Δευτέρα 5 Σεπτεμβρίου 2022

P11.71.B Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) in a patient with blastic plasmacytoid dendritic cell neoplasm: a rare neurologic manifestation in a rare disease

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Abstract
Background
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid hematological malignancy. Skin lesions, bone marrow, lymph nodes or visceral organs can be involved. 30% of patients will have infiltration to the nervous system,occult asymptomatic infiltration is frequent. Immunophenotype express CD4, CD56, and CD123, and flow cytometry is essential.
Material and Methods
70-yo Hispanic male with a 1-month history of multiple violaceous cutaneous nodules and adenopathies.Neurological complaints included diplopia, hypoesthesia in the left face, dysphagia, gait difficulties, and generalized weakness with distal hypoesthesia. Examination revealed multiple cranial neuropathy (bilateral VI and VII nerve palsies, left V3 and VIII palsies and IX, X involvement), global areflexia, length-dependent weakness, ataxic gait and cerebellar syndrome. An inguinal ganglionar biopsy retrieved cells positive for CD4, TCL 1, CD68 and CD123, whereas CD3, CD20, CD7, CD8, CD30 and myeloperoxidase were negative. PET/CT showed multiple supra and infradiaphragmatic adenopathies, bilateral pleural, pericardial and abdominal implants. Bone marrow biopsy was negative. Brain MRI showed contrast enhancement in the cerebellar folia and in the roots of the cranial nerves clinically involved. Multiple CSFs demonstrated high protein count (281- 310mg/dl), normal glucose and cell count; CSF flow cytometry and cytology reported no blastic infiltration (negative CD4, CD56 and CD123), CSF onconeuronal antibodies were negative. Nerve conduction studies fulfilled definite electrodiagnostic EFNS criteria for CIDP. Sural nerve biopsy reported inflammatory demyelination without infiltration. Systemic chemotherapy (Cyclophosphamide/Vincristine) with intrathecal cytarbine/methotrexate was administered.
Results
Favorable initial, but brief response was noticed for the cranial nerves and gait. He had neurological relap se with gait impossibility. Neuraxis MRI showed no contrast enhancement in the brain but new contrast enhancement of lumbosacral roots. Nerve conduction studies reported severe worsening criteria of CIDP. The PET/CT demonstrated complete response. Five days of methylprednisolone (1gr IV) followed by oral prednisone were prescribed (50 mg qd). However, two weeks later he suffered clinical neurological worsening with respiratory failure. IVIg was started (.4g/kg/day for 5 days) with no improvement; palliative care decision was consented.
Conclusion
We report the case of an adult male with multiple cranial nerve palsy, cerebellar syndrome and refractory rapidly progressive asymmetric polyneuropathy with BPDCN. CIDP in the absence of multiple attempts to demonstrate nervous system infiltration led us to consider this as a paraneoplastic phenomenon refractory to treatment. To our knowledge no CIDP has been reported in this rare disease
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P17.06.B Different dosage of bevacizumab treatment in recurrent IDHwt glioblastoma/IDHmut grade 4 astrocytoma and its impact on outcome

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Abstract
Background
Angiogenesis is one of the most distinctive hallmarks of glioblastoma (GBM). Although bevacizumab did not show to improve overall survival in phase 3 trials, it was approved by FDA and is often prescribed as off-label therapy in the recurrent clinical setting. The aim of this study is to evaluate the difference in terms of survival and safety between the 5 mg/m2 and 10 mg/m2 bevacizumab schedule in recurrent GBM.
Material and methods
All pts treated at Veneto Institute of Oncology from May 2013 to March 2022 were retrospectively reviewed. Major inclusion criteria were: histologically confirmed diagnosis of IDHwt GBM/IDHmut grade 4 astrocytoma (according to the WHO 2021 classification), relapse after first or subsequent line of therapy, treatment with bevacizumab at 5 mg/m2 or/and 10 mg/m2 every 2 weeks until progression/death or unacceptable toxicity. Bevacizumab was admini stered as off-label therapy. The treatment schedule was at physician's discretion. RANO criteria and CTCAE v5.0 were used for response and toxicity assessment.
Results
81 pts were enrolled. From starting bevacizumab the median follow-up was 10.9ms [95% CI 9.8-14.0] and median age was 53ys (range 18-81). 33 (41%) pts received the 5 mg/m2 schedule. Among them, 2 (6%) were IDHmut grade 4, 8 (24%) had ≥65ys and ECOG-PS was 0-1 in 16 (48%) and ≥2 in 17 (51%), respectively. MGMT was methylated in 15 of 30 (50%) evaluable pts. Median number of prior lines of treatment was 2 (range 1-4) and 30% of pts received bevacizumab at first recurrence. 28 (84.9%) pts were evaluable for response: 7 (21%) and 5 (15%) showed PR and SD. 48 pts received the 10 mg/m2 schedule: 5 (10%) were IDHmut grade 4 astrocytoma; 29 (60%) had an ECOG-PS of 0 or 1 and 4 (8%) had ≥65ys, MGMT was methylated in 20 of 44 (45%) evaluable pts. 36 (75%) pts received bevacizumab beyond the second line of therapy. 46 (96%) pts were evaluable for response: 6 (12%) had PR, 19 (39%) SD. mOS from the start of bevacizumab was 7.3ms (95% CI 4.3-6.4), mPFS was 4.4ms [95% CI 3.7 - 6.4]. At univariate analysis, pts who received the 5 mg/m2 or the 10 mg/m2 schedule had a mOS of 5.4 and 7.7ms (p=0.08); mOS for pts with ECOG-PS < or ≥2 was 9.0 and 5.4ms (p=0.04) while mOS for pts with <2 or ≥2 lines of therapy was 4.7 and 7.7ms (p=0.056). Age and type of the tumor were not statistically significant. At multivariate analysis, MGMT methylated status was the only factor statistically associated with OS (HR=0.48, 95% CI, p=0.002) and PFS (HR=0.33, 95% CI, p=0.001), while a number of prior lines of therapy ≥2 (HR=2.07, 95% CI, p=0.02) was significantly associated only with PFS. Grade 3-4 most common adverse events were hypertension (18%) in pts treated with 5 mg/m2 and hypertension (16%) and proteinuria (2%) in pts treated with 10 mg/m2.
Conclusions
Bevacizumab tr eatment with a dosage of 5 mg/m2 and 10 mg/m2 seems to give comparable outcome in terms of survival in recurrent GBM pts. No difference was demonstrated for safety.
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KS05.5.A Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients

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Abstract
Background
In glioma patients, multimodal therapy and recurrent tumor result in local brain tissue changes, characterized by pathologic findings in structural MRI and metabolic PET images. Little is known about these different lesion types' impact on the local white matter fiber architecture and clinical outcome.
Patients and Methods
This study included data from 121 pretreated patients (median age, 52 years; ECOG, 01) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median time of 14 months (range, 1-214 months), post-therapeutic structural and metabolic findings were evaluated using anatomical MRI and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET acquired on a 3T hybrid PET/MR scanner. Local fiber densi ty was estimated from tractography based on highangular resolution diffusion-weighted imaging. A cohort of 121 healthy subjects selected from the 1000BRAINS study and matched for age, gender and education served as a control group.
Results
The median volume of resection cavities, contrast-enhancing regions, regions with pathologically increased FET uptake, and T2/FLAIR hyperintense regions amounted to 20.9, 7.9, 30.3, and 53.4 mL, respectively. Compared to the control group, the average local fiber density in these regions was significantly reduced (p<0.001). Resection cavities showed the highest reduction, followed by contrast-enhancing lesions and metabolically active tumors on FET PET (relative fiber density reduction, -87%, -65%, -55%, respectively). The local fiber density was inversely related (p=0.005) to the FET uptake in recurrent tumors. T2/FLAIR hyperintense lesions, either assigned to peritumoral edema in recurrent glioma or radiation-induced gliosis, had a c omparable impact on reducing fiber density (48% and 41%, respectively). The total fiber loss (average fiber loss multiplied by lesion volume) associated with contrast-enhancing lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on the general performance status of the patients (ECOG score).
Conclusions
Our results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients' performance due to the larger volume affected.
Funding
Funded by the 1000BRAINS study (INM, Research Centre Juelich, Germany), Horizon 2020 (Grant No. 945539 (HBP SGA3; SC)), and Heinz Nixdorf Foundation.
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Κυριακή 4 Σεπτεμβρίου 2022

Outcomes of Partial Oral Antibiotic Treatment for Complicated S. aureus Bacteremia in People Who Inject Drugs

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Abstract
Background
Staphylococcus aureus represents the leading cause of complicated bloodstream infections among persons who inject drugs (PWID). Standard of care (SOC) intravenous (IV) antibiotics result in high rates of treatment success, but are not feasible for some PWID. Transition to oral antibiotics may represent an alternative treatment option.
Methods
We evaluated all adult patients with a history of injection d rug use hospitalized from 1/2016 through 12/2021 with complicated S. aureus bloodstream infections, including infective endocarditis, epidural abscess, vertebral osteomyelitis, and septic arthritis. Patients were compared by antibiotic treatment (SOC IV antibiotics, incomplete IV therapy, or transition from initial IV to partial oral) using the primary composite endpoint of death or readmission due to microbiologic failure within 90 days of discharge.
Results
Patients who received oral antibiotics after an incomplete IV antibiotic course were significantly less likely to experience microbiologic failure or death than patients discharged without oral antibiotics (p < 0.001). There was no significant difference in microbiologic failure rates when comparing patients who were discharged on partial oral antibiotics after receiving at least 10 days of IV antibiotics to SOC regimens (P > 0.9).
Conclusion
Discharge of P WID with partially treated complicated S. aureus bacteremias without oral antibiotics results in high rates of morbidity and should be avoided. For PWID hospitalized with complicated S. aureus bacteremias who have received at least 10 days of effective IV antibiotic therapy after clearance of bacteremia, transition to oral antibiotics with outpatient support represents a potential alternative if the patient does not desire SOC IV antibiotic therapy.
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Estimating Waning of Vaccine Effectiveness: a Simulation Study

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Abstract
Background
Developing accurate and reliable methods to estimate vaccine protection is a key goal in immunology and public health. While several statistical methods have been proposed, their potential inaccuracy in capturing fast intra-seasonal waning of vaccine-induced protection needs to be rigorously investigated.
Methods
To compare statistical methods for vaccine effectiveness (VE) estimation, we generated simulated data using a multiscale agent-base d model of an epidemic with an acute viral infection and differing extents of VE waning. We apply a previously proposed framework for VE measures based on the observational data richness to assess changes of vaccine-induced protection over time.
Results
While VE measures based on hard-to-collect information (e.g. the exact timing of exposures) were accurate, usually VE studies rely on time-to-infection data and the Cox proportional hazard model. We found that its extension utilizing scaled Schoenfeld residuals, previously proposed for capturing VE waning, was unreliable in capturing both the degree of waning and its functional form and identified the mathematical factors contributing to this unreliability. We showed that partitioning time and including a time-vaccine interaction term in the Cox model significantly improved estimation of VE waning, even in the case of dramatic, rapid waning. We also proposed how to optimize the partitioning scheme.
Conclusions
While appropriate for rejecting the null hypothesis of no waning, scaled Schoenfeld residuals are unreliable for estimating the degree of waning. We propose a Cox-model-based method with a time-vaccine interaction term and further optimization of partitioning time. These findings may guide future analysis of VE waning data.
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COVID‐19 immunopathology: From acute diseases to chronic sequelae

alexandrossfakianakis shared this article with you from Inoreader

ABSTRACT

The clinical manifestation of COVID-19 mainly targets the lung as a primary affected organ, which is also a critical site of immune cells activation by SARS-CoV-2. However, recent reports also suggest the involvement of extrapulmonary tissues in COVID-19 pathology. The interplay of both innate and adaptive immune responses is key to COVID-19 management. As a result, a robust innate immune response provides the first line of defense, concomitantly, adaptive immunity neutralizes the infection and builds memory for long-term protection. However, dysregulated immunity, both innate and adaptive, can skew towards immunopathology both in acute and chronic cases. Here we have summarized some of the recent findings that provide critical insight into the immunopathology caused by SARS-CoV-2, in acute and post-acute cases. Finally, we further discuss some of the immunomodulatory drugs in preclinical and clinical trials for dampening the immunopathology caused by COVID- 19.

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Translucency, color stability, and biaxial flexural strength of advanced lithium disilicate ceramic after coffee thermocycling

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Abstract

Objective

To compare the color stability, translucency, and biaxial flexural strength (BFS) of differently glazed advanced lithium disilicate (ALDS) with those of lithium disilicate (LDS) and zirconia-reinforced lithium silicate (ZLS) after coffee thermocycling.

Materials and methods

Forty disk-shaped specimens were prepared from three lithium silicate based materials (CEREC Tessera, ALDS; IPS e.max CAD, LDS; Vita Suprinity, ZLS). ALDS specimens were divided into two subgroups according to glazing procedures (reduced glaze duration, ALDS-S and normal glaze duration, ALDS-N), while LDS and ZLS specimens were crystallized and glazed. Color coordinate measurements were performed before and after coffee thermocycling. Color differences (ΔE 00) and relative translucency parameters (RTP) were calculated. Specimens were then subjected to BFS test. Statistical analysis was performed by using 1- (ΔE 00 and BFS) and 2-way (RTP) ANOVA tests (α = 0.05).

Results

ΔE 00 values of tested materials were similar (df = 3, F = 0.150, p = 0.929). Two-way ANOVA showed the significant effect of material type, coffee thermocycling, and the interaction between these parameters on RTP values (p < 0.001). Both before and after thermocycling, LDS had the highest (p ≤ 0.001) and ZLS had the lowest (p < 0.001) RTP values, while ALDS-N had higher RTP than ALDS-S (p ≤ 0.001). Among tested materials, only LDS had similar RTP values before and after thermocycling (p = 0.865) as the other materials had lower RTP values after thermocycling (p < 0.001). ALDS-N had higher BFS values than ALDS-S (p = 0.005), while LDS had similar values to ALDS specimens (p ≥ 0.201). ZLS had the highest BFS (p ≤ 0.007).

Conclusions

ALDS had comparable values to those of other materials. However, reduced glazing duration resulted in decreased translucency and BFS of ALDS.

Clinical significance

ALDS may be an appropriate restorative material for those patients with increased coffee consumption considering its color stability and ability to maintain translucency, particularly when glazed by using a conventional porcelain furnace.
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