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.

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.

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.

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.

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.

Differential effects of selective and non-selective NOS inhibition on renal arginine and protein metabolism during endotoxemia in rats.

BACKGROUND AND AIMS: The kidney is the main endogenous producer of circulating arginine. Renal arginine disposal is directed to protein synthesis, urea production and nitric oxide synthesis. The administration of nitric oxide synthase inhibitors during sepsis may be beneficial or detrimental depending on the specificity of the inhibitor. We aimed to measure the effects of two NOS inhibitors, with different specificity, on renal arginine and protein turnover in a rat model of sepsis. METHODS: Rats were subject to double hit endotoxemia and either L-NAME (non-specific), SMT (iNOS specific) or saline. Under anesthesia, vessels supplying and draining the kidney were catheterized. Systemic and intra-renal arginine and protein metabolism were measured using a primed continuous infusion of L-[2,3-(3)H]arginine and L-[2,6-(3)H]phenylalanine. RESULTS: Non-specific NOS reduced systemic protein and arginine turnover, whereas selective iNOS inhibition did not. In the kidney, blood flow was reduced by L-NAME, but not by SMT. In conjunction with this, non-selective NOS inhibition increased renal protein breakdown, whereas selective iNOS inhibition increased renal arginine production. CONCLUSIONS: This study shows that non-selective NOS inhibition using L-NAME is detrimental for systemic and renal protein metabolism. Selective NOS inhibition stimulates renal arginine synthesis, without changing circulating arginine levels.

Bio-electrical impedance spectroscopy: alternatives for the conventional hand-to-foot measurements.

BACKGROUND AND AIMS: Bio-impedance spectroscopy (BIS) is a very attractive method for measuring body composition. The standard method measures impedance from hand to foot. However, in patients a hand or foot is not always accessible. In these cases alternative methods would be helpful. The objective of this study was to compare BIS measurements from hand to foot (HF) with foot to foot (FF) and hand to hand (HH) measurements as alternatives. Aims were firstly, to assess the relationship between resistance (R) values measured by the different methods, secondly, to study the influence of body geometry on this relationship and lastly, to assess the predictive capacity of the methods for measuring body fluid volumes. METHODS: In 53 subjects with different degrees of obesity (mean BMI = 38; SD = 9 kg/m(2)) three BIS measurements were performed from HF, HH and FF with a Xitron 4000B machine. Resistances of extracellular (Recw) and intracellular water (Ricw) were extrapolated by fitting the data to a Cole-Cole plot. Total body water (TBW) and extracellular water (ECW) were measured by deuterium and bromide dilution respectively. Intracellular water (ICW) was calculated as TBW-ECW. Anthropometric measurements, including length and circumference of limbs and trunk, were performed as measures for body geometry. RESULTS: The Recw, Ricw and R50 values of HF measurements could be accurately described as a function of the Recw, Ricw and R50 values of HH or FF measurements. The relative circumference of arms and legs and the length of the trunk influenced the relationship between R values of the three different measurements. The degree of overweight did not affect this relationship. The precision of the predictions of TBW, ECW and ICW based on R values of the HH measurements were comparable with the traditional HF measurements while the FF measurements gave slightly less accurate results. CONCLUSIONS: Under circumstances where total body BIS measurements cannot be performed, FF or HH measurements may be used as alternatives. However, for clinical use the effect of changes in fluid distribution on the accuracy of these methods needs to be studied further.

Case study of the clinical usefulness of bioelectrical impedance spectroscopy in evaluating nutritional status.

Bioelectrical impedance spectroscopy (BIS) can be a valuable tool in assessing changes in body composition. Although the validity of BIS in healthy subjects is relatively good, in patients considerably larger measurement errors have been reported. In this article the clinical usefulness of BIS in assessing nutritional status of one case study will be discussed. Interpretation of the predictions of BIS in this unstable patient was difficult. This is in agreement with the consensus that BIS does not give accurate prediction of body composition in individual patients. It is recommended that validation studies of BIS should focus on clinical aspects which can influence BIS measurements.