The prevalence of zinc deficiency in morbidly obese patients before and after different types of bariatric surgery.

BACKGROUND: The prevalence of obesity is considered to be increased worldwide. Lack of mineral elements is one of the essential side effects of bariatric surgery as a trending treatment for obesity. We aimed to assess zinc deficiency among morbidly obese patients before and following different types of bariatric surgical procedures. METHODS: In the present retrospective cohort study, 413 morbidly obese patients (body mass index (BMI) ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 with a complication or risk factor, e.g., diabetes mellitus) were enrolled who received bariatric surgery, aged between 18 and 65 years old, and had a negative history of active consumption of alcohol and illicit drugs. Patients were assigned into three groups of bariatric surgeries: mini-gastric bypass, Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG). We recorded baseline clinical and demographic characteristics and zinc serum levels during the preoperative and postoperative follow-up periods at three, six, and 12 months after the operation. RESULTS: All patients with a mean age of 40.57 ± 10.63 years and a mean preoperative BMI of 45.78 ± 6.02 kg/m2 underwent bariatric surgery. 10.2% of the bariatric patients experienced zinc deficiency before the surgery, and 27.1% at 1 year after the surgery. The results showed that 27.7% of mini-gastric bypass patients, 29.8% of RYGB, and 13.3% of SG experienced zinc deficiency 12 months following surgery. We observed no statistical differences in the preoperative and postoperative zinc deficiency between different types of surgeries. CONCLUSION: A high prevalence of preoperative zinc deficiency among morbidly obese patients who underwent bariatric surgery was observed, which increased during the postoperative periods. We recommend assessing zinc serum levels and prescribing zinc supplements before the bariatric operation to alleviate the prevalence of zinc deficiency after the operation.

Cilia signaling and obesity.

An emerging number of rare genetic disorders termed ciliopathies are associated with pediatric obesity. It is becoming clear that the mechanisms associated with cilia dysfunction and obesity in these syndromes are complex. In addition to ciliopathic syndromic forms of obesity, several cilia-associated signaling gene mutations also lead to morbid obesity. While cilia have critical and diverse functions in energy homeostasis including their roles in centrally mediated food intake as well as in peripheral tissues, many questions remain. Here, we briefly discuss the syndromic ciliopathies and monoallelic cilia signaling gene mutations associated with obesity. We also describe potential ways cilia may be involved in common obesity. We discuss how neuronal cilia impact food intake potentially through leptin signaling and changes in ciliary G protein-coupled receptor (GPCR) signaling. We highlight several recent studies that have implicated the potential for cilia in peripheral tissues such as adipose and the pancreas to contribute to metabolic dysfunction. Then we discuss the potential for cilia to impact energy homeostasis through their roles in both development and adult tissue homeostasis. The studies discussed in this review highlight how a comprehensive understanding of the requirement of cilia for the regulation of diverse biological functions will contribute to our understanding of common forms of obesity.

Efficacy and safety of direct oral factor Xa inhibitors compared with warfarin in patients with morbid obesity: a single-centre, retrospective analysis of chart data.

BACKGROUND: Because studies of direct oral anticoagulants in patients with venous thromboembolism and non-valvular atrial fibrillation have had minimal representation of morbidly obese patients (ie, body-mass index [BMI] ≥40 kg/m2), their efficacy and safety in this population are unclear. We investigated whether apixaban and rivaroxaban are as effective and safe as warfarin in morbidly obese patients. METHODS: We did a single-centre, retrospective analysis of chart data for all adult patients aged at least 18 years at Montefiore Medical Center (Bronx, NY, USA) with a BMI of at least 40 kg/m2 who were prescribed apixaban, rivaroxaban, or warfarin for either venous thromboembolism or atrial fibrillation between March 1, 2013, and March 1, 2017. Patients who had both venous thromboembolism and atrial fibrillation were excluded, as were patients with indications other than atrial fibrillation and venous thromboembolism. Outcomes of recurrent venous thromboembolism, stroke, and bleeding were measured from the first prescription date to the earliest of a thrombotic event, medication discontinuation, death, or end of study on June 30, 2017. Analyses were stratified by anticoagulation indication and adjusted for comorbidities, CHA2DS2-VASc score, and age where appropriate. Outcome rates were compared using Pearson's χ2 or Fisher's exact test. Time-to-event analyses accounting for length of follow-up were used to compare risks of outcomes. FINDINGS: We obtained data for 795 patients: 150 prescribed apixaban, 326 rivaroxaban, and 319 warfarin. In 366 patients prescribed an anticoagulant for venous thromboembolism, the incidence of recurrent venous thromboembolism was similar between the apixaban, rivaroxaban, and warfarin cohorts (1/47 [2·1%, 95% CI 0·0-6·3], 3/152 [2·0%, 0·0-4·2], and 2/167 [1·2%, 0·0-2·9], respectively; p=0·74). Incidence of major bleeding in this patient group was also similar between the treatment cohorts (1/47 patients on apixaban [2·1%, 95% CI 0·0-6·3], 2/152 on rivaroxaban [1·3%, 0·0-3·1], and 4/167 on warfarin [2·4%, 0·1-4·7]; p=0·77). In 429 patients prescribed an anticoagulant for atrial fibrillation, incidence of stroke was similar between the treatment cohorts (1/103 patients on apixaban [1·0%, 95% CI 0·0-2·9], 4/174 on rivaroxaban [2·3%, 0·1-4·5], and 2/152 on warfarin [1·3%, 0·0-3·1], p=0·71). In this patient group, major bleeding occurred in 3/103 patients on apixaban (2·9%, 95% CI 0·0-6·2), 5/174 on rivaroxaban (2·9%, 0·4-5·4), and 12/152 on warfarin (7·9%, 3·6-12·2); p=0·063. Time-to-event analyses showed that risk of all outcomes in patients with venous thromboembolism, and stroke and composite bleeding in patients with atrial fibrillation, were similar between the anticoagulant cohorts. INTERPRETATION: Our retrospective study provides further evidence of similar efficacy and safety between the direct oral anticoagulants apixaban and rivaroxaban, and warfarin in morbidly obese patients with atrial fibrillation and venous thromboembolism. These data, if confirmed in prospective studies, might enable patients with a BMI of at least 40 kg/m2 to benefit from more convenient, and possibly safer, anticoagulants. FUNDING: None.

Nutritional issues in patients with obesity and cirrhosis.

Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.

Ceftolozane/tazobactam dose regimens in severely/morbidly obese patients with complicated intra-abdominal infection or complicated urinary tract infection.

Ceftolozane/tazobactam is approved for treatment of complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI) with renal function-based dose adjustment. Given that creatinine clearance, body weight and sex are highly correlated in severely/morbidly obese patients, this study investigated whether approved dosing regimens for ceftolozane/tazobactam are appropriate in severely/morbidly obese patients based on simulated pharmacokinetic/pharmacodynamic target attainment, with confirmation from observed clinical outcomes data from the phase 3 clinical development programme. Using a previously published population pharmacokinetic model, 1000 patients were randomly sampled from an internal pooled database of 201 severely/morbidly obese patients (BMI ≥ 35 kg/m2) and were used for Monte Carlo simulation to test whether the labelled dose regimens can achieve ≥90% probability of a target of 32.2% (1-log kill) time above free ceftolozane concentration against pathogens at an MIC up to 8 mg/L. Clinical outcomes data for severely/morbidly obese patients with cIAI or cUTI from pivotal phase 3 studies were summarised to calculate clinical and composite cure rates as a complimentary support. With the approved renal function-based dosing regimens, >90% target attainment of bactericidal activity was achieved at MICs up to 8 mg/L in the simulated severely/morbidly obese patients with cIAI or cUTI, similar to target attainment in non-obese patients and further confirmed by phase 3 outcomes where cure rates in severely/morbidly obese patients and non-obese patients are similar. Approved dosing regimens of ceftolozane/tazobactam, adjusted according to renal function, can achieve adequate target attainment and high clinical cure rates in severely/morbidly obese patients with cIAI or cUTI.

Hyperoxaluria in a Model of Mini-Gastric Bypass Surgery in Rats.

BACKGROUND: Bariatric surgery is associated with hyperoxaluria hence predisposing to nephrolithiasis. The present study aimed to investigate the underlying mechanisms contributing to increased urinary oxalate in a mini-gastric bypass (MGB) surgery model in rats under different dietary conditions. The expression of intestinal oxalate transporters was also evaluated. METHODS: Male rats underwent MGB (n = 21) or Sham procedure (n = 21) and after recovery were fed a standard or high-fat diet with or without oxalate for 8 weeks. Stool and urine were collected before surgery (baseline) and at the end of protocol (final), when intestinal fragments were harvested for expression of Slc26a3 and Slc26a6 oxalate transporters. RESULTS: MGB groups fed with fat, irrespective of oxalate supplementation, presented steatorrhea. In MGB animals fed with fat and oxalate (Fat + Ox), final values of urinary oxalate and calcium oxalate supersaturation risk were markedly and significantly increased versus baseline or Sham animals under the same diet, as well as MGB groups under other diets. Slc26a3 was decreased in biliopancreatic limbs of MGB rats, probably reflecting a physiological adaptation to the restriction of food passage. Slc26a6 was not altered in any harvested intestinal fragment. CONCLUSIONS: A high-fat and oxalate diet induced hyperoxaluria and elevation in calcium oxalate supersaturation risk in a MGB rat model. The presence of fat malabsorption and increased dietary oxalate absorption, but not modifications of Slc26a3 and Slc26a6 oxalate transporters, accounted for these findings, suggesting that bariatric patients may benefit from a low-fat and low-oxalate diet.

Elevated fasting and postprandial C-terminal telopeptide after Roux-en-Y gastric bypass.

Background Roux-en-Y gastric bypass increases circulating bile acid concentrations, known mediators of postprandial suppression of markers of bone resorption. Long-term data, however, indicate that Roux-en-Y gastric bypass confers an increased risk of bone loss on recipients. Methods Thirty-six obese individuals, median age 44 (26-64) with median body mass index at baseline of 42.5 (40.4-46) were studied before and 15 months after Roux-en-Y gastric bypass. After an overnight fast, patients received a 400 kcal mixed meal. Blood samples were collected premeal then at 30-min periods for 120 min. Pre and postmeal samples were analysed for total bile acids, parathyroid hormone and C-terminal telopeptide. Results Body weight loss post Roux-en-Y gastric bypass was associated with a median 4.9-fold increase in peak postprandial total bile acid concentration, and a median 2.4-fold increase in cumulative food evoked bile acid response. Median fasting parathyroid hormone, postprandial reduction in parathyroid hormone and total parathyroid hormone release over 120 min remained unchanged after surgery. After surgery, median fasting C-terminal telopeptide increased 2.3-fold, peak postprandial concentrations increased 3.8-fold and total release was increased 1.9-fold. Conclusions Fasting and postprandial total bile acids and C-terminal telopeptide are increased above reference range after Roux-en-Y gastric bypass. These changes occur in spite of improved vitamin D status with supplementation. These results suggest that post-Roux-en-Y gastric bypass increases in total bile acids do not effectively oppose an ongoing resorptive signal operative along the gut-bone axis. Serial measurement of C-terminal telopeptide may be of value as a risk marker for long-term skeletal pathology in patients post Roux-en-Y gastric bypass.

Mamoplastia pós-cirurgia bariátrica usando suporte protético complementar de contenção glandular / Breast augmentation after bariatric surgery by using complementary prosthetic support for glandular containment

INTRODUÇÃO: A pele de pacientes emagrecidas pós-cirurgia bariátrica apresenta alterações estruturais e proteômicas e não resiste ao peso das mamas, levando-as à flacidez residual precoce, exigindo suporte auxiliar. O objetivo é aplicar suporte auxiliar de lâmina de polipropileno não absorvível mais poliglecaprone absorvível ou lâmina de silicone de bustos, em forma de "soutien interno" como auxiliar de sustentação da pele, para manutenção da forma das mamas, e flacidez no mínimo comparável a outras pacientes sem emagrecimento pela cirurgia bariátrica. MÉTODOS: Nove pacientes foram submetidas à mamoplastia em T invertido com modelagem dos tecidos mamários, com redução do volume e envolvidos com lâmina de sustentação auxiliar. RESULTADOS: Não houve flacidez precoce e em observação de até 4 anos ela era aceitável. Uma delas apresentou seroma, drenado com boa resolução. Serão operadas outras 24 pacientes dentro do protocolo, acompanhadas e observadas por 2 anos com controle mamográfico, ultrassônico e ressonância magnética. CONCLUSÃO: A mamoplastia redutora pós-cirurgia bariátrica requer suporte extra à glândula mamária. A pele estruturalmente alterada não suporta o seu peso e haverá flacidez precoce.

INTRODUCTION: The skin presents structural and proteomic changes after bariatric surgery and cannot withstand the weight of the breasts, which leads to early residual flaccidity, requiring auxiliary support. The goal is to apply a nonabsorbable polypropylene-poliglecaprone absorbable auxiliary mesh support or Bustos silicone sheet, in the form of an "internal brassiere," to support the skin in order to maintain the shape and flaccidity of the breasts comparable with those of normal breasts. METHODS: Nine patients underwent mammoplasty in inverted T with modeling of tissue implants, reduction of breast volume, and wrapping with an auxiliary support mesh. RESULTS: Flaccidity was not observed at an early stage and the condition was acceptable for up to 4 years of follow-up. One of the patients had a seroma, which was drained with good resolution. Another 24 patients will be operated according to the protocol and observed for 2 years by using mammography, ultrasonography, and magnetic resonance imaging. CONCLUSION: Reduction mammoplasty after bariatric surgery requires additional support for the mammary gland. The structurally altered skin could not support the weight of the breasts, resulting in early flaccidity.

The influence of the percentage of the common limb in weight loss and nutritional alterations after laparoscopic gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is considered the gold standard for the treatment of morbid obesity. There is no consensus over ideal limb length when the bypass is created and published studies do not take into account the influence of the common limb (CL) on weight loss. The objective was to study the influence of the common limb after RYGB. The setting was the Virgen de la Arrixaca University Clinical Hospital in Murcia, Spain. MATERIAL AND METHODS: This prospective study includes 151 patients undergoing laparoscopic RYGB surgery for morbid obesity. The patients were divided into 2 groups according to their body mass index. The small intestine (SI) was measured using micro forceps so that the percentage of common limb (%CL) could then be compared against the total SI in each patient. The percentage of excess weight loss (%EWL) in relation to the %CL was calculated at 3, 12, and 24 months. A series of tests was conducted simultaneously to analyze nutritional deficiencies and their relation to the %CL. RESULTS: The total jejunoileal segment and the %CL in the groups of both obese and super-obese patients had no influence on the %EWL in either group for any of the periods studied. The patients with a %CL<50% had greater nutritional deficiencies in the follow-up period and required supplements and more frequent laboratory tests. CONCLUSIONS: The %CL has no effect on weight loss in RYGB patients. A lower %CL is related to greater nutritional deficiencies.

Apronectomy combined with laparotomy for morbidly obese endometrial cancer patients.

BACKGROUND: The surgical management of morbidly (BMI >40) and super obese (BMI >50) women with endometrial cancer is challenging. The aim of this study was to describe the short and long term outcomes of apronectomy combined with laparotomy for endometrial cancer staging and tumour debulking. METHODS: A retrospective case note review of morbidly obese patients undergoing combined apronectomy and laparotomy for suspected endometrial cancer between 2007 and 2009 was performed. Short term (operating time, estimated blood loss, complication rates, duration of hospital stay) and long term outcomes (weight profile over 24-month follow up period) were evaluated. RESULTS: Twenty-one patients were identified with a median age of 58 years and a median BMI of 49 (range 37-64). Apronectomy combined with laparotomy took 192 min on average to complete, with a mean estimated blood loss of 497 ml. There were no intra-operative complications. Postoperative complications included anaemia (14% required a blood transfusion), urinary tract infection (5%) and wound complications (wound infection in 29% and partial wound dehiscence in 5%). The median post-operative stay was 9 days. At twenty-four months, one-third of patients were heavier (mean 5 kg, range 2-8 kg) but almost two-thirds of patients were considerably lighter than they had been pre-operatively (mean 13 kg lighter, range 9-17 kg). CONCLUSIONS: Apronectomy combined with laparotomy was safe and well tolerated in this group of patients. Sustained weight loss by two-thirds of the patients over the two-year follow up period may reflect lifestyle changes instigated by individual patients following surgery. Combined apronectomy and laparotomy may provide an alternative to standard surgery for this challenging group of patients.

Calciphylaxis in a morbidly obese woman with rheumatoid arthritis presenting with severe weight loss and vitamin D deficiency.

OBJECTIVE: To present an unusual case of calciphylaxis in an obese patient with inactive rheumatoid arthritis and normal renal function. METHODS: We describe a 46-year-old morbidly obese Caucasian woman who had previously weighed 200 kg and presented with painful leg ulcers following a rapid weight loss of 102 kg in 1 year. RESULTS: The subject was admitted with a 6-week history of painful leg ulcers that progressed to her thighs. Vasculitis and active rheumatoid arthritis were excluded clinically and biochemically. A skin biopsy confirmed calciphylaxis in the context of normal renal function. Serum 25-hydroxyvitamin D was low at 14 ng/mL (reference range, 20 to 200 ng/mL), with an elevated serum parathyroid hormone level of 241 pg/mL (reference range, 10 to 65 pg/mL), but normal serum calcium and phosphorus levels. The skin lesions persisted despite local wound care, daily hyperbaric oxygen, and parenteral sodium thiosulfate therapies. After normalizing the serum vitamin D level through oral supplementation, she responded well to pamidronate infusion with complete healing of the ulcers and regained 13% of her premorbid weight. CONCLUSION: This is the first case of calciphylaxis preceded by weight loss of greater than 100 kg in a patient with hypovitaminosis D who responded to pamidronate therapy.

Systemic inflammation and carotid diameter in obese patients: pilot comparative study with flaxseed powder and cassava powder.

BACKGROUND: Botanical omega-3 fatty acid (alphalinolenic acid/ALA) has been shown to alleviate the prothrombotic and proinflammatory profile of metabolic syndrome, however clinical protocols are still scarce. Aiming to focus an obese population, a pilot study was designed. METHODS: Morbidly obese candidates for bariatric surgery (n = 29, age 46.3 ± 5.2 years), 82.8% females (24/29), BMI 44.9 ± 5.2 kg/m², with C-reactive protein/CRP > 5 mg/L were recruited. Twenty were randomized and after exclusions, 16 were available for analysis. Flaxseed powder (60 g/day, 10 g ALA) and isocaloric roasted cassava powder (60 g/day, fat-free) were administered in a double-blind routine for 12 weeks. RESULTS: During flaxseed consumption neutrophil count decreased and fibrinogen, complement C4, prothrombin time and carotid diameter remained stable, whereas placebo (cassava powder) was associated with further elevation of those measurements. CONCLUSIONS: Inflammatory and coagulatory markers tended to exhibit a better outlook in the flaxseed group. Also large-artery diameter stabilized whereas further increase was noticed in controls. These findings raise the hypothesis of a less deleterious cardiovascular course in seriously obese subjects receiving a flaxseed supplement.

A potential and novel therapy for obesity: "appendix" electrical stimulation in dogs.

BACKGROUND: Intestinal electrical stimulation (IES) has been introduced as a potential therapy for obesity. However, it is unknown whether the effects of IES on gastrointestinal motility and food intake are location-specific. The aim of this study was to assess the effects of "appendix" (cecum in dog) electrical stimulation (AES) on gastric tone, gastric emptying, and food intake in dogs. METHODS: Twelve healthy dogs were used in three experiments. In experiments 1 and 2, gastric tone and food intake were studied in six dogs implanted with a gastric cannula and one pair of stimulation electrodes in the "appendix." Experiment 3 was performed to study gastric emptying in six dogs with a duodenal cannula and one pair of stimulation electrodes in the "appendix." RESULTS: (1) AES resulted in proximal gastric distention, with gastric volume increased from 114.9 ± 10.7 mL at baseline to 301.7 ± 37.1 mL during AES (p = 0.001), and the effect was completely blocked by a nitric oxide synthase inhibitor. (2) Gastric emptying was delayed at 90 min from 69.8 ± 9.5% in the control session to 15.2 ± 3.6% in the AES session (p = 0.002). 3) AES reduced food intake (average daily intake over a 1-week period) by 55.4% (550.4 ± 17.6 g at control vs. 245.7 ± 17.1 g with AES, p < 0.001). CONCLUSIONS: AES reduces gastric tone via the nitrergic pathway, delays gastric emptying, and inhibits food intake in healthy dogs. These data suggest the therapeutic potential of AES for obesity. Additionally, AES is technically more feasible than electrical stimulation of the stomach or duodenum because a stimulator with electrodes may be placed into the appendix via colonoscopy.

Alteration of the leptin network in late morbid obesity induced in mice by brain infection with canine distemper virus.

Viruses can induce progressive neurologic disorders associated with diverse pathological manifestations, and therefore, viral infection of the brain can impair differentiated neural functions, depending on the initial viral tropism. We have previously reported that canine distemper virus (CDV) targets certain mouse brain structures, including the hypothalamus, early and selectively. Infected mice exhibit acute encephalitis, with late disease, characterized by motor impairment or obesity syndrome, appearing in some of the surviving mice several months after the initial viral replication. In the present study, we show viral persistence in the hypothalami of obese mice, as demonstrated by low, but still significant, levels of CDV nucleoprotein transcripts, associated with a dramatic decrease in F gene mRNAs. Given the pivotal role of the hypothalamus in obesity (eating behavior, energy consumption, and neuroendocrine function) and that of leptin, the adipose tissue-derived satiety factor acting through hypothalamic receptors, we analyzed the leptin networks in both obese and nonobese mice. The discrepancy found between the chronic and dramatic increase in blood leptin levels and the occurrence of obesity may be due to leptin resistance in the brain. In fact, expression of the long leptin receptor isoform, representing the functional leptin receptor, was specifically downregulated in the hypothalami of obese mice, explaining their inability to generate an adequate response to leptin in the brain. Intriguingly, during the acute phase of infection, its expression was increased in CDV-targeted structures in all infected mice and remained high in obese mice in all CDV-targeted structures, except for the hypothalamus. The biphasic change in hypothalamic leptin receptor expression seen during the progression of CDV-induced obesity provides a new paradigm for understanding mechanisms of neuroendocrinological, virus-induced abnormalities.