Closure of Temporary Ileostomy 2 Versus 12 Weeks After Rectal Resection for Cancer: A Word of Caution From a Prospective, Randomized Controlled Multicenter Trial.

BACKGROUND: The optimum timing for temporary ileostomy closure after low anterior resection is still open. OBJECTIVE: This trial aimed to compare early (2 wk) versus late (12 wk) stoma closure. DESIGN: The study included 2 parallel groups in a multicenter, randomized controlled clinical trial. SETTINGS: The study was conducted at 3 Swiss hospitals. PATIENTS: Patients undergoing low anterior resection and temporary ileostomy for cancer were included. INTERVENTIONS: Patients were randomly allocated to early or late stoma closure. Before closure, colonic anastomosis was examined for integrity. MAIN OUTCOME MEASURES: The primary efficacy outcome was the Gastrointestinal Quality of Life Index 6 weeks after resection. Secondary end points included safety (morbidity), feasibility, and quality of life 4 months after low anterior resection. RESULTS: The trial was stopped for safety concerns after 71 patients were randomly assigned to early closure (37 patients) or late closure (34 patients). There were comparable baseline data between the groups. No difference in quality of life occurred 6 weeks (mean Gastrointestinal Quality of Life Index: 99.8 vs 106.0; p = 0.139) and 4 months (108.6 vs 107.1; p = 0.904) after index surgery. Intraoperative tendency of oozing (visual analog scale: 35.8 vs 19.3; p = 0.011), adhesions (visual analog scale: 61.3 vs 46.2; p = 0.034), leak of colonic anastomosis (19% vs 0%; p = 0.012), leak of colonic or ileal anastomosis (24% vs 0%; p = 0.002), and reintervention (16% vs 0%; p = 0.026) were significantly higher after early closure. The concept of early closure failed in 10 patients (27% vs 0% in the late closure group (95% CI for the difference, 9.4%-44.4%)). LIMITATIONS: The trial was prematurely stopped because of safety issues. The aimed group size was not reached. CONCLUSIONS: Early stoma closure does not provide better quality of life up to 4 months after low anterior resection but is afflicted with significantly adverse feasibility and higher morbidity when compared with late closure. See Video Abstract at http://links.lww.com/DCR/B665. CIERRE DE LA ILEOSTOMA TEMPORAL VERSUS SEMANAS POSTERIOR A LA RESECCIN RECTAL POR CNCER UNA ADVERTENCIA DE UN ESTUDIO MULTICNTRICO CONTROLADO RANDOMIZADO PROSPECTIVO: ANTECEDENTES:El momento óptimo para el cierre temporal de la ileostomía posterior a la resección anterior baja es aun controversial.OBJETIVO:Este estudio tuvo como objetivo comparar el cierre del estoma temprano (2 semanas) versus tardío (12 semanas).DISEÑO:Estudio clínico controlado, randomizado, multicéntrico, de dos grupos paralelos.ENTORNO CLINICO:El estudio se llevó a cabo en 3 hospitales suizos.PACIENTES:Se incluyeron pacientes sometidos a resección anterior baja e ileostomía temporal por cáncer.INTERVENCIONES:Los pacientes fueron asignados aleatoriamente al cierre del estoma temprano o tardío. Antes del cierre, se examinó la integridad de la anastomosis colónica.PRINCIPALES MEDIDAS DE VALORACION:El principal resultado de eficacia fue el Índice de Calidad de Vida Gastrointestinal 6 semanas después de la resección. Los criterios secundarios incluyeron la seguridad (morbilidad), factibilidad y calidad de vida 4 meses posterior a la resección anterior baja.RESULTADOS:El estudio se detuvo por motivos de seguridad después de que 71 pacientes fueron asignados aleatoriamente a cierre temprano (37 pacientes) o cierre tardío (34 pacientes). Hubo datos de referencia comparables entre los grupos. No se produjeron diferencias en la calidad de vida 6 semanas (índice de calidad de vida gastrointestinal, media 99,8 vs. 106; p = 0,139) y 4 meses (108,6 vs 107,1, p = 0,904) después de la cirugía inicial. Tendencia intraoperatoria de supuración (escala analógica visual 35,8 vs 19,3, p = 0,011), adherencias (escala analógica visual 61,3 vs 46,2, p = 0,034), fuga de anastomosis colónica (19% vs 0%, p = 0,012), fuga de anastomosis colónica o ileal (24% vs 0%, p = 0,002) y reintervención (16% vs 0%, p = 0,026) fueron significativamente mayores después del cierre temprano. El concepto de cierre temprano fracasó en 10 pacientes (27% vs ninguno en el grupo de cierre tardío (intervalo de confianza del 95% para la diferencia: 9,4% a 44,4%)).LIMITACIONES:El estudio se detuvo prematuramente debido a problemas de seguridad. No se alcanzó el tamaño del grupo previsto.CONCLUSIÓN:El cierre temprano del estoma no proporciona una mejor calidad de vida hasta 4 meses posterior a una resección anterior baja, esto se ve afectado por efectos adversos significativos durante su realización y una mayor morbilidad en comparación con el cierre tardío. Consulte Video Resumen en http://links.lww.com/DCR/B665.

qPET - a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma.

BACKGROUND: Interim FDG-PET is used for treatment tailoring in lymphoma. Deauville response criteria consist of five ordinal categories based on visual comparison of residual tumor uptake to physiological reference uptakes. However, PET-response is a continuum and visual assessments can be distorted by optical illusions. OBJECTIVES: With a novel semi-automatic quantification tool we eliminate optical illusions and extend the Deauville score to a continuous scale. PATIENTS AND METHODS: SUVpeak of residual tumors and average uptake of the liver is measured with standardized volumes of interest. The qPET value is the quotient of these measurements. Deauville scores and qPET-values were determined in 898 pediatric Hodgkin's lymphoma patients after two OEPA chemotherapy cycles. RESULTS: Deauville categories translate to thresholds on the qPET scale: Categories 3, 4, 5 correspond to qPET values of 0.95, 1.3 and 2.0, respectively. The distribution of qPET values is unimodal with a peak representing metabolically normal responses and a tail of clearly abnormal outliers. In our patients, the peak is at qPET = 0.95 coinciding with the border between Deauville 2 and 3. qPET cut values of 1.3 or 2 (determined by fitting mixture models) select abnormal metabolic responses with high sensitivity, respectively, specificity. CONCLUSIONS: qPET methodology provides semi-automatic quantification for interim FDG-PET response in lymphoma extending ordinal Deauville scoring to a continuous scale. Deauville categories correspond to certain qPET cut values. Thresholds between normal and abnormal response can be derived from the qPET-distribution without need for follow-up data. In our patients, qPET < 1.3 excludes abnormal response with high sensitivity.

[Treatment of acute ankle distortion in footballers : Are we doing it particularly right or particularly wrong?] / Die Behandlung der akuten oberen Sprunggelenksdistorsion beim Fußballer : Machen wir es beim Profi besonders richtig oder besonders falsch?

BACKGROUND: Despite the high incidence of ankle sprains, the ideal treatment is controversial and a significant percentage of patients who have suffered an ankle sprain never fully recover. Even professional athletes are affected by this post-traumatic complication. There is strong evidence that permanent impairment after an ankle injury is often due to an inadequate rehabilitation and training program and too early return to sport. THERAPY AND REHABILITATION: Therefore, athletes should start a criteria-based rehabilitation after ankle sprain and gradually progress through the programmed activities, including e.g. cryotherapy, edema reduction, optimal load management, range of motion exercises to improve ankle dorsiflexion and digital guidance, stretching of the triceps surae with isometric exercises and strengthening of the peroneus muscles, balance and proprioception training, and bracing/taping. The fact that this is professional sport does not exempt it from consistent, stage-appropriate treatment and a cautious increase in load. However, there are a number of measures and tools that can be used in the intensive care of athletes to improve treatment and results.

Injection of Autologous Adipose Stromal Vascular Fraction in Combination with Autologous Conditioned Plasma for the Treatment of Advanced Knee Osteoarthritis Significantly Improves Clinical Symptoms.

(1) Background: Osteoarthritis (OA) is the most common joint disease in the world. It is chronic, systemic, progressive and disabling. Orthobiologics have the potential to positively alter the course of this disease. Therefore, the aim of this study is to evaluate the efficacy of SVF/ACP in the treatment of advanced osteoarthritis of the knee in an unfiltered patient population. We hypothesize that this therapy can improve the symptoms associated with osteoarthritis of the knee. We also hypothesize that there are patient-related factors that influence the efficacy of therapy. (2) Methods: Two hundred and thirteen patients with moderate to severe OA of the knee and SVF/ACP injection were recruited for this study. Patients were excluded if they did not provide informed consent or were not receiving SVF/ACP therapy. Pain, function, symptoms and quality of life were assessed using standardized scores (KOOS, WOMAC) before and after treatment. (3) Results: The VAS pain score was significantly reduced by at least 30% (p < 0.001). Knee function, as measured by the KOOS daily activity and sport scores, showed significant increases of 21% and 45%, respectively, at 6 months (p < 0.04). (4) Conclusions: Treatment of knee OA with SVF/ACP injection positively modifies the disease by significantly reducing pain and improving function.

The Effect of Therapeutic Adherence on the Effectiveness of a Digital Therapeutic Exercise Program: A Propensity Score Matching Analysis.

Nonspecific back pain (NSBP) contributes greatly to the overall burden of disease from musculoskeletal conditions. Digital therapeutics (DTx) aims to address the excess demand for movement and exercise therapy resulting from this spectrum of conditions. This study aims to investigate the differential therapeutic response of NSBP to different use profiles of a digital home exercise program. METHODS: This study used a PSM model to comparatively assess the achievement of a clinically relevant pain improvement among patients who exhibit a high use (HU), intermediate use (IU), low use (LU), or sub-LU use profile. Sensitivity analyses with commonly accepted thresholds for clinically relevant improvements were conducted. RESULTS: Higher use profiles show a higher probability of achieving a clinically relevant improvement of self-reported pain intensities. Additionally, the achievement of any higher use level is associated with a significant increase in the probability of achieving a clinically relevant improvement. CONCLUSION: To enable the optimal effectiveness of DTx home exercise programs, an HU use profile should be pursued. This finding is in line with earlier guidance for the achievement of optimal therapeutic benefit from conventional movement and exercise therapy and underscores the importance of a cross-disciplinary effort from patients, healthcare professionals and system stakeholders alike to maximize the therapeutic effect from DTx.

Virtual Reality for Upper Extremity Rehabilitation-A Prospective Pilot Study.

Applications related to virtual reality are a rapidly growing area. Thus, these technologies are also increasingly used in the field of medicine and rehabilitation. The primary objective of this prospective pilot study was to investigate the feasibility, user experience and acceptance of a virtual-reality-based system for upper extremity rehabilitation. The study was conducted as a single-center trial over 16 weeks. The eligibility criteria included rehabilitants with upper extremity injuries of at least 18 years of age who were fluent in spoken and written German. After detailed instruction, each participant was asked to complete daily 30 min exercises over 15 training sessions with the virtual reality system consisting of three different training modules. Outcomes were assessed pre-study and post-study using standardized clinical measures. In addition, qualitative interviews with rehabilitants as well as therapists regarding user experience and acceptance were conducted. Six participants were recruited for the pilot study, of which five underwent virtual-reality-based rehabilitation. Overall, the clinical measures showed a positive tendency over the course of the study, even if the results were not significant. Furthermore, the virtual-reality-based training was well accepted by the participants as well as therapists. Given these findings, it will be beneficial to evaluate virtual reality for rehabilitation in further research.

COVID-19 after the first wave of the pandemic among employees from a German university hospital: prevalence and questionnaire data.

The SARS-CoV-2 pandemic has changed lives around the world. In particular, healthcare workers faced significant challenges as a result of the pandemic. This study investigates the seroprevalence of SARS-CoV-2 in March-April 2020 in Germany among healthcare workers and relates it to questionnaire data. In June 2020, all employees of the reporting hospital were offered a free SARS-CoV-2 antibody test. The first 2,550 test results were sent along with study documents. The response rate was 15.1%. The COVID-19 PCR test prevalence amongst health care workers in this study was 1.04% (95% CI 0.41-2.65%), higher by a factor of 5 than in the general population (p=0.01). The ratio of seroprevalence to PCR prevalence was 1.5. COVID-19-associated symptoms were also prevalent in the non-COVID-19-positive population. Only two symptoms showed statistically significant odds ratios, loss of smell and loss of taste. Health care workers largely supported non-pharmaceutical interventions during the initial lockdown (93%). Individual behavior correlated significantly with attitudes toward policy interventions and perceived individual risk factors. Our data suggest that healthcare workers may be at higher risk of infection. Therefore, a discussion about prioritizing vaccination makes sense. They also support offering increased SARS-CoV-2 testing to hospital workers. It is concluded that easier access to SARS-CoV-2 testing reduces the number of unreported cases. Furthermore, individual attitudes toward rules and regulations on COVID-19 critically influence compliance. Thus, one goal of public policy should be to maintain high levels of support for non-pharmaceutical interventions to keep actual compliance high.

Total ankle arthroplasty in patients with hereditary hemochromatosis.

BACKGROUND: More than half of patients with hereditary hemochromatosis (HH) have painful arthritis, often including hindfoot osteoarthritis. Total ankle arthroplasty (TAA) is increasingly recommended for patients with painful ankle osteoarthritis. However, the pain relief and function experienced by patients continues to be debated particularly as compared with ankle fusion. QUESTIONS/PURPOSES: We asked whether (1) the complication rates were low; (2) the components were stable; (3) the patients achieved pain relief; and (4) the patients had satisfactory midterm function, ROM, and quality of life. PATIENTS AND METHODS: We retrospectively reviewed all 16 prospectively followed patients (21 implants) with HH who underwent ankle arthroplasty. They had an average age of 59.5 years at the time of surgery. We obtained a visual analog scale for pain, the SF-36, and the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score. Component stability was assessed using weightbearing radiographs. The minimum followup was 3.1 years (average, 5.3 years; range, 3.1-8.6 years). RESULTS: Postoperatively, one patient had débridement of a painful cyst on the tibial side and one patient had a subfibular débridement with a lateral ligament reconstruction. The tibial and talar components were stable in all ankles. The average pain score decreased from 6.7 (range, 3-10) to 1.9 (range, 0-4). All eight categories of SF-36 score showed improvement. The hindfoot score increased from 46 (range, 22-67) to 84 (range, 74-94). CONCLUSIONS: Our data suggest TAA in patients with ankle osteoarthritis secondary to HH is associated with a low risk of postoperative complications and produces pain relief and good function.

Insert position in three-component total ankle replacement.

BACKGROUND: Total ankle replacement has become a valuable treatment option for end-stage osteoarthritis. The most recent generation of implants comprises a second interface between the polyethylene insert and the tibial prosthetic component. This may permit a better adaptation of position between the implant components and thereby prevent unphysiological loading of ankle ligaments and reduce polyethylene wear. To date, no available data have evaluated whether the relative position of talar and tibial implant components change over time. MATERIALS AND METHODS: We assessed the radiographs of 368 ankles that underwent primary arthroplasty with a HINTEGRA® (Newdeal SA, Lyon, France / Integra, Plainsboro, NJ) ankle to determine the spatial relationship between talar and tibial components at the time of surgery and during followup. The mean time to final followup was 51.2 months (range 11 to 98). We analyzed the anteroposterior offset as the distance between the center of the tibiotalar joint and the longitudinal axis of the tibia. RESULTS: The mean anteroposterior offset ratio was 0.0 ± 0.06 (range -0.21 to 0.16), and it remained constant over time. CONCLUSION: Our data suggest that the latest three-component prosthesis functions similar to the two-component prosthesis, but we believe with an added advantage of allowing an individualized position of the polyethylene insert in response to the individual soft tissue load due to different ankle joint configurations.

Lambrinudi arthrodesis with posterior tibialis transfer in adult drop-foot.

BACKGROUND: The adult drop-foot is one of the most disabling disorders that affects gait and quality of life. Despite orthoses and orthopaedic shoes, the disability often progresses. We have used the Lambrinudi arthrodesis to correct the bony component of drop-foot in association with a posterior tibial tendon transfer to provide lateral ankle stability and active dorsiflexion. This study presents results obtained in a consecutive series of 19 patients. MATERIALS AND METHODS: Nineteen patients (mean age, 54.7 years) were treated for drop-foot with an osseous dorsiflexing procedure according to Lambrinudi's original technique and a posterior tibial tendon transfer to the lateral cuneiforme bone. Outcome measurements included extended radiographic and clinical investigations, including the AOFAS Hindfoot Score, SF-36, ROM and VAS. The mean followup time was 39 (range, 24 to 62) months. RESULTS: The AOFAS Hindfoot Score improved from 38.9 preoperatively to 73.2 (p < 0.001) at last followup, and the SF-36 scores improved from 38.3 to 70.5 (p < 0.001). All patients were able to wear normal shoes at final followup. CONCLUSION: In this study of 19 patients, Lambrinudi arthrodesis combined with posterior tibial transfer proved to be a reliable and reproducible treatment for semi-rigid and rigid adult drop-foot caused by several aetiologies. It provided a stable correction of the adult drop-foot and high patient satisfaction in the mid- to long-term. In particular, it enabled the patient to wear normal shoes.

Quantitative myocardial perfusion PET combined with coronary anatomy derived from CT angiography: validation of a new fusion and visualisation software.

AIM: Dynamic perfusion PET offers a clinical relevant advantage over myocardial perfusion scintigraphy due to its ability to measure myocardial blood flow quantitatively. This leads to an improved detection of multivessel disease and the possibility to assess not only the culprit lesion but lower grade stenoses as well. For appropriate revascularization, perfusion defects must be matched to coronary lesions. It has been shown that image fusion of morphological and functional images is superior to side-by-side analysis. Still, software for quantitative perfusion PET combined with CT angiography is rare. In this paper we present a new software tool for image fusion and visualization of quantitative perfusion PET and coronary morphology derived from CT angiography. METHODS: In our software, a PET uptake image is used for manual co-registration. Co-registration results are then applied to the functional data derived from compartment modelling. To evaluate the reproducibility of the manual co-registration, we calculated the deviation between a series of manual co-registrations performed on nine pairs of unregistered PET and CT datasets by five trained participants. Two dimensional transfer functions were used to highlight the coronary arteries from the CT study in the combined data sets. RESULTS: The average Euclidian distances for three references points were between 3.7 and 4.1 mm. The maximum distance was 10.6 mm. By the use of the two dimensional transfer functions, coronary anatomy could be easily visualised either by user-interaction or automatically by use of neuronal networks. CONCLUSIONS: With this approach it is possible to combine quantitative perfusion PET with coronary anatomy derived from CT angiography. Our first experiences indicate that manual image fusion with our tool is reproducible and that visualisation of the combined datasets is achieved within short time.

Apparently isolated partial articular fractures of the radial head: prevalence and reliability of radiographically diagnosed displacement.

The purpose of this study was to measure the prevalence and reliability of the radiographic diagnosis of displacement of apparently isolated partial articular radial head fractures and use these factors to assess treatment considerations. Among 119 radiographically visible partial fractures of the radial head not associated with other wrist, forearm, or elbow injury, 101 were classified as Mason type 1 (85%), 11 as borderline between Mason type 1 and Mason type 2 fractures (9%), and 7 as Mason type 2 fractures (6%) according to Broberg and Morrey's modification of the Mason classification. The intraobserver reliability of the classification of Mason type 1 and type 2 fractures was excellent (mean kappa, 0.85), but the interobserver reliability was only moderate (multirater kappa, 0.45). Because apparently isolated, stable partial fractures of the radial head are infrequently displaced and observers have moderate disagreement regarding the diagnosis of displacement, it is likely that displacement is overdiagnosed.

The venous pump of the first metatarsophalangeal joint: clinical implications.

BACKGROUND: Although the anatomy and physiology of the venous circulation of the ankle and midfoot are well documented, the physiologic importance of forefoot mobility has not been reported in the literature. The question of this study was whether the first metatarsophalangeal (MTP) joint may operate, like the ankle, as a "pump" to encourage venous return. METHODS: Forty-nine cadaver foot specimens were examined using dissection, plastination, vessel infiltration, and maceration, and radiographic (including venography, MRI, and magnetic resonance angiography) techniques. The anatomy and physiology were described and compared to the ankle joint. Forty patients had biphasic Doppler flow studies. RESULTS: The major finding was the medial drainage of the plantar venous sinus, which is fibrotically bound to the joint capsule. Functional venous valves were evident distally and within fibrous vascular lumens. Mobilization of the first MTP joint led to compression and emptying of the veins. Passive mobilization of the first MTP joint led to an average flow increase of 55% +/- 7 (p < 0.0001), while active movement led to an average increase of 78% +/- 7 (p < 0.0001). CONCLUSIONS: Our described connection between the joint capsule and veins indicates a "toe-ankle pump" with a significant increase of venous blood flow during motion of the MTP joint. Possible clinical applications for an external MTP pump include anti-edema or thromboprophylactic therapy, especially in patients with foot or ankle injuries. A new toe-pump has been designed based on these results.

Reduced collagen degradation in polytraumas with traumatic brain injury causes enhanced osteogenesis.

Patients with traumatic brain injury (TBI) and skeletal injuries have increased rates of excessive bone healing (EH = hypertrophic callus formation and/or heterotopic ossification). Polytrauma patients are often attributed higher rates of delayed fracture union. This study compares 182 total fractures in 29 isolated polytrauma patients (POLY) and 48 patients after TBI and polytrauma (TBI+POLY), examining the clinical parameters of EH versus delay. A subset of 28 patients (13 TBI+POLY, 15 POLY) underwent serological testing for the following bone turnover parameters: carboxy-terminal extension peptide of type 1 procollagen (P1CP), pyridinolene cross-linked carboxy-terminal telopeptide (1CTP), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and basic fibroblast growth factor (bFGF). There were higher rates of delayed union in the POLY patients (45% vs. 23%) and EH in the TBI+POLY patients (33% vs. 17%) (not significant = NS). More delayed unions were observed in diaphyseal fractures suffered by POLY (28%) than in TBI+POLY (15%) patients (NS). EH after pelvic fracture was apparent in 52% TBI+POLY and in 21% POLY fractures (NS). P1CP levels did not differ between the groups, but the collagen breakdown parameter 1CTP was significantly higher in the POLY group (p = 0.01-0.04). IGF-1 levels were below normal in both groups, and did not differ. IGFBP-3, an IGF-1-inhibiting and collagenase-3-activating protein, was significantly higher in POLY patients (p = 0.017-0.037). bFGF levels did not vary between groups. Increased serum levels of 1CTP and IGFBP-3 in POLY patients suggest that EH in TBI patients is secondary to decreased collagen breakdown rather than increased synthesis.

Symptomatic giant peritoneal loose body in the pelvic cavity: A case report.

INTRODUCTION: Giant peritoneal loose bodies (gPLB) occur rarely and therefore only few have been described. Often they are found incidentally and have no clinical relevance, whereas symptomatic forms may require surgical removal. PRESENTATION OF CASE: We report the case of a male patient suffering from abdominal discomfort with alternating localizations for several years, actually presenting with a proctitis. With elevated inflammatory markers, a conspicuous resistance in the lower abdomen and in order to evaluate further affection of the colon, an abdominal CT-scan was performed. It revealed a spherical mass in the lesser pelvis. A colonoscopy confirmed the proctitis, showing no further pathologies. Due to the symptoms and the uncertain entity of the mass, a diagnostic laparoscopy was performed and a boiled egg-like structure (diameter 5.2cm) was removed. The patient recovered well and was free of symptoms. DISCUSSION: The patient had two potential reasons for his symptoms, one of them being a suspected leftover foreign body years after an appendectomy. The proctitis was treated conservatively but without complete remission of the abdominal discomfort. Therefore, a diagnostic laparoscopy was performed and the mass turned out to be a gPLB. CONCLUSION: To obtain a fast diagnosis and to perform an adequate conservative or surgical therapy, the knowledge about the rare entity of a gPLB is necessary. An exact anamnesis, clinical examination and the knowledge about the diagnostic values of radiological and endoscopic investigations are crucial.

Automated biological target volume delineation for radiotherapy treatment planning using FDG-PET/CT.

BACKGROUND: This study compared manually delineated gross tumour volume (GTV) and automatically generated biological tumour volume (BTV) based on fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT to assess the robustness of predefined PET algorithms for radiotherapy (RT) planning in routine clinical practice. METHODS: RT-planning data from 20 consecutive patients (lung- (40%), oesophageal- (25%), gynaecological- (25%) and colorectal (10%) cancer) who had undergone FDG-PET/CT planning between 08/2010 and 09/2011 were retrospectively analysed, five of them underwent neoadjuvant chemotherapy before radiotherapy. In addition to manual GTV contouring, automated segmentation algorithms were applied-among these 38%, 42%, 47% and 50% SUVmax as well as the PERCIST total lesion glycolysis (TLG) algorithm. Different ratios were calculated to assess the overlap of GTV and BTV including the conformity index and the ratio GTV included within the BTV. RESULTS: Median age of the patients was 66 years and median tumour SUVmax 9.2. Median size of the GTVs defined by the radiation oncologist was 43.7 ml. Median conformity indices were between 30.0-37.8%. The highest amount of BTV within GTV was seen with the 38% SUVmax algorithm (49.0%), the lowest with 50% SUVmax (36.0%). Best agreement was obtained for oesophageal cancer patients with a conformity index of 56.4% and BTV within GTV ratio of 71.1%. CONCLUSIONS: At present there is only low concordance between manually derived GTVs and automatically segmented FDG-PET/CT based BTVs indicating the need for further research in order to achieve higher volumetric conformity and therefore to get access to the full potential of FDG-PET/CT for optimization of radiotherapy planning.

The effect of three-component total ankle replacement malalignment on clinical outcome: pain relief and functional outcome in 317 consecutive patients.

BACKGROUND: Total ankle replacement has become an increasingly popular treatment for patients with end-stage ankle osteoarthritis. The surgery is technically demanding and generally performed by only experienced foot and ankle surgeons. An important complication of total ankle replacement is malposition of the talar component. The biomechanical effect of malposition has been reported; however, the functional outcomes of patients with varying degrees of talar component malposition have not. The purpose of this study was to assess the influence of talar component malposition on postoperative pain relief and functional outcome. METHODS: This retrospective cohort study included 317 total ankle replacements in 317 patients. The anteroposterior offset ratio was measured with use of lateral ankle radiographs made with the patient in a standing, weight-bearing position. Patients were classified into one of three groups: those with an anteroposterior offset ratio of 0 (127 ankles), those with a ratio of >0 (103 ankles), and those with a ratio of <0 (eighty-seven ankles). Postoperative pain relief was assessed with use of a visual analogue scale. Functional outcome was assessed with the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score and measurement of ankle range of motion. The mean duration of follow-up (and standard deviation) was 53.2 ± 18.4 months (range, twenty-four to ninety-eight months). RESULTS: The postoperative pain level in the group with an anteroposterior offset ratio of 0 was significantly lower than that for both the group with a ratio of >0 (p < 0.001) and the group with a ratio of <0 (p = 0.017). Also, the functional outcome, measured with use of the AOFAS hindfoot score, was significantly higher, and ankle motion was significantly greater, in the group with an anteroposterior offset ratio of 0 than in the group with a ratio of >0 (p = 0.003 and p < 0.001, respectively) and the group with a ratio of <0 (p = 0.007 and p = 0.080). CONCLUSIONS: The anteroposterior offset ratio may be a useful predictor of outcome in patients with total ankle replacement with regard to both pain and function. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

A universally applicable 68Ga-labeling technique for proteins.

UNLABELLED: Although protein-based PET imaging agents are projected to become important tracer molecules in the future, the labeling of complex biomolecules with PET radionuclides is inexpedient and, most of the time, challenging. METHODS: Here we present a straightforward labeling chemistry to attach the versatile radionuclide (68)Ga to proteins. Introducing the (68)Ga chelating agent NODA-GA-T (2,2'-(7-(1-carboxy-4-(2-mercaptoethylamino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid) by reaction with proteins chemically processed with sulfo-SMCC (4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt) results in labeling precursors, enabling a simple and rapid kit-labeling procedure that requires no workup of the radiolabeled proteins. Various (68)Ga- proteins were labeled using this method, and the radiochemical yields and specific activities of the labeled proteins were determined. To show that the radiotracers are applicable for in vivo studies, proof-of-concept small-animal PET images were acquired in healthy rats using (68)Ga rat serum albumin for blood-pool imaging and (68)Ga-annexin V for apoptosis imaging in mice with a left ventricular myocardial infarction. RESULTS: The proteins could be modified, yielding 1.2-1.7 (68)Ga-labeling sites per protein molecule. All investigated proteins could be labeled in high radiochemical yields of 95% or more in less than 10 min in 1 step, using acetate-buffered medium (pH 3.5-4.0) at room temperature without any further purification. The labeled proteins displayed specific activities of 20-45 GBq/µmol (540-1,200 Ci/mmol). In the proof-of-concept in vivo studies, (68)Ga rat serum albumin and (68)Ga-annexin V were successfully used for in vivo imaging. Both radiotracers showed a favorable biodistribution in the animal models, thus demonstrating the usefulness of the developed approach for the kit (68)Ga labeling of proteins. CONCLUSION: The preprocessing of proteins proceeds in high chemical yields and with high protein recovery rates after purification. These precursors can be stored for several months at -20°C without degradation, and (68)Ga labeling can be performed in a 1-step kit-labeling reaction in high radiochemical yields. Two of the derivatized model proteins were successfully used in proof-of-concept in vivo imaging studies to prove the applicability of this kit (68)Ga-labeling technique.