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Competing Interests: The authors have no conflict of interest or financial disclosures to declare., (© 2023 Aerzteverlag medinfo AG.)

Introduction: Functional constipation is one of the common disorders of gut-brain interaction in infancy, and decreases the quality of life of infants and parents., Areas Covered: Relevant articles up to November 2022 were reviewed. We searched in PubMed, Google Scholar, and MEDLINE for guidelines, position papers, reviews, and randomized controlled trials on infant constipation., Expert Opinion: Randomized controlled trials in this specific age group are mostly limited to trials with infant formula. The prevalence of infant constipation in formula-fed infants is decreasing, and can be associated with adaptations in formula composition. While the supplementation of infant formula with pro-, pre- and/or synbiotics decreases the prevalence of constipation, their efficacy in constipated infants is disappointing. There is limited evidence to support the addition of magnesium to infant formula to treat constipation. The evidence for the efficacy and safety of polyethylene glycol in children < 2 years has expanded over the past years. The administration of lactulose or polyethylene glycol is the preferred medical management, in case nutritional management does result in insufficient improvement.

Objectives: The determinants of refractory ascites have not been fully characterized. The aims of this study were to assess liver histopathological alterations associated with refractory ascites and their relationship with comorbidities., Methods: Consecutive patients with cirrhosis who underwent liver transplantation were retrospectively included. Patients' characteristics at the time of listing were analysed. The native livers were reviewed and lesions associated with refractory ascites were examined., Results: Out of the 89 patients included, 30 had refractory ascites and 59 did not (including 35 without ascites and 24 with diuretic-sensitive ascites). Patients with and without refractory ascites had a similar amount of fibrous tissue and features of fatty liver disease. By contrast, microvascular changes, namely sinusoidal dilatation (P < 0.001), diffuse perisinusoidal fibrosis (P = 0.001), hepatic venous thromboses (P = 0.004) and vascular proliferation (P = 0.01) were more frequently observed in the livers of patients with refractory ascites. Diabetes (57% vs. 31%, P = 0.02) and alcohol as a causal factor for cirrhosis (80% vs. 42%, P = 0.001) were more frequent in patients with refractory ascites than in those without. By multivariate analysis, refractory ascites was independently associated with diabetes mellitus [odds ratio (OR) (95% confidence interval, CI) 6.15 (1.47-25.71); P = 0.01], alcohol as a causal factor for cirrhosis [OR (95% CI) 4.63 (1.07-20.02); P = 0.04], higher Model For End Stage Liver Diseases [OR (95% CI) 1.21 (1.05-1.38); P = 0.008] and lower serum sodium [OR (95% CI) 0.87 (0.78-0.98); P = 0.03]., Conclusion: Liver microcirculatory changes are associated with refractory ascites. Diabetes and alcohol may explain refractory ascites by causing microangiopathy., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The current epidemic of SARS-CoV-2 infection poses new challenges in the management of patients with gastrointestinal or liver disease. Consultations with patients with chronic diseases should ideally be done via telemedicine and treatments administered at home if possible. The latter should be maintained in non-infected subjects to limit the risk of decompensation of their underlying disease. In the event of proven infection, immunomodulatory or biological treatments will tend to be reduced or discontinued unless the disease is in a severely active phase. Elective endoscopy should be postponed, and urgent procedures should be performed with appropriate personal protective equipment., Competing Interests: Les auteurs n’ont declare aucun conflit d’interets en relation avec cet article.

Purpose: To describe gastrointestinal emergencies in cancer patients., Methods: All cancer patients admitted to the medical ICU of Saint-Louis Hospital for an acute abdominal syndrome during the study period (1997-2011) were included., Results: A total of 164 patients were included. The most common diagnoses were: neutropenic enterocolitis (NE) (n=54, 33%), infectious colitis and peritonitis (n=51, 31%), bowel infiltration by malignancy (n=14, 9%), and mucosal toxicity of chemotherapy (n=12, 7%). Microbiologically documented infections were reported in 82 patients (50%), including 12 fungal infections. Twenty-seven patients (16%) underwent urgent surgery. The hospital mortality rate was 35%. Five factors were independently associated with hospital mortality: the Simplified Acute Physiology Score II (SAPS II) score on day 1 (OR 1.03/SAPS II point, 95% CI 1.01 to 1.05), microbiological documentation (OR 0.27, 95% CI 0.11 to 0.64), neutropenia (OR 0.42, 95% CI 0.19 to 0.95), allogenic hematopoietic stem-cell transplantation (HSCT) (OR 5.13, 95% CI 1.71 to 15.4), and mechanical ventilation (OR 3.42, 95% CI 1.37 to 8.51)., Conclusions: Gastrointestinal emergencies in cancer patients are associated with significant mortality. Mortality correlated both with the severity of organ failure upon ICU admission and the underlying diagnosis. Interestingly, patients admitted to the ICU with neutropenia had better survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background & Aims: Waiting-list mortality in patients with cirrhosis and a relatively low MELD score is a matter of concern. The aim of this study was to determine whether a marker of muscle waste could improve prognostication., Methods: A pre-MELD cohort (waiting time-based allocation; n=186) and a MELD-era cohort (n=376) were examined. At evaluation, transversal psoas muscle thickness (TPMT) was measured on a computed tomography (CT) image at the level of the umbilicus. In the pre-MELD cohort, TPMT/height (mm/m) and the MELD score were entered in univariate and multivariate models to predict mortality after registration. Applicability of pre-MELD findings was tested in the MELD-era., Results: In the pre-MELD cohort, the MELD score and TPMT/height were significantly associated with mortality. The discrimination of a score combining MELD and TPMT/height (MELD-psoas) was 0.84 (95% CI, 0.62-0.95). In the MELD-era, TPTM/height was significantly associated with mortality, independent of the MELD and MELD-Na scores. There was a 15% increase in mortality risk per unit decrease in TPMT/height. The discrimination of MELD-psoas score (0.82; 95% CI, 0.64-0.93) was superior to that of the MELD score and similar to that of the MELD-Na score. In patients with refractory ascites, mortality was significantly higher when TPMT/height was <16.8 mm/m (42% vs. 9%, p=0.02)., Conclusions: TPMP/height on CT at the level of the umbilicus, an objective marker of muscle waste, may be predictive of mortality in cirrhotic patients, independent of the MELD and MELD-Na scores. It may help to better assess the prognosis of patients with refractory ascites., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: To correlate human herpesvirus 6 (HHV-6) viral load with pathologic features in graft acute hepatitis of unknown origin., Methods: Liver frozen samples from 26 patients with graft hepatitis of unknown origin were available for HHV-6 DNA quantification., Results: In 10 (38.5%) of 26 liver samples, HHV-6 DNA was detectable, with a median viral load of 3.84 log10 copies/10⁶ cells. Confluent periportal necrosis was observed in 4 of 10 patients and associated with high viral load. These 4 patients responded to antiviral therapy. Mild unspecific hepatitis was observed in 4 patients with low intragraft viral load and in 2 patients with high viral load in a context of deep immunosuppression. Patients with HHV-6-negative graft hepatitis disclosed lobular necrotico-inflammatory activity without periportal necrosis., Conclusions: Our study provides data supporting the pathogenic role of HHV-6 for liver allografts. The presence of confluent periportal necrosis could be a clue for prompt diagnosis of HHV-6-induced graft hepatitis.

Objective: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition associated with multiple organ dysfunction. We sought to describe ICU management and outcomes in HLH patients meeting HLH-2004 criteria and to identify determinants of mortality., Design: Retrospective study between January 1998 and January 2009., Setting: Medical ICU of a teaching hospital., Patients: Among the 72 patients fulfilling the HLH-2004 criteria, we report the 56 patients with complete follow-up and no missing data., Interventions: None., Measurements and Main Results: Clinical and laboratory data were abstracted from the medical records. Median SOFA score at admission was 6.5 (IQR, 4-8). At ICU admission, the number of HLH-2004 criteria was 6 (5-7). Sixty-six precipitating factors were found in 52 patients and consisted of 43 tumoral causes (8 Castleman's diseases, 18 B cell lymphoma and 17 various malignancies), 13 non-viral infections and 10 viral infections. Underlying immune deficiency was present in 38 (67.8%) patients. Etoposide was used in 45 patients, corticosteroids in 31 and intravenous immunoglobulins in 3. Mechanical ventilation was required in 32 patients, vasoactive agents in 30 and renal replacement therapy in 19. Hospital mortality was 29/56 patients. By multivariate analysis, factors associated with increased hospital death were shock at ICU admission [OR, 4.33; 95% confidence interval (95% CI), 1.11-16.90; P = 0.03] and platelet count <30 g/l (OR, 4.75; 95% CI, 1.20-18.81; P = 0.02). B cell lymphoma [odds ratio (OR), 0.17; 95% CI, 0.04-0.80; P = 0.02] and Castleman's disease (OR, 0.11; 95% CI, 0.02-0.90; P = 0.04) were associated with increased hospital survival., Conclusions: Aggressive supportive care combined with specific treatment of the precipitating factor can produce meaningful survival in patients with HLH responsible for multiple organ failures. Survival is highest in patients with HLH related to Castleman's disease or B cell lymphoma.

Background: Cutaneous involvement has been reported in 30-40% of children with the familial form of haemophagocytic syndrome. However, few studies have focused on cutaneous manifestations in patients with reactive haemophagocytic syndrome (RHS)., Objectives: To describe the frequency, clinical features and prognosis of skin involvement in adult patients with RHS., Methods: We conducted a retrospective study in a French university-based tertiary centre. The medical records of all adult patients with a suspected or confirmed diagnosis of RHS during a 2-year period were reviewed. Demographic, clinical, biological and histological data of patients were compared using nonparametric tests., Results: The medical charts of 151 patients were reviewed, 69 of whom had a definite diagnosis of RHS (35% women; mean +/- SD age 49 +/- 17 years). The aetiology of RHS was mainly B-cell or T-cell lymphoma (n = 33) or herpesvirus infection (n = 19). Cutaneous manifestations were observed in 32 (46%) patients and were of three types: (i) specific to the underlying malignancy (Kaposi sarcoma n = 8, cutaneous lymphoma n = 4), (ii) reflecting the biological consequences of RHS (thrombopenic purpura n = 10, conjunctival jaundice n = 7), and (iii) a generalized, transient, nonpruriginous maculopapular rash (n = 18). None presented with erythroderma, or with eczematiform, ichthyosiform, psoriasiform or bullous lesions. One patient had cytophagic histiocytic panniculitis. Histological features of maculopapular rash biopsies were usually nonspecific. The rate of in-hospital death was not significantly associated with cutaneous involvement., Conclusions: A generalized, nonpruriginous, transient, maculopapular rash is frequently observed in patients with RHS. Although nonspecific, awareness of this cutaneous involvement may assist physicians in the initial diagnosis of RHS.

IL-15 drives chronic inflammation in several human diseases. We have recently shown that IL-15 inhibits the immunosuppressive effects of TGF-beta through blockage of the Smad3-signaling pathway. Data pointing to reciprocal interactions between TGF-beta and CD4(+) regulatory T cells led us to investigate the impact of IL-15 on the de novo generation and function of regulatory T cells in humans. Our data indicate that IL-15 does not counteract, but rather promotes the effect of TGF-beta on the de novo generation of regulatory T cells (Treg). Thus, in the presence of TGF-beta, IL-15 enhanced the acquisition of regulatory functions by CD4(+)CD25(-) T cells stimulated by anti-CD3 and anti-CD28 Abs. In contrast, IL-15 impaired the functions of Tregs by acting on effector CD4 and CD8 T cells. Accordingly, in the presence of IL-15, proliferation and IFN-gamma production by peripheral CD4 and CD8 T cells could not be efficiently inhibited by Tregs. IL-15-induced resistance of effector T cells to Tregs resulted from activation of the PI3K signaling pathway but did not involve the rescue of effector T cells from apoptosis. Altogether, these data point to the ambiguous role of IL-15 in the control of Treg functions. This dual role may be instrumental to mount rapid but transient proinflammatory immune responses against pathogens but may become deleterious in situations associated with protracted IL-15 over-expression.

Objective: This review aims to help critical care clinicians maintain a high level of suspicion regarding the diagnosis of Hemophagocytic Histiolymphocytosis (HLH). It describes the clinical and laboratory features of HLH, outlines its pathophysiology and reviews the most frequent etiologies related to HLH. Prognostic factors and therapeutic options are also reported., Data Sources: Review of the literature., Results: The diagnosis of HLH relies on the association of clinical abnormalities and hemophagocytosis in bone marrow, spleen, or lymph node specimens. Liver, pulmonary, renal, cardiac and skin involvement may occur at various degrees possibly leading to multiple organ failure. Three main etiologies can be found, namely infections, lymphoproliferative diseases, or connective tissue diseases. Immune deficiency is often retrieved. Mortality can be as high as 50%. Although clinically mimicking severe sepsis, HLH has a distinct pathophysiology on which specific therapy is based. Early diagnosis and treatment is mandatory to increase the chances of survival., Conclusion: The comprehensive management of severe HLH requires the involvement of a multidisciplinary team in order to determine the best therapeutic strategy and to identify the underlying cause.

The liver plays a key role in the metabolism of nutrients. Therefore, liver failure is often associated with malnutrition. It is well-established that malnutrition is an independent prognostic factor in patients with cirrhosis and liver failure. Since standard anthropometric and biological indexes are associated with liver dysfunction, nutritional assessment is difficult in patients with cirrhosis. In this review, we explain the various causes and mechanisms leading to malnutrition in cirrhosis. We also describe reliable methods used to assess the nutritional condition of these patients. Finally, we stress the importance of nutritional care in cirrhosis and liver dysfunction, describing its specific characteristics and indications.

The liver plays a key-role in carbohydrates metabolism. Glucose intole-rance, overt diabetes mellitus and insulin resistance are characteristic features of patients with cirrhosis. Central hyperinsulinemia and peripheral insulin-resistance are the main explanations for the high prevalence of diabetes in patients with cirrhosis. On the other hand, type 2 diabetes is associated with a wide spectrum of liver diseases ranging from nonalcoholic fatty liver to cirrhosis and hepatocellular carcinoma. Carbohydrate metabolism abnormalities are a major aggravating risk factor in cirrhosis. Diabetes is also an independent negative prognostic factor in cirrhotic patients. This leads to specific diagnostic procedures and therapeutic issues. Patients with diabetes and liver disease frequently need insulin treatment. The presence of liver disease makes the treatment of diabetes complex, and additional research is needed to determine the best treatment strategies in these patients.

Drug-induced hepatotoxicity is an important cause of hepatocellular injury. Non-nucleoside retroviral transcriptase inhibitors are known to cause hepatotoxicity. We describe a detailed case of fulminant hepatitis induced by nevirapine (Viramune) and treated by liver transplantation.

We report the case of an 18-year-old man, with no previous medical history, presenting with recurrent hemorrhagic duodenal ulcers revealing a Zollinger-Ellison syndrome. The initial diagnosis of sporadic gastrinoma of the antrum associated with satellite lymph nodes led to surgical treatment. The evolution of clinical and secretory tests associated with the outbreak of a primary hyperparathyroïdism demonstrated that the patient had a type I multiple endocrine neoplasia. To our knowledge, this is the first described case of primitive gastrinoma of the antrum occurring in a type I multiple endocrine neoplasia.

A 56-year-old patient with a non-parasitic hepatic cyst developed acute dyspnoea. Pulmonary embolism was diagnosed. Bleeding into the hepatic cyst, leading to its enlargement and compression of the inferior vena cava, was the only likely cause of the pulmonary embolism. This complication of a non-parasitic liver cyst has not been reported previously. The patient was treated with heparin. Surgical evacuation of the cyst using the 'fenestration' technique was also performed. There was no recurrent pulmonary embolism or hepatic cyst during a 1-year follow-up period.