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This HEMATO-MADRID COVID-19 study assessed COVID-19 outcomes in 1818 hematologic cancer patients from February 2020 to October 2022 across different phases, including the Omicron period. Severe cases were more common in patients over 70 years with comorbidities or chronic lymphocytic leukemia. However, during the Omicron period, rates of severe illness reduced notably, especially among vaccinated individuals. Hospitalization, intensive care admissions, and overall mortality decreased in the Omicron phase compared to pre-Omicron, yet mortality rates in hospitalized patients remained high. Older age consistently correlated with higher mortality risk in both phases. Factors like prior stem cell transplantation, vaccination, and specific treatments were linked to improved survival rates among hematologic cancer patients facing COVID-19., A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64–2.87), with >1 comorbidity (2.44, 1.85–3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19–2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2–0.37) or BA.4/BA.5 (0.13, 0.08–0.19) periods and among patients vaccinated with one or two (0.51, 0.34–0.75) or three or four (0.22, 0.16–0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03–3.25) and Omicron (3.19, 95% CI 1.59–6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients., Depto. de Medicina, Fac. de Medicina, TRUE, pub, Descuento UCM

Producción Científica, This article studies some algebraic structures known as twisted-skew group rings in the context of public key cryptography. We first present some background related to these structures to then specifically introduce particular twisted-skew group rings and show how to utilize them as the underlying algebraic structure to build cryptographic protocols. We closely follow an incremental-like methodology to construct these protocols by putting parts together. As as result, we first introduce a key-agreement protocol and then generalize it to a group key-agreement protocol. We then proceed to construct a probabilistic public key encryption from our two-party key agreement and, finally, introduce a key-encapsulation mechanism from a well-known generic construction applied to probabilistic public encryption. Furthermore, we provide an in-depth security analysis for each cryptographic construction under new related algebraic assumptions and supply a proof-of-concept implementation for various candidate chosen groups., Fundación para la Promoción de la Investigación y la Tecnología del Banco de la República - (project 4649), Ministerio de Ciencia, Innovación/Agencia Estatal de Investigación (AEI)/10.13039/501100011033 y Unión Europea NextGenerationEU/PRTR - (Grant TED2021-130358B-I00)

From November 2014 to May 2017, 332 patients homogeneously treated with bortezomib, lenalidomide, and dexamethasone (VRD) induction, autologous stem cell transplant, and VRD consolidation were randomly assigned to receive maintenance therapy with lenalidomide and dexamethasone (RD; 161 patients) vs RD plus ixazomib (IRD; 171 patients). RD consisted of lenalidomide 15 mg/d from days 1 to 21 plus dexamethasone 20 mg/d on days 1 to 4 and 9 to 12 at 4-week intervals, whereas in the IRD arm, oral ixazomib at a dose of 4 mg on days 1, 8, and 15 was added. Therapy for patients with negative measurable residual disease (MRD) after 24 cycles was discontinued, whereas those who tested positive for MRD remained on maintenance with RD for 36 more cycles. After a median follow-up of 69 months from the initiation of maintenance, the progression-free survival (PFS) was similar in both arms, with a 6-year PFS rate of 61.3% and 55.6% for RD and IRD, respectively (hazard ratio, 1.136; 95% confidence interval, 0.809-1.603). After 2 years of maintenance, treatment was discontinued in 163 patients with negative MRD, whereas 63 patients with positive MRD continued with RD therapy. Maintenance discontinuation in patients tested negative for MRD resulted in a low progression rate (17.2% at 4 years), even in patients with high-risk features. In summary, our results show the efficacy of RD maintenance and support the safety of maintenance therapy discontinuation in patients with negative MRD at 2 years. This trial was registered at www.clinicaltrials.gov as #NCT02406144 and at EudraCT as 2014-00055410.

CRUE-CSIC (Acuerdos Transformativos 2022), Purpose: Clinical guidelines have been developed to standardize the management of mild traumatic brain injury (mTBI) in the emergency room, in particular the indication of brain CT scan and the use of blood biomarkers. The objective of this study was to determine the degree of adherence to guidelines in the management of these patients across four countries of Southern Europe. Methods: An electronic survey including structural and general management of mTBI patients and six clinical vignettes was conducted. In-charge physicians from France, Spain, Greece and Portugal were contacted by telephone and email. Diferences among countries were searched using an unconditional approach test on contingency tables. Results: One hundred and eighty eight physicians from 131 Hospitals (78 Spain, 36 France, 12 Greece and 5 Portugal) completed the questionnaire. There were diferences regarding the in-charge specialist across these countries. There was variability in the use of guidelines and their adherence. Spain was the country with the least guideline adherence. There was a global agreement in ordering a brain CT for patients receiving anticoagulation or platelet inhibitors, and for patients with seizures, altered consciousness, neurological defcit, clinical signs of skull fracture or signs of facial fracture. Aging was not an indication for CT in French centres. Loss of consciousness and posttraumatic amnesia were considered as indications for CT more frequently in Spain than in France. These fndings were in line with the data from the 6 clinical vignettes. The estimated use of CT reached around 50% of mTBI cases. The use of S100B is restricted to fve French centres. Conclusions: There were large variations in the guideline adherence, especially in the situations considered to order brain CT after mTBI., Depto. de Cirugía, Fac. de Medicina, TRUE, pub

[Purpose]: Patients with multiple myeloma (MM) may show patchy bone marrow (BM) infiltration and extramedullary disease. Notwithstanding, quantification of plasma cells (PCs) continues to be performed in BM since the clinical translation of circulating tumor cells (CTCs) remains undefined. [Patients and methods]: CTCs were measured in peripheral blood (PB) of 374 patients with newly diagnosed MM enrolled in the GEM2012MENOS65 and GEM2014MAIN trials. Treatment included bortezomib, lenalidomide, and dexamethasone induction followed by autologous transplant, consolidation, and maintenance. Next-generation flow cytometry was used to evaluate CTCs in PB at diagnosis and measurable residual disease (MRD) in BM throughout treatment. [Results]: CTCs were detected in 92% (344 of 374) of patients with newly diagnosed MM. The correlation between the percentages of CTCs and BM PCs was modest. Increasing logarithmic percentages of CTCs were associated with inferior progression-free survival (PFS). A cutoff of 0.01% CTCs showed an independent prognostic value (hazard ratio: 2.02; 95% CI, 1.3 to 3.1; P = .001) in multivariable PFS analysis including the International Staging System, lactate dehydrogenase levels, and cytogenetics. The combination of the four prognostic factors significantly improved risk stratification. Outcomes according to the percentage of CTCs and depth of response to treatment showed that patients with undetectable CTCs had exceptional PFS regardless of complete remission and MRD status. In all other cases with detectable CTCs, only achieving MRD negativity (and not complete remission) demonstrated a statistically significant increase in PFS. [Conclusion]: Evaluation of CTCs in PB outperformed quantification of BM PCs. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible MM.

[Purpose] Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG)., [Patients and methods] In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1,100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10−6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial., [Results] Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%., [Conclusions] The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM.

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate–severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.

There is limited information on the characteristics, pre-admission prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with coronavirus disease 2019 (COVID-19). This retrospective case series investigated characteristics and outcomes of 167 MM patients hospitalized with COVID-19 reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in Spain between March 1 and April 30, 2020. Outcomes were compared with a randomly selected contemporary cohort of 167 age-/sex-matched non-cancer patients with COVID-19 admitted at 6 participating hospitals. Common demographic, clinical, laboratory, treatment, and outcome variables were collected; specific disease status and treatment data were collected for MM patients. Among the MM and non-cancer patients, median age was 71 years and 57% of patients were male in each series, and 75% and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77% and 89% of patients and critical in 8% and 4%, respectively. Supplemental oxygen was required by 47% and 55% of MM and non-cancer patients, respectively, and 21%/9% vs 8%/6% required non-invasive/invasive ventilation. Inpatient mortality was 34% and 23% in MM and non-cancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors of inpatient mortality on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.