Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting.

Immunoglobulin heavy chain variable ( IGHV ) region mutations, TP53 mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify IGHV mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, p < 0.0001), and shorter OS (112 vs. 246 months, p < 0.0001) than the mutated CLL. IGHV3 was the most frequently used IGHV family (46%), followed by IGHV1 (30%) and IGHV4 (16%). IGHV5-51 and IGHV1-69 subfamilies were associated with poor prognosis, while IGHV4 and IGHV2 showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, IGHV2 gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, IGHV and TP53 mutations, IGHV gene families, and CK information could help clinicians in the decision-making process.

Hypermetabolic abdominal and cervical lymph nodes mimicking Hodgkin lymphoma relapse on FDG PET/CT after adenovirus-vectored COVID-19 vaccine.

Vaccine-associated hypermetabolic lymphadenopathy (VAHL) has been reported as a common post-vaccination side effect, especially with mRNA-based COVID-19 vaccines. Most VAHL cases present normal or enlarged regional lymph nodes close to the injection site, usually with mild-moderate FDG (18 F-Fluorodeoxyglucose) uptake on FDG positron emission tomography (PET)/CT. Here, we describe the case of a 33-year-old woman with past history of Classic Hodgkin Lymphoma (CHL) who underwent follow-up FDG PET/CT 3 days (d) after the first dose of the adenovirus-vectored Oxford-AstraZeneca COVID-19 vaccine. FDG PET/CT showed unexpected small hypermetabolic cervical and abdominal lymph nodes in the same location as at the onset of the disease, suggesting radiological relapse. Considering temporal relationship and other cases of VAHL, a new image was performed 2 months later, which revealed decreased lymph nodes and normalization of FDG uptake. This case illustrates that the possibility of a false-positive should always be considered by physicians in this new context, even when hypermetabolic lymph nodes appear far from the vaccination site.

Systemic thrombosis in a large cohort of COVID-19 patients despite thromboprophylaxis: A retrospective study.

BACKGROUND: Incidence of thrombotic events associated to Coronavirus disease-2019 (COVID-19) is difficult to assess and reported rates differ significantly. Optimal thromboprophylaxis is unclear. OBJECTIVES: We aimed to analyze the characteristics of patients with a confirmed thrombotic complication including inflammatory and hemostatic parameters, compare patients affected by arterial vs venous events and examine differences between survivors and non-survivors. We reviewed compliance with thromboprophylaxis and explored how the implementation of a severity-adjusted protocol could have influenced outcome. METHODS: Single-cohort retrospective study of COVID-19 patients admitted, from March 3 to May 3 2020, to the Infanta Leonor University Hospital in Madrid, epicenter of the Spanish outbreak. RESULTS: Among 1127 patients, 80 thrombotic events were diagnosed in 69 patients (6.1% of the entire cohort). Forty-three patients (62%) suffered venous thromboembolism, 18 (26%) arterial episodes and 6 (9%) concurrent venous and arterial thrombosis. Most patients (90%) with a confirmed thrombotic complication where under low-molecular-weight heparin treatment. Overt disseminated intravascular coagulation (DIC) was rare. Initial ISTH DIC score and pre-event CRP were significantly higher among non-survivors. In multivariate analysis, arterial localization was an independent predictor of mortality (OR = 18, 95% CI: 2.4-142, p < .05). CONCLUSIONS: Despite quasi-universal thromboprophylaxis, COVID-19 lead to a myriad of arterial and venous thrombotic events. Considering the subgroup of patients with thrombotic episodes, arterial events appeared earlier in the course of disease and conferred very poor prognosis, and an ISTH DIC score ≥ 3 at presentation was identified as a potential predictor of mortality. Severity-adjusted thromboprophylaxis seemed to decrease the number of events and could have influenced mortality. Randomized controlled trials are eagerly awaited.

Methotrexate-Induced Subacute Neurotoxicity Surrounding an Ommaya Reservoir in a Patient with Lymphoma.

BACKGROUND Intraventricular administration of methotrexate (MTX) using an Ommaya reservoir is a useful therapeutic maneuver for malignant CNS involvement in patients with hematological malignancies. MTX-induced subacute neurotoxicity is a rare complication that typically progresses with involvement of the basal ganglia. Local toxicity due to misplaced catheters has been described, although the impact of normally positioned catheters on toxicity is not clear. CASE REPORT We report the case of a 21-year-old man diagnosed with stage IV diffuse large B-cell lymphoma who experienced a central nervous system relapse. While receiving intraventricular MTX using an Ommaya reservoir and systemic MTX, he experienced sudden left-side hemiparesis. All diagnostic tests were negative except for altered MRI findings with FLAIR hyperintensity in the basal ganglia and restricted diffusion in the same location that followed the track of the Ommaya catheter. The syndrome resolved after administration of high-dose steroids, and the patient received subsequent MTX courses without recurrence. CONCLUSIONS MTX-induced neurotoxicity is a rare adverse event related to systemic and intrathecal administration of the drug. Many cases of Ommaya-related CNS symptoms have been described, although most were related to misplaced or malfunctioning catheters. Here we present a case of subacute MTX toxicity affecting the area around a correctly positioned catheter, suggesting that the catheter track could be more susceptible to MTX-induced toxicity.

Holter monitoring of central and peripheral temperature: possible uses and feasibility study in outpatient settings.

BACKGROUND: Conventional clinical thermometry has important limitations. A continuous monitoring of temperature may offer significant advantages, including the use of chronobiological and complexity analysis of temperature profile and eventually the identification of a "pre-febrile" pattern. OBJECTIVE: We present a clinical model designed to measure, store and/or transmit in real time a central and a peripheral temperature reading. The results of its use in a healthy, free-living population is reported. METHODS: Thirty subjects (15 women, 15 men, 20-70 years old), were monitored for 24 h while following their normal life. Temperatures were recorded every minute at the external auditory channel (EAC) and on the skin, at the intersection of the 5th intercostal space and the anterior axillary line. A Cosinor analysis and Approximate Entropy (ApEn) (m = 2, r = 0.15*SD, N = 180) were calculated for both temperatures. RESULTS: Median temperature was 35.55 degrees C [interquartile range (IR) 0.77 degrees C] in the external auditory channel (EAC) and 34.62 degrees C (IR 1.61) in the specified skin location. Median gradient between AEC and skin was 0.93 (IR 1.57). A circadian rhythm was present both in EAC and skin temperature, with a mean amplitude of 0.44 degrees C and an acrophase at 21:02 for the EAC and 0.70 degrees C and 00:42 for the skin. During the night there was a sizable increase in peripheral temperature, with a decrease in gradient and a loss of complexity in the temperature profile, most significantly in the peripheral temperature. CONCLUSIONS: Continuous monitoring of central and peripheral temperature may be a helpful tool in both ambulatory and admitted patients and may offer new approaches in clinical thermometry.

The route to diabetes: Loss of complexity in the glycemic profile from health through the metabolic syndrome to type 2 diabetes.

AIMS: In many physiologic systems, the evolution from health to disease correlates with a loss of complexity in the system's output. We analyze the difference in complexity of the glycemic profile in healthy volunteers (H), patients with the metabolic syndrome (MS), and patients with type 2 diabetes mellitus (DM). METHODS: We measured interstitial fluid glucose every 5 minutes for 3 days in 10 H, 10 MS, and 10 DM. Complexity of the glycemic profile was evaluated by means of detrended fluctuation analysis (DFA). Mean amplitude of glycemic excursions (MAGE) was also calculated. RESULTS: GLUCOSE PROFILE WAS MORE COMPLEX (LOWER DFA) IN HEALTHY SUBJECTS THAN IN PATIENTS WITH MS OR DM (MEAN DFA [SD]: H: 1.25 (0.10), MS: 1.39 (0.07), DM: 1.42 (0.10). ANOVA: F(2,27) = 9.94, p = 0.001). DM had also a less complex profile than MS, but this difference was not statistically significant. There was an inverse relation between complexity (lower DFA) and the number of MS defining criteria (rho = 0.55, p = 0.002) and between complexity and MAGE (r = 0.68, p < 0.0001). CONCLUSIONS: There is a progressive loss of complexity in the glycemic profile from health, through the metabolic syndrome to type 2 diabetes mellitus. This loss of complexity precedes hyperglycemia and correlates with other markers of disease progression. Complexity analysis may be a useful tool to track the evolution from health to type 2 diabetes. Furthermore, it may provide a way to measure glycemic control in real-life situations and has some distinct advantages over other conventional variability metrics.

Temperature curve complexity predicts survival in critically ill patients.

RATIONALE: Temperature curve complexity is inversely related to clinical status in critically ill patients. OBJECTIVE: To study if temperature curve complexity analysis predicts clinical outcome and how this test compares to other well-established conventional measures. METHODS: Temperature was continuously recorded in 50 patients with multiple organ failure. Time-series complexity was analyzed using hourly approximate entropy (ApEn) and detrended fluctuation analysis (DFA) values. Sequential Organ Failure Assessment (SOFA) score was obtained every other day, and correlation between complexity and SOFA values was evaluated. Differences in complexity between nonsurviving and surviving patients were likewise analyzed. Logistic regression models were calculated to predict outcome, and receiver operating characteristic (ROC) curves were plotted to compare the predictive power of complexity values versus SOFA. MEASUREMENTS AND RESULTS: There was good correlation between complexity results and clinical scores for each patient. Nonsurvivors exhibited lower complexity values than survivors (minimum ApEn = 0.230 vs. 0.378; maximum DFA = 1.636 vs. 1.507; mean ApEn = 0.459 vs. 0.596; mean DFA = 1.376 vs. 1.288; p < 0.001 for all comparisons). In the logistic regression model, a change of 0.1 in the minimum complexity resulted in severe increases in the odds ratio of dying (7.6-fold for ApEn, 5.4-fold for DFA). In terms of predicting outcome, there were no significant differences in the areas under the ROC curves for complexity values versus SOFA scores. CONCLUSIONS: Low levels of complexity in the temperature curve are indicators of poor prognosis in patients with multiple organ failure. The predictive ability of temperature curve complexity is similar to that of the SOFA score.