ProtekDuo Cannula for Pre-, Intra-, and Postoperative Lung Transplantation Management.

ABSTRACT: We present a 61-year-old patient with pulmonary hypertension, acute respiratory failure, and acute severe right ventricular (RV) dysfunction. Preoperatively, a ProtekDuo® was inserted for extracorporeal membrane oxygenation (ECMO) and RV protection with venopulmonary (VP) ECMO in (dl) V-P ECMO configuration. Intraoperatively, it provided venous drainage for venoarterial (VA) ECMO in (dl) VP-/AO configuration for bilateral orthotopic lung transplantation (BOLT). Postoperatively, the patient remained on (dl) V-P ECMO for RV support and was decannulated with mild RV dysfunction after 5 days. This is the first description of the ProtekDuo® used in (dl) V-P to (dl) VP-/AO to (dl) V-P configuration for the entire perioperative period of BOLT.

Veno-arterial extracorporeal membrane oxygenation as bridge for fluid resuscitation in a patient with acute respiratory failure and circulatory shock two years post lung transplantation.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) continues to evolve and is recognized as an important adjunct as a bridge to recovery or a bridge to transplant. We wanted to share our experience of using veno-arterial (VA) ECMO as an adjunct to lung recovery and an aide for fluid resuscitation. CASE DESCRIPTION: We present the case of a 77-year-old man with a history of previous single lung transplant who had acute respiratory decompensation and cardiovascular collapse secondary to CMV pneumonia and septic shock. He was cannulated for VA ECMO, treated for CMV pneumonia and resuscitated with 5 L of albumin 5% and antibiotics, within 12 hours of cannulation. He required two days of VA ECMO and was ultimately decannulated and discharged to a rehabilitation facility on hospital day 73. CONCLUSION: This case emphasizes the challenging clinical scenario of fluid resuscitation in a lung transplant patient. With adequate patient selection, a multidisciplinary team and the use of VA ECMO, success can be achieved.

Deep spectral improvement for unsupervised image instance segmentation.

Recently, there has been growing interest in deep spectral methods for image localization and segmentation, influenced by traditional spectral segmentation approaches. These methods reframe the image decomposition process as a graph partitioning task by extracting features using self-supervised learning and utilizing the Laplacian of the affinity matrix to obtain eigensegments. However, instance segmentation has received less attention than other tasks within the context of deep spectral methods. This paper addresses that not all channels of the feature map extracted from a self-supervised backbone contain sufficient information for instance segmentation purposes. Some channels are noisy and hinder the accuracy of the task. To overcome this issue, this paper proposes two channel reduction modules, Noise Channel Reduction (NCR) and Deviation-based Channel Reduction (DCR). The NCR retains channels with lower entropy, as they are less likely to be noisy, while DCR prunes channels with low standard deviation, as they lack sufficient information for effective instance segmentation. Furthermore, the paper demonstrates that the dot product, commonly used in deep spectral methods, is not suitable for instance segmentation due to its sensitivity to feature map values, potentially leading to incorrect instance segments. A novel similarity metric called Bray-curtis over Chebyshev (BoC) is proposed to address this issue. This metric considers the distribution of features in addition to their values, providing a more robust similarity measure for instance segmentation. Quantitative and qualitative results on the Youtube-VIS 2019 and OVIS datasets highlight the improvements achieved by the proposed channel reduction methods and using BoC instead of the conventional dot product for creating the affinity matrix. These improvements regarding mean Intersection over Union (mIoU) and extracted instance segments are observed, demonstrating enhanced instance segmentation performance. The code is available on: https://github.com/farnooshar/SpecUnIIS.

Increased expression of ABO blood group antigens secretion phenotype with O blood group and age advances.

OBJECTIVES: To ascertain the prevalence of ABH antigen secretors and non-secretors among Yemenis. In addition to explore the factors that may affect the expression of the secretion phenotype. METHODS: This cross-sectional study was carried out between May and September 2022 on 215 healthy Yemeni individuals at the International Malaysian University, Ibb, Yemen. The participants were tested for blood group antigen on their blood samples using standard test tube method using the suitable ABH antisera. Saliva was collected and tested for secretion using hemagglutination inhibition test with suitable A, B, and H antisera. Before collecting the blood samples, informed consent was obtained from each participant and complete data and history questionnaire were collected by the research team. RESULTS: In general, 78.1% of Yemini participants were found to be secretor (80% men and 73.3% females). This percentage increased within O blood group (95%) and decreased within AB blood group (54%) individuals. Both O and AB blood groups showed statistically significant association with secretor trait. Also, it was noticed that age advance increases the expression of Se gene. In addition, the secretor state increased among Rh-negative people. CONCLUSION: The frequency of ABH secretors was 78.1% among Ibb province population in Yemen. Blood group O revealed the greatest frequency (95%), whereas blood group AB showed the lowest secretor frequency (54%). The secretor phenotype was highly expressed gradually with advance age then decline.

Establishing the Foundations of Emotional Intelligence in Care Companion Robots to Mitigate Agitation Among High-Risk Patients With Dementia: Protocol for an Empathetic Patient-Robot Interaction Study.

BACKGROUND: An estimated 6.7 million persons are living with dementia in the United States, a number expected to double by 2060. Persons experiencing moderate to severe dementia are 4 to 5 times more likely to fall than those without dementia, due to agitation and unsteady gait. Socially assistive robots fail to address the changing emotional states associated with agitation, and it is unclear how emotional states change, how they impact agitation and gait over time, and how social robots can best respond by showing empathy. OBJECTIVE: This study aims to design and validate a foundational model of emotional intelligence for empathetic patient-robot interaction that mitigates agitation among those at the highest risk: persons experiencing moderate to severe dementia. METHODS: A design science approach will be adopted to (1) collect and store granular, personal, and chronological data using Personicle (an open-source software platform developed to automatically collect data from phones and other devices), incorporating real-time visual, audio, and physiological sensing technologies in a simulation laboratory and at board and care facilities; (2) develop statistical models to understand and forecast the emotional state, agitation level, and gait pattern of persons experiencing moderate to severe dementia in real time using machine learning and artificial intelligence and Personicle; (3) design and test an empathy-focused conversation model, focused on storytelling; and (4) test and evaluate this model for a care companion robot (CCR) in the community. RESULTS: The study was funded in October 2023. For aim 1, architecture development for Personicle data collection began with a search for existing open-source data in January 2024. A community advisory board was formed and met in December 2023 to provide feedback on the use of CCRs and provide personal stories. Full institutional review board approval was received in March 2024 to place cameras and CCRs at the sites. In March 2024, atomic marker development was begun. For aim 2, after a review of open-source data on patients with dementia, the development of an emotional classifier was begun. Data labeling was started in April 2024 and completed in June 2024 with ongoing validation. Moreover, the team established a baseline multimodal model trained and validated on healthy-person data sets, using transformer architecture in a semisupervised manner, and later retrained on the labeled data set of patients experiencing moderate to severe dementia. In April 2024, empathy alignment of large language models was initiated using prompt engineering and reinforcement learning. CONCLUSIONS: This innovative caregiving approach is designed to recognize the signs of agitation and, upon recognition, intervene with empathetic verbal communication. This proposal has the potential to have a significant impact on an emerging field of computational dementia science by reducing unnecessary agitation and falls of persons experiencing moderate to severe dementia, while reducing caregiver burden. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55761.

Deep Conformal Supervision: Leveraging Intermediate Features for Robust Uncertainty Quantification.

Trustworthiness is crucial for artificial intelligence (AI) models in clinical settings, and a fundamental aspect of trustworthy AI is uncertainty quantification (UQ). Conformal prediction as a robust uncertainty quantification (UQ) framework has been receiving increasing attention as a valuable tool in improving model trustworthiness. An area of active research is the method of non-conformity score calculation for conformal prediction. We propose deep conformal supervision (DCS), which leverages the intermediate outputs of deep supervision for non-conformity score calculation, via weighted averaging based on the inverse of mean calibration error for each stage. We benchmarked our method on two publicly available datasets focused on medical image classification: a pneumonia chest radiography dataset and a preprocessed version of the 2019 RSNA Intracranial Hemorrhage dataset. Our method achieved mean coverage errors of 16e-4 (CI: 1e-4, 41e-4) and 5e-4 (CI: 1e-4, 10e-4) compared to baseline mean coverage errors of 28e-4 (CI: 2e-4, 64e-4) and 21e-4 (CI: 8e-4, 3e-4) on the two datasets, respectively (p < 0.001 on both datasets). Based on our findings, the baseline results of conformal prediction already exhibit small coverage errors. However, our method shows a significant improvement on coverage error, particularly noticeable in scenarios involving smaller datasets or when considering smaller acceptable error levels, which are crucial in developing UQ frameworks for healthcare AI applications.

Ninety-Day Outcomes in Primary Hypercoagulable Disease Patients Undergoing Total Joint Arthroplasty Vs Normal: A Matched Case-Control Series.

Background: Perioperative complications of deep vein thrombosis are well described in the total joint arthroplasty (TJA) literature. Few studies have investigated short-term perioperative outcomes of patients with primary hypercoagulable diseases (PHDs). Optimal perioperative management of PHD patients remains unknown, and they are often referred to tertiary centers for care. We investigated the influence perioperative hematology consultation and anti-coagulation use had on PHD patient outcomes following TJA surgery within the 90-day postoperative period. Methods: This retrospective cohort study examined perioperative outcomes of PHD patients undergoing TJA. Thirty-eight PHD patients were identified and compared to a 3:1 matched control group in a consecutive series of 6568 cases (2007-2019). Perioperative hematology consultations, use of anticoagulants (AC) or antiplatelet therapy, emergency department (ED) visits, readmissions, and complications within 90 days of surgery were determined. Results: The PHD cohort exhibited more frequent hematology consultations (odds ratio 5.88, 95% confidence interval: 2.59-16.63) and AC use (odds ratio 7.9, 95% confidence interval: 3.38-23.80) than controls. PHD patients did not show significantly greater rates of deep vein thrombosis, transfusion, infection, ED visits, or need for operative intervention. Similarly, AC vs antiplatelet therapy yielded comparable ED visits and readmissions within 90 days postoperatively (11.0% vs 9.7%, P = .85 and 5.5% vs 5.5%, P = 1, respectively). Conclusions: These findings suggest that despite increased hematology consultation and AC use, PHD patients do not demonstrate significantly elevated perioperative risks post-TJA, favoring careful preoperative workup and outpatient postoperative follow-up.

Hyaluronan-based Hydrogels for 3D Modelling of Tumour Tissues.

Although routine 2D cell culture techniques have advanced basic cancer research owing to their simplicity, cost-effectiveness, and reproducibility, they have limitations that necessitate the development of advanced 3D tumour models that better recapitulate the tumour microenvironment. Various biomaterials have been used to establish these 3D models, enabling the study of cancer cell behaviour within different matrices. Hyaluronic acid (HA), a key component of the extracellular matrix in tumour tissues, has been widely studied and employed in the development of multiple cancer models. This review first examines the role of HA in tumours, including its function as an extracellular matrix (ECM) component and regulator of signalling pathways that affect tumour progression. It then explores HA-based models for various cancers, focusing on HA as a central component of the 3D matrix and its mobilization within the matrix for targeted studies of cell behaviour and drug testing. The tumour models discussed included those for breast cancer, glioblastoma, fibrosarcoma, gastric cancer, hepatocellular carcinoma, and melanoma. The review concludes with a discussion of future prospects for developing more robust and high-throughput HA-based models to more accurately mimic the tumour microenvironment and improve drug testing.

The common Sting1 HAQ, AQ alleles rescue CD4 T cellpenia, restore T-regs, and prevent SAVI (N153S) inflammatory disease in mice.

The significance of STING1 gene in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common human STING1 alleles R71H-G230A-R293Q (HAQ) and G230A-R293Q (AQ) are carried by ~60% of East Asians and ~40% of Africans, respectively. Here, we examine the modulatory effects of HAQ, AQ alleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human STING1 mutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using Sting1 knock-in mice expressing common human STING1 alleles HAQ, AQ, and Q293, we found that HAQ, AQ, and Q293 splenocytes resist STING1-mediated cell death ex vivo, establishing a critical role of STING1 residue 293 in cell death. The HAQ/SAVI(N153S) and AQ/SAVI(N153S) mice did not have CD4 T cellpenia. The HAQ/SAVI(N153S), AQ/SAVI(N153S) mice have more (~10-fold, ~20-fold, respectively) T-regs than WT/SAVI(N153S) mice. Remarkably, while they have comparable TBK1, IRF3, and NFκB activation as the WT/SAVI, the AQ/SAVI mice have no tissue inflammation, regular body weight, and normal lifespan. We propose that STING1 activation promotes tissue inflammation by depleting T-regs cells in vivo. Billions of modern humans have the dominant HAQ, AQ alleles. STING1 research and STING1-targeting immunotherapy should consider STING1 heterogeneity in humans.

Comparison of Dexamethasone at Three Doses Administered Postoperatively for Improving Pain Control and Sleep Quality in Patients Who Underwent Total Knee Arthroplasty: A Triple Blind Randomized Controlled Trial.

BACKGROUND: Dexamethasone has been shown to alleviate pain, yet the optimal dosing and safety profiles remain unclear. This study aimed to evaluate the analgesic efficacy and impact on sleep quality of three different doses of intravenous dexamethasone in patients undergoing total knee arthroplasty (TKA). METHODS: In this randomized, triple-blind, clinical trial, we assessed the analgesic effects of three doses of intravenous dexamethasone (four, eight, and 16 mg) in adult patients who underwent TKA. Pain was measured using the visual analog scale at one, 12, 24, and 48 hours postoperatively, and sleep quality was assessed two weeks postsurgery. RESULTS: A total of 90 participants were enrolled in the study, with 30 participants in each dosing group. The mean visual analog scale scores at 12, 24, and 48 hours postoperatively showed significant improvement from baseline in all groups. Notably, the 16 mg and eight mg dexamethasone groups demonstrated significantly greater pain reduction compared to the four mg group (P < 0.05). Additionally, sleep quality significantly improved in the 16 mg and eight mg groups (P < 0.05). CONCLUSIONS: Dexamethasone at doses of four, eight, and 16 mg effectively reduces pain and enhances sleep quality in patients undergoing TKA, with the 16 mg dose showing the most pronounced effects at 12, 24, and 48 hours postoperatively.

The human health risks assessment posed by the presence of heavy metals in the rice varieties available in the Neyshabur market.

The present study was designed to determine the levels of heavy metals (Cu, Pb, Ni, Cr, Zn, Mn, Cd, and Co), Mn, and As in Iranian-grown rice and imported rice consumed in Neyshabur City. For this research, 90 samples from 30 different brands widely consumed in this city were collected. The content of heavy metals and the health risks associated with their use were then studied. The study found that Zn (14.21 mg kg-1) had the highest content in Iranian and imported rice varieties, whereas Cd (0.02 mg kg-1) had the lowest value. The health risk assessment was also done in three scenarios and separately for two types of rice. The results showed that the total hazard quotient (i.e., THQ) was measured for all metals and all three scenarios, and for both types of rice, it is THQ > 1, which indicates the risk of non-carcinogenic in rice. The cancer risk for three scenarios and two types of imported and Iranian rice is in the unsafe range for As (8.80 × 10-4 to 7.00 × 10-3), Ni (4.60 × 10-4 to 3.60 × 10-3) and Cr (2.20 × 10-4 to 1.90 × 10-3) and negligible for Pb (1.09 × 10-6 to 1.49 × 10-5) and Cd (7.83 × 10-6 to 8.20 × 10-5).

Health effects and user perceptions of the US Customs and Border Patrol One™ mobile application: A qualitative analysis among asylum seekers at the Mexico-US border.

Background: The number of migrants at the Mexico-US border has increased to historic levels, and frequently changing immigration policy impacts this population as they await entry into the US. This study evaluated the usability and health effects of the Customs and Border Protection (CBP) One™ mobile application among asylum seekers near the US port of entry in Reynosa, Mexico. Methods: We conducted semi-structured qualitative interviews with 20 asylum seekers in Reynosa, Mexico, in February 2023. Our objective was to explore the subjective experiences of migrants, usability of CBP One™, and presence of perceived health effects from using the application. Interviews were conducted until saturation occurred, transcribed verbatim into Word, coded in NVivo using a validated, team-based coding methodology, and analyzed according to internal domains, external domains, and health effects regarding CBP One™. Results: Twenty participants originated from eight countries throughout Latin America and the Caribbean. In total, 18 subthemes were identified among internal, external, and effects domains. Internal themes included a confusing application interface (80%), technical malfunction (60%), and perceived racial bias from the photo-capture features (15%). External themes challenging CBP One™ use included unavailable appointment slots (80%), inequity and inaccessibility (35%), and inadequate internet (25%). Most perceived effects were negative (85%), including worsening mental health effects (40%), exacerbation of pre-existing physical conditions (35%), and forgoing health expenditures to pay for internet (25%). Conclusions: Our findings suggest that asylum seekers at the Reynosa port of entry perceive CBP One™ negatively, with detrimental effects towards their mental and physical health. This study highlights how immigration policy can influence health and suggests that more creative and humane approaches are needed for people seeking asylum at the Mexico-US border.

A case report of successful combined intra-arterial immunotherapy and cytokine genetic therapy treatment in a patient with recurrent glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor with very poor prognosis due to frequent recurrence and short overall survival (OS) time, which according to different sources, is not longer than 17 months after the diagnosis. Infiltrative growth pattern often leads to tumor propagation into functionally significant brain areas while surgery is cytoreductive and does not necessarily alter the prognosis. Many patients are in the working age, thus finding conservative approaches to the treatment of this type of neoplasms is of utmost importance. The aim of the work is to demonstrate the effectiveness of treatment of GBM using cytokine genetic therapy (CGT) and present an algorithm for patient management. CASE DESCRIPTION: This paper describes the first case of successful intra-arterial (IA) bevacizumab therapy with following CGT of a 46-year-old patient with recurrent GBM after a combined treatment. Sixteen courses of 15 mg/kg IA bevacizumab with hyperosmolar opening of blood-brain barrier (BBB) resulted in stabilization of the neoplastic process. After that, 9 courses of CGT with recombinant interferon gamma (IFN-γ) and tumor necrosis factor (TNF)-thymosin α1 were performed. Both magnetic resonance imaging (MRI) with contrast and positron emission tomography (PET) confirmed a complete response to the combined treatment. OS time is currently more than 25 months from the diagnosis. The observation continues. CONCLUSIONS: This case study expands the range of treatment options for GBM, especially in the context of intolerance and high toxicity of cytostatic drugs, and may lead to improved recurrence-free survival (RFS).

Enhancing flood risk mitigation by advanced data-driven approach.

Flood events in the Sefidrud River basin have historically caused significant damage to infrastructure, agriculture, and human settlements, highlighting the urgent need for improved flood prediction capabilities. Traditional hydrological models have shown limitations in capturing the complex, non-linear relationships inherent in flood dynamics. This study addresses these challenges by leveraging advanced machine learning techniques to develop more accurate and reliable flood estimation models for the region. The study applied Random Forest (RF), Bagging, SMOreg, Multilayer Perceptron (MLP), and Adaptive Neuro-Fuzzy Inference System (ANFIS) models using historical hydrological data spanning 50 years. The methods involved splitting the data into training (50-70 %) and validation sets, processed using WEKA 3.9 software. The evaluation revealed that the nonlinear ensemble RF model achieved the highest accuracy with a correlation of 0.868 and an root mean squared error (RMSE) of 0.104. Both RF and MLP significantly outperformed the linear SMOreg approach, demonstrating the suitability of modern machine learning techniques. Additionally, the ANFIS model achieved an exceptional R-squared accuracy of 0.99. The findings underscore the potential of data-driven models for accurate flood estimating, providing a valuable benchmark for algorithm selection in flood risk management.

Outcomes of COVID-19 in 24 hospitalized liver transplant recipients: an observational study.

BACKGROUND: Although liver transplant (LT) recipients are considered a population at risk of severe features of coronavirus disease 2019 (COVID-19), data in this regard are scarce and controversial. In this study, we reported the outcome of 24 cases of LT recipients who were hospitalized due to COVID-19 and investigated the role-playing factors in the severity of the disease. METHODS: In this single-center, analytic case-series study, eligible patients were among LT recipients who were hospitalized due to the diagnosis of COVID-19 based on positive results of polymerase chain reaction. Participants were categorized as severe COVID-19 if they were admitted to the intensive care unit, experienced respiratory failure demanding mechanical ventilation, or eventually died. Demographic and clinical data, COVID-19 symptoms and specific treatments, laboratory biomarkers, and immunosuppressive regimens and their alteration during the admission were recorded. Analysis was done using SPSS software. RESULTS: Twenty-four hospitalized LT patients were included, of which nine had severe and fifteen had non-severe COVID-19. Out of 9 patients with severe COVID-19, four sadly died. The analysis and comparison between the two groups revealed longer hospital stays (P = 0.02), lower lymphocyte counts (P = 0.002), and higher levels of C-reactive protein (CRP) (P = 0.006) in patients with severe COVID-19. Patients with non-severe COVID-19 had higher doses of tacrolimus and mycophenolate in their baseline immunosuppressive regimen (both P = 0.02). CONCLUSION: Lymphopenia and high CRP levels are associated with more severe forms of COVID-19 in LT patients. Mycophenolate may have protective properties against severe COVID-19. The role of severity indicators in LT patients with COVID-19 needs to be systematically recognized.

MerTK-dependent efferocytosis by monocytic-MDSCs mediates resolution of ischemia/reperfusion injury after lung transplant.

Lung transplantation (LTx) outcomes are impeded by ischemia/reperfusion injury (IRI) and subsequent chronic lung allograft dysfunction (CLAD). We examined the undefined role of receptor Mer tyrosine kinase (MerTK) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis to facilitate resolution of lung IRI. Single-cell RNA sequencing of lung tissue and bronchoalveolar lavage (BAL) from patients after LTx were analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with BALB/c (WT), Cebpb-/- (MDSC-deficient), Mertk-/-, or MerTK-cleavage-resistant mice. A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of patients with CLAD was observed compared with healthy individuals. In the murine IRI model, a significant increase in M-MDSCs, MerTK expression, and efferocytosis and attenuation of lung dysfunction was observed in WT mice during injury resolution that was absent in Cebpb-/- and Mertk-/- mice. Adoptive transfer of M-MDSCs in Cebpb-/- mice significantly attenuated lung dysfunction and inflammation. Additionally, in a murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can substantially contribute to the resolution of post-LTx IRI.

Examining Hemin and its Derivatives: Induction of Heme-Oxygenase-1 Activity and Oxidative Stress in Breast Cancer Cells through Collaborative Experimental Analysis and Molecular Dynamics Simulations.

Hemin triggers intracellular reactive oxygen species (ROS) accumulation and enhances heme oxygenase-1 (HOX-1) activity, indicating its potential as an anticancer agent, though precise control of its intracellular levels is crucial. The study explores the impact of hemin and its derivatives, hemin-tyrosine, and hemin-styrene (H-Styr) conjugates on migration, HOX-1 expression, specific apoptosis markers, mitochondrial functions, and ROS generation in breast cancer cells. Molecular docking and dynamics simulations were used to understand the interactions among HOX-1, heme, and the compounds. Hemin outperforms its derivatives in inducing HOX-1 expression, exhibiting pro-oxidative effects and reducing cell migration. Molecular simulations show that heme binds favorably to HOX-1, followed by the other compounds, primarily through van der Waals and electrostatic forces. However, only van der Waals forces determine the H-Styr complexation. These interactions, influenced by metalloporphyrin characteristics, provide insights into HOX-1 regulation and ROS generation, potentially guiding the development of breast cancer therapies targeting oxidative stress.

Engineering hemin-loaded hyaluronan needle-like microparticles with photoprotective properties against UV-induced tissue damage.

This study aimed to develop hyaluronan (HA)-based hydrogel microparticles (MPs) loaded with hemin to address the limitations of traditional macroscale hydrogels. The objective is to design MPs such that they can modulate their physicochemical properties. Given the widespread use of ultraviolet C (UVC) light in various industries and the need for protective measures against accidental exposure, this study evaluated the potential of hemin-loaded MPs to protect human dermal fibroblasts from oxidative stress and cell death caused by UVC exposure. Multiple MP formulations were developed and analysed for size, surface charge, swelling behaviour, degradation rate, and radical scavenging capabilities, both with and without hemin loading. The most promising formulations were tested against UVC-exposed cells to assess cell viability, intracellular nitric oxide (˙NO) and reactive oxygen species levels, and protein carbonylation. The fabricated particles were in the form of microneedles, and the degree of their crosslinking and the role of hemin in the chemical crosslinking reaction were found to influence the surface charge and hydrodynamic diameter of the MPs. Increased crosslinking resulted in reduced swelling, slower degradation, and decreased hemin release rate. MPs with a higher degree of swelling were capable of releasing hemin into the culture medium, leading to enhanced bilirubin generation in dermal fibroblasts following cellular uptake. Pre-treatment with these MPs protected the cells from UVC-induced cell death, nitrosative stress, and protein carbonylation. These findings highlight the potential of the studied MPs to release hemin and to minimise the harmful effects of UVC on dermal fibroblasts.

A rare case of spontaneous hemoperitoneum in a bone marrow transplant recipient on VV-ECMO.

A 53-year-old man with acute myeloid leukemia received an allogeneic hematopoietic cell transplant (HCT) from a matched unrelated donor. One month after his transplantation, he developed ARDS requiring initiation of VV-ECMO. He suffered from pancytopenia, managed with frequent transfusions, granulocyte-colony stimulating factor (G-CSF) and weekly thrombopoietin receptor agonist. On ECMO day 17, the patient developed severe hypotension after insertion of a chest tube for a large right-sided pneumothorax. CT angiography of the abdomen showed hemoperitoneum. Exploratory laparotomy revealed approximately 4 L of blood and a ruptured splenic hilum. A splenectomy was performed. Unfortunately, the patient continued to require multiple daily blood products and his condition continued to decline despite two reoperations. His family chose to discontinue ECMO and he passed away peacefully. Spontaneous splenic rupture after GM-CSF has never been reported in patients on VV-ECMO. This manuscript reviews the literature regarding the pathophysiology and clinical manifestation of this rare occurrence.