Multiple polymerase chain reaction (RT-PCR) is considered the gold standard diagnostic investigation for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease ...2019 (COVID-19).
However, false negative multiple polymerase chain reaction (RT-PCR) results can be diagnostically challenging. We report three patients with history of fever and different clinical signs. During the height of the pandemic in Italy (March to May 2020), these patients underwent chest computed tomography (CT) scans that showed lung alterations typical of COVID-19 with multiple negative RT-PCR tests and positive serology for SARS-CoV-2. Two of the three patients showed residual pneumonia on CT after the onset of the first clinical signs. One patient presented with diarrhoea without respiratory symptoms. These cases suggest that in the COVID-19 pandemic period, to provide an earlier specific treatment in patients with positive serology, a chest CT scan can be useful in those presenting with a fever or a history of fever associated with persistent mild respiratory symptoms or with abdominal complaints despite repeated negative RT-PCR results.
The precision and accuracy of mass spectrometry (MS) made it a fundamental tool in anti-doping analysis. High-resolution (HR) mass spectrometers significantly improved compound identification. This ...study systematically analyzes data from an athlete (Subject 1) who tested positive for meldonium and compares it with data from a healthy volunteer (Subject 2) to examine the correctness of the doping verdict.
The documentation related to Subject 1 was thoroughly processed and analyzed. A study involving a volunteer (Subject 2) replicated Subject 1 regimen and urine sample collection for data alignment with anti-doping results, with Subject 2 reporting not using meldonium. The anti-doping agency's analysis of Subject 1 showed the presence of meldonium at a concentration close to the established cut-off level. However, a closer examination revealed that one specific ion, crucial for meldonium identification, was absent from the mass spectra. Analyzing Subject 2 data, using the same methodology, the absence of the specific ion was confirmed, even though the volunteer did not consume meldonium. The European directive and the method that was validated and cited by the anti-doping agency identified meldonium on at least four specific ions, whereas the anti-doping analysis used only three ions. This discrepancy compromises the specificity of meldonium identification.
To enhance the analytical methodology, two strategic interventions are suggested: adjusting the meldonium cut-off value and expanding the analysis to include meldonium metabolites. By addressing these avenues, the precision of meldonium detection and doping verdicts can be improved. In conclusion, this study challenges the anti-doping agency's verdict and prompts a reevaluation of meldonium detection methodologies in anti-doping measures.
Highlights • It provides a prolonged prospective study on development in Dravet syndrome. • The evolution of visual function impairment expanding in higher cognitive abilities is analyzed. • A ...specific involvement of visual dorsal stream skills seems to appear. • Possible consequences on prognosis and rehabilitation strategies are considered.
Among physicians there is still a reluctant attitude in the employment of combined treatment with surgery and intraoperative placement of carmustina 7.7 mg wafers (Gliadel®), followed by standard ...adjuvant treatment with radiotherapy and concomitant and subsequent chemiotherapy with temozolomide (TMZ), for supratentorial high grade gliomas at first diagnosis. To determine the safety and feasibility of this multimodality sequential adjuvant therapy, we reviewed our single-institution experience, in the light to provide more insights on this continuous multi-stage chemotherapy approach to such a challenging disease as glioblastoma multiforme.
From February 2006 to January 2008, 32 patients were treated at our institution for cerebral supratentorial high grade glioma with surgery and intraoperative placement of carmustine wafers. No postsurgical complications could be observed. After a median time of 4,8 weeks all patients began adjuvant concomitant radiotherapy with a mean of 60 Gy and TMZ chemotherapy 75 mg/m2 during which weekly hematologic assessments were performed. After 3 to 6 weeks patients commenced adjuvant TMZ, administered 5 days every 28, 200 mg/m2 for not less than 12 cycles. A contrast-enhanced magnetic resonance imaging (MRI) was routinely performed. Median follow-up after surgery was of 6.5 months, ranging from 4 to 23 months.
The mean presurgical KPS was of 80 (range: from 60 to 100), and it remained unmodified after adjuvant therapies even at suspension of steroids. In 4 cases there was a radiologic evidence of progression of the disease and the necessity of steroids, with a progression-free survival (PFS) of 6, 8, 9,5 and 13,6 months. One case died 14 months after first operation. All other patients are still alive.
The integration of local chemiotherapy with carmustine wafers and the standard adjuvant regimen with radiotherapy and concomitant chemiotherapy appears to be safe and feasible, without any adjunctive complication. Promising results on the efficacy require more follow up to be quantified.
Givinostat is a novel orally active histone deacetylase (HDAC) inhibitor being developed for the treatment of DMD. The Epidys Study is a randomized, double blind, placebo controlled, multicenter ...Phase 3 study to evaluate the efficacy and safety of givinostat in ambulant patients with DMD (Clinicaltrials.gov ID: NCT02851797). One-hundred and seventy-nine boys aged ≥6 years at baseline affected by DMD were enrolled and 95% of them completed the study. The primary efficacy assessment was the time to climb 4 standard stairs (4SC). Six key secondary efficacy endpoints included: physical function assessed by North Star Ambulatory Assessment (NSAA), time to rise from floor, distance walked in 6 minutes using 6-Minute Walk Test, knee extension and elbow flexion quantitative muscle strength, and fat fraction of vastus lateralis muscle (VL MFF) evaluated by magnetic resonance spectroscopy. Treatment duration was 18 months. The Epidys Study met its primary endpoint and givinostat demonstrated a statistically significant difference in change from baseline at 18 months in 4SC (GLSmean ratio SD = 0.86 0.071; p=0.0345). Overall, treatment effect estimates relating to the key secondary endpoints consistently favored givinostat over placebo supporting the primary endpoint result. NSAA was evaluated both as change from baseline at 18 months of the Total Score and as the cumulative loss of NSAA items. Givinostat treatment was associated with less decline in NSAA Total Score (Mean difference: 1.91 points; nominal p=0.021) as well as 39% less cumulative item loss (nominal p=0.02). Analysis of the effect on the 17 specific items of NSAA showed a difference between groups, in particular in the items which are mostly affected in patients of this age and disease stage. Givinostat treatment in patients with DMD showed a good tolerability profile in Study 48 with primary issues being reversible and manageable and related to thrombocytopenia, and hypertriglyceridemia. In conclusion, the Epidys Study met its primary endpoint with consistent results in the key secondary endpoints. The treatment effects on physical function assessed by the NSAA are considered clinically important and are related to how DMD boy function in clinically meaningful motor tasks. Givinostat tolerability profile in study 48 was in line with results in previous studies in DMD and in other diseases.
TTN myopathies include a heterogeneous group with variable skeletal and cardiac muscle involvement. The congenital forms have prenatal onset or clinical signs at birth or within the first years of ...life. We report clinical and muscle MRI findings in 6 patients with congenital-onset recessive TTN myopathies. Five of our six cases presented at birth with contractures or arthrogryposis and severe motor impairment with limited antigravity movements. In all 5, there was a progressive improvement in ROM and motor function. All acquired the ability to stand, and 3 of the 5 also walk independently. In the remaining one, the onset was around the age of 1 year with mild delay. Weakness became more obvious by the age of 2. Muscle MRI at pelvic and thigh level shows a predominant involvement of gluteus maximus and vasti with a striking involvement of the semitendinosus; adductor magnus and rectus femori were relatively spared. In the lower legs soleus, gastrocnemius medialis, and peronei muscles were most involved; tibialis anterior showed a variable impairment. Our series of early-onset recessive TTN myopathies shows a consistent pattern of muscle MRI involvement with predominant semitendinosus fatty replacement and the sparing of adductor magnus. This pattern is similar to the one reported in the dominant forms, even if in our series there was a more variable involvement of the tibialis anterior muscle. The identification of this MRI pattern can be of help in cases in whom the results of genetic testing are not completely clear.
Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically ...characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years’ clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.
The aim of the study was to assess various aspects of visual and visuoperceptual function in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) with mutations affecting the PTPN11, SOS1 and ...RAF1 genes. Twenty-four patients were assessed with a battery of tests assessing visual function including ophthalmological and orthoptic evaluation and age appropriate behavioural visual tests, including measures of crowding acuity (Cambridge crowding cards), and stereopsis (TNO test). Twenty-one subjects were also assessed with the visuo-motor integration (VMI) test. Twenty of the 24 patients (83%) had abnormalities of visual function on at least one of the tests used to assess visual function or on ophthalmological examination, and 7 of 21 (33%) also had abnormalities on VMI. Ocular movements and stereopsis were most frequently abnormal (50% and 79%, respectively). Our results suggest that visual and visuoperceptual abilities are commonly impaired in patients with Noonan and LEOPARD syndrome and they are probably related to a multifactorial etiology.
PDF
