Afferent vagal stimulation via gastric electrical stimulation alters sympathetic-vagal balance in domestic pigs - a pilot trial.

The disturbance of the sympathetic-vagal balance with increasing sympathetic activity and consecutive increase in cytokine release is a major threat in numerous hyperinflammatory syndromes. Therapeutic interventions that modulate the activity in the sympathetic-vagal system are suggested as an effective treatment in these incidences. The purpose of this pilot study was to investigate the effect of electrical stimulation of the gastric wall on sympathetic-vagal balance. German domestic pigs (n=5) were prepared with a modified gastric tube (mGT) for repetitive gastric electrical stimulation (GES). Electrocardiogram was recorded continuously and heart rate variability (HRV) as measure of sympathetic-vagal activity was calculated for three-minute epochs at baseline condition before GES and during GES condition. In comparison to baseline, activity of the autonomic nervous system (ANS) shifted significantly toward increased dominance of vagal activity during GES with a decrease of normalized low frequency (nLF from 58.00 to 25.52) as marker of sympathetic dominance and parallel increase of normalized high frequency (nHF from 41.48 to 74.16) as marker of vagal dominance. During GES, compared to baseline, no difference in heart rate was found. These results indicate that electrical stimulation of the gastric wall may result in shifting the sympathetic-vagal balance toward a parasympathetic predominance.

Longstanding diplopia after ethmoidal artery ligation for epistaxis.

PURPOSE: In the rare case of intractable, posterior, non-sphenopalatine artery epistaxis, ligation of ethmoidal arteries using an external approach like a Lynch-type incision is required. Orbital complications, especially extra-ocular motility disorders with diplopia, are known, but in the literature rarely described. Our aim was to analyse the complication type, rate, and outcome of ethmoidal artery ligation for epistaxis. MATERIALS AND METHODS: Data between 2012 and 2017 of patients treated with ethmoidal artery ligation were analysed retrospectively and through a telephone interview using a non-standardized questionnaire. RESULTS: Data of 18 patients (m/f = 3/15) aged 53-83 years were reviewed. Epistaxis recurred in only one patient after 1 month. Five patients (28%) suffered from diplopia shortly after surgery. Motility analysis revealed full recovery with free motility in four out of five reported cases after 4-8 months, one patient still reports intermittent mild diplopia more than 1 year postoperatively. CONCLUSION: In patients with intractable, non-sphenopalatine artery epistaxis, anterior ethmoidal artery ligation was highly effective. Diplopia, however, occurred in one-third of our patient group. Information about motility restriction with longer standing diplopia are mandatory when consenting patients for ligation of ethmoidal arteries. Special care needs to be taken during dissection in the region of the trochlea and superior oblique muscle. LEVEL OF EVIDENCE: Case Series, level 4.

Trigeminal endonasal perception - an outcome predictor for septoplasty.

BACKGROUND: No adequate test exists to predict outcome after septoplasty. Despite adequate surgery, patients still might experience nasal breathing impairment. The aim of this study was to determine if pre-operative trigeminal sensitivity can predict satisfaction after septoplasty. METHODS: Single centre prospective cohort study in tertiary referral centre with follow-up time of 6 weeks postoperatively. Patients scheduled for septoplasty or septorhinoplasty with turbinoplasty were consecutively selected the day before surgery. Standard preoperative examinations (acoustic rhinometry and Sniffin’ Sticks 12 test), the evaluation of nasal obstruction on a visual analogue scale (VAS) and the trigeminal lateralisation task were performed before and 6 weeks after surgery. Biopsies were taken during surgery and TRPV1 mRNA expression was measured by PCR. RESULTS: Thirty patients were included with a median age of 29 years and equal gender distribution. Trigeminal perception and sensation of nasal obstruction showed a significant correlation: preoperative lateralisation test scores, representing endonasal trigeminal sensitivity, correlated significantly with the mean VAS change scores, which demonstrate subjective improvement. A lateralisation test score of 31.5 and more had a sensitivity of 88% to predict an improvement of more than 3 VAS points. Additionally, high TRPV1 mRNA expression was linked with good postoperative VAS scores. CONCLUSION: The preoperative evaluation of the trigeminal sensitivity could improve patients’ selection for septoplasty with a higher rate of satisfaction. Endonasal trigeminal sensitivity is directly linked with subjective outcome. Therefore, patients with low trigeminal sensitivity should undergo septoplasty only after thorough counselling.

Endotypes of chronic rhinosinusitis with nasal polyps with and without NSAID â€" intolerance.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2-dominated inflammatory disease of the upper air- ways. A subgroup of patients with CRSwNP suffer from intolerance to nonsteroidal anti-inflammatory drugs (NSAID) and develop NSAID-exacerbated respiratory disease (NERD). The aim of the study was to compare the cytokine based inflammatory endotype of nasal secretions of CRSwNP patients with and without NSAID intolerance. METHODS: Nasal secretions were collected from twenty-six patients suffering from CRSwNP, thirteen with NERD and thirteen without NSAID intolerance. As control, nasal secretions were collected from fifteen healthy donors. Tryptase and ten human cyto- kines were analyzed: interleukin (IL)-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, IL-17A, IL-23, IFN-g, and TNF-a by a cytokine multiple array on a Luminex 200 platform. RESULTS: Grade of polyposis and frequency of polyp surgery was more severe in NERD- compared to non-NERD patients. IL-6 and IL-5 in CRSwNP was significantly increased compared to healthy participants. IL-5 and IL-13 were significantly increased in subjects suffering from NERD compared to CRSwNP patients without NERD. CONCLUSION: We identified IL-13 as a possible specific biomarker in nasal secretions of patients with NERD, which allows us to differentiate between CRSwNP with vs. without NERD. The characterization of inflammatory endotypes in CRSwNP enables the introduction of the best available therapy in the context of precision medicine.

Development of a smartphone app for neuromuscular facial training.

BACKGROUND: Several studies have demonstrated a significant benefit of neuromuscular facial training in the rehabilitation of patients with facial palsy. However, printed instructions for home training are often not of optimum quality and associated with low adherence to therapy. Professional guidance, e.g., by occupational therapists, is regarded as being of high quality, but is associated with a high cost burden, particularly in chronic forms of disease. OBJECTIVE: The idea to develop a smartphone app for facial training arose from the above-described situation. The aim was to provide structured exercises for the mimic muscles in the sense of neuromuscular training with visual feedback via the front camera of the device. MATERIALS AND METHODS: A native app architecture in iOS was chosen to implement the graphical and content-related concept. In the Apple Xcode (Apple, Cupertino, CA, US) development environment, the app's code was written in the Swift programming language (Apple) and the graphical user interface was created. RESULTS: An app prototype was implemented that provides step-by-step instructions on selected mimic exercises via animated smileys. The duration and speed of the exercise can be varied within a limited range. In the development environment, the correct functionality of both physical and virtual devices was successfully tested. CONCLUSION: App-based facial training offers attractive opportunities to motivate patients for improved adherence to treatment, which could hypothetically lead to a better outcome. Evaluation of this question is planned in a clinical trial after completion of the development.

[Development of a smartphone app for neuromuscular facial training. German Version]. / Entwicklung einer Smartphone-App für neuromuskuläres Fazialistraining.

BACKGROUND: Several studies have demonstrated a significant benefit of neuromuscular facial training in the rehabilitation of patients with facial palsy. However, printed instructions for home training are often not of optimum quality and associated with low adherence to therapy. Professional guidance, e.g., by occupational therapists, is regarded as being of high quality, but is associated with a high cost burden, particularly in chronic forms of disease. OBJECTIVE: The idea to develop a smartphone app for facial training arose from the above-described situation. The aim was to provide structured exercises for the mimic muscles in the sense of neuromuscular training with visual feedback via the front camera of the device. MATERIALS AND METHODS: A native app architecture in iOS was chosen to implement the graphical and content-related concept. In the Apple Xcode (Apple, Cupertino, California, US) development environment, the app's code was written in the Swift programming language (Apple) and the graphical user interface was created. RESULTS: An app prototype was implemented that provides step-by-step instructions on selected mimic exercises via animated smileys. The duration and speed of the exercise can be varied within a limited range. In the development environment, the correct functionality of both physical and virtual devices was successfully tested. CONCLUSION: App-based facial training offers attractive opportunities to motivate patients for improved adherence to treatment, which could hypothetically lead to a better outcome. Evaluation of this question is planned in a clinical trial after completion of the development.

Does the identification of seniors at risk (ISAR) score effectively select geriatric patients on emergency admission?

The number of older patients admitted to emergency departments (ED) increases continuously. The Identification of Seniors at Risk (ISAR) score is currently recommended to screen patients in German ED, but its appropriateness is being criticized. ISAR scores and clinical characteristics from 98 emergency admissions (EA), 80 from acute geriatrics (AG) and 89 from a geriatric rehabilitation (GR) unit were compared retrospectively. No significant differences were found between groups, being the ISAR score positive in 87.7% of EA, 94.9% of AG and 94.4% of GR cases. None of positively identified geriatric patients in the EA was transferred to the geriatric ward of competence. EA patients showed significantly higher number of functional impairments (p = 0.001) and higher BI score (p < 0.0001) compared to AG and GR groups. A higher ISAR score threshold and additional functional information might be needed to better select patients in need of prompt treatment by a geriatric team.

[Injury prevention in amateur football with FIFA 11+ : What is implemented on the football pitch?] / Verletzungsprävention im Amateurfußball mit FIFA 11+ : Was kommt auf dem Sportplatz an?

BACKGROUND: The warm-up and injury prevention program FIFA 11+ was developed to reduce injuries in recreational and amateur level football. Despite systematic education it is uncertain what amount of knowledge is passed down to the lower recreational level football players and what exercises are implemented in the daily routine. This study presents the summarized experiences of German coaches about the implementation of exercises on the football pitch. MATERIAL AND METHODS: In this study 142 coaches who participated in 1 (of 5) of the 2­day courses between 2013 and 2017 were sent a questionnaire. The questionnaire consisted of 24 questions, which were developed by the football union of Lower Saxony. Incomplete questionnaires were excluded from the study. RESULTS: A total of 121 questionnaires could be analyzed, which is a response rate of 85.2%. The mean time period between the 2­day training and answering the questionnaire was 29 months. Of the participating coaches 82.6% indicated that they use the program regularly (22% of the coaches use it twice a week or more frequently, 34% use it only once a week) and 6% of the coaches use additional programs to prevent injuries. A total of 86% of the participants believed in a reduction in the incidence of injuries induced by the FIFA 11+ concept, 89% of the participants rated the FIFA 11+ program as good ors very good, 91% rated the teaching concept as good or very good and 94% of the participants would recommend the 2­day advanced course to others. DISCUSSION: The prevention program as well as the advanced training concept were evaluated very positively. Most coaches use the program regularly. Nevertheless, many coaches use the FIFA 11+ exercises less than the recommended twice a week. Most coaches praised the good structure of the program, but also wished for the possibility of variations. CONCLUSION: The prevention program FIFA 11+ is seen by coaches in recreational and amateur football as an effective tool to prevent injury. Implementation on the football pitch is regular but not as frequent as the evidence-based recommendations in the training concept.

[Decision aids in complex polypharmacy : Medication data bases and counselling by clinical pharmacists]. / Entscheidungshilfen bei komplexer Polypharmazie : Medikationsdatenbanken und Beratung durch den klinischen Apotheker.

The number of older people with polypharmacy (more than six drugs taken simultaneously) is increasing. The greatest proportion consists of guideline drugs, analgesics and psychopharmaceuticals because in many cases of geriatric multimorbidity several underlying main diseases are present which must be treated according to the guidelines. Polypharmacy is a complex and difficult situation for all treating physicians because substantial side effects and intoxication can be induced but it can also be very difficult to recognize which drug was at fault and how a reduction can be safely made. This article describes the exemplary case of a 77-year-old patient with drug-induced delirium and demonstrates the procedure followed. The question of rapid assistance by the utilization of medication data bases is described and the importance of clinical pharmacists is demonstrated. In the future working with medication data bases will possibly become increasingly more important for physicians and hopefully simpler. The case presented here also shows that the effective and justified reduction of drugs can show a very good effect and is possible.

[Medical treatment of rheumatoid arthritis in 2014 : Current data from the German Collaborative Arthritis Centers]. / Versorgung der rheumatoiden Arthritis 2014 : Aktuelle Daten aus der Kerndokumentation.

BACKGROUND: Since the introduction of biologic treatment in rheumatoid arthritis (RA), disease activity and treatment modalities have changed substantially. The current provision and developments in recent years are analyzed with annual data from the National Database of the Collaborative Arthritis Centers in Germany. METHODS: To analyze disease activity, diagnostics and treatment in RA patients in 2014 with regard to seropositivity and disease duration. Time trends from 2007-2014 are reported for disease activity (DAS28) distribution and biologic treatment. RESULTS: In 2014, a total of 8,084 RA patients were analyzed: 72 % were rheumatoid factor and/or ACPA positive, the mean age was 62 years and the mean disease duration 12 years. According to DAS28, 35.9 % were in remission, 19.2 % had low, 37.1 % moderate and 7.8 % high disease activity. An increase since 2007 was only observed in patients with a disease duration >2 years. Synthetic DMARDS were used for treatment in 78 %. Biologic treatment increased from 16 % (2007) to 27 % (2014). Especially those patients with a disease duration >5 years were treated more frequently with biologics. Seronegative patients had slightly less severe mean disease activity parameters. They were treated equally frequent with DMARDS but only half as often with biologics compared to seropositive patients. CONCLUSION: The use of biologics in RA patients has increased since 2007; however this was not observed in patients with short disease duration. Early intensive treatment adaption seems justified to improve disease activity in the large portion of patients who do not reach low disease activity under conventional DMARDs.

[The intestinal microbiome and metabolic diseases : From obesity to diabetes and nonalcoholic steatohepatitis]. / Intestinales Mikrobiom und metabolische Erkrankungen : Von der Adipositas zu Diabetes und nichtalkoholischer Steatohepatitis.

BACKGROUND: The intestinal microbiome consists of about 10 million genes, many of which encode digestive enzymes. This explains why animal and human experiments revealed that the intestinal microbiome adapts to food intake and optimizes energy harvest from food. This function is considered beneficial in states of lack of food, but following overnutrition, it might support the development of obesity. OBJECTIVES: The relevance of the intestinal microbiome for the pathogenesis of obesity and associated metabolic diseases such as fatty liver disease and type 2 diabetes mellitus and for the clinical management of such diseases shall be discussed. MATERIALS AND METHODS: Recent literature related to the topic has been selected, presented, and discussed with regard to the objectives. RESULTS: The intestinal microbiome plays a role in the pathogenesis of both obesity (by increasing the energy absorption from food) and fatty liver disease as well as type 2 diabetes mellitus (via induction of low-grade inflammation following translocation of lipopolysaccharides from the gut and dysregulation of metabolic pathways). CONCLUSIONS: The findings might have consequences for diagnosis (identification of risk groups) and therapy (usage of known and novel probiotics or bacterial metabolites) of metabolic diseases.

SPARC expression in resected pancreatic cancer patients treated with gemcitabine: results from the CONKO-001 study.

BACKGROUND: Previous investigations in pancreatic cancer suggested a prognostic role for secreted protein acidic and rich in cysteine (SPARC) expression in the peritumoral stroma but not for cytoplasmic SPARC expression. The aim of this study was to evaluate the impact of SPARC expression in pancreatic cancer patients treated with gemcitabine compared with untreated patients. PATIENTS AND METHODS: CONKO-001 was a prospective randomized phase III study investigating the role of adjuvant gemcitabine when compared with observation. Tissue samples of 160 patients were available for SPARC immunohistochemistry on tissue microarrays to evaluate its impact on patient outcome. RESULTS: Strong stromal SPARC expression was associated with worse disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P = 0.005, OS: P = 0.033). Its negative prognostic impact was restricted to patients treated with gemcitabine (DFS: P = 0.007, OS: P = 0.006). High cytoplasmic SPARC expression also was associated with worse patient outcome (DFS: P = 0.041, OS: P = 0.011). Again the effect was restricted to patients treated with gemcitabine (DFS: P = 0.002, OS: P = 0.003). In multivariable analysis, SPARC expression was independently predictive of patient outcome. CONCLUSIONS: Our data confirm the prognostic significance of SPARC expression after curatively intended resection. The negative prognostic impact was restricted to patients who received adjuvant treatment with gemcitabine, suggesting SPARC as a predictive marker for response to gemcitabine.

IL-33 is a mediator rather than a trigger of the acute allergic response in humans.

BACKGROUND: IL-33 enhances FcεRI-induced mediator release in human basophils without inducing degranulation itself. In contrast, studies in mice suggested that in the presence of high IgE levels, IL-33 triggers degranulation and anaphylaxis of similar severity as specific allergen. Consistent with this view, sera of atopic patients contain elevated levels of IL-33 after anaphylaxis. In this study, we determined whether IL-33 is potentially anaphylactogenic in humans with high IgE levels by regulating exocytosis independent of FcεRI cross-linking. Furthermore, we investigated whether IL-33 is released upon allergen provocation in vivo. METHODS: In subjects with high serum IgE levels, we measured IL-33-induced histamine/LTC4 in vitro, CD63 translocation ex vivo, and responsiveness of mast cells in vivo by skin prick test (SPT). In asthma patients, release of IL-33 and its correlation with early (tryptase)- and late-phase markers (IL-13 levels, eosinophil numbers) of the allergic response were assessed in bronchoalveolar lavage fluids (BALFs) after allergen challenge. RESULTS: IL-33 itself does not trigger basophil degranulation in vitro and ex vivo, even in subjects with high serum IgE levels, and negative SPTs demonstrate that skin mast cells do not degranulate in response to IL-33. However, in response to allergen challenge, IL-33 is rapidly released into BALFs at levels that do not correlate with other immediate- and late-phase parameters. CONCLUSION: IL-33 is unlikely an independent trigger of anaphylaxis even in subjects with high IgE levels. However, the rapid release of IL-33 upon allergen provocation in vivo supports its role as a mediator of immediate allergic responses.

Cinnamon extract inhibits degranulation and de novo synthesis of inflammatory mediators in mast cells.

BACKGROUND: Mast cells (MC) are main effector cells of allergic and other inflammatory reactions; however, only a few anti-MC agents are available for therapy. It has been reported that cinnamon extract (CE) attenuates allergic symptoms by affecting immune cells; however, its influence on MC was not studied so far. Here, we analyzed the effects of CE on human and rodent MC in vitro and in vivo. METHODS: Expression of MC-specific proteases was examined in vivo in duodenum of mice following oral administration of CE. Release of mediators and phosphorylation of signaling molecules were analyzed in vitro in human MC isolated from intestinal tissue (hiMC) or RBL-2H3 cells challenged with CE prior to stimulation by FcεRI cross-linking. RESULTS: Following oral treatment with CE, expression of the mast cell proteases MCP6 and MC-CPA was significantly decreased in mice. In hiMC, CE also caused a reduced expression of tryptase. Moreover, in hiMC stimulated by IgE cross-linking, the release of ß-hexosaminidase was reduced to about 20% by CE. The de novo synthesis of cysteinyl leukotrienes, TNFα, CXCL8, CCL2, CCL3, and CCL4, was almost completely inhibited by CE. The attenuation of mast cell mediators by CE seems to be related to particular signaling pathways, because we found that activation of the MAP kinases ERK, JNK, and p38 as well as of Akt was strongly reduced by CE. CONCLUSION: CE decreases expression of mast cell-specific mediators in vitro and in vivo and thus is a new plant-originated candidate for anti-allergic therapy.

[Validation of the IBS-SSS]. / Validierung des IBS-SSS.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterised by abdominal pain, associated with stool abnormalities and changes in stool consistency. Diagnosis of IBS is based on characteristic symptoms and exclusion of other gastrointestinal diseases. A number of questionnaires exist to assist diagnosis and assessment of severity of the disease. One of these is the irritable bowel syndrome - severity scoring system (IBS-SSS). The IBS-SSS was validated 1997 in its English version. In the present study, the IBS-SSS has been validated in German language. To do this, a cohort of 60 patients with IBS according to the Rome III criteria, was compared with a control group of healthy individuals (n = 38). We studied sensitivity and reproducibility of the score, as well as the sensitivity to detect changes of symptom severity. The results of the German validation largely reflect the results of the English validation. The German version of the IBS-SSS is also a valid, meaningful and reproducible questionnaire with a high sensitivity to assess changes in symptom severity, especially in IBS patients with moderate symptoms. It is unclear if the IBS-SSS is also a valid questionnaire in IBS patients with severe symptoms because this group of patients was not studied.

Medical graphics to improve patient understanding and anxiety in elderly and cognitively impaired patients scheduled for transcatheter aortic valve implantation (TAVI).

BACKGROUND: Anxiety and limited patient comprehension may pose significant barriers when informing elderly patients about complex procedures such as transcatheter aortic valve implantation (TAVI). OBJECTIVES: We aimed to evaluate the utility of medical graphics to improve the patient informed consent (IC) before TAVI. METHODS: In this prospective, randomized dual center study, 301 patients were assigned to a patient brochure containing medical graphics (Comic group, n = 153) or sham information (Control group, n = 148) on top of usual IC. Primary outcomes were patient understanding of central IC-related aspects and periprocedural anxiety assessed by the validated Spielberger State Trait Anxiety Inventory (STAI), both analyzed by cognitive status according to the Montreal Cognitive Assessment (MoCA). RESULTS: Patient understanding was significantly higher in the Comic group [mean number of correct answers 12.8 (SD 1.2) vs. 11.3 (1.8); mean difference 1.5 (95% CI 1.2-1.8); p < 0.001]. This effect was more pronounced in the presence of cognitive dysfunction (MoCA < 26) [12.6 (1.2) in the Comic vs. 10.9 (1.6) in the Control group; mean difference 1.8 (1.4-2.2), p < 0.001]. Mean STAI score declined by 5.7 (95% CI 5.1-6.3; p < 0.001) in the Comic and 0.8 points (0.2-1.4; p = 0.015) in the Control group. Finally, mean STAI score decreased in the Comic group by 4.7 (3.8-5.6) in cognitively impaired patients and by 6.6 (95% CI 5.8 to 7.5) in patients with normal cognitive function (p < 0.001 each). CONCLUSIONS: Our results prove beneficial effects for using medical graphics to inform elderly patients about TAVI by improving patient understanding and reducing periprocedural anxiety (DRKS00021661; 23/Oct/2020). Medical graphics entailed significant beneficial effects on the primary endpoints, patient understanding and periprocedural anxiety, compared to the usual patient informed consent (IC) procedure. Patient understanding of IC-related aspects was significantly higher in the Comic group, with a more pronounced benefit in patients with cognitive impairment (p for IC method and cognitive status < 0.001, respectively; p for IC method x MoCA category interaction = 0.017). There further was a significant decline of periprocedural anxiety in patients with and without cognitive impairment (p for IC method x measuring time point < 0.001; p for IC method x MoCA category x measuring time point interaction = 0.018).

Multicenter evaluation of an interdisciplinary 52-week weight loss program for obesity with regard to body weight, comorbidities and quality of life--a prospective study.

OBJECTIVES: To determine the effectiveness of a structured multidisciplinary non-surgical obesity therapy program on the basis of a temporary low-calorie-diet for 12 weeks, and additional intervention modules to enhance nutritional education, to increase physical activity and to modify eating behavior. DESIGN: Prospective multicenter observational study in obese individuals undergoing a medically supervised outpatient-based 52-week treatment in 37 centers in Germany. SUBJECTS: A total of 8296 participants with a body mass index (BMI) of >30 kg m(-2) included within 8.5 years. MEASUREMENTS: Main outcome measures were body weight loss, waist circumference (WC), blood pressure, quality of life and adverse events. RESULTS: In females, initial body weight was reduced after the 1-year-intervention by 19.6 kg (95% confidence intervals 19.2-19.9 kg) and in males by 26.0 kg (25.2-26.8) according to per protocol analysis of 4850 individuals. Intention-to-treat (ITT) analysis revealed a weight reduction of 15.2 kg (14.9-15.6) in females and 19.4 kg (18.7-20.1) in males. Overall, the intervention resulted in mean reduction in WC of 11 cm; it reduced the prevalence of the metabolic syndrome by 50% and the frequency of hypertension from 47 to 29% of all participants (ITT, all P<0.001). The beneficial effects could be documented for up to 3 years and comprised significant improvement of health-related quality of life. The incidence of adverse effects was low; the only event repeatedly observed and possibly related to either the intervention or the underlying disease was biliary disorders. CONCLUSION: The present non-surgical intervention program is a highly effective treatment of obesity grades I-III and obesity-related diseases, and therefore, could be a valuable basis for future weight maintenance strategies required for sustained success.