A Randomized Controlled Study of Efficacy and Safety of Accelerated Versus Standard Hepatitis B Vaccination in Patients With Advanced CKD.

Introduction: Hepatitis B virus (HBV) vaccination is crucial for seronegative patients with advanced chronic kidney disease (CKD) for protection during dialysis while preparing for transplantation. A standard regimen for HBV vaccination requires 24 weeks to be completed. An accelerated HBV vaccination regimen completed within 8 weeks has shown early effective seroconversion in healthcare workers. However, data for patients with advanced CKD are limited. Methods: A randomized controlled trial was conducted in patients with advanced CKD (estimated glomerular filtration rate [GFR] <30 ml/min per 1.73 m2) and patients on dialysis. The patients were randomly assigned to either a standard HBV vaccination regimen (Engerix B; 40 µg at 0, 4, 8, and 24 weeks) or an accelerated regimen (40 µg at 0, 1, 4, and 8 weeks). The hepatitis B surface antibodies (anti-HBs) were measured at 12, 28, and 52 weeks. Seroconversion were defined as anti-HBs ≥10 IU/l. Results: At 12 weeks, among the intention-to-treat (ITT) population of 133 participants (65 in the accelerated and 68 in the standard groups), the accelerated group demonstrated significantly higher rates of seroconversion (83.08% vs. 63.24%, P = 0.01). In the per-protocol (PP) analysis of 125 patients (62 in the standard and 63 in the accelerated groups), the accelerated group exhibited higher seroconversion rate compared with the standard group (85.71% vs. 69.35%, P = 0.03). At 28 and 52 weeks, the seroconversion rates were similar between the 2 groups. Conclusion: In patients with advanced CKD, the accelerated HBV vaccination regimen demonstrated a significantly higher seroconversion rate at 12 weeks of vaccination. This finding suggests that the accelerated regimen is an effective option to achieve rapid seroconversion before initiating hemodialysis or before undergoing kidney transplantation.

Bacterial DNA Translocation Is Associated With Overt Hepatic Encephalopathy and Mortality in Patients With Cirrhosis.

INTRODUCTION: Data on the relationship between bacterial translocation, hepatic encephalopathy (HE), and mortality are scarce. This study aimed to assess the association between bacterial DNA (bactDNA) translocation, inflammatory response, ammonia levels, and severity of HE in patients with cirrhosis, as well as the role of bactDNA translocation in predicting mortality. METHODS: Cirrhotic patients without bacterial infection were prospectively enrolled between June 2022 and January 2023. Grading of HE was classified by the West Haven Criteria and Psychometric Hepatic Encephalopathy Score ≤ -5. RESULTS: Overall, 294 cirrhotic patients were enrolled, with 92 (31.3%) and 58 (19.7%) having covert and overt HE, respectively. BactDNA translocation was detected in 36.1% of patients (n = 106). Patients with overt HE had more bactDNA translocation and higher serum lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, interleukin-6 (IL-6), and ammonia levels than those without HE. Patients with detectable bactDNA had higher white cell counts and serum LBP and IL-6 levels than those without. By contrast, bactDNA, serum LBP, and soluble CD14 levels were comparable between patients with covert HE and those without HE. The multivariate Cox regression analysis revealed that bactDNA translocation (hazard ratio [HR] = 2.49, 95% confidence interval [CI]: 1.22-5.11), Model for End-Stage Liver Disease score (HR = 1.12, 95% CI: 1.09-1.16), age (HR = 1.05, 95% CI: 1.000-1.002), and baseline IL-6 (HR = 1.001, 95% CI: 1.000-1.002) were independent factors associated with 6-month mortality. DISCUSSION: Apart from hyperammonemia, bactDNA translocation is a possible factor associated with overt HE in cirrhotic patients. BactDNA translocation and IL-6 are independent factors associated with 6-month mortality.

Serum Galactomannan: A Predictor of Poor Outcomes in Peritoneal Dialysis Patients With Fungal Peritonitis.

Introduction: The potential value of serum galactomannan index (GMI) in monitoring treatment response in patients with fungal peritonitis who are receiving peritoneal dialysis (PD) was assessed in the present study. Methods: The study included all Thailand fungal PD-related infectious complications surveillance (MycoPDICS) DATA study participants who had timely PD catheter removal and availability of both baseline and ≥2 subsequent serum GMI measurements after starting antifungal therapy (if available). Serum GMI was assessed by direct double-sandwich enzyme-linked immunosorbent assay with reference to positive and negative control samples. Comparisons of categorical variables among groups were analyzed by Fisher's exact test for categorical data and the Wilcoxon rank-sum test for continuous variables. Mortality outcomes were analyzed by survival analyses using Kaplan-Meier curves with Log-rank test. Results: Seventy-six (46%) of 166 participants from 21 PD centers between 2018 and 2022 were included. The median age was 58 (50-65) years, and a half of the patients (50%) had type II diabetes. Nineteen (25%) and 57 (75%) episodes were caused by yeast and mold, respectively. Death occurred in 11 (14%) patients at 3 months, and no differences were observed in demographics, laboratories, treatment characteristics, or in baseline serum GMI between those who died and those who survived. Serum GMI progressively declined over the follow-up period after the completion of treatment. Patients who died had significantly higher posttreatment serum GMI levels and were more likely to have positive GMI after treatment. Conclusion: Serum GMI is an excellent biomarker for risk stratification and treatment response monitoring in patients on PD with fungal peritonitis.

Intractable ascites in a female receiving hemodialysis.

We report a case of a 60-year-old female who presented with intractable ascites 2 months after switching from peritoneal dialysis (PD) to hemodialysis (HD) due to an episode of refractory culture-negative peritonitis (CNP). Abdominal paracentesis yielded inflammatory ascites, which later grew Cladosporium cladosporioides, establishing the diagnosis of fungal peritonitis. She was successfully treated with a 4-week course of oral voriconazole. Cladosporium spp. are common fungi in the environment but rarely cause PD-associated peritonitis and can be challenging to diagnose with conventional microbiologic evaluation. In summary, PD-associated peritonitis can worsen after a patient switches to HD. Therefore, it is essential to maintain a high level of suspicion for such complications related to their previous dialysis modality to arrive at an accurate diagnosis.

Bacterial Urinary Tract Infection and Early Asymptomatic Bacteriuria in Kidney Transplantation Still Negatively Affect Kidney Transplant Outcomes in the Era of Modern Immunosuppression and Cotrimoxazole Prophylaxis.

Risk factors and consequences of urinary tract infection (UTI) post-kidney transplant have been variously reported by studies that were heterogenous in immunosuppressants and prophylactic protocols. We aimed to clarify the risks and consequences of UTI in kidney transplant recipients with post-transplantation cotrimoxazole prophylaxis in the context of modern immunosuppression. This retrospective cohort included kidney transplant recipients receiving tacrolimus, mycophenolate, prednisolone, and cotrimoxazole for bacterial UTI prophylaxis. Recipients were categorized into non-UTI and UTI groups. Asymptomatic bacteriuria (ASB) was screened in the first 3 months and was evaluated for association with UTI. Of 348 kidney transplant recipients, 129 were in the UTI group and 219 in the non-UTI group. UTI risk factors were female sex, body mass index ≥ 25 kg/m2, human leukocyte antigen mismatch, and panel reactive antibody ≥ 50%. Recipients with recurrent UTI had inferior allograft function compared with non-UTI recipients. Patient survival was significantly lower in recipients with UTI in the first post-transplant month. Higher degree of immunosuppressions was associated with recurrent UTI and drug-resistant organisms. In conclusion, UTI continues to negatively affect graft function and survival of kidney transplant recipients. Treating ASB in the first 3 months did not reduce the UTI incidence in the first transplantation year.

Comparison of the Immune Response After an Extended Primary Series of COVID-19 Vaccination in Kidney Transplant Recipients Receiving Standard Versus Mycophenolic Acid-sparing Immunosuppressive Regimen.

Two doses of coronavirus disease 2019 vaccination provide suboptimal immune response in transplant patients. Mycophenolic acid (MPA) is one of the most important factors that blunts the immune response. We studied the immune response to the extended primary series of 2 doses of AZD1222 and a single dose of BNT162b2 in kidney transplant patients who were on the standard immunosuppressive regimen compared to those on the MPA-sparing regimen. Methods: The kidney transplant recipients who were enrolled into the study were divided into 2 groups based on their immunosuppressive regimen. Those on the standard immunosuppressive regimen received tacrolimus (TAC), MPA, and prednisolone (standard group). The patients in the MPA-sparing group received mammalian target of rapamycin inhibitors (mTORi) with low dose TAC plus prednisolone (MPA-sparing group). The vaccination consisted of 2 doses of AZD1222 and a single dose of BNT162b2. Results: A total of 115 patients completed the study. There were 76 (66.08%) patients in the standard group and 39 (33.91%) patients in the MPA-sparing group. The overall median anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S antibody level at 4 wk after vaccine completion was 676.64 (interquartile range = 6.02-3644.03) BAU/mL with an 80% seroconversion rate. The MPA-sparing group achieved higher anti-SARS-CoV-2 S antibody level compared to the standard group (3060.69 and 113.91 BAU/mL, P < 0.001). The seroconversion rate of MPA-sparing and standard groups were 97.4% and 71.1%, respectively (P < 0.001). The anti-HLA antibodies did not significantly increase after vaccination. Conclusions: The extended primary series of 2 doses of AZD1222 and a single dose of BNT162b2 provided significant humoral immune response. The MPA-sparing regimen with mTORi and low dose TAC had a higher ant-SARS-CoV-2 S antibody level and seroconversion rate compared to the participants in the standard regimen.

Benefits of Switching Mycophenolic Acid to Sirolimus on Serological Response after a SARS-CoV-2 Booster Dose among Kidney Transplant Recipients: A Pilot Study.

Kidney transplant recipients (KTRs) have a suboptimal immune response to COVID-19 vaccination due to the effects of immunosuppression, mostly mycophenolic acid (MPA). This study investigated the benefits of switching from the standard immunosuppressive regimen (tacrolimus (TAC), MPA, and prednisolone) to a regimen of mammalian target of rapamycin inhibitor (mTORi), TAC and prednisolone two weeks pre- and two weeks post-BNT162b2 booster vaccination. A single-center, opened-label pilot study was conducted in KTRs, who received two doses of ChAdOx-1 and a single dose of BNT162b2. The participants were randomly assigned to continue the standard regimen (control group, n = 14) or switched to a sirolimus (an mTORi), TAC, and prednisolone (switching group, n = 14) regimen two weeks before and two weeks after receiving a booster dose of BNT162b2. The anti-SARS-CoV-2 S antibody level after vaccination in the switching group was significantly greater than the control group (4051.0 [IQR 3142.0-6466.0] BAU/mL vs. 2081.0 [IQR 1077.0-3960.0] BAU/mL, respectively; p = 0.01). One participant who was initially seronegative in the control group remained seronegative after the booster dose. These findings suggest humoral immune response benefits of switching the standard immunosuppressive regimen to the regimen of mTORi, TAC, and prednisolone in KTRs during vaccination.

Methylene Blue-Mediated Antimicrobial ​Photodynamic Therapy Against Clinical Isolates of Extensively Drug Resistant ​Gram-Negative Bacteria Causing Nosocomial Infections in Thailand, An In Vitro Study.

Background/Purpose: Some multidrug-resistant gram-negative bacteria as a global threat have been recently prioritized for research and development of new treatments. We studied the efficacy of methylene blue-mediated antimicrobial photodynamic therapy (MB-aPDT) for the reduction of extensively drug-resistant Acinetobacter baumannii (XDR-AB) and Pseudomonas aeruginosa (XDR-PS) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) isolated in a university hospital setting in Thailand. Method: Two isolates of each selected bacterium were collected, XDR-AB1 and AB2, XDR- PS1 and PS2, and MDR-KP1 and KP2. Three triplicate experiments using various MB concentrations alone, various red light fluences alone, as well as the selected non-toxic doses of MB and fluences of red light combined as MB-aPDT were applied on each selected isolate. The colonies were counted [colony forming units (CFU)/ml]. Estimation of the lethal treatment dose defined as reduction of > 2 log10 in CFU/ml compared with untreated bacteria. Result: There were generally negligible changes in the viable counts of the bacterial suspensions treated with all the MB concentrations (p > 0.05). In the second experiment with the only red light treatments, at fluences higher than 2 J/cm, reduction trend in viable counts across all the isolates was observed. Only for MDR-KP1, however, the lethal dose was achieved with the highest fluence of red light (80 J/cm). With the concentration of MB, 50 and 150 mg/L in the third experiment (MB-aPDT), the greater bacterial reduction was observed in all clinical isolates leading to their lethal viable cell reduction when escalating the light fluence to 80 J/cm. Conclusions: MB-aPDT evidently killed the selected XDR and MDR-gram negative bacteria. In highly drug-resistant crisis era, MB-aPDT could be a promising option, particularly for local infections and infection complicating chronic wounds.

The first report of kidney transplantation in a human immunodeficiency virus-positive recipient in Thailand and literature review: Encouragement for developing countries in Southeast Asia.

Patients with human immunodeficiency virus infection are at risk of chronic kidney disease and end-stage renal disease. Human immunodeficiency virus infection impedes patients' accessibility to transplantation in Thailand and other developing countries in Southeast Asia, where the burdens of human immunodeficiency virus infection and chronic kidney disease are rapidly increasing. We report the successful kidney transplantation in a human immunodeficiency virus-positive recipient in Thailand and provide brief information about the current knowledge of human immunodeficiency virus medicine and transplantation that are needed for conducting kidney transplantations in such patients. Patient selection and evaluation, the choice of antiretroviral therapy, immunosuppressive regimens, and infectious complications are reviewed and discussed. The aim is to encourage kidney transplantation in end-stage renal disease patients with well-controlled human immunodeficiency virus infection, especially in countries where the prevalence of human immunodeficiency virus infection is high and the accessibility to transplantation is still limited.

A randomized controlled trial of comparative effectiveness between the 2 dose and 3 dose regimens of hepatitis a vaccine in kidney transplant recipients.

Hepatitis A virus (HAV) is able to cause a spectrum of illnesses ranging from no symptom to fulminant hepatitis which may lead to acute kidney injury. Although hepatitis A vaccine is recommended in non-immune solid organ transplant recipients who live in or travel to endemic areas, the standard 2-dose vaccination regimen demonstrated less favorable immunogenicity among these population. The 3-dose regimen showed higher response rate and immune durability in patients with human immunodeficiency virus. However, this strategy has never been studied in solid organ transplant recipients. A single-center, open-labeled, computer-based randomized controlled trial (RCT) with a 2:1 allocation ratio was conducted from August 2017 to December 2018. The study compared the seroconversion rate after receiving 2- or 3-dose regimen of hepatitis A vaccine at 0, 6 and 0, 1, 6 months, respectively, in non-immune kidney transplant recipients. A total of 401 adult kidney transplant recipients were screened for anti-HAV IgG and 285 subjects had positive results so the seroprevalence was 71.1%. Of 116 seronegative recipients, 93 (80.2%) completed vaccination; 60 and 33 participants completed 2- and 3-dose vaccination, respectively. The baseline characteristics were comparable between both groups. The seroconversion rate at 1 month after vaccination was 51.7% in the standard 2-dose regimen and 48.5% in the 3-dose regimen (p = 0.769). Overall, the seroconversion rate appeared to be associated with high estimated glomerular infiltration rate, high serum albumin, and low intensity immunosuppressive regimen. Seroconversion rate after hepatitis A vaccination in kidney transplant recipients was less favorable than healthy population. Three-dose regimen did not show superior benefit over the standard 2-dose regimen. Other strategies of immunization may increase immunogenicity among kidney transplant recipients.

Risk factors and clinical outcomes of tuberculosis among kidney transplant recipients in high endemic country.

BACKGROUND: Tuberculosis (TB) is considered as a challenge issue in solid organ transplant recipients because of high morbidity and mortality. Active TB after transplant mostly occurs from reactivation of latent infection. Understanding risk factors and clinical information of TB may provide an appropriate prevention and treatment strategies in this specific patient population, however data from high endemic area is scarce. METHODS: A matched single-center, case-control study was conducted in our institute. Cases were defined as newly diagnosed confirmed or clinical active TB in patients who underwent kidney transplant (KT) between April 1992 and October 2018. For each case, 5 controls were matched by age and sex. Risk factor associated with TB was determined using univariate and multivariate conditional logistic regression. RESULTS: Between study period, KT was performed in 787 patients. Twenty-seven patients (3.43%) were diagnosed with active TB including 20 confirmed and 7 clinical diagnosed cases. The global incidence of TB in our population was 315 cases per 100 000 patients per year. Among 27 cases, pulmonary involvement was the most common (48.1%) followed by disseminated (18.5%), extrapulmonary (14.8%), pleura (11.1%) and pleuropulmonary (7.4%) TB. Allograft rejection was significantly associated with active TB (P < .001). The median onset duration of infection was 17 months (IQR, 4-59 months) after KT. Twenty-four (88.9%) patients received rifampicin containing regimen for treatment with median duration of 10 months (IQR, 6-12 months). All patients were cured after complete treatment, however those with TB remained having unfavorable outcomes including higher all-cause mortality and graft loss. CONCLUSIONS: Incidence rate of TB in KT recipients is higher than normal population. Allograft rejection was identified as a significant risk factor. Increase unfavorable outcomes including graft loss and mortality were also observed among patients with TB.

Successful challenge of voriconazole in a patient with posaconazole-associated minor drug eruption: A case report.

WHAT IS KNOWN AND OBJECTIVE: Triazole antifungal-associated skin rash is rare. Data on cross-reaction triazole antifungals remain inconclusive and poorly defined. We report successful voriconazole challenge in a patient allergic to posaconazole. CASE SUMMARY: A 38-year-old female diagnosed with acute myeloid leukaemia and receiving chemotherapy treatment in our institution developed a maculopapular rash after receiving oral posaconazole for invasive fungal infection prophylaxis. Other potential causes that may have attributed to this response, such as other drugs that the patient was taking and infections, were excluded. Voriconazole, another triazole antifungal, was successfully substituted for posaconazole. WHAT IS NEW AND CONCLUSION: This is the first case report of a patient, with a history of posaconazole allergy, successfully challenged with voriconazole.

Sporotrichosis: The case series in Thailand and literature review in Southeast Asia.

Human Sporotrichosis is an infection caused by dimorphic fungus, Sporothrix schenckii complex, via direct inoculation. We are herein report proven 2 cases of sporotrichosis along with a literature review about human sporotrichosis in the southeast Asian region. The first case was a 76-year-old female with a non-progressive erythematous plaque at the right ankle. The second case was a 36-year-old female with sporotrichoid lesion for six weeks. Both were treated with itraconazole with an excellent outcome.

Post-transplant Lymphoproliferative Disorder of Naso-orbital Region in Adult Renal Transplant Recipients: A Case Report and Literature Review.

Post-transplant lymphoproliferative disorder (PTLD) is an uncommon but fatal complication following both solid organ and hematologic stem cell transplantations. Epstein-Barr virus (EBV) has been considered a main etiologic agent causing PTLD, especially in the first year after transplantation. Extranodal manifestations are frequently found in PTLD; however, naso-orbital involvement in adults is rare. We report a case of EBV-associated PTLD of the naso-orbital region in a 72-year-old patient that occurred 10 years after kidney transplant. Six additional adults with naso-orbital PTLD were identified after completing this literature review, including 2 cases with eyelid swelling, 3 cases with proptosis, and 1 case with facial numbness. The majority of cases occurred after 1 year of transplantation and were associated with EBV. This report emphasizes recognizing PTLD as differential diagnosis in transplant recipients who present with naso-orbital symptoms.

Maximizing anti-HBs seroresponsiveness in kidney transplant waitlist patients: A tertiary-center perspective
.

BACKGROUND: Patients on dialysis are at risk of hepatitis B virus (HBV) infection, and antibodies against the hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L are required. However, a high percentages of HBV vaccine nonresponders have been reported. We aimed to determine the optimal HBV vaccination protocol. MATERIALS AND METHODS: Kidney transplant waitlisted patients were followed for 12 months and categorized into two groups. Group A included patients with sustained anti-HBs ≥ 10 IU/L who did not require vaccination. Group B consisted of patients with anti-HBs < 10 IU/L who were treated with a course of 4 double-dose HBV vaccinations. Without seroconversion after the first course, a second course was initiated. A third course, coadministered with the tetanus-diphtheria (Td) vaccine, was performed upon failure of the second course. RESULTS: A total of 266 patients were included, 140 were categorized into group A and 126 into group B. Higher serum phosphorus, hemoglobin, and antibodies against the hepatitis core antigen (anti-HBc) were associated with sustaining anti-HBs ≥ 10 IU/L without vaccination. Diabetes mellitus (DM) was associated with the need for vaccination. For group B, 107 patients required 1 course of vaccination, 15 patients required 2 courses, and 4 patients required the third course with Td vaccine coadministration. Long dialysis vintage and low hemoglobin level were associated with seroconversion failure after the first course. CONCLUSION: Serum phosphorus, hemoglobin, DM, anti-HBc, and dialysis vintage were associated with the anti-HBs seroresponsiveness and sustainability. Our 3-course of 4 double-dose HBV vaccines regimen (with Td vaccine in the final course) conferred immunity to all patients.

The Cytochrome P450 3A5 Non-Expressor Kidney Allograft as a Risk Factor for Calcineurin Inhibitor Nephrotoxicity.

BACKGROUND: Tacrolimus is mainly metabolized by cytochrome P450 3A5 (CYP3A5), which is expressed in the liver. However, CYP3A5 is also expressed in the kidney tissue and may contribute to local tacrolimus clearance in the kidney allograft. We aimed to evaluate the association between the allograft CYP3A5 genotype and transplant outcomes. METHODS: We conducted a retrospective cohort study at the King Chulalongkorn Memorial Hospital, Thailand, comparing 2 groups of donor and recipient CYP3A5 genotypes, the expressor (*1/*1 and *1/*3) and the non-expressor (*3/*3). The primary outcomes were allograft complications including calcineurin inhibitor (CNI) nephrotoxicity and acute rejection episode. RESULTS: Of the 50 enrolled patients, 21 donors were expressors and 29 donors were the non-expressors. Tacrolimus trough concentrations were similar between the 2 genotypes. The incidence of CNI nephrotoxicity was higher in recipients with non-expressor donor genotype compared with the expressor donor genotype (72.4 vs. 33.3%, p = 0.006). CNI nephrotoxicity incidence was not different when recipient's genotypes were compared. Multivariate analysis from Cox-regression showed a hazard ratio of 3.18 (p = 0.026) for CNI nephrotoxicity in the non-expressor compared with the expressor donor. The recipient CYP3A5 genotypes did not significantly contribute to CNI nephrotoxicity. Kaplan-Meier analysis demonstrated the lowest CNI nephrotoxicity-free survival in recipients with the expressor genotype who received allograft from the non-expressor donors (p = 0.005). CONCLUSION: In conclusion, our results suggest that donor CYP3A5 non-expressor genotype (*3/*3) is a risk for CNI nephrotoxicity.

Influenza in patients with hematological malignancies: Experience at two comprehensive cancer centers.

The burden of influenza infections in patients with hematological malignancies (HMs) is not well defined. We describe the clinical presentation and associated outcomes of influenza at two comprehensive cancer centers (center 1 in the United States and center 2 in Mexico). Clinical and laboratory data on patients with HMs and influenza infection diagnosed from April 2009 to May 2014 at the two centers were reviewed retrospectively. A total of 190 patients were included, the majority were male (63%) with a median age of 49 years (range, 1-88 years), and had active or refractory HMs (76%). Compared to center 1, patients in center 2 were significantly sicker (active cancer, decreased albumin levels, elevated creatinine levels, or hypoxia at influenza diagnosis) and experienced higher lower respiratory tract infection (LRI) rate (42% vs 7%; P < 0.001). In multivariable logistic regression analysis (odds ratio, 95% confidence interval), leukemia, (3.09, 1.23-7.70), decreased albumin level (3.78, 1.55-9.20), hypoxia at diagnosis (14.98, 3.30-67.90), respiratory co-infection (5.87, 1.65-20.86), and corticosteroid use (2.71, 1.03-7.15) were significantly associated with LRI; and elevated creatinine level (3.33, 1.05-10.56), hypoxia at diagnosis (5.87, 1.12-30.77), and respiratory co-infection (6.30, 1.55-25.67) were significantly associated with 60 day mortality in both centers. HM patients with influenza are at high risk for serious complications such as LRI and death, especially if they are immunosuppressed. Patients with respiratory symptoms should seek prompt medical care during influenza season.