Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, with median age at diagnosis in the seventh decade. FL in young adults (YAs), defined as diagnosis at ≤40 years, is ...uncommon. No standard approaches exist guiding the treatment of YA FL, and little is known about their disease characteristics and outcomes. To gain further insights into YA FL, we analyzed the National LymphoCare Study (NLCS) to describe characteristics, initial treatments, and outcomes in this population versus patients aged >40 years.
Using the NLCS database, we stratified FL patients by age: 18–40 (YA), 41–60, 61–70, 71–80, and >80 years. Survival probability was estimated using Kaplan–Meier methodology. We examined associations between age and survival using hazard ratios and 95% confidence intervals (CIs) from multivariable Cox models.
Of 2652 eligible FL patients in the NLCS, 164 (6%) were YAs. Of YA patients, 69% had advanced disease, 80% had low-grade histology, and 50% had good-risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI). Nineteen percent underwent observation, 12% received rituximab monotherapy, and 46% received chemoimmunotherapy in 59% of these: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). With a median follow-up of 8 years, overall survival (OS) at 2, 5, and 8 years was 98% (95% CI 93–99), 94% (95% CI 89–97), and 90% (95% CI 83–94), respectively. Median progression-free survival (PFS) was 7.3 years (95% CI 5.6–not reached).
In one of the largest cohorts of YA FL patients treated in the rituximab era, disease characteristics and outcomes were similar to patients aged 41–60 years, with favorable OS and PFS in YAs. Longer-term outcomes and YA-specific survivorship concerns should be considered when defining management. These data may not support the need for more aggressive therapies in YA FL.
Roche/Genentech ML01377 (U2963n).
During the last decades, X-ray (micro-)computed tomography has gained increasing attention for the description of porous skeletal and shell structures of various organism groups. However, their ...quantitative analysis is often hampered by the difficulty to discriminate cavities and pores within the object from the surrounding region.
Herein, we test the ambient occlusion (AO) algorithm and newly implemented optimisations for the segmentation of cavities (implemented in the software Amira). The segmentation accuracy is evaluated as a function of (i) changes in the ray length input variable, and (ii) the usage of AO (scalar) field and other AO-derived (scalar) fields. The results clearly indicate that the AO field itself outperforms all other AO-derived fields in terms of segmentation accuracy and robustness against variations in the ray length input variable. The newly implemented optimisations improved the AO field-based segmentation only slightly, while the segmentations based on the AO-derived fields improved considerably.
Additionally, we evaluated the potential of the AO field and AO-derived fields for the separation and classification of cavities as well as skeletal structures by comparing them with commonly used distance-map-based segmentations. For this, we tested the zooid separation within a bryozoan colony, the stereom classification of an ophiuroid tooth, the separation of bioerosion traces within a marble block and the calice (central cavity)-pore separation within a dendrophyllid coral. The obtained results clearly indicate that the ideal input field depends on the three-dimensional morphology of the object of interest. The segmentations based on the AO-derived fields often provided cavity separations and skeleton classifications that were superior to or impossible to obtain with commonly used distance-map-based segmentations. The combined usage of various AO-derived fields by supervised or unsupervised segmentation algorithms might provide a promising target for future research to further improve the results for this kind of high-end data segmentation and classification. Furthermore, the application of the developed segmentation algorithm is not restricted to X-ray (micro-)computed tomographic data but may potentially be useful for the segmentation of 3D volume data from other sources.
•The ambient occlusion principle allows reproducible pore segmentations in 3D objects.•Ambient occlusion-derived data fields improve the separation of connected pores.•Objects can be spatially characterised based on ambient occlusion-derived data fields.
Category:
Midfoot/Forefoot
Introduction/Purpose:
Nonunion is one of the most common and devastating complications following midfoot joint arthrodesis. Many different types of bone grafts and bone ...substitutes have been used to promote osseous fusion. However, there is no consensus on the gold standard bone grafting material and whether biologic materials should be used alone or in combination. The purpose of this study is to investigate the efficiency of highly porous β-tricalcium phosphate (β-TCP) with Bone Marrow Aspirate Concentrate (BMAC) in midfoot joint arthrodesis.
Methods:
This retrospective comparative study included patients who underwent midfoot joint arthrodesis using compression screws from January 2014 to May 2019. A total of 44 patients (46 feet) including 89 joints were included in this study. The cohort was then stratified into two groups: 25 patients (26 feet) in arthrodesis with highly porous β-TCP and BMAC (group A) and 19 patients (20 feet) in arthrodesis without highly porous β-TCP and BMAC (group B). The osseous union rate was compared between the two groups. Demographic and operative data including age, sex, body mass index (BMI), smoking, etiology of arthritis, comorbidities such as diabetes mellitus and rheumatoid arthritis, number of joints fixed, use of bone graft or bone substitute, and postoperative midfoot anatomic alignment in the two groups were compared.
Results:
There was a significant difference in the union rate between the two groups: 91.5 % (43 out of 47 joints) in arthrodesis with highly porous β-TCP and BMAC (group A) and 76.2 % (32 out of 42 joints) in arthrodesis without highly porous β-TCP and BMAC (group B) (P = 0.048). During the follow-up period, a total of four postoperative complications were reported in this study. In group A, two patients developed hardware irritation, and all of them underwent removal of hardware procedure. In group B, one patient had a superficial wound infection, which was resolved completely without further treatment. The other patient in group B developed a deep wound infection with dehiscence, and it was managed with irrigation and debridement followed by vacuum assisted wound closure therapy.
Conclusion:
This study investigated the efficiency of highly porous β-TCP and BMAC to promote bony healing in midfoot joint arthrodesis. A significantly higher union rate was shown when arthrodesis was performed with highly porous β-TCP and BMAC compared to arthrodesis without them, suggesting that highly porous β-TCP and BMAC can be a viable and effective adjunct to the fixation in midfoot joint arthrodesis.
Category:
Midfoot/Forefoot
Introduction/Purpose:
There is still a controversy regarding the most optimal fixation instruments and bone graft materials for midfoot joint arthrodesis. We present the ...results of midfoot joint arthrodesis using compression plate highly porous β-tricalcium phosphate (β-TCP) and bone marrow aspirate concentrate (BMAC).
Methods:
We performed a retrospective review of patients undergoing midfoot joint arthrodesis using compression plate with lag screw augmenting with highly porous β - tricalcium phosphate (β - TCP) and bone marrow aspirate concentrate (BMAC) from January 2014 to May 2019. The radiographic bony union rate was investigated. Postoperative complications and reoperations were also noted. A total of 36 patients (37 feet) including 75 joints were available in this study.
Results:
A high bony union rate was achieved as of 97.3% in 73 out of 75 joints. Nonunion was seen in two patients including two joints: one for 1st TMT joint and the other for medial NC joint. There was no delayed union in this study. Time to radiographic union was 10.5 +- 1.9 (range, 7-15) weeks. A total of five postoperative complications were noted. All of them were related to hardware irritation, and all five patients underwent removal of hardware procedure. There was no major complication such as infection during the follow-up period. Of the two nonunion patients, only one with medial NC joint nonunion underwent a revision arthrodesis surgery.
Conclusion:
Based on our results, the fixation construct of compression plate with lag screw augmenting with highly porous β - tricalcium phosphate (β - TCP) and bone marrow aspirate concentrate (BMAC) is safe and effective for midfoot joint arthrodesis with an excellent union rate and a low complication rate.
Category:
Sports; Basic Sciences/Biologics
Introduction/Purpose:
Achilles tendon ruptures have increased 10-fold in the past three decades, leading to long-term functional deficits in nearly ...two-thirds of patients. To counter this, rehabilitation protocols have been developed to strike a balance between protecting the healing tendon from re-rupture while allowing patients to return to activities of daily living as early as possible. However, Achilles tendon loading is neither prescribed nor quantified during immobilization and there is no standardized method of immobilization. Therefore, the purpose of this study was to quantify the amount of tendon loading experienced while walking in 3 different kinds immobilizing boot with respect to prescribed ankle angle and walking speed.
Methods:
Two healthy-young adults (2M; Age: 29.6 +- 2.3 y/o; BMI: 30 +- 7) walked over flat ground while wearing 3 different immobilizing boots and athletic shoes after providing written informed consent in this IRB approved study. We calculated Achilles tendon loading while subjects walked in 3 boots that positioned the ankle in 30 degrees of plantar flexion (Figure A, Air Cam Walker, United Ortho; AirSelect Walker, Aircast, VACOped, OPED). In all three boots, an instrumented insole (Loadsol, Novel) was placed under the foot to quantify load experienced by the tendon. We calculated the Achilles tendon loading profiles during gait for each immobilizing boot and compared them against the normal shod condition. We also provided the surgical repair threshold of 0.5 bodyweights to visualize the potential efficacy of each immobilizing boot for early rehabilitation when the tendon is early in the healing phase.
Results:
As expected, tendon loading was highest in the shod condition with no ankle bracing and lowest in the fully plantarflexed adjustable boot (Figure B). On average, the immobilizing boots reduced tendon loading decreased by 68% compared to unsupported walking in shoes but there were differences among the boots. The 3 different immobilizing boots provided differing levels of support. The 2 walking boots that use heel wedges to support the ankle in plantar flexion provided the least support, reducing loading by an average of 60-68%. The more rigid boot that constrained ankle angle using a posterior strut reduced tendon loading by 77% compared to gait in a normal walking shoe. Based on biomechanical studies of Achilles tendon repair strength in cadaveric experiments, only the rigid boot with the posterior strut reduced tendon loading biomechanics to levels that could be resisted by the surgical repair (Figure B).
Conclusion:
In this study, we used an instrumented insole to quantify Achilles tendon loading in a variety of immobilizing boots used by rupture patients. Our initial findings show that tendon loading is varies greatly between boot types and patients, highlighting the importance of understanding how these loads change in patients. Our future work centers around identifying the tendon loading profiles that promote tendon healing and optimize patient outcomes. These loading profiles will then provide the quantitative data needed to personalize loading for patients and guide rehabilitation to improve outcomes.
Category:
Bunion; Midfoot/Forefoot
Introduction/Purpose:
The majority of hallux valgus (HV) corrections have been historically performed via a two-dimensional, transverse plane-focused approach, ...which has demonstrated high long-term recurrence rates. Recent research demonstrates that 87% of HV deformities are three-dimensional with abnormal frontal-plane rotation of the metatarsal, which cannot be completely addressed with a two-dimensional metatarsal osteotomy alone. While correction at the 1st tarsometatarsal (TMT) joint may provide the optimal surgical approach for 3D anatomic restoration at the apex of the deformity, 1st TMT fusion historically entails an extended period of non-weightbearing. This study evaluated the clinical, radiographic, and patient-reported outcomes in patients undergoing instrumented triplanar 1st TMT arthrodesis (TMTA) with a biplanar plating system and protected near- immediate weightbearing.
Methods:
A prospective multicenter study that will continue for 60 months post-operatively. Patients 14-58 years old with symptomatic HV (intermetatarsal and HV angles between 10-22° and 16-40°, respectively) and no prior HV surgery on the operative foot were eligible for this study. Patients were treated with an instrumented TMTA procedure using a biplanar plating system with protected early weightbearing. The primary endpoint of this study is radiographic recurrence of HV deformity at 24 months for subjects with successful correction (defined as IMA < 9°, HVA < 15° and TSP ≤ 3 at 6 weeks post-procedure).
Recurrence is defined by any two of the three conditions: IMA of ≥12°, HVA ≥20° and TSP ≥4. Secondary outcomes (return to weightbearing and activities, pain measured by visual analog scale (VAS), Manchester-Oxford Foot Questionnaire (MOxFQ), and Patient Reported Outcomes Measurement Information System (PROMIS)) were evaluated post-operatively. Two independent fellowship trained musculoskeletal radiologists reviewed all radiographic data.
Results:
173 patients underwent TMTA with mean age of 41.0 (range:14-58) years; 92% females. Median (range) time-to-follow-up is 25 (1.5-49.2) months. Eighteen (10.4%) patients have discontinued. Mean (SD) days to protected weightbearing in CAM boot and return to full work were 8.4 (7.4) and 57.9 (46.2), respectively. At 24 months post-procedure, 99.3% (134/135) of patients were recurrence-free. Statistically significant improvements from baseline in HVA, IMA, and TSP (Table 1), VAS score, MOxFQ and PROMIS domains were observed as early as 6 weeks post-operatively and maintained over time. In 143 patients, mean (95% CI) 24-month improvements were VAS: 3.9 (3.5, 4.2); Walking/Standing (MOxFQ): 39.2 (34.9, 43.4); Physical Function (PROMIS): 9.7 (8.3, 11.2). Nineteen (11.0%) patients experienced hardware complications yet maintained radiographic correction.
Conclusion:
The results of this study’s primary and secondary endpoints provide supporting evidence that TMTA with biplanar plating is successful in correcting the 3D hallux valgus deformity with early return to weightbearing and low recurrence while demonstrating favorable clinical and patient-reported outcomes. Patients exhibited meaningful pain reduction after surgery and were able to return to full, unrestricted work and activities in less than two months, on average. Statistically significant improvements in patients’ health-related quality-of-life were observed through 36 months, post-operatively. Patients will continue to be followed for up to 60 months with additional evaluations for complications, recurrence, and patient satisfaction.
Identification of the genes and polymorphisms underlying quantitative traits, and understanding how these genes and polymorphisms affect economic traits, are important for successful marker-assisted ...selection and more efficient management strategies in commercial cattle populations. Signal transducer and activator of transcription 6 (STAT6) gene is tightly connected to IL-4 and IL-13 signalling and plays a key role in TH2 polarization of the immune system. In addition, STAT6 acts as a mediator of leptin signalling and has been associated with body weight regulation. The objective of this study was to determine if SNPs within the bovine STAT6 gene are associated with economically important traits in feedlot cattle. The approach consisted of resequencing STAT6 using a panel of DNA from unrelated animals of different beef breeds. Specifically, 16 kb of STAT6 was resequenced in 47 animals and the process revealed 39 SNPs. From the 39 SNPs, a panel of 15 tag SNPs was genotyped in 1500 beef cattle samples with phenotypes to perform a marker-trait association analysis. Among the 15 tag SNPs, five and six were polymorphic in Bos taurus and Bos indicus respectively. An association analysis was performed between the 15 tag SNPs and 14 performance and production traits. SNP ss115492459:C > A, ss115492461:A > G and ss115492458:G > C were significantly associated with back fat, calculated yield grade, cutability, hot carcass weight, dry matter intake, days on feed, back fat rate and average daily gain. These three SNPs were present in all Bos taurus beef breeds examined. Our results provide evidence that polymorphisms in STAT6 are associated with carcass and growth efficiency traits, and may be used for marker-assisted selection and management in feedlot cattle.
Prader–Willi syndrome (PWS) results from the loss of paternal contributions for a 2-Mb imprinted region on the proximal long arm of human chromosome 15. Hitherto, five paternally active genes have ...been identified in this region (ZNF127, NDN, MAGEL2, SNURF–SNRPN, and IPW). Here we report the identification of a novel gene in the PWS critical region, which has been designated “chromosome 15 open reading frame 2” (C15orf2). C15orf2 is an intronless gene located between MAGEL2 and SNURF–SNRPN. It is associated with a CpG island, which is methylated in all tissues tested except for germ cells. C15orf2 is transcribed as a 7.5-kb mRNA and contains an open reading frame encoding a predicted 1156-amino-acid protein of unknown function. Transcription of C15orf2 occurs exclusively in the testis, and in adult testis samples, we observed biallelic expression. By zoo-blot analysis, we found related sequences in DNA from other primates, but not in nonprimate DNA. We conclude that C15orf2 may play a role in primate spermatogenesis.
Category:
Midfoot/Forefoot; Bunion
Introduction/Purpose:
The most common joint preparation techniques mentioned in literature for 1st metatarsophalangeal (MTP) joint arthrodesis are 'cup and cone' ...and 'flat-cuts'. A third option of an 'in-situ' technique, has rarely been studied. This study compares the clinical, radiographic, and patients-reported outcomes of 'in-situ' joint preparation with a traditional 1st MTP joint preparation technique.
Methods:
The 'in-situ' technique utilizes the same dorsal surgical incision as traditional techniques. Cartilage and osteophyte removal are carried out using standard techniques without the use of specific reamers or a sagittal saw. The arthrodesis is performed in-situ with the similar freedom of joint positioning as the cup and cone technique, and traditional fixation constructs are applied. In this study, A retrospective chart review was performed for patients who underwent 1st MTP joint arthrodesis between January 2015 and December 2019. The complication, revision and non-union rates were examined in a multivariable logistic regression model. Patient reported outcome were analyzed in a repeated measures general linear model. Analysis of variance and Receiver Operating Characteristic were used to assess radiographic measurements.
Results:
Total of 388 1st MTP joint arthrodesis cases were included. Overall, 262 'Flat-Cuts' and 126 'In-Situ' cases were analyzed. Mean follow-up time was 292 days (median 174, SD 305). Joint-preparation technique did not have statistically significant impact on union rates (p=0.311) or revision rates (p=0.898). Diabetes-Mellitus was the most powerful predictor of non-union (p<0.001, OR 6.558, 95% CI: 2.534-16.969) and revision (p=0.02, OR 3.662, 95% CI: 1.230-10.905). The rate of transfer- metatarsalgia was significantly higher in 'flat-cuts' (p=0.015, OR 6.808, 95% CI: 1.460-31.744). Visual-Analogue-Scale and PROMIS- CAT-Physical significantly improved at 6-weeks, 3-months, and at last follow-up in both techniques (p<0.001, p=0.001), and the improvement was comparable between the techniques (p=0.078, p=0.100).'In-situ' technique resulted in significantly less mean 1st- ray shortening (3.05mm vs 7.64mm, p<0.001). In a Receiver-Operating-Characteristic analysis of transfer metatarsalgia and 1st ray shortening, the optimal diagnostic cut-off was 6.87 mm (LR 1.67, AUC 0.652, p=0.005, 95% CI: 0.56-0.74).
Conclusion:
'In-situ' joint preparation technique is a simple, safe, and cost-effective technique for 1st MTP joint arthrodesis. In our series, 'in-situ' technique had a similar or better complication profile than the 'flat-cuts', while providing similar patient- reported outcomes. 'In-situ' technique resulted in significantly less 1st ray shortening, which was a predictor of transfer metatarsalgia.
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