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Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

Introduction: This study examines whether the use of inpatient Continuous Glucose Monitors provides improved glycemic control over finger‐stick glucose monitoring post‐transplant. Methods: This is a single‐site, prospective randomized controlled trial of 40 patients receiving conventional finger‐stick glucose monitoring or continuous monitoring using the Medtronic Guardian Sensor 3 during the first 5 days post‐transplant. Included patients were adult renal transplant recipients with a diagnosis of diabetes. Assessed endpoints included post‐transplant daily median glucose level, hyperglycemic (≥180 mg/dL) and hypoglycemic (≤80 mg/dL) episodes, number of post‐transplant bacterial infections and length of stay. Results: Groups were well matched in demographic variables. Median daily glucose was significantly lower in the intervention group. There were also significantly less episodes of hyperglycemia on postoperative days 2, 3, 4, and 5. There were no differences in the incidences of hypoglycemia, postoperative bacterial infections, or length of stay. Conclusion: In this randomized study, the use of a continuous glucose monitor to guide post‐transplant glucose management significantly lowered the incidence of hyperglycemic episodes and median glucose levels through the first 5 days post‐transplant without increasing the number of hypoglycemic episodes. The use of these devices can be considered in the immediate post‐renal transplant setting. [ABSTRACT FROM AUTHOR]

Background Recent improvement in treatment and patient survival has opened the eligibility of kidney transplantation to patients who developed end-stage kidney disease (ESKD) from plasma cell dyscrasias (PCDs). Data on clinical outcomes in this population are lacking. Methods We conducted a retrospective study of United Network for Organ Sharing/Organ Procurement and Transplantation Network dataset (2006–2018) to compare patient and graft outcomes of kidney transplant recipients with ESKD due to PCD versus other causes. Results Among 168   369 adult first kidney transplant recipients, 0.22–0.43% per year had PCD as the cause of ESKD. The PCD group had worse survival than the non-PCD group for both living and deceased donor types {adjusted hazard ratio [aHR] 2.24 [95% confidence interval (CI) 1.67–2.99] and aHR 1.40 [95% CI 1.08–1.83], respectively}. The PCD group had worse survival than the diabetes group, but only among living donors [aHR 1.87 (95% CI 1.37–2.53) versus aHR 1.16 (95% CI 0.89–1.2)]. Graft survival in patients with PCD were worse than non-PCD in both living and deceased donors [aHR 1.72 (95% CI 1.91–2.56) and aHR 1.30 (95% CI 1.03–1.66)]. Patient and graft survival were worse in amyloidosis but not statistically different in multiple myeloma compared with the non-PCD group. Conclusion The study data are crucial when determining kidney transplant eligibility and when discussing transplant risks in patients with PCD. [ABSTRACT FROM AUTHOR]

The interaction and effects of corporate external governance and internal shareholder governance on the firm's equity prices are evaluated.

There have been significant advances in the treatment of multiple myeloma in the last two decades. Approximately 25% of patients with newly diagnosed myeloma have some degree of kidney impairment. During the course of illness, nearly 50% of myeloma patients will develop kidney disease. Moreover, ∼10% of myeloma patients have advanced kidney disease requiring dialysis at presentation. Hemodialysis is associated with a significantly reduced overall survival (OS). In the setting of prolonged long-term OS due to the use of newer immunotherapeutic agents in the treatment of myeloma, patients with myeloma and advanced kidney disease may benefit from more aggressive management with kidney transplantation (KTx). Unfortunately, most data regarding outcomes of KTx in patients with myeloma come from single-center case series. With the advent of novel treatment choices, it remains unclear if outcomes of kidney transplant recipients with myeloma have improved in recent years. In this descriptive systematic review, we coalesced published patient data over the last 20 years to help inform clinicians and patients on expected hematologic and KTx outcomes in this complex population. We further discuss the future of KTx in patients with paraproteinemia. [ABSTRACT FROM AUTHOR]

The Circulation Water Channel (CWC) is an experimental facility available at Indian Maritime University, Visakhapatnam Campus. A study for comparing the flow pattern and velocity in the test section, for different configurations of the CWC, is complex. To study the flow, a physical model of the CWC, with different configurations, should be made, which in overall is a complicated and timeconsuming exercise. But this difficulty can be overcome through using Computational Fluid Dynamics (CFD) analysis, as in this study, where a CFD analysis is done using 'STAR-CCM+' software. A CFD model of the existing CWC [corresponding to the 1:4 scale setup at IMUV], is first made, and its validity is checked, by comparing the results of the CFD analysis, against those results obtained from the experimental analysis. On successfully validating the results, modifications are suggested for rectifying the disturbance which is present in the test section. The test section is the area in the CWC where experimental activities are carried out. In order to carry out the experiments with a certain degree of accuracy, it is important to have a smooth streamlined flow in the test section. To ensure this, a honeycomb structure is positioned such that the flow enters the test section through the honeycomb, which streamlines the flow. On successfully rectifying the disturbance, studies are carried out to improve the streamlined flow in the test section, for which, different configurations of honeycomb structure are studied. The optimum honeycomb structure, which produces a smooth flow in the test section of a CWC is found out, by conducting analyses for different shapes - i.e. for shapes ranging from rectangular to hexagonal and circular, against different inlet velocities. The present paper sums up the findings of our earlier work which were presented in conferences at IIT Madras and IMU Visakhapatnam respectively. [ABSTRACT FROM AUTHOR]

Background: Several studies have shown that transplanting a hepatitis C virus (HCV)‐negative recipients with a HCV‐positive donor is feasible in a research setting. In February 2018, we began transplanting HCV‐negative recipients with HCV‐positive donors as standard of care. Methods: All patients, except those with previously cured HCV and those with cirrhosis, were consented for HCV NAT‐positive donor kidneys. After transplantation, patients were tested for HCV RNA until viremic. A direct‐acting antiviral (DAA) agent was prescribed based on genotype and insurance approval. Sustained virologic response (SVR) at weeks 4 and 12 was recorded. Renal function and death censored graft survival at 1 year were evaluated and compared to recipients of HCV NAT‐negative kidneys. Results: A total of 25 HCV NAT‐positive donor kidney transplants from February to October 2018 were performed. All patients received basiliximab and maintained with tacrolimus, mycophenolate mofetil, and prednisone. Median time from viremia to start of DAA was 13 (8‐22) days. The most common genotype was 1a (60%), followed by 3a (28%). The most commonly prescribed DAA was ledipasvir/sofosbuvir (56%), followed by velpatasvir/sofosbuvir (32%), and then glecaprevir/pibrentasvir (12%). All patients achieved initial SVR12, except one. One patient had a mixed‐genotype infection requiring retreatment to achieve SVR12. Death censored graft survival was 96%. Recipients of HCV NAT‐positive organs compared to HCV NAT‐negative organs received younger donors (mean 35 ± 8.9 vs 45.1 ± 15.7 years; P <.01) and spent less time on the waitlist (median 479 (93‐582) vs 1808 (567‐2263) days; P =.02). Conclusion: HCV NAT‐negative recipients can be safely and successfully transplanted with HCV NAT‐positive donor kidneys outside of a research protocol. Access to DAA and timely administration of therapy is important and an insurance approval process within the transplant center can be beneficial to patients. A case of mixed‐genotype infection was presented, and although not as common, can be successfully treated. HCV organs can expand the organ pool and should no longer be considered experimental. The use of these organs in HCV‐negative recipient's decreases waiting time, have excellent outcomes, and should be considered standard of care. [ABSTRACT FROM AUTHOR]

This paper considers the impact of the takeover likelihood on firm valuation. If firms are more likely to acquire when there is more free cash or lower required rates of return, the targets become more sensitive to shocks to cash flows or the price of risk. Ceteris paribus, firms exposed to takeovers have different rates of return than protected firms. Using takeover likelihood estimates, we create a "takeover factor." buying (selling) firms with a high (low) takeover likelihood, which generates "abnormal" returns. Several tests confirm that the takeover factor helps explaining cross-sectional differences in equity returns and is related to takeover activity. [ABSTRACT FROM AUTHOR]

We investigate the effects of shareholder governance mechanisms on bondholders and document two new findings. First, the impact of shareholder control (proxied by large institutional blockholders) on credit risk depends on takeover vulnerability. Shareholder control is associated with higher (lower) yields if the firm is exposed to (protected from) takeovers. In the presence of shareholder control, the difference in bond yields due to differences in takeover vulnerability can be as high as 66 basis points. Second, event risk covenants reduce the credit risk associated with strong shareholder governance. Therefore, without bond covenants, shareholder governance, and bondholder interests diverge. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen allosensitization prior to transplant can increase the risk of early graft loss and prolong waitlist times for intestinal transplant candidates. Desensitization offers a potential therapeutic option to reduce the quantity of preformed antibodies prior to organ allocation and facilitate transplantation with a more immunologically compatible donor allograft. However, there remains a paucity of data to guide the use of desensitization in the setting of intestinal transplantation. As a result, in this review we evaluate the existing literature supporting the role of desensitization therapy in intestinal transplant, describe our own experience with the implementation of a risk-stratified desensitization protocol, and finally explore barriers and unanswered questions that continue to limit the widespread adoption of desensitization as a management strategy for highly sensitized intestinal transplant candidates. [ABSTRACT FROM AUTHOR]

Transmembrane potential (Vm) plays critical roles in cell signaling and other functions. However, the impact of Vm on the structure and dynamics of membrane lipids and proteins, which are critical for the regulation of signaling, is still an open question. All-atom molecular dynamics (MD) simulation is emerging as a useful technique to address this issue. Previous atomistic MD simulations of pure or binary model membranes indicated that both ion imbalance and electric field can be used to generate Vm, but both approaches failed to yield structural changes in lipids with statistical significance. We hypothesized that a possible reason for this could be oversimplified membrane composition or limited sampling. In this work, we tested if and how Vm modulates the structure and dynamics of lipids in a physiologically relevant model membrane. Using a detailed side-by-side comparison, we first show that while both ion imbalance and electric field generate Vm in our complex membranes, only the latter could produce physiologically relevant Vm. We further show that double bonds in lipid acyl chains have a relatively large sensitivity to Vm. A single-bilayer model with an electric field showed the highest sensitivity in simulations under the isothermal–isobaric (NPT) ensemble, reproducing expected responses of head-group dipoles to Vm and suggesting that this approach may be more suitable for studying the structural effects of Vm. Our findings also shed light on the relationship between the macroscopic Vm and its atomic-level underpinnings. [ABSTRACT FROM AUTHOR]

In kidney transplant recipients, cancer is one of the leading causes of death with a functioning graft beyond the first year of kidney transplantation, and malignancies account for 8–10% of all deaths in the USA (2.6 deaths/1000 patient-years) and exceed 30% of deaths in Australia (5/1000 patient-years) in kidney transplant recipients. Patient-, transplant- and medication-related factors contribute to the increased cancer risk following kidney transplantation. While it is well established that the overall immunosuppressive dose is associated with an increased risk for cancer following transplantation, the contributive effect of different immunosuppressive agents is not well established. In this review we will discuss the different risk factors for malignancies after kidney transplantation. [ABSTRACT FROM AUTHOR]

Belatacept is a non-nephrotoxic immunosuppressive agent, which may make it the ideal agent for patients with delayed or slow graft function on calcineurin inhibitors. There are limited data on conversion of patients to belatacept within 6 months of transplantation. Between January 2012 and December 2015, 16 patients were converted to belatacept for delayed or poor graft function (eGFR<30 mL/min/1.73 m2, MDRD); three were HIV positive. Conversion protocols were analyzed in patients ≤4 months and 4-6 months post-transplantation. Mean serum creatinine levels after belatacept conversion were compared with preconversion levels. Patient survival was 100%, and graft survival was 88%. The mean creatinine fell from 3.9±1.82 mg/dL prebelatacept conversion to 2.1±1.1 mg/dL at 6 months and 1.9±0.47 mg/dL (median 1.8 mg/dL) at 12 months postconversion. There was no significant increased risk of rejection, infection, or malignancy. HIV parameters remained largely stable. Early conversion to belatacept in patients with DGF or slow graft function is safe and efficacious, in a single-center nonrandomized retrospective analysis. [ABSTRACT FROM AUTHOR]

Patients with end-stage renal diseases on hemodialysis have a high prevalence of hepatitis C infection ( HCV). In most patients, treatment for HCV is delayed until postrenal transplant. We assessed the effectiveness and tolerance of ledipasvir/sofosbuvir ( LDV/ SOF) in 32 postkidney transplant patients infected with HCV. The group was composed predominantly of treatment-naïve (75%) African American (68.75%) males (75%) infected with genotype 1a (62.5%). Most patients received a deceased donor kidney graft (78.1%). A 96% sustained viral response ( SVR) was reported (27/28 patients). One patient relapsed. One patient with baseline graft dysfunction developed borderline rejection. No graft loss was reported. Six HIV-coinfected patients were included in our analysis. Five of these patients achieved SVR 12. There were four deaths, and one of the deaths was in the HIV group. None of the deaths were attributed to therapy. Coinfected patients tolerated therapy well with no serious adverse events. Serum creatinine remained stable at baseline, end of therapy, and last follow-up, (1.351±.50 mg/dL; 1.406±.63 mg/dL; 1.290±.39 mg/dL, respectively). In postkidney transplant patients with HCV infection with or without coinfection with HIV, a combination of LDV/ SOF was well tolerated and effective. [ABSTRACT FROM AUTHOR]

Introduction Using data from the Scientific Registry of Transplant Recipients ( SRTR), cumulative incidence, risk factors for, and impact on survival of severe chronic kidney disease ( CKD) in intestinal transplantation ( ITx) recipients were assessed. Methods First-time adult ITx recipients transplanted in the United States between January 1, 1990 and December 31, 2012 were included. Severe CKD after ITx was defined as: glomerular filtration rate ( GFR) <30 mL/min/1.73 m2, chronic hemodialysis initiation, or kidney transplantation ( KTx). Survival analysis and extended Cox model were conducted. Results The cumulative incidence of severe CKD 1, 5, and 10 years after ITx was 3.2%, 25.1%, and 54.1%, respectively. The following characteristics were significantly associated with severe CKD: female gender ( HR 1.34), older age ( HR 1.38/10 year increment), catheter-related sepsis ( HR 1.58), steroid maintenance immunosuppression ( HR 1.50), graft failure ( HR 1.76), ACR ( HR 1.64), prolonged requirement for IV fluids ( HR 2.12) or TPN ( HR 1.94), and diabetes ( HR 1.54). Individuals with higher GFR at the time of ITx ( HR 0.92 for each 10 mL/min/1.73 m2 increment), and those receiving induction therapies ( HR 0.47) or tacrolimus ( HR 0.52) showed lower hazards of severe CKD. In adjusted analysis, severe CKD was associated with a significantly higher hazard of death ( HR 6.20). Conclusions The incidence of CKD after ITx is extremely high and its development drastically limits post-transplant survival. [ABSTRACT FROM AUTHOR]

Context--Transferring out of pediatrics is a vulnerable time for transplant recipients. Use of a transition coordinator before and after transfer improves outcomes, although it is unclear whether placing a transition coordinator in pediatrics alone is beneficial. Objective--To determine if incorporating a transition coordinator in pediatrics only is associated with stable outcomes for kidney transplant recipients. Design--A retrospective chart review was conducted on outcomes for kidney transplant recipients who shifted service location between 2008 and 2012. Setting--A pediatric and adult transplant unit. Patients--Twenty-two patients transferred during the study period. Intervention--Twelve patients received more intensified preparation from the team's social worker, whose role was aligned with a transition coordinator position; 10 patients received standard care. Main Outcome Measures--The primary outcome was medication adherence, using a validated measure, standard deviations of tacrolimus blood levels. A standard deviation greater than 2.5 has been established as a threshold associated with poor outcomes such as rejection. Standard deviation of tacrolimus levels was compared for 1 year before and 1 year after transfer. Results--Medication adherence worsened from 1 year before (2.03 [SD, 0.75]) to 1 year after transfer (2.95 [SD, 1.38]; t = -3.07, P = .007). A repeated-measures analysis of variance indicated that this pattern was the same for patients who did and patients who did not receive intensified services in pediatrics (F1,16 = 1.07, P = .32). [ABSTRACT FROM AUTHOR]

Communication between the organ transplant team and dentist is important in formulating individual-ized care plans to reduce the incidence of pre- and post-transplant complications. Periodontal diseases and other oral infections may present serious risks that could compromise the success of a solid organ transplant. This article reviews why dentistry is an im-portant component of total transplant care while the patient is on the waiting list for a transplant and after the transplantation. Recommendations regarding the care of the organ transplant patient are given. [ABSTRACT FROM AUTHOR]

This article studies the interaction between takeover defenses and competition. We find that firms in more competitive industries have more takeover defenses. This suggests that product market competition can be a substitute for the market for corporate control, with more information available in competitive markets making monitoring less costly. A novel instrument for the incentives of stakeholders in the product market to monitor is provided by the nature of the relationship between the firm and its customers. For firms in industries with long-term relationships with customers and suppliers, these stakeholders have greater incentives to monitor. We document that stronger competition is linked to more defenses only in these “relationship” industries. Finally, we discuss the implications for the design of other governance mechanisms. [ABSTRACT FROM AUTHOR]

Background/Aim: Community-acquired pneumonia (CAP) is a frequent cause for hospitalization and may result in a number of different renal and electrolyte complications. The purpose of this study was to describe the incidence of hyponatremia in CAP and to analyze risk factors for its occurrence. Methods: Records were reviewed for all 342 subjects who participated in the Community-Acquired Pneumonia Standardized Order Set study, a 2-year trial of supplemental treatment tools in hospital pneumonia treatment. Results: Hyponatremia (serum sodium concentration <136 mg/dl) was present at hospital admission in 27.9% of patients. The magnitude was generally mild, only 4.1% of patients had serum sodium <130 mEq/l. Patients with hyponatremia had greater initial heart rate (100.2 vs. 93.2 beats/min, p = 0.03), white blood cell count (15,100 vs. 12,100/μl, p < 0.0001) and pneumonia severity index class 4 or 5 (35.7 vs. 25.1% of patients, p = 0.05). Hyponatremia at admission was associated with greater risk for death and increased length of hospital stay. Hyponatremia developed during the hospitalization in 10.5% of subjects, with most cases being mild, only 2.6% of all patients having serum sodium decrease to <130 mEq/l. Patients developing hyponatremia were more likely to have end-stage renal disease and to have had initial intravenous fluids other than isotonic saline, but had similar severity of illness on admission to those without acquired hyponatremia. Conclusion: Hyponatremia is a common complication present at the time of admission for CAP. It is associated with more severe illness, increased mortality risk and extended hospital stays. Hyponatremia develops less frequently during the hospitalization and is unrelated to severity of illness on admission, but is an iatrogenic complication and thus initial treatment with isotonic saline may reduce the risk of this complication. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Human Herpes Virus‐8 (HHV‐8) may reactivate in immunocompromised patients including recipients of solid organ transplants. Reactivation of HHV‐8 may result in Kaposi sarcoma (KS). KS typically occurs with dermatologic involvement but can affect virtually any other organ; most commonly the gastrointestinal tract. We present a diagnostically challenging case of KS in a South American woman 7 months after kidney transplant. She presented with recurrent urinary tract infection manifested by pelvic pain and dysuria. Imaging studies revealed bladder thickening with pelvic lymphadenopathy. Findings on tissue biopsied from the bladder and lymph nodes were consistent with KS. Her skin was not affected. This case illustrates that KS and other HHV‐8–related diseases should be on the differential diagnosis as a cause of mass lesions as well as lymphadenopathy in transplant recipients. The case exemplifies the need to pursue a tissue diagnosis in immunocompromised patients when a diagnosis is uncertain. [ABSTRACT FROM AUTHOR]

Simultaneous liver‐kidney allocation protocols allocate dual organs based on a sustained eGFR of 30 mL/min or less. A 2017‐UNOS update includes CKD3 as dual organ candidates but only when the listing eGFR is <30 mL/min while recommending a "safety net" for prioritized kidney listing post‐LT. We retrospectively reviewed adult LTs examine whether the UNOS proposal captured the LT population at highest risk for developing post‐LT ESRD. Among 290 LT recipients, 67 had pre‐LT CKD3, 141 had AKI, of whom 47 required dialysis (<4 weeks). During follow‐up, 25 (8.62%) developed ESRD, while 70 (24.1%) died. In adjusted Cox models, CKD3 had an independent association with post‐LT ESRD (adjusted HR 4.8; P = 0.001), independent of AKI. Interestingly, CKD3 with listing GFR >30 mL/min was still significantly associated with post‐LT ESRD. AKI was associated with reduced post‐LT survival (adjusted HR 1.9; P = 0.02), albeit only in the first‐year post‐LT. Severe AKI‐D was associated with post‐LT ESRD and mortality. The safety net would have captured only 60% of all post‐LT ESRD cases in our cohort. Pre‐LT CKD3 was associated with increased risk of post‐LT ESRD above the recommended cutoff for listing GFR. These findings, if generalizable in larger cohorts have important implications for dual organ allocation. [ABSTRACT FROM AUTHOR]

Kidney transplantation is the preferred treatment for end-stage renal disease, but it involves risks, including an increased chance of malignancy due to several variables. We present a rare case of primary renal squamous cell carcinoma (SCC) in an allograft kidney. This patient, who had a renal transplant one year prior, presented with oliguria, elevated creatinine, and asthenia. Imaging done raised suspicion of a mass-like structure and biopsy subsequently done confirmed a primary SCC in the transplanted kidney, leading to a total nephrectomy and hemodialysis initiation. This case highlights the different cancer risks faced by transplant recipients, particularly due to immunosuppressive medications. We discuss emerging alternatives in immunosuppression that may mitigate these risks. Given the rarity of primary SCC in allografts, determining the cancer's origin whether primary or metastatic is critical for effective management since this distinction could shape future approaches to managing allograft malignancies. We also emphasize the importance of establishing imaging and monitoring guidelines and how combining imaging with serum and urine studies may enhance cancer surveillance, aiding in long-term graft health and transplant longevity., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Pagan Santini et al.)