The aim of this study was to analyze first year renal outcomes in a nationwide prospective multic... more The aim of this study was to analyze first year renal outcomes in a nationwide prospective multicenter cohort comprising 2215 renal transplants, with a special emphasis on the presence of pre‐transplant donor‐specific HLA antibodies (DSA). All transplants had a complete virtual crossmatch and DSA were detected in 19% (411/2215). The investigated composite endpoint was a poor first‐year outcome defined as (i) allograft failure or (ii) death or (iii) poor allograft function (eGFR ≤25 ml/min/1.73 m2) at one year. Two hundred and twenty‐one (221/2215; 10%) transplants showed a poor first‐year outcome. Rejection (24/70; 34%) was the most common reason for graft failure. First‐year patient’s death was rare (48/2215; 2%). There were no statistically significant differences between DSA‐positive and DSA‐negative transplants regarding composite and each individual endpoint, as well as reasons for graft failure and death. DSA‐positive transplants experienced more frequently rejection episodes, mainly antibody‐mediated rejection (both P < 0.0001). The combination of DSA and any first year rejection was associated with the overall poorest death‐censored allograft survival (P < 0.0001). In conclusion, presence of pre‐transplant DSA per se does not affect first year outcomes. However, DSA‐positive transplants experiencing first year rejection are a high‐risk population for poor allograft survival and may benefit from intense clinical surveillance.
PurposeThe Swiss Transplant Cohort Study (STCS) is a prospective multicentre cohort study which s... more PurposeThe Swiss Transplant Cohort Study (STCS) is a prospective multicentre cohort study which started to actively enrol study participants in May 2008. It takes advantage of combining data from all transplant programmes in one unique system to perform comprehensive nationwide reporting and to promote translational and clinical post-transplant outcome research in the framework of Swiss transplantation medicine.ParticipantsOver 5500 solid organ transplant recipients have been enrolled in all six Swiss transplant centres by end of 2019, around three-quarter of them for kidney and liver transplants. Ninety-three per cent of all transplanted recipients have consented to study participation, almost all of them (99%) contributed to bio-sampling. The STCS genomic data set includes around 3000 patients.Findings to dateDetailed clinical and laboratory data in high granularity as well as patient-reported outcomes from transplant recipients and activities in Switzerland are available in the l...
Zusammenfassung Gegenstand und Ziel: Mit dieser Studie sollte das Vorkommen von Bordetella (B.) b... more Zusammenfassung Gegenstand und Ziel: Mit dieser Studie sollte das Vorkommen von Bordetella (B.) bronchiseptica in Mehrkatzenhaushalten mit und ohne respiratorische Symptome untersucht werden. Material und Methoden: Die Studie umfasste insgesamt 258 Katzen aus 40 Beständen. Antikörper gegen B. bronchiseptica wurden mittels ELISA nachgewiesen. Zudem erfolgten eine PCR und eine Erregeranzüchtung. Ergebnisse: Die Antikörperprävalenz lag bei 41,9%. Bei Katzen mit respiratorischen Symptomen ergab sich eine Prävalenz von 56,5%, bei gesunden Katzen betrug sie 39,9%. Dieser Unterschied war statistisch signifikant. Die Antikörperprävalenz lag in Tierheimen signifikant höher als in Privat- und Zuchtbeständen. Ältere Katzen wiesen signifikant häufiger Antikörper gegen B. bronchiseptica auf. Die PCR war nur bei 4,6% von 219 untersuchten Katzen positiv; die Anzüchtung gelang bei keinem von 28 untersuchten Tieren. Schlussfolgerung und klinische Relevanz: B. bronchiseptica zeigt in Mehrkatzenhausha...
In solid organ transplant recipients (sOTRs), 5 years after transplantation cancer is a relevant ... more In solid organ transplant recipients (sOTRs), 5 years after transplantation cancer is a relevant cause of death. We aimed to report cancer incidence in the Swiss Transplant Cohort Study (STCS) between 2008 and 2014 and conducted a prospective cohort study of kidney, heart, lung, pancreas and liver transplant recipients enrolled into the STCS by retrospective analysis of collected data. The STCS provided data on 2758 solid organ transplants. In total, 134 cases of cancer were observed (30 liver, 21 prostate, 18 lung, 13 kidney, 52 other cancers). Standardised incidence ratios (SIRs) were highest for liver cancer, kidney cancer, thyroid cancer, gastric cancer, bladder cancer, cancer of the oral cavity and the pharynx and for lung cancer. Cancer occurrence differed according to the transplanted organ. Cancers were mainly diagnosed at World Health Organisation (WHO) stages I and IV. Treatment received was mainly surgery and, in some cases, included also radiation and/or chemotherapy. Bladder, kidney, liver, lung and prostate cancer were detected at a younger age compared with the general population. Cumulative hazards for death were increased for transplant recipients with cancer. Solid organ transplant recipients show an organ specific increase of cancer compared with the general Swiss population. Clinical trial registration number: NCT02333279
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jan 31, 2016
We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex viru... more We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infe...
Galactose-deficient IgA1 (Gd-IgA1) and IgA-IgG complexes are known to play an important role in t... more Galactose-deficient IgA1 (Gd-IgA1) and IgA-IgG complexes are known to play an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed therefore to determine the impact of immunosuppression on the serum levels of Gd-IgA1, total IgA1 and IgA-IgG complexes in IgAN patients. In a retrospective study, serum samples from IgAN patients collected before transplantation (t0) and at 3- and 6-month posttransplant (t3 & t6) were used to measure the levels of Gd-IgA1, total IgA1 and IgA-IgG complexes. The area under the curves (AUC) of immunosuppressants was calculated by the plot of plasma trough level or dosage of each immunosuppressant versus time and was interpreted as the extent of drug exposure. Thirty-six out of 64 IgAN patients, who underwent kidney transplantation between 2005 and 2012, were enrolled. From t0 to t3, serum Gd-IgA1 and total IgA1 decreased significantly (24.7 AU (18.6-36.1) to 17.2 (13.1-29.5) (p<0.0001); 4.1 mg/ml (3.6-5.1) to 3.4 (3.0-4.1) (p = 0.0005)...
The objective of this investigation was to determine the clinical and radiographic outcome of a o... more The objective of this investigation was to determine the clinical and radiographic outcome of a one-piece alumina-toughened zirconia (ATZ) oral implant for single tooth replacement after 1 year. A total of 27 patients received one ATZ implant each in a one-stage implant surgery with immediate temporization. Standardized radiographs were taken at implant insertion and after 1 year to monitor peri-implant bone loss. Several soft tissue parameters were evaluated at prosthesis insertion and at the 1-year follow-up. Three patients did not receive a prosthetic reconstruction due to implant loss during the healing period. As a result, 24 patients were seen at the 1-year follow-up, giving a cumulative survival rate of 88.9%. The average marginal bone loss after 1 year was 0.77 mm. Only two implants (8.3%) lost at least 2 mm bone, whereas none of the implants lost more than 3 mm. Probing depth and clinical attachment level increased over 1 year at the implant sites, whereas gingival recessio...
The Journal of the American Dental Association, 2014
Background: The recent increase in computer-aided design and computer-aided manufacturing (CAD/CA... more Background: The recent increase in computer-aided design and computer-aided manufacturing (CAD/CAM)-assisted surgery has warranted a thorough evaluation of the accuracy of virtual plan execution. Mandibular reconstructions with a fibula free flap were evaluated by comparing the fibular segments postoperatively with the virtual surgical plans. Methods: This study included computed tomography data for 20 patients (11 males; mean age 61.3 years, range 47-74) that received a mandibular reconstruction with a fibula free flap. Linear distances (superior and inferior borders) of 41 fibula segments and intercoronoid distances were measured. Results: The mean difference was 3.11 AE 2.80 mm for superior borders (range 0.02-12.20 mm), and 2.75 AE 2.61 mm for inferior borders (range 0.22-13.58 mm). The mean intercoronoid difference was 3.57 AE 1.80 mm (range 0.91-6.11 mm). Conclusion: This study confirmed the presumed accuracy regarding the use of fibular and mandibular cutting guides. CAD/CAM is an attractive technique which enhances efficiency and assurance during surgery and preoperative planning.
When prospectively applied for regenerative therapies, human bone-marrow-derived mesenchymal stem... more When prospectively applied for regenerative therapies, human bone-marrow-derived mesenchymal stem cells (hMSCs) interact with the locally residing host cells. With respect to the developmentally particular origin of oral cells, little is known about the putatively discriminative behavioral responses of hMSCs in interaction with various oral cell types, including human alveolar bone osteoblasts (hOAs), periodontal ligament fibroblasts (hPDLs), and gingival fibroblasts (hGFs). To assess the crosstalk between hMSCs and oral cells, interactive cocultures were established by combining well-characterized hMSCs with hOAs, hPDLs, or hGFs, and the behavioral hMSC aspects, that is, proliferation and gene expression, were measured by employing a 5-bromo-2¢deoxyuridine assay and real-time polymerase chain reaction, while apoptosis was quantified by in situ cell death detection kit. hMSCs expressed the typical antigen spectrum lacking CD34, CD45, CD14, CD19, and HLA-DR, while expressing CD73, CD90, and CD105, and could successfully be transformed into adipocytes, osteocytes, and chondrocytes. Monocultured control hMSCs proliferated readily, whereas a general reduction of BrdUlabeled cells was observed in cocultures. Globally, upon extending time periods, interactive coculture combinations of hMSCs with hOAs reduced both osteogenic gene and stem cell marker transcription in hMSCs, a phenomenon appearing less pronounced by combining hMSCs with hPDLs, such that the observed effects in terms of proliferation and gene expression followed the same ranking: hOAs > hGFs > hPDLs. Vice versa, in interactive hMSC cocultures, the cell survival rate was significantly increased, irrespective from the combined coculture cell counterpart. Our results show for the first time that behavior of hMSCs reflected by proliferation and gene expression was governed by interaction with various oral cells in a cell-type-discriminative manner. In addition, hMSC coculture restrains apoptosis, such that influences on cell behavior appear as a crosstalk. In summary, interactive cocultures render the basis for a prospective prediction of mutual cell behavior in hMSCbased oral tissue regeneration disclosing that oral cells shift hMSC behavior from proliferation to differentiation and apoptosis-repressing features.
Objective: To investigate the incidence of postoperative generalized seizures in patients undergo... more Objective: To investigate the incidence of postoperative generalized seizures in patients undergoing aortic valve replacement (AVR) under extracorporeal circulation, who received either high-dose tranexamic acid (TXA) or epsilon aminocaproic acid (EACA) as an antifibrinolytic agent. Methods: This retrospective analysis comprised 682 consecutive patients undergoing AVR with or without simultaneous coronary artery bypass surgery. Patients operated on before March 2008 were treated intra-operatively with TXA (100 mg kg À1 ; n = 341), patients operated on after March 2008 received EACA (50 mg kg À1 loading dose, followed by 25 mg kg À1 h À1 , and an additional 5 g in the extracorporeal circuit; n = 341). Results: Clinically diagnosed generalized seizures were observed within the first 24 h postoperatively, more frequently in patients receiving TXA compared with EACA (6.4% vs 0.6%, p < 0.001, difference = 5.8%, 95% confidence interval 3.1-8.5%). Besides the antifibrinolytic agent, three other variables differed significantly between patients with and without postoperative seizures: age (mean (SD), 77.0 (5.9) years vs 73.2 (9.0) years, p = 0.039), preoperative creatinine clearance (55.4 (16.5) ml min À1 vs 72.6 (28.5) ml min À1 , p = 0.002), and administration of recombinant activated factor VIIa (3 out of 24 patients (12.5%) vs 8 out of 658 patients (1.2%), p = 0.005). Logistic regression analysis demonstrated a significant impact of the antifibrinolytic drug, creatinine clearance, and the application of recombinant activated factor VIIa on the occurrence of generalized seizures. Conclusions: Our results indicate that high-dose TXA is associated with an increased incidence of postoperative generalized seizures in patients undergoing AVR compared with EACA, especially when suffering from renal impairment. A possible association between recombinant activated factor VIIa and the occurrence of postoperative seizures needs further investigation.
The aim of this study was to evaluate the accuracy of two-dimensional (2D) and three-dimensional ... more The aim of this study was to evaluate the accuracy of two-dimensional (2D) and three-dimensional (3D) root canal length measurements in molar teeth using cone beam computed tomography (CBCT). Root canal lengths of twenty molar teeth were measured with two different CBCT approaches. After adjusting the CBCT images, 2D measurements were performed within the sagittal plane between the apical foramen and the coronal reference (cusp). The 3D approach measured centrically in axial planes. A linear mixed model with random intercepts was fitted to compare differences between methods (2D and 3D). The correlation between CBCT measurements and the actual root canal length was evaluated using the Pearson correlation coefficient. Differences between 3D measurements and the actual root canal lengths were significantly smaller compared to the 2D approach (p &lt; 0.001). Mean differences were 0.32 and 0.58 mm, respectively. A high correlation was found between the actual root canal length and 3D measurements (Pearson correlation coefficient = 0.97). Compared to the actual root canal length, 80 % of the 3D measurements were within the limits of ±0.5 mm. 3D measurements of root canals in molar teeth are more accurate than simple 2D measurements and show a high correlation to the actual lengths. In cases where a CBCT is already available, root canal lengths in molar teeth can be accurately predetermined using a standardized 3D approach.
Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency syndrome with alte... more Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency syndrome with alterations in T cell regulation and function in a subgroup of patients. We assessed phenotype and function of bulk and virus-specific CD8+ T cells of a cohort of 34 HLA-A2+ CVID patients by pentamer technology and flow cytometry in relationship to their immunological and clinical phenotypes. Bulk CD8+ T cells displayed a shift toward a more antigen experienced and activated differentiation state. The advanced differentiation pattern was mainly found in a subgroup of CVID patients with lymphadenopathy and granulomatous disease. This effect existed independently of the patients' CMV status even so CMV-associated immunosenescence was more evident in CVID patients than in CMV-positive immunocompetent controls. As the phenotype and function of virus-specific CD8+ T cells were normal in CVID the induction of antiviral immunity by prophylactic immunization appears to be a logical and desirable aim for this group of patients.
Kidney transplantation from older and marginal donors is effective to confront organ shortage. Ho... more Kidney transplantation from older and marginal donors is effective to confront organ shortage. However, limitations after transplantation of kidneys from very marginal kidney donors remain unclear. We compared patient and graft outcome, achieved allograft function and quality of life of renal transplantations from Very Senior Donors (VSD, defined as donors aged 70 years and older) with Senior Donors (SD, aged 60-70 years) and Regular Donors (RD, aged younger than 60 years) in Switzerland. We evaluated the outcome of 1554 adult recipients of deceased donor kidney transplantations from 05/2008 to 12/2019; median follow-up was 4.7 years. Failure-free survival (freedom from graft loss or death), glomerular filtration rate (eGFR), and quality of life at 12 months were analyzed for RD (reference group, n = 940), SD (n = 404), and VSD (n = 210). Failure-free survival decreased with increasing donor age, mainly attributable to premature graft loss. Still, overall 5-year failure-free survival reached 83.1%, 81.0%, and 64.0% in the RD, SD, and VSD subgroups, respectively. eGFR 12 months post-transplantation was significantly higher in RD compared with SD and VSD. The acceptance rate of donor candidates for kidney TPL was 78% for the entire cohort (87% for RD, 79% for SD, and 56% for VSD). Deceased donor kidney transplantation from donors aged 70 years or older is associated with an inferior, yet acceptable failure-free outcome, with sustained quality of life.
The long-term success of indirect restorations depends on the clinical behavior of luting cements... more The long-term success of indirect restorations depends on the clinical behavior of luting cements. In the oral environment, properties such as water sorption and solubility negatively affect the cements&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; clinical performance over time, jeopardizing the restoration&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s longevity. The purpose of this in vitro study was to compare the water sorption and solubility characteristics of self-etching, self-adhesive, and conventional resin cements. One conventional (Calibra), 1 self-etching (Panavia F), and 2 self-adhesive (Clearfil SA) dual-polymerized resin cements were used. Fourteen disks of each material were prepared. Water sorption and solubility were calculated according to International Organization for Standards (ISO) specification 4049:2009. According to the water sorption test, all materials were found to interact with water. No statistically significant differences were found between the water sorption of Panavia F and Clearfil SA (P=.911). These cements exhibited higher water sorption values than the other materials (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05), whereas Calibra exhibited the lowest values (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05). Statistically significant differences were found among all materials regarding their water solubility (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05). Panavia F and Clearfil SA were found to have higher solubility values than the other materials. G-Cem Automix and Calibra exhibited negative solubility. However, all water sorption and solubility values were below the threshold values proposed by the ISO standard. Within the limitations of the present in vitro study, the interaction of resin cements with water is not type-related (conventional, self-etching, or self-adhesive).
The aim of this prospective randomised controlled clinical trial was to evaluate the clinical out... more The aim of this prospective randomised controlled clinical trial was to evaluate the clinical outcome of shrinkage-free ZrSiO4 -ceramic full-coverage crowns on premolars and molars in comparison with conventional gold crowns over a 5-year period. Two hundred and twenty-three patients were included and randomly divided into two treatment groups. One hundred and twenty-three patients were restored with 123 ZrSiO4 -ceramic crowns, and 100 patients received 100 gold crowns, which served as the control. All crowns were conventionally cemented with glass-ionomer cement. After an observation period of 6, 12, 24, 36, 48 and 60 months, the survival probability (Kaplan-Meier) for the shrinkage-free ZrSiO4 -ceramic crowns was 98·3%, 92·0%, 84·7%, 79% and 73·2% and for the gold crowns, 99%, 97·9%, 95·7%, 94·6% and 92·3%, respectively. The difference between the test and control group was statistically significant (P = 0·0027). The gold crowns showed a better marginal integrity with less marginal discoloration than the ceramic crowns. The most common failure in the ceramic crown group was fracture of the crown. The 60-month results of this prospective randomised controlled clinical trial suggest that the use of these shrinkage-free ZrSiO4 -ceramic crowns in posterior tooth restorations cannot be recommended.
The aim of this study was to analyze first year renal outcomes in a nationwide prospective multic... more The aim of this study was to analyze first year renal outcomes in a nationwide prospective multicenter cohort comprising 2215 renal transplants, with a special emphasis on the presence of pre‐transplant donor‐specific HLA antibodies (DSA). All transplants had a complete virtual crossmatch and DSA were detected in 19% (411/2215). The investigated composite endpoint was a poor first‐year outcome defined as (i) allograft failure or (ii) death or (iii) poor allograft function (eGFR ≤25 ml/min/1.73 m2) at one year. Two hundred and twenty‐one (221/2215; 10%) transplants showed a poor first‐year outcome. Rejection (24/70; 34%) was the most common reason for graft failure. First‐year patient’s death was rare (48/2215; 2%). There were no statistically significant differences between DSA‐positive and DSA‐negative transplants regarding composite and each individual endpoint, as well as reasons for graft failure and death. DSA‐positive transplants experienced more frequently rejection episodes, mainly antibody‐mediated rejection (both P < 0.0001). The combination of DSA and any first year rejection was associated with the overall poorest death‐censored allograft survival (P < 0.0001). In conclusion, presence of pre‐transplant DSA per se does not affect first year outcomes. However, DSA‐positive transplants experiencing first year rejection are a high‐risk population for poor allograft survival and may benefit from intense clinical surveillance.
PurposeThe Swiss Transplant Cohort Study (STCS) is a prospective multicentre cohort study which s... more PurposeThe Swiss Transplant Cohort Study (STCS) is a prospective multicentre cohort study which started to actively enrol study participants in May 2008. It takes advantage of combining data from all transplant programmes in one unique system to perform comprehensive nationwide reporting and to promote translational and clinical post-transplant outcome research in the framework of Swiss transplantation medicine.ParticipantsOver 5500 solid organ transplant recipients have been enrolled in all six Swiss transplant centres by end of 2019, around three-quarter of them for kidney and liver transplants. Ninety-three per cent of all transplanted recipients have consented to study participation, almost all of them (99%) contributed to bio-sampling. The STCS genomic data set includes around 3000 patients.Findings to dateDetailed clinical and laboratory data in high granularity as well as patient-reported outcomes from transplant recipients and activities in Switzerland are available in the l...
Zusammenfassung Gegenstand und Ziel: Mit dieser Studie sollte das Vorkommen von Bordetella (B.) b... more Zusammenfassung Gegenstand und Ziel: Mit dieser Studie sollte das Vorkommen von Bordetella (B.) bronchiseptica in Mehrkatzenhaushalten mit und ohne respiratorische Symptome untersucht werden. Material und Methoden: Die Studie umfasste insgesamt 258 Katzen aus 40 Beständen. Antikörper gegen B. bronchiseptica wurden mittels ELISA nachgewiesen. Zudem erfolgten eine PCR und eine Erregeranzüchtung. Ergebnisse: Die Antikörperprävalenz lag bei 41,9%. Bei Katzen mit respiratorischen Symptomen ergab sich eine Prävalenz von 56,5%, bei gesunden Katzen betrug sie 39,9%. Dieser Unterschied war statistisch signifikant. Die Antikörperprävalenz lag in Tierheimen signifikant höher als in Privat- und Zuchtbeständen. Ältere Katzen wiesen signifikant häufiger Antikörper gegen B. bronchiseptica auf. Die PCR war nur bei 4,6% von 219 untersuchten Katzen positiv; die Anzüchtung gelang bei keinem von 28 untersuchten Tieren. Schlussfolgerung und klinische Relevanz: B. bronchiseptica zeigt in Mehrkatzenhausha...
In solid organ transplant recipients (sOTRs), 5 years after transplantation cancer is a relevant ... more In solid organ transplant recipients (sOTRs), 5 years after transplantation cancer is a relevant cause of death. We aimed to report cancer incidence in the Swiss Transplant Cohort Study (STCS) between 2008 and 2014 and conducted a prospective cohort study of kidney, heart, lung, pancreas and liver transplant recipients enrolled into the STCS by retrospective analysis of collected data. The STCS provided data on 2758 solid organ transplants. In total, 134 cases of cancer were observed (30 liver, 21 prostate, 18 lung, 13 kidney, 52 other cancers). Standardised incidence ratios (SIRs) were highest for liver cancer, kidney cancer, thyroid cancer, gastric cancer, bladder cancer, cancer of the oral cavity and the pharynx and for lung cancer. Cancer occurrence differed according to the transplanted organ. Cancers were mainly diagnosed at World Health Organisation (WHO) stages I and IV. Treatment received was mainly surgery and, in some cases, included also radiation and/or chemotherapy. Bladder, kidney, liver, lung and prostate cancer were detected at a younger age compared with the general population. Cumulative hazards for death were increased for transplant recipients with cancer. Solid organ transplant recipients show an organ specific increase of cancer compared with the general Swiss population. Clinical trial registration number: NCT02333279
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jan 31, 2016
We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex viru... more We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infe...
Galactose-deficient IgA1 (Gd-IgA1) and IgA-IgG complexes are known to play an important role in t... more Galactose-deficient IgA1 (Gd-IgA1) and IgA-IgG complexes are known to play an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed therefore to determine the impact of immunosuppression on the serum levels of Gd-IgA1, total IgA1 and IgA-IgG complexes in IgAN patients. In a retrospective study, serum samples from IgAN patients collected before transplantation (t0) and at 3- and 6-month posttransplant (t3 & t6) were used to measure the levels of Gd-IgA1, total IgA1 and IgA-IgG complexes. The area under the curves (AUC) of immunosuppressants was calculated by the plot of plasma trough level or dosage of each immunosuppressant versus time and was interpreted as the extent of drug exposure. Thirty-six out of 64 IgAN patients, who underwent kidney transplantation between 2005 and 2012, were enrolled. From t0 to t3, serum Gd-IgA1 and total IgA1 decreased significantly (24.7 AU (18.6-36.1) to 17.2 (13.1-29.5) (p<0.0001); 4.1 mg/ml (3.6-5.1) to 3.4 (3.0-4.1) (p = 0.0005)...
The objective of this investigation was to determine the clinical and radiographic outcome of a o... more The objective of this investigation was to determine the clinical and radiographic outcome of a one-piece alumina-toughened zirconia (ATZ) oral implant for single tooth replacement after 1 year. A total of 27 patients received one ATZ implant each in a one-stage implant surgery with immediate temporization. Standardized radiographs were taken at implant insertion and after 1 year to monitor peri-implant bone loss. Several soft tissue parameters were evaluated at prosthesis insertion and at the 1-year follow-up. Three patients did not receive a prosthetic reconstruction due to implant loss during the healing period. As a result, 24 patients were seen at the 1-year follow-up, giving a cumulative survival rate of 88.9%. The average marginal bone loss after 1 year was 0.77 mm. Only two implants (8.3%) lost at least 2 mm bone, whereas none of the implants lost more than 3 mm. Probing depth and clinical attachment level increased over 1 year at the implant sites, whereas gingival recessio...
The Journal of the American Dental Association, 2014
Background: The recent increase in computer-aided design and computer-aided manufacturing (CAD/CA... more Background: The recent increase in computer-aided design and computer-aided manufacturing (CAD/CAM)-assisted surgery has warranted a thorough evaluation of the accuracy of virtual plan execution. Mandibular reconstructions with a fibula free flap were evaluated by comparing the fibular segments postoperatively with the virtual surgical plans. Methods: This study included computed tomography data for 20 patients (11 males; mean age 61.3 years, range 47-74) that received a mandibular reconstruction with a fibula free flap. Linear distances (superior and inferior borders) of 41 fibula segments and intercoronoid distances were measured. Results: The mean difference was 3.11 AE 2.80 mm for superior borders (range 0.02-12.20 mm), and 2.75 AE 2.61 mm for inferior borders (range 0.22-13.58 mm). The mean intercoronoid difference was 3.57 AE 1.80 mm (range 0.91-6.11 mm). Conclusion: This study confirmed the presumed accuracy regarding the use of fibular and mandibular cutting guides. CAD/CAM is an attractive technique which enhances efficiency and assurance during surgery and preoperative planning.
When prospectively applied for regenerative therapies, human bone-marrow-derived mesenchymal stem... more When prospectively applied for regenerative therapies, human bone-marrow-derived mesenchymal stem cells (hMSCs) interact with the locally residing host cells. With respect to the developmentally particular origin of oral cells, little is known about the putatively discriminative behavioral responses of hMSCs in interaction with various oral cell types, including human alveolar bone osteoblasts (hOAs), periodontal ligament fibroblasts (hPDLs), and gingival fibroblasts (hGFs). To assess the crosstalk between hMSCs and oral cells, interactive cocultures were established by combining well-characterized hMSCs with hOAs, hPDLs, or hGFs, and the behavioral hMSC aspects, that is, proliferation and gene expression, were measured by employing a 5-bromo-2¢deoxyuridine assay and real-time polymerase chain reaction, while apoptosis was quantified by in situ cell death detection kit. hMSCs expressed the typical antigen spectrum lacking CD34, CD45, CD14, CD19, and HLA-DR, while expressing CD73, CD90, and CD105, and could successfully be transformed into adipocytes, osteocytes, and chondrocytes. Monocultured control hMSCs proliferated readily, whereas a general reduction of BrdUlabeled cells was observed in cocultures. Globally, upon extending time periods, interactive coculture combinations of hMSCs with hOAs reduced both osteogenic gene and stem cell marker transcription in hMSCs, a phenomenon appearing less pronounced by combining hMSCs with hPDLs, such that the observed effects in terms of proliferation and gene expression followed the same ranking: hOAs > hGFs > hPDLs. Vice versa, in interactive hMSC cocultures, the cell survival rate was significantly increased, irrespective from the combined coculture cell counterpart. Our results show for the first time that behavior of hMSCs reflected by proliferation and gene expression was governed by interaction with various oral cells in a cell-type-discriminative manner. In addition, hMSC coculture restrains apoptosis, such that influences on cell behavior appear as a crosstalk. In summary, interactive cocultures render the basis for a prospective prediction of mutual cell behavior in hMSCbased oral tissue regeneration disclosing that oral cells shift hMSC behavior from proliferation to differentiation and apoptosis-repressing features.
Objective: To investigate the incidence of postoperative generalized seizures in patients undergo... more Objective: To investigate the incidence of postoperative generalized seizures in patients undergoing aortic valve replacement (AVR) under extracorporeal circulation, who received either high-dose tranexamic acid (TXA) or epsilon aminocaproic acid (EACA) as an antifibrinolytic agent. Methods: This retrospective analysis comprised 682 consecutive patients undergoing AVR with or without simultaneous coronary artery bypass surgery. Patients operated on before March 2008 were treated intra-operatively with TXA (100 mg kg À1 ; n = 341), patients operated on after March 2008 received EACA (50 mg kg À1 loading dose, followed by 25 mg kg À1 h À1 , and an additional 5 g in the extracorporeal circuit; n = 341). Results: Clinically diagnosed generalized seizures were observed within the first 24 h postoperatively, more frequently in patients receiving TXA compared with EACA (6.4% vs 0.6%, p < 0.001, difference = 5.8%, 95% confidence interval 3.1-8.5%). Besides the antifibrinolytic agent, three other variables differed significantly between patients with and without postoperative seizures: age (mean (SD), 77.0 (5.9) years vs 73.2 (9.0) years, p = 0.039), preoperative creatinine clearance (55.4 (16.5) ml min À1 vs 72.6 (28.5) ml min À1 , p = 0.002), and administration of recombinant activated factor VIIa (3 out of 24 patients (12.5%) vs 8 out of 658 patients (1.2%), p = 0.005). Logistic regression analysis demonstrated a significant impact of the antifibrinolytic drug, creatinine clearance, and the application of recombinant activated factor VIIa on the occurrence of generalized seizures. Conclusions: Our results indicate that high-dose TXA is associated with an increased incidence of postoperative generalized seizures in patients undergoing AVR compared with EACA, especially when suffering from renal impairment. A possible association between recombinant activated factor VIIa and the occurrence of postoperative seizures needs further investigation.
The aim of this study was to evaluate the accuracy of two-dimensional (2D) and three-dimensional ... more The aim of this study was to evaluate the accuracy of two-dimensional (2D) and three-dimensional (3D) root canal length measurements in molar teeth using cone beam computed tomography (CBCT). Root canal lengths of twenty molar teeth were measured with two different CBCT approaches. After adjusting the CBCT images, 2D measurements were performed within the sagittal plane between the apical foramen and the coronal reference (cusp). The 3D approach measured centrically in axial planes. A linear mixed model with random intercepts was fitted to compare differences between methods (2D and 3D). The correlation between CBCT measurements and the actual root canal length was evaluated using the Pearson correlation coefficient. Differences between 3D measurements and the actual root canal lengths were significantly smaller compared to the 2D approach (p &lt; 0.001). Mean differences were 0.32 and 0.58 mm, respectively. A high correlation was found between the actual root canal length and 3D measurements (Pearson correlation coefficient = 0.97). Compared to the actual root canal length, 80 % of the 3D measurements were within the limits of ±0.5 mm. 3D measurements of root canals in molar teeth are more accurate than simple 2D measurements and show a high correlation to the actual lengths. In cases where a CBCT is already available, root canal lengths in molar teeth can be accurately predetermined using a standardized 3D approach.
Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency syndrome with alte... more Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency syndrome with alterations in T cell regulation and function in a subgroup of patients. We assessed phenotype and function of bulk and virus-specific CD8+ T cells of a cohort of 34 HLA-A2+ CVID patients by pentamer technology and flow cytometry in relationship to their immunological and clinical phenotypes. Bulk CD8+ T cells displayed a shift toward a more antigen experienced and activated differentiation state. The advanced differentiation pattern was mainly found in a subgroup of CVID patients with lymphadenopathy and granulomatous disease. This effect existed independently of the patients' CMV status even so CMV-associated immunosenescence was more evident in CVID patients than in CMV-positive immunocompetent controls. As the phenotype and function of virus-specific CD8+ T cells were normal in CVID the induction of antiviral immunity by prophylactic immunization appears to be a logical and desirable aim for this group of patients.
Kidney transplantation from older and marginal donors is effective to confront organ shortage. Ho... more Kidney transplantation from older and marginal donors is effective to confront organ shortage. However, limitations after transplantation of kidneys from very marginal kidney donors remain unclear. We compared patient and graft outcome, achieved allograft function and quality of life of renal transplantations from Very Senior Donors (VSD, defined as donors aged 70 years and older) with Senior Donors (SD, aged 60-70 years) and Regular Donors (RD, aged younger than 60 years) in Switzerland. We evaluated the outcome of 1554 adult recipients of deceased donor kidney transplantations from 05/2008 to 12/2019; median follow-up was 4.7 years. Failure-free survival (freedom from graft loss or death), glomerular filtration rate (eGFR), and quality of life at 12 months were analyzed for RD (reference group, n = 940), SD (n = 404), and VSD (n = 210). Failure-free survival decreased with increasing donor age, mainly attributable to premature graft loss. Still, overall 5-year failure-free survival reached 83.1%, 81.0%, and 64.0% in the RD, SD, and VSD subgroups, respectively. eGFR 12 months post-transplantation was significantly higher in RD compared with SD and VSD. The acceptance rate of donor candidates for kidney TPL was 78% for the entire cohort (87% for RD, 79% for SD, and 56% for VSD). Deceased donor kidney transplantation from donors aged 70 years or older is associated with an inferior, yet acceptable failure-free outcome, with sustained quality of life.
The long-term success of indirect restorations depends on the clinical behavior of luting cements... more The long-term success of indirect restorations depends on the clinical behavior of luting cements. In the oral environment, properties such as water sorption and solubility negatively affect the cements&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; clinical performance over time, jeopardizing the restoration&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s longevity. The purpose of this in vitro study was to compare the water sorption and solubility characteristics of self-etching, self-adhesive, and conventional resin cements. One conventional (Calibra), 1 self-etching (Panavia F), and 2 self-adhesive (Clearfil SA) dual-polymerized resin cements were used. Fourteen disks of each material were prepared. Water sorption and solubility were calculated according to International Organization for Standards (ISO) specification 4049:2009. According to the water sorption test, all materials were found to interact with water. No statistically significant differences were found between the water sorption of Panavia F and Clearfil SA (P=.911). These cements exhibited higher water sorption values than the other materials (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05), whereas Calibra exhibited the lowest values (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05). Statistically significant differences were found among all materials regarding their water solubility (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05). Panavia F and Clearfil SA were found to have higher solubility values than the other materials. G-Cem Automix and Calibra exhibited negative solubility. However, all water sorption and solubility values were below the threshold values proposed by the ISO standard. Within the limitations of the present in vitro study, the interaction of resin cements with water is not type-related (conventional, self-etching, or self-adhesive).
The aim of this prospective randomised controlled clinical trial was to evaluate the clinical out... more The aim of this prospective randomised controlled clinical trial was to evaluate the clinical outcome of shrinkage-free ZrSiO4 -ceramic full-coverage crowns on premolars and molars in comparison with conventional gold crowns over a 5-year period. Two hundred and twenty-three patients were included and randomly divided into two treatment groups. One hundred and twenty-three patients were restored with 123 ZrSiO4 -ceramic crowns, and 100 patients received 100 gold crowns, which served as the control. All crowns were conventionally cemented with glass-ionomer cement. After an observation period of 6, 12, 24, 36, 48 and 60 months, the survival probability (Kaplan-Meier) for the shrinkage-free ZrSiO4 -ceramic crowns was 98·3%, 92·0%, 84·7%, 79% and 73·2% and for the gold crowns, 99%, 97·9%, 95·7%, 94·6% and 92·3%, respectively. The difference between the test and control group was statistically significant (P = 0·0027). The gold crowns showed a better marginal integrity with less marginal discoloration than the ceramic crowns. The most common failure in the ceramic crown group was fracture of the crown. The 60-month results of this prospective randomised controlled clinical trial suggest that the use of these shrinkage-free ZrSiO4 -ceramic crowns in posterior tooth restorations cannot be recommended.
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