Advantages of high cell concentration prior to cryopreservation of initial leukapheresis in CAR-T cell therapy.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is increasingly used in patients affected by B-cell lymphoma and acute lymphoblastic leukemia. For logistical reasons, initial apheresis products may be cryopreserved for shipment to manufacturing centers. Due to the characteristics of these patients, cells are often collected in large volumes, meaning more bags must be cryopreserved. This requires increased storage, time and monetary costs. In this context, we aimed to evaluate a high cell concentration cryopreservation protocol by centrifugation to standardize the initial CAR-T manufacturing procedure. MATERIALS AND METHODS: Sixty-eight processes of leukapheresis of 57 patients affected by refractory/relapsed B cell lymphoma and 9 patients affected by acute lymphoblastic leukemia who were eligible for anti-CD19 CAR-T cell treatment performed between June 2019 and October 2022 were analyzed. Whole blood count, percentage and number of T cells were assessed on the apheresis final product. The apheresis product, which was alternatively stored overnight at 4°C, was centrifuged, adjusting the volume to approximately 40 mL. The product was immediately cryopreserved to achieve a final cell concentration of 50-200×106 cells/ml for cryopreservation. RESULTS: Leukapheresis volume was reduced by almost fivefold (median: 185 to 40 mL), resulting in a higher product concentration in one bag. In addition, the number of non-target cells (monocytes, platelets and erythrocytes) was also reduced during the development of CAR T cell therapy, thereby maintaining T lymphocyte levels and providing a purer starting material. DISCUSSION: The advantages of the protocol include reducing economic costs, saving storage space, simplifying the manufacturing process, and facilitating shipping logistics. In conclusion, we present a validated, simple, and cost-effective cell enrichment processing protocol that provides high-quality cryopreserved products as starting material for the CAR-T cell manufacturing process.

Processing, Characterization and Disintegration Properties of Biopolymers Based on Mater-Bi® and Ellagic Acid/Chitosan Coating.

Among the most promising synthetic biopolymers to replace conventional plastics in numerous applications is MaterBi® (MB), a commercial biodegradable polymer based on modified starch and synthetic polymers. Actually, MB has important commercial applications as it shows interesting mechanical properties, thermal stability, processability and biodegradability. On the other hand, research has also focused on the incorporation of natural, efficient and low-cost active compounds into various materials with the aim of incorporating antimicrobial and/or antioxidant capacities into matrix polymers to extend the shelf life of foods. Among these is ellagic acid (EA), a polyphenolic compound abundant in some fruits, nuts and seeds, but also in agroforestry and industrial residues, which seems to be a promising biomolecule with interesting biological activities, including antioxidant activity, antibacterial activity and UV-barrier properties. The objective of this research is to develop a film based on commercial biopolymer Mater-Bi® (MB) EF51L, incorporating active coating from chitosan with a natural active compound (EA) at two concentrations (2.5 and 5 wt.%). The formulations obtained complete characterization and were carried out in order to evaluate whether the incorporation of the coating significantly affects thermal, mechanical, structural, water-vapor barrier and disintegration properties. From the results, FTIR analysis yielded identification, through characteristic peaks, that the type of MB used is constituted by three polymers, namely PLA, TPS and PBAT. With respect to the mechanical properties, the values of tensile modulus and tensile strength of the MB-CHI film were between 15 and 23% lower than the values obtained for the MB film. The addition of 2.5 wt.% EA to the CHI layer did not generate changes in the mechanical properties of the system, whereas a 5 wt.% increase in ellagic acid improved the mechanical properties of the CHI film through the addition of natural phenolic compounds at high concentrations. Finally, the disintegration process was mainly affected by the PBAT biopolymer, causing the material to not disintegrate within the times indicated by ISO 20200.

Safety and Glycemic Outcomes With a Tubeless Automated Insulin Delivery System in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Clinical Trial.

OBJECTIVE: Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population. RESEARCH DESIGN AND METHODS: A total of 80 children aged 2.0-5.9 years used the investigational system in a single-arm study for 13 weeks following 14 days of baseline data collection with their usual therapy. RESULTS: There were no episodes of severe hypoglycemia or diabetic ketoacidosis. By study end, HbA1c decreased by 0.55% (6.0 mmol/mol) (P < 0.0001). Time with sensor glucose levels in target range 70-180 mg/dL increased by 10.9%, or 2.6 h/day (P < 0.0001), while time with levels <70 mg/dL declined by median 0.27% (P = 0.0204). CONCLUSIONS: Use of the automated insulin delivery system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline.

Specific Abnormalities in White Matter Pathways as Interface to Small Vessels Disease and Cognition in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Individuals.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by leukoencephalopathy leading to cognitive impairment. Subtle cognitive deficits can be observed early in the course of the disease, before the occurrence of the first stroke. Therefore, markers that can predict disease progression at this early stage, when interventions are likely to alter disease course, are needed. We aimed to examine the biological cascade of microstructural and macrostructural white matter (WM) abnormalities underlying cognitive deficits in CADASIL. Methods: We examined 20 nondemented CADASIL mutation carriers and 23 noncarriers who underwent neuropsychological evaluation and magnetic resonance imaging. Using probabilistic tractography of key WM tracts, we examined group differences in diffusivity measures and WM hyperintensity volume. Successive mediation models examined whether tract-specific WM abnormalities mediated subtle cognitive differences between CADASIL mutation carriers and noncarriers. Results: The largest effect size differentiating the two groups was observed for left superior longitudinal fasciculus-temporal (SLFt) diffusivity (Cohen's f = 0.49). No group differences were observed with a global diffusion measure. These specific microstructural differences in the SLFt were associated with higher WM hyperintensities burden, and subtle executive deficits in CADASIL mutation carriers. Discussion: Worse diffusivity in the left SLFt is related to greater severity of small vessel disease and worse executive functioning in the asymptomatic stage of the disease. Worse diffusivity of the left SLFt may potentially hold promise as an indicator of disease progression. Impact statement Diffusion tensor imaging outperforms conventional imaging of subcortical small vessel disease as a potential marker of future disease progression. Here we identified the left superior longitudinal temporal fasciculus as a critical white matter fiber bundle, of which worse diffusivity can link presence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy mutations to greater severity of small vessel disease and worse executive functioning in asymptomatic stages of the disease. This tract may hold promise and deserves further examination as an early indicator of disease progression.

Obtaining Active Polylactide (PLA) and Polyhydroxybutyrate (PHB) Blends Based Bionanocomposites Modified with Graphene Oxide and Supercritical Carbon Dioxide (scCO2)-Assisted Cinnamaldehyde: Effect on Thermal-Mechanical, Disintegration and Mass Transport Properties.

Bionanocomposites based on Polylactide (PLA) and Polyhydroxybutyrate (PHB) blends were successfully obtained through a combined extrusion and impregnation process using supercritical CO2 (scCO2). Graphene oxide (GO) and cinnamaldehyde (Ci) were incorporated into the blends as nano-reinforcement and an active compound, respectively, separately, and simultaneously. From the results, cinnamaldehyde quantification values varied between 5.7% and 6.1% (w/w). When GO and Ci were incorporated, elongation percentage increased up to 16%, and, therefore, the mechanical properties were improved, with respect to neat PLA. The results indicated that the Ci diffusion through the blends and bionanocomposites was influenced by the nano-reinforcing incorporation. The disintegration capacity of the developed materials decreased with the incorporation of GO and PHB, up to 14 and 23 days of testing, respectively, without compromising the biodegradability characteristics of the final material.

Effect of supercritical incorporation of cinnamaldehyde on physical-chemical properties, disintegration and toxicity studies of PLA/lignin nanocomposites.

Poly (lactic acid)/lignin nanocomposites (PLA/Lig-Np) containing cinnamaldehyde (Ci) were obtained by a combination of melt extrusion and supercritical impregnation process. In this work, Ci impregnation tests were carried out in a high-pressure cell at 40 °C for 3 h using 12 MPa and 1 MPa min-1 of depressurization rate, obtaining impregnation yields ranging from 5.7 to 10.8% w/w. Thermal, mechanical and colorimetric properties of the developed films were affected by the incorporation of lignin nanoparticles and the active compound, obtaining biodegradable plastic materials with a strong UV-light barrier property compared to PLA films. In addition, disintegrability tests under composting conditions confirmed the biodegradable character of nanocomposites developed. On day 23, a disintegration percentage greater than 90% was determined for all bionanocomposites. Finally, to establish the possible toxicity effect of the nanocomposites obtained, studies in vivo were performed in normal rats. Toxicity studies showed normal blood parameters after a single dose of nanocomposites. PLA/Ci/Lig-Np bionanocomposite films could be potentially applied to design biodegradable UV-light barrier materials for food packaging and biomedical applications.

Sickle cell trait: a cause of abdominal pain and pulmonary embolism.

INTRODUCTION: Sickle cell trait (SCT) is a rare and underdiagnosed disorder in the Argentinian population. In this condition, individuals carry the mutation of the HbS gene in one of the two beta-globin genes. In general, SCT does not present with the typical manifestations of sickle cell anemia. However, under certain circumstances, some clinical characteristics of the disease may develop. METHODS: We discussed the case of a 39-Year old man who presented with persistent abdominal pain of unknown origin after traveling to a high-altitude place. He underwent laparotomy without a definite diagnosis. After that, the patient developed signs of splenic infarction and pulmonary thromboembolism that were confirmed by computed tomography. RESULTS: A sickling test was positive, and a hemoglobin electrophoresis revealed an abnormal fraction at the HbS level. In this context a diagnosis of SCT was made. Additional, tests revealed a strongly positive lupus anticoagulant. CONCLUSION: SCT presentation as abdominal pain and thromboembolic disease in adult patients after exposure to high altitudes is a rarely suspected diagnosis.

Clinical course and risk factors for mortality from COVID-19 in patients with haematological malignancies.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) in haematological patients (HP) has not been comprehensively reported. METHODS: We analysed 39 patients with SARS-CoV-2 infection and haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non-cancer patients with COVID-19. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome. RESULTS: The most frequent haematological diseases were lymphoma (30%) and multiple myeloma (30%). Eighty-seven % HP developed moderate or severe disease. Patients with haematological malignancies had a significantly higher mortality rate compared to non-cancer patients (35.9% vs 13.2%; P = .003 (odds ratio 6.652). The worst outcome was observed in chronic lymphocytic leukaemia patients. Only age >70 years and C reactive protein >10 mg/dl at admission were associated with higher risk of death (odds ratio 34.86, P = .003 and 13.56,P = .03). Persistent viral sheddind was detected in 5 HP. Active chemotherapy, viral load at diagnosis and COVID-19 therapy were not predictors of outcome. CONCLUSION: Mortality of COVID-19 is significantly higher in patients with haematological malignancies compared to non-cancer patients. The impact of persistent viral shedding must be considered in order to re-start therapies and maintain infectious control measures.

La formación del talento humano en el área de la salud en las zonas económicas especiales de Venezuela. Retos y logros II / The formation of human talent in the area of health in the special economic zones of Venezuela. Challenges and achievements II

En esta segunda parte del estudio sobre las políticas del gobierno para el incremento de la inclusión a la educación universitaria (EU), especialmente para el sector salud, quisimos hacer el análisis descriptivo y comparativo en las cuatro Zonas Económicas Especiales (ZEE) que ha creado el presidente Nicolás Maduro en su primera gestión, recordando que la primera parte las estudiamos a escala nacional. En esta oportunidad, realizamos el estudio con similares parámetros académicos, enfocados al área de las Ciencias de la Salud. Es decir, la demanda de cupos universitarios por parte del estudiantado, la oferta de plazas por las Instituciones de Educación Universitaria (IEU) y la asignación de cupos por el Sistema Nacional de Ingreso (SNI). Sin embargo, la matrícula y los valores de egresados de las IEU se estudiaron en tres periodos diferentes: Los tres últimos años de la presidencia de Rafael Caldera (1996-1998); los tres últimos años del presidente Hugo Chávez (2010-2012) y los cuatro primeros años de la primera gestión del presidente Nicolás Maduro (2013-2016). Finalmente, se investigó sobre los proyectos académicos aprobados por el CNU que han introducido las IEU de gestión pública de las ZEE desde 2006 hasta el 2013. Los resultados obtenidos evidencian que los primeros años de la revolución se ha logrado incrementar notablemente los valores de todos estos parámetros, indicando el aumento de la inclusión a la EU en las regiones, pero existen deficiencias notables sobre la oferta académica, algunas veces divorciadas de la realidad circundante de la ZEE, la demanda no satisfecha aún y los pocos proyectos académicos aprobados por el CNU

In this second part of the study on government policies for increasing inclusion in university education (EU), especially for the health sector, we wanted to do a descriptive and comparative analysis in the four Special Economic Zones (EEZ) that it has created President Nicolás Maduro in his first term, remembering that we studied the first part on a national scale. In this opportunity, we carried out the study with similar academic parameters, focused on the area of Health Sciences. That is, the demand for university quotas by the student body, the offer of places by the University Education Institutions (IEU) and the allocation of quotas by the National Income System (SNI). However, the enrollment and values of IEU graduates were studied in three different periods: The last three years of Rafael Caldera's presidency (1996-1998); the last three years of President Hugo Chávez (2010-2012) and the first four years of President Nicolás Maduro's first term (2013-2016). Finally, research was carried out on the academic projects approved by the CNU that have been introduced by the UIS of public management of the EEZs from 2006 to 2013. The results obtained show that the first years of the revolution have managed to significantly increase the values of all these parameters, indicating the increase of the inclusion to the EU in the regions, but there are notable deficiencies in the academic offer, sometimes divorced from the surrounding reality of the ZEE, the demand not yet satisfied and the few academic projects approved by the CNU

Modifying an Active Compound's Release Kinetic Using a Supercritical Impregnation Process to Incorporate an Active Agent into PLA Electrospun Mats.

The main objective of this work was to study the release of cinnamaldehyde (CIN) from electrospun poly lactic acid (e-PLA) mats obtained through two techniques: (i) direct incorporation of active compound during the electrospinning process (e-PLA-CIN); and (ii) supercritical carbon dioxide (scCO2) impregnation of CIN within electrospun PLA mats (e-PLA/CINimp). The development and characterization of both of these active electrospun mats were investigated with the main purpose of modifying the release kinetic of this active compound. Morphological, structural, and thermal properties of these materials were also studied, and control mats e-PLA and e- PLA CO 2 were developed in order to understand the effect of electrospinning and scCO2 impregnation, respectively, on PLA properties. Both strategies of incorporation of this active compound into PLA matrix resulted in different morphologies that influenced chemical and physical properties of these composites and in different release kinetics of CIN. The electrospinning and scCO2 impregnation processes and the presence of CIN altered PLA thermal and structural properties when compared to an extruded PLA material. The incorporation of CIN through scCO2 impregnation resulted in higher release rate and lower diffusion coefficients when compared to active electrospun mats with CIN incorporated during the electrospinning process.

Bone marrow biopsy superiority over PET/CT in predicting progression-free survival in a homogeneously-treated cohort of diffuse large B-cell lymphoma.

Several studies have reported uneven results when evaluating the prognostic value of bone marrow biopsy (BMB) and PET/CT as part of the staging of diffuse large B-cell lymphoma (DLBCL). The heterogeneity of the inclusion criteria and not taking into account selection and collinearity biases in the analysis models might explain part of these discrepancies. To address this issue we have carried a retrospective multicenter study including 268 DLBCL patients with a BMB and a PET/CT available at diagnosis where we estimated both the prognosis impact and the diagnostic accuracy of each technique. Only patients treated with R-CHOP/21 as first line (n = 203) were included in the survival analysis. With a median follow-up of 25 months the estimated 3-year progression-free survival (PFS) and overall survival (OS) were 76.3% and 82.7% respectively. In a multivariate analysis designed to avoid a collinearity bias with IPI categories, BMB-BMI [bone marrow involvement](+) (HR: 3.6) and ECOG PS > 1 (HR: 2.9) were independently associated with a shorter PFS and three factors, age >60 years old (HR: 2.4), ECOG PS >1 (HR: 2.4), and abnormally elevated B2-microglobulin levels (HR: 2.2) were independently associated with a shorter OS. In our DLBCL cohort, treated with a uniform first-line chemotherapy regimen, BMI by BMB complemented performance status in predicting those patients with a higher risk for relapse or progression. In this cohort BMI by PET/CT could not independently predict a shorter PFS and/or OS.

Supercritical impregnation of cinnamaldehyde into polylactic acid as a route to develop antibacterial food packaging materials.

Supercritical impregnation was used to incorporate a natural compound with antibacterial activity into biopolymer-based films to develop active food packaging materials. Impregnation tests were carried out under two pressure conditions (9 and 12MPa), and three depressurization rates (0.1, 1 and 10MPamin-1) in a high-pressure cell at a constant temperature equal to 40°C. Cinnamaldehyde (Ci), a natural compound with proven antimicrobial activity, was successfully incorporated into poly(lactic acid) films (PLA) using supercritical carbon dioxide (scCO2), with impregnation yields ranging from 8 to 13% w/w. Higher pressure and slower depressurization rate seem to favor the Ci impregnation. The incorporation of Ci improved thermal, structural and mechanical properties of the PLA films. Impregnated films were more flexible, less brittle and more resistant materials than neat PLA films. The tested samples showed strong antibacterial activity against the selected microorganisms. In summary, this study provides an innovative route to the development of antibacterial biodegradable materials, which could be used in a wide range of applications of active food packaging.

Impact of azacitidine on red blood cell alloimmunisation in myelodysplastic syndrome.

BACKGROUND: The incidence of alloimmunisation in myelodysplastic syndromes (MDS) during the era of supportive treatment ranges from 9 to 56%. However, it is unknown if the widespread use of hypomethylating agents has changed the risk of immunisation. The aim of this study is to evaluate the impact of azacitidine (AZA) therapy on red blood cell (RBC) alloimmunisation in transfused patients with MDS, myelodysplastic syndromes/myeloproliferative syndromes (MDS/MPS) and secondary acute myeloid leukaemia (AML). MATERIAL AND METHODS: We have analysed retrospectively all patients with MDS, MDS/MPS and secondary AML from MDS, who received their first transfusion in our hospital between January 1995 and December 2014. We have assessed the impact of age, sex, RBC and platelets units transfused, and AZA treatment on developing alloantibodies. RESULTS: In our study, the number of RBC units transfused increased the risk of developing alloantibodies. However aging and the treatment with AZA were associated with a lower rate of alloimmunisation. DISCUSSION: Patients with MDS, MDS/MPS and secondary AML who received treatment with AZA developed RBC antibodies at a lower rate than control group. We suggest that aging and immunosuppression due to AZA therapy could develop an immunological tolerance with a weak response to allotransfusions.

The role of bone marrow biopsy and FDG-PET/CT in identifying bone marrow infiltration in the initial diagnosis of high grade non-Hodgkin B-cell lymphoma and Hodgkin lymphoma. Accuracy in a multicenter series of 372 patients.

Bone marrow infiltration (BMI), categorized as an extra-nodal site, affects stage and is associated with poor prognosis in newly diagnosed lymphoma patients. We have evaluated the accuracy of PET/CT and bone marrow biopsy (BMB) to assess BMI in 372 lymphoma patients [140 Hodgkin Lymphoma (HL) and 232 High Grade B-cell non-Hodgkin Lymphoma (HG B-NHL), among them 155 Diffuse Large B-Cell Lymphoma (DLCL)]. For HL cases, and taking into account PET/CT, sensitivity, negative predictive value (NPV) and accuracy were 96.7, 99.3, and 99.3% while those of BMB were 32.3, 83.8, and 85%, respectively. For HG B-NHL and considering PET/CT, sensitivity, NPV, and accuracy were 52.7, 81.7, and 84.1%, while those of BMB were 77.6, 90.2, and 90.7%, respectively. In the HG B-NHL group, 25 patients would have been under-staged without BMB. These results lead us to recommend PET/CT and the avoidance of BMB to assess BMI in HL. In the case of HG B-NHL, bone marrow status should be assessed firstly by means of PET/CT; only in either focal or diffuse PET/CT with low borderline SUV max values or in negative cases, should BMB be carried out afterwards. In the HG B-NHL setting and at the present moment, both techniques are complementary.

El DHEAS incrementa la expresión de GluR2/3 y GLUR2 del receptor AMPA en el hipocampo de ratones C57/BL6 / DHEAS increases levels of GluR2/3 and GluR2, AMPA receptor subunits, in C57BL/6 mice hippocampus

El DHEAS es un neuroesteroide con efecto neuromodulador de la transmisión sináptica y en la neuroprotección, sin embargo las vías moleculares a través de las cuales se inducen estos cambiosno están completamente claras. Como varios de los neuroesteroides actúan a través de los recetores ionotrópicos de glutamato, se evaluó el efecto del DHEAS en las subunidades GluR2 y GluR3 del receptor AMPA para esclarecer sus efectos. Con este fin se administró DHEAS o una sustancia control durante 7 días a ratones C57/BL6. La expresión de las subunidades se evaluó por Westernblotting.Los resultados presentados muestran que la administración prolongada de 40mg/kg/día de DHEAS a ratones C57/BL6 produce un incremento en los niveles de proteína de las subunidades GluR2/3 yGluR2 del receptor AMPA en el hipocampo. Dado el papel específico que juega la subunidad GluR2 del receptor AMPA en el control de la entrada de calcio durante los procesos de muerte celular y de plasticidad sináptica, este hallazgo contribuye al estudio de los neuroesteroides como una estrategia terapéutica relevante en enfermedades neurodegenerativas y eventos cerebrovasculares.

Dehydroepiandrosterone sulfate (DHEA-S) is a neurosteroid that has effects such as neuromodulator of synaptic transmission and neuroprotection. The specific signaling pathways for these effects are not elucidated yet. Given that, some neurosteroids act through the activation of ionotropic glutamate receptors, therefore the effect of DHEA-S on the subunits GluR2 and GluR3of the AMPA receptor was evaluated. Either DHEA-S or a control substance was administered to C57/BL6 mice. Subunit expression of the AMPA receptor was analyzed by Western blotting. Results show that long-term DHEA-S administration toC57/BL6 mice, increases the protein levels of the subunits GluR2 and GluR2/3 of the AMPA receptors located in the hippocampus. Due to the role of AMPA receptor, specifically GluR2subunit in the regulation of intracellular calcium levels, cellular apoptosis, and synaptic plasticity, the study of neurosteroids as a therapeutic strategy in neurodegenerative diseases and cerebrovascular events is very relevant.

Tolerance of an enterally administered simulated amniotic fluid-like solution by neonates recovering from surgery for congenital bowel abnormalities.

OBJECTIVE: We report a single-centered, Phase I pilot trial, testing the enteral administration of an experimental amniotic fluid-like solution to 10 neonates who were otherwise "NPO" following surgery for congenital bowel abnormalities. The overall hypothesis was that the trophic effect of the solution on intestinal villi would facilitate advancement to full enteral feedings. The specific hypothesis tested in this pilot trial was that the solution would be tolerated. STUDY DESIGN: Ten neonates who were NPO following surgery for congenital bowel abnormalities, were studied before any "trophic" feedings were begun. Each received an experimental, sterile, isotonic, amniotic fluid-like solution at a dose of 20 ml/kg/day enterally. When milk feedings were begun they were mixed with the experimental solution. Increases in the volume of milk feedings occurred at the discretion of the neonatologist and surgeon, and the experimental solution was discontinued any time the neonatologist or surgeon felt it was not tolerated, or when 100 ml of milk feedings/kg/day was achieved. We quantified the amount and character of emesis, stools, and gastric residuals, measured abdominal girth and blood pressure, looked for skin rashes, and sought any signs of intolerance or adverse events. We recorded the days to achieve milk feedings of 20, 50, 100, and 120 ml/kg/day and length of hospital stay. RESULTS: The experimental solution was begun 4 to 32 days after surgery, invariably prior to the institution of "trophic" milk feedings. All subjects completed the doses with no evidence of intolerance. All achieved 100 ml/kg of milk feedings 14 days, or fewer, following institution of the experimental solution (mean 11.1 days, range, 3 to 14). All lived and were discharged home 20.2 days (range, 8 to 42) after the experimental solution was begun. CONCLUSIONS: In this pilot trial involving 10 neonates who had surgery for congenital bowel abnormalities, the enteral administration of a sterile, isotonic, amniotic fluid-like solution was tolerated.