Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice.

Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin-the most concentrated flavonoid in HK-as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16-CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16-CDK6 interaction.

Short-term reduction of ankle spasticity after surgical lengthening of the triceps surae in chronic post-stroke patients: a retrospective cohort study.

Introduction: In post-stroke patients with equinovarus foot deformity (EVFD), soft tissue rearrangements may contribute to muscle overactivity when a muscle is stretched or tension is applied. Therefore, we investigated the effects of surgically restoring the triceps surae (TS) length and lengthening ability on TS spasticity. Methods: This retrospective study included chronic post-stroke patients who underwent neuro-orthopedic surgery inclusive of TS lengthening. TS spasticity was measured using the Modified Tardieu Scale (MTS) before and 1 month after surgery, both with the knee extended (KE) and flexed (KF). MTS variations were analyzed using the Wilcoxon test. The time from stroke onset was compared between patients with and without post-surgical spasticity using the t-test. Statistical significance was set at 5%. Results: A total of 120 patients with EVFD, aged 57 (12) years, ranging from 1 to 36 years from stroke, were included in the study. The median MTS_KE score significantly decreased from 3 (range 0-4) to 2 (0-4) (p < 0.001) after surgery. The MTS score decreased by ≥1 point in more than half of the sample. Notably, 19 and 32 patients were completely relieved from spasticity (MTS = 0) in the KE and KF conditions, respectively. Post-surgical spasticity did not depend on the time since stroke onset (p = 0.560). Discussion: TS lengthening led to a short-term reduction of spasticity in 41% and 63% of chronic post-stroke patients in the gastro-soleus complex and soleus, respectively, with complete relief observed in 21% and 30% of the sample. Surgical lengthening can be considered an effective treatment that not only restores joint range of motion but also may reduce spasticity, even in chronic patients.

Effect of intra-articular injection of a hyaluronic acid-alendronate conjugate on post-traumatic osteoarthritis induced by destabilization of the medial meniscus in rats.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and cartilage damage. Intra-articular (i.a) viscosupplementation with hyaluronic acid (HA) is frequently used for the management of OA. Preclinical studies have reported that bisphosphonates (BPs) may have a therapeutic potential to slow down or reverse the progression of OA. Among these, alendronate (ALN) has demonstrated chondroprotective effects in both in vitro and vivo experiments. This study evaluated the effects of a novel alendronate-hyaluronic acid (ALN-HA) conjugate on an OA in vivo model induced by medial meniscus destabilization (DMM). DMM surgery was performed on the knees of Sprague Dawley rats that received, after four weeks, one intra-articular (i.a.) injection of: (1) ALN-HA; (2) HA; (3) sodium chloride (NaCl). Sham-operated rats were used as control. Allodynia was assessed by Von Frey test. Joint degeneration was evaluated eight weeks after treatment by micro-computed tomography (micro-CT), histology, and immunohistochemistry. Collagen cross-linked C-telopeptides (CTX-I and CTX-II) serum levels were determined by ELISA. Paw withdrawal threshold increased in ALN-HA group when compared to rats treated with NaCl or HA. Micro-CT did not show differences between ALN-HA, HA and NaCl groups. ALN-HA injection produced significant improvements in articular cartilage degeneration showing an OARSI score lower than those of HA and NaCl, and reduced matrix metalloproteinase (MMP)-13, MMP-3, interleukin-6, vascular endothelial growth factor and Caspase-3 expression. CTX-I was reduced after ALN-HA treatment when compared to NaCl. Our results indicate that i.a. use of ALN after conjugation with HA limits OA development and progression in the rat DMM model, and may lead to the development of novel therapeutic strategies in OA management.

Corrigendum: Diagnostic and therapeutic management of the thoracic outlet syndrome. Review of the literature and report of an Italian experience.

[This corrects the article DOI: 10.3389/fcvm.2022.802183.].

Exploring the potential role of health resort medicine in the management of breast cancer-related lymphedema: a viable alternative for innovative rehabilitation opportunities?

Lymphedema is a chronic and progressive disorder of the lymphatic system that impairs the return of lymphatic fluid. Breast cancer treatment can cause breast cancer-related lymphedema (BCRL), with axillary lymph node dissection and regional lymph node radiation being established risk factors. BCRL can cause severe morbidity, disability, and reduced quality of life. Early detection and treatment are essential to prevent the disease from progressing and causing complications. According to the International Society of Lymphology, complex decongestive therapy (CDT) is the most effective conservative treatment for lymphedema. Aquatic exercise is a safe and effective form of therapeutic CDT exercise that can improve joint range of motion, reduce pain, and positively impact limb volume. Additionally, health resort medicine and thermal mineral-rich waters may provide synergistic benefits for therapeutic exercise programs. Therefore, we believe that consideration should be given to whether the spa setting could represent a viable alternative for the rehabilitation of BCRL patients.

The Potential Role of Spa Therapy in Managing Frailty in Rheumatic Patients: A Scoping Review.

Frailty is not limited to the elderly, as patients with rheumatic diseases can also experience this condition. The present scoping review aimed to investigate the possibility of using the health resort setting as an alternative location for managing rheumatic patients with frailty. The research resulted in finding several in vitro, in vivo, and clinical studies, resulting in evidence supporting the effectiveness of spa treatments in reducing pain, improving function, and managing comorbidity in rheumatic diseases. Additionally, spa treatments were demonstrated to modulate the MAPK/ERK pathway and the NF-kB pathway's activation and to reduce proinflammatory molecules' secretion in rheumatic diseases, thus suggesting their potential effective role in the regulation of inflammaging in frailty. Moreover, the health resort setting may offer potential resources to reduce risk factors, such as drug consumption, inactivity, and disease severity, and may serve as a setting for developing prevention protocols for frailty. Future research should explore innovative approaches, such as exercise training and early diagnostics, for the overall management of frailty in rheumatic patients in the spa setting.

Short-time effects of spa rehabilitation on pain, mood and quality of life among patients with degenerative or post-surgery musculoskeletal disorders.

Clinical trials have demonstrated traditional spa therapy effects in musculoskeletal disorders (MSDs). This is the first observational study in Italy aimed at evaluating in real-life the short-time effects of spa rehabilitation on pain, mood and quality of life (QoL) among degenerative or post-surgery MSDs patients. Through the involvement of six Italian spa facilities, 160 patients were enrolled; data from 123 patients were finally analysed. Seventy-nine patients (64.3%) accessed the spa for degenerative MSDs, while 44 (35.8%) had a post-surgical condition. All the patients included in the study underwent 12 sessions of water-based exercise (joint exercises, muscle strengthening, gait training, proprioceptive and balance techniques) conducted in thermal or in warm water pools, six sessions per week, for a period of 2 weeks from March 2019 up to October 2019. A group of 45 patients (36.6%) also received traditional thermal therapies, including 12 mud therapy sessions and 12 thermal baths, six times each week, for 2 weeks. Evaluation before and after the treatment included the Numerical Rating Scale (NRS), the Short Form Health Survey (SF-12) and the EuroQol-5D (EQ-5D). The analysis of the scores reported in the questionnaires after the treatment showed a significant improvement in all the scores evaluated. Comparison between patients that performed water-based exercise protocols alone (group A) and patients that in addition to water exercise performed traditional thermal interventions (group B) showed no statistically significant differences in NRSp, NRSa, NRSm, SF-12 PCS, SF-12 MCS and EQ-5D variations; only NRSa value reduction was lower in group B. Sulphate water was found to be associated with a lower reduction of all the scores considered, when compared to the other water types. Patients with degenerative or post-surgery MSDs showed favourable effects on pain, mood and QoL after water exercise training alone or in combination with traditional thermal therapy. Our research provides the first proof that spa rehabilitation can be in real-life conditions an appropriate alternative strategy for post-orthopaedic surgical outcomes recovery. In the future, these results will need to be further investigated.

Water-based exercise for upper and lower limb lymphedema treatment.

BACKGROUND: Lymphedema is a debilitating illness caused by insufficient lymph drainage, which can have serious physical and psychological consequences. Although water-based exercise can be useful, at present, little evidence is available regarding the outcomes of aquatic treatment for patients with lymphedema. Therefore, the aim of the present scoping review was to evaluate, from reported studies, the effects of water-based exercise on pain, limb motor function, quality of life (QoL), and limb volume among patients affected by primary and secondary upper and lower limb lymphedema. METHODS: We performed a scoping review to examine clinical studies and randomized controlled trials reported in English from 2000 to 2021 by screening the MEDLINE (PubMed) and PEDro databases. RESULTS: The search produced a total of 88 studies. Eight randomized controlled trials and one clinical study of patients with primary or secondary lymphedema of upper or lower limbs who had undergone water-based treatment were included in the present study. Most trials had focused on breast cancer-related lymphedema. The shoulder range of flexion, external rotation, and abduction have been shown to improve after performing a water-based exercise protocol. Some evidence has also demonstrated that the lymphedematous limb strength can improve. Moreover, water-based exercise seemed to improve pain perception and QoL for patients with upper or lower limb lymphedema. In contrast, in the control groups, the QoL showed a tendency to worsen over time. Although some studies had not reported beneficial effects on the lymphedematous limb volume, most of the studies examined had reported a reduction in volume, especially in the short term. No adverse events were reported in the included studies. CONCLUSIONS: The findings from the present review have shown the potential for aquatic exercise in lymphedema management. However, at the same time, the findings underline the multiple limitations resulting from the heterogeneity in the study populations and related physical activity protocols. The role of aquatic exercise in the conservative treatment of lymphedema requires further investigation in the future to define specific protocols of application.

Short-term effects of foot surgery on walking-related pain, function, and satisfaction in patients with Charcot-Marie-Tooth disease: a prospective cohort study.

Introduction: Patients with Charcot-Marie-Tooth disease (CMT) often suffer from walking-related pain (WRP), muscle weakness, foot deformities, and reduced ankle dorsiflexion (DF), which affects their ability to walk and daily activities. Functional surgery (FS) can restore foot deviations, affecting the loading ability during gait. We assessed the short-term effects of FS in patients with CMT on WRP, foot and ankle structure, and function, along with patients' perceived improvement. Methods: This is a prospective cohort study on CMT patients who had undergone FS and rehabilitation. We analyzed the changes after 1 month, focusing on WRP, DF, the center of pressure progression (COPP) during walking, and measures of walking ability. The non-parametric Wilcoxon test was used. Results: Ten patients were included. One month after FS, WRP reduced from 5.5 (IQR = 3.5) to 2 (IQR = 3.5), p = 0.063, with an effect size of 0.615. The highest decrease was found in patients with very high pre-surgical pain levels. DF almost reached 10° for both active and passive movements (p < 0.05), and COPP improved from 44 to 60% (p = 0.009) of foot length. Gait speed, lower limb functioning, and balance did not change. More than half of the sample felt improved or much improved after FS. Conclusion: FS can be effective in reducing WRP and restoring foot posture in CMT patients in the short-term, which allows them to wear shoes, and leads to a perceived improvement and satisfaction. Lack of improvement in functional skills may be due to muscle weakness typical of CMT. Studies with longer follow-ups may confirm these hypotheses.

Surgical quadriceps lengthening can reduce quadriceps spasticity in chronic stroke patients. A case-control study.

Background: Muscle overactivity is one of the positive signs of upper motor neuron lesions. In these patients, the loss of muscle length and extensibility resulting from soft tissue rearrangement has been suggested as a contributing cause of muscle overactivity in response to stretching. Objective: To assess the effects of surgical lengthening of the quadriceps femoris (QF) muscle-tendon unit by aponeurectomy on muscle spasticity. Methods: This is a case-control study on chronic stroke patients with hemiparesis that have undergone lower limb functional surgery over a 8-year period. CASEs underwent corrective surgery for both the foot and knee deviations, inclusive of a QF aponeurectomy. Controls (CTRLs) underwent corrective surgery for foot deviations only. QF spasticity was assessed with the Modified Tardieu Scale (MTS) before and 1 month after surgery. The Wilcoxon test was used to assess MTS variations over time and the Mann-Whitney test was used to verify the presence of group differences at the 1 month mark. Results: Ninety-three patients were included: 57 cases (30F, 1-34 years from lesion) and 36 controls (12F, 1-35 years from lesion). Before surgery, both CASEs and CTRLs had similar MTS scores (median MTS = 3) and functional characteristics. One month after surgery, QF spasticity was significantly lower in the CASEs compared to CTRLs (p = 0.033) due to a significant reduction of the median MTS score from 3 to 0 in the CASE group (p < 0.001) and no variations in the CTRL group (p = 0.468). About half of the cases attained clinically significant MTS reductions and complete symptom relief even many years from the stroke. Conclusions: Functional surgery inclusive of QF aponeurectomy can be effective in reducing or suppressing spasticity in chronic stroke patients. This is possibly a result of the reduction in neuromuscular spindle activation due to a decrease in muscle shortening, passive tension, and stiffness.

Diagnostic and Therapeutic Management of the Thoracic Outlet Syndrome. Review of the Literature and Report of an Italian Experience.

The Thoracic Outlet Syndrome is a clinical potentially disabling condition characterized by a group of upper extremity signs and symptoms due to the compression of the neurovascular bundle passing through the thoracic outlet region. Because of the non-specific nature of signs and symptoms, to the lack of a consensus for the objective diagnosis, and to the wide range of etiologies, the actual figure is still a matter of debate among experts. We aimed to summarize the current evidence about the pathophysiology, the diagnosis and the treatment of the thoracic outlet syndrome, and to report a retrospective analysis on 324 patients followed for 5 years at the Padua University Hospital and at the Naples Fatebenefratelli Hospital in Italy, to verify the effectiveness of a specific rehabilitation program for the syndrome and to evaluate if physical therapy could relieve symptoms in these patients.

A New CT Analysis of Abdominal Wall after DIEP Flap Harvesting.

The abdominal microsurgical flap based on the deep inferior epigastric artery perforator (DIEP) flap has become the most popular option worldwide for autologous breast reconstruction. Several authors have investigated the results of reconstructed breasts, but the literature lacks systematic reviews exploring the donor site of the abdominal wall. To fulfil our aims, a new diagnostic muscle imaging analysis was designed and implemented. This study focused on rectus abdominal muscle morphology and function in a single series of 12 consecutive patients analysed before and after breast reconstruction with a microsurgical DIEP flap. Patients were divided into two groups, namely, "ipsilateral reconstruction" and "contralateral reconstruction", depending on the side of the flap harvest and breast reconstruction, then evaluated by computed tomography (CT) scans scheduled for tumor staging, and clinically examined by a physiatrist. Numerous alterations in muscle physiology were observed due to surgical dissection of perforator vessels, and rectus muscle distress without functional impairment was a common result. Postoperatively, patients undergoing "contralateral reconstruction" appeared to exhibit fewer rectus muscle alterations. Overall, only three patients were impacted by a long-term deterioration in their quality of life. On the basis of the newly developed and implemented diagnostic approach, we concluded that DIEP microsurgical breast reconstruction is a safe procedure without major complications at the donor site, even if long-term alterations of the rectus muscle are a common finding.

The outbreak of the SARS-CoV-2 Omicron variant make imperative the adoption of telerehabilitation in the Bulgarian health care system.

The rapid spread of the highly contagious Omicron variant of SARS-CoV-2 globally will challenge the accessibility and the delivery of physical and rehabilitation medicine (PRM) services. Many health care systems throughout the world performed effective reforms such as the transition to telerehabilitation (TR). In Bulgaria, TR is still not regulated by law, and terms such as teleconsultation and tele-education have not yet been introduced. The adoption of TR in the Bulgarian health care system will undoubtedly increase the accessibility to rehabilitation treatment for a larger group of Bulgarian patients with various neurological, cardiorespiratory, musculoskeletal, and oncological conditions and will significantly contribute to the PRM services modernization in Bulgaria.

Neuropathic Pain and Ultrasonography: A Multiperspective Literature Evaluation.

Among the tools useful for the management of neuropathic pain, ultrasound presents several advantages, shown by the literature. We assessed the scientific production about neuropathic pain and ultrasound from different points of view: general topics, journal categories, geographical origin and lexical analysis. We searched papers on PubMed using the Medical Subject Headings "neuropathic pain" AND "ultrasound". We collected data about the journals where the papers were published, the country of the affiliation of the first author. For the lexical analysis, we evaluated the presence of selected words in the papers, and we built a graph representing the connections among words and papers. The papers were focused on the use of ultrasound as a diagnostic tool and guide for the therapy, assessing its application in different diseases such as Morton's neuroma and piriformis syndrome. The most represented journal category was anesthesia while the most common country the United States of America. The lexical analysis confirmed the importance of ultrasound for diagnosis of specific disease and treatment of pain. The described approaches provide a multiperspective evaluation of the literature and may support the interpretation of the information contained by the papers.

Skeletal muscle weakness in older adults home-restricted due to COVID-19 pandemic: a role for full-body in-bed gym and functional electrical stimulation.

Persons suffering with systemic neuromuscular disorders or chronic organ failures, spend less time for daily physical activity, aggravating their mobility impairments. From 2020, patients at risk are also older adults, who, though negative for the SARS-Cov-2 infection, suffer with a fatigue syndrome due to home restriction/quarantine. Besides eventual psycological managements, it could be useful to offer to these patients a rehabilitation workouts easy to learn and to independently repeat at home (Full-Body In-Bed Gym). Inspired by the proven capability to recover skeletal muscle contractility and strength by home-based volitional exercises and functional electrical stimulation (FES), we suggest for this fatigue syndrome a 10-20 min long daily routine of easy and safe physical exercises that may recover from muscle weakness the main 400 skeletal muscles used for every-day activities. Leg muscles could be trained also by an adjunctive neuro-muscular electrical stimulation (NMES) in frail old persons. Many of the exercises could be performed in bed (Full-Body in-Bed Gym), thus hospitalized patients can learn this light training before leaving the hospital. Full-Body in-Bed Gym is, indeed, an extension of well-established cardiovascular-ventilation rehabilitation training performed by patients after heavy surgery. Blood pressure readings, monitored before and after daily routine of Full-Body in-Bed Gym, demonstrate a transient decrease in peripheral resistance due to increased blood flow to major body muscles. Continued regularly, Full-Body in-Bed Gym may help maintaining independence of frail people, including those suffering with the fatigue syndrome related to the restrictions/quarantine imposed to the general population during the COVID-19 pandemic.

The Important Impact of COVID-19 Pandemic on the Reorganization of a Rehabilitation Unit in a National Healthcare System Hospital in Italy: Lessons From Our Experience.

ABSTRACT: Since March 2020, when COVID-19 pandemic broke out, the world's healthcare systems' main concern has been fighting the pandemic. However, patients with other diseases, also requiring rehabilitation evaluations and treatments, continued to need care. Our rehabilitation unit managed to maintain contact with patients through alternative communication methods even during the lockdown period and in a situation of staff shortage. If face-to-face evaluations and treatments were necessary, preventive measures were followed to avoid hospital-associated contagion. Rehabilitation beds were cleared to leave them to the acute wards, and consultations for the acute care patients were carried out using personal protective equipment. In the future, the lessons from our experience could contribute toward drawing a plan of measures applicable in similar situations and some of these actions could become part of the rehabilitative practice.