Psychosocial and physical long-term outcome in patients with a history of takotsubo cardiomyopathy or myocardial infarction - a multi-centered case control study.

Physical long-term impacts of Takotsubo Cardiomyopathy (TTC) remain controversial and an underestimation of their severity becomes increasingly evident. Even less is known about mental long-term impacts of TTC. This study aims at a better understanding of the physical and mental long-term effects of TTC in comparison to myocardial infarctions (MI). On average 5 years after disease onset, 68 TTC patients and 68 age- and sex-matched MI patients were assessed for disease-related quality of life, depression, anxiety, chronic stress, social support, resilience, and life events prior to disease onset. Scores of TTC and MI patients were compared to each other and to normative references values. Regression analyses were used to evaluate the predictive value of the number of life events prior to disease onset for physical and mental long-term outcomes. Both groups displayed higher scores in depression and anxiety, higher levels of chronic stress, and lower scores in physical and mental quality of life in comparison to norm samples, while social support did not differ from norms. No differences between the two patient groups were observed. Within both groups, the majority of patients (TTC: 69.1%; MI: 60.3%) reported stressful life events prior to disease onset. In TTCs and MIs, the number of events had a significant impact on long-term mental health and chronic stress. Notably, both patient collectives scored higher in resilience than healthy controls. Results suggest negative long-term impacts of TTC on mental and physical wellbeing, comparable to those of MI. Besides a good somatic-medical care, psychotherapeutic support, including the development of functional coping strategies, might be warranted for TTC patients. The long-term impact of TTC should be taken as serious as that of MI.

RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8(+) T cells.

Pancreatic cancer is characterized by a microenvironment suppressing immune responses. RIG-I-like helicases (RLH) are immunoreceptors for viral RNA that induce an antiviral response program via the production of type I interferons (IFN) and apoptosis in susceptible cells. We recently identified RLH as therapeutic targets of pancreatic cancer for counteracting immunosuppressive mechanisms and apoptosis induction. Here, we investigated immunogenic consequences of RLH-induced tumor cell death. Treatment of murine pancreatic cancer cell lines with RLH ligands induced production of type I IFN and proinflammatory cytokines. In addition, tumor cells died via intrinsic apoptosis and displayed features of immunogenic cell death, such as release of HMGB1 and translocation of calreticulin to the outer cell membrane. RLH-activated tumor cells led to activation of dendritic cells (DCs), which was mediated by tumor-derived type I IFN, whereas TLR, RAGE or inflammasome signaling was dispensable. Importantly, CD8α(+) DCs effectively engulfed apoptotic tumor material and cross-presented tumor-associated antigen to naive CD8(+) T cells. In comparison, tumor cell death mediated by oxaliplatin, staurosporine or mechanical disruption failed to induce DC activation and antigen presentation. Tumor cells treated with sublethal doses of RLH ligands upregulated Fas and MHC-I expression and were effectively sensitized towards Fas-mediated apoptosis and cytotoxic T lymphocyte (CTL)-mediated lysis. Vaccination of mice with RLH-activated tumor cells induced protective antitumor immunity in vivo. In addition, MDA5-based immunotherapy led to effective tumor control of established pancreatic tumors. In summary, RLH ligands induce a highly immunogenic form of tumor cell death linking innate and adaptive immunity.

[Development of an interprofessional train-the-trainer programme to implement shared decision-making in medical rehabilitation clinics]. / Entwicklung eines interprofessionellen Train-the-Trainer-Programms zur Implementierung der partizipativen Entscheidungsfindung in Rehabilitationskliniken.

BACKGROUND AND AIMS: Until now, training programmes on shared decision-making (SDM) have been designed exclusively for medical decision-making and predominantly for physicians. How-ever, interprofessional treatment, such as in medical rehabilitation, is very important in the treatment of chronic diseases. This requires an extended understanding of shared decision-making. Therefore the aim of the study is to develop an interprofessional training (IPT) for implementation of shared decision-making (SDM) in rehabilitation clinics. METHODS: The needs and preferences of the persons undergoing rehabilitation were collected in 4 focus groups, with frequency of answers analyzed by means of inductive category formation. The providers' preferences and requirements concerning a training programme on shared decision-making were assessed through an expert survey and underwent a mainly descriptive-explorative evaluation as well as a partial content analysis. RESULTS: 36 patients took part in the focus groups. Besides the wish for more participation in treatment decisions, they expressed further needs, such as more time and respect. The -experts of the 4 clinics (n=34, rate of response: 71%) also assessed these aspects of the patient-provider interaction as relevant. However, they saw the highest training need in the area of interdisciplinary team interactions. CONCLUSION: The interprofessional training programme "Fit for SDM" was developed on the basis of these results, and consists of 2 modules for the implementation of shared decision-making in medical rehabilitation. Module 1 focuses on external participation (provider-patient interaction), Module 2 on internal participation (team interaction). Module 2 was additionally used for preparing executives in their role as multipliers in the team. The training is currently being evaluated in a cluster-randomized multicentre study.

Case report: inflammatory myofibroblastic tumor of the duodenum.

INTRODUCTION: We report a very rare case of inflammatory myofibroblastic tumor of the duodenum. A 16-year-old boy underwent esophagogastroduodenoscopy for intermittent epigastric pain, night sweats, and malaise. CASE REPORT: An exophytic mass lesion was found in the first part of the duodenum, but biopsies were non-diagnostic. Computed tomography confirmed a 60-mm mass with no lymphadenopathy, and the patient underwent surgical resection. Histology revealed spindle cells with the morphological and immunophenotypical profile of myofibroblasts on a background of mixed inflammatory infiltrate, typical of inflammatory myofibroblastic tumor. Six months after surgery, the patient developed a recurrence, and this was successfully treated by immunosuppression. Currently, the patient is asymptomatic, and there is no radiological or pathological evidence of disease.

Pancreas and cystic fibrosis: the implications of increased survival in cystic fibrosis.

Pancreatitis affects 0.5% people with cystic fibrosis (CF) in the UK and 0.01% of the normal population. Why do some with CF get pancreatitis and some not? And does pancreatitis in neonates result in pancreatic failure with no further inflammation or risk of pancreatic cancer? Review of the literature would suggest that 85% of those with CF have pancreatic destruction as children with minimal risk of further inflammatory or neoplastic changes. Those with a functioning pancreas are at risk of developing pancreatitis. There are several case series of pancreatic cancer reported in CF patients, but overall the risk is unknown. As patients with CF and pancreatic sufficiency are living longer, further studies to assess the risk of developing pancreatic cancer in this subgroup should be considered.

Pancreatic cancer--is an aggressive approach justified?

INTRODUCTION: Surgery is the only curative treatment for carcinoma of the pancreas. Resection rates can be low (4.5%), figures of 30% have also been suggested as possible. The approach undertaken in this unit is to consider all patients as potentially resectable unless otherwise proven. PATIENTS & METHODS: 140 patients were studied over 6-year period; 113 underwent palliative treatment (48% distant metastases, 40% local spread, 11% high operative risk); 14 had a triple bypass (14/113 = 12%), 99 were managed conservatively, 43 received palliative chemotherapy. 23/140 (16%) underwent Whipple's procedure (n = 23; 12 females, 11 males; mean age, 60 years); 4/23 had chronic pancreatitis. Distal pancreatectomy was undertaken in 4 patients. RESULTS: Median survival time for patients undergoing a triple bypass was 5 months (range, 0.1-20 months), 3 months for patients treated conservatively (range, 0.1-30 months) and 5 months for patients undergoing palliative chemotherapy (range, 1-30 months). 30-day mortality for Whipple's procedure was 4% (1/23) with median survival rate for patients with carcinoma of 13 months (range, 5-66 months); 31 months for patients with clear resection margins and negative nodes (n = 5). CONCLUSION: This policy allows a resection rate of 19% with increased median survival rate for patients with cancer by 8 months more than those who where not resected. Aggressive staging and pancreatic biopsies allow patients to be entered into chemotherapy trials with improvement in survival and potential future benefits.

Benign complications of expandable metal stents used in the palliation of oesophageal carcinoma: two case reports.

We describe two patients who were treated with self-expanding metal stent (SEMS) insertion as palliation of malignant oesophageal strictures. Both patients re-presented with dysphagia several months after SEMS insertion due to benign strictures. Initial treatment with balloon dilation and medical management had limited success so both patients had further SEMS inserted across the secondary benign strictures. This provided very good symptomatic relief. Chemotherapy and chemo-radiation in patients with inoperable oesophageal carcinoma are prolonging patient survival. As patients survival lengthens benign complications of SEMS may become an increasing clinical problem.

Risk-adjusted prediction of operative mortality in oesophagogastric surgery with O-POSSUM.

INTRODUCTION: The present study was designed to develop a dedicated oesophagogastric model for the prediction of risk-adjusted postoperative mortality in upper gastrointestinal surgery (O-POSSUM). METHODS: Using 1042 patients undergoing oesophageal (n = 538) or gastric (n = 504) surgery between 1994 and 2000 the Portsmouth predictor equation for mortality (P-POSSUM) scoring system was compared with a standard logistic regression O-POSSUM model and a multilevel O-POSSUM model using the following independent factors: age, physiological status, mode of surgery, type of surgery and histological stage. RESULTS: The overall mortality rate was 12.0 per cent (elective mortality rate 9.4 per cent and emergency mortality rate 26.9 per cent). P-POSSUM overpredicted mortality (14.5 per cent), particularly in the elective group of patients. The multilevel model offered higher discrimination than the single-level O-POSSUM and P-POSSUM models (area under receiver-operator characteristic curve 79.7 versus 74.6 and 74.3 per cent). When observed to expected outcomes were evaluated, the multilevel O-POSSUM model was found to offer better calibration (Hosmer-Lemeshow chi(2) statistic 10.15 versus 10.52 and 28.80). CONCLUSION: The multilevel O-POSSUM model provided an accurate risk-adjusted prediction of death from oesophageal and gastric surgery for individual patients. In conjunction with a multidisciplinary approach to patient management, the model may be used in everyday practice for perioperative counselling of patients and their carers.

[Use of human intravenous immunoglobulin in dogs with primary immune mediated hemolytic anemia]. / Anwendung von humanem Immunglobulin bei Hunden mit primärer immunbedingter hämolytischer Anämie.

Immune mediated hemolytic anemia (IMHA) in dogs is a severe disease with a high mortality rate. As human immunoglobulin (HIG) was reported to be beneficial for the treatment of IMHA in dogs we examined the influence of HIG on the course of the disease in our dogs with IMHA. Of 22 dogs with primary IMHA 9 dogs received in addition to routine immunosuppressive therapy HIG at a dose of 0.19 to 0.68 g/kg (median 0.35 g/kg), 13 dogs did not receive HIG (-HIG group). Both groups were similar in terms of age, weight, the presence of autoagglutination, spherocytosis, positive Coombs' test, icterus and pigmenturia. The lowest hematocrit measured during the disease was significantly lower in the +HIG group compared to the -HIG group and dogs in the +HIG group received significantly more transfusions than those of the -HIG group. This is an indication for more severe disease signs of the +HIG group dogs. Although mortality during hospitalization and the time from hospital admission to release or death was not significantly different between the two groups, we interpret this similar course of the IMHA despite more severe signs of the +HIG group dogs as a potential positive effect of the HIG therapy.

Chest pain following oesophageal stenting for malignant dysphagia.

AIM: The palliative use of self-expanding metallic stents has been widely reported to relieve dysphagia in cases of oesophageal carcinoma. Little has been documented on the severity of chest pain following oesophageal stenting. The aim of this study was to investigate the association of pain with oesophageal stenting for malignant dysphagia. METHODS: Fifty-two patients with inoperable oesophageal carcinoma underwent stent placement between 1995-1999. Daily opioid analgesic requirements (mg of morphine equivalent doses) were monitored for 3 days before and 7 days after stenting. The degree of palliation was expressed as a dysphagia score (0-3). Hospital stay, readmission days, stent complications and patient survival time were also recorded. RESULTS: Twenty-six patients (50%) required opioid analgesia for chest pain (median dose: 80 mg morphine/day) within 48 h of the procedure compared to 11 (21.2%) patients before stenting (P = 0.0041). A significant increase was evident in the analgesic consumption following stent deployment (P < 0.001). The dysphagia score improved by a median value of 1 (CI 0.25)P < 0.001, with a re-intervention rate of 11.5%. The median survival time was 40 days post stenting (range 1-120). CONCLUSION: A significant proportion of patients developed chest pain after oesophageal stenting, requiring high dose opioid analgesia. As the origin of the pain is still unknown, pre-emptive analgesia may a play role in reducing stent-related morbidity and possibly in-hospital stay.

Abnormal liver function tests in a patient fed with total parenteral nutrition and treated with octreotide.

Octreotide is a long-acting analog of somatostatin, a hypothalamic release-inhibiting hormone. It is sometimes used therapeutically to relieve symptoms associated with acromegaly and gastroenteropancreatic endocrine tumors. It has also been used in the treatment of short-bowel syndrome and gastrointestinal and biliary fistulae. We report a patient with biliary leakage due to Marizzi's syndrome treated with total parenteral nutrition and octreotide who developed abnormal liver function tests that improved when the two treatments were stopped. We also review the literature regarding abnormal liver function tests in patients on total parenteral nutrition.

A phase II study evaluating the tolerability and efficacy of CAELYX (liposomal doxorubicin, Doxil) in the treatment of unresectable pancreatic carcinoma.

BACKGROUND: Preclinical studies of liposomal doxorubicin (CAELYX) have demonstrated significant inhibition of growth of human pancreatic cancer explants in nude mice. This study evaluated the efficacy of CAELYX in chemotherapy-naïve patients with unresectable, histologically confirmed pancreatic carcinoma. Secondary endpoints were quality of life (QOL). time to progression and overall survival. PATIENTS AND METHODS: Twenty-two patients (median age 65) were enrolled. CAELYX was administered to the first five patients at a dose of 30 mg/m2 three-weekly. Two of these patients were dose escalated to 50 mg/m2 four-weekly. Subsequent patients were all treated on the latter schedule. RESULTS: Two patients died after consenting to enter the study but before treatment was commenced and are not included in the analysis. Sixteen patients were evaluable for response. No objective responses were seen. Six patients had stable disease. One patient experienced grade 4 toxicity with palmar plantar dysaesthesia (PPE), but continued treatment after dose reduction and delay. Four patients experienced grade 3 stomatitis and two grade 3 nausea. Median survival from time of starting chemotherapy was 3.2 months (range 21 days to 19 months) and one year survival was 10%. Eight patients completed at least two EORTC QLQ C-30 questionnaires. There was no significant change in either global QOL or in any functional or symptom subscale score. CONCLUSION: No objective responses were seen with CAELYX in this study. CAELYX was however associated with stable disease, but data were inconclusive with regard to clinical benefit. It warrants further investigation in the context of combination trials.

Fatal hemorrhage in stented esophageal carcinoma: tumor necrosis of the aorta.

We report a case of fatal hematemesis in a patient with an esophageal stent for palliation of malignant dysphagia. Post-mortem examination showed tumor thrombi in the vasa vasorum of the aorta causing aortic wall necrosis and perforation. Massive delayed hemorrhage is reported as a complication of metallic esophageal endoprostheses but in the majority of cases there have been no post-mortem examinations. In this case the post-mortem examination demonstrated that the cause of death was not stent-related. We feel that this case report adds important information to the current literature regarding the delayed complications seen in patients with esophageal carcinoma who have been palliated with metallic stents.

Sensitization and lung function in workers occupationally exposed to natural thickening products.

BACKGROUND: Three workers engaged in the manufacture of natural thickener products (Cassia spp., guar, and tamarind flour) were occupationally sensitized to Cassia spp. Therefore, a cross-sectional study on the prevalence of sensitization among and respiratory health of the employees of this plant was conducted. METHODS AND RESULTS: Sixty-two workers (36 with high, 26 with low exposure) participated in the survey. Skin prick tests and specific IgE tests with extracts of these components revealed that 11.3% were sensitized to Cassia spp. and 9.7% to at least one species of storage mites, with a significantly higher portion of atopic subjects in the sensitized group. Overall, 55% of the subjects reported work-related symptoms (upper and lower airways, eyes, or skin). FVC % pred. was significantly lower in highly exposed workers, while RV % pred. and RV%TLC % pred. were significantly higher in this group. In the multivariate model, sensitization was not a risk factor for impairment of lung function. CONCLUSIONS: Dust exposure to flours may not only cause allergic sensitization but also induce chronic changes in lung function.

Laparoscopic cholecystectomy injury: an unusual indication for liver transplantation.

The introduction of laparoscopic cholecystectomy has been associated with a rise in the number of reported bile duct injuries (0.3%-0.8%). Significant vascular injuries are rare (0.16%), but may lead to life-threatening complications. We present a case report of a patient undergoing transplantation for a laparoscopic cholecystectomy injury.

Complete development of the porcine coccidium Isospora suis Biester, 1934 in cell cultures.

Development from inoculated sporozoites to unsporulated oocysts of Isospora suis Biester, 1934 is described in a swine testicular (ST) cell line. Sporozoites penetrated ST cells within 1 hr postinoculation (PI). Development was initially by endodyogeny to produce binucleate type I meronts and type I merozoites. Division by endodyogeny continued during the 13-day observation period and type I merozoites were the developmental stages most abundant at observation periods >3 days PI. Mutinucleate type II meronts and type II merozoites were first observed 7 days PI. Gamonts and oocysts were present 12 days PI. Oocysts did not sporulate in vitro. The ultrastructural features of stages were similar to those that occur in the pig host.

Does pre-scan oxygen improve ultrasonic imaging of the pancreas?

Ultrasonic imaging of the pancreas is often impaired by overlying bowel gas. Oxygen therapy has, in the past, been shown to be effective in reducing the gas in the cysts of pneumatosis coli. Using the same hypothesis, a randomized, single blind study comparing ultrasonic imaging of the pancreas with and without prior oxygen therapy was carried out. Fifty-eight consecutive patients with acute abdominal complaints were randomized to two groups: Group 1, control - no oxygen (n = 30, 14 male, 16 female, mean age 61.9 +/- 17.8 years); Group 2, treatment (n = 28, 14 male, 14 female, mean age 61.4 +/- 14.5 years) received oxygen therapy (100% humidified at 101/min for 8-10 h prior to the ultrasound). Pancreatic visualization was graded good, moderate or poor. Mean paO2 in Group 1 was 10.9 +/- 1kP and in Group 2 was 36 +/- 10.5kP (P < 0.001 unpaired t-test). Pancreatic visualization was: GOOD-Group 1, 8; Group 2, 19; MODERATE - Group 1, 8; Group 2, 4; POOR - Group 1, 14; Group 2, 5. Oxygen therapy is a safe, cheap, non-invasive method of improving pancreatic visualization and may act by reducing overlying bowel gas.