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Mohamad S Alabdaljabar,1,2 Babar Hasan,3 Peter A Noseworthy,4 Joseph F Maalouf,4,5 Naser M Ammash,4,5 Shahrukh K Hashmi5,6 1Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; 2College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 3Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan; 4Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA; 5Department of Medicine, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates; 6Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USACorrespondence: Shahrukh K Hashmi, Department of Medicine, SSMC, Abu Dhabi, United Arab Emirates, Email shhashmi@ssmc.aeAbstract: Artificial intelligence (AI) and machine learning (ML) is a promising field of cardiovascular medicine. Many AI tools have been shown to be efficacious with a high level of accuracy. Yet, their use in real life is not well established. In the era of health technology and data science, it is crucial to consider how these tools could improve healthcare delivery. This is particularly important in countries with limited resources, such as low- and middle-income countries (LMICs). LMICs have many barriers in the care continuum of cardiovascular diseases (CVD), and big portion of these barriers come from scarcity of resources, mainly financial and human power constraints. AI/ML could potentially improve healthcare delivery if appropriately applied in these countries. Expectedly, the current literature lacks original articles about AI/ML originating from these countries. It is important to start early with a stepwise approach to understand the obstacles these countries face in order to develop AI/ML-based solutions. This could be detrimental to many patients’ lives, in addition to other expected advantages in other sectors, including the economy sector. In this report, we aim to review what is known about AI/ML in cardiovascular medicine, and to discuss how it could benefit LMICs.Keywords: artificial intelligence, machine learning, cardiology, low, middle, income, countries

Background and Aims: Bowel smooth muscle experiences mechanical stress constantly during normal function, and pathologic mechanical stressors in disease states. We tested the hypothesis that pathologic mechanical stress could alter transcription to induce smooth muscle phenotypic class switching., Methods: Primary human intestinal smooth muscle cells (HISMCs), seeded on electrospun aligned poly-ε-caprolactone nano-fibrous scaffolds, were subjected to pathologic, high frequency (1 Hz) uniaxial 3% cyclic stretch (loaded) or kept unloaded in culture for 6 hours. Total RNA sequencing, qRT-PCR, and quantitative immunohistochemistry defined loading-induced changes in gene expression. NicheNet predicted how differentially expressed genes might impact HISMCs and other bowel cells., Results: Loading induced differential expression of 4537 genes in HISMCs. Loaded HISMCs had a less contractile phenotype, with increased expression of synthetic SMC genes, proinflammatory cytokines, and altered expression of axon guidance molecules, growth factors and morphogens. Many differentially expressed genes encode secreted ligands that could act cell-autonomously on smooth muscle and on other cells in the bowel wall., Discussion: HISMCs demonstrate remarkably rapid phenotypic plasticity in response to mechanical stress that may convert contractile HISMCs into proliferative, fibroblast-like cells or proinflammatory cells. These mechanical stress-induced changes in HISMC gene expression may be relevant for human bowel disease.

Autologous peripheral blood stem cell (PBSC) transplantation is a standard treatment of multiple myeloma (MM), Hodgkin lymphoma and various subtypes of non-Hodgkin lymphoma. Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of conditioning regimen prior to cell infusion. The aim of this Worldwide Network for Blood & Marrow Transplantation (WBMT) work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. We searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Identified literature was reviewed for information on mobilization, apheresis, preservation and viability, conditioning regimen, engraftment, response, and survival. Results highlight collective experience from 19 transplant centers (1686 patients), that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 10 6 /kg. Stem cell viability at transplantation was >90% in MM and >75% in lymphomas, after a storage time of 24-144 h at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively. Non-cryopreservation of apheresed autologous PBSCs appears feasible and safe., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

It has been four years since long COVID-the protracted consequences that survivors of COVID-19 face-was first described. Yet, this entity continues to devastate the quality of life of an increasing number of COVID-19 survivors without any approved therapy and a paucity of clinical trials addressing its biological root causes. Notably, many of the symptoms of long COVID are typically seen with advancing age. Leveraging this similarity, we posit that Geroscience-which aims to target the biological drivers of aging to prevent age-associated conditions as a group-could offer promising therapeutic avenues for long COVID. Bearing this in mind, this review presents a translational framework for studying long COVID as a state of effectively accelerated biological aging, identifying research gaps and offering recommendations for future preclinical and clinical studies., Competing Interests: Declaration of Competing Interest S.K.H received Honoraria/grants from Pfizer, Novartis, Janssen, Therakos Mallinckrodt, and Sanofi and Roche. T.T and J.L.K have a financial interest related to this research, including patents and pending patients covering senolytic drugs and their uses that are held by Mayo Clinic. The remaining authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives : Non-Hodgkin lymphoma (NHL) has the sixth-highest malignancy-related mortality in the United States (US). However, inequalities exist in access to advanced care in specific patient populations. We aim to study the racial disparities in major adverse cardiovascular and cerebrovascular events (MACCEs) in NHL patients. Materials and Methods : Using ICD-10 codes, patients with NHL were identified from the US National Inpatient Sample 2016-2019 database. Baseline characteristics, comorbidities, and MACCE outcomes were studied, and results were stratified based on the patient's race. Results : Of the 777,740 patients with a diagnosis of NHL, 74.22% (577,215) were White, 9.15% (71,180) were Black, 9.39% (73,000) were Hispanic, 3.33% (25,935) were Asian/Pacific Islander, 0.36% (2855) were Native American, and 3.54% (27,555) belonged to other races. When compared to White patients, all-cause mortality (ACM) was significantly higher in Black patients (aOR 1.27, 95% CI 1.17-1.38, p < 0.001) and in Asian/Pacific Islander patients (aOR 1.27, 95% CI 1.12-1.45, p < 0.001). Sudden cardiac death was found to have a higher aOR in all racial sub-groups as compared to White patients; however, it was statistically significant in Black patients only (aOR 1.81, 95% CI 1.52-2.16, p < 0.001). Atrial fibrillation (AF) risk was significantly lower in patients who were Black, Hispanic, and of other races compared to White patients. Acute myocardial infarction (AMI) was noted to have a statistically significantly lower aOR in Black patients (0.70, 95% CI 0.60-0.81, p < 0.001), Hispanic patients (0.69, 95% CI 0.59-0.80, p < 0.001), and patients of other races (0.57, 95% CI 0.43-0.75, p < 0.001) as compared to White patients. Conclusions : Racial disparities are found in MACCEs among NHL patients, which is likely multifactorial, highlighting the need for healthcare strategies stratified by race to mitigate the increased risk of MACCEs. Further research involving possible epigenomic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL is imperative.

Any conflict in countries that process nuclear power plants raises concerns of the potential radiation injuries to the people in that region and beyond such as the current conflict in Ukraine. International healthcare organizations and societies should prepare for the potential scenarios of nuclear incidents. The Worldwide Network for Blood and Marrow Transplantation (WBMT) and its members, have recent experience preparing for this type of events such as the Fukushima incident in 2011. In this article, we discuss the risks of radiation exposure, current guidelines, and scientific evidence on hematopoietic support, including the role of hematopoietic stem cell transplant (HCT) for those exposed to nuclear radiation, and the role that the WBMT and other global BMT societies can play in triaging and managing people suffering from radiation injuries., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Current advances in cancer therapy have increased survival, emphasizing the need for life quality improvement. Fertility loss is common post-chemotherapy. Current guidelines establish embryo and oocyte cryopreservation to address premature ovarian insufficiency (POI). Ovarian tissue cryopreservation has also recently become an acceptable option for fertility preservation, particularly as it is the only option for pre-pubertal patients. Few definitions for optimum fertility outcomes, and few systematic reviews comparing embryo, oocyte, and ovarian tissue cryopreservation as a means of fertility preservation (FP) in pre- and post-pubertal female cancer patients exist. This systematic review aims to improve understanding of gonadotoxic effects of chemoradiation therapy in cancer patients, to analyze the different fertility preservation techniques and procedures available to women with chemoradiation induced ovarian insufficiency, and to compare and recognize the benefits of each technique in restoring fertility, sexual hormone function, and quality of life. Searches were conducted electronically on PubMed, Cochrane, and EBSCOHost, including clinical trials, prospective, and retrospective studies of female cancer patients undergoing anti-cancer therapy, with predefined MeSH terminology. Data were collected, analyzed, and compared. Non-randomized clinical studies were evaluated for risk bias through the Newcastle-Ottawa Scale. In total, 23 studies were included. From there, 647 patients opted for oocyte cryopreservation, 267 for embryo cryopreservation, and 1382 for ovarian tissue cryopreservation (OTC). A total of 175, 18, and 121 live births resulted respectively from oocyte, embryo, and OTC, respectively. Studies without live births discussed other fertility markers as indicators of improvement in sexual hormone function and fertility. The gonadotoxic effects of chemotherapy call for FP intervention. Oocyte and embryo cryopreservation/implantation are well-established procedures. With changing trends and life quality consideration, OTC is a promising interventional method for pre-pubertal patients facing the prospect of fertility loss.

Importance: COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and long-term outcomes., Objective: To describe the clinical presentation of COVID-19 and chemotherapy modifications in pediatric patients with ALL/LLy., Design, Setting, and Participants: This is a retrospective case series of patients at St Jude Children's Research Hospital and its affiliate sites with newly diagnosed ALL/LLy who were treated on the Total XVII protocol (NCT03117751) between March 30, 2020, and June 20, 2022. Participants included patients aged 1 to 18 years who were receiving protocol chemotherapy. Acute symptoms and chemotherapy modifications were evaluated for 60 days after the COVID-19 diagnosis, and viral clearance, adverse events, and second SARS-CoV-2 infections were followed up during the 27-month study period., Exposures: SARS-CoV-2; all patients were screened at least weekly and at symptom onset and/or after known exposure to SARS-CoV-2., Main Outcomes and Measures: Description of the spectrum of COVID-19 illness and chemotherapy modifications., Results: Of 308 pediatric patients, 110 (36%) developed COVID-19 at a median age of 8.2 (IQR, 5.3-14.5) years. Sixty-eight patients (62%) were male. Most patients were in the continuation/maintenance phase of chemotherapy (101 [92%]). Severe disease was rare (7 [6%]) but was associated with older age, higher white blood cell counts at ALL/LLy diagnosis, lower absolute lymphocyte counts at COVID-19 diagnosis, abnormal chest imaging findings, and SARS-CoV-2 reinfection. Rare but serious thrombotic events included pulmonary embolism and cerebral venous sinus thrombosis (n = 1 for each). No multisystem inflammatory syndrome in children or death was seen. SARS-CoV-2 reinfection occurred in 11 patients (10%) and was associated with older age and with receiving standard or high-risk vs low-risk ALL/LLy therapy. Chemotherapy interruptions occurred in 96 patients (87%) and were longer for patients with severe disease, SARS-CoV-2 reinfection, and/or a COVID-19 diagnosis during the pre-Omicron variant period vs the post-Omicron period (after December 27, 2021)., Conclusions and Relevance: In this case series of COVID-19 in pediatric patients with ALL/LLy, severe COVID-19 was rare, but chemotherapy administration was affected in most patients. Long-term studies are needed to establish the outcomes of COVID-19 in this population.

Chronic graft-versus-host-disease (cGvHD) remains the leading cause of morbidity among transplant recipients. The efficacy of second-line treatments varies widely based on many factors, including wide differences in the organ overall response-rate response and in the current era where multiple agents are approved, and optimal sequencing of drugs based on organ ORR is unknown. We aimed to evaluate outcomes based on ORRs to the most common agents for the treatment of steroid-refractory/steroid-dependent cGvHD by conducting a systematic literature review. A total of 387 studies were evaluated for the ORRs of 12 cGvHD treatments. The highest skin ORR was observed to be 77% though some agents had an acceptable ORR. Most agents had an ocular response ranging from 17 to 50% Some agents resulted in a GI ORR of ≥88%. Rituximab showed the best response for musculoskeletal-GvHD. In the case of lung-GvHD (bronchiolitis obliterans syndrome [BOS]), negligible response was observed in patients treated with various agents. No clinically meaningful responses to treatments were reported for genital-GvHD. Most GvHD trials are focused on the ORR and partial response rates (PRR). The evidence for optimal agents for each organ is limited, and therefore, our study results are striking for differences in organ-ORR yields for a clinically meaningful difference. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD could result in favorable outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Pediatric residents lack training in expressing condolences to bereaved families after a child's death. We previously developed a novel curriculum that improved residents' comfort with expressing condolences, and now we report assessment of the longitudinal impact of this curriculum on residents' practices of condolence expression. Methods: We applied Kern's 6-step approach to develop, implement, and evaluate a condolence expression curriculum. Residents completed surveys before, immediately after, and six months after participating in the educational intervention to assess curricular impact over time. Results: Twenty pediatric residents participated in the curriculum. Residents reported an increase in their practice of expressing condolences following participation in the curriculum, as well as appreciation for the value of the intervention. Conclusion: A condolence expression curriculum has potential to increase residents' practice of condolence expression to bereaved families over time. Future work will focus on the impact of curricular dissemination across pediatric residency programs.

Cellular senescence is a biological aging hallmark that plays a key role in the development of neurodegenerative diseases. Clinical trials are currently underway to evaluate the effectiveness of senotherapies for these diseases. However, the impact of senescence on brain aging and cognitive decline in the absence of neurodegeneration remains uncertain. Moreover, patient populations like cancer survivors, traumatic brain injury survivors, obese individuals, obstructive sleep apnea patients, and chronic kidney disease patients can suffer age-related brain changes like cognitive decline prematurely, suggesting that they may suffer accelerated senescence in the brain. Understanding the role of senescence in neurocognitive deficits linked to these conditions is crucial, especially considering the rapidly evolving field of senotherapeutics. Such treatments could help alleviate early brain aging in these patients, significantly reducing patient morbidity and healthcare costs. This review provides a translational perspective on how cellular senescence plays a role in brain aging and age-related cognitive decline. We also discuss important caveats surrounding mainstream senotherapies like senolytics and senomorphics, and present emerging evidence of hyperbaric oxygen therapy and immune-directed therapies as viable modalities for reducing senescent cell burden., Competing Interests: TT and JK have a financial interest related to this research, including patents and pending patients covering senolytic drugs and their uses that are held by Mayo Clinic. SH received Honoraria from Pfizer, Novartis, Janssen, Therakos Mallinckrodt, and Sanofiand Roche. 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 © 2023 Shafqat, Khan, Omer, Niaz, Albalkhi, AlKattan, Yaqinuddin, Tchkonia, Kirkland and Hashmi.)

Purpose of Review: This review delves into the potential of artificial intelligence (AI), particularly machine learning (ML), in enhancing graft-versus-host disease (GVHD) risk assessment, diagnosis, and personalized treatment., Recent Findings: Recent studies have demonstrated the superiority of ML algorithms over traditional multivariate statistical models in donor selection for allogeneic hematopoietic stem cell transplantation. ML has recently enabled dynamic risk assessment by modeling time-series data, an upgrade from the static, "snapshot" assessment of patients that conventional statistical models and older ML algorithms offer. Regarding diagnosis, a deep learning model, a subset of ML, can accurately identify skin segments affected with chronic GVHD with satisfactory results. ML methods such as Q-learning and deep reinforcement learning have been utilized to develop adaptive treatment strategies (ATS) for the personalized prevention and treatment of acute and chronic GVHD., Summary: To capitalize on these promising advancements, there is a need for large-scale, multicenter collaborations to develop generalizable ML models. Furthermore, addressing pertinent issues such as the implementation of stringent ethical guidelines is crucial before the widespread introduction of AI into GVHD care., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype-phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first 'European Forum on Visceral Myopathy'. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy., (© 2023. The Author(s).)

Dysfunction of visceral smooth muscle ("visceral myopathy") impairs bowel, bladder, and uterine function. Symptoms of this life-threatening condition include massive intestinal distension with slow transit, vomiting, feeding intolerance, growth failure, poor bladder emptying, and difficult vaginal delivery. The most common genetic cause of visceral myopathy is a heterozygous point mutation (R257C) in gamma smooth muscle actin (ACTG2). We genetically modified the WAe0009-A human embryonic stem cell line to carry the c.769C>T p.R257C/+ mutation. This cell line will facilitate studies of how the ACTG2 R257C heterozygous variant affects smooth muscle development and function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Visceral myopathies are debilitating conditions characterized by dysfunction of smooth muscle in visceral organs (bowel, bladder, and uterus). Individuals affected by visceral myopathy experience feeding difficulties, growth failure, life-threatening abdominal distension, and may depend on intravenous nutrition for survival. Unfortunately, our limited understanding of the pathophysiology of visceral myopathies means that current therapies remain supportive, with no mechanism-based treatments. We developed a patient-derived iPSC line with a c.769C > T p.R257C/+ mutation, the most common genetic cause of visceral myopathy. This cell line will facilitate studies of how the ACTG2 R257C heterozygous variant affects smooth muscle development and function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

We surveyed the performance of ponatinib, as salvage therapy, in a real-world setting of chronic phase chronic myeloid leukemia (CML-CP). Among 55 consecutive patients (median age 49 years) with relapsed/refractory CML-CP, 35 (64%) had failed ≥3 tyrosine kinase inhibitors (TKIs), 35 (64%) were pre-treated with nilotinib, and 14 (28%) harbored ABL1T315I. At start of ponatinib (median dose 30 mg/day), 40 patients were already in complete hematologic (CHR), 4 in complete cytogenetic (CCyR), 3 in major molecular (MMR) remission, while 8 had not achieved CHR (NR). Ponatinib improved the depth of response in 13 (33%), 3 (75%), 2 (66%), and 4 (50%) patients with CHR, CCyR, MMR, and NR, respectively (p = 0.02). At a median follow-up of 42 months, 13 (23%) deaths, 5 (9%) blast transformations, and 25 (45%) allogeneic transplants were recorded. Five/10-year post-ponatinib survival was 77%/58% with no significant difference when patients were stratified by allogeneic transplant (p = 0.94), ponatinib-induced deeper response (p = 0.28), or a post-ponatinib ≥CCyR vs CHR remission state (p = 0.25). ABL1T315I was detrimental to survival (p = 0.04) but did not appear to affect response. Prior exposure to nilotinib was associated with higher risk of arterial occlusive events (AOEs; 11% vs 0%; age-adjusted p = 0.04). Ponatinib starting/maintenance dose (45 vs 15 mg/day) did not influence either treatment response or AOEs. Our observations support the use of a lower starting/maintenance dose for ponatinib in relapsed/refractory CML-CP but a survival advantage for deeper responses was not apparent and treatment might not overcome the detrimental impact of ABL1T315I on survival. The association between prior exposure to nilotinib and a higher risk of post-ponatinib AOEs requires further validation., (© 2023. Springer Nature Limited.)

Calculated panel reactive antibody (CPRA) is used to help increase sensitized patient's access to transplantation. United Arab Emirates (UAE) has a diverse resident population hence we developed a UAE-CPRA calculator based on HLA antigen frequencies of the different ethnic groups that represent the UAE population. HLA antigen frequencies at serological split antigen level for HLA-A, -B, -C, -DRB1 and -DQB1 of 1002 healthy unrelated donors were performed. We subsequently compared the performance of the UAE CPRA calculator with the Organ Procurement and Transplantation Network (OPTN) and the Canadian CPRA calculators in 110 Kidney Transplant waitlist patients from January 2016 to December 2018. Lin's concordance correlation coefficient showed a moderate agreement between the UAE and OPTN calculator (Rc = 0.949, 95% CI 0.929-0.963) and the UAE and Canadian calculators (Rc = 0.952, 95% CI 0.932-0.965). While there continued to be a moderate agreement (Rc = 0.937, UAE versus OPTN calculator) in the lower sensitized group, a poor agreement (Rc = 0.555, UAE versus OPTN calculator) was observed in the higher sensitized group. In this study, we provide a template for countries to develop their own population-specific CPRA calculator. Implementation of the CPRA algorithm based on HLA frequencies of the multi-ethnic UAE population will be more fitting to increase access to transplantation and improve transplant outcomes. Our study demonstrates that the CPRA calculators developed using the data from the western population had poor correlation in our higher sensitized patients disadvantaging them in potential organ allocations systems. We plan to further refine this calculator by using high resolution HLA typing to address the problem of a genetically diverse population., (© 2023. The Author(s).)

Literature discussing endemic and regionally limited infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America is scarce. This Worldwide Network for Blood and Marrow Transplantation (WBMT) article is part one of two papers aiming to provide guidance to transplantation centres around the globe regarding infection prevention and treatment, and considerations for transplantation based on current evidence and expert opinion. These recommendations were initially formulated by a core writing team from the WBMT and subsequently underwent multiple revisions by infectious disease experts and HSCT experts. In this paper, we summarise the data and provide recommendations on several endemic and regionally limited viral and bacterial infections, many of which are listed by WHO as neglected tropical diseases, including Dengue, Zika, yellow fever, chikungunya, rabies, brucellosis, melioidosis, and leptospirosis., Competing Interests: Declaration of interests MBK declares honoraria from Gilead and an advisory board role at Gilead. RDLC declares honoraria from Gilead. NW declares honoraria and consultancy fees from Novartis; travel and honoraria from Kite Gilead; honoraria and research funding from Sanofi Genzyme; honoraria and speaker fees from Therakos Mallinckrodt; and travel fees from BMS Celgene. EB declares honoraria Novartis, Astellas, Alexion, Gilead, MSD, Keocyt, Jazz Pharmaceuticals, and Amgen; and travel fees from Jazz Pharmaceuticals, Novartis, and Amgen. JeS declares honoraria from Alexion, Sobi, and Takeda; consultancy fees from Alexion, Sobi, and Takeda; travel fees from Sobi; and an advisory board role at Prevail Therapeutics. JaS declares honoraria from MSD, Glead, TEVA, Atara, and Takeda. DW declares research funding from FATE therapeutics: Research Funding and Incyte. SKH declares honoraria from Pfizer, Novartis, Janssen, Therakos Mallinckrodt, Sanofi, and Roche. YA declares lecture fees from Novartis, AbbVie GK, and Astellas and consultancy honoraria from Meiji Seika, JCR Pharmaceuticals, and Kyowa Kirin. PL declares honoraria from Takeda, OctaPharma, and MSD. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

There is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres worldwide regarding prevention, diagnosis, and treatment based on the currently available evidence and expert opinion. These recommendations were created and reviewed by physicians with expertise in HSCT or infectious disease, representing several infectious disease and HSCT groups and societies. In this paper, we review the literature on several endemic and regionally limited parasitic and fungal infections, some of which are listed as neglected tropical diseases by WHO, including visceral leishmaniasis, Chagas disease, strongyloidiasis, malaria, schistosomiasis, histoplasmosis, blastomycosis, and coccidioidomycosis., Competing Interests: Declaration of interests MBCK declares honoraria from Gilead and an advisory board role at Gilead. RDLC declares honoraria from Gilead. NW: declares honoraria from Novartis, Kite Gilead, Sanofi Genzyme, and Therakos Mallinckrodt; consultancy fees from Novartis; travel fees from Kite Gilead and BMS Celgene; research funding from Sanofi Genzyme; and speaker fees from Therakos Mallinckrodt. EB declares honoraria from Novartis, Astellas, Alexion, Jazz Pharmaceuticals, Gilead, MSD, Keocyt, and Amgen; and travel fees from Novartis, Jazz Pharmaceuticals, and Amgen. JeS declares consultancy fees from Alexion, Sobi, and Takeda; honoraria from Alexion, Sobi, and Takeda; travel fees from Sobi; and an advisory board role at Prevail Therapeutics. JaS declares honoraria from MSD, Glead, TEVA, Atara, and Takeda. DW declares research funding from FATE therapeutics and Incyte. SKH declares honoraria from Pfizer, Novartis, Janssen, Therakos Mallinckrodt, Sanofi, and Roche. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To evaluate the impact of killer immunoglobulin-like receptor (KIR) genotyping in allogeneic hematopoietic stem cell transplantation for myeloid disorders at our institution, retrospective KIR genotyping was performed on 77 patients and their 10/10 matched unrelated donors. In a multivariate model including donor age, HLA-DPB1 permissiveness, and presence of donor KIR B/x, an association with overall survival was observed ( p  = .047). Within the model, increasing donor age increased risk (RR 1.03 [1.00-1.06]/year, p  = .046), while donor KIR and HLA-DPB1 permissiveness were not associated with risk (RR 0.51 [0.26-1.03] and RR 0.68 [0.34-1.36]). Grouping recipients by conditioning regimen or limiting the analysis to recipients of peripheral blood stem cells, no association between donor KIR and survival or relapse was identified. No significant associations were observed between overall survival, relapse, grade III-IV acute, or chronic graft versus host disease and presence of KIR B (B/x), quantity of donor KIR B haplotype motifs, or centromeric KIR type (all p  > .05).

The Internet of Things (IoT) has penetrated many aspects of everyday human life. The use of IoT in healthcare has been expanding over the past few years. In this review, we highlighted the current applications of IoT in the medical literature, along with the challenges and opportunities. IoT use mainly involves sensors and wearables, with potential applications in improving the quality of life, personal health monitoring, and diagnosis of diseases. Our literature review highlights that the current main application studied in the literature is physical activity tracking. In addition, we discuss the current technologies that would help IoT-enabled devices achieve safe, quick, and meaningful data transfer. These technologies include machine learning/artificial intelligence, 5G, and blockchain. Data on current IoT-enabled devices are still limited, and future research should address these devices' effect on patients' outcomes and the methods by which their integration in healthcare will avoid increasing costs.

Background and Aims: Smooth muscle cells (SMCs), interstitial cells of Cajal (ICCs), and platelet-derived growth factor receptor alpha (PDGFR α +) cells (P α Cs) form a functional syncytium in the bowel known as the "SIP syncytium." The SIP syncytium works in concert with the enteric nervous system (ENS) to coordinate bowel motility. However, our understanding of individual cell types that form this syncytium and how they interact with each other remains limited, with no prior single-cell RNAseq analyses focused on human SIP syncytium cells., Methods: We analyzed single-nucleus RNA sequencing data from 10,749 human colon SIP syncytium cells (5572 SMC, 372 ICC, and 4805 P α C nuclei) derived from 15 individuals., Results: Consistent with critical contractile and pacemaker functions and with known enteric nervous system interactions, SIP syncytium cell types express many ion channels, including mechanosensitive channels in ICCs and P α Cs. P α Cs also prominently express extracellular matrix-associated genes and the inhibitory neurotransmitter receptor for vasoactive intestinal peptide ( VIPR2 ), a novel finding. We identified 2 P α C clusters that differ in the expression of many ion channels and transcriptional regulators. Interestingly, SIP syncytium cells co-express 6 transcription factors ( FOS , MEIS1 , MEIS2 , PBX1 , SCMH1 , and ZBTB16 ) that may be part of a combinatorial signature that specifies these cells. Bowel region-specific differences in SIP syncytium gene expression may correlate with regional differences in function, with right (ascending) colon SMCs and P α Cs expressing more transcriptional regulators and ion channels than SMCs and P α Cs in left (sigmoid) colon., Conclusion: These studies provide new insights into SIP syncytium biology that may be valuable for understanding bowel motility disorders and lead to future investigation of highlighted genes and pathways., Competing Interests: Conflicts of Interest: This author discloses the following: R.O.H. was a consultant for BlueRock Therapeutics and served on a Scientific Advisory Panel for Takeda. The remaining authors disclose no conflicts.

As cellular therapies gradually become the mainstay of treatment for several nonmalignant diseases, there appears to be varied accessibility to these therapies globally. Despite considerable burden of nonmalignant conditions, such as sickle cell disease, thalassemia, and aplastic anemia in populations of low-middle-income countries, the utilization of cellular therapies remain sparse because of lack of resources. Globally, the frequency of hematopoietic stem cell transplant (HSCT) has increased disproportionately in countries with higher gross national income (GNI) per capita, governmental healthcare expenditures, and a high human development index. This leads to a large subset of international patients seeking care in the United States. This review summarizes the unique set of challenges that often arise when offering sophisticated therapies such as HSCT to international patients constituting of cross-cultural, logistical, financial, and medical challenges and the opportunities that are available to bridge the gap., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Hematopoietic cell transplantation (HCT) health care providers report a desire to improve long-term outcomes and quality of life for their patients. One of the items frequently cited by patients in terms of transitioning from being a patient back to pre-HCT life is return to work (RTW). However, these patients report little support from their health care providers in facilitating this process, and only 50% to 60% achieve RTW, at a median of 3 years post-HCT. Barriers are physical, psychological, and logistical, as well as poor communication between the patient and their employer. We convened a group of experts in survivorship, rehabilitation, social work, and psychology to draft an evidence-based document to assist health care providers in guiding their patients' RTW journey. Guidance is drawn from the existing literature for HCT and general cancer patients and is divided into pre-HCT, peri-HCT, and post-HCT categories. Collaboration among health care providers, patients, and their employers is key to this transition. Suggested referrals and evaluations also are provided. The goal is for this guidance to be continually updated as we advance the field with more HCT-specific literature., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The number of non-Hodgkin lymphoma (NHL) survivors is increasing. With the advancement of NHL therapies, it is crucial to focus on the challenges these survivors may face. Three main categories are to be considered in NHL survivorship, including quality of life and uncertainty about the future, possible physical health complications (including cardiovascular disease, infertility, and subsequent neoplasms), and the impact of novel NHL treatments and their potential complications. The latter includes CAR T-cell therapy, monoclonal antibodies, checkpoint inhibitors, and hematopoietic stem cell transplantation. In this report, we aim to shed the light on these aspects and to discuss survivorship care plan for NHL., (© 2022 Wiley Periodicals LLC.)

Background: Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal approach to AL-CA., Objective: We conducted this systematic review to summarize current evidence from published studies about the safety and efficacy of various treatment regimens for patients with AL-CA, mainly focusing on autologous stem cell transplant (ASCT) and heart transplant., Methods: An electronic literature search of PubMed, Web of Science, Scopus, EBSCO, and CINAHL Plus was conducted through December 2019 using the relevant keywords and prespecified MeSH terminology. Records were screened, and eligible studies were selected and narratively discussed. Data on the hematologic and cardiac responses as well as the safety of the treatment regimens were extracted and synthesized narratively in the context of the systematic review., Results: Thirty published articles were included in this systematic review. The most commonly used first-line treatment in the included studies was bortezomib-based therapy followed by high-dose melphalan and ASCT, with recent evidence of improved outcome with the addition of daratumumab. Heart transplant was found to extend survival for selected patients who were not eligible for ASCT; however, it was found to affect the patients' tolerance of further chemotherapy in some studies. Published data on longterm outcomes with immunomodulatory agents were scarce., Conclusion: Current evidence suggests several possible regimens for the treatment of AL-CA. Effective treatment approaches for AL-CA include induction therapy with bortezomib-based or immunotherapy-based combinations in moderate/severe forms of cardiac involvement, followed by high-dose melphalan and ASCT in eligible patients, and heart transplant for selected severe cases. Therefore, we highlight the necessity of conducting well-designed, randomized controlled trials to provide evidence about the efficacy of these drugs with respect to ASCT.

Young adults (YA), age 18 to 39 years, are at a stage of life that may make them more vulnerable than older adults to impairments in health-related quality of life (HRQOL) during and after hematopoietic cell transplantation (HCT). Health self-efficacy (HSE), the belief that one can implement strategies to produce a desired health outcome, has been associated with health outcomes in oncology research. Little is known about HRQOL or HSE in YA HCT survivors compared with older HCT survivors. Given the age-specific psychosocial challenges facing YA HCT recipients and research on non-transplant YA cancer survivors, we hypothesized that YA survivors would have worse post-HCT HRQOL compared with older adults, and that among YA HCT survivors, higher levels of HSE would be associated with higher levels of HRQOL and lower levels of cancer-related distress. This was a cross-sectional secondary analysis of 2 combined baseline datasets from multicenter studies of HCT survivors approached for participation in clinical trials of survivorship interventions. Participants from 20 transplantation centers in the United States were at 1 to 10 years post-HCT and age ≥18 years at the time of study enrollment, had no evidence of disease relapse/progression or subsequent malignancies, and could read English adequately to consent for and complete assessments. Medical record and patient-reported data were obtained for demographics and HCT-related clinical factors and complications (eg, total body irradiation, chronic graft-versus-host disease [cGVHD]). Participants completed surveys on HRQOL, including the Short-Form [SF]-12, HSE, and Cancer and Treatment Distress (CTXD), which includes 6 subscales and reports an overall mean score. On the SF-12, both the Mental Component Score (MCS) and Physical Component Score (PCS) were calculated. Two cohorts were compared: YAs (age 18 to 39 years at transplantation) and older adults (age ≥40 years at transplantation). Multiple linear regression analyses identified factors associated with HSE, PCS, MCS, and CTXD in YAs. In this analysis of 979 survivors, compared with the older adults, the YA participants had lower median mental health scores (SF-12 MCS: 48.40 versus 50.23; P = .04) and higher cancer-related distress (CTXD: .96 versus .85; P = .04), but better physical health (SF-12 PCS: 48.99 versus 47.18; P = .049). Greater overall cancer-related distress was driven by higher levels of uncertainty, financial concern, and medical demand subscales for YAs compared with older adults. Young adults also had lower HSE (2.93 versus 3.08; P = .0004). In a multivariate model, HSE was strongly associated with age group (P = .0005) after adjusting for multiple other transplantation-related factors. Among YAs, HSE was associated with the SF-12 MCS and PCS and the CTXD, and HSE remained significant after adjusting for other transplantation-related factors. Overall, the YA HCT survivors had lower mental health, increased cancer-related distress, and lower levels of HSE compared with the older adults. Although the direction of these effects cannot be determined with these data, the strong association between HSE and HRQOL among YAs suggests that targeting interventions to improve HSE may have broad impact on health outcomes., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Recent improvements in cancer treatment have increased the lifespan of pediatric and adult cancer survivors. However, cancer treatments accelerate aging in survivors, which manifests clinically as the premature onset of chronic diseases, such as endocrinopathies, osteoporosis, cardiac dysfunction, subsequent cancers, and geriatric syndromes of frailty, among others. Therefore, cancer treatment-induced early aging accounts for significant morbidity, mortality, and health expenditures among cancer survivors. One major mechanism driving this accelerated aging is cellular senescence; cancer treatments induce cellular senescence in tumor cells and in normal, nontumor tissue, thereby helping mediate the onset of several chronic diseases. Studies on clinical monitoring and therapeutic targeting of cellular senescence have made considerable progress in recent years. Large-scale clinical trials are currently evaluating senotherapeutic drugs, which inhibit or eliminate senescent cells to ameliorate cancer treatment-related aging. In this article, we survey the recent literature on phenotypes and mechanisms of aging in cancer survivors and provide an up-to-date review of the major preclinical and translational evidence on cellular senescence as a mechanism of accelerated aging in cancer survivors, as well as insight into the potential of senotherapeutic drugs. However, only with time will the clinical effect of senotherapies on cancer survivors be visible.

A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Alabdaljabar et al.)

The hematopoietic cell transplantation practice has changed significantly over the years. More than 1500 centers around the globe are offering transplant for different types of diseases. This growth was driven by improving the efficacy and the safety of the procedure and the ability to use alternate donors. These improvements made the procedure feasible in virtually all patients in need for it. With the availability of novel therapies and targeted agents, we may be witnessing a new transplant-era. These agents may help to circumvent some of the remaining limitations of the procedure and open the doors for new indications. Herein, we review historical transplant milestones, the accomplishments that led to the modern transplant practice and we discuss the idea of minimal-intensity conditioning and the possibility to adopt chemotherapy and radiation-free preparative regimens in the near future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Outcomes in multiple myeloma (MM) have significantly improved necessitating focus on survivorship., Methods: We undertook a web-based survey in collaboration with International Myeloma Foundation (IMF) to explore patient awareness and psycho-physical impacts of MM. The survey was viewed on the IMF website by 1,324 individuals from 32 countries., Results: The survey responses were available from 959 individuals, with 62% who completed the survey. Treating doctors were the most frequent source of MM-related information. Only 56% patients admitted full compliance with treatment. Treatment side effects bothered 86% responders, including >50% admitting to pain, peripheral neuropathy and asthenia. Majority (57%) reported some degree of depression, 82% had discontent with their quality of life and only 35% reported being satisfied with their coping mechanisms. Patients ≥65 years of age reported more peripheral neuropathy (p = 0.007) and difficulty with ability to work (p = 0.015)., Conclusions: We report the prevalence of psychologic, social and physical domains as well as patient-physician relationship dynamics. This knowledge can help improve MM survivorship.Introduction.

Background: Thrombocytopenia remains a life-threatening late complication of HCT with an incidence of 5-20%. Currently, there is no approved drug for the treatment of persistent thrombocytopenia post HCT and platelet transfusion is the maintain stay of treatment. Eltrombopag is approved for the treatment of thrombocytopenia associated with different diseases, however; data on eltrombopag treatment post HCT are limited., Methods: This is a retrospective cohort study evaluating the effect of eltrombopag on platelet recovery in patients with persistent thrombocytopenia post HCT. The primary endpoint was platelet recovery to ≥ 20,000/μL for 7 consecutive days without transfusion support after starting eltrombopag. Secondary endpoint was platelet recovery to ≥ 50,000/μL for 7 consecutive days., Results: Twenty-one patients were included. Twelve (75%) of 16 patients became independent from platelet transfusions. Median time from starting eltrombopag to last transfusion was 60 days (range, 9-226 days). Ten (63%) of 16 transfusion dependent patients with platelet count < 20,000/μL achieved the primary endpoint. Seven (33%) patients of 21 included had successful platelet recovery (ie, ≥50,000/μL without transfusion support) and the median time to platelet recovery in patients who achieved it was 32 days (range, 13-265 days). Ten patients (48%) were able to successfully discontinue eltrombopag without recurrence of thrombocytopenia., Conclusion: Our findings demonstrated that eltrombopag appears to have a clinically significant impact on platelet recovery in persistent thrombocytopenic patients post HCT.

In this study, we evaluated the association of ISUP/WHO-grade groups with various pathological prognostic parameters and cancer-specific survival in patients with prostatic adenocarcinoma. We found 27 (15.7%) cases of grade group 1, 22 (12.8%) grade group 2, 30 (17.4%) grade group 3, 40 (23.3%) grade group 4 and 53 (30.8%) grade group 5 prostatic adenocarcinoma. We found that high-grade tumors (grade 3-5) had a higher frequency of perineural invasion and higher tumor volumes (>50%). Moreover, a significant association of tumor grade was noted with cancer-specific survival of patients, signifying prognostic significance of grade grouping in prostatic adenocarcinoma.

Gene therapy (GT) has been reported to improve bone marrow function in individuals with Fanconi anemia (FA); however, its clinical application is still in the initial stages. We conducted this systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess the long-term safety and clinical outcomes of GT in FA patients. Electronic searches from PubMed, Web of Science, Cochrane Library, and Google Scholar were conducted and full texts of articles meeting our inclusion criteria were reviewed. Three clinical trials were included, with a total of nine patients and mean age of 10.7 ± 5.7 years. All patients had lentiviral-mediated GT. A 1-year follow-up showed stabilization in blood lineages, without any serious adverse effects from GT. A metaregression analysis could not be conducted, as very little long-term follow-up data of patients was observed, and the median survival rate could not be calculated. Thus, we can conclude that GT seems to be a safe procedure in FA; however, further research needs to be conducted on the longitudinal clinical effects of GT in FA, for a better insight into its potential to become a standard form of treatment., Competing Interests: Declaration of Competing Interest The authors declare the following disclosures, which may not be considered as potential competing interests: SKH has received honoraria from Novartis, Pfizer, Mallinckrodt, and Janssen. SKH has received travel grants from Sanofi, Gilead, MSD, and GSK. ADP has received research funding from Genentech and Takeda, has participated in Advisory Boards for Bayer, Shire/Takeda, Sigilon, and UniQure, and consulted for I-Mab and Sunovion. The other authors declare no conflicts of interest., (Copyright © 2021 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this study is to highlight the importance of having a central case managing team and to make some strong recommendations that can have a positive impact on the lives of hematopoietic stem cell transplantation survivors., Case Presentation: A 2-year-old white child who was diagnosed with acute myeloid leukemia and underwent hematopoietic stem cell transplantation in May 2014 relapsed in March 2017, and underwent a second hematopoietic stem cell transplantation in July 2017, at which point he suffered from graft-versus-host disease. This case report presents his journey and that of his caregivers, and the challenges they faced as patient and parents in pursuit of optimal quality of life during the survivorship period. The case study emphasizes not only the challenges faced by patients but also identified gaps in post-hematopoietic cell transplantation care service delivery. Furthermore, the case study also highlights the importance of involving caregivers in post-transplant care and having a better communication process and service facilitation process throughout the journey of the patient and their carer., Conclusions: Transplant centers have a duty of care, and a proactive approach with a well-defined pathway is needed for managing post-transplant complications and reducing stress and anxiety for patients and their caregivers., (© 2021. The Author(s).)

Background: In the era of big data, artificial intelligence (AI), and the Internet of Things (IoT), digital data have become essential for our everyday functioning and in health care services. The sensitive nature of health care data presents several crucial issues such as privacy, security, interoperability, and reliability that must be addressed in any health care data management system. However, most of the current health care systems are still facing major obstacles and are lacking in some of these areas. This is where decentralized, secure, and scalable databases, most notably blockchains, play critical roles in addressing these requirements without compromising security, thereby attracting considerable interest within the health care community. A blockchain can be maintained and widely distributed using a large network of nodes, mostly computers, each of which stores a full replica of the data. A blockchain protocol is a set of predefined rules or procedures that govern how the nodes interact with the network, view, verify, and add data to the ledger., Objective: In this article, we aim to explore blockchain technology, its framework, current applications, and integration with other innovations, as well as opportunities in diverse areas of health care and clinical research, in addition to clarifying its future impact on the health care ecosystem. We also elucidate 2 case studies to instantiate the potential role of blockchains in health care., Methods: To identify related existing work, terms based on Medical Subject Headings were used. We included studies focusing mainly on health care and clinical research and developed a functional framework for implementation and testing with data. The literature sources for this systematic review were PubMed, Medline, and the Cochrane library, in addition to a preliminary search of IEEE Xplore., Results: The included studies demonstrated multiple framework designs and various implementations in health care including chronic disease diagnosis, management, monitoring, and evaluation. We found that blockchains exhibit many promising applications in clinical trial management such as smart-contract application, participant-controlled data access, trustless protocols, and data validity. Electronic health records (EHRs), patient-centered interoperability, remote patient monitoring, and clinical trial data management were found to be major areas for blockchain usage, which can become a key catalyst for health care innovations., Conclusions: The potential benefits of blockchains are limitless; however, concrete data on long-term clinical outcomes based on blockchains powered and supplemented by AI and IoT are yet to be obtained. Nonetheless, implementing blockchains as a novel way to integrate EHRs nationwide and manage common clinical problems in an algorithmic fashion has the potential for improving patient outcomes, health care experiences, as well as the overall health and well-being of individuals., (©Hanaa Fatoum, Sam Hanna, John D Halamka, Douglas C Sicker, Peter Spangenberg, Shahrukh K Hashmi. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 02.11.2021.)

Chronic graft-versus-host disease (cGVHD), a potentially debilitating complication of hematopoietic cell transplantation, confers increased risk for mortality. Whereas treatment decisions rely on an accurate assessment of disease activity/severity, validated methods of assessing cutaneous cGVHD activity/severity appear to be limited. In this study, we aimed to identify and evaluate current data on the assessment of disease activity/severity in cutaneous cGVHD. Using modified PRISMA methods, we performed a critical literature review for relevant articles. Our literature search identified 1741 articles, of which 1635 were excluded as duplicates or failure to meet inclusion criteria. Of the included studies (n = 106), 39 (37%) addressed clinical and/or histopathologic parameters, 53 (50%) addressed serologic parameters, 8 (7.5%) addressed imaging parameters, and 6 (5.5%) addressed computer-based technologies. The only formally validated metric of disease activity/severity assessment in cutaneous cGVHD is the National Institutes of Health consensus scoring system, which is founded on clinical assessment alone. The lack of an objective marker for cGVHD necessitates further studies. An evaluation of the potential contributions of serologic, imaging, and/or computer-based technologies is warranted., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. All rights reserved.)

Proteasome inhibitors (PIs) are an integral component of multiple myeloma therapies. Peripheral neuropathy (PN) is a well-knownconsequence of PIs, most frequently reported with earlier generations such as bortezomib (BTZ). There is a paucity of data highlighting the risk of developing PN with the new-generation PIs carfilzomib (CFZ) and ixazomib (IZB). This study evaluated reports of PN encountered with all three PIs using the Food and Drug Administration Adverse Event (AE) Reporting System (FAERS). Signal disproportionality analysis was reported using the reporting odds ratio (ROR) with 95% confidence interval (CI). PN was reported in a total of 2.1%, 5.0%, and 10.9% of AEs with CFZ, IZB, and BTZ, respectively. The ROR (95% CI) for PN secondary to BTZ, CFZ, and IZB was 34.10 (32.76-35.49), 6.37 (5.50-7.37), and 14.97 (13.63-16.44), respectively. Compared to BTZ, CFZ and IZB have lower rates of reported PN, with RORs of 0.19 (0.16-0.22) and 0.48 (0.43-0.54), respectively.

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD., Methods: This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24; key secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24., Results: A total of 329 patients underwent randomization; 165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7% vs. 25.6%; odds ratio, 2.99; P<0.001). Ruxolitinib led to longer median failure-free survival than control (>18.6 months vs. 5.7 months; hazard ratio, 0.37; P<0.001) and higher symptom response (24.2% vs. 11.0%; odds ratio, 2.62; P = 0.001). The most common (occurring in ≥10% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the control group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups., Conclusions: Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte; REACH3 ClinicalTrials.gov number, NCT03112603.)., (Copyright © 2021 Massachusetts Medical Society.)

The current paper seeks to inform healthcare professionals on how adapting various components of return to work (RTW) programs that are already in use by other musculoskeletal rehabilitation settings can help optimize return to work process for patients with or without musculoskeletal manifestations, posthematopoietic cell transplantation. Since there is no universally agreed RTW structure for hematopoietic cell transplant patients, a narrative approach has been taken utilizing evidence from the existing musculoskeletal return to work assessment publications to help draw parallel for the hematopoietic cell transplant patients. Databases were searched including PUBMED, CINHAL, AMED, SCOPUS, and Cochrane using keywords RTW, functional restoration program, hematopoietic cell transplant, bone marrow transplant, stem cell transplant, and musculoskeletal functional assessment. The authors have managed to outline and propose a structured RTW assessment and monitoring program which can aid in getting patients back to employment by utilizing the functional capacity and job evaluation to help hematopoietic cell transplantation patients reintegrate socially. Patients undergoing hematopoietic cell transplant require additional support and a robust assessment system to allow safe RTW. The proposed model of RTW assessment can prove to be beneficial in helping patients return to work safely. Clinical Significance . To acknowledge the individuality in functional limitation is important in determining not only the rehab needs but also the RTW capabilities. The proposed RTW plan not only promotes an individualized approach to patients but also provides a structure for return to work assessments for hematopoietic cell transplantation patients, thus, eliminating the need for guess work by healthcare professionals. In line with the International Classification of Functioning, Disability, and Health (ICF) recommendations, a RTW assessment combined with a job evaluation helps healthcare professionals and stakeholders to understand the unique challenges and strengths of a patient and thereby design an individualized therapy approach., Competing Interests: None of the authors declare any relevant conflicts of interest., (Copyright © 2021 Jaleel Mohammed et al.)