Suitable Donor Research Articles

Clinical Application of Saphenous Nerve Transfer for Sensory Reconstruction of the Sole After Sciatic Nerve Injury: A Case Series

Sole sensation is essential for standing and walking. Moreover, lack of protective sensation of sole increases the risk of fall-related injuries. In the light of recent developments in nerve transfer, reconstruction of sole sensation can be achieved even in sciatic nerve injuries. Few researchers have addressed the problem of lack of potential donor nerve in proximal sciatic nerve injuries. The saphenous nerve has sufficient sensory fibers and is anatomically feasible to be used as a donor nerve to reconstruct sensation. To outline a new approach to restore the sensation of the sole using terminal branches of the saphenous nerve. In an attempt to restore sole sensation, 4 patients underwent saphenous nerve transfer to medial plantar and calcaneal branches. Highet-Zachary system scoring was used to evaluate sensory recovery in target regions (heel, metatarsal heads, and big toe). Of the study population, heel sensation recovered up to S3 in 1 case, S2 in 2 cases, and S1 in 1 case. Partial recovery of the metatarsal heads and the big toe was achieved in 2 cases. The findings of this study indicate that the saphenous nerve is a suitable and available donor to restore sole sensation in sciatic or posterior tibial nerve injuries.

Role of carbon and hydrogen in limiting n -type doping of monoclinic (AlxGa1−x)2O3

We use hybrid density functional calculations to assess $n$-type doping in monoclinic $({\mathrm{Al}}_{x}{\mathrm{Ga}}_{1\ensuremath{-}x}{)}_{2}{\mathrm{O}}_{3}$ alloys. We focus on silicon, the most promising donor dopant, and study the structural properties, formation energies, and charge-state transition levels of its various configurations. We also explore the impact of carbon and hydrogen, which are common impurities in metal-organic chemical vapor deposition (MOCVD). In ${\mathrm{Ga}}_{2}{\mathrm{O}}_{3}, {\mathrm{Si}}_{\mathrm{Ga}}$ is an effective shallow donor, but in ${\mathrm{Al}}_{2}{\mathrm{O}}_{3}\phantom{\rule{4pt}{0ex}}{\mathrm{Si}}_{\mathrm{Al}}$ acts as a $\mathit{DX}$ center with a ($+/\ensuremath{-}$) transition level in the band gap. Interstitial hydrogen acts as a shallow donor in ${\mathrm{Ga}}_{2}{\mathrm{O}}_{3}$ but behaves as a compensating acceptor in $n$-type ${\mathrm{Al}}_{2}{\mathrm{O}}_{3}$. Interpolation indicates that Si is an effective donor in $({\mathrm{Al}}_{x}{\mathrm{Ga}}_{1\ensuremath{-}x}{)}_{2}{\mathrm{O}}_{3}$ up to 70% Al, but it can be compensated by hydrogen already at 1% Al. We also assess the diffusivity of hydrogen and study complex formation. ${\mathrm{Si}}_{\mathrm{cation}}\text{\ensuremath{-}}\mathrm{H}$ complexes have relatively low binding energies. Substitutional carbon on a cation site acts as a shallow donor in ${\mathrm{Ga}}_{2}{\mathrm{O}}_{3}$, but can be stable in a negative charge state in $({\mathrm{Al}}_{x}{\mathrm{Ga}}_{1\ensuremath{-}x}{)}_{2}{\mathrm{O}}_{3}$ when $x>5%$. Substitutional carbon on an oxygen site (${\mathrm{C}}_{\mathrm{O}}$) always acts as an acceptor in $n$-type $({\mathrm{Al}}_{x}{\mathrm{Ga}}_{1\ensuremath{-}x}{)}_{2}{\mathrm{O}}_{3}$, but will incorporate only under relatively oxygen-poor conditions. ${\mathrm{C}}_{\mathrm{O}}\text{\ensuremath{-}}\mathrm{H}$ complexes can actually incorporate more easily, explaining observations of carbon-related compensation in ${\mathrm{Ga}}_{2}{\mathrm{O}}_{3}$ grown by MOCVD. We also investigate ${\mathrm{C}}_{\mathrm{cation}}\text{\ensuremath{-}}\mathrm{H}$ complexes, finding they have high binding energies and act as compensating acceptors when $x>56%$; otherwise the hydrogen just passivates the unintentional carbon donors. C-H complex formation explains why MOCVD-grown ${\mathrm{Ga}}_{2}{\mathrm{O}}_{3}$ can exhibit record-low free-carrier concentrations, in spite of the unavoidable incorporation of carbon. Our study highlights that, while Si is in principle a suitable shallow donor in $({\mathrm{Al}}_{x}{\mathrm{Ga}}_{1\ensuremath{-}x}{)}_{2}{\mathrm{O}}_{3}$ alloys up to high Al compositions, control of unintentional impurities is essential to avoid compensation.

Successful Percutaneous Mechanical Suction Thrombectomy of Extracorporeal Filtration System Following Bilateral Lung Transplantation Secondary to COVID-Pneumonia

IntroductionCOVID infections show increased risk of thromboembolic events. We report a case of a 43 year old male with acute Covid-19 pneumonia necessitating veno-venous ECMO and RVAD support as bridge to pulmonary transplantation. At transplant, he had thrombus along his extra-corporeal pulmonary artery cannula necessitating percutaneous mechanical thrombectomy.Case ReportThe patient presented as a transfer to our institution with COVID-19 related ARDS in refractory respiratory failure with multiple bronchopleural fistulas. Shortly after admission, veno-venous ECMO was initiated and over time was fully ECMO dependent due to extensive tissue destruction with essentially no functional lung tissue. He was converted to right internal jugular-left subclavian vein ECMO-RVAD configuration while assessing for transplantation. After 135 days of support, a suitable donor was identified and was taken for bilateral lung transplantation with ECMO/RVAD support. This was complicated by a frozen chest, massive transfusion, and primary graft dysfunction necessitating postoperative maintenance of circulatory support. Intraoperatively, a large thrombus burden was found along the pulmonary artery outflow cannula. His chest was left open at that time while his graft recovered. Three days later, a percutaneous suction thrombectomy device was inserted through his right femoral vein and under TEE guidance, he underwent suction thrombectomy of the pulmonary artery cannula clot burden (Figure 1). He was decannulated and underwent chest closure thereafter. He was anticoagulated post-operatively and has not had any further thromboembolic events.SummaryAcute COVID-19 infection leads to a known increased risk of thromboembolic phenomena. We present an interesting approach to removal of ECMO-cannula associated thrombus in severe SARS-CoV-2 infection necessitating bilateral lung transplantation.

Axillary IABP Migration into SMA

<h3>Introduction</h3> Percutaneous insertion of IABP through the axillary artery has been validated as a bridge to transplant strategy in patients who require MCS. This strategy allows patients to participate with physical therapy preventing deconditioning while awaiting advanced therapies or recovery from primary insult. With this technique relatively low adverse events were reported which mostly pertained to upper extremity vascular or neurologic complications. Although rare, there have been few reports of migration into the abdominal vasculature which can lead to severe complications such as mesenteric ischemia. <h3>Case Report</h3> 60 yo M with CAD s/p CABG, ICM who presented with cardiogenic shock. IABP was placed in the axillary position after poor response to inotropes and the patient was listed for transplant after stabilization. 10 days after placement the patient had developed severe diffuse non-positional abdominal pain. There were no peritoneal signs such as rebound or guarding. Serum lactate was within normal range. Abdominal x-ray showed stable position from initial placement and days prior. Given a high clinical suspicion the patient was taken to the cardiac catheterization lab in urgent fashion. Under fluoroscopic guidance a Steelcore wire was advanced revealing migration of the distal tip into the superior mesenteric artery. The IABP was exchanged and the patient had complete resolution of abdominal pain. Two days later a suitable donor was identified and he was successfully transplanted. <h3>Summary</h3> Review articles which describe placement technique of IABP from the axillary position lack descriptions for optimal positioning of the distal tip. Unexplained abdominal pain can be the first clinical presentation of IABP migration. In patients with cardiogenic shock this can be confounded as abdominal pain can be attributed to hepatic congestion and decreased perfusion. Despite imaging and serum lactate a high clinical suspicion is necessary to identify and prevent complications of IABP migration into the abdominal vasculature.

Aortic Root Thrombus Complicating Left Ventricular Assist Device Implantation

<h3>Introduction</h3> Aortic root thrombus (ART) is a recognized complication associated with left ventricular assist devices (LVADs) and is associated with significant morbidity and mortality. <h3>Case Report</h3> A 49 year-old male with recently diagnosed non-ischemic cardiomyopathy on inotropic support underwent HeartMate 3 implantation. He initially did well, but subsequently deteriorated and had altered mental status. CT head revealed vertebral artery thrombus and multiple ischemic changes. TEE showed large thrombus on aortic valve (AV) extending into the right coronary artery (RCA) despite therapeutic anticoagulation(Figure 1B). Hypercoagulable work up showed positive lupus anti-coagulant. He had progressive RV failure requiring right ventricular assist device as well as intractable ventricular fibrillation. Decision was made to list status 1 for heart transplant and suitable donor was identified within 72 hours. Post-operatively, unresponsive off sedation with dysconjugate gaze and minimal reflexes. Head CT showed extensive infarcts with swelling and mass effect. He was transitioned to comfort measures and compassionately extubated. <h3>Summary</h3> ART remains a rare, but significant complication post-implant despite improvements in contemporary LVADs. Pre-implant hypercoagulable workup in all patients has shown low utility. This case highlights the importance of intermittent AV opening and the significant complications that can occur in LVAD patients with ART.

Results of Heart Transplants from Donation After Circulatory Death (DCD) Donors Using Thoraco-Abdominal Normothermic Regional Perfusion (TA-NRP) Compared to Donation After Brain Death (DBD)

<h3>Purpose</h3> In the U.S., heart transplantation from donation after circulatory death (DCD) is increasing. We present our institutional experience of DCD transplantation by using a thoracoabdominal-normothermic regional perfusion (TA-NRP) protocol and compare the results to a cohort concomitantly transplanted, from standard brain death (DBD) donation. <h3>Methods</h3> For TA-NRP protocol, suitable local DCD donors were transferred to our institution and co-located with the recipient in proximate operating rooms. Standard DCD procurement involved resuscitation of the donor on cardiopulmonary bypass after declaration of death and assessment for suitability by echocardiogram and hemodynamic data. Heart transplant from DBD was performed per standard protocol. Immunosuppression and management followed the same standardized protocol for all recipients. <h3>Results</h3> Between January 2020 and October 2021, we performed 10 DCD transplantations with TA-NRP protocol (7 isolated heart, 2 heart-lung and 1 heart-kidney). The median age was 54 years (44-72), and 70% were male. One heart-lung transplant recipient required VA ECMO post-op, for 3 days. During the same period, 70 patients received heart transplant from a DBD donor (71.4% isolated heart, 7.1% heart-lung, 21.4% heart-kidney). The median age was 56 years (24-77) - p=0.916, 84.% were male p=0.27. At mean follow-up of 397.6 days (DCD recipients) and 305.9 days (DBD recipients), there were no significant differences in acute cellular, antibody mediated rejection, cardiac allograft vasculopathy, heart graft function, and survival. Compared to DBD recipients, DCD recipients received transplant at lower listed statuses. <h3>Conclusion</h3> Short-term results suggest that transplant outcomes from DCD TA-NRP are comparable to recipients from DBD. Expanding heart transplantation by using DCD is a viable option for lower-status listed patients and wide adoption should be considered.

Longitudinal Echocardiographic Assessment of Donor Hearts in DCD Donors Using Thoracoabdominal Normothermic Regional Perfusion

<h3>Purpose</h3> In the U.S., multiple centers are beginning to develop protocols for DCD organ donation. We describe our intraoperative echo thoracoabdominal normothermic regional perfusion (TA-NRP) DCD protocol for initial donor acceptance and mid-term follow up <h3>Methods</h3> After identification of a suitable DCD donor, withdrawal of life support is performed in the OR until circulatory death occurs. After 5 minutes of observation, circulatory death is declared. The sternum is opened, cerebral vessels are ligated, and cardiopulmonary bypass (CPB) is initiated. Transesophageal echocardiogram (TEE) monitors the following parameters to ensure the heart is acceptable: left ventricular ejection fraction (LVEF) ≥50%, mitral valve annulus lateral S wave (MV S wave) ≥10 cm/sec, left ventricular outflow tract time integral (LVOT VTI) ≥15 cm, and right ventricular systolic function (RVEF) normal by visual estimation. The recipient's LVEF and global longitudinal strain rate (GLS) were followed longitudinally for up to 18 months <h3>Results</h3> From January 2020 to October 2021, 10 TA-NRP DCD transplants were performed: 7 isolated hearts, 2 heart-bilateral lung, and 1heart-kidney. Median donor age was 43.5 years (26-51) and there were 9 males (90%). Fifty percent of donors had a history of opioid drug overdose. The mean preoperative donor LVEF was 68%. Mean TEE parameters while weaning off CPB: LVEF 65%, MV lateral S wave 12 cm/sec, and LVOT VTI 19 cm. RVSF was normal for all donors. None of the donors required inotropic support. The recipient median age was 54 years (44-72) and 70% were male. None of the recipients developed cardiac graft failure. At mean follow-up of 392 days, mean LVEF is 64% and mean GLS is -16.7% and all patients are alive. <h3>Conclusion</h3> A standardized intraoperative TEE protocol to assess TA-NRP DCD donor heart function while weaning CPB is of paramount importance to ensure excellent longitudinal recipient graft function.

Peri-Operative Desensitization for Highly Sensitized Lung Transplant Recipients Following COVID-19 Acute Respiratory Distress Syndrome (ARDS) - Report of Two Cases

IntroductionSensitized lung transplant (LTx) candidates have longer waiting times, decreased likelihood of transplant, and increased risk of death while on the waitlist. Patients with SARS-Cov-2 ARDS on ECMO support due to end-stage lung disease have a short window of opportunity for LTx. We report two cases in which the Toronto LTx peri-operative strategy was performed with good outcomes in highly sensitized Covid-19 patients.Case ReportCase 1: 31-yo female patient with Covid-19 ARDS, transferred for LTx evaluation after 46 days on VV-ECMO. She was pregnant when she presented with Covid -19 acute respiratory failure, and underwent an urgent C-section due to fetal distress. She required blood transfusions during ICU stay. At LTx assessment: PRA class I: 95%; class II: 0%. A decision to proceed with LTx with perioperative desensitization was made considering the low probability of finding a suitable donor. After seven days on the waiting list, she underwent bilateral LTx. Virtual crossmatch (XM) positive (B35); CDC-XM negative. Desensitization protocol was performed with perioperative plasma exchange (PLEX) without basiliximab induction, followed by five sessions of PLEX and intravenous immunoglobulin 1 mg/kg. Due to postoperative acute cholecystitis with positive cultures after biliary drainage, anti thymocyte globulin (ATG) infusion (3 mg/kg) was held, and infusion postponed until four weeks post LTx. Tacrolimus, mycophenolate, and prednisone were used as maintenance immunosuppression. The patient was discharged home on PO day 53 with excellent graft function. Case 2: 35-yo female patient with Covid-19 ARDS, transferred for LTx after 69 days on VV-ECMO. History of 3 previous pregnancies and multiple blood transfusions due to transitory coagulopathy during her ICU stay. PRA class I: 83%; class II: 94%. VCM positive (B7, Cw7, DRB1*11:01, DR52, DQA1*05/DQB1*03). Desensitization protocol was performed, but ATG infusion was held due to C. albicans bloodstream infection and colonization with pan-resistant K. pneumoniae. DSAs at six weeks were negative. She remains hospitalized for mechanical ventilation withdrawal and inpatient rehabilitation.SummaryIn selected cases, peri-operative desensitization is feasible and can be safely implemented in highly sensitized patients with Covid-19 ARDS.

Systemic Right Ventricle Mechanical Support with Impella 5.5 as a Bridge to Cardiac Transplantation

<h3>Introduction</h3> A 39-year-old man with Senning atrial switch for dextro-transposition of the great arteries (d-TGA) presented with systemic right ventricle (RV) failure and cardiogenic shock. He had Impella 5.5 percutaneous mechanical support for his systemic RV and received cardiac transplantation 42 days later. To our knowledge, this has not been previously reported in the literature. <h3>Case Report</h3> A 39-year-old man with Senning atrial switch for d-TGA and long-standing systemic RV dysfunction on heart failure medical and resynchronization therapy was transferred for cardiogenic shock. Diuresis was unsuccessfully attempted with a furosemide drip, so inotropes and evaluation for advanced heart failure therapies were initiated. His condition initially improved, but on hospital day 8, he had a ventricular fibrillation cardiac arrest, requiring cardiopulmonary resuscitation and emergent femoral intra-aortic balloon pump (IABP) placement. Right heart catheterization showed cardiac index of 2.16 L/min/m^2 on milrinone, dobutamine, and IABP. He continued to clinically deteriorate. After multidisciplinary discussions, an axillary Impella 5.5 device was placed under fluoroscopic and TEE guidance. The device could not be rotated posteriorly away from the RV free wall due to the opposing posterior orientation of the atrioventricular valve and anterior course of the innominate artery (figure). However, there was significant hemodynamic improvement and no arrhythmias, so device was secured. He was listed for heart transplantation as UNOS Status 2. Forty-two days after Impella placement, a suitable donor heart became available. He underwent successful transplant with initial biopsy showing no rejection. He was discharged on post-operative day 12 and continues to do well as an outpatient. <h3>Summary</h3> Impella 5.5 device implantation in the systemic RV is a feasible strategy for patients with d-TGA and atrial switch awaiting durable VAD or transplant.

Methodological study of directed differentiation of pluripotent stem cells into corneal endothelial cells.

BackgroundCorneal transplantation is the most effective clinical treatment for irreversible corneal endothelial decompensation. However, while visual rehabilitation can be achieved by corneal transplantation, transplant rejection, poor postoperative visual acuity, and lack of suitable donor tissue are currently the greatest obstacles to corneal transplantation. As a result, endothelial cell-based therapy has emerged as an alternative to corneal transplantation treatment. Human induced pluripotent stem cells (hiPSCs) were induced to differentiate into human corneal endothelial cell (hCEC)-like cells in our study, which aimed to provide an experimental basis for studying the clinical translation and application of induced PSC (iPSC) to corneal endothelial cell (CEC) differentiation.MethodsA two-step method to convert hiPSCs into hCEC-like cells was applied in the study. First, the transforming growth factor beta (TGF-β) and Wnt signaling pathways were regulated by adding SB4315542 and CHIR99021, and hiPSCs were induced to differentiate into neural crest cells (NCCs) by a chemically defined and serum-free in vitro induction method. Subsequently, NCCs were induced to differentiate into hCEC-like cells by adding B27, platelet-derived growth factor (PDGF)-BB, and XAV939 (Wnt pathway inhibitor) to CEC culture medium.ResultsIPSCs were directionally differentiated into NCCs. During the process of differentiation, iPSCs gradually lost the monoclonal morphology of PSCs. Moreover, β-catenin and SRY-related HMG-box gene 10 (SOX10) proteins were immunohistochemically expressed on the 7th day of differentiation. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) results demonstrated that the cells expressed SOX9, SOX10, nerve growth factor receptor (NGFR), human natural killer-1 (HNK-1), and β-catenin, indicating that they were successfully directionally differentiated from iPSCs to NCCs. After 5–7 days of differentiation, the cells demonstrated a hexagonal morphology of monolayer tight junctions. Immunofluorescence results demonstrated that the cells expressed CEC indicator zonula occludens-1 (ZO-1) protein. QRT-PCR results demonstrated that the cells expressed collagen type IV alpha 1 (COL4A1), COL8A2, COL8A1, and ZO-1, which indicated that they were successfully directionally differentiated from NCC to CEC.ConclusionsOur study successfully provided a simple and efficient method with clear chemical composition and serum-free media to directionally differentiate hiPSCs into hCEC-like cells, thereby advancing the results of previous studies on directional transformation into epithelial cells.

Sequential Redo Bilateral Lung Transplantation in a Patient with a Prior Heart-Lung Transplantation with Tracheal Anastomosis

<h3>Introduction</h3> Redo lung transplantation (LT) for chronic lung allograft dysfunction (CLAD) is technically complex. We present a redo bilateral LT after previous heart-lung transplantation (HLT) with salvage of tracheal anastomosis and donor-to-donor main bronchi anastomoses. <h3>Case Report</h3> Patient is a 22-year-old male with previous HLT 17 years prior for pulmonary arterial hypertension now with preserved cardiac function, CLAD (FEV1 36%) with chronic hypercapnic respiratory failure, and pulmonary fungal infection with multidrug resistant <i>Lomentospora prolificans</i>. Prior to listing sputum culture was negative for fungal growth. His LAS was 45.8, and he spent 36 days on the wait list prior to a suitable donor being identified. Surgical approach involved redo clamshell thoracotomy. To control for possible fungal dissemination both lungs were explanted simultaneously under cardiopulmonary bypass, and extensive irrigation of chest cavities and trachea was completed with amphotericin B and caspofungin. The prior tracheal anastomosis was left intact. Pump suction and cell salvage was avoided. Standard sequential implantation with donor-to-donor main bronchi anastomoses was completed. Lung explant pathology demonstrated active subtotal and total bronchiolitis obliterans (C1) associated and necrotizing and non-necrotizing granulomas. Primary graft dysfunction was grade 1 at time 0, 24, 48, and 72 hrs. Postoperative antifungal regimen was Olorofim, caspofungin, and inhaled amphotericin B. No short-term airway complications were encountered. First transbronchial biopsy (TBBx) demonstrated moderate acute cellular rejection (ACR; A3B2), and <i>Lomentospora prolificans</i> growth. Due to persistent fungal growth, but no evidence of fungal pneumonia on chest imaging, systemic antifungal regimen was adjusted to fosmanogepix, miltefosine, posaconazole, and caspofungin. After 5 days of new antifungal regimen, 500 mg methylprednisone x 3 days was administered for ACR. Patient was discharged home on POD32. Second TBBx demonstrated no ACR but fungal elements persisted. <h3>Summary</h3> Redo bilateral LT after HLT with salvage of tracheal anastomosis and donor-to-donor main bronchial anastomosis is feasible without airway complications. Antifungal regimen will continue with re-evaluation at 6 months postoperatively.

COVID-19 in Combination with HLH in a Child with Severe Aplastic Anemia

Since December 2019, the coronavirus (COVID-19) has spread all over the world. This disease may present differently in immune-compromised persons. Some of the virus's impacts have yet to be identified. In this case report, we report a three-year-and-three-month-old child with aplastic anemia who was concurrently infected with COVID-19 and HLH (hemophagocytic lymphohistiocytosis). She was referred to our center for further investigation of aplastic anemia with concurrent fever. Through examination due to splenomegaly, more evaluations were done. During admission, the PCR test for COVID-19 became positive, however, because of the fulfillment of the HLH criteria, she was diagnosed with this disease development. She was treated for HLH with IVIG and Dexamethasone while getting COVID-19 treatment. Following medicines and follow-up, her WBC and Hb count started to rise, aside from the PLT count. She continues to receive PLTs because of her thrombocytopenia till a suitable donor for BMT (Bone Marrow Transplant) is found. This case scenario highlights the COVID-19 concurrent complications for paying attention to underlying disease for better diagnosis and management.

VCA in the Era of the COVID-19 Pandemic.

VCA in the Era of the COVID-19 Pandemic.

Comparing Donor Site Morbidity for Autologous Breast Reconstruction: Thigh vs. Abdomen.

Background:Although abdominally-based free flaps have long been the gold standard, the profunda artery perforator (PAP) flap has emerged as an important alternative option for autologous breast reconstruction. The aim of this study was to directly compare the donor site morbidity of using the PAP versus deep inferior epigastric perforator (DIEP) free flap.Methods:We performed a retrospective review of patients undergoing autologous breast reconstruction using a DIEP and/or PAP flap from January 2017 to December 2020. In total, 30 PAP flap patients were matched with 60 DIEP flap patients. Outcomes included donor site wound dehiscence, length of stay, narcotic consumption, and pain scores. Patient-reported outcomes for the thigh versus abdomen were compared using questions derived from the BREAST-Q.Results:There was no significant difference in length of stay (P = 0.182), reoperation rates (P = 0.999), flap failure rates (P = 0.999), or donor site complications (P = 0.999). Both groups had similar mean pain scores, maximum pain scores, daily and total narcotic requirements. In comparing the thigh or abdomen as a donor site, there was no difference in frequency of negative symptoms (difficulty with daily activities, discomfort, tightness, and negative impact on ability to work) or satisfaction scores as related to their appearance in and out of clothing and the appearance of the scar.Conclusions:The thigh and abdomen are both suitable donor sites for autologous breast reconstruction with similar flap-related and patient-reported outcomes. The ultimate decision regarding whether to use a PAP or DIEP flap for breast reconstruction should be tailored based on patient anatomy and preference.

A Novel 3D Culture System Using a Chitin-Based Polysaccharide Material Produces High-Quality Allogeneic Human UCMSCs with Dispersed Sphere Morphology.

Mesenchymal stem cell (MSC) transplantation, in particular allogeneic transplantation, is a promising therapy for a variety of diseases. However, before performing allograft treatment it is necessary to find suitable donors, establish culture methods that maintain cell quality, and reduce cell production costs. Here, we present a new method of producing allogeneic MSCs combining human umbilical cord-derived mesenchymal stem cells (UCMSCs) and chitin-based polysaccharide fibers (Cellhesion® MS). UCMSC numbers significantly increased, and cells grew as dispersed spheres on Cellhesion® MS. Subsequent biological analyses showed that the expression levels of stemness-related and migration-related genes were significantly upregulated, including octamer-binding transcription factor 4 (OCT4), Nanog homeobox (NANOG), and C-X-C chemokine receptor type 4 (CXCR4). The secretion levels of paracrine factors such as prostaglandin E2 (PGE2), TNFα-stimulating gene (TSG)-6, fibroblast growth factor 2 (bFGF), and Angiogenin (Ang) from UCMSCs using Cellhesion® MS were significantly higher than with microcarrier and U-bottom plate culture. In addition, culture supernatant from UCMSCs with Cellhesion® MS had better angiogenic potential than that from monolayer cultured UCMSCs. Furthermore, we succeeded in a scaled-up culture of UCMSCs with Cellhesion® MS using a closed culture bag. Therefore, Cellhesion® MS is a key material for producing high-quality UCMSCs in a three-dimensional (3D) culture system.

Angiotensin (1−7) peptide replacement therapy with plasma transfusion in COVID-19

AimTo determine whether convalescent angiotensin (1−7) peptide replacement therapy with plasma (peptide plasma) transfusion can be beneficial in the treatment of critically ill patients with severe coronavirus 2 (SARS-CoV-2) infection. Study designCase series of 9 critically ill patients with laboratory-confirmed COVID-19 who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment.Peptide plasma: Plasma with angiotensin (1−7) content 8–10 times higher than healthy plasma donors was obtained from suitable donors. Peptide plasma transfusion was applied to 9 patients whose clinical status and/or laboratory profile deteriorated and who needed intensive care for 2 days. ResultsIn our COVID-19 cases, favipiravir, low molecular weight heparin treatment, which is included in the treatment protocol of the ministry of health, was started. Nine patients with oxygen saturation of 93% and below despite nasal oxygen support, whose clinical and/or laboratory deteriorated, were identified. The youngest of the cases was 36 years old, and the oldest patient was 85 years old. 6 of the 9 cases had male gender. 3 cases had been smoking for more than 10 years. 4 cases had at least one chronic disease.In all of our cases, SARS CoV2 lung involvement was bilateral and peptide plasma therapy was administered in cases when oxygen saturation was 93% and below despite nasal oxygen support of 5 liters/minute and above, and intensive care was required. Although it was not reflected in the laboratory parameters in the early period, 8 patients whose saturations improved with treatment were discharged without the need for intensive care. However, a similar response was not obtained in one case. Oxygen requirement increased gradually and, he died in intensive care process. An increase of the platelet count was observed in all cases following the peptide plasma treatment. ConclusionIn this preliminary case series of 9 critically ill patients with COVID-19, administration of plasma containing angiotensin (1−7) was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.

Transformation of inherent microorganisms in Wyoming-type bentonite and their effects on structural iron

Bentonite is one of the materials used to construct engineered barriers in high-level radioactive nuclear waste geological disposal with its many advantageous features such as low hydraulic conductivity, self-sealing ability, durability, adsorption and immobilization of metals and radionuclides and reduction of microbial activity. Many of these properties are linked with the bentonite swelling capability. Transformations of indigenous microorganism communities from Wyoming-type bentonite and the Finnish repository site groundwater and their effects on the bentonite structural iron over five years were studied in repository relevant anoxic and oxic slurry conditions. Active sulfate reduction (0.06 nmol mL−1 day−1) was detected in the anoxic microcosm waters after a year, however after two years sulfate reduction was not active anymore. Microbial numbers determined by quantitative PCR in the bentonite slurry of both experiment types supported the finding of decrease of overall microbial activity after a year of incubation that was not maintained anymore by the dissolving organic carbon from the bentonite. Regular electron donor additions (final concentration of 2 mM for formate and acetate each, three times per year) activated the microbiome resulting in increasing numbers of bacterial 16S rRNA gene copies and sulfate reducers (dsrB gene copies) as well as detection of sulfide in the water phase of both experiment types. After 4.9 years the structural iron in the fine portion of the montmorillonite had become completely reduced in all microbial microcosms and minor smectite illitization was detected especially in anoxic microcosms. Dominating bacterial groups at the end of the experiment were mainly known sulfur/sulfate and iron reducers. Archaea and fungi constituted a minor part of the microbiomes. In originally oxic microcosms, the bacterial 16S RNA and dsrB gene copy numbers were lower than in the anoxic experiment but started to significantly increase after the electron donor additions. Microorganisms originating from the repository environment could reduce the bentonite structural iron in a few years to an extent likely to affect the bentonite swelling ability if sufficient amounts of suitable electron donors are available in localized areas where bentonite is not at high density and pressure in the geological disposal.

Hematopoietic Cell Transplantation for Congenital Dyserythropoietic Anemia: A Report from the Pediatric Transplant and Cellular Therapy Consortium

Hematopoietic cell transplantation (HCT) is the sole curative option for congenital dyserythropoietic anemia (CDA), a rare type of hemolytic anemia characterized by anemia, ineffective erythropoiesis, and secondary hemochromatosis. In this retrospective multicenter study, wereport the outcomes of children with CDA who underwent HCT at participating Pediatric Transplantation and Cellular Therapy Consortium centers. Clinical information on HCT and associated outcomes was collected retrospectively using a common questionnaire. Data were analyzed using descriptive statistics and appropriate analysis. Eighteen patients with CDA who underwent allogeneic HCT between 2002 and 2020 were identified. The majority of patients (n= 13) had CDA type II, and the remainder had either CDA type I (n=2) or CDA of unknown type (n=3). Mutations were identified in 7 patients (39%), includingSEC23Bin 5,GATA1in 1, and abnormality of chromosome 20 in 1. Thirteen patients had evidence of iron overload pre-HCT and received chelation therapy for a median duration of 10 months (range, 2 months to 17 years) pre-HCT. The median age at the time of HCT was 5.5 years (range, 0.7 to 26 years). Donors were HLA-matched (sibling, 4; unrelated, 10) and mismatched (haploidentical, 1; unrelated, 3). Graft sources were bone marrow in 15 patients, umbilical cord blood in 2 patients, or both in 1 patient. Conditioning included busulfan-based myeloablative (67%), fludarabine-based reduced-intensity (27%), or nonmyeloablative (6%) regimens. Five patients developed veno-occlusive disease, and 4 had viral reactivation. The cumulative incidence of acute graft-versus-host disease (GVHD) was 33%, and that of chronic GVHD was 22%. Four patients (22%) experienced graft failure; all engrafted following either a second HCT (n=2) or third HCT (n=2) but sustained considerable morbidities (3 GVHD, 1 death, 2 viral reactivation). With a median follow-up of 3.2 years (range, 0.6 to 14 years)), the 2-year overall survival, event-free survival (EFS), and GVHD-free EFS were 88% (95% confidence interval [CI], 73% to 100%), 65% (95% CI, 45% to 92%), and 60% (95% CI, 40% to 88%), respectively.Univariate analysis did not identify any patient- or transplantation-related variables impacting outcomes. Our study indicates that HCT can be curative for patients with CDA. Strategies such as aggressive chelation, use of preconditioning therapy, and early HCT in the presence of a suitable donor before comorbidities occur are needed to improve engraftment without increasing the risk for toxicity and mortality.

A New Immunosuppressive Therapy for Very Severe Aplastic Anemia in Children with Autoantibodies.

At present, a number of very severe aplastic anemia (VSAA) patients cannot receive hematopoietic stem cell transplantation (HSCT) or standard immunosuppressive therapy (IST) due to the high cost of therapy, shortage of sibling donors, and lack of resources to support the HSCT. In addition, some VSAA patients with autoantibodies have no life-threatening infections or bleeding at the time of initial diagnosis. Considering the disease condition, economics and other factors, the present study designed a new and relatively mild treatment strategy: cyclosporine A plus pulsed high-dose prednisone (CsA+HDP). The present study retrospectively analyzed 11 VSAA patients, who were treated with CsA+HDP in our hospital from August 2017 to August 2019. The median follow-up time for these patients was 24.9 months. The overall response rate was 54.5% (6/11) at six months after the initiation of IST and 81.8% (9/11) at deadline. Five patients achieved complete remission and four patients met the criteria for partial response at the last follow-up. The median time to response for responders was 110 days. Three patients underwent HSCT due to the poor effect of CsA+HDP or to find a suitable transplant donor. Recurrence and clonal evolution were not found in any of these patients. The estimated 3-year overall survival rate and 3-year failure-free survival rate were 100.0% and 72.7%, respectively. In addition, the results revealed that the cyclosporine-prednisone-associated toxicity was mild and well-tolerated by most patients. The novel CsA+HDP regimen has good therapeutic effect and safety for VSAA patients with autoantibodies, who have no serious life-threatening infections or bleeding at the time of initial diagnosis.

Various approaches for accessing the influence of human leukocyte antigens disparity in haploidentical stem cell transplantation.

We investigated the association of HLA on clinical outcomes in our cohort of patients in the haplo-HSCT program using the HLAMatchmaker (EM) and PIRCHE score (PS) algorithms. The group comprised 64 patients (male=35-54.7%, female 29-45.3%; median age 43years) and their related haplo-HSCT donors (male=30-46.9%, female 34-53.1%). HLA-A/B/C/DRB1/DQB1/DPB1loci were analyzed. Multivariate analysis of the association between different HLA or patient/donor-related parameters and clinical outcome revealed the following associations with statistical significance: GvHD and HLA class I PS in the GvH direction (p=.0420) and relapse with diagnosis (p=.0163). For OS, the only variable showing a tendency of association was the source of HSCT (p=.0965). Combined results of univariate and multivariate analysis suggest that the patients awaiting the selection of the best haplo-HSCT donor could benefit the most from the combination of all three approaches, in cases when a suitable donor can be chosen from a number of potential donors.