroke in two prospective studies.

BACKGROUND: Guanidino compounds, including asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine (hArg), have been associated with cardio- and cerebrovascular events and risk. We aimed to study if low hArg/ADMA and hArg/SDMA ratios are associated with mortality and outcome after stroke. METHODS: In two prospective cohorts of acute stroke patients from Germany and the UK, we analyzed hArg, ADMA, and SDMA to determine hArg/ADMA and hArg/SDMA ratios. The guanidino compound levels were associated with mortality, adverse events, and neurological impairment, i.e., National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). RESULTS: During 7.4 years, high hArg/ADMA and hArg/SDMA ratios were both associated with a reduction in all-cause mortality in patients with ischemic stroke in a UK stroke cohort (hArg/ADMA: hazard ratio (HR) 0.75 [95% confidence interval (CI) 0.62-0.92]; n = 394; P = 0.006; hArg/SDMA: HR 0.68 [0.54-0.85]; n = 394; P = 0.001). In a German stroke cohort, patients with high hArg/SDMA ratio experienced fewer adverse events compared with those with low hArg/SDMA ratios within 30 days after stroke (HR 0.73 [0.57-0.92]; n = 135; P = 0.009), whereas hArg/ADMA was not predictive. Furthermore, hArg/SDMA ratios inversely correlated with the degree of neurological impairment (NIHSS) (r = - 0.27; P = 0.001; n = 138). Lower hArg/SDMA ratios were also found in dependent (mRS 3-6) compared with independent patients (mRS < 3; P = 0.007; n = 138), whereas hArg/ADMA did not. CONCLUSION: These results from two prospective stroke studies reveal that hArg/SDMA ratio could prove a valuable blood-based biomarker to discriminate patients with poor short- and long-term outcome, increased neurological impairment, and severe disability after stroke.

Course of cervical intraepithelial neoplasia diagnosed during pregnancy.

PURPOSE: Management of high-grade cervical intraepithelial neoplasia [CIN grade 2 or 3 (CIN2-3)] diagnosed during pregnancy is controversial. Monitoring with colposcopy and cytology every 8-12 weeks is advised by the most current guidelines. STUDY DESIGN: This study analyzes the course of disease in pregnant women with abnormal cytologies or clinically suspicious cervixes. RESULTS: In total, 139 pregnant women, at a median age of 31 years (range 19-49), treated at the Colposcopy Unit of the University Medical Center Hamburg-Eppendorf between 2011 and 2017 were identified. During pregnancy, at least one biopsy was performed on 70.5% of patients. In 84.7% of cases, CIN2-3 (CIN2 n = 14 (14.3%), CIN3 n = 69 (70.4%)) was detected, 7.1% (n = 7) of women were diagnosed with CIN1, while no dysplasia was found in 8.2% (n = 8) of cases. No interventions were necessary during pregnancy. Despite explicit invitation, only 72.3% of women with CIN2-3 attended postpartal consultations. While 61.7% showed persistent lesions, 5% were diagnosed with CIN1 and 33.3% with complete remission. During pregnancy, 68.7% of women with prepartal CIN2-3 were tested for HPV infection. Later, 49.1% were followed up postpartally by means of HPV testing and histology. HPV clearance was observed in 36.4% of women with complete histological remission. Postpartum conization was performed on 44.6% of patients with prepartal CIN2-3 diagnosis. CIN2-3 was histologically confirmed in 97.3% cases. Progression from persistent CIN3 to microinvasive carcinoma was observed in a single case. CONCLUSIONS: High-grade CIN lesions, diagnosed during pregnancy, show a high rate of regression postpartum; whereas, progression to carcinoma is rare. Close and continuous monitoring rarely has any therapeutic consequences. Compliance for postpartal follow-up needs to be improved.

Obstructive sleep apnea and craniofacial appearance in MPS type I-Hurler children after hematopoietic stem cell transplantation.

OBJECTIVES: Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder characterized by severe multi-systemic organ manifestations including obstructive sleep apnea syndrome (OSAS). Hematopoietic stem cell transplantation (HSCT) is the treatment of choice in severe MPS I (MPS IH, Hurler syndrome). However, the effect of HSCT on OSAS in MPS IH still remains unclear. The purpose of this study was to analyze respiratory patterns during sleep following HSCT in MPS IH children and to relate these findings to craniofacial abnormalities. METHODS: Overnight polysomnographies of nine MPS IH children (mean age: 8.2 years) previously treated with HSCT were retrospectively analyzed. Magnetic resonance images of the head were assessed with regard to soft and hard tissue abnormalities of the upper respiratory tract. RESULTS: The mean apnea hypopnea index (AHI) was 5.3 events/h (range, 0.3-12.2), and the majority of apnea/hypopneas were obstructive. Whereas two patients had severe OSAS (AHI > 10) and two moderate OSAS (5 > AHI < 10), five patients had no evidence of OSAS (AHI < 2.0). Donor cell chimerism was significantly lower in MPS IH patients with OSAS as compared to patients without OSAS (p < 0.001). The upper airway space and the maxilla were significantly smaller and the adenoids larger in MPS IH patients with OSAS as compared to those of non-OSAS patients. CONCLUSION: OSAS was only observed in MPS IH patients with graft failure or low donor cell chimerism. Conversely, successful HSCT seems to ameliorate adenoid hyperplasia and maxillary constriction in MPS IH patients and thereby minimizes the risk of OSAS at least at younger ages.

Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival.

BACKGROUND: Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular and immune function. NO is generated by nitric oxide synthases (NOS) from L-arginine. Cellular L-arginine uptake is inhibited by symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NOS. Increased inhibitor blood concentrations lead to reduce NO bioavailability. The aim of this study was to determine whether plasma concentrations of SDMA and ADMA are markers for sepsis survival. METHOD: This prospective, single center study involved 120 ICU patients with sepsis. Plasma SDMA and ADMA were measured on admission (day 1), day 3 and day 7 by mass spectrometry together with other laboratory markers. The sequential organ failure assessment (SOFA) score was used to evaluate sepsis severity. Survival was documented until day 28. Groups were compared using the Mann-Whitney U test, chi-squared test or non-parametric analysis of variance (ANOVA). Mortality was assessed using Kaplan-Meier curves and compared using the log-rank test. Specific risk groups were identified using a decision tree algorithm. RESULTS: Median plasma SDMA and ADMA levels were significantly higher in non-survivors than in survivors of sepsis: SDMA 1.14 vs. 0.82 µmol/L (P = 0.002) and ADMA 0.93 vs. 0.73 µmol/L (P = 0.016). ANOVA showed that increased plasma SDMA and ADMA concentrations were significantly associated with SOFA scores. The 28-day mortality was compared by chi-square test: for SDMA the mortality was 12% in the lower, 25% in the intermediate and 43% in the 75th percentile (P = 0.018); for ADMA the mortality was 18-20% in the lower and intermediate but 48% in the 75th percentile (P = 0.006). The highest mortality (61%) was found in patients with plasma SDMA > 1.34 together with ADMA levels > 0.97 µmol/L. CONCLUSIONS: Increased plasma concentrations of SDMA and ADMA are associated with sepsis severity. Therefore, our findings suggest reduced NO bioavailability in non-survivors of sepsis. One may use individual SDMA and ADMA levels to identify patients at risk. In view of the pathophysiological role of NO we conclude that the vascular system and immune response are most severely affected when SDMA and ADMA levels are high.

Health-related quality of life after combined liver and kidney transplantation in children.

While reduced HRQOL following isolated organ transplantation has been previously reported, there are no data in the context of children following CLKT. Twenty-three children who underwent CLKT at our institution were included in the study. The indication for CLKT was PH1 in 13 patients and ARPKD in 10 patients. Quantification of HRQOL was facilitated through the use of the PedsQL 4.0 Generic Core Scale. The results of the study were compared to healthy children and published data of children who had undergone LTx or KTx. The CLKT samples' child self-report showed good HRQOL. No statistically significant difference was found between the patients with PH1 and patients with ARPKD (P=.4). Compared to healthy children, a significant difference in the total scale score, the physical health score, and the school functioning was reported. HRQOL did not differ significantly when compared to patients following isolated LTx or KTx. To improve HRQOL after CLKT, a focus on patients' physical health, educational performances, and overall quality of life is crucial. Thus, coordinated medical care across disciplines and psychological and social support is essential to achieve this goal.