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•PBI is valid alternative to WBI in patients at low-risk of local relapse.•PBI is delivered by means of various techniques, one of which is IOeRT.•After IOeRT, an unexpectedly high LR ...rate was observed in the only phase III RCT.•Patient selection impacts on LR rates after IOeRT.•With appropriate patient selection IOeRT outcomes overlap with other RT techniques.
The therapeutic landscape of metastatic prostate cancer has undergone a profound revolution in recent years. In addition to the introduction of novel molecules in the clinics, the field has witnessed ...a tremendous development of functional imaging modalities adding new biological insights which can ultimately inform tailored treatment strategies, including local therapies. The evolution and rise of Stereotactic Body Radiotherapy (SBRT) have been particularly notable in patients with oligometastatic disease, where it has been demonstrated to be a safe and effective treatment strategy yielding favorable results in terms of disease control and improved oncological outcomes. The possibility of debulking all sites of disease, matched with the ambition of potentially extending this treatment paradigm to polymetastatic patients in the not-too-distant future, makes Biology-guided Radiotherapy (BgRT) an attractive paradigm which can be used in conjunction with systemic therapy in the management of patients with metastatic prostate cancer.
While previous studies have described the time course of the dissipation of motor sleep inertia (around 70 min after wake-up time) and motor wake inertia (around 20 min after bedtime) in healthy ...controls (HCs), the corresponding knowledge for persons with early relapsing–remitting multiple sclerosis (RRMS) is lacking. To fill in this knowledge gap, we carried out a secondary analysis of previously collected data in 35 persons (24 females; mean age = 31.51 ± 7.74 years) with early relapsing–remitting multiple sclerosis (RRMS) and 35 (24 females; mean age = 31.29 ± 8.02) healthy controls (HCs). Each participant wore an actigraphic Micro Motionlogger Watch (Ambulatory Monitoring, Ardlsey, NY, USA) for seven consecutive days. The Functional Linear Modeling statistical framework was adopted to compare the dissipation of motor sleep inertia as well as motor wake inertia between RRMS and HC. As regards motor sleep inertia, no significant differences in motor activity were observed in the first 70 min after the wake-up time; however, with reference to motor wake inertia, the motor activity of RRMS persons was significantly higher than HCs in approximately the first 30 min after bedtime. Despite the small sample size, this pattern of results suggests that the dissipation of motor wake inertia is only slower in persons with RRMS as opposed to HCs.
A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence ...dynamics and long-term functional outcome.
The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death.
Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively;
= 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (
= 0.29, 95% CI 0.05-0.50;
= 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%).
Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.
Background:
The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, ...serological tests became routinely available.
Objective:
To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test.
Methods:
We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model.
Results:
Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002).
Conclusion:
Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.
While relapsing-remitting is the most prevalent course of multiple sclerosis, the prognostic/predictive markers of the worsening of symptomatology are still debated. With reference to other diseases, ...the study of the circadian activity rhythm, according to the theoretical framework of the two-process model of sleep regulation and applying functional linear modeling, proved to be useful to identify a possible marker. The usefulness of the study of circadian activity rhythm in multiple sclerosis is strengthened by recent findings indicating a potential involvement of circadian factors in the multifactorial etiopathology of the disorder. The aim of the present study was to verify whether circadian activity rhythm of early relapsing-remitting multiple sclerosis patients presents specific alterations, through functional linear modeling. Thirty-five relapsing-remitting multiple sclerosis patients (24 females; mean age ± SD = 31.51 ± 7.74) and 35 healthy controls (24 females; mean age ± SD = 31.29 ± 8.02) were enrolled. They wore an actigraph around the non-dominant wrist for one week. Relapsing-remitting multiple sclerosis patients showed a peak in motor activity around 5:00 a.m., higher than that of healthy controls. The timing of the peak in motor activity in the patients could be explained according to the hyperactive hypothalamus-pituitary-adrenal axis and higher cortisol awakening response reported in these patients.
Background
Assessing the safety of SARS-CoV-2 mRNA vaccines and the effect of immunotherapies on the seroconversion rate in patients with autoimmune neurological conditions (ANC) is relevant to ...clinical practice. Our aim was to assess the antibody response to and safety of SARS-CoV-2 mRNA vaccines in ANC.
Methods
This longitudinal study included ANC patients vaccinated with two doses of BNT162b2 or mRNA-1273 between March and August 2021. Side effects were assessed 2–10 days after each dose. Neurological status and anti-spike receptor binding domain antibody levels were evaluated before vaccination and 4 weeks after the second dose. Healthcare-workers served as controls for antibody levels.
Results
We included 300 ANC patients (median age 52, IQR 40–65), and 347 healthcare-workers (median age 45, IQR 34–54). mRNA-1273 vaccine was associated with an increased risk of both local (OR 2.52 95% CI 1.45–4.39,
p
= 0.001) and systemic reactions (OR 2.51% CI 1.49–4.23,
p
= 0.001). The incidence of relapse was not different before and after vaccine (Incidence rate ratio 0.72, 95% CI 0.29–1.83). Anti-SARS-CoV-2 IgG were detected in 268 (89.9%) patients and in all controls (
p
< 0.0001). BNT162b2 vaccine (OR 8.84 95% CI 2.32–33.65,
p
= 0.001), anti-CD20 mAb (OR 0.004 95% CI 0.0007–0.026,
p
< 0.0001) and fingolimod (OR 0.036 95% CI 0.002–0.628,
p
= 0·023) were associated with an increased risk of not developing anti-SARS-CoV-2 IgG.
Conclusion
SARS-CoV-2 mRNA vaccines were safe in a large group of ANC patients. Anti-CD20 and fingolimod treatment, as well as vaccination with the BNT162b2 vaccine, led to a reduced humoral response. These findings could inform vaccine policies in ANC patients undergoing immunotherapy.
•BMV is a novel prognostic score for OS in patients with BMs from solid cancers.•To date, three versions of the BMV have been proposed: Classic, initial and volume-based.•This is the first study to ...attempt to externally validate all three BMV scores in a large cohort.•cBMV and iBMV were successfully validated, while validation of vBMV was not achieved.•External validation and easy transferability suggest clinical potential for cBMV and iBMV.
Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores.
Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS.
For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, “classic” BMV was validated as categorical (p < 0.0001) and continuous variable (HR 1.02; 95% CI 1.02–1.03; p < 0.0001). In a sub-group of 284 patients, “initial” BMV was validated as categorical variable (high-risk vs. low-risk; p < 0.01), but not as continuous variable (HR 1.02; 95% CI 0.99–1.04; p = 0.224). “Volume-based” BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01–3.38; p < 0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p < 0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30–6.91; p < 0.05).
This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved.
It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the ...outcomes expected in the age- and sex-matched Italian population.
Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale EDSS score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ
test, and the risk excess was quantified by risk ratios (RRs).
The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (
< 0.001), RR = 2.19 for ICU admission (
< 0.001), and RR = 2.43 for death (
< 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03,
= 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events,
= 0.04).
Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon.
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