Patients' perceived walking abilities, daily-life gait behavior and gait quality before and 3 months after total knee arthroplasty.

INTRODUCTION: Functional outcome and patients' daily-life activities after total knee arthroplasty are becoming more important with a younger and more active patient population. In addition to patient-reported outcome measures (PROMs), trunk-based accelerometry has shown to be a promising method for evaluating gait function after total knee arthroplasty. The aim of this study was to evaluate daily-life perceived walking abilities, gait behavior and gait quality before and 3 months after total knee arthroplasty, using PROMs and trunk-based accelerometry. MATERIALS AND METHODS: A cohort of 38 patients completed questionnaires including the Oxford Knee Score and modified Gait Efficacy Scale before and 3 months after primary unilateral total knee arthroplasty. At both time points, they wore a tri-axial accelerometer at the lower back for seven consecutive days and nights. Gait behavior was calculated using gait quantity and walking speed, and multiple gait quality parameters were calculated. RESULTS: Significant improvements were seen after 3 months in the Oxford Knee Score [median (interquartile range) 29 (10) vs 39 (8), p < 0.001] and modified Gait Efficacy Scale [median (interquartile range) 67 (24) vs 79 (25), p = 0.001]. No significant changes were observed in gait behavior (quantity and speed) or gait quality variables. CONCLUSIONS: In contrast to the significant improvements in patients' perception of their walking abilities and PROMs, patients did not show improvements in gait behavior and gait quality. This implies that after 3 months patients' perceived functional abilities after total knee arthroplasty do not necessarily represent their actual daily-life quantity and quality of gait, and that more focus is needed on postoperative rehabilitation to improve gait and functional behavior.

Insight in Information Provision Prior to Obtaining Surgical Informed Consent-by Audiotaping Outpatient Consultations.

BACKGROUND: Literature suggests that patient-informing process prior to obtaining surgical informed consent (SIC) does not function well. This study aimed to provide insight into the current practice of SIC in the Netherlands. METHODS: This is a prospective, observational, and multicenter study, conducted in one academic and two non-academic teaching hospitals in the Netherlands. Audio recordings were made during outpatient consultations with patients presenting with Dupuytren Disease. The recorded informing process was scored according to a checklist. Written documentation of the SIC process in the patient's chart was compared to these scored checklists. Time spent on SIC during the consultations was also recorded. RESULTS: A total of 41 outpatient consultations were included in the study. Consultations were conducted by 25 plastic surgeons and their residents. Average time spent on SIC was 55.6% of the total consultation time. Considerable variation was observed concerning the amount and type of information given and discussed. In 59% of the consultations, discrepancies were observed between written documentation of consultations and audio recordings. Information on treatment risks, the postoperative period, and the operating surgeon was addressed the least. CONCLUSION: Despite a relatively large part of the consultation time being spent on SIC, patients received scarce information concerning treatment risks, postoperative period, and who their operating surgeon would be. Discrepancies were observed between the written documentation of SIC and information recorded on the audio recordings. This occurred predominantly in one hospital that used a pre-made list of 'discussed information' in its digital patient chart.

Survival and functional outcome of high tibial osteotomy for medial knee osteoarthritis: a 10-20-year cohort study.

BACKGROUND: The primary aim of this study was to identify independent predictors of long-term survivorship after high tibial osteotomy (HTO). The secondary aims were to describe the functional outcome of surviving HTO 10-20 years after surgery. METHODS: A retrospective cohort of 223 HTO that were performed for the treatment of medial osteoarthritis was identified. Details were recorded from the patient notes. All surviving patients were contacted and asked to complete a Tegner Activity Scale, Lysholm Knee Score and rate pain using the Visual Analogue Scale (VAS). Survival analysis was performed, using conversion to arthroplasty as the definition of failure. RESULTS: The mean age was 54 years (24-80 years). There were 123 (55.2%) in males and 100 (44.8%) in females. The mean BMI was 27.2 (SD 3.9). Twenty (9%) patients were lost to follow-up. The mean follow-up was 12 (SD 4) years. Survival at 10 years was 75 and 55% at 15 years and less than 40% at 20 years. Cox regression analysis demonstrated age of 50 years or more, female gender and surgical technique to be significant independent predictors of failure. The median Tegner score was 3 (inter-quartile range (IQR) 1-3). The mean Lysholm score was 75.5 (SD 18.4). The median VAS was 5 (IQR 0-6). CONCLUSIONS: The medium- to long-term survival and functional outcome after HTO was good to excellent at 10-20 years of follow-up. Age, gender, surgeon and surgical technique were identified as independent predictors of failure.

What patients really think about asthma guidelines: barriers to guideline implementation from the patients' perspective.

BACKGROUND: Treatment of asthma does not always comply with asthma guidelines (AG). This may be rooted in direct or indirect resistance on the doctors' and/or patients' side or be caused by the healthcare system. To assess whether patients' concepts and attitudes are really an implementation barrier for AG, we analysed the patients' perspective of a "good asthma therapy" and contrasted their wishes with current recommendations. METHODS: Using a qualitative exploratory design, topic centred focus group (FG) discussions were performed until theoretical saturation was reached. Inclusion criteria were an asthma diagnosis and age above 18. FG sessions were recorded audio-visually and analysed via a mapping technique and content analysis performed according to Mayring (supported by MAXQDA®). Participants' speech times and the proportion of time devoted to different themes were calculated using the Videograph System® and related to the content analysis. RESULTS: Thirteen men and 24 women aged between 20 and 77 from rural and urban areas attended five FG. Some patients had been recently diagnosed with asthma, others years previously or in childhood. The following topics were addressed: (a) concern about or rejection of therapy components, particularly corticosteroids, which sometimes resulted in autonomous uncommunicated medication changes, (b) lack of time or money for optimal treatment, (c) insufficient involvement in therapy choices and (d) a desire for greater empowerment, (e) suboptimal communication between healthcare professionals and (f) difficulties with recommendations conflicting with daily life. Primarily, (g) participants wanted more time with doctors to discuss difficulties and (h) all aspects of living with an impairing condition. CONCLUSIONS: We identified some important patient driven barriers to implementing AG recommendations. In order to advance AG implementation and improve asthma treatment, the patients' perspective needs to be considered before drafting new versions of AG. These issues should be addressed at the planning stage. TRIAL REGISTRATION: DRKS00000562 (German Clinical Trials Registry).

Novel TMC8 splice site mutation in epidermodysplasia verruciformis and review of HPV infections in patients with the disease.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a genodermatosis leading to infections with cutaneous HPV, persistent plane warts and a high rate of non-melanoma skin cancer (NMSC). Biallelic loss-of-function mutations in TMC6 and TMC8 are known to be causative. OBJECTIVE: The aim of this study was to report EV-causing mutations in four patients with EV and to give an overview of all described patients with EV. PATIENTS AND METHODS: We investigated four patients with classical features of EV from two families. All patients were affected by plane warts with typical EV histology since early childhood, and ß-HPVs were detected on their skin. One patient had recurring cutaneous squamous cell carcinomas (cSCC) and carcinomas in situ (Bowen type). We sequenced both TMC6/8 for disease-causing mutations and quantified levels of gene expression. We also performed a systematic literature review to discuss these patients in the context of previously reported cases, mutations already identified, as well as HPV types. RESULTS: Three patients of one family carried a homozygous splice site mutation in TMC8 resulting in aberrantly spliced transcripts that were not degraded. By contrast, no TMC6/8 mutation was detected in the patient from the other family. A systematic literature review revealed 501 described patients with EV. Around 40% of patients with EV analysed for genetic alterations carried no mutation in TMC6/8. While ß-HPVs were identified in the majority of cases, α-HPVs were detected in several individuals. CONCLUSION: The relatively high proportion of EV patients without mutation in TMC6/8 indicates the existence of EV-causing mutations in additional, presently unknown gene(s). However, a homozygous TMC8 splice site mutation in our patients resulted in aberrant transcripts which cannot retain the healthy phenotype. The literature review revealed that HPV-5 is the most commonly identified HPV in patients with EV, but HPV-3, HPV-14 and HPV-20 were unexpectedly identified more frequently than HPV-8.

No differences between fixed- and mobile-bearing total knee arthroplasty.

PURPOSE: For years, numerous studies have been performed to determine whether mobile-bearing total knee arthroplasty (MB-TKA) or fixed-bearing total knee arthroplasty (FB-TKA) is the preferential design in total knee arthroplasty. Reviews and meta-analyses on this subject have focused on a relatively small number of randomised controlled trials, possibly missing important results of smaller studies. The goal of this review was to provide a comprehensive overview of all literature comparing MB-TKA and FB-TKA in the treatment of osteoarthritis of the knee. METHODS: An extensive literature search was performed in the PubMed database. All studies that compared MB-TKA with FB-TKA and looked at one of four theorised advantages (insert wear, signs of loosening, survival rate of the prosthesis and clinical outcome) were included. RESULTS: The initial search yielded 258 articles, of which 127 were included after the first screening. The included studies consisted of 9 meta-analyses, 3 systematic reviews, 48 RCT's, 44 comparative studies, 10 reviews and 13 studies that examined patients who received bilateral TKA (one MB-TKA and one FB-TKA). Combining the results of all studies showed that almost all studies found no difference between MB-TKA and FB-TKA. CONCLUSIONS: Even when examining all different types of studies on MB-TKA and FB-TKA, the results of this review showed no difference in insert wear, risk of loosening, survivorship or clinical outcome. In daily practice, the choice between MB-TKA and FB-TKA should be based on the experience and judgment of the surgeon, since no clear differences are observed in the scientific literature. LEVEL OF EVIDENCE: III.

A prospective 24 months follow-up of a three component press-fit prosthesis for hallux rigidus.

BACKGROUND: The aim of this study was to evaluate the results following total first metatarsophalangeal (FMTP) joint replacement arthroplasty using a modular three component press fit prosthesis at two year follow up. METHODS: All patient data was collected in a prospective way in four study centres. Both preoperative and postoperative evaluation consisted of an assessment using the AOFAS-HMI score, visual analogue scale for pain, evaluation of the range of motion and patient satisfaction scores. Postoperative X-rays were reviewed for loosening and radiolucency up to two years. RESULTS: Fifty-five feet were available for analysis at 24 months. Two implants were removed during the study. Six more feet had additional surgery due to stiffness or malalignment. Postoperative AOFAS-HMI scores improved significantly by 32.4 points at two year follow-up (p<0.001). The visual analogue scale for pain improved significantly from 6.8 (std 1,6) preoperatively to 1.6 (std 1,9) postoperatively (p<0.0001). Mean dorsiflexion improved from 12.6 (std 10,1) degrees preoperatively to 31.2 (std 16,8) degrees postoperatively. Eighty-seven percent of patients were moderately to well satisfied with the end result. Eighteen prostheses showed radiolucency at 24 months. CONCLUSION: Implantation of a Metis® modular three component press fit prosthesis for the metatarsophalangeal joint in hallux rigidus shows significant improvement in AOFAS-HMI scores and a decrease in pain. Concerns remain with regard to early reoperation rate (14.5%) and long term survival of the implant. Future studies will have to address these aspects.

Mutations in SMARCAD1 cause autosomal dominant adermatoglyphia and perturb the expression of epidermal differentiation-associated genes.

BACKGROUND: Autosomal dominant adermatoglyphia (ADG) is characterized by lack of palmoplantar epidermal ridges. Recently, ADG was found to be caused in one family by a mutation in SMARCAD1, a member of the SNF subfamily of the helicase protein superfamily. OBJECTIVES: To investigate the genetic basis of ADG. METHODS: We used direct sequencing and global gene expression analysis. RESULTS: We identified three novel heterozygous mutations in SMARCAD1 (c.378 + 2T > C, c.378 + 5G > C and c.378 + 1G > A) in a total of six patients. Surprisingly, all four ADG-causing mutations identified to date disrupt a single conserved donor splice site adjacent to the 3' end of a noncoding exon and are predicted to result in haploinsufficiency for a skin-specific isoform of SMARCAD1. These data indicate a pivotal role for the SMARCAD1-skin specific isoform in dermatoglyph formation. In order to better understand the consequences of ADG-associated mutations, we ascertained the global transcription profiles of primary keratinocytes downregulated for SMARCAD1 and of patient-derived keratinocytes. A total of eight genes were found to be differentially expressed in both patient-derived and knocked down keratinocytes. Of interest, these differentially expressed genes have been implicated in epidermal ontogenesis and differentiation, and in psoriasis, which is characterized by abnormal finger ridge patterns. CONCLUSIONS: The present data suggest that ADG is genetically homogeneous and result from perturbed expression of epidermal differentiation-associated genes.

Description of the natural course and clinical manifestations of ichthyosis with confetti caused by a novel KRT10 mutation.

Ichthyosis with confetti (IWC) was first described as ichthyose en confettis and subsequently as congenital reticular ichthyosiform erythroderma. Because of the development of hundreds to thousands of pale, normal-appearing confetti-like spots during childhood, the disease was named IWC. Patients with IWC show erythroderma, prominent scaling and palmoplantar keratoderma. Our female index patient was described in 1990 as the fourth patient reported worldwide; at that time she did not show any confetti-like spots. She was periodically examined at our clinic from birth until adulthood; hence we are able to describe the natural course of IWC in detail for the first time. We furthermore identified two novel deletions in KRT10, one of them leading to a frameshift and consequently to an arginine tail of keratin 10. Our report is the first independent confirmation of the KRT10 gene defect and revertant mosaicism mechanism in patients with IWC and it expands the clinical findings.

Influence of diet on calcium metabolism, tissue calcification and urinary sludge in rabbits (Oryctolagus cuniculus).

Rabbits absorb more calcium (Ca) from their diet than they require, and excrete surplus via urine, which therefore contains a typical 'sludge'. This makes rabbits susceptible to Ca-containing uroliths. But given the Ca content of diets of free-ranging specimens, and the limited reports of urinary sludge and Ca contents in free-ranging lagomorphs, we can suspect that rabbits are naturally adapted to high urinary Ca loads. We fed four groups of New Zealand hybrid rabbits [n = 28, age at start 5-6 weeks) pelleted diets consisting of lucerne hay only (L, Ca 2.32% dry matter (DM)], lucerne:oats 1:1 (LG, Ca 1.36%), grass hay only (G, Ca 1.04%), or grass:oats 1:1 (GG, 0.83%) for 25 weeks, with water available ad libitum. Diets were not supplemented with Ca, phosphorus, or vitamin D. Rabbits on diets LG and GG had lower food and water intakes, lower faeces and urine output, grew faster and had higher body mass at slaughter (mainly attributable to adipose tissue). Apparent Ca digestibility decreased in the order L-LG-G/GG. Rabbits on L had larger and heavier kidneys, more urinary sediment at sonography, and a higher urinary Ca content than the other groups. No animal showed signs of urolithiasis/calcinosis at X-ray, sonography, or gross pathology. Kidney/aorta histology only sporadically indicated Ca deposits, with no systematic difference between groups. Under the conditions of the experiment, dietary Ca loads in legume hay do not appear problematic for rabbits, and other factors, such as water supply and level of activity may be important contributors to urolithiasis development in veterinary patients. However, due to the lower Ca content of grass hay, the significantly lower degree of urinary sludge formation, and the significantly higher water intake related with grass hay feeding, grass hay-dominated diets are to be recommended for rabbits in which urolithiasis prevention is an issue.

Detection of Merkel cell polyomavirus in epidermodysplasia-verruciformis-associated skin neoplasms.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. OBJECTIVE: To examine whether EV is associated with cutaneous MCPyV infection. METHODS: We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. RESULTS: In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. CONCLUSIONS: The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.

First metatarsophalangeal joint replacement: long-term results of a double stemmed flexible silicone prosthesis.

BACKGROUND: The aim of this retrospective study was to evaluate the long-term results of a Swanson type silicone prosthesis used for the first metatarsophalangeal (FMTP) joint replacement. It compares implants with and without the use of grommets. METHODS: Fifty-nine FMTP joints were replaced. The average follow-up period was 9 years. Subjective and clinical findings were scored according to the AOFAS-HMI (American Orthopedic Foot and Ankle Society-Hallux Metatarsophalangeal-Interphalangeal) score. X-ray examination was carried out by evaluation of the presence of reactive bone areas around the implant. RESULTS: Ninety-five percent of patients had relief of pain. Clinical findings showed a reasonable function (range of motion >30°) in 77% of the FMTP joints. A trend for decrease in radiolucency and lytic bone was seen in areas around the implant with the use of grommets. CONCLUSION: The prosthesis shows good results concerning pain relief and a reasonable to good function (>30° range of motion) of the FMTP joint in most patients. Reactive bone areas around the implant decreased by the use of grommets.

Mild clinical phenotype of Kindler syndrome associated with late diagnosis and skin cancer.

Kindler syndrome (KS) is a heritable skin disorder with a complex phenotype consisting of congenital skin blistering, photosensitivity, progressive generalized poikiloderma and extensive skin atrophy. Here we describe 2 siblings with KS, who are, to the best of our knowledge, the oldest patients reported so far in the literature. The diagnosis was established in their seventh and eighth decades of life, and confirmed by mutation analysis. Both patients were homozygous for the recurrent FERMT1 mutation, c.328C→T, p.R110X. Because of a relatively mild course of the disease, mucosal membranes in the eyes and oesophagus being predominantly affected in recent years, they had been treated under other diagnoses, such as scleroderma. Cutaneous precancerous lesions and epithelial skin cancer arose in both siblings after the age of 50 years and were treated in an early stage. Taken together, we describe the natural course of KS, the morphological abnormalities occurring in the skin of older KS patients, we discuss the differential diagnosis and the association between KS and squamous cell carcinoma.

Semiochemicals of the Scarabaeinae VIII. Identification of active constituents of the abdominal sex-attracting secretion of the male dung beetle, Kheper bonellii, using gas chromatography with flame ionization and electroantennographic detection in parallel.

Using gas chromatography with flame ionization detection and electroantennographic detection in parallel (GC-FID/EAD), the active constituents of the sex attractant of male dung beetles of Kheper bonellii were located in the gas chromatogram of an extract of the secretion. These constituents were identified as propanoic acid, butanoic acid, indole, 3-methylindole (skatole) and methyl cis-cascarillate (methyl cis-2-2'-hexylcyclopropylacetate) by, inter alia, GC-MS, (1)H and (13)C NMR analysis, and synthesis. These compounds elicited EAD responses in male as well as female antennae. Racemic methyl cis-cascarillate was synthesized for comparison with the natural methyl ester. Enantioselective GC-FID/EAD using a capillary column coated with OV-1701-OH containing 10% heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin showed that the natural compound co-eluted with the first-eluting enantiomer of the racemic methyl cis-cascarillate, which was the only enantiomer that elicited EAD responses in the antennae of male and female K. bonellii. The absolute configuration of this enantiomer was established by a stereoselective synthesis, which gave methyl (R,R)-cascarillate [methyl (1'R,2'R)-2-2'-hexylcyclopropylacetate] in an enantiomeric excess of 69%.

A comparison of hydrological and topological watersheds.

We introduce the hydrological watershed, a watershed where water can penetrate the soil, and compare it with the topological watershed for a two-dimensional landscape. For this purpose, we measure the fractal dimension of the hydrological watershed for different penetration depths and different grid sizes. Through finite size scaling, we find that the fractal dimension is 1.31 ± 0.02 which is significantly higher than the fractal dimension of the topological watershed. This indicates that the hydrological watershed belongs to a new universality class. We also find that, as opposed to the topological watershed, the hydrodynamic watershed can exhibit disconnected islands.

Blockade and stimulation of renal, adrenal, and vascular angiotensin II receptors with 1-Sar, 8-Ala angiotensin II in normal man.

We have assessed the capacity of an analogue of angiotensin II (A II), 1-Sar, 8-Ala A II (P113) in normal man to stimulate and block responses to A II in four systems: blood pressure was monitored directly from an arterial catheter, and renal blood flow was measured with 133Xe and arterial renin and aldosterone concentrations by radioimmunoassay. The 31 normal subjects were in balance on a daily intake of 200 meg sodium and 100 meq potassium to suppress endogenous renin. P113 administered intravenously induced a dose-related renal blood flow reduction, with a threshold dose of 0.1 mug/kg/min. This dose also induced a small but significant increase in arterial blood pressure and plasma aldosterone as well as a reduction in plasma renin activity. In contrast to its effect on the renal vasculature, no tendency to a progressive response in the latter three parameters was noted as the P113 dose was increased 30-fold, to 3.0 mug/kg/min. P113 also reduced the clearance of para-aminohippurate, creatinine, sodium, and potassium, a pattern similar to that induced by A II. P113 at 0.1 mug/kg/min reduced significantly the blood pressure and renal vascular and aldosterone responses to graded doses of A II. Higher P113 doses totally obliterated all three responses to A II infused at 10 ng/kg/min, a dose that provides arterial A II concentrations in the range found in angiotensin-mediated hypertension. When A II was infused first, to induce a pressor, renal vascular, and aldosterone response, P113 induced a dose-related reversal of the response in each system. In conclusion, P113 is a partial agonist in normal man, inducing an angiotensin-like response in settings in which endogenous A II is not playing a tonic role, and displaying dominant antagonist activity in settings in which A II is active. Moreover, the studies suggest that the receptors mediating the responses to A II are different in the renal vasculature and other systemic vascular beds. The adrenal receptor must also differ. This agent should be useful in dissecting the role of A II in diseases characterized by hypertension or abnormalities of renal and adrenal function.