Post-operative rehabilitation after surgical repair of the rotator cuff

Today advances in techniques and materials for rotator cuff surgery allow the repair of a large variety of types or extensions of cuff lesions in patients from a wide range of age groups who have different kinds of jobs and participate in different kinds of sports, and who have widely different expectations in terms of recovery of functions and pain relief. A large number of factors must be taken into account before implementing a rehabilitation protocol after rotator cuff surgery. These mainly include the technique (materials and procedure) used by the surgeon. Moreover, tissue quality, retraction, fatty infiltration and time from rupture are important biological factors while the patient’s work or sport or daily activities after surgery and expectations of recovery must also be assessed. A rehabilitation protocol should also take into account the timing of biological healing of bone to tendon or tendon to tendon interface, depending on the type of rupture and repair. This timing should direct the therapist’s choice of correct passive or assisted exercise and mobilisation manoeuvres and the teaching of correct active mobilisation movements the patient has to do. Following accepted knowledge about the time of biological tissue healing, surgical technique and focused rehabilitation exercise, a conceptual protocol in four phases could be applied, tailoring the protocol for each patient. It starts with sling rest with passive small self-assisted arm motion in phase one, to prevent post-op stiffness. In phase two passive mobilisation by the patient dry or in water, integrated with scapular mobilisation and stabiliser reinforcement, are done. Phase three consists of progressive active arm mobilisation dry or in water integrated with proprioceptive exercise and “core” stabilisation. In phase four full strength recovery integrated with the recovery of work or sports movements will complete the protocol. Because of the multi-factorial aspects of the problem, the best results can be obtained through a full transfer of information from the surgeon to the therapist to optimise timing and sizing of the individual rehabilitation protocol for each patient.     

A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer

Only a fraction of patients with metastatic colorectal cancer receive clinical benefit from therapy with anti-epidermal growth factor receptor (EGFR) antibodies, which calls for the identification of novel biomarkers for better personalized medicine. We produced large xenograft cohorts from 85 patient-derived, genetically characterized metastatic colorectal cancer samples ("xenopatients") to discover novel determinants of therapeutic response and new oncoprotein targets. Serially passaged tumors retained the morphologic and genomic features of their original counterparts. A validation trial confirmed the robustness of this approach: xenopatients responded to the anti-EGFR antibody cetuximab with rates and extents analogous to those observed in the clinic and could be prospectively stratified as responders or nonresponders on the basis of several predictive biomarkers. Genotype-response correlations indicated HER2 amplification specifically in a subset of cetuximab-resistant, KRAS/NRAS/BRAF/PIK3CA wild-type cases. Importantly, HER2 amplification was also enriched in clinically nonresponsive KRAS wild-type patients. A proof-of-concept, multiarm study in HER2-amplified xenopatients revealed that the combined inhibition of HER2 and EGFR induced overt, long-lasting tumor regression. Our results suggest promising therapeutic opportunities in cetuximab-resistant patients with metastatic colorectal cancer, whose medical treatment in the chemorefractory setting remains an unmet clinical need. SIGNIFICANCE: Direct transfer xenografts of tumor surgical specimens conserve the interindividual diversity and the genetic heterogeneity typical of the tumors of origin, combining the flexibility of preclinical analysis with the informative value of population-based studies. Our suite of patient-derived xenografts from metastatic colorectal carcinomas reliably mimicked disease response in humans, prospectively recapitulated biomarker-based case stratification, and identified HER2 as a predictor of resistance to anti-epidermal growth factor receptor antibodies and of response to combination therapies against HER2 and epidermal growth factor receptor in this tumor setting.     

Dendritic cell-based vaccine in advanced melanoma: update of clinical outcome

Dendritic cells (DCs) are unique specialized antigen-presenting cells capable of priming naive T cells and inducing antigen-specific cytotoxic T lymphocytes. This study presents an update of clinical results from a DC-based phase I-II clinical vaccine trial in stage IV melanoma. From 2003 to 2010, 27 patients with metastatic melanoma were treated with mature DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin and with subcutaneous low-dose interleukin-2. Delayed-type hypersensitivity (DTH) tests for in-vivo immunomonitoring were performed at baseline and every four vaccinations thereafter. Two complete, two mixed and six partial responses, and five stable diseases were observed (overall response, 37.0%; clinical benefit, 55.5%). All 15 responders showed DTH positivity. A median overall survival of 22.9 months [95% confidence interval (CI): 13.4-61.3] for DTH-positive patients (19) and 4.8 months (95% CI: 3.9-11.9) for DTH-negative patients (8; log rank=7.26; P=0.007) was observed. The overall median overall survival was 16 months (95% CI: 9-33). Our results would seem to highlight a relationship between positive-DTH test and an improved survival.     

A validation study of the Italian Short-Form Leeds Dyspepsia Questionnaire

Assessment of symptoms should be one of the main outcome measures in dyspepsia clinical trials. This requires a reliable, valid and responsive questionnaire that measures the frequency and severity of dyspeptic symptoms. The Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) has been proven to fulfil these criteria in its original version in the English language. The aim of the study was to assess the internal consistency, reliability, validity and responsiveness of the Italian version of the SF-LDQ in primary and secondary care. Unselected primary and secondary care patients completed the Italian version of the SF-LDQ. Test–retest reliability was assessed after 2 days. Validity was measured by comparison with diagnosis made by physicians. Responsiveness was determined before and after treatment for endoscopically proven disease. The SF-LDQ was administered to 311 patients in primary care and 179 in secondary care patients. Internal consistency, as judged by the Cronbach’s α, was 0.90. Pearson’s correlation coefficient for test–retest reliability was 0.92. The SF-LDQ had a sensitivity of 80% and a specificity of 82%. A highly significant response to change was also observed (p = 0.001). The Italian SF-LDQ is a reliable, valid and responsive self-completed outcome measure for quantifying the frequency and severity of dyspeptic symptoms.     

A standardized clinical evaluation of patients affected by facioscapulohumeral muscular dystrophy: The FSHD clinical score

To define numerically the clinical severity of facioscapulohumeral muscular dystrophy (FSHD), we developed a protocol that quantifies muscle weakness by combining the functional evaluation of six muscle groups affected in this disease. To validate reproducibility of the protocol, 69 patients were recruited. Each patient was evaluated by at least five neurologists, and an FSHD severity score was given by each examiner. The degree of agreement among clinicians' evaluations was measured by kappa‐statistics. Nineteen subjects received a score between 0 and 1, 9 had a score between 2 and 4, 20 received a score between 5 and 10, and 8 had a score between 11 and 15. Of the 13 subjects with D4Z4 alleles within the normal range (ranging from 10 to 150 repeats), 12 obtained a score of 0 and only 1 had a score of 1. Kappa‐statistics showed a very high concordance for all muscle groups. We developed a simple, reliable, easily used tool to define the clinical expression of FSHD. Longitudinal studies will assess its sensitivity and utility in measuring changes for widespread use. Muscle Nerve, 2010     

Heart rate variability in facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent form of muscular dystrophy. Heart rate variability (HRV) analysis is a means of evaluating the activity of the autonomic nervous system. The aim of this study was to evaluate HRV in FSHD patients. Fifty-five consecutive FSHD patients were enrolled (31 men, age 26-72 years). Muscular impairment was measured using a clinical severity scale (CSS). Patients were compared with a control group of 55 healthy subjects, matched for age and sex. HRV was analyzed in the time domain and in the frequency domain. Patients showed increased spectral power of the low-frequency band. Spectral power of the high-frequency band was inversely correlated with CSS score. FSHD is associated with a slight increase in sympathetic output and with a decrease in parasympathetic output. These modifications become more evident with the progression of the disease and could increase the risk of arrhythmias and other cardiovascular events.     

Cerebellar degeneration and ocular myasthenia gravis in a patient with recurring ovarian carcinoma

Myasthenia gravis (MG) and paraneoplastic cerebellar degeneration (PCD) are immune-mediated syndromes that can represent paraneoplastic disorders. We report a patient with history of ovarian carcinoma that presented with ptosis, diplopia and gait ataxia. Neurophysiological examination and laboratory tests revealed the presence of MG and PCD. An integrated FDG-PET/contrast-enhanced CT scan showed tumor recurrence. This is to the best of our knowledge the first association of MG and PCD with recurring ovarian carcinoma.