Assessment, pharmacological therapy and rehabilitation management of musculoskeletal pain in children with mucopolysaccharidoses: a scoping review.

BACKGROUND: Pain of musculoskeletal origin is very common in young patients affected by Mucopolysaccharidoses. This scoping review evaluates the evidence for assessment, pharmacological treatment and rehabilitation management for musculoskeletal pain of the latter. METHODS: A Medline search through PubMed has been performed for studies published in English at least for the past twenty years. Two investigators independently reviewed all search results and extracted those that met the inclusion criteria. RESULTS: 29 studies have been selected and analysed in depth, of which 10 related to pain assessment, 11 concerned pharmacological approach, and 8 reported rehabilitation approaches. CONCLUSION: Few data are available in literature concerning the classification and management of pain in children with Mucopolysaccharidoses. Notwithstanding, pain evaluation methods are effectively used to classify pain intensity, according to the age group and communication abilities of young Mucopolysaccharidoses patients. The review emphasizes that drug therapies have a palliative purpose, while rehabilitation reduces musculoskeletal pain and can provide a therapeutic effect on disabilities.

Predictors of in-hospital mortality of COVID-19 patients and the role of telemetry in an internal medicine ward during the third phase of the pandemic.

OBJECTIVE: The first pandemic phase of COVID-19 in Italy was characterized by high in-hospital mortality ranging from 23% to 38%. During the third pandemic phase there has been an improvement in the management and treatment of COVID-19, so mortality and predictors may have changed. A prospective study was planned to identify predictors of mortality during the third pandemic phase. PATIENTS AND METHODS: From 15 December 2020 to 15 May 2021, 208 patients were hospitalized (median age: 64 years; males: 58.6%); 83% had a median of 2 (IQR,1-4) comorbidities; pneumonia was present in 89.8%. Patients were monitored remotely for respiratory function and ECG trace for 24 hours/day. Management and treatment were done following the timing and dosage recommended by international guidelines. RESULTS: 79.2% of patients necessitated O2-therapy. ARDS was present in 46.1% of patients and 45.4% received non-invasive ventilation and 11.1% required ICU treatment. 38% developed arrhythmias which were identified early by telemetry and promptly treated. The in-hospital mortality rate was 10%. At multivariate analysis independent predictors of mortality were: older age (R-R for≥70 years: 5.44), number of comorbidities ≥3 (R-R 2.72), eGFR ≤60 ml/min (RR 2.91), high d-Dimer (R-R for≥1,000 ng/ml:7.53), and low PaO2/FiO2 (R-R for <200: 3.21). CONCLUSIONS: Management and treatment adherence to recommendations, use of telemetry, and no overcrowding appear to reduce mortality. Advanced age, number of comorbidities, severe renal failure, high d-Dimer and low P/F remain predictors of poor outcome. The data help to identify current high-risk COVID-19 patients in whom management has yet to be optimized, who require the greatest therapeutic effort, and subjects in whom vaccination is mandatory.

Clinical application of lung ultrasound score on COVID-19 setting: a regional experience in Southern Italy.

OBJECTIVE: We aimed to assess the correlation between LUS Soldati proposed score and clinical presentation, course of disease and the possible need of ventilation support/intensive care. PATIENTS AND METHODS: All consecutive patients with laboratory confirmed SARS-CoV-2 infection and hospitalized in two COVID Centers were enrolled. All patients performed blood gas analysis and lung ultrasound (LUS) at admission. The LUS acquisition was based on standard sequence of 14 peculiar anatomic landmarks with a score between 0-3 based on impairment of LUS picture. Total score was computed with their sum with a total score ranging 0 to 42, according to Soldati LUS score. We evaluated the course of hospitalization until either discharge or death, the ventilatory support and the transition in intensive care if needed. RESULTS: One hundred and fifty-six patients were included in the final analysis. Most of patients presented moderate-to-severe respiratory failure (FiO2 <20%, PaO2 <60 mmHg) and consequent recommendation to invasive mechanic ventilation (CPAP/NIV/OTI). The median ultrasound thoracic score was 28 (IQR 18-36) and most of patients could be ascertained either in a score 2 (40%) or score 3 pictures (24.4%). The bivariate correlation analysis displayed statistically significant and high positive correlations between the LUS score and the following parameters: ventilation (rho=0.481, p<0.001), lactates (rho=0.464, p<0.001), dyspnea (rho=0.398, p=0.001) mortality (rho=0.410, p=0.001). Conversely, P/F (rho= -0.663, p<0.001), pH (rho = -0.363, p=0.003) and pO2 (rho = -0.400 p=0.001) displayed significant negative correlations. CONCLUSIONS: LUS score improve the workflow and provide an optimal management both in early diagnosis and prognosis of COVID-19 related lung pathology.

Surgical treatment of sacral chordoma: survival and prognostic factors.

INTRODUCTION: Sacral chordoma is a rare low-to-intermediate grade malignant tumour. The mainstay of treatment is still surgery with en bloc and wide resection margins, which can grant the best chances of a long-term control or cure of this disease. The first aim of this paper is to collect data about survival, time to local recurrence and metastasis among patients affected by sacral chordoma and primarily treated with surgery. The second aim is to analyze the influence of level resection, tumor volume and surgical margins on local recurrence. MATERIALS AND METHODS: The study population was composed of 14 patients treated with sacral chordoma resection at the National Tumour Institute of Naples-Pascale (Italy) from January 2000 to June 2013. The median follow-up was 84 months (range 24-132 months). The follow-up was characterized by: standard radiographs, MRI, and a CT scan of the chest annually. Time to recurrence or metastasis was calculated from the date of resection to the date of diagnosis of first recurrence or metastasis. RESULTS: Out of all the patients, six died (42.86 %) during the follow-up; 6 (42.86 %) had local recurrence; 4 (28.57 %) had metastasis. At univariate analysis wide surgical margins (R0) were associated with increased survival up to a local recurrence (OR = 0.0286; 95 % CI = 0.0014-0.5739; P = 0.026); the level of resection (OR = 3.33; 95 % CI = 0.3619-30.7025; P = 0.592) and tumour volume (P = 1) did not show a statistically significant correlation. DISCUSSION: Based on our experience, we hope all patients to be treated by surgery, the only good standard treatment of this disease. The resection should result in margins as wide as possible. For these reasons, it is essential for this disease to be treated in highly specialized centres because only a complete surgery can offer a chance to care for these patients. CONCLUSIONS: Solid survival at long-term follow-up can be achieved by a surgical resection performed with wide margins.

Magnetic resonance imaging and ultrasound evaluation of "healthy" joints in young subjects with severe haemophilia A.

Magnetic resonance imaging (MRI) and ultrasonography (US) are increasingly used in haemophilia A (HA) to detect early joint changes. A total of 40 clinically asymptomatic joints, never involved by bleeding events ["healthy joints" (HJ)], were evaluated by MRI and, in parallel, by US in 20 young subjects with severe HA (22.45 ± 2.72 years old; no history of arthritides, of viral infections or of inhibitors against factor VIII). The same joints were evaluated in 20 matched non-haemophilic (no-HA) subjects (mean age 23.90 ± 2.31 years, P = 0.078 vs. HA subjects). US images were obtained with specific probe positions according to validated procedures. A validated US score and progressive (P-MRI) and additive (A-MRI) MRI scores were employed for data collection and analysis. The US score was higher in HA than in no-HA subjects (3.40 ± 1.72 vs. 0.80 ± 1.10, P < 0.001). Taking into account only moderate/severe alterations, joint effusion was found in 55% of HA and in 5% of no-HA joints (P < 0.001); synovial hypertrophy was found in 20% of HA and in none of the no-HA joints; cartilage erosion was found in 30% of HA and in none of no-HA joints. MRI examinations confirmed these findings and the US score correlated with the A-MRI (r = 0.732, P < 0.001) and with the P-MRI (r = 0.598, P < 0.001) scores. MRI and US data significantly correlated as to effusion (r = 0.819, P = 0.002), synovial hypertrophy (r = 0.633, P = 0.036) and cartilage erosion (r = 0.734, P = 0.010). Despite inherent limitations, joint US examination identified subclinical abnormalities of HJ in young subjects with severe HA.

The acromegalic arthropathy.

Since the initial definition of acromegaly over 100 yr ago, extraordinary efforts have been made to control GH levels and the pituitary tumor. Criteria of cure have been evolving constantly and all previous statements should be revised according to modern criteria of disease control. Arthropathy is undoubtedly the most important cause of morbidity and functional disability of acromegaly, and bone alterations are highly characteristic of this syndrome. They involve theoretically all bones and, particularly, the appendicular and the axial skeleton. Radiographic changes at different joint sites are more common than symptoms related to their involvement. There is a progression in the acromegalic arthropathy, resembling that described for the acromegalic cardiomyopathy or for the acromegalic features at other organs, such as thyroid, breast and prostate. At early stage, cartilage hypertrophy predominates, and then degenerative changes start until osteoarthritis features occur. Arthropathy can be reversed by normalizing GH and IGF-I levels only at the initial stage. If the disease is left untreated for long time, the osteo-articular sequelae cannot be modified by any treatment of acromegaly.

Prevention of venous thromboembolism in spinal surgery.

Deep vein thrombosis (DVT), and its most feared complication, pulmonary embolism (PE), still have a high incidence with high risk for patients' health. Proven prophylactic measures are available but are generally underused, and DVT is still considered the most common cause of preventable death among hospitalized patients. The rationale for prophylaxis of venous thromboembolism is based on the clinically silent nature of the disease, the relatively high prevalence among hospitalized patients and the potentially tragic consequences of a missed diagnosis. During the last 15-20 years, spine surgery has changed radically, developing into a well-defined area of specialist surgery, and some attention is now being given to DVT events in spine surgery. The incidence of DVT during spine surgery is not documented in the literature, because only case reports or retrospective studies are reported. It would therefore be very helpful to initiate a multicenter study in order to understand this problem better and to develop, if possible, some guidelines on prophylactic measures in spine surgery. In doing so, we need to consider each patient's pattern, any risk factors and every kind of surgical technique related to DVT, in order to improve the outcome of the patient and to reduce any medicolegal problems that could arise from a thrombotic complication or an epidural hematoma, with its high potential for irreversible consequences.

Uncommon clinical course of multiple osteochondromatosis in a patient with a long-term history of Cushing's disease.

Cushing's disease (CD), the chronic endogenous hypercortisolism derived from an ACTH-secreting pituitary adenoma, and multiple osteochondromatosis (MO), a congenital mesoderm dyschondroplasia, represent two distinct rare neoplastic diseases. Clinical appearance of MO usually occurs during the first-second decade of life. In fact, the growth of osteochondromas parallels the patient's growth, then becoming quiescent after the closure of the epiphyses and the achievement of final stature. Here we describe an uncommon case of a patient with a long-term history of childhood-onset CD, who surprisingly developed MO during the third decade of life, after the remission of CD. Indeed, a female patient had been followed for CD from the age of 12 to the age of 24 years, when CD definitively remitted. At the age of 26 the patient complained progressively worsening backache and pain at level of hips and feet. Standard radiography of skeleton showed multiple bone dysmorphisms at level of the four limbs, spine and pelvis consistent with multiple osteochondromas and exostoses. A diagnosis of MO was performed. Total body bone scintigraphy with 99mTc-MDP revealed an increased uptake of the radioligand, suggesting an increased metabolic turnover in correspondence of the majority of the osteochondromas. However, the negativity of the majority of the lesions at 99mTc-DMSA scintigraphy and the histological diagnosis of benign osteochondroma of the only positive lesion at 99mTc-DMSA evidenced that the high metabolic activity of the osteochondromas was not due to malignant transformation. However, the activity of the lesions was highly surprising considering that they usually become quiescent after the achievement of the final stature. In last analysis, the uncommon characteristics of MO and, particularly, its occurrence after stable remission of hypercortisolism, suggests a possible role of glucocorticoids in influencing the clinical course of the skeletal disease. The inhibitory effect of hypercortisolism on bone growth and maturation could explain the block in the proliferation of skeletal lesions during the developmental age, where CD was in the active phase, and the opposite effect of stimulation of the ostochondromas growth during stable normalization of cortisol secretion, after CD remission.

Intervertebral disc herniation at D3-4 Case report.

The authors report a case of intervertebral disc herniation at D3.4 which they removed surgically from a posterior approach. They emphasize the extreme rarity of this localisation. The hernia was calcified, extruded and displaced posterolaterally and medially, causing pressure on the anterior aspect of the spinal cord with neurological signs of the pareto-spastic type. The operation was successful, with relief of pain and regression of the neurological symptoms.