Author
Nicola Maffulli
Other affiliations: University of Aberdeen, University of Sydney, The Chinese University of Hong Kong ...read more
Bio: Nicola Maffulli is an academic researcher from University of Salerno. The author has contributed to research in topics: Achilles tendon & Tendinopathy. The author has an hindex of 115, co-authored 1570 publications receiving 59548 citations. Previous affiliations of Nicola Maffulli include University of Aberdeen & University of Sydney.
Topics: Achilles tendon, Tendinopathy, Medicine, Tendon, Ankle
Papers published on a yearly basis
Papers
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TL;DR: The best evidence to date does demonstrate that eccentric exercise is likely a useful management for tendinopathy, but this evidence is currently insufficient to suggest it is superior or inferior to other forms of therapeutic exercise.
Abstract: Painful tendon disorders are a major problem in competitive and recreational sports [1, 2]. Tendon injuries are difficult to manage, and current conservative and surgical management options have shown limited and often unpredictable success [3, 4]. Even when early diagnosis of Achilles tendinopathy is combined with appropriate and intensive management, rehabilitation can take several months. Conservative management options for tendinopathy of the main body of the Achilles tendon include modified rest, exercise, analgesics, injections, electrotherapy, identification and correction of possible intrinsic and extrinsic causes [4]. This abundance of management modalities has arisen from the lack of consensus as to the cause of tendinopathy [5–8]. The lack of suitable evidence in support of a given management method does not necessarily imply that it is ineffective. Rather, there may be a lack of adequately powered studies to demonstrate its effectiveness [9]. Mechanical conditioning can be used as a treatment for enhancing tendon healing [10]. Mechanotransduction is the process of a cell converting mechanical stimuli into biochemical signals. Cells able to sense the mechanical signals are described as being mechanosensitive. Tendon responds to mechanical forces by adapting its metabolism and structural and mechanical properties [11]. Tendons adapt to alterations in the mechanical load being applied by changing their structure and composition. The tenocytes in the tendon are responsible for its adaptive response, and respond to mechanical forces by altering their gene expression patterns, protein synthesis and cell phenotype [12], which can be used to aid the healing process. However, the duration, frequency, magnitude and type of mechanical stimulation applied to a tendon greatly affect the outcome of the loading regime. Therefore, the amount of loading necessary to improve and/or accelerate the healing process without causing damage to the healing tissue remains unclear [13, 14]. There is some evidence that eccentric strengthening programmes may be effective in the management of tendinopathy of the main body of the Achilles tendon [15, 16]. Graded eccentric exercises regimen was proven to be effective in case–control studies and in prospective randomized control trials [15–19]. Stanish et al. [20] introduced the concept of eccentric training in the rehabilitation of tendon injuries in the mid-1980s, and Scandinavian authors popularized it [19] more than a decade later, with some important differences. Stanish et al. [20], for example, recommend that patients should perform the eccentric exercises with no pain, while Scandinavian authors [19] recommend pushing through pain. Though effective in Scandinavian population [17, 18], the results of eccentric exercises observed from other study groups [16, 21] are less convincing than those reported from Scandinavia, with only around 60% of good outcome after a regime of eccentric training both in athletic [15] and sedentary patients [16]. The best evidence to date does demonstrate that eccentric exercise is likely a useful management for tendinopathy, but this evidence is currently insufficient to suggest it is superior or inferior to other forms of therapeutic exercise [21, 22]. There is little consensus regarding which variables may influence the outcome of eccentric training, including whether training should be painful, homevs clinic-based training, the speed of the exercise, the duration of eccentric training and the method of progression. Large randomized controlled trials that consider these parameters and include blinded assessors and extended follow-up periods are required. Three basic principles in an eccentric loading regime have been proposed:
83 citations
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TL;DR: Unruptured Achilles tendons, even at an advanced age, and ruptured Achilles tendon are clearly part of two distinct populations, with the latter demonstrating histopathological evidence of failed healing response even in areas macroscopically normal.
Abstract: A laboratory study was performed to evaluate the histopathological features of the macroscopically intact portion of the Achilles tendon in patients undergoing surgery for an acute rupture of the Achilles tendon. Tendon samples were harvested from 29 individuals (21 men, 8 women; mean age: 46 ± 12) who underwent repair of an Achilles tendon tear tear, and from 11 male patients who died of cardiovascular events (mean age: 61). Three pieces of tendon were harvested: at the rupture site, 4 cm proximal to the site of rupture, 1 cm proximal to the insertion of the Achilles tendon on the calcaneum. Slides were assessed using a semiquantitative grading scale assessing fiber structure and arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, and hyalinization. Intra-observer reliability of the subscore readings was calculated. The pathological features were significantly more pronounced in the samples taken from the site of rupture than in the samples taken proximally and distal to it (0.008 < P < 0.01). There were no significant differences in the mean pathologic sum-scores in the samples taken proximally and distal to the site of rupture. Unruptured Achilles tendons, even at an advanced age, and ruptured Achilles tendons are clearly part of two distinct populations, with the latter demonstrating histopathological evidence of failed healing response even in areas macroscopically normal.
82 citations
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TL;DR: Tenocytes from tendons from patients with calcific insertional Achilles tendinopathy exhibit chondral metaplasia, and produce abnormally high quantities of collagen type II and III.
Abstract: Objective To ascertain whether tendon samples harvested from patients with calcific insertional Achilles tendinopathy showed features of failed healing response, and whether abnormal quantities of type II collagen had been produced in that area by these tenocytes. Design Comparative laboratory study. Design University teaching hospitals. Patients Tendon samples were harvested from eight otherwise healthy male individuals (average age 47.5±8.4 years, range 38 to 60) who were operated for calcific insertional Achilles tendinopathy and from nine male patients who died of cardiovascular events (mean age 63.1±10.9 years) while in hospital. Interventions Open surgery for calcific insertional Achilles tendinopathy. Main Outcome Measure Semi-quantitative histochemical, immunohistochemical, and immunocytochemical methods to ascertain whether tendinopathic tendons were morphologically different from control tendons, and whether abnormal types of collagen were produced. Results Tenocytes from tendons from patients with calcific insertional Achilles tendinopathy exhibit chondral metaplasia, and produce abnormally high quantities of collagen type II and III. Conclusions The altered production of collagen may be one reason for the histopathological alterations described in the present study. Areas of calcific insertional Achilles tendinopathy have been subjected to abnormal loads. These tendons may be less resistant to tensile forces. Further studies should investigate why some tendons undergo these changes.
81 citations
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TL;DR: The main growpoints concerning OM are the identification of a correct laboratory test array to allow a prompt diagnosis and provide a sensitive and specific detection of the bacterial species involved, along with antibiotic drug resistance.
Abstract: Background and purpose Osteomyelitis (OM) is considered one of the most challenging medical conditions an orthopaedic surgeon has to face. Much debate is present concerning diagnosis and treatment, especially about differences between acute and chronic forms of the condition. The main aim of the present work is to show the key points where research should be implemented. Methods Online database were searched to find evidence about the clinical management of osteomyelitis. Clinical randomized trials, case series, prospective cohort studies reporting on diagnosis and treatment of acute and chronic osteomyelitis were taken into consideration. Cadaveric studies, laboratory studies, case reports, review articles and meta-analyses were excluded. Furthermore, studies concerning implant related OM were excluded. Studies in English, Spanish and French were considered in this process of inclusion. The cohorts of all the included studies were composed of adult patients. Results The main growpoints concerning OM are the identification of a correct laboratory test array to allow a prompt diagnosis and provide a sensitive and specific detection of the bacterial species involved, along with antibiotic drug resistance; optimal imaging techniques, according to the phase of the infection, have to be performed, to avoid unnecessary medical expenses; the identification of a suitable compromise between intravenous and oral drugs administration. A flow chart is proposed for optimal clinical management of this pathology. Conclusion More work should be carried out to clarify the main issues concerning the clinical management of osteomyelitis in adult patients.
81 citations
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TL;DR: Prolonged systemic, low-grade inflammation and impaired insulin sensitivity act as a risk factor for a “failed healing response” after an acute tendon insult, and predispose to the development of chronic overuse tendinopathies.
Abstract: Overuse tendinopathies are a common cause of pain and disability in athletes. According to histological findings, it is a failed healing response to overuse tendon injury. In obesity, macrophages and mast cells migrate to adipose tissue, and the resulting decreased availability of immune circulating cells should be responsible for less effective immune responses to acute tendon injury. In diabetic patients, free glucose molecules attach to collagen, alter collagen solubility, increase resistance to enzymatic degradation, and impair cross linking, contributing to the subsequent development of chronic tendinopathy secondary to a failed healing response to a tendon insult. Prolonged systemic, low-grade inflammation and impaired insulin sensitivity act as a risk factor for a failed healing response after an acute tendon insult, and predispose to the development of chronic overuse tendinopathies. Further studies may reveal novel therapeutic treatment approaches.
81 citations
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TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.
Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …
33,785 citations
01 Jan 2014
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care.
Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.
9,618 citations
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TL;DR: In this paper, a randomized clinical trial was conducted to evaluate the effect of preterax and Diamicron Modified Release Controlled Evaluation (MDE) on the risk of stroke.
Abstract: ABI
: ankle–brachial index
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
AGREE
: Appraisal of Guidelines Research and Evaluation
AHA
: American Heart Association
apoA1
: apolipoprotein A1
apoB
: apolipoprotein B
CABG
: coronary artery bypass graft surgery
CARDS
: Collaborative AtoRvastatin Diabetes Study
CCNAP
: Council on Cardiovascular Nursing and Allied Professions
CHARISMA
: Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance
CHD
: coronary heart disease
CKD
: chronic kidney disease
COMMIT
: Clopidogrel and Metoprolol in Myocardial Infarction Trial
CRP
: C-reactive protein
CURE
: Clopidogrel in Unstable Angina to Prevent Recurrent Events
CVD
: cardiovascular disease
DALYs
: disability-adjusted life years
DBP
: diastolic blood pressure
DCCT
: Diabetes Control and Complications Trial
ED
: erectile dysfunction
eGFR
: estimated glomerular filtration rate
EHN
: European Heart Network
EPIC
: European Prospective Investigation into Cancer and Nutrition
EUROASPIRE
: European Action on Secondary and Primary Prevention through Intervention to Reduce Events
GFR
: glomerular filtration rate
GOSPEL
: Global Secondary Prevention Strategies to Limit Event Recurrence After MI
GRADE
: Grading of Recommendations Assessment, Development and Evaluation
HbA1c
: glycated haemoglobin
HDL
: high-density lipoprotein
HF-ACTION
: Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing
HOT
: Hypertension Optimal Treatment Study
HPS
: Heart Protection Study
HR
: hazard ratio
hsCRP
: high-sensitivity C-reactive protein
HYVET
: Hypertension in the Very Elderly Trial
ICD
: International Classification of Diseases
IMT
: intima-media thickness
INVEST
: International Verapamil SR/Trandolapril
JTF
: Joint Task Force
LDL
: low-density lipoprotein
Lp(a)
: lipoprotein(a)
LpPLA2
: lipoprotein-associated phospholipase 2
LVH
: left ventricular hypertrophy
MATCH
: Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke
MDRD
: Modification of Diet in Renal Disease
MET
: metabolic equivalent
MONICA
: Multinational MONItoring of trends and determinants in CArdiovascular disease
NICE
: National Institute of Health and Clinical Excellence
NRT
: nicotine replacement therapy
NSTEMI
: non-ST elevation myocardial infarction
ONTARGET
: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial
OSA
: obstructive sleep apnoea
PAD
: peripheral artery disease
PCI
: percutaneous coronary intervention
PROactive
: Prospective Pioglitazone Clinical Trial in Macrovascular Events
PWV
: pulse wave velocity
QOF
: Quality and Outcomes Framework
RCT
: randomized clinical trial
RR
: relative risk
SBP
: systolic blood pressure
SCORE
: Systematic Coronary Risk Evaluation Project
SEARCH
: Study of the Effectiveness of Additional Reductions in Cholesterol and
SHEP
: Systolic Hypertension in the Elderly Program
STEMI
: ST-elevation myocardial infarction
SU.FOL.OM3
: SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids
Syst-Eur
: Systolic Hypertension in Europe
TNT
: Treating to New Targets
UKPDS
: United Kingdom Prospective Diabetes Study
VADT
: Veterans Affairs Diabetes Trial
VALUE
: Valsartan Antihypertensive Long-term Use
VITATOPS
: VITAmins TO Prevent Stroke
VLDL
: very low-density lipoprotein
WHO
: World Health Organization
### 1.1 Introduction
Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …
7,482 citations
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TL;DR: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors.
Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many
6,968 citations