Ping-Chin Lai

Aim: Rabbit anti‐thymocyte globulin (rATG) is widely used for induction immunosuppression in kidney transplantation, but conventional dosing is largely weight based and may not reflect dynamic interindividual immune responses. We aimed to evaluate a predefined, individualized dosing strategy guided by peripheral CD4‐to‐total lymphocyte (CD4/TLC) and CD8‐to‐total lymphocyte (CD8/TLC) ratios and to assess its feasibility and 1‐year outcomes. Methods: In this single‐center retrospective cohort study conducted in Taiwan from 2018 to 2024, 76 adult kidney transplant recipients received rATG titrated by serial flow cytometry to a predefined target of both CD4/TLC and CD8/TLC ratios < 10%. We evaluated cumulative rATG exposure, lymphocyte‐subset response, for‐cause biopsy‐proven acute rejection (BPAR), graft function, graft loss, hospitalization‐requiring infections, and mortality over 1 year. Results: The median cumulative rATG dose was 1.2 mg/kg (IQR, 1.1–1.5; maximum, 3.8). Thirty‐eight recipients (50.0%) reached the immunologic target after a single intraoperative dose (1–1.5 mg/kg). At 1 year, for‐cause BPAR occurred in 1 recipient (1.3%), mean serum creatinine was 1.20 mg/dL, and no graft loss occurred. Seventeen recipients experienced hospitalization‐requiring infections, accounting for 22 episodes. No CMV disease or biopsy‐proven BK virus nephropathy was observed. Four recipients (5.3%) died, including two deaths related to opportunistic fungal infections. Conclusion: CD4/TLC‐ and CD8/TLC‐guided rATG dosing was feasible and achieved predefined immunologic targets with low cumulative rATG exposure in this cohort. These findings support prospective controlled studies to evaluate the clinical utility, safety, and comparative effectiveness of this individualized dosing strategy.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy. Definitive biomarkers for disease diagnosis and activity remain elusive, making the exploration of molecular markers paramount. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 unaffected family members of aHUS patients, and 4 healthy controls. We identified 32 distinct subpopulations encompassing 5 B-cell types, 16 T- and natural killer (NK) cell types, 7 monocyte types, and 4 other cell types. Notably, we observed a significant increase in intermediate monocytes in unstable aHUS patients. Subclustering analysis revealed seven elevated expression genes, including NEAT1, MT-ATP6, MT-CYB, VIM, ACTG1, RPL13, and KLRB1, in unstable aHUS patients, and four heightened expression genes, including RPS27, RPS4X, RPL23, and GZMH genes, in stable aHUS patients. Additionally, an increase in the expression of mitochondria-related genes suggested a potential influence of cell metabolism on the clinical progression of the disease. Pseudotime trajectory analysis revealed a unique immune cell differentiation pattern, while cell—cell interaction profiling highlighted distinctive signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.

Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, necessitating differentiation from other thrombotic microangiopathy disorders. Definitive biomarkers for disease diagnosis and activity are currently lacking, and identifying molecular markers is essential. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 aHUS family members, and 4 healthy controls. Analysis included clustering, cell type annotation, pseudotime estimation, and cell-cell communication. Immune cell populations differ among aHUS, aHUS families, and healthy controls. Disease activity and treatment influence T, NK, B, and monocyte subpopulations, with increased intermediate monocyte levels distinguishing aHUS from controls and aHUS groups with varying disease activity. Subclustering revealed differential gene expression in patients compared to controls; higher expression of mitochondria-related genes suggests cell metabolism may influence clinical course. Pseudotime trajectory analysis demonstrated unique immune cell differentiation, and cell-cell interaction analysis identified distinct signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.

Background: Historically, acute kidney injury (AKI) has been a common severe complication of acute myocardial infarction (MI). As percutaneous coronary interventions have become more widely used, AMI outcomes have significantly improved. However, post-AMI AKI epidemiology and its associated factors are not well-understood in the age of interventional cardiology. Materials and methods: This is a retrospective study examining changes in creatinine levels in all patients admitted for AMI in a single medical center between August 2009 and February 2019. KDIGO criteria were used to define the different stages of post-AMI AKI. Results: The study included 1299 eligible cases, among which 213 (16.4%) developed AKI during AMI index admission; and 128 (60.1%), 46 (21.6%), and 39 (18.3%) were classified as KDIGO stages 1, 2, and 3, respectively. Compared with non-AKI subjects, the AKI group had a higher prevalence of non-STEMI (48.4% vs. 29.1%, p < 0.001), higher Killip class (3 or 4), and higher in-hospital mortality (15% vs. 2.5%, p < 0.001). During the index MI hospitalization, 13.6% (29/213) of the post-MI AKI patients received hemodialysis. Baseline abnormal creatinine (≥1.5 mg/dL), dyslipidemia, and more advanced KDIGO stages (2 or 3) were associated with an increased risk of requiring in-hospital hemodialysis. Moreover, a more advanced KDIGO stage (≥2) was correlated with higher all-cause in-hospital mortality. Conclusion: AMI patients remain at risk of AKI, which negatively affects their survival in the modern age.

Vascular access (VA) is the cornerstone for carrying out hemodialysis, yet it may bring in complications and leads to hemodialysis quality decline. This study aimed to explore the impact of vascular access types, including arteriovenous shunts and central venous catheter on all-cause mortality after adjustment of other risk factors. Total 738 ESRD patients aged over 40 year old receiving regular hemodialysis therapies were recruited between January 2001 and December 2010 from a single hemodialysis center in northern Taiwan. We ascertained the causes and date of death by linking our hospital database with Nationwide Mortality Registry Database. VA types and biochemistry parameters were extracted from the electronic hospital records. Patients were categorized into three groups, including (1)arteriovenous shunts (AVF)/arteriovenous shunts with Gortex®(AVG); (2)AVF/AVG combined central venous catheter; (3)catheter only. The time-dependent influence of vascular types i.e. initiation and follow-up period was also assessed. The mean follow-up time was 4.5 years. In patients using central venous catheter for initiation of hemodialysis, the adjusted hazard ratio (HR) for all-cause mortality was 1.55(95%CI: 1.09, 2.21), when compared with AVF/AVG. In the follow-up period, after adjustment for other risk factors, the multivariable analysis showed that the adjusted HRs were 3.23(95%CI: 1.85, 5.64) and 1.45(95%CI: 1.11, 1.91) for catheter only and AVF/AVG plus catheter, respectively. Our results showed that vascular accesses used for hemodialysis had different and time-dependent impact on patients’ long-term survival. Patients who started hemodialysis with central venous catheter had significantly higher all-cause mortality rate. Furthermore, in the follow-up period, patients both in the catheter only and AVF/AVG plus catheter groups also had the significant all-cause mortality rates. Our results support the early establishment of arteriovenous shunt for the chronic kidney disease patients.

Rituximab is associated with a higher incidence of Pneumocystis jirovecii pneumonia infection. Pneumocystis prophylaxis is advised in many immunocompromised populations treated with rituximab. However, the beneficial effect of pneumocystis prophylaxis in HIV-uninfected, rituximab-treated non-Hodgkin lymphoma (NHL) patients has not been assessed. Thus, we conducted this retrospective study to explore pneumocystis infection in HIV-uninfected NHL patients who received at least three courses of chemotherapy without haematopoietic stem cell transplantation using the Taiwan National Health Insurance Research Database. Patients who had rituximab-based chemotherapy were included in the experimental (rituximab) group, while the rest of the patients who did not receive any rituximab-based chemotherapy throughout the study period formed the control group. The prevalence rate of pneumocystis infection in the rituximab group (N = 7,554) was significantly higher than that in the control group (N = 4,604) (2.95% vs. 1.32%). The onset of pneumocystis infection occurred between 6 and 16 weeks after chemotherapy. Patients who had pneumocystis prophylaxis, whether or not they had a pneumocystis infection later in their treatment course, had significantly better first-year survival rates (73% vs. 38%). Regular pneumocystis prophylaxis should be considered in this group of patients.

With increasing use of cardiac fluoroscopic intervention, the incidence of fluoroscopy-induced radiation ulcer is increasing. Radiation ulcer is difficult to manage and currently there are no treatment guidelines. To identify the optimal treatment approaches for managing cardiac fluoroscopy-induced radiation ulcers, we retrospectively reviewed medical records of 13 patients with fluoroscopy-induced radiation ulcers receiving surgical interventions and following up in our hospital from 2012 to 2015. Conventional wound care and hyperbaric oxygen therapy were of little therapeutic benefit. Twelve patients received reconstruction with advancement flap or split thick skin graft. One-stage radical excision of radiation damaged area in eight cases with immediate reconstruction led to better outcomes than conservative excisions in four cases. Radical surgical excision to remove all the radiation damaged tissues in combination with immediate reconstruction appears to offer the optimal treatment results for cardiac fluoroscopy-induced radiation ulcers. Adequate excision of the damaged areas in both vertical (to the muscular fascia) and horizontal (beyond the sclerotic areas) dimension is pivotal to achieve good treatment outcomes.

With increasing numbers of percutaneous coronary intervention (PCI) and complex cardiac procedures, higher accumulated radiation dose in patient has been observed. We speculate cardiac catheter intervention induced radiation skin damage is no longer rare. To study the incidence of cardiac fluoroscopic intervention induced radiation ulcer. We retrospectively reviewed medical records of those who received cardiac fluoroscopic intervention in our hospital during 2012 to 2013 for any events of radiation ulcer. Only patients, whose clinical photos were available for reviewing, would be included for further evaluation. The diagnosis of radiation ulcers were made when there is a history of PCI with pictures proven skin ulcers, which presented typical characteristics of radiation injury. Nine patients with radiation ulcer were identified and the incidence was 0.34% (9/2570) per practice and 0.42% (9/2124) per patient. Prolonged procedure time, cumulative multiple procedures, right coronary artery occlusion with chronic total occlusion, obesity, and diabetes are frequent characteristics. The onset interval between the first skin manifestation and the latest radiation exposure varied from 3 weeks to 3 months. The histopathology studies failed to make diagnosis correctly in 5 out of 6 patients. To make thing worse, skin biopsy exacerbated the preexisting radiation dermatitis. Notably, all radiation ulcers were refractory to conventional wound care. Surgical intervention was necessary to heal the wound. Diagnosis of cardiac fluoroscopy intervention induced radiation skin damage is challenging and needs high index of clinical suspicion. Minimizing the radiation exposure by using new approaches is the most important way to prevent this complication. Patient education and a routine postprocedure dermatology follow up are mandatory in high-risk groups for both radiation skin damage and malignancies. This is a retrospective study, thus the true incidence of radiation ulcer caused by cardiac fluoroscopic intervention could be higher.