Citations

Abstract Hemorrhagic shock is a common emergency that accounts for more than 10% of global mortality and up to 40% of trauma-related mortality. The Advanced Trauma Life Support (ATLS) guidelines outline resuscitation strategies in patients with massive hemorrhage based on clinical trial and observational data. Early intervention with fluids and/or blood products is recommended during resuscitation as key to maintaining vascular patency, stabilizing a patient’s blood pressure, maintaining tissue oxygenation, and limiting shock. From a transfusion perspective, there is wide heterogeneity in the quality of blood products due to donor and manufacturing variation. The optimal transfusion strategy for massive hemorrhage remains unclear. In silico models of resuscitation may offer a means to evaluate the effectiveness and safety of various resuscitation protocols. Here we describe a stochastic multicompartment model of fluid balance and resuscitation that includes (i) cardiovascular hemodynamics, (ii) body fluid compartments and capillary solute exchange, (iii) the ability to alter hemorrhage, resuscitation, and hemostasis parameters, and (iv) tissue oxygenation and capillary-alveolar gas exchange. Building upon deterministic frameworks, this stochastic model more faithfully reflects the clinical heterogeneity of bleeding patients at a level I trauma center. This allows for a proof of concept in silico trial comparing crystalloids, conventional component therapy (CCT), i.e. red cell, platelet and plasma components, to cold-stored low titer group O whole blood (LTOWB). In an in silico cohort of ATLS class III (>30% and ≤40% blood volume lost) hemorrhage, LTOWB resuscitation reduced the time spent in the critical hemostatic window (platelet count <50x109/L, INR≥2, hemoglobin (Hgb) <8 g/dL and fibrinogen <150 mg/dL) compared with CCT (90.59 vs. 147.62 minutes; p=0.04), with no difference in predicted event-free survival (t = 240 minutes; cardiac < 1.5, fluid overload > 10% or SBP > 150% of the starting SBP, or Hgb < 3.0 g/dL). In a separate cohort of ATLS class IV (>40% blood volume lost) hemorrhage, LTOWB yielded a higher predicted event-free survival (74%) versus the CCT arm (69%, p < 0.01). We demonstrate how this in silico platform can function as a digital twin for hemorrhagic trauma enabling precision transfusion strategies, and in parallel, an operational twin to support blood banks to forecast blood product demand and inform massive transfusion protocols and clinical trial design.

Abstract Background Preterm premature rupture of membranes (PPROM) and preterm labor (PTL) are adverse obstetrical outcomes that are strongly associated with cervical high-risk human papilloma virus (cHPV) infection at the time of pregnancy. Persistent cHPV may lead to oncogenic changes in the cervico-vaginal tract and can cause inflammation in gestational tissues, but it is unknown how persistent cHPV infection may affect obstetrical outcomes. The aim of this study is to evaluate whether persistent cHPV infection is associated with recurrent PPROM or PTL among patients with a prior spontaneous preterm birth due to PPROM/PTL, and to examine clinical and pathologic characteristics of cHPV infection in this population. Methods We conducted a retrospective cohort study of patients delivering at Mayo Clinic Rochester or Mayo Clinic Health System (5/1/2018–12/31/2023). Eligible patients had ≥ 1 spontaneous preterm birth due to PPROM/PTL and positive cHPV testing. Demographics and pregnancy outcomes from index and subsequent pregnancies were abstracted. Persistent cHPV was defined as > 1 pregnancy with positive cHPV testing. Results Of 191 index pregnancies, 90 (47.1%) and 30 (33.3%) had one and two subsequent pregnancies, respectively. Patients were predominantly White (91.3%), non‑Hispanic (94.2%), non-smokers (72.0%), and 34.8% were unvaccinated for HPV. Approximately one‑third (31%) experienced recurrent PPROM/PTL in the second pregnancy, with recurrence in 40.7% of those with persistent cHPV and 27.4% without (p = 0.69). Excisional procedures occurred before 12.0% of index pregnancies and 20–24% of subsequent pregnancies; recurrence of PTL/PPROM remained high regardless of procedure history. HPV strain data were available for 132 index pregnancies, and types 16 and 18 were more likely to persist into a subsequent pregnancy (p = 0.0043). CIN persistence occurred at similar rates in patients with and without persistent cHPV infection. Placental inflammation rates were high in both patients with persistent and non-persistent cHPV. Conclusion Recurrent PPROM/PTL, CIN persistence, and placental inflammation were common; a finding independent of persistent cHPV infection, excisional procedure history, or HPV vaccination status. These findings suggest that factors other than cHPV persistence may play a larger role in recurrent preterm birth. Larger studies with higher cHPV prevalence and subsequent pregnancies are needed to provide clarity.

Abstract Background Central nervous system (CNS) infections are significant causes of morbidity and mortality, especially when diagnosis is delayed. Traditional cerebrospinal fluid diagnostic methods for CNS infections have limited sensitivity. Metagenomic next-generation sequencing of cerebrospinal fluid (MSCSF) is a newer diagnostic tool capable of detecting a broad range of pathogens in a single assay. Methods This retrospective cohort study evaluated the first-year experience with MSCSF at Mayo Clinic. A total of 422 tests performed during calendar year 2024 on adult patients at Mayo Clinic facilities and those tested through Mayo Clinic Laboratories were analyzed, with a subcohort analysis of the 210 Mayo Clinic patients performed to define patient characteristics associated with positive results and clinical outcomes. Results The sensitivity of MSCSF for detecting neuroinfection in the subcohort was 64%, with 43% of confirmed neuroinfections diagnosed by MSCSF only. Subjects who were immunosuppressed (odds ratio [OR]: 3.5, P = .008) and those with a high pretest probability of CNS infection (OR: 20.1, P &lt; .001) were more likely to have positive results. Also, those who tested positive were more likely to die within the ensuing 30 days than those who tested negative (OR: 5.2, P = .001). Conclusions MSCSF can be a valuable tool for diagnosing CNS infection but should not be used indiscriminately. It appears to be most beneficial when there is a high clinical suspicion of CNS infection and conventional diagnostics, and available molecular tests, yield negative results. Its integration into clinical practice should be guided by diagnostic stewardship to maximize cost-effectiveness and clinical utility.

Abstract Obstetric training programs typically offer limited formal education on placental pathology; yet, in practice, obstetric providers are expected to incorporate placental pathology findings into the overall evaluation of obstetric complications. In this narrative review, we briefly review pathology classifications and then delve deeper into pathology findings that may change clinical decision‐making, specifically highlighting pathologic lesions with a recurrence risk and recommended management for subsequent pregnancies. Last, we present specific recommendations on how to improve clinical interpretability and utility of placental pathology reports for obstetrical practice.

AbstractBackgroundTandem mass spectrometry (MS/MS) has become a common clinical laboratory testing modality has demonstrated success in distinguishing between small protein variations in transthyretin amyloidosis. Since many common clinically significant RBC antigens are also small protein variations, this study aimed to determine if MS/MS could correctly detect common RBC antigens within the Rh, Kell, Duffy, MNS, Kidd, Diego, and Lutheran blood group systems.Study Design and MethodsResidual samples from serotyped/genotyped blood donors at a hospital‐based blood donation center from February to August 2021 were analyzed. RBC membrane protein preparations underwent protease digestion prior to MS/MS analysis for RhD, RhCE, Kell, atypical chemokine receptor 1 (Duffy), glycophorin A (MNS), glycophorin B (MNS), urea transporter 1 (Kidd), band 3 anion transport protein (Diego), and basal cell adhesion molecule (Lutheran). Untargeted liquid chromatography (LC)‐MS/MS detected protein‐specific peptides, while targeted LC‐selected reaction monitoring (LC‐SRM) detected RBC antigen‐containing peptides.ResultsThrough the use of multiple proteases, untargeted LC–MS/MS detected protein‐specific peptides in all but glycophorin B, with band 3 anion transport protein, basal cell adhesion molecule, Kell, and glycophorin A having the greatest protein sequence coverage. Targeted LC‐SRM detected antigen‐specific peptides for Cw, Dia/Dib, Kpb, and Wra/Wrb, which agreed with the donors' previous typing results.DiscussionMS/MS can successfully detect peptides from several blood group systems but only detected a subset of their common RBC antigens. Further sample enrichment and MS/MS detection improvements will need to occur before MS/MS could be considered a clinical RBC phenotyping modality.

Withdrawal Statement The authors have withdrawn the manuscript because the data it contained has been updated. Consequently, they request that this work should not be cited as a reference for any projects to ensure the use of the most current information. For any questions or further clarifications, readers are encouraged to contact the corresponding author directly

The placenta is susceptible to infection by a number of viral pathogens, including severe acute respiratory syndrome coronavirus 2, which is associated with poor fetal outcomes. The histologic pattern of injury, termed severe acute respiratory syndrome coronavirus 2 placentitis, is characterized by a triad of increased perivillous fibrin deposition, intervillous histiocytes, and trophoblast necrosis. While the etiology of massive perivillous fibrin deposition (MPVFD) is mostly unknown, previous case reports of MPVFD in association with maternal Enterovirus (ENT) suggest that a subset of these cases are a consequence of undiagnosed viral infection. We evaluated 46 placentas collected between 2011 and 2022 with a diagnosis of MPVFD (n = 41) or chronic histiocytic intervillositis (CHI; n = 4). Combining methods of pan-viral metagenomic sequencing and targeted viral PCR, we detected Enterovirus DNA in 8 of 45 (18%) MPVFD and/or CHI cases. Seven of these positive cases were from MPVFD, and 1 was associated with a CHI diagnosis. Enterovirus A species (n = 7) were commonly identified, whereas one case had Enterovirus B. Histologic evaluation of these cases, including immunohistochemical staining for CD68, demonstrated increased intervillous histiocytes in Enterovirus-positive MPVFD cases in comparison with Enterovirus -negative, as well as evidence of trophoblast necrosis. Thus, we favor the terminology Enterovirus placentitis to describe this pathology. Overall, these findings suggest that Enterovirus is an underrecognized etiology of histologic MPVFD and, possibly, CHI. Further study to evaluate the recurrence risk of Enterovirus placentitis in comparison to MPVFD may help inform future fertility planning in patients with these diagnoses.