BK polyomavirus DNAemia, allograft rejection, and de novo donor-specific antibodies after lowering target tacrolimus levels in pediatric kidney transplant recipients.

BACKGROUND: BK polyomavirus (BKV) DNAemia is a challenging infectious complication after kidney transplant (KT). Reduction of immunosuppression is the mainstay of management, and tacrolimus is often the first immunosuppressive medication adjusted upon the diagnosis of BKV DNAemia. This study aimed to evaluate the impact of a new institutional protocol with lower target tacrolimus levels on BKV DNAemia, allograft rejection, and de novo donor-specific antibodies (dnDSA) among pediatric KT recipients. METHODS: We conducted a retrospective chart review of all KT episodes between January 2013 and December 2018. The new protocol with lower target tacrolimus levels was implemented in March 2015. One hundred twenty-seven patients were included in primary analysis. All patients received induction with basiliximab and methylprednisolone and were maintained on a steroid-based immunosuppressive regimen. RESULTS: In the post-intervention cohort, cumulative incidence of BKV DNAemia at 100 days (13.4% vs. 17.8%, p = .605) and 18 months post-KT (34.1% vs. 26.7%, p = .504) was not significantly different from the pre-intervention cohort. Biopsy-proven rejection rate did not change. However, we observed a trend toward earlier development of dnDSA in the post-intervention cohort using the Kaplan-Meier survival analysis (log-rank p = .06). Younger recipient age at the time of transplant was found to slightly increase the risk of BKV DNAemia (OR: 1.09, 95% CI [1.01, 1.16], p = .024). There was an association between BKV DNAemia and biopsy-proven rejection of any type (adjustedOR: 2.77, 95% CI [1.26, 6.23], p = .012), especially acute T-cell-mediated rejection grade 1A and above (adjustedOR: 2.95, 95% CI [1.06, 8.30], p = .037), after adjusted for recipient age at the time of transplant. CONCLUSIONS: Targeting lower tacrolimus levels did not decrease the incidence of BKV DNAemia within 100 days or 18 months post-KT, nor did it increase the risk of biopsy-proven rejection among pediatric KT recipients in our center. However, there was a trend toward earlier development of dnDSA, which may portend worse long-term graft outcome post-KT. Our findings highlight the need for individualized immunosuppressive regimens based on immunologic and infectious risk factors and the importance of implementing innovative biomarkers to guide therapy and improve outcomes.

Multidisciplinary and multidimensional approaches to transplantation in children with rare genetic kidney diseases.

In this review, we describe the multidisciplinary, multidimensional care required to optimize outcomes for pediatric transplant recipients with rare genetic kidney diseases. Transplant success, recipient survival, and improvement in quality of life depend on collaboration between patients, families, and a team of specialists with medical, as well as nonmedical expertise. A multidisciplinary transplant team composed of experts from medicine, surgery, nursing, nutrition, social services, transplant coordination, psychology, and pharmacology, is now standard in most transplant centers and is critical to the success of a transplant. In addition to these professionals, other specialists, such as cardiologists, urologists, geneticists, metabolic disease specialists, occupational therapists, case management, child life, chaplain, and palliative care services, have a crucial role to play in the preparation, surgery, and follow-up care, especially when a pediatric patient has a rare genetic disorder leading to renal involvement, and the need for transplantation. In order to describe this multidisciplinary care, we divide the genetic renal diseases into five subgroups-metabolic and tubular disorders, glomerular diseases, congenital anomalies of the kidney and urinary tract, ciliopathies including cystic diseases, and miscellaneous renal conditions; and describe for each, the need for care beyond that provided by the standard transplant team members.

Diagnostic utility of urine neutrophil gelatinase-associated lipocalin and renal resistive index in patients of decompensated cirrhosis with acute kidney injury.

BACKGROUND: The differentiation between types of acute kidney injury(AKI) in decompensated cirrhosis(DC) patients in clinical practice is done by clinical adjudication. Biomarkers have good diagnostic accuracy for predicting acute tubular necrosis(ATN), however they are not available routinely. AIMS: We compared the diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin(UNGAL) and renal resistive index(RRI) in predicting type of AKI among DC patients. METHODS: Consecutive DC patients with AKI stage≥1B seen between June/2020 to May/2021 were evaluated. UNGAL levels and RRI were measured at diagnosis of AKI(Day 0) and 48hrs(Day 3) after volume expansion. Diagnostic accuracy of UGNAL and RRI was compared for differentiating ATN and non-ATN AKI by area under receiver operating characteristic curve(AUROC), using clinical adjudication as gold standard. RESULTS: 388 DC patients were screened, 86 patients(Pre-renal AKI[PRA] n=47,55%; Hepatorenal syndrome[HRS] n=25,29%;ATN n= 14,16%) were included. The AUROC of UNGAL for differentiating ATN-AKI and non-ATN AKI at day 0 was 0.97(95%CI, 0.95-1.0) and on day 3 was 0.97(95%CI, 0.94-1.0). The AUROC of RRI for differentiating ATN and non-ATN AKI at day 0 was 0.68(95%CI, 0.55-0.80) and on day 3 was 0.74(95%CI, 0.63-0.84). CONCLUSION: UNGAL has an excellent diagnostic accuracy in predicting ATN-AKI in DC patients both at day 0 and 3.

Enhanced Liver Fibrosis Score: Is It Useful for Evaluation of Fibrosis Severity in Chronic Hepatitis C Infection?

INTRODUCTION: The assessment of liver fibrosis is important in patients with chronic hepatitis C (CHC). In recent years, non-invasive tests like enhanced liver fibrosis (ELF) have been developed as an alternative to liver biopsy for estimating the severity of liver fibrosis. Therefore, we aimed to assess whether the ELF score can be used for fibrosis severity estimation using liver biopsy as the gold standard. MATERIALS AND METHODS: Forty-nine patients with CHC were enrolled in this study. Liver biopsy, ELF assessment, and transient elastography (TE) were performed in all patients, and severity of fibrosis on histopathology was assessed by meta-analysis of histological data in viral hepatitis (METAVIR) score. In addition, the diagnostic performance of ELF was evaluated by receiver operator characteristic curve (ROC) analyses, and liver biopsy histopathology was taken as the gold standard for the severity of liver fibrosis. RESULTS: The area under receiver operator characteristic curve (AUROC) for significant fibrosis of ELF score was 0.64 (95% confidence interval {CI}, 0.48-0.79) and of TE was 0.85 (95% CI, 0.73-0.96). The AUROC for advance fibrosis of ELF was 0.77 (95% CI, 0.57-0.97) and TE was 0.98 (95% CI, 0.94-1.0). The calculated cut-offs of ELF overestimated fibrosis in 53.06% (26/49) of patients and underestimated fibrosis in 6.12% (3/49) patients. AUROC of TE was significantly better than ELF for diagnosis of significant fibrosis (p=0.004) and advanced fibrosis (p=0.034). CONCLUSION: The ELF score can be used for estimating the severity of fibrosis but it is inferior to TE in estimating liver fibrosis severity.

Recurrence of Primary Breast Lymphoma Presenting as Bilateral Vitreoretinal Lymphoma.

PURPOSE: This report describes a case of relapsed primary breast lymphoma (PBL) presenting as vitreoretinal lymphoma (VRL). METHODS: We describe the clinical and hematopathologic findings in a patient with relapsed PBL involving the vitreous of both eyes. RESULTS: A 59-year-old woman was treated for PBL with systemic and intrathecal chemotherapy 5 years prior to presentation. Three years later, she presented to an outside clinic with blurred vision in both eyes and bilateral vitritis. She was referred to our clinic with concern for ocular lymphoma. On presentation, the patient's best-corrected visual acuity was 20/40 in the right eye and 20/25 in the left eye with 3+ vitreous cells in the right eye and 2+ vitreous cells in the left eye. Vitreous biopsy of the right eye revealed CD5-negative/CD10-negative B-cell lymphoma cells on flow cytometry. She had no evidence of disease on brain MRI, lumbar puncture, bone marrow biopsy, or full-body CT scans. She was treated with a regimen of rituximab, methotrexate, procarbazine, and vincristine for central nervous system penetration as well as multiple intraocular injections of methotrexate and rituximab with improvement in vision and ocular inflammation bilaterally. CONCLUSION: Relapsed PBL can present as bilateral VRL.

Cystatin C and interleukin-6 for prognosticating patients with acute decompensation of cirrhosis.

BACKGROUND AND AIM: Systemic inflammation and organ dysfunction/failure can complicate acute decompensation (AD) of cirrhosis with progression to acute-on-chronic liver failure (ACLF), leading to increased mortality. There are few studies on serum biomarkers predicting renal dysfunction (RD) or ACLF in AD. Serum cystatin C (CysC) and interleukin-6 (IL-6) were evaluated for predicting RD, ACLF, and mortality in AD patients. METHODS: Consecutive AD patients seen from January 2018 to June 2019 were included. IL-6 and CysC were measured in serum at the time of index presentation. Patients were followed for 90 days or until primary (development of RD) or secondary outcomes (development of ACLF or mortality). Multivariate analysis was performed to find whether CysC and IL-6 can independently predict primary and secondary outcomes. RESULTS: A total of 124 patients were screened; 88 patients were included. On follow up, 22 (27.3%) developed RD, 11 (11/57, 19.3%) developed ACLF, and 21 (24%) died. The CysC predicted RD (odds ratio [OR] 7.97, 95% confidence interval [CI] 2.70-23.53, P = 0.001) and ACLF (OR 5.486, 95% CI 1.456-20.6, P = 0.012) development. IL-6 was not an independent predictor of RD (P = 0.315), ACLF (P = 0.168), and mortality (P = 0.225). CONCLUSION: Serum CysC can predict the development of RD and ACLF in patients of cirrhosis with AD.

Ocular Syphilis Causing Panophthalmitis.

Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum which is undergoing a global resurgence since its initial decline in the late 1980s. The authors present the case of a 30-year-old Caucasian female who was transferred to our institution for left-sided orbital cellulitis and ultimately diagnosed with ocular syphilis causing panophthalmitis. She was treated with intravenous penicillin and other broad-spectrum antibiotics, topical prednisolone, and cycloplegia, resulting in full recovery. Timely recognition of ocular syphilis by healthcare professionals is key in the prevention of visual sequelae from the infection.

Simultaneous Presentation of Crohn's Disease and Takayasu Arteritis in a Teenage Patient.

A 14-year-old female with no significant medical history presented with hypertensive urgency, in the setting of 4 to 6 weeks of diarrhea, abdominal pain, headaches, anemia, weight loss, and high blood pressures. Her evaluation revealed signs of a systemic inflammatory process that was most suspicious for inflammatory bowel disease. However, when her hypertension was evaluated with a renal Doppler ultrasound, there were signs of narrowing, stenosis, and hypoplasia that led to a diagnostic angiogram of the abdominal aorta. Full body positron emission tomography scan revealed multiple areas of stenosis and aortic thickening with enhancement compatible with Takayasu arteritis. She received prednisone, methotrexate, and infliximab with marked improvement in her clinical symptoms and inflammatory markers.

Brincidofovir for the treatment of human adenovirus infection in pediatric solid organ transplant recipients: A case series.

HAdV viremia can cause significant morbidity among pediatric recipients of SOT with variability in incidence and severity of disease based on the type of allograft. Currently, there are no US FDA-approved treatments for HAdV infections, and historically, the mainstay of treatment has been decreasing immunosuppression, with antiviral therapies reserved for those with severe disease. We describe the treatment of four pediatric SOT recipients (two kidney, one combined kidney-liver, and one liver) presenting with HAdV disease at our institution using brincidofovir. Our case series highlights the variability in presentation and the potential for severe disease in pediatric SOT recipients as we review disease presentation, disease course, complications, and treatment with brincidofovir.

Suprasellar Cyst Presenting With Bobble-Head Doll Syndrome.

BACKGROUND: Bobble-head doll syndrome is a rare neurological syndrome presenting with repetitive anteroposterior head movements. It is usually associated with expansile cystic lesions in the third ventricular region. CASE DESCRIPTION: An 8-year-old boy presented with involuntary bobbling head movements. Magnetic resonance imaging of the brain revealed an extensive suprasellar cyst resulting in obstructive hydrocephalus. Endoscopic ventriculo-cysto-cisternostomy resulted in improved clinical outcome. CONCLUSIONS: Endoscopic ventriculo-cysto-cisternostomy is an effective, less-invasive technique in the treatment of suprasellar cysts that results in resolution of the bobbling head movements.

Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder.

Posttransplant lymphoproliferative disorder (PTLD) is a known complication of solid organ transplantation. The majority are B cell in origin and related to Epstein-Barr virus infection. T-cell PTLD is much less common; most are Epstein-Barr virus negative and have a worse prognosis. Primary cutaneous T-cell lymphoma (CTCL) as a presentation of PTLD is rare. CTCL has a less favorable prognosis in transplant patients compared with that in immune-competent patients. Herein, we report a case of a 13-year-old boy who developed folliculotropic mycosis fungoides, a rare subtype of CTCL, subsequent to renal transplantation. To our knowledge, this is the first report of this type of PTLD in a pediatric patient.

Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?

Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change.

Hollow polycarbonate waveguides with inner Cu coatings for delivery of terahertz radiation.

Terahertz (THz) radiation has important applications in spectroscopy, imaging, and space science. Fiber optics for the THz region have been limited to rigid hollow metallic waveguides or short lengths of solid-core transparent dielectrics such as sapphire and plastic. We have fabricated flexible, hollow polycarbonate waveguides with interior Cu coatings for broadband THz transmission using simple liquid-phase chemistry techniques. The losses for these hollow-core guides were measured using a tunable, cw single-mode far IR laser. The losses for the best guides were found to be less than four dB/m and the single mode of the laser was preserved for the smaller bore waveguides.