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.

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.

[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.

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.

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.

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.

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.

Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity.

Caveolin-1 expression and function were investigated in human colon cancer. Low levels of caveolin-1 mRNA and protein were detected in several colon carcinoma cell lines. Moreover, caveolin-1 protein levels were significantly reduced in human tumor epithelial mucosa (3.6 +/- 1.4-fold) when compared with normal colon mucosa for a majority (10 of 15) of the patients characterized. To directly assess the role of caveolin-1 in tumor development, caveolin-1 was reexpressed in the HT29 and DLD1 colon carcinoma cells, and the resulting HT29-cav-1 or DLD1-cav-1 cells were tested for tumorigenicity in nude mice. In most experiments, tumor formation was either blocked or retarded for HT29-cav-1 cells (10 of 13 mice) and DLD1-cav-1 cells (5 of 7 mice), as compared with both mock-transfected and parental HT29 or DLD1 cells. Interestingly, basal caveolin-1 levels were significantly reduced in HT29-cav-1 and DLD1-cav-1 cells isolated from tumors. Likewise, endogenous caveolin-1 mRNA and protein levels were found to be reduced in NIH-3T3 cells recovered from tumors after injection into nude mice. Thus, reexpression of caveolin-1 in colon carcinoma lines reduced the probability of tumor formation in vivo, and when tumors did develop from either HT29-cav-1, DLD1-cav-1, or NIH-3T3 cells, lower basal levels of caveolin-1 were detected. Finally, evidence was obtained indicating that initial caveolin-1 down-regulation in colon cancer cells need not be an entirely irreversible process because cell survival on selection for either drug resistance or increased metastatic potential correlated with increased caveolin-1 expression levels.

Bioequivalence of subcutaneous calcium and sodium heparins.

The bioequivalence of subcutaneous porcine calcium and sodium heparins was studied in 48 normal male subjects randomly assigned to 1 of 4 study groups. Each subject received a single subcutaneous injection of 15,000 U of calcium heparin or 1 of 3 sodium heparins. Serial coagulation studies (Lee-White clotting time, activated partial thromboplastin time, thrombin calcium clotting time, and heparin level) were performed over 10 hr. There were no significant differences in anticoagulant effect between groups.

Sarcoidosis after renal transplantation.

This is the case of a 41-year-old renal transplant recipient taking tacrolimus immunosuppressive therapy, who had a large pleural effusion, found on a chest radiograph during the work-up of digital clubbing. The patient had undergone a renal transplant 17 months earlier for end-stage renal disease secondary to immunoglobulin A nephropathy. Analysis of the effusion fluid demonstrated a lymphocytic exudate. Biopsy specimens of pleural and lung tissues showed noncaseating granulomas. Fluid and tissue cultures were negative for viral, fungal, and bacterial pathogens. Diagnosis of sarcoidosis was established by identification of noncaseating granulomas in pleural and lung tissue, the exclusion of other conditions, and rapid resolution of the effusion after the institution of corticosteroid therapy. The patient has remained free of pulmonary symptoms and had normal chest radiographs during the 20-month follow-up period.

Study of factors that may condition scintigraphic detection of venous thrombi and pulmonary emboli with indium-111-labeled platelets.

Incorporation of indium-111-labeled platelets (In-111-P) into venous thrombi and pulmonary emboli may permit rapid detection of these thromboemboli by gamma imaging. In a series of dogs in which femoral-vein thromboses and/or pulmonary embolism were induced experimentally by stasis and small amounts of thrombin, we addressed several questions pertinent to the sensitivity, specificity, and potential applicability of this approach. We found that when In-111-P were injected intravenously before thrombus induction or embolus release, femoral-thrombus images were consistently detectable within 15 min, whereas control femoral-vein images were unremarkable. Pulmonary emboli were also promptly imaged, and such In-111-P images agreed well with defects on Tc-99m MAA perfusion scans. When thrombi were aged in vivo for up to 10 hr after formation, they could still be imaged within 20-90 min after In-111-P injection. Administration of heparin, as an initial bolus followed by constant infusion, blocked platelet deposition on femoral-vein thrombi as assessed by both thrombus-to-blood ratios and failure to image. Injection of protamine at 6 hr, however, resulted in prompt thrombus imaging. These data indicate that this approach may well have applicability to the detection of thromboemboli in humans, since imaging remains possible in canine thrombi aged in vivo for 10 hr so long as heparin therapy has not been instituted. The dose of heparin required to inhibit imaging is not known. However, if these data prove comparable in humans, they suggest that imaging of thromboemboli could be achieved so promptly that only modest delay in the institution of heparin therapy would be required.

Benefit-risk ratio in the treatment of tachyarrhythmias. A clinical judgement.

The goal of antiarrhythmic treatment--the well-being of the patient and improvement of prognosis--requires careful clinical investigation and observation with monitoring of the arrhythmia during long term treatment. A few compounds now in use are under investigation for their efficacy in selectively depressing sinus tachycardia, or tachycardias involving the atrioventricular node. No ideal drug is yet available, nor is likely in the near future, for treating the complex problem of arrhythmogenesis. A favourable benefit-risk ratio for flecainide has been shown by many authors during the last 7 years and greatest interest now centres on its use in malignant arrhythmias. More studies in high risk patients are necessary for a better understanding of the proarrhythmic properties of antiarrhythmic drugs, thus paving the way for prevention and treatment of these unwanted effects.

Successful treatment of severe hyponatremia in a patient with renal failure using continuous venovenous hemodialysis.

Both hyponatremia and its rapid correction can cause neurological disorders. Slowly correcting hyponatremia (especially when asymptomatic) at a rate of 0.5 mEq/L/h is recommended; however, little information exists about treatment of hyponatremia in patients requiring dialysis. We report a case of successfully treated hyponatremia using continuous venovenous hemodialysis with a specially prepared dialysate containing a lower than usual sodium concentration.

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.

A comparison of clearances on tidal peritoneal dialysis and intermittent peritoneal dialysis.

OBJECTIVES: To compare the small molecule clearances on tidal peritoneal dialysis (TPD) and intermittent peritoneal dialysis (IPD), controlling for dialysate flow rate. DESIGN: Alternating 8-hour treatments on IPD and TPD (2 of each in 6 patients), each treatment separated by 3 or more days [patients returning to continuous ambulatory peritoneal dialysis (CAPD) in the interim] were performed. IPD treatments consisted of 15 exchanges with 2 L/exchange for a total of 30 L/treatment. TPD treatments consisted of 29 exchanges, with an initial fill volume of 2 L, followed by 1 L tidal volume for the subsequent exchanges (reserve volume of 1 L) for a total of 30 L/treatment. PATIENTS: Six patients, with a mean dialysate/plasma (D/P) creatinine as determined by the peritoneal equilibration test (PET) of 0.64 +/- 0.10, were studied. Four had a low-average D/P creatinine, while 2 had a high-average D/P creatinine. MEASUREMENTS: Urea nitrogen, creatinine, phosphate, and potassium clearances on TPD and IPD were compared using the paired t-test. RESULTS: The dialysate flow rates were 3.7 +/- 0.1 L/hour for IPD and 3.8 +/- 0.2 L/hour for TPD. The mean dialysate dextrose was 1.9 +/- 0.5 g/dL for both. The creatinine clearances were 9 +/- 2 versus 10 +/- 3 mL/minute, the urea nitrogen clearances 19 +/- 3 versus 20 +/- 3 mL/minute, and phosphate clearances 10 +/- 3 versus 11 +/- 3 mL/minute for IPD and TPD, respectively (all not different). The ultrafiltration rates were 2.9 +/- 0.9 mL/minute on IPD and 3.3 +/- 1.6 mL/minute on TPD (not different). On both IPD and TPD the clearances of urea nitrogen, creatinine, and phosphate for the 2 patients with high-average D/P creatinine were higher than for the 4 patients with low-average D/P creatinine. CONCLUSIONS: When the dialysate flow rate is controlled and a TPD prescription of 1 L reserve and tidal volumes is used, the small molecule clearances on IPD are similar to those on TPD.

Efficacy of different hepatitis B vaccination strategies in patients receiving hemodialysis.

Patients with end-stage renal disease have an impaired immune response to vaccination against Hepatitis B. The efficacy of different vaccines and vaccine schedules was studied in a group of patients receiving long-term hemodialysis. All patients received an initial 6 month course of intramuscular vaccine with either three doses of Recombivax (48 patients) or four doses of Engerix B (50 patients). This was successful in 71% and 74% of patients, respectively. In 10 patients unresponsive to 4 doses of Engerix B, a second course (2-4 doses) was successful in 5, thus increasing the overall success rate to 84%. Repetitive doses of vaccine intradermally were used as an alternative approach in eight patients who were unresponsive to intramuscular vaccination resulting in seroconversion in six. Finally, booster doses of intramuscular Engerix B have been used in 26 patients who lost their antibodies after successful vaccination.

A concentration dependent study of acoustic plate mode immunosensor response using antigen/antibody systems with different binding ability.

Acoustic plate mode sensors have been used to monitor immunochemical reactions as a function of antigen concentration. In the studies, antibodies were covalently linked to the gold-coated sensing surface via mercaptoethanol, aminosilane, and glutaraldehyde. Two antigen/antibody model systems that differ in their ability to mutually bind one another have been used. For sensor operation at about 150 MHz, a detection limit of approximately 0.5 microg/ml was obtained in both cases. No significant difference between the two systems was found for the value of the binding constants. They amount to about 1.10(8) 1/mole and fall well into the range of binding constants reported for homogeneous immunoassays. A comparison of the sensor response obtained for the two model systems shows that about 70% of the immobilized antibodies are active.

Acoustic wave-based sensors using mode conversion in periodic gratings.

Using periodic gratings etched into the surface of a piezoelectric plate, surface acoustic waves (SAW) can be converted into bulk waves and vice versa with high efficiency. If parallel grating structures are fabricated on opposite surfaces of a piezoelectric plate, a SAW also can be directed from one surface to the other. Using such structures, acoustic wave-based sensors can be designed that utilize SAW for the detection of chemical analytes on an electrode-free surface, i.e., the back surface. As a result, spurious sensor response and electrode aging that may occur when a chemical analyte comes in contact with the transducers are minimized. The design principles of these grating-based SAW sensors are explained, and the mass sensitivity is investigated using chemical vapor deposited thin polymer films, a type of material used in many practical chemical sensor applications. Experimental results are presented for the detection of nitrogen dioxide (NO(2 )) in sub-ppm concentrations.

Polycythemia in diabetic patients on CAPD.

Polycythemia in CAPD patients has been rarely described. Over an eight year period, 4 out of 123 CAPD patients (3%) were identified as having Hct values exceeding 50% for 1 month or longer. All of the 4 patients were insulin dependent diabetics (4/47 diabetic patients, 8.5%). Charts were reviewed on 3 of these 4 patients. Polycythemia developed after a mean of 21 +/- 7 months on peritoneal dialysis. Prior to the development of polycythemia, ferritin levels were low and ferrous sulfate therapy was begun at a time the Hct values were 36 to 40%. Erythropoietin levels were obtained in 2 patients, and were 22 U/L (Hct 51%) and less than 5 U/L (Hct 55%). Renal ultrasound failed to show renal masses or cysts. One patient had a plasma volume of 2.1 L (normal 2.4-3.2 L); another patient was clinically volume depleted. Complications during the period of polycythemia included gangrenous feet requiring amputation in 2 patients, CVA in 2 patients, and splenic infarct in 1 patient. One patient died of cerebral thrombosis. We conclude that polycythemia is uncommon in CAPD patients and occurs most often in diabetic patients. Volume depletion and iron therapy may play a role in its etiology. In this high risk group of patients polycythemia may contribute to vascular complications and should be avoided.