No differences in mid-term survival and clinical outcome between CT- and MRI-based patient-specific instrumentation for total knee arthroplasty, a randomized controlled trial.

PURPOSE: The purpose of this prospective randomized controlled trial was to compare the clinical outcome and the survival rate of total knee arthroplasty between CT- and MRI-based patient-specific instrumentation 5 years after initial surgery. METHODS: At a mean follow-up of 5.8 years (SD 0.3), 98 patients (64% women, loss to follow-up 28%) were included in this analysis. To assess the differences in clinical outcome, patients fulfilled PROMs preoperatively and at each follow-up moment. At final follow-up, the Forgotten Joint Score was adjusted. RESULTS: At final follow-up, no new patients underwent revision surgery in both groups. Regarding the clinical outcome, no statistically significant difference between the groups was found. The Forgotten Joint Score was only performed at final follow-up and showed no significant difference between both groups. CONCLUSION: At mid-term follow-up, survival rates between CT- and MRI-based patient-specific instrumentation did not show a significant difference. Regarding clinical outcome, only the EQ-5D-VAS (p < 0.040) showed a statistically significant difference over time, in favor of the MRI-group. LEVEL OF EVIDENCE: Level I.

Cemented versus uncemented hemiarthroplasty of the hip in patients with a femoral neck fracture: a comparison of two modern stem design implants.

PURPOSE: We wished to compare the outcome of two types of cemented and uncemented modern stem design implants after hemiarthroplasty, with both an Orthopaedic Data Evaluation Panel rating of 10A. METHODS: This retrospective study compares data obtained from two centres, with a total study population of 655 (n = 393 cemented, n = 262 uncemented). Patients were matched at baseline for gender, age, surgery side, American Society of Anesthesiologists score, body mass index and pre-operative haemoglobin level. Outcome measurements were prosthesis-related complications, pre- and post-operative, with reoperation rate and mortality and other complications after 1 year, surgery time, blood loss and immobility at discharge. RESULTS: There were no significant differences in mortality after 1 year, total other complications, immobility at the time of discharge and total prosthesis-related complications between both groups. Significantly more periprosthetic fractures and post-operative infections were seen in the uncemented group with significantly more reoperations compared to the cemented group. Significant differences were seen in cardiovascular complications, blood loss and surgery time in favour of the uncemented group. CONCLUSIONS: In consequence of the significant higher prosthesis-related complications (e.g. infections, periprosthetic fractures and reoperations) in the uncemented group in this study, we recommend cemented hemiarthroplasty in patients with a femoral neck fracture. LEVEL OF EVIDENCE: Level III, Case Controlled Study.

Near-anatomical correction using a CT-guided technique of a forearm malunion in a 15-year-old girl: A case report including surgical technique.

BACKGROUND: In this case report, we describe a left-arm both-bone forearm fracture in a 15-year-old girl who fell off a swing. Conservative treatment with an above-elbow cast failed, resulting in a malunion with functional impairment. The pro- and supination were 90/0/10, respectively. The patient complained of difficulties performing daily activities. For this pediatric case, a corrective osteotomy was proposed using a CT-guided technique aiming for maximum anatomical and functional outcome. It was the first time this technique was used in our hospital. METHODS: A corrective osteotomy of the patient's left arm was performed using 3D printed templates to guide the osteotomy orientation. These templates were produced using specialized software in which CT images of her malunited left forearm were overlaid with the mirrored images of her healthy right forearm. RESULTS: The postoperative CT-scan showed a near-anatomical reduction with close to 1° correction in all three planes, as compared to the preoperative planning. Three months after surgery, the patient had regained full function of her left forearm. CONCLUSION: Although this was the first time this technique was used in our hospital, it resulted in excellent anatomical and functional outcomes making it a safe, reliable and precise treatment option that may be useful for even more complex corrections. LEVEL OF EVIDENCE: Level V.

A radiological analysis of the difference between MRI- and CT-based patient-specific matched guides for total knee arthroplasty from the same manufacturer: a randomised controlled trial.

AIMS: This prospective randomised controlled trial was designed to evaluate the outcome of both the MRI- and CT-based patient-specific matched guides (PSG) from the same manufacturer. PATIENTS AND METHODS: A total of 137 knees in 137 patients (50 men, 87 women) were included, 67 in the MRI- and 70 in the CT-based PSG group. Their mean age was 68.4 years (47.0 to 88.9). Outcome was expressed as the biomechanical limb alignment (centre hip-knee-ankle: HKA-axis) achieved post-operatively, the position of the individual components within 3° of the pre-operatively planned alignment, correct planned implant size and operative data (e.g. operating time and blood loss). RESULTS: The patient demographics (e.g. age, body mass index), correct planned implant size and operative data were not significantly different between the two groups. The proportion of outliers in the coronal and sagittal plane ranged from 0% to 21% in both groups. Only the number of outliers for the posterior slope of the tibial component showed a significant difference (p = 0.004) with more outliers in the CT group (n = 9, 13%) than in the MRI group (0%). CONCLUSION: The post-operative HKA-axis was comparable in the MRI- and CT-based PSGs, but there were significantly more outliers for the posterior slope in the CT-based PSGs. TAKE HOME MESSAGE: Alignment with MRI-based PSG is at least as good as, if not better, than that of the CT-based PSG, and is the preferred imaging modality when performing TKA with use of PSG. Cite this article: Bone Joint J 2016;98-B:786-92.

Accuracy of CT-based patient-specific guides for total knee arthroplasty in patients with post-traumatic osteoarthritis.

Published clinical trials who studied the accuracy of patient-specific guides (PSG) for total knee arthroplasty exclude patients with articular deformity of the knee joint. We prospectively analysed a series of 30 patients with post-traumatic osteoarthritis of the knee joint with use of PSG. At 1 year post-operative, the achieved biomechanical (HKA) axis and varus/valgus of the femur and tibia components were measured on anterior-posterior (AP) long-standing weight-bearing radiographs. Flexion/extension of the femoral and AP slope of the tibia component was measured on standard lateral radiographs. Percentages >3° deviation of the pre-operative planned HKA axis and individual implant components were considered as outliers. Approved and used implant size, median blood loss (ml) and operation time (min) were obtained from the operation records. Pre- and 1-year post-operative patient-reported outcome measures (PROMs) were performed. Eighty-three per cent of the patients had a HKA axis restored <3° of the pre-operative planned alignment. Varus/valgus outliers were 0.0 and 6.7 % for the femoral and tibial components, respectively. Percentages of outliers of flexion/extension were 36.7 % for the femoral component and 10.0 % for the AP slope of the tibial component. Median blood loss was 300 ml (50-700), while operation time was 67 min (44-144). In 20 % of all cases, the approved implant size was changed into one size smaller. One-year post-operative PROMs improved significantly. We conclude that the accuracy of CT-based PSG is not impaired in patients with post-traumatic osteoarthritis and this modality can restore biomechanical limb alignment.

Screening for genetic variants in BDNF that contribute to childhood obesity.

UNLABELLED: What is already known about this subject BDNF is involved in the regulation of food intake and body weight. BDNF deficient animal models are obese. Chromosomal abnormalities cause obesity in humans. What this study adds Evaluation of point mutations in BDNF. Identification of BDNF mutations in obese children. Point mutations in BDNF are not a common cause of childhood obesity. INTRODUCTION: There is ample evidence that BDNF has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that BDNF deficiency leads to the development of obesity. Functional loss of one copy of the BDNF gene, due to chromosomal rearrangements or microdeletions, can cause an obesity phenotype in humans. Therefore, we wanted to investigate whether point mutations in the gene also result in a comparable phenotype. METHODS: We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of BDNF. Mutation screening was performed by high-resolution melting curve analysis and direct sequencing. RESULTS: Screening of obese patients led to the identification of two synonymous variations (V37V and H65H) and two non-synonymous coding mutations (T2I and V46M) in the BDNF gene. When we subsequently screened our control population, we found T2I with comparable frequency and confirmed that this is a rare and non-pathogenic variant. In addition, we found another non-synonymous mutation (N187S) in the control population. CONCLUSIONS: In silico analysis of the V46M variant did not support a clear disease-causing effect and no family data were available in order to determine whether the mutation segregates with obesity. However, we cannot rule out a possible pathogenic effect for this variant. In general, we tend to conclude that mutations in the coding region of BDNF are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.

Mutation screen of the SIM1 gene in pediatric patients with early-onset obesity.

BACKGROUND: The transcription factor SIM1 (Single-minded 1) is involved in the control of food intake and in the pathogenesis of obesity. In mice, Sim1 is involved in the development of the paraventricular nucleus, and Sim1 deficiency leads to severe obesity and hyperphagia. In humans, chromosomal abnormalities in the SIM1 gene region have been reported in obese individuals. Furthermore, recent data also suggest that loss-of-function point mutations in SIM1 are responsible for SIM1 haplo-insufficiency that is involved in causing human obesity. In this study, we therefore wanted to expand the evidence regarding the involvement of SIM1 mutations in the pathogenesis of severe early-onset obesity. METHODS: We screened 561 severely overweight and obese children and adolescents and 453 lean adults for mutations in the coding region of the SIM1 gene. Mutation screening in all patients and lean individuals was performed by high-resolution melting curve analysis combined with direct sequencing. To evaluate the effect of the mutations on SIM1 transcriptional activity, luciferase reporter assays were performed. RESULTS: Mutation analysis identified four novel nonsynonymous coding variants in SIM1 in four unrelated obese individuals: p.L242V, p.T481K, p.A517V and p.D590E. Five synonymous variants, p.P57P, p.F93F, p.I183I, p.V208V and p.T653T, were also identified. Screening of the lean control population revealed the occurrence of four other rare SIM1 variants: p.G408R, p.R471P, p.S492P and p.S622F. For variants p.T481K and p.A517V, which were found in obese individuals, a decrease in SIM1 transcriptional activity was observed, whereas the transcriptional activity of all variants found in lean individuals resembled wild type. CONCLUSIONS: In this study, we have demonstrated the presence of rare SIM1 variants in both an obese pediatric population and a population of lean adult controls. Further, we have shown that functional in vitro analysis of SIM1 variants may help in distinguishing benign variants of no pathogenic significance from variants which contribute to the obesity phenotype.

Ankle fusion using a 2-incision, 3-screw technique.

OBJECTIVE: Reliable fusion and optimal correction of the alignment of the ankle joint using a 2-incision, 3-screw technique. INDICATIONS: Symptomatic osteoarthritis of the ankle joint after insufficient other treatment, severe deformity of the osteoarthritic ankle joint, or salvation procedure after failed arthroplasty. CONTRAINDICATIONS: Active osteomyelitis, very poor soft tissues, or severe peripheral arterial occlusive disease. SURGICAL TECHNIQUE: Osteotomy and excision medial malleolus. Osteotomy, dislocation, and denudation of the distal fibula. Osteotomy of distal tibia and talus in the desired position for optimal alignment. Temporary tibiotalar fixation with two Weber reposition clamps. Final tibiotalar fixation with a medial and lateral 4.5 mm full threaded cortical lag screw. Reduction of the distal fibula and fibulotibial fixation using a similar technique. POSTOPERATIVE MANAGEMENT: A nonweight-bearing circular below knee cast for 6 weeks, followed by a walker or weight-bearing cast for another 6 weeks. RESULTS: A total of 30 ankle fusions in 26 patients were analyzed. Mean age at fusion was 50 years (range 11-72.1 years). Mean follow-up time was 9.2 years (3.4-18.8 years). Radiological and clinical fusion in 28 (93%) of the primary arthrodeses. The mean American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score was 66 ± 12. Of the 26 patients, 22 (85%) were satisfied. Deep wound infection occurred once (3%). No other serious complications were encountered. The described technique provides reliable long-term follow-up results for a wide range of indications for ankle fusion.

Phagocytosis and killing of suspended and adhered bacteria by peritoneal cells after dialysis.

OBJECTIVE: To determine the effect of dialysis fluid containing various glucose concentrations on the phagocytosis and killing of Staphylococcus aureus by rat peritoneal cells under conditions mimicking the in vivo situation. DESIGN: Phagocytosis and killing were evaluated by quantitation of the killing capacity of macrophages after in vivo phagocytosis of the bacteria as well as by an in vitro flow cytometric assay of the phagocytosis and killing of adhered bacteria by peritoneal cells. ANIMALS: Male Wistar rats. MAIN OUTCOME MEASURE: It was expected that the intraperitoneal administration of dialysis fluid would impair the capacity of peritoneal cells to eliminate bacteria. RESULTS: The first test revealed no effects of glucose concentration or dwell time on the killing of phagocytosed bacteria by macrophages, median percentages ranging between 29% and 64%. In the second series of experiments no effect of glucose concentration on the phagocytosis and killing of adhered bacteria was found either; however, longer dwell times significantly enhanced both the phagocytosis (at a dwell time of 1 hour, under 20%; at dwell times of 4 or 18 hours, above 20%, p < 0.02) and the killing (at a dwell time of 1 hour, under 53%; at dwell times of 4 and 18 hours, above 70%, p < 0.01). CONCLUSIONS: Glucose concentration has no effect on the phagocytosis and killing of Staphylococcus aureus, whereas the dwell time significantly enhances both of these functional capacities of peritoneal cells if the bacteria are adhered to surfaces.

Effect of glucose in dialysis fluid on antibacterial defence in the peritoneal cavity.

To study the effect of glucose concentration and dwell time of dialysis fluid on peritoneal antibacterial defence, an experimental infection with Staphylococcus aureus was induced in rats. For this purpose rats were inoculated intraperitoneally with Staphylococcus aureus at different intervals after the administration of various dialysis fluids. Twenty-four hours later the numbers of bacteria and cells in the peritoneal cavity were determined. The number of bacteria was correlated positively with the glucose concentration. Furthermore, an inverse correlation between dwell time and the number of bacteria was observed. Neither finding could be attributed to a glucose-dependent growth of the bacteria or disruption of the killing capacity of peritoneal cells in vitro. A glucose-dependent increase in the volume of the peritoneal fluid could partially explain the differences found in vivo. It is concluded that the glucose in dialysis fluid impairs antibacterial defence in the peritoneal cavity and that longer dwell times enhance this defence.

Effect of interferon-gamma in dialysis fluid on peritoneal defence in rats.

BACKGROUND: A major drawback of continuous ambulatory peritoneal dialysis (CAPD) is the occurrence of peritoneal infection. This might be explained by a non-optimal phagocytic capacity of peritoneal cells which can be improved by stimulating factors. AIM: To investigate the effect of addition of interferon-gamma (IFN) to dialysis fluid with various glucose concentrations or to saline (as control) on the peritoneal defence against Staphylococcus aureus in an experimental dialysis model in rats. METHODS: Twenty-four hours after the administration of either dialysis fluid containing various glucose concentrations or saline with or without IFN, bacteria were injected intraperitoneally. At the time of the bacterial infection and 24 h later cellular and bacterial parameters were studied. RESULTS: The addition of IFN to dialysis fluid or saline resulted in a significant (P < 0.01) increase in the number of peritoneal macrophages at the time of infection; this was accompanied by a significant increase in both the number of Ia-positive peritoneal macrophages (P < 0.01) and the production of nitrite by macrophages (P < 0.05) at the time. IFN in dialysis fluid as well as in saline significantly (P < 0.01) reduced the recovery of bacteria from the peritoneal cavity 24 h after infection. Only the absence of IFN glucose increased the recovery of bacteria from the peritoneal cavity at the same time. CONCLUSION: In this experimental model the addition of IFN to dialysis fluid lowered the recovery of staphylococci from the peritoneal cavity by means of activation of an increased number of macrophages.

Establishing an experimental infection model for peritoneal dialysis: effect of inoculum and volume.

The effect of the number of bacteria and the volume of the inoculum was studied in an experimental infection model to establish a peritoneal dialysis model in the rat. Staphylococcus aureus was used in all experiments, and Staphylococcus epidermidis only in the volume experiments. A bacterial number between 10(8) and 10(9) colony-forming units (cfu) resulted in a time-dependent decrease of bacteria collected from the peritoneal cavity. Higher concentrations resulted in the death of animals, while lower concentrations were rapidly cleared. There was a positive correlation between the volume in which 3 x 10(8) cfu were dissolved and the number of bacteria isolated from the peritoneal cavity 24 hours after infection. The results of this study led to an experimental dialysis model using 10 mL of dialysis fluid and 0.5 mL of a suspension containing 3 x 10(8) cfu of Staphylococcus aureus.

Milky spots in the mouse omentum may play an important role in the origin of peritoneal macrophages.

In the milky spots, precursors of cells belonging to the mononuclear phagocyte system (MPS), such as monoblasts, can be found on the basis of ultrastructural endogenous peroxidase cytochemistry. Therefore, in the present study, we investigated the milky spots using a panel of monoclonal antibodies, especially antibodies (ER-MP) that recognize macrophage precursor antigens. Early macrophage precursor antigens ER-MP12 and ER-MP58 were detected only on cells localized inside the milky spots. On the other hand, an antigen which disappears late in the course of macrophage differentiation, ER-MP20, was detected in high amounts on cells both inside and around the milky spots. This clearly indicates that macrophage precursors are centrally localized inside the milky spots, while more differentiated cells are found in peripheral areas. Moreover, long-term culture of milky spot tissue resulted in the forming of a monolayer of stromal cells which supported macrophage proliferation in vitro. In conclusion, both in situ and in vitro studies demonstrated that mouse milky spots have a microenvironment in which precursor cells of the MPS can home and proliferate, illustrating that milky spots play a role as a source of local macrophage generation, e.g. that of the free peritoneal macrophages.

Effect of glucose concentration and dwell time of dialysis fluid on the antibacterial defense in the peritoneal cavity of rats.

To study the influence of dialysis fluid on the antibacterial defense in the peritoneal cavity of rats, especially glucose concentration and dwell time, an experimental infection was developed. Rats were injected intraperitoneally with dialysis fluid with a glucose concentration of 1.36%, 2.27%, or 3.86% or physiological saline. Subsequently 1, 4 or 18 hr thereafter an inoculum of approximately 3 x 10(8) colony forming units of Staphylococcus aureus was administered intraperitoneally (i.p.) Next, 24 hr after the inoculation the number of viable bacteria was determined. Peritoneal cells (PC) isolated 1, 4 and 18 hr after the administration of dialysis fluid were tested for their capacity to kill S. aureus in vitro. A positive relation was observed between the glucose concentration and the number of bacteria isolated; the longer the dwell time the lower this number. In vitro PC isolated at the various intervals did not differ in their capacity to kill S. aureus. It is concluded that the glucose concentration in dialysis fluid impairs the antistaphylococcal defense in the peritoneal cavity of rats. A relatively long dwell time enhances this defense. These results cannot be explained by a lower capacity of the PC to kill S. aureus in vitro.

Antimycotic azoles. 6. Synthesis and antifungal properties of terconazole, a novel triazole ketal.

The preparation and antifungal properties of cis-1-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1, 3-dioxolan-4-yl]methoxy]phenyl]-4-(1-methylethyl)piperazine are reported. Terconazole has a high topical in vivo activity against vaginal candidosis in rats and against dermatophytosis in guinea pigs.

[Granulomatous cheilitis and Crohn's disease]. / Cheilitis granulomatosa und Crohnsche Krankheit.

A case of Cheilitis granulomatosa is described. The various etiologic hypotheses concerning the disease are summarized and a relation with Crohn's disease is emphasized in this case. The Cheilitis granulomatosa Miescher is to be considered as a cutaneous symptom which can be observed in various diseases (e.g. sarcoidosis, herpetic infections. Crohn's disease, panniculitis).