Publications by authors named "Aviv A"

Background: Telomere length (TL) has been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, with some studies finding associations with shorter TL and others with longer TL. In men, studies mostly report associations between shorter TL and sperm quality. To our knowledge, no studies have thus far investigated associations between TL and fecundability or the use of assisted reproductive technologies (ART).

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  • A phase II clinical study evaluated the effectiveness of a treatment combo (ibrutinib, bendamustine, and rituximab) in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma after stem cell transplants or in elderly patients.
  • The study showed a 49.1% overall response rate among patients who received at least one cycle, with better outcomes for those with relapsed disease (72.3%) versus refractory disease (37.8%).
  • Patients experiencing complete or partial responses had significantly longer median overall survival of 28.1 months, while common side effects included fatigue, diarrhea, and nausea, indicating that the treatment is both safe and effective for those needing potential transplantation.
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  • Autoimmune hepatitis (AIH) is a chronic liver disease where the immune system attacks liver cells, treated primarily with glucocorticoids and immunosuppressive drugs like azathioprine or MMF.
  • A study investigated the risk of developing non-Hodgkin lymphoma (NHL) in a large cohort of AIH patients over two decades, finding that NHL incidence was significantly higher than in the general population.
  • The study revealed that older patients (45 and up) were more affected, especially within the first seven years post-AIH diagnosis, but no link was found between NHL risk and the specific treatment drug used.
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  • * In the phase 2 trial, 20 patients received anti-CD19 CAR-T therapy combined with nivolumab, which was found to be safe; results showed an impressive 84% overall response rate and notable progression-free and overall survival rates at both 6 and 12 months.
  • * Although CAR-T cell expansion was similar in patients eligible and ineligible for nivolumab, those eligible had a higher proportion of specific beneficial immune cell types, indicating that further
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Telomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype.

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  • Polygenic scores (PGSs) of telomere length (TL) alleles explain a small percentage of TL variance in adults (4.5%) and are linked to aging-related diseases; this study aims to see how PGSs affect TL in newborns.
  • The research found that PGSs explained 6.6% of TL variance in parents and 5.2% in newborns, with a notable maternal effect of 214 bp in newborn girls, highlighting genetic influences on TL from early life.
  • The study suggests that understanding TL genetics can help identify susceptibility to aging diseases and notes a significant difference in how TL genes affect newborns based on sex, with more accurate results using Southern blotting for TL
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In women, shorter telomeres have been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, whereas other studies have reported the opposite. In men, studies mostly report associations between shorter telomeres and sperm quality. To our knowledge, no studies have thus far investigated the associations between TL and fecundability or the use of ART.

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Cancer is a consequence of stochastic (mutations, genetic, and epigenetic instabilities) and deterministic (evolutionary bottlenecks) events. Stochastic events are less amenable to prediction, whereas deterministic events yield more predictable results. The relative contribution of these opposing forces determines cancer predictability, which affects the accuracy of our prognostic predictions and is critical for treatment planning.

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Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n = 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon.

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Lymphocyte telomere length (TL) is highly variable and shortens with age. Short telomeres may impede TL-dependent T-cell clonal expansion with viral infection. As SARS-CoV-2 infection can induce prolonged and severe T-cell lymphopenia, infected adults, and particularly older adults with short telomeres, may display severe T-cell lymphopenia.

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Approximately 25 trillion erythrocytes (red blood cells) circulate in the bloodstream of an adult human, surpassing the number of circulating leukocytes (white blood cells) by a factor of about 1000. Moreover, the erythrocyte turnover rate accounts for approximately 76% of the turnover rate of all circulating blood cells. This simple math shows that the hematopoietic system principally spends its telomere length-dependent replicative capacity on building and maintaining the erythrocyte blood pool.

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Objectives: To compare end-of-life (EOL) care for solid tumor and hematologic malignancy (HM) patients.

Methods: We collected data on the last 100 consecutive deceased HM and 100 consecutive deceased solid tumor patients who died prior to June 1st 2020, treated at a single center. We compared demographic parameters, cause of death as ascertained by review of medical records by two independent investigators, and EOL quality indicators including: place of death, use of chemotherapy or targeted/biologic treatment, emergency department visits as well as hospital, inpatient hospice and Intensive Care Unit admissions and the time spent as inpatient over the last 30 days of life; mechanical ventilation and use of blood products during the last 14 days of life.

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Individuals with telomere biology disorders (TBDs) have very short telomeres, high risk of bone marrow failure (BMF), and reduced survival. Using data from TBD patients, a mean leukocyte Southern blot telomere length (TL) of 5 kilobases (kb) was estimated as the 'telomere brink' at which human survival is markedly reduced. However, the shortest telomere, not the mean TL, signals replicative senescence.

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The GALLIUM study showed a progression-free survival advantage of 7% in favor of obinutuzumab vs. rituximab-based immunochemotherapies as first-line therapy in follicular lymphoma (FL) patients. Yet, the toxicity appears to be increased with obinutuzumab-based therapy.

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Telomere length (TL) limits somatic cell replication. However, the shortest among the telomeres in each nucleus, not mean TL, is thought to induce replicative senescence. Researchers have relied on Southern blotting (SB), and techniques calibrated by SB, for precise measurements of TL in epidemiological studies.

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The age of allogeneic hematopoietic cell transplant (HCT) donors and their hematopoietic cell telomere length (TL) might affect recipients' outcomes. Our goals were to examine the possible effect of these donors' factors on the recipients' hematopoietic cell TL and quantify hematopoietic cell TL shortening in the critical first three-month post-HCT. We measured hematopoietic cell TL parameters in 75 recipient-donor pairs, from the Blood and Marrow Transplant Clinical Trials Network (protocol#1202), by Southern blotting (SB), the Telomeres Shortest Length Assay (TeSLA), and quantitative PCR (qPCR).

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Both myeloid cells, which contribute to innate immunity, and lymphoid cells, which dominate adaptive immunity, partake in defending against SARS-CoV-2. In response to the virus, the otherwise slow haematopoietic production supply chain quickly unleashes its preconfigured myeloid element, which largely resists a bullwhip-like effect. By contrast, the lymphoid element risks a bullwhip-like effect when it produces T cells and B cells that are specifically designed to clear the virus.

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Chronic lymphocytic leukemia (CLL), the most common adult's leukemia in the western world, is caused in 95% of the cases by uncontrolled proliferation of monoclonal B-lymphocytes. The complement system in CLL is chronically activated at a low level the classical pathway (CP). This chronic activation is induced by IgG-hexamers, which are formed after binding to alpha-2-macroglobulin (A2M).

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Early palliative care (EPC) significantly improves quality of life, symptoms, and satisfaction with care for patients with advanced cancer. International organizations have recognized and promoted the role of palliative care as a distinct specialty, advocating its involvement throughout the cancer trajectory. Although patients with haematologic malignancies (HMs) have a comparable symptom burden to patients with solid tumours, they face multiple barriers to EPC integration.

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Patients with Gaucher disease (GD) have been shown previously to carry an increased risk for cancer, most commonly multiple myeloma (MM). It is currently unknown whether treatment for GD has an effect on the prevention or amelioration of MM. We present the case of a 41-year-old patient simultaneously diagnosed with GD and smouldering MM.

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  • - This study investigates the genetic basis of telomere length (TL) across a diverse group of 109,122 individuals from various ancestries, marking the first such analysis that includes non-European populations.
  • - Researchers identified 59 significant genetic variants linked to TL, with 20 novel associations; these findings suggest that the genetic factors influencing TL are consistent across different populations.
  • - The analysis further revealed connections between telomere length and increased cancer risk, highlighting the potential implications of telomere genetics in age-related diseases.
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Background: Severe COVID-19 T-cell lymphopenia is more common among older adults and entails poor prognosis. Offsetting the decline in T-cell count during COVID-19 demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent.

Methods: We developed a model of TL-dependent T-cell clonal expansion capacity with age and virtually examined the relation of T-cell clonal expansion with COVID-19 mortality in the general population.

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