Use of teduglutide in adults with short bowel syndrome-associated intestinal failure.

Short bowel syndrome (SBS) is a rare gastrointestinal disorder associated with intestinal failure (SBS-IF) and poor health-related outcomes. Patients with SBS-IF are unable to absorb sufficient nutrients or fluids to maintain significantly metabolic homeostasis via oral or enteral intake alone and require long-term intravenous supplementation (IVS), consisting of partial or total parenteral nutrition, fluids, electrolytes, or a combination of these. The goal of medical and surgical treatment for patients with SBS-IF is to maximize intestinal remnant absorptive capacity so that the need for IVS support may eventually be reduced or eliminated. Daily subcutaneous administration of the glucagon-like peptide 2 analog, teduglutide, has been shown to be clinically effective in reducing IVS dependence and potentially improving the health-related quality of life of patients with SBS-IF. The management of patients with SBS-IF is complex and requires close monitoring. This narrative review discusses the use of teduglutide for patients with SBS-IF in clinical practice. The screening of patient eligibility for teduglutide treatment, initiation, monitoring of efficacy and safety of treatment, adapting or weaning off IVS, and the healthcare setting needed for SBS-IF management are described, taking into consideration data from clinical trials, observational studies, and clinical experience.

Immunonutrition in patients who underwent major abdominal surgery: A comprehensive systematic review and component network metanalysis using GRADE and CINeMA approaches.

BACKGROUND: The benefits of immunonutrition in patients who underwent major abdominal surgery have been recently established, but the optimal combination of immunonutrients has remained unclear. The aim is to clarify this point. METHODS: A systematic search of randomized clinical trials about immunonutrition in major abdominal surgery was made. A frequentist random-effects component network meta-analysis was conducted, reporting the P score and odds ratio or mean difference with a 95% confidence interval. The best components and best plausible strategies were described. The critical endpoints were morbidity and mortality rates. The important endpoints were infectious complication rate and length of stay. RESULTS: The meta-analysis includes 87 studies and 8,375 patients. The best approach for morbidity rate, with a moderate grade of certainty, was the use of perioperative enteral/oral immunonutrition with arginine, glutamine, and polyunsaturated fatty acids (odds ratio 0.32; 0.10 to 0.98; P score of 0.93). The mortality rate was reduced by postoperative enteral immunonutrition with RNA, arginine, and polyunsaturated fatty acids (odds ratio 59; 0.29 to 1.22; P score 0.84) but with a low grade of certainty. No significant heterogeneity or incoherence is observed. The length of stay and infectious results are "at risk" for high heterogeneity or network meta-analysis incoherence. The component analysis confirmed that postoperative oral/enteral use of 2 or 3 components is crucial to reducing morbidity rate. CONCLUSION: The oral/enteral immunonutrition in the postoperative period, with multiple immunonutrients, can reduce the morbidity rate in patients undergoing major abdominal surgery. The effect of immunonutrition on mortality, infectious disease, and length of stay is unclear.

Value of immunonutrition in patients undergoing pancreatic resection: a trial sequential meta-analysis.

BACKGROUND: The benefits of immunonutrition (IM) in patients who underwent pancreatic surgery are unclear. METHODS: A meta-analysis of randomized clinical trials (RCTs) comparing IM with standard nutrition (SN) in pancreatic surgery was carried out. A random-effects trial sequential meta-analysis was made, reporting Risk Ratio (RR), mean difference (MD), and required information size (RIS). If RIS was reached, false negative (type II error) and positive results (type I error) could be excluded. The endpoints were morbidity, mortality, infectious complication, postoperative pancreatic fistula (POPF) rates, and length of stay (LOS). RESULTS: The meta-analysis includes 6 RCTs and 477 patients. Morbidity (RR 0.77; 0.26 to 2.25), mortality (RR 0.90; 0.76 to 1.07), and POPF rates were similar. The RISs were 17,316, 7,417, and 464,006, suggesting a type II error. Infectious complications were lower in the IM group, with a RR of 0.54 (0.36-0.79; 95 CI). The LOS was shorter in IM (MD -0.3 days; -0.6 to -0.1). For both, the RISs were reached, excluding type I error. CONCLUSION: The IM can reduce infectious complications and LOS The small differences in mortality, morbidity, and POPF make it impossible to exclude type II error due to large RISs.

Management of acute mesenteric ischaemia: Results of a worldwide survey.

BACKGROUND: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide. METHODS: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected. RESULTS: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity. CONCLUSIONS: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes.

Patients, family members and healthcare professionals' top ten research priorities for adults receiving home parenteral nutrition for malignant or benign disease.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) is the primary treatment for chronic intestinal failure (CIF) due to non-malignant disease and is increasingly used in patients with a diagnosis of cancer. This project engaged with patients, family members and healthcare professionals to ascertain what questions they want researched. METHODS: This study followed the five-stage process of the James Lind Alliance that involved (1) setting up a steering group, (2) carrying out an initial survey to gather participants' questions, (3) data processing, (4) an interim priority setting survey and (5) final priority setting workshop. Surveys were translated and back translated into Italian, Danish and French. RESULTS: The project was delivered by an international steering committee with representation from Denmark, Italy, the United Kingdom and United States consisting of three patients, six healthcare professionals and facilitated by University researchers. For the first survey, 633 questions were submitted by 292 respondents from 12 countries. There were 79 questions removed as out of scope or already in the published literature. Responses were collated into two interim surveys of 41 questions for benign CIF and 13 questions for HPN and cancer. In the second survey, 216 respondents prioritised their top ten questions. The ordering from the cancer and HPN survey was taken as definitive; top priorities were quality of life, survival, when to commence HPN, using HPN with anti-cancer treatments, access barriers, measuring benefit and ethical implications. For CIF with benign disease, 18 questions were discussed in two workshops attended by 13 patients and 7 healthcare professionals. The questions were ranked using a modified nominal group technique; the top research priorities were prevention and treatment of liver disease, improving central infusion lines, oral absorption, avoiding long-term negative consequences, vascular access, side effects, line infections, decreasing stoma output, quality of life and sleep. CONCLUSIONS: Priorities identified will assist researchers to focus on research questions important to patients, family members and healthcare professionals.

Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant.

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.

Effect of malnutrition on postoperative results after pancreatic resection: An entropy balancing analysis.

BACKGROUND & AIMS: Malnutrition is a well-recognized risk factor for major surgery-related complications, but the impact of preoperative nutritional therapy is still debated due to a lack of high-level evidence. The study aims to evaluate the role of preoperative malnutrition in the postoperative course of patients who underwent pancreatic resection. METHODS: This is a retrospective study involving 488 patients who underwent pancreatic resection. An entropy balance was applied to 134 patients at risk for moderate or severe malnutrition (M/S-MAL) to obtain a cohort equal to 354 patients, with the null or low risk of malnutrition (N/L-MAL). The reweighting scheme was made in two steps. In the 1st reweighting, the two cohorts were homogenized for confounding factors not modifiable. In the 2nd reweighting, the two cohorts were matched for modifiable factors by preoperative dietary support. The entropy balance was evaluated with the d-value. The postoperative results were reported as mean differences (MD) or odds ratio (OR) with a confidence interval at 95% (95 CI). RESULTS: The M/S-MAL included patients with lower values of BMI (d < 0.750), hemoglobin (d = 0.671), serum albumin (d = 0.554), total protein (d = 0.381). The M/S-MAL patients were more frequent ECOG 1-2 (d = 0.418), with jaundice (d = 0.445) or back pain (d = 0.366). The pancreaticoduodenectomy (d = 0.440) and vascular resection (d = 0.620) in the M/S-MAL group were performed more frequently. The pancreatic remnant was more often hard (d = 0.527), and the Wirsung duct dilated (d = 0.459) in the N/L-MAL group. The rate of pancreatic ductal adenocarcinoma was higher in M/S-MAL (d = 0.399). After 1st weighting, M/S-MAL patients have a high comprehensive complication index (CCI) (MD = 5.5; 0.3 to 10.7), were more frequently discharged not at home (OR 2.3; 1.1 to 5.4) with a prolonged mean hospital stay (MD 6.1.1; 0.1 to 12.1, days), After 2nd weighting, the two groups have similar postoperative results. CONCLUSION: The correction of malnutrition could play an independent role in reducing the severity of complication, length of stay, and type of discharge in patients who underwent pancreatic resection.

Preoperative carbohydrate loading before elective abdominal surgery: A systematic review and network meta-analysis of phase II/III randomized controlled trials.

BACKGROUND & AIMS: The preoperative use of carbohydrate loading (CHO) is recommended in patients undergoing abdominal surgery, even if the advantages remain debatable. The aim was to evaluate the CHO benefits in patients undergoing abdominal surgery. METHODS: A systematic search of randomized clinical trials was made. A frequentist random-effects network meta-analysis was carried out, reporting the surface under the cumulative ranking (SUCRA). The primary endpoint regarded the morbidity rate. The secondary endpoints were aspiration/regurgitation rates, the length of stay (LOS), the rate of postoperative nausea and vomiting (PONV), the changes (Δ) in insulin sensitivity or resistance, and the postoperative C- reactive protein (CRP) values. RESULTS: CHO loading and water administration had a similar probability of being the approach with a lower morbidity rate (SUCRA = 62.4% and 64.7%). CHO and clear water also had a similar chance of avoiding the PONV (SUCRA of 80.8% and 77%). The aspiration regurgitation rate was not relevant in non-fasting patients (0.06%). CHO administration was associated with the shorter hospitalization (SUCRA 86.9%), with the best metabolic profile (SUCRA values for insulin resistance and sensitivity were 81.1% and 76%). CHO enriched was the best approach for postoperative CRP values. Preoperative fasting was the worst approach for morbidity, PONV, insulin resistance and sensitivity, and CRP (SUCRA values of 32.1%, 21.7%, 10.2%, 3.2%, and 2.0%). CONCLUSION: Both preoperative CHO loading and clear water use were superior to the fasting about morbidity. CHO drinks use could provide specific advantages, reduce the PONV rate, and improve carbohydrate homeostasis, inflammatory pathway, and hospitalization.

Factors affecting antidepressant use by patients requiring home parenteral nutrition.

BACKGROUND: Home parenteral nutrition (HPN) is a life-saving therapy for patients with chronic intestinal failure but can be associated with a degree of psychological distress. The factors associated with the need for antidepressants (ADs) in this cohort have not yet been described. METHODS: The study involved prospective data collection from patients attending an HPN clinic at a national intestinal failure referral center. Patients requiring HPN as a result of active malignancy were excluded. Patients were divided in 2 groups according to AD usage; demographic, anthropometric, socioeconomic characteristics, and intravenous supplementation (IVS) regimens were compared between groups. RESULTS: A total of 184 patients were recruited between July 2018 and April 2019, with an overall prevalence of AD use of 41.7% (70/168 patients). Daily mean IVS volume was significantly higher among patients taking AD ("AD" group; 2125.48 ± 991.8 ml/day, "no-AD" group; 1828.54 ± 847.0 ml/day, P = .039), with the proportion of patients needing high-volume IVS (≥3000 ml/day) being 3 times higher in the AD group (20.0%(14/70 patients) vs 6.1% (6/98 patients), P = .006). The average energy IVS infusion per day was similar between the groups. CONCLUSION: This is the first study to demonstrate that AD use correlates with higher IVS volume rather than energy requirements in HPN patients, suggesting that high IVS volume requirements may be better associated with the patient's disease burden. Early and tailored mental health intervention may be beneficial in those with high IVS volume requirements.

Paraneoplastic vs. non-paraneoplastic anti-Hu associated dysmotility: a case series and literature review.

OBJECTIVES: This work aimed to report the demographic and clinical characteristics of two new cases with non-paraneoplastic anti-Hu-associated gut motility impairment, and perform a thorough revision covering anti-Hu-associated paraneoplastic (PGID) and non-paraneoplastic (nPGID) gastrointestinal dysmotility. BACKGROUND: Several case series have clearly established a relationship between certain type of cancers, the development of circulating anti-Hu antibodies, and the concomitant usually severe gastrointestinal dysmotility; in contrast, a few studies focused on anti-Hu-associated nPGID. METHODS: We searched for studies regarding anti-Hu-associated gastrointestinal manifestations and extracted data concerning clinical characteristics of patients, including specific demographic, oncological, neurological, gastrointestinal, histological, and treatment response features. RESULTS: Forty-nine articles with a total of 59 cases of anti-Hu-associated gastrointestinal dysmotility were analyzed. The patients' age at symptom onset significantly differed between PGID and nPGID (median 61 vs 31 years, p < 0.001). Most cancers (95%) in PGID were detected within 24 months from the beginning of gastrointestinal symptoms. The impairment of gastrointestinal motility was generalized (i.e., involving the whole gut) in 59.3% of patients, with no significant differences between PGID vs nPGID group. nPGID patients showed a better response to immunomodulatory/immunosuppressive treatment and a longer life expectancy. CONCLUSIONS: Anti-Hu-associated gastrointestinal dysmotility covers a wide clinical spectrum. Patients with otherwise unexplained gastrointestinal dysmotility, especially when associated with other neurological symptoms, should be tested for anti-Hu antibodies regardless age of onset and disease duration. Compared to PGID, nPGID occurs in younger patients with a long duration of disease.

The safety of available treatment options for short bowel syndrome and unmet needs.

INTRODUCTION: Short bowel syndrome (SBS) is a rare, highly disabling, life-threatening condition due to extensive intestinal resections, characterized by diarrhea, malabsorption, and malnutrition. SBS is the main cause of intestinal failure (SBS-IF). The primary therapy for SBS-IF is intravenous supplementation (IVS) of nutrients. The pharmacological therapy aims to improve the remnant bowel function, leading to the decrease of IVS requirement. AREAS COVERED: This review provides a safety perspective and discusses unmet clinical needs on pharmacotherapy for SBS, ranging from symptomatic agents traditionally used off-label to manage hypersecretion and diarrhea, to curative drugs with selective intestinotrophic properties. Real-world evidence on symptomatic drugs is lacking. Data on teduglutide - the first-in-class glucagon-like peptide-2 (GLP-2) receptor agonist approved in SBS - are mainly derived from clinical trials, with several unsettled safety issues, including the risk of malignancies. EXPERT OPINION: Defining the long-term safety of drugs used for SBS is a priority; a unified list of commonly used drugs with consolidated proof of effectiveness is needed to harmonize the symptomatic pharmacological approach to SBS. GLP-2 receptor agonists are a promising curative pharmaco-therapeutic approach, although long-term safety and effectiveness deserve further real-world assessment. Pharmacovigilance and global data sharing are crucial to support safe prescribing in SBS.

Choice of access route for artificial nutrition in cancer patients: 30 y of activity in a home palliative care setting.

OBJECTIVES: Malnutrition negatively affects the quality of life, survival, and clinical outcome of patients with cancer. Home artificial nutrition (HAN) is an appropriate nutritional therapy to prevent death from cachexia and to improve quality of life, and it can be integrated into a home palliative care program. The choice to start home enteral nutrition (HEN) or home parenteral nutrition (HPN) is based on patient-specific indications and contraindications. The aim of this observational study was to analyze the changes that occurred in the criteria for choosing the access route to artificial nutrition during 30 y of activity of a nutritional service team (NST) in a palliative home care setting, as well as to compare indications, clinical nutritional outcomes, and complications between HEN and HPN. METHODS: The following parameters were analyzed and compared for HEN and HPN: tumor site and metastases; nutritional status (body mass index, weight loss in the past 6 mo); basal energy expenditure and oral food intake; Karnofsky performance status; access routes to HEN (feeding tubes) and HPN (central venous catheters); water and protein-calorie support; and survival and complications of HAN. RESULTS: From 1990 to 2020, HAN was started in 1014 patients with cancer (592 men, 422 women; 65.6 ± 12.7 y of age); HPN was started in 666 patients (66%); and HEN was started in 348 patients (34%). At the end of the study, 921 patients had died, 77 had suspended HAN for oral refeeding and 16 were in the progress of HAN. The oral caloric intake was <50% basal energy expenditure in all patients: 721 (71.1%) were unable to eat at all (HEN 270, HPN 451), whereas in 293 patients (28.9%), artificial nutrition was supplementary to oral intake. From 2010 to 2020, the number of central venous catheters for HPN, especially peripherally inserted central catheters, doubled compared with that in the previous 20 y, with a decrease of 71.6% in feeding tubes for HEN. At the beginning, patients on HEN and HPN had comparable nutrition and performance status, and there was no difference in nutritional outcome after 1 mo of HAN. In 215 patients who started supplemental parenteral nutrition to oral feeding, total protein-calorie intake allowed a significant increase in body mass index and Karnofsky performance status. The duration of HEN was longer than that of HPN but was similar to that of supplemental parenteral nutrition. CONCLUSIONS: Over 30 y of nutritional service team activity, the choice of central venous catheters as an access route to HAN increased progressively and significantly due to personalized patient decision-making choices. Nutritional efficacy was comparable between HEN and HPN. In patients who maintained food oral intake, supplemental parenteral nutrition improved weight, performance status, and survival better than other types of HAN.

Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by thymidine phosphorylase (TP) enzyme defect. As gastrointestinal changes do not revert in patients undergone TP replacement therapy, one can postulate that other unexplored mechanisms contribute to MNGIE pathophysiology. Hence, we focused on the local TP angiogenic potential that has never been considered in MNGIE. In this study, we investigated the enteric submucosal microvasculature and the effect of hypoxia on fibrosis and enteric neurons density in jejunal full-thickness biopsies collected from patients with MNGIE. Orcein staining was used to count blood vessels based on their size. Fibrosis was assessed using the Sirius Red and Fast Green method. Hypoxia and neoangiogenesis were determined via hypoxia-inducible-factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) protein expression, respectively. Neuron-specific enolase was used to label enteric neurons. Compared with controls, patients with MNGIE showed a decreased area of vascular tissue, but a twofold increase of submucosal vessels/mm2 with increased small size and decreased medium and large size vessels. VEGF positive vessels, fibrosis index, and HIF-1α protein expression were increased, whereas there was a diminished thickness of the longitudinal muscle layer with an increased interganglionic distance and reduced number of myenteric neurons. We demonstrated the occurrence of an angiopathy in the GI tract of patients with MNGIE. Neoangiogenetic changes, as detected by the abundance of small size vessels in the jejunal submucosa, along with hypoxia provide a morphological basis to explain neuromuscular alterations, vasculature breakdown, and ischemic abnormalities in MNGIE.NEW & NOTEWORTHY Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is characterized by a genetically driven defect of thymidine phosphorylase, a multitask enzyme playing a role also in angiogenesis. Indeed, major gastrointestinal bleedings are life-threatening complications of MNGIE. Thus, we focused on jejunal submucosal vasculature and showed intestinal microangiopathy as a novel feature occurring in this disease. Notably, vascular changes were associated with neuromuscular abnormalities, which may explain gut dysfunction and help to develop future therapeutic approaches in MNGIE.

Candidacy of adult patients with short bowel syndrome for treatment with glucagon-like peptide-2 analogues: A systematic analysis of a single centre cohort.

BACKGROUND AND AIMS: The glucagon-like peptide-2 (GLP-2) analogue, teduglutide, allows to reduce the intravenous supplementation (IVS) dependency of patients with short bowel syndrome and intestinal failure (SBS-IF). The rate of candidacy of SBS-IF patients for the treatment is unknown. The candidacy for teduglutide treatment of our patient cohort was investigated by a systematic analysis. METHODS: The indications, contraindications, special warnings and precautions for use of teduglutide, listed in the drug monographs and in the phase-III trial protocol were adopted to categorize the patients as non-candidates (NC), potential candidates (PC) or straight candidates (SC) for the treatment. All the SBS-IF adult patients who were cured at our centre were assessed according to their clinical status on January 1st, 2020. RESULTS: Seventy-nine patients were evaluated: 34.2% were NC due to risk of digestive malignancy, recent history of any other cancer, or listing for intestinal transplantation; 30.4% were PC, because of other premalignant conditions, risk of intestinal obstruction, entero-cutaneous fistulas, or severe co-morbidities; 35.4% were SC. The SC group showed the lowest requirement of IVS: the lowest number of days of infusion per week (p = 0.0054), the lowest amount of energy (p = 0.0110) and volume (p = 0.0136). CONCLUSIONS: This systematic analysis allowed a pragmatic categorization of the candidacy of patients with SBS-IF for GLP-2 analogue treatment. The SC group appeared to have the highest probability of a successful response to the treatment. A systematic analysis of SBS-IF patient candidate for GLP-2 analogue therapy would allow a homogeneous patient selection and facilitate the worldwide comparison of the results of clinical practice and research.

A Call to Action: Now Is the Time to Screen Elderly and Treat Osteosarcopenia, a Position Paper of the Italian College of Academic Nutritionists MED/49 (ICAN-49).

Aging is a risk factor for the development of multiple chronic diseases, including cardiovascular disease, cancer and dementia. Life expectancy has increased in certain countries but this phenomenon is associated with a reduction of years of healthy life. Aging is associated with a number of physical and functional changes, especially sarcopenia. Sarcopenia is a clinical condition associated with a decrease in skeletal muscle and muscle strength, however, sarcopenia is a reversible condition. On the basis of the current scientific literature, sarcopenia could more appropriately capture an individual's vulnerability to negative health-related outcomes since it represents an early form of the chronic diseases. Recognition of this clinical condition can improve the management of older individuals in many different clinical settings. Despite the limitations of the indirect methods used to study body composition, the Italian College of the Academic Nutritionists ME/49 recommends that health authorities and health professionals around the world should make a greater effort to diagnose sarcopenia earlier and to manage it more effectively. In line with the development of cancer screening, the use of two diagnostic tools for sarcopenia (BIA and DXA) should be implemented.

Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications.

We report the longest follow-up of clinical and biochemical features of two previously reported adult mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients treated with liver transplantation (LT), adding information on a third, recently transplanted, patient. All three patients overcame the early post-operative period and tolerated immunosuppressive therapy. Plasma nucleoside levels dramatically decreased, with evidence of clinical improvement of ambulation and neuropathy. Conversely, other features of MNGIE, as gastrointestinal dysmotility, low weight, ophthalmoparesis, and leukoencephalopathy were essentially unchanged. A similar picture characterized two patients treated with allogenic hematopoietic stem cell transplantation (AHSCT). In conclusion, LT promptly and stably normalizes nucleoside imbalance in MNGIE, stabilizing or improving some clinical parameters with marginal periprocedural mortality rate as compared to AHSCT. Nevertheless, restoring thymidine phosphorylase (TP) activity, achieved by both LT and AHSCT, does not allow a full clinical recovery, probably due to consolidated cellular damage and/or incomplete enzymatic tissue replacement.

Teduglutide for the treatment of adults with intestinal failure associated with short bowel syndrome: pooled safety data from four clinical trials.

BACKGROUND: In multiple clinical studies, teduglutide reduced parenteral support (PS) with a consistent safety profile in adults with short bowel syndrome-associated intestinal failure (SBS-IF). The objective of this study was to assess adverse events (AEs) from a pooled data set. METHODS: Safety data from four prospective clinical trials of teduglutide in patients with SBS-IF were assimilated. AEs were evaluated in patient groups based on treatment received in each study and in populations stratified to create distinct subgroups based on aetiology, bowel anatomy and baseline PS volume requirements. RESULTS: Safety data are reported for up to 2.5 years, totalling 222 person-years exposure to teduglutide. In most patients, AEs were reported as mild or moderate in severity in all patient groups and occurred at comparable rates between patients who received teduglutide or placebo. Several common gastrointestinal AEs, including abdominal pain, nausea and abdominal distension, were reported more frequently earlier in the course of treatment, with their frequency declining over time. Fewer gastrointestinal AEs were reported in patients with vascular causes of SBS-IF and patients with most of their colon-in-continuity than in other patient subgroups. Across the patient stratification subgroups, the predominant treatment-emergent AEs for which patients receiving teduglutide had a significantly increased relative risk were abdominal distension and gastrointestinal stoma complication compared with patients receiving placebo. CONCLUSIONS: Teduglutide had a safety profile consistent with prior adult data and no new safety concerns were identified. The most frequently reported AEs were gastrointestinal in origin, consistent with the underlying disease condition and intestinotrophic actions of teduglutide. CLINICAL TRIAL REGISTRY INFORMATION: NCT00081458/EudraCT, 2004-000438-35; NCT00798967/EudraCT, 2008-006193-15; NCT00172185/EudraCT, 2004-000439-27; NCT00930644/EudraCT, 2009-011679-65.

Home artificial nutrition in palliative care cancer patients: Impact on survival and performance status.

BACKGROUND AND AIMS: The prevalence of malnutrition is over 70% in advanced cancer patients and impacts negatively on survival and quality of life. Artificial nutrition can be integrated into a home palliative care program. This observational study aims to describe the criteria for identifying the cancer patients that could benefit from home artificial nutrition (HAN) and to evaluate its impact on survival and performance status. METHODS: The selection criteria for patient's eligibility to HAN were: Karnofsky Performance Status (KPS) ≥40, life expectancy ≥6 weeks, inadequate caloric intake ± malnutrition, suitable psycho-physical conditions and informed consent. The access route for nutritional therapy (home parenteral nutrition, HPN; home enteral nutrition, HEN) was chosen according to the ESPEN Guidelines. The parameters considered were: primary site of the tumor; oral food intake; nutritional status; stage of cachexia; fluid, energy and protein supplied by HAN; survival. RESULTS: From 1990 to 2019, 43,474 cancer patients were assisted at home in Bologna (Italy). HAN started in 969 patients (2.2% of total patients, 571 men and 398 women, mean age 65.7 ± 12.7 years): HPN in 629 patients (64.9%), with gastrointestinal obstruction as the main indication; HEN in 340 patients (35.1%), with dysphagia as the main indication. Considering the 890 deceased patients, the mean survival after the start of HAN was 18.3 weeks and 649 patients (72.9%) survived more than 6 weeks. The mean survival was higher in HEN (22.1 weeks) compared to HPN patients (16.1 weeks) (p < .001). After one month, KPS was unchanged in 649 (67.0%), increased in 232 (23.9%) and decreased in 88 patients (9.1%). The mean KPS increased in patients starting HAN in pre-cachexia and cachexia (p < .001). Cachexia and refractory cachexia at the entry were associated with a reduced survival [odds ratio: 1.5 and 2.3 respectively, p < .001 for both condition] respect to pre-cachexia. CONCLUSIONS: The selection criteria allow the identification of the patient who can take advantage of HAN. HAN can be effective in avoiding death from malnutrition in 73% of patients, and in maintaining or improving the KPS at one month in 90% of cases. The benefits provided by HAN on survival and performance status depend on the cachexia degree at the entry.