Emerging drugs for the treatment of short bowel syndrome.

INTRODUCTION: SBS is a rare and disabling condition. The standard management is based on diet optimization with parenteral supplementation. In addition, glucagon-like peptide-2 (GLP-2)analogs, have shown promising results as disease-modifying therapies for SBS. AREAS COVERED: Short bowel syndrome (SBS) is defined as a reduction in functional intestinal length to less than 200 cm, leading to intestinal failure (IF) leading to malnutrition and parenteral support dependency. This review discusses the current management of SBS-CIFpatients, the place of GLP-2 analog treatment in terms of efficacy, safety and availability, and the new perspectives opened by the use of enterohormones. EXPERT OPINION: Clinical trials and real-world experience demonstrated that Teduglutide   reduces dependence on parenteral support and has a place in the management of patients with SBS-CIF.  The use of Teduglutide should be discussed in patients stabilized after resection and its introduction requires the advice of an expert center capable of assessing the benefit-risk ratio. The complex, individualized management of SBS-C IF requires theexpertise of a specialized IF center which a multidisciplinary approach. The arrival of new treatments will call for new therapeutic strategies, and the question of how to introduce and monitor them will represent a new therapeutic challenge.

Pancytopenia related to acquired sea-blue histiocytosis during chronic parenteral nutrition.

Bone marrow smear showing histiocytes (black arrow) containing sea blue granules stained with May-Grünwald Giemsa.

The indications and results of the use of teduglutide in patients with short bowel.

Short bowel syndrome (SBS) is a rare condition defined as a reduced residual functional small intestinal length to less than 200 cm often resulting from extensive intestinal resection, and can lead to chronic intestinal failure (CIF). Patients with SBS-CIF are unable to absorb sufficient nutrients or fluids to maintain metabolic homeostasis through oral or enteral intake and require long-term parenteral nutrition and/or fluids and electrolytes. However, complications may arise from both SBS-IF and life-sustaining intravenous support, such as intestinal failure-associated liver disease (IFALD), chronic renal failure, metabolic bone disease and catheter-related complications. An interdisciplinary approach is required to optimize intestinal adaptation and decrease complications. In the last two decades, glucagon-like peptide 2 (GLP-2) analogs have sparked pharmacological interest as a potential disease-modifying therapy for SBS-IF. Teduglutide (TED) is the first developed and marketed GLP-2 analog for SBS-IF. It is approved in the United States, Europe, and Japan for use in adults and children with SBS-IF who are intravenous supplementation dependent. This article discusses the indications, candidacy criteria and results of the use of TED in patients with SBS.

Short Bowel Syndrome: A Paradigm for Intestinal Adaptation to Nutrition?

Short bowel syndrome (SBS) is a rare disease that results from extensive resection of the intestine. When the remaining absorption surface of the intestine cannot absorb enough macronutrients, micronutrients, and water, SBS results in intestinal failure (IF). Patients with SBS who suffer from IF require parenteral nutrition for survival, but long-term parenteral nutrition may lead to complications such as catheter sepsis and metabolic diseases. Spontaneous intestinal adaptation occurs weeks to months after resection, resulting in hyperplasia of the remnant gut, modification of gut hormone levels, dysbiosis, and hyperphagia. Oral nutrition and presence of the colon are two major positive drivers for this adaptation. This review aims to summarize the current knowledge of the mechanisms underlying spontaneous intestinal adaptation, particularly in response to modifications of luminal content, including nutrients. In the future, dietary manipulations could be used to treat SBS.

State-of-the-art colorectal disease: conservative surgical management of intestinal failure in adults.

PURPOSE: Intestinal failure (IF) is defined by the reduction of gut function under the minimum necessary for adequate absorption of macronutrients and/or electrolytes, requiring home parenteral nutrition (HPN) to maintain health and/or growth. Among the different causes of IF, short bowel syndrome (SBS) is one of the main causes of IF in adults. Management of IF and SBS is complex and requires a multidisciplinary approach. The aim of this study was to review the place and the modalities of conservative surgical procedures performed for IF in adults. RESULTS-CONCLUSION: HPN has drastically modified the poor prognosis of these patients, leading to an overall survival around 70-75% at 5 years in patients without cancer. However, HPN is associated with life-threatening long-term complications, including liver failure and catheter-related complications, main causes of deaths for these patients. Surgery can be proposed, in order to try to reduce SBS consequences with either conservative or non-conservative procedures. Simple bowel continuity restoration should be performed as often as possible in order to wean or at least to reduce HPN. Lengthening procedures are proposed to increase the absorption surface of the remnant bowel. These procedures can be only performed on a dilated small bowel. The slowing transit time procedure is represented by segmental reversal of the small bowel. Intestinal transplantation is the last surgical option for patients with IF but is still today associated with high mortality and failure rates. Thus, conservative procedures have a major role in the surgical armentarium for patients with IF.

What's new in short bowel syndrome?

PURPOSE OF REVIEW: Short bowel syndrome (SBS) is a rare disease but with many complications due to intestinal failure, parenteral nutrition and underlying disease. A better prevention, comprehension and treatment could improve the outcome of these patients. RECENT FINDINGS: Recent studies have been published on acute intestinal failure, first cause of SBS, and gives us strategy to avoid extended intestinal resection and thus SBS. There has been progress in the comprehension of intestinal adaptation, characterized by improvements in intestinal absorption, changes on hormonal secretion, development of a hyperphagia and dysbiosis of the gut microbiota. Hormonal treatment focusing on intestinal rehabilitation by promoting intestinal hyperadaptation has been proposed in patients with SBS, who require parenteral nutrition and intravenous fluids, such as glucagon-like peptide-2 (GLP-2) analog which is now recommended by the latest European Society for Clinical Nutrition and Metabolism Guidelines. SUMMARY: Multimodal treatment of acute meseteric ischemia may avoid intestinal resection and is an effective prevention strategy for SBS. New understandings in intestinal adaptation can help us to optimize this adaptation, including with hormonal therapy. GLP-2 analog is now the treatment of reference in SBS patients with chronic intestinal failure.

Ultra-short bowel is an independent risk factor for liver fibrosis in adults with home parenteral nutrition.

BACKGROUND & AIMS: Intestinal failure-associated liver disease is rare in adults and risk factors are unclear. The aim of this study was to determine risk factors of liver fibrosis in adults receiving home parenteral nutrition for intestinal failure and its impact on survival. METHODS: We retrospectively analysed patients with irreversible intestinal failure who underwent a liver biopsy between 2000 and 2013. Significant liver fibrosis was defined as ≥F2 according to NASH-CRN score. RESULTS: Thirty-two patients (46 years [29-60]) underwent liver biopsy 55 months (9-201) after beginning parenteral nutrition. Twenty-six patients (81%) had a short bowel (gut < 200 cm), including 12 (37%) with an ultra-short bowel (gut < 20 cm). Eighteen patients (56%) had liver fibrosis (4 F2, 10 F3, 4 F4), associated with steatohepatitis (72%) and/or cholestasis (17%). Factors associated with occurrence of liver fibrosis included ultra-short bowel (83% vs 13% at 60 months; P < .001), alcohol consumption (73% vs 33% at 60 months; P < .001) and diabetes (80% vs 34% at 60 months; P = .01). Home parenteral nutrition composition, quantity, or duration, episodes of sepsis, abandoned bowel segment were not associated with fibrosis. Ultra-short bowel [risk ratio 12.4, P < .001] and alcohol consumption [risk ratio 7.4, P = .009] independently predicted the development of liver fibrosis on multivariate analysis. After a median follow-up of 118 months (72-155), survival was poorer in patients who developed liver fibrosis than in those without (59% vs 92% at 120 months; P = .02). CONCLUSION: An ultra-short bowel and alcohol consumption are independent risk factors for liver fibrosis in adults requiring HPN.

Iloprost Use in Patients with Persistent Intestinal Ischemia Unsuitable for Revascularization.

BACKGROUND: Persistent or chronic intestinal ischemic injury (i3) can lead to severe malnutrition and acute mesenteric ischemia. Although recommended, revascularization of splanchnic arteries is sometimes unrealizable. METHODS: We report a case series of iloprost use in consecutive stable patients with persistent i3 unsuitable for revascularization followed in a tertiary care center. The feasibility of revascularization was discussed and ruled out by a multidisciplinary team, and informed consent was obtained prior to consideration of a vasoactive therapy. Therapeutic response was defined at 6 months by a decrease in the use of analgesic and parenteral nutrition, and no need for intestinal resection. RESULTS: Between 2006 and 2015, 6 patients (mean age: 51) were included. Splanchnic vascular insufficiency was due to superior mesenteric artery (SMA) thrombosis (n = 4), dissection of the celiac trunk and SMA (n = 1), or repeated vasospasm resulting in chronic nonocclusive mesenteric ischemia (n = 1). Iloprost was delivered via continuous intravenous perfusion at a maximum dosage of 2 ng/kg/min for 6 hours/day on 4 consecutive days, without severe adverse events. Therapeutic response was observed in 4 patients, 3 of which completely stopped parenteral nutrition and analgesic with no need for intestinal resection. CONCLUSIONS: Our results are consistent with findings of a favorable effect of iloprost in patients with persistent splanchnic ischemia that should be confirmed in prospective trials.

Dysmotility disorders: a nutritional approach.

PURPOSE OF REVIEW: Chronic intestinal pseudo-obstruction (CIPO) results in markedly compromised peristalsis mimicking an intestinal occlusion. The main goals of CIPO management are to improve intestinal propulsion and to maintain adequate nutrition status. The review describes the global management of CIPO including methods of diagnosis and nutritional, pharmacological and surgical therapies. RECENT FINDINGS: The principles of CIPO management are to perform a physiological assessment of the gastrointestinal tract involved, to improve symptoms and to prevent malnutrition. We shall discuss the place of physiological motility tests such as intestinal manometry and the cine-magnetic resonance imaging to facilitate diagnosis. Home parenteral nutrition (HPN) is a frequently used therapy with a high dependence level. However, recent data are consistent with a good long-term prognosis. Currently, CIPO becomes a significant cause of chronic intestinal failure. We discuss the outcomes of HPN and surgery. SUMMARY: CIPO is a rare and complex disease. Small bowel manometry remains a gold standard for diagnosis, but new imaging tools appear promising. The management of CIPO requires the cooperation of specialists involved in the intestinal failure field. The better knowledge of CIPO prognosis should encourage clinicians to propose intestinal transplantation in selected cases.

[Prehabilitation in chronic inflammatory bowel disease: the Proactive care pathway]. / Préhabilitation dans les maladies inflammatoires chroniques de l'intestin : le parcours de soins Proactive.

Inflammatory Bowel Diseases (IBD) cause diarrhea and abdominal pain that impair quality of life. Digestive damage frequently leads to undernutrition and sarcopenia, which worsen the prognosis of the disease. This led to the development of PROACTIVE, a multimodal prehabilitation program designed to improve the functional capacities, nutritional status and quality of life of IBD patients. 19 patients have been included in our pilot program, with an initial personalized multimodal assessment, 10 group sessions with 4 patients, and a final multimodal assessment proposing personalized care for home. Initial data are positive, showing an improvement in patients' physical capacity and quality of life after 6 weeks.

Central venous catheter (CVC) salvage in case of central line-associated bloodstream infection (CLABSI): A monocentric prospective study in patients on long-term home parenteral nutrition (HPN).

BACKGROUND & AIMS: CLABSI is a major complication in HPN and frequently leads to central venous catheter (CVC) removal. We developed a salvaging attitude in long term HPN patients due to the necessity of venous preservation. The main objective of this study is to determine the prognosis of CLABSI. METHODS: We followed-up for three months, in an approved HPN centre, a cohort of 250 adult patients receiving HPN with CLABSI from 2018 to 2020. CLABSI was defined by a blood culture growth differential [peripheral blood] - [CVC blood] ≥ 2h. A therapeutic approach to conserve CVC was established according to the department's protocol. The primary endpoint was conservation of CVC with negative CVC and peripheral blood cultures at 3 months without complications. RESULTS: Data from 30 CLABSIs were collected for 22 HPN patients. The incidence rate of CLABSIs was 0.28 infections/1000 catheter days. Sixteen CVCs were removed immediately, with causes due to the type of germ (staphylococcus aureus: n = 6, candida parapsilosis: n = 4, klebsiella: n = 2), chronic colonization (n = 4) or initial complications (n = 4). Among the 14 non-removed CVC, 11 were maintained at 3 months with blood cultures on CVC and peripheral negative for 9 (80%) of them. 3 CVC were removed during the 3 months follow-up (non-CVC-related sepsis n = 2, and resistant pseudomonas aeruginosa n = 1). CONCLUSION: The incidence rate of CLABSIs in an expert HPN centre remains low. In case of CLABSIs, according to specific protocol, approximately 50% of CVC were removed immediately (essentially due to bacteriological characteristics). In case of CLABSIs and without initial complication, 80% of CVCs can be maintained at 3 months. These results justify a conservative attitude according to standardized protocol.

Post-Marketing Use of Teduglutide in a Large Cohort of Adults with Short Bowel Syndrome-Associated Chronic Intestinal Failure: Evolution and Outcomes.

Teduglutide, a GLP-2 analogue, has been available in France since 2015 to treat short-bowel-syndrome (SBS)-associated chronic intestinal failure (CIF) but it remains very expensive. No real-life data on the number of potential candidates are available. The aim of this real-life study was to assess teduglutide initiation and outcomes in SBS-CIF patients. All SBS-CIF patients cared for in an expert home parenteral support (PS) center between 2015 and 2020 were retrospectively included. Patients were divided into two subpopulations: prevalent patients, already cared for in the center before 2015, and incident patients, whose follow-up started between 2015 and 2020. A total of 331 SBS-CIF patients were included in the study (156 prevalent and 175 incident patients). Teduglutide was initiated in 56 patients (16.9% of the cohort); in 27.9% of prevalent patients and in 8.0% of incident patients, with a mean annual rate of 4.3% and 2.5%, respectively. Teduglutide allowed a reduction in the PS volume by 60% (IQR: 40-100), with a significantly higher reduction in incident versus prevalent patients (p = 0.02). The two- and five-year treatment retention rates were 82% and 64%. Among untreated patients, 50 (18.2%) were considered ineligible for teduglutide for non-medical reasons. More than 25% of prevalent SBS patients were treated with teduglutide compared to 8% of incident patients. The treatment retention rate was >80% at 2 years, which could be explained by a careful selection of patients. Furthermore, this real-life study confirmed the long-term efficacy of teduglutide and showed a better response to teduglutide in incident patients, suggesting a benefit in early treatment.

Malnutrition with Low Muscle Mass Is Common after Weaning off Home Parenteral Nutrition for Chronic Intestinal Failure.

The differences in outcomes after weaning off intravenous support (IVS) for chronic intestinal failure (IF) are unclear. Adult IF patients who are weaned off IVS at a tertiary care center (June 2019−2022) were included in this study, and nutritional and functional markers were assessed before, during, and after weaning. Short bowel syndrome (SBS) was present in 77/98 of the IF patients, with different outcomes according to the final anatomy. The body weight and the BMI increased during IVS in those with a jejunocolonic (JC) anastomosis (p < 0.001), but weight loss was significant during follow-up (p < 0.001). Malnutrition was present in >60%, with a reduced muscle mass, which was found using bioelectrical impedance analysis (BIA), in >50% of SBS-JC patients. Although reduced hand-grip strength and sarcopenia were less common, the muscle quality, or phase angle (BIA), decreased during follow-up, also correlating with serum albumin and muscle mass (p ≤ 0.01). The muscle quality and albumin were low in the patients restarting IVS, which was only the case with ≤60 cm of small bowel. Closer follow-up and earlier treatment with teduglutide (TED) should be considered in these patients, as none of the TED-treated patients were malnourished or sarcopenic. Studies on the potential benefits of nutritional and physical interventions for low muscle mass and associations with outcomes are needed in chronic IF patients.

Unexpected upper gastrointestinal polyps in patients with short bowel syndrome treated with teduglutide: need for close monitoring.

BACKGROUND: Teduglutide is a GLP-2 analog indicated for the treatment of short bowel syndrome (SBS) since 2015. Its efficacy in reducing parenteral nutrition (PN) has been shown in patients with SBS. OBJECTIVES: Because teduglutide is a trophic factor, the aim of this study was to assess risk of developing polypoid intestinal lesions during treatment. METHODS: A retrospective study was conducted in 35 patients with SBS treated with teduglutide for ≥1 y in a home PN expert center. All patients underwent ≥1 follow-up intestinal endoscopy during treatment. RESULTS: In the 35 patients, the small bowel length was 74 cm (IQR: 25-100), and 23 patients (66%) had a colon in continuity. Upper and lower gastrointestinal endoscopy was performed after a mean treatment duration of 23 mo (IQR: 13-27), and polypoid lesions were found in 10 patients (6 with a colon in continuity, 4 with an end jejunostomy) and no lesion in 25 patients. In 8 out of the 10 patients, the lesion was found in the small bowel. Five of these lesions presented an aspect of hyperplastic polyp without dysplasia, and 3 of a traditional adenoma with low-grade dysplasia. CONCLUSIONS: Our study highlights the importance of performing follow-up upper and lower gastrointestinal endoscopy in SBS patients treated with teduglutide and the potential need to make changes to the recommendations with respect to treatment initiation and follow-up.

Management of Central Venous Catheters in Children and Adults on Home Parenteral Nutrition: A French Survey of Current Practice.

Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers' practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers' responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.

Imaging as predictor of clinical response to teduglutide in adult patients with short bowel syndrome with chronic intestinal failure.

BACKGROUND: Teduglutide (TED) is a glucagon-like peptide 2 analogue approved in patients with short bowel syndrome with chronic intestinal failure. Bowel epithelial hyperplasia has been reported after TED treatment. OBJECTIVE: The aim of this study was to describe small bowel modifications at imaging in patients with SBS-CIF receiving TED and to assess their predictive value for clinical response. METHODS: Monocentric retrospective study including patients with SBS-CIF treated with TED from 2009 to 2018 with available computed tomography (CT) scans at baseline and during follow-up (≥12 mo). Small bowel (SB) wall thickness was measured as the average of 3 measurements on different SB segments. Clinical response to TED was defined as a ≥20% reduction of weekly parenteral support (PS) volume at 12 mo. RESULTS: Thirty-one patients [20 male (65%), median age 51 y (IQR: 37-59)] were included. Baseline weekly PS volume was a median 7500 mL (IQR: 3500-15,000). After a median (IQR) follow-up of 16 mo (14-27), 26 of 31 patients (84%) had a clinical response. During follow-up, patients underwent 1 (n = 18/31, 58%), 2 (10/31, 32%), or 3 (3/31 10%) CT scans. Median SB wall thickness was 4.0 mm (IQR: 2.8-4.7) and 8.5 mm (IQR: 6.1-9.8) at baseline and after treatment, respectively [paired P < 0.001, median +122% increase (IQR: +65% to +172%)]. Patients with a clinical response had a trend toward a higher SB wall thickness increase [median +133% (IQR: +70% to +176%) compared with +90% (IQR: +52% to +93%), P = 0.061]. All patients with a ≥95% SB wall thickness increase (n = 18) had a clinical response, whereas only 8 of 13 (62%) patients with a <95% SB thickness increase did (P = 0.008). CONCLUSIONS: Teduglutide induces a significant SB wall thickness increase that can be depicted by imaging <6 mo after treatment initiation, and the degree of such increase may be associated with clinical response. Bowel imaging in response to pharmacologic treatments may represent an important outcome to follow.

Emerging treatments for short bowel syndrome in adult patients.

INTRODUCTION: Short bowel syndrome (SBS) is the major cause of chronic intestinal failure (IF), defined as 'the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth'. Areas covered: Spontaneous intestinal adaptation, including increased hormonal secretion, development of hyperphagia and gut microbiota dysbiosis, occurs 2 years after resection, improving intestinal absorption and decreasing PN dependency. Hormonal treatments, promoting intestinal hyperadaptation, have been proposed in patients with SBS with chronic IF. Clinical studies showed teduglutide to increase urine production and reduce the need for parenteral support volume in these patients. According to the latest ESPEN Guidelines, if a growth factor treatment is considered, the GPL2 analog, teduglutide, should be the first-choice treatment. Expert opinion: These therapies underline the importance of patient monitoring at home and the complexity for HPN adaptation. A multidisciplinary approach should be a gold standard.

Intestinal adaptation in short bowel syndrome. What is new?

Short bowel syndrome (SBS) is a well-known cause of intestinal failure (IF) (1). SBS occurs after extensive resection of the small bowel (RSB) resulting in a bowel length of less than 150/200 cm. The colon may have been partially or completely removed. SBS patients experience severe water and nutrient malabsorption, so that they are often managed with parenteral nutrition (PN) to supplement their oral intake (2-4). A complete understanding of the pathophysiology of SBS and postoperative adaptations may allow identifying the spontaneous processes that compensate for the reduction in absorptive surface. A better knowledge of these adaptive mechanisms may help to improve the management of patient nutrition, to reduce the need for PN and to prevent D-encephalopathy episodes. This review focuses on the overall adaptations described in adult SBS patients but does not review pediatric cases.

Teduglutide for treatment of adult patients with short bowel syndrome.

INTRODUCTION: The European Society for Clinical Nutrition has published recommendations on the 'definition and classification of intestinal failure (IF)'. Two criteria must be present: a 'decreased absorption of macronutrients and/or water and electrolytes due to a loss of gut function' and the 'need for parenteral support'. Home parenteral support (HPS) is the primary treatment for chronic IF but is associated with complications. Areas covered: The principal cause of chronic IF is short bowel syndrome (SBS). The aim of treatment is to maximize intestinal absorption and reduce or eliminate the need for HPS to achieve the best possible quality of life. Teduglutide, an analog of glucagon-like peptide 2, improves intestinal rehabilitation by promoting mucosal growth, reducing intestinal loss and promoting intestinal absorption. This article provides an overview and opinion on teduglutide for SBS. Expert opinion: Teduglutide may provide a new treatment strategy for SBS patients with chronic IF. When prescribed, patients should be informed of the benefits and risks of the drug and must be closely monitored in an expert center. Furthermore, as this treatment is costly, cost-effectiveness analysis as well as the risk-benefit ratio needs to be better evaluated.

Pregnancy is possible on long-term home parenteral nutrition in patients with chronic intestinal failure: Results of a long term retrospective observational study.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) improves survival and quality of life in patients with chronic intestinal failure (IF). Few cases of pregnancy on HPN have been published. The aim of this study was to report pregnancy cases on long-term HPN in benign IF. METHODS: This retrospective study included all pregnant patients on HPN from 4 HPN referral centers. Data on demographics, ongoing pathology, HPN type, maternal and newborn complications were collected. RESULTS: From 1984 to 2014, 21 pregnancies occurred in 15 patients (short bowel syndrome (n = 11), motility disorders (n = 3), mucosal disease (n = 1)) of whom 14 occurred after 2010. Median follow-up was 12 years. Median HPN duration before pregnancy was 8 years. HPN was adapted monthly during pregnancy, with close monitoring and supplementations. Energy intake was regularly increased and median maternal weight gain was 10 kg. Median age at the first pregnancy was 27 years. In 55% of cases, the newborn was preterm. Maternal complications occurred in 67% of cases (mainly due to underlying disease or HPN complications). There were 3 post-partum hemorrhages and 6 hypotrophic newborns. Eighteen infants were healthy and 2 chronic intestinal pseudo-obstruction (CIPO) were suspected. CONCLUSION: Our series, the largest reported to date, shows that pregnancy is possible in HPN patients but the complication rate is high. A specific support is necessary, particularly in CIPO patients. As pregnancies have increased over the last 15 years, physicians practicing in HPN referral centers should be aware of the need for implementing a specific multidisciplinary monitoring in HPN patients considering pregnancy.