Here, we report the case of a 36-year-old patient with a diagnosis of de novo mutation of the WDR45 gene, responsible for beta-propeller protein-associated neurodegeneration, a phenotypically distinct, X-linked dominant form of Neurodegeneration with Brain Iron Accumulation. The clinical history is characterized by a relatively stable intellectual disability and a hypo-bradykinetic and hypertonic syndrome with juvenile onset. Genetic investigations and T1 and T2-weighted MR images align with what is described in literature. The patient was also subjected to PET with 18-FDG investigation and DaT-Scan study. In reporting relevant clinical data, we want to emphasize the fact that the patient received a chelation therapy with deferiprone (treatment already used in other forms of NBIA with encouraging results), which, however, had to be interrupted because the parkinsonian symptoms worsened. Conversely, the patient has benefited from non-drug therapies and, in particular, from an adapted motor activity with assisted pedaling (method in the process of validation in treatments of parkinsonian syndromes), which started before the treatment with deferiprone and still continues.
ObjectiveTo investigatethe prevalence, predictors and prognostic impact of hematoma expansion (HE) inintracerebral hemorrhage (ICH) patients with unclear symptom onset (USO).MethodsRetrospective analysis of patients with primary spontaneous ICH admitted at 5 academic medical centers in USA and Italy.HE (volume increase >6 mL and/or >33% from baseline to follow-up non-contrast CT [NCCT]) and mortality at 30 days were the outcomes of interest. Baseline NCCT was also analyzed for presence of hypodensities (any hypodense region within the hematoma margins). Predictors of HE and mortality were explored with multivariable logistic regression.ResultsWe enrolled 2,165 subjects, 1,022 in the development cohort and 1,143 in the replication cohort, of whom 352 (34.4%) and 407 (35.6%) had ICH with USO respectively. When compared with subjects having a clear symptom onset, USO patients had a similar frequency of HE (25.0% vs 21.9%, p = 0.269 and 29.9% vs 31.5%, p = 0.423). Among USO patients, HE was independently associated with mortality after adjustment for confounders (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.43–4.89, p = 0.002). This finding wassimilar in the replication cohort (OR 3.46, 95% CI 1.86–6.44, p < 0.001). The presence of NCCT hypodensities in USO subjects was an independent predictor of HE in the development (OR 2.59, 95% CI 1.27–5.28, p = 0.009) and replication (OR 2.43, 95% CI 1.42–4.17, p = 0.001) population.ConclusionHE is common in USO patients and independently associated with worse outcome. These findings suggest that USO patients may be enrolled in clinical trials on medical treatments targeting HE.
The complex karyotype (CK) is an established negative prognostic marker in a number of haematological malignancies. After the introduction of effective mitogens, a growing body of evidence has suggested that the presence of 3 or more aberrations by conventional banding analysis (CBA) is associated with an unfavorable outcome in chronic lymphocytic leukemia (CLL). Thus, the importance of CBA was recognized by the 2018 guidelines of the International Workshop on CLL, which proposed the introduction of CBA in clinical trials to validate the value of karyotype aberrations.Indeed, a number of observational studies showed that cytogenetic aberrations and, particularly, the CK may have a negative independent impact on objective outcome measures (i.e. time to first treatment, progression free survival, time to chemorefractoriness and overall survival) both in patients treated with chemoimmunotherapy and, possibly, in patients receiving novel mechanism-based treatment.Here, we set out to present the scientific evidence supporting the significance of CK as a prognostic marker in CLL and to discuss the biological basis showing that the CK is a consequence of genomic instability.
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