Whole genome microarray expression analysis in blood identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia.

A child, 2 years with the 'hypercalprotectinaemia with hyperzincaemia' clinical syndrome, presented with atypical symptoms and signs, notably persistent fever of approximately 38°C, thrombocythaemia of > 700 × 109 /l and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analysed whole-genome mRNA expression by the Affymetrix HG U133 Plus 2·0 array in blood on three occasions 3-5 months apart. Major up-regulation was demonstrated for the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway including, in particular, CD177, S100A8, S100A9 and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors and activators, accounting for the febrile apathic state; and the high mobility group box 1 (HMBG1) gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic work-up of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways.

Screening of more than 2000 Hungarian healthcare workers' anti-measles antibody level: results and possible population-level consequences.

Due to the European measles epidemic and the increased number of imported cases, it can be theorised that the risk of exposure among Hungarian healthcare workers (HCWs) has increased. In 2017, the increased measles circulation in the region led to the emergence of smaller local and hospital epidemics. Therefore, our objective was to determine the herd immunity in the high-risk group of HCWs. A hospital-based study of detecting anti-measles IgG activity was performed in 2017 and included 2167 employees of the Military Medical Centre (Hungary). The screening of HCWs presented a good general seropositivity (90.6%). The highest seroprevalence value (99.1%) was found in the age group of 60 years or older. The lowest number of seropositive individuals was seen in the 41-45 years (86.2%) age group, indicating a significant herd immunity gap between groups. Regarding the Hungarian data, there might be gaps in the seroprevalence of the analysed HCWs, implying that susceptible HCWs may generate healthcare-associated infections. This study suggests that despite the extensive vaccination and high vaccine coverage, it is still important to monitor the level of protective antibodies in HCWs, or in a representative group of the whole population of Hungary, and possibly in other countries as well.

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial.

OBJECTIVES: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. BACKGROUND: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. METHODS: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. RESULTS: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. CONCLUSIONS: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

Comparison of test specificities of commercial antigen-based assays and in-house PCR methods for detection of rotavirus in stool specimens.

Seven commercial rotavirus antigen assays were compared with in-house PCR methods for detecting rotavirus in stool specimens. The assay sensitivities were 80% to 100%, while the specificities were 54.3% for one commercial immunochromatographic (ICT) method and 99.4% to 100% for other assays. Thus, except for one commercial ICT, all the assays were generally reliable for rotavirus detection.

Full-genome sequencing of a Hungarian canine G3P[3] Rotavirus A strain reveals high genetic relatedness with a historic Italian human strain.

A canine Rotavirus A strain was identified in the fecal specimen of a young dog during 2012 in Hungary. The strain RVA/Dog-wt/HUN/135/2012/G3P[3] shared complete genotype constellation (G3-P[3]-I3-R3-C3-M3-A15-N2-T3-E3-H6) and high genome sequence similarity (nt, 98.8 %) with a historic human strain, RVA/Human-tc/ITA/PA260-97/1997/G3P[3]. This study provides evidence for the canine origin of the unusual NSP1 genotype, A15, and reinforces the hypothesis of direct interspecies transmission of canine rotaviruses to humans.

[Operative therapy of hepatocellular carcinoma]. / Operative Therapie des hepatozellulären Karzinoms.

BACKGROUND: Curative surgical strategies for hepatocellular carcinoma are liver resection and transplantation. METHODS: This overview is based on a selective literature search on therapeutic strategies for hepatocellular carcinoma. The new German S3 guidelines are outlined in detail but guidelines from other societies were also taken into consideration. RESULTS: The question of resectability is of utmost importance and should not only be evaluated in an interdisciplinary tumor board but also in an experienced liver center. Primary resectable hepatocellular carcinoma in patients without portal hypertension should be resected. Most patients without cirrhosis qualify for resection. In patients with Child grade A cirrhosis but without severe portal hypertension and a stable health status, a liver resection should be considered. At resection intraoperative ultrasound is standard. Intrahepatic tumor recurrences also can be re-resected or thermally ablated. New techniques for extended liver resections or minimally invasive liver resections are commonly used and have to be studied further. CONCLUSION: In addition to liver resection, liver transplantation now represents a standard therapy for hepatocellular carcinoma in cirrhosis. Observing the Milan selection criteria 5-year survival rates of 70-90 % can be achieved; however, increasing organ shortage leads to longer waiting times and thus higher risk of tumor progression. Therefore, patients on the waiting list should have follow-up imaging and bridging with surgical resection, radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) by interventional radiology. Living donor liver transplantation should be considered in all these patients with expected longer waiting times.

[Surgical technique for laparoscopic kidney donation]. / Die chirurgische Technik der laparoskopischen Nierenlebendspende.

OBJECTIVE: Dialysis cannot fully replace kidney function in patients diagnosed with end-stage renal disease. Patients undergoing dialysis therapy show a significantly reduced quality of life, morbidity and mortality compared to healthy individuals. Every patient diagnosed with end-stage renal disease should be evaluated for a potential kidney transplant, potentially by means of living-donor kidney donation. INDICATIONS: Via living-donor kidney donation, patients diagnosed with end-stage renal disease can receive a kidney transplant already before dialysis therapy needs to be initiated. Those patients show a significantly improved long-term graft and patient survival in comparison to patients transplanted after cadaveric organ donation. PROCEDURE: We here describe the evaluation process of living-donor kidney donation and the procedure of transperitoneal laparoscopic donor-nephrectomy. CONCLUSION: Although technically demanding, laparoscopic donor nephrectomy after careful donor evaluation is a safe procedure. An interdisciplinary medical-surgical management is important for both careful patient selection and life-long aftercare.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

FOXP3+ regulatory T-cells in renal allografts: correlation with long-term graft function and acute rejection.

BACKGROUND: The interpretation of a cellular infiltrate as cytotoxic or tolerogen represents an unsolved challenge in current transplantation. The so-called regulatory CD4+ CD25+ T-cells which express the FOXP3 gene have received increasing interest with respect to this question. The existing studies concerning the role of FOXP3+ Tregs for transplant tolerance yielded contradictory results. METHODS: We examined the numbers of the FOXP3+ Tregs in two groups of renal allograft biopsies both showing cellular infiltration, but either without (n=29) or with signs of acute cellular rejection (n=26), by means of immunofluorescence and correlated the amount of FOXP3+ Tregs to renal function at the time of biopsy and after 1 and 2 years of follow up. RESULTS: The number of FOXP3+ Tregs within infiltrates in non-rejecting biopsies did not correlate with renal function after 1 and 2 years. There were no significant differences in the numbers of FOXP3+ Tregs between biopsies with or without borderline infiltrates. Increased numbers of FOXP3+ Tregs were not associated with an ameliorated severity of graft rejection and did not correlate with outcome after the rejection episode and renal function after 1 and 2 years. CONCLUSIONS: The identification of the FOXP3+ regulatory cells within the allograft cannot be considered as an appropriate marker for the interpretation of infiltrates as cytotoxic or tolerogenic or as a prognostic marker for later transplant function.

Giant cell hepatitis: an unusual cause of fulminant liver failure.

Giant cell hepatitis is a very rare disease of unknown origin. It has been hypothesized that drugs, viral infections, or autoimmune reactions may play a pathogenetic role. Here, we describe a 33 year old patient with bacterial bronchitis who was treated with doxycycline (100 mg/d) for one week. Furthermore the patient complained of malaise and a distinct jaundice. Liver parameters increased dramatically (AST 4670 U/l, ALT 5350 U/l, bilirubin 226 µmol/l) and liver function was impaired (INR = 1,45). The ultrasound scan showed a hepatomegaly with no signs of cirrhosis, normal spleen size and normal bile ducts; liver perfusion was normal. No evidence of Wilson's disease, hemochromatosis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, hepatitis A, B, C and E, HIV, CMV, VZV, adenoviral infections, or paracetamol intoxication was found. Subsequently, the patient developed acute liver failure (AST 2134 U/l, ALT 2820 U/l, bilirubin 380 µmol/l, INR 3.0) and a beginning renal failure. Therefore, he was transferred to our transplant center. Due to increasing confusion and somnolence due to cerebral edema mechanical ventilation was needed. Because of an acute renal failure and severe hepatic encephalopathia MARS-hemodialysis was performed. Three weeks after the appearance of the jaundice he underwent liver transplantation (MELD 40). Surprisingly, in the explanted liver the diagnosis of giant cell hepatitis was made. Today--2 years after successful liver transplantation--the patient is in very good condition with normal liver function. In conclusion, giant cell hepatitis is a rare cause of acute liver failure that is often recognized only histologically.

[Recommendations on treatment of acute appendicitis : Recommendations of an expert group based on the current literature]. / Empfehlungen zur Therapie der akuten Appendizitis : Empfehlungen einer Expertengruppe vor dem Hintergrund der aktuellen Literatur.

The paradigm shift in the treatment concept for acute appendicitis is currently the subject of intensive discussions. The diagnosis and differentiation of an uncomplicated from a complicated appendicitis as well as the selection of an adequate treatment is very challenging, especially since nonoperative treatment models have been published. The laparoscopic appendectomy is still the standard for most cases. Guidelines for the treatment of acute appendicitis do not exist in Germany. Therefore, a group of experts elaborated 21 recommendations on the treatment of acute appendicitis after 3 meetings. After initial definition of population, intervention, comparison and outcome (PICO) questions, recommendations have been finalized through the Delphi voting system. The results were evaluated according to the current literature. The aim of this initiative was to define a basic support for decision making in the clinical routine for treatment of acute appendicitis.

Chemical trail-following by flying insects: a mechanism for orientation to a distant odor source.

An aerial trail of odorous pheromone molecules extends downwind from a female pink bollworm moth that is receptive for mating. Males apparently sense the boundaries of the trail during their characteristic zigzag flights across it. Contrary to previous beliefs, the mechanism by which the males steer toward the odor source does not require a sensing of wind direction.

Percutaneous transluminal angioplasty as first-line treatment of transplant renal artery stenosis.

BACKGROUND: Transplant renal artery stenosis (TRAS) is a frequent complication after renal transplantation, however long-term follow-up data after interventional treatment are rare. PATIENTS: In our transplant center 11 of 264 consecutive renal transplant recipients (4.17%) were diagnosed with TRAS. In addition, TRAS occurred in 2 renal transplant recipients that had been transplanted at other centers but who had their follow-up examinations in our center. Either a rise of the serum creatinine level and/or worsened systemic hypertension or routine examination with color Doppler sonography were indications for further diagnostic workup. METHODS: Direct angiography of the transplant renal artery was performed followed by percutaneous transluminal angioplasty (PTA) after the diagnosis of TRAS was confirmed in all of these patients. RESULTS: The immediate success rate for PTA was 92.3% (12/13). Only 1 patient with a severe kinking of the transplant renal artery had to undergo surgery to restore renal function. No complications occurred after the interventions. Thereafter the patients were monitored for a mean observation period of 33.15 months. Serum creatinine levels were significantly lower after the intervention, and estimated glomerular filtration rate (eGFR) increased accordingly. With regard to blood pressure there was only a trend for lower blood pressure levels and less antihypertensive use, whereas the dose of the prescribed drugs decreased significantly with time after interventional treatment of TRAS. In addition, a long-lasting rise of the hemoglobin levels could also be demonstrated. CONCLUSION: In summary, the beneficial effect of PTA of TRAS on renal function is long-lasting. Therefore, PTA, usually combined with stent placement, should be first-line treatment in TRAS in all patients. Surgical revascularization is only warranted, if PTA fails.

Severe renal vein stenosis of a kidney transplant with beneficial clinical course after successful percutaneous stenting.

A 51-year-old renal transplant recipient presented with marked renal function deterioration 13 months after renal transplantation. After exclusion of ureteral obstruction, transplant artery stenosis and acute rejection, the diagnosis of a severe renal vein stenosis was made by an MR scan. After angiographic confirmation of the stenosis, treatment was attempted with percutaneous stent angioplasty. The long-term clinical course was favorable, with marked improvement in renal function. Transplant renal vein stenosis is a rare, but potentially curable, cause of renal allograft functional deterioration.

[3 D laparoscopy versus 2 D laparoscopy : An up to date evaluation]. / 3-D-Laparoskopie vs. 2­D­Laparoskopie : Eine aktuelle Bewertung.

BACKGROUND: The 3D laparoscopy is currently under intensive discussion. At the moment the majority of newly acquired laparoscopy systems include the 3D technique. New 4K systems, which will be offered in combination with 3D, are complicating the decision-making when buying new laparoscopic systems. The aim of the article is to show the advantages and possible limitations of 3D laparoscopy. Furthermore, the position of 3D laparoscopy in the current video market is evaluated. MATERIAL AND METHODS: This study was based on an up to date literature search in PubMed. Concerning the question whether the 3D is replacing the 2D laparoscopy, observations from the industry and a personal evaluation were included in the analysis. RESULTS: The current studies show clear advantages of 3D laparoscopy concerning operation time, efficiency and workload. A major proportion of the studies were conducted on simulation trainers; however, some clinical trials also confirmed these results. The learning curve in laparoscopic surgery is clearly improved with the 3D technique and 3D also seems be useful for operations by experts. The limitation is that not every surgeon can see three dimensionally. Furthermore, the set-up in the operation room needs to be optimized so that a 3D system can be successfully implemented with the nursing staff and side effects, such as exhaustion, dizziness or headache can be prevented. CONCLUSION: The choice of video system will depend on the personal interest of the surgeon and the ability to see 3D. It can be assumed that the majority of the systems will include 3D laparoscopy but 2D laparoscopy will not be completely replaced. A dynamic development of 3D in association with 4K and robotics can be expected.

Pretransplant calcium levels have no predictive value for delayed graft function, long-term graft function, cardiovascular events, or graft and patient survival in renal transplantation.

BACKGROUND: Disorders of calcium homeostasis are one of the most common problems in patients with end-stage renal disease (ESRD). Elevated calcium levels increase the incidence of cardiovascular mortality in ESRD patients, and appear to be a risk factor for the occurrence of delayed graft function (DGF) after kidney transplantation. Therefore, we investigated the impact of pretransplant serum calcium levels on outcomes after kidney transplantation: DGF, acute rejection, graft function, and survival, as well as the incidence of cardiovascular events. METHODS: We studied 285 patients (96.9% of all transplanted patients) who underwent their first transplantation between 1995 and 2004. Demographic data were extracted from hospital records or were documented during follow-up; serum samples were collected at the time of transplantation. RESULTS: In our cohort the incidence of DGF was 16.5% and 35.4% of acute rejection episodes (ARE). However, pretransplant calcium levels were not related to DGF or ARE in our patient cohort. Furthermore, there was no correlation between pretransplant serum calcium level with the incidence of cardiovascular events or mortality, as well as graft function or survival. CONCLUSION: In our study population pretransplant calcium levels showed no effect on DGF, ARE rate, the occurrence of cardiovascular events or death, renal graft function, or survival. Therefore, pretransplant calcium level is not a helpful marker for risk stratification at the time of transplantation.

New benzoyl urea derivatives as novel NR2B selective NMDA receptor antagonists.

A novel series of benzoyl urea derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of the substitution of the piperidine ring on the biological activity of the compounds was studied. Compound 9 was active in the formalin test in mice.

[Pararectal mini-incision for strictly retroperitoneal nephrectomy in living kidney donation]. / Pararektale Miniinzision zur streng retroperitonealen Nephrektomie in der Lebendspende.

PURPOSE: In this study we present the technique of a strictly retroperitoneal donor nephrectomy via a pararectal mini-incision. MATERIAL AND METHODS: Data of 34 living kidney donations were analyzed. All donors underwent a pararectal mini-incision and strictly retroperitoneal nephrectomy (MIDN). RESULTS: Total operation time, perioperative use of pain medication, length of hospital stay after successful mobilization, and return to full enteral nutrition and regular digestion were evaluated retrospectively. Total operation time for MIDN was 132+/-26 min. The total average application was 22.2+/-19.4 mg of opioid in morphine equivalent dosage (MED), 7.7+/-6.1 g metamizol, and 512+/-325 mg NSAR during hospital stay, which was 4.9+/-1.4 days. Patients were mobilized primarily 2.9+/-8.0 h after surgery. Mobility was achieved 33.8+/-15.8 h after surgery. Enteral nutrition with fluids was started after 1.9+/-7.0 h, full enteral nutrition was accomplished after 37.4+/-19.0 h, and normal digestion returned 58.6+/-23.0 h after the procedure. CONCLUSIONS: The strictly retroperitoneal nephrectomy via a mini-incision is an elegant, minimally traumatic, safe, and quickly learnable method, resulting in short hospital stays, good cosmetic results, and a low grade of complications.

Conditioning of liver grafts with prostaglandins improves bile acid transport.

INTRODUCTION: Conditioning of liver grafts by bolus pretreatment with prostaglandins has been previously demonstrated to improve hepatic bile flow. However, the underlying mechanisms have not been investigated. To elucidate whether improved bile flow after prolonged ischemia is due to maintained bile acid secretion or due to increased paracellular permeability, we performed a study using increasing doses of the marker acid taurocholate in the isolated perfused rat liver system. METHODS: Livers were harvested from adult Lewis rats and stored for 24 hours in UW solution. Pretreatment of livers was performed 1 minute before preservation. One group received prostaglandin I2, the second group received prostaglandin E1, and the control group was treated with saline. After 24 hours of cold storage the grafts were investigated in the isolated perfused rat liver system by perfusion with an oxygenated Krebs-Ringer-Henseleit buffer. Increasing doses of the radiolabeled marker bile acid taurocholate were infused to investigate bile acid transport. RESULTS: Bile flow and bile acid output were increased by pretreatment of the livers with prostaglandin I2 and prostaglandin E1, as compared to the control group. More specifically, the maximum transport rate was tripled by prostaglandin I2 and by prostaglandin E1 preconditioning of liver grafts, in comparison to the control group (P < .01 vs prostaglanin I2 and E1). CONCLUSION: The results clearly demonstrate that increased bile flow after conditioning of liver grafts with prostaglandins is not due to increased paracellular permeability but is based on markedly improved bile acid output.