Sarcopenia of kidney transplant recipients as a predictive marker for reduced graft function and graft survival after kidney transplantation.

PURPOSE: The association between sarcopenia of kidney transplant recipients and outcome after kidney transplantation (KT) has not yet been fully understood and is still considered controversial. The aim of our study was to analyze the impact of pre-transplant sarcopenia on graft function, postoperative complication rates, and survival of the patients after renal transplantation. METHODS: In this retrospective single-center study, all patients who underwent KT (01/2013-12/2017) were included. Demographic data, rejection rates, delayed graft function, and graft and patient survival rates were analyzed. Sarcopenia was measured in computed tomography images by the sex-adjusted Hounsfield unit average calculation (HUAC). RESULTS: During the study period, 111 single KTs (38 women and 73 men) were performed. Living donor kidney transplants were performed in 48.6%. In total, 32.4% patients had sarcopenia. Sarcopenic patients were significantly older (59.6 years vs. 49.8 years; p < 0.001), had a higher body mass index (BMI = 27.6 kg/m2 vs. 25.0 kg/m2; p = 0.002), and were more likely to receive deceased donor kidneys (72.2% vs. 41.3%; p = 0.002). Interestingly, 3 years after KT, the creatinine serum levels were significantly higher (2.0 mg/dl vs. 1.5 mg/dl; p = 0.001), whereas eGFR (39.9 ml/min vs. 53.4 ml/min; p = 0.001) and graft survival were significantly lower (p = 0.004) in sarcopenic transplant recipients. Sarcopenic patients stayed in hospital significantly longer postoperatively than those who were non-sarcopenic. CONCLUSIONS: At the time of kidney transplantation, sarcopenia was found to predict reduced long-term graft function and diminished graft survival after KT. The early identification of sarcopenic patients can not only enable an optimized selection of recipients, but also the initiation of pre-habilitation programs during the waiting period.

[Current WSES-AAST guidelines on anorectal emergencies-Summary and comments]. / Aktuelle WSES-AAST-Leitlinie zu anorektalen Notfällen ­ Zusammenfassung und Kommentar.

In 2019, the World Society of Emergency Surgery (WSES) and the American Association for the Surgery of Trauma (AAST) generated consensus recommendations for the treatment of anorectal emergencies in Parma, Italy, and published a guideline in 2021. This is the first global guideline dealing with this important topic for surgeons' everyday work. Seven anorectal emergencies were discussed and the guideline recommendations were given according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

Really just a little prick? A meta-analysis on adverse events in placebo control groups of seasonal influenza vaccination RCTs.

BACKGROUND: The Corona pandemic and ongoing mass vaccinations raise the question of the nocebo mechanisms involved. Since immunization is usually administered to healthy people as a preventive health measure, adverse events (AE) following immunization are less accepted and could contribute to vaccine hesitancy. Assuming that vaccinees experience nocebo responses, the aim of this meta-analysis was to investigate the effect sizes of solicited adverse events (or assumed reactogenicity) reported in placebo groups in RCTs on seasonal influenza vaccination. METHODS: Literature search via PubMed, Web of Science, and CENTRAL was conducted considering gray literature. Only RCTs with placebo groups using pharmacologically inert substances (like saline) were included. Quality was assessed using Cochrane Collaboration's Risk of Bias Tool. Effect sizes were estimated using a random mixed effects model based on k = 31 studies covering 14,326 participants in placebo groups. RESULTS: Reported solicited AEs in placebo groups showed significant effect sizes of proportions (ESp). In k = 13 analyzed placebo groups, 35 % of the participants reported at least one solicited systemic AE (p = 0.007). The most common particular solicited systemic AEs were headache (k = 27; 17 %; p = 0.001), malaise (k = 13; 12 %; p = 0.004), and hyperhidrosis (k = 4; 12 %; p < 0.001) within one week after vaccination. CONCLUSION: The results show significant solicited AEs in placebo groups, indicating substantial nocebo responses after vaccination. Based on the fact that most vaccination programs include similar groups of healthy people, we expect that comparable nocebo effects occur during other campaigns. Health care professionals should be aware of the nocebo response and take action to prevent or decrease the burden of adverse events following immunization. Fear of side effects must be addressed early in order to diminish vaccine hesitancy. Prospero identifier: CRD42020156287, October 2019.

Morgagni-Larrey diaphragmatic hernia repair in adult patients: a retrospective single-center experience.

PURPOSE: Morgagni-Larrey congenital diaphragmatic hernia (MLH) is rare in adult patients and surgery is performed infrequently. The evidence regarding the most beneficial treatment modality is low. Nevertheless, with increasing experience in minimally-invasive surgery, the literature proves the laparoscopic approach as being safely feasible. However, knowledge on the disease as well as treatment options are based on single surgeon's experiences and small case series in the literature. METHODS: Retrospective single-center analysis on adult patients (≥ 18 years) with MLH from 01/2003 to 06/2019 regarding symptoms, hernia sac contents, surgical technique and perioperative outcome. RESULTS: 4.0% of diaphragmatic hernia repair procedures were performed for MLH (n = 11 patients). 27.3% of these patients were asymptomatic. Dyspnea or gastrointestinal symptoms were frequently observed (both in 45.5% of the patients). Colon transversum (63.6%), omentum majus (45.5%) and/or stomach (27.3%) were the most common hernia sac contents. Correct diagnosis was achieved preoperatively in 10/11 patients by cross-sectional imaging. All procedures were performed by trans-abdominal surgery (laparotomy in four and laparoscopy in seven patients). All hernias were reinforced by mesh after primary closure. No differences were observed in the perioperative outcome between patients who underwent hernia repair by laparotomy versus laparoscopy. Pleural complications requiring drainage were the most common postoperative complications. CONCLUSION: MLH repair seems to be safely feasible by laparoscopic surgery. The benefit of mesh augmentation in MLH repair is not clear yet. In contrast to the current literature, all patients in this study received mesh augmentation after primary closure of the hernia. This should be evaluated in larger patient cohorts with long-term follow-up.

Reliable detection of mucopolysacchariduria in dried-urine filter paper samples.

BACKGROUND: The mucopolysaccharidoses (MPS) are inherited metabolic disorders with bone, joint, and visceral abnormalities, leading to multi-organ dysfunction and, sometimes, neurological manifestations. These diseases are caused by storage of glycosaminoglycans (GAGs) and other complex molecules in tissues, among other pathogenic mechanisms. Definitive diagnosis of the affected individual is mainly based on the identification of the specific enzyme deficiency. New therapies are available or are in development for these pathologies, and early diagnosis seems to be important for the therapy outcomes. Almost all MPS patients have increased levels of GAGs in urine being their evaluation usually the first step in the screening of these conditions. Test on urine may be challenging as transportation of liquid urine samples in appropriate conditions for long distances, especially across international borders, could be difficult. METHODS: With the aim of overcoming the difficulties related to the use of liquid samples, we extended and validated previous studies about colorimetric determination of GAGs in dried-urine filter paper (DUFP) samples. RESULTS: In the conditions we described, there are no differences in the concentration of GAGs between urine and DUFP samples. Untreated patients with MPS and normal controls were well discriminated using any of the samples. CONCLUSIONS: Dried-urine filter paper is a suitable sample for the colorimetric quantitation of GAGs, and that its incorporation as an additional tool for screening of MPS should be considered by reference laboratories.

Trehalose-6-phosphate synthase from the cat flea Ctenocephalides felis and Drosophila melanogaster: gene identification, cloning, heterologous functional expression and identification of inhibitors by high throughput screening.

Trehalose phosphate synthase (EC 2.4.1.15; TPS) is the crucial enzyme for the biosynthesis of trehalose, the main haemolymph sugar of insects, and therefore a potential insecticidal molecular target. In this study, we report the functional heterologous expression of Drosophila melanogaster TPS, the gene identification, full length cDNA cloning and functional expression of cat flea (Ctenocephalides felis) TPS, and the Michaelis-Menten constants for their specific substrates glucose-6-phosphate and uridinediphosphate-glucose. A novel high throughput screening-compatible TPS assay and its use for the identification of the first potent insect TPS inhibitors from a large synthetic compound collection (>115 000 compounds) is described. One compound class that emerged in this screening, the 4-substituted 2,6-diamino-3,5-dicyano-4H-thiopyrans, was further investigated by analysing preliminary structure-activity relationships. Here, compounds were identified that show low µM to high nM half maximal inhibitory concentrations on insect TPS and that may serve as lead compounds for the development of insecticides with a novel mode of action.

Altered first-trimester screening markers after IVF/ICSI: no relationship with small-for-gestational-age and number of embryos transferred.

First-trimester serum markers in 110 in-vitro fertilization (IVF) and 331 intracytoplasmatic sperm injection (ICSI) pregnancies were compared with 1431 pregnancies with spontaneous conception. Alterations of serum markers were evaluated with respect to small-for-gestational-age (SGA) growth and number of embryos transferred. For pregnancy-associated plasma protein A (PAPP-A), significantly lower concentrations were observed in IVF and ICSI pregnancies compared with controls (0.86 and 0.9 versus 1.06; P<0.001). Free beta-human chorionic gonadotrophin (betaHCG) values were significantly higher in the IVF/ICSI groups than in controls (1.1 and 1.1 versus 0.94; P<0.005). IVF and ICSI pregnancies showed higher rates of SGA (10.0% and 8.2%) compared with natural conception (4.6%), but differences in PAPP-A concentrations remained significant (P<0.005) after the exclusion of SGA pregnancies. No relationship between serum values and the transfer of one, two or three embryos was observed. Centre-specific corrections may be needed to adjust screening parameters for assisted reproductive technology.

Parametric color coding of digital subtraction angiography.

BACKGROUND AND PURPOSE: Color has been shown to facilitate both visual search and recognition tasks. It was our purpose to examine the impact of a color-coding algorithm on the interpretation of 2D-DSA acquisitions by experienced and inexperienced observers. MATERIALS AND METHODS: Twenty-six 2D-DSA acquisitions obtained as part of routine clinical care from subjects with a variety of cerebrovascular disease processes were selected from an internal data base so as to include a variety of disease states (aneurysms, AVMs, fistulas, stenosis, occlusions, dissections, and tumors). Three experienced and 3 less experienced observers were each shown the acquisitions on a prerelease version of a commercially available double-monitor workstation (XWP, Siemens Healthcare). Acquisitions were presented first as a subtracted image series and then as a single composite color-coded image of the entire acquisition. Observers were then asked a series of questions designed to assess the value of the color-coded images for the following purposes: 1) to enhance their ability to make a diagnosis, 2) to have confidence in their diagnosis, 3) to plan a treatment, and 4) to judge the effect of a treatment. The results were analyzed by using 1-sample Wilcoxon tests. RESULTS: Color-coded images enhanced the ease of evaluating treatment success in >40% of cases (P < .0001). They also had a statistically significant impact on treatment planning, making planning easier in >20% of the cases (P = .0069). In >20% of the examples, color-coding made diagnosis and treatment planning easier for all readers (P < .0001). Color-coding also increased the confidence of diagnosis compared with the use of DSA alone (P = .056). The impact of this was greater for the naïve readers than for the expert readers. CONCLUSIONS: At no additional cost in x-ray dose or contrast medium, color-coding of DSA enhanced the conspicuity of findings on DSA images. It was particularly useful in situations in which there was a complex flow pattern and in evaluation of pre- and posttreatment acquisitions. Its full potential remains to be defined.

C-arm CT measurement of cerebral blood volume in ischemic stroke: an experimental study in canines.

BACKGROUND AND PURPOSE: CBV is a key parameter in distinguishing penumbra from ischemic core. The purpose of this study was to compare CBV measurements acquired with standard PCT with ones obtained with C-arm CT in a canine stroke model. MATERIALS AND METHODS: Under an institutionally approved protocol, unilateral MCA strokes were created in 10 canines. Four hours later, DWI was used to confirm the presence of an infarct. CBV maps acquired with PCT were compared with ones acquired by using C-arm CT. Three experienced observers, blinded to the technique used for acquisition, evaluated the CBV maps. RESULTS: An ischemic stroke was achieved in 9 of the 10 animals. Areas of reduced CBV were detected in 70%-75% of the PCT studies and in 83%-87% of the C-arm CT examinations, with false-positives in 1.7% and 3.3%, respectively. False-negatives were found in 25% of the PCT and 12.2% of the C-arm CT studies. In all studies, there was a significant difference between the absolute CBV values in normal and abnormal tissue (P < .005) and no significant difference between PCT and C-arm CT CBV values in either the normal or the abnormal parenchyma (P > .05). CONCLUSIONS: CBV measurements made with C-arm CT compare well with ones made with PCT. While further work is required both to fully validate the technique and to define its ultimate clinical value, it appears that it offers a feasible method for assessing CBV in the angiography suite.

Atrioventricular septal defect in the fetus--associated conditions and outcome in 246 cases.

PURPOSE: To evaluate the associated conditions and the outcome of atrioventricular septal defects (AVSD) detected in fetal life. MATERIALS AND METHODS: Retrospective review of all cases of AVSD detected prenatally between 1998 and 2006 in two tertiary referral centers in Germany. RESULTS: 246 cases of AVSD were detected in the study period: 129 (52.4 %) chromosomal anomalies; 72 (29.3 %) heterotaxy syndromes; 17 (6.9 %) non-chromosomal malformation syndromes; 16 (6.5 %) isolated complex cardiac malformations; 5 (2.0 %) singular extracardiac malformations; 7 (2.8 %) isolated AVSD. Chromosomal anomalies were detected significantly earlier in pregnancy (p < 0.01). Associated intracardiac malformations were present in 109/246 (44.3 %) cases. Fetuses with trisomy 21 were significantly associated with balanced ventricular morphology and isolated AVSD (p < 0.01). Among the 246 cases, 144 (58.5 %) underwent termination of pregnancy, 18 (7.3 %) died in utero, 17 (6.9 %) in the neonatal period and 19 (7.7 %) in infancy. Forty-eight children (19.5 %) survived with a mean follow-up of 34.94 +/- 18.6 months. After exclusion of lethal malformations, the survival rate among live births was 64.9 % (48 / 74). Fetuses with trisomy 21 had significantly better survival rates among continued pregnancies (p < 0.01) and significantly higher rates of successful biventricular repair among survivors who received their final corrective procedure (p < 0.01) than fetuses with normal karyotypes. CONCLUSION: Among fetuses with AVSD, those with trisomy 21 are detected earlier in pregnancy, have less distorted cardiac anatomy, higher rates of biventricular repair and better survival rates. Due to the limited sample size in euploid fetuses, it remains unclear whether this apparent protection afforded to Down syndrome accounts also for cohorts with isolated and balanced AVSD.

Prevention of infectious complications in peritoneal dialysis: best demonstrated practices.

Peritoneal dialysis (PD) related infections continue to be a serious complication for PD patients. Peritonitis can be associated with pain, hospitalization and catheter loss as well as a risk of death. Peritonitis risk is not evenly spread across the PD population or programs. Very low rates of peritonitis in a program are possible if close attention is paid to the causes of peritonitis and protocols implemented to reduce the risk of infection. Protocols to decrease infection risk in PD patients include proper catheter placement, exit-site care that includes Staphylococcus aureus prophylaxis, careful training of patients with periodic retraining, treatment of contamination, and prevention of procedure-related and fungal peritonitis. Extensive data have been published on the use of antibiotic prophylaxis to prevent exit site infections. There are fewer data on training methods of patients to prevent infection risk. Quality improvement programs with continuous monitoring of infections, both of the catheter exit site and peritonitis, are important to decrease the PD related infections in PD programs. Continuous review of every episode of infection to determine the root cause of the event should be routine in PD programs. Further research is needed examining approaches to decrease infection risk.

Right aortic arch detected in fetal life.

OBJECTIVE: To evaluate the prenatal distribution, associated conditions and outcome of the different types of right aortic arch (RAA) detected in fetal life. METHODS: This was a retrospective review of all cases of RAA detected prenatally between 1998 and 2005 in two tertiary referral centers. RESULTS: In the study period 71 cases of RAA were detected; 26 (37%) had RAA with aberrant left subclavian artery, 23 (32%) had RAA with mirror-image branching, 20 (28%) had RAA of unknown type and two (3%) had double aortic arch. While 20/26 cases with RAA and aberrant left subclavian artery were isolated findings, all 23 cases with RAA and mirror-image branching were associated with cardiac defects, namely tetralogy of Fallot (43%) or pulmonary atresia with ventricular septal defect (22%). Of the 20 cases with RAA, 19 of unknown type were associated with heterotaxy syndromes and had additional cardiac malformations and ambiguities of the situs. The two cases with DAA were isolated findings. Seven cases in our series (10%) had a microdeletion 22q11 and these were significantly associated with extracardiac malformations. The outcome in our series depended solely on the associated cardiac and extracardiac malformations, with the exception of one infant with isolated DAA, in whom a surgical correction was warranted. CONCLUSIONS: RAA detected in fetal life is associated frequently with other cardiac/non-cardiac malformations, heterotaxy syndromes and microdeletions 22q11. The associated conditions vary depending on the branching type of the brachiocephalic vessels and the presence of extracardiac malformations.

Caveolin-1 interacts with the chaperone complex TCP-1 and modulates its protein folding activity.

We report that caveolin-1, one of the major structural protein of caveolae, interacts with TCP-1, a hetero-oligomeric chaperone complex present in all eukaryotic cells that contributes mainly to the folding of actin and tubulin. The caveolin-TCP-1 interaction entails the first 32 amino acids of the N-terminal segment of caveolin. Our data show that caveolin-1 expression is needed for the induction of TCP-1 actin folding function in response to insulin stimulation. Caveolin-1 phosphorylation at tyrosine residue 14 induces the dissociation of caveolin-1 from TCP-1 and activates actin folding. We show that the mechanism by which caveolin-1 modulates TCP-1 activity is indirect and involves the cytoskeleton linker filamin. Filamin is known to bind caveolin-1 and to function as a negative regulator of insulin-mediated signaling. Our data support the notion that the caveolin-filamin interaction contributes to restore insulin-mediated phosphorylation of caveolin, thus allowing the release of active TCP-1.

Dynamic characterization of hysteresis elements in mechanical systems. II. Experimental validation.

The industrial demand for machine tools with ever increasing speed and accuracy calls for a closer look at the physical phenomena that are present at small movements of those machine's slides. One of these phenomena, and probably the most dominant one, is the dependence of the friction force on displacement that can be described by a rate-independent hysteresis function with nonlocal memory. The influence of this highly nonlinear effect on the dynamics of the system has been theoretically analyzed in Part I of this paper. This part (II) aims at verifying these theoretical results on three experimental setups. Two setups, consisting of linearly driven rolling element guideways, have been built to specifically study the hysteretic friction behavior. The experiments performed on these specially designed setups are then repeated on one axis of an industrial pick-and-place device, driven by a linear motor and guided by commercial guideways. The results of the experiments on all the setups agree qualitatively well with the theoretically predicted ones and point to the inherent difficulty of accurate quantitative identification of the hysteretic behavior. They further show that the hysteretic friction behavior has a direct bearing on the dynamics of machine tools and its presence should therefore be carefully considered in the dynamic identification process of these systems.

Dynamic characterization of hysteresis elements in mechanical systems. I. Theoretical analysis.

The pre-sliding-pre-rolling phase of friction behavior is dominated by rate-independent hysteresis. Many machine elements in common engineering use exhibit, therefore, the characteristic of "hysteresis springs," for small displacements at least. Plain and rolling element bearings that are widely used in motion guidance of machine tools are typical examples. While the presence of a hysteresis element may mark the character of the resulting dynamics, little is to be found about this topic in the literature. The study of the nonlinear dynamics caused by such elements becomes imperative if we wish to achieve accurate control of such machines. In this Part I of the investigation, we examine a single-degree-of-freedom mass-hysteresis-spring system and show that, while the free response case is amenable to an exact solution, the more important case of forced response has no closed form solution and requires other methods of treatment. We consider harmonic-balance analysis methods (which are common analysis tools in engineering) suitable for frequency-domain treatment, in particular the approximate describing function (DF) method, and compare those results with "exact" numerical simulations. The DF method yields basically a linear equation with amplitude-dependent modal parameters. We find that agreement in the frequency response function, between DF and exact solution, is good for small excitation amplitudes and for very large amplitudes. Intermediate values, however, show high sensitivity to amplitude variations and, consequently, no regular solution is obtainable by either approach. This appears to be an inherent property of the system pointing to the need for developing further analysis methods. Experimental verification of the analysis outlined in this Part I is given in Part II of the paper.

Improvement of surface acoustic wave gas and biosensor response characteristics using a capacitive coupling technique.

As for many other electronic devices and circuits, electrical contact to surface acoustic wave sensors is usually made using bonding wires. This technique is known to result in reliable contact under most conditions, but it does so with several disadvantages. First, electrical contact is not reversible, impeding replacement of sensor devices. Second, bonding wires are quite delicate and should not be exposed to high gas or liquid flows. Third, the presence of bonding wires may limit the potential to miniaturize a sensor housing or flow cell. Therefore, a capacitive coupling technique was developed to replace bonding wires. This permitted redesign of flow cells and sensor arrays, resulting in flow cell volumes of 80 microL to 60 nL. As a consequence, response times were reduced to 1-2 s in gas sensing and a few minutes in liquid sensing, respectively. At the same time, sensor devices can be easily replaced, and the system is less susceptible to malfunction.

Identification of pre-sliding friction dynamics.

The hysteretic nonlinear dependence of pre-sliding friction force on displacement is modeled using different physics-based and black-box approaches including various Maxwell-slip models, NARX models, neural networks, nonparametric (local) models and dynamical networks. The efficiency and accuracy of these identification methods is compared for an experimental time series where the observed friction force is predicted from the measured displacement. All models, although varying in their degree of accuracy, show good prediction capability of pre-sliding friction. Finally, we show that even better results can be achieved by using an ensemble of the best models for prediction.

Sensitivity of the acoustic waveguide biosensor to protein binding as a function of the waveguide properties.

The aim of this work is to study the effect of operating frequency, piezoelectric substrate and waveguide layer thickness on the sensitivity of the acoustic waveguide sensor during the specific binding of an antibody by a protein. Shear horizontal (SH) wave devices consisting of (a) a LiTaO3 substrate operating at 104 MHz, (b) a quartz substrate operating at 108 MHz and (c) a quartz substrate operating at 155 MHz were coated with a photoresist polymer layer in order to produce acoustic waveguide devices supporting a Love wave. The effect of the thickness of the polymer layer on the Love wave was assessed by measuring the amplitude and phase of the wave before and after coating. The sensitivity of the above three biosensors was compared during the detection of the specific binding of different concentrations of Immunoglobulin G in the range of 0.7-667 nM to a protein A modified surface. Results indicate that the thickness of the polymer guiding layer is critical for obtaining the maximum sensitivity for a given geometry but a trade-off has to be made between the theoretically determined optimum thickness for waveguiding and the device insertion loss. It was also found that increasing the frequency of operation results in a further increase in the device sensitivity to protein detection.

Comparative study of IgG binding to proteins G and A: nonequilibrium kinetic and binding constant determination with the acoustic waveguide device.

The aim of this work was to measure and compare the binding constants of antibody immunoglobulin G (IgG) to bacterial cell wall proteins, streptococcal protein G and Staphylococcus aureus protein A, using an acoustic wave sensor. Devices, which used shear-horizontal acoustic waves propagating in a waveguide configuration at 108 and 155 MHz, were employed in the detection of apparent IgG binding constants at the solid-liquid interface in the range of 6.7-667 nM IgG. Real-time data during IgG-protein G and IgG-protein A binding yielded apparent association constants of 3.29 x 10(4) and 8.02 x 10(3) M(-1) s(-1) leading to equilibrium constants of 1.13 x 10(8) and 2.90 x 10(7) M(-1), respectively. The measured apparent rate constants are consistent with literature reports of higher affinity of protein G for IgG. Furthermore, protein binding through the Fc region of IgG is suggested to occur below 333 nM, while different mechanisms are suggested to occur above 333 nM. For the first time, nonequilibrium studies of IgG-protein G and A binding at a solid-liquid interface has yielded valuable quantitative kinetic information about binding mechanisms. The promise of this detection method is shown by providing quick determination of binding constants with low sample volumes.