The safety of living donor liver transplantation (LDLT) has improved over the years, and yet biliary anastomotic complications remain substantial occurring in up to 25%, affecting short-term and long-term outcomes. The meta-analyses is performed to compare biliary complication rates, based on the number of ducts, including bile leaks and strictures, in right-lobe living donor liver transplantation (RLLDLT) using duct-to-duct (DD) anastomosis versus Roux en Y Hepaticojejunostomy (HJ). PubMed, Cochrane and Embase databases were searched comprehensively for studies on adult LDLT, focusing on the bile duct reconstruction method for RLLDLT. Fifteen retrospective studies with 1770 patients were included. DD anastomosis is associated with a significantly reduced rate of all biliary complications compared to HJ (OR 1.16, 95% CI (0.82-1.64), p= 0.40), and particularly a lower incidence of bile leak (OR 0.61, 95% CI (0.38-0.98), p=0.04), while the rates of biliary strictures (OR 1.49, 95% CI (0.83-2.69), p=0.18) did not differ significantly. Grafts with multiple bile ducts (1 vs. >1) were associated with higher complication rates (OR 0.80, 95% CI (0.54-1.19), p=0.27). The meta-analyses supports DD over HJ where both are feasible, and highlights the importance of individualised biliary reconstruction strategies to improve patient outcomes in RLLDLT.
Somatic mutation testing in solid tumours represents a rapidly advancing field which increases opportunities for access to molecularly targeted therapeutics and clinical trials. This systematic review determined whether socio-demographic inequalities affect utilisation of novel somatic mutation testing. Following PRISMA 2020 guidance, MEDLINE, EMBASE, Scopus, CINAHL, Web of Science, PubMed and PsycINFO were searched for peer-reviewed studies (January 2018-March 2025). Data was extracted reporting utilisation of novel somatic mutation testing panels, including Oncotype DX, for solid tumours by socio-demographic measures. A modified International Society for Pharmacoeconomics and Outcomes Research (ISPOR) checklist assessed study quality. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated where needed and narrative synthesis undertaken. Data was stratified by receipt of Oncotype DX testing and next-generation sequencing (NGS) panels. The 27,749 citations screened identified 24 studies meeting the inclusion criteria. These reported on two modalities of testing (Oncotype DX and other NGS sequencing panels) across five cancers. Twenty-three studies were from US populations. These highlighted disparities in utility of testing across socio-demographic measures and particularly decreased utilisation with increased age, non-white ethnicity, lower socio-economic status, and non-private insurance. The mean study quality score by a modified ISPOR checklist was 8.3/10. These results provide a contemporary update on evidence of disparities in access to novel genomic testing. As an expanding field, this requires further investigation to prevent accentuations in inequitable implementation of precision oncology and differences in outcomes between different socio-demographic groups.
Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in 'spontaneous' inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission. REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination. The protocol was approved by East Midlands-Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications. ISRCTN18217497.
Sudden sensorineural hearing loss (SSNHL) is a rare manifestation of COVID-19. Cochlear implantation (CI) has been reported for definitive management of COVID-19 related single sided deafness (SSD) in adults. We present the first cases of pediatric CI for presumed COVID-19 related SSD. Patients under 18 years were included who underwent CI following SSNHL after COVID-19 infection via retrospective review. Literature review was performed on PubMed for "cochlear implant" and "COVID" and "deafness or hearing loss." A 13-year-old boy (patient A) and 6-year-old girl (patient B) met inclusion criteria; both patients underwent round window insertion of a perimodiolar electrode. For patient A, audiogram showed SNHL in the left ear; pre-operative word recognition score (WRS) and speech awareness threshold (SAT) were 20% at 100 dB HL and 90 dB HL, respectively. The patient underwent CI 9 months post-infection; SAT for patient A improved to 25 dB HL at 2.5 months after surgery. Patient B's pre-operative WRS and SAT in the affected ear were 0% at 100 dB HL and non-responsive, respectively. She underwent right CI 10 months post-infection; her SAT improved post-operatively to 20 dB HL at 2 post-operative months. Neither patient suffered from intra- or post-operative complication. Both patients and their caregivers reported subjective benefit from CI. Single-sided deafness is a rare neurological complication from COVID-19. CI is a valuable tool for restoring hearing localization and awareness in this scenario. Early success with these cases demonstrates technical feasibility and benefit with this management of pediatric COVID-19 related SSD.
The management of drug-use associated endocarditis (DUA-IE) has historically been piece-meal with variable involvement of multiple specialties - cardiology, addictions medicine, infectious disease, surgery and others. The literature was reviewed and combined with the writing group's insights from years of clinical experience to come up with recommendations for care. In this review, the potential benefits of providing holistic, person-centered, multidisciplinary care to these patients are discussed. The diagnosis of a patient with DUA-IE provides an opportunity to not only treat their presenting condition, but to screen for co-infections, address socioeconomic barriers, and connect with longitudinal care. Moreover, there is an ongoing paradigm shift towards the use of partial-oral antibiotic regimens which may reduce barriers to access and adherence for this population. Variability in whether surgery is offered for persons who inject drugs exists, especially in relation to first expecting abstinence, however this is a non-evidence-based criterion to determine operative candidacy. Decisions around timing and type of surgical intervention should be made systematically with the support of a multi-disciplinary team to avoid bias and achieve the best possible clinical outcome. Regarding management of substance use, data exists to support harm reduction strategies including provision of sterile substance use equipment, opioid agonist therapy, overdose prevention, take-home naloxone programs, drug checking services, and supportive housing programs. The mobilization of a multi-disciplinary endocarditis team is fundamental for providing the best possible care, which should be individualized.
This study aimed to explore the bibliometric characteristics of pediatric fracture research from its inception until 2024, specifically focusing on high-cited publications (HCPs) defined as those with 100 or more citations. Key indicators evaluated include publication frequency, citation counts, and collaboration metrics. The Scopus database was utilized to identify global publications related to pediatric fractures. The top HCPs were retrieved for detailed analysis, employing bibliometric and network analyses with VOSviewer and Biblioshiny software to uncover key contributors, including organizations, authors, and journals, along with their collaborative interactions and significant keyword co-occurrences. 262 HCPs in pediatric fracture research were identified and indexed in Scopus from 1929 to 2024 (95 years), accumulating a cumulative citation count of 42,675 and an average of 162.9 citations per publication. This body of work involved 931 authors from 160 organizations across 31 countries, with external funding at 9.16% and international collaboration at 7.25%. The United States of America was the leading contributor with 145 publications (55.34%), followed by the United Kingdom (11.83%) and Canada (11.45%). The Children's Hospital of Philadelphia emerged as the most productive organization, while the Journal of Pediatric Orthopaedics published the highest number of HCPs (n = 59). The journal 'Bone' exhibited the highest citation impact per paper, averaging 271.33 citations. This study elucidates research trends and influential contributions in pediatric fracture research, offering valuable insights into past, present, and future research priorities in this domain. The online version contains supplementary material available at 10.1007/s43465-025-01551-x.
We present a computational framework for electron-molecule scattering that is intended as a step toward a more accurate and unified description over a broad energy range relevant to applications. The approach combines a spherical complex optical potential (SCOP), constructed from multiconfiguration Dirac-Fock atomic densities via a group-additivity scheme, with a partial-wave solution of the Dirac equation. Methane (CH4) and silane (SiH4) are used as benchmark targets because of their simple tetrahedral structure and well-documented cross sections. The comparison among exchange models is used to highlight the sensitivity of predicted cross sections to the target model potential and the need for improved model descriptions. In addition, the present Dirac-based implementation is benchmarked against our existing [Joshipura et al., Phys. Rev. A, 2004, 69, 022705] nonrelativistic optical-potential treatment that employs the Numerov method to solve the Schrödinger equation, allowing us to quantify both relativistic kinematic and spinor effects. Although relativistic effects on integral cross sections are minimal, the Dirac treatment has a pronounced impact on the phase shifts and large-angle differential cross sections. Among the exchange models tested, the modified Furness-McCarthy exchange shows the most consistent agreement with benchmark data and represents a clear improvement over our earlier group-additivity SCOP results. This enhancement lays the groundwork for extending the method to larger and strongly polar molecules.
Inactivating NOTCH1 mutations in head and neck squamous cell carcinoma (HNSCC) were described over a decade ago, suggesting a tumor suppressor function - unlike its oncogenic role in other tumors. Today, much debate persists regarding a putative oncogenic role in HNSCC as well, with reports that NOTCH1 signaling drives tumor growth and a cancer stem cell (CSC) phenotype. In this work, comprehensive experiments unequivocally demonstrate that NOTCH1 is a tumor suppressor in HNSCC regardless of mutation or activation status and that it reduces CSC frequency. We developed a signature of NOTCH1 activation showing the pathway is associated with very early differentiation, an altered tumor microenvironment, and better prognosis. Clarifying whether NOTCH1 occasionally functions as an oncogenic driver in HNSCC is crucial to prognosis and personalized therapy. The results presented unify the field, reconcile conflicting data, and provide critical insights into the biological and clinical significance of NOTCH1, with broader implications in other squamous carcinomas with NOTCH1 mutations.
The utility of combination treatment with gemcitabine and camonsertib, an ataxia telangiectasia and Rad3-related kinase inhibitor, in mediating tumor cell death was assessed in preclinical models, prompting clinical investigation. The phase Ib TRESR study (NCT04497116) aimed to evaluate the safety, tolerability, and preliminary efficacy of the combination in patients with advanced solid tumors harboring DNA damage repair (DDR) gene alterations. Cell lines and tumor xenografts were tested across a range of dose levels and schedules. Patients (N = 76) harboring tumors with DDR gene alterations received camonsertib (80-120 mg) and de-escalating gemcitabine (1,000-100 mg/m2) in 21- or 28-day cycles on an intermittent dosing regimen. Safety, tolerability, and preliminary efficacy were assessed to identify an optimal dosing regimen. In preclinical models, low-dose camonsertib (1/3 maximum tolerated dose) and gemcitabine led to tumor regression and was well tolerated with minimal body weight loss observed. In patients, synergistic toxicities were observed, primarily myelosuppression, resulting in gemcitabine de-escalation. The introduction of a 1 week on/1 week off schedule in combination with low-dose gemcitabine allowed for spontaneous neutrophil recovery, fewer dose modifications, and improved tolerability. Tumor responses were primarily observed in patients with gynecologic cancers, with tumor control maintained for greater than 1 year in some patients. Camonsertib and low-dose gemcitabine demonstrated preliminary clinical activity, but due to challenging tolerability, further evaluation is warranted to identify the optimal dosing regimen and subset of patients who may benefit most from this combination.
The North-East London Type 1 Diabetes Transformation (NATALIE) Project aimed to accurately provide data on place of care for people with type 1 diabetes (T1D) and assess the impact of interventions to engage people with T1D not accessing specialist care or those assigned to a high-risk register. Systematic searches were carried out to identify dual coding/no coding for type of diabetes and were followed by practice level case note review by a healthcare professional (HCP). The Clinical Effectiveness Group (CEG), which is a local primary care-led clinical academic group, was commissioned to aid with data searches. In City & Hackney, following the audit, the impact of pilot interventions was evaluated. These included a primary care toolkit, to improve engagement and of focused clinical care for those assigned to a high-risk register (HbA1c >75 mmol/mol) were analysed. One hundred and fifty general practitioner (GP) practices engaged and 2499 patient records were reviewed. The proportion of people with T1D receiving care in primary care alone varied from 12.9 % to 37.7 % with a mean of 30 %. Following interventions including secondary care referral, referring for Freestyle Libre monitoring or structured education, the number of people with T1D under primary care alone reduced from 36 % to 24 %. The 85/133 people with T1D on the high-risk register who engaged with focused clinical intervention decreased their HbA1c from 93 mmol/mol to 83 mmol/mol. In an area of high socioeconomic deprivation, the NATALIE project showed that an average of 30 % of people with type 1 diabetes are under primary care alone, and simple interventions improved this by up to 10 %. Furthermore, focused clinical contacts with high-risk people with T1D can reduce HbA1c by 10 mmol/mol.
Anemia in pregnancy, predominantly due to iron deficiency, is a significant public health concern in India, contributing to 40% of maternal deaths. Despite initiatives like Anemia Mukt Bharat, progress in reducing anemia remains slow, particularly in states with high healthcare coverage like Puducherry. To evaluate the changes in anemia, hemoglobin (Hb) levels, and iron biomarkers among pregnant women receiving iron supplementation at primary health centres (PHCs) in Puducherry, India. A prospective cohort study followed 150 pregnant women from their first to third trimesters across four PHCs in Puducherry. Hb and iron parameters, including serum ferritin and transferrin saturation (TSAT), were measured in each trimester. Compliance with iron-folic acid (IFA) supplementation was assessed using pill counts. Dietary iron intake was recorded using a 24-h dietary recall. Anemia prevalence increased from 40.7% in the first trimester to 60% in the second, decreasing to 44% in the third trimester. Iron deficiency was prevalent in >70% of the cohort across all trimesters. Despite high compliance (90%) with IFA, anemic women received inadequate doses relative to their anemia status. Biomarkers like serum ferritin showed no significant improvement, while transferrin and TSAT levels remained suboptimal. Dietary iron intake was insufficient throughout pregnancy, highlighting the need for additional micronutrient supplementation. While IFA supplementation improved compliance, it was inadequate to reduce anemia effectively. Programmatic gaps, such as insufficient IFA supply for anemic women and lack of targeted supplementation, need to be addressed. National indicators should emphasize "screen and treat" strategies over tablet counts for anemia management. Résumé Contexte:L’anémie pendant la grossesse, principalement due à une carence en fer, constitue un problème de santé publique majeur en Inde, contribuant à 40 % des décès maternels. Malgré des initiatives telles que Anemia Mukt Bharat, les progrès dans la réduction de l’anémie restent lents, en particulier dans les États bénéficiant d’une couverture sanitaire élevée comme Puducherry.Objectif:Évaluer l’évolution de l’anémie, des taux d’hémoglobine (Hb) et des biomarqueurs du fer chez les femmes enceintes recevant une supplémentation en fer dans les centres de soins de santé primaires (CSSP) de Puducherry, en Inde.Matériel et Méthodes:Une étude de cohorte prospective a suivi 150 femmes enceintes du premier au troisième trimestre dans quatre CSSP de Puducherry. Les paramètres de l’Hb et du fer, notamment la ferritine sérique et le coefficient de saturation de la transferrine (CST), ont été mesurés à chaque trimestre. L’observance du traitement par supplémentation en fer et acide folique (IFA) a été évaluée par comptage des comprimés. L’apport alimentaire en fer a été enregistré à l’aide d’un rappel alimentaire de 24 heures.Résultats:La prévalence de l’anémie est passée de 40,7 % au premier trimestre à 60 % au deuxième, puis a diminué à 44 % au troisième trimestre. Une carence en fer était présente chez plus de 70 % de la cohorte à tous les trimestres. Malgré une observance élevée (90 %) du traitement par supplémentation en fer et en acide folique (IFA), les femmes anémiques ont reçu des doses insuffisantes compte tenu de leur anémie. Les biomarqueurs tels que la ferritine sérique n’ont montré aucune amélioration significative, tandis que les taux de transferrine et de coefficient de saturation de la transferrine (CST) sont restés sous-optimaux. L’apport alimentaire en fer était insuffisant tout au long de la grossesse, soulignant la nécessité d’une supplémentation en micronutriments.Conclusion:Bien que la supplémentation en IFA ait amélioré l’observance, elle s’est avérée insuffisante pour réduire efficacement l’anémie. Les lacunes des programmes, telles que l’insuffisance de l’approvisionnement en IFA pour les femmes anémiques et le manque de supplémentation ciblée, doivent être comblées. Les indicateurs nationaux devraient privilégier les stratégies de dépistage et de traitement plutôt que le nombre de comprimés pour la prise en charge de l’anémie.
Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative diseases caused by the misfolding of proteins generated in the exon 3 region of the prion protein gene (PRNP). Recent investigations using protein misfolding cyclic amplification assays indicated that some canids displayed a low susceptibility to TSE due to a specific nonsynonymous substitution (human: N159D/E; canid: N163D/E; alignment herein: N302D/E) in the prion protein that may confer protection against prion seeding activity and propagation. To examine the molecular evolution underlying this observation, we determined the mammalian taxonomic distribution of the N159D/E substitution in 882 PRNP sequences representing 26 Orders, 132 families, and 686 species. Two families each in Carnivora (Canidae and Mustelidae) and Chiroptera (Mormoopidae and Vespertilionidae), and one family each in Artiodactyla (Moschidae) and Rodentia (Erethrizontidae), possessed N159D/E that has been reported to confer resistance to TSEs. Although no direct evidence linked a pattern of resistance (phylogenetic relatedness, geographic location, etc.) in these diverse species, it may be that coevolutionary pressures led 53 of the examined 686 species (1 domestic species, 52 wild species) to possess N159D/E. Therefore, the presence of N159D/E may not be the only factor in determining sensitivity to prion diseases; consequently, a more detailed investigation into the 53 species, such as knockout experiments, is warranted.
Nasal airway obstruction (NAO) is prevalent with substantial health and quality of life burdens. Nasal valve collapse (NVC) is one structural cause of NAO. Temperature-controlled radiofrequency (TCRF) nasal valve remodeling offers an alternative to invasive surgery. Clinical efficacy is established, but the impacts of TCRF on healthcare resource utilization (HRU) and cost in real-world settings remain underexplored. Two cohorts with NAO were defined from a large general NAO population: the TCRF cohort with an isolated TCRF (index) procedure and a propensity-matched medically managed (MM) cohort without nasal procedures. HRU and costs were evaluated within a 24-month pre-/post-index period for both. A total of 10,206 TCRF and 50,766 MM patients were analyzed. Significant post-index reductions were observed for TCRF across all-cause Evaluation & Management (E&M) visits, ENT-related procedures, and sleep-related claim categories. A large reduction in mean daily post-index costs was seen for the TCRF cohort: $68.07 pre-index to $38.75 post-index (-43.1%). Mean daily costs went up in the MM cohort from $42.08 pre-index to $63.26 post-index (+50.4%), resulting in total cost savings of $21,418.26 for the TCRF cohort and a total cost increase of $15,471.99 in the MM cohort in the 24-month post-index period. TCRF cost reductions were driven by reductions in NAO-related HRU. In this large, real-world analysis, TCRF treatment for NVC-related NAO demonstrated substantial reductions in HRU and total costs of care, demonstrating sustained savings over 2 years relative to MM patients.
Arachnoid cysts (AC) are benign, cerebrospinal fluid (CSF)-filled sacs. In the cerebellopontine angle (CPA), these cysts may be intimately associated with cranial nerves, the brainstem, and the cerebellum. There are small series associating CPA AC with sensorineural hearing loss, vestibulopathy, and facial paresis. To date, there is a paucity of data regarding factors related to AC that might predict which cysts are associated with sensorineural hearing loss (SNHL). Herein, we investigate the characteristics of AC in the CPA for patients with SNHL. A single-institution, retrospective study of pediatric patients with AC and audiological evaluations from 2009 to 2024 was conducted. ACs in the CPA were categorized based on contact with the CN VII/VIII complex. The data collected included cyst location, estimated volume, the presence/degree of CN VIII distortion, nerve length, site of contact, and audiologic data. Descriptive statistics analyzed associations between AC and SNHL in the absence of other known pathologies. A total of 19 patients had 21 ACs involving the CPA. From this group, 11 patients had 11 cysts with contact/distortion of the CN VIII complex (study group), while 8 patients had 10 cysts without contact with the CN VIII (control group). Four (36%) patients in the study group had SNHL ipsilateral to the AC, significantly more than controls ( P <0.03). While the study group had significantly larger cysts ( P <0.03), there was no association with the amount of distortion, length of CN VIII, or contact with the root entry zone (REZ). Arachnoid cysts in the cerebellopontine angle are associated with ipsilateral SNHL; however, it remains unclear which factors predict SNHL beyond contact/compression of the CN VIII complex. All patients with CPA AC should be referred for audiometric evaluation.
Canine prostatic adenocarcinoma is a rare but highly aggressive cancer that is typically diagnosed at an advanced stage, due to the lack of effective screening methods and poor recognition of early lesions. Cancer stem cells are known to drive tumour progression and treatment resistance in human prostate cancer, but their role in naturally occurring canine disease remains poorly defined. A deeper understanding of the biology of canine prostatic adenocarcinoma is therefore essential to improve prognosis and to develop relevant comparative models. We established and comprehensively characterised two novel canine prostatic adenocarcinoma cell lines, Kodiak and Bobby, with detailed comparison to their tumours of origin and, for Kodiak, xenografts generated in immunodeficient mice. Both lines displayed variable epithelial morphology influenced by culture conditions, and Kodiak xenografts recapitulated key histopathological patterns of the primary tumour. Expression of the luminal epithelial marker CK8/18 and the basal marker CK14 was largely retained across tumour, cell line, and xenograft, whereas the basal markers CK5 and p63, and the urothelial marker UPIII, were diminished or lost during in vitro culture. Evaluation of cancer stem cell-associated markers showed consistent expression of CD44, Nanog, Oct3/4, and Sox2 in the original tumours and cell lines, while CD133, Nestin, and Trop2 were present in the tumours but absent in vitro, indicating selective loss of specific stem-like populations. Media-dependent plasticity was evident in the Bobby line. These models retain key epithelial and stemness features and provide robust platforms for translational prostate cancer research in dogs and humans.
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Assessment of the effect of cytotoxic chemotherapy on the indices of iron homeostasis to elucidate the aetiology of anaemia in breast cancer. Forty-two newly diagnosed breast cancer patients with Hb > 10 g/dL were recruited. Iron indices were estimated before and after neoadjuvant chemotherapy (NACT). Anaemia of chronic disease (ACD) and anaemia of chronic disease + iron deficiency anaemia (IDA) were identified by sTfR, sTfR index, and algorithm by Skikne et al. Anaemia was 52% at the presentation time, which increased to 93% at the end of NACT. Among the anaemic breast cancer patients, 75% belonged to the group of ACD + IDA, and only 25% belonged to the group of ACD at the time of presentation. After NACT, the number of patients in the ACD + IDA group significantly increased to 93%, while the members of the ACD group significantly reduced to 7%. Ferritin, Hepcidin, Transferrin, sTfR, and sTfR index increased after NACT. The primary aetiology of anaemia among Indian breast cancer patients is a combination of ACD and IDA. Indian breast cancer patients were more vulnerable to developing iron deficiency anaemia when compared to anaemia of chronic disease during NACT.
Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo.