Wilson disease: copper deficiency and iatrogenic neurological complications with zinc therapy.

A 17-year-old female was diagnosed with Wilson disease and commenced on oral zinc therapy. She re-presented 6 months later with a fall and had classical signs of subacute combined degeneration of the spinal cord confirmed on nerve conduction studies, as a result of zinc-induced copper deficiency. After 6 months of copper therapy, she made a complete recovery with no residual neurological deficits. Early detection of zinc-induced copper deficiency and stringent follow-up mechanisms are crucial. Early initiation of copper replacement may both limit and completely reverse neurological deficits.

Effect of Intravenous Fluids and Analgesia on Dysmotility in Patients With Acute Pancreatitis: A Prospective Cohort Study.

OBJECTIVES: Analgesia and intravenous fluid resuscitation are cornerstones of initial patient management in acute pancreatitis (AP). The aim was to investigate the effect of intravenous fluids and analgesia on gastrointestinal motility in the early course of AP. METHODS: Gastrointestinal dysmotility was assessed using the Gastroparesis Cardinal Symptom Index (GCSI). One-way analysis of variance and analysis of covariance were conducted, adjusting for age, sex, body mass index, severity of AP, preexisting diabetes mellitus, and time from first symptom onset to hospital admission. RESULTS: A total of 108 patients with AP were prospectively enrolled. Opioid analgesia, when compared with nonopioid analgesia, was significantly associated with increase in total GCSI score in both unadjusted and adjusted analyses. There was no significant difference between aggressive and nonaggressive fluid resuscitation in both unadjusted and adjusted analyses. A combination of opioids and any intravenous fluids was associated with a significantly increased total GCSI score compared with opioids and no intravenous fluids in both unadjusted and adjusted analyses. Duration of symptoms was the confounder that significantly affected 6 of 9 studied associations. CONCLUSIONS: Intravenous fluids and analgesia significantly affect motility independent of severity and other covariates. Guidelines on prudent use of opioids and fluids in AP need to be developed, particularly taking into account duration of symptoms from onset to hospitalization.

Ectopic fat accumulation in the pancreas and its clinical relevance: A systematic review, meta-analysis, and meta-regression.

OBJECTIVE: Growing evidence suggests that individuals with excessive fat in the pancreas are at an increased risk of chronic metabolic disorders. The aim was to systematically review studies on non-alcoholic fatty pancreas disease (NAFPD) with a view to determine its prevalence, associations with metabolic co-morbidities, and to suggest normal pancreatic fat percentage threshold. METHODS: Three electronic databases (MEDLINE, Scopus, and Embase) were queried. Studies in humans were eligible for inclusion if they provided data on NAFPD and/or pancreatic fat percentage. Where possible, data were pooled using random-effects meta-analysis and the effect of covariates analysed using meta-regression. RESULTS: Pooling data on pancreatic fat percentage from nine studies (1209 healthy individuals who underwent magnetic resonance imaging), yielded the weighted mean and weighted standard deviation of 4.48% and 0.87%, respectively. Pooling data on NAFPD from eleven studies (12,675 individuals), yielded the pooled prevalence of 33% (95% confidence interval, 24% - 41%). Meta-regression analysis showed that the prevalence of NAFPD was independent of age and sex. The presence of NAFPD was associated with a significantly increased risk of arterial hypertension (risk ratio 1.67; 95% confidence interval, 1.32-2.10; p<0.0001), diabetes mellitus (risk ratio 2.08; 95% confidence interval, 1.44-3.00; p=0.0001), and metabolic syndrome (risk ratio 2.37; 95% confidence interval, 2.07-2.71; p<0.0001). CONCLUSION: The findings indicate that NAFPD is a frequent clinical entity, associated with significantly increased risk of metabolic syndrome and its components. The normal pancreatic fat cut-off point of 6.2% may be recommended for use in future prospective studies.

Incidence and predictors of oral feeding intolerance in acute pancreatitis: A systematic review, meta-analysis, and meta-regression.

BACKGROUND: Tolerance of oral food is an important criterion for hospital discharge in patients with acute pancreatitis. Patients who develop oral feeding intolerance have prolonged hospitalisation, use additional healthcare resources, and have impaired quality of life. This study aimed to quantify the incidence of oral feeding intolerance, the effect of confounders, and determine the best predictors of oral feeding intolerance. METHODS: Clinical studies indexed in three electronic databases (EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials) were reviewed. Incidence and predictor data were meta-analysed and possible confounders were investigated by meta-regression analysis. RESULTS: A total of 22 studies with 2024 patients met the inclusion criteria, 17 of which (with 1550 patients) were suitable for meta-analysis. The incidence of oral feeding intolerance was 16.3%, and was not affected by WHO region, age, sex, or aetiology of acute pancreatitis. Nine of the 22 studies investigated a total of 62 different predictors of oral feeding intolerance. Serum lipase level prior to refeeding, pleural effusions, (peri)pancreatic collections, Ranson score, and Balthazar score were found to be statistically significant in meta-analyses. CONCLUSIONS: Oral feeding intolerance affects approximately 1 in 6 patients with acute pancreatitis. Serum lipase levels of more than 2.5 times the upper limit of normal prior to refeeding is a potentially useful threshold to identify patients at high risk of developing oral feeding intolerance.

Ghrelin and gastroparesis as early predictors of clinical outcomes in acute pancreatitis.

BACKGROUND: Impaired motor and hormonal gastrointestinal functions have been implicated in the pathogenesis of acute pancreatitis. The aim of the present study was to investigate the predictive value of the Gastroparesis Cardinal Symptom Index and serum ghrelin in the development of clinically meaningful outcomes in patients with acute pancreatitis. METHODS: This was a prospective clinical study. The Gastroparesis Cardinal Symptom Index and serum ghrelin were measured for 48 h after hospitalization. Univariate and multivariate logistic regression analyses were conducted. RESULTS: The Gastroparesis Cardinal Symptom Index total score alone on day 2 was a significant predictor of oral feeding intolerance in both unadjusted (odds ratio 1.21 (1.01-1.46), P = 0.04) and adjusted (odds ratio 1.30 (1.01-1.69), P = 0.05) analyses. Adding ghrelin to Gastroparesis Cardinal Symptom Index further improved prediction in both unadjusted (odds ratio 1.26 (1.02-1.56), P = 0.03) and adjusted (odds ratio 1.53 (1.00-2.35), P = 0.05) analyses. CONCLUSION: This pilot study demonstrates that the Gastroparesis Cardinal Symptom Index has a potential to be used as a predictor of oral feeding intolerance. Ghrelin, when combined with the Gastroparesis Cardinal Symptom Index, may further improve the predictive accuracy. These findings need to be confirmed in larger studies.

Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies.

BACKGROUND: There is a lack of robust estimates of the worldwide incidence and mortality of acute pancreatitis, chronic pancreatitis, pancreatic cysts, and pancreatic cancer in the general population. Our aim was to quantitate and compare the incidence and mortality of major pancreatic diseases in high-quality population-based cohort studies. METHODS: Three databases (PubMed, Embase, and Scopus) were searched independently by two reviewers. Data from eligible studies were subject to meta-analysis to obtain global estimates. A number of prespecified subgroup analyses and meta-regression analyses were also done. FINDINGS: 48 population-based cohort studies (35 on pancreatic cancer, ten on acute pancreatitis, three on chronic pancreatitis, and none on pancreatic cysts) were identified, with a total study population of 296 million individuals and 119 000 patients with pancreatic diseases. Global estimates of incidence and mortality were 8·14 cases (95% CI 6·63-9·98) per 100 000 person-years and 6·92 deaths (95% CI 3·72-12·89) per 100 000 person-years for pancreatic cancer, 33·74 cases (95% CI 23·33-48·81) per 100 000 person-years and 1·60 deaths (95% CI 0·85-1·58) per 100 000 person-years for acute pancreatitis, and 9·62 cases (95% CI 7·86-11·78) per 100 000 person-years and 0·09 deaths (95% CI 0·02-0·47) per 100 000 person-years for chronic pancreatitis. Subgroup analysis based on the WHO regions showed that the incidences of both pancreatic cancer and acute pancreatitis, and mortality from pancreatic cancer, were significantly higher in the American region than in the European and Western Pacific regions, while the incidence of chronic pancreatitis was significantly higher in the European region than in the American region. Mortality from pancreatic cancer was lowest in the Southeast Asian region. The incidence of chronic pancreatitis was twice as high in men as in women, although there was no difference between sexes for pancreatic cancer or acute pancreatitis. INTERPRETATION: Globally, acute pancreatitis is the most common pancreatic disease whilst pancreatic cancer is the most lethal. However, their burden is not equal across the globe. The epidemiological estimates reported in this study could inform future high-quality studies. FUNDING: None.

Association between oral feeding intolerance and quality of life in acute pancreatitis: A prospective cohort study.

OBJECTIVE: Oral feeding intolerance (OFI) is a common complication of nutritional management in acute pancreatitis (AP) and is associated with significantly worse clinical outcomes and increased cost of treatment. However, changes in patient-reported outcomes associated with OFI during AP and effect of OFI on quality of life (QoL) have, to our knowledge, never been studied. The aim of this study was to investigate the relationship between OFI and QoL in patients with AP. METHODS: We conducted a prospective cohort study of patients with AP. Patients were grouped according to whether they developed OFI during hospitalization. QoL was recorded daily during hospitalization and at 1 and 4 wk after discharge. One-way analysis of covariance and repeated measures analysis were conducted. P < 0.05 was accepted as statistically significant. RESULTS: The study included 131 patients with AP. Fifty-two (40%) developed OFI during hospitalization. Overall QoL was significantly impaired in the OFI group (mean difference = -16.1; 95% confidence interval, -24.4 to -7.8; P ≤ 0.001). Five individual domains-physical limitations, psychological function, sleep, pain, and visceral function-were significantly impaired in the OFI group during hospitalization. Overall QoL improved significantly within each group from hospitalization to follow-up (P < 0.001) with no significant difference between the two groups at follow-up (mean difference = -2; 95% confidence interval, -7.1 to 3.2; P = 0.449). CONCLUSIONS: QoL is significantly impaired in patients with AP who develop OFI. Nutritional management of acute pancreatitis needs to be optimized to prevent the occurrence of OFI.

Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis.

BACKGROUND & AIM: Acute pancreatitis (AP) and chronic pancreatitis (CP) traditionally have been thought to be distinct diseases, but there is evidence that AP can progress to CP. Little is known about the mechanisms of pancreatitis progression. We performed a meta-analysis to quantify the frequency of transition of AP to CP and identify risk factors for progression. METHODS: We searched PubMed, Scopus, and Embase for studies of patients with AP who developed CP, published from 1966 through November 2014. Pooled prevalence and 95% confidence intervals (CIs) were calculated for these outcomes, and sensitivity, subgroup, and meta-regression analyses were conducted. RESULTS: We analyzed 14 studies, which included a total of 8492 patients. The pooled prevalence of recurrent AP was 22% (95% CI, 18%-26%), and the pooled prevalence of CP was 10% (95% CI, 6%-15%). Sensitivity analyses yielded a pooled prevalence of CP of 10% (95% CI, 4%-19%) and 36% (95% CI, 20%-53%) in patients after the first occurrence and recurrent AP, respectively. Subgroup analyses found alcohol use and smoking to be the largest risk factors for the development of CP, with pooled prevalence values of 65% (95% CI, 48%-56%) and 61% (95% CI, 47%-73%), respectively. Meta-regression analysis found that men were more likely than women to transition from AP to CP. CONCLUSIONS: Ten percent of patients with a first episode of AP and 36% of patients with recurrent AP develop CP; the risk is higher among smokers, alcoholics, and men. Prospective clinical studies are needed to study pancreatitis progression.