New European initiatives in colorectal cancer screening: Budapest Declaration. Official appeal during the Hungarian Presidency of the Council of the European Union under the Auspices of the United European Gastroenterology Federation, the European Association for Gastroenterology and Endoscopy and the Hungarian Society of Gastroenterology

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the 'Budapest Declaration' (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis'. The 'Budapest Declaration' together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU - the chance of equal access - be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.     

NKG2C deletion is a risk factor of HIV infection

NK cell function is important in the immune response to HIV infection. NKG2C and NKG2A are activating and inhibitory NK cell receptors, respectively, and their only known ligand, HLA-E, demonstrates increased expression in HIV infection and presents at least one HIV-derived peptide. A variation in chromosome 12 exists in which the 16-kb section of DNA encompassing the nkg2c gene is completely absent. DNA samples of 433 HIV-1-infected patients and 280 controls were genotyped by PCR, and revealed an association of the absence variation with a higher risk of HIV infection, as well as faster progression and higher pretreatment viral loads (p<0.05, respectively). Surface NKG2C expression, analyzed by FACS, on the freshly isolated lymphocytes of 20 control and 19 HIV-infected donors revealed that NKG2C expression is genotype dependent in both populations: no NKG2C expression in the -/- groups, intermediate expression in the +/- groups, and highest expression in the +/+ groups. The comparison of NKG2C and NKG2A expression in HIV and control groups (+/- and +/+ included) indicates an increased NKG2C expression on HIV patient NK cells (p<0.05) and decreased inhibitory NKG2A expression on CD8 T cells (p<0.001), and both these effects are more striking in the +/+ genotype (p<0.005). Furthermore, a positive correlation was found between HIV viral load and the proportion of NKG2C(+) NK cells. The increased expression of NKG2C in HIV patients, in combination with the genetic association of the absence variation with an increased susceptibility to HIV infection, higher HIV viral set point, and a faster progression, indicate that NKG2C is important in the defense against HIV infection and progression.     

Dichotomous effects of C-C chemokines in HIV-1 pathogenesis

Whilst many physiological functions of nitric oxide (NO) have been revealed so far, recent evidence proposes an essential role for NO in T lymphocyte activation and signal transduction. NO acts as a second messenger, activating soluble guanyl cyclase and participating in signal transduction pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial biogenesis in many cell types, including lymphocytes. Several studies undertaken on patients with RA and SLE have documented increased endogenous NO synthesis, although the effects of NO may be distinct. Here, we discuss recent evidence that NO contributes to T cell dysfunction in both SLE and RA by altering multiple signaling pathways in T cells. Although NO may play a physiological role in lymphocyte cell signaling, its overproduction may perturb T cell activation, differentiation and effector responses, each of which may contribute in different ways to the pathogenesis of autoimmunity.     

Die Einwilligung in die medizinische Behandlung minderjähriger Patienten und die Neuregelung der Patientenverfügung

Ohne Zusammenfassung     

Rupture of the spleen following thoracoscopic spine surgery in a patient with chronic pancreatitis

Purpose

To highlight the perioperative risk of intracapsular haematoma of the spleen or splenic ruptures during thoracoscopic spine surgery in patients with chronic pancreatitis.

Methods

A 38-year-old patient with an L1 burst fracture (AO A3.3) underwent a standard thoracoscopic corpectomy and replacement of the vertebral body with an extendable vertebral body replacement 10 days after posterior instrumentation of T12–L2. In patients history chronic abusive alcoholism with related diseases such as pancreatitis, followed by hemipancreatectomy was found. Six hours after the surgery, the patient became hemodynamically unstable. An emergency CT scan revealed a splenic rupture. Emergent splenectomy was performed.

Results

After surgical treatment of the L1 burst fracture, a rupture of the spleen was detected. An immediate splenectomy was performed. At the 18-month follow-up, an unchanged stable position of the cage was observed on CT.

Conclusions

Due to its proximity to the thoracolumbar junction, the spleen is vulnerable to injury during spine surgery. If the patient has undergone previous intra-abdominal operations or chronic inflammation of the pancreas is found, special care of the spleen during the operation is necessary.

     

PVA gel as a potential adhesion barrier: a safety study in a large animal model of intestinal surgery

Background

Intra-abdominal adhesions following surgery are a major source of morbidity and mortality including abdominal pain and small bowel obstruction. This study evaluated the safety of PVA gel (polyvinyl alcohol and carboxymethylated cellulose gel) on intestinal anastomoses and its potential effectiveness in preventing adhesions in a clinically relevant large animal model.

Methods

Experiments were performed in a pig model with median laparotomy and intestinal anastomosis following small bowel resection. The primary endpoint was the safety of PVA on small intestinal anastomoses. We also measured the incidence of postoperative adhesions in PVA vs. control groups: group A (eight pigs): stapled anastomosis with PVA gel compared to group B (eight pigs), which had no PVA gel; group C (eight pigs): hand-sewn anastomosis with PVA gel compared to group B (eight pigs), which had no anti-adhesive barrier. Animals were sacrificed 14 days after surgery and analyzed.

Results

All anastomoses had a patent lumen without any stenosis. No anastomoses leaked at an intraluminal pressure of 40 cmH₂O. Thus, anastomoses healed very well in both groups, regardless of whether PVA was administered. PVA-treated animals, however, had significantly fewer adhesions in the area of stapled anastomoses. The hand-sewn PVA group also had weaker adhesions and trended towards fewer adhesions to adjacent organs.

Conclusion

These results suggest that PVA gel does not jeopardize the integrity of intestinal anastomoses. However, larger trials are needed to investigate the potential of PVA gel to prevent adhesions in gastrointestinal surgery.     

Treatment strategies for infection after reverse shoulder arthroplasty

Introduction

Infection after reverse shoulder arthroplasty (RSA) is a disastrous complication. No clear guidelines describing specific management strategies for infection after RSA are available.

Methods

We retrospectively analyzed 20 patients treated for deep infection after RSA. Initial irrigation and debridement and exchange of the polyethylene inlay were performed in seven patients, and initial two-stage revision was performed in 12 and initial resection arthroplasty in one patient. Patient charts were reviewed for risk factors, clinical symptoms and investigations of those symptoms, pre- and postoperative X-rays, interval until revision surgery, causative bacteria, complications, final clinical outcome and patient satisfaction.

Results

The mean overall postoperative Constant–Murley Score (CMS) was 42.6 points, the mean UCLA score was 20.8, the mean simple shoulder test (SST) was 5.5, and the mean VAS was 1.5. When comparing the CMS, UCLA score and the SST between the revision RSA group and the resection group, significant differences between the groups were found (p < 0.05). Irrigation, debridement and exchange of the polyethylene inlay were successful only in two of the four patients with acute infection. The three patients with subacute infections were treated with initial irrigation and debridement and exchange of the polyethylene inlay, which were not successful.

Conclusion

The relatively high patient satisfaction can be explained by the low pain level once the patient is free from infection. However, functional results are poor in most cases, and this possible outcome must be discussed with the patient in the preoperative setting.     

Flupirtine-induced liver injury—Seven cases from the Berlin Case–control Surveillance Study and review of the German spontaneous adverse drug reaction reporting database

Purpose

The hepatotoxic potential of the analgesic flupirtine has attracted increased attention over the past years. Recently, risk minimisation measures such as maximum treatment duration of 2 weeks have been requested by the European Medicines Agency (EMA). This study was conducted to further elucidate the clinical pattern of flupirtine-induced liver injury (FILI).

Methods

Seven FILI patients were ascertained in all Berlin hospitals in the Berlin Case–control Surveillance Study (FAKOS) between 2002 and 2011. Furthermore, we reviewed the severe cases of flupirtine-associated hepatotoxicity included in the adverse drug reaction database of the Federal Institute for Drugs and Medical Devices (BfArM) in Germany from between 1991 and 2012.

Results

All seven FILI patients of FAKOS were hospitalised. Six of them were female, mean age was 55 years, and the most common symptoms were fatigue and jaundice. Three patients developed acute liver failure (ALF). Discontinuation of flupirtine invariably led to clinical and laboratory improvement. Review of the BfArM cases (n?=?248) showed female sex predominance and high prevalence of jaundice and ALF. Time to onset of symptoms was less than 2 weeks in 9 % of the patients with respective data.

Conclusions

Our results corroborate previous findings on FILI’s clinical pattern and on its potentially severe course. Although the hepatotoxic risk might be higher after the first 2 weeks of treatment, earlier onset of severe FILI cannot be ruled out. Postauthorisation safety studies are needed to evaluate EMA’s risk minimisation measures and to quantify flupirtine’s risk according to its duration of use.