Clodronate Reduces ATP-Containing Microvesicle Releasing Induced by Nociceptive Stimuli in Human Keratinocytes.

Clodronate (Clod), a first-generation bisphosphonate, acts as a natural analgesic inhibiting vesicular storage of the nociception mediator ATP by vesicular nucleotide transporter (VNUT). Epidermal keratinocytes participate in cutaneous nociception, accumulating ATP within vesicles, which are released following different stimulations. Under stress conditions, keratinocytes produce microvesicles (MVs) by shedding from plasma membrane evagination. MV secretion has been identified as a novel and universal mode of intercellular communication between cells. The aim of this project was to evaluate if two nociceptive stimuli, Capsaicin and Potassium Hydroxide (KOH), could stimulate MV shedding from human keratinocytes, if these MVs could contain ATP, and if Clod could inhibit this phenomenon. In our cellular model, the HaCaT keratinocyte monolayer, both Capsaicin and KOH stimulated MV release after 3 h incubation, and the released MVs contained ATP. Moreover, Clod (5 µM) was able to reduce Caps-induced MV release and abolish the one KOH induced, while the Dansylcadaverine, an endocytosis inhibitor of Clod uptake, partially failed to block the bisphosphonate activity. Based on these new data and given the role of the activation of ATP release by keratinocytes as a vehicle for nociception and pain, the "old" bisphosphonate Clodronate could provide the pharmacological basis to develop new local analgesic drugs.

Rehabilitation for Functioning and Quality of Life in Patients with Malignant Pleural Mesothelioma: A Scoping Review.

Malignant pleural mesothelioma (MPM) represents a significant clinical challenge due to limited therapeutic options and poor prognosis. Beyond mere survivorship, setting up an effective framework to improve functioning and quality of life is an urgent need in the comprehensive management of MPM patients. Therefore, this study aims to review the current understanding of MPM sequelae and the effectiveness of rehabilitative interventions in the holistic approach to MPM. A narrative review was conducted to summarize MPM sequelae and their impact on functioning, disability, and quality of life, focusing on rehabilitation interventions in MPM management and highlighting gaps in knowledge and areas for further investigation. Our findings showed that MPM patients experience debilitating symptoms, including fatigue, dyspnea, pain, and reduced exercise tolerance, decreasing quality of life. Supportive and rehabilitative interventions, including pulmonary rehabilitation, physical exercise improvement, psychological support, pain management, and nutritional supplementation, seem promising approaches in relieving symptoms and improving quality of life but require further research. These programs emphasize the pivotal synergy among patient-tailored plans, multidisciplinary team involvement, and disease-specific focus. Despite advancements in therapeutic management, MPM remains a challenging disease with limited effective interventions that should be adapted to disease progressions. Rehabilitative strategies are essential to mitigate symptoms and improve the quality of life in MPM patients. Further research is needed to establish evidence-based guidelines for rehabilitative interventions tailored to the unique needs of MPM patients.

Comprehensive Pulmonary Rehabilitation for Patients with Malignant Pleural Mesothelioma: A Feasibility Pilot Study.

Malignant pleural mesothelioma (MPM) represents a significant health burden, with limited treatment options and poor prognosis. Despite advances in pharmacological and surgical interventions, the role of rehabilitation in MPM management remains underexplored. This study aims to assess the feasibility of a tailored pulmonary rehabilitation intervention addressing physical and respiratory function in MPM patients. A prospective pilot study was conducted on surgically treated MPM patients referred to a cardiopulmonary rehabilitation service. The intervention comprised multidisciplinary educational sessions, physical rehabilitation, and respiratory physiotherapy. Feasibility was evaluated based on dropout rates, adherence to the rehabilitation program, safety, and patient-reported outcomes. Twelve patients were initially enrolled, with seven completing the study. High adherence to physical (T1: 93.43%, T2: 82.56%) and respiratory (T1: 96.2%, T2: 92.5%) rehabilitation was observed, with minimal adverse events reported. Patient satisfaction remained high throughout the study (GPE scores at T1: 1.83 ± 1.17; T2: 2.0 ± 1.15), with improvements noted in physical function, pain management, and health-related quality of life. However, some issues, such as time constraints and lack of continuous supervision, were reported by participants. This pilot study demonstrates the feasibility and potential benefits of a tailored pulmonary rehabilitation intervention in MPM patients. Despite its promising outcomes, further research with larger samples is warranted to validate its efficacy and integrate rehabilitation as a component into the multidisciplinary management of MPM.

Efficacy of rehabilitation treatments in improving functioning in patients with fibromyalgia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Fibromyalgia is a debilitating condition marked by persistent pain and reduced functionality. Various therapeutic methods have been suggested to alleviate symptoms in individuals with fibromyalgia, yet the impact of diverse rehabilitation strategies remains unclear. OBJECTIVE: This systematic review and meta-analysis aimed at assessing the efficacy of rehabilitation interventions in improving functioning in fibromyalgia patients. METHODS: We conducted a comprehensive literature search of multiple international databases (PubMed, Scopus, and Web of Science) from their inception until November 22nd, 2023. We identified 23 randomized controlled trials (RCTs) assessing multiple rehabilitation strategies. The primary outcome was the Fibromyalgia Impact Questionnaire (FIQ). Study quality was assessed using the Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2). The study protocol was registered in PROSPERO (CRD42020197666). RESULTS: Our meta-analysis rehabilitation interventions significantly reduce FIQ scores (MD =-11.74, 95% CI: -16.88 to -6.59, p< 0.0001). Notably, the subgroup analysis showed that different rehabilitation modalities seem to induce different therapeutic responses. CONCLUSIONS: Rehabilitation strategies hold promise in addressing the functional impairments and improving the overall well-being of individuals with fibromyalgia. The study underscores the need for further research to determine the optimal rehabilitation approach and its potential impact on the multilevel disability characterizing patients with fibromyalgia.

Botulinum Toxin for Pain Relief in Cancer Patients: A Systematic Review of Randomized Controlled Trials.

Cancer pain is one of the most disabling symptoms complained by cancer patients, with a crucial impact on physical and psychological well-being. Botulinum neurotoxins (BoNTs) type A and B have emerged as potential interventions for chronic pain; however, their role in these patients is still debated. Thus, this systematic review of randomized controlled trials aimed at assessing the effects of BoNT treatment for cancer pain to guide physicians in an evidence-based approach integrating BoNT in cancer care. Out of 5824 records, 10 RCTs satisfied our eligibility criteria and were included in the present work for a total of 413 subjects with several cancer types (breast, head and neck, esophageal, and thoracic/gastric cancers). While some studies demonstrated significant pain reduction and improved quality of life post-BoNT-A injections, outcomes across different cancer types were inconclusive. Additionally, several effects were observed in functioning, dysphagia, salivary outcomes, esophageal strictures, gastric emptying, and expansions. This review emphasizes the need for further standardized research to conclusively establish the efficacy of BoNT in comprehensive cancer pain management.

Obesity and Cancer Rehabilitation for Functional Recovery and Quality of Life in Breast Cancer Survivors: A Comprehensive Review.

Obesity is a global health challenge with increasing prevalence, and its intricate relationship with cancer has become a critical concern in cancer care. As a result, understanding the multifactorial connections between obesity and breast cancer is imperative for risk stratification, tailored screening, and rehabilitation treatment planning to address long-term survivorship issues. The review follows the SANRA quality criteria and includes an extensive literature search conducted in PubMed/Medline, Web of Science, and Scopus. The biological basis linking obesity and cancer involves complex interactions in adipose tissue and the tumor microenvironment. Various mechanisms, such as hormonal alterations, chronic inflammation, immune system modulation, and mitochondrial dysfunction, contribute to cancer development. The review underlines the importance of comprehensive oncologic rehabilitation, including physical, psychological, and nutritional aspects. Cancer rehabilitation plays a crucial role in managing obesity-related symptoms, offering interventions for physical impairments, pain management, and lymphatic disorders, and improving both physical and psychological well-being. Personalized and technology-driven approaches hold promise for optimizing rehabilitation effectiveness and improving long-term outcomes for obese cancer patients. The comprehensive insights provided in this review contribute to the evolving landscape of cancer care, emphasizing the importance of tailored rehabilitation in optimizing the well-being of obese cancer patients.

Effects of blood flow restriction on spine postural control using a robotic platform: A pilot randomized cross-over study.

BACKGROUND: Blood flow restriction (BFR) training improves muscle strength and functional outcomes, but the proprioceptive implications of this technique in the rehabilitation field are still unknown. OBJECTIVE: The present study aimed at assessing the effects of BFR in terms of stabilometric and balance performance. METHODS: In this pilot randomized cross-over study, healthy young adults were included and randomly assigned to Groups A and B. Both groups underwent a postural assessment with and without wearing a BFR device. Study participants of Group A underwent postural baseline assessment wearing BFR and then removed BFR for further evaluations, whereas subjects in Group B performed the baseline assessment without BFR and then with BFR. Stabilometric and balance performance were assessed by the robotic platform Hunova, the Balance Error Scoring System (BESS), the self-reported perceived balance (7-point Likert scale), and discomfort self-rated assessment. Moreover, the safety profile was recorded. RESULTS: Fourteen subjects were included and randomly assigned to Group A (n: 7) and Group B (n: 7). Significant differences were shown in balance tests in static conditions performed on the Hunova robot platform in terms of average distance RMS (root-mean-square) with open eyes (OE), anteroposterior (AP) trunk oscillation range with OE, mediolateral (ML) average speed of oscillation with OE, and total excursion AP range with closed eyes (CE) (BFR: 3.44 ± 1.06; without BFR: 2.75 ± 0.72; p= 0.041). Moreover, elastic balance test showed differences in Romberg index (BFR: 0.16 ±0.16; without BFR: 0.09 ± 0.07; p= 0.047). No adverse events were reported. CONCLUSION: Taken together, our data showed that BFR affects balance performance of healthy subjects. Further studies are needed to better characterize the possible role of BFR treatment in the context of a specific rehabilitation protocol.

Role of Prehabilitation and Rehabilitation on Functional Recovery and Quality of Life in Thyroid Cancer Patients: A Comprehensive Review.

BACKGROUND: This narrative review aims to provide a comprehensive overview of the current prehabilitation and rehabilitation strategies for thyroid cancer survivors to optimize functional outcomes and enhance their quality of life. METHODS: The review follows the SANRA quality criteria and includes an extensive literature search conducted in PubMed/Medline, Web of Science, and Scopus. RESULTS: The review emphasizes the role of a comprehensive rehabilitation approach in targeting the different domains that generate disability in thyroid cancer patients. In this context, physical activity, range of motion exercises, myofascial release, joint mobilization, and postural exercises are crucial for improving functional outcomes and reducing treatment-related discomfort and disability. Moreover, tailored rehabilitative management addressing dysphonia and dysphagia might have a positive impact on the quality of life of these patients. Despite these considerations, several barriers still affect the implementation of a multimodal rehabilitative approach in common clinical practice. Thus, sustainable and effective strategies like digital innovation and patient-centered approaches are strongly needed in order to implement the rehabilitative treatment framework of these subjects. CONCLUSIONS: This narrative review provides valuable insights into the current prehabilitation and rehabilitation strategies to treat thyroid cancer survivors, addressing physical, psychological, and vocational needs to optimize functional outcomes and enhance their quality of life.

Impact of COVID-19 Era on the Anterior Cruciate Ligament Injury Rehabilitation: A Scoping Review.

The surgical intervention rate and the subsequent rehabilitation plan for anterior cruciate ligament (ACL) injury was crucially affected by the COVID-19 pandemic due to the necessity in the face of the emergency. This review aimed to evaluate potential persistent and residual symptoms after COVID-19 disease, including fatigue and neuromuscular disorders. A scoping review design and methodology were used due to the exploratory nature of the research question, according to literature searches on PubMed/Medline, Scopus, Web of Science (WoS), and Physiotherapy Evidence Database (PEDro) electronic databases using the following keywords: "Anterior Cruciate Ligament", "ACL", "SARS-CoV-2", and "COVID-19". Undertraining and muscular knee imbalance might cause inefficient movement strategies, lack of knee stability, and increasing load with negative implications in ACL injuries. In the post-surgery period, during COVID-19, telerehabilitation approaches appeared to be successfully applied to maintain strength and range of motion in this condition. However, no definitive data are available regarding the most effective interventions. This scoping review showed the influence of the COVID-19 pandemic and associated restrictions on postoperative and rehabilitative care of ACL injuries.

The impact of rehabilitation in bone loss management of patients with spinal cord injury: A systematic review.

BACKGROUND: Spinal cord injury (SCI) is a disabling condition characterized by multilevel skeletal muscle impairment and rapid cortical and trabecular bone loss. Rehabilitation is a cornerstone of the long-term management of patients with SCI; however, the optimal rehabilitation strategy for improving bone health has not been fully characterized. OBJECTIVE: To characterize the current evidence supporting different rehabilitation interventions improving bone health in patients with SCI. METHODS: On November 17th, 2022, five databases (PubMed, Scopus, Web of Science, Cochrane, and PEDro) were systematically searched for randomized controlled trials (RCTs) assessing SCI patients undergoing rehabilitation interventions. The primary outcomes were bone macroscopical effects. Secondary outcomes were changes in bone metabolisms and functional outcomes. RESULTS: Out of 499 records, 11 RCTs met the eligibility criteria and were included. Electrical stimulation combined with physical exercise was assessed by 5 studies, standing intervention was assessed by 3 studies, vibration was assessed by 1 study, ultrasound therapy was assessed by 1 study, and electroacupuncture combined with a pulsed magnetic field was assessed by 1 study. The rehabilitation intervention was administered combined with pharmacological treatment (3 studies) or alone (8 studies). Positive effects in terms of BMD were reported by 3 studies. The quality assessment revealed some concerns in 9 out of 11 studies, in accordance with the Cochrane Risk of Bias assessment - version 2. CONCLUSION: Our data suggest that multicomponent interventions including rehabilitation might be considered a suitable option to improve bone health management in SCI patients. Further studies are mandatory to characterize the optimal combination of non-pharmacological interventions reducing bone loss and improving the risk of fractures in patients with SCI.

Technical aspects and validation of custom digital algorithms for hand volumetry.

BACKGROUND: Establishing baseline measurements on normative data is essential to evaluate standards of care and the impact of clinical or surgical treatments. Hand volume determination is relevant in pathological conditions where the anatomical structures might undergo modifications like post-treatment chronic edema. For example, one of the consequences of breast cancer treatment is the possibility of developing uni-lateral lymphedema on the upper limbs. OBJECTIVE: Arm and forearm volumetrics are well-studied techniques, whereas hand volumetry computation poses several challenges both from the clinical and digital perspectives. The current work has explored routine clinical and customized digital methodologies for hand volume appraisal on healthy subjects. METHODS: Clinical hand volumes computed by water displacement or circumferential measurements were compared to digital volumetry calculated from 3D laser scans. Digital volume quantification algorithms exploited the gift wrapping concept or cubic tessellation of acquired 3D shapes. This latter digital technique is parametric, and a calibration methodology to define the resolution of the tessellation has been validated. RESULTS: Results on a group of normal subjects demonstrated that the volumes computed from digital hand representations extracted by tessellation return values similar to the clinical water displacement volume assessment at low tolerances. CONCLUSIONS: The current investigation suggested that the tessellation algorithm could be considered a digital equivalent of water displacement for hand volumetrics. Future studies are needed to confirm these results in people with lymphedema.

Efficacy of kinesio taping on upper limb volume reduction in patients with breast cancer-related lymphedema: a systematic review of randomized controlled trials.

INTRODUCTION: One of the most common disabling complications in breast cancer (BC) patients is breast cancer-related lymphedema (BCRL), a pathological condition affecting both physical and psychological function, with detrimental consequences on health-related quality of life (HR-QoL). Rehabilitation has a key role in the comprehensive management of this condition with several studies reporting positive results after performing complex decongestive therapies (CDT) in these women. Kinesio taping (KT) is a rather recent therapeutic approach to treat BCRL, however, evidence in literature regarding its effectiveness is far from being fully characterized. Therefore, this systematic review aimed at assessing the role of KT among the CDT to treat BCRL. EVIDENCE ACQUISITION: PubMed, Scopus, and Web of Science were systematically searched from inception until May 5th, 2022 to determine randomized control trials (RCTs) reporting patients with BCRL; KT as intervention; limb volume as outcome (PROSPERO number: CRD42022349720). EVIDENCE SYNTHESIS: Out of the documents identified, 123 were eligible for data screening, and only 7 RCTs satisfied the eligibility criteria and were included. We found that KT might have a positive effect on limb volume reduction in patients with BCRL, albeit there is little evidence for low quality of the included studies. CONCLUSIONS: Taken together, this systematic review showed that KT did not significantly reduce the upper limb volume in BCRL women, albeit it seemed to increase the flow rate during the passive exercise. Further high-quality-studies are mandatory to improve the knowledge in order to include the KT might into a multidisciplinary rehabilitative approach for the management of BC survivors affected by lymphedema.

Impact of Physical Rehabilitation on Bone Biomarkers in Non-Metastatic Breast Cancer Women: A Systematic Review and Meta-Analysis.

Rehabilitation might improve bone health in breast cancer (BC) patients, but the effects on bone biomarkers are still debated. Thus, this meta-analysis of randomized controlled trials (RCTs) aims at characterizing the impact of rehabilitation on bone health biomarkers in BC survivors. On 2 May 2022, PubMed, Scopus, Web of Science, Cochrane, and PEDro were systematically searched for RCTs assessing bone biomarker modifications induced by physical exercise in BC survivors. The quality assessment was performed with the Jadad scale and the Cochrane risk-of-bias tool for randomized trials (RoBv.2). Trial registration number: CRD42022329766. Ten studies were included for a total of 873 patients. The meta-analysis showed overall significant mean difference percentage decrease in collagen type 1 cross-linked N-telopeptide (NTX) serum level [ES: -11.65 (-21.13, -2.17), p = 0.02)] and an increase in bone-specific alkaline phosphatase (BSAP) levels [ES: +6.09 (1.56, 10.62). According to the Jadad scale, eight RCTs were considered high-quality studies. Four studies showed a low overall risk of bias, according to RoBv.2. The significant effects of rehabilitation on bone biomarkers suggested a possible implication for a precision medicine approach targeting bone remodeling. Future research might clarify the role of bone biomarkers monitoring in rehabilitation management of cancer treatment induced bone-loss.

Algorithm-Based Risk Identification in Patients with Breast Cancer-Related Lymphedema: A Cross-Sectional Study.

Background: Breast cancer-related lymphedema (BCRL) could be one consequence of breast cancer (BC). Although several risk factors have been identified, a predictive algorithm still needs to be made available to determine the patient's risk from an ensemble of clinical variables. Therefore, this study aimed to characterize the risk of BCRL by investigating the characteristics of autogenerated clusters of patients. Methods: The dataset under analysis was a multi-centric data collection of twenty-three clinical features from patients undergoing axillary dissection for BC and presenting BCRL or not. The patients' variables were initially analyzed separately in two low-dimensional embeddings. Afterward, the two models were merged in a bi-dimensional prognostic map, with patients categorized into three clusters using a Gaussian mixture model. Results: The prognostic map represented the medical records of 294 women (mean age: 59.823±12.879 years) grouped into three clusters with a different proportion of subjects affected by BCRL (probability that a patient with BCRL belonged to Cluster A: 5.71%; Cluster B: 71.42%; Cluster C: 22.86%). The investigation evaluated intra- and inter-cluster factors and identified a subset of clinical variables meaningful in determining cluster membership and significantly associated with BCRL biological hazard. Conclusions: The results of this study provide potential insight for precise risk assessment of patients affected by BCRL, with implications in prevention strategies, for instance, focusing the resources on identifying patients at higher risk.

Tolerability, Safety and Efficacy of a Specific Rehabilitation Treatment Protocol for Axillary Web Syndrome: An Observational Retrospective Study.

Axillary web syndrome (AWS) is a highly prevalent surgical complication affecting BC survivors. It presents as a subcutaneous cording that limits the upper limb range of motion (ROM) and causes pain. Its etiology is still debated, and its treatment is not well defined. Therefore, we aimed to investigate the safety, tolerability and efficacy of our specific AWS rehabilitative treatment protocol. We conducted an observational retrospective study on a cohort of 92 AWS patients referred to the oncological outpatient service of a university hospital. We collected data from medical records before (T0) and after (T1) the treatment. The studied protocol was composed of 60-min sessions, carried out 3 times/week by specialized physiotherapists, until the clinical resolution of AWS. We found that a mean of 8.74 ± 2.12 rehabilitative sessions were needed, and only one patient stopped early. At T1, shoulder ROM was complete in both abduction and flexion in 98% of patients; AWS was no longer detectable in 64% of them, and pain significantly decreased compared to T0. In conclusion, our protocol proved to be safe, well-tolerated and seemed to be effective in treating AWS.

Effects of Ultrasound-Guided Injection Combined with a Targeted Therapeutic Exercise in Breast Cancer Women with Subacromial Pain Syndrome: A Randomized Clinical Study.

In this randomized controlled study, we aimed to assess the effects of US-guided injections of the subacromial bursa followed by a personalized rehabilitation program for breast cancer (BC) survivors. We assessed patients with subacromial pain syndrome without tendon lesions and with a history of post-surgical non-metastatic BC. Thirty-seven patients were enrolled and randomly assigned 1:1 to receive US-guided corticosteroid injections combined with a personalized rehabilitation program (Group A; n: 19) or US-guided corticosteroid injections alone (Group B; n: 18). The primary outcome was pain relief, assessed using a numerical pain rating scale (NPRS). The secondary outcomes were muscle strength, shoulder function, and quality of life. No major or minor late effects were reported after the multidisciplinary intervention. Statistically significant within-group differences were found in terms of NPRS (p ≤ 0.05) in both groups. No significant between-group differences were reported after one week. However, the between-group analysis showed significant differences (p ≤ 0.05) after three months of follow-up in terms of pain intensity, muscle strength, shoulder function, and quality of life. Our findings suggested positive effects of a multidisciplinary approach including US-guided corticosteroid injections combined with a personalized rehabilitation program in improving pain intensity and quality of life of BC survivors with subacromial pain syndrome.

Osteosarcopenia in Patients with Chronic Obstructive Pulmonary Diseases: Which Pathophysiologic Implications for Rehabilitation?

Chronic obstructive pulmonary disease (COPD) is a burdensome condition affecting a growing number of people worldwide, frequently related to major comorbidities and functional impairment. In these patients, several factors might have a role in promoting both bone and muscle loss, including systemic inflammation, corticosteroid therapies, sedentary behaviours, deconditioning, malnutrition, smoking habits, and alcohol consumption. On the other hand, bone and muscle tissues share several linkages from functional, embryological, and biochemical points of view. Osteosarcopenia has been recently defined by the coexistence of osteoporosis and sarcopenia, but the precise mechanisms underpinning osteosarcopenia in patients with COPD are still unknown. In this scenario, a deeper understanding of the molecular basis of osteosarcopenia might guide clinicians in a personalized approach integrating skeletal muscle health with the pulmonary rehabilitation framework in COPD. Taken together, our results summarized the currently available evidence about the multilevel interactions between osteosarcopenia and COPD to pave the way for a comprehensive approach targeting the most common risk factors of these pathological conditions. Further studies are needed to clarify the role of modern clinical strategies and telemedicine solutions to optimize healthcare delivery in patients with COPD, including osteopenia, osteoporosis, and sarcopenia screening in these subjects.

Integrating molecular biomarkers in breast cancer rehabilitation. What is the current evidence? A systematic review of randomized controlled trials.

Background: Quality of life issues is a crucial burden in breast cancer (BC) survivors with relevant implications in terms of survivorship and health-care costs. The increasing long-term survival of these patients provides new challenges, with translational research now focusing on innovative and tailored approaches to improve their complex management. In this scenario, several emerging biomarkers have the potential to improve the clinical rehabilitative management of patients with BC. However, to date, guidelines supporting biomarker implementation in this area are still lacking. Therefore, the aim of this systematic review was to summarize the currently available biomarkers that might be potentially integrated into rehabilitation practice to promote a precision medicine approach to BC survivorship issues. Methods: On 9th March 2022, PubMed, Scopus, Web of Science, Cochrane, and PEDro were systematically searched for randomized controlled trials (RCTs) assessing rehabilitation interventions in BC patients. Molecular biomarker modifications induced by physical exercise have been assessed through the review of the study protocols and published results. The Jadad scale was used to assess the quality of the studies included. Results: Out of 2,224 records, 22 studies were included in the present systematic review. Exercise therapy showed significant results in 15 RCTs, in terms of metabolic biomarkers, including glycemic and insulin profile, and lipid profile (p ≤ 0.05). Similarly, 12 studies underlined significant effects in inflammation and immune response biomarkers, including TNF-α, IL-6, IL-10, C-reactive protein, leptin, and adiponectin (p ≤ 0.05). On the other hand, cardiac biomarkers were assessed in three studies without reporting significant differences after exercise therapy (p = NS). The quality assessment identified 19 RCTs as high-quality studies and three RCTs of low quality. Conclusion: Our findings reveal significant biochemical perturbations in key molecules induced by physical exercise in patients with BC, suggesting room for the implementation of actionable biomarkers. Future research might clarify the role of biomarkers on treatment effectiveness monitoring, to optimize rehabilitative strategies tailored to patient's needs.

Oral Health in Breast Cancer Women with Vitamin D Deficiency: A Machine Learning Study.

Breast cancer (BC) survivors treated with aromatase inhibitors (AIs) commonly show several pathological issues, including poor oral health, bone health impairment, and vitamin D deficiency. However, to date, oral health issues in BC survivors treated with AIs have been poorly investigated and their relationship with vitamin D deficiency are far from being understood. This study aimed to evaluate the correlation between oral health and vitamin D status in BC survivors undergoing treatment with AIs through a machine learning approach. In this cross-sectional study, we included post-menopausal BC women with vitamin D deficiency undergoing AIs therapy. The outcome measures were the following: oral health indexes as the Decayed, Missing, and Filled Permanent Teeth Index (DMFT); serum levels of 25(OH)D3; Bone Mineral Density (BMD); and the diagnosis of osteoporosis. We included 41 post-menopausal BC women, mean aged 66.10 ± 8.47 years, with mean serum levels of vitamin D of 14.63 ± 6.62 ng/mL. Furthermore, 56.10% of patients had a diagnosis of osteoporosis and 36.59% were osteopenic. DMFT was significantly related to smoking (p-value = 0.005) and dental floss use (p-value = 0.001). There was a significant correlation between DMFT and vitamin D levels (Pearson's r: -0.73; p-value = 0.001). The regression machine learning model showed that vitamin D status and the use of dental floss were the most relevant variables in terms of correlation with DMFT. In conclusion, vitamin D deficiency, inadequate use of dental floss, and smoking had a negative impact on oral health in BC women. Thus, vitamin D deficiency screening and supplementation and a prompt oral rehabilitation plan should be suggested and implemented in the complex treatment framework of BC survivors undergoing treatment with AIs.

Surgical Treatment and Rehabilitation Strategies for Upper and Lower Extremity Lymphedema: A Comprehensive Review.

Lymphedema is a chronic disabling condition affecting a growing number of patients worldwide. Although lymphedema is not life-threatening, several reports underlined detrimental consequences in terms of distress, pain, functional impairment, and infections with a relevant decrease in quality of life. Currently, there is no cure, and the therapeutic management of this condition aims at slowing down the disease progression and preventing secondary complications. Early diagnosis is paramount to enhance the effects of rehabilitation or surgical treatments. On the other hand, a multidisciplinary treatment should be truly integrated, the combination of microsurgical and reductive procedures should be considered a valid strategy to manage extremity lymphedema, and rehabilitation should be considered the cornerstone of the multidisciplinary treatment not only for patients not suitable for surgical interventions but also before and after surgical procedures. Therefore, a specialized management of Plastic Reconstructive Surgeons and Physical and Rehabilitative Medicine physicians should be mandatory to address patients' needs and optimize the treatment of this disabling and detrimental condition. Therefore, the aim of this review was to characterize the comprehensive management of lymphedema, providing a broad overview of the potential therapy available in the current literature to optimize the comprehensive management of lymphedema and minimize complications.