Exploring the impact of vitamin D on tendon health: a comprehensive review.

Tendons are vital components of the musculoskeletal system, facilitating movement and supporting mechanical loads. Emerging evidence suggests that vitamin D, beyond its well-established role in bone health, exerts significant effects on tendon physiology. The aim of this manuscript is to review the impact of vitamin D on tendons, focusing on its mechanisms of action, clinical implications, and therapeutic applications. A comprehensive search of scientific electronic databases was conducted to identify articles on the effects of vitamin D on tendon health. Fourteen studies were included in this review. Five studies were performed in vitro, and nine studies were conducted in vivo. Despite some conflicting results, the included studies showed that vitamin D regulates collagen synthesis, inflammation, and mineralization within tendons through its interaction with vitamin D receptors. Epidemiological studies link vitamin D deficiency with tendon disorders, including tendinopathy and impaired healing. Supplementation with vitamin D shows promise in improving tendon strength and function, particularly in at-risk populations such as athletes and the elderly. Future research should address optimal supplementation strategies and explore the interplay between vitamin D and other factors influencing tendon health. Integrating vitamin D optimization into clinical practice could enhance tendon integrity and reduce the burden of tendon-related pathologies.

Neutrophil, lymphocyte count, and neutrophil to lymphocyte ratio predict multimorbidity and mortality-results from the Baltimore Longitudinal Study on Aging follow-up study.

Immunosenescence is the age-related changes in the immune system, namely, progressively higher levels of circulating inflammatory markers, characteristics changes of circulating immune subset cells and altered immune function. The neutrophil to lymphocyte ratio (NL ratio) has been identified as a prognostic indicator for neoplastic disease progression, in predicting chronic degenerative diseases, and as a potential indirect marker of healthy aging. This study aims to examine the longitudinal association of neutrophil, lymphocyte absolute count, and their ratio with longitudinal risk for multimorbidity and mortality. The Baltimore Longitudinal Study of Aging (BLSA) is an open observational cohort study of community-dwelling volunteers that are followed every 1-4 years depending on their age. The sample considered in the study consists of 1769 participants (5090 follow-ups) with completed data for physical examination, health history assessment, and donated a blood sample. The NL ratio increased with age and was associated with a higher risk of mortality, while a lower NL ratio was inversely correlated with multimorbidity. Neutrophils increased with aging and an increase in their absolute number predicted mortality risk. However, the absolute number of lymphocytes was associated with age only in a cross-sectional analysis. In conclusion, this study supports the importance of the NL ratio and absolute neutrophil count as markers of aging health status, and as significant predictors of all-cause mortality and multimorbidity in aging individuals. It remains to be demonstrated whether interventions contrasting these trends in circulating cells may result in improved health outcomes.

Muscle quality, physical performance, and comorbidity are predicted by circulating procollagen type III N-terminal peptide (P3NP): the InCHIANTI follow-up study.

Sarcopenia is characterized by skeletal muscle quantitative and qualitative alterations. A marker of collagen turnover, procollagen type III N-terminal peptide (P3NP), seems to be related to those conditions. This study aims to assess the predictive role of P3NP in muscle density and physical performance changes. In the InCHIANTI study, a representative sample from the registry lists of two towns in Tuscany, Italy, was recruited. Baseline data was collected in 1998, and follow-up visits were conducted every 3 years. Out of the 1453 participants enrolled at baseline, this study includes 1052 participants. According to P3NP median levels, population was clustered in two groups; 544 (51.7%) of the 1052 subjects included were classified in the low median levels (LM-P3NP); at the baseline, they were younger, had higher muscle density, and performed better at the Short Physical Performance Battery (SPPB), compared to the high-median group (HM-P3NP).LM-P3NP cases showed a lower risk to develop liver chronic diseases, CHF, myocardial infarction, and osteoarthritis. HM-P3NP levels were associated with a longitudinal reduction of muscle density, and this effect was potentiated by the interaction between P3NP and leptin. Moreover, variation in physical performance was inversely associated with high level of P3NP, and directly associated with high fat mass, and with the interaction between P3NP and muscle density. Our data indicate that P3NP is associated with the aging process, affecting body composition, physical performance, and clinical manifestations of chronic degenerative age-related diseases.

Beyond Inflammaging: The Impact of Immune System Aging on Age-Related Muscle Decline, Results From the InCHIANTI Study.

Aging is characterized by chronic low-level inflammation and is associated with geriatric syndromes such as sarcopenia and frailty. Our aim was to evaluate the longitudinal variation of muscle area, muscle quality, and muscle strength, relative to the variation of leukocyte-derived markers, and to assess the presence of a pathway of associations among derived leukocyte ratios, and the components of muscle health. The InCHIANTI is a longitudinal cohort study of aging that began in 1998 with follow-up visits every 3 years. Out of the 1 453 participants enrolled at baseline, this study includes 1 179 participants with complete data. Muscle strength was assessed by hand grip strength test, whereas muscle density and fat area were considered as indirect markers of muscle quality, derived from peripheral quantitative computed tomography of the calf. Muscle area was associated with neutrophil-to-lymphocyte ratio (NL-ratio), age, gender, comorbidities, and body mass index (BMI). Muscle density variation over time was inversely associated with age, comorbidities, and BMI, while being positively associated with monocyte-to-lymphocyte ratio (ML-ratio) and male gender. Fat area was inversely associated with age, interleukine-6 (IL-6), male gender, and NL-ratio, while being positively associated with ML-ratio, comorbidities, and BMI. Handgrip strength decreased with age, IL-6 levels, comorbidities, and NL-ratio, but increased with ML-ratio, being male, and having a higher BMI. In a path-analysis model, ML-ratio positively correlates with muscle mass, density, and strength, while NL-ratio only correlates inversely with muscle mass and density. NL-ratio and ML-ratio are associated with aging and may be implicated in age-related mechanisms that affect body composition and muscle strength. These ratios may represent a link between aging of the immune system and decline of muscle health with aging. However, further studies are needed to identify their usefulness for early detection of sarcopenia, myosteatosis, and frailty in the older adult.

Robotic-Assisted Rehabilitation for Post-Stroke Shoulder Pain: A Systematic Review.

Post-stroke shoulder pain (PSSP) is a debilitating consequence of hemiplegia, often hindering rehabilitation efforts and further limiting motor recovery. With the advent of robotic-assisted therapies in neurorehabilitation, there is potential for innovative interventions for PSSP. This study systematically reviewed the current literature to determine the effectiveness of robotic-assisted rehabilitation in addressing PSSP in stroke patients. A comprehensive search of databases was conducted, targeting articles published up to August 2023. Studies were included if they investigated the impact of robotic-assisted rehabilitation on PSSP. The outcome of interest was pain reduction. The risk of bias was assessed using the Cochrane database. Of the 187 initially identified articles, 3 studies met the inclusion criteria, encompassing 174 patients. The reviewed studies indicated a potential benefit of robotic-assisted rehabilitation in reducing PSSP, with some studies also noting improvements in the range of motion and overall motor function. However, the results varied across studies, with some showing more significant benefits than others, because these use different protocols and robotic equipment.

Temporal trends, sex differences, and age-related disease influence in Neutrophil, Lymphocyte count and Neutrophil to Lymphocyte-ratio: results from InCHIANTI follow-up study.

BACKGROUND: Neutrophils and lymphocytes represent the larger percentage of all white blood cells, they vary with age, with a progressive increase of the ratio in the first years of life, and then tend to remain at similar levels in steady state condition during adult age. Neutrophils to lymphocytes-ratio (NL-ratio) was proposed as an effective and low-cost marker to monitor and predict the evolution of several clinical conditions. The main objective of the study is to analyze its temporal trend variation, over twenty years' follow-up, according to age, sex, and main clinical diagnosis, in a large representative Italian population. METHODS: The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998, and last follow-up visits were made in 2015-18. 1343 out of the 1453 participants enrolled were included, and consented to donate a blood sample. All subjects were assessed and followed for life-style, clinical condition, physical performance, and underwent an instrumental diagnostic session. RESULTS: The NL-ratio showed a statistically significant interaction between birth-cohort and time of the study (p-value = 0.005). A gender dimorphism was recognized in the neutrophils absolute count and in the NL-ratio. Moreover, in female participants only, those who reported CHF had lower neutrophil-count and NL-ratio; whereas an increase in creatinine clearance was directly associated with NL-ratio. In male subjects, an increase of BMI was inversely associated with both NL-ratio and neutrophils-count during the follow-up; a similar association but in the opposite direction was observed in female participants. CONCLUSION: NL-ratio is a more reliable predictor of healthy aging than absolute lymphocytes and/or neutrophils counts. It is associated with the changes induced by disease, lifestyle, and environmental challenges in the immune system. NL-ratio confirms the gender dimorphism in the occurrence of inflammation-driven diseases, thus providing additional evidence for the necessity of tailored sex-specific measures to prevent and treat such diseases.

Achilles Tendinopathy Pathogenesis and Management: A Narrative Review.

The Achilles tendon is the thickest and strongest tendon of the human body, and it is frequently injured during sports activity. The incidence of Achilles tendon pathologies has increased over recent decades, especially in the last few years, because of increased sports participation among the general population and due to the diffusion of competitive sports at a high level. Tendinopathies are common in athletes and in middle-aged overweight patients. The term "tendinopathy" refers to a condition characterised clinically by pain and swelling, with functional limitations of tendon and nearby structures, and consequently to chronic failure of healing response process. Tendinopathies can produce marked morbidity, and at present, scientifically validated management modalities are limited. Despite the constantly increasing interest and number of studies about Achilles tendinopathy (AT), there is still not a consensual point of view on which is the best treatment, and its management is still controversial. AT can be treated conservatively primarily, with acceptable results and clinical outcomes. When this approach fails, surgery should be considered. Several surgical procedures have been described for both conditions with a relatively high rate of success with few complications and the decision for treatment in patients with AT should be tailored on patient's needs and level of activity. The aim of this article is to give insights about the pathogenesis and most used and recent treatment options for AT.

Stem cell therapy in sports medicine: current applications, challenges and future perspectives.

Stem cells have demonstrated significant potential for tissue repair and regeneration, making them a promising therapeutic avenue in sports medicine. This review aims to provide a comprehensive overview of the current state of research on the application of stem cells in sports medicine. We will discuss the types of stem cells used, their mechanisms of action, and the clinical outcomes of stem cell therapy in different sports-related injuries. Furthermore, we will delve into the challenges and ethical considerations associated with stem cell therapy, as well as future directions and potential applications of stem cells in sports medicine.

Temporal trends, sex differences, and age-related disease influence in Neutrophil, Lymphocyte count and Neutrophil to Lymphocyte-ratio. Results from InCHIANTI follow-up study.

Background Neutrophils and lymphocytes represent the larger percentage of all white bloodcells, they vary with age, with a progressive increase of the ratio in the first years of life, and then tend to remain at similar levels in steady state condition during adult age. Neutrophils to lymphocytes-ratio (NL-ratio) was proposed as an effective and low-cost marker to monitor and predict the evolution of severalclinical conditions. The main objective of the study is to analyze its temporal trend variation, over twenty years' follow-up, according to age, sex, and main clinical diagnosis, in a large representative Italian population. Methods The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998, and last follow-up visits were made in 2015-18. 1343 out of the 1453 participants enrolled were included, and consented to donate a blood sample. All subjects were assessed and followed for life-style, clinical condition, physical performance, and underwent an instrumental diagnostic session. Results The NL-ratio showed a statistically significant interaction between birth-cohort and time of the study (p-value=0.005). A gender dimorphism was recognized in the neutrophils absolute count and in the NL-ratio. Moreover, in female participants only, those who reported CHF had lower neutrophil-count and NL-ratio; whereas an increase in creatinine clearance was directly associated with NL-ratio. In male subjects, an increase of BMI was inversely associated with both NL-ratio and neutrophils-count during the follow-up; a similar association but in the opposite direction was observed in female participants. Conclusion NL-ratio is a more reliable predictor of healthy aging than absolute lymphocytes and/or neutrophils counts. It is associated with the changes induced by disease, lifestyle, and environmental challenges in the immune system. NL-ratio confirms the gender dimorphism in the occurrence of inflammation-driven diseases, thus providing additional evidence for the necessity of tailored sex-specific measures to prevent and treat such diseases.

High-Intensity Training for Knee Osteoarthritis: A Narrative Review.

Knee osteoarthritis (OA) is the most common joint disease worldwide. Exercise therapy has been identified as a first-line treatment option in patients suffering from knee OA. High-intensity training (HIT) is an innovative exercise modality with potential in improving various disease-related outcomes. The purpose of this review is to explore the impact of HIT on knee OA symptoms and physical functioning. A comprehensive search of scientific electronic databases was conducted to identify articles on the effects of HIT on knee OA. Thirteen studies were included in this review. Ten compared the effects of HIT with those of low-intensity training, moderate-intensity continuous training, or a control group. Three evaluated the effects of HIT alone. Eight reported a decrease in knee OA symptoms (especially pain), and eight reported an increase in physical functioning. HIT was shown to improve knee OA symptoms and physical functioning, but also aerobic capacity, muscle strength, and quality of life with minimal or no adverse events. However, compared with other exercise modalities, no clear superiority of HIT was found. HIT is a promising exercise strategy in patients with knee OA; nonetheless, the actual quality of evidence remains very low, and more high-quality studies are needed to confirm these promising outcomes.

Ultrasound Imaging and Guidance for Cervical Myofascial Pain: A Narrative Review.

Cervical myofascial pain is a very common clinical condition in the daily practice of musculoskeletal physicians. Physical examination is currently the cornerstone for evaluating the cervical muscles and identifying the eventual presence of myofascial trigger points. Herein, the role of ultrasound assessment in precisely localizing them is progressively mounting in the pertinent literature. Moreover, using ultrasound, not only the muscle tissue but also the fascial and neural elements can be accurately located/evaluated. Indeed, several potential pain generators, in addition to paraspinal muscles, can be involved in the clinical scenario of cervical myofascial pain syndrome. In this article, the authors extensively reviewed the sonographic approach for cervical myofascial pain in order to better diagnose or guide different procedures that can be performed in the clinical practice of musculoskeletal physicians.

Radial or Focal Extracorporeal Shock Wave Therapy in Lateral Elbow Tendinopathy: A Real-Life Retrospective Study.

Lateral elbow tendinopathy (LET) is characterized by pain, poor muscle strength of the wrist ex-tensors, and disability. Among the conservative rehabilitative approaches, focal as well as radial extracorporeal shock wave therapy (ESWT), are considered effective in LET management. The objective of this study was to compare the safety and effectiveness of focal (fESWT) and radial (rESWT) in terms of LET symptoms and the strength of wrist extensors, taking into account potential gender differences. This is a retrospective longitudinal cohort study of patients with LET treated with ESWT that had received a clinical and functional evaluation, including visuo-analogic scale (VAS), muscle strength using an electronic dynamometer during Cozen's test, and the patient-rated tennis elbow evaluation (PRTEE) questionnaire. Follow-ups were carried out weekly in four visits after enrollment, and at 8 and 12 weeks. During the follow-ups, the VAS score decreased in both treatments, even if patients receiving fESWT reported early pain relief compared to those treated with rESWT (time for treatment p-value < 0.001). Additionally, peak muscle strength increased independently of the device used, and again more rapidly in the fESWT group (time for treatment p-value < 0.001). In the stratified analysis for sex and for the type of ESWT, rESWT appears to be less effective in female participants in terms of mean muscle strength and PRTEE scores, without differences according to the type of device used. The rESWT group reported a higher rate of minor adverse events (i.e., discomfort, p = 0.03) compared to fESWT. Our data suggest that both fESWT and rESWT might be effective in improving LET symptoms, even if the higher rate of painful procedures were reported in patients treated with rESWT.

Intra-Articular Collagen Injections for Osteoarthritis: A Narrative Review.

Osteoarthritis (OA) is the most frequent degenerative progressive joint disease worldwide, with the hand, hip, and knee being the most-affected joints. Actually, no treatment can alter the course of OA, and therapy is directed at reducing pain and improving function. The exogenous administration of collagen has been investigated as a possible symptomatic adjuvant or stand-alone treatment for OA. The aim of this review is to assess if intra-articular collagen administration can be considered as a valid and safe therapeutic option for OA. A search in the main scientific electronic databases to identify the available scientific articles about the effects of intra-articular collagen as an OA treatment was performed. The results of the seven included studies showed that the intra-articular administration of collagen may stimulate chondrocytes to produce hyaline cartilage and hinder the normal inflammatory response leading to fibrous tissue formation, reducing symptoms, and improving functionality. The use of type-I collagen as an intra-articular treatment for knee OA was found not only to be effective, but also safe with negligible side effects. The reported findings are strongly promising, highlighting the need for further high-quality research to confirm the consistency of these findings.

Spinal Orthosis in Adolescent Idiopathic Scoliosis: An Overview of the Braces Provided by the National Health Service in Italy.

Adolescent idiopathic scoliosis (AIS) is a lateral, rotated curvature of the spine. It is a 3-dimensional deformity that arises in otherwise healthy children at or around puberty. AIS is the most common form of scoliosis in the pediatric population. The etiology is multifactorial, including genetic and environmental factors. The incidence is roughly equal between males and females, while there is a higher risk of progression in females. Guidelines for AIS treatment identify three levels of treatment: observation, physiotherapy scoliosis-specific exercises, and braces. In this paper, we carried out a review of the scientific literature about the indication and success rates of the braces provided for free by the National Health Service in Italy (SSN). Despite a general consensus on the efficacy of rigid bracing treatment and its use in AIS, an important heterogeneity about the treatment is present in the scientific literature, demonstrating a high degree of variability. The overall success rate of the braces provided by the SSN is high, suggesting an important therapeutic role in the treatment of AIS. Robust guidelines are needed to ensure uniform and effective treatments.

High-intensity interval training for chronic pain conditions: a narrative review.

Chronic pain is defined as pain that persists past the normal healing time. Physical activity and exercise programs are increasingly being promoted and used for a variety of chronic pain conditions. Evidence suggests that physical exercise is an intervention with few adverse events that may improve pain severity and physical function, thus improving the quality of life. High-intensity interval training (HIIT) has been shown to improve physical outcome measures and to decrease disorder-related disability in people with chronic disorders. Since an overview of the benefits of HIIT on chronic pain conditions has not been published yet, this review aims to report the effects of HIIT alone or in combination with other forms of training on different kind of chronic pain conditions. A search in the main scientific electronic databases was performed. The results of the studies included in this review showed that HIIT is beneficial for several chronic pain conditions, improving pain and physical function. Since HIIT could represent a valid help to conventional drug therapies, it could improve the quality of life of these subjects. The actual quality of evidence remains very low, and further high evidence studies are needed to confirm the promising outcomes reported in this review.

Indirect Structural Muscle Injuries of Lower Limb: Rehabilitation and Therapeutic Exercise.

Muscle injuries are the most common trauma in team and individual sports. The muscles most frequently affected are those of the lower limb, and in particular hamstrings, adductors, rectus femoris and calf muscles. Although several scientific studies have tried to propose different rehabilitation protocols, still too often the real rehabilitation process is not based on scientific knowledge, especially in non-elite athletes. Moreover, the growing use of physical and instrumental therapies has made it increasingly difficult to understand what can be truly effective. Therefore, the aim of the present paper is to review proposed therapeutic algorithms for muscle injuries, proposing a concise and practical summary. Following a three-phase rehabilitation protocol, this review aims to describe the conservative treatment of indirect structural muscle injuries, which are the more routinely found and more challenging type. For each phase, until return to training and return to sport are completed, the functional goal, the most appropriate practitioner, and the best possible treatment according to current evidence are expressed. Finally, the last section is focused on the specific exercise rehabilitation for the four main muscle groups with a structured explanatory timetable.

The effects of COVID-19 pandemic countermeasures on patients receiving botulinum toxin therapy and on their caregivers: a study from an Italian cohort.

COVID-19 outbreak had a huge worldwide impact, and several countermeasures to contain its spread have been adopted, such as the interruption of nonurgent outpatient clinics. We wanted to describe the effects of the national lockdown on the well-being of a cohort of Italian patients with cerebral palsy (CP) receiving botulinum toxin (BT) therapy and of their caregivers. Twenty-five patients receiving BT therapy were surveyed using the structuralized questionnaire by Dressler and Adib Saberi, while the caregivers were assessed using the Caregiver Burden Scale. The lockdown delayed BT therapy by 9 ± 2.8 months. Around 44% of the selected patients noticed increased muscle cramps, 24% increased muscle pain, and 32% both of them. Due to the lockdown, the patient's quality of life was reduced by 68.4 ± 21.1%. After the lockdown, 100% of patients perceived BT therapy as more important than before. Around 76% of the patients perceived the lockdown as inadequate and felt that their rights were not respected. The overall score of the Caregiver Burden Scale, as regarded before the lockdown, was 29.12 ± 11.63, while the overall score as regarded after the lockdown was 37.44 ± 14.85. The overall score increased, from before the lockdown to after the lockdown, for 92% of caregivers. The BT outpatient clinic's interruption was seen to significantly worsen the psychophysical condition of subjects with CP and the care burden of their caregivers, exposing them to greater stress than before. Therefore, any kind of BT treatment suspension or delay should be avoided.

Achilles Tendon Rupture: Mechanisms of Injury, Principles of Rehabilitation and Return to Play.

The Achilles tendon is the thickest, strongest and largest tendon in the human body, but despite its size and tensile strength, it frequently gets injured. Achilles tendon ruptures (ATRs) mainly occur during sports activities, and their incidence has increased over the last few decades. Achilles tendon tears necessitate a prolonged recovery time, sometimes leaving long-term functional limitations. Treatment options include conservative treatment and surgical repair. There is no consensus on which is the best treatment for ATRs, and their management is still controversial. Limited scientific evidence is available for optimized rehabilitation regimen and on the course of recovery after ATRs. Furthermore, there are no universally accepted outcomes regarding the return to play (RTP) process. Therefore, the aim of this narrative review is to give an insight into the mechanism of injuries of an ATR, related principles of rehabilitation, and RTP.

Radiographic, Bone Densitometry and Clinic Outcomes Assessments in Femoral Shaft Fractures Fixed by Plating or Locking Retrograde Nail.

INTRODUCTION: Distal femoral shaft fractures are characterized by increasing incidence and complexity and are still considered a challenging problem (high morbidity and mortality). No consensus on best surgical option has been achieved. AIM: This study aims is to investigate radiographic, mineral bone densitometry and clinical outcomes of locking retrograde intramedullary (LRN) nailing and anatomical locking plate to surgically treat distal femoral shaft fractures in young adults based on the hypothesis that there is no statistical difference among the two surgical options in terms of results (radiographic, bone densitometry and outcomes assessment). METHODS: Retrospective study: 30 patients divided into 2 groups (Group 1 LRN, Group 2 Nailing). Average age was 42.67±18.32 for Group 1 and 42.84 ±18.32 for Group 2 (range of age 18-65 for both groups). Gender Ratio (male: female) was 2.75 (11:4) for both Group 1 and 2. AO Classification, NUSS and RUSH score, VAS, Dexa scans, plain radiographs were used. Evaluation endpoint: 12 months after surgery (mean follow up 16.24). RESULTS: No statistical difference in terms of surgery time, transfusions, wound healing. Similar results with regard to average time of bone healing, RUSH scores, VAS, regression between RUSH and VAS, average correlation clinical-radiographic results and patients outcomes. Only one patient of each group had reduction of mineral bone densitometry values. CONCLUSION: No statistical difference about the use of LNR or Nailing for treatment of distal femur shaft fractures in terms of radiographic, bone densitometry and outcomes has been found accordingly to our results. Good subjective and objective results are provided by both techniques. The choice among the two techniques must be based on surgeons' experience, indications and subjective patients' aspects. The absence of relevant similar data in the published literature does not allow definitive validation (or rejection) of our hypothesis. A more powered study with bigger cohort is needed for definitive validation.

Biological and chemical changes in fluoroquinolone-associated tendinopathies: a systematic review.

INTRODUCTION: The present systematic review investigates the biological and chemical mechanisms that affect the health and structure of tendons following the use of fluoroquinolones (FQs). SOURCES OF DATA: A total of 12 articles were included, organized, and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. AREAS OF AGREEMENT: Five mechanisms were identified: arrest of proliferation through a decreased activity of cyclin B, CDK-1, CHK-1, and increased PK-1; decrease tenocytes migration through decreased phosphorylation of FAK; decrease type I collagen metabolism through increased MMP-2; chelate effect on ions that influence epigenetics and several enzymes; fluoroquinolones-induced ROS (radical oxygen species) production in mitochondria. AREAS OF CONTROVERSY: There is no definite structure-damage relationship. The dose-effect relationship is unclear. GROWING POINTS: Knowing and defining the damage exerted by FQs plays a role in clinical practice, replacing FQs with other antibacterial drugs or using antioxidants to attenuate their pathological effects. AREAS TIMELY FOR DEVELOPING RESEARCH: Clinical and basic sciences studies for each FQs are necessary.