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A stroke represents a significant medical condition characterized by the sudden interruption of blood flow to the brain, leading to cellular damage or death. The impact of stroke on individuals can vary from mild impairments to severe disability. Treatment for stroke often focuses on gait rehabilitation. Notably, assessing muscle activation and kinematics patterns using electromyography (EMG) and stereophotogrammetry, respectively, during walking can provide information regarding pathological gait conditions. The concurrent measurement of EMG and kinematics can help in understanding disfunction in the contribution of specific muscles to different phases of gait. To this aim, complexity metrics (e.g., sample entropy; approximate entropy; spectral entropy) applied to EMG and kinematics have been demonstrated to be effective in identifying abnormal conditions. Moreover, the conditional entropy between EMG and kinematics can identify the relationship between gait data and muscle activation patterns. This study aims to utilize several machine learning classifiers to distinguish individuals with stroke from healthy controls based on kinematics and EMG complexity measures. The cubic support vector machine applied to EMG metrics delivered the best classification results reaching 99.85% of accuracy. This method could assist clinicians in monitoring the recovery of motor impairments for stroke patients.
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PURPOSE: Chest trauma is a severe and frequent cause of admission to the emergency department (ED). The serratus anterior plane (SAP) block seems to be an effective method of pain management; however, data on efficacy and safety of a single SAP block performed in the ED by emergency physicians (EP) are limited. This study aimed to compare SAP block performed by the EP in the ED plus standard therapy to standard therapy alone in terms of pain severity at 0-3-6-12-18 and 24 h, total opioid consumption (milligrams of morphine equivalents, MME), respiratory function (SpO2/FiO2 ratio), and adverse events (i.e. pneumothorax, infections in the site of injection, or Local Anaesthetic Systemic Toxicity syndrome due to SAP block) in the first 24 h. METHODS: This retrospective, monocentric study included adult patients admitted to the Sub-intensive Care Unit (SICU) of the ED with multiple rib fractures between 01/2022 and 03/2023. RESULTS: 156 patients (65.4% male; median age 62 years; median injury severity score 16; median thoracic trauma severity score 8) were included. 75 (48.2%) underwent SAP block. Patients undergoing SAP block showed significantly less pain 3-6-18 h after a single block, required less MME (0 [0-20] vs. 20 [0-40], p < 0.001), showed higher SpO2/FiO2 ratio, and no adverse events were reported. CONCLUSION: The SAP block, in combination with standard therapy, appeared to be more effective in providing pain relief than standard therapy alone in patients admitted to the SICU for traumatic rib fractures.
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BACKGROUND: The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. METHODS: Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. RESULTS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patient's directives, family feelings and representatives' desires, and all decisions should be shared. CONCLUSIONS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.
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Anciano Frágil , Heridas y Lesiones , Humanos , Heridas y Lesiones/terapia , Anciano , Fragilidad , Anciano de 80 o más Años , Guías de Práctica Clínica como Asunto , Evaluación Geriátrica/métodosRESUMEN
The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patient's directives, family feelings and representatives' desires, and all decisions should be shared. The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.
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Humanos , Anciano , Centros Traumatológicos/normas , Heridas y Lesiones/terapia , Anciano Frágil , Servicios de Salud para Ancianos , Cuidados Paliativos , Trombosis/tratamiento farmacológico , Factores de Riesgo , Triaje , Inhibidores del Factor XaRESUMEN
Robert's uterus is a rare Müllerian duct anomaly (MDA) characterized by complete asymmetric septum dividing uterine cavity into two non-communicating parts. This study offers insights into diagnosing and management of this condition in a young patient, and a systematic literature review. The review included 19 studies from 2013 to 2023. 11.4% of women reported a history of miscarriage and 5.7% primary infertility. Dysmenorrhea was the most frequent symptom (54.3%), and 14.3% of patients had a coexisting endometriosis. The surgical interventions most commonly combine laparoscopic and hysteroscopic techniques. Robert's uterus requires heightened clinical awareness for early diagnosis, particularly in young women.
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Útero , Femenino , Humanos , Histeroscopía/métodos , Conductos Paramesonéfricos/anomalías , Conductos Paramesonéfricos/cirugía , Anomalías Urogenitales/cirugía , Anomalías Urogenitales/diagnóstico por imagen , Útero/anomalías , Útero/diagnóstico por imagen , Útero/cirugía , NiñoRESUMEN
BACKGROUND: Visceral adiposity has been associated with an increased risk of critical illness in COVID-19 patients. However, if it also associates to a poor survival is still not well established. The aim of the study was to assess the relationship between abdominal fat distribution and COVID-19 mortality. METHODS: In this six-month longitudinal cohort study, abdominal visceral (VAT) and subcutaneous adipose tissues (SAT) were measured by computed tomography in a cohort of 174 patients admitted to the emergency department with a diagnosis of COVID-19, during the first wave of pandemic. The primary exposure and outcome measures were VAT and SAT at hospital admission, and death at 30 and 180 days, respectively. RESULTS: Overall survival was not different according to VAT (p = 0.94), SAT (p = 0.32) and VAT/SAT ratio (p = 0.64). However, patients in the lowest SAT quartile (thickness ≤ 11.25 mm) had a significantly reduced survival compared to those with thicker SAT (77 vs. 94% at day 30; 74 vs. 91% at day 180, p = 0.01). Similarly, a thinner SAT was associated with lower survival in Intensive Care Unit (ICU) admitted patients, independently of sex or age (p = 0.02). The VAT/SAT ratio showed a non-linear increased risk of ICU admission, which plateaued out and tended for inversion at values greater than 1.9 (p = 0.001), although was not associated with increased mortality rate. CONCLUSIONS: In our cohort, visceral adiposity did not increase mortality in patients with COVID-19, but low SAT may be associated with poor survival.
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COVID-19 , Grasa Intraabdominal , Humanos , Estudios Longitudinales , Estudios Retrospectivos , Grasa Intraabdominal/diagnóstico por imagen , COVID-19/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Grasa Abdominal/diagnóstico por imagen , Estudios de Cohortes , Grasa Subcutánea/diagnóstico por imagen , Obesidad Abdominal/complicaciones , Obesidad Abdominal/diagnóstico por imagenRESUMEN
The aim of this study is to evaluate the effectiveness of electrosuit therapy in the clinical treatment of children with Cerebral Palsy, focusing on the effect of the therapy on spasticity and trunk control. Moreover, the compliance of caregivers with respect to the use of the tool was investigated. During the period ranging from 2019 to 2022, a total of 26 children (18 M and 8 F), clinically stable and affected by CP and attending the Neurorehabilitation Unit of the "Padre Pio Foundation and Rehabilitation Centers", were enrolled in this study. A subset of 12 patients bought or rented the device; thus, they received the administration of the EMS-based therapy for one month, whereas the others received only one-hour training to evaluate the feasibility (by the caregivers) and short-term effects. The Gross Motor Function Classification System was utilized to evaluate gross motor functions and to classify the study sample, while the MAS and the LSS were employed to assess the outcomes of the EMS-based therapy. Moreover, between 80% and 90% of the study sample were satisfied with the safety, ease of use, comfort, adjustment, and after-sales service. Following a single session of electrical stimulation with EMS, patients exhibited a statistically significant enhancement in trunk control. For those who continued this study, the subscale of the QUEST with the best score was adaptability (0.74 ± 0.85), followed by competence (0.67 ± 0.70) and self-esteem (0.59 ± 0.60). This study investigates the impact of the employment of the EMS on CP children's ability to maintain trunk control. Specifically, after undergoing a single EMS session, LSS showed a discernible improvement in children's trunk control. In addition, the QUEST and the PIADS questionnaires demonstrated a good acceptability and satisfaction of the garment by the patients and the caregivers.
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The introduction of pathways to enrol deceased donors after cardio-circulatory confirmation of death (donation after circulatory death, DCD) is expanding in many countries to face the shortage of organs for transplantation. The implementation of normothermic regional reperfusion (NRP) with warm oxygenated blood is a strategy to manage in-situ the organs of DCD donors. This approach, an alternative to in-situ cold preservation, and followed by prompt retrieval and cold static storage and/or ex-vivo machine perfusion (EVMP), could be limited to abdominal organs (A-NRP) or extended to the thorax (thoraco-abdominal, TA-NRP. NRP is also referred to as extracorporeal interval support for organ retrieval (EISOR). The use of EISOR is increasing in Europe, even if variably regulated. A-NRP has been demonstrated to be effective in decreasing the risk associated with transplantation of abdominal organs from DCD donors, and was recommended by the European Society for Organ Transplantation (ESOT) in a recent consensus document. We aim to explain how we select the candidates for DCD, to describe our regionalized model for implementing EISOR provision, and to introduce the health care professionals involved in this complex process, with their strictly defined roles, responsibilities, and boundaries. Finally, we report the results of our program, recruiting cDCD donors over a large network of hospitals, all pertaining to a Local Health Authority (Azienda Unità Sanitaria Locale, AUSL) in Romagna, Italy.
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BACKGROUND: Postoperative analgesia in breast surgery is difficult due to the extensive nature of the surgery and the complex innervation of the breast; general anesthesia can be associated with regional anesthesia techniques to control intra- and post-postoperative pain. This randomized comparative study aimed to compare the efficacy of the erector spinae plane block and the thoracic paravertebral block in radical mastectomy procedures with or without axillary emptying. METHODS: This prospective randomized comparative study included 82 adult females who were randomly divided into two groups using a computer-generated random number. Both groups, Thoracic Paraverterbal block group and Erector Spinae Plane Block group (41 patients each), received general anesthesia associated with a multilevel single-shot thoracic paravertebral block and a multilevel single-shot erector spinae plane block, respectively. Postoperative pain intensity (expressed as Numeric Rating Scale), patients who needed rescue analgesic, intra- and post-operative opioid consumption, post-operative nausea and vomiting, length of stay, adverse events, chronic pain at 6 months, and the patient's satisfaction were recorded. RESULTS: At 2 h (p < 0.001) and 6 h (p = 0.012) the Numeric Rating Scale was significantly lower in Thoracic Paraverterbal block group. The Numeric Rating Scale at 12, 24, and 36 postoperative hours did not show significant differences. There were no significant differences also in the number of patients requiring rescue doses of NSAIDs, in intra- and post-operative opioid consumption, in post-operative nausea and vomiting episodes and in the length of stay. No failures or complications occurred in the execution of techniques and none of the patients reported any chronic pain at six months from the surgery. CONCLUSIONS: Both thoracic paravertebral block and erector spinae plane block can be effectively used in controlling post-mastectomy pain with no significant differences between the two blocks. TRIAL REGISTRATION: The study was prospectively registered on Clinicaltrials.gov (trial identifier NCT04457115) (first registration 27/04/2020).
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Analgesia , Neoplasias de la Mama , Dolor Crónico , Bloqueo Nervioso , Adulto , Femenino , Humanos , Mastectomía Radical Modificada , Mastectomía , Analgésicos Opioides , Estudios Prospectivos , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/prevención & control , Dolor Postoperatorio/prevención & control , Ultrasonografía IntervencionalRESUMEN
Electrical stimulation through surface electrodes is a non-invasive therapeutic technique used to improve voluntary motor control and reduce pain and spasticity in patients with central nervous system injuries. The Exopulse Mollii Suit (EMS) is a non-invasive full-body suit with integrated electrodes designed for self-administered electrical stimulation to reduce spasticity and promote flexibility. The EMS has been evaluated in several clinical trials with positive findings, indicating its potential in rehabilitation. This review investigates the effectiveness of the EMS for rehabilitation and its acceptability by patients. The literature was collected through several databases following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Positive effects of the garment on improving motor functions and reducing spasticity have been shown to be related to the duration of the administration period and to the dosage of the treatment, which, in turn, depend on the individual's condition and the treatment goals. Moreover, patients reported wellbeing during stimulation and a muscle-relaxing effect on the affected limb. Although additional research is required to determine the efficacy of this device, the reviewed literature highlights the EMS potential to improve the motor capabilities of neurological patients in clinical practice.
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BACKGROUND: Erector spinae plane block is a locoregional anaesthetic technique widely used in several different surgeries due to its safety and efficacy. The aim of this study is to assess its utility in spinal degenerative and traumatic surgery in western countries and for patients of Caucasian ethnicity. METHODS: Patients undergoing elective lower-thoracic and lumbar spinal fusion were randomised into two groups: the case group (n = 15) who received erector spinae plane block (ropivacaine 0.4% + dexamethasone 4 mg, 20 mL per side at the level of surgery) plus postoperative opioid analgesia, and the control group (n = 15) who received opioid-based analgesia. RESULTS: The erector spinae plane block group showed significantly lower morphine consumption at 48 h postoperatively, lower need for intraoperative fentanyl (203.3 ± 121.7 micrograms vs. 322.0 ± 148.2 micrograms, p-value = 0.021), lower NRS score at 2, 6, 12, 24, and 36 h, and higher satisfaction rates of patients (8.4 ± 1.2 vs. 6.0 ± 1.05, p-value < 0.0001). No differences in the duration of the hospitalisation were observed. No erector spinae plane block-related complications were observed. CONCLUSIONS: Erector spinae plane block is a safe and efficient opioid-sparing technique for postoperative pain control after spinal fusion surgery. This study recommends its implementation in everyday practice and incorporation as a part of multimodal analgesia protocols. TRIAL REGISTRATION: The study was approved by the local ethical committee of Romagna (CEROM) and registered on ClinicalTrials.gov (NCT04729049). It also adheres to the principles outlined in the Declaration of Helsinki and the CONSORT 2010 guidelines.
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Bloqueo Nervioso , Fusión Vertebral , Humanos , Manejo del Dolor/métodos , Analgésicos Opioides , Bloqueo Nervioso/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Estudios Prospectivos , Ultrasonografía Intervencional/métodosRESUMEN
Introduction: Patients with poor-grade subarachnoid hemorrhage (SAH) admitted to the intensive care unit (ICU) often require prolonged invasive mechanical ventilation due to prolonged time to obtain neurological recovery. Impairment of consciousness and airway protective mechanisms usually require tracheostomy during the ICU stay to facilitate weaning from sedation, promote neurological assessment, and reduce mechanical ventilation (MV) duration and associated complications. Percutaneous dilatational tracheostomy (PDT) is the technique of choice for performing a tracheostomy. However, it could be associated with particular risks in neurocritical care patients, potentially increasing the risk of secondary brain damage. Methods: We conducted a single-center, prospective, observational study aimed to assess PDT-associated variations in main cerebral, hemodynamic, and respiratory variables, the occurrence of tracheostomy-related complications, and their relationship with outcomes in adult patients with SAH admitted to the ICU of a neurosurgery/neurocritical care hub center after aneurysm control through clipping or coiling and undergoing early PDT. Results: We observed a temporary increase in ICP during early PDT; this increase was statistically significant in patients presenting with higher therapy intensity level (TIL) at the time of the procedural. The episodes of intracranial hypertension were brief, and appeared mainly due to the activation of cerebral autoregulatory mechanisms in patients with impaired compensatory mechanisms and compliance. Discussion: The low number of observed complications might be related to our organizational strategy, all based on a dedicated "tracheo-team" implementing both PDT following a strictly defined protocol and accurate follow-up.
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BACKGROUND: Aggressive angiomyxoma is a rare mesenchymal tumour of the genital tract with a high incidence in women of reproductive age. The aim of our work is to understand which is the best management strategy for this condition, starting from the description of a rare case report up to the performance of a narrative review of the literature. METHODS: We report a case of a 46-year-old woman who came to our attention because of the growth of a 10-centimetre pedunculated, non-soft, non-tender mass of the left labium majus. She underwent surgical excision, and the histologic diagnosis was aggressive angiomyxoma. Due to a lack of tumour-free margins, radicalization surgery was carried out after three months. A review of the literature of the last ten years was performed following the PRISMA statement on MEDLINE (PubMed). We obtained data from twenty-five studies describing thirty-three cases. RESULTS: Aggressive angiomyxoma is characterized by a high recurrence rate of between 36 and 72% after surgery. There is no universal consensus about hormonal therapy, and most studies (85%) describe surgical excision followed by only clinical and radiological follow-up. CONCLUSION: Wide surgical excision is the gold-standard treatment for aggressive angiomyxoma, succeeded by either clinical or radiological (ultrasound or MRI) follow-up.
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BACKGROUND: Trauma is a leading cause of death and disability. Patients with trauma undergoing invasive mechanical ventilation (IMV) are at risk for ventilator-associated events (VAEs) potentially associated with a longer duration of IMV and increased stay in the intensive care unit (ICU). METHODS: We conducted a retrospective cohort study aimed to evaluate the incidence of infection-related ventilator-associated complications (IVACs), possible ventilator-associated pneumonia (PVAP), and their characteristics among patients experiencing severe trauma that required ICU admission and IMV for at least four days. We also determined pathogens implicated in PVAP episodes and characterized the use of antimicrobial therapy. RESULTS: In total, 88 adult patients were included in the main analysis. In this study, we observed that 29.5% of patients developed a respiratory infection during ICU stay. Among them, five patients (19.2%) suffered from respiratory infections due to multi-drug resistant bacteria. Patients who developed IVAC/PVAP presented lower total GCS (median value, 7; (IQR, 9) vs. 12.5, (IQR, 8); p = 0.068) than those who did not develop IVAC/PVAP. CONCLUSIONS: We observed that less than one-third of trauma patients fulfilling criteria for ventilator associated events developed a respiratory infection during the ICU stay.
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Adolescent idiopathic scoliosis (AIS) is a lateral, rotated curvature of the spine. It is a 3-dimensional deformity that arises in otherwise healthy children at or around puberty. AIS is the most common form of scoliosis in the pediatric population. The etiology is multifactorial, including genetic and environmental factors. The incidence is roughly equal between males and females, while there is a higher risk of progression in females. Guidelines for AIS treatment identify three levels of treatment: observation, physiotherapy scoliosis-specific exercises, and braces. In this paper, we carried out a review of the scientific literature about the indication and success rates of the braces provided for free by the National Health Service in Italy (SSN). Despite a general consensus on the efficacy of rigid bracing treatment and its use in AIS, an important heterogeneity about the treatment is present in the scientific literature, demonstrating a high degree of variability. The overall success rate of the braces provided by the SSN is high, suggesting an important therapeutic role in the treatment of AIS. Robust guidelines are needed to ensure uniform and effective treatments.
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Escoliosis , Masculino , Femenino , Humanos , Adolescente , Niño , Escoliosis/terapia , Medicina Estatal , Tirantes , Columna Vertebral , ItaliaRESUMEN
Cerebral palsy (CP) is a non-progressive neurologic condition that causes gait limitations, spasticity, and impaired balance and coordination. Robotic-assisted gait training (RAGT) has become a common rehabilitation tool employed to improve the gait pattern of people with neurological impairments. However, few studies have demonstrated the effectiveness of RAGT in children with CP and its neurological effects through portable neuroimaging techniques, such as functional near-infrared spectroscopy (fNIRS). The aim of the study is to evaluate the neurophysiological processes elicited by RAGT in children with CP through fNIRS, which was acquired during three sessions in one month. The repeated measure ANOVA was applied to the ß-values delivered by the General Linear Model (GLM) analysis used for fNIRS data analysis, showing significant differences in the activation of both prefrontal cortex (F (1.652, 6.606) = 7.638; p = 0.022), and sensorimotor cortex (F (1.294, 5.175) = 11.92; p = 0.014) during the different RAGT sessions. In addition, a cross-validated Machine Learning (ML) framework was implemented to estimate the gross motor function measure (GMFM-88) from the GLM ß-values, obtaining an estimation with a correlation coefficient r = 0.78. This approach can be used to tailor clinical treatment to each child, improving the effectiveness of rehabilitation for children with CP.
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Cerebral palsy (CP) is a non-progressive neurologic pathology representing a leading cause of spasticity and concerning gait impairments in children. Robotic-assisted gait training (RAGT) is widely employed to treat this pathology to improve children's gait pattern. Importantly, the effectiveness of the therapy is strictly related to the engagement of the patient in the rehabilitation process, which depends on his/her psychophysiological state. The aim of the study is to evaluate the psychophysiological condition of children with CP during RAGT through infrared thermography (IRT), which was acquired during three sessions in one month. A repeated measure ANOVA was performed (i.e., mean value, standard deviation, and sample entropy) extracted from the temperature time course collected over the nose and corrugator, which are known to be indicative of the psychophysiological state of the individual. Concerning the corrugator, significant differences were found for the sample entropy (F (1.477, 5.907) = 6.888; p = 0.033) and for the mean value (F (1.425, 5.7) = 5.88; p = 0.047). Regarding the nose tip, the sample entropy showed significant differences (F (1.134, 4.536) = 11.5; p = 0.041). The findings from this study suggests that this approach can be used to evaluate in a contactless manner the psychophysiological condition of the children with CP during RAGT, allowing to monitor their engagement to the therapy, increasing the benefits of the treatment.
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Parálisis Cerebral , Trastornos Neurológicos de la Marcha , Procedimientos Quirúrgicos Robotizados , Humanos , Niño , Femenino , Masculino , Parálisis Cerebral/diagnóstico por imagen , Parálisis Cerebral/rehabilitación , Terapia por Ejercicio/métodos , Marcha/fisiologíaRESUMEN
Multidrug resistance has become a serious threat for health, particularly in hospital-acquired infections. To improve patients' safety and outcomes while maintaining the efficacy of antimicrobials, complex interventions are needed involving infection control and appropriate pharmacological treatments in antibiotic stewardship programs. We conducted a multicenter pre-post study to assess the impact of a stewardship program in seven Italian intensive care units (ICUs). Each ICU was visited by a multidisciplinary team involving clinicians, microbiologists, pharmacologists, infectious disease specialists, and data scientists. Interventions were targeted according to the characteristics of each unit. The effect of the program was measured with a panel of indicators computed with data from the MargheritaTre electronic health record. The median duration of empirical therapy decreased from 5.6 to 4.6 days and the use of quinolones dropped from 15.3% to 6%, both p < 0.001. The proportion of multi-drug-resistant bacteria (MDR) in ICU-acquired infections fell from 57.7% to 48.8%. ICU mortality and length of stay remained unchanged, indicating that reducing antibiotic administration did not harm patients' safety. This study shows that our stewardship program successfully improved the management of infections. This suggests that policy makers should tackle multidrug resistance with a multidisciplinary approach based on continuous monitoring and personalised interventions.
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Control over intracellular release of therapeutic compounds incorporated into nano-carriers will open new possibilities for targeted treatments of various diseases including cancer, and viral and bacterial infections. Here we report our study on mechanoresponsive nano-sized liposomes which, following internalization by cells, achieve intracellular delivery of encapsulated cargo on application of external ultrasound stimulus. This is demonstrated in a bespoke cell reporter system designed to assess free drug in cytoplasm. Biophysical analyses show that drug release is attributable to the action of a mechanoresponsive spiropyran-based compound embedded in the liposomal lipid membrane. Exposure to external ultrasound stimulus results in opening of the molecular structure of the embedded spiropyran, a consequent increase in liposomal lipid membrane fluidity, and size-dependent release of encapsulated model drugs, all pointing to lipid bilayer perturbation. The study hence illustrates feasibility of the proposed concept where intracellular drug release from mechanoresponsive liposomes can be triggered on demand by external ultrasound stimulus.