Using machine learning algorithms to determine the post-COVID state of a person by his rhythmogram

In this study we applyed machine-learning algorithms to determine the post-COVID state of a person. During the study, a marker of the post-COVID state of a person was found in the electrocardiogram data. We have shown that this marker in the patient's ECG signal can be used to diagnose a post-COVID state

Long-Term Results of the FOLL05 Trial Comparing R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Symptomatic Follicular Lymphoma

Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM (rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%), respectively. The hazard ratio for progression-free survival adjusted by FL International Prognostic Index 2 versus R-CVP was 0.73 for R-CHOP (95% CI, 0.54 to 0.98; P = .037) and 0.67 for R-FM (95% CI, 0.50 to 0.91; P = .009). The 8-year overall survival (OS) rate was 83% (95% CI, 79% to 87%), with no significant differences among study arms. Overall, we observed a higher risk of dying as a result of causes unrelated to lymphoma progression with R-FM versus R-CVP. Conclusion With an 83% 8-year OS rate, long-term follow-up of the FOLL05 trial confirms the favorable outcome of patients with advanced-stage FL treated with immunochemotherapy. The three study arms had similar OS but different activity and toxicity profiles. Patients initially treated with R-CVP had a higher risk of lymphoma progression compared with those receiving R-CHOP, as well as a higher risk of requiring additional therapy

Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.This project was supported by the “Fundação para a Ciência e Tecnologia”, program “Research 4 Covid-19 Apoio especial a projetos de implementação rápida para soluções inovadoras de resposta à pandemia de COVID-19”. It was also partially supported by each institution.info:eu-repo/semantics/publishedVersio

Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

BACKGROUND: Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. RESULTS: Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased "in situ transcriptomics" analysis-gene expression profiling of laser-captured TAMs to establish their activation signature in situ-we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. CONCLUSIONS: In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy

Follicular B-Cell Lymphoma Embedded in a Pulmonary Chondroid Hamartoma: A Case Report

Background: Here we report a rare case of concomitant pulmonary chondroid hamartoma and follicular non Hodgkin lymphoma in a 65-year-old woman with a history of 4-month nonspecific symptoms like fever, sweating and weight loss.Methods: Chest CT scan revealed a 12-mm nodule with relatively regular margins in the right middle lung field, adhering to the chest wall, with no involvement of hilar or mediastinal lymph nodes. The patient underwent thoracoscopy and resection of the lesion. Following histological exam and immunohistochemical staining, the patient was diagnosed as having follicular b-cell lymphoma embedded in a pulmonary chondroid hamartoma. FISH analysis was performed and showed the presence of typical follicular lymphoma chromosomal translocation t (14;18) (q32;q21).Conclusions: Following the final diagnosis, we decided not to refer the patient to chemotherapy and she enter watch and wait regimen with imaging control every 6 months. After 18 months, the chest X-ray and abdominal ultrasound are still negative with no evidence of recurrence.</p

The use of Deauville 5-point score could reduce the risk of false-positive fluorodeoxyglucose-positron emission tomography in the posttherapy evaluation of patients with primary bone lymphomas

Primary bone lymphoma (PBL) is a rare disease. Little is reported about response evaluation procedures in these patients. Our aim was to evaluate response to therapy according to fluorodeoxyglucose-positron emission tomography (FDG-PET) results, and in particular to test the Deauville 5-point scale as compared to the visual evaluation of FDG-PET scans in PBL. In this single-center study, we diagnosed 31 consecutive patients with PBL, of which 24 were evaluated with end-of-treatment FDG-PET. Patients' ages ranged from 19 to 82 years. Six patients were treated with chemotherapy, 24 with chemotherapy and radiotherapy, and one patient with radiotherapy alone. Six patients were affected by a pathological fracture. Four patients died within the range of 3 to 36 months after diagnosis. The average follow-up of the remaining patients was 70 (24–173) months. Overall survival was 87% at 5 years. The only positive prognostic factor was complete remission after chemotherapy. According to visual criteria, end-of-treatment FDG-PET was evaluated in 24 patients and it was positive in 11 (46%) and negative in 13 patients. We organized a retrospective central-blinded revision of end-of-therapy FDG-PET scans using the 5-point Deauville Score (DS). We reviewed 17 out of 24 patients and obtained the following results: at the end of therapy, 12 patients with DS score 2, three patients with DS score 3, one patient with DS score 4, and none with DS score 5. Considering that all the 24 patients achieved complete remission after treatment, visual interpretation produced 11/24 false-positive results, and DS interpretation produced 1/17 false-positive results, thus significantly reducing the number of false positives. In PBL, the final evaluation at the end of therapy with FDG-PET should be evaluated using Deauville 5-point scale in order to significantly reduce the risk of false-positive scans

Radiotherapy plus rituximab as first-line regimen for localized follicular lymphoma

Early-stage follicular lymphoma (FL) can be cured with involved-field radiotherapy (IF-RT); however, many patients relapse in non-irradiated areas. A combined association with chemotherapy could increase treatment efficacy, but toxic effects could be unacceptable. In vitro synergistic effect between rituximab (R) and RT has been observed, but clinical data are limited. We retrospectively analyzed 41 early-stage FL patients receiving R and IF-RT as first-line treatment. We administered R 375mg/m2weekly for four courses, before or after IF-RT (median dose 24â\u80\u89Gy). Primary outcome was PFS, secondary endpoints were CR rate, OS and safety. All patients achieved CR, after a median follow-up of 46 months only three patients relapsed after 18, 26 and 42 months; estimated 5-year PFS was 90%. We suggest R in association with IF-RT could represent a feasible first-line treatment option for early-stage FL and could increase efficacy without additional toxicity compared to available data about RT alone

Second Neoplasms in Italian Patients with Hairy Cell Leukemia after Treatment with Cladribine: A Multicenter Investigation and Literature Review

Simple Summary The prevalence of second neoplasms among patients with hairy cell leukemia (HCL) treated with cladribine is not negligible. Immunosuppression, high rate of cure, and aging may have a role in the pathogenesis of second cancers after HCL. We aimed to compare the risk of cancer between patients with HCL treated with cladribine and the general population.Abstract Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2-169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4-409.2 months), while the median OS from second cancer was 27.6 months (range: 1-117.8 months). The SIR was 0.86 (95% CI: 0.54-1.30) for males and 1.13 (95% CI: 0.36-2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm

Ibrutinib in patients with relapsed/refractory mantle cell lymphoma: a real-life, retrospective, multicenter trial on behalf of the "RTL" (regional Tuscan lymphoma network)

Background: Relapsed or refractory (R/R) mantle-cell lymphoma (MCL) patients have a poor prognosis and their management is challenging, in absence of a golden standard as salvage treatment. Bruton's tyrosine kinase inhibitor ibrutinib represents an effective treatment for R/R MCL patients. We investigated ibrutinib efficacy and safety in daily clinical practice, together with factors that could predict disease outcome. Patients and methods: We retrospectively analyzed 69 consecutive R/R MCL patients managed in 10 Tuscan onco-hematological centers. The treatment regimen consisted of oral, continuous, single-agent ibrutinib, maximum dosage of 560 mg once per day, until disease progression. Results: Overall response rate was 62.3%, with a CR rate of 39.1%. After a median follow-up of 15.6 months, 40/69 patients (58%) were alive, the main cause of death was progressive disease (PD, 22/69 cases, 31.9%). Median progression-free survival (PFS) and overall survival (OS) were 17 and 34.8 months. Inferior PFS was associated with &gt;1 prior line of therapy and B symptoms. Ibrutinib refractoriness was associated with inferior OS, median OS after ibrutinib failure was only 5 months. Discussion and conclusion: In this real-life setting ibrutinib treatment prolonged survival in R/R MCL patients, without unexpected adverse events. Patients receiving ibrutinib as 2nd line regimen had the most favorable outcome