Association between anemia and vitamin D deficiency in German seniors : A retrospective data analysis.

BACKGROUND: Anemia and deficiency of vitamin D (VDD) are frequently seen in seniors and an association is suspected. Approximately one third of the German population is affected by VDD, with a rising prevalence among seniors. AIM: To analyze the association between anemia and VDD among German seniors aged ≥ 60 years. METHODS: Retrospective cross-sectional data analysis (n = 4008) in a nationwide working laboratory medical center (January-December 2019). Study parameters included amongst others: hemoglobin (Hb), calcifediol (25D) and calcitriol (1.25D), glomerular filtration rate (GFR) to assess the kidney disease outcomes quality initiative (KDOQI) state. The inclusion criteria were age ≥ 60 years, normal C­reactive protein (CRP) and leucocyte levels. RESULTS: The 25D was estimated in 4008 patients and 1.25D only in 411 patients. Mean age 75 years (± 8.61 years; 60-99 years) with 30.6% males; mean GFR 62 ml/min/1.73 m3 (± 22.74); 20% of patients were anemic, 35% were deficient for 25D (< 50 nmol/l), with men > women (p = 0.014). Linear regression analysis revealed a significant effect of 25D values < 30 nmol/l on hemoglobin in males of KDOQI I-III and females of KDOQI I-IV (R2 = 0.052; p = 0.005; and R2 = 0.124; p < 0.001, respectively). For 1.25D a weak but significant effect on hemoglobin independent of KDOQI was only seen in women (R2 = 0.200; p = 0.005). CONCLUSION: In this cohort deficiency of 25D and 1.25D was significantly associated with hemoglobin independent of renal function only in women but not in men.

Three Tesla magnetic resonance imaging detects oxalate osteopathy in patients with primary hyperoxaluria type I.

BACKGROUND: With declining kidney function and therefore increasing plasma oxalate, patients with primary hyperoxaluria type I (PHI) are at risk to systemically deposit calcium-oxalate crystals. This systemic oxalosis may occur even at early stages of chronic kidney failure (CKD) but is difficult to detect with non-invasive imaging procedures. METHODS: We tested if magnetic resonance imaging (MRI) is sensitive to detect oxalate deposition in bone. A 3 Tesla MRI of the left knee/tibial metaphysis was performed in 46 patients with PHI and in 12 healthy controls. In addition to the investigator's interpretation, signal intensities (SI) within a region of interest (ROI, transverse images below the level of the physis in the proximal tibial metaphysis) were measured pixelwise, and statistical parameters of their distribution were calculated. In addition, 52 parameters of texture analysis were evaluated. Plasma oxalate and CKD status were correlated to MRI findings. MRI was then implemented in routine practice. RESULTS: Independent interpretation by investigators was consistent in most cases and clearly differentiated patients from controls. Statistically significant differences were seen between patients and controls (p < 0.05). No correlation/relation between the MRI parameters and CKD stages or Pox levels was found. However, MR imaging of oxalate osteopathy revealed changes attributed to clinical status which differed clearly to that in secondary hyperparathyroidism. CONCLUSIONS: MRI is able to visually detect (early) oxalate osteopathy in PHI. It can be used for its monitoring and is distinguished from renal osteodystrophy. In the future, machine learning algorithms may aid in the objective assessment of oxalate deposition in bone. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

The other colon cancer: a population-based cohort study of appendix tumour trends and prognosis.

AIM: Appendiceal neoplasms are rare subtypes of colorectal tumours that mainly affect younger patients some 20 years earlier than other colon tumours. The aim of this study was to gain more insight into the histological subtypes of this rare disease and include cases previously excluded, such as mucinous neoplasia. METHOD: The cohort study included 1097 patients from the Munich Cancer Registry (MCR) diagnosed between 1998 and 2020. Joinpoint analysis was used to determine trend in incidence. Baseline demographic comparisons and survival analyses using competing risk and univariate/multivariate methods were conducted according to tumour histology: adenocarcinoma (ADENO), neuroendocrine neoplasia (NEN), mixed adeno-neuroendocrine carcinoma (MANEC), and low- (LAMN) and high-grade mucinous neoplasia (HAMN). RESULTS: Up to 2016 the number of cases increased significantly [annual per cent change (APC) = 6.86, p < 0.001] followed by a decline in the following years (APC = -14.82, p = 0.014; average APC = 2.5, p = 0.046). Comparison of all patients showed that NEN (48.4%) and mucinous neoplasms (11.6%) had a considerably better prognosis than ADENO (36.0%) and MANEC (3.0%, p < 0.0001). A multivariate analysis within the NEN and ADENO subgroups revealed that further histological classification was not prognostically relevant, while older age and regional tumour spread at diagnosis were associated with a poor prognosis. ADENO histology with high tumour grade and appendectomy only was also associated with poorer survival. CONCLUSION: Appendiceal neoplasms are histologically heterogeneous; however, this diversity becomes less relevant compared with the marked difference from cancers of the remaining colon. The previously observed increase in cases appears to be abating; fewer cases of appendicitis and/or appendectomies or changes in histopathological assessment may be behind this trend.

The multidimensional prognostic index in hospitalized older adults: practicability with regard to time needs.

BACKGROUND: Comprehensive Geriatric Assessment (CGA) is decisive in patient-centered medicine of the aged individual, yet it is not systematically used. AIM: The aim of this study was to provide precise practice-relevant time expenditure data for the Multidimensional Prognostic Index (MPI), a questionnaire-based frailty assessment tool. METHODS: MPI was determined in ninety older multimorbid adults in three geriatric departments (cohorts 1, 2 and 3). The time needed to perform the MPI (tnpMPI) was recorded in minutes. Follow-up data were collected after 6 months. RESULTS: The median tnpMPI was 15.0 min (IQR 7.0) in the total collective. In the last visited cohort 3, the median was 10.0 min and differed significantly from cohorts 1 and 2 with medians of 15.5 and 15.0 (p < 0.001). CONCLUSION: These findings indicate, that MPI, as a highly informative frailty tool of individualized medicine, can be performed in an adequately practicable time frame.

[Profiling of patients in a specialized geriatric outpatient clinic]. / Profilanalyse ambulanter Patienten einer geriatrischen Spezialsprechstunde.

BACKGROUND: In Germany geriatric outpatient care is predominantly done by family doctors and general practitioners (GP). There are regionally different concepts for additional specialized geriatric outpatient care but they have not yet been validated and established. Still, it remains unclear whether a geriatric patient has to be diagnosed rather in a specialized outpatient or inpatient setting. The aim of the present study is the profiling of geriatric outpatients to find key distinctions from geriatric patients that have to be admitted to hospital. METHODS: Retrospective data analysis of patients sent to a specialized geriatric outpatient clinic by their GP, compared with data of geriatric inpatients sent to hospital by their GP during the same time period. Study parameters comprised elements of the comprehensive geriatric assessment as well as results of routinely applied laboratory tests. RESULTS: Patients sent to the specialized geriatric outpatient clinic showed better results of functional assessments. Regression analysis: improvement of Barthel Index, GFR and total protein increased the chance of outpatient treatment. CONCLUSION: Early identification of geriatric patients who can be treated in a specialized outpatient setting would ease the burden for GPs by interdisciplinary cooperation and prevent cost-intensive readmissions to hospital.

Endurance-oriented training program with children and adolescents on maintenance hemodialysis to enhance dialysis efficacy-DiaSport.

OBJECTIVE: Pediatric patients spend significant time on maintenance hemodialysis (HD) and traveling. They are often not capable of participating in sports activities. To assess the effects of exercise training during HD on dialysis efficacy in children and adolescents, we set up a multi-center randomized controlled trial (RCT). METHODS: Patients on HD, age 6 to 18 years, were randomized either to 3× weekly bicycle ergometer training or to no training during HD for 12 weeks. Change in single-pool Kt/V (spKt/V) was the primary outcome parameter. RESULTS: We randomized 54 patients of whom 45 qualified (23 in the intervention and 22 in the waiting control group, 14.5 ± 3.01 years, 32 male and 13 female) for the intention-to-treat (ITT) population. Only 26 patients finished study per-protocol (PP). Training was performed for an average of 11.96 weeks (0.14-13.14) at 2.08 ± 0.76 times per week and for a weekly mean of 55.52 ± 27.26 min. Single-pool Kt/V was similar in the intervention compared to the control group (1.70 [0.33] vs. 1.79 [0.55]) at V0 and (1.70 [0.36] vs. 1.71 [0.51]) at V1; secondary endpoints also showed no difference in both ITT and PP analysis. No significant adverse events were reported. No bleeding or needle dislocation occurred in 1670 training sessions. CONCLUSIONS: Intradialytic bicycle training is safe, but does not improve dialysis efficacy and physical fitness. However, the study can be considered underpowered, particularly because of high dropout rates. Future studies need better strategies to increase motivation and compliance and other more effective/intensive exercise measures should be evaluated. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.Gov ( Clinicaltrials.gov identifier: NCT01561118) on March 22, 2012.

Role of a multidimensional prognosis in-hospital monitoring for older patients with prolonged stay.

OBJECTIVES: The Multidimensional Prognostic Index (MPI) is a prognostic tool-amongst others-validated for mortality, length of hospital stay (LHS) and rehospitalisation risk assessment. Like the Comprehensive Geriatric Assessment (CGA), the MPI is usually obtained at hospital admission and discharge, not during the hospital stay. The aim of the present study was to address the role of an additional CGA-based MPI measurement during hospitalisation as an indicator of "real-time" in-hospital changes. STUDY DESIGN AND MAIN OUTCOME MEASURES: Two-hundred consecutive multimorbid patients (128 M, 72 F, median age 75 (78-82)) admitted to an internal medicine ward of a German metropolitan university hospital prospectively underwent a CGA and a prognosis calculation using the MPI on admission and discharge. Seven to 10 days later, an intermediate assessment (IA) was performed for patients needing a longer stay. RESULTS: The median LHS was 10 (6-19) days. As expected, patients who received an IA had poorer prognosis as measured by higher MPI values (P = .037) and a worse functional status at admission than patients who had a shorter stay (P = .025). In case of prolonged hospitalisation, significant changes in the MPI were detected between admission and IA, both in terms of improvement and deterioration (P < .001). Different overtime courses were observed during prolonged hospitalisation according to the severity of prognosis (P < .001). CONCLUSION: A CGA-based MPI evaluation during hospitalisation can be used as an objective instrument to detect changes in multidimensional health course. Prompt identification of the latter may enable quick tailored interventions to ensure overall better outcomes at and after discharge.

Delivery room skin-to-skin contact for preterm infants-A randomized clinical trial.

AIM: To investigate the effects of 60 minutes delivery room skin-to-skin contact (DR-SSC) compared with 5 minutes visual contact (VC) on mother-child interaction (MCI), salivary cortisol, maternal depression, stress and bonding at 6 months corrected age. METHODS: A single-centre randomized controlled trial conducted in a German level III NICU. Eighty-eight preterm infants (25-32 weeks of gestational age) were randomized after initial stabilization to either 60 minutes DR-SSC or 5 minutes VC. Forty-five infants were allocated to DR-SSC, 43 to VC. RESULTS: Delivery room skin-to-skin contact dyads showed a higher quantity of maternal motoric (18 vs 15, P = .030), infant's vocal (7 vs 5, P = .044) and motoric (20 vs 15, P = .032) responses. Moreover, the combined score of maternal and infant responsive behaviour was higher (86 vs 71, P = .041) in DR-SSC dyads. DR-SSC mothers had lower risk of both, early postpartum depression (15% vs 45%, P = .003) and impaired bonding (Score 3 vs 5, P = .031). CONCLUSION: In addition to regular intermittent kangaroo mother care, DR-SSC promotes MCI and decreases risk of maternal depression and bonding problems. Thus, DR-SSC may have positive effects on preterm development.

The prognostic significance of geriatric syndromes and resources.

BACKGROUND: Geriatric syndromes (GS) do not fit into discrete disease categories and are often underdiagnosed in hospitalized older adults. Geriatric resources (GR) are also not routinely collected in clinical settings, although this may potentiate the beneficial effects of clinical decisions. The prognostic relevance of GS and GR has never been systematically evaluated through clinical tools developed for clinical decision purposes. AIM: To ascertain the impact of common GS and GR on patients' prognosis as assessed by means of the comprehensive geriatric assessment (CGA)-based Multidimensional Prognostic Index (MPI). METHODS: One hundred and thirty-five hospitalized patients aged 70 years and older underwent a CGA evaluation with calculation of the MPI on admission and discharge. Accordingly, patients were subdivided in low (MPI-1, score 0-0.33), moderate (MPI-2, score 0.34-0.66), and severe (MPI-3, score 0.67-1)-risk of mortality at 1 month and 1 year. Nine GR and 17 GS were identified and collected accordingly. RESULTS: A lower number of GS and a higher number of GR were shown to be highly significantly correlated with a lower MPI, as well as years of education, grade of care, and number of medications independent of age, sex and number of GS or GR. Underweight and obesity according to the BMI were significantly correlated to higher number of GS. Patients with more GR had a significantly higher chance of being discharged home. CONCLUSIONS: The MPI evaluation together with GS and GR in acute care for older patients should be encouraged to improve clinical decision-making.

Intravascular Cooling Device Versus Esophageal Heat Exchanger for Mild Therapeutic Hypothermia in an Experimental Setting.

BACKGROUND: Targeted temperature management is a standard therapy for unconscious survivors of cardiac arrest. To date, multiple cooling methods are available including invasive intravascular cooling devices (IVDs), which are widely used in the clinical setting. Recently, esophageal heat exchangers (EHEs) have been developed providing cooling via the esophagus that is located close to the aorta and inferior vena cava. The objective was to compare mean cooling rates, as well as differences, to target temperature during maintenance and the rewarming period of IVD and EHE. METHODS: The study was conducted in 16 female domestic pigs. After randomization to either IVD or EHE (n = 8/group), core body temperature was reduced to 33°C. After 24 hours of maintenance (33°C), animals were rewarmed using a target rate of 0.25°C/h for 10 hours. All cooling phases were steered by a closed-loop feedback system between the internal jugular vein and the chiller. After euthanasia, laryngeal and esophageal tissue was harvested for histopathological examination. RESULTS: Mean cooling rates (4.0°C/h ± 0.4°C/h for IVD and 2.4°C/h ± 0.3°C/h for EHE; P < .0008) and time to target temperature (85.1 ± 9.2 minutes for IVD and 142.0 ± 21.2 minutes for EHE; P = .0008) were different. Mean difference to target temperature during maintenance (0.07°C ± 0.05°C for IVD and 0.08°C ± 0.10°C for EHE; P = .496) and mean rewarming rates (0.2°C/h ± 0.1°C/h for IVD and 0.3°C/h ± 0.2°C/h for EHE; P = .226) were similar. Relevant laryngeal or esophageal tissue damage could not be detected. There were no significant differences in undesired side effects (eg, bradycardia or tachycardia, hypokalemia or hyperkalemia, hypoglycemia or hyperglycemia, hypotension, overcooling, or shivering). CONCLUSIONS: After insertion, target temperatures could be reached faster by IVD compared to EHE. Cooling performance of IVD and EHE did not significantly differ in maintaining target temperature during a targeted temperature management process and in active rewarming protocols according to intensive care unit guidelines in this experimental setting.

Validation of a palliative care outcome measurement tool supplemented by neurological symptoms (HOPE+): Identification of palliative concerns of neurological patients.

BACKGROUND: There is growing interest to integrate palliative care and its structures into the care of neurological patients. However, in Germany there is no comprehensive assessment tool capturing the symptoms of patients with advanced neurological diseases. AIM: To validate a newly developed palliative care measurement tool based on an extension of the validated core documentation system Hospice and Palliative Care Evaluation considering additional neurological issues (HOPE+). DESIGN: Prospective, observational study using HOPE+ and as external criteria, the Eastern Cooperative Oncology Group (ECOG) performance status and the 12 months "surprise" question (12-SQ) in a neurological population, and assessment for its construct validity and diagnostic accuracy. SETTING/PARTICIPANTS: All newly admitted patients to the Department of Neurorehabilitation, Dr. Becker Rhein-Sieg-Clinic aged 18-100 years (#DRKS00010947). RESULTS: Data from 263 patients (63 ± 14 years of age) were analyzed. HOPE+ revealed a moderately correlated six-factor structure (r = -0.543-0.525). Correlation analysis to evaluate discriminant validity using ECOG as external criterion was high (rs(261) = 0.724, p < 0.001) and confirmed for severely affected patients by adding the 12-SQ ("No"-group: 48.00 ± 14.92 vs "Yes"-group: 18.67 ± 7.57, p < 0.009). Operating characteristics show satisfactory diagnostic accuracy (area under the curve: 0.746 ± 0.049, 95% confidence interval = 0.650-0.842). CONCLUSION: HOPE+ demonstrates promising psychometric properties. It helps to assess palliative care issues of patients in neurological settings and, in combination with the 12-SQ, conceivably conditions when to initiate the palliative care approach in a population underrepresented in palliative care structures so far.

The Multidimensional Prognostic Index in general practice: One-year follow-up study.

BACKGROUND: Older patients' health problems in general practice (GP) can often not be assigned to a specific disease, requiring a paradigm shift to goal-oriented, personalised care for clinical decision making. PURPOSE: To investigate the predictive value of the comprehensive geriatric assessment (CGA)-based Multidimensional Prognostic Index (MPI) in a GP setting with respect to the main healthcare indicators during the 12 months following initial evaluation. METHODS: One hundred twenty-five consecutive patients aged 70 years and older were enrolled in a GP and followed up to one year. All patients underwent a CGA based on which the MPI was calculated and subdivided into three risk groups (MPI-1, 0-0.33 = low risk, MPI-2, 0.34-0.66 = moderate risk and MPI-3, 0.67-1, severe risk). Grade of Care (GC), hospitalization rate, mortality, nursing home admission, use of home care services, falls, number of general practitioner contacts (GPC), of geriatric resources (GR) and geriatric syndromes (GS) during the 12 months following initial evaluation were collected. RESULTS: The MPI was significantly associated with number of GS (P < .001), GR (P < .001), GC (P < .001) as well as with the average number of GPC per year (mean 10.4, P = .046). Interestingly, the clinical judgement of the general practitioner, in this case knowing his patients for 16 years on average, was associated with adverse outcomes to a similar extent than the prediction offered by the MPI (GP/adverse outcomes and MPI/adverse outcomes P < .001). CONCLUSION: The MPI is strongly associated with adverse outcomes in older GP patients and strongly predicts the number of GPC up to one year after initial evaluation. Considering the feasibility and the strong clinimetric properties of the MPI, its collection should be encouraged as early as possible to disclose risk conditions, implement tailored preventive strategies and improve cost-effectiveness of healthcare resources use.

Prescription rate of anti-atherosclerotic drugs in German nursing homes and its impact on outcome.

BACKGROUND: Peripheral arterial disease (PAD) is one of the major manifestations of general atherosclerosis and strongly associated with increased cardiovascular morbidity and mortality. Because only few epidemiologic studies are available concerning the prevalence of PAD in inhabitants ≥ 80 years of age, we screened inhabitants of nursing care homes in Germany for PAD and cardiovascular diseases and to assess the one year mortality. PATIENTS AND METHODS: We conducted a prospective cohort study, screening inhabitants of 42 nursing homes for PAD. Demographic data, comorbidities, cardiovascular risk factors and daily medication were collected. PAD was defined as ankle-brachial index < 0.9. During a follow up period of one year, cardio- and cerebrovascular events and mortality were recorded, as well as the rate of falls and major amputation. RESULTS: 1,329 probands (391 men, 938 women) > 60 years were eligible for further analysis. The mean age was 84.1 years (range 61-107 years) and the prevalence of PAD was 31.5 % . Media sclerosis was found in up to 17 %, and an existing diagnosis of PAD (in case of pathological ABI) and undertreatment was common. Probands with PAD were less likely to be treated according to guideline recommendations (antiplatelet therapy, beta blockers, statins) than probands with coronary artery disease (CAD). The overall one-year mortality was 19.8 % (n = 236), significantly higher than for a gender and age matched German population (p < 0.001). CONCLUSIONS: The current study shows a high prevalence of PAD in German nursing care homes. The one year mortality was not significantly different between probands with PAD and those with severe PAD (defined as an ABI of ≤ 0.5), whereas a media sclerosis was associated with an increased risk in probands with CAD in comparison to those without. Use of anti-diabetic agents and aspirin in monotherapy was associated with a reduced one-year mortality risk.

New associations of the Multidimensional Prognostic Index.

BACKGROUND: The multidimensional prognostic index (MPI) is a validated, sensitive, and specific prognosis estimation tool based on a comprehensive geriatric assessment (CGA). The MPI accurately predicts mortality after 1 month and 1 year in older, multimorbid patients with acute disease or relapse of chronic conditions. OBJECTIVE: To evaluate whether the MPI predicts indicators of healthcare resources, i.e. grade of care (GC), length of hospital stay (LHS) and destination after hospital discharge in older patients in an acute medical setting. MATERIAL AND METHODS: In this study 135 hospitalized patients aged 70 years and older underwent a CGA evaluation to calculate the MPI on admission and discharge. Accordingly, patients were subdivided in low (MPI­1, score 0-0.33), moderate (MPI-2, score 0.34-0.66) and high (MPI-3, score 0.67-1) risk of mortality. The GC, LHS and the discharge allocation were also recorded. RESULTS: The MPI score was significantly related to LHS (p = 0.011) and to GC (p < 0.001). In addition, MPI-3 patients were significantly more often transferred from other hospital settings (p = 0.007) as well as significantly less likely to be discharged home (p = 0.04) than other groups. CONCLUSION: The CGA-based MPI values are significantly associated with use of indicators of healthcare resources, including GC, LHS and discharge allocation. These findings suggest that the MPI may be useful for resource planning in the care of older multimorbid patients admitted to hospital.

Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: a systematic review and meta-analysis of randomized clinical trials.

Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto's method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs. chemotherapy alone; more extended vs. involved-field radiotherapy; radiation at higher doses vs. radiation at 20 Gy; more vs. fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs. intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival rates (P=0.007) as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (P=0.0028). No progression-free or overall survival differences were observed between combined-modality treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (P=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.

Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An Observational Multicenter International Study.

BACKGROUND: Hyponatremia is a frequent and potentially life-threatening adverse side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry database focuses on current management practices of thiazide-associated hyponatremia (TAH) and compares differences between TAH and syndrome of inappropriate antidiuretic hormone secretion (SIADH). METHODS: We analyzed 477 patients from 225 US and EU sites with euvolemic hyponatremia ([Na+] ≤130 mEq/L) who were receiving a thiazide diuretic. Of these, 118 met criteria for true thiazide-induced hyponatremia (TIH). RESULTS: Thiazide was withdrawn immediately after hyponatremia was diagnosed only in 57% of TAH; in these patients, the median rate of [Na+] change (Δdaily[Na+]) was significantly higher than those with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8] mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%), fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic saline (5.2%). Hypertonic saline produced the greatest Δdaily[Na+] (8.0[6.4] mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5 [3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic saline. Although there are highly significant differences in the biochemical profiles between TIH and SIADH, no predictive diagnostic test could be derived. CONCLUSIONS: Despite its high incidence and potential risks, the management of TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment success. Hypertonic saline is most effective in correcting hyponatremia but associated with a high rate of overly rapid correction. We could not establish a diagnostic laboratory-based test to differentiate TIH from SIADH.

Optimisation of chemotherapy and radiotherapy for untreated Hodgkin lymphoma patients with respect to second malignant neoplasms, overall and progression-free survival: individual participant data analysis.

BACKGROUND: Efficacy and the risk of severe late effects have to be well-balanced in treatment of Hodgkin lymphoma (HL). Late adverse effects include secondary malignancies which often have a poor prognosis. To synthesise evidence on the risk of secondary malignancies after current treatment approaches comprising chemotherapy and/or radiotherapy, we performed a meta-analysis based on individual patient data (IPD) from patients treated for newly diagnosed HL. OBJECTIVES: We investigated several questions concerning possible changes in the risk of secondary malignancies when modifying chemotherapy or radiotherapy (omission of radiotherapy, reduction of the radiation field, reduction of the radiation dose, use of fewer chemotherapy cycles, intensification of chemotherapy). We also analysed whether these modifications affect progression-free survival (PFS) and overall survival (OS). SEARCH METHODS: We searched MEDLINE and Cochrane CENTRAL trials databases comprehensively in June 2010 for all randomised trials in HL since 1984. Key international trials registries were also searched. The search was updated in March 2015 without collecting further IPD (one further eligible study found) and again in July 2017 (no further eligible studies). SELECTION CRITERIA: We included randomised controlled trials (RCTs) for untreated HL patients which enrolled at least 50 patients per arm, completed recruitment by 2007 and performed a treatment comparison relevant to our objectives. DATA COLLECTION AND ANALYSIS: Study groups submitted IPD, including age, sex, stage and the outcomes secondary malignant neoplasm (SMN), OS and PFS as time-to-event data. We meta-analysed these data using Petos method (SMN) and Cox regression with inverse-variance pooling (OS, PFS) for each of the five study questions, and performed subgroup and sensitivity analyses to assess the applicability and robustness of the results. MAIN RESULTS: We identified 21 eligible trials and obtained IPD for 16. For four studies no data were supplied despite repeated efforts, while one study was only identified in 2015 and IPD were not sought. For each study question, between three and six trials with between 1101 and 2996 participants in total and median follow-up between 6.7 and 10.8 years were analysed. All participants were adults and mainly under 60 years. Risk of bias was assessed as low for the majority of studies and outcomes. Chemotherapy alone versus same chemotherapy plus radiotherapy. Omitting additional radiotherapy probably reduces secondary malignancy incidence (Peto odds ratio (OR) 0.43, 95% confidence interval (CI) 0.23 to 0.82, low quality of evidence), corresponding to an estimated reduction of eight-year SMN risk from 8% to 4%. This decrease was particularly true for secondary acute leukemias. However, we had insufficient evidence to determine whether OS rates differ between patients treated with chemotherapy alone versus combined-modality (hazard ratio (HR) 0.71, 95% CI 0.46 to 1.11, moderate quality of evidence). There was a slightly higher rate of PFS with combined modality, but our confidence in the results was limited by high levels of statistical heterogeneity between studies (HR 1.31, 95% CI 0.99 to 1.73, moderate quality of evidence). Chemotherapy plus involved-field radiation versus same chemotherapy plus extended-field radiation (early stages) . There is insufficient evidence to determine whether smaller radiation field reduces SMN risk (Peto OR 0.86, 95% CI 0.64 to 1.16, low quality of evidence), OS (HR 0.89, 95% C: 0.70 to 1.12, high quality of evidence) or PFS (HR 0.99, 95% CI 0.81 to 1.21, high quality of evidence). Chemotherapy plus lower-dose radiation versus same chemotherapy plus higher-dose radiation (early stages). There is insufficient evidence to determine the effect of lower-radiation dose on SMN risk (Peto OR 1.03, 95% CI 0.71 to 1.50, low quality of evidence), OS (HR 0.91, 95% CI 0.65 to 1.28, high quality of evidence) or PFS (HR 1.20, 95% CI 0.97 to 1.48, high quality of evidence). Fewer versus more courses of chemotherapy (each with or without radiotherapy; early stages). Fewer chemotherapy courses probably has little or no effect on SMN risk (Peto OR 1.10, 95% CI 0.74 to 1.62), OS (HR 0.99, 95% CI 0.73 to1.34) or PFS (HR 1.15, 95% CI 0.91 to 1.45).Outcomes had a moderate (SMN) or high (OS, PFS) quality of evidence. Dose-intensified versus ABVD-like chemotherapy (with or without radiotherapy in each case). In the mainly advanced-stage patients who were treated with intensified chemotherapy, the rate of secondary malignancies was low. There was insufficient evidence to determine the effect of chemotherapy intensification (Peto OR 1.37, CI 0.89 to 2.10, low quality of evidence). The rate of secondary acute leukemias (and for younger patients, all secondary malignancies) was probably higher than among those who had treatment with standard-dose ABVD-like protocols. In contrast, the intensified chemotherapy protocols probably improved PFS (eight-year PFS 75% versus 69% for ABVD-like treatment, HR 0.82, 95% CI 0.7 to 0.95, moderate quality of evidence). Evidence suggesting improved survival with intensified chemotherapy was not conclusive (HR: 0.85, CI 0.70 to 1.04), although escalated-dose BEACOPP appeared to lengthen survival compared to ABVD-like chemotherapy (HR 0.58, 95% CI 0.43 to 0.79, moderate quality of evidence).Generally, we could draw valid conclusions only in terms of secondary haematological malignancies, which usually occur less than 10 years after initial treatment, while follow-up within the present analysis was too short to record all solid tumours. AUTHORS' CONCLUSIONS: The risk of secondary acute myeloid leukaemia and myelodysplastic syndrome (AML/MDS) is increased but efficacy is improved among patients treated with intensified chemotherapy protocols. Treatment decisions must be tailored for individual patients. Consolidating radiotherapy is associated with an increased rate of secondary malignancies; therefore it appears important to define which patients can safely be treated without radiotherapy after chemotherapy, both for early and advanced stages. For early stages, treatment optimisation methods such as use of fewer chemotherapy cycles and reduced field or reduced-dose radiotherapy did not appear to markedly affect efficacy or secondary malignancy risk. Due to the limited amount of long-term follow-up in this meta-analysis, further long-term investigations of late events are needed, particularly with respect to secondary solid tumours. Since many older studies have been included, possible improvement of radiotherapy techniques must be considered when interpreting these results.

Ten-Year Single-Center Results of Abdominal Aortic Aneurysm Treatment: Endovascular versus Open Repair.

BACKGROUND: The purpose of the present study was to compare the long-term survival in matched cohorts of patients with infrarenal abdominal aortic aneurysm (AAA) undergoing an elective open repair (OR) or an endovascular aneurysm repair (EVAR). METHODS: Patients with a primary elective repair of an infrarenal aortic aneurysm between 1998 and 2006 were identified in a retrospective review of our single-center database. EVAR and OR patients were matched with respect to age, gender, renal disease, tobacco use, hypertension, chronic obstructive pulmonary disease, and coronary artery disease. The primary end points were the early mortality and all-cause mortality during follow-up. RESULTS: A total of 465 patients with elective infrarenal aortic aneurysm repair were identified in the database. The EVAR and OR patients were matched according to the above-mentioned characteristics, and finally, 108 patients were included in each group. The early mortality encountered was only one death in the open group (P = 0.316). The Kaplan-Meier survival analysis by the log-rank test showed no difference in cumulative survival between OR group and EVAR group (P = 0.458). Seventeen reinterventions (16.7%) in the EVAR group vs. 7 (6.5%) in the OR group (P = 0.018) were necessary during follow-up. CONCLUSIONS: OR and EVAR can be performed safely for elective treatment of AAA. The reintervention rate is, as expected, significantly higher in the EVAR group, but the long-term survival remains equal in both groups.