Trends in Bariatric Surgery: a 5-Year Analysis of the Israel National Bariatric Surgery Registry.

BACKGROUND: The worldwide prevalence of obesity nearly tripled between 1975 and 2016. There are limited data quantifying national trends. The aim of this study is to evaluate and summarize current trends in bariatric surgery in Israel. METHODS: Data for all bariatric surgeries (BS) performed between January 2014 and December 2018 was collected from the Israel National Bariatric Surgery Registry (INBSR) and analyzed. RESULTS: During the study period, 42,296 BS were included in the INBSR. Females accounted for 68% and the mean age and body mass index were 41.6 ± 12.6 years and 42.0 ± 5.4 kg/m2, respectively. Most of the patients were Jewish, but there was a significant rise in number of Arabs undergoing BS during the study period. There was a gradual decline in the annual numbers of BS, except for a small rise in 2015. There was a significant rise in the rate of One Anastomosis-Mini Gastric Bypass (OAGB-MGB), from 0.1% in 2014 to 46.1% in 2018, making it the most prevalent BS in that year. Laparoscopic sleeve gastrectomy (SG) surgeries decreased steadily, from 80% in 2014 to 37% in 2018. The annual rate of Roux-en-Y gastric bypass (RYGB) remained essentially constant at 10%. The annual rates of gastric banding decreased sharply and the annual rates of duodenal switch, single anastomosis duodenal switch and biliopancreatic diversion were negligible. Bariatric surgery was distributed evenly between private (50.4%) and public (49.6%) hospitals. CONCLUSIONS: The numbers of BS are decreasing in Israel. There is a gradual but noticeable shift from SG to OAGB-MGB.

Correction to: Incidence and Risk Factors for Mortality Following Bariatric Surgery: a Nationwide Registry Study.

In Table 5 the P value for the parameter "More than one chronic disease" is incorrect. The correct value is 0.387, not 0.0387.

Incidence and Risk Factors for Mortality Following Bariatric Surgery: a Nationwide Registry Study.

BACKGROUND: Although bariatric surgery (BS) is considered safe, concern remains regarding severe post-operative adverse events and mortality. Using a national BS registry, the aim of this study was to assess the incidence, etiologies, and risk factors for mortality following BS. METHODS: Prospective data from the National Registry of Bariatric Surgery in Israel (NRBS) including age, gender, BMI, comorbidities, and surgical procedure information were collected for all patients who underwent BS in Israel between June 2013 and June 2016. The primary study outcome was the 3.5-year post-BS mortality rate, obtained by cross-referencing with the Israel population registry. RESULTS: Of the 28,755 patients analyzed (67.3% females, mean age 42.0 ± 12.5 years, and preoperative BMI 42.14 ± 5.21 kg/m2), 76% underwent sleeve gastrectomy (SG), 99.1% of the surgeries were performed laparoscopically, and 50.8% of the surgeries were performed in private medical centers. Overall, 95 deaths occurred during the study period (146.9/100,000 person years). The 30-day rate of post-operative mortality was 0.04% (n = 12). Male gender (HR = 1.94, 95%CI 1.16-3.25), age (HR = 1.06, 95%CI 1.04-1.09), BMI (HR = 1.08, 95%CI 1.05-1.11), and depression (HR = 2.38, 95%CI 1.25-4.52) were independently associated with an increased risk of all-cause 3.5-year mortality, while married status (HR = 0.43, 95%CI 0.26-0.71) was associated with a decreased risk. CONCLUSION: Mortality after BS is low. Nevertheless, a variety of risk factors including male gender, advanced age, unmarried status, higher BMI, and preoperative depressive disorder were associated with higher mortality rates. Special attention should be given to these "at-risk" BS patients.

Intragastric Balloons for Overweight Populations-1 Year Post Removal.

BACKGROUND: Endoscopic balloons have been used for years to treat obese seeking weight loss. This study evaluated the safety and effectiveness of our lifestyle modification program. METHODS: Retrospective analysis of prospectively collected data from patients who underwent End-ball® (Endalis) intragastric balloon insertion with a multidisciplinary follow-up program. Demographic data, weight loss complications, and satisfaction rates were assessed. RESULTS: In total, 114 overweight/obese individuals from July 2012 to December 2015 were included. Mean age 36.5 years (72% females). Initial body mass index (BMI) was 33.5 kg/m2. Twelve early removals (10.52%) due to intolerance (n = 7), dissatisfaction (n = 4), and esophagitis (n = 1); 102 patients completed the program. BMI reduction ranged 5.5-6.4 at balloon removal and 4.1 1-year post removal. Average excess BMI loss (EBMIL) was 46-48% at balloon removal and 39.1% after 1 year; 75% of participants maintained > 60% of their weight loss 1 year after removal. EBMIL was 17 and 48% when initial BMI > 35 and ≤ 35 kg/m2, respectively. At removal, 80% of patients were satisfied with the process. CONCLUSION: The End-ball® program resulted in significant weight loss that continued for 1 year after balloon removal, with minimal complications. When treating overweight/obese populations, the main principles of the balloon insertion process should be no complications, high safety, and significant effectiveness. The process was most beneficial in the overweight and class I obese populations since average BMI was 33 and the class II obese had less weight loss and can possibly prevent future bariatric surgery.

Feasibility and Importance of Enteroscopy after Gastric Bypass.

BACKGROUND: Bariatric surgery has increased in popularity, with Roux-en-Y Gastric Bypass (RYGB) being one of the most frequently performed. This leads to many cases in which the stomach is removed from routine gastroscopy access, sometimes being a major source of concern. Performing enteroscopy in these patients is technically difficult. We present our experience with 24 cases in which the aim was to access the detached stomach. METHODS: Retrospective analysis on RYGB enteroscopy procedures aimed to access the detached stomach. Data recorded: demographic parameters, indication, gas insufflation, time to bypass stomach, total procedure and recovery times, and endoscopic and pathological findings. RESULTS: This study included 24 patients who underwent RYGB in the previous 3-36 months. Indications were chronic abdominal pain, refractory anemia, or unexplainable weight loss. Detached stomach was accessed in 79% of patients. Access time ranged from 25 to 55 min. Recovery time for all procedures was 86.66 min on average and shorter with CO2 insufflation (42.5 min). All detached stomachs showed macroscopic gastritis; four of them were Helicobacter pylori positive. Significant findings included three patients with jejunojejunostomy stenosis and one patient with a marginal gastrojejunal ulcer, which was later diagnosed with Signet ring cell carcinoma of the proximal anastomosis. CONCLUSIONS: We present the feasibility and importance of enteroscopy of the detached stomach and believe that this procedure should be performed more frequently. A high index of suspicion is needed for postoperative symptoms in order to exclude significant pathologies and reassure symptomatic patients that there is no abnormality in the bypassed stomach.

Digital Recording and Documentation of Endoscopic Procedures: Do Patients and Doctors Think Alike?

Aims and Methods. Conducting a survey study of a large number of patients and gastroenterologists aimed at identifying relevant predictors of interest in digital recording and documentation (DRD) of endoscopic procedures. Outpatients presenting to the endoscopy unit at our institution for an endoscopy examination were anonymously surveyed, regarding their views and opinions of a possible recording of the procedure. A parallel survey for gastroenterologists was conducted. Results. 417 patients and 62 gastroenterologists participated in two parallel surveys regarding DRD of endoscopic procedures. 66.4% of the patients expressed interest in digital documentation of their endoscopic procedure, with 90.5% of them requesting a copy. 43.6% of the physicians supported digital recording while 27.4% opposed it, with 48.4% opposing to making a copy of the recording available to the patient. No sociodemographic or background factors predicted patient's interest in DRD. 66% of the physicians reported having recording facilities in their institutions, but only 43.6% of them stated performing recording. Having institutional guidelines for DRD was found to be the only significant predictor for routine recording. Conclusions. Our study exposes patients' positive views of digital recording and documentation of endoscopic procedures. In contrast, physicians appear to be much more reluctant towards DRD and are centrally motivated by legal concerns when opposing DRD, as well as when supporting it.

Dexamethasone-suppressed corticotropin-releasing hormone stimulation test in morbid obese adults.

PURPOSE: In order to differentiate between Cushing's syndrome (CS) and Pseudo-Cushing's syndrome, it is customary to use a test that is conducted by cortisol suppression with low-dose dexamethasone, followed by the administration of corticotropin releasing hormone (Dex-CRH test). In children with severe obesity, Dex-CRH test has shown a specificity of 55%. The aim of current study was to evaluate the specificity of Dex-CRH test in morbid obese adults. METHODS: The study included a total of 19 subjects with a body mass index (BMI) equal or higher than 40kg/m(2). In all subjects Dex-CRH test was performed, and 24h urinary free cortisol was collected prior the test and during the second day of dexamethasone administration (2nd-day-UFC). RESULTS: BMI was 45.1±4.6kg/m(2) and 45.7±3.3kg/m(2) in women and men, respectively. 14 subjects underwent bariatric surgery. No subject had surgical or perioperative complications and surgically treated subjects had mean body weight loss of 46.5±16.6kg. All except for 2 subjects had normal Dex-CRH test, as 15-min cortisol falling below 1.4µg/dl. During follow-up, no subject gained additional weight, neither developed signs of CS. 15-min-cortisol concentration of 1.4µg/dl revealed a specificity of 89% and 2nd-day-UFC of 16µg/24h showed a specificity of 100%. CONCLUSIONS: Morbid obesity in adults seems not to comprise a significant confounder in Dex-CRH test, and 15-min-cortisol concentration of 1.4µg/dl had a higher specificity than previously reported in obese children.

Correlation between incidental FDG PET/CT colorectal observations and endoscopic and histopathological results.

Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is used in the imaging workup of various malignancies. Incidental gastrointestinal observations on FDG PET/CT may be of clinical significance. The aim of the present study was to evaluate endoscopic and histopathological observations in patients referred for colonoscopy due to incidental FDG colonic uptake on a PET/CT study. Fifty-six patients with incidental colonic findings on FDG PET/CT underwent colonoscopy. Normal colonoscopies were observed in 63% of the patients. In 37% of the colonoscopies, we identified an endoscopic observation, including 67% with benign adenomatous polyps, 3% with hyperplastic polyps, 20% with advanced histological lesions and 10% with a malignancy.

Lifestyle modification parallels to sleeve success.

BACKGROUND: The role of laparoscopic sleeve gastrectomy (LSG) has increased over the past 10 years. We present our results of patients who were 5 years out from surgery with regard to safety and long-term efficacy. METHODS: Retrospective analysis was carried out from prospectively collected data of patients who underwent LSG for morbid obesity. Bariatric Analysis and Reporting Outcome System (BAROS) and Food Tolerance Scores (FTS) were assessed. At 5 years, two lifestyle modification questions (regarding nutrition habits and physical fitness) were separately assessed. RESULTS: One hundred fourteen patients underwent LSG and were available for postoperative visits. Mean excess weight loss (EWL) was >65% during the initial 3 years and declined to 45.3% in 5 years. Of the patients, 71.92% did not reach 50% EWL at 60 months and were considered objective failures. BAROS and FTS scores were 7.15 and 4.32, and 23.5 and 22.5 at 30 and 60 months, respectively. Analyzing the 32 patients with EWL >50% in the 5-year group, 26 (81.25%) of them had scored ≥0.5 on the two lifestyle modification questions compared with 6 (18.75%) that scored <0.5 (P < 0.001). CONCLUSION: LSG is an effective bariatric surgical procedure with significant long-term (5 year) weight loss, resolution of comorbid medical conditions and significant improvement in the quality of life. The basis for this success, which must be always emphasized preoperatively by the bariatric team, is knowledge and implementation of better nutritional habits and increasing physical fitness or, in other words, in significant lifestyle modification.

Getting the most from the sleeve: the importance of post-operative follow-up.

BACKGROUND: Bariatric approach to obesity provides substantial weight loss and comorbidity resolution. Our unique service includes pre- and postoperative visits to the Health and Nutrition Clinic headed by a specialist in gastroenterology and nutrition. We compared patients attending regular clinic routine with those who were lost to follow-up with regard to anthropometry, comorbidity, quality of life, and food tolerance and determined who benefited most from the operation. METHODS: A retrospective review was performed on patients 30 months after undergoing sleeve gastrectomy. Body mass index was used to report weight loss. Bariatric Analysis and Reporting Outcome System (BAROS) and Food Tolerance Score were (FTS) completed by all patients at the 30-month follow-up visit and compared between two groups (group I-30 months of active postoperative follow-up; group II-without). RESULTS: A total of 119 patients participated in the study. For groups I and II, the mean percentage of excess BMI loss at 30 months was 82.08 ± 9.83 and 74.88 ± 8.75, respectively, with better comorbidity improvement in group I. BAROS scores were 7.62 ± 0.72 and 6.92 ± 0.92. FTS was 24.30 ± 2.09 and 22.55 ± 2.27, respectively. CONCLUSIONS: From our experience, getting the most from the sleeve is attributed to two main factors: surgery and nutrition. Surgery results in optimal restriction and improved satiety, whereas nutrition relies on a professional medical team providing constant, ongoing patient support throughout all the bariatric process stages. These teams of surgeons and gastroenterologists specializing in nutrition, working side by side, each in their area of specialty, are the main pillars leading to the success of the sleeve.

A nine-year audit of open-access upper gastrointestinal endoscopic procedures: results and experience of a single centre.

BACKGROUND: The appropriateness and safety of open-access endoscopy are very important issues as its use continues to increase. OBJECTIVE: To present a review of a nine-year experience with open-access upper gastrointestinal endoscopy with respect to indications, diagnostic efficacy, safety and diseases diagnosed. METHODS: A retrospective, observational case series of all patients who underwent open-access endoscopy between January 2000 and December 2008 was conducted. Indications were classified as appropriate or not appropriate according to American Society of Gastrointestinal Endoscopy (ASGE) guidelines. Endoscopic diagnoses were based on widely accepted criteria. Major complication rates were assessed. RESULTS: A total of 20,620 patients with a mean age of 58 years were assessed, of whom 11,589 (56.2%) were women and 9031 (43.8%) were men. Adherence to ASGE indications led to statistically significant, clinically relevant findings. The most common indications in patients older than age 45 years of age were dyspepsia (28.5%) and anemia (19.7%) in the ASGE-appropriate group, and dyspepsia in patients younger than 45 years of age without therapy trial (6.6%) in the nonappropriate group. Of the examinations, 38.57% were normal. Hiatal hernia and nonerosive gastritis were the most common findings. Important diagnoses such as malignancies and duodenal ulcers would have been missed if endoscopies were performed only according to appropriateness. There were only two major complications and no mortalities. CONCLUSIONS: Open-access upper gastrointestinal endoscopy is a safe and effective system. More relevant findings were found when adhering to the ASGE guidelines. However, using these guidelines as the sole determining factor in whether to perform an endoscopy is not advisable because many clinically relevant diagnoses may be overlooked.

Colorectal cancer among Arab-Israeli women--possible reasons for increased incidence and mortality.

BACKGROUND: Colorectal cancer (CRC) screening is effective in reducing its incidence by discovering precancerous polyps and detecting early cancer. Evidence indicates lower participation in screening programs among minority ethnic groups. In addition, the Israel Cancer Registry published an increase in the incidence of CRC among Israeli-Arab women. It is important to attempt to understand attitudes toward screening among Israeli-Arab women, assuming it has to do to lack of knowledge and compliance. METHODS: During the study period, a female team gave lectures in Arabic regarding CRC to women in 16 Arab villages. Prior to the lecture, the participants were asked to complete a questionnaire, obtaining information regarding CRC knowledge and screening. Following the lecture, FOBT kits were distributed. Two weeks later, a telephone survey was performed, regarding whether the FOBT was performed, the result of the test, and, if FOBT was not performed, the reasons for not completing the test. RESULTS: FOBT was performed by 17.8% prior to the lecture; 61% performed the FOBT following our lecture. Reasons cited for avoiding FOBT: 37% was "afraid of a positive result," 32% avoided performing the test as they were concerned they would be further examined by a male physician; 47.8% concluded that Arab women lack knowledge regarding screening interventions; 23.9% neglect themselves from a health point of view; 11.6% advised that Arab women have no free time to perform tests. CONCLUSIONS: Israeli-Arab women may be less knowledgeable concerning CRC. Educational efforts must be made to increase awareness and promote benefits of CRC screening, by targeting ethnic minorities and women in Israel.

Sleeve gastrectomy leads to Helicobacter pylori eradication.

BACKGROUND: The role of Helicobacter pylori (HP) in patients scheduled and undergoing laparoscopic sleeve gastrectomy (LSG) has not been previously evaluated. METHODS: Included were obese patients presenting to our institution for LSG over 24 months. All patients had presurgical HP breath test, and the symptomatic ones received triple therapy with symptom follow-up. Post surgery, all excluded stomachs were evaluated for HP, and those that were positive performed a second 13C-urea breath test (UBT) 3 months later. RESULTS: Forty patients underwent LSG. Male to female sex ratio was 1:3; mean age-42 years; mean weight-122 kg; and mean BMI of 43.4 kg/m2. Presurgical HP was positive in 15 (37.5%) patients (11 symptomatic and four asymptomatic). Only these 11 patients were given HP eradication therapy and all experienced complete subsequent symptom resolution. HP was detected in 17 out of the 40 (42.5%) cases of excluded stomachs. All performed a 13C-UBT 3 months post operation and only three (17.6%) tested positive. CONCLUSIONS: HP infection is frequent in biopsies from patients with previous LSG and the majority of follow-up 13C-UBT were negative. In our small initial sample, we treated only symptomatic patients preoperatively. Routine screening for HP for all LSG patients and/or treatment for all positive ones would subject patients to expensive and unnecessary investigations. We propose that this stomach-reducing, pylorus-preserving surgery might even lead to HP eradication. The clinical implications of HP and this gastrectomy for a non-neoplastic, non-peptic indication deserve further study.

Incidental colorectal computed tomography abnormalities: would you send every patient for a colonoscopy?

BACKGROUND: The clinical significance of colorectal wall thickening (CRWT) in patients undergoing abdominal computed tomography (CT) has not yet been definitively established. OBJECTIVES: To compare alleged findings on abdominal CT with those of a follow-up colonoscopy. METHODS: Ninety-four consecutive patients found to have large-bowel abnormalities on abdominal CT were referred for colonoscopy. Of these patients, 48 were referred for a suspected colorectal tumour and 46 for CRWT. Colonoscopy was performed and findings were compared. RESULTS: Of the 48 suspected colorectal tumours, 34 were determined to be neoplastic lesions on colonoscopy. Of these, 26 were malignant and eight were benign. Colonoscopy revealed no abnormality in 30 of 46 patients with CRWT as a solitary finding, and revealed some abnormality in 16 patients (12 had diverticular disease, four had benign neoplastic lesions). CONCLUSIONS: CRWT as an incidental and solitary finding on CT should not be regarded as a pathology prompting a colonoscopy. Approximately two-thirds of the patients had a normal colonoscopy and the remaining patients had benign lesions (12 had diverticular disease and four had benign neoplastic lesions). However, many of these patients seem to warrant colonoscopy regardless of CT findings, particularly patients who have a family history of colorectal cancer, have positive fecal occult blood test results or who are older than 50 years of age.

Significant colonic neoplasia prevalence and ASGE recommendations: is it time for a change?

GOALS AND BACKGROUND: To Evaluate the indications versus diagnostic yield of significant colonic neoplasia (SCN) in the open-access era and screening colonoscopy. STUDY: During 6-year period, all procedural data were obtained from all consecutive patients who underwent colonoscopies. Indications were compared with American Society for Gastrointestinal Endoscopy guidelines. RESULTS: In all 22,341 procedures were included in the study. Indications were divided into 3 groups: Screening (21.89% of the procedures), surveillance (17.60%) and symptoms/signs (60.51%). A total of 2867 patients (12.83%) had SCNs. Of these, 278 (7.00%) SCNs were found in the group less than 50 years of age and 2589 in the group over the age of 50 years (14.10%). SCN as per indication frequency was 12.69% in the symptom/sign group (subdivided to 7.24% and 14.01% in the under 50 and over 50, age groups, respectively); screening 13.37% (5.48% and 15.09%, respectively); surveillance 12.64% (8.48% and 13.19%, respectively). The indications leading to the highest SCN rate (over 25%) were: abnormal imaging, elevated carcinoembryonic antigen, and rectal pain. CONCLUSIONS: Colonoscopy is a unique screening tool that can detect neoplastic lesions. SCN prevalence in our study was between 13% and 15% for all indications in patients above 50 years of age. This emphasizes performing a screening colonoscopy for the entire population over the age of 50 years, regardless of the indication. We feel that American Society for Gastrointestinal Endoscopy guidelines should be reassessed. The revised criteria should state that the primary indication, are all people over the age of 50 years, who should have a colonoscopy performed, unless otherwise contraindicated.

Diagnostic yield and safety of colonoscopy in Israeli patients in an open access referral system.

BACKGROUND: Open access endoscopy allows reference of patients for endoscopic procedures without prior gastrointestinal consultation, allowing the procedure to be more accessible. This practice is becoming increasingly widespread in the United States and other countries and has become commonplace in clinical practice in Israel. The objective of our study is to bring forward our experience with an open access referral system for colonoscopy and to measure the yield and safety of colonoscopy in this system. METHODS: Between January 2001 and September 2003, 10,866 colonoscopies were performed. Patient's charts were reviewed for the following data: demographics, indication for endoscopy, endoscopic and histopathologic findings, and complications. The practice guidelines of the American Society for Gastrointestinal Endoscopy were used to assess appropriateness of colonoscopy. RESULTS: 3533 pathologic findings were found, in 2978 colonoscopies. 2336 polyps were removed, including 18% hyperplastic, 26% tubular adenomata, 13% villous adenomata, 11% tubulovillous adenomata. Advanced disease was found in 41% of pathologic findings, 11% were invasive cancer. Rate of colonoscopies "generally indicated" according to American Society for Gastrointestinal Endoscopy guidelines was 78% with a rate of colonoscopies "generally not indicated" of 22%. Colonoscopy was completed successfully to the cecum in 93% of patients. 0.08% had serious complications during or immediately after colonoscopy. CONCLUSIONS: Our results suggest that open access colonoscopy is a reliable and safe method for screening average risk population. As colonoscopy is becoming the recommended screening model for colorectal cancer this attitude of performing screening in an open access system could both cut costs in the future and improve availability, in an aim to become common practice.

[Open access colonoscopy: do primary care physicians use it properly?].

BACKGROUND: Open access endoscopy facilitates the performance of colonoscopy on a physician's request, without a prior consultation with a gastroenterologist. OBJECTIVES: To investigate: (1) the rates of relevant endoscopic findings in patients referred by family physicians compared to other specialists; (2) whether there is overuse of open-access colonoscopy in our country where the examination is free of charge for the patient; (3) whether a high rate of pre-malignant and malignant incidental findings might justify a more liberal approach to the indications of colonoscopy. METHODS: Prospective study including all consecutive ambulatory patients referred for open access colonoscopy. The indication for the examination was tabulated according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines. Endoscopic findings were classified into relevant or normal; each relevant finding was correlated with the indication for which the examination was performed. RESULTS: A total of 34.2% of patients had a colonoscopy performed for an inappropriate indication; family physicians had a slightly higher rate of appropriate indications compared with the other specialists. However, a relevant endoscopic finding was diagnosed only in 14.0% of their referred cases, compared with 22.8% of the other specialists (p = 0.032). Polyps larger than 5 mm or a malignant tumor were diagnosed in 20.7% of the colonoscopies; 19 out of the 83 cases (23%) were diagnosed in examinations performed for inappropriate indications. CONCLUSION: It was found that 34% of the colonoscopies were performed for inappropriate indications. A higher proportion of relevant endoscopic findings was diagnosed among patients referred by surgeons, oncologists and internists as compared with those referred by family physicians. Considering that as much as 23% of polyps and malignant tumors were found in cases performed for inappropriate indications, we suggest that a liberal approach to the indications for colonoscopy--probably age over 50 years--may benefit the patients.

Acute pancreatitis and upper gastrointestinal bleeding as presenting symptoms of duodenal Brunner's gland hamartoma.

Brunner's gland hamartomas are rare, benign small bowel tumours. There were fewer than 150 cases reported in the English literature until the end of the last century. These hamartomas may be discovered incidentally during an upper gastrointestinal tract endoscopy. Otherwise, they may be diagnosed in patients presenting with acute upper gastrointestinal bleeding, anemia or symptoms of intestinal obstruction. The case of a young woman admitted for acute upper gastrointestinal bleeding along with acute pancreatitis is presented. The investigation revealed a giant Brunner's gland hamartoma in the second part of the duodenum. After total endoscopic resection of the tumour, the patient has remained completely asymptomatic for a follow-up period of seven months.