A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia

We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count>32.0x103/microliter, 1 point. Low, intermediate and high-risk categories were established by recursive partitioning in a training cohort of 478 cases, and then validated in four independent cohorts of 144/395/540/322 cases, as well as in the composite validation cohort. Concordance indices were 0.75 in the training cohort and ranged from 0.63 to 0.74 in the four validation cohorts (0.69 in the composite validation cohort). These findings advocate potential application of our novel prognostic calculator to better stratify early-stage chronic lymphocytic leukemia, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 chronic lymphocytic leukemia being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemo-free era

CyberKnife for Recurrent Malignant Gliomas: A Systematic Review and Meta-Analysis

Background and Objective: Possible treatment strategies for recurrent malignant gliomas include surgery, chemotherapy, radiotherapy, and combined treatments. Among different reirradiation modalities, the CyberKnife System has shown promising results. We conducted a systematic review of the literature and a meta-analysis to establish the efficacy and safety of CyberKnife treatment for recurrent malignant gliomas. Methods: We searched PubMed, MEDLINE, and EMBASE from 2000 to 2021 for studies evaluating the safety and efficacy of CyberKnife treatment for recurrent WHO grade III and grade IV gliomas of the brain. Two independent reviewers selected studies and abstracted data. Missing information was requested from the authors via email correspondence. The primary outcomes were median Overall Survival, median Time To Progression, and median Progression-Free Survival. We performed subgroup analyses regarding WHO grade and chemotherapy. Besides, we analyzed the relationship between median Time To Recurrence and median Overall Survival from CyberKnife treatment. The secondary outcomes were complications, local response, and recurrence. Data were analyzed using random-effects meta-analysis. Results: Thirteen studies reporting on 398 patients were included. Median Overall Survival from initial diagnosis and CyberKnife treatment was 22.6 months and 8.6 months. Median Time To Progression and median Progression-Free Survival from CyberKnife treatment were 6.7 months and 7.1 months. Median Overall Survival from CyberKnife treatment was 8.4 months for WHO grade IV gliomas, compared to 11 months for WHO grade III gliomas. Median Overall Survival from CyberKnife treatment was 4.4 months for patients who underwent CyberKnife treatment alone, compared to 9.5 months for patients who underwent CyberKnife treatment plus chemotherapy. We did not observe a correlation between median Time To Recurrence and median Overall Survival from CyberKnife. Rates of acute neurological and acute non-neurological side effects were 3.6% and 13%. Rates of corticosteroid dependency and radiation necrosis were 18.8% and 4.3%. Conclusions: Reirradiation of recurrent malignant gliomas with the CyberKnife System provides encouraging survival rates. There is a better survival trend for WHO grade III gliomas and for patients who undergo combined treatment with CyberKnife plus chemotherapy. Rates of complications are low. Larger prospective studies are warranted to provide more accurate results

Neurosurgical Practice During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic: A Worldwide Survey

Background and Objective: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has consistently changed medical practice throughout specialties, regardless of their contribution in facing the disease itself. We surveyed neurosurgeons worldwide to investigate the situation they are experiencing. Methods: A 17-question, web-based survey was administered to neurosurgeons worldwide through the World Federation of Neurosurgical Societies and the Neurosurgery Cocktail from March 28 to April 5, 2020, by web link or e-mail invitation. Questions were divided into 3 subgroups: general information, health system organization, and institutional plans for the SARS-CoV-2 outbreak. Collected data were initially elaborated using SurveyMonkey software. Country-specific data were extracted from the World Health Organization website. Statistical analysis was performed using R, version 3.6.3. Results: Of the 446 respondents, most were from Italy (20%), India (19%), and Pakistan (5%). Surgical activity was significantly reduced in most centers (79%) and dedicated in-hospital routes were created for patients with SARS-CoV-2 (58%). Patient screening was performed only when there were symptoms (57%) and not routinely before surgery (18%). The preferred methods included a nasopharyngeal swab and chest radiograph. Health professionals were rarely screened (20%) and sometimes, even if SARS-CoV-2 positive, were asked to work if asymptomatic (26%). Surgical planning was changed in most institutions (92%), whereas indications were modified for nonurgent procedures (59%) and remained unchanged for subarachnoid hemorrhages (85%). Conclusions: Most neurosurgeons worldwide reported work reorganization and practices that respond to current international guidelines. Differences in practice might be related to the perception of the pandemic and significant differences in the health systems. Sharing data and experiences will be of paramount importance to address the present moment and challenges in the near future

Multiregional sequencing and circulating tumour DNA analysis provide complementary approaches for comprehensive disease profiling of small lymphocytic lymphoma

We aimed at molecularly dissecting the anatomical heterogeneity of small lymphocytic lymphoma (SLL), by analysing a cohort of 12 patients for whom paired DNA from a lymph node biopsy and circulating cells, as well as plasma-circulating tumour DNA (ctDNA) was available. Notably, the analyses of the lymph node biopsy and of circulating cells complement each other since a fraction of mutations (20·4% and 36·4%, respectively) are unique to each compartment. Plasma ctDNA identified two additional unique mutations. Consistently, the different synchronous sources of tumour DNA complement each other in informing on driver gene mutations in SLL harbouring potential prognostic and/or predictive value

Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia.

Fludarabine, cyclophosphamide, and rituximab (FCR) has represented a significant treatment advancement in chronic lymphocytic leukemia (CLL). In the new scenario of targeted agents, there is an increasing interest in identifying patients who gain the maximum benefit from FCR. In this observational multicenter retrospective analysis of 404 CLL patients receiving frontline FCR, the combination of three biomarkers that are widely tested before treatment (IGHV mutation status, 11q deletion and 17p deletion; available in 80% of the study cohort) allowed to identify a very low-risk category of patients carrying mutated IGHV genes but neither 11q or 17p deletion that accounted for 28% of all cases. The majority of very low-risk patients (71%) remained free of progression after treatment and their hazard of relapse decreased after 4 years from FCR. The life expectancy of very low-risk patients (91% at 5 years) was superimposable to that observed in the matched normal general population, indicating that neither the disease nor complications of its treatment affected survival in this favorable CLL group. These findings need a prospective validation and may be helpful for the design of clinical trials aimed at comparing FCR to new targeted treatments of CLL, and, possibly, for optimized disease management

Influenza (Flu)

Flu and you [Somali]CDC-INFO Pub ID 220580Prevention and ControlInfectious Diseas

Preliminary Validation of FoRCaSco: A New Grading System for Cerebral and Cerebellar Cavernomas

Objective: Surgical indications for cerebral cavernous malformations (CCMs) remain significantly center- and surgeon-dependent; available grading systems are potentially limited, as they do not include epileptologic and radiologic data. Several experienced authors proposed a new grading system for CCM and the first group of patients capable of providing its statistical validation was analyzed. Methods: A retrospective series of 289 CCMs diagnosed between 2008 and 2021 was collected in a shared anonymous database among 9 centers. The new grading system ranges from –1 to 10. For each patient with cortical and cerebellar cavernous malformations the grading system was applied, and a retrospective outcome analysis was performed. We proposed a score of 4 as a cutoff for surgical indication. Results: Operated patients with a score ≥4 were grouped with non-operated patients with a score <4, as they constituted the group that received correct treatment according to the new grading system. Patients with a score ≥4, who underwent surgery and had an improved outcome, were compared to patients with a score ≥4 who were not operated (P = 0.04), and to patients with a score <4 who underwent surgery (P < 0.001). Conclusions: This preliminary statistical analysis demonstrated that this new grading would be applicable in surgical reality. The cutoff score of 4 correctly separated the patients who could benefit from surgical intervention from those who would not. The outcome analysis showed that the treated patients in whom the grading system has been correctly applied have a better outcome than those in whom the grading system has not been applied