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Background: Flatback deformity, or lumbar hypolordosis, can cause sagittal imbalance, causing back pain, fatigue, and functional limitation. Surgical correction through osteotomies and interbody fusion techniques can restore sagittal balance and relieve pain. This study investigated sagittal vertical alignment (SVA) and lumbar lordosis correction achieved through sequential procedures on human spine specimens. Methods: Human T10-sacrum specimens were stratified into 2 groups: degenerative flatback specimens had smaller L1-S1 lordosis compared to the iatrogenic group (26.1°±15.0° vs. 47.8°±19.3°, p<.05). Specimens were mounted in the apparatus in simulated standing posture with a nominal sacral slope of 45 degrees and subjected to a 400N compressive follower preload. Sequential correction of degenerative lumbar flatback deformity involved: anterior lumbar interbody fusion (ALIF) at L5-S1, ALIF at L4-5, lateral lumbar interbody fusion (LLIF) at L2-3 and L3-4, and posterior column osteotomy (PCO) at L2-3 and L3-4. In iatrogenic specimens, flatback deformity was created by performing a posterior in-situ immobilization using pedicle screw instrumentation at L4-L5-S1 followed by distraction across the pedicle screws. We then performed LLIF at L2-3 and L3-4, followed by PCO at L2-3 and L3-4. Results: Statistically significant incremental corrections were noted in SVAs and lordosis after L5-S1 ALIF, L4-5 ALIF, and PCO in degenerative flatback specimens. For the iatrogenic group, statistically significant worsening was noted in measures of standing alignment after L4-L5-S1 hypolordotic fusion. Subsequent LLIF at L2-3 and L3-4 did not significantly improve sagittal alignment. However, after PCO at L2-3 and L3-4, final alignment parameters were not significantly different than preoperative baseline values prior to hypolordotic fusion. Conclusions: ALIF cages in the lower lumbar segments significantly improved sagittal alignment in degenerative flatback specimens. In the upper lumbar segments, LLIF cages alone were ineffective at enhancing lumbar lordosis. LLIF cages in conjunction with PCO improved alignment parameters in degenerative and iatrogenic flatback deformities.
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First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014-2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72-1.09) and OS (HR = 0.93; 95% CI, 0.73-1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, -0.4%-34.1% and OS = 12.1%; 95% CI, -5.4-29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research.
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Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Linfoma de Células B Grandes Difuso , Prednisona , Rituximab , Vincristina , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Adulto , Anciano de 80 o más Años , Estadificación de Neoplasias , Resultado del Tratamiento , Países Bajos/epidemiologíaRESUMEN
Importance: The use of real-world data (RWD) external control arms in prospective studies is increasing. The advantages, including the immediate availability of a control population, must be balanced with the requirements of meeting evidentiary standards. Objective: To address the question of whether and to what extent the methods of RWD studies compare to standard methods used in randomized clinical trials. Evidence Review: A systematic search across 4 electronic databases and Google Scholar was conducted from January 1, 2000, to October 23, 2023. Studies were included in the systematic review if they compared an intervention arm in a clinical trial to an RWD control arm in patients with hematological cancers and if they were published between 2000 and 2023. Findings: Thirty-two prospective intervention studies incorporating external control data from RWD sources of patients with hematological cancers were identified. A total of 4306 patients from intervention arms and 10â¯594 from RWD control arms were included across all studies. Only 2 studies (6%) included prospectively collected RWD. The complete trial inclusion criteria were applied to the RWD cohort in 7 studies (22%). Four studies (13%) published the statistical analysis plan and prespecified use of RWD. A total of 23 studies (72%) applied matching algorithms for trial and RWD cohorts, including matching for demographic, disease, and/or therapy-related characteristics. The end point criteria were the same as the trial in 8 studies (25%). In contrast, 12 studies (38%) used different end points, and 12 (38%) did not provide an end point definition for the RWD. Twelve studies (38%) had a median follow-up difference of less than a year between arms. Eight studies (25%) reported toxic effect data for the trial arm, of which 5 studies reported toxic effect data for the RWD arm. Conclusions and Relevance: In this systematic review, limitations were observed in the application of clinical trial eligibility criteria to RWD, statistical rigor and application of matching methods, the definition of end points, follow-up, and reporting of adverse events, which may challenge the conclusions reported in studies using RWD.
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The Earth's atmosphere contains ultrafine particles known as aerosols, which can be either liquid or solid particles suspended in gas. These aerosols originate from both natural sources and human activities, termed primary and secondary sources respectively. They have significant impacts on the environment, particularly when they transform into ultrafine particles or aerosol nanoparticles, due to their extremely fine atomic structure. With this context in mind, this review aims to elucidate the fundamentals of atmospheric-derived aerosol nanoparticles, covering their various sources, impacts, and methods for control and management. Natural sources such as marine, volcanic, dust, and bioaerosols are discussed, along with anthropogenic sources like the combustion of fossil fuels, biomass, and industrial waste. Aerosol nanoparticles can have several detrimental effects on ecosystems, prompting the exploration and analysis of eco-friendly, sustainable technologies for their removal or mitigation.Despite the adverse effects highlighted in the review, attention is also given to the generation of aerosol-derived atmospheric nanoparticles from biomass sources. This finding provides valuable scientific evidence and background for researchers in fields such as epidemiology, aerobiology, and toxicology, particularly concerning atmospheric nanoparticles.
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Aerosoles , Atmósfera , Ecosistema , Nanopartículas , Aerosoles/análisis , Nanopartículas/química , Atmósfera/química , Contaminantes Atmosféricos/análisis , Humanos , Monitoreo del Ambiente , Material Particulado/análisisRESUMEN
Accurately predicting agricultural commodity prices is crucial for India's economy. Traditional parametric models struggle with stringent assumptions, while machine learning (ML) approaches, though data-driven, lack automatic feature extraction. Deep learning (DL) models, with advanced feature extraction and predictive abilities, offer a promising solution. However, their application to agricultural price data ignored the exogenous factors. Hence, the study explored advanced versions of the well-known univariate models, NBEATSX and TransformerX. The research employed price data for essential crops like Tomato, Onion, and Potato (TOP) from major Indian markets and complemented it with corresponding weather data (precipitation and temperature). To provide a comprehensive analysis, the study also evaluated traditional statistical methods (ARIMAX and MLR) and a suite of ML algorithms (ANN, SVR, RFR, and XGBoost). The performance of these models was rigorously evaluated using error metrics like RMSE, MAE, sMAPE, MASE and QL. The findings were significant indicating DL models, particularly when augmented with exogenous variables, consistently outshone other methods with NBEATSX and TransformerX showing an average RMSE of 110.33 and 135.33, MAE of 60.08 and 74.92, sMAPE of 22.14 and 24.00, MASE of 1.02 and 1.32 and QL of 30.04 and 34.07, respectively. They exhibited lower error metrics, as compare to the statistical and ML models underscoring their effectiveness and potential in agricultural crop price forecasting. This study not only bridged a crucial research gap but also highlighted the robust potential of DL models in enhancing the accuracy of agricultural commodity price predictions in India.
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[This corrects the article DOI: 10.1039/D3MD00630A.].
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Ethion is a class II moderately toxic organothiophosphate pesticide. The main objective of this study was to evaluate the maternal and foetal toxicity of ethion in rats. Pregnant rats were divided into 5 groups. Group I served as control. Group II, III, IV, and V were orally administered with 0.86, 1.71, 3.43, and 6.9â¯mg/kg of ethion respectively, from gestational day (GD) 6-19. Dams were sacrificed on GD 20. Maternal toxicity was assessed by body weight gain, foetal resorptions, oxidative stress, liver and kidney function tests, and histopathology. Foetal toxicity was assessed by physical status, gross, teratological and histopathological examination. Ethion caused dose-dependent reduction in maternal body weight gain, increased resorptions, and reduced gravid uterine weights. Elevated MDA levels and altered levels of GSH, SOD and catalase were recorded in pregnant dam serum and tissues. SGOT, SGPT, total bilirubin, urea, uric acid, and creatinine were elevated in ethion groups indicating liver and kidney toxicity. Histology of uterus revealed myometrial degeneration and mucosal gland atrophy in uterus of pregnant dams and degenerative changes in placenta. It showed histological alterations in liver, kidney, and lungs. There was reduction in the foetal body weights and placental weights, and degenerative changes in the foetal liver and kidney. Gross evaluation of foetuses showed subcutaneous hematoma. Skeletal evaluation showed partial ossification of skull bones, costal separation, and agenesis of tail vertebrae, sternebrae, metacarpals and metatarsals. The findings reveal that prenatal exposure to ethion caused maternal and foetal toxicity in rats.
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Riñón , Hígado , Animales , Femenino , Embarazo , Ratas , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Útero/efectos de los fármacos , Útero/patología , Estrés Oxidativo/efectos de los fármacos , Etilenotiourea/toxicidad , Exposición Materna , Feto/efectos de los fármacos , Feto/patología , Tamaño de los Órganos/efectos de los fármacos , Ratas Wistar , Insecticidas/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Placenta/efectos de los fármacos , Placenta/patología , Reabsorción del Feto/inducido químicamente , Intercambio Materno-Fetal , Desarrollo Fetal/efectos de los fármacosRESUMEN
The biomechanical literature describes axial rotation occurring coupled with lateral bending and flexion in the cervical spine. Since the head is kept level during some activities of daily living, we set out to investigate the changes in total and segmental motion that occur when a level gaze constraint is applied to cadaveric cervical spine specimens during axial rotation. 1.5Nm of left and right axial rotation moment was applied to sixteen C2-T1 cadaveric specimens with C2 unconstrained and C2 constrained to simulate level gaze. Overall and segmental motions were determined using optoelectronic motion measurement and specimen-specific kinematic modeling. Without a kinematic constraint on C2, motions were as described in the literature; namely, flexion and lateral bending to the same side as axial rotation. Keeping C2 level reduced that total axial rotation range of motion of the specimens. Changes were also produced in segmental coupled rotation in all specimens. The observed changes included completely opposite coupled motion than in the uncoupled specimens, and traditional coupled behavior at one load extreme and the opposite at the other extreme. Constraining C2 during axial rotation to simulate level gaze can produce coupled motion that differs from the classically described flexion and lateral bending to the same side as axial rotation. Statement of Clinical Significance: Activities of daily living that require the head to be kept level during axial rotation of the cervical spine may produce segmental motions that are quite different from the classically described motions with implications for biomechanical experiments and implant designers.
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Actividades Cotidianas , Vértebras Cervicales , Humanos , Rotación , Fenómenos Biomecánicos , Rango del Movimiento Articular , CadáverRESUMEN
BACKGROUND CONTEXT: The functional goals of cervical disc arthroplasty (CDA) are to restore enough range of motion (ROM) to reduce the risk of accelerated adjacent segment degeneration but limit excessive motion to maintain a biomechanically stable index segment. This motion-range is termed the "Physiological mobility range." Clinical studies report postoperative ROM averaged over all study subjects but they do not report what proportion of reconstructed segments yield ROM in the Physiological mobility range following CDA surgery. PURPOSE: To calculate the proportion of reconstructed segments that yield flexion-extension ROM (FE-ROM) in the Physiological mobility range (defined as 5°-16°) by analyzing the 24-month postoperative data reported by clinical trials of various cervical disc prostheses. STUDY DESIGN/SETTING: Analysis of 24-month postoperative FE-ROM data from clinical trials. PATIENT SAMPLE: Data from 1,173 patients from single-level disc replacement clinical trials of 7 cervical disc prostheses. OUTCOME MEASURES: 24-month postoperative index-level FE-ROM. METHODS: The FE-ROM histograms reported in Food and Drug Administration-Investigational Device Exemption (FDA-IDE) submissions and available for this analysis were used to calculate the frequencies of implanted levels with postoperative FE-ROM in the following motion-ranges: Hypomobile (0°-4°), Physiological (5°-16°), and Hypermobile (≥17°). The ROM histograms also allowed calculation of the average ROM of implanted segments in each of the 3 motion-ranges. RESULTS: Only 762 of 1,173 patients (implanted levels) yielded 24-month postCDA FE-ROM in the physiological mobility range (5°-16°). The proportions ranged from 60% to 79% across the 7 disc-prostheses, with an average of 65.0%±6.2%. Three-hundred and two (302) of 1,173 implanted levels yielded ROM in the 0°-4° range. The proportions ranged from 15% to 38% with an average of 25.7%±8.9%. One-hundred and nine (109) of 1,173 implanted levels yielded ROM of ≥17° with a range of 2%-21% and an average proportion of 9.3%±7.9%. The prosthesis with built-in stiffness due to its nucleus-annulus design yielded the highest proportion (103/131, 79%) of implanted segments in the physiological mobility range, compared to the cohort average of 65% (p<.01). Sixty-five of the 350 (18.6%) discs implanted with the 2 mobile-core designs in this cohort yielded ROM≥17° as compared to the cohort average of 9.3% (109/1,173) (p<.05). At 2-year postCDA, the "hypomobile" segments moved on average 2.4±1.2°, those in the "physiological-mobility" group moved 9.4±3.2°, and the hypermobile segments moved 19.6±2.6°. CONCLUSIONS: Prosthesis design significantly influenced the likelihood of achieving FE-ROM in the physiological mobility range, while avoiding hypomobility or hypermobility (p<.01). Postoperative ROM averaged over all study subjects provides incomplete information about the prosthesis performance - it does not tell us how many implanted segments achieve physiological mobility and how many end up with hypomobility or hypermobility. We conclude that the proportion of index levels achieving postCDA motions in the physiological mobility range (5°-16°) is a more useful outcome measure for future clinical trials.
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Vértebras Cervicales , Diseño de Prótesis , Rango del Movimiento Articular , Reeemplazo Total de Disco , Humanos , Rango del Movimiento Articular/fisiología , Vértebras Cervicales/cirugía , Reeemplazo Total de Disco/métodos , Reeemplazo Total de Disco/instrumentación , Disco Intervertebral/cirugía , Femenino , Masculino , Adulto , Persona de Mediana Edad , Artroplastia/métodos , Resultado del Tratamiento , Ensayos Clínicos como AsuntoAsunto(s)
Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Países Bajos/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoAsunto(s)
Linfoma no Hodgkin , Niño , Adolescente , Humanos , Adulto Joven , Países Bajos/epidemiología , Linfoma no Hodgkin/epidemiologíaRESUMEN
The present study was designed to evaluate the testicular toxicity of triazophos in rats and to check the ameliorative effect of nano-quercetin against triazophos-induced toxicity. Nano-quercetin was synthesized from quercetin and characterized. Male Wistar rats were divided into seven groups. The control group received olive oil as a vehicle orally. The high-dose triazophos group and the low-dose triazophos group received 1/10th LD50 of triazophos (7.6 mg/kg) and 1/20th LD50 of triazophos (3.8 mg/kg), respectively. Two groups of animals were dosed with quercetin and nano-quercetin, both at 50 mg/kg body weight orally. The final two groups received high-dose triazophos with co-administration of quercetin and nano-quercetin, respectively. Triazophos disrupted the male endocrine axis by reducing the levels of steroidogenic enzymes 3-ß-HSD and 17-ß-HSD in testicular cells, further reducing FSH and testosterone. Also, triazophos increased the reactive oxygen species, induced lipid peroxidation, decreased the mitochondrial membrane potential, and elevated the number of apoptotic cells in rat testes. Nano-quercetin ameliorated the testicular oxidative stress and apoptotic and endocrine parameters more efficiently than quercetin. Besides, nano-quercetin alleviated the histopathological and biochemical alterations of triazophos. It is concluded that nano-quercetin has higher anti-oxidant efficacy than quercetin in protecting rats against triazophos-induced testicular toxicity.
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Quercetina , Testículo , Ratas , Masculino , Animales , Ratas Wistar , Antioxidantes/metabolismo , Estrés Oxidativo , Testosterona/metabolismo , ApoptosisRESUMEN
Myelodysplastic and myeloproliferative neoplasms (MDS/MPN) with neutrophilia, until recently called atypical chronic myeloid leukemia (aCML), being part of the MDS/MPN is a very rare disease with poor prognosis. Although emerging data reveal its cytogenetic and molecular profile, integrated survival and treatment data remain scarce. We analyzed a cohort of 347 adult patients diagnosed with MDS/MPN with neutrophilia, registered in the Netherlands Cancer Registry between 2001 and 2019. Our demographic baseline data align with other cohorts. We observed cytogenetic aberrations exclusively in patients aged >65 years, with trisomy 8 being the most common abnormality. We identified 16 distinct molecular mutations, with some patients (16/101) harboring up to 3 different mutations; ASXL1 being the most frequent one (22%). In a multivariable Cox regression analysis, only age, hemoglobin level and allogeneic hematopoietic stem cell transplant (alloHSCT) were associated with overall survival (aged >65 years; hazard ratio [HR] 1.85; P = .001 and alloHSCT HR, 0.51; P = .039). Because no other treatment modality seemed to affect survival and might cause toxicity, we propose that all patients eligible for alloHSCT should, whenever possible, receive an allogeneic transplant. It is imperative that we strive to improve outcomes for patients who are not eligible for alloHSCT. Tackling this challenge requires international collaborative efforts to conduct prospective intervention studies.
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Leucemia Mieloide Crónica Atípica BCR-ABL Negativa , Síndromes Mielodisplásicos , Enfermedades Mielodisplásicas-Mieloproliferativas , Adulto , Humanos , Anciano , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/terapia , Síndromes Mielodisplásicos/genética , Estudios Prospectivos , Enfermedades Mielodisplásicas-Mieloproliferativas/genética , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/terapia , Aberraciones Cromosómicas , LeucocitosisRESUMEN
This study aimed to explore non-pyridinium oxime acetylcholinesterase (AChE) reactivators that could hold the potential to overcome the limitations of the currently available compounds used in the clinic to treat the neurologic manifestations induced by intoxication with organophosphorus agents. Fifteen compounds with various non-pyridinium oxime moieties were evaluated for AChE activity at different concentrations, including aldoximes, ketoximes, and α-ketoaldoximes. The therapeutic potential of the oxime compounds was evaluated by assessing their ability to reactivate AChE inhibited by paraoxon. Among the tested compounds, α-Ketoaldoxime derivative 13 showed the highest reactivation (%) reaching 67â¯% and 60â¯% AChE reactivation when evaluated against OP-inhibited electric eel AChE at concentrations of 1,000 and 100⯵M, respectively. Compound 13 showed a comparable reactivation ability of AChE (60â¯%) compared to that of pralidoxime (56â¯%) at concentrations of 100⯵M. Molecular docking simulation of the most active compounds 12 and 13 was conducted to predict the binding mode of the reactivation of electric eel AChE. As a result, a non-pyridinium oxime moiety 13, is a potential reactivator of OP-inhibited AChE and is taken as a lead compound for the development of novel AChE reactivators with enhanced capacity to freely cross the blood-brain barrier.
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Reactivadores de la Colinesterasa , Oximas , Oximas/farmacología , Oximas/química , Paraoxon/farmacología , Acetilcolinesterasa/metabolismo , Reactivadores de la Colinesterasa/farmacología , Reactivadores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Simulación del Acoplamiento Molecular , Compuestos de Piridinio/farmacología , Compuestos de Piridinio/química , Acetamidas , Compuestos Organofosforados/químicaRESUMEN
OBJECTIVES: Acquired missense mutations in the BCR::ABL1 kinase domain (KD) may cause tyrosine kinase inhibitor (TKI) treatment failure. Based on mutation-specific in vitro derived IC50-values, alternative TKI may be selected. We assessed clinical practice of BCR::ABL1 KD mutation testing, clinical response in relation to IC50-values, and clinical outcome of tested patients. METHODS: Patients from six Dutch CML reference centers and a national registry were included once a mutational analysis was performed. Reasons for testing were categorized as suboptimal TKI response, and primary or secondary TKI resistance. RESULTS: Four hundred twenty analyses were performed in 275 patients. Sixty-nine patients harbored at least one mutation. Most analyses were performed because of suboptimal TKI response but with low mutation incidence (4%), while most mutations were found in primary and secondary resistant patients (21% and 51%, respectively). Harboring a BCR::ABL1 mutation was associated with inferior overall survival (HR 3.2 [95% CI, 1.7-6.1; p < .001]). Clinically observed responses to TKI usually corresponded with the predicted TKI sensitivity based on the IC50-values, but a high IC50-value did not preclude a good clinical response per se. CONCLUSIONS: We recommend BCR::ABL1 KD mutation testing in particular in the context of primary or secondary resistance. IC50-values can direct the TKI choice for CML patients, but clinical efficacy can be seen despite adverse in vitro resistance.
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Proteínas de Fusión bcr-abl , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Proteínas de Fusión bcr-abl/genética , Resistencia a Antineoplásicos/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
Background: Soft tissue complications after Achilles tendon repair has led to increased interest in less invasive techniques. Various limited open techniques have gained popularity as an alternative to open operative repair. The purpose of this study was to biomechanically compare an open Krackow and limited open repair for Achilles tendon rupture. We hypothesized that there would be no statistical difference in load to failure, work to failure, and initial linear stiffness. Methods: A simulated Achilles tendon rupture was created 4 cm proximal to its insertion in 18 fresh-frozen cadaveric below-knee lower limbs. Specimens were randomized to open or limited open PARS Achilles Jig System repair. Repairs were loaded to failure at a rate of 25.4 mm/s to reflect loading during normal ankle range of motion. Load to failure, work to failure, and initial linear stiffness were compared between the 2 repair types. Results: The average load to failure (353.8 ± 88.8 N vs 313.3 ± 99.9 N; P = .38) and work to failure (6.4 ± 2.3 J vs 6.3 ± 3.5 J; P = .904) were not statistically different for Krackow and PARS repair, respectively. Mean initial linear stiffness of the Krackow repair (17.8 ± 5.4 N/mm) was significantly greater than PARS repair (11.8 ± 2.5 N/mm) (P = .011). Conclusion: No significant difference in repair strength was seen, but higher initial linear stiffness for Krackow repair suggests superior resistance to gap formation, which may occur during postoperative rehabilitation. With equal repair strength, but less soft tissue devitalization, the PARS may be a favorable option for patients with risk factors for soft tissue complications.
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BACKGROUND: The outcome in older patients with acute lymphoblastic leukemia (ALL) remains unsatisfactory due to high relapse and nonrelapse mortality (NRM) rates. Allogeneic stem cell transplantation (alloHSCT) as postremission therapy has an important role in reducing relapse rate, albeit its application is limited in older adult patients due to alloHSCT-related morbidity and mortality. Reduced-intensity conditioning (RIC) alloHSCT has been developed as a less toxic conditioning regimen, but comparative studies with myeloablative conditioning (MAC) are limited in patients with ALL. METHODS: In this retrospective study, RIC-alloHSCT (n = 111) was compared with MAC-alloHSCT (n = 77) in patients aged 41 to 65 y with ALL in first complete remission. MAC was predominantly applied by combining high-dose total body irradiation and cyclophosphamide, whereas RIC mainly consisted of fludarabine and 2 Gy total body irradiation. RESULTS: Unadjusted overall survival was 54% (95% confidence interval [CI], 42%-65%) at 5 y in MAC recipients compared with 39% (95% CI, 29%-49%) in RIC recipients. Overall survival and relapse-free survival were not significantly associated with type of conditioning after adjusted for the covariates age, leukemia risk status at diagnosis, donor type, and donor and recipient gender combination. NRM was significantly lower after RIC (subdistribution hazard ratio: 0.41, 95% CI, 0.22-0.78; P = 0.006), whereas relapse was significantly higher (subdistribution hazard ratio: 3.04, 95% CI, 1.71-5.40; P < 0.001). CONCLUSIONS: Collectively, RIC-alloHSCT has resulted in less NRM, but it was also found to be associated with a significantly higher relapse rate. These results suggest that MAC-alloHSCT may provide a more effective type of consolidation therapy for the reduction of relapse and that RIC-alloHSCT may be restricted to patients at higher risk for NRM.