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Bushra Abdallah, Mariah Arif, Maryam Al-Malki, Razan Hourani, Tamader Al-Maadeed, Nidal Khodr, Ghaith Al-Kuwari, Mashael Al-Siddiqi, Tanya Kane, Tawanda Chivese Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, QatarCorrespondence: Tawanda Chivese, Department of Population Medicine, College of Medicine, QU Health, Qatar University, P O BOX 2713, Doha, Qatar, Tel +974 4403 7831, Email tchivese@qu.edu.qaObjective: This research investigated the association between childhood and adulthood tobacco smoking exposure with ulcerative colitis (UC) and Crohn’s disease (CD) in Qatar.Study Design and Setting: In this case-control study, CD and UC cases were matched to controls of the same age and sex. The associations between UC and CD and childhood passive smoking and adulthood active smoking were assessed using conditional multivariable logistic regression.Results: A total of 89 CD cases, median age of 37 years (IQR 29– 47), and 362 UC cases, median age of 35 years (IQR 28– 44), and equal numbers of controls were included. After multivariable logistic regression, CD was associated with higher odds of being a current smoker (OR 2.51, 95% CI 0.85– 7.37, p=0.095), with weak evidence against the null hypothesis. This association was more pronounced in women, where CD was associated with both adulthood current smoking (OR 42.71, 95% CI, 1.17– 1559.57, p=0.041), and childhood smoking exposure (OR 8.23, 95% CI, 1.36– 49.66, p=0.021). In males, no associations were observed between CD and the smoking exposures. No associations were observed between UC and both smoking variables.Conclusion: In Qatar, adulthood tobacco smoking appears to increase the odds of CD. Further, our findings suggest that both childhood and adulthood cigarette smoke exposure may possibly have a detrimental effect on the odds of CD in females but not in males, although further research is needed.Keywords: Crohn’s disease, ulcerative colitis, inflammatory bowel disease, smoking, childhood passive smoking, Middle East and North Africa

Atypical bacteria grow very slowly in culture or they do not grow at all leading to delays in detection and diagnosis. PCR multiplex was performed on template DNAs extracted from seventy three collected specimens. Thirty seven showed positive indication for the presence of bacterial infection. The incidence of Mycoplasma pneumoniae, Chlamydia pneumonia and Legionella pneumophila as a single infecting agent was 31.5%, 27.5% and 20 % respectively. Dual agent infection caused by Mycoplasma + Chlamydia, Mycoplasma + Legionella and Legionella + Chlamydia was 24%, 20% and 15% respectively. Triple agent infection caused by Legionella + Mycoplasma + Chlamydia was 17.5%. The etiology of the infection was M. pneumoniae, L. pneumophila or C. pneumoniae as a single etiology or in combination of two or three organisms.

Anion exchanger (Amberlite IRA-420; AMB) has been used in the removal of permanganate ions from potassium permanganate contaminated water. Operational conditions such as permanganate concentration, adsorption time, adsorption temperature, adsorption pH, agitation speed, and finally adsorbent dosage have been investigated, and its impact on the removal process efficiency has been presented. Moreover, the kinetic and equilibrium results obtained for permanganate ions sorption with different initial concentrations onto AMB were analyzed. Kinetic modeling analysis with three different types of kinetic sorption models (pseudo-first-order, pseudo-second-order, and simple Elovich models) was applied to simulate the permanganate ions sorption data. The analysis of the kinetic data indicated that the sorption was a second-order process. An ion-exchange mechanism may have existed in the permanganate ions-sorption process with AMB. The permanganate ions uptake by AMB was quantitatively evaluated with equilibrium sorption isotherms. To describe the isotherms mathematically, the experimental data of the removal equilibrium were correlated with the Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich (D-R) isotherm models, and the applicability of these isotherm equations to the sorption systems was compared by the correlation coefficients. The maximum sorption capacities, determined from the Langmuir isotherm was 20.54 mg/g at 25°C. Moreover, diffusion mechanism of permanganate ions was described by different adsorption diffusion models. The diffusion rate equations inside particulate of Dumwald-Wagner and intraparticle models were used to calculate the diffusion rate. The actual rate-controlling step involved in the permanganate ions sorption process was determined by further analysis of the sorption data applying the kinetic expression given by Boyd. [ABSTRACT FROM AUTHOR]

Dammam City was affected by strong earthquakes from Zagros fold-fault belt of subduction zone. These distant earthquakes of magnitude greater than 6.0 produced great site effects on the sedimentary layers that in turn significantly influenced earthquake ground motions in the area. Site effect in terms of fundamental frequency ( f) has been estimated using microtremor measurements and borehole geotechnical data. Microtremor measurements were carried out at 113 sites distributed well through Dammam City. These sites present two peaks of f. The 1st peak ranges from 0.25 to 3.0 Hz, while the 2nd one ranges from 4 to 8 Hz. The 1st peak is due to the impedance contrast between the limestone and the overlying sediments, while the 2nd peak originated from the upper most surface sediments and the underlying layer. Tests to ensure that natural origin of these peaks were conducted. The northwestern and southeastern parts of Dammam City have the lowest f indicating great thickness of sediments. Whereas, the rest zones have higher f values illustrating shallow depths of bedrock. In addition, the geotechnical data in terms of shear wave velocity, density, and soil thickness of different layers have been compiled at 30 boreholes where f and average shear wave velocities up to 30 m depth have been calculated. Results of borehole data clarified that the fundamental frequencies range between 2.9 and 7 Hz, which correlated well with that of microtremor measurements. These results can be used for land use planning, preparedness purposes through improving of building design code in Dammam City. [ABSTRACT FROM AUTHOR]

Number of vehicles registered and population growth are predictors for traffic injuries and fatalities. Qatar has witnessed during the last two decades considerable increase both in terms of population growth and vehicle registration. Ever since 1940s many researchers have tried to define a model that could be implemented to predict road traffic fatalities anywhere in the world. To this date there is no universal model that could accurately predict traffic fatalities in any country due to the existence of difference in environmental and infrastructures. The objective of this paper was to estimate the road traffic fatalities using regression analyses formula and compare the results with Smeed's equation for estimating fatalities. The study also aimed to examine the relationship between economic growth and traffic fatalities. We have used the data on Gross Domestic Product, vehicles, population and fatalities during the period from 1990 to 2006 of the State of Qatar and analysed the data for fatalities estimate using both the equations of regression and Smeed to find the error. The results of this study show that Smeed's formula leads to a remarkably higher estimation of road traffic fatalities in Qatar than the estimate fatality by regression. The fatality estimate has been consistently rising over the past two decades. The figure shows that there is a positive association between the economic growth and traffic fatalities. In conclusion, the current study has shown that the regression analysis estimate gives better and reliable road traffic fatalities than Smeed's fatality estimation in Qatar. In Qatar, it appeared that GDP growth is associated with a rise in traffic deaths. [ABSTRACT FROM AUTHOR]

In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil. METHODS In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide–tacrolimus–mycophenolate mofetil (experimental prophylaxis) or tacrolimus–methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause. RESULTS In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P=0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups. CONCLUSIONS Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide–tacrolimus–mycophenolate mofetil than among those who received tacrolimus–methotrexate. [ABSTRACT FROM AUTHOR]

CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has led to unprecedented rates of complete remission (CR) in children and adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), yet the majority of adults relapse after initial response. One proposed method to extend the durability of remission in adults following response to CAR-T therapy is consolidation with allogeneic hematopoietic cell transplantation (alloHCT). Considering the limited published data for the utility of post CAR-T therapy consolidative alloHCT in r/r B-ALL, especially data related to patients receiving a second alloHCT, we sought to describe outcomes of patients with r/r B-ALL at our institution who received their first or second alloHCT following response to CAR-T therapy. We performed a retrospective analysis of adult patients with r/r B-ALL who responded to either investigational or standard of care (SOC) CD19-targeted CAR-T therapy and underwent consolidation with alloHCT while in CR without interim therapy. We identified 45 patients, of whom 26 (58%) and 19 (42%) received their first and second alloHCT as consolidation post CAR-T therapy, respectively. The median age was 31 years (range: 19-67) and 31 (69%) patients were Hispanic. Ph-like was the most common genetic subtype and comprised over half of cases (53%; n = 24). The median number of prior therapies pre-transplant was 5 (range: 2-7), and disease status at the time of alloHCT was CR1, CR2 or ≥CR3 in 7 (16%), 22 (49%) and 16 (35%) patients, respectively. The median time from CAR-T therapy until alloHCT was 93 (range: 42-262) days. The conditioning regimen was radiation-based myeloablative (MAC) in 22 (49%) patients. With a median follow-up of 2.47 years (range: 0.13-6.93), 2-year overall survival (OS), relapse free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 57.3% (95% CI: 0.432-0.760), 56.2% (95% CI: 0.562-0.745), 23.3% (95% CI: 0.13-0.42), and 20.4% (95% CI: 0.109-0.384), respectively. Two-year OS (52% vs. 68%, P = .641), RFS (54% vs. 59%, P = .820), CIR (33.5% vs. 8.5%, P = .104), and NRM (12.5% vs. 32.2%, P = .120) were not significantly different between patients who underwent their first vs. second transplant, respectively. In univariate analysis, only Ph-like genotype was associated with inferior RFS (P = .03). AlloHCT post CAR-T response is associated with a relatively low early mortality rate and encouraging survival results in high-risk adults with r/r B-ALL, extending to the second alloHCT for fit and eligible patients., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Continuing antifungal prophylaxis (AFPx) to prevent invasive mold infections (IMIs) in recipients of allogeneic hematopoietic cell transplantation (alloHCT) after primary hospital discharge from alloHCT admission varies among transplant centers despite recommendations to continue prophylaxis through day +75. Characteristics driving AFPx prescribing at hospital discharge and outcomes are unknown., Methods: In this retrospective analysis, we reviewed patients continuing AFPx vs no AFPx at hospital discharge. We included patients with a hospital stay ≥7 days and ≤40 days. We excluded patients with a history of IMI prior to alloHCT, new IMI during admission, or death prior to discharge. Our primary objective was incidence of probable or proven IMI per the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Our secondary objectives were nonrelapse mortality at day +100, overall survival at day +100, and characteristics driving AFPx discontinuation at hospital discharge., Results: Of the 430 patients identified, 387 met inclusion criteria. At discharge, 56% (217/387) continued AFPx, and 44% (170/387) had no AFPx. At day +100, 3 probable IMI cases occurred in the group with continued AFPx vs 1 probable IMI case in the no-AFPx group (no proven IMI). Univariate analysis showed no difference in cumulative incidence of probable IMI ( P = .440), nonrelapse mortality ( P = .072), and overall survival ( P = .855) between groups. Multivariable logistic regression demonstrated that patients were less likely to continue AFPx if they had a diagnosis other than acute myeloid leukemia, a length of stay ≤30 days, acute graft-vs-host disease grade 0 or 1, and corticosteroid use ≤5 days., Conclusions: There was no difference in probable IMI at day +100 after alloHCT based on continuing vs discontinuing AFPx at hospital discharge after alloHCT admission supporting a risk-adapted prophylaxis approach., Competing Interests: Potential conflicts of interest. S. J. F. serves as an Science Advisory Board member of Allogene Therapeutics, Lixte Bio Board of Directors, Science Advistory Board, Director, T-Cell Therapeutics Research Laboratories and Hematologic Malignancies Research Institute, City of Hope, Mustang CAR-T cell consultant. R. T. serves as a consultant for Merck and Karius advisory boards. R. N. serves as a consultant for Omeros Corporation, Ono Pharmaceutical, and Pfizer. S. S. D. is a consultant/advisory board member for Merck, Ansun Biopharma, Allovir, Aseptiscope Inc, Takeda, and Karius Research; has received grant support (paid to institution) from Merck, Allovir, Karius, Ansun Biopharma, and F2G; and is on the speakers bureau for Karius, Takeda, and Astellas. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Therapy-related acute lymphoblastic leukaemia (tr-ALL) is a disease entity attributed to previous exposure to chemotherapy and/or radiation for antecedent malignancy. There is observed female predominance for tr-ALL, likely due to high prevalence and excellent curable rate for non-metastatic breast cancer as well as the frequent use of carcinogenic agents as part of adjuvant therapy. Here, we reviewed 37 women with diagnosis of ALL following breast cancer treatment with focus on cytogenetic categorization. Philadelphia chromosome positivity (Ph+), KMT2A alterations and other cytogenetic change groups were observed in 32%, 22% and 46% of patients respectively. Median overall survival (OS) and relapse-free survival (RFS) were 19.4 and 12.9 months, overall while both OS and RFS were superior in tr-ALL with Ph+ disease compared to KMT2Ar and other cytogenetics respectively. Seventeen (45.9%) patients underwent consolidative allogeneic haematopoietic cell transplantation (alloHCT) in CR1 out of which 4 (24%) relapsed following transplant. Both OS and RFS were superior in the KMT2Ar cytogenetics group following alloHCT. Ph chromosome represents the largest genetic entity of tr-ALL following breast cancer therapy, and it may be associated with superior survival outcomes while KMT2Ar may be associated with poorer outcomes that can perhaps be mitigated by alloHSCT., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Abstract: Graft-versus-host disease (GVHD) is a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Algorithms containing either the gastrointestinal (GI) GVHD biomarker amphiregulin (AREG) or a combination of 2 GI GVHD biomarkers (suppressor of tumorigenicity-2 [ST2] + regenerating family member 3 alpha [REG3α]) when measured at GVHD diagnosis are validated predictors of NRM risk but have never been assessed in the same patients using identical statistical methods. We measured the serum concentrations of ST2, REG3α, and AREG by enzyme-linked immunosorbent assay at the time of GVHD diagnosis in 715 patients divided by the date of transplantation into training (2004-2015) and validation (2015-2017) cohorts. The training cohort (n = 341) was used to develop algorithms for predicting the probability of 12-month NRM that contained all possible combinations of 1 to 3 biomarkers and a threshold corresponding to the concordance probability was used to stratify patients for the risk of NRM. Algorithms were compared with each other based on several metrics, including the area under the receiver operating characteristics curve, proportion of patients correctly classified, sensitivity, and specificity using only the validation cohort (n = 374). All algorithms were strong discriminators of 12-month NRM, whether or not patients were systemically treated (n = 321). An algorithm containing only ST2 + REG3α had the highest area under the receiver operating characteristics curve (0.757), correctly classified the most patients (75%), and more accurately risk-stratified those who developed Minnesota standard-risk GVHD and for patients who received posttransplant cyclophosphamide-based prophylaxis. An algorithm containing only AREG more accurately risk-stratified patients with Minnesota high-risk GVHD. Combining ST2, REG3α, and AREG into a single algorithm did not improve performance., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The efficient detection of the foodborne pathogen Salmonella typhimurium has historically been hampered by the constraints of traditional methods, characterized by protracted culture periods and intricate DNA extraction processes for PCR. To address this, our research innovatively focuses on the crucial and relatively uncharted virulence factor, the Outer Membrane Protein D (OmpD) in Salmonella typhimurium . By harmoniously integrating the power of virtual screening and site-directed mutagenesis, we unveiled aptamers exhibiting marked specificity for OmpD. Among these, aptamer 7ZQS stands out with its heightened binding affinity. Capitalizing on this foundation, we further engineered a repertoire of mutant aptamers, wherein APT6 distinguished itself, reflecting unmatched stability and specificity. Our rigorous validation, underpinned by cutting-edge bioinformatics tools, amplifies the prowess of APT6 in discerning and binding OmpD across an array of Salmonella typhimurium strains. This study illuminates a transformative approach to the prompt and accurate detection of Salmonella typhimurium , potentially redefining boundaries in applied analytical chemistry and bolstering diagnostic precision across diverse research and clinical domains.Communicated by Ramaswamy H. Sarma.

Entropy-engineered materials are garnering considerable attention owing to their excellent mechanical and transport properties, such as their high thermoelectric performance. However, understanding the effect of entropy on thermoelectrics remains a challenge. In this study, we used the PbGeSnCd x Te 3+ x family as a model system to systematically investigate the impact of entropy engineering on its crystal structure, microstructure evolution, and transport behavior. We observed that PbGeSnTe 3 crystallizes in a rhombohedral structure at room temperature with complex domain structures and transforms into a high-temperature cubic structure at ∼373 K. By alloying CdTe with PbGeSnTe 3 , the increased configurational entropy lowers the phase-transition temperature and stabilizes PbGeSnCd x Te 3+ x in the cubic structure at room temperature, and the domain structures vanish accordingly. The high-entropy effect results in increased atomic disorder and consequently a low lattice thermal conductivity of 0.76 W m -1 K -1 in the material owing to enhanced phonon scattering. Notably, the increased crystal symmetry is conducive to band convergence, which results in a high-power factor of 22.4 μW cm -1 K -1 . As a collective consequence of these factors, a maximum ZT of 1.63 at 875 K and an average ZT of 1.02 in the temperature range of 300-875 K were obtained for PbGeSnCd 0.08 Te 3.08 . This study highlights that the high-entropy effect can induce a complex microstructure and band structure evolution in materials, which offers a new route for the search for high-performance thermoelectrics in entropy-engineered materials.

Several epidemiological studies demonstrated that coxsackievirus B4 (CVB4) causes viral pancreatitis and can ultimately result in type 1 diabetes mellitus (T1D). Prevention of CVB4 infection is therefore highly desirable. There is currently no vaccine or antiviral therapeutic reagent in clinical use. VLP are structurally similar to native virus particles and therefore are far better immunogens than any other subunit vaccines. Many studies have shown the potential of capsid protein VP1 on providing protective effects from different viral strains. In this study, we contributed towards the development of a CVB4 VLP-based vaccine from the total protein VP1 of the diabetogenic CVB4E2 strain and assessed whether it could induce a protective immunity against both the wild-type CVB4JBV and the diabetogenic CVB4E2 strains in mice model. Serum samples, taken from mice immunized with VLP, were assayed in vitro for their anti-CVB4 neutralizing activity and in vivo for protective activity. We show that VLP vaccine generates robust immune responses that protect mice from lethal challenges. Results demonstrate that CVB4 VP1 capsid proteins expressed in insect cells have the intrinsic capacity to assemble into non-infectious VLP, which afforded protection from CVB4 infection to mice when used as a vaccine.

Total marrow irradiation (TMI) is an alternative to total body irradiation (TBI) as a component of the conditioning regimen for hematopoietic cell transplantation (HCT), offering the ability to deliver more targeted doses and facilitating organ-sparing. The organ-sparing effect of TMI is theorized to decrease the risk of complications associated with radiation, including subsequent malignant neoplasms (SMNs), while allowing for dosage escalation to improve oncologic outcomes. The purpose of this study was to compare SMNs rates among patients treated with TBI- or TMI-based conditioning regimens. We hypothesized that TMI would yield a rate of SMNs comparable to, if not lower than, TBI. A retrospective matched-pair analysis of patients who underwent allogeneic HCT and received either TBI- or TMI-based conditioning regimens to a total dose of 12 to 20 Gy was performed. A total of 171 patients received TMI-based conditioning and 171 received TBI-based conditioning, matched based on age, sex, diagnosis, and length of follow-up. SMNs were identified from an established long-term follow-up protocol, our institutional cancer registry, and the California Cancer Registry. There were no significant differences in patient and clinical characteristics between the TMI and TBI cohorts except for clinical response status at transplantation and radiation dose. As expected, patients in the TMI received higher radiation doses (median dose, 16.0 Gy for the TMI cohort versus 13.2 Gy for the TBI cohort; P < .001). The median follow-up for both cohorts was 2.0 years (range, .5 to 12.3 years). There was no significant difference in the risk of developing SMNs between the 2 cohorts (P = .81). A total of 9 patients (5.3%) conditioned with TBI and 10 patients (5.8%) conditioned with TMI developed SMNs, at a median of 3.3 years and 1.7 years following HCT, respectively. Excluding nonmelanoma skin cancers and noninvasive neoplasms, 2 patients in the TBI cohort developed SMNs (both melanomas), and 1 patient in the TMI cohort developed an SMN (colon cancer). No patients developed a subsequent hematologic malignancy. TMI-based conditioning is not associated with a significant difference in the risk of developing SMNs compared with TBI-based conditioning during early post-HCT follow-up. Future studies with longer follow-up may be needed to further characterize the risk of SMNs associated with TMI-based conditioning regimens compared with TBI-based regimens., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Total body irradiation (TBI) is a commonly used conditioning regimen for hematopoietic stem cell transplant (HCT), but dose heterogeneity and long-term organ toxicity pose significant challenges. Total marrow irradiation (TMI), an evolving radiation conditioning regimen for HCT can overcome the limitations of TBI by delivering the prescribed dose targeted to the bone marrow (BM) while sparing organs at risk. Recently, our group demonstrated that TMI up to 20 Gy in relapsed/refractory AML patients was feasible and efficacious, significantly improving 2-year overall survival compared to the standard treatment. Whether such dose escalation is feasible in elderly patients, and how the organ toxicity profile changes when switching to TMI in patients of all ages are critical questions that need to be addressed. We used our recently developed 3D image-guided preclinical TMI model and evaluated the radiation damage and its repair in key dose-limiting organs in young (~8 weeks) and old (~90 weeks) mice undergoing congenic bone marrow transplant (BMT). Engraftment was similar in both TMI and TBI-treated young and old mice. Dose escalation using TMI (12 to 16 Gy in two fractions) was well tolerated in mice of both age groups (90% survival ~12 Weeks post-BMT). In contrast, TBI at the higher dose of 16 Gy was particularly lethal in younger mice (0% survival ~2 weeks post-BMT) while old mice showed much more tolerance (75% survival ~13 weeks post-BMT) suggesting higher radio-resistance in aged organs. Histopathology confirmed worse acute and chronic organ damage in mice treated with TBI than TMI. As the damage was alleviated, the repair processes were augmented in the TMI-treated mice over TBI as measured by average villus height and a reduced ratio of relative mRNA levels of amphiregulin/epidermal growth factor ( areg / egf ). These findings suggest that organ sparing using TMI does not limit donor engraftment but significantly reduces normal tissue damage and preserves repair capacity with the potential for dose escalation in elderly patients., Competing Interests: Susanta K. Hui receives honoraria from and consults for Janssen Research & Development, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lim, Sargur Madabushi, Vishwasrao, Song, Abdelhamid, Ghimire, Vanishree, Lamba, Dandapani, Salhotra, Lemecha, Pierini, Zhao, Storme, Holtan, Aristei, Schaue, Al Malki and Hui.)

Background: Total Marrow and Lymphoid Irradiation (TMLI) is a promising component of the preparative regimen for hematopoietic cell transplantation in patients with high-risk acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Extramedullary (EM) relapse after TMLI is comparable to TBI and non-TBI conditioning regimens. This study evaluates outcomes of patients treated with radiotherapy (RT) with EM relapse previously treated with TMLI., Methods: A retrospective analysis of five prospective TMLI trials was performed. TMLI targeted bones and major lymphoid tissues using image-guided tomotherapy, with total dose ranging from 12 to 20 Gy. EM recurrences were treated at the discretion of the hematologist and radiation oncologist using RT ± chemotherapy. Descriptive statistics and survival analysis were then performed on this cohort., Results: In total, 254 patients with refractory or relapsed AML or ALL were treated with TMLI at our institution. Twenty-one patients were identified as receiving at least one subsequent course of radiation. A total of 67 relapse sites (median=2 sites/patient, range=1-16) were treated. Eleven relapsed patients were initially treated with curative intent. Following the initial course of subsequent RT, 1-year, 3-year and 5-year estimates of OS were 47.6%, 32.7% and 16.3%, respectively. OS was significantly better in patients treated with curative intent, with median OS of 50.7 months vs 1.6 months (p<0.001). 1-year, 3-year and 5-year estimates of PFS were 23.8%, 14.3% and 14.3%, respectively. PFS was significantly better in patients treated with curative intent, with median PFS of 6.6 months vs 1.3 months (p<0.001). Following RT, 86.6% of the sites had durable local control., Conclusions: RT is an effective modality to treat EM relapse in patients with acute leukemia who relapse after HCT achieving high levels of local control. In patients with limited relapse amenable to curative intent, radiation confers favorable long-term survival. Radiation as salvage treatment for EM relapse after HCT warrants further evaluation., Competing Interests: SD has received grant funding from Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ladbury, Semwal, Hong, Yang, Hao, Han, Liu, Marcucci, Rosenthal, Hui, Salhotra, Ali, Nakamura, Stein, Al Malki, Wong and Dandapani.)

We used a rigorous PRoBE (prospective-specimen collection, retrospective-blinded-evaluation) study design to compare the ability of biomarkers of systemic inflammation and biomarkers of gastrointestinal (GI) tissue damage to predict response to corticosteroid treatment, the incidence of clinically severe disease, 6-month nonrelapse mortality (NRM), and overall survival in patients with acute graft-versus-host disease (GVHD). We prospectively collected serum samples of newly diagnosed GVHD patients (n = 730) from 19 centers, divided them into training (n = 352) and validation (n = 378) cohorts, and measured TNFR1, TIM3, IL6, ST2, and REG3α via enzyme-linked immunosorbent assay. Performances of the 4 strongest algorithms from the training cohort (TNFR1 + TIM3, TNFR1 + ST2, TNFR1 + REG3α, and ST2 + REG3α) were evaluated in the validation cohort. The algorithm that included only biomarkers of systemic inflammation (TNFR1 + TIM3) had a significantly smaller area under the curve (AUC; 0.57) than the AUCs of algorithms that contained ≥1 GI damage biomarker (TNFR1 + ST2, 0.70; TNFR1 + REG3α, 0.73; ST2 + REG3α, 0.79; all P < .001). All 4 algorithms were able to predict short-term outcomes such as response to systemic corticosteroids and severe GVHD, but the inclusion of a GI damage biomarker was needed to predict long-term outcomes such as 6-month NRM and survival. The algorithm that included 2 GI damage biomarkers was the most accurate of the 4 algorithms for all endpoints., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Measurement of glucose levels is the mainstay method of ensuring good glycemic control and preventing complications associated with uncontrolled diabetes. Continuous glucose monitoring enables easy and effective monitoring of interstitial glucose around the clock and hence improves glycemic control., Objectives: This study aimed to measure the effect of continuous glucose monitoring on glycated hemoglobin (HbA1c) at 3, 6, and 9 months following sensor insertion., Methods: A retrospective cohort study of pediatric and adolescent type 1 diabetes mellitus patients randomly sampled from 32 Ministry of Health diabetes centers across Saudi Arabia was performed. Patients were subjected to flash glucose monitoring using the FreeStyle ® Libre flash glucose monitoring system (Abbott Diabetes Care, Witney, UK), an intermittently scanned continuous glucose monitoring device approved by the Conformité Européenne in 2014. These patients were first-time users of any kind of continuous glucose monitoring system, aged 4-18 years, and received insulin via multiple dose injection or continuous subcutaneous insulin infusion for at least 6 months prior to study start. Patients were excluded if they had used flash glucose monitoring or other interstitial glucose monitoring systems in the past 3 months, were pregnant, or had existing hemoglobinopathies. The flash glucose monitoring sensor was attached to the back of the upper arm at the baseline visit. HbA1c (%) was measured at baseline and 3, 6, and 9 months. Patient demographics were collected from electronic health records., Results: 1,307 patients were included, with a mean age of 11.1 years (standard deviation 3.6 years). Where specified, 51.4% were female. Mean HbA1c significantly reduced from baseline (10.8%) to 3 months (9.8%, p < 0.001), 6 months (9.2%, p < 0.001), and 9 months (9.1%, p < 0.001). For individuals with baseline HbA1c > 9%, mean HbA1c was significantly reduced from baseline (11.7%) to 3 months (10.3%, p < 0.001), 6 months (9.6%, p < 0.001), and 9 months (9.5%, p < 0.001)., Conclusions: Flash glucose monitoring significantly reduced HbA1c levels at 3, 6, and 9 months following sensor insertion. This reduction was greatest in those patients with higher HbA1c at baseline (> 9%)., (© 2022. The Author(s).)

We report results of our prospective pilot trial evaluating safety/feasibility of peritransplantation ruxolitinib for myelofibrosis treatment. Primary objectives were to determine safety and maximum tolerated dose (MTD) of ruxolitinib. Ruxolitinib was administered at 2 dose levels (DLs) of 5 and 10 mg twice daily, with fludarabine/melphalan conditioning regimen and tacrolimus/sirolimus graft-versus-host disease (GVHD) prophylaxis. We enrolled 6 and 12 patients at DL1 and DL2, respectively. Median age at transplantation was 65 years (range, 25-73). Per Dynamic International Prognostic Scoring System, 4 patients were high and 14 intermediate risk. Peripheral blood stem cells were graft source from matched sibling (n = 5) or unrelated (n = 13) donor. At each DL, 1 patient developed dose-limiting toxicities (DLTs): grade 3 cardiac and gastrointestinal with grade 4 pulmonary DLTs in DL1, and grade 3 kidney injury in DL2. All patients achieved engraftment. Grade 2 to 4 and 3 to 4 acute GVHD cumulative incidence was 17% (95% confidence interval [CI], 6-47) and 11% (95% CI, 3-41), respectively. Cumulative incidence of 1-year chronic GVHD was 42% (95% CI, 24-74). With 22.6-month (range, 6.2-25.8) median follow-up in surviving patients, 1-year overall and progression-free survival were 77% (95% CI, 50-91) and 71% (95% CI, 44-87), respectively. Causes of death (n = 4) were cardiac arrest, GVHD, respiratory failure, and refractory GVHD of liver. Our results show peritransplantation ruxolitinib is safe and well tolerated at MTD of 10 mg twice daily and associated with dose-dependent pharmacokinetic and cytokine profile. Early efficacy data are highly promising in high-risk older patients with myelofibrosis. This trial was registered at www.clinicaltrials.gov as #NCT02917096., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)