Femoral vs sciatic nerve block to provide analgesia after medial open wedge high tibial osteotomy in the setting of multimodal analgesia: A randomized, controlled, single-blinded trial.

STUDY OBJECTIVE: Medial open wedge high tibial osteotomy (MOW HTO) is associated with moderate to severe postoperative pain. The proximal part of the tibia is innervated by branches from the femoral nerve anteriorly and the sciatic nerve posteriorly. There is a paucity of information regarding the optimal peripheral nerve block for postoperative analgesia with minimal impact on motor function. This study tested the hypothesis that a femoral nerve block provides superior analgesia to a sciatic nerve block after MOW HTO in the setting of multimodal analgesia. DESIGN: Randomized controlled single-blind trial. SETTING: Operating room, postoperative recovery area and ward, up to 6 postoperative months. PATIENTS: Fifty patients undergoing MOW HTO. INTERVENTIONS: Interventions were femoral or sciatic nerve block under ultrasound guidance. For each intervention, a total of 100 mg of ropivacaine was injected. Postoperative pain treatment followed a pre-defined protocol with intravenous patient-controlled analgesia of morphine, paracetamol, and ibuprofen. MEASUREMENTS: The primary outcome was intravenous morphine consumption at 24 h postoperatively. Secondary outcomes included rest and dynamic pain scores (on a numeric rating scale out of 10) at 2, 24 and 48 h postoperatively. Functional outcomes included the Short Form-12, Knee injury and Osteoarthritis Outcome Score, and International Knee Documentation Committee (IKDC) scores measured at 6 months postoperatively. MAIN RESULTS: Mean [95% confidence interval] i.v. morphine consumption at 24 postoperative hours were 24 mg [15 mg,33 mg] in the femoral nerve block group and 24 mg [16 mg,32 mg] in the sciatic nerve block group (p = 0.98). There were no significant differences in the secondary outcomes between groups. CONCLUSIONS: This trial failed to demonstrate that a femoral nerve block provides superior analgesia to a sciatic nerve block after MOW HTO under general anesthesia in the setting of multimodal analgesia. There was no significant difference in quality of life and functional outcomes at 6 months postoperatively between groups. Trial registry number:Clinicaltrials.com - NCT05728294; Kofam.ch - SNCTP000003048 | BASEC2018-01774.

Toxidrome of an Easily Obtainable Nootropic: A Case Report of Phenibut Intoxication and Withdrawal Delirium.

PURPOSE/BACKGROUND: Phenibut (4-amino-3-phenyl-butyric acid) is a structural analog of GABA with central nervous system depressant and anxiolytic properties, developed in the former Soviet Union for anxiety, insomnia, and alcohol withdrawal. Its primary mechanism of action is believed to be a GABA-B receptor agonist-with high affinity at the α 2 δ subunit-containing voltage-dependent calcium channels and therefore gabapentinoid activity-as well as, to a lesser extent, GABA-A agonist activity. While not approved or regulated by the FDA, phenibut is easily obtainable online, where it is marketed as a nootropic, or cognitive enhancer. However, phenibut can lead to problems related to intoxication, dependency, and withdrawal, similar to other sedatives. METHODS/PROCEDURES: We present a case of phenibut intoxication and withdrawal delirium that provided diagnostic and management challenges because of a patient that was initially not forthcoming about his phenibut use which resulted in five presentations to the hospital including two admissions. FINDINGS/RESULTS: Initial differential including adrenergic, serotonergic or anticholinergic toxidrome based on clinical picture and history reported at that time, however phenibut use of 50 g daily was eventually revealed, an amount exceeding the highest reported cases in our review of the English literature. IMPLICATIONS/CONCLUSIONS: High-dose phenibut intoxication and withdrawal can appear as dramatic and dangerous as high-dose sedative withdrawal, however given its specified receptor affinity and binding profile we found that a pharmacotherapeutic approach targeting GABA-B, GABA-A, and gabapentenoid receptors were effective in stabilizing this patient, eventually leading to the patient's full and sustained recovery.

Ex Vivo Functional Benchmarking of Hyaluronan-Based Osteoarthritis Viscosupplement Products: Comprehensive Assessment of Rheological, Lubricative, Adhesive, and Stability Attributes.

While many injectable viscosupplementation products are available for osteoarthritis (OA) management, multiple hydrogel functional attributes may be further optimized for efficacy enhancement. The objective of this study was to functionally benchmark four commercially available hyaluronan-based viscosupplements (Ostenil, Ostenil Plus, Synvisc, and Innoryos), focusing on critical (rheological, lubricative, adhesive, and stability) attributes. Therefore, in vitro and ex vivo quantitative characterization panels (oscillatory rheology, rotational tribology, and texture analysis with bovine cartilage) were used for hydrogel product functional benchmarking, using equine synovial fluid as a biological control. Specifically, the retained experimental methodology enabled the authors to robustly assess and discuss various functional enhancement options for hyaluronan-based hydrogels (chemical cross-linking and addition of antioxidant stabilizing agents). The results showed that the Innoryos product, a niacinamide-augmented linear hyaluronan-based hydrogel, presented the best overall functional behavior in the retained experimental settings (high adhesivity and lubricity and substantial resistance to oxidative degradation). The Ostenil product was conversely shown to present less desirable functional properties for viscosupplementation compared to the other investigated products. Generally, this study confirmed the high importance of formulation development and control methodology optimization, aiming for the enhancement of novel OA-targeting product critical functional attributes and the probability of their clinical success. Overall, this work confirmed the tangible need for a comprehensive approach to hyaluronan-based viscosupplementation product functional benchmarking (product development and product selection by orthopedists) to maximize the chances of effective clinical OA management.

Autologous and Allogeneic Cytotherapies for Large Knee (Osteo)Chondral Defects: Manufacturing Process Benchmarking and Parallel Functional Qualification.

Cytotherapies are often necessary for the management of symptomatic large knee (osteo)-chondral defects. While autologous chondrocyte implantation (ACI) has been clinically used for 30 years, allogeneic cells (clinical-grade FE002 primary chondroprogenitors) have been investigated in translational settings (Swiss progenitor cell transplantation program). The aim of this study was to comparatively assess autologous and allogeneic approaches (quality, safety, functional attributes) to cell-based knee chondrotherapies developed for clinical use. Protocol benchmarking from a manufacturing process and control viewpoint enabled us to highlight the respective advantages and risks. Safety data (telomerase and soft agarose colony formation assays, high passage cell senescence) and risk analyses were reported for the allogeneic FE002 cellular active substance in preparation for an autologous to allogeneic clinical protocol transposition. Validation results on autologous bioengineered grafts (autologous chondrocyte-bearing Chondro-Gide scaffolds) confirmed significant chondrogenic induction (COL2 and ACAN upregulation, extracellular matrix synthesis) after 2 weeks of co-culture. Allogeneic grafts (bearing FE002 primary chondroprogenitors) displayed comparable endpoint quality and functionality attributes. Parameters of translational relevance (transport medium, finished product suturability) were validated for the allogeneic protocol. Notably, the process-based benchmarking of both approaches highlighted the key advantages of allogeneic FE002 cell-bearing grafts (reduced cellular variability, enhanced process standardization, rationalized logistical and clinical pathways). Overall, this study built on our robust knowledge and local experience with ACI (long-term safety and efficacy), setting an appropriate standard for further clinical investigations into allogeneic progenitor cell-based orthopedic protocols.

Leader-member exchange (LMX) quality and follower well-being: A daily diary study.

Guided by self-determination and social exchange theories, we examine how leader-member exchange (LMX) quality impacts follower well-being. Despite LMX relationships being dynamic in nature, the way relationship quality varies over time and its impact on well-being has not been examined in detail. To address this important issue, a daily diary study is reported of employees from a variety of organizations. One hundred and fifty-eight participants completed a daily diary in the morning and evening for five consecutive workdays (k = 603 observations). Measures included hedonic and eudaimonic well-being, and social and economic LMX exchanges. There was a significant variation of LMX quality over the diary days. Daily LMX quality predicted daily follower well-being (while controlling for morning well-being). Further, for those that interacted with their manager, social LMX exchanges but not economic LMX exchanges predicted daily well-being. Interaction characteristics (frequency, time, content) had a relatively small impact on daily well-being. As predicted, work engagement mediated the relation between daily LMX quality and social LMX exchanges (but not daily economic LMX exchanges) with well-being. The results show how LMX quality affects followers' well-being that varies daily, that is affected by leaders' behaviors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Automatic Body Segment and Side Recognition of an Inertial Measurement Unit Sensor during Gait.

Inertial measurement unit (IMU) sensors are widely used for motion analysis in sports and rehabilitation. The attachment of IMU sensors to predefined body segments and sides (left/right) is complex, time-consuming, and error-prone. Methods for solving the IMU-2-segment (I2S) pairing work properly only for a limited range of gait speeds or require a similar sensor configuration. Our goal was to propose an algorithm that works over a wide range of gait speeds with different sensor configurations while being robust to footwear type and generalizable to pathologic gait patterns. Eight IMU sensors were attached to both feet, shanks, thighs, sacrum, and trunk, and 12 healthy subjects (training dataset) and 22 patients (test dataset) with medial compartment knee osteoarthritis walked at different speeds with/without insole. First, the mean stride time was estimated and IMU signals were scaled. Using a decision tree, the body segment was recognized, followed by the side of the lower limb sensor. The accuracy and precision of the whole algorithm were 99.7% and 99.0%, respectively, for gait speeds ranging from 0.5 to 2.2 m/s. In conclusion, the proposed algorithm was robust to gait speed and footwear type and can be widely used for different sensor configurations.

Optimizing multiparametric magnetic resonance imaging-targeted biopsy and detection of clinically significant prostate cancer: the role of core number and location.

PURPOSE: There is currently no consensus regarding the optimal number of multiparametric magnetic resonance imaging (MRI)-targeted biopsy (TB) cores and their spatial distribution within the MRI lesion. We aim to determine the number of TB cores and location needed to adequately detect csPCa. METHODS: We conducted a retrospective cohort study of 505 consecutive patients undergoing TB for positive MRI lesions defined by a PI-RADS score ≥ 3 between June 2016 and January 2022. Cores chronology and locations were prospectively recorded. The co-primary outcomes were the first core to detect clinically significant prostate cancer (csPCa) and the first highest ISUP grade group. The incremental benefit of each additional core was evaluated. Analysis was then performed by distinguishing central (cTB) and peripheral (pTB) within the MRI lesion. RESULTS: Overall, csPCa was detected in 37% of patients. To reach a csPCa detection rate of 95%, a 3-core strategy was required, except for patients with PI-RADS 5 lesions and those with PSA density ≥ 0.2 ng/ml/cc who benefited from a fourth TB core. At multivariable analysis, only a PSA density ≥ 0.2 ng/ml/cc was an independent predictive factor of having the highest ISUP grade group on the fourth TB cores (p = 0.03). No significant difference in the cancer detection rate was found between cTB and pTB (p = 0.9). Omitting pTB would miss 18% of all csPCa. CONCLUSION: A 3-core strategy should be considered for TB to optimize csPCa detection with additional cores needed for PI-RADS 5 lesions and high PSA density. Biopsy cores from both central and peripheral zones are required.

Activation of healing and reduction of pain by single-use automated microcurrent electrical stimulation therapy in patients with hard-to-heal wounds.

Evidence shows that Electrical Stimulation Therapy (EST) accelerates healing and reduces pain, but EST has yet to become widely used. One reason is the historical use of complex, clinic-based EST devices. This evaluation assessed the early response of different hard-to-heal wounds to a simple, wearable, single-use, automated microcurrent EST device (Accel-Heal, Accel-Heal Technologies Limited - Hever, UK). Forty wounds (39 patients: 18 female - 21 male), mean age 68.9 ± 14.0 years comprised of: seven post-surgical, three trauma, 12 diabetic foot (DFU), 10 venous (VLU), four pressure injuries (PI), four mixed venous or arterial ulcers (VLU/arterial) received automated microcurrent EST for 12 days. Early clinical responses were scored on a 0-5 scale (5-excellent-0-no response). Pain was assessed at 48 h, seven days, and 14 days on a 0-10 visual analogue scale (VAS). Overall, 78% of wounds showed a marked positive clinical response (scores of 5 and 4). Sixty eight percent of wounds were painful with a mean VAS score of 5.5. Almost every patient (96%) with pain experienced reduction within 48 h. All patients with painful wounds experienced pain reduction after seven days: 2.50 VAS (45% reduction) and further pain reduction after 14 days: 1.83 VAS (33%).

Optimizing multiparametric magnetic resonance imaging-targeted biopsy and detection of clinically significant prostate cancer: the role of perilesional sampling.

BACKGROUND: The added-value of systematic biopsy (SB) in patients undergoing magnetic resonance imaging (MRI)-targeted biopsy (TB) remains unclear and the spatial distribution of positive cores relative to the MRI lesion has been poorly studied. The aim of this study was to determine the utility of perilesional biopsy in detecting clinically significant prostate cancer (csPCa). METHODS: We enrolled 505 consecutive patients that underwent SB and TB for suspicious MRI lesions (PI-RADS score 3-5) at Jules Bordet Institute between June 2016 and January 2022. Patient-specific tridimensional prostate maps were reviewed to determine the distance between systematic cores containing csPCa and the MRI index lesion. Primary outcomes were the cancer detection rate (CDR) per patient and the cumulative cancer distribution rate of positive cores for each 5 mm interval from the MRI index lesion. The secondary outcome was the identification of risk groups for the presence of csPCa beyond a 10 mm margin using the chi-square automated interaction detector (CHAID) machine learning algorithm. RESULTS: Overall, the CDR for csPCa of TB, SB, and combined method were 32%, 25%, and 37%, respectively. While combined method detected more csPCa compared to TB (37% vs. 32%, p < 0.001), no difference was found when TB was associated with perilesional sampling within 10 mm (37% vs. 35%, p = 0.2). The cumulative cancer distribution rate for csPCa reached 86% for the 10 mm margin. The CHAID algorithm identified three risk groups: (1) PI-RADS3 ("low-risk"), (2) PI-RADS4 or PI-RADS5 and PSA density <0.15 ng/ml ("intermediate-risk"), and (3) PI-RADS 5 and PSA density ≥0.15 ng/ml ("high-risk"). The risk of missing csPCa was 2%, 8%, and 29% for low-, intermediate- and high-risk groups, respectively. Avoiding biopsies beyond a 10 mm margin prevented the detection of 19% of non-csPCa. CONCLUSIONS: Perilesional biopsy template using a 10 mm margin seems a reasonable alternative to the combined method with a comparable detection of csPCa. Our risk stratification may further enhance the selection of patients.

[Treatment of extensive chondral and osteochondral knee defects with autologous chondrocytes implantation]. / Grands défects chondraux et ostéochondraux du genou : traitement par greffe chondrocytaire autologue.

Treatment of extensive chondral and osteochondral defects in the knee remains a challenge. The traditional bone marrow stimulation and osteochondral mosaicplasty are effective but this is indicated only for lesions smaller than 4 cm2. In addition, while they are offered in young patients, functional deterioration is often observed after 2 years. In contrast, Autologous Chondrocyte Implantation (ACI) has proven to be efficient and durable even in larger lesions. These factors have encouraged our team to consider ACI as a valuable tool, but it was not readily available in Switzerland. In this article, we describe why and how we have developed and refined the technique in our University Hospital for the clinical implementation of this cell-based therapy, performed under a quality assurance system and following good manufacturing practices.

Dans le traitement des défects chondraux et ostéochondraux du genou, les techniques classiques de réparation par stimulation de la moelle osseuse et de greffe ostéochondrale autologue (mosaicplastie) présentent d'importantes limites quant à la taille des lésions traitables (< 4 cm2, soit < 22 mm de diamètre). De plus, alors qu'elles sont destinées à des patients jeunes, une dégradation des résultats a été rapportée après 2 ans. Ces éléments nous ont incités à nous orienter vers la greffe chondrocytaire autologue afin de pouvoir proposer aux patients le traitement de lésions plus étendues avec une meilleure durabilité. Cet article décrit pourquoi et comment nous avons implémenté cette voie thérapeutique dans notre centre universitaire, en assurant une traçabilité et des contrôles qualités stricts tout au long de la chaîne de production.

Knee adduction moment decomposition: Toward better clinical decision-making.

Knee adduction moment (KAM) is correlated with the progression of medial knee osteoarthritis (OA). Although a generic gait modification can reduce the KAM in some patients, it may have a reverse effect on other patients. We proposed the "decomposed ground reaction vector" (dGRV) model to 1) distinguish between the components of the KAM and their contribution to the first and second peaks and KAM impulse and 2) examine how medial knee OA, gait speed, and a brace influence these components. Using inverse dynamics as the reference, we calculated the KAM of 12 healthy participants and 12 patients with varus deformity and medial knee OA walking with/without a brace and at three speeds. The dGRV model divided the KAM into four components defined by the ground reaction force (GRF) and associated lever arms described with biomechanical factors related to gait modifications. The dGRV model predicted the KAM profile with a coefficient of multiple correlations of 0.98 ± 0.01. The main cause of increased KAM in the medial knee OA group, the second component (generated by the vertical GRF and mediolateral distance between the knee and ankle joint centers), was decreased by the brace in the healthy group. The first peak increased, and KAM impulse decreased with increasing velocity in both groups, while no significant change was observed in the second peak. The four-component dGRV model successfully estimated the KAM in all tested conditions. It explains why similar gait modifications produce different KAM reductions in subjects. Thus, more personalized gait rehabilitation, targeting elevated components, can be considered.

Enhancing mHealth data collection applications with sensing capabilities.

Smart mobile devices such as smartphones or tablets have become an important factor for collecting data in complex health scenarios (e.g., psychological studies, medical trials), and are more and more replacing traditional pen-and-paper instruments. However, simply digitizing such instruments does not yet realize the full potential of mobile devices: most modern smartphones have a variety of different sensor technologies (e.g., microphone, GPS data, camera, ...) that can also provide valuable data and potentially valuable insights for the medical purpose or the researcher. In this context, a significant development effort is required to integrate sensing capabilities into (existing) data collection applications. Developers may have to deal with platform-specific peculiarities (e.g., Android vs. iOS) or proprietary sensor data formats, resulting in unnecessary development effort to support researchers with such digital solutions. Therefore, a cross-platform mobile data collection framework has been developed to extend existing data collection applications with sensor capabilities and address the aforementioned challenges in the process. This framework will enable researchers to collect additional information from participants and environment, increasing the amount of data collected and drawing new insights from existing data.

Review of K.H. Pridie (1959) on "A method of resurfacing osteoarthritic knee joints".

This classic discusses the original publication "A method of resurfacing osteoarthritic knee joints" by Dr K.H. Pridie (1959), where this pioneer surgeon described a newly developed method for the treatment of osteoarthritic joint surfaces of the knee, which he named subchondral drilling. This short and concise 11-line publication appeared in the Proceedings of the Congress of the British Orthopaedic Association. It has generated 464 citations since 1959, becoming part of the hundred most-cited publications in knee research. Pridie introduced in clinical experimentation the entity of Marrow Stimulation Techniques to liberate mesenchymal stem cells from cancellous bone. He was aware that the results induced, in terms of quality of the regrown tissue, was limited and "only" fibrocartilage. His idea might have been raised from the work of numerous animal researchers who confirmed repeatedly since 1905 that cartilage needed an osseous perforation to heal. Although the past 60 years brought modifications from the technique described in the original article, the concept of marrow stimulation introduced by Pridie remains the most frequently used in cartilage repair surgery today.

Isolated Femoral LCL Avulsion Fracture in the Adult Knee: Two Patient Cases and Literature Review.

Avulsion injuries of the LCL most commonly occur at the fibular insertion. Femoral LCL avulsion injuries have only been previously described in pediatric patients or as multiligament knee injury components among adults. This case series with comprehensive literature review describes for the first time 2 cases of isolated LCL femoral avulsion fractures in adults including conservative treatment outcomes. Both patients sustained a strong varus stress mechanism to their right knee, following sport injury or road traffic accident. For both patients, a complete radiographic evaluation including X-rays, MRI, and CT scan confirmed no other associated knee lesions. The femoral LCL avulsion fractures that were observed were minimally displaced and noncomminuted. Furthermore, imagery suggested preserved integrity at the superior lateral genicular artery, adjacent articular capsule, and IT band. Based on clinical and imaging evaluations, the decision was made to follow conservative treatment. By 10 weeks postinjury, both patients were asymptomatic with early radiological fracture healing evidence. Comparative varus stress radiographs at 20° knee flexion revealed no side-to-side differences and clinical exam showed no posterolateral rotatory instability. The second patient case presented with mild femoral LCL attachment calcification on follow-up CT-scan. Following a detailed analysis of anatomic injury characteristics, we suggest that patients with isolated femoral LCL avulsion fractures have low secondary displacement risk provided SLGA, articular capsule, and IT band integrity are present. In contrast to high-grade ligamentous and distal avulsion LCL injuries, we recommend conservative treatment for patients who sustain these lesions.

Retrospective Analysis of Autologous Chondrocyte-Based Cytotherapy Production for Clinical Use: GMP Process-Based Manufacturing Optimization in a Swiss University Hospital.

Cultured autologous human articular chondrocyte (HAC) implantation has been extensively investigated for safe and effective promotion of structural and functional restoration of knee cartilage lesions. HAC-based cytotherapeutic products for clinical use must be manufactured under an appropriate quality assurance system and follow good manufacturing practices (GMP). A prospective clinical trial is ongoing in the Lausanne University Hospital, where the HAC manufacturing processes have been implemented internally. Following laboratory development and in-house GMP transposition of HAC cell therapy manufacturing, a total of 47 patients have been treated to date. The main aim of the present study was to retrospectively analyze the available manufacturing records of the produced HAC-based cytotherapeutic products, outlining the inter-individual variability existing among the 47 patients regarding standardized transplant product preparation. These data were used to ameliorate and to ensure the continued high quality of cytotherapeutic care in view of further clinical investigations, based on the synthetic analyses of existing GMP records. Therefore, a renewed risk analysis-based process definition was performed, with specific focus set on process parameters, controls, targets, and acceptance criteria. Overall, high importance of the interdisciplinary collaboration and of the manufacturing process robustness was underlined, considering the high variability (i.e., quantitative, functional) existing between the treated patients and between the derived primary HAC cell types.

Large Diameter Advanta V12 Covered Stent Trial for Coarctation of the Aorta: COARC Study.

BACKGROUND: Covered stent implantation for treatment of coarctation of the aorta (CoA) is effective and can prevent aortic wall injury. Prospective studies with long-term follow-up, including imaging, are lacking. We report the acute and long-term outcomes for use of the Large Diameter Advanta V12 covered stent for treatment of native and recurrent CoA. METHODS: A prospective, multicenter, nonrandomized study was performed including 70 patients (43 male), median age 17 years, median weight 57.4 kg with CoA who underwent implantation of the Large Diameter Advanta V12 covered stent. Annual follow-up for 5 years included Doppler echocardiography to calculate diastolic velocity: systolic velocity ratio. RESULTS: CoA diameter increased from 5.6±3.6 to 14.9±3.9 mm (P<0.0001) and the pressure gradient decreased from 35.8±16.2 to 5.6±7.9 mm Hg (P<0.0001). Preimplantation diastolic velocity:systolic velocity of 0.6±0.16 dropped to 0.34±0.13 (P<0.0001) and was maintained at 5 years. Computed tomography angiograms at 12 months postimplantation demonstrated the stent:transverse arch diameter to be similar, 0.91±0.09 to postprocedure 0.86±0.14. Major adverse vascular events at 30 days and 12 months were 1.4% and 4.3%, respectively. Significant adverse events included three patients who required stent implantation to treat infolding. There were no mortalities. CONCLUSIONS: The Large Diameter Advanta V12 covered stent is safe and effective for the treatment of CoA with an immediate and sustained reduction of the pressure gradient over 12 months and 5 years as assessed by preimplantation and postimplantation Doppler echocardiography and 12-month computed tomography angiography. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00978952. URL: http://www.anzctr.org.au; Unique identifier: ACTRN12612000013864.

Electrical stimulation for pain reduction in hard-to-heal wound healing.

OBJECTIVE: Despite treatment advances over the past 30 years, the societal impact of hard-to-heal wounds is increasingly burdensome. An unresolved issue is wound pain, which can make many treatments, such as compression in venous leg ulcers, intolerable. The aim of this review is to present the evidence and stimulate thinking on the use of electrical stimulation devices as a treatment technology with the potential to reduce pain, improve adherence and thus hard-to-heal wound outcomes. METHOD: A literature search was conducted for clinical studies up to August 2020 reporting the effects of electrical stimulation devices on wound pain. Devices evoking neuromuscular contraction or direct spinal cord stimulation were excluded. RESULTS: A total of seven publications (three non-comparative and four randomised trials) were identified with four studies reporting a rapid (within 14 days) reduction in hard-to-heal wound pain. Electrical stimulation is more widely known for accelerated healing and is one of the most evidence-based technologies in wound management, supported by numerous in vitro molecular studies, five meta-analyses, six systematic reviews and 30 randomised controlled trials (RCTs). Despite this wealth of supportive evidence, electrical stimulation has not yet been adopted into everyday practice. Some features of electrical stimulation devices may have hampered adoption in the past. CONCLUSION: As new, pocket-sized, portable devices allowing convenient patient treatment and better patient adherence become more widely available and studied in larger RCTs, the evidence to date suggests that electrical stimulation should be considered part of the treatment options to address the challenges of managing and treating painful hard-to-heal wounds.

Human Platelet Lysate as an Alternative to Autologous Serum for Human Chondrocyte Clinical Use.

OBJECTIVE: A pivotal aspect of cartilage tissue engineering resides in cell culture medium supplementation, in view of maximizing in vitro cell proliferation and preserving cellular functionality. Autologous human serum (aHS) is commonly used as an inducive supplement for safe human articular chondrocyte (HAC) proliferation prior to clinical implantation. However, practical clinical use of aHS is hindered by constraining manufacturing requirements and quality assurance-driven downstream processing. The present study investigated potential alternative use of commercial human platelet lysate (hPL) supplements in HAC manufacturing workflows related to clinical therapeutic pathways. DESIGN: Differential effects of hPL, aHS, and fetal bovine serum were assessed on primary cultured HAC parameters (viability, proliferative rates, and morphology) in 2-dimensional in vitro systems. A 3-dimensional HAC pellet model served for postexpansion assessment of cellular functionality, by visualizing proteoglycan production (Alcian blue staining), and by using qRT-PCR relative quantification of chondrogenic marker (SOX9, COL2-A1, and ACAN) genetic expression. RESULTS: We found that monolayer HAC culture with hPL or aHS supplements presented similar characteristics (elongated cell morphology and nearly identical growth kinetics). Chondrogenic activity appeared as conserved in HACs expanded with human or bovine supplements, wherein histologic analysis indicated a progressive sGAG accumulation and SOX9, COL2-A1, ACAN gene expression was upregulated in 3-dimensional HAC pellet models. CONCLUSION: This study therefore supports the use of hPL as a functional equivalent and alternative to aHS for cultured HAC batch preparation, with the potential to effectively alleviate pressure on clinical and manufacturing bottlenecks in cell therapy approaches for cartilage regeneration.