Vitamin D: A magic bullet or a myth?

The interest in Vitamin D (Vit D) is increased after the finding of Vit D receptors in many different cells. This led to the hypothesis that Vit D may have more impact on human health than its role in bone health. Epidemiological studies found associations between low plasma levels of Vit D and the prevalence of many diseases. However, Large RCTs did not find convincing evidence for a positive effect of Vit D supplementation on cancer, cardiovascular disease, auto-immune disease and inflammatory diseases. In this review, the results are described of a literature search regarding the relationship between Vit D status and different diseases. Pubmed was used to find systematic reviews of observational studies describing the association between Vit D status, diseases (cancer, coronary heart diseases, auto-immune diseases, sepsis) and mortality. Subsequently, a search was performed for RCTs and the results of large RCTs are described. Studies with a positive intervention effect on primary or secondary outcome variables are summarized. No exclusion criteria were used. The metabolism of Vit D is reviewed, its endogenous production and the intake from food, its activation and transport in the body. The article addresses the effects of diseases on the metabolism of Vit D with special focus on the role of Vit D Binding Protein and its effects on assessing Vit D status. Studies addressing the association between vitamin D status and cancer, cardiovascular diseases, auto-immune diseases, inflammation and severe illness are reviewed. A search for RCTs with positive effects of Vit D supplementation on different diseases yielded only a few studies. The vast majority of RCTs showed no significant positive effects. The presumed high prevalence of Vit D deficiency is questioned based on these results and on altered concentrations of Vit D binding protein, leading to low Vit D levels in plasma but not to low active Vit D levels during disease related inflammation In these conditions, plasma levels of Vit D are therefore not a valid reflection of Vit D status. Reversed causality is described as a possible factor interfering with the correct assessment of the Vit D status. It is concluded that further widespread fortification of foods and stimulation of supplement use should be reconsidered.

Defining malnutrition: A plea to rethink.

In a recent consensus report in Clinical Nutrition the undernourished category of malnutrition was proposed to be defined and diagnosed on the basis of a low BMI or unintentional weight loss combined with low BMI or FFMI with certain cut off points. The definition was endorsed by ESPEN despite recent endorsement of a very different definition. The approach aims to assess whether nutritional intake is sufficient but is imprecise because a low BMI does not always indicate malnutrition and individuals with increasing BMI's may have decreasing FFM's. The pathophysiology of individuals, considered to be malnourished in rich countries and in areas with endemic malnutrition, results predominantly from deficient nutrition combined with infection/inflammation. Both elements jointly determine body composition and function and consequently outcome of disease, trauma or treatment. When following the consensus statement only an imprecise estimate is acquired of nutritional intake without knowing the impact of inflammation. Most importantly, functional abilities are not assessed. Consequently it will remain uncertain how well the individual can overcome stressful events, what the causes are of dysfunction, how to set priorities for treatment and how to predict the effect of nutritional support. We therefore advise to consider the pathophysiology of malnourished individuals leading to inclusion of the following elements in the definition of malnutrition: a disordered nutritional state resulting from a combination of inflammation and a negative nutrient balance, leading to changes in body composition, function and outcome. A precise diagnosis of malnutrition should be based on assessment of these elements.

A prospective non-randomized two-centre study of patients with passive faecal incontinence after birth trauma and patients with soiling after anal surgery, treated by elastomer implants versus rectal irrigation.

AIM: This study is a prospective evaluation of patients with passive faecal incontinence and patients with soiling treated by elastomer implants and rectal irrigation. PATIENTS AND METHODS: Patients with passive faecal incontinence after birth trauma resulting from a defect of the internal sphincter and patients with soiling after previous anal surgery were included. All patients underwent endo-anal ultrasound, magnetic resonance imaging, and anal manometry. The patients with passive faecal incontinence were initially treated by anal sphincter exercises and biofeedback therapy during half a year. The patients completed incontinence scores, a quality of life questionnaire, and a 2-week diary card. RESULTS: The elastomer group consisted of 30 males and 45 females with a mean age of 53 years (25-77). The rectal irrigation group consisted of 32 males and 43 females with a mean age of 50 years (25-74). At 6 months follow-up, 30 patients with soiling of the rectal irrigation group and only nine patients of the elastomer group were completely cured (p = 0.02). Only three patients with passive faecal incontinence were cured in the rectal irrigation group and none in the elastomer group. Three distal migrations of elastomer implants required removal at follow-up. CONCLUSIONS: After patients had performed anal sphincter exercises, no clear improvement of passive faecal incontinence was obtained by elastomer implants or rectal irrigation. However, rectal irrigation is far more effective than elastomer implants in patients with soiling.

Transvaginal posterior colporrhaphy combined with laparoscopic ventral mesh rectopexy for isolated Grade III rectocele: a prospective study of 27 patients.

AIM: The aim of this study was to evaluate prospectively transvaginal posterior colporrhaphy (TPC) combined with laparoscopic ventral mesh rectopexy (LVR) in patients with a symptomatic isolated rectocele. METHOD: Patients with these complaints underwent dynamic and static MRI. All consecutive patients with a Grade III (4 cm or more) rectocele and without internal/external rectal prolapse, enterocele and external sphincter damage were operated on. The patients completed the Obstructed Defecation Syndrome (ODS) score and the Cleveland Clinic Incontinence Score (CCIS). All tests were repeated after treatment. Dynamic disorders of the pelvic floor detected by MRI were recorded. RESULTS: In 27 patients [median age 67 (46-73) years], TPC combined with LVR was feasible. Complications were limited to port site infection in two patients. Sexual discomfort (n = 8) due to prolapse diminished in six (75%) patients and in one (4%) de novo dyspareunia developed after treatment. The median follow-up was 12 (10-18) months. The median CCIS was 12 (10-16) before treatment and 8 (7-10) after (P < 0.0001). The median ODS score was 19 (17-23) before and 6 (3-10) after treatment (P < 0.0001). There was no change in urinary symptoms. CONCLUSION: TPC combined with LVR for obstructed defaecation and faecal incontinence in patients with Grade III rectocele significantly relieves the symptoms of these disorders.

Have we enough glutamine and how does it work? A clinician's view.

There is a gap between the scientific basis of the claim that in several disease states glutamine is lacking and the widespread belief that supplementation of glutamine to the nutritional regimen is beneficial in severely ill patients. Glutamine shortage exists when consuming tissues, playing a crucial role in the response to trauma and disease, receive insufficient amounts of glutamine. In these tissues (immune system, wound), glutamine is only partly oxidized but has more specific roles as nontoxic nitrogen carrier, precursor of several crucial metabolites required for cell proliferation and for maintenance of the redox potential, and as osmolyte. In inflammatory states, glutamine concentrations in plasma and tissues are decreased due to many disease-related factors, precluding its use as a reliable indicator of shortage. Isotope studies have yielded equivocal results, precluding their use as a reliable indicator of glutamine shortage or adequacy. The increase in the net release of glutamine from peripheral tissues to central tissues (immune system, liver, spleen, wound) in inflammatory states provides a better basis for the necessity to supplement the organism with extra glutamine in these conditions. Glutamine supplementation was beneficial in a few studies in burn or trauma patients. The clinical benefit of parenteral glutamine supplementation in patients with severe inflammation has been demonstrated more convincingly. The amounts of glutamine supplemented approximate the amounts released by peripheral tissues and utilized by central organs operative in host defense and are therefore in the physiological range.

Staged Mucosal Advancement Flap versus Staged Fibrin Sealant in the Treatment of Complex Perianal Fistulas.

Background. In this prospective randomised study, the staged mucosal advancement flap is compared with staged fibrin sealant application in the treatment of perianal fistulas. Methods. All patients with high complex cryptoglandular fistulas were randomised to closure of the internal opening by a mucosal advancement flap (MF) or injection with fibrin sealant (FS) after treatment with setons. Recurrence rate and incontinence disorders were explored. Results. The MF group (5 females and 10 males) with a median age of 51 years and a median followup of 52 months. The FS group (4 females and 11 males) with a median age of 45 years and a median followup of 49 months. Three (20%) patients of the MF group had a recurrent fistula compared to 9 (60%) of the FS group (P = 0.03). No new continence disorders developed. Conclusion. Staged FS injection has a much lower success rate compared to MF.

Conservative treatment of patients with faecal soiling.

PURPOSE: A prospective evaluation of fifty patients with faecal soiling but normal sphincter function treated by a conservative treatment algorithm. PATIENTS AND METHODS: Between January 2010 and January 2011, 50 consecutive patients of two different clinical centres, with faecal soiling and normal anorectal function as assessed by endoanal ultrasound, MRI and anal manometry, were eligible for the purpose of this study. All patients started the therapy by psyllium (PS) and a fibre-rich diet daily after 2 months followed by rectal irrigation (RI) in case of incomplete response and after 4 months by 4 g colestyramine (CO), respectively. The patients completed the Vaizey incontinence score and a 2-week diary card. All tests were performed repeated after 2, 4 and 8 months, respectively. RESULTS: The study group consisted of 41 men and 9 women and a mean age of 38 years (21-70). The soiling complaints resolved completely in 37 (79%) patients. After treatment with PS, RI and CO, 12 (24%) patients, 24 (73%) patients and 1 (79%) patient, respectively, resolved completely of faecal soiling. Average weekly soiling frequency, the amount of patients wearing pads daily and the Vaizey incontinence score diminished significantly after treatment with psyllium and after treatment with rectal irrigation (P < 0.001). CONCLUSION: Conservative treatment focussed on complete evacuation or clearing the anorectal canal is effective in the treatment of patients with faecal soiling.

Autologous platelet-derived growth factors (platelet-rich plasma) as an adjunct to mucosal advancement flap in high cryptoglandular perianal fistulae: a pilot study.

AIM: The aim of this study was to explore autologous platelet-rich plasma as an adjunct to the staged mucosal advancement flap in the treatment of perianal fistulae. METHOD: Between February 2006 and May 2007, 10 patients with fistula tracts transversing from the middle-third or upper part of the anal sphincter were treated for at least 3 months with noncutting setons prior to definitive closure by autologous platelet-rich plasma as an adjunct to a mucosal advancement flap. Five patients smoked tobacco. RESULTS: The study group consisted of six women and four men with a median age of 44 (range 30-75) years and a median follow up of 26 (range 17-32) months. One (10%) patient had a recurrent fistula. No new continence disorders developed after definitive treatment in both groups. CONCLUSION: Platelet-rich plasma as an adjunct to a staged mucosal advancement flap for the treatment of perianal cryptoglandular fistulae is a promising treatment modality and seems to establish a high healing rate.

ESPEN Guidelines on Parenteral Nutrition: surgery.

In modern surgical practice it is advisable to manage patients within an enhanced recovery protocol and thereby have them eating normal food within 1-3 days. Consequently, there is little room for routine perioperative artificial nutrition. Only a minority of patients may benefit from such therapy. These are predominantly patients who are at risk of developing complications after surgery. The main goals of perioperative nutritional support are to minimize negative protein balance by avoiding starvation, with the purpose of maintaining muscle, immune, and cognitive function and to enhance postoperative recovery. Several studies have demonstrated that 7-10 days of preoperative parenteral nutrition improves postoperative outcome in patients with severe undernutrition who cannot be adequately orally or enterally fed. Conversely, its use in well-nourished or mildly undernourished patients is associated with either no benefit or with increased morbidity. Postoperative parenteral nutrition is recommended in patients who cannot meet their caloric requirements within 7-10 days orally or enterally. In patients who require postoperative artificial nutrition, enteral feeding or a combination of enteral and supplementary parenteral feeding is the first choice. The main consideration when administering fat and carbohydrates in parenteral nutrition is not to overfeed the patient. The commonly used formula of 25 kcal/kg ideal body weight furnishes an approximate estimate of daily energy expenditure and requirements. Under conditions of severe stress requirements may approach 30 kcal/kg ideal body weights. In those patients who are unable to be fed via the enteral route after surgery, and in whom total or near total parenteral nutrition is required, a full range of vitamins and trace elements should be supplemented on a daily basis.

Health-related quality of life in patients treated for enterocutaneous fistula.

BACKGROUND: Patients with enterocutaneous fistulas undergo long intensive treatment. The aim of this study was to investigate the long-term health-related quality of life (HRQL) of these patients. METHODS: Consecutive patients treated for enterocutaneous fistula between 1990 and 2005 were eligible for this retrospective study. The Karnofsky Performance Scale (KPS), Short Form 36 (SF-36) and the Inflammatory Bowel Disease Questionnaire were used to measure HRQL. The SF-36 was matched with results from healthy controls. Patients also gave information on concurrent medical illnesses. RESULTS: Of 135 patients, 44 died, 14 were lost to follow-up and 12 refused to participate; of the remaining 65, 62 participated (response rate 81 per cent). HRQL was independent of patient characteristics during treatment. Scores for SF-36 domains were lower than in their matched controls (P < 0.050). Concurrent medical illness (cancer, depression and gastrointestinal disease) significantly reduced HRQL (for example with a 40 per cent reduction in vitality). The median KPS score was 80, indicating that activities could be performed with effort and patients had some signs of disease. CONCLUSION: HRQL is lower in patients treated for enterocutaneous fistula than in matched controls, particularly in those with concurrent medical illnesses. Patients treated successfully have normal independence in daily functioning.

ESPEN Guidelines on Enteral Nutrition: Surgery including organ transplantation.

Enhanced recovery of patients after surgery ("ERAS") has become an important focus of perioperative management. From a metabolic and nutritional point of view, the key aspects of perioperative care include: Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and if necessary tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in surgical patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1980. The guideline was discussed and accepted in a consensus conference. EN is indicated even in patients without obvious undernutrition, if it is anticipated that the patient will be unable to eat for more than 7 days perioperatively. It is also indicated in patients who cannot maintain oral intake above 60% of recommended intake for more than 10 days. In these situations nutritional support should be initiated without delay. Delay of surgery for preoperative EN is recommended for patients at severe nutritional risk, defined by the presence of at least one of the following criteria: weight loss >10-15% within 6 months, BMI<18.5 kg/m(2), Subjective Global Assessment Grade C, serum albumin <30 g/l (with no evidence of hepatic or renal dysfunction). Altogether, it is strongly recommended not to wait until severe undernutrition has developed, but to start EN therapy early, as soon as a nutritional risk becomes apparent.

Long-term outcome following mucosal advancement flap for high perianal fistulas and fistulotomy for low perianal fistulas: recurrent perianal fistulas: failure of treatment or recurrent patient disease?

BACKGROUND: In this study, we determined the long-term outcome of perianal fistulas treated with mucosal advancement flap (MF) or fistulotomy (FT). METHODS: One hundred three patients with perianal fistulas were treated by MF for high fistulas or FT for low fistulas and were retrospectively assessed by case-note review and examined at the out-patient clinic. The localization and time of recurrence of the fistula were recorded. RESULTS: Forty-one patients [median follow-up of 72 months (range 48-99)] were treated by an MF, and 62 patients [median follow up of 75 months (range 48-99)] were treated by FT. After 12, 48, and 72 months, the fistula had recurred in 9 (22%), 26 (63%), and 26 (63%) patients of the MF group and in 4 (7%), 16 (26%), and 24 (39%) patients of the FT group, respectively. Eighteen (69%) of the recurrences in the MF group and ten (33%) of the FT group occurred within 24 months after surgery (p=0.01). Four (15%) of the recurrences in the MF group and 13 (54%) of the recurrences in the FT group were present in a different localization (p=0.007). CONCLUSION: The success rate of both FT and MF techniques decreases with time. Recurrence appears to be caused by failure of treatment and by recurrent patient disease.

Application of subjective global assessment as a screening tool for malnutrition in surgical patients in Vietnam.

BACKGROUND AND AIMS: In most hospitals in Vietnam, clinical assessment of nutritional status has yet to become part of the routine clinical history taking and physical examination. It is the aim of this study to apply subjective global assessment (SGA) of nutritional status in surgical patients in the Mekong Delta, Vietnam, to determine the incidence of malnutrition according to SGA and to know whether there was an association between SGA class and infectious complications. METHODS: A prospective, cross-sectional study design was used. SGA of nutritional status was applied. Patients were rated as well nourished (A), moderately malnourished (B) or severely malnourished (C). Infectious complications (wound infection, intra-abdominal abscesses, anastomotic leakage) were recorded. RESULTS: Of the 438 patients assessed, 194 (44.3%) were classified as A, 126 patients (28.8%) were classified as B and 118 patients (26.9%) were classified as C. Of the 274 patients who underwent major abdominal surgery assessed, 61 patients (22.3%) were classified as A, 97 patients (35.4%) were classified as B and 116 patients (42.3%) were classified as C. Weight loss and percent weight loss, muscle wasting, loss of subcutaneous fat, functional capacity and significant gastrointestinal symptoms correlate significantly with the severity of SGA class (P<0.001). The rate of postoperative infectious complications was higher in patients classified as SGA class C (33.6%) than as class A (6%) and B (11%). CONCLUSIONS: A high rate of malnutrition was found, applying SGA of nutritional state in surgical patients in Vietnam. Malnutrition was associated with an increase in infectious complications. Special attention should be paid to weight loss, muscle wasting, loss of subcutaneous fat, functional capacity and gastrointestinal symptoms.

Laparoscopic adjustable gastric banding versus open vertical banded gastroplasty: a prospective randomized trial.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) and open vertical banded gastroplasty (VBG) are treatment modalities for morbid obesity. However, few prospective randomized clinical trials (RCT) have been performed to compare both operations. METHODS: 100 patients (50 per group) were included in the study. Postoperative outcomes included hospital length of stay (LOS), complications, percent excess weight loss (%EWL), BMI and reduction in total comorbidities. Follow-up in all patients was 2 years. RESULTS: LOS was significantly shorter in the LAGB group. 3 LAGB were converted to open (1 to gastric bypass). Directly after VBG, 3 patients needed relaparotomies due to leakage, of which one (2%) died. After 2 years, 100% follow-up was achieved. BMI and %EWL were significantly decreased in both groups but significantly more in the VBG group compared to the LAGB group (31.0 kg/m2 and 70.1% vs 34.6 and 54.9% respectively). Co-morbidities significantly decreased in both groups in time. 2 years after LAGB, 20 patients needed reoperation for pouch dilation/slippage (n=12), band leakage (n=2), band erosion (n=2) and access-port problems (n=4). In the VBG group, 18 patients needed revisional surgery due to staple-line disruption (n=15), narrow outlet (n=2) or insufficient weight loss (n=1). Furthermore, 8 VBG patients developed an incisional hernia. CONCLUSION: This RCT demonstrates that, despite the initial better weight loss in the VBG group, based on complication rates and clinical outcome, LAGB is preferred. It had a shorter LOS and less postoperative morbidity.

Staged mucosal advancement flap for the treatment of complex anal fistulas: pretreatment with noncutting Setons and in case of recurrent multiple abscesses a diverting stoma.

OBJECTIVE: To assess the efficacy of a staged strategy for the treatment of complex perianal fistula. METHODS: Between January 1999 and April 2003 all consecutive patients with complex perianal fistulas were treated according to a staged strategy. Fistula tracks originating from the middle third or upper part of the anal sphincter were included. Patients were examined for recurrent fistulas and complaints of incontinence and soiling. Initial treatment consisted of a noncutting seton with or without a diverting stoma. Definitive surgical treatment consisted of an advancement flap or fistulotomy. RESULTS: Thirty patients were included (median age; 42 years, range 22-68 years). Seven had Crohn's disease without signs of rectal and anal involvement other than the fistula. At a median follow up of 22 months (range 8-52 months) in 29 (97%) patients, the wounds had healed completely; 7 (22%) patients subsequently developed a recurrent fistula and minor soiling occurred in 7 (23%) patients. CONCLUSION: Initial treatment with a seton with and without a diverting stoma minimizing inflammatory activity at the fistula site before definitive surgical treatment gave good results in this difficult group of patients.

Physiological functions should be considered as true end points of nutritional intervention studies.

With the beginning of this millennium it has become fashionable to only follow 'evidence-based' practices. This generally-accepted approach cruelly negates experience or intelligent interpretation of pathophysiology. Another problem is that the great 'meta-analysts' of the present era only accept end points that they consider 'hard'. In the metabolic and nutritional field these end points are infection-related morbidity and mortality, and all other end points are considered 'surrogate'. The aim of this presentation is to prove that this claim greatly negates the contribution of more-fundamentally-oriented research, the fact that mortality has multifactorial causes, and that infection is a crude measure of immune function. The following problems should be considered: many populations undergoing intervention have low mortality, requiring studies with thousands of patients to demonstrate effects of intervention on mortality; nutrition is only in rare cases primary treatment, and in many populations is a prerequisite for survival rather than a therapeutic modality; once the effect of nutritional support is achieved, the extra benefit of modulation of the nutritional support regimen can only be modest; cost-benefit is not a valid end point, because the better it is done the more it will cost; morbidity and mortality are crude end points for the effect of nutritional intervention, and are influenced by many factors. In fact, it is a yes or no factor. In the literature the most important contributions include new insights into the pathogenesis of disease, the diminution of disease-related adverse events and/or functional improvement after therapy. In nutrition research the negligence of these end points has precluded the development and validation of functional end points, such as muscle, immune and cognitive functions. Disability, quality of life, morbidity and mortality are directly related to these functional variables. It is, therefore, of paramount importance to validate functional end points and to consider them as primary rather than surrogate end points.

Effects of long-term intravenous and intragastric L-arginine intervention on jejunal motility and visceral nitric oxide production in the hyperdynamic compensated endotoxaemic pig.

Alterations in L-arginine availability and nitric oxide (NO) synthesis in the intestinal muscularis may contribute to disturbed small intestinal motility that is observed during endotoxaemia. The aim of this study was to evaluate the effect of L-arginine infusion on visceral NO production and jejunal motility in hyperdynamic compensated endotoxaemic pigs. Fasted and saline-resuscitated pigs were intravenously infused for 24 h with endotoxin (lipopolysaccharide, 50 ng kg(-1) min(-1)) or saline (n = 6). Endotoxaemic pigs received either intravenous L-arginine (n = 6, 5.3 micromol kg(-1) min(-1)) or L-alanine (isocaloric, n = 6). After 24 h, intravenous L-arginine or L-alanine infusion was continued intragastrically for 32-h in an enteral meal. During (0-24 h) and 1 day postendotoxaemia (48-56 h), jejunal motility was recorded by manometry and analysed for migrating motor complex (MMC) characteristics. Visceral NO production was measured at 24 and 48 h by 15N2-arginine-to-15N-citrulline conversion. Visceral NO production was increased during endotoxaemia and was higher in L-arginine than in L-alanine-treated pigs. One day postendotoxaemia, visceral NO synthesis was still increased in L-arginine but not in L-alanine-treated animals. Endotoxaemia shortened the MMC cycle duration and accelerated the MMC propagation velocity. Both were restored by L-arginine. Similar motility disturbances were observed one day postendotoxaemia and were also compensated by L-arginine infusion.