Compartments of the crural fascia: clinically relevant ultrasound, anatomical and histological findings.

PURPOSE: Compartment syndrome is a surgical emergency that can occur in any part of the body and can cause cell necrosis when maintained over time. The resulting defects can affect the nerves, muscle cells, bone tissue, and other connective tissues inside the compartment, and fasciotomy has to be performed. The anatomical and histological characteristics of the leg make acute, chronic, and exertional compartment syndrome more likely in this limb. For these reasons, knowledge of the ultrasound, anatomical, and histological features of the crural fascia can help in the treatment of leg compartment syndrome. METHODS: Twenty-one cryopreserved lower limbs from adult cadavers and from one 29-week-old fetus were obtained from the dissection room. They were examined by ultrasound and a subsequent anatomical dissection and microscopy to study the crural fascia and its relationship with the different muscles. Anthropometric measurements were taken of the distances from the head of the fibula and lateral malleolus to the origin of the tibialis anterior muscle in the crural fascia, the exit of the superficial fibular nerve, and the fascia covering the deep posterior muscles of the leg. RESULTS: The crural fascia has very important clinical relationships, which can be identified by ultrasound, as the origin of the tibialis anterior muscle at 16.25 cm from the head of the fibula and the exit of the superficial fibular nerve that crosses this fascia at 21.25 cm from the head of the fibula. Furthermore, the presence of a septum that fixes the deep posterior muscles of the leg and the vessels and nerve can be seen by ultrasound and can explain the possible development of a posterior compartmental syndrome of the leg. Awareness of these features will help to keep these structures safe during the surgical treatment of compartment syndrome. CONCLUSION: The ultrasound study allows identification of anatomical structures in the leg and, thus, avoids damage to them during surgery for compartmental syndromes.

Compartments of the antebrachial fascia of the forearm: clinically relevant ultrasound, anatomical and histological findings.

PURPOSE: Acute compartment syndrome is defined as a limb-threatening condition caused by bleeding or oedema in a closed muscle compartment surrounded by fascia or bone. It is most commonly encountered in the forearm, which has three compartments: posterior, anterior and lateral. These are surrounded and closed in by the antebrachial fascia, formed by dense connective tissue that facilities their study on ultrasound and is key to fasciotomy treatment. The purpose of this study was to broaden existing ultrasound, anatomical and histological knowledge of the fascia of the forearm to facilitate their identification on ultrasound, with possible clinical and therapeutic applications. METHODS: The study was performed in 50 cryopreserved upper limbs from adult cadavers from the dissection room of the Faculty of Medicine and Health Sciences. They were examined on ultrasound and subsequent anatomical dissection and microscopy to study the fascia and its relationship with different muscles of the forearm compartments. RESULTS: Distinct anatomical relationships were observed on ultrasound and dissection between the fascia and the extensor carpi ulnaris, extensor digiti minimi, and anconeus muscle in the posterior compartment, and the flexor carpi radialis and flexor carpi ulnaris in the anterior compartment. They were isolated by the antebrachial fascia and had distinct relationships with the neurovascular structures. CONCLUSION: These results demonstrate that high-definition ultrasound enables us to locate the antebrachial fascia and particular muscles with a distinct relationship with neurovascular structures. This helps better identify these structures, facilitating diagnosis of any pathology in the area, with potential therapeutic and clinical applications.

Endoneural abscess of common popliteal nerve as first clinical manifestation of leprosy: the first reported case in history in a low-incidence country.

A migrant from Palestine came to our attention for weakness of dorsiflexion of the left foot and hypoesthesia of the homolateral common peroneal nerve territory. Skin biopsies from skin lesions in the hypoesthetic area were not diagnostic. Radiological investigation showed focal nerve enlargement with a possible focal lesion. At this time, and given the uncertainty of the diagnosis, we had to choose between medical therapy with steroid and a surgical exploration of the nerve. We decided for the latter option. Intraoperatively, we found a focal round enlargement of the nerve. Epineurotomy was performed at that level, revealing a round caseous granulomatous mass that was excised. Microbiological examination revealed presence of Mycobacterium Leprae allowing diagnosis of leprosy. Medical therapy was then started, leading to resolution of clinical symptoms. Endoneural lepromatous abscesses are uncommon lesions that should be suspected in patients presenting with peripheral nerve dysfunction with anamnesis of travel in leprosy endemic regions or contacts with people from endemic regions with or even without skin lesions. Detection of endoneural abscesses is of critical importance because prompt surgical excision in conjunction with medical therapy leads to improvement of symptoms and permits correct diagnosis. In times of large human migrations from leprosy endemic areas, knowledge of this uncommon presentation of leprosy and its management will help lead to the best management of these patients.

Baseline neutrophil-to-lymphocyte ratio (NLR) is associated with outcome of patients treated with BRAF inhibitors.

PURPOSE: The aim of this study is to verify if baseline hematological markers, in patients with advanced melanoma receiving BRAF inhibitor (BRAFi)-based therapies, are independently associated with progression free survival (PFS) and overall survival (OS). METHODS: We retrospectively analyzed 90 patients with metastatic melanoma harboring BRAF V600 mutation, who received treatment with either BRAFi alone or combined with a MEK inhibitor (MEKi) at the recommended dosages. Study population included 28 women and 62 men. Median age was 53 years. Seventy-three (82%) patients presented with M1c disease, 49 (56%) had elevated LDH and 54 (60%) had three or more metastatic sites. RESULTS: The median PFS was 9.1 and 3.5 months, respectively, for patients with baseline NLR < 5 and NLR ≥ 5, while median OS was 17.2 and 5.5 months, respectively, for patients with NLR < 5 and NLR ≥ 5. Multivariate analysis confirmed that baseline NLR < 5 was significantly associated with half risk of relapse (HR = 0.49; 95% CI = 0.28-0.85; p = 0.01) and half risk of death (HR = 0.46; 95% CI = 0.23-0.76; p = 0.004), independent of age, sex, stage, LDH > 2xULN, previous treatments, concomitant use of steroids and type of therapy. In patients with LDH ≥ ULN, NLR < 5 remained significantly and independently associated with improved PFS (HR = 0.28; 95% CI = 0.13-0.62; p = 0.002,) and OS (HR = 0.23; 95% CI = 0.10-0.55; p = 0.001). CONCLUSIONS: These biomarkers are easily reproducible, affordable and costless and NLR could help to identify patients who have the best benefit from BRAF inhibitors.

Causas anatómicas de compresión del nervio ciático en la pelvis. Síndrome piriforme / Anatomical causes of compression of the sciatic nerve in the pelvis. Piriform syndrome

Objetivo: El síndrome piriforme constituye una de las causas de dolor pélvico debido al atrapamiento del nervio ciático por el músculo piriforme. En la actualidad es un síndrome de difícil diagnóstico. El objetivo de este estudio es conocer la prevalencia de variaciones anatómicas en nuestra población que puedan contribuir a la aparición del síndrome piriforme. También se estudian medidas antropométricas del músculo piriforme y el nervio ciático para su posible aplicación en procedimientos de la región glútea. Material y método: El estudio se realizó en 59 pelvis de 32 cadáveres criopreservados. Las variaciones anatómicas del músculo piriforme y del nervio ciático encontradas se describieron según la clasificación de Beaton y Anson. Se realizaron mediciones antropométricas de ambas estructuras con referencia al trocánter mayor del fémur. Resultados: El nervio ciático y el músculo piriforme presentaban una variación anatómica en un 28,13%. La variación más frecuente fue la de tipo II (21,64%) y la de tipo III (6,49%). La inserción observada con mayor frecuencia fue un tendón independiente del músculo piriforme insertado en la fosa trocantérea, con un 53,85%. Conclusión: La incidencia de variaciones anatómicas en la población estudiada indica que son importantes como diagnóstico diferencial de posibles dolores en la región glútea ya que los síntomas y signos del síndrome piriforme se asemejan a la patología discal vertebral con afectación radicular. Además, el conocimiento anatómico de esta región puede ser útil en la interpretación con técnicas de imagen, especialmente cuando se realizan inyecciones guiadas por ecografía

Objective: The piriformis syndrome is one of the etiologies of pelvic pain due to the sciatic nerve's entrapment by the piriformis muscle. Nowadays this syndrome might be difficult to be diagnosed. The aim of this study is to know the prevalence of anatomic variations in our population that may contribute to the appearance of piriformis syndrome. Furthermore, anthropometric measurements of the piriformis muscle and the sciatic nerve procedures are studied for a possible application in the gluteal region. Material and method: The study was carried out in 59 pelvis of 32 cryopreserved bodies. The anatomical variations of piriformis and sciatic nerve founded were described following the Beaton and Anson's classification. Anthropometric measurements of both structures with reference to the greater trochanter of the femur were performed. Results: The sciatic nerve and the piriformis had an anatomical variation in a 28.13%. The most frequent variation found was tipus II (21.64%) and tipus III (6.49%).Insertion most frequently observed was an independent piriformis tendon inserted into the trochanteric fossa with 53.85%. Conclusion: The anatomic variations' incidence in the population studied indicates that those have to be evaluated as a differential diagnosis of gluteal region pain due to the symptoms and signs resemblance with the vertebral disc pathology involving nerve root injury. In addition, anatomical knowledge of this region can be useful for the interpretation of imaging techniques, especially when ultrasound-guided injections are performed

Don't forget the jumper's knee in the young sportsman: evaluation of patellar tendinopathy with a high frequency ultrasound probe.

Patellar tendinopathy, or Jumper's knee, is a painful knee condition caused by inflammation of the patella tendon. This condition is most frequently observed in subjects who play sports that require repetitive regular jumping. Jumper's knee is frequently misdiagnosed as a minor injury and many athletes, like our patient, keep on training and competing and either tend to ignore the injury or attempt to treat it themselves. However, jumper's knee is a serious condition that requires a correct and timely diagnosis, which often necessitates ultrasound investigation in order to start the most appropriate treatment.

Anatomical causes of compression of the sciatic nerve in the pelvis. Piriform syndrome. / Causas anatómicas de compresión del nervio ciático en la pelvis. Síndrome piriforme.

OBJECTIVE: The piriformis syndrome is one of the etiologies of pelvic pain due to the sciatic nerve's entrapment by the piriformis muscle. Nowadays this syndrome might be difficult to be diagnosed. The aim of this study is to know the prevalence of anatomic variations in our population that may contribute to the appearance of piriformis syndrome. Furthermore, anthropometric measurements of the piriformis muscle and the sciatic nerve procedures are studied for a possible application in the gluteal region. MATERIAL AND METHOD: The study was carried out in 59 pelvis of 32 cryopreserved bodies. The anatomical variations of piriformis and sciatic nerve founded were described following the Beaton and Anson's classification. Anthropometric measurements of both structures with reference to the greater trochanter of the femur were performed. RESULTS: The sciatic nerve and the piriformis had an anatomical variation in a 28.13%. The most frequent variation found was tipus II (21.64%) and tipus III (6.49%).Insertion most frequently observed was an independent piriformis tendon inserted into the trochanteric fossa with 53.85%. CONCLUSION: The anatomic variations' incidence in the population studied indicates that those have to be evaluated as a differential diagnosis of gluteal region pain due to the symptoms and signs resemblance with the vertebral disc pathology involving nerve root injury. In addition, anatomical knowledge of this region can be useful for the interpretation of imaging techniques, especially when ultrasound-guided injections are performed.

Joint disease in haemophilia: Pathophysiology, pain and imaging.

Haemarthroses cause major morbidity in patients with haemophilia. Blood has devastating effects on all joint components, resulting in synovitis, osteochondral degeneration and ultimately end-stage haemophilic arthropathy. Key players in this process are iron and inflammation. Preventing joint bleeds is of utmost importance to maintain joint health as targeted therapies directed against blood-induced inflammation and iron-mediated processes are lacking. Joint bleeds result in acute pain as well as chronic pain due to synovitis or arthropathy. Acute pain originates from nociceptors activated by tissue damage. In chronic inflammation, central and peripheral sensitization of nociceptors might occur resulting in chronic pain. This also triggers a series of brain disorders such as emotional fear, anxiety, mood depression and impairment of cognitive functions. Treatment of haemophilia-related pain not only consists of analgesics, but also of exercise, education and in selected cases antidepressants and anticonvulsants. For objective assessment of joint structural outcome and detecting earlier changes of haemophilic arthropathy, both ultrasound (US) and magnetic resonance (MR) imaging have shown valuable. Both can be considered equally able to reveal signs of disease activity. MR imaging is able to visualize haemosiderin deposition and is more comprehensive in depicting osteochondral changes. Disadvantages of MR imaging are the duration of the examination, evaluation of a single joint at a time, costs and may require sedation, and it may need intraarticular contrast injection to depict initial osteochondral changes with accuracy. As such, US is a more useful screening tool and can be used for repeated follow-up examinations.

Dabrafenib in metastatic melanoma: a monocentric 'real life' experience.

Dabrafenib is a potent BRAF-kinase inhibitor. Its activity was evaluated on 40 consecutive metastatic melanoma patients (pts) harboring the V600BRAF mutations. Dabrafenib was administered orally at the dosage of 150 mg b.i.d. daily. ORR was 82%, with 7% CR, 62% PR, 13% SD and 18% PD. The median PFS and OS were seven and 17 months, respectively (median follow-up: 8.5 months). Increased risk of progression was found in pts with elevated LDH, ECOG PS >1 and more than two metastatic sites. Grade 3-4 adverse events were recorded in 4 pts. In this retrospective analysis, Dabrafenib confirmed its role as the standard clinical option in metastatic melanoma pts.

Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab.

BACKGROUND: Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely or unlikely to benefit from treatment is a major need. PATIENTS AND METHODS: Prospectively collected data from 720 advanced melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access program were analyzed. The derived neutrophil-to-lymphocyte ratio (dNLR) was calculated from baseline peripheral blood cell counts, and receiver operating characteristic curve was used to evaluate the best cutoff for this marker. Patients were stratified according to dichotomized baseline absolute neutrophil counts (ANC), dNLR and their combination. The prognostic values of ANC and dNLR for survival were assessed using multivariate Cox proportional hazard models. A subgroup analysis including LDH in the models was also carried out. RESULTS: The median follow-up was 16.5 months. The optimal cutoff for dNLR was 3. Baseline ANC and dNLR were significantly associated with the outcome of ipilimumab-treated melanoma patients, in terms of disease progression and death (P < 0.0001 for all). Furthermore, for each elevated variable, prognosis worsened. Patients with both ANC ≥ 7500 and dNLR ≥ 3 had a significantly and independently increased risk of death [hazard ratio(HR) = 5.76; 95% confidence interval (CI) 4.29-7.75] and of progression (HR = 4.10; 95% CI 3.08-5.46) compared with patients with both lower ANC and dNLR. Patients with one of the two factors elevated displayed an intermediate risk of progression and death. The 1- and 2-year survival rates were 2% and 0%, respectively, for patients with ANC ≥ 7500 and dNLR ≥ 3, and 43% and 24%, respectively, for patients with both lower ANC and dNLR. CONCLUSIONS: Although these findings need to be confirmed and validated, we suggest that a neutrophil-based index may help risk-group stratification and assist disease-management strategies. Furthermore, the potential predictive value of this index for response to ipilimumab should be investigated in randomized clinical trials.

Personalised medicine: Development and external validation of a prognostic model for metastatic melanoma patients treated with ipilimumab.

PURPOSE: The purpose of this study was to set up a prognostic model for the identification of survival predictors specific for melanoma patients treated with ipilimumab. EXPERIMENTAL DESIGN: The following prospectively collected data were utilised: patient and primary tumour characteristics, relapse-free-interval, site and number of metastases, previous therapies and level of serum biomarkers (lactic dehydrogenase (LDH), C-reactive protein, ß2-microglobulin, vascular endothelial growth factor (VEGF), IL2, IL6, S-100, alkaline phosphatase (ALP), transaminases, leucocyte count, lymphocytes subpopulations). A multivariate prognostic model was developed using the Cox regression model fitted to the data of 113 consecutive metastatic patients treated with ipilimumab (3 mg/kg, q3w) at Veneto Institute of Oncology (IOV). External validation was obtained using the data of 69 and 34 patients treated at European Oncology Institute (IEO) and University of Torino (UT), respectively. RESULTS: Median survival was 8.3, 4.9 and 7.1 months from first ipilimumab administration at IOV, IEO and UT, respectively. Both higher baseline levels of LDH (Hazard Ratio [HR] v=1.36, 95% Confidence Interval [CI] 1.16-1.58, P<.001) and neutrophils (HR=1.76, 95% CI 1.41-2.10, P<.001) were associated with worse prognosis. Model performance was satisfactory both upon internal validation (Dxy=0.42) and external validation (Dxy=0.40). Serum LDH and neutrophil count discriminated patients who lived more (low neutrophils and low LDH) or less (high LDH or neutrophils) than 24 months. CONCLUSION: Serum LDH and neutrophil count were significant independent prognostic factors. This externally validated prognostic nomogram, could help clinicians to identify the patients who would benefit most from ipilimumab and consequently to improve resource allocation. These easily available biomarkers deserve further validation.

Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients.

BACKGROUND: Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit. METHODS: A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg(-1) ipilimumab, and 27 patients treated with 10 mg kg(-1) ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors. RESULTS: In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22-0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13-0.46; P<0.0001) compared with those with a NLR⩾5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients. CONCLUSION: Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.

Sonoelastographic Findings of Carpal Tunnel Injection.

PURPOSE: The objectives of this study were to compare sonoelastographic color findings of the perineural area between carpal tunnel syndrome patients and healthy volunteers, and to analyze elastographic findings in that area before and immediately after intracarpal tunnel injection in carpal tunnel syndrome patients. MATERIALS AND METHODS: We studied both hands of 15 healthy volunteers (7 men, 8 women; mean age: 60.1 years, range: 41 - 88 years) and 72 hands from 70 patients with symptomatic carpal tunnel syndrome (24 men, 46 women; mean age: 54.2 years, range: 24 - 83 years). Sonoelastographic color distribution was assessed in the perineural area between the median nerve and adjacent flexor tendons. The color elastograms were graded using the following system: Grade 1 as red (softest), grade 2 as yellow (soft), grade 3 as green (hard), grade 4 as blue (hardest). The patients were treated with corticosteroid injection and were reassessed with sonoelastography immediately after the injection. RESULTS: The median color grading in the perineural area of carpal tunnel syndrome patients was grade 3 (3.1 ±â€Š0.3, mean ±â€Š95 % Cl), which was stiffer than that of healthy volunteers (grade 1, 1.9 ±â€Š0.4) (p < 0.0001). Immediately after injection, the diffusion of the injected fluid was observed as having a softer appearance (grade 1, 1.4 ±â€Š0.2) (p < 0.0001). CONCLUSION: The perineural area surrounding the median nerve in carpal tunnel syndrome patients was stiffer than that in healthy volunteers. Diffusion of the injected fluid in the carpal tunnel was seen as a softer finding after injection in real time using sonoelastography.

Managing haemophilia for life: 4th Haemophilia Global Summit.

The 4th Haemophilia Global Summit was held in Potsdam, Germany, in September 2013 and brought together an international faculty of haemophilia experts and delegates from multidisciplinary backgrounds. The programme was designed by an independent Scientific Steering Committee of haemophilia experts and explored global perspectives in haemophilia care, discussing practical approaches to the optimal management of haemophilia now and in the future. The topics outlined in this supplement were selected by the Scientific Steering Committee for their relevance and potential to influence haemophilia care globally. In this supplement from the meeting, Jan Astermark reviews current understanding of risk factors for the development of inhibitory antibodies and discusses whether this risk can be modulated and minimized. Factors key to the improvement of joint health in people with haemophilia are explored, with Carlo Martinoli and Víctor Jiménez-Yuste discussing the utility of ultrasound for the early detection of haemophilic arthropathy. Other aspects of care necessary for the prevention and management of joint disease in people with haemophilia are outlined by Thomas Hilberg and Sébastian Lobet, who highlight the therapeutic benefits of physiotherapy and sports therapy. Riitta Lassila and Carlo-Federico Perno describe current knowledge surrounding the risk of transmission of infectious agents via clotting factor concentrates. Finally, different types of extended half-life technology are evaluated by Mike Laffan, with a focus on the practicalities and challenges associated with these products.

Heterogeneity of root and nerve ultrasound pattern in CIDP patients.

OBJECTIVE: The few published ultrasound (US) studies on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) report diffusely increased cross-sectional area (CSA) of nerves. The data are, however, heterogeneous and correlations with clinical history or disease severity are lacking. METHODS: Thirty-four patients with CIDP underwent US nerve evaluation by two neurologists blinded to clinical data. US nerve pattern for each patient was defined by a third neurologist blinded to clinical data. Three US classes were identified based on CSA and echogenicity: large nerves with hypoechoic nerves/fascicles (class 1); large nerves with heterogeneous hypo- and hyperechoic fascicles (class 2); normal size nerve but abnormal hyperechoic array (class 3). RESULTS: In all patients, US nerve changes were observed: in most of the cases, enlarged nerves or nerve segments were observed. The three 'classes' of US nerve changes significantly correlated (R: 0.68, p<0.001) with disease duration, but not with age or Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. CONCLUSIONS: US may be of adjunctive diagnostic value in CIDP assessment. Nerve morphological changes may mirror the underlying pathophysiological mechanisms and seem to correlate with disease duration. SIGNIFICANCE: These results offer the possibility of exploring the use of US to assess CIDP disease activity and treatment.

Ultrasound as a useful tool in the diagnosis and management of traumatic nerve lesions.

OBJECTIVE: The possibility of depicting through ultrasound (US) the nerve and its surroundings should be very useful in traumatic nerve lesion (TNL) management. Our study aimed at evaluating the contribution of US as complementary tool in a neurophysiological laboratory for the diagnosis and management of TNL. METHODS: A total of 112 nerves from 98 consecutive patients with clinical suspicion of TNL were considered. Two independent and blinded clinicians, different from the examiners performing electrodiagnosis and US, classified clinical, neurophysiological and US findings and classified the contribution of US as follows: 'contributive' and 'non-contributive' if US confirmed the clinical and neurophysiological diagnosis or if US findings were unremarkable. RESULTS: US was 'contributive' (strongly modified the diagnostic and therapeutic path) in 58% of cases (n: 65) providing information on therapeutic approach (immediate or delayed surgery), diagnosis and follow-up. US specifically contributed to the (1) assessment of nerve continuity/discontinuity, hence neurotmesis/axonotmesis; (2) identification of aetiology; and (3) demonstration of multiple sites of damage. US was contributive mainly in cases with neurophysiological evidence of complete axonal damage. CONCLUSIONS: US should be used, when available, in all patients in whom TNL is suspected as it provides a more comprehensive diagnosis than neurophysiologic studies alone. Anatomical information is often crucial for choosing the most appropriate therapeutic strategies (and for surgical planning). SIGNIFICANCE: US can improve the outcome of TNL.