Analysis and Report of the Physical and Rehabilitation Medicine Evaluation Activity in Patients Admitted to Acute Care Setting: An Observational Retrospective Study.

BACKGROUND: Disability (both temporary and transitory, or definitive) might occur for the first time in a given patient after an acute clinical event. It is essential, whenever indicated, to undergo a Physical Medicine and Rehabilitation assessment to detect disability and any need for rehabilitation early. Although access to rehabilitation services varies from country to country, it should always be governed by a PRM prescription. OBJECTIVE: The aim of the present observational retrospective study is to describe consultancy activity performed by PRM specialists in a university hospital in terms of requests' typology, clinical questions, and rehabilitation setting assignment. METHODS: Multiple parameters were analyzed (clinical condition, patient's socio-family background, and rehabilitation assessment scale scores) and a correlation analysis was performed between the analyzed characteristics and both the different clinical conditions and the assigned rehabilitation setting. RESULTS: PRM evaluations of 583 patients from 1 May 2021 to 30 June 2022 were examined. Almost half of the total sample (47%) presented disability due to musculoskeletal conditions with a mean age of 76 years. The most frequently prescribed settings were home rehabilitation care, followed by intensive rehabilitation and long-term care rehabilitation. CONCLUSIONS: Our results suggest the high public health impact of musculoskeletal disorders, followed by neurological disorders. This is, however, without forgetting the importance of early rehabilitation to prevent other types of clinical conditions such as cardiovascular, respiratory, or internal diseases from leading to motor disability and increasing costs.

Non-Surgical and Rehabilitative Interventions in Patients with Frozen Shoulder: Umbrella Review of Systematic Reviews.

Background: Frozen shoulder (FS) is a painful condition characterized by progressive loss of shoulder function with passive and active range of motion reduction. To date, there is still no consensus regarding its rehabilitative treatment for pain management. Purpose: The aim of this umbrella review of systematic reviews was to analyze the literature, investigating the effects of non-surgical and rehabilitative interventions in patients suffering from FS. Patients and Methods: A review of the scientific literature was carried out from 2010 until April 2020 using the following search databases: PubMed, Medline, PEDro, Scopus and Cochrane Library of Systematic Reviews. A combination of terms was used for the search: frozen shoulder OR adhesive capsulitis AND systematic review OR meta-analysis AND rehabilitation NOT surgery NOT surgical intervention. We included systematic reviews that specifically dealt with adults with FS, treated with non-surgical approaches. All the systematic reviews and meta-analyses included in the study that met the inclusion criteria were assessed using the Assessment of Multiple Systematic Reviews as a quality assessment tool. Results: Out of 49 studies, only 14 systematic reviews respected the eligibility criteria and were included in this study. Their results showed an important heterogeneity of the studies and all of them agree on the lack of high-quality scientific work to prove unequivocally which rehabilitative treatment is better than the other. Due to this lack of gold standard criteria, there may be also a heterogeneity in the diagnosis of the reviews analyzed. Conclusion: Non-surgical and rehabilitative interventions are undoubtedly effective in treating FS, but there is no evidence that one approach is more effective than the other regarding the methods reported. Future high-quality RCTs are needed to standardize the treatment modalities of each physiotherapy intervention to provide strong recommendations in favor.

State of the evidence about rehabilitation interventions in patients with dysphagia.

INTRODUCTION: Rather than a separate nosological entity, dysphagia must be considered as a symptom of other pathological conditions, which afflicts patients admitted to numerous medical departments (rehabilitation, neurology, geriatrics, internal medicine, etc.) These disorders share the need for timely access to quality care and multidisciplinary treatment, including rehabilitation. The purpose of this study was to conduct a review of the current guidelines' recommendations in the literature and provide recommendations on the rehabilitative management of the patient with dysphagia. EVIDENCE ACQUISITION: The search was carried out through the main databases (Medline, Pedro, Cochrane Database and Google Scholar). All the articles concerning rehabilitation management of dysphagia, published in the last 10 years, have been included. EVIDENCE SYNTHESIS: Bibliographic research has provided thirteen guidelines. The literature analysed focuses mainly on the screening, the evaluation and the planning of multidisciplinary treatment. The literature agrees in recommending as cornerstones in the treatment of the dysphagic patient dietary changes, rehabilitation training (particularly muscle strengthening exercises and coordination) and early use of alternative nutrition in patients severely compromised. CONCLUSIONS: The dysphagic patient requires the deployment of a range of skills by a multi-professional and multi-disciplinary team. Speech and language pathologists in cooperation with specialists of rehabilitation have the task of managing the various stages, ranging from the early identification of the symptom to the setting of the treatment plan. Due to the lack of standardized protocols, it is necessary to implement the research path, especially regarding rehabilitation intervention.

Motor Recovery After Stroke: From a Vespa Scooter Ride Over the Roman Sampietrini to Focal Muscle Vibration (fMV) Treatment. A 99mTc-HMPAO SPECT and Neurophysiological Case Study.

Focal repetitive muscle vibration (fMV) is a safe and well-tolerated non-invasive brain and peripheral stimulation (NIBS) technique, easy to perform at the bedside, and able to promote the post-stroke motor recovery through conditioning the stroke-related dysfunctional structures and pathways. Here we describe the concurrent cortical and spinal plasticity induced by fMV in a chronic stroke survivor, as assessed with 99mTc-HMPAO SPECT, peripheral nerve stimulation, and gait analysis. A 72-years-old patient was referred to our stroke clinic for a right leg hemiparesis and spasticity resulting from a previous (4 years before) hemorrhagic stroke. He reported a subjective improvement of his right leg's spasticity and dysesthesia that occurred after a30-min ride on a Vespa scooter as a passenger over the Roman Sampietrini (i.e., cubic-shaped cobblestones). Taking into account both the patient's anecdote and the current guidelines that recommend fMV for the treatment of post-stroke spasticity, we then decided to start fMV treatment. 12 fMV sessions (frequency 100 Hz; amplitude range 0.2-0.5 mm, three 10-min daily sessions per week for 4 consecutive weeks) were applied over the quadriceps femoris, triceps surae, and hamstring muscles through a specific commercial device (Cro®System, NEMOCOsrl). A standardized clinical and instrumental evaluation was performed before (T0) the first fMV session and after (T1) the last one. After fMV treatment, we observed a clinically relevant motor and functional improvement, as assessed by comparing the post-treatment changes in the score of the Fugl-Meyer assessment, the Motricity Index score, the gait analysis, and the Ashworth modified scale, with the respective minimal detectable change at the 95% confidence level (MDC95). Data from SPECT and peripheral nerve stimulation supported the evidence of a concurrent brain and spinal plasticity promoted by fMV treatment trough activity-dependent changes in cortical perfusion and motoneuron excitability, respectively. In conclusion, the substrate of post-stroke motor recovery induced by fMV involves a concurrently acting multisite plasticity (i.e., cortical and spinal plasticity). In our patient, operant conditioning of both cortical perfusion and motoneuron excitability throughout a month of fMV treatment was related to a clinically relevant improvement in his strength, step symmetry (with reduced limping), and spasticity.

Peroneus Brevis flap in Achilles tendon reconstruction. Clinical, radiological and functional analysis.

BACKGROUND: We would like to describe our experience with Peroneus Brevis flap in complicated Achilles tendon re-ruptures with fringed stumps. METHODS: Eight patients with monolateral re-rupture of Achilles tendon were selected as eligible for surgical repair with Peroneus Brevis flap. Patients' outcome was evaluated clinically (ATRS and ROM), functionally (Gait analysis) and MRI was performed before and after surgery. RESULTS: Effective coverage of tissue defect was reached in all patients. Functional assessment evaluation results were registered in a follow-up time that ranged from 12 to 18 months. ATRS and ROM tests' results showed good functional recovery without functional limitations or subjective reports pain. Post-operative MRI showed no signs of inflammation or tissue gaps. Gait analysis showed a partial reduction of performance in the affected side that did not affect patients' quality of life. CONCLUSIONS: In the presence of fringed stumps in Achilles tendon re-rupture, tendon flaps have the benefits of autologous tissues transfers and present less risks of failure than free flaps. Among them, Peroneus Brevis flap is easy to perform and leads to donor site's low morbidity. Our preliminary experience provides support for this technique to be potentially validated in larger more controlled trial.

Short-Term Effects of Focal Muscle Vibration on Motor Recovery After Acute Stroke: A Pilot Randomized Sham-Controlled Study.

Repetitive focal muscle vibration (rMV) is known to promote neural plasticity and long-lasting motor recovery in chronic stroke patients. Those structural and functional changes within the motor network underlying motor recovery occur in the very first hours after stroke. Nonetheless, to our knowledge, no rMV-based studies have been carried out in acute stroke patients so far, and the clinical benefit of rMV in this phase of stroke is yet to be determined. The aim of this randomized double-blind sham-controlled study is to investigate the short-term effect of rMV on motor recovery in acute stroke patients. Out of 22 acute stroke patients, 10 were treated with the rMV (vibration group-VG), while 12 underwent the sham treatment (control group-CG). Both treatments were carried out for 3 consecutive days, starting within 72 h of stroke onset; each daily session consisted of three 10-min treatments (for each treated limb), interspersed with a 1-min interval. rMV was delivered using a specific device (Cro®System, NEMOCO srl, Italy). The transducer was applied perpendicular to the target muscle's belly, near its distal tendon insertion, generating a 0.2-0.5 mm peak-to-peak sinusoidal displacement at a frequency of 100 Hz. All participants also underwent a daily standard rehabilitation program. The study protocol underwent local ethics committee approval (ClinicalTrial.gov NCT03697525) and written informed consent was obtained from all of the participants. With regard to the different pre-treatment clinical statuses, VG patients showed significant clinical improvement with respect to CG-treated patients among the NIHSS (p < 0.001), Fugl-Meyer (p = 0.001), and Motricity Index (p < 0.001) scores. In addition, when the upper and lower limb scales scores were compared between the two groups, VG patients were found to have a better clinical improvement at all the clinical end points. This study provides the first evidence that rMV is able to improve the motor outcome in a cohort of acute stroke patients, regardless of the pretreatment clinical status. Being a safe and well-tolerated intervention, which is easy to perform at the bedside, rMV may represent a valid complementary non-pharmacological therapy to promote motor recovery in acute stroke patients.

Percutaneous Fat Transfer to Treat Knee Osteoarthritis Symptoms: Preliminary Results.

Purpose This study aims to evaluate the safety and efficacy of autologous aspirated and purified fat tissue injected percutaneously into the knee joint for the treatment of symptomatic osteoarthritis (OA). Methods We reviewed 30 patients, who received an autologous percutaneous fat injection for the treatment of knee OA, from January 2012 to March 2015. Mean patients' age was 63.3 ± 5.3 years (range, 50-80 years). Body mass index was 25.1 ± 1.7. Clinical evaluation was based on pain visual analog scale (VAS) and WOMAC score for functional and subjective assessment. We also noted the adverse reactions and the consumption of nonsteroidal anti-inflammatory drugs in the posttreatment period. Results All patients reported improvements with respect to pain: average VAS was 7.7 ± 1.2 at baseline, 5.2 ± 0.2 at 1-month follow-up, and 4.3 ± 1 at 3-month follow-up. A slight deterioration (5.0 ± 1.1) was evidenced at 1 year. Total WOMAC score was 89.9 ± 1.7 at baseline, 66.3 ± 1 at 1 month, 68.6 ± 1.7 at 3 months, and 73.2 ± 1.8 at 12 months of follow-up. Conclusion Our preliminary findings suggest that autologous percutaneous fat injections are a valid treatment option for knee OA. Level of Evidence Level IV, therapeutic case series.

The effectiveness of negative pressure therapy on infected wounds: preliminary results.

Vacuum-assisted closure (VAC) therapy is a sophisticated system that maintains a closed, humid, sterile and isolated environment. Wound infection is considered a relative contraindication. The objective of this study is to extend the indications for VAC therapy to include infected wounds by demonstrating its ability to increase the antibiotic concentration in the damaged and infected tissues. Patients who presented with ulcers infected with daptomycin-sensitive bacteria were eligible to be enrolled in this prospective study. They were given antibiotic therapy with daptomycin with a specific protocol. A biopsy of the lesion was carried out to detect tissue concentration of the drug at time 0. Afterwards, the patients were subjected to VAC therapy. At the end of VAC therapy, a second lesion biopsy was performed and analysed to detect tissue concentration of the drug at time 1. A control group was enrolled in which patients followed the same protocol, but they were treated with traditional dressings. Fisher's exact test was used to compare the two groups. The results highlighted a significant increase in the concentration of antibiotics in the study group tissue; the improvement was sensibly lower in the control group. Statistical differences were not found between the two groups. The preliminary analysis of the data showed an important increase of antibiotic concentration in the tissue after VAC therapy. Despite the encouraging data, it is necessary to broaden the sample of patients and perform the same study with other antibiotics.

Is chondroitin sulfate responsible for the biological effects attributed to the GC protein-derived Macrophage Activating Factor (GcMAF)?

We hypothesize that a plasma glycosaminoglycan, chondroitin sulfate, may be responsible for the biological and clinical effects attributed to the Gc protein-derived Macrophage Activating Factor (GcMAF), a protein that is extracted from human blood. Thus, Gc protein binds chondroitin sulfate on the cell surface and such an interaction may occur also in blood, colostrum and milk. This interpretation would solve the inconsistencies encountered in explaining the effects of GcMAF in vitro and in vivo. According to our model, the Gc protein or the GcMAF bind to chondroitin sulfate both on the cell surface and in bodily fluids, and the resulting multimolecular complexes, under the form of oligomers trigger a transmembrane signal or, alternatively, are internalized and convey the signal directly to the nucleus thus eliciting the diverse biological effects observed for both GcMAF and chondroitin sulfate.

Effects of Pre-surgical Vitamin D Supplementation and Ketogenic Diet in a Patient with Recurrent Breast Cancer.

BACKGROUND: A woman, mother of one at the age of 19 years, was diagnosed with mammary adenocarcinoma in the right breast in 1985 at the age of 37 years. The patient underwent surgery (quadrantectomy), lymphadenectomy and radiotherapy. In 1999, an adenocarcinoma was diagnosed in the left breast, followed by adequate resection, radiotherapy and anti-oestrogen receptor treatment for 6 years. In March 2014, an infiltrating adenocarcinoma was diagnosed in the remaining part of the right breast that had been operated on and irradiated in 1985. CASE REPORT: The pre-surgical biopsy, showed weak positivity for progesterone receptor (PgR) (<1%), high positivity for oestrogen receptor (ER) (90%), high positivity for human epidermal growth factor receptor (HER2) (>10%, score 2+), and high positivity for the nuclear protein Ki67 (30%). In the three weeks between diagnosis and operation, when no other treatment had been planned, the patient decided to self-administer high doses of oral vitamin D3 (10,000 IU/day), and to follow a strict ketogenic diet. RESULTS: Following right mastectomy, analysis of the surgical specimen showed no positivity for HER2 expression (negative, score 0), and significant increase in positivity of PgR (20%). Positivity for ER and Ki67 were unaltered. CONCLUSION: This observation indicates that a combination of high-dose vitamin D3 and ketogenic diet leads to changes in some biological markers of breast cancer, i.e. negativization of HER2 expression and increased expression of PgR.

Effects of oxaliplatin and oleic acid Gc-protein-derived macrophage-activating factor on murine and human microglia.

The biological properties and characteristics of microglia in rodents have been widely described, but little is known about these features in human microglia. Several murine microglial cell lines are used to investigate neurodegenerative and neuroinflammatory conditions; however, the extrapolation of the results to human conditions is frequently met with criticism because of the possibility of species-specific differences. This study compares the effects of oxaliplatin and of oleic acid Gc-protein-derived macrophage-activating factor (OA-GcMAF) on two microglial cell lines, murine BV-2 cells and human C13NJ cells. Cell viability, cAMP levels, microglial activation, and vascular endothelial growth factor (VEGF) expression were evaluated. Our data demonstrate that oxaliplatin induced a significant decrease in cell viability in BV-2 and in C13NJ cells and that this effect was not reversed with OA-GcMAF treatment. The signal transduction pathway involving cAMP/VEGF was activated after treatment with oxaliplatin and/or OA-GcMAF in both cell lines. OA-GcMAF induced a significant increase in microglia activation, as evidenced by the expression of the B7-2 protein, in BV-2 as well as in C13NJ cells that was not associated with a concomitant increase in cell number. Furthermore, the effects of oxaliplatin and OA-GcMAF on coculture morphology and apoptosis were evaluated. Oxaliplatin-induced cell damage and apoptosis were nearly completely reversed by OA-GcMAF treatment in both BV-2/SH-SY5Y and C13NJ/SH-SY5Y cocultures. Our data show that murine and human microglia share common signal transduction pathways and activation mechanisms, suggesting that the murine BV-2 cell line may represent an excellent model for studying human microglia.

Metopic suture and RUNX2, a key transcription factor in osseous morphogenesis with possible important implications for human brain evolution.

BACKGROUND: Overall, the comparative data available on the timing of metopic suture closure in present-day and fossil members of human lineage, as well as great apes, seem to indicate that human brain evolution occurred within a complex network of fetopelvic constraints, which required modification of frontal neurocranial ossification patterns, involving delayed fusion of the metopic suture. It is very interesting that the recent sequencing of the Neanderthal genome has revealed signs of positive selection in the modern human variant of the RUNX2 gene, which is known to affect metopic suture fusion in addition to being essential for osteoblast development and proper bone formation. It is possible that an evolutionary change in RUNX2, affecting aspects of the morphology of the upper body and cranium, was of importance in the origin of modern humans. Thus, to contribute to a better understanding of the molecular evolution of this gene probably implicated in human evolution, we performed a comparative bioinformatic analysis of the coding sequences of RUNX2 in Homo sapiens and other non-human Primates. RESULTS: We found amino-acid sequence differences between RUNX2 protein isoforms of Homo sapiens and the other Primates examined, that might have important implications for the timing of metopic suture closure. CONCLUSIONS: Further studies are needed to clear the potential distinct developmental roles of different species-specific RUNX2 N-terminal isoforms. Meantime, our bioinformatic analysis, regarding expression of the RUNX2 gene in Homo sapiens and other non-human Primates, has provided a contribution to this important issue of human evolution.

Gc-protein-derived macrophage activating factor counteracts the neuronal damage induced by oxaliplatin.

Oxaliplatin-based regimens are effective in metastasized advanced cancers. However, a major limitation to their widespread use is represented by neurotoxicity that leads to peripheral neuropathy. In this study we evaluated the roles of a proven immunotherapeutic agent [Gc-protein-derived macrophage activating factor (GcMAF)] in preventing or decreasing oxaliplatin-induced neuronal damage and in modulating microglia activation following oxaliplatin-induced damage. The effects of oxaliplatin and of a commercially available formula of GcMAF [oleic acid-GcMAF (OA-GcMAF)] were studied in human neurons (SH-SY5Y cells) and in human microglial cells (C13NJ). Cell density, morphology and viability, as well as production of cAMP and expression of vascular endothelial growth factor (VEGF), markers of neuron regeneration [neuromodulin or growth associated protein-43 (Gap-43)] and markers of microglia activation [ionized calcium binding adaptor molecule 1 (Iba1) and B7-2], were determined. OA-GcMAF reverted the damage inflicted by oxaliplatin on human neurons and preserved their viability. The neuroprotective effect was accompanied by increased intracellular cAMP production, as well as by increased expression of VEGF and neuromodulin. OA-GcMAF did not revert the effects of oxaliplatin on microglial cell viability. However, it increased microglial activation following oxaliplatin-induced damage, resulting in an increased expression of the markers Iba1 and B7-2 without any concomitant increase in cell number. When neurons and microglial cells were co-cultured, the presence of OA-GcMAF significantly counteracted the toxic effects of oxaliplatin. Our results demonstrate that OA-GcMAF, already used in the immunotherapy of advanced cancers, may significantly contribute to neutralizing the neurotoxicity induced by oxaliplatin, at the same time possibly concurring to an integrated anticancer effect. The association between these two powerful anticancer molecules would probably produce the dual effect of reduction of oxaliplatin-induced neurotoxicity, together with possible synergism in the overall anticancer effect.

Oleic Acid, deglycosylated vitamin D-binding protein, nitric oxide: a molecular triad made lethal to cancer.

BACKGROUND: Oleic Acid (OA) has been shown to have anticancer properties mediated by interaction with proteins such as α-lactalbumin and lactoferrins. Therefore, we synthesized complexes of OA and Gc protein-derived macrophage activating factor (GcMAF) that inhibits per se cancer cell proliferation and metastatic potential. We hypothesised that OA-GcMAF complexes could exploit the anticancer properties of both OA and GcMAF in a synergistic manner. We postulated that the stimulating effects of GcMAF on macrophages might lead to release of nitric oxide (NO). PATIENTS AND METHODS: Patients with advanced cancer were treated at the Immuno Biotech Treatment Centre with OA-GcMAF-based integrative immunotherapy in combination with a low-carbohydrate, high-protein diet, fermented milk products containing naturally-produced GcMAF, Vitamin D3, omega-3 fatty acids and low-dose acetylsalicylic acid. RESULTS: Measuring the tumour by ultrasonographic techniques, we observed a decrease of tumour volume of about 25%. CONCLUSION: These observations demonstrate that OA, GcMAF and NO can be properly combined and specifically delivered to advanced cancer patients with significant effects on immune system stimulation and tumour volume reduction avoiding harmful side-effects.

A New Methodology of Viewing Extra-Axial Fluid and Cortical Abnormalities in Children with Autism via Transcranial Ultrasonography.

BACKGROUND: Autism spectrum disorders (ASDs) are developmental conditions of uncertain etiology which have now affected more than 1% of the school-age population of children in many developed nations. Transcranial ultrasonography (TUS) via the temporal bone appeared to be a potential window of investigation to determine the presence of both cortical abnormalities and increased extra-axial fluid (EAF). METHODS: TUS was accomplished using a linear probe (10-5 MHz). Parents volunteered ASD subjects (N = 23; males 18, females 5) for evaluations (mean = 7.46 years ± 3.97 years), and 15 neurotypical siblings were also examined (mean = 7.15 years ± 4.49 years). Childhood Autism Rating Scale (CARS2(®)) scores were obtained and the ASD score mean was 48.08 + 6.79 (Severe). RESULTS: Comparisons of the extra-axial spaces indicated increases in the ASD subjects. For EAF we scored based on the gyral summit distances between the arachnoid membrane and the cortical pia layer (subarachnoid space): (1) <0.05 cm, (2) 0.05-0.07 cm, (3) 0.08-0.10 cm, (4) >0.10 cm. All of the neurotypical siblings scored 1, whereas the ASD mean score was 3.41 ± 0.67. We also defined cortical dysplasia as the following: hypoechoic lesions within the substance of the cortex, or disturbed layering within the gray matter. For cortical dysplasia we scored: (1) none observed, (2) rare hypoechogenic lesions and/or mildly atypical cortical layering patterns, (3) more common, but separated areas of cortical hypoechogenic lesions, (4) very common or confluent areas of cortical hypoechogenicity. Again all of the neurotypical siblings scored 1, while the ASD subjects' mean score was 2.79 ± 0.93. CONCLUSION: TUS may be a useful screening technique for children at potential risk of ASDs which, if confirmed with repeated studies and high resolution MRI, provides rapid, non-invasive qualification of EAF, and cortical lesions.

A novel role for a major component of the vitamin D axis: vitamin D binding protein-derived macrophage activating factor induces human breast cancer cell apoptosis through stimulation of macrophages.

The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH)(2)D3), its two binding proteins that are the vitamin D receptor (VDR) and the vitamin D-binding protein-derived macrophage activating factor (GcMAF). In this study we demonstrate that GcMAF stimulates macrophages, which in turn attack human breast cancer cells, induce their apoptosis and eventually phagocytize them. These results are consistent with the observation that macrophages infiltrated implanted tumors in mice after GcMAF injections. In addition, we hypothesize that the last 23 hydrophobic amino acids of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF located at the external part of the plasma membrane. This allows 1,25(OH)(2)D3 and oleic acid to become sandwiched between the two vitamin D-binding proteins, thus postulating a novel molecular mode of interaction between GcMAF and VDR. Taken together, these results support and reinforce the hypothesis that GcMAF has multiple biological activities that could be responsible for its anti-cancer effects, possibly through molecular interaction with the VDR that in turn is responsible for a multitude of non-genomic as well as genomic effects.