In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of ...hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively.
In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias.
Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 75%) than in those treated with FDI (1 out of 13 8%; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants.
While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI.
Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Objective To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH 1-34) reciprocally affect the integrity of the articular cartilage within a naïve ...osteochondral unit in vivo. Design Daily subcutaneous injections of 10 μg PTH 1-34/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH 1-34 receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. Results PTH 1-34 enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P < 0.05). Moreover, PTH 1-34 led to cartilage surface irregularities and reduced matrix staining (both P < 0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer ( P = 0.026) and enhanced mineral density of the subarticular spongiosa ( P = 0.001). Conclusions Modifications of the subarticular spongiosa by PTH 1-34 cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis.
Intensive chemotherapy, with or without following autologous or allogeneic stem cell transplantation (HSCT), is often the only curative treatment option for patients with hematological malignancies ...and leave many survivors physically and psychologically impaired. Electrical muscle stimulation (EMS) is a proven tool to improve physical performance in seniors and patients with chronic diseases. We therefore investigated the safety and feasibility of EMS in 45 patients undergoing autologous HSCT (
n
= 13), allogeneic HSCT (
n
= 11) and intensive chemotherapy (
n
= 21). Furthermore, physical (assessed by 6-min walking distance (6MWD) and short physical performance battery (SPPB)) and psychological performance (assessed by multidimensional fatigue inventory (MFI) and the EORTC QOL-C30 questionnaire) were measured before chemotherapy (T1) and at discharge from hospital (T2). Four patients died due to septic shock, two withdrew consent before the start of EMS training and five stopped EMS training during the study because of chemotherapy-related complications, loss of motivation or loss of ability to use EMS autonomously. Thirty-four out of 45 (76%) patients used EMS throughout the study period and participated in physical and psychological tests at time points 1 and 2. EMS-related adverse events were hematoma (
n
= 1) and muscle pain (
n
= 2). No bleeding events > 1 according to the WHO bleeding scale occurred. Decline in 6MWD from T1 to T2 was 24 m. The SPPB score stayed the same with 11 points at T1 and T2. Most MFI subscales showed stable fatigue levels and quality of life (QoL) did not decrease significantly throughout therapy. EMS is feasible and safe in patients undergoing intensive chemotherapy. Trial registration: NCT03467087
With the advent of technologies that allow simultaneous genotyping of thousands of single-nucleotide polymorphisms (SNPs) across the genome, the genetic contributions to complex diseases can be ...explored at an unprecedented detail. This study is among the first to apply the genome-wide association study (GWAS) approach to Alzheimer disease (AD). We present our GWAS results from the German population for genes included in the 'Top Results' list on the AlzGene database website. In addition to the apolipoprotein E locus, we identified nominally significant association signals in six of the ten genes investigated, albeit predominantly for SNPs other than those already published as being disease associated. Further, all of the four AD genes previously identified through GWAS also showed nominally significant association signals in our data. The results of our comparative study reinforce the necessity for replication and validation, not only of GWAS but also of candidate gene case-control studies, in different populations. Furthermore, cross-platform comparison of genotyping results can also identify new association signals. Finally, our data confirm that GWAS, regardless of the platform, are valuable for the identification of genetic variants associated with AD.
Acupuncture is widely used by patients with chronic pain although there is little evidence of its effectiveness. We investigated the efficacy of acupuncture compared with minimal acupuncture and with ...no acupuncture in patients with osteoarthritis of the knee.
Patients with chronic osteoarthritis of the knee (Kellgren grade ≤2) were randomly assigned to acupuncture (n=150), minimal acupuncture (superficial needling at non-acupuncture points; n=76), or a waiting list control (n=74). Specialised physicians, in 28 outpatient centres, administered acupuncture and minimal acupuncture in 12 sessions over 8 weeks. Patients completed standard questionnaires at baseline and after 8 weeks, 26 weeks, and 52 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index at the end of week 8 (adjusted for baseline score). All main analyses were by intention to treat.
294 patients were enrolled from March 6, 2002, to January 17, 2003; eight patients were lost to follow-up after randomisation, but were included in the final analysis. The mean baseline-adjusted WOMAC index at week 8 was 26·9 (SE 1·4) in the acupuncture group, 35·8 (1·9) in the minimal acupuncture group, and 49·6 (2·0) in the waiting list group (treatment difference acupuncture
vs minimal acupuncture −8·8, 95% CI −13·5 to −4·2, p=0·0002; acupuncture
vs waiting list −22·7 −27·5 to −17·9, p<0·0001). After 52 weeks the difference between the acupuncture and minimal acupuncture groups was no longer significant (p=0·08).
After 8 weeks of treatment, pain and joint function are improved more with acupuncture than with minimal acupuncture or no acupuncture in patients with osteoarthritis of the knee. However, this benefit decreases over time.
Background
In eosinophilic esophagitis (EoE), dysphagia, which might reflect esophageal dysmotility, is the most common symptom. High‐resolution manometry (HRM) has become widely accepted for ...evaluating esophageal motility disorders, but to date has been sparsely examined in EoE patients, particularly under therapy. The aim of this study was to evaluate HRM in symptomatic EoE‐patients under topical steroid treatment.
Methods
In this prospective observational study, symptomatic EoE patients received HRM‐examinations before and after 8 weeks of topical steroid treatment with budesonide. All HRM‐abnormalities were assessed and interpreted according to the Chicago classification. The primary endpoint was the influence of topical steroid treatment on the intrabolus pressure (IBP). Clinical symptoms, endoscopic findings and histological esophageal eosinophilic load were also reported.
Key Results
Twenty symptomatic EoE patients were included. Overall success of budesonide therapy was 85% regarding complete histologic remission and 80% regarding complete clinical remission. High‐resolution manometry showed abnormal esophageal motility in 35% of patients at baseline, which was resolved after therapy in 86% of these patients. Most frequent HRM‐findings were early pan‐esophageal pressurizations and weak persitalsis. There was no significant reduction of the IBP under therapy (before: 12.5 ± 4.9 mmHg, after: 10.9 ± 2.9 mmHg; p = 0.119).
Conclusions & Inferences
Although dysphagia is the leading symptom of EoE, HRM is able to identify esophageal motility disorders in only some EoE patients. Observed motility disorders resolve after successful treatment in almost all of these patients. Intrabolus pressure does not seem an optimal parameter for the monitoring of successful treatment response in EoE patients.
In order to identify potential HRM‐abnormalities in EoE‐patients and to evaluate the effect of topical steroid treatment on these abnormalities, 20 EoE‐patients were examined by HRM before and after 8 weeks of steroid therapy. High‐resolution manometry showed abnormal findings in 35% of EoE‐patients at baseline, most frequently early pan‐esophageal pressurizations, which resolved after therapy in 86% of these patients.
Catheter-related infections are a serious complication of continuous thoracic epidural analgesia. Tunnelling catheters subcutaneously may reduce infection risk. We thus tested the hypothesis that ...tunnelling of thoracic epidural catheters is associated with a lower risk of catheter-related infections.
Twenty-two thousand, four hundred and eleven surgical patients with continuous thoracic epidural analgesia included in the German Network for Regional Anaesthesia registry between 2007 and 2014 were grouped by whether their catheters were tunnelled (n+12 870) or not (n+9541). Catheter-related infections in each group were compared with Student’s unpaired t and χ2 tests. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with logistic regression, adjusting for potential confounding factors, including age, ASA physical status score, use of catheter for ≥4 days, multiple skin puncture, hospital, and surgical department.
There were fewer catheter-related infections in patients with tunnelled catheters (4.5 vs 5.5%, P<0.001). Mild infections were also less common (4.0 vs 4.6%, P+0.009), as were moderate infections (0.4 vs 0.8%, P<0.001). After adjustment for potential confounding factors, tunnelling remained an independent prevention for any grade of infection (adjusted OR 0.51, 95% CI 0.42–0.61, P<0.001) and for mild infections (adjusted OR 0.54, 95% CI 0.43–0.66, P<0.001) and moderate and severe infections (adjusted OR 0.44, 95% CI 0.28–0.70, P+0.001).
Tunnelling was associated with a lower risk of thoracic epidural catheter-related infections.
Objective
To compare the effects of two different intraoperative CO2 pressures (8 and 15 mmHg) during laparoscopic hysterectomy for benign uterine pathologies in terms of postoperative abdominal and ...shoulder pain, laparoscopy‐mediated vegetative alterations, pain medication requirement, arterial CO2 pressure (pCO2), surgical parameters, and safety.
Design
Prospective randomised controlled study.
Setting
German university hospital.
Population
Female patients undergoing laparoscopic hysterectomy for benign uterine pathologies.
Methods
Patients were randomised to a standard pressure (SP; 15 mmHg, control) or low‐pressure (LP; 8 mmHg, experimental) group.
Main outcome measures
Primary outcomes were postoperative abdominal and shoulder pain intensities, measured via numeric rating scale (NRS) and vegetative parameters (fatigue, nausea, vomiting, bloating) at 3, 24, and 48 hours postoperatively. Secondary outcomes were pain medication requirement (mg) and arterial pCO2 (mmHg). Surgical parameters and intra‐ and postoperative complications were also recorded.
Results
In total, 178 patients were included. Patients in the LP group (n = 91) showed significantly lower postoperative abdominal and shoulder pain scores, fewer vegetative alterations, lower pain medication requirements, a shorter postoperative hospitalization, and lower intra‐ and postoperative arterial pCO2 values compared with the SP group (n = 87; P ≤ 0.01). No differences in intra‐ and postoperative complications were observed between groups.
Conclusions
Low‐pressure laparoscopy seems to be an effective and safe technique for the reduction of postoperative pain and laparoscopy‐induced metabolic and vegetative alterations following laparoscopic hysterectomy for benign indications.
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Low‐pressure laparoscopy seems to be an effective and safe technique for reduction of pain following laparoscopic hysterectomy.
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Low‐pressure laparoscopy seems to be an effective and safe technique for reduction of pain following laparoscopic hysterectomy.
The specific delivery of chemotherapeutic agents to their desired targets with a minimum of systemic side effects is an important, ongoing challenge of chemotherapy. One approach, developed in the ...past to address this problem, is the i.v. injection of magnetic particles ferrofluids (FFs) bound to anticancer agents that are then concentrated in the desired area (e.g., the tumor) by an external magnetic field. In the present study, we treated squamous cell carcinoma in rabbits with FFs bound to mitoxantrone (FF-MTX) that was concentrated with a magnetic field. Experimental VX-2 squamous cell carcinoma was implanted in the median portion of the hind limb of New Zealand White rabbits (n = 26). When the tumor had reached a volume of approximately 3500 mm3, FF-MTX was injected intraarterially (i.a.; femoral artery) or i.v. (ear vein), whereas an external magnetic field was focused on the tumor. FF-MTX i.a. application with the external magnetic field resulted in a significant (P < 0.05), complete, and permanent remission of the squamous cell carcinoma compared with the control group (no treatment) and the i.v. FF-MTX group, with no signs of toxicity. The intratumoral accumulation of FFs was visualized both histologically and by magnetic resonance imaging. Thus, our data show that i.a. application of FF-MTX is successful in treating experimental squamous cell carcinoma. This "magnetic drug targeting" offers a unique opportunity to treat malignant tumors locoregionally without systemic toxicity. Furthermore, it may be possible to use these magnetic particles as a "carrier system" for a variety of anticancer agents, e.g., radionuclides, cancer-specific antibodies, and genes.
Bispectral index (BIS) monitoring provides a non-invasive measure of the level of sedation. The purpose of this randomized, single-blind clinical trial was to evaluate whether BIS monitoring of ...sedation would lead to improved oxygenation and a reduced rate of cardiopulmonary complications during endoscopy.
Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) under procedural sedation with a combination of low dose midazolam and propofol were randomly assigned to either standard monitoring of sedation only (BIS-blinded arm) or an open arm in which additional BIS monitoring was available (BIS-open arm). In the BIS-open arm, propofol administration was to be withheld if BIS values were <55. The primary study end point was the mean oxygen saturation per patient. Secondary end points were the rates of cardiopulmonary complications, propofol dose, quality of sedation (patient cooperation as rated by the endoscopist and patient satisfaction), and recovery.
A total of 144 patients were enrolled and included in the intention-to-treat analysis. Mean oxygen saturation per patient was 97.7% in the BIS-open arm and 97.6% in the BIS-blinded arm (P=0.71). Total rates of cardiopulmonary complications, single numbers of hypoxemic, bradycardic, and hypotensive events, mean propofol doses, and quality of sedation also showed no statistically significant differences between the groups. However, BIS monitoring did result in faster recovery of patients as reflected by shorter times to eye opening (P=0.001), first verbal response (P=0.02), and leaving the procedure room (P<0.001).
The use of additional BIS monitoring did not lead to improved oxygenation or a reduced rate of cardiopulmonary complications. Recovery times after the procedure were shorter than with standard monitoring alone, but the clinical benefit for daily practice may be limited.
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