Glycemic and sleep effects of daytime compared with those of overnight infusions of home parenteral nutrition in adults with short bowel syndrome: A quasi-experimental pilot trial.

BACKGROUND: Patients with short bowel syndrome (SBS) dependent on home parenteral nutrition (HPN) commonly cycle infusions overnight, likely contributing to circadian misalignment and sleep disruption. METHODS: The objective of this quasi-experimental, single-arm, controlled, pilot trial was to examine the feasibility, safety, and efficacy of daytime infusions of HPN in adults with SBS without diabetes. Enrolled patients were fitted with a continuous glucose monitor and wrist actigraph and were instructed to cycle their infusions overnight for 1 wk, followed by daytime for another week. The 24-h average blood glucose, the time spent >140 mg/dL or <70 mg/dL, and sleep fragmentation were derived for each week and compared using Wilcoxon signed-rank test. Patient-reported quality-of-life outcomes were also compared between the weeks. RESULTS: Twenty patients (mean age, 51.7 y; 75% female; mean body mass index, 21.5 kg/m2) completed the trial. Overnight infusions started at 21:00 and daytime infusions at 09:00. No serious adverse events were noted. There were no differences in 24-h glycemia (daytime-median: 93.00 mg/dL; 95% CI: 87.7-99.9 mg/dL, compared with overnight-median: 91.1 mg/dL; 95% CI: 89.6-99.0 mg/dL; P = 0.922). During the day hours (09:00-21:00), the mean glucose concentrations were 13.5 (5.7-22.0) mg/dL higher, and the time spent <70 mg/dL was 15.0 (-170.0, 22.5) min lower with daytime than with overnight HPN. Conversely, during the night hours (21:00-09:00), the glucose concentrations were 16.6 (-23.1, -2.2) mg/dL lower with daytime than with overnight HPN. There were no differences in actigraphy-derived measures of sleep and activity rhythms; however, sleep timing was later, and light at night exposure was lower with daytime than with overnight HPN. Patients reported less sleep disruptions due to urination and fewer episodes of uncontrollable diarrhea or ostomy output with daytime HPN. CONCLUSIONS: Daytime HPN was feasible and safe in adults with SBS and, compared with overnight HPN, improved subjective sleep without increasing 24-h glucose concentrations. This trial was registered at clinicaltrials.gov as NCT04743960 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04743960).

Sleep patterns of patients receiving home parenteral nutrition: A home-based observational study.

BACKGROUND: Patients supported with home parenteral nutrition (HPN) often report poor sleep; however, limited research has been conducted to objectively measure sleep patterns of HPN-dependent patients. METHODS: We aimed to characterize the sleep patterns of patients receiving HPN through 7-day actigraphy in a home-based observational study. Sleep measures of clinical importance were derived from actigraphy, including sleep duration, sleep efficiency, sleep onset latency, and wake after sleep onset. Participants also completed validated sleep surveys. RESULTS: Twenty participants completed all study procedures (mean [SD]: age = 51.6 [13.9] years, body mass index = 21.4 [4.6], and 80% female). The population median (IQR) for sleep duration, sleep efficiency, sleep onset latency, and wake after sleep onset was 6.9 (1.1) h, 83.3% (7.8%), 11.8 (7.1) min, and 57.2 (39.9) min, respectively, and 55%, 60%, 35%, and 100% of participants did not meet the recommendations for these measures from the National Sleep Foundation. Sixty-five percent of participants reported napping at least once during the 7-day period. Based on the Insomnia Severity Index, 70% of participants were classified as having subthreshold or more severe insomnia. Based on the Pittsburgh Sleep Quality Index, 85% were classified as having significant sleep disturbance. CONCLUSION: Most HPN-dependent patients likely have disrupted sleep largely driven by difficulty maintaining sleep. The extent to which HPN contributed to poor sleep cannot be elucidated from this observational study. Addressing known factors that contribute to sleep disruption and considering sleep interventions may improve the overall quality of life of patients receiving HPN.

Supplementation of arachidonic acid plus docosahexaenoic acid in cirrhotic patients awaiting liver transplantation: a preliminary study.

BACKGROUND: In patients with cirrhotic liver diseases, supplementation of linoleic acid and alpha-linolenic acid often does not alter the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting the necessity to directly provide these nutrients. METHODS: In a double-blind, placebo-controlled fashion, 9 cirrhotic patients listed for liver transplantation at Lahey Clinic Center were given daily supplementation with either 10 gel caps containing 500 mg of AA and 1000 mg of DHA (AA/DHA) or 250 mg of linolenic acid (LA) and 125 mg of oleic acid (OA; OA/LA) for 6 weeks. alpha-Tocopherol at 200 IU was provided daily. No other dietary prescription was made. Plasma fatty acid profiles were determined in triglyceride and phospholipids fractions. Plasma levels of C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin 6 (IL-6), and soluble TNF receptor II (sTNFRII) were also measured. RESULTS: Four patients receiving OA/LA and 5 patients receiving AA/DHA completed the study without evidence of any adverse effects or intolerance. The supplementation of LA, AA, and DHA effectively raised their levels in either one or both plasma lipid fractions in this limited number of subjects. DHA plus AA also lowered 22:4omega-6, 22:5omega-6, and 22:5omega-3, suggesting that DHA reduced the elongation and desaturation of AA and EPA. CONCLUSIONS: It is feasible to improve the liver disease-associated deficiency of AA or DHA with modest intakes of AA and DHA. Whether this maneuver will affect the systemic inflammatory responsiveness and ultimately clinical outcome will require a large-scale and well-controlled intervention.

Severe ataxia, myelopathy, and peripheral neuropathy due to acquired copper deficiency in a patient with history of gastrectomy.

BACKGROUND: In animal studies, copper absorption has been demonstrated to occur in the proximal gut via duodenal enterocytes. Acquired copper deficiency is known as "swayback" in ruminant animals and Menkes' disease in humans. Copper is an essential micronutrient necessary for the hematologic and neurologic systems. Acquired copper deficiency in humans has been described, causing a syndrome similar to the subacute combined degeneration of vitamin B(12) deficiency. METHODS: This is a single case report. Our patient developed a neurologic constellation of ataxia, myelopathy, and peripheral neuropathy similar to vitamin B(12) deficiency many years after gastrectomy for severe peptic ulcer disease. The patient was maintained for decades with enteral feedings via jejunostomy that provided the recommended dietary allowance (RDA) for copper. RESULTS: Copper deficiency was suspected, identified, and treated. Over 3 months of follow-up, serum copper levels increased from 4 microg/dL to 20 microg/dL (70-150 microg/dL), and ceruloplasmin increased from 6 mg/dL to 8 mg/dL (14-58 mg/dL). During this short time of follow-up, the patient has had no further progression of his neurologic symptoms. CONCLUSIONS: Ataxia and myelopathy secondary to acquired copper deficiency are rare complications of major gastric resection. This is quite similar to the syndrome of vitamin B(12) deficiency. Vitamin B(12) repletion does not improve symptoms. Bariatric procedures such as gastric bypass surgery result in a similar functional anatomy of the proximal gut and may place more patients at increased risk. Early recognition and therapy with oral or parenteral copper may lead to a decrease in both neurologic and hematologic consequences.

Recurrent Clostridium difficile colitis. Tackling a tenacious nosocomial infection.

C difficile infection recurs in about 20% of previously treated hospitalized patients. The elderly and patients with underlying colonic disease who have recently used antibiotics are at high risk. Signs and symptoms include diarrhea, abdominal pain, and leukocytosis. Diagnosis is dependent on a high degree of clinical suspicion and ELISA testing of a stool sample for toxins. Recurrence is thought to be due to the persistence of C difficile spores. Treatment can be difficult. Oral vancomycin or metronidazole for 10 to 14 days may be helpful as first-line therapy. Tapering the dose over 1 month helps destroy the spores while enabling the normal colonic flora to regrow. Probiotics, such as lactobacillus GG and S boulardii, are being developed to help restore normal colonic flora. Immunization may help prevent C difficile infection in the first place.

Recurrent Clostridium difficile colitis.

Clostridium difficile is the most common cause of nosocomial infectious diarrhea that is usually treated adequately with standard treatment of metronidazole or vancomycin. Relapse or recurrent infection can occur in certain patients and this can be very difficult to treat.

Reversal of parenteral nutrition-associated liver disease with a fish oil-based lipid emulsion (Omegaven) in an adult dependent on home parenteral nutrition.

Patients with intestinal failure and short bowel syndrome usually require chronic parenteral nutrition (PN). PN is associated with risks, including infections, vascular thrombosis, and liver disease. PN-associated liver disease (PNALD) can progress from steatosis to chronic hepatitis and ultimately to cirrhosis. The etiology of PNALD is not completely understood. Therapies for PNALD include carbohydrate or lipid calorie reduction, antibiotics, or the use of ursodeoxycholic acid. When these efforts fail, therapeutic options are limited and liver transplantation may be required. The transition from a soybean- to a fish oil-based lipid formulation, such as the ω-3 parenteral lipid formulation (Omegaven), has shown a dramatic reversal of PNALD within the pediatric population. This is the first report of a PN-dependent adult in the United States complicated by PNALD and hepatic failure who had improvement of liver disease with an ω-3 fish oil-based parenteral formulation.

Conservative management of small bowel perforation in Ehlers-Danlos syndrome type IV.

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. EDS type IV, or vascular EDS, is caused by loss-of-function mutations in the type III pro-collagen gene (COL3A1). Common complications of EDS type IV include gastrointestinal bleeding and bowel perforations, posing diagnostic and therapeutic dilemmas for both surgeons and gastroenterologists. Here, we describe a complicated case of EDS type IV in a 35-year-old caucasian female who presented with overt gastrointestinal bleeding. The patient had a prior history of spontaneous colonic perforation, and an uncomplicated upper endoscopy was performed. A careful ileoscopy was terminated early due to tachycardia and severe abdominal pain, and a subsequent computed tomography scan confirmed the diagnosis of ileal perforation. The patient was managed conservatively, and demonstrated daily improvement. At the time of hospital discharge, no further episodes of gastrointestinal blood loss had occurred. This case highlights the benefit of conservative management for EDS patients with gastrointestinal hemorrhage. It is recommended that surgical treatment should be reserved for patients who fail conservative treatment or in cases of hemodynamic instability. Finally, this case demonstrates the necessity for a higher threshold of operative or endoscopic interventions in EDS type IV patients.

Low-protein diets for hepatic encephalopathy debunked: let them eat steak.

Hepatic encephalopathy (HE) is an incompletely understood phenomenon and serves as a poor prognosis in patients with cirrhosis. Confusion from HE can affect the ability to eat adequately. Despite the prevalence of malnutrition in cirrhotic patients in the 1950s, it was reported that bouts of overt HE were controlled with low protein intake. This largely uncontrolled observation led to restriction of protein intake in cirrhotic patients with or without HE and was an accepted standard of care for many decades to follow. Published in 2004, the pivotal article "Normal Protein Diet for Episodic Hepatic Encephalopathy: Results of a Randomized Study" by Cordoba and colleagues was the first controlled study randomizing cirrhotic patients with HE to receive different amounts of dietary protein. At the completion of the study, the authors concluded that a normal-protein diet was safe and did not exacerbate HE. The Cordoba study suggests that low-protein diets should be abandoned. In light of this evidence, nutrition guidelines have proposed that protein restriction should be avoided in patients with HE as protein requirements are increased in cirrhosis. Despite the advice of experts in the field, it has been shown in recent years that some physicians still believe that protein restriction is needed in patients with HE. This belief has not been substantiated in controlled studies, and societal recommendations have changed. There is no real evidence documenting the advantages of protein restriction in HE. On the contrary, Cordoba and colleagues' article has shown that there are disadvantages to restricting protein in HE.