BACKGROUND: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management. METHODS: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate. RESULTS: A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd-generation cephalosporin (37%) or piperacillin-tazobactam (21%) monotherapy. Several patient-level factors dictated the selection of broader-spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended-spectrum ß-lactamase-producing organisms, 90% for carbapenemase-producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries. CONCLUSION: High-quality studies are needed to guide the empirical management of post-transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post-transplant pyelonephritis.
- Keywords
- antimicrobial stewardship, kidney transplantation, questionnaire, urinary tract infection,
- MeSH
- Anti-Bacterial Agents * therapeutic use MeSH
- beta-Lactamases MeSH
- Cephalosporins therapeutic use MeSH
- Adult MeSH
- Piperacillin, Tazobactam Drug Combination therapeutic use MeSH
- Practice Patterns, Physicians' statistics & numerical data MeSH
- Middle Aged MeSH
- Humans MeSH
- Transplant Recipients statistics & numerical data MeSH
- Surveys and Questionnaires MeSH
- Pseudomonas aeruginosa drug effects isolation & purification MeSH
- Pyelonephritis * drug therapy microbiology MeSH
- Kidney Transplantation * adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Bacterial Agents * MeSH
- beta-Lactamases MeSH
- Cephalosporins MeSH
- Piperacillin, Tazobactam Drug Combination MeSH
INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.
- Keywords
- immunosuppression, organ transplantation, skin cancer, squamous cell carcinoma,
- MeSH
- Adult MeSH
- Incidence MeSH
- Neoplasm Invasiveness MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local epidemiology MeSH
- Head and Neck Neoplasms epidemiology pathology MeSH
- Skin Neoplasms * epidemiology pathology MeSH
- Transplant Recipients statistics & numerical data MeSH
- Prospective Studies MeSH
- Risk Factors MeSH
- Aged MeSH
- Carcinoma, Squamous Cell * epidemiology MeSH
- Neoplasm Staging MeSH
- Organ Transplantation * adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe epidemiology MeSH
PURPOSE OF REVIEW: In this review, we discuss achievements in immunosuppression in kidney transplant recipients published at last 18 months. RECENT FINDINGS: Results of recent trials with everolimus in low-risk primary kidney transplant recipients suggest that lowTAC/EVR combination is noninferior and CMV and BKV viral infections are less frequent to standTAC/MPA. Iscalimab monoclonal antibody, which prevents CD40 to CD154 binding, has just recently entered phase II clinical studies in kidney transplantation. Eculizumab, anti-C5 monoclonal antobody was recently shown to improve outcomes in DSA+ living-donor kidney transplant recipients requiring pretransplant desensitization because of crossmatch positivity. Proximal complement C1 inhibition in patients with antibody-mediated rejection was studied in several phase I trials. SUMMARY: Recent knowledge creates a path towards future immunosuppression success in sensitized recipients and in those in high risk of viral infections or CNI nephrotoxicity.
- MeSH
- Everolimus therapeutic use MeSH
- Antibodies, Monoclonal, Humanized therapeutic use MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Immunosuppression Therapy methods MeSH
- Humans MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- Transplant Recipients statistics & numerical data MeSH
- Randomized Controlled Trials as Topic MeSH
- Graft Rejection immunology prevention & control MeSH
- Kidney Transplantation methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- eculizumab MeSH Browser
- Everolimus MeSH
- Antibodies, Monoclonal, Humanized MeSH
- Immunosuppressive Agents MeSH
- iscalimab MeSH Browser
- Antibodies, Monoclonal MeSH
There are scarce data on the impact of COVID-19 pandemic on liver transplantation (LT) in Europe. The aim of this study was to obtain a preliminary data on incidence, management, and outcome of COVID-19 in liver transplant recipients and candidates in Europe. An Internet-based survey was sent to the centers affiliated with European Liver Transplant Registry (ELTR). One hundred nine out of 149 (73%) of ELTR centers located in 28 European countries (93%) responded. Ninety-four (86%) of the centers tested all donors, and 75 (69%) centers tested all LT recipients for SARS-CoV-2. Seventy-three (67%) centers selected recipients for LT in the COVID-19 pandemic, whereas 33% did not. Eighty-eight centers reported COVID-19 infection in 57 LT candidates and in 272 LT recipients. Overall crude incidence of COVID-19 among LT candidates and recipients was estimated 1.05% (range 0.5-20%) and 0.34% (range 0.1-4.8%), respectively, and it was significantly higher among candidates (P < 0.001). Crude rate of death was 18% (10/57) among candidates and 15% (36/244) among recipients. This first large-scale European snapshot study clearly shows that both LT candidates and recipients are at a high risk for COVID-19. These results plead for an early and pro-active screening of COVID-19 symptoms in these populations.
- Keywords
- COVID-19, SARS-CoV-2, liver recipient, liver transplantation, mortality, survey,
- MeSH
- Early Diagnosis MeSH
- COVID-19 diagnosis epidemiology MeSH
- Tissue Donors statistics & numerical data MeSH
- Immunocompromised Host MeSH
- Incidence MeSH
- Comorbidity MeSH
- Humans MeSH
- Liver Diseases epidemiology surgery MeSH
- Pandemics * MeSH
- Mass Screening MeSH
- Postoperative Complications epidemiology MeSH
- Transplant Recipients statistics & numerical data MeSH
- Health Care Surveys MeSH
- Registries MeSH
- Risk MeSH
- SARS-CoV-2 * MeSH
- COVID-19 Testing MeSH
- Liver Transplantation statistics & numerical data MeSH
- Donor Selection standards MeSH
- Procedures and Techniques Utilization MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe epidemiology MeSH
BACKGROUND: The rs58542926 polymorphism in transmembrane 6 superfamily member 2 (TM6SF2) is a genetic factor predisposing to nonalcoholic fatty liver disease. We aimed to explore the effect of recipient and donor TM6SF2 rs58542926 genotypes on liver graft fat content after liver transplantation. METHODS: Steatosis was evaluated in liver biopsies from 268 adult recipients. The influence of recipient and donor TM6SF2 genotypes, patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 genotypes, and nongenetic factors on the steatosis grade assessed 6-30 months after transplantation was analyzed by ordinal logistic regression. RESULTS: The presence of the TM6SF2 c.499A allele in the donor (P = 0.014), PNPLA3 c.444G allele in the donor (P < 0.001), posttransplant body mass index (P < 0.001), and serum triglycerides (P = 0.047) independently predicted increased liver fat content on multivariable analysis, whereas noncirrhotic liver disease, as an indication for liver transplantation, was associated with lower risk of steatosis (P = 0.003). The effects of the donor TM6SF2 A and PNPLA3 G alleles were additive, with an odds ratio of 4.90 (95% confidence interval, 2.01-13.00; P < 0.001), when both minor alleles were present compared with an odds ratio of 2.22 (95% confidence interval, 1.42-3.61; P = 0.002) when only one of these alleles was present. CONCLUSIONS: The donor TM6SF2 c.499A allele is an independent risk factor of liver graft steatosis after liver transplantation that is additive to the effects of donor PNPLA3 c.444G allele.
- MeSH
- Alleles MeSH
- Allografts pathology MeSH
- Biopsy MeSH
- Tissue Donors statistics & numerical data MeSH
- Adult MeSH
- Genotyping Techniques statistics & numerical data MeSH
- Liver pathology MeSH
- Polymorphism, Single Nucleotide MeSH
- Middle Aged MeSH
- Humans MeSH
- Lipase genetics MeSH
- Membrane Proteins genetics MeSH
- Young Adult MeSH
- Follow-Up Studies MeSH
- Non-alcoholic Fatty Liver Disease diagnosis epidemiology genetics pathology MeSH
- Postoperative Complications diagnosis epidemiology genetics pathology MeSH
- Prevalence MeSH
- Transplant Recipients statistics & numerical data MeSH
- Risk Factors MeSH
- Severity of Illness Index MeSH
- Liver Transplantation adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- adiponutrin, human MeSH Browser
- Lipase MeSH
- Membrane Proteins MeSH
- TM6SF2 protein, human MeSH Browser
BACKGROUND: High prevalence of arterial hypertension is known in pediatric renal transplant patients, but how blood pressure (BP) distribution and control differ between age groups and whether sex and age interact and potentially impact BP after transplantation have not been investigated. METHODS: This retrospective analysis included 336 pediatric renal transplant recipients (62% males) from the Cooperative European Pediatric Renal Transplant Initiative Registry (CERTAIN) with complete BP measurement at discharge and 1, 2 and 3 years post-transplant. RESULTS: At discharge and 3 years post-transplant, arterial hypertension was highly prevalent (84% and 77%); antihypertensive drugs were used in 73% and 68% of the patients. 27% suffered from uncontrolled and 9% from untreated hypertension at 3 years post-transplant. Children transplanted at age < 5 years showed sustained high systolic BP z-score and received consistently less antihypertensive treatment over time. Younger age, shorter time since transplantation, male sex, higher body mass index (BMI), high cyclosporine A (CSA) trough levels, and a primary renal disease other than congenital anomalies of the kidney and urinary tract (CAKUT) were significantly associated with higher systolic BP z-score. Sex-stratified analysis revealed a significant association between high CSA and higher systolic BP in older girls that likely had started puberty already. An association between BP and estimated glomerular filtration rate was not detected. CONCLUSIONS: BP control during the first 3 years was poor in this large European cohort. The description of age- and sex-specific risk profiles identified certain recipient groups that may benefit from more frequent BP monitoring (i.e. young children) or different choices of immunosuppression (i.e. older girls).
- Keywords
- Children, Cyclosporine, Hypertension, Immunosuppression, Kidney transplantation, Sex differences,
- MeSH
- Time Factors MeSH
- Cyclosporine administration & dosage adverse effects pharmacokinetics MeSH
- Child MeSH
- Hypertension diagnosis epidemiology etiology MeSH
- Immunosuppressive Agents administration & dosage adverse effects pharmacokinetics MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Blood Pressure Determination statistics & numerical data MeSH
- Adolescent MeSH
- Follow-Up Studies MeSH
- Child, Preschool MeSH
- Prevalence MeSH
- Transplant Recipients statistics & numerical data MeSH
- Registries statistics & numerical data MeSH
- Graft Rejection immunology prevention & control MeSH
- Retrospective Studies MeSH
- Sex Factors MeSH
- Tacrolimus administration & dosage adverse effects pharmacokinetics MeSH
- Kidney Transplantation adverse effects MeSH
- Age Factors MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe epidemiology MeSH
- Names of Substances
- Cyclosporine MeSH
- Immunosuppressive Agents MeSH
- Tacrolimus MeSH
BACKGROUND AND AIMS: This multicenter trial compared immediate-release tacrolimus (IR-T) vs prolonged-release tacrolimus (PR-T) in de novo kidney, liver, and heart transplant recipients aged <16 years. Each formulation had similar pharmacokinetic (PK) profiles. Follow-up efficacy and safety results are reported herein. MATERIALS AND METHODS: Patients, randomized 1:1, received once-daily, PR-T or twice-daily, IR-T within 4 days of surgery. After a 4-week PK assessment, patients continued randomized treatment for 48 additional weeks. At Year 1, efficacy assessments included the number of clinical acute rejections, biopsy-confirmed acute rejection (BCAR) episodes (including severity), patient and graft survival, and efficacy failure (composite of death, graft loss, BCAR, or unknown outcome). Adverse events were assessed throughout. RESULTS: The study included 44 children. At Year 1, mean ± standard deviation tacrolimus trough levels were 6.6 ± 2.2 and 5.4 ± 1.6 ng/mL, and there were 2 and 7 acute rejection episodes in the PR-T and IR-T groups, respectively. No cases of graft loss or death were reported during the study. The overall efficacy failure rate was 18.2% (PR-T n = 1; IR-T n = 7). CONCLUSIONS: In pediatric de novo solid organ recipients, the low incidence of BCAR and low efficacy failure rate suggest that PR-T-based immunosuppression is effective and well tolerated to 1-year post-transplantation.
- Keywords
- calcineurin inhibitor: tacrolimus, heart (allograft) function/dysfunction, immunosuppressant, kidney transplantation: living donor, liver transplantation: living donor,
- MeSH
- Child MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Humans MeSH
- Survival Rate MeSH
- Adolescent MeSH
- Follow-Up Studies MeSH
- Postoperative Complications drug therapy etiology MeSH
- Child, Preschool MeSH
- Graft Survival drug effects MeSH
- Transplant Recipients statistics & numerical data MeSH
- Prognosis MeSH
- Graft Rejection drug therapy etiology MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Tacrolimus therapeutic use MeSH
- Organ Transplantation adverse effects MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Names of Substances
- Immunosuppressive Agents MeSH
- Tacrolimus MeSH
The study objective is to quantify the impact of donor and recipient variables on heart transplant survival in recipients with a significant proportion of implanted continuous-flow left ventricular assist devices (LVADs). This is a prospective cohort study of International Society for Heart and Lung Transplantation (ISHLT) Registry that includes all primary heart-alone transplants in adult recipients (January 2005 and June 2013, N = 15 532, 27% LVADs). Donor and recipient characteristics were assessed for association with death or graft failure within 90 days and between 90 days and 5 years after transplantation. On Cox proportional hazard model donor cause of death other than head trauma (hazard ratio [HR] 1.985, P < 0.0001), recipient congenital (HR 2.7555, P < 0.0001) and ischemic (HR 1.165, P = 0.0383) vs dilated etiology and female donor heart transplanted into male recipient (HR 1.207, P = 0.0354) were predictors of death or graft failure within 90 days. Between 90 days and 5 years, donor cigarette use (HR 1.232, P = 0.0001), recipient cigarette use (HR 1.193, P = 0.0003), diabetes (HR 1.159, P = 0.0050), arterial hypertension (HR 1.129, P = 0.0115), and ischemic vs dilative cardiomyopathy had an increased probability of death or graft failure.
- Keywords
- donor characteristics, donor-recipient matching, heart transplantation, left ventricular assist device, mechanical assist device, recipient characteristics,
- MeSH
- Tissue Donors supply & distribution MeSH
- Adult MeSH
- Factor Analysis, Statistical MeSH
- Risk Assessment methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Young Adult MeSH
- Follow-Up Studies MeSH
- Heart-Assist Devices statistics & numerical data MeSH
- Postoperative Complications mortality MeSH
- Graft Survival MeSH
- Transplant Recipients statistics & numerical data MeSH
- Prognosis MeSH
- Prospective Studies MeSH
- Graft Rejection mortality MeSH
- Risk Factors MeSH
- Heart Transplantation mortality MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT). METHODS: GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors for resistance to fluoroquinolones, noncarbapenem anti-Pseudomonas β-lactams (noncarbapenems), carbapenems, and multidrug resistance. RESULTS: Sixty-five HSCT centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%; nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant. The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired infections. Noncarbapenem resistance and multidrug resistance were higher in auto-HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis (P < .01). Resistance rates were higher in southeast vs northwest Europe and similar in children and adults, excluding higher fluoroquinolone- and β-lactam/β-lactamase inhibitor resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; noncarbapenem resistance: hospital-acquired infection, breakthrough on noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems, carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; multidrug resistance: longer hospitalization, breakthrough on β-lactam/β-lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and mortality were significantly more common in infections caused by resistant bacteria. CONCLUSIONS: Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols. Knowledge of pathogen-specific resistance enables early appropriate empiric therapy. Monitoring of resistance is crucial. CLINICAL TRIALS REGISTRATION: NCT02257931.
- Keywords
- antimicrobial resistance, bacteremia, gram-negative rods, hematopoietic stem cell transplantation,
- MeSH
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Bacteremia drug therapy epidemiology microbiology MeSH
- Child MeSH
- Adult MeSH
- Gram-Negative Bacterial Infections drug therapy epidemiology microbiology MeSH
- Gram-Negative Bacteria drug effects MeSH
- Internationality MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Drug Resistance, Multiple, Bacterial * MeSH
- Child, Preschool MeSH
- Transplant Recipients * statistics & numerical data MeSH
- Prospective Studies MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged MeSH
- Hematopoietic Stem Cell Transplantation * MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe epidemiology MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
BACKGROUND: Repolarization processes in female and male are different. This study provided pilot data on automatic measurements of QT intervals in heart transplant (HT) recipients stratified according to the sex of the recipient and the donor. METHODS AND RESULTS: The following groups were analyzed: Group A-20 males with male heart, group B-14 females with male heart, group C-13 females with female heart, group D-11 males with female heart, group E-20 healthy males, and group F-20 healthy females. Twelve-lead electrocardiograms were digitally captured during autonomic provocative test of five postural 8-minute stages-supine, unsupported sitting, supine, unsupported standing, and supine. Fridericia formula was used for heart rate correction together with a generic correction for QT/RR hysteresis. Neither female nor male HT recipients exhibit any differences in QTc interval duration related to the sex of the donor. There was, however, a trend towards longer QTc intervals in female HT recipients compared to male HT recipients irrespective of the sex of the donor. The QTc differences between healthy control females and males were highly statistically significant proving the assay sensitivity of the study. CONCLUSION: The available pilot data suggest that in HT patients, the sex of the donor has little influence on the QTc interval of the transplanted heart.
- Keywords
- Cardiac repolarization, Heart transplantation, Sex differences,
- MeSH
- Tissue Donors statistics & numerical data MeSH
- Adult MeSH
- Electrocardiography, Ambulatory statistics & numerical data MeSH
- Middle Aged MeSH
- Humans MeSH
- Pilot Projects MeSH
- Sex Characteristics MeSH
- Transplant Recipients statistics & numerical data MeSH
- Sex Distribution MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Heart Rate * MeSH
- Heart Failure epidemiology physiopathology surgery MeSH
- Heart Transplantation statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic epidemiology MeSH