Transplantation Group Research Articles

Islet-after-kidney transplantation versus kidney alone in kidney transplant recipients with type 1 diabetes (KAIAK): a population-based target trial emulation in France

Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes. In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis. Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 0·44 (95% CI 0·23-0·88; p=0·022), mainly explained by a protective effect on the risk of death (HR 0·41, 0·13-0·91; p=0·042). There was no meaningful association between IAK and death-censored graft survival (0·73, 0·30-1·89; p=0·36). In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide. Programme Hospitalier de la Recherche Clinique, Fondation pour la Recherche Medicale, and Fonds de Dotation Line Renaud-Loulou Gasté.

Examining intra-host genetic variation of RSV by short read high-throughput sequencing.

Every viral infection entails an evolving population of viral genomes. High-throughput sequencing technologies can be used to characterize such populations, but to date there are few published examples of such work. In addition, mixed sequencing data are sometimes used to infer properties of infecting genomes without discriminating between genome-derived reads and reads from the much more abundant, in the case of a typical active viral infection, transcripts. Here we apply capture probe-based short read high-throughput sequencing to nasal wash samples taken from a previously described group of adult hematopoietic cell transplant (HCT) recipients naturally infected with respiratory syncytial virus (RSV). We separately analyzed reads from genomes and transcripts for the levels and distribution of genetic variation by calculating per position Shannon entropies. Our analysis reveals a low level of genetic variation within the RSV infections analyzed here, but with interesting differences between genomes and transcripts in 1) average per sample Shannon entropies; 2) the genomic distribution of variation 'hotspots'; and 3) the genomic distribution of hotspots encoding alternative amino acids. In all, our results suggest the importance of separately analyzing reads from genomes and transcripts when interpreting high-throughput sequencing data for insight into intra-host viral genome replication, expression, and evolution.

Kidney re-transplantation in the ipsilateral iliac fossa: a surgeon's perspective on perioperative outcome.

Compared with primary transplantation, ipsilateral renal re-transplantation is associated with an increased risk of surgical complications and inferior graft outcomes. This study investigates whether an ipsilateral re-transplantation approach per se is an independent risk factor for surgical complications and early graft loss. In this retrospective, single-centre analysis, surgical complications and early graft outcomes of ipsilateral kidney re-transplantations from January 2007 to December 2017 were compared with primary transplantations and contralateral re-transplantations. Univariate and multivariate binary logistic regression analyses were performed to identify risk factors for surgical complications requiring surgical revision and graft loss within the first year after transplantation. Of the 1489 kidney transplantations, 51 were ipsilateral, 159 were contralateral re-transplantations and 1279 were primary transplantations. Baseline characteristics did not differ between the ipsilateral and contralateral re-transplant recipients except for current and highest panel reactive antibody levels. Major complications requiring surgical revision were significantly more frequent in ipsilateral re-transplantations (P=.010) than in primary transplantations but did not differ between ipsilateral and contralateral re-transplantations (P=.217). Graft loss within the first year after transplant was 15.7% in the ipsilateral versus 8.8% in the contralateral re-transplant group (P=.163) versus 6.4% in the primary transplantation group (P=.009). In a multivariate regression model, ipsilateral re-transplantation was not identified as an independent risk factor for complications requiring surgical revision or first-year graft loss. Ipsilateral renal re-transplantation is not a risk factor for inferior outcomes. Graft implantation into a pre-transplanted iliac fossa is a feasible and valid therapeutic option.

Effect of umbilical cord mesenchymal stem cell-derived mitochondrial transplantation on ischemia-reperfusion injury in a rat model.

Despite advancements in reconstructive procedures, ischemia-reperfusion (I/R) injury remains a significant challenge in reconstructive surgery, with mitochondrial dysfunction playing a pivotal role. Mitochondrial transplantation has emerged as a promising therapeutic strategy to address this issue. This study aims to evaluate the impact of umbilical cord mesenchymal stem cell-derived mitochondrial transplantation on skin flap I/R models in rats. Twenty male rats underwent I/R injury on skin flaps, with or without mitochondrial transplantation administered via intravenous or subcutaneous routes. Analysis encompassed histopathology, inflammatory, apoptotic, oxidative stress, and hypoxia markers. Results revealed a reduction in inflammation, apoptosis, oxidative stress, and hypoxia in the transplantation group compared to controls. The findings suggest that umbilical cord mesenchymal stem cell-derived mitochondrial transplantation shows promise in enhancing flap viability and attenuating I/R injury, offering valuable insights for improved outcomes in reconstructive surgery. However, further exploration in larger animal models and refinement of delivery methods and dosage are warranted to fully elucidate its clinical translatability.

Platelet-rich Fibrin Membrane Transplantation for the Treatment of Highly Myopic Macular Hole Retinal Detachment.

Highly myopic macular hole retinal detachment (MHRD) is often associated with a poor prognosis, and there is currently no optimal treatment. Platelet-rich fibrin (PRF), an autologous blood product, has been shown to promote tissue regeneration. This prospective, randomized, controlled study investigated the efficacy of conventional internal limiting membrane (ILM) peeling versus PRF membrane transplantation in highly myopic MHRD. Eyes with highly myopic MHRD were randomly assigned to either a conventional ILM peeling group (IP group, n = 19) or a PRF membrane transplantation group (PMT group, n = 21). The study followed participants for a period of 6months. The primary outcome measure was macular hole (MH) closure assessed using optical coherence tomography. Secondary outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), superficial vascular density (SVD), deep vascular density (DVD), rate of retinal reattachment, and any complications encountered. MH closure was achieved in a significantly greater proportion of eyes in the PMT group (21/21, 100.00%) compared to the IP group (15/19, 78.95%) (P = 0.042). Retinal reattachment was accomplished in all patients (100.00%) within both groups. Except for an insignificant difference in BCVA observed at 1week post-surgery in the IP group, significant improvements in BCVA and CRT were documented in both groups across all other post-operative time points. Final BCVA (P = 0.040), CRT (P = 0.002), SVD (P = 0.002), and DVD (P = 0.013) were all significantly higher in the PMT group compared to the IP group. No serious complications were identified in either group. This study demonstrated the superiority of PRF membrane transplantation compared to conventional ILM peeling in promoting MH closure and enhancing retinal vascular density in patients with highly myopic MHRD. Additionally, PRF membrane transplantation effectively restores retinal reattachment, improves visual function, and increases retinal thickness without introducing additional complications. www. gov , NCT06200727.

The effect of itching on sleep quality and comfort in patients with hemodialysis and renal transplantation: A multi-center cross-sectional study

BackgroundThe aim of this study was to determine the effect of itching on sleep quality and comfort in hemodialysis (HD) and renal transplant (Tx) patients with itching. MethodsThis descriptive, correlational seeking and cross-sectional study was conducted in four hospitals affiliated with a private health group in Istanbul between April and June 2021. The sample of the study consisted of 42 patients receiving HD treatment and 49 patients with renal transplantation. Data were collected using the Patient Information Form, 5-D Itch Scale, Richards-Campbell Sleep Questionnaire and General Comfort Questionnaire. ResultsThere was a significant difference between the HD and renal transplantation groups in the Direction (p = 0.01) and Disability dimension (p = 0.002) of the 5- D Itch scale in favor of the renal transplant group. The mean sleep quality and comfort scores of the groups were similar and moderate. Itching negatively affects sleep quality in patients receiving HD treatment, and 22 % of the change in sleep quality is explained by disability of itching (R2 = 0.22; p = 0.002). Itching negatively affects comfort in both groups. Itching explains 27 % of the change in comfort level in the HD group (R2 = 0.27; p = 0.002) and 25 % of the change in comfort level in the renal transplantation group (R2 = 0.25; p = 0.001). ConclusionsAccording the study results during the hemodialysis treatment process, itching is more intense in terms of distribution and disability and affects the quality of sleep of patients. Itching has a significant impact on patients' perception of comfort. Patients experience itching both during HD treatment and after renal transplantation, which significantly impairs their comfort. Therefore, itching should be carefully monitored during renal replacement therapy and its effects on patients should be evaluated.

Management of airway complications following lung transplantation: first interventional bronchoscopy report from Türkiye.

Lung transplantation is the treatment of last resort for many chronic lung diseases. Airway complications (AC) following lung transplantation, such as bronchial stenosis, dehiscence, malacia, and fistula, account for frequent hospital admissions, additional treatment costs, decreased quality of life, and reduced survival rates. Beyond surgical and medical preventive efforts, interventional bronchoscopy (IB) can be used in the management of these complications. The aim of the study is to evaluate the efficacy of IB on the management of AC following lung transplantation. A retrospective analysis was done using the data of lung transplant patients with AC referred to the interventional pulmonology unit between December 2012 and December 2019. From a total of 116 lung transplants, the data of 14/116 (12%) patients and 14/220 (6.3%) anastomoses in the same lung transplant group with AC requiring IB were analyzed. In these 14 patients, the diseases leading to lung transplantation were interstitial lung diseases (ILD) (50.0%), bronchiectasis (28.6%), pulmonary arterial hypertension (PAH) (7.1%), chronic obstructive pulmonary disease (COPD) (7.1%), and COPD + bronchiectasis (7.1%). Airway stenosis was the most common airway complication, and it developed mostly in the right bronchial system.The 14 patients underwent 27 total sessions of IB with an average of 2-3 per patient. Airway patency was successfully achieved in 74.1% of the procedures. Mechanical dilatation with a balloon and/or a rigid tube was the most preferred procedure (81.5%). Permanent airway patency was achieved in eight (57.4%) patients. No early complications were encountered (0%). The late complication rate was 48.1%. The most frequent late complication was restenosis, which cannot be directly attributed to IB. IB is safe to perform on lung transplant patients with AC. It has low procedural complication rates and can be performed repeatedly. Because of the high rate of restenosis, interventional pulmonologists should find out treatment modalities with lower rates of restenosis.

Amelioration of behavioral and histological impairments in somatosensory cortex injury rats by limbal mesenchymal stem cell transplantation.

Cortical lesions can cause major sensory and motor impairments, representing a significant challenge in neuroscience and clinical medicine. Limbal mesenchymal stem cells (LMSCs), renowned for their remarkable ability to proliferate and distinct characteristics within the corneal epithelium, offer a promising opportunity for regenerative treatments. This study aimed to assess whether the transplantation of LMSCs could improve tactile ability in rats with lesions of the barrel cortex. In this experimental study, we divided 21 rats into three groups: a control group, a lesion group with cortical cold lesion induction but no stem cell treatment, and a group receiving LMSC transplantation following cold lesion induction. We conducted 3-week sensory assessments using a texture discrimination test and an open-field test. We also performed Nissl staining to assess changes on the cellular level. Rats in the LMSC transplantation group demonstrated significant improvements in their ability to discrimination textures during the second and third weeks compared to those in the lesion group. The open-field test results showed an increased exploratory behavior of rats in the LMSC transplantation group by the third week compared to the lesion group. Additionally, Nissl staining revealed cellular alterations in the damaged cortex, with a significant distinction observed between rats in the LMSCs and lesion group. The findings suggest that LMSC transplantation enhances sensory recovery in rats with cortical lesions, particularly their ability to discriminate textures. LMSC transplantation benefits brain tissue reparation after a cold lesion on the somatosensory cortex.

Treatment of acute and chronic graft-versus-host disease with extracorporeal photopheresis: Update of best practice recommendations from Italian Society of Hemapheresis and Cell Manipulation (SIdEM) and the Italian Transplant Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO)

These guidelines represent a GRADE-method revision of the recommendations produced by the Italian Society of Hemapheresis and Cell Manipulation (SIDEM) and the Italian Transplant Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) in 2013. Since 2013 several studies have been published that have strengthened the role of ECP in the management of GVHD. Thus, it was deemed appropriate to proceed with an update, with the aim to define uniform criteria for the application of ECP in adult and pediatric patients affected by GVHD throughout the national territory, in line with international guidelines, in maintaining of high standards of safety for patients and quality of the procedures provide. Post-HSCT GvHD therapies other than ECP and ECP therapy of other diseases, such as CTCL, are not covered by these guidelines.The development panel for this guideline includes professionals from various specialties who routinely interact in the management of the patient with GVHD, namely the transfusionist, the adult and pediatric hematologist, and the hospital pharmacist. A hematologist experienced in systematic reviews and GRADE guideline development ccordinated the development process, and an experienced transfusionist coordinated the assignment of tasks and reporting. External reviewers of the guideline included a patient representative.

Quality of life in children at different stages of chronic kidney disease in a developing country.

Children with chronic kidney disease (CKD) require comprehensive assessments, including medical and quality of life (QoL) evaluations. Few studies have been conducted in developing countries. This cross-sectional study included 2-18-year-old patients who were categorized into 4 groups: the CKD stage 2-3, stage 4-5, stage 5 with dialysis (D), and kidney transplantation (KT) groups. QoL was measured using the Pediatric Quality of Life Inventory™ (PedsQL™) version 4.0; relationships between different factors and QoL were determined using multivariable linear regression analysis. Eighty-seven patients (mean age: 13.3 (4.1) years) were included. The self-reported total scores were 77.5 (12.5), 78.9 (11.2), 77.4 (16.2), and 76.1 (10.9) in the stage 2-3, stage 4-5, stage 5D and KT groups, respectively. Parent-reported scores showed a weak-to-moderate correlation with self-reported scores (r = 0.12-0.42), with total scores of 71.8 (12.7), 69.5 (14.9), 63.4 (14.8), and 70.8 (18.1) in the stage 2-3, 4-5, 5D and KT groups, respectively. Multivariable linear regression revealed that the parent-reported score in the stage 5D group was 15.92 points lower than that in the stage 2-3 group (p = 0.02); the score in the low maternal education group was 10.13 points lower than that in the high maternal education group (p = 0.04). Parent-reported scores showed weak-to-moderate correlation with self-reported scores. Patients with CKD stage 5D and patients with low maternal education had lower QoL. Regular QoL assessment is recommended for patients with advanced CKD and those with socioeconomic vulnerabilities.

Outcomes of Colonic and Gastric Tube Transplants after Caustic Esophageal Burn in Children: A 33-Year Review.

Introduction: Accidental caustic burns of the esophagus in children represent a significant global health challenge, often necessitating esophageal reconstruction. The aim of this study is to compare the efficacy and morbidity related to esophagus replacement with colonic and gastric tube transplants in a pediatric population followed for caustic stenosis. Methods: This retrospective study was conducted at a tertiary pediatric surgery unit for children treated from January 1989 to December 2022. We compared colonic and gastric tube esophageal replacement. Short term (within 30 days) and mid-term outcomes and complications were reviewed. Statistical evaluation was considered using a Chi-square test for categorical data analysis. Results: A total of 124 children with caustic esophageal burns were included. Among them, 23 (18.5%) had a gastric tube transplant for esophagus replacement and 101 (81.5%) a colonic transplant. During surgical intervention, we found a significantly higher risk of complications when using a colonic transplant (34%, p < 0.001). There was no significant statistical difference in postoperative short term and mid-term complications between the two techniques. Twenty-six (26%) of the children required a reoperation, with a higher risk in the gastric tube transplant group (p < 0.001). Endoscopic dilatation after surgery was also performed on a higher number of children who had received a gastric tube transplant (p = 0.005). Overall, 97.6% recovered full normal oral feeding. Conclusions: We found that colonic and gastric tube replacement are both good options for pediatric esophageal replacement after a caustic injury and show effectiveness over time. Gastric tube transplants carried a slightly higher risk of reoperations and a higher number of dilatations post-surgery. However, our groups are not really comparable, due to the much higher number of colonic transplants. Both surgical options have to be considered during surgery, and the choice depends on the anatomy of the patient. Our future research will focus on assessing long term quality of life and the potential risk of neoplastic complications.

Efficacy of chemically induced human hepatic progenitor cells from diseased liver against nonalcoholic steatohepatitis model.

Numerous chemical reprogramming techniques have been reported, rendering them applicable to regenerative medicine research. The aim of our study was to evaluate the therapeutic potential of human CLiP derived from clinical specimens transplanted into a nonalcoholic steatohepatitis (NASH) mouse model of liver fibrosis. We successfully generated chemically induced liver progenitor (CLiP), which exhibited progenitor-like characteristics, through stimulation with low-molecular-weight compounds. We elucidated their cell differentiation ability and therapeutic effects. However, the therapeutic efficacy of human CLiP generated from clinical samples on liver fibrosis, such as liver cirrhosis, remains unproven. Following a 4 week period, transplanted human CLiP in the NASH model differentiated into mature hepatocytes and demonstrated suppressive effects on liver injury markers (i.e., aspartate transaminase and alanine transaminase). Although genes related to inflammation and fat deposition did not change in the human CLiP transplantation group, liver fibrosis-related factors (Acta2 and Col1A1) showed suppressive effects on gene expression following transplantation, with approximately a 60% reduction in collagen fibers. Importantly, human CLiP could be efficiently induced from hepatocytes isolated from the cirrhotic liver, underscoring the feasibility of using autologous hepatocytes to produce human CLiP. Our findings demonstrate the effectiveness of human CLiP transplantation as a viable cellular therapy for liver fibrosis, including NASH liver. These results hold promise for the development of liver antifibrosis therapy utilizing human CLiP within the field of liver regenerative medicine.

Management of deceased and living kidney donor with lithiasis: a multicenter retrospective studyon behalf of the renal transplant group of the Spanish urological association.

To maximize the availability of suitable grafts and ensure effective management, several reports have demonstrated successful outcomes when using kidney grafts with urolithiasis. This multicenterstudy reports onthe management and long-term outcomes of kidney transplantation using renal grafts with lithiasis. Retrospective data from three Spanish hospitals were analyzed for kidney transplants involving grafts with nephrolithiasis performedbetween December 2009 and August 2023. The study included adult patients, excluding those with incomplete records. It evaluated stone characteristics, complications, and outcomes in recipientsand in living kidney donors. Out of 38 analyzed kidney transplants, 57.9% were cadaveric and 42.1% were from living kidney donors. Most diagnoses were incidental during donor evaluation, with an average stone size of 7.06mm. After follow-up (median 26months), all recipients but one had functioning grafts, and there were no stone recurrences in bothrecipients andliving kidney donors. Conservative management was adopted in 28 cases, while 10 cases required ex-vivo flexible ureterorenoscopy for stone removal. Following conservative management, 5 patients needed additional treatments for stone-related events. Kidneys with lithiasis can be considered for transplantation in selected cases, resulting in good functional outcomes with no stone recurrence in recipients or living donors.

Impact of Pre- and Post-therapeutic Exercises in Sarcopenia and Pain in Liver Transplant Patients.

Sarcopenia, a state considered by the loss of muscle function and mass, is progressively recognized as a common complication of advanced cirrhosis and is related to negative clinical consequences. Liver transplantation (LT) is one of the options in the treatment of cirrhosis. This study aimed to evaluate the impact of exercise in newly developed (ND) sarcopenia through measurement of the psoas major muscle at the level of the third lumbar vertebra by abdominal computed tomography (CT) images in liver transplant patients. This analytical case-control longitudinal study was conducted on patients aged between 16 and 70 years at King Fahad Specialist Hospital (KFSH-D) in Dammam, Saudi Arabia. The patients were divided into two groups:an intervention group consisting of liver transplant patients (LTx, n=26) and a control group consisting of end-stage liver disease patients (ESLD, n=23) who were not candidates for LT. All participants were treated with a therapeutic exercise program through three phases. The first phase included pre-operative exercises, the second phase included early post-operative exercises, and the last phase included late post-operative exercises. CT scan of the psoas major muscle was performed pre- and post-LT to assess sarcopenia. Pain was measured with a numerical pain scale before and after exercise to evaluate the impact of exercise on pain. Psoas muscle index (PMI) for post-therapeutic exercises in the control and liver transplant groups showed significant differences for both male and female patients compared with the normal range (p<0.05). The liver transplant group showed a significant difference in mean weight loss, body mass index (BMI), and numerical pain rating scale (NPRS) observed on post-therapeutic exercises compared to baseline data. Conclusion: By and large, the finding revealed a substantial impact of therapeutic exercise on patient outcomes in terms of anthropometric characteristics, abdominal pain, handgrip strength (HGS), and PMI. The mean PMI at post-therapeutic exercises showed a significant increase by measuring the psoas major muscle at the level of the third lumbar vertebra by abdominal CT, which may indicate the extent of improvement and recovery from the ND sarcopenia in LTx.The results emphasize the potential advantages of pre- and post-therapeutic exercise in LTx, including enhancements in muscle strength and mass, as well as pain management associated with liver function and general health. Optimizing patient outcomes and promoting a more comprehensive approach to liver disease treatment may be achieved by including exercise activities in pre- and post-LT care procedures.

Mitochondria Transplantation: Rescuing Innate Muscle Bioenergetic Impairment in a Model of Aging and Exercise Intolerance.

Arroum, T, Hish, GA, Burghardt, KJ, Ghamloush, M, Bazzi, B, Mrech, A, Morse, PT, Britton, SL, Koch, LG, McCully, JD, Hüttemann, M, and Malek, MH. Mitochondria transplantation: Rescuing innate muscle bioenergetic impairment in a model of aging and exercise intolerance. J Strength Cond Res 38(7): 1189-1199, 2024-Mitochondria, through oxidative phosphorylation, are crucial for energy production. Disease, genetic impairment, or deconditioning can harm muscle mitochondria, affecting energy production. Endurance training enhances mitochondrial function but assumes mobility. Individuals with limited mobility lack effective treatments for mitochondrial dysfunction because of disease or aging. Mitochondrial transplantation replaces native mitochondria that have been damaged with viable, respiration-competent mitochondria. Here, we used a rodent model selectively bred for low-capacity running (LCR), which exhibits innate mitochondrial dysfunction in the hind limb muscles. Hence, the purpose of this study was to use a distinct breed of rats (i.e., LCR) that display hereditary skeletal muscle mitochondrial dysfunction to evaluate the consequences of mitochondrial transplantation. We hypothesized that the transplantation of mitochondria would effectively alleviate mitochondrial dysfunction in the hind limb muscles of rats when compared with placebo injections. In addition, we hypothesized that rats receiving the mitochondrial transplantation would experience an improvement in their functional capacity, as evaluated through incremental treadmill testing. Twelve aged LCR male rats (18 months old) were randomized into 2 groups (placebo or mitochondrial transplantation). One LCR rat of the same age and sex was used as the donor to isolate mitochondria from the hindlimb muscles. Isolated mitochondria were injected into both hindlimb muscles (quadriceps femoris, tibialis anterior (TA), and gastrocnemius complex) of a subset LCR (n = 6; LCR-M) rats. The remaining LCR (n = 5; LCR-P) subset received a placebo injection containing only the vehicle without the isolated mitochondria. Four weeks after mitochondrial transplantation, rodents were euthanized and hindlimb muscles harvested. The results indicated a significant (p < 0.05) increase in mitochondrial markers for glycolytic (plantaris and TA) and mixed (quadricep femoris) muscles, but not oxidative muscle (soleus). Moreover, we found significant (p < 0.05) epigenetic changes (i.e., hypomethylation) at the global and site-specific levels for a key mitochondrial regulator (transcription factor A mitochondrial) between the placebo and mitochondrial transplantation groups. To our knowledge, this is the first study to examine the efficacy of mitochondrial transplantation in a rodent model of aging with congenital skeletal muscle dysfunction.

Ocular characteristics and outcomes of phacoemulsification in patients with cataract after renal transplantation.

To explore ocular characteristics of patients with cataracts after renal transplantation and analyze the results of phacoemulsification combined with intraocular lens (IOL) implantation. Patients with cataracts after renal transplantation and control patients who underwent phacoemulsification combined with IOL implantation were enrolled. All patients underwent phacoemulsification combined with IOL implantation. Visual acuity, intraocular pressure, type of lens opacity, corneal endothelial cell density, and ocular biological parameters were evaluated before surgery. Visual prognosis, dry eye, and postoperative complications were monitored for 6months after phacoemulsification. We analyzed 25 eyes of 16 patients after renal transplantation and 30 eyes of 21 control patients. The most common type of cataract of renal transplantation group was posterior subcapsular, while the most common type of cataract of control group was cortical. Significant differences in corneal astigmatism, white-to-white ratio, and keratometry values were observed between the groups. The postoperative visual acuity of both groups significantly improved following surgery. Postoperative complications, such as the degree of anterior and posterior capsule opacification and the incidence of a requirement of neodymium-doped yttrium aluminum garnet laser capsulotomy, were significantly lower in the renal transplantation group. Moreover, secondary glaucoma occurred in two eyes in the renal transplantation group. This study showed that cataracts after renal transplantation were mostly posterior subcapsular. Postoperative visual acuity recovered well in most patients, with reduced incidence of postoperative complications. This study suggested that phacoemulsification combined with IOL implantation was safe and effective, providing a reference for multi-focal IOL implantation in kidney transplant recipients.

Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy.

Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era. To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting. A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed. Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality. The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.

Kidney Failure from Kidney Stones: An ANZDATA Registry Study.

Kidney stones is common with an increasing trend over time and has been well studied in the general population. However, incidence and outcomes of kidney stones leading to kidney failure (KF) and receiving kidney replacement therapy (KRT) is poorly examined. We examined the incidence of KF due to kidney stones and compared outcomes to KRT patients due to other causes. Adult patients who started KRT (January 1981-December 2020) and based in the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Exposure was KRT patients due to kidney stones comparing them to those with other causes. We examined incidence, prevalence, patient survival (KRT and transplant) and graft survival (transplant). Cox regression models were fit to compare patient survival between kidney stones and non-kidney stones groups, overall KRT, dialysis and patient and graft survival after kidney transplant. A total of 834 (1.1%) patients commenced KRT due to kidney stones. Incidence was 1.17 per million population per year and remained stable during the study period (annual percentage change -0.3% [95%CI -1.5% to 0.9%]. Survival was higher in kidney stone patients receiving dialysis compared to the non-kidney stone group (hazard ratio [HR], 0.89, 95%CI 0.82- 0.96) with similar estimates in a matched cohort. In kidney transplant patients, time to transplant was longer for patients with kidney stone compared to non-kidney stone patients (2.5 vs 1.7 years, P=0.001). There was no mortality difference (HR 1.02, 95%CI 0.82- 1.28) or graft loss (HR 1.07, 95%CI 0.79- 1.45) between kidney stones vs non-kidney stones in the kidney transplant group. KF due to kidney stones incidence is unchanged over the study period. Survival of patients with kidney stones who require KRT was better compared to patients from other causes. For the kidney transplant group, survival and risk of graft failure were similar.

Real-World Experience with Isavuconazole in Allogeneic Stem Cell Transplantation in Spain

Invasive fungal infections (IFI) pose a significant complication after hematopoietic stem cell transplantation (HSCT). Isavuconazole (ISV) is a new generation azole with a favourable adverse effect and interaction profile approved for the treatment of invasive aspergillosis and mucormycosis. We analyzed the indications, effectiveness, adverse event profile and drug interaction management of ISV in the real-world setting in adults who received allogeneic-HSCT (allo-HSCT) within the Spanish Group of HSCT and Cell Therapy (GETH-TC). We conducted a multicenter retrospective study of all consecutive adult allo-HSCT recipients (≥18 years) who received ISV either for IFI treatment or prophylaxis, from December 2017 to August 2021, in 20 centers within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cell Therapy (GETH-TC). A total of 166 adult allografted patients who received ISV from 2017 to 2021 were included. Median age was 48 years with 43% females. In 81 (49%) patients, ISV was used for treatment of IFI, and in 85 (51%) for prophylaxis. Median duration of ISV administration for IFI treatment was 57 days (range 31-126) and 86 days (range 33-196) for prophylaxis. Most frequent indication for treatment was invasive aspergillosis (78%), followed by mucormycosis (6%). Therapeutic success (45%) was the most frequent reason for ISV withdrawal. In the prophylaxis group, the resolution of IFI risk factors was the most frequent reason for withdrawal (62%). Six (7%) breakthrough IFI were reported. The majority of patients (80%) presented pharmacologic interactions. Twenty-one patients (13%) reported adverse events related to ISV, mainly liver biochemistry abnormalities, which led to ISV withdrawal in 7 patients (4%). ISV was effective and well tolerated for IFI treatment and prophylaxis, with a manageable interaction profile.

Comorbidity and Medication Trends in Chronic Kidney Disease and Incident Atrial Fibrillation: A Nationwide Cohort Study.

Chronic kidney disease (CKD) is associated with an increased incidence of atrial fibrillation (AF). Also, patients with AF are prone to adverse kidney outcomes. We examined comorbidities and medication use in patients with CKD and incident AF. The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide retrospective register-linkage study including data from 168,233 patients with incident AF from 2007 to 2018, with laboratory data from 2010 onwards. Estimated glomerular filtration rate (eGFR) was available for 124,936 patients. The cohort was divided into 5 CKD stages with separate groups for dialysis and kidney transplantation. At AF diagnosis eGFR &lt;60 mL/min/1.73 m2 was found in 27%, while 318 (0.3%) patients were on dialysis, and 188 (0.2%) had a functioning kidney transplant. Lowering eGFR yielded more comorbidities and medications. During 2010-2018 in patients with eGFR &lt;60 mL/min/1.73 m2 prevalence of hypertension, dyslipidaemia, and diabetes increased from 82 to 88%, from 50 to 66% and from 25 to 33%, respectively (&lt;0.001). Throughout the observation period, lipid-lowering medication was underused. More than one-fourth of patients with incident AF also had CKD stage 3-5 (eGFR &lt;60 mL/min/1.73 m2). Both comorbidities and medication use increased with worsening kidney function. Prevalence of major cardiovascular (CV) risk factors increased during 2010-2018, but the use of survival-affecting medications, such as lipid-lowering medication, was suboptimal at all stages of CKD. More attention should be given to the optimal treatment of risk factors in this high CV risk population.