Eccentric cycling rehabilitation after anterior cruciate ligament reconstruction: a randomised controlled trial of strength and biomechanical outcomes

After anterior cruciate ligament reconstruction (ACL-R), persistent strength and biomechanical deviations remain. Reducing these by training may reduce risk of re-injury or osteoarthritis for these patients. A cross-sectional study investigated biomechanics of ACL-R male patients long-term (~5 years) post surgery. Fifteen ACL-R and fifteen healthy controls were tested in walking and running using motion capture. Devi- ations were found, primarily between-limbs, and also between groups. Largest deviations were lower knee angles and moments in the affected limb during running. However, these were not found during walking; thus, differences were highlighted by the higher-intensity task. During running, knee abduction moment was lower (more valgus) for the affected compared to unaffected and control limbs. The larger effects in moment show greater clinical potential than knee valgus angle. The ACL-R patients had lower impact foot strike during running than controls. The above results indicate chronic, clinical changes in joint loading. A randomised controlled intervention trial evaluated progressive eccentric cycling for ACL-R males, compared to concentric controls. This is one of the first trials of eccentric vs. concentric training for ACL-R, matched by rating of perceived exertion. Twenty-six adult males, 12 weeks post hamstring-graft ACL-R trained three times/week for 8 weeks under supervision. During training the eccentric group limb powers absorbed were higher than those produced by the concentric group, with a lower heart rate. For both groups, pain scores were low, and one of the patient-reported outcomes (IKDC) improved. Hamstring strength increased in the eccentric group by 15%, but this was not seen in the concentric group. For both groups, 60°/s quadriceps strength increased by a similar amount, approximately 28%. Biomechanically, eccentric training was more effective than matched concen- tric training at resolving knee (P=0.022, walk) and hip (P =0.010, run) flexion angle deviations in the affected limb. In both groups, knee extension moments increased, reducing asymmetries. Large knee abduction moment deviations at baseline were not reduced by either programme (P >0.05). At follow-up (~6 months), both groups showed similar return-to-sports progress; several patients passed using one criterion (IKDC), and none passed using a stricter four-criteria method (Univ. Delaware). Thus it can be concluded that for adult ACL-R males, eccentric cycle training is clinically acceptable, with similar or in some cases better outcomes than concentric cycle training. It improves patient-reported outcomes, strength recovery, biomechanical deviations, and return-to-sports measures

Quick assessment of cell-free DNA in seminal fluid and fragment size for early non-invasive prostate cancer diagnosis

Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the characterization of seminal cfDNA (scfDNA) has been reported as a possible biomarker for prostate cancer (PCa) diagnosis

Survey of transfemoral amputee experience and priorities for the user-centered design of powered robotic transfemoral prostheses

BACKGROUND: Transfemoral amputees experience a complex host of physical, psychological, and social challenges, compounded by the functional limitations of current transfemoral prostheses. However, the specific relationships between human factors and prosthesis design and performance characteristics have not yet been adequately investigated. The present study aims to address this knowledge gap. METHODS: A comprehensive single-cohort survey of 114 unilateral transfemoral amputees addressed a broad range of demographic and clinical characteristics, functional autonomy, satisfaction and attitudes towards their current prostheses, and design priorities for an ideal transfemoral prosthesis, including the possibility of active assistance from a robotic knee unit. The survey was custom-developed based on several standard questionnaires used to assess motor abilities and autonomy in activities of daily living, prosthesis satisfaction, and quality of life in lower-limb amputees. Survey data were analyzed to compare the experience (including autonomy and satisfaction) and design priorities of users of transfemoral prostheses with versus without microprocessor-controlled knee units (MPKs and NMPKs, respectively), with a subsequent analyses of cross-category correlation, principal component analysis (PCA), cost-sensitivity segmentation, and unsupervised K-means clustering applied within the most cost-sensitive participants, to identify functional groupings of users with respect to their design priorities. RESULTS: The cohort featured predominantly younger (< 50 years) traumatic male amputees with respect to the general transfemoral amputee population, with pronounced differences in age distribution and amputation etiology (traumatic vs. non-traumatic) between MPK and NMPK groups. These differences were further reflected in user experience, with MPK users reporting significantly greater overall functional autonomy, satisfaction, and sense of prosthesis ownership than those with NMPKs, in conjunction with a decreased incidence of instability and falls. Across all participants, the leading functional priorities for an ideal transfemoral prosthesis were overall stability, adaptability to variable walking velocity, and lifestyle-related functionality, while the highest-prioritized general characteristics were reliability, comfort, and weight, with highly variable prioritization of cost according to reimbursement status. PCA and user clustering analyses revealed the possibility for functionally relevant groupings of prosthesis features and users, based on their differential prioritization of these features—with implications towards prosthesis design tradeoffs. CONCLUSIONS: This study’s findings support the understanding that when appropriately prescribed according to patient characteristics and needs in the context of a proactive rehabilitation program, advanced transfemoral prostheses promote patient mobility, autonomy, and overall health. Survey data indicate overall stability, modularity, and versatility as key design priorities for the continued development of transfemoral prosthesis technology. Finally, observed associations between prosthesis type, user experience, and attitudes concerning prosthesis ownership suggest both that prosthesis characteristics influence device acceptance and functional outcomes, and that psychosocial factors should be specifically and proactively addressed during the rehabilitation process. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12984-021-00944-x

Phase II study of gemcitabine, doxorubicin and paclitaxel (GAT) as first-line chemotherapy for metastatic breast cancer: a translational research experience

BACKGROUND: Patients with metastatic breast cancer are frequently treated with anthracyclines and taxanes, which are among the most active agents in this disease. Gemcitabine is an interesting candidate for a three-drug combination because of its different mechanism of action and non-overlapping toxicity with respect to the other two drugs. We aimed to evaluate the activity and toxicity of the GAT (gemcitabine, doxorubicin and paclitaxel) regimen, derived from experimental preclinical studies, as first-line chemotherapy in patients with stage IIIB-IV breast cancer. METHODS: Patients with locally advanced or metastatic breast cancer and at least one bidimensionally measurable lesion were included in the present study. Adequate bone marrow reserve, normal cardiac, hepatic and renal function, and an ECOG performance status of 0 to 2 were required. Only prior adjuvant non anthracycline-based chemotherapy was permitted. Treatment consisted of doxorubicin 50 mg/m(2 )on day 1, paclitaxel 160 mg/m(2 )on day 2 and gemcitabine 800 mg/m(2 )on day 6, repeated every 21–28 days. RESULTS: Thirty-three consecutive breast cancer patients were enrolled onto the trial (7 stage IIIB and 26 stage IV). All patients were evaluable for toxicity and 29 were assessable for response. A total of 169 cycles were administered, with a median of 6 cycles per patient (range 1–8 cycles). Complete and partial responses were observed in 6.9% and 48.3% of patients, respectively, for an overall response rate of 55.2%. A response was reported in all metastatic sites, with a median duration of 16.4 months. Median time to progression and overall survival were 10.2 and 36.4 months, respectively. The most important toxicity was hematological, with grade III-IV neutropenia observed in 69% of patients, sometimes requiring the use of granulocyte colony-stimulating factor (27%). Non hematological toxicity was rare and mild. One patient died from sepsis during the first treatment cycle before the administration of gemcitabine. CONCLUSION: The strong synergism among the three drugs found in the preclinical setting was confirmed in terms of both clinical activity and hematological toxicity. Our results seem to indicate that the GAT regimen is effective in anthracycline-naïve metastatic breast cancer and provides a feasible chemotherapeutic option in this clinical setting

Randomized phase II study with two gemcitabine- and docetaxel-based combinations as first-line chemotherapy for metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Docetaxel and gemcitabine combinations have proven active for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate and compare two treatment schedules, one based on our own preclinical data and the other selected from the literature.</p> <p>Methods</p> <p>Patients with stage IV NSCLC and at least one bidimensionally-measurable lesion were eligible. Adequate bone marrow reserve, normal hepatic and renal function, and an ECOG performance status of 0 to 2 were required. No prior chemotherapy was permitted. Patients were randomized to arm A (docetaxel 70 mg/m²on day 1 and gemcitabine 900 mg/m²on days 3–8, every 3 weeks) or B (gemcitabine 900 mg/m2 on days 1 and 8, and docetaxel 70 mg/m2 on day 8, every 3 weeks).</p> <p>Results</p> <p>The objective response rate was 20% (95% CI:10.0–35.9) and 18% (95% CI:8.6–33.9) in arms A and B, respectively. Disease control rates were very similar (54% in arm A and 53% in arm B). No differences were noted in median survival (32 vs. 33 weeks) or 1-year survival (33% vs. 35%). Toxicity was mild in both treatment arms.</p> <p>Conclusion</p> <p>Our results highlighted acceptable activity and survival outcomes for both experimental and empirical schedules as first-line treatment of NSCLC, suggesting the potential usefulness of drug sequencing based on preclinical models.</p> <p>Trial registration number</p> <p>IOR 162 02</p

Seakeeping control of HYSUCATs

Thesis (MScEng (Mechanical and Mechatronic Engineering))--University of Stellenbosch, 2006.This thesis investigates practical methods of modelling and control of the vertical motions of a hydrofoil assisted catamaran, the HYSUCAT. The aim of the control application is to reduce the motions, and consequently the motion sickness of the passengers. First, a potential flowcommercial program, POWERSEA,was used to model the system. This uses 2-D strip methods to model the planing hull-form of the vessel, and the Peter du Cane hydrofoil theory for modelling of the foils. These simulations are compared to experimental towing tank results, with fair agreement at lower speeds, but limited applicability at high speeds. Thus for the control design the agreement was insufficient. As an alternative, a simple coupled 2 degree-of-freedom spring - mass - damper model is proposed, for which the equations of motion are derived. This has 9 unknown parameters; three of these aremeasured directly, two are modelled, and the remaining four were identified using an experimental parameter estimation technique. Representative parameter values were calculated frommultiple experiments for application in the control design. The design of a control system was based on the above model. First, an output-weighted Linear Quadratic Regulator (LQR) was designed to obtain the full state feedback gains. A non-linear ’bang-bang’ control design was then implemented to try and speed up the response of the system. These control strategies, as well as no control, were applied in the towing tank in regular waves, with good results at low and medium frequencies. At the design point, 32% and 65% reductions in rms motions were achieved for pitch and heave, respectively. At high frequencies, though, not much improvement was achieved due to the bandwidth limitation of the control system. The LQR results were better overall (reduced motions) across the frequency range than the bang-bang controller, as well as having a lower added resistance in waves. The control design of the output-weighted LQR was then revised to be based on alternative outputs, as a possible improvement. However, a further two controller designs did not yield any noticeable improvement and were not developed further

Finite element modeling of an energy storing and return prosthetic foot and implications of stiffness on rollover shape

Energy storing and return (ESAR) prosthetic feet showed continuous improvements during the last 30 years. Despite this, standard guidelines are still missing to achieve an optimal foot design in terms of performances. One of the most important design parameters in ESAR feet is the Rollover Shape (RoS). This represents the foot Center of Pressure (CoP) path in a shank-based coordinate system during stance. RoS objectively describes the foot behavior according to its stiffness, which depends on foot geometry and material. This work presents the development of a finite element modeling methodology able to predict the stiffness characteristic of an ESAR foot and its RoS. The validation of the model is performed on a well-known commercially available prosthetic foot both in bench tests and realistic walking scenario. The obtained results confirm an error of +6.1% on stiffness estimation and +10.2% on RoS evaluation, which underlines that the proposed method is a powerful tool able to replicate the mechanical behavior of a prosthetic foot

Seminal cell free DNA concentration levels discriminate between prostate cancer and benign prostatic hyperplasia

Background/Aim: Seminal plasma cfDNA (scfDNA) was recently proposed as a novel PCa biomarker. Our aim was to evaluate whether scfDNA could discriminate PCa from benign prostate hyperplasia (BPH) patients. Patients and Methods: A cohort of 43 patients (18 and 25 pathology proven PCa and BPH patients), and 13 healthy age-matched control subjects were enrolled. scfDNA quantification was performed. Data were analyzed through ANOVA testing. Results: Average scfDNA concentrations were 1,407.83 ng/\u3bcl, 128.13 ng/\u3bcl and 78.09 ng/\u3bcl for PCa patients, BPH patients and healthy subjects, respectively. Statistical analysis showed a significant difference among the groups, allowing for distinction of patients with optimal accuracy. A cut-off level of 450 ng/\u3bcl scfDNA was identified for the differentiation of PCa and BPH patients. Conclusion: scfDNA concentrations are significantly different between PCa patients and BPH patients. scfDNA is a promising biomarker with several applications in PCa diagnosis, screening programs and therapeutic monitoring

Non-invasive tests for the prediction of post-hepatectomy liver failure in the elderly

Post-hepatectomy liver failure (PHLF) is associated with great morbidity and mortality after resection of hepatocellular carcinoma. Previous studies have underlined that advanced age could be a potential factor influencing post-operative complications and long-term survival.In the past, candidates for resection were based on the Child-Pugh classification, the predictive value of which was rather low. The selection of patients undergoing resection in Western countries is based on the assessment of portal hypertension (PH), which is clinically assessed by measurement of the hepatic venous pressure gradient, an invasive and costly process. Thus, there have been several attempts to identify the best non-invasive test (NIT) to accurately predict PHLF. Most biochemical NITs for the prediction of PHLF are focused on evaluation of underlying liver cirrhosis and PH. Amongst them, FIB-4, which also includes the patient’s age, seems to have more robust supporting results. In Europe and the USA., the most tested and reliable NIT for predicting PHLF is the evaluation of liver stiffness measurement, which is also influenced by age. Imaging parameters are promising tools which are used only in specialized centers however, and when available. Liver volume parameters, as well as contrast-enhanced data, demonstrate good accuracy in predicting PHLF. In this scenario, the evaluation of sarcopenia and bone mineral density through contextual imaging allows the delineation of PHLF in at-risk elderly patients. Further studies focused on parameters for the evaluation of PHLF in elderly patients are needed