Dental care and oral health in solid organ transplant recipients: a single center cross-sectional study and survey of German transplant centers

Aim of this study was to collect information about oral health of patients before and after SOT as well as information about center‐based recommendations for dental care. In a single center cross‐sectional study, the oral situation of 20 patients before and 20 after SOT were examined including dental (DMF‐T), periodontal (PSR^®/PSI), and oral hygiene findings (modified QHI). In a second project, a survey among 50 transplant centers in Germany was questioned regarding their recommendations for dental care of SOT recipients. Patients before and after SOT showed similar quality of dental findings (DMF‐T), but worse compared to the general population. In addition, most patients in both groups showed pronounced periodontal treatment need (PSR^®/PSI score 3 or 4). Oral hygiene findings (modified QHI) after SOT were significantly worse than in patients on the waiting list (P = 0.032). In a second project, the questionnaire was returned by 28 of 50 centers. Interpretation of data showed that 89% carry out a dental examination before SOT and 67% contacted the patients’ dentists. After SOT, 83% of the transplant centers recommend antibiotic cover before dental measures. The results of our study revealed lacks in the dental care of SOT recipients. Consistent recommendations regarding the dental care of patients before and after SOT should be determined.     

The protective role of Smad7 in diabetic kidney disease: mechanism and therapeutic potential

OBJECTIVE

Although Smad3 has been considered as a downstream mediator of transforming growth factor-β (TGF-β) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear. The current study tests the hypothesis that Smad7 may play a protective role and has therapeutic potential for diabetic kidney disease.

RESEARCH DESIGN AND METHODS

Protective role of Smad7 in diabetic kidney disease was examined in streptozotocin-induced diabetic mice that have Smad7 gene knockout (KO) and in diabetic rats given Smad7 gene transfer using an ultrasound-microbubble-mediated technique.

RESULTS

We found that mice deficient for Smad7 developed more severe diabetic kidney injury than wild-type mice as evidenced by a significant increase in microalbuminuria, renal fibrosis (collagen I, IV, and fibronectin), and renal inflammation (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α], monocyte chemoattractant protein-1 [MCP-1], intracellular adhesion molecule-1 [ICAM-1], and macrophages). Further studies revealed that enhanced renal fibrosis and inflammation in Smad7 KO mice with diabetes were associated with increased activation of both TGF-β/Smad2/3 and nuclear factor-κB (NF-κB) signaling pathways. To develop a therapeutic potential for diabetic kidney disease, Smad7 gene was transferred into the kidney in diabetic rats by an ultrasound-microbubble-mediated technique. Although overexpression of renal Smad7 had no effect on levels of blood glucose, it significantly attenuated the development of microalbuminuria, TGF-β/Smad3-mediated renal fibrosis such as collagen I and IV and fibronectin accumulation and NF-κB/p65-driven renal inflammation including IL-1β, TNF-α, MCP-1, and ICAM-1 expression and macrophage infiltration in diabetic rats.

CONCLUSIONS

Smad7 plays a protective role in diabetic renal injury. Overexpression of Smad7 may represent a novel therapy for the diabetic kidney complication.Diabetic nephropathy is a major complication of diabetes (1–4). Approximately 20–40% of patients with type 1 or type 2 diabetes mellitus (DM) develop diabetic nephropathy (5,6). Diabetic nephropathy is characterized by excessive deposition of extracellular matrix (ECM) proteins in the mesangium and tubulointerstitium, thickness of basement membrane of the glomeruli, and loss of podocytes with the development of microalbuminuria and a decline of renal function (2,3,7). Both in vivo and in vitro studies have demonstrated that renal fibrosis and inflammation play an important role in the pathogenesis of diabetic kidney disease (2–4,7–10). Transforming growth factor-β (TGF-β) family is a crucial mediator in the development of diabetic nephropathy (11–15).It is now clear that after binding to its receptors, TGF-β signals through two critical downstream mediators, Smad2 and Smad3, to exert its biological activities such as ECM production. In addition, TGF-β₁ also induces an inhibitory Smad called Smad7, which negatively regulates activation of Smad2/3 by TGF-β receptor competition and degradation via the ubiquitin-proteasome degradation mechanism (16,17). Recent studies have demonstrated that overexpression of Smad7 is capable of inhibiting renal fibrosis and inflammation by blocking the activation of both TGF-β/Smad and nuclear factor-κB (NF-κB) signaling pathway (18–22). In contrast, deletion of Smad7 promotes renal fibrosis and inflammation (23), suggesting that Smad7 may be a key regulator and a therapeutic agent for renal fibrosis and inflammation (24). Although it has been reported that Smad3 is pathogenic in fibrosis including diabetic kidney disease (25,26), the role of Smad7 in diabetes complications remains unexplored, and it is unknown whether blockade of the TGF-β signaling pathway by Smad7 has therapeutic potential for diabetes complications. Thus, in the current study, we uncovered the role of Smad7 in diabetic kidney disease induced in Smad7 knockout (KO) mice and developed new therapeutic strategy for diabetic kidney complication by targeting the TGF-β/Smad pathway with ultrasound-microbubble-mediated Smad7 gene therapy.     

Three-dimensional constructive interference in steady-state magnetic resonance imaging in syringomyelia: advantages over conventional imaging

OBJECT: Neuroradiology has become indispensable in detecting the pathophysiology in syringomyelia. Constructive interference in steady-state (CISS) magnetic resonance (MR) imaging can provide superior contrast at the sub-arachnoid tissue borders. As this region is critical in preoperative evaluation, the authors hypothesized that CISS imaging would provide superior assessment of syrinx pathology and surgical planning. METHODS: Based on records collected from a database of 130 patients with syringomyelia treated at the authors' institution, 59 patients were prospectively evaluated with complete neuroradiological examinations. In addition to routine acquisitions with FLAIR, T1- and T2-weighted, and contrast-enhanced MR imaging series, the authors obtained sagittal cardiac-gated sequences to visualize cerebrospinal fluid (CSF) pulsations and axial 3D CISS MR sequences to detect focal arachnoid webs. Statistical qualitative and quantitative evaluations of spinal cord/CSF contrast, spinal cord/CSF delineation, motion artifacts, and artifacts induced by pulsatile CSF flow were performed. RESULTS: The 3D CISS MR sequences demonstrated a contrast-to-noise ratio significantly better than any other routine imaging sequence (p < 0.001). Moreover, 3D CISS imaging can detect more subarachnoid webs and cavitations in the syrinx than T2-weighted MR imaging with less flow-void artifact. The limitation of 3D CISS imaging is a susceptibility to motion artifacts that can cause reduced spatial resolution. Lengthy acquisition times for axial segments can be reduced with multiplanar reconstruction of 3D CISS-generated sagittal images. CONCLUSIONS: Constructive interference in steady-state imaging is the MR sequence of choice in the preoperative evaluation of syringomyelia, allowing significantly higher detection rates of focal subarachnoid webs, whereas standard T2-weighted MR imaging shows turbulent CSF flow voids. Constructive interference in steady-state MR imaging enables the neurosurgeon to accurately identify cases requiring decompression for obstructed CSF. Motion artifacts can be eliminated with technical variations.     

Transplantation of tracheal epithelial cells onto a prefabricated capsule pouch with fibrin glue as a delivery vehicle

OBJECTIVE: The purpose of this study was to investigate whether in vitro cultured tracheal epithelial cells can be transplanted onto a prefabricated capsule surface in vivo for possible use in tracheal reconstruction. METHODS: Tracheal epithelial cells from 12 donor inbred rats were harvested for culture and expansion. In 16 recipient inbred rats, 2 sterile cylinders made of silicone rubber were implanted in each rat bilaterally in the folds of both the left and right anterior rectus sheath by wrapping the sheaths around the cylinders to induce a capsule formation. Ten days later, the cell cultures were divided and suspended in 1 of 2 delivery vehicles (standard culture medium or fibrin glue) and implanted onto the capsule surface. To compare the 2 delivery vehicles, we used fibrin glue on one side and the standard culture medium on the other. RESULTS: After 2 (group 1, n = 8) and 4 (group 2, n = 8) weeks, histologic findings, immunohistochemical staining, and electron microscopy demonstrated the capsule to be covered with a tracheal neoepithelium in group 1 and additional ciliated cells and secretory cells in a confluent layer in group 2 but only on the side with fibrin glue as the delivery vehicle. No viable epithelial cells were identified on the side with the standard culture medium in either group. CONCLUSION: We conclude that cultured epithelial cells can be successfully transplanted onto a prefabricated capsule surface with fibrin glue, which will differentiate into morphologic, nearly normal epithelium, showing potential for tracheal reconstruction.     

Failure of Autologous Fresh Frozen Plasma to Reduce Blood Loss and Transfusion Requirements in Coronary Artery Bypass Surgery

Background: Previous studies failed to demonstrate any benefit from prophylaxis with fresh frozen plasma (FFP) after cardiopulmonary bypass (CPB). The results, however, were limited by either retrospective study design or use of FFP in subtherapeutic doses (2-3 units). The authors evaluated whether a therapeutic dose (15 ml/kg) of FFP reduces blood loss and transfusion requirements in elective coronary artery bypass surgery. The risks of multiple allogeneic blood donor exposure were circumvented by using autologous plasma.

Methods: Sixty adult patients scheduled for elective primary coronary artery bypass grafting were randomized to receive, after CPB, an intravenous infusion of 15 ml/kg of either autologous FFP (30 patients) or 6% hydroxyethyl starch 450/0.7 (HES; 30 patients). Autologous plasma was obtained by platelet-poor plasmapheresis several weeks before surgery. Perioperative blood transfusions were administered per protocol. Postoperative blood loss was defined as the chest tube drainage during the first 24 h after surgery.

Results: The data from 56 patients (FFP group, 27 patients; HES group, 29 patients) who completed the study according to protocol were analyzed. Median postoperative blood loss was 630 ml (range, 450-1,840 ml) and 830 ml (range, 340-1,980 ml) in the FFP and HES groups, respectively (P = 0.08). Both postoperative (0-24 h) and total perioperative erythrocyte transfusion requirements did not differ significantly between the groups (P = 0.32 and 0.14, respectively).     

Left ventricular architecture after valve replacement due to critical aortic stenosis: an approach to dis-/qualify the myth of valve prosthesis–patient mismatch?

Objectives: Left ventricular hypertrophy in patients with critical aortic stenosis (AS) is an adaptive process that compensates for high intracavitary pressure and reduces systolic wall stress followed by an increase in myocardial masses. In the present prospective clinical trial, we investigated long-term compensatory changes in left ventricular geometry and function after aortic valve replacement using mechanical bileaflet prostheses with the main emphasis on the small-sized aortic annulus and valve prosthesis–patient mismatch. Methods: A total of 58 patients with critical AS were assigned to the following groups according to the predictive value of prosthetic valve area index (VAI): group EXMIS: 29 patients (VAI≤0.99), expected mismatch; group NOMIS: 29 patients (VAI≤0.99), no mismatch. At controls T₀ (before operation/operation (OP), T₁ and T₂ (4 and 20 months after OP) the left ventricular geometry was recorded by means of Imatron^® electron beam tomography and the transprosthetic velocities were measured by echocardiography. Results: Statistical analysis showed a consistent reduction in the absolute (P=0.04) and indexed (P=0.04) left ventricular myocardial mass for both cohorts; furthermore, there was a significant difference between EXMIS and NOMIS patients concerning the factors, time and mass reduction (P=0.005), because of distinct baselines. A logistic regression report revealed preoperative cardiac output, absolute left ventricular myocardial mass, perfusion, body surface area and the native valve orifice area as predicting coefficients and factors for a minimum mass reduction of 25%. We explain a mathematical formula that turned out to be the most sensitive for correctly classified factors. Conclusions: The left ventricular geometry and transprosthetic velocities resulted in the same postoperative recovery for both EXMIS and NOMIS patients. The presented data showed that valve prosthesis–patient mismatch had no influence in several stepwise logistic regression models. We conclude that modern mechanical bileaflet prostheses allow both acceptable hemodynamics and recovery of left ventricular hypertrophy, even in small aortic annuli.     

Assessment of Depth of Anesthesia and Postoperative Respiratory Recovery after Remifentanil-versus Alfentanil-based Total Intravenous Anesthesia in Patients Undergoing Ear-Nose-Throat Surgery

Background: The authors investigated whether total intravenous anesthesia (TIVA) with precalculated equipotent infusion schemes for remifentanil and alfentanil would ensure appropriate analgesia and that remifentanil would result in better recovery characteristics.

Methods: Forty consenting patients (classified as American Society of Anesthesiologists physical status I-III) scheduled for microlaryngoscopy were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 [mu]g/kg; maintenance infusion, 0.25 [mu]g [middle dot] kg-1 [middle dot] min-1) or alfentanil (loading dose, 50 [mu]g/kg; maintenance infusion, 1 [mu]g [middle dot] kg-1 [middle dot] min-1) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg/kg; maintenance infusion, 100 [mu]g [middle dot] kg-1 [middle dot] min-1). To insure an equal state of anesthesia, the opioids were titrated to maintain heart rate and mean arterial pressure within 20% of baseline, and propofol was titrated to keep the bispectral index (BIS) less than 60. Neuromuscular blockade was achieved with succinylcholine. Drug dosages and the times from cessation of anesthesia to extubation, verbal response, recovery of ventilation, and neuropsychological testing, orientation, and discharge readiness were recorded.

Results: Demographics, duration of surgery, and anesthesia were similar between the two groups. Both groups received similar propofol doses. There were no difference in BIS values preoperatively (mean, 96), intraoperatively (mean, 55), and postoperatively (mean, 96). Recovery of BIS and times for verbal response did not differ. At 20, 30, and 40 min after terminating the opioid infusion, the peripheral oxygen saturation and respiratory rate were significantly higher in the remifentanil group compared with the alfentanil group.     

Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections.

BACKGROUND AND METHODS: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. RESULTS: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 +/- 0.23 to 0.80 +/- 0.18 micromol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. CONCLUSIONS: Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.     

Cervical soft tissue imaging using a mobile CBCT scanner with a flat panel detector in comparison with corresponding CT and MRI data sets.

OBJECTIVE: The aim of this study was to evaluate soft tissue image quality of a mobile cone-beam computed tomography (CBCT) scanner with an integrated flat-panel detector. STUDY DESIGN: Eight fresh human cadavers were used in this study. For evaluation of soft tissue visualization, CBCT data sets and corresponding computed tomography (CT) and magnetic resonance imaging (MRI) data sets were acquired. Evaluation was performed with the help of 10 defined cervical anatomical structures. RESULTS: The statistical analysis of the scoring results of 3 examiners revealed the CBCT images to be of inferior quality regarding the visualization of most of the predefined structures. Visualization without a significant difference was found regarding the demarcation of the vertebral bodies and the pyramidal cartilages, the arteriosclerosis of the carotids (compared with CT), and the laryngeal skeleton (compared with MRI). Regarding arteriosclerosis of the carotids compared with MRI, CBCT proved to be superior. CONCLUSIONS: The integration of a flat-panel detector improves soft tissue visualization using a mobile CBCT scanner.     

Long-term tolerance to kidney allografts in a preclinical canine model

Durable immune tolerance supporting vascularized allotransplantation offers the possibility of extending graft survival and avoiding harmful complications of chronic immunosuppression. Immune tolerance to renal allografts was induced in a preclinical canine model through engraftment of donor hematopoietic cells using a combination of low-dose total body irradiation and a short course of immunosuppression. Subsequently, donor renal allografts were transplanted accompanied by bilateral native nephrectomies. With 5-year follow up, we found normal renal function in all recipients and no histological evidence of acute or chronic rejection. This tolerance does not extend universally to donor skin grafts, however, with two of four animals rejecting delayed donor skin grafts. Hematopoietic chimerism produces durable and robust immune tolerance to kidney allografts, although incomplete tolerance to donor skin grafting.