The current landscape of in situ and ex situ machine perfusion utilization for liver grafts from cardiac donation after circulatory death donors in the US.

Donation after circulatory death (DCD) is driving the increase in deceased organ donors in the United States. Normothermic regional perfusion (NRP) and ex situ machine perfusion (es-MP) have been instrumental in improving liver transplant outcomes and graft utilization. This study examines the current landscape of liver utilization from cardiac DCD donors in the United States. Using the United Network for Organ Sharing Standard Transplant Analysis and Research file, all adult (≥18 years old) DCD donors in the United States from which the heart was used for transplantation from October 1, 2020, to September 30, 2023, were compared by procurement technique (NRP versus super rapid recovery [SRR]) and storage strategy (es-MP versus static cold storage). One hundred eighty-eight livers were transplanted from 309 thoracoabdominal NRP donors (61% utilization) versus 305 (56%) liver transplants from 544 SRR donors. es-MP was used in 20% (n = 38) of NRP cases versus 32% (98) of SRR cases. Of the liver grafts, 281 (59%) were exposed to NRP, es-MP, or both. While there is widespread utilization of machine perfusion, more research is needed to determine optimal graft management strategies, particularly concerning the use of multiple technologies in complementary ways. More complete data collection is necessary at a national level to address these important research questions.

Impedance Spectroscopy Unveiled the Surfactant-Induced Unfolding and Subsequent Refolding of Human Serum Albumin.

Protein-surfactant interaction is a dynamic interplay of electrostatic and hydrophobic forces that ensues from the folding of a protein. We employ impedance spectroscopy (IS), a label-free method, to investigate the unfolding and refolding of human serum albumin (HSA), a globular plasma protein, in the presence of two surfactants: polysorbate-20 (Tween-20), a nonionic surfactant, and sodium dodecyl sulfate (SDS), an anionic surfactant. The equivalent electrical analog circuit was predicted from impedance spectra of HSA in an aqueous solution at physiological pH and room temperature, focusing on varying the concentration of codissolved surfactants. A change in the dielectric constant (ε') and ionic conductivity (κ) is observed by comparing the surfactant-treated protein samples to the bare surfactant solutions to assess the conformational changes induced by surfactants in HSA. Far-UV circular dichroism analysis revealed a decrease in α-helices and an increase in ß-sheets and random coils upon SDS addition, which were reversed by Tween-20. Dynamic light scattering supported the findings by measuring changes in the hydrodynamic diameter (dh) of HSA. Unfolding and refolding of HSA with surfactants were also observed through photoluminescence spectroscopy by examining the microenvironment surrounding the single tryptophan (W) within the protein, and the thermodynamic parameters were obtained using the modified Stern-Volmer equation. Our research explores the intriguing domain of protein-surfactant interactions, offering insights with promising applications across diverse biological processes and IS as a suitable alternative technique for investigating protein conformational changes by studying the electrical response of the samples.

Uterus Transplant in Women With Absolute Uterine-Factor Infertility.

Importance: Uterus transplant in women with absolute uterine-factor infertility offers the possibility of carrying their own pregnancy. Objective: To determine whether uterus transplant is feasible and safe and results in births of healthy infants. Design, Setting, and Participants: A case series including 20 participants with uterine-factor infertility and at least 1 functioning ovary who underwent uterus transplant in a large US tertiary care center between September 14, 2016, and August 23, 2019. Intervention: The uterus transplant (from 18 living donors and 2 deceased donors) was surgically placed in an orthotopic position with vascular anastomoses to the external iliac vessels. Participants received immunosuppression until the transplanted uterus was removed following 1 or 2 live births or after graft failure. Main Outcomes and Measures: Uterus graft survival and subsequent live births. Results: Of 20 participants (median age, 30 years [range, 20-36]; 2 Asian, 1 Black, and 16 White), 14 (70%) had a successful uterus allograft; all 14 recipients gave birth to at least 1 live-born infant. Eleven of 20 recipients had at least 1 complication. Maternal and/or obstetrical complications occurred in 50% of the successful pregnancies, with the most common being gestational hypertension (2 [14%]), cervical insufficiency (2 [14%]), and preterm labor (2 [14%]). Among the 16 live-born infants, there were no congenital malformations. Four of 18 living donors had grade 3 complications. Conclusions and Relevance: Uterus transplant was technically feasible and was associated with a high live birth rate following successful graft survival. Adverse events were common, with medical and surgical risks affecting recipients as well as donors. Congenital abnormalities and developmental delays have not occurred to date in the live-born children. Trial Registration: ClinicalTrials.gov Identifier: NCT02656550.

Total pancreatectomy with islet autotransplantation outcomes in patients with pancreatitis of genetic etiology: A single-center experience with a large cohort of patients.

PURPOSE: Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment for patients with chronic pancreatitis (CP) when other interventions are unsuccessful. CP has many etiologies including heredity. Metabolic and pain relief outcomes after TPIAT are presented among patients with a genetic CP etiology compared with those with a nongenetic etiology in a large cohort of patients who underwent this procedure at our center. METHODS: A retrospective analysis was performed of 237 patients undergoing TPIAT between 2006 and 2023. We analyzed the differences in patients with genetic (n = 56) vs nongenetic CP etiologies (n = 181) in terms of pre-TPIAT factors including patient characteristics and disease state, results from the isolation process, and outcomes such as long-term glycemic and pain control. RESULTS: Patients with genetic CP underwent TPIAT at a significantly younger age (32.3 vs 41.3 years nongenetic; P < .0001) and endured symptoms for a significantly longer period (10 vs 6 years; P < .01). A significantly lower mass of islets was isolated from patients with genetic CP (P < .01), which increased with body mass index in both groups. Despite lower yields, patients with genetic CP maintained metabolic function similar to patients with nongenetic CP, as indicated by insulin independence and C-peptide, blood glucose, and hemoglobin A1C levels after TPIAT. Post-transplant narcotic usage and pain scores significantly decreased compared with those before TPIAT, and more patients with genetic CP were pain free and narcotic free after TPIAT. CONCLUSION: Our data validate TPIAT as a beneficial procedure for patients enduring CP of genetic etiology. Pain that is inevitably recurrent after minor interventions owing to the nature of the disease and favorable TPIAT outcomes should be considered in the decision to perform early TPIAT in cases of genetic CP.

Abdominal normothermic regional perfusion in the United States: current state and future directions.

PURPOSE OF REVIEW: Normothermic regional perfusion (NRP) is a novel procurement technique for donation after circulatory death (DCD) in the United States. It was pioneered by cardiothoracic surgery programs and is now being applied to abdominal-only organ donors by abdominal transplant programs. RECENT FINDINGS: Liver and kidney transplantation from thoracoabdominal NRP (TA-NRP) donors in the United States was found to have lower rates of delayed kidney graft function and similar graft and patient survival versus recipients of cardiac super rapid recovery (SRR) DCD donors. The excellent outcomes with NRP have prompted the expansion of NRP technology to abdominal transplant programs. SUMMARY: Excellent early outcomes with liver and kidney transplantation have prompted the growth of NC-NRP procurement for abdominal-only DCD donors across the US, and now requires standardization of technical and nontechnical aspects of this procedure.

Stepwise development and expansion of an abdominal normothermic regional perfusion program for donation after circulatory determination of death organ procurement.

INTRODUCTION: Normothermic regional perfusion (NRP) represents an innovative technology that improves the outcomes for liver and kidney recipients of donation after circulatory determination of death (DCD) organs but protocols for abdominal-only NRP (A-NRP) DCD are lacking in the US. METHODS: We describe the implementation and expansion strategies of a transplant-center-based A-NRP DCD program that has grown in volume, geographical reach, and donor acceptance parameters, presented as four eras. RESULTS: In the implementation era, two donors were attempted, and one liver graft was transplanted. In the local expansion era, 33% of attempted donors resulted in transplantation and 42% of liver grafts from donors who died within the functional warm ischemic time (fWIT) limit were transplanted. In the Regional Expansion era, 25% of attempted donors resulted in transplantation and 50% of liver grafts from donors who died within the fWIT limit were transplanted. In the Donor Acceptance Expansion era, 46% of attempted donors resulted in transplantation and 72% of liver grafts from donors who died within the fWIT limit were transplanted. Eight discarded grafts demonstrated a potential opportunity for utilization. CONCLUSION: The stepwise approach to building an A-NRP program described here can serve as a model for other transplant centers.

Oxidative stress induced conformational changes of human serum albumin.

Oxidative stress, generated by reactive oxygen species (ROS), is responsible for the loss of structure and functionality of proteins and is associated with several aging-related diseases. Here, we report an in vitro study to gauge the effect of ROS on the structural rearrangement of human serum albumin (HSA), a plasma protein, through metal-catalyzed oxidation (MCO) at physiological temperature through various biophysical techniques like UV-vis absorption, circular dichroism (CD), differential scanning calorimetry (DSC), MALDI-TOF, FTIR, and Raman spectroscopy. The UV-vis spectra of oxidized HSA show an early blueshift, signifying the unfolding of the protein because of ROS followed by the broadening of the absorption peak at a longer time. The DSC data corroborate the observation, revealing an exothermic transition for the oxidized sample at a longer time, suggesting in situ aggregation. The CD and FTIR spectra indicate the associated secondary structural changes occurring with time, depicting the variation of the helical content of HSA. The amide-III analysis of Raman data also complements the structural changes, and MALDI-TOF data show the mass distribution with time. Overall, this work might help determine the effect of oxidation on the biological activity of serum albumin as it can impact the physiological properties of HSA.

A cost comparison of liver acquisition fees for donation after circulatory death versus donation after brain death donors.

Donation after circulatory death (DCD) donors now represent over 30% of the deceased donor pool in the United States. Compared to donation after brain death, DCD is less likely to result in transplantation. For each potential donor whose organs cannot be utilized for transplantation (ie, dry run), fees are associated with the attempted donation, which add to the overall costs of organ acquisition. To better characterize the true costs of DCD liver acquisition, we performed a cost comparison of the fees associated with organ acquisition for DCD versus donation after brain death at a single transplant institute that comprises 2 liver transplant centers. Cost, recipient, and transportation data for all cases, including fees associated with liver acquisition from July 1, 2019, to October 31, 2021, were collected. We found that the total cost of DCD liver acquisition per liver transplant was $15,029 more than that for donation after brain death donation, with 18% of the costs of the DCD transplant attributed to dry runs. Overall, the costs associated with DCD transplantation accounted for 34.5% of the total organ acquisition costs; however, DCD transplantation accounted for 30.3% of the transplantation volume. Because the expansion of DCD is essential to increasing the availability of liver grafts for transplantation, strategies need to be implemented to decrease the costs associated with dry runs, including using local recovery, transferring donors to hospitals close to transplant centers, and performing more prerecovery organ analysis. Moreover, these strategies are needed to ensure that financial disincentives to DCD procurement and utilization do not reverse the gains made by expanding the organ donor pool using machine perfusion technologies.

An Approach to Anesthetic Management of Venous Anomalies and Outflow Reconstruction in Liver Transplants.

Hepatic venous outflow is a pivotal factor in liver transplant. However, venous anomalies and the potential for hepatic venous congestion continue to remain major points of concern to ensure the viability of transplanted livers and maximize regenerative capacity. We present a 66-year-old patient undergoing liver transplantation who was found to have anomalous venous drainage requiring venous anastomoses. To ensure adequate venous flow and minimize the possibility of graft congestion and liver dysfunction, the anesthetic management of the patient's hemodynamic status was of utmost importance. The use of osmotic diuretics and intraoperative sonography was used to ensure adequate perfusion.

Elucidating the molecular responses to waterlogging stress in onion (Allium cepa L.) leaf by comparative transcriptome profiling.

Introduction: Waterlogging is a major stress that severely affects onion cultivation worldwide, and developing stress-tolerant varieties could be a valuable measure for overcoming its adverse effects. Gathering information regarding the molecular mechanisms and gene expression patterns of waterlogging-tolerant and sensitive genotypes is an effective method for improving stress tolerance in onions. To date, the waterlogging tolerance-governing molecular mechanism in onions is unknown. Methods: This study identified the differentially expressed genes (DEGs) through transcriptome analysis in leaf tissue of two onion genotypes (Acc. 1666; tolerant and W-344; sensitive) presenting contrasting responses to waterlogging stress. Results: Differential gene expression analysis revealed that in Acc. 1666, 1629 and 3271 genes were upregulated and downregulated, respectively. In W-344, 2134 and 1909 genes were upregulated and downregulated, respectively, under waterlogging stress. The proteins coded by these DEGs regulate several key biological processes to overcome waterlogging stress such as phytohormone production, antioxidant enzymes, programmed cell death, and energy production. The clusters of orthologous group pathway analysis revealed that DEGs contributed to the post-translational modification, energy production, and carbohydrate metabolism-related pathways under waterlogging stress. The enzyme assay demonstrated higher activity of antioxidant enzymes in Acc. 1666 than in W-344. The differential expression of waterlogging tolerance related genes, such as those related to antioxidant enzymes, phytohormone biosynthesis, carbohydrate metabolism, and transcriptional factors, suggested that significant fine reprogramming of gene expression occurs in response to waterlogging stress in onion. A few genes such as ADH, PDC, PEP carboxylase, WRKY22, and Respiratory burst oxidase D were exclusively upregulated in Acc. 1666. Discussion: The molecular information about DEGs identified in the present study would be valuable for improving stress tolerance and for developing waterlogging tolerant onion varieties.

Diffuse calcification of pancreas impairs endocrine function and predicts poor outcome in total pancreatectomy with islet autotransplantation.

In patients with chronic pancreatitis, pancreatic calcification is a risk factor for diabetes development, poor islet yield, and metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT). We investigated whether calcification pattern based on computed tomography is associated with outcomes using our database of 200 consecutive TPIAT procedures. Three groups were compared: noncalcification (NC); focal calcification, limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections. Maximum changes in outcomes were seen in the DC vs focal calcification group. In the DC group, preoperative hemoglobin A1c levels were higher (P < .01), and stimulated C-peptide levels were lower (P < .01) than in the NC group. Islet isolation from the DC pancreas resulted in the lowest islet equivalent (IEQ) yield and IEQ/kg among the 3 groups (P < .0001), with no insulin independence 12 months posttransplant (P < .05 vs NC group). Notably, at 12 months, the DC group was 91.7% narcotic-free, significantly higher than the NC group (P < .05). Although DC is a sign of diabetes risk after TPIAT, the DC group showed exceptional pain relief. These findings suggest that TPIAT can be beneficial for patients with chronic pancreatitis with severe calcification.

Plasmid DNA Undergoes Two Compaction Regimes under Macromolecular Crowding.

The laser light scattering experiments were performed to explore the role of dextran (size (d): 2.6, 6.9, and 17.0 nm) in compacting the plasmids (pBS: 2.9 kbps; pCMV-Tag2B: 4.3 kbps; and pET28a: 5.3 kbps) in vitro in the volume fraction (ϕ) range 0.01 to 0.15 of the macromolecular crowder. Two compaction regimes were observed in terms of the radius of gyration (Rg) for plasmid-dextran combinations, wherein the plasmid diffusivity is governed by normal diffusion and subdiffusion, respectively. Generalized scaling, Rg ∼ ϕ-1/(1+x), where x represents the conformational geometry of plasmids, is reported. The plasmid conformation depends on the crowder's size, with larger conformational changes observed in the presence of smaller crowders. The second virial coefficient (A2) and translational diffusion coefficient (Dt) indicate that entropically driven depletion of crowders, excluded volume, and interplasmid repulsive interactions govern plasmids' conformational changes, validated herein from the scaling of Dt with molecular weight.

Early outcomes of kidney transplant recipients from donors with severe SARS-CoV-2 pneumonia: A report of 5 cases.

BACKGROUND: Transplanting kidneys from donors with a recent history of severe SARS-CoV-2 pneumonia is uncommon due to concerns about the risk of viral transmission and the quality of kidneys from these donors. To date, there are no conclusive data on viral transmission from extrapulmonary solid organ transplants. Given the prevalence of SARS-CoV-2 infections in potential donors, shortage of kidneys available for transplantation, and low risk of viral transmission, we developed a clinical protocol for accepting kidneys from donors with recent severe SARS-CoV-2 pneumonia who demonstrate preserved kidney function. MATERIALS AND METHODS: We collected data on early outcomes of 5 kidney transplant recipients from 4 deceased donors hospitalized for severe SARS-CoV-2 infection. RESULTS: Donor creatinine ranged from 0.51 to 0.60 mg/dL and kidney donor profile index (KDPI) from 14 to 52%. Three of the five kidneys were from donation after circulatory death. All recipients were fully vaccinated, and 4/5 received post-exposure prophylactic monoclonal antibody treatment. While 3 recipients had delayed graft function, all had excellent graft function at 3 or 4 weeks post-operatively. None of the recipients displayed signs or symptoms of SARS-CoV-2 infection post-transplant. CONCLUSION: Our findings suggest that kidney grafts from donors with a recent history of severe SARS-CoV-2 infection but with preserved kidney function can be safely used and have good early outcomes.

Living donor liver transplantation versus donation after brain death and donation after circulatory death liver transplantation in the US.

While previous research has compared outcomes between living donor liver transplantation (LDLT) and deceased donor liver transplantation, evidence is lacking regarding how donation after circulatory death (DCD) vs donation after brain death (DBD) affects this comparison. Using data from the Scientific Registry of Transplant Recipients for adults listed for liver transplant from 2012 to 2018, we compared 5-year patient and graft survival, readmissions, posttransplant chronic kidney disease (CKD), and return to work for 25,151 patients who underwent LDLT (1223 [4.9%]), DCD-LT (1431 [6.4%]), and DBD-LT (22,497 [89.4%]). LDLT recipients were significantly more likely to have a Model for End-Stage Liver Disease (MELD) score < 15 and to be working prior to transplant (P < 0.001 for both). At 5 years posttransplant, LDLT recipients had significantly more readmissions, but significantly less CKD and better survival than DBD-LT and DCD-LT recipients, as well as significantly better graft survival than DCD-LT recipients (P ≤ 0.01 for all). Significantly more LDLT recipients also returned to work for income (P < 0.01). This study shows a clear advantage of LDLT vs DCD-LT. This information should be weighed in transplantation decisions for patients such as those with low MELD scores who will realistically only be considered for DCD-LT.

Delayed Granulomas as a Complication Secondary to Lip Augmentation with Dermal Fillers: A Systematic Review.

Introduction Lip augmentation with dermal filler is rising in popularity. There are generally minimal side effects that are mild and transient. However, long-term complications may occur and include lumps, bumps, nodules, or granulomas. To better understand this uncommon but challenging outcome, we aim to perform a thorough systematic review of the published literature related to nodule or granuloma formation after cosmetic soft tissue augmentation of the lips. Methods A search of published literature was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in April 2021 and included PubMed, ScienceDirect, Embase, Google Scholar, and Cochrane databases. The Medical Subject Headings (MeSH) terms used included the following terms: "lip filler," "hyaluronic acid," "lip injection," "lip augmentation," "silicone," "poly-L-lactic acid," "calcium hydroxyapatite," "polymethylmethacrylate," "complications," "reaction," "granuloma," and "nodule." All studies were reviewed by two independent reviewers. Any discrepancies were resolved by a third reviewer. Results The initial search for filler-related nodules or granulomas yielded 2,954 articles and 28 were included in the final analysis containing 66 individual cases of lip nodules. All but one patient was female. The mean age was 50 years. Nodules presented on average 35.2 months or 2.9 years after initial treatment. Thirty-seven nodules underwent histological analysis, the majority of which identified the presence of a foreign-body granuloma. Silicone was the most reported filler used followed by hyaluronic acid. Most cases resolved following multiple treatments including oral antibiotics or steroids followed by surgical excision. Conclusion Understanding the sequelae of lip augmentation with filler products allows clinicians to provide safe and effective treatment. Nodules that present months to years following dermal treatment may represent a foreign-body granuloma. A combination of oral antibiotics, intralesional or oral steroids, and surgical excision successfully treated the majority of cases in our study.

Has the COVID-19 Pandemic Impacted Interest in Cosmetic Facial Plastic Surgery? A Google Trends Analysis.

Facial cosmetic surgery trends are evolving in the current climate of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to evaluate public interest in elective facial plastic surgery during the COVID-19 pandemic including the period of the COVID-19 vaccine distribution using Google Trends. A Google Trends analysis was completed using popular terms related to facial cosmetic surgery and procedures from March 2017 to August 2021. Three stages were identified (baseline, pre-COVID-19 vaccine distribution, and post-COVID-19 vaccine distribution). Descriptive statistics were calculated and two-tailed t-tests were performed between the pre-vaccine and the post-vaccine phases. Linear regression analysis was also performed to determine percent deflection of search terms. There was significantly greater interest in facial aesthetic procedure search terms, except for tear trough filler, during the post-COVID-19 vaccine phase compared with the pre-COVID-19 vaccine phase. There was greater interest in lower facial procedure interest during this phase compared with upper facial procedures (p-value = 0.0011). The search terms with the greatest deflection percentage during the post-vaccine phase were lip filler, brow lift, and lip flip. There continues to be high demands of facial plastic surgery and procedures despite COVID-19 pandemic.

Addressing the Upper Third of the Nose in Endonasal Rhinoplasty.

Effective management of the upper nasal vault is based on a thorough preoperative analysis and detailed understanding of the requisite principles and techniques utilized to modify the anatomic structures in this region. The surgeon must equally consider form and function when performing manipulation of the upper nasal vault. Special considerations apply when managing this anatomic region via an endonasal or closed approach. A review of this topic is presented with a focus on techniques as they apply to the endonasal rhinoplasty patient.

Delayed Complications following Dermal Filler for Tear Trough Augmentation: A Systematic Review.

Tear trough deformity is a popular target for the treatment with filler injections. The side effects are generally mild and transient. However, delayed complications may occur. We aim to perform a thorough systematic review of the published literature related to delayed complications after tear trough filler injections. A search of published literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in June 2021 and included PubMed, ScienceDirect, and Embase databases. The Medical Subject Headings (MeSH) terms used included the following terms: delayed complications, nodules, granulomas, swelling, discoloration, dermal filler, hyaluronic acid (HA), polyacrylamide, calcium hydroxyapatite (CaHA), poly-L-lactic acid (PLLA), eyelid, periorbital, periocular, and tear trough. Twenty-eight articles consisting of 52 individual cases were included in the final analysis. 98% (51/52) of patients were female and had an average age of 48.3 years. HA was the most reported product (71.2%, 37/52), followed by PLLA (4/52, 7.7%), and CaHA (4/52, 7.7%). The most common delayed complication with any dermal filler was swelling (42.3%, 22/52) followed by lumps or nodules (25.0%, 13/52). Xanthelasma-like reaction (17.3%, 9/52), migration (7.7%, 4/52), discoloration (3%, 3/52) also occurred. The average time of onset of any complication was 16.8 months with xanthelasma-like reaction appearing soonest (mean: 10 months) and discoloration appearing latest (mean: 52 months). Most swelling cases were caused by HA. Semi-permanent fillers such as PMMA and synthetic fillers such as PLLA were more likely to be associated with lumps and nodules than other complications. It is important that clinicians who perform tear trough augmentation with dermal fillers have a thorough understanding of the risks of the procedure to diagnose and manage them promptly as well as provide patients with accurate information regarding the potential adverse effects.