Previous Transplantation Research Articles

Corneal Artificial Endothelial Layer (EndoArt): Literature Review and Our Experience.

Background/Objectives: The objective of this study was to examine the morphological corneal changes and outcomes following the implantation of an artificial endothelial layer (EndoArt) in patients with chronic corneal oedema. Methods: A systematic review of the literature was conducted alongside a detailed analysis of two clinical cases with chronic corneal oedema that were treated using EndoArt. Our experience with these two cases is included to provide practical insights and real-world outcomes. Results: Across the 24 cases reported (including the two presented here), an analysis was possible in 23 cases. Notably, 82% of patients had undergone at least one previous corneal transplant, with 39% having undergone three or more transplants. Additionally, 78% of cases had ocular comorbidities, with glaucoma surgery being the most prevalent (83%), which could have impacted visual outcomes. The follow-up period ranged from 3 to 17 months with a median of 3 months. After EndoArt implantation, the average reduction in the central corneal thickness (CCT) was 29%, and the rebubbling rate was 47.8%, with some cases requiring no rebubbling, while others required it up to 100% of the time. Visual acuity significantly improved from a mean best-corrected visual acuity (BCVA) value of 1.61 ± 0.5 logMAR to 1.07 ± 0.59 logMAR (p < 0.001). The CCT decreased from 771 ± 146 µm to 580 ± 134 µm (p < 0.001). These findings are consistent with our experience. Conclusions: EndoArt shows promise as an alternative treatment for chronic corneal oedema in complex cases where conventional corneal transplantation has failed or carries a high risk of failure. The morphological changes observed using anterior segment optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM) were similar to those reported after endothelial keratoplasty, with the notable exception of the absence of the hyper-reflective donor-host interface.

Prognostic outcome of ACS in HTX patients after PCI

Abstract Background Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide, particularly in countries with limited access to healthcare [1,2]. Acute coronary syndrome is a collective term for several clinical conditions resulting from narrowing or occlusion of the coronary arteries [3,4]. Another group of patients affected by cardiovascular disease are those who have undergone heart transplantation. Long-term survival after transplantation is limited by cardiac allograft vasculopathy, a condition that affects the coronary arteries of the donor heart and causes diffuse narrowing [5,6]. Our retrospective analysis aims to compare the prognostic outcomes of HTX patients with ACS who underwent PCI with patients without a history of HTX. Results A total of 3194 patients with ACS were enrolled, of whom 1.16% (37) had a previous heart transplant. Patients with prior transplantation were on average younger (52.54 ± 15.13 vs. 69.76 ± 12.16, p &amp;lt; 0.001), had less dyspnea (p &amp;lt; 0.001) and a different distribution of ACS types (p &amp;lt; 0.001), as shown in Figure 1. There were no differences in sex (p = 0.287), BMI (p = 0.123), hypertension (p = 0.557), diabetes mellitus (p = 0.188) and previous myocardial infarction (p = 0.681). The majority of HTX patients were diagnosed with ISHLT CAV III (58.54%) and the average time to PCI was 12 years after transplantation. Multi-vessel disease was more common in HTX patients (p &amp;lt; 0.001). In addition, calcification was less frequent in the HTX group than in the control group (p &amp;lt; 0.001), and the lesion morphology was more diffuse in the HTX group (p &amp;lt; 0.001). On the other hand, there was no difference in the distribution of target vessels (p = 0.424), with the left anterior descending being the most frequently treated coronary artery, followed by the left circumflex and right coronary arteries. HTX patients received more stents (p &amp;lt; 0.001). There was also a difference in post-procedural TIMI flow achieved (p = 0.047), with less TIMI 3 flow achieved after PCI in the HTX group (80% vs. 93.59%). Technical success was less likely to be achieved in the HTX group (62.50% vs. 96.29%, p &amp;lt; 0.001), as was procedural success (47.06% vs. 89.68%, p &amp;lt; 0.001). There was no difference in the incidence of complications, which include perforation and bleeding (p = 0.284). All-cause mortality at three years (39.02% vs. 17.50%, p &amp;lt; 0.001), stroke (7.32% vs. 1.59%, p = 0.035) and myocardial infarction (p = 0.026) were higher in the HTX group. Over a period of three years, MACCE was more likely to occur in the HTX sub-group, which is shown graphically in Figure 2. Conclusion Interventional treatment of ACS in HTX patients is an option with a complication rate comparable to non-HTX patients and with a lower technical and procedural success - partly due to the diffuse nature of CAV and the involvement of distal and microvascular vessels. Overall MACCE and survival are inferior to the control population.Figure 1Figure 2

Isolated fungal sphenoid sinusitis with unilateral lateral rectus palsy six years post lung transplant

Rhino-orbital-cerebral mucormycosis (ROCM) infections are rare and usually occur in patients with diabetes, malignancy, or organ transplantation. The most common presenting symptoms include facial pain and swelling, fever, and rhinorrhea. Mortality rates reach nearly 50%. Those with previous organ transplants typically present with sinus symptoms a few weeks to months after transplantation. A 75-year-old man presented with headache. His history was significant for bilateral lung transplantation in 2017. On his fourth presentation, he was admitted to the hospital for work up. Imaging showed small fluid levels within the right maxillary and sphenoid sinuses. Infectious work-up revealed no meningitis. On day three, the patient complained of diplopia on the right. His examination was significant for right lateral rectus palsy. Repeat imaging was performed and showed increasing fluid levels of the right maxillary and sphenoid sinuses, and the otolaryngology consultation service was consulted. Nasal endoscopy was significant for pink, vascularised mucosa with no obvious regions of pallor or necrosis. Endoscopic sinus surgery was performed. There were no findings suggestive of fungus but purulence of the right sphenoid grew Rhizopus. The patient’s nerve palsy did not resolve and progressed to the contralateral orbit. Repeat nasal endoscopy continued to show healthy mucosa while MRI showed enhancement worrisome for meningitis. To our knowledge, this is the only reported case of fungal sphenoid sinusitis resulting in meningitis and death six years after transplant. Current literature documents fungal infection in post-transplant patients up to four years after surgery, with most occurring within the first year. Suspicion for fungal infection should remain high in this patient population. Keywords: mucormycosis, lung transplant, sinusitis, lateral rectus palsy

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.

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. 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 5L of albumin 5% and antibiotics, within 12 hours of cannulation. He required twodays of VA ECMO and was ultimately decannulated and discharged to a rehabilitation facility on hospital day 73. 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.

Delayed graft function has comparable associations with early outcomes in primary and repeat transplant among deceased-donor kidney transplant recipients.

Delayed graft function (DGF) is a common complication and is associated with worse outcomes among kidney transplant recipients (KTRs). There are various risk factors for DGF including previous transplant. We hypothesized that DGF among KTRs undergoing repeat transplant has a greater impact on outcomes compared to primary KTRs. All deceased-donor KTRs between 01/2000 and 12/2020 at our center were included. Recipients were categorized as primary KTR or repeat KTR (any number of previous kidney transplants). Outcomes of interest included acute rejection, death-censored graft failure, and patient mortality within 12months post-transplant. A total of 3137 deceased-donor KTRs were included; 2498(80%) were primary KTRs and 639(20%) were repeat KTRs. The rates of DGF were similar between the groups at 29% and 28%, respectively. Compared to KTRs without DGF, DGF was associated with a greater incidence of death and graft failure in both primary and repeat transplants; however, the risk of rejection was not significantly higher in repeat KTRs (p = 0.72). Comparing primary and repeat KTRs, there were no significant differences in either acute rejection (p-interaction = 0.11), death-censored graft failure (p-interaction = 0.38), or death (p-interaction = 0.37). In subgroup analysis among repeat KTRs with DGF, a repeat transplant with no prior DGF was associated with increased risk for death-censored graft failure and death but not for acute rejection. DGF in the prior transplant was protective against death-censored graft failure (HR: 0.07, 95% CI 0.005-0.98, p = 0.05) (p-interaction = 0.04), but this was not significantly associated with acute rejection or death. DGF is associated with similar detrimental outcomes among primary and repeat KTRs.

The association between pretransplant malignancy and post-transplant survival and cancer recurrence in bilateral lung transplantation: An analysis of 23,291 recipients

BackgroundGiven the increasing need for lung transplants among older patients with a history of cancer, this study analyzed database registry to assess outcomes for BLT recipients with Pre-TM. MethodsThis study evaluated the United Network for Organ Sharing (UNOS) registry for adult BLT performed between 2005 and 2023. Patients with a history of previous or multi-organ transplants, and those with donors who had cancer history, were excluded. Propensity-score matching was used to compare patients with or without Pre-TM. Overall and Post-TM-free survival were analyzed. ResultsAmong the 23,291 recipients of BLT, 8.0%(1,870) had Pre-TM. Compared to those without Pre-TM, patients with Pre-TM had worse overall (hazard ratio[HR] 1.20, 95% confidence interval[CI] 1.12-1.29, p<0.001) and Post-TM-free survival (HR 1.32, 95% CI 1.24-1.41, p<0.001). However, after adjusting for age, sex, and race through propensity-score matching, the survival difference between the groups became non-significant (HR 1.05, 95% CI 0.97-1.13, p=0.229). While the Pre-TM group still had worse Post-TM-free survival, this difference diminished after excluding cutaneous Post-TM (HR 1.06, 95% CI 0.99-1.15, p=0.116). Additionally, the recurrence rate of Pre-TM after transplant wasn't higher than de novo cancers in patients without Pre-TM. ConclusionPatients with Pre-TM had similar overall survival rates after BLT as those without Pre-TM. Importantly, there was no increased risk of the primary Pre-TM type recurring post-transplant compared to patients without Pre-TM. If patients with PreTM are free from recurrence or metastasis for a significant amount of time, there could be some who can benefit from BLT. Further data regarding timeline between PreTM and BLT would be necessary to draw conclusion in this issue.

Allogeneic CD5-specific CAR-T therapy for relapsed/refractory T-ALL: a phase 1 trial.

Refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL) patients have poor prognoses, due to the lack of effective salvage therapies. Recently, CD7-targeting chimeric antigen receptor (CAR)-T therapies show efficacy in patients with r/r T-ALL, but relapse with CD7 loss is common. This study evaluates a CD5-gene-edited CAR-T cell therapy targeting CD5 in 19 r/r T-ALL patients, most of whom had previously failed CD7 CAR-T interventions. CAR-T products were derived from previous transplant donors (Cohort A) or newly matched donors (Cohort B). Primary endpoints were dose-limiting toxicity at 21 days and adverse events within 30 days. Secondary endpoints were responses, pharmacokinetics and severe adverse events after 30 days. A total of 16 received infusions, 10 at target dose of 1 × 106 kg-1. All encountered grade 3-4 cytopenias and one had a grade 3 infection within 30 days. All patients (100%) achieved complete remission or complete remission with incomplete blood count recovery by day 30. At a median follow-up of 14.3 months, four received transplantation; three were in remission and one died of infection. Of 12 untransplanted patients, 2 were in remission, 3 relapsed, 5 died of infection and 2 of thrombotic microangiopathy. CAR-T cells persisted and cleared CD5+ T cells. CD5- T cells, mostly CD5-gene-edited, increased but remained below normal levels. These results suggest this CD5-specific CAR-T intervention has a high remission rate for T-ALL patients. Evidence also suggests the risk of late-onset severe infection may be mitigated with consolidative transplantation. This study provides insights that could help to optimize this promising intervention. ClinicalTrials.gov registration: NCT05032599 .

Confounding variables such as previous transplants, gender, ethnicity, and primary disease complicate the diagnostic validity of single-antigen bead-based non-HLA antibody assays

Confounding variables such as previous transplants, gender, ethnicity, and primary disease complicate the diagnostic validity of single-antigen bead-based non-HLA antibody assays

Safety and Pharmacokinetics of Nirsevimab in Immunocompromised Children.

Immunocompromised children may have increased risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI), potentially leading to prolonged hospitalization, intensive care, and death. The open-label phase II MUSIC trial evaluated the safety and pharmacokinetics of nirsevimab, an extended half-life monoclonal antibody against RSV, in immunocompromised children aged ≤24 months. Participants received a single intramuscular injection of nirsevimab (first RSV season: 50 mg if <5 kg/100 mg if ≥5 kg; second season: 200 mg). Safety, antidrug antibodies, and pharmacokinetics were evaluated to day 361. Participants (n = 100) had ≥1 immunocompromising conditions: primary immunodeficiency (n = 33), previous transplantation (n = 16), HIV infection (n = 8) or treatment with high-dose systemic corticosteroids (n = 29), immunosuppressive chemotherapy (n = 20), or other immunosuppressive therapies (n = 15). Six children experienced eight treatment-related adverse events (none categorized as serious). Three deaths occurred, all were unrelated to treatment. Eleven children, developed antidrug antibodies, with minimal effects on pharmacokinetics and no apparent impact on safety. Nirsevimab serum concentrations at day 151 were similar to those effective in preventing medically attended RSV LRTI in healthy infants. Fourteen children had increased nirsevimab clearance. No protocol-defined medically attended RSV LRTIs occured through day 151. Among immunocompromised children aged ≤24 months, nirsevimab was well tolerated with no safety concerns and serum concentrations were supportive of efficacy. A subset of children with increased nirsevimab clearance, had conditions potentially associated with protein loss; however, the impact on efficacy is unknown.

Procurement Trends, Indications, and Outcomes of Heart-Lung Transplantation in the Contemporary Era.

Evolving trends in organ procurement and technological innovation prompted an investigation into recent trends, indications, and outcomes following combined heart-lung transplantation (HLTx). The United Network for Organ Sharing database was queried for all adult (≥18 years) HLTx performed between July 1, 2013 and June 30, 2023. Patients with previous transplants were excluded. The primary endpoint was the effect of donor, recipient, and transplantation characteristics on 1- and 5-year survival. Secondary analyses included a comparison of HLTx at high- and low-volume centers, an assessment of HLTx following donation after circulatory death (DCD), and an evaluation of HLTx volume over time. Cox proportional-hazards models were used to assess factors associated with mortality. Temporal trends were evaluated with linear regression. After exclusions, 319 patients were analyzed, of whom 5 (1.6%) were DCD. HLTx volume increased from 2013 to 2023 (p<0.001). One- and 5-year survival following HLTx was 84.0% and 59.5%, respectively. One-year survival was higher for patients undergoing HLTx at a high-volume center (88.3%vs. 77.9%; p=0.012). After risk adjustment, extracorporeal membrane oxygenation support 72 h posttransplant and predischarge dialysis were associated with increased 1-year mortality (HR=3.19, 95% CI=1.86-5.49 and HR=3.47, 95% CI=2.17-5.54, respectively) and 5-year mortality (HR=2.901, 95% CI=1.679-5.011 and HR=3.327, 95% CI=2.085-5.311, respectively), but HLTx at a high-volume center was not associated with either. HLTx volume has resurged, with DCD HLTx emerging as a viable procurement strategy. Factors associated with 1- and 5-year survival may be used to guide postoperative management following HLTx.

Use of Cefiderocol in Adult Patients: Descriptive Analysis from a Prospective, Multicenter, Cohort Study.

Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01-6.46, p=0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05-72.54, p=0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16-0.91, p=0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Dental Sedation and General Anesthesia Considerations for Patients Posthepatic Transplantation.

Hepatic compromise poses significant impacts upon the care of patients undergoing routine dental treatment. When sedation or general anesthesia is planned for dental treatment or oral and maxillofacial surgery, an understanding of basic liver function and clinical evaluation can assist in adapting treatment modifications for patients with limited function due to previous disease and resultant organ transplantation efforts. Beginning with a basic overview of hepatic physiology, this review will outline the specific functions of digestion, metabolism, synthesis, and detoxification involving the liver. Specific clinical considerations will be reviewed regarding comorbidities that develop prior to and after liver transplantation that often impact a patient's suitability for ambulatory and office-based care. Lastly, choices in both local anesthetics, sedative medications, general anesthetics, and postoperative analgesics utilized in dental treatment will be discussed.

P.432: Short-term outcomes of cardiac surgery in patients with previous abdominal solid organ transplant: A tertiary center experiences.

P.432: Short-term outcomes of cardiac surgery in patients with previous abdominal solid organ transplant: A tertiary center experiences.

MRI-serum-based score accurately identifies patients undergoing liver transplant without rejection avoiding the need for liver biopsy: A multisite European study.

Serum liver tests (serum tests) and histological assessment for T-cell-mediated rejection are essential for post-liver transplant monitoring. Liver biopsy carries a risk of complications that are preferably avoided in low-risk patients. Multiparametric magnetic resonance imaging (mpMRI) is a reliable noninvasive diagnostic method that quantifies liver disease activity and has prognostic utility. Our aim was to determine whether using mpMRI in combination with serum tests could noninvasively identify low-risk patients who underwent liver transplants who are eligible to avoid invasive liver biopsies. In a multicenter prospective study (RADIcAL2), including 131 adult and pediatric (children and adolescent) patients with previous liver transplants from the Netherlands, Portugal, and the United Kingdom, concomitant mpMRI and liver biopsies were performed. Biopsies were centrally read by 2 expert pathologists. T-cell-mediated rejection was assessed using the BANFF global assessment. Diagnostic accuracy to discriminate no rejection versus indeterminate or T-cell-mediated liver transplant rejection was performed using the area under the receiver operating characteristic curve. In this study, 52% of patients received a routine (protocol) biopsy, while 48% had a biopsy for suspicion of pathology. Thirty-eight percent of patients had no rejection, while 62% had either indeterminate (21%) or T-cell-mediated rejection (41%). However, there was a high interobserver variability (0 < Cohen's Kappa < 0.85) across all histology scores. The combined score of mpMRI and serum tests had area under the receiver operating characteristic curve 0.7 (negative predictive value 0.8) to identify those without either indeterminate or T-cell-mediated rejection. Combining both imaging and serum biomarkers into a composite biomarker (imaging and serum biomarkers) has the potential to monitor the liver graft to effectively risk stratify patients and identify those most likely to benefit from a noninvasive diagnostic approach, reducing the need for liver biopsy.

Disease progression of side-branch intraductal papillary mucinous neoplasms following solid organ transplant

BackgroundBranch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) are becoming more prevalent with advanced medical imaging and account for most of pancreatic cystic neoplasms (PCNs). Most incidental lesions should be surveyed, with resection reserved for specific, high-risk cases. Solid organ transplantation candidates may be high risk of resection before transplant and will require systemic immunosuppression after transplant, which has been theorized to alter the natural history of the IPMN. We aimed to describe the progression in surveilled cysts after solid organ transplantation. MethodsA prospectively maintained database of PCNs was queried for patients with IPMN. Patients who had received a previous solid organ transplantation and with ≥2 imaging studies >6 months apart after transplantation were included. Clinically relevant (CR) progression was defined as symptoms, worrisome/high-risk stigmata, or invasive carcinoma (IC). Growth ≥5 mm in 2 years is considered CR progression; size ≥3 cm alone is not. ResultsBetween 1997 and 2023, 252 patients received solid organ transplantation (liver, 86; kidney, 113; and lung, 54) and were diagnosed as having an IPMN. This cohort was compared with a set of 770 patients surveilled for IPMN who did not have previous transplantation. Median follow-up period was 3.7 years (IQR, 1.6–6.8). Moreover, 2 transplant patients (0.8%) developed IC, and 4 developed (1.6%) high-grade dysplasia (HGD). Both were less common in transplant patients than the nontransplant population (IC, 3.3%; HGD, 2.9%), although this was not significant on time-to-event analysis (IC, P = .152; HGD, P = .352). The rate of CR progression was high in the transplant cohort (n = 118; 47%). Features of CR progression included size growth (n = 79; 67%), other worrisome/high-risk stigmata (n = 25; 21%), and new main duct involvement (n = 14; 12%). Compared with the nontransplant (n = 128; 17%), transplant patients had a higher rate of CR progression (P < .001), which was mostly explained by a more frequent size growth (31% vs 9%; P < .001). However, no transplant patients with size growth CR progression developed IC. Moreover, 17 (6.7%) required pancreatic surgery for CR progression after transplant vs 58 (7.5%) in the nontransplant population. Furthermore, 6 resected cysts (35%) harbored high-risk pathology after transplant (IC, 2; HGD, 4) vs 40 (69%) in the general population (P < .001; IC, 29; HGD, 11). ConclusionMalignant transformation of BD-IPMNs is rare despite systemic immunosuppression in solid organ transplant patients. This supports transplantation in patients with IPMN without fear of worsening their risk of pancreatic cancer, although it was associated with a higher risk of disease progression. Patients with IPMNs should be surveilled with yearly scans after transplant, with pancreatic resection reserved for only high-risk features as we continue to define the optimal criteria for those with CR progression.

Revision of antifungal strategies definitions for invasive fungal infections (proven/probable/possible) in 461 patients with haematological malignancies (REDEFI-SEIFEM).

Invasive fungal infections (IFI) are a relevant cause of morbidity and mortality among patients with haematological neoplasms (HMs). Since 2002, a classification of IFI based on host factors, clinical and radiological features and mycological tests was published for research purpose. These criteria are widely used in clinical practice to identify patients at risk for IFI. The aim of the study was to evaluate the clinical applicability of EORTC/MSG 2008 criteria for the diagnosis of IFI in daily practice. This multicentre, non-interventional, observational, prospective study gathered all consecutive inpatients with HMs in which an intravenous antifungal treatment was started. Exclusion criteria were a previous or concomitant transplant procedure, outpatient status and oral antifungal therapy. EORTC/MSG 2008 criteria were used to classify patients at the beginning of antifungal therapy and at 30 days. An independent board reviewed the classification of IFI given by local clinicians at T0 and T30. The highest percentage of agreement was found for possible IFI (96%), while a lower agreement was reported for proven IFI (74%), and the highest variability was observed for probable IFI (56%). At T30, the board re-evaluation confirmed a strict agreement for possible IFI only (98%). Among 306 patients classified as possible, 156 (51%) patients showed non-typical radiological findings and 45 (15%) patients presented host factors only. In real life, the EORTC/MSG criteria can be applicable only for possible IFI. As non-typical radiological findings are reported in possible IFI, introducing a new IFI category should be considered.

Out of the ice age: Preservation of cardiac allografts with a reusable 10 °C cooler

ObjectiveStatic cold storage with ice has been the mainstay of cardiac donor preservation. Early preclinical data suggest that allograft preservation at 10 °C may be beneficial. We tested this hypothesis by using a static 10 °C storage device to preserve and transport cardiac allografts. MethodsIn total, 52 allografts were recovered between July 2023 and March 2024 and transported using a 10 °C storage cooler. Results were compared to a 3:1 propensity match of allografts transported on ice. Patients were excluded for the following reasons: dual viscera transplant, previous heart transplant, complex congenital heart disease, or allograft injury during procurement. ResultsAmong the 10 °C cooler cohort, median total ischemic time was 222 minutes at 10 °C versus 193 minutes on ice (P < .0001). Intraoperative change in lactate was statistically lower at 10 °C (3.6 vs 5.1 mmol/L, P = .0016). Cardiac index score was greater in 10 °C cooler hearts at 24 (3.2 vs 3.0, P = .016) and 72 hours (3.3 vs 2.9, P = .037), despite similar vasoactive inotrope scores. There was no difference in severe primary graft dysfunction (1.9 vs 2.6%, P > .99). 10 °C hearts demonstrated less change in lactate but no difference in vasoactive inotrope scores or cardiac index. In hearts with extended ischemic time, delta lactate was lower in 10 °C cooler hearts. There was no statistical difference in outcomes for donor hearts >40 years old. ConclusionsThis is an early experience of static preservation in a 10 °C cooler. Postoperative allograft function was excellent, and lactate profiles lower in those allografts with extended ischemic times. Static cold storage targeting 10 °C may offer an inexpensive method for extended heart preservation. Further investigation is needed to assess long-term outcomes of 10 °C storage.

Lung transplant list withdrawal in a liver transplant patient thanks to elexacaftor-tezacaftor-ivacaftor: a case report

BackgroundElexacaftor-tezacaftor-ivacaftor (ETI) is a transmembrane conductance regulator modulator that significantly improves lung function in patients affected by cystic fibrosis (CF). This triple drug is currently not indicated in liver transplant patients, as clinical trials including subjects with previous solid organ transplantation are lacking.Case presentationWe report on a liver transplant girl with CF-related advanced pulmonary disease meeting clinical criteria for lung transplant, who started the triple modulator because she could not get on the lung transplant waiting list due to psycho-social motivations. Since initiation of ETI therapy, she has experienced a significant improvement in respiratory function and quality of life, without adverse effects.ConclusionsThis case shows that ETI therapy can represent a lifesaving drug for individuals without alternatives, even in liver transplant patients. The clinical benefits of the modulator overcome risks, which may be limited with a close drug monitoring of immunosuppressants serum levels and functional liver tests.

Ceftolozane/Tazobactam for the Treatment of Adults With Cystic Fibrosis: Results From a French Prospective Cohort Study.

People with cystic fibrosis (pwCF) are particularly susceptible to respiratory infections, including those caused by multidrug-resistant (MDR) pathogens. Ceftolozane/tazobactam (C/T) is an antibacterial agent combination active against MDR gram-negative bacteria that has shown promising results in isolates from pwCF. This subanalysis is the first extensive observation of real-world C/T use in pwCF. The multicenter observational CONDUCT study included consecutive patients, some with cystic fibrosis, who received ≥1 dose of C/T at 28 centers throughout France. Patients were treated according to hospital standards and followed up until the end of C/T treatment (EOT). Among 260 patients who had received ≥1 dose of C/T, 63 were pwCF, including 12 with previous lung transplant. The median age was 34 years and 55.6% of patients were female. Pseudomonas aeruginosa was the most frequently isolated pathogen (n = 40/41 [97.6%]). Most tested P aeruginosa strains (n = 65/73 [91.5%]) and all other isolated strains (Escherichia coli, Citrobacter koseri, Proteus mirabilis, and Serratia marcescens) were susceptible to C/T. Most patients completed the treatment duration, including those with historical β-lactam hypersensitivity. Reasons for stopping treatment were planned EOT and improvement in condition; overall, 88.9% of patients (n = 56/63) experienced improvement in condition. No new safety signals were identified. Mean forced expiratory volume in 1 second improved from 1.33 L to 1.47 L before and after C/T treatment, respectively (n = 52; P = .057). C/T treatment was well tolerated and effective in pwCF, including those with previous β-lactam hypersensitivity.

Sex hormone binding globulin (SHBG) serum levels and insulin resistance in men on chronic hemodialysis

BackgroundIn males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance.MethodsIn a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose.Results27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other.ConclusionsOur findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.