Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma.

Patients diagnosed with B-cell non-Hodgkin lymphoma (B-NHL), particularly if recently treated with anti-CD20 antibodies, are at risk of severe COVID-19 disease. Because studies evaluating humoral response to COVID-19 vaccine in these patients are lacking, recommendations regarding vaccination strategy remain unclear. The humoral immune response to BNT162b2 messenger RNA (mRNA) COVID-19 vaccine was evaluated in patients with B-NHL who received 2 vaccine doses 21 days apart and compared with the response in healthy controls. Antibody titer, measured by the Elecsys Anti-SARS-CoV-2S assay, was evaluated 2 to 3 weeks after the second vaccine dose. Patients with B-NHL (n = 149), aggressive B-NHL (a-B-NHL; 47%), or indolent B-NHL (i-B-NHL; 53%) were evaluated. Twenty-eight (19%) were treatment naïve, 37% were actively treated with a rituximab/obinutuzumab (R/Obi)-based induction regimen or R/Obi maintenance, and 44% had last been treated with R/Obi >6 months before vaccination. A seropositive response was achieved in 89%, 7.3%, and 66.7%, respectively, with response rates of 49% in patients with B-NHL vs 98.5% in 65 healthy controls (P < .001). Multivariate analysis revealed that longer time since exposure to R/Obi and absolute lymphocyte count ≥0.9 × 103/µL predicted a positive serological response. Median time to achieve positive serology among anti-CD20 antibody-treated patients was longer in i-B-NHL vs a-B-NHL. The humoral response to BNT162b2 mRNA COVID-19 vaccine is impaired in patients with B-NHL who are undergoing R/Obi treatment. Longer time since exposure to R/Obi is associated with improved response rates to the COVID-19 vaccine. This study is registered at www.clinicaltrials.gov as #NCT04746092.

Factors affecting mortality following myeloablative cord blood transplantation in adults: a pooled analysis of three international registries.

A retrospective analysis was conducted to examine factors affecting early mortality after myeloablative, single-unit cord blood transplantation (CBT) for hematological malignancies in adolescents and adults. Data were collected from the three main CBT registries pooling 514 records of unrelated, single, unmanipulated, first myeloablative allogeneic CBTs conducted in North America or Europe from 1995 to 2005, with an HLA match ≥ 4/6 loci, in patients aged 12-55. Overall 100-day, 180-day and 1-year survival (Kaplan-Meier method) were 56, 46 and 37%, respectively, with no significant heterogeneity across registries. Multivariate analysis showed cell dose < 2.5 × 107/kg (odds ratio (OR) 2.76, P < 0.0001), older age (P = 0.002), advanced disease (P = 0.02), positive CMV sero-status (OR 1.37 P = 0.11), female gender (OR 1.43, P = 0.07) and limited CBT center experience (< 10 records contributed, OR 2.08, P = 0.0003) to be associated with higher 100-day mortality. A multivariate model predictive of 1-year mortality included similar prognostic factors except female gender. Transplant year did not appear as a significant independent predictor. This is the first analysis to pool records from three major CBT registries in the United States and Europe. In spite of some differences in practice patterns, survival was remarkably homogeneous. The resulting model may contribute to better understanding factors affecting CBT outcomes.

Antitumor Activity of VB-111, a Novel Antiangiogenic Virotherapeutic, in Thyroid Cancer Xenograft Mouse Models.

VB-111 is an engineered antiangiogenic adenovirus that expresses Fas-c in angiogenic blood vessels and has previously been shown to have significant antitumor activity in vitro and in vivo in Lewis lung carcinoma, melanoma, and glioblastoma models. To evaluate the efficacy of VB-111 in thyroid cancer, we conducted in vivo xenograft nude mouse studies using multiple thyroid cancer-derived cell lines models. VB-111 treatment resulted in 26.6% (P = 0.0596), 34.4% (P = 0.0046), and 37.6% (P = 0.0249) inhibition of tumor growth in follicular, papillary and anaplastic thyroid cancer models, respectively. No toxicity was observed in any model. All tumor types showed a consistent and significant reduction of CD-31 staining (P < 0.05), reflecting a reduction of angiogenic activity in the tumors, consistent with the intended targeting of the virus. A phase 2 clinical trial of VB-111 in patients with advanced differentiated thyroid cancer is ongoing.

MS-CANE: a computer-aided instrument for neurological evaluation of patients with multiple sclerosis: enhanced reliability of expanded disability status scale (EDSS) assessment.

Kurtzke's EDSS remains the most widely-used measure for clinical evaluation of MS patients. However, several studies have demonstrated the limited reliability of this tool. We introduce a computerized instrument, MS-CANE (Multiple Sclerosis Computer-Aided Neurological Examination), for clinical evaluation and follow up of patients with multiple sclerosis (MS) and to compare its reliability to that of conventional Expanded Disability Status Scale (EDSS) assessment. We developed a computerized interactive instrument, based on the following principles: structured gathering of neurological findings, reduction of compound notions to their basic components, use of precise definitions, priority setting and automated calculations of EDSS and functional systems scores. An expert panel examined the consistency of MS-CANE with Kurtzke's specifications. To determine the effect of MS-CANE on the reliability of EDSS assessment, 56 MS patients underwent paired conventional EDSS and MS-CANE-based evaluations. The inter-observer agreement in both methods was determined and compared using the kappa statistic. The expert panel judged the tool to be compatible with the basic concepts of Kurtzke's EDSS. The use of MS-CANE increased the reliability of EDSS assessment: Kappa statistic was found to be 0.42 (i.e. moderate agreement) for conventional EDSS assessment versus 0.69 (i.e. substantial agreement) for MS-CANE (P=0.002). We conclude that the use of this tool may contribute towards a standardized and reliable assessment of EDSS. Within clinical trials, this could increase the power to detect effects, thus reducing trial duration and the cohort size required. Multiple Sclerosis (2000) 6 355 - 361

The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts.

BACKGROUND: No firm data are available on the natural history of idiopathic thrombocytopenic purpura (ITP) or on mortality rates or frequency of major bleeding episodes associated with this condition. The disease is thought to have a relatively benign course, despite the frequent occurrence of very low platelet counts. This prevailing conception often guides therapeutic decisions. OBJECTIVE: To estimate the bleeding risk of ITP involving persistent low platelet counts (<30 x 10(9)/L) and its impact on prognosis. DESIGN: Age-adjusted bleeding risk was derived from a pooled analysis of ITP clinical series based on a systematic literature search. The risk estimate was incorporated into a Markov model to determine its impact on prognosis. RESULTS: Seventeen case series complied with inclusion criteria, including 1,817 patients with ITP. There were 49 cases of fatal hemorrhage over an estimated 1,258 to 3,023 patient-years at risk. The rate of fatal hemorrhage before age adjustment was estimated at between 0.0162 and 0.0389 cases per patient-year. Age-adjusted rates were 0.004, 0.012, and 0.130 cases per patient-year for age groups younger than 40, 40 to 60, and older than 60 years, respectively. Predicted 5-year mortality rates ranged from 2.2% for patients younger than 40 years to 47.8% for those older than 60 years. A 30-year-old woman remaining thrombocytopenic due to ITP was predicted to lose 20.4 years (14.9 quality-adjusted life years) of her potential life expectancy. At age 70, predicted loss was 9.4 years (5.0 quality-adjusted life years). CONCLUSIONS: Idiopathic thrombocytopenic purpura with persistent low platelet counts carries a grave prognosis. Therefore, an active therapeutic approach in the clinical management of affected patients should be considered. In view of the significant potential implications of the model results, we call for initiating a well-designed prospective inception cohort study of patients with ITP.

Use of a clustered model to identify factors affecting hospital length of stay.

Predictive models have been used to identify factors that may prolong hospital length of stay (LOS). However, because predictors of LOS are collinear, the proportion of variance associated with each factor in a multivariate stepwise regression model may not reflect its mathematical contribution in explaining LOS. In an attempt to model factor contribution to LOS more realistically, we evaluated a clinically based clustered model. This model uses classes of candidate predictors, that is, patient attributes, adverse events, treatment modality, and health provider identity. Clusters of variables are permitted to enter into the model in a theoretically based predetermined sequence, so that the additional contribution of each cluster of factors can be assessed while the contribution of preceding factors is preserved. The clustered model was tested and compared with a free stepwise multivariate analysis in a cohort of patients undergoing prostatectomy for benign prostatic hypertrophy. We found that both models explained a similar proportion of the variance in LOS (56%-57%). However, some important differences were evident. Prostate size, associated with 12% of the variance in the clustered model, was not an independent predictor in the free model. A higher proportion of variance was associated with process variables, such as treatment modality in the free model. We conclude that use of a clustered model may facilitate more realistic assessment of the relative contribution of factors to LOS.

Two-dimensional outcome analysis as a guide for quality assurance of prostatectomy.

PURPOSE: To find outlier centers in different aspects of quality of care by comparing two different outcomes and adjusting to case mix in benign prostatic hypertrophy (BPH) patients undergoing prostatectomy. MATERIALS AND METHODS: An observational study including 537 consecutive patients undergoing prostatectomy for BPH in three medical centers in Israel between 1991 and 1992. Data were collected from medical charts and by a structured interview. Outcomes examined included immediate surgical complications and postoperative symptom effect level. Regression analysis was employed to adjust for case mix and to determine the additional contribution of medical centers. RESULTS: We found significant variability among centers in crude symptom effect, but not after case mix adjustment. An outlier was detected in both the crude and case mix-adjusted urological complications. CONCLUSIONS: Centers may differ with various outcomes. This may reflect variability in different levels of performance within different aspects of the process of care in prostatectomy procedures.

Factors affecting change in quality of life after prostatectomy for benign prostatic hypertrophy: the impact of surgical techniques.

PURPOSE: The impact of prostatectomy on quality of life was assessed in patients with benign prostatic hypertrophy (BPH) who were classified according to the expected benefit from surgical intervention. The relative impact of the 2 surgical techniques (open versus closed) on short-term quality of life was compared. MATERIALS AND METHODS: An observational study was done on 545 consecutive patients with BPH undergoing prostatectomy at 3 medical centers in Israel between 1991 and 1992. Repeated structured interviews preoperatively, and at 4 and 12 months postoperatively were performed, including 6 quality of life questionnaires evaluating BPH specific (symptom severity and symptom effect) and generic (activity, independence, mental health and health perception) parameters. In addition, the interviews consisted of socio-demographic data elements. Clinical details regarding severity of prostatic disease and co-morbidity were obtained from the medical charts. RESULTS: We found a correlation between postoperative change in symptom effect and in generic quality of life measures (r-0.11 to 0.20, p < 0.04). The postoperative decrease in the mean symptom effect score was 56% and 52% for severe and moderate preoperative levels, respectively. There was no decrease in the mean symptom effect score for the mild preoperative level (18% of these patients had postoperative deterioration). A secondary operation, and the combination of diabetes mellitus and poor activity level were risk factors for lack of improvement in patients with moderate preoperative symptom effects. We found that the impact of open prostatectomy on quality of life was similar to that of the closed technique after adjustment for patient attributes, except for those with an indwelling urinary catheter in whom an open operation was advantageous. CONCLUSIONS: In patients with BPH and mild symptom effects, and in subgroups of patients with moderate symptom effects surgery should not be recommended. Based on short-term measures of quality of life there is no justification for a preference between open and closed operations.