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Abstract Background The decision to allocate hospitals for the initial reception of hostages abducted on the October 7th Hamas attack introduced an array of unprecedented challenges. These challenges stemmed from a paucity of existing literature and protocols, lack of information regarding captivity conditions, and variability in hostage characteristics and circumstances. Objective To describe the rapid development, implementation and evaluation of the Hostage-ReSPOND protocol, a comprehensive trauma-informed procedure for the care of hostages, including young children, their caregivers and families, immediately following their release from prolonged captivity. Methods A multidisciplinary expert focus group conducted a comprehensive literature review to develop the ReSPOND protocol, consisting of: Readiness of teams via multifaceted trainings, utilizing live simulations and video debriefings; Specialized professional teams experienced in providing holistic trauma-informed care; Personalized care tailored to individualized and developmentally-informed needs; Optimal safety rooted in creating a secure environment and trauma-informed response to young children, adolescents, caregivers and families; and Navigating Discharge, through coordination with community-based care systems. Results A designated facility at the Children’s hospital was carefully prepared for receiving 29 hostages, aged 3.9–80 years, 28% under the age of 18. Implementation of the ReSPOND protocol, which prioritized holistic psychosocial interventions above urgent medical care, proved feasible and effective in managing the diverse and complex needs of returnees as per provider report. Finally, systemic assessment of returnee’s immediate and long-term mental health needs proved highly challenging. Conclusions There is currently no literature addressing the response to released hostages, especially those involving infants, young children and families within a children’s hospital facility. This study has the potential to fill a crucial gap in knowledge by introducing a novel protocol which could offer valuable insights for public health organizations tasked with providing acute care to diverse individuals and families experiencing extreme, multi-layered mass traumatization.

IntroductionEarly diagnosis of cancer enhances treatment planning and improves prognosis. Many masses presenting to veterinary clinics are difficult to diagnose without using invasive, time-consuming, and costly tests. Our objective was to perform a preliminary proof-of-concept for the HT Vista device, a novel artificial intelligence-based thermal imaging system, developed and designed to differentiate benign from malignant, cutaneous and subcutaneous masses in dogs.MethodsForty-five dogs with a total of 69 masses were recruited. Each mass was clipped and heated by the HT Vista device. The heat emitted by the mass and its adjacent healthy tissue was automatically recorded using a built-in thermal camera. The thermal data from both areas were subsequently analyzed using an Artificial Intelligence algorithm. Cytology and/or biopsy results were later compared to the results obtained from the HT Vista system and used to train the algorithm. Validation was done using a "Leave One Out" cross-validation to determine the algorithm's performance.ResultsThe accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the system were 90%, 93%, 88%, 83%, and 95%, respectively for all masses.ConclusionWe propose that this novel system, with further development, could be used to provide a decision-support tool enabling clinicians to differentiate between benign lesions and those requiring additional diagnostics. Our study also provides a proof-of-concept for ongoing prospective trials for cancer diagnosis using advanced thermodynamics and machine learning procedures in companion dogs.

Abstract A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL.

IntroductionEarly diagnosis of cancer enhances treatment planning and improves prognosis. Many masses presenting to veterinary clinics are difficult to diagnose without using invasive, time-consuming, and costly tests. Our objective was to perform a preliminary proof-of-concept for the HT Vista device, a novel artificial intelligence-based thermal imaging system, developed and designed to differentiate benign from malignant, cutaneous and subcutaneous masses in dogs.MethodsForty-five dogs with a total of 69 masses were recruited. Each mass was clipped and heated by the HT Vista device. The heat emitted by the mass and its adjacent healthy tissue was automatically recorded using a built-in thermal camera. The thermal data from both areas were subsequently analyzed using an Artificial Intelligence algorithm. Cytology and/or biopsy results were later compared to the results obtained from the HT Vista system and used to train the algorithm. Validation was done using a “Leave One Out” cross-validation to determine the algorithm's performance.ResultsThe accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the system were 90%, 93%, 88%, 83%, and 95%, respectively for all masses.ConclusionWe propose that this novel system, with further development, could be used to provide a decision-support tool enabling clinicians to differentiate between benign lesions and those requiring additional diagnostics. Our study also provides a proof-of-concept for ongoing prospective trials for cancer diagnosis using advanced thermodynamics and machine learning procedures in companion dogs.

Ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor (BTKi), is a commonly deployed therapeutic option for previously untreated and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia (CLL). The use of ibrutinib is, however, partially limited by off-target side effects. Zanubrutinib (zanu) is a second-generation BTKi with enhanced target selectivity and occupancy of the kinase binding site. The SEQUOIA study showed that zanu significantly prolonged progression-free survival (PFS) when compared to bendamustine–rituximab (BR) in treatment-naive CLL patients. More recently, data from the phase III ALPINE trial, which directly compared zanu with ibrutinib, demonstrated that zanu’s advantages include an improved safety profile as well as enhanced clinical efficacy. Based on the results of the SEQUOIA and ALPINE pivotal trials, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) licensed zanu for the treatment of patients with CLL or small lymphocytic lymphoma (SLL) in January 2023. The updated (v2.2023) National Comprehensive Cancer Network (NCCN) guidelines and the most recent German CLL algorithm suggest that zanu may replace first-generation BTKis as a preferred therapeutic option for patients with CLL/SLL due to its increased selectivity for the kinase binding site, improved therapeutic efficacy, and favorable toxicity profile. Some drug class-related characteristics such as drug resistance, low complete remission (CR) rates, and indefinite treatment duration still remain with zanu, and the results from recently completed and ongoing fixed-duration clinical trials, combining zanu with an anti-BCL2 agent, are eagerly awaited with the possible promise of a reduced treatment duration and lower financial burden.

BackgroundChronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma.MethodsWe randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee.ResultsThe median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P

Patients with chronic lymphocytic leukemia (CLL) have a suboptimal humoral response to vaccination. Recently, BNT162b2, an mRNA COVID-19 vaccine with a high efficacy of 95% in immunocompetent individuals, was introduced. We investigated the safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with CLL from nine medical centers in Israel, Overall 400 patients were included, of whom 373 were found to be eligible for the analysis of antibody response. The vaccine appeared to be safe and only grade 1-2 adverse events were seen in 50% of the patients. Following the second dose, an antibody response was detected in 43% of the cohort. Among these CLL patients, 61% of the treatment-na ve patients responded to the vaccine, while responses developed in only 18% of those with ongoing disease, 37% of those previously treated with a BTK inhibitor and 5% of those recently given an anti-CD20 antibody. Among patients treated with BCL2 as monotherapy or in combination with anti-CD20, 62% and 14%, respectively, developed an immune response. There was a high concordance between neutralizing antibodies and positive serological response to spike protein. Based on our findings we developed a simple seven-factor score including timing of any treatment with anti-CD20, age, treatment status, and IgG, IgA, IgM and hemoglobin levels. The sum of all the above parameters can serve as a possible estimate to predict whether a given CLL patient will develop sufficient antibodies. In conclusion, the BNT162b2 mRNA COVID-19 vaccine was found to be safe in patients with CLL, but its efficacy is limited, particularly in treated patients.

In the modern era of Chronic Lymphocytic Leukemia (CLL) targeted therapy, the loss of p53 function due to genetic abnormalities remains a significant challenge. This is because even targeted agents, which are currently the mainstay of treatment for CLL, do not directly target p53 or restore its disrupted pathway. Consequently, resistance to therapy and unfavorable clinical outcomes often accompany these p53‐related abnormalities. An essential goal of future clinical research should be to address the ostensibly "undruggable" p53 pathway. Currently, multiple therapeutic approaches are being explored to tackle TP53 dysfunction and improve outcomes in high‐risk CLL. These approaches include the use of oncoprotein murine double minute 2 inhibitors, small‐molecule p53 reactivators, exportin 1 (XPO1) inhibitors, and ataxia‐telangiectasia mutated and Rad3‐related (ATR) inhibitors. Combinations of these p53‐targeting strategies, along with established novel therapies such as B‐cell receptor or B‐cell lymphoma‐2 (BCL‐2) inhibitors, may shape the future of therapeutic trials in this challenging‐to‐treat disease. [ABSTRACT FROM AUTHOR]

Abstract Background The overreliance on dwindling fossil fuel reserves and the negative climatic effects of using such fuels are driving the development of new clean energy sources. One such alternative source is hydrogen (H2), which can be generated from renewable sources. Parageobacillus thermoglucosidasius is a facultative anaerobic thermophilic bacterium which is frequently isolated from high temperature environments including hot springs and compost. Results Comparative genomics performed in the present study showed that P. thermoglucosidasius encodes two evolutionary distinct H2-uptake [Ni-Fe]-hydrogenases and one H2-evolving hydrogenases. In addition, genes encoding an anaerobic CO dehydrogenase (CODH) are co-localized with genes encoding a putative H2-evolving hydrogenase. The co-localized of CODH and uptake hydrogenase form an enzyme complex that might potentially be involved in catalyzing the water-gas shift reaction (CO + H2O → CO2 + H2) in P. thermoglucosidasius. Cultivation of P. thermoglucosidasius DSM 2542T with an initial gas atmosphere of 50% CO and 50% air showed it to be capable of growth at elevated CO concentrations (50%). Furthermore, GC analyses showed that it was capable of producing hydrogen at an equimolar conversion with a final yield of 1.08 H2/CO. Conclusions This study highlights the potential of the facultative anaerobic P. thermoglucosidasius DSM 2542T for developing new strategies for the biohydrogen production.