12-year survival analysis of 322 Hintegra total ankle arthroplasties from an independent center

Background and purpose — Total ankle arthroplasties (TAAs) have larger revision rates than hip and knee implants. We examined the survival rates of our primary TAAs, and what different factors, including the cause of arthritis, affect the success and/or revision rate.Patients and methods — From 2004 to 2016, 322 primary Hintegra TAAs were implanted: the 2nd generation implant from 2004 until mid-2007 and the 3rd generation from late 2007 to 2016. A Cox proportional hazards model evaluated sex, age, primary diagnosis, and implant generation, pre- and postoperative angles and implant position as risk factors for revision.Results — 60 implants (19%) were revised, the majority (n = 34) due to loosening. The 5-year survival rate (95% CI) was 75% (69–82) and the 10-year survival rate was 68% (60–77). There was a reduced risk of revision, per degree of increased postoperative medial distal tibial angle at 0.84 (0.72–0.98) and preoperative talus angle at 0.95 (0.90–1.00), indicating that varus ankles may have a larger revision rate. Generation of implant, sex, primary diagnosis, and most pre- and postoperative radiological angles did not statistically affect revision risk.Interpretation — Our revision rates are slightly above registry rates and well above those of the developer. Most were revised due to loosening; no difference was demonstrated with the 2 generations of implant used. Learning curve and a low threshold for revision could explain the high revision rate.

Arthritis in the ankle often develops earlier than in the hip or knee, and 70% have a traumatic etiology (Saltzman et al. 2005, Brown et al. 2006). Total ankle arthroplasty (TAA) can be indicated for severe arthritis in the ankle joint, but the anatomical preconditions, like a small surface area and high stress from compression and torque (Bouguecha et al. 2011, Kakkar and Siddique 2011), makes it less durable than hip and knee prosthetics. The Hintegra TAA, a 3-component mobile bearing, uncemented implant (Hintermann et al. 2004) is widely used and results from the development center demonstrate survival rates of 94% and 84% after 5 and 10 years’ follow-up (Barg et al. 2013). This is considerably more than the survival rates from national registries. Labek et al. (2011) demonstrated that development centers report only half of the revision rate that can be found in the few existing national registers. In a systematic review of primary Agility total ankle arthroplasty (DePuy Synthes Orthopedics, Warsaw, IN, USA), the author (Roukis 2012) found that the incidence of complications increased from 7% to 12%, in studies where the inventor was excluded. Similar results were found by Prissel and Roukis (2013), who found an increased incidence of complications from 6% to 13% in studies where the inventor or faculty consultants were excluded. These studies indicated the risk of selection (inventor) and publication (conflict of interest) bias.Planning and surgical technique, including significant experience, are mandatory for a successful outcome. The better result from development centers may reflect, besides the above-mentioned bias, that there is a long learning curve and that the indication for revision surgery varies.We examined the survival rates of primary Hintegra TAAs performed at Hvidovre Hospital, with revision rate as outcome. We report primary diagnosis for primary TAA and examine whether sex, generation of the implant, preoperative angles and implant position affect the revision rate.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Velopharyngeal function during vocalization in infants.

OBJECTIVE: To determine the age at which infants achieve velopharyngeal closure during vocalization. DESIGN: Longitudinal with repeated measures. SETTING: Laboratory. PARTICIPANTS: Six healthy infants were studied monthly from ages 2 to 6 months while they interacted with a parent and an investigator. MAIN OUTCOME MEASURES: The presence or absence of velopharyngeal closure, as determined by sensing ram pressure at the anterior nares. RESULTS: The velopharynx was open for windups, whimpers, and laughs, and it was closed for cries, screams, and raspberries, regardless of age. The frequency with which the velopharynx closed during syllable utterances increased significantly with age. CONCLUSIONS: Velopharyngeal closure for speech-like utterance increases with age, but is not complete and is still undergoing development at 6 months of age. Velopharyngeal closure during infancy may be influenced by pressure demands of the utterance; however, support for this speculation is stronger for other types of utterances than it is for speech-like utterances. The method used in this study holds promise for evaluating infants with suspected velopharyngeal impairment.     

Detergent fractionation with subsequent subtractive suppression hybridization as a tool for identifying genes coding for plasma membrane proteins

Abstract:  The identification of tumor-specific proteins located at the plasma membrane is hampered by numerous methodological pitfalls many of which are associated with the post-translational modification of such proteins. Here, we present a new combination of detergent fractionation of cells and of subtractive suppression hybridization (SSH) to gain overexpressed genes coding for membrane-associated or secreted proteins. Fractionation of subcellular components by digitonin allowed sequestering mRNA of the rough Endoplasmatic reticulum and thereby increasing the percentage of sequences coding for membrane-bound proteins. Fractionated mRNAs from the cutaneous T-cell lymphoma (CTCL) cell line HuT78 and from normal peripheral blood monocytes were used for SSH leading to the enrichment of sequences overexpressed in the tumor cells. We identified some 21 overexpressed genes, among them are GPR137B, FAM62A, NOMO1, HSP90, SLIT1, IBP2, CLIF, IRAK and ARC. mRNA expression was tested for selected genes in CTCL cell lines, skin specimens and peripheral blood samples from CTCL patients and healthy donors. Several of the detected sequences are clearly related to cancer, but have not yet been associated with CTCL. qPCR confirmed an enrichment of these mRNAs in the rough endoplasmic reticulum fraction. RT-PCR confirmed the expression of these genes in skin specimens and peripheral blood of CTCL patients. Western blotting verified protein expression of HSP90 and IBP2 in HuT78. GPR137B could be detected by immunohistology in HuT78 and in keratinocytes of dysplastic epidermis, but also in sweat glands of healthy skin. In summary, we developed a new technique, which allows identifying overexpressed genes coding preferentially for membrane-associated proteins.     

Ultrasonic root-end preparation in apical surgery: a prospective randomized study.

OBJECTIVE: The purpose of this study was to evaluate the potential benefit of an ultrasonic device in apical surgery on the outcome of treatment. STUDY DESIGN: A randomized prospective design was used in a standardized treatment protocol. Patients were allocated to treatment with an ultrasonic device (P-Max Newtron) or treatment with a bur in an otherwise similar protocol. One year after treatment the results were evaluated by 2 oral and maxillofacial surgeons who were blinded for the therapy. RESULTS: Out of a total group of 399 patients who were included in the study, adequate follow-up could be obtained in 290 patients. The overall success rate in the ultrasonic group was 80.5% and in the group treated with a bur 70.9% (P = .056). In molars, the difference in success rate was significant (P = .02). CONCLUSION: The use of an ultrasonic device in apical surgery improved the outcome of treatment. In molars this effect was significant.     

Ventilation imaging of the lung: Comparison of hyperpolarized helium-3 MR imaging with Xe-133 scintigraphy

RATIONALE AND OBJECTIVES: To compare hyperpolarized helium-3 (HHe) magnetic resonance imaging (MRI) of the lung with standard Xe-133 lung ventilation scintigraphy. MATERIALS AND METHODS: We performed a retrospective review of 15 subjects who underwent HHe MRI and Xe-133 lung ventilation imaging. Coronal MRI sections were acquired after a single inhalation of HHe gas, and standard posterior planar lung ventilation scintigraphy was performed during continuous breathing of Xe-133 gas. The first breath scintigram of each patient was compared with a composite MR image composed of the sum of the individual MR images and with the individual helium-3 MR images. Ventilation defects on the two imaging modalities were compared for size, conspicuity, and concordance in presence and location. Assessment was done separately for each of four lung quadrants. RESULTS: Comparing the composite HHe MR images with Xe-133 scintigraphy, ventilation defect size, conspicuity and concordance were the same in 67% (40/60), 63% (38/60), and 62% (37/60) quadrants, respectively. Comparing the individual HHe MR image sections with the Xe-133 ventilation scan, there was concordance between the ventilation defects in 27% (16/60) of quadrants. More defects were identified on the individual HHe MR images in 62% (37/60) of quadrants. CONCLUSION: There was good agreement between composite HHe MR image and first breath Xe-133 scintigraphic images, supporting the widely held assumption that HHe MRI likely depicts first breath lung ventilation.     

Ureteral catheterization and manipulations using flexible cystoscope on patients in semiprone position

Cystoscopy using the flexible cystoscope was performed on 15 patients in the semiprone position. Ureteral catheters were placed to facilitate percutaneous nephrolithotomy in 8 patients, and indwelling ureteral stents were removed in 7. The procedure offers the urologist an additional technique in select situations.     

Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man

Aims Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations.
Methods Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25  mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p.l.c. up to 24  h post-dose.
Results Maximum plasma concentrations ( C _max ) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25  mg), were higher compared with the unbuffered tablets by about 50–80%. The area under concentration-time data (AUC) was unaffected, and, hence, C _max/AUC was increased by buffering. Time to C _max ( t _max ) and mean residence time (MRT) tended to be or was shortened by buffering.
Conclusions It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected.