Low-Dose vs Standard-Dose Valganciclovir for Cytomegalovirus Prophylaxis After Kidney Transplantation: A Single-Center Retrospective Analysis.

BACKGROUND: Prophylactic administration of valganciclovir (VG) is an accepted method for the prevention of cytomegalovirus (CMV) infection after kidney transplantation (KTx). The standard dosage of oral VG is 900 mg/day, adjusted to renal function. There is growing evidence that low-dose 450 mg/day VG might be safe and effective. We compared low-dose vs standard-dose prophylaxis after KTx in a single-center follow-up study. METHODS: Data from 603 renal transplantations at a single center were retrospectively analyzed (2011-2014, 12-month follow-up). Recipients with donor IgG positive-recipient IgG positive (D+/R+), (D+/R-), and (D-/R+) CMV serostatus were routinely treated with 450 mg/day VG for 3 months. Based on the same prophylactic dose, patients could be categorized into two groups according to their postoperative renal function: those receiving standard-dose VG due to a lower estimated glomerular filtration rate (eGFR) (average eGFR<60 mL/min/1.73 m2) and those receiving low-dose VG due to higher eGFR (average eGFR>60 mL/min/1.73 m2). RESULTS: Estimated glomerular filtration rate-based VG serum alterations significantly affected the risk of CMV infection with a higher incidence in higher VG levels (standard-dose: 357 patients, CMV: 33 cases (9.2 %); low-dose: 246 patients, CMV: 10 cases (4.1%). The occurrence of known risk factors: serologic risk distribution and rate of induction therapy were not statistically different between the 2 groups. Treatment of an acute rejection episode influenced the infection rate significantly in the standard-dose group. As a side effect of prophylaxis, leucopenia (<3G/L) was 2.46 times higher in standard-dose vs low-dose group. CONCLUSION: Low-dose VG administration is safe and non-inferior to the standard dose in the prophylaxis of CMV infection after KTx.

Prototheca Infections and Ecology from a One Health Perspective.

Prototheca microalgae were only recognized as pathogens of both humans and animals in the 1960s; however, since then, these microbes have been drawing increasing interest in both human and veterinary medicine. The first human outbreak of protothecosis in a tertiary care chemotherapy ward in 2018 further highlighted the need to understand in more depth and detail their ecology, etiology, pathogenesis and routes of transmission between different hosts, environments and habitats from a One Health perspective. Protothecal infections have been reported in a growing number of cattle herds around the world in recent decades, and Prototheca has become an important bovine mastitis pathogen in certain countries and regions. The survival of Prototheca in the environment and its ability to spread in the herd pose a serious challenge to the management of infected dairy farms. Prevention of the disease is particularly important, as there is no effective and reliable treatment for it and the chances of self-healing are minimal. Therefore, the development of more effective drugs is needed for the treatment of human and animal protothecosis. The prudent use of antibiotics and their replacement by alternative or preventive measures, when possible, may further contribute to the control of protothecal infections.

Situs Inversus Totalis: A Clinical Review.

Situs inversus totalis is a rare congenital abnormality characterized by a mirror-image transposition of both the abdominal and the thoracic organs. While this anomaly is known since the ancient times, practicing doctors do not have much experience with it. Laterality is established early in development, and any failure in that process might lead to a wide variety of disorders which may be partial or complete. Situs solitus describes the normal anatomy, situs inversus is the complete reversal, and situs ambiguous is used for any other abnormality of left-right development. Sidedness is regulated by genes: over 100 genes have been linked to laterality defects. Frequency of situs inversus is 1:10,000 and is more frequent in males: 1.5:1. Advanced imaging modalities can be used to assess fine anatomical details, which play a crucial role in these cases to plan radiologic or surgical interventions. Percutaneous biliary procedures, portal vein embolization are really challenging procedures in SIT patients due to the mirror effect. As most surgeons are right-handed, SIT operations can cause difficulties: handling the instruments with their left hand or the pedals with their left foot can be uncomfortable Organ, especially liver transplantation represents an extraordinary surgical challenge. Solutions to overcome the anatomic differences include the use of segment or reduced size graft with rotation, modified piggy-back technique, side to-side caval anastomosis, and vascular conduit. Because of its rarity and special nature, surgical patients with situs inversus may require more flexibility and creativity from the surgical team.

Outcomes of first versus third kidney transplantations: propensity score matching and paired subgroup analysis-a single-centre experience.

BACKGROUND: In the Eurotransplant, 12.6% of kidney transplantations are a repeat procedure. Third transplants are significantly more complex than first and second ones. We compared the results of first (PRT) versus third (TRT) transplantations. METHODS: Between 2011 and 2016, we performed 779 deceased donor adult kidney transplantations, 14.2% out of them were second, 2.6% (20) third, and 0.3% fourth. We compared the pre-, intra-, and postoperative data, kidney function, and survival rate. RESULTS: Recipients of TRT were younger (53.4 vs. 47.3 p = 0.02). HCV infection rate (20%, p = 0.00) is ten times higher. The operation time is longer (132 vs. 152 min, p = 0.02), and delayed graft function is much more frequent (22.4% vs. 60%, p = 0.00). Induction therapy was given to every TRT (7.9% vs.100%), but as a result, the rejection rate was the same (~ 15%). Hospital stay is a week longer. Patient's survival at 1, 3, and 5 years for PRT is 96.4%, 93.9%, and 91.2% and for TRT is 90%, 85%, and 78.4%, respectively (p = 0.023). TRT's odds ratio of fatal outcome is 4.35 (1.5-12.5). Graft survival at 1, 3, and 5 years for PRT is 93.1%, 91.4%, and 90.3% and for TRT is 75%, 75%, and 75%, respectively (p = 0.020). TRT's odds ratio of graft loss is 3.14 (1.1-8.9). Of PRT 85.76%, out of PRT 85.76%, while out of TRT 60% live with a functioning graft, p=0.00149. CONCLUSION: In a third transplant, both graft and patient survival are significantly inferior to primer ones. Careful selection is required to minimize the patient risk and graft loss.

[Can urinary neutrophil gelatinase-associated lipocalin predict acute rejection following deceased donor kidney transplantation?]. / Alkalmas-e a vizelet neutrofil gelatináz asszociálta lipokalin meghatározása a rejekció elorejelzésére veseátültetés után?

INTRODUCTION: Delayed graft function and acute rejection have negative impact on graft survival. AIM: To asses the predictive value of urinary neutrophil gelatinase-associated lipocalin, which has been found to be a promising biomarker for the diagnosis of acute kidney injury. METHOD: In this prospective study urinary neutrophil gelatinase-associated lipocalin levels of 27 kidney recipients were measured. RESULTS: Patients were grouped as follows: group 1, no complication; group 2, rejection; group 3, delayed graft function requiring dialysis; group 4, rejection plus delayed graft function. There were no significant differences between groups 1 and 2, and between groups 3 and 4. Patients in groups 3 and 4 had significantly higher urinary neutrophil gelatinase-associated lipocalin levels as compared to those in groups 3 and 4. There was a paralIel change in urinary neutrophil gelatinase-associated lipocalin levels in groups 1 and 2. CONCLUSIONS: In these patients urinary neutrophil gelatinase-associated lipocalin levels failed to provide useful information in both cases of normal and impaired function.

Molecular pathogenesis of post-transplant acute kidney injury: assessment of whole-genome mRNA and miRNA profiles.

Acute kidney injury (AKI) affects roughly 25% of all recipients of deceased donor organs. The prevention of post-transplant AKI is still an unmet clinical need. We prospectively collected zero-hour, indication as well as protocol kidney biopsies from 166 allografts between 2011 and 2013. In this cohort eight cases with AKI and ten matched allografts without pathology serving as control group were identified with a follow-up biopsy within the first twelve days after engraftment. For this set the zero-hour and follow-up biopsies were subjected to genome wide microRNA and mRNA profiling and analysis, followed by validation in independent expression profiles of 42 AKI and 21 protocol biopsies for strictly controlling the false discovery rate. Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p). Next to several established biomarkers such as lipocalin-2 also novel candidates of interest were identified in the signature. In further experimental evaluation the elevated transcript expression level of the secretory leukocyte peptidase inhibitor (SLPI) in AKI allografts was confirmed in plasma and urine on the protein level (p<0.001 and p = 0.003, respectively). miR-182-5p was identified as a molecular regulator of post-transplant AKI, strongly correlated with global gene expression changes during AKI. In summary, we identified an AKI-specific molecular signature providing the ground for novel biomarkers and target candidates such as SLPI and miR-182-5p in addressing AKI.

High frequency of ulcers, not associated with Helicobacter pylori, in the stomach in the first year after kidney transplantation.

BACKGROUND: Although gastrointestinal (GI) symptoms are very frequent in organ transplant patients, there is a paucity of data about the endoscopic findings of kidney recipients. METHODS: Two thousand one hundred and thirty-five kidney transplants were performed between 1994 and 2007. During that period, 672 gastroscopies were performed in 543 of those patients. Their mean age was 49.5 years and 56.9% were male. Immunosuppressive combinations included cyclosporine-mycophenolate-steroids, cyclosporine-steroids and tacrolimus-mycophenolate mofetil-steroids. Ninety-eight percent of the patients received acid suppression therapy. RESULTS: The rate of clinically significant endoscopic findings was 84%. Macroscopic findings included inflammation in 46.7%, oesophagitis in 24.7%, ulcer in 16.9% and erosions in 14.8% of cases. Twenty-nine percent of endoscopies showed ulcer disease more frequently in the first 3 months (P=0.0014) after transplantation than later, and 45.7% of all ulcers developed in the first year. The presence of Helicobacter pylori was verified in 20.9% of cases, less than in the general, and also in the uraemic population (P<0.0001). There was no association between the presence of H. pylori and ulcers (P=0.28). Steroid pulse treatment for rejection was not associated with more ulcers (P=0.11); the use of mycophenolate mofetil increased the risk of erosions by 1.8-fold. CONCLUSION: More than 25% of all kidney recipients required upper endoscopy in their 'post-transplant life'; the prevalence of 'positive findings' and ulcer disease was higher than in the general population (P<0.0001). The most vulnerable period is the first 3 months. Mycophenolate mofetil had an impact on GI complications, whilst the presence of H. pylori in the transplant population is not associated with the presence of ulcers.

[Gastrointestinal cytomegalovirus infections in organ transplant patients]. / A gastrointestinalis traktus cytomegalovirus-fertozése szervtranszplantált betegeken.

Cytomegalovirus (CMV) is a major pathogen of immunocompromised organ transplant patients. 80-90% of all transplant patients are infected by the virus; however, the incidence of CMV disease is 30-40%. Gastrointestinal CMV disease occurs in 10% of all transplants involving any part of the gastrointestinal tract. Mucosal injury, ulcerations, erosions, hemorrhage, gastrointestinal dysmotility, rarely gastrointestinal masses, perforations are the most common pathological findings of the CMV disease. The method of specific diagnostics is endoscopy with mucosal biopsy. The biopsy samples must be investigated histopathologically for specific cytomegalic cells with intranuclear ("owl's eye") and intracytoplasmatic inclusions. Different microbiological, immunohistochemical and molecular biological assays can be performed to detect CMV in the mucosa. In case of gastrointestinal CMV disease, both gastroenterological and antiviral treatment are needed by ganciclovir i.v. and/or valganciclovir orally. The prevention of the disease should be achieved by general prophylaxis in high-risk patients (oral valganciclovir, in special cases hyperimmune globulin), and by preemptive therapy using microbiological surveillance in middle-risk patients.

Seroprevalence of Helicobacter pylori in Central-European uraemic patients and its possible association with presence of HLA-DR12 allele.

OBJECTIVES: Renal disease at any stage is often accompanied by significant gastrointestinal symptoms, and Helicobacter pylori (H. pylori) is closely related to these disorders. A debate is still ongoing on the clinical significance of coexisting uraemia and H. pylori. HLA-class II genes have been repeatedly investigated for predisposition to H. pylori infection. The aim of our work was to evaluate the infection rate among uraemic patients, and study the relationship between HLA antigens and H. pylori serologic status in the same cohort. MATERIALS AND METHODS: Data of 709 uraemic patients were collected and analyzed from 2001-2006. 58.7% of patients were male, 41.3% were female, mean age was 45.1 years (SD: +/-14.65). Microlymphocytotoxicity assay was used for typing of HLA class I, PCR-SSP for typing HLA class II alleles and enzyme immunofluorescency for specific H. pylori IgG. RESULTS: Of 709 patients, 49.37% were seropositive for H. pylori. Age of H. pylori positive patients was 48.9 versus 41 years of negatives (P<0.0001). Prevalence of H. pylori decreased strongly with year of birth. Significant difference was observed in the occurrence of HLA-DR12 according to H. pylori serology. Of patients carrying DR12, 27 (73%) were H. pylori positive and 10 (27%) were negative [P=0.0037; risk ratios (RR): 2.76]. CONCLUSION: H. pylori infection rate and its decrease with year of birth was the same in the uraemic patients and in the normal population, according to specific prevalence figures. Frequency of HLA-DR12 was the same as in the general population; consequently, it might be a possible risk factor for H. pylori seropositivity, at least in a Central-European population.

HLA-DQ3 is a probable risk factor for CMV infection in high-risk kidney transplant patients.

BACKGROUND: Cytomegalovirus (CMV) infection in transplant patients with special risk factors remains a major hazard. CMV-seronegative recipients with seropositive donors have the highest risk of developing acute CMV disease. We suggest that the HLA-type may influence the occurrence and the severity of primary CMV infection of these recipients and the measurement of the special HLA-types may be useful in the prediction of acute infection. METHODS: Since 1999 1213 cadaver kidney transplantations have been performed in our clinic. 163 of 1213 recipients were CMV-seronegative (13%) and 129 of them received the kidney from seropositive donors. All 129 patients received CMV infection prophylaxis. Of 129 CMV-seronegative patients 49 developed acute CMV infection (38%) during the first posttransplant year. CMV infection was diagnosed by CMV antigenemia test and serologic measurements (ELISA). The particular HLA-genotypes of the recipients were studied before the transplantation. The occurrence and the severity of CMV infection was investigated in association with HLA-types. RESULTS: We found different acute CMV infection distribution in the careers and non-careers of investigated HLA-types: HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6 and HLA-DR11, but the differences were not significant in these HLA-types (P = 0.26, P = 0.37, P = 0.83, P = 0.07 and P = 0.37). While investigating HLA-DQ3, we found that of 68 DQ3-positive patients 32 (47%), of 61 DQ3-negative patients 17 (28%) had acute CMV infection and this difference was found to be significant. This result was confirmed by univariate and multivariate Cox Regression (P = 0.001) and the appropriate significance level was considered by Bonferroni correction. CONCLUSIONS: HLA-DQ3 was found to be an independent predictor of CMV infection. Our data suggest that patients positive for HLA-DQ3 are more susceptible to CMV infection than a comparable group of patients negative for HLA-DQ3. This result was not due to rejection and/or treatment for rejection and was not influenced by induction therapy. Although we found more symptomatic infections among DQ3+ patients the difference was not significant (P = 0.19). Comparing the gender proportion among all 1213 kidney recipients and among CMV-seronegative recipients we found that the proportion of males is significantly higher among CMV-seronegative recipients (P < 0.001).

Endoscopic diagnosis of cytomegalovirus infection of upper gastrointestinal tract in solid organ transplant recipients: Hungarian single-center experience.

BACKGROUND: Cytomegalovirus (CMV) is considered to be the major cause of upper gastrointestinal (GI) symptoms in organ transplant recipients. In the diagnosis of GI CMV infection the detection of the virus in the mucosa is essential. The aim of the study was to evaluate the significance of CMV, detected in biopsy specimens from stomach and duodenum of solid organ transplant recipients. METHODS: Data of 227 elective upper endoscopies on symptomatic organ transplant recipients were evaluated for clinical symptoms, endoscopic changes and conventional histologic alterations of mucosal biopsy samples. Qualitative PCR was performed for detection of the presence of CMV-DNA in each biopsy materials. RESULTS: CMV-DNA was detected in biopsy samples of 91 patients (40.1%) while only in 20 cases (8.8%) the signs of CMV infections were found by conventional histology (p < 0.00001). No considerable differences could be observed in symptomatic, histologic alterations between CMV-PCR positive and negative groups. There were no endoscopic changes in 25.3% of CMV-PCR positive and 5.1% of negative patients. CONCLUSIONS: Qualitative PCR is an accurate method for the detection of CMV in the mucosa of the GI tract. Further investigations are needed for determination of the exact pathological role of detected CMV.

[Our experiences with surgical treatment of gastrointestinal stromal tumors]. / A GastroIntestinalis Stroma Tumorok sebészi kezelésében szerzett tapasztalataink néhány eset kapcsán.

INTRODUCTION: Stromal tumors of the gastrointestinal tract are rare neoplasms, but they are the most common ones of mesenchymal origin. In a large proportion of patients clinical onset is represented by surgical emergencies. Incidence of GIST is calculated to be 10-20 cases per million per year. GISTs account for 0.1-3% of all gastrointestinal tumors, up to 20% of small bowel malignancies. At least 30-70% of the cases are malignant. PATIENTS: We summary our experiences of surgical treatment of GIST, apropos of five patients handled at our department in 2003. There were 3 male, 2 female, 55.8 years. The 5 patients had altogether 21 operations. Diagnosis was recognized before op. in three cases. RESULTS: In one case the tumor was inoperable, in one other technical operable, but oncologically not complete. In another case recurrence is known, and in one dissemination was observed during operation. There is only one case of fives, where we can hope, that a tumor-free situation had been left. Diagnosis was confirmed in every case with CD117 strain. SUMMARY: Surgery remains the standard treatment for GISTs. Disease recurrence is quite common, the rate is 65-75%, even when surgery is performed with intent to cure. In a surgical emergency or in the absence of a perioperative diagnosis, the surgeon is responsible for recognizing and treating these tumors. The benefit of surgical exercises for recurrent disease is unclear. In our opinion it is worth operating these cases, because in some cases amazing survival can be available.