Hallux Valgus Plantar Pressure Distribution before and after a Distal Metatarsal Osteotomy.

Background: Hallux valgus (HV) morphological alterations impact forefoot kinetics. Surgery aims to restore both the morphology and function. Plantar pressure (PP) distribution systems represent an innovative additional tool to evaluate the hallux functional outcome after surgery in order to assess the hallux dorsiflexion, coupled with plantar flexion of the first ray. However, the literature reports limited evidence regarding the rebalancing of the plantar pressure distribution following surgery. The purpose of the present study was to examine the PP distribution in HV patients before and after a distal metatarsal osteotomy using a novel anatomically based protocol for in-shoe plantar load analysis during gait. Methods: A consecutive series of 18 patients with mild-to-moderate symptomatic HV who underwent a distal metatarsal osteotomy (S.E.R.I. technique) were prospectively evaluated using clinical scores (AOFAS and NRS), radiographic parameters (hallux valgus angle, intermetatarsal angle), and PP measurements via W-INSHOE© (Medicapteurs, Balma, France). Data were collected preoperatively and 12 months after surgery. Results: At 12 months follow-up, 3 patients were lost to follow-up, leaving 15 patients (24 HV) for examination. Both clinical and radiographical outcomes showed significant improvements from the pre- to postoperative periods. The PP distribution pattern revealed a significant increase in the peak pressure under the first metatarsal head associated with a significant increase in the peak pressure under the central metatarsals area between the pre- and postoperative periods. Conclusions: PP measurement systems hold promise as an additional clinical tool, yet current findings remain inconclusive. Further long-term follow-up studies that incorporate additional parameters are warranted.

Hallux Valgus Plantar Pressure Distribution Before and After Surgery.

Hallux valgus is a common foot deformity that may cause pain and functional limitation, and often requires surgical correction. Clinical and radiographic parameters are typically used to assess postoperative outcomes. Plantar pressure distribution systems represent an innovative additional tool to evaluate hallux functional outcome after surgery. A systematic review of the current literature was performed to assess evaluation systems used for plantar pressure analysis and differences before and after hallux valgus surgery, and a possible relationship between different surgical techniques and clinical and radiographic results. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for this review. Initial search results yielded 40 studies. Two additional studies were found through cross-reference. Twenty-five studies were screened. A total of 10 articles were included in the review process. Two main plantar pressure analysis systems were identified. Hallux function restoration based on plantar pressure measurement did not always occur. No relevant relationships between plantar pressure distribution data and different surgical techniques were established. All patients achieved satisfactory clinical and radiographic outcomes, regardless of surgical techniques used; however, no clear relationships were observed between clinical and radiographic results and the change in foot plantar pressure patterns. The current literature on this topic showed several methodologic limitations. Therefore, it is not possible to provide sufficiently supported evidence-based data regarding plantar pressure distribution rebalance after surgery using current plantar pressure analysis systems. Further investigations are needed to fill these gaps in evidence.

Head Down Tilt 15° in Acute Ischemic Stroke with Poor Collaterals: A Randomized Preclinical Trial.

Cerebral collaterals are recruited after arterial occlusion with a protective effect on tissue outcome in acute ischemic stroke. Head down tilt 15° (HDT15) is a simple, low cost and accessible procedure that could be applied as an emergency treatment, before recanalization therapies, with the aim to increase cerebral collateral flow. Spontaneously hypertensive rats have been shown to display anatomical differences in morphology and function of cerebral collaterals, compared to other rat strains, resulting in an overall poor collateral circulation. We investigate the efficacy and safety of HDT15 in spontaneously hypertensive (SHR) rats, which were considered as an animal stroke model with poor collaterals. Cerebral ischemia was induced by 90 minute endovascular occlusion of the middle cerebral artery (MCA). SHR rats were randomized to HDT15 or flat position (n = 19). HDT15 was applied 30 minutes after occlusion and lasted 60 minutes, until reperfusion. HDT15 application increased cerebral perfusion (+16.6% versus +6.1%; p = 0.0040) and resulted in a small reduction of infarct size (83.6 versus 107.1 mm3; - 21.89%; p = 0.0272), but it was not associated with early neurological improvement, compared to flat position. Our study suggests that the response to HDT15 during MCA occlusion is dependent on baseline collaterals. Nonetheless, HDT15 promoted a mild improvement of cerebral hemodynamics even in subjects with poor collaterals, without safety concerns.

Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL).

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (- 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of - 3.0 °C.

Treatment with ROS detoxifying gold quantum clusters alleviates the functional decline in a mouse model of Friedreich ataxia.

Friedreich ataxia (FRDA) is caused by the reduced expression of the mitochondrial protein frataxin (FXN) due to an intronic GAA trinucleotide repeat expansion in the FXN gene. Although FRDA has no cure and few treatment options, there is research dedicated to finding an agent that can curb disease progression and address symptoms as neurobehavioral deficits, muscle endurance, and heart contractile dysfunctions. Because oxidative stress and mitochondrial dysfunctions are implicated in FRDA, we demonstrated the systemic delivery of catalysts activity of gold cluster superstructures (Au8-pXs) to improve cell response to mitochondrial reactive oxygen species and thereby alleviate FRDA-related pathology in mesenchymal stem cells from patients with FRDA. We also found that systemic injection of Au8-pXs ameliorated motor function and cardiac contractility of YG8sR mouse model that recapitulates the FRDA phenotype. These effects were associated to long-term improvement of mitochondrial functions and antioxidant cell responses. We related these events to an increased expression of frataxin, which was sustained by reduced autophagy. Overall, these results encourage further optimization of Au8-pXs in experimental clinical strategies for the treatment of FRDA.

Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study.

Inborn errors of immunity (IEI) are genetic disorders characterized by a wide spectrum of clinical manifestations, ranging from increased susceptibility to infections to significant immune dysregulation. Among these, primary immune regulatory disorders (PIRDs) are mainly presenting with autoimmune manifestations, and autoimmune cytopenias (AICs) can be the first clinical sign. Significantly, AICs in patients with IEI often fail to respond to first-line therapy. In pediatric patients, autoimmune cytopenias can be red flags for IEI. However, for these cases precise indicators or parameters useful to suspect and screen for a hidden congenital immune defect are lacking. Therefore, we focused on chronic/refractory AIC patients to perform an extensive clinical evaluation and multiparametric flow cytometry analysis to select patients in whom PIRD was strongly suspected as candidates for genetic analysis. Key IEI-associated alterations causative of STAT3 GOF disease, IKAROS haploinsufficiency, activated PI3Kδ syndrome (APDS), Kabuki syndrome and autoimmune lymphoproliferative syndrome (ALPS) were identified. In this scenario, a dysregulated immunophenotype acted as a potential screening tool for an early IEI diagnosis, pivotal for appropriate clinical management and for the identification of new therapeutic targets.