Energy Metabolism in Residents in the Low- and Moderate Altitude Regions of Central Asia with MAFLD and Type 2 Diabetes Mellitus.

The knowledge about the features of energy metabolism in MAFLD in the population living at different climatic and geographic heights is lacking. The goal of this study is to explore the biochemical parameters of blood and erythrocyte energy consumption in patients with MAFLD with and without DM2 living in the low- and moderate-altitude regions of Central Asia. Our study was carried out on patients living in low-altitude mountains: Bishkek, altitude=750-800 m; n=67 (MAFLD with DM 2: n=24; MAFLD without DM2: n=25; control: n=18), and At-Bashy District, Naryn Region, altitude=2046-2300 m; n=58 (MAFLD with DM2: n=28; MAFLD without DM2: n=18; control: n=12). Non-alcoholic fatty liver disease was diagnosed according to history, laboratory tests, liver ultrasound, and exclusion of other liver diseases. The level of liver fibrosis was determined using the FIB-4 score. Blood adenosine 5'-triphosphate (ATP) was determined using the CellTiter-Glo method. Healthy residents living in moderate altitudes have significantly higher levels of cytosolic ATP in their blood (p+≤+0.05) than residents living in low mountains. MAFLD is characterized by an increase in the level of ATP concentration in their blood. ATP concentration decreased significantly in patients with MAFLD with DM2 living in moderate-altitude in comparison to those living in low-altitude mountains. The results suggest that chronic altitude hypoxia leads to a breakdown in adaptive mechanisms of energy metabolism of ATP in patients with MAFLD with type 2 DM.

Nutrition-related care needs of older patients in hospital: A qualitative multimethod study.

PURPOSE: To investigate the nutrition-related care needs of older patients in hospitals. METHODS: A qualitative multimethod study was performed. By purposive sampling, older patients were included for observations of the nutrition process and interviews from a perioperative unit, an internal Medicine unit, and one acute geriatric care ward of an acute care hospital. Preliminary findings were discussed, validated, and further explored in two focus group discussions with interprofessional nutritional healthcare experts. FINDINGS: Seventeen women and five men with a mean age of 86 years participated in patient observations and interviews. Eight experts with at least 10 years of professional experience who were employed in this setting for 3 years or more participated in interviews. Three themes of nutrition-related care needs were elaborated: The need to assess and address older patients' attitudes toward life, the need for nutrition-related education, and the need for food intake support. These care needs added to the development and validation of a new nursing diagnosis "risk for inadequate protein energy nutrition" and in consequence to develop a complex nursing intervention to optimize the nutrition of older patients. CONCLUSIONS: It is crucial to assess and understand the patients' attitudes toward life, which affect purposes of treatment, diet, and menu choices. IMPLICATIONS FOR NURSING PRACTICE: Implementation of assessing nutrition-related care needs of older inpatients is needed. Addressing these care needs within the Advanced Nursing Process can lead to appropriate nursing diagnoses, nursing outcomes, and interventions, which enhance person-centered care, patients' self-care abilities, and consequently patients' nutritional status.

ZIEL: Untersuchung der ernährungsbezogenen Pflegebedürfnisse älterer Patient*innen im Krankenhaus. METHODE: Es wurde eine qualitative Multimethodenstudie durchgeführt. Mittels zielgerichteter Rekrutierung wurden ältere Patient*innen aus den Abteilungen allgemeine Chirurgie, innere Medizin und universitäre Klinik für Akutgeriatrie eines Krankenhauses für Beobachtungen des Ernährungsprozesses und Interviews einbezogen. Die vorläufigen Ergebnisse wurden in zwei Fokusgruppengesprächen mit Expert*innen aus verschiedenen Berufsgruppen diskutiert, validiert und weiter analysiert. ERGEBNISSE: Siebzehn Frauen und fünf Männer mit einem Durchschnittsalter von 86 Jahren nahmen an Patient*innenbeobachtungen und -interviews teil. Es wurden drei Themen ernährungsbezogener Pflegebedürfnisse herausgearbeitet: Das Bedürfnis, die Lebenseinstellung älterer Patient*innen zu erfassen; das Bedürfnis, ernährungsbezogene Informationen zu erhalten und das Bedürfnis nach Unterstützung bei der Nahrungsaufnahme. Diese Pflegebedürfnisse unterstützten die Entwicklung und Validierung einer neuen Pflegediagnose "Risiko für inadequate Protein-Energie-Ernährung" und infolgedessen einer komplexen pflegerischen Intervention zur Optimierung der Ernährung älterer Patient*innen. SCHLUSSFOLGERUNG: Es ist von entscheidender Bedeutung, die Lebenseinstellung der Patient*innen einzuschätzen und zu verstehen, da sich diese auf die Behandlungsziele, die Ernährung und die Menüwahl auswirkt. AUSWIRKUNGEN AUF DIE PFLEGEPRAXIS: Die Erfassung der ernährungsbezogenen Pflegebedürfnisse älterer stationärer Patient*innen muss implementiert werden. Die Berücksichtigung dieser Pflegebedürfnisse im Rahmen des Advanced Nursing Process kann zu angemessenen Pflegediagnosen, Pflegeergebnissen und Interventionen führen, welche die personenzentrierte Versorgung, Selbstpflegefähigkeiten der Patient*innen und damit deren Ernährungszustand verbessern.

[Management of persistent colitis after successful immunotherapy for non-small cell carcinoma of the lung]. / Management einer persistierenden Kolitis nach erfolgreicher Immuntherapie eines nicht-kleinzelligen Karzinoms der Lunge.

Immune checkpoint inhibitors have shown remarkable efficacy as new-generation drugs in anti-tumor therapy. However, the nonspecific activation of the immune system leads to a number of adverse side effects, so-called immune-related adverse events (irAEs), including the occurrence of diarrhea and colitis in about one third of treated patients.Endoscopically and histologically, there is significant overlap of immune-mediated colitis with classic IBD, making differentiation difficult.Therapeutically, high-dose glucocorticoids are used in grade 3 (severe) to grade 4 (life-threatening) colitis, in addition to discontinuation of ICI therapy. Steroid-refractory cases (up to 42%) benefit from the TNF inhibitor infliximab. Vedolizumab, analogous to inflammatory bowel disease, represents second-line therapy for infliximab-refractory cases. Little data exist to date on the efficacy of tofacitinib in refractory cases.We describe the case and therapeutic management of severe and persistent immune-mediated colitis after successful immunochemotherapy with pembrolizumab in an 80-year-old man with metastatic non-small cell carcinoma of the lung and pre-existing colitis unclassified and other comorbidities.

[Risk of malnutrition in elderly patients in acute hospitals - implications for nursing practice]. / Gefahr einer Mangelernährung älterer Patient_innen im Akutspital.

Risk of malnutrition in elderly patients in acute hospitals - implications for nursing practice Abstract. Background: The risk of malnutrition is increased in advanced age and acute illness, and its assessment and needs-based support are part of the responsibility of nursing. Research question / objective: The following research question aims to analyse the nutritional status and possible correlations with nursing diagnoses and other patient characteristics from persons who are 80 years old and older: Which patterns in the sense of clusters can be identified concerning calorie and protein requirements and other patient characteristics? METHODS: Explorative cross-sectional study with cluster analysis based on food intake protocols and nursing documentation. Patients from surgery, internal medicine and university acute geriatric care wards were included in this non-probability sample. RESULTS: Four groups were formed out of the data from 135 patients (protein requirement coverage): Well-nourished (116 %), sufficiently-nourished (77 %), insufficiently-nourished (59 %) and poorly-nourished (40 %). A significant correlation between calorie and protein requirement coverage and treatment area has been shown. CONCLUSIONS: The degree of coverage of protein- and energy requirement is related to the treatment area and consequently to its team culture and treatment concept. Based on the characteristics of the well-nourished, a positive effect of interprofessional cooperation and systematic recording of the risk of malnutrition, as implemented in the treatment area of acute geriatric care, might be concluded.

Interventions to optimise nutrition in older people in hospitals and long-term care: Umbrella review.

BACKGROUND: Inpatients have a high need for protein-energy intake because of increased physical stress metabolism due to illnesses. Protein-energy undernutrition in older patients increases the risk of complications such as falls, pressure ulcers and even death. An overview of effective interventions addressing this complex issue of malnutrition in older people is missing. AIMS: To give an overview of effective interventions to optimise nutrition in older people in hospitals and long-term care. DESIGN: An umbrella review, according to the Joanna Briggs Institute and PRISMA statement, was conducted in April 2020. METHODS: A systematic search of publications from 2010 until 2020 was conducted in CINAHL, PubMed and Cochrane Database. Included were studies reporting nutrition interventions that involved nurses or the interprofessional team in optimising older hospitalised people's nutrition. Excluded were studies investigating the effects of parenteral nutrition, certain food supplements or tube feeding and research from intensive, community or palliative care. Components of interventions were classified according to the intervention Nutrition management: Patients' assistance, patients' instruction, foodservice, environment for meals and nutrient-dense snacks. FINDINGS: Included were 13 reviews from 19 countries of the continents Asia, Australia, Europe and North America from hospitals and long-term care settings. An interprofessional food promoting culture, including staff training as part of a multi-component measure, has shown to be a successful element in implementing activities of Nutrition Management. CONCLUSION: Several studies synthesised that optimising nutrition in older people in hospitals and long-term care is achievable. Interventions were effective if-on a meta-level-staff training was addressed as part of a multi-component measure to reach an interprofessional food promoting culture. IMPLICATIONS FOR PRACTICE: Interventions to optimise older people's nutrition have to consider an interprofessional food promoting culture, including staff training about the importance of nutrition, patients' assistance and an appropriate environment for meals.

Developing a nursing diagnosis for the risk for malnutrition: a mixed-method study.

AIM: As the risk for malnutrition in older people in hospitals is often underreported, we aimed to develop a risk nursing diagnosis, including label, definition and risk factors. DESIGN: A convergent parallel mixed-methods design was employed. METHODS: A literature review led to risk factors, validated by 22 hospitalized older people's perspectives and observations, including their nursing records. Per participant, one interview (qualitative), one non-participatory observation of three meals (198 hr; qualitative) and one nursing record evaluation (quantitative) were conducted. FINDINGS: According to the classification system of NANDA International, the risk for protein-energy malnutrition is defined with 18 risk factors, including associated conditions. Content validated risk factors are presented from three participants with the most, medium and least coherent nursing record, measured with the Quality of Diagnosis, Intervention and Outcomes tool. CONCLUSION: This new nursing diagnosis supports nurses to manage the risk for malnutrition and optimize older people's nutrition.

Functional Molecular Network Analysis Enables Prediction of Response to Vedolizumab Therapy in Anti-TNF Refractory IBD Patients.

BACKGROUND: We applied for the first time 2 label-free technologies, physiological intermolecular modulation spectroscopy (PIMS) and nematic protein organization technic (NPOT) in anti-tumor necrosis factor (TNF) refractory inflammatory bowel disease (IBD) patients to identify clinical responders to vedolizumab therapy and elucidate their underlying functional molecular network. METHODS: PIMS analysis was performed in peripheral blood taken prior to the first vedolizumab application in 20 IBD patients (Crohn disease n = 13; ulcerative colitis n = 7) refractory to at least 1 previous anti-TNF agent therapy. Peripheral blood taken from clinical responders and nonresponders at week 14 of vedolizumab therapy were additionally subjected to NPOT analysis. Response to therapy was assessed by respective clinical disease activity scores (partial Mayo Score and Harvey-Bradshaw Index). RESULTS: Clinical response to vedolizumab treatment was observed in 7 of 13 Crohn disease and 4 of 7 ulcerative colitis patients at week 14. Response to therapy was accurately predicted by PIMS blood analysis in 100% of ulcerative colitis and 77% of Crohn disease patients. Overall prediction of clinical response with PIMS blood analysis was achieved with a 89% positive predictive value and a 82% negative predictive value. NPOT analysis revealed the heightened expression of the proteins ITGB7, ITGAV, ITG3, PF4, and ASGH in the peripheral blood of vedolizumab responders compared to nonresponders. CONCLUSIONS: PIMS analysis of the blood of anti-TNF refractory IBD patients was able to stratify responders to vedolizumab therapy with high accuracy and specificity. NPOT technology could decipher underling molecular networks in the blood of responders, enabling subsequent personalized therapeutic approaches in IBD.

[Full thickness resection of a pyloric adenoma in the proximal duodenum in a 67-year-old patient with attenuated polyposis coli]. / Vollwandresektion eines Pylorusdrüsenadenoms im proximalen Duodenum bei einem 67-jährigen Patienten mit attenuierter Polyposis coli.

BACKGROUND: Pyloric gland adenomas (PGAs) are very rare and underdiagnosed, mostly be founded in the stomach. Similar to colorectal adenomas they have a high risk of malignant transformation to adenocarcinoma up to 12-47 %. Endoscopic resections in the duodenum harbor a significant risk of complications. EMR is the current standard technique for treatment of duodenal non-ampullary adenomas. Complete resection rates are considerably high at about 90 %. Adverse events as bleeding was reported up to 25 %. ESD is not recommended for resection of duodenal lesions since the perforation rate may be as high as 35 %. Use of EFTR in the duodenum are limited to a single case study of 20 patients. CASE: A 67 year old patient with attenuated polyposis coli presented for screening. Gastroscopy showed a 20 mm large, non-ampullary lesions in the proximal duodenum (pars I). The margins of the duodenal lesions were marked with a high-frequency (HF) probe. An integrated balloon dilatation (20 mm) of the upper esophageal sphincter and the pylorus was performed to facilitate advancing of the gastroduodenal FTRD® (Ovesco Endoscopy AG). After pulling the duodenal lesion into the cap with a grasper the FTRD clip was deployed and the lesion immediately resected with the preloaded snare. A single-shot antibiotic prophylaxis with 2 g ceftriaxone i. v. was administered during the intervention. Second-look endoscopy was scheduled 24 h after resection. The resectat showed histologically a gastric type adenoma of 18 mm in the proximal duodenum (immunohistochemistry positive for Mucin-1, Mucin-5, Mib 1). CONCLUSION: Herein we present the first case of duodenal EFTR in a patient with attenuated FAP and a PGA. There are currently no specific guidelines for the removal and surveillance. ASGE recommends resection and surveillance endoscopy at 3-5 years interval.

Energy and protein intake in 330 geriatric orthopaedic patients: Are the current nutrition guidelines applicable?

BACKGROUND AND AIMS: Elderly orthopaedic patients are potentially at a high nutritional risk. The reasons for this are numerous as i.e. reduced appetite, sensation of satiety after eating small amounts of food, multi-medication or immobility. This is in contrast to the increased energy and protein recommendations for geriatric orthopaedic patients. METHODS: Oral intake during hospitalization of more than 1000 geriatric orthopaedic patients aged over 80, with or without fracture, was recorded, calculated and then compared to energy and protein requirements by clinical dietitians according to international guidelines. RESULTS: 330 patients were included in the sample of which 76.7% were female (n = 253) and 23.3% male (n = 77). The mean age was 87.4 (+/-4.7) years. Most patients (204 = 61.8%) had lived at home prior to hospital admission. 72 patients (21.8%) lived in a retirement home, 54 (16.4%) lived in a nursing home. 98.5% of the included patients were unable to cover their energy needs and 99% were unable to achieve their protein needs. Only five patients (1.5%) were able to achieve their energy needs and one single patient (0.3%) achieved his recommended protein intake. CONCLUSION: Orthogeriatric patients are at high risk of malnutrition. Very few of these patients were able to cover their estimated energy and protein needs through dietary intake. This suggests that there is a high need of dietetic interventions in this multimorbid elderly patient group. The aim of the nutritional therapy and its interventions should be its continuity, especially after hospital discharge so that long-term optimization of the nutritional status can occur. Future research should further investigate if current recommendations are applicable and the best way to achieve a better nutritional status in this population risk group.

Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.

OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.

Physiological intermolecular modification spectroscopy for the prediction of response to anti-tumor necrosis factor therapy in patients with inflammatory bowel diseases.

BACKGROUND/AIMS: Anti-tumor necrosis factor (TNF) antibodies have clinical efficiency only in a subgroup of patients with inflammatory bowel diseases (IBD). Prediction of clinical response is a critical clinical problem. Physiological intermolecular modification spectroscopy (PIMS) is a label-free technology performed in physiological conditions. PIMS enables real-time monitoring of dynamic molecular resonance of entire proteins and macromolecules of an individual. The aim of this study was to explore the capacity of PIMS to discriminate IBD patients regarding response to anti-TNF treatment. METHODS: Protein extracts of peripheral blood mononuclear cells (PBMC) from 30 outpatients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and treated with infliximab were subjected to PIMS analysis in a blinded transversal study. Total protein from each patient's PBMCs was challenged with infliximab. Dynamic changes in macromolecular interaction were registered while the temperature rose from -37 to 37°C. Individual macromolecular volume and molecular elasticity were determined for each patient. RESULTS: Clinical data revealed that 67% of UC and 79% of CD patients responded to infliximab therapy during the 3-month study period based on their respective clinical activity score. These results confirm that PIMS data predicted response to anti-TNF therapy with an accuracy of 96%. CONCLUSION: PIMS stratified IBD patients into two groups, responders and nonresponders, which correlated with the clinical efficacy of anti-TNF therapy. PIMS seems to be a powerful technology to adapt IBD treatment to the individual patient. Further studies with PIMS might enable to predict clinical response to biological treatment in IBD patients before the therapy is initiated.

Early recurrence of pancreatic cancer after resection and during adjuvant chemotherapy.

BACKGROUND/AIM: Adjuvant chemotherapy for 6 months is the current standard of care after potentially curative resection of pancreatic cancer and yields an overall survival of 15-20 months. Early tumor recurrence before or during adjuvant chemotherapy has not been evaluated so far. These patients may not benefit from adjuvant treatment. PATIENTS AND METHODS: Thirty-five patients with resection of ductal pancreatic carcinoma and adjuvant chemotherapy with gemcitabine were analyzed between 2005 and 2007. All patients had a computed tomography (CT) scan before and during adjuvant chemotherapy after 2-3 months, 12/35 patients had a histologically confirmed R1 resection. Recurrence of pancreatic cancer was determined by CT scan and the clinical course. RESULTS: Median survival of 35 patients with resected pancreatic cancer was 19.7 months, and the 2-year survival was 44%. Thirteen (37%) of the 35 patients analyzed with a CT scan showed tumor recurrence during adjuvant chemotherapy. Overall survival of patients with tumor recurrence was 9.3 months with a 2-year survival rate of 13%, whereas median overall survival of patients without early relapse was 26.3 months (P<0.001). Local recurrence of pancreatic cancer occurred in 38% (5/13); 46% (6/13) of patients developed distant metastasis, and 38% (5/13) developed lymph node metastasis. Early tumor recurrence during or adjuvant chemotherapy did not correlate with R status (R1 vs R0, P=0.69), whereas histologically confirmed lymph node invasion (pN0 vs pN1) and grading showed a statistically significant correlation with early relapse (P<0.05). CONCLUSION: A significant fraction of patients with resected pancreatic cancer have early relapse during adjuvant chemotherapy, especially those with lymph node metastasis. Radiologic examinations prior to and during adjuvant chemotherapy will help to identify patients with tumor recurrence who are unlikely to benefit from adjuvant treatment and will need individualized palliative chemotherapy.

Treatment of unresectable cholangiocarcinoma: conventional transarterial chemoembolization compared with drug eluting bead-transarterial chemoembolization and systemic chemotherapy.

BACKGROUND: Unresectable cholangiocarcinoma (CCC) has a poor prognosis. Patients with intrahepatic CCC have a very limited benefit from systemic chemotherapy (ChT). The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of conventional transarterial chemoembolization (cTACE) with mitomycin-C and of irinotecan-eluting beads (iDEB-TACE), and to retrospectively compare them with ChT with oxaliplatin and gemcitabine. MATERIALS AND METHODS: Between June 2002 and June 2010, three independent prospective trials were carried out and compared retrospectively. Following predefined study protocols, 26 patients with histologically proven intrahepatic CCC were treated with iDEB-TACE (200 mg irinotecan), 10 patients were treated with cTACE using 15 mg mitomycin-C mixed with 5-10 ml of ionized oil (lipiodol), followed by embolization with gelfoam, and 31 patients received systemic ChT with gemcitabine and oxaliplatin. Treatment response and progression-free survival (PFS) were assessed by computer tomography or MRI every 2 months according to Response Evaluation Criteria in Solid Tumors. Clinical and laboratory data were assessed for side-effects according to National Cancer Institute-Common Toxicity Criteria. RESULTS: iDEB-TACE resulted in PFS of 3.9 months and overall survival (OS) of 11.7 months, compared with a PFS of 1.8 months and OS of 5.7 months, respectively, in patients treated with cTACE, and a PFS of 6.2 months and OS of 11.0 months, respectively, in patients treated with oxaliplatin and gemcitabine. The medium follow-up of patients treated with iDEB-TACE was 12 months; 2 months after treatment, 13 patients (50%) had progressive disease, 11 patients (42%) had stable disease, and one patient had a partial response and became eligible for secondary liver resection. Local tumor control was achieved in 66% of patients; 4% had a partial response, 62% had stable disease, and 27% progressive disease. Common Toxicity Criteria grade III or IV toxicities for iDEB-TACE were abdominal pain (n=7), hepatic abscess (n=1), pleural empyema due to biliary leakage (n=1), and one death due to cholangitis with hepatic failure in a patient with liver cirrhosis. No hematological side-effects were observed. Almost every patient experienced a 'postembolization syndrome' with low-grade fever, nausea, and abdominal pain for up to 2 weeks. CONCLUSION: This is the first study demonstrating that treatment of patients suffering from intrahepatic CCC with iDEB-TACE is safe in patients with normal liver function, and results in a prolongation of PFS and OS. Local tumor control, PFS and OS seem similar to systemic ChT with oxaliplatin and gemcitabine, but superior to cTACE.

Acute hepatitis after autologous stem cell transplantation and rapid progression to liver cirrhosis.

A 51-year-old woman was diagnosed with a diffuse cerebral large cell lymphoma. During the period of a combined chemotherapy followed by autologous stem cell transplantation with multiple blood donations, an acute hepatitis without hepatitis C antibodies was diagnosed. Liver biopsy showed steatohepatitis, initially thought to be related to chemotherapy. Sixteen months after the transplantation, liver cirrhosis appeared with circulatory bypass. Retrospectively, testing of serum samples showed a hepatitis C infection. Infection with the hepatitis C virus (HCV) from a blood donation was excluded through retrospective testing for HCV-RNA of blood donors. Finally, the cause of infection remained elusive. Hepatitis serology is not a reliable test under immunosuppressive therapy. The course of progression to liver cirrhosis in the presented short period of 22 months after HCV infection is remarkable and has - to our knowledge - not been reported in literature before.

Placebo: misunderstandings and prejudices.

BACKGROUND: The role of placebos is often misunderstood, leading both to overvaluation and to inappropriate disdain. The effect of a placebo that contains no pharmacologically active substance is often confused with the effect of administration by a physician. The aim of this article is to review the current data on placebos, evaluate these data critically, and provide a well-founded and understandable explanation of the effects that placebos do and do not possess. METHODS: Selective literature review. RESULTS: Recent studies employing modern imaging techniques have provided objective correlates of the effect of placebo administration for certain indications. A recent paper even suggested a genetic basis for it. Two main mechanisms underlie the effect of placebo administration: conditioned reflexes, which are subconscious, and the patient's expectations, which are conscious. Further factors include the physician's personality and the setting in which the treatment takes place. CONCLUSIONS: The mechanisms of action of placebo administration, with which positive therapeutic effects can be achieved with little effort, should be consciously exploited by physicians when giving their patients pharmacologically active medications as well.

Anti-melanocortin-4 receptor autoantibodies in obesity.

BACKGROUND: The melanocortin-4 receptor (MC4R) is part of an important pathway regulating energy balance. Here we report the existence of autoantibodies (autoAbs) against the MC4R in sera of obese patients. METHODS: The autoAbs were detected after screening of 216 patients' sera by using direct and inhibition ELISA with an N-terminal sequence of the MC4R. Binding to the native MC4R was evaluated by flow cytometry, and pharmacological effects were evaluated by measuring adenylyl cyclase activity. RESULTS: Positive results in all tests were obtained in patients with overweight or obesity (prevalence, 3.6%) but not in normal weight patients. The selective binding properties of anti-MC4R autoAbs were confirmed by surface plasmon resonance and by immunoprecipitation with the native MC4R. Finally, it was demonstrated that these autoAbs increased food intake in rats after passive transfer via intracerebroventricular injection. CONCLUSION: These observations suggest that inhibitory anti-MC4R autoAbs might contribute to the development of obesity in a small subpopulation of patients.