20 results on '"Mueller, Nicolas J."'
Search Results
2. Central nervous system infections in solid organ transplant recipients: Results from the Swiss Transplant Cohort Study
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van den Bogaart, Lorena, Lang, Brian M, Rossi, Simona, Neofytos, Dionysios, Walti, Laura N, Khanna, Nina, Mueller, Nicolas J, Boggian, Katia, Garzoni, Christian, Mombelli, Matteo, Manuel, Oriol, van den Bogaart, Lorena, Lang, Brian M, Rossi, Simona, Neofytos, Dionysios, Walti, Laura N, Khanna, Nina, Mueller, Nicolas J, Boggian, Katia, Garzoni, Christian, Mombelli, Matteo, and Manuel, Oriol
- Abstract
OBJECTIVES To describe the epidemiology and clinical presentation of central nervous system (CNS) infections in solid organ transplant (SOT) recipients in the current era of transplantation. METHODS Patients from the Swiss Transplant Cohort Study (STCS) transplanted between 2008 and 2018 were included with a median follow-up of 3.8 years. Epidemiological, microbiological, and clinical data were extracted from the STCS database and patients' medical records. We calculated incidence rates and 90-day survival of transplant recipients with CNS infection. RESULTS Among 4762 patients, 42 episodes of CNS infection in 41 (0.8%) SOT recipients were identified, with an overall incidence rate of 2.06 per 1000 patient-years. Incidence of CNS infections was similar across all types of transplantations. Time to CNS infection onset ranged from 0.6 to 97 months after transplant. There were 22/42 (52.4%) cases of viral infections, 11/42 (26.2%) of fungal infections, 5/42 (11.9%) of bacterial infections and 4/42 (9.5%) of probable viral/bacterial etiology. Clinical presentation was meningitis/encephalitis in 25 cases (59.5%) and brain-space occupying lesions in 17 cases (40.5%). Twenty-three cases (60.5%) were considered opportunistic infections. Diagnosis were achieved mainly by brain biopsy/necropsy (15/42, 36%) or by cerebrospinal fluid analysis (20/42, 48%). Up to 40% of cases (17/42) had concurrent extra-neurological disease localizations. Overall, 90-day mortality rate was 29.0% (73.0% for fungal, 14.0% for viral and 11.0% for bacterial and probable infections, p<0.0001). CONCLUSIONS CNS infections were rare in the STCS, with viral meningoencephalitis being the most common disease. Fungal infections were associated with a high mortality.
- Published
- 2022
3. Long-term follow-up of antibody titers against measles, mumps, and rubella in recipients of allogenic hematopoietic cell transplantations
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Bögeholz, Jan, Russkamp, Norman F, Wilk, Christian M, Gourri, Elise, Haralambieva, Eugenia, Schanz, Urs, Mueller, Nicolas J, Manz, Markus G, Müller, Antonia M S, Bögeholz, Jan, Russkamp, Norman F, Wilk, Christian M, Gourri, Elise, Haralambieva, Eugenia, Schanz, Urs, Mueller, Nicolas J, Manz, Markus G, and Müller, Antonia M S
- Abstract
Outbreaks of viral infections, such as measles, are regularly observed and pose a serious threat to allogeneic HCT-recipients. The question how long cellular and humoral protective host immunity persists, and whether donor immunity can be transferred has not been clarified. Here, we present a retrospective analysis of humoral immunity, i.e. serial antibody titers against measles, mumps, and rubella in 331 patients who underwent allogeneic HCT at our single center between 2002-2015. Associations between the loss of protective antibody levels and clinical patient characteristics and transplant parameters were examined. In general, antibody protection against measles persisted longer with 72% of patients maintaining sufficient titers at 5 years post HCT even without re-vaccination while at that time only 65% and 50% of patients had protective immunity against rubella and mumps, respectively. The great majority of donors were seropositive for all three viruses, however, it appeared that donor humoral immunity could not be transferred and had no impact on the post-HCT serostatus. Rather, the most relevant factor for persistence of protective antibody titers against measles and rubella was whether patients were born before introduction of the respective vaccine, and thus were immunized by the wild-type disease inducing virus instead of the vaccine. Moreover, the presence of moderate and severe chronic graft-versus host disease (GVHD) was associated with more rapid loss of immune protection. In contrast, underlying disease, intensity of the conditioning regimen, use of anti-thymocyte globulin, age, and graft source did not have an influence on antibody titers. Overall, our findings suggest that the majority of antibodies against measles, mumps, and rubella originate from residual host cells, whereas the donor immune status appears to have no influence on antibody protection post-HCT.
- Published
- 2020
4. Cytomegalovirus: why viral dynamics matter
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Mueller, Nicolas J and Mueller, Nicolas J
- Published
- 2015
5. BK Polyomavirus (BKPyV) Serotype-Specific Antibody Responses in Blood Donors and Kidney Transplant Recipients with and without new-onset BKPyV-DNAemia: A Swiss Transplant Cohort Study.
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Hillenbrand CA, Bani DA, Follonier O, Kaur A, Weissbach FH, Wernli M, Wilhelm M, Leuzinger K, Binet I, Bochud PY, Golshayan D, Hirzel C, Manuel O, Mueller NJ, Schaub S, Schachtner T, Van Delden C, and Hirsch HH
- Abstract
BK polyomavirus (BKPyV) causes premature renal failure in 10%-30% of kidney transplant recipients (KTRs). Current guidelines recommend screening for new-onset BKPyV-DNAemia/nephropathy and reducing immunosuppression to regain BKPyV-specific immune control. Since BKPyV encompasses 4 major genotype(gt)-encoded serotypes (st1,-2,-3,-4), st-specific antibodies may inform risk and course of BKPyV-DNAemia/nephropathy. Using BKPyV st-virus-like particle (VLP) ELISA, we analyzed plasma from 399 blood donors (BDs) and 428 KTRs (134 KTR-cases with BKPyV-DNAemia, 294 KTR-controls). BDs were anti-BKPyV-VLP IgG-seropositive in 85% compared to 93% of KTRs at T0 (p<0.001). Anti-st1 were predominant in both groups followed by anti-st4, anti-st2, and anti-st3. Antibody levels and quadruple sero-reactivity at T0 were higher in KTR-controls than in KTR-cases (p=0.026) or in BDs (p<0.001). In KTR-cases, anti-st increased post-transplant (p<0.0001) and independently of ongoing or cleared BKPyV-DNAemia. However, anti-st levels were significantly higher at T0 in KTR-cases able to clear at T6 or T12. In 34 KTR-cases with deep genome sequencing, BKPyV-gtI was predominant, and anti-st1 and st1-neutralizing antibodies were significantly lower at T0 than in KTR-controls. Thus, BKPyV st-specific antibody levels at transplantation might reflect gt/st-BKPyV-specific immunity clearing or preventing BKPyV-DNAemia in KTR-cases or KTR-controls, respectively. Accordingly, active or passive immunization may be most efficient pretransplant or early post-transplant., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
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6. Invasive aspergillosis in liver transplant recipients in the current era.
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Kimura M, Rinaldi M, Kothari S, Giannella M, Anjan S, Natori Y, Phoompoung P, Gault E, Hand J, D'Asaro M, Neofytos D, Mueller NJ, Kremer AE, Rojko T, Ribnikar M, Silveira FP, Kohl J, Cano A, Torre-Cisneros J, San-Juan R, Aguado JM, Mansoor AE, George IA, Mularoni A, Russelli G, Luong ML, AlJishi YA, AlJishi MN, Hamandi B, Selzner N, and Husain S
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- Humans, Male, Female, Middle Aged, Case-Control Studies, Risk Factors, Prognosis, Follow-Up Studies, Postoperative Complications, Transplant Recipients statistics & numerical data, Survival Rate, Retrospective Studies, Graft Rejection etiology, Adult, Aged, Aspergillus isolation & purification, Liver Transplantation adverse effects, Aspergillosis etiology, Aspergillosis epidemiology, Aspergillosis mortality
- Abstract
Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted antimold prophylactic and appropriate treatment strategies against IA., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. J. Hand reports research grant funding from Pfizer, Janssen, Scynexis, and GlaxoSmithKline. D. Neofytos has received research support from MSD and Pfizer and consulting fees from MSD, Pfizer, Basilea, and Gilead. N.J. Mueller is on the scientific advisory board of Takeda MSD, and Pfizer and has received travel support from Biotest. M. Luong is on the Scientific Advisory Board of Takeda and Merck. S. Husain reports grant funding from Merck, Astellas, ScynexisInc, Pulmocide, Ltd, and Gilead Sciences Inc, outside the submitted work. All other authors have no potential conflicts., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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7. Invasive fungal disease in the immunocompromised host: changing epidemiology, new antifungal therapies, and management challenges.
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Giannella M, Lanternier F, Dellière S, Groll AH, Mueller NJ, Alastruey-Izquierdo A, and Slavin MA
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Background: Invasive fungal disease (IFD) causes morbidity and mortality in immunocompromised hosts (ICHs). Based on increasing recognition of the impact of IFD on human disease, a recent WHO priority list identified key areas of need., Objectives: This review examines changes in the epidemiology of IFD, in particular the emergence of antifungal-resistant pathogens and the current availability of rapid diagnostic tests and antifungal treatment options., Sources: Literature between 2000 and January 2024 regarding fungal epidemiology, diagnostic tests, antifungal resistance, emerging fungal pathogens, and novel antifungal agents in both adult and paediatric ICH were reviewed., Content: We describe the changing epidemiology and continued burden and mortality of IFD in ICH. Furthermore, we discuss the emergence of antifungal-resistant organisms driven by new immunosuppressed populations, climate change, and antifungal exposure in the individual and environment. We highlight novel antifungal agents and how they will address current unmet needs., Implications: The changing epidemiology and increased population at risk for IFD, lack of recognition or quantification of risks for IFD with new therapies, current gaps in the availability of rapid diagnostic tests, and the imminent availability of novel antifungals with distinct spectra of activity argue for improved availability of and access to rapid diagnostics, antifungal stewardship programmes, and global access to antifungal agents., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2024
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8. Surgical site infections after kidney transplantation are independently associated with graft loss.
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Schreiber PW, Hoessly LD, Boggian K, Neofytos D, van Delden C, Egli A, Dickenmann M, Hirzel C, Manuel O, Koller M, Rossi S, Banz V, Schmied B, Guerke L, Matter M, de Rougemont O, Bonani M, Golshayan D, Schnyder A, Sidler D, Haidar F, Kuster SP, Stampf S, and Mueller NJ
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- Humans, Male, Female, Middle Aged, Risk Factors, Retrospective Studies, Follow-Up Studies, Kidney Failure, Chronic surgery, Prognosis, Adult, Glomerular Filtration Rate, Prospective Studies, Delayed Graft Function etiology, Aged, Switzerland epidemiology, Kidney Function Tests, Kidney Transplantation adverse effects, Surgical Wound Infection etiology, Surgical Wound Infection microbiology, Surgical Wound Infection epidemiology, Graft Survival, Graft Rejection etiology
- Abstract
Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m
2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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9. Adjunctive glucocorticoid therapy for Pneumocystis jirovecii pneumonia in solid organ transplant recipients: A multicenter cohort, 2015-2020.
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Hosseini-Moghaddam SM, Kothari S, Humar A, Albasata H, Yetmar ZA, Razonable RR, Neofytos D, D'Asaro M, Boggian K, Hirzel C, Khanna N, Manuel O, Mueller NJ, Imlay H, Kabbani D, Tyagi V, Smibert OC, Nasra M, Fontana L, Obeid KM, Apostolopoulou A, Zhang SX, Permpalung N, Alhatimi H, Silverman MS, Guo H, Rogers BA, MacKenzie E, Pisano J, Gioia F, Rapi L, Prasad GVR, Banegas M, Alonso CD, Doss K, Rakita RM, and Fishman JA
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- Female, Humans, Middle Aged, Europe, Glucocorticoids therapeutic use, Retrospective Studies, Transplant Recipients, Male, Aged, Organ Transplantation adverse effects, Pneumocystis carinii, Pneumonia, Pneumocystis drug therapy, Pneumonia, Pneumocystis etiology
- Abstract
Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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10. 'Which trial do we need? Culture of preservation fluid in abdominal organ transplant recipients' Author's reply.
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Manuel O, van den Bogaart L, Mueller NJ, and Neofytos D
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- Humans, Abdomen, Transplant Recipients, Organ Transplantation adverse effects, Kidney Transplantation
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- 2023
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11. Epidemiology and outcomes of bone and joint infections in solid organ transplant recipients.
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Pham TT, Andrey DO, Stampf S, Burkhard SH, Hirzel C, Tschopp J, Ullrich K, Strahm C, Schreiber PW, Boillat-Blanco N, Garzoni C, Khanna N, Manuel O, Mueller NJ, Suva D, van Delden C, Uçkay I, and Neofytos D
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- Humans, Male, Case-Control Studies, Cohort Studies, Transplant Recipients, Organ Transplantation adverse effects, Osteomyelitis epidemiology, Osteomyelitis etiology
- Abstract
Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008-31.12.2019) were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p < .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2022
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12. Epidemiology and outcomes of medically attended and microbiologically confirmed bacterial foodborne infections in solid organ transplant recipients.
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van den Bogaart L, Lang BM, Neofytos D, Egli A, Walti LN, Boggian K, Garzoni C, Berger C, Pascual M, van Delden C, Mueller NJ, Manuel O, and Mombelli M
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- Humans, Incidence, Prospective Studies, Transplant Recipients, Bacterial Infections epidemiology, Bacterial Infections etiology, Organ Transplantation adverse effects
- Abstract
Food-safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years with systematic collection of data on infections, and patient and graft-related outcomes. We identified 151 episodes of microbiologically confirmed bacterial foodborne infections occurring in median 1.6 years (IQR 0.58-3.40) after transplantation (131 [88%] Campylobacter spp. and 15 [10%] non-typhoidal Salmonella). The cumulative incidence of bacterial foodborne infections was 4% (95% CI 3.4-4.8). Standardized incidence rates were 7.4 (95% CI 6.2-8.7) and 4.6 (95% CI 2.6-7.5) for Campylobacter and Salmonella infections, respectively. Invasive infection was more common with Salmonella (33.3% [5/15]) compared to Campylobacter (3.2% [4/125]; p = .001). Hospital and ICU admission rates were 47.7% (69/145) and 4.1% (6/145), respectively. A composite endpoint of acute rejection, graft loss, or death occurred within 30 days in 3.3% (5/151) of cases. In conclusion, in our cohort bacterial foodborne infections were late post-transplant infections and were associated with significant morbidity, supporting the need for implementation of food-safety recommendations., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2022
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13. Burden, epidemiology, and outcomes of microbiologically confirmed respiratory viral infections in solid organ transplant recipients: a nationwide, multi-season prospective cohort study.
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Mombelli M, Lang BM, Neofytos D, Aubert JD, Benden C, Berger C, Boggian K, Egli A, Soccal PM, Kaiser L, Hirzel C, Pascual M, Koller M, Mueller NJ, van Delden C, Hirsch HH, and Manuel O
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- Cohort Studies, Humans, Prospective Studies, Seasons, Switzerland, Transplant Recipients, Influenza, Human epidemiology, Organ Transplantation adverse effects, Respiratory Tract Infections epidemiology, Respiratory Tract Infections etiology
- Abstract
Solid organ transplant (SOT) recipients are exposed to respiratory viral infection (RVI) during seasonal epidemics; however, the associated burden of disease has not been fully characterized. We describe the epidemiology and outcomes of RVI in a cohort enrolling 3294 consecutive patients undergoing SOT from May 2008 to December 2015 in Switzerland. Patient and allograft outcomes, and RVI diagnosed during routine clinical practice were prospectively collected. Median follow-up was 3.4 years (interquartile range 1.61-5.56). Six hundred ninety-six RVIs were diagnosed in 151/334 (45%) lung and 265/2960 (9%) non-lung transplant recipients. Cumulative incidence was 60% (95% confidence interval [CI] 53%-69%) in lung and 12% (95% CI 11%-14%) in non-lung transplant recipients. RVI led to 17.9 (95% CI 15.7-20.5) hospital admissions per 1000 patient-years. Intensive care unit admission was required in 4% (27/691) of cases. Thirty-day all-cause case fatality rate was 0.9% (6/696). Using proportional hazard models we found that RVI (adjusted hazard ratio [aHR] 2.45; 95% CI 1.62-3.73), lower respiratory tract RVI (aHR 3.45; 95% CI 2.15-5.52), and influenza (aHR 3.57; 95% CI 1.75-7.26) were associated with graft failure or death. In this cohort of SOT recipients, RVI caused important morbidity and may affect long-term outcomes, underlying the need for improved preventive strategies., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2021
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14. First experience of SARS-CoV-2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study.
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Tschopp J, L'Huillier AG, Mombelli M, Mueller NJ, Khanna N, Garzoni C, Meloni D, Papadimitriou-Olivgeris M, Neofytos D, Hirsch HH, Schuurmans MM, Müller T, Berney T, Steiger J, Pascual M, Manuel O, and van Delden C
- Subjects
- Aged, COVID-19, Comorbidity, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Pandemics, Prospective Studies, SARS-CoV-2, Survival Rate trends, Switzerland epidemiology, Betacoronavirus, Coronavirus Infections epidemiology, Disease Transmission, Infectious prevention & control, Organ Transplantation methods, Pneumonia, Viral epidemiology, Postoperative Complications epidemiology, Transplant Recipients
- Abstract
Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, comprehensive data of SARS-CoV-2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS-CoV-2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%), and diarrhea (33%). Ninety-five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow-up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS-CoV-2 infection in middle-aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2020
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15. Heart or lung transplant outcomes in HIV-infected recipients.
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Koval CE, Farr M, Krisl J, Haidar G, Pereira MR, Shrestha N, Malinis MF, Mueller NJ, Hannan MM, Grossi P, and Huprikar S
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- Female, Graft Survival, Humans, Male, Middle Aged, Retrospective Studies, Survival Rate, Treatment Outcome, HIV Infections complications, Heart Diseases etiology, Heart Diseases surgery, Heart Transplantation, Lung Diseases etiology, Lung Diseases surgery, Lung Transplantation
- Abstract
Background: Limited published data exist on outcomes related to heart and/or lung transplantation in human immunodeficiency virus (HIV)-infected individuals., Methods: We conducted a multicenter retrospective study of heart and lung transplantation in HIV-infected patients and describe key transplant- and HIV-related outcomes., Results: We identified 29 HIV-infected thoracic transplant recipients (21 heart, 7 lung, and 1 heart and/or lung) across 14 transplant centers from 2000 through 2016. Compared with an International Society for Heart and Lung Transplantation registry cohort, we demonstrated similar 1-, 3-, and 5-year patient and allograft survivals for each organ type with a median follow up of 1,064 (range, 184-3,745) days for heart and 1,540 (range, 116-3,206) days for lung recipients. At 1 year, significant rejection rates were high (62%) for heart transplant recipients (HTRs). Risk factors for rejection were inconclusive, likely because of small numbers, but may be related to cautious early immunosuppression and infrequent use of induction therapy. Pulmonary bacterial infections were high (86%) for lung transplant recipients (LTRs). Median CD4 counts changed from baseline to 1 year from 399 to 411 cells/µl for HTRs and 638 to 280 cells/µl for LTRs. Acquired immunodeficiency syndrome-related events, including infections and malignancies, were rare. Rates of severe renal dysfunction suggest a need to modify nephrotoxic anti-retrovirals and/or immunosuppressants., Conclusions: HIV-infected HTRs and LTRs have similar survival rates to their HIV-uninfected counterparts. Although optimal immunosuppression is not defined, it should be at least as aggressive as that for HIV-uninfected recipients. Such data may help pave the way for the use of hearts and lungs from HIV-infected donors in HIV-infected recipients through HIV Organ Policy Equity Act protocols., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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16. Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients.
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Quteineh L, Wójtowicz A, Bochud PY, Crettol S, Vandenberghe F, Venetz JP, Manuel O, Golshayan D, Lehmann R, Mueller NJ, Binet I, van Delden C, Steiger J, Mohacsi P, Dufour JF, Soccal PM, Kutalik Z, Marques-Vidal P, Vollenweider P, Recher M, Hess C, Pascual M, and Eap CB
- Subjects
- Adolescent, Adult, Aged, Diabetes Mellitus immunology, Female, Gene-Environment Interaction, Heterozygote, Homozygote, Humans, Immunosuppression Therapy, Immunosuppressive Agents therapeutic use, Inflammation immunology, Male, Middle Aged, Odds Ratio, Prospective Studies, Switzerland epidemiology, Young Adult, Diabetes Mellitus etiology, Diabetes Mellitus genetics, Inflammation genetics, Organ Transplantation, Polymorphism, Single Nucleotide, Transplant Recipients
- Abstract
New-onset diabetes mellitus after transplantation (NODAT) is a complication following solid organ transplantation (SOT) and may be related to immune or inflammatory responses. We investigated whether single nucleotide polymorphisms (SNPs) within 158 immune- or inflammation-related genes contribute to NODAT in SOT recipients. The association between 263 SNPs and NODAT was investigated in a discovery sample of SOT recipients from the Swiss Transplant Cohort Study (STCS, n
1 = 696). Positive results were tested in a first STCS replication sample (n2 = 489) and SNPs remaining significant after multiple test corrections were tested in a second SOT replication sample (n3 = 156). Associations with diabetic traits were further tested in several large general population-based samples (n > 480 000). Only SP110 rs2114592C>T remained associated with NODAT in the STCS replication sample. Carriers of rs2114592-TT had 9.9 times (95% confidence interval [CI]: 3.22-30.5, P = .00006) higher risk for NODAT in the combined STCS samples (n = 1184). rs2114592C>T was further associated with NODAT in the second SOT sample (odds ratio: 4.8, 95% CI: 1.55-14.6, P = .006). On the other hand, SP110 rs2114592C>T was not associated with diabetic traits in population-based samples, suggesting a specific gene-environment interaction, possibly due to the use of specific medications (ie, immunosuppressants) in transplant patients and/or to the illness that may unmask the gene effect., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)- Published
- 2019
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17. How should we evaluate organ donors with active or prior infections?
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Mueller NJ and Fishman JA
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- Humans, Liver Failure epidemiology, Risk Factors, Tissue Donors supply & distribution, Infections epidemiology, Infections transmission, Liver Failure surgery, Liver Transplantation statistics & numerical data, Tissue Donors statistics & numerical data
- Published
- 2006
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18. Risk factors for the development of post-transplant lymphoproliferative disorder in a large animal model.
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Cho PS, Mueller NJ, Cameron AM, Cina RA, Coburn RC, Hettiaratchy S, Melendy E, Neville DM Jr, Patience C, Fishman JA, Sachs DH, and Huang CA
- Subjects
- Animals, B-Lymphocytes immunology, Cyclosporine pharmacology, Disease Models, Animal, Flow Cytometry, Haplotypes, Humans, Immunosuppressive Agents pharmacology, Lymphoproliferative Disorders pathology, Major Histocompatibility Complex, Polymerase Chain Reaction, Risk Factors, Swine, Swine, Miniature, T-Lymphocytes metabolism, Thymus Gland pathology, Time Factors, Cell Transplantation adverse effects, Cell Transplantation methods, Lymphoproliferative Disorders etiology, Transplantation adverse effects
- Abstract
A high incidence of a post-transplant lymphoproliferative disorder (PTLD) is observed in miniature swine conditioned for allogeneic hematopoietic cell transplantation using a protocol involving T-cell depletion and cyclosporine therapy. This study was designed to assess contributing factors to disease development. Forty-six animals were studied including 12 (26%) that developed PTLD. A number of risk factors for PTLD were examined, including degree of immunosuppression, degree of MHC mismatch and infection by a porcine lymphotrophic herpesvirus (PLHV-1). Flow cytometry was used to measure host and donor T- and B-cell levels in the peripheral blood. Porcine lymphotrophic herpesvirus viral load was determined by quantitative PCR. Animals developing PTLD had significantly lower levels of T cells on the day of transplant. Cyclosporine levels did not differ significantly between animals with and without PTLD. Animals receiving transplants across a two-haplotype mismatch barrier showed an increased incidence of PTLD. All animals with PTLD had significant increases in PLHV-1 viral loads. Porcine lymphotrophic herpesvirus viral copy numbers remained at low levels in the absence of disease. The availability of a preclinical large-animal model with similarities to PTLD of humans may allow studies of the pathogenesis and treatment of that disorder.
- Published
- 2004
- Full Text
- View/download PDF
19. Correlation of biochemical and hematological changes with graft failure following pig heart and kidney transplantation in baboons.
- Author
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Knosalla C, Gollackner B, Bühler L, Mueller NJ, Houser S, Mauiyyedi S, Sachs DH, Robson SC, Fishman J, Schuurman HJ, Awwad M, and Cooper DK
- Subjects
- Animals, Disseminated Intravascular Coagulation immunology, Graft Rejection blood, Hematocrit, Hemoglobins metabolism, L-Lactate Dehydrogenase metabolism, Papio immunology, Swine immunology, Time Factors, Graft Rejection immunology, Heart Transplantation immunology, Kidney Transplantation immunology, Transplantation, Heterologous immunology
- Abstract
We have explored biochemical and hematologic parameters that might indicate acute humoral xenograft rejection (AHXR) following pig organ transplantation in baboons. Baboons (n = 15) received an immunosuppressive regimen, and underwent a miniature swine or hDAF kidney (Group 1, n = 6) or heart (Group 2, n = 7) transplantation. Control baboons (Group 3, n = 2) received the immunosuppressive regimen without organ transplantation. Blood chemistry and hematologic parameters were measured daily. Baboon and porcine cytomegalovirus were monitored. In Groups 1 and 2, organ grafts survived for up to 29 days. A plasma fibrinogen of <80 mg/dL on 2 consecutive days, and a serum lactate dehydrogenase of >600 U/L and aspartate transaminase of >300 U/L, were associated with the development of AHXR in both heart and kidney grafts. In Group 1, a decrease in platelet count of >150,000/microL within 3 days, or a count of <50,000/microL, were associated with AHXR. In Group 2, a creatine phosphokinase of >500 U/L was associated with graft failure. In Group 3, no abnormalities were observed. The possibility that porcine CMV may play a role in graft injury could not be excluded. Noninvasive parameters were identified that have predictive potential for AHXR. Monitoring of these might enable therapeutic intervention to reverse rejection.
- Published
- 2003
- Full Text
- View/download PDF
20. Reduced efficacy of ganciclovir against porcine and baboon cytomegalovirus in pig-to-baboon xenotransplantation.
- Author
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Mueller NJ, Sulling K, Gollackner B, Yamamoto S, Knosalla C, Wilkinson RA, Kaur A, Sachs DH, Yamada K, Cooper DK, Patience C, and Fishman JA
- Subjects
- Animals, Animals, Genetically Modified, CD55 Antigens genetics, Cytomegalovirus isolation & purification, Disease Models, Animal, Heart Transplantation, Humans, Kidney Transplantation, Papio, Polymerase Chain Reaction, Reproducibility of Results, Swine, Thymus Gland transplantation, Viral Load, Cytomegalovirus Infections drug therapy, Cytomegalovirus Infections prevention & control, Ganciclovir therapeutic use, Transplantation, Heterologous
- Abstract
In pig-to-baboon xenotransplantation, porcine cytomegalovirus (PCMV) causes viremia, consumptive coagulopathy, and tissue-invasive disease. Baboon cytomegalovirus (BCMV) is associated with invasive disease in xenograft recipients. The efficacy of prophylaxis with intravenous ganciclovir (GCV) was studied for prevention of PCMV and BCMV infections in pig-to baboon xenotransplantation. GCV prophylaxis did not alter the incidence of BCMV activation in recipients, but reduced the amount of virus in tissues (mean 8.38 x 10(2) vs. 3.24 x 10(5) copies/ micro g DNA without treatment) and prevented tissue-invasive infections. PCMV viral loads were unaltered by GCV prophylaxis (8.36 x 10(8) copies/ micro g DNA without prophylaxis vs. 1.20 x 10(9) copies/ micro g DNA with prophylaxis). In vitro, PCMV was relatively resistant to GCV [90% inhibitory concentration (IC90) of 10 micro m, IC50 = 3 micro m], acyclovir (100 micro m), and leflunomide (not achievable). Only cidofovir (IC90 1 micro m) and foscarnet (IC90 100 micro m) might have therapeutic efficacy for PCMV in vivo in achievable concentrations, although these agents often carry significant toxicity in transplant recipients. GCV has limited activity against BCMV and no therapeutic efficacy against PCMV at standard doses in vivo. GCV and other antiviral agents have limited activities against PCMV in vitro. Breeding of PCMV-free xenograft donors may be necessary to prevent PCMV infections in clinical trials.
- Published
- 2003
- Full Text
- View/download PDF
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