Work from our laboratory documents pathological events, including myofiber oxidative damage and degeneration, myofibrosis, micro-vessel (diameter = 50–150 μm) remodeling, and collagenous investment of terminal micro-vessels (diameter ≤ 15 µm) in the calf muscle of patients with Peripheral Artery Disease (PAD). In this study, we evaluate the hypothesis that the vascular pathology associated with the legs of PAD patients encompasses pathologic changes to the smallest micro-vessels in calf muscle. Biopsies were collected from the calf muscle of control subjects and patients with Fontaine Stage II and Stage IV PAD. Slide specimens were evaluated by Quantitative Multi-Spectral and Fluorescence Microscopy. Inter-myofiber collagen, stained with Masson Trichrome (MT), was increased in Stage II patients, and more substantially in Stage IV patients in association with collagenous thickening of terminal micro-vessel walls. Evaluation of the Basement Membrane (BM) of these vessels reveals increased thickness in Stage II patients, and increased thickness, diameter, and Collagen I deposition in Stage IV patients. Coverage of these micro-vessels with pericytes, key contributors to fibrosis and BM remodeling, was increased in Stage II patients, and was greatest in Stage IV patients. Vascular pathology of the legs of PAD patients extends beyond atherosclerotic main inflow arteries and affects the entire vascular tree—including the smallest micro-vessels. Full article

Acute kidney injury (AKI), a critical syndrome characterized by a sudden reduction of renal function, is a common disorder among elderly patients particularly in Intensive Care Unit (ICU). AKI is closely associated with both short- and long-term mortality and length of hospital stay and is considered a predictor of chronic kidney disease (CKD). Specific hemodynamic, metabolic, and molecular changes lead to increased susceptibility to injury in the aged kidney; therefore, certain causes of AKI such as the prerenal reduction in renal perfusion or vascular obstructive conditions are more common in the elderly; moreover, AKI is often multifactorial and iatrogenic. Older patients present several comorbidities (diabetes, hypertension, heart failure) and are exposed to multiple medical interventions such as the use of nephrotoxic contrasts media and medications, which can also trigger AKI. Considering the emerging relevance of this condition, prevention and treatment of AKI in the elderly should be crucial in the internist and emergency setting. This review article summarizes the incidence, the risk factors, the pathophysiology, the molecular mechanisms and the strategies of prevention and treatment of AKI in elderly patients. Full article

Melanoma is one of the most aggressive and highly resistant tumors. Cell plasticity in melanoma is one of the main culprits behind its metastatic capabilities. The detailed molecular mechanisms controlling melanoma plasticity are still not completely understood. Here we combine mathematical models of phenotypic switching with experiments on IgR39 human melanoma cells to identify possible key targets to impair phenotypic switching. Our mathematical model shows that a cancer stem cell subpopulation within the tumor prevents phenotypic switching of the other cancer cells. Experiments reveal that hsa-mir-222 is a key factor enabling this process. Our results shed new light on melanoma plasticity, providing a potential target and guidance for therapeutic studies. Full article

Background: Community pharmacies in many countries around the world provide healthcare services for patients. Pharmacists trained as medication experts provide a wide range of patient care services related to medication therapy, patient education, disease prevention, and health promotion. Professional training, expertise, and skills qualify pharmacists to engage in health screenings. These screening programs performed by community pharmacists can help to identify risk factors, facilitate early detection of common diseases, and assist physicians with making effective diagnoses. Objectives: In this study, we created and tested a novel model to provide professional monitoring and counseling on blood pressure by community pharmacists. The aims of the study were to identify the prevalence of elevated blood pressure among patients visiting a community pharmacy and describe the demographic characteristics of patients with hypertension (sex, age, education, body weight, and hypertension risk factors). Methods: The research project was conducted in an accredited community pharmacy in Poznan, Poland, from January to April 2019. A total of 118 anonymous patients (30.5% men and 69.5% women) participated in this study. To qualify for this study, participants had to be older than 18 years of age and have no previous diagnosis of hypertension or other cardiovascular disease. Results: Based on the blood pressure screenings, 61.9% of patients were qualified for the standard consultation (SC: normal blood pressure), 21.2% for the intensive consultation (IC: normal blood pressure and hypertension risk factor), 16.9% patients with elevated blood pressure for the high-risk consultation (HRC: referred to a physician), and 3.4% received a diagnosis of hypertension. We qualified 35.6% with a high-pressure value (greater than 140/90 mmHg). Conclusions: The novel model for blood pressure control screening and counseling implemented in a generally accessible community pharmacy may help with early detection of hypertension problems, lead to initiation of effective patient counseling by a community pharmacist, and result in early referral of the patient to a physician. Full article

Background: A lead-reactive fibrous capsule (FC) identified by ultrasounds as an atrial or ventricular lead thickness of more than 1 mm above the vendor-declared lead diameter (TL) and its local fibrotic attachment to the cardiac wall (FAC) have never been investigated in vivo, so their relationship with post-extraction masses (ghost) is not known. Methods: Intracardiac echocardiography (ICE) was performed twice during the same extraction procedure in 40 consecutive patients: before and immediately after infected lead extraction Results: The ghost detection rate was high: 60% (24/40 patients); ICE could identify both TL and FAC, TL being noted in 25/40 (62%) patients and FAC in 12/40 patients (30%). Both TL and FAC were significantly associated with ghosts (p < 0.001 and p = 0.002, respectively), but TL had a higher prediction power. The specificity was similar: 94% (15/16) and 100% (16/16), respectively, but TL showed a much higher sensitivity: 100%, (24/24) vs 50% (12/24) (p = 0.016). The ghost group did not show a higher event rate in the follow-up (mean follow-up time = 20 ± 17 months). Conclusion: ICE is able to evaluate both TL and FAC in vivo; ghosts are mostly benign remnants of fibrotic lead capsule cut off during extraction and retained inside the heart by FAC. Full article

Spinopelvic mobility represents the complex interaction of hip, pelvis, and spine. Understanding this interaction is relevant for both arthroplasty and spine surgeons, as a predicted increasing number of patients will suffer from hip and spinal pathologies simultaneously. We conducted a comprehensive literature review, defined the nomenclature, summarized the various classifications of spinopelvic mobility, and outlined the corresponding treatment algorithms. In addition, we developed a step-by-step workup for spinopelvic mobility and total hip arthroplasty (THA). Normal spinopelvic mobility changes from standing to sitting; the hip flexes, and the posterior pelvic tilt increases with a concomitant increase in acetabular anteversion and decreasing lumbar lordosis. Most classifications are based on a division of spinopelvic mobility based on ΔSS (sacral slope) into stiff, normal, and hypermobile, and a categorization of the sagittal spinal balance regarding pelvic incidence (PI) and lumbar lordosis (LL) mismatch (PI–LL = ± 10° balanced versus PI–LL > 10° unbalanced) and corresponding adjustment of the acetabular component implantation. When performing THA, patients with suspected pathologic spinopelvic mobility should be identified by medical history and examination, and a radiological evaluation (a.p. pelvis standing and lateral femur to L1 or C7 (if EOS (EOS imaging, Paris, France) is available), respectively, for standing and sitting radiographs) of spinopelvic parameters should be conducted in order to classify the patient and determine the appropriate treatment strategy. Spine surgeons, before planned spinal fusion in the presence of osteoarthritis of the hip, should consider a hip flexion contracture and inform the patient of an increased risk of complications with existing or planned THA. Full article

Introduction: Traumatic cervical artery dissections are associated with high mortality and morbidity in severely injured patients. After finding even higher incidences than reported before, we decided to incorporate a dedicated head-and-neck computed tomography angiogram (CT-A) in our imaging routine for patients who have been obviously severely injured or, according to trauma mechanism, are suspected to be severely injured. Materials and Methods: A total of 134 consecutive trauma patients with an ISS ≥ 16 admitted to our level I trauma center during an 18 month period were included. All underwent standardized whole-body CT in a 256-detector row scanner with a dedicated head-and-neck CT-A realized as single-bolus split-scan routine. Incidence, mortality, patient and trauma characteristics, and concomitant injuries were recorded and analyzed in patients with carotid artery dissection (CAD) and vertebral artery dissection (VAD). Results: Of the 134 patients included, 7 patients had at least one cervical artery dissection (CeAD; 5.2%; 95% CI 1.5–9.0%). Six patients (85.7%) had carotid artery dissections, with one patient having a CAD of both sides and one patient having a CAD and contralateral VAD combined. Two patients (28.6%) showed a VAD. Overall mortality was 14.3%, neurologic morbidity was 28.6%. None of the patients showed any attributable neurologic symptoms on admission. The new scanning protocol led to further 5 patients with suspected CeAD during the study period, all ruled out by additional magnetic resonance imaging with angiogram (MRI/MR-A). Conclusion: A lack of specific neurologic symptoms on admission urges the need for a dedicated imaging pathway for severely injured patients, reliable for the detection of cervical artery dissections. Although our modified CT protocol with mandatory dedicated CT-A led to false positives requiring additional magnetic resonance imaging, it likely helped reduce possible therapeutic delays. Full article

Background: Remote virtual rehabilitation aroused growing interest in the last decades, and its role has gained importance following the recent spread of COVID19 pandemic. The advantages of virtual reality (VR), augmented reality (AR), gamification, and telerehabilitation have been demonstrated in several medical fields. In this review, we searched the literature for studies using these technologies for orthopedic rehabilitation and analyzed studies’ quality, type and field of rehabilitation, patients’ characteristics, and outcomes to describe the state of the art of VR, AR, gamification, and telerehabilitation for orthopedic rehabilitation. Methods: A comprehensive search on PubMed, Medline, Cochrane, CINAHL, and Embase databases was conducted. This review was performed according to PRISMA guidelines. Studies published between 2015 and 2020 about remote virtual rehabilitations for orthopedic patients were selected. The Methodological Index for Non-Randomized Studies (MINORS) and Cochrane Risk-of-Bias assessment tool were used for quality assessment. Results: 24 studies (9 randomized controlled trials (RCTs) and 15 non-randomized studies) and 2472 patients were included. Studies mainly concern telerehabilitation (56%), and to a lesser extent VR (28%), AR (28%), and gamification (16%). Remote virtual technologies were used following knee and hip arthroplasty. The majority of included patients were between 40 and 60 years old and had a university degree. Remote virtual rehabilitation was not inferior to face-to-face therapy, and physical improvements were demonstrated by increased clinical scores. Orthopedic virtual remote rehabilitation decreased costs related to transports, hospitalizations, and readmissions. Conclusion: The heterogeneity of included studies prevented a meta-analysis of their results. Age and social context influence adaptability to technology, and this can modify compliance to treatment and outcomes. A good relationship between patient and physiotherapist is essential for treatment compliance and new technologies are useful to maintain clinical interactions remotely. Remote virtual technologies allow the delivery of high-quality care at reduced costs. This is a necessity given the growing demand for orthopedic rehabilitation and increasing costs related to it. Future studies need to develop specific and objective methods to evaluate the clinical quality of new technologies and definitively demonstrate advantages of VR, AR, gamification, and telerehabilitation compared to face-to face orthopedic rehabilitation. Full article

Autism spectrum disorder (ASD) often co-occurs with attention deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) efficacy and safety are well-demonstrated for ADHD, evidences are scant in the context of ASD. This naturalistic study aimed to analyze long-term MPH efficacy and safety in 40 ADHD children and adolescents with comorbid ASD, comparing them with 40 ones affected by ADHD without ASD. Treatment lasted from 6 to 156 months (longer than 24 months in more than three quarters of patients). Efficacy and safety were measured by clinical global impression and children global assessment scales; influence of intellectual functioning was examined. Comparisons between groups were made by Wilcoxon or Friedmann tests; relationships between functioning scores and other characteristics were analyzed by ordinal logistic and linear regression. Results demonstrated that MPH in patients with ASD was associated with significative reduction of illness severity, clinical improvement and amelioration of global functioning, without significant differences with patients having ADHD without ASD. The trend of reduction of illness severity and increase of global functioning were favorably related with intellectual functioning. No serious adverse events were reported. The findings showed that long-term MPH was effective and well-tolerated in ADHD children and adolescents with comorbid high functioning ASD. Full article

The human gastrointestinal microbiota (GIM) is a complex and diverse ecosystem that consists of community of fungi, viruses, protists and majorly bacteria. The association of several human illnesses, such as inflammatory bowel disease, allergy, metabolic syndrome and cancers, have been linked directly or indirectly to compromise in the integrity of the GIM, for which some medical interventions have been proposed or attempted. This review highlights and gives update on various technologies, including microfluidics, high-through-put sequencing, metabolomics, metatranscriptomics and culture in GIM research and their applications in gastrointestinal microbiota therapy, with a view to raise interest in the evaluation, validation and eventual use of these technologies in diagnosis and the incorporation of therapies in routine clinical practice. Full article

Recent studies indicate the existence of a maternal-autoantibody-related subtype of autism spectrum disorder (ASD). To date, a large number of studies have focused on describing patterns of brain-reactive serum antibodies in maternal-autoantibody-related (MAR) autism and some have described attempts to define the antigenic targets. This article describes evidence on MAR autism and the various autoantibodies that have been implicated. Among other possibilities, antibodies to neuronal surface protein Contactin Associated Protein 2 (CASPR2) have been found more frequently in mothers of children with neurodevelopmental disorders or autism, and two independent experimental studies have shown pathogenicity in mice. The N-methyl-D-aspartate receptor (NMDAR) is another possible target for maternal antibodies as demonstrated in mice. Here, we discuss the growing evidence, discuss issues regarding biomarker definition, and summarise the therapeutic approaches that might be used to reduce or prevent the transfer of pathogenic maternal antibodies. Full article

Objective: To determine the prevalence of myofascial trigger points (MTrPs) and the correlation between the number of MTrPs and pain and function in patients presenting knee pain osteoarthritis (OA). Methods: This was a secondary analysis of data from a cross-sectional study. The prevalence of MTrPs located in tensor fasciae latae, hip adductors, hamstrings, quadriceps, gastrocnemius, and popliteus muscles was studied in 114 patients (71 men and 43 women) with knee OA. Pain and functionality were assessed with a numerical pain rating scale (NPRS), the Western Ontario, McMaster Universities Osteoarthritis Index (WOMAC) score, the Barthel Index, and the timed up and go test. Results: The prevalence of latent MTrPs was detected via palpation and was estimated to be 50%, 35%, 25%, 29%, 33%, and 12% for tensor fasciae latae, hip adductors, hamstrings, quadriceps, gastrocnemius, and popliteus muscles, respectively. The prevalence of active MTrPs was estimated to be 11%, 17%, 30%, 18%, 25%, and 17% for tensor fasciae latae, hip adductors, hamstrings, quadriceps, gastrocnemius, and popliteus muscles, respectively. Pain was measured with the NPRS scale and was poorly correlated with the prevalence of latent MTrPs (r = 0.2; p = 0.03) and active MTrPs (r = 0.23; p = 0.01) in the hamstrings. Disability was moderately correlated with the number of latent MTrPs in the tensor fasciae latae muscle (Barthel, r = 0.26; p = 0.01 and WOMAC, r = 0.19; p = 0.04). Conclusions: This secondary analysis found that the prevalence of the MTrPs varied from 11% to 50% in different muscles of patients with mild to moderate painful knee osteoarthritis. Pain was correlated poorly with the prevalence of latent and active MTrPs in the hamstring muscles, and disability correlated moderately with the number of latent MTrPs in tensor fasciae latae. Full article