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Background: Despite the development of Checkpoint Inhibitor Treatments (Immunotherapy) and Targeted anticancer agents, cytotoxic (chemotherapy) agents remain the mainstay of breast cancer treatments. However, treatment failure is often encountered in breast cancers owing to innate or acquired chemoresistance. Real time monitoring of inherent or incipient chemoresistance is an unmet need to minimize or prevent treatment failures and improve outcomes. However, prior efforts to determine chemoresistance have used tumor tissue or explants and are hence not suitable for repetitive monitoring. We present findings from a large cohort perspective observational study which shows that Circulating Tumor Associated Cells (CTACs) be isolated in sufficient numbers from peripheral blood and can be profiled in vitro for chemoresistance characteristics. Methods: 15 ml of peripheral blood was obtained from 1410 breast cancer patients, of whom 719 were treatment naïve and 691 had received prior systemic therapies. Matched tumor tissue was obtained by a biopsy (post-blood collection) in a subset of 68 cases. Peripheral blood mononuclear cells (PBMCs) were isolated from all blood samples and treated with an epigenetically activating treatment medium which exerts selective cytotoxicity towards non-malignant hematolymphoid cells and allows survival of apoptosis resistant malignant CTACs, which were defined as cells which were EpCAM+, PanCK+ and CD45+/-. Viable Tumor Derived Cells (TDCs) were harvested from biopsied tumor tissue (N=68). CTACs and TDCs were treated in vitro with cytotoxic chemotherapy agents that are used in Standard of Care (SoC) treatment protocols for breast cancer as single agents or in combinations. In 68 cases, concordance in Chemoresistance Profiles (CRP) was determined between CTACs and corresponding TDCs. In 681 pretreated cases, CRP of CTACs evaluated cumulative (innate and acquired) resistance following prior exposure to chemotherapy agents. In 685 therapy naïve cases, CRP of CTACs evaluated innate chemoresistance towards chemotherapy agents. Results: Among the 68 paired samples of CTACs and TDCs, there were 733 unique combinations of CTAC-TDC-drug, among which 366 pairs (50%) were concordant for chemo-resistance, 336 pairs (46%) were concordant for absence of resistance, and 31 pairs (4%) showed absence of concordance leading to a cumulative concordance of 96% in CRP between TDC and CTACs. Among the 681 pretreated cases, resistance towards ≥1 anticancer agents was observed in 67% of the samples. Among the 685 therapy naïve cases, resistance towards ≥1 anticancer agents was observed in 39% of the samples. Conclusion: The present study shows that sufficient CTACs can be harvested from peripheral blood for meaningful non-invasive chemoresistance profiling and that the resistance profiles of CTACs are concordant with that of tumor tissue. The present approach can identify innate as well as acquired chemoresistance and can guide selection of appropriate therapies. This approach can facilitate real time monitoring of chemoresistance and therapeutic course correction to minimize the risk of treatment failures. Citation Format: Darshana Patil, Dadasaheb Akolkar, Sanket Patil, Vishakha Mhase, Sachin Apurwa, Sushant Pawar, Rutuja Bhave, Mahesh Ukade, Samruddhi Raut, Harshal Bodke, Shabista Khan, Raja Dhasarathan, Vineet Datta, Stefan Schuster, Cynthe Sims, Jatinder Bhatia, Chirantan Bose, Ajay Srinivasan, Rajan Datar. Non-invasive evaluation of chemoresistance in breast cancers using circulating tumor associated cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-36.

Background: Common modalities for breast cancer screening include self-breast examination (SBE) for detection of palpable lumps as well as Mammography scans for detection of suspicious nodules or masses. While both approaches have low specificity, SBE has lower sensitivity for early stage cancers while mammography is associated with radiation exposure risks. A blood-based non-invasive approach for determination of breast cancer risk in asymptomatic individuals can facilitate early detection and improve prognosis and survival. Circulating Ensembles of Tumor Associated Cells (C-ETACs) are heterotypic clusters of malignant cells which originate in a tumor and are ubiquitously detected in peripheral blood of individuals with solid organ cancers. We present findings from two large-cohort prospective observational studies showing the suitability of C-ETACs for non-invasive, non-radiological screening for breast cancer. Methods: 15 ml of peripheral blood was collected from 14,962 female volunteers among whom 832 were suspected cases of breast cancer and 14,962 were asymptomatic individuals with age-associated risk of breast cancer. The 832 suspected cases underwent a foundational (first diagnostic) biopsy following collection of blood while the 14,962 asymptomatic individuals underwent a mammography scan following collection of blood. Peripheral blood mononuclear cells (PBMCs) were isolated from all blood samples and treated with an epigenetically activating treatment medium which exerts selective cytotoxicity towards non-malignant hematolymphoid cells and allows survival of apoptosis resistant malignant cells and their clusters (C-ETACs). C-ETACs were defined as clusters of 3 or more cells which were EpCAM+, PanCK+ and CD45+/-. Results: Among the 832 suspected cases, 779 were eventually diagnosed with breast cancer and 53 with benign breast conditions. C-ETACs were detected in 701 / 779 cases of breast cancer (90.0% sensitivity) with comparable detection rates in metastatic (365/408 = 89.5%) as well as non-metastatic (336/371 = 90.6%). C-ETACs were also detected in 1 / 53 (1.9%) cases of benign breast tumor. Among the asymptomatic cohort of 14,130, C-ETACs were detected in 657 cases (4.7%), which included 509 / 10,859 (4.7%) individuals with BIRADS 1 and in 148 / 3,271 (4.5%) of individuals with BIRADS ≥2. These individuals have been advised clinical follow-up. Conclusions: We show that C-ETACs are ubiquitous in breast cancers and rare in individuals with benign conditions as well as asymptomatic individuals. Being derived from the tumor mass, C-ETACs are specific for cancer and thus provide direct visual evidence of malignancy in cancer cases and risk of malignancy in asymptomatic cases. The non-invasive nature of the approach is well suited for screening of large asymptomatic populations for breast cancer. Citation Format: Dadasaheb Akolkar, Darshana Patil, Pradip Fulmali, Pooja Fulmali, Revati Patil, Archana Adhav, Shoeb Patel, Sachin Apurwa, Sushant Pawar, Harshal Bodke, Vishal Ranjan, Rohit Chougule, Pradyumna Shejwalkar, Shabista Khan, Raja Dhasarathan, Pradip Devhare, Sanket Patil, Vineet Datta, Cynthe Sims, Stefan Schuster, Jatinder Bhatia, Chirantan Bose, Ajay Srinivasan, Rajan Datar. Non-invasive screening for breast cancer risk based on circulating ensembles of tumor associated cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-13.

Background: Central venous catheter infection and sepsis are significant causes of morbidity and mortality in neonatal intensive care unit patients. This complication may result in a significant cost burden, prolonged antibiotic treatment, and increased length of stay. Objectives: The objective of this study was to determine the difference in post-catheter removal clinical sepsis (PCRCS) in neonatal intensive care unit patients who received antibiotics prior to central venous catheter removal when compared to those who did not. Methods: This was a retrospective cohort study of 200 critically ill neonates comparing those who received one-time doses of vancomycin and cefazolin prior to central venous catheter removal to those who did not. Results: There was no statistically significant association between antibiotic treatment and PCRCS when the analysis was controlled for gender, time the catheter was in place, birth weight, gestational age, or type of central catheter (OR 1.19; 95% CI: 0.18-8.00; P = .8558). No statistical difference was seen in adverse renal outcomes or total antibiotic treatment received for the treatment of PCRCS. Conclusions: Administration of one-time doses of vancomycin and cefazolin did not reduce the incidence of PCRCS when administered to critically ill neonates prior to umbilical venous catheter or peripherally inserted central catheter removal.

Introduction: The objectives of this retrospective cohort study were to examine the effect of vitamin K administration on hemorrhagic and thrombotic complications, blood product utilization, and outcomes in neonatal extracorporeal membrane oxygenation (ECMO). Methods: In the pilot study, complications, blood product use, and outcome data for neonates who received ( n = 21) or did not receive ( n = 18) a single dose of vitamin K (5 mg) immediately after initiation of ECMO for respiratory failure between 2006 and 2010 were compared. In the validation cohort, complications and outcomes were compared for 74 consecutive neonates supported with ECMO for respiratory failure who received ( n = 45) or did not receive ( n = 29) additional vitamin K once daily for prothrombin time (PT) ⩾14 seconds during ECMO from 2014 to 2019. Results: In the pilot study, vitamin K at ECMO initiation was associated with fewer thrombotic complications and similar hemorrhagic complications. The volume of fresh frozen plasma was higher in neonates who received vitamin K, but total blood product and other component volume did not differ between groups. ECMO run time, survival off ECMO, survival to discharge, and length of stay did not differ between cohorts. In the validation cohort, neonates who received additional vitamin K during ECMO had longer ECMO run time and length of stay, but no difference in mortality was observed. Further, thrombotic and hemorrhagic complications as well as blood product exposure were similar between cohorts. Conclusions: These data suggest that routine vitamin K administration may have limited or no benefit during neonatal ECMO.

Objective To compare efficacy and safety of a new synthetic surfactant, CHF5633, enriched with surfactant proteins, SP-B and SP-C peptide analogues, with porcine surfactant, poractant alfa, for the treatment of respiratory distress syndrome in infants born preterm. Study design Neonates born preterm on respiratory support requiring fraction of inspired oxygen (FiO2) ≥0.30 from 240/7 to 266/7 weeks and FiO2 ≥0.35 from 270/7 to 296/7 weeks of gestation to maintain 88%-95% oxygen saturation were randomized to receive 200 mg/kg of CHF5633 or poractant alfa. If necessary, redosing was given at 100 mg/kg. Efficacy end points were oxygen requirement (FiO2, respiratory severity score [FiO2 × mean airway pressure]) in the first 24 hours, 7 and 28 days, discharge home, and/or 36 weeks of postmenstrual age; mortality and bronchopulmonary dysplasia at 28 days and 36 weeks of PMA. Adverse events and immunogenicity were monitored for safety. Results Of the 123 randomized neonates, 113 were treated (56 and 57 in CHF5633 and poractant alfa groups, respectively). In both arms, FiO2 and respiratory severity score decreased from baseline at all time points (P Conclusions Treatment with CHF5633 showed similar efficacy and safety as poractant alfa in neonates born preterm with moderate-to-severe respiratory distress syndrome. Trial registration ClinicalTrials.gov : NCT02452476 .

BACKGROUND The objective of this study was to assess complications and patient outcomes associated with a lower reflexive red blood cell (RBC) transfusion threshold for neonates undergoing extracorporeal membrane oxygenation (ECMO) for hypoxic respiratory failure. STUDY DESIGN AND METHODS A retrospective cohort study was conducted at a single tertiary neonatal intensive care unit of neonates undergoing ECMO support for refractory hypoxic respiratory failure for more than 24 hours between December 2009 and December 2014. Seventy-two neonates received ECMO support for hypoxic respiratory failure for longer than 24 hours during the study period. Patient cohorts were determined based on transfusion threshold of hematocrit (Hct) level of less than 40% (December 2009-October 2012) and Hct level of less than 35% (November 2012-December 2014). RESULTS Patients who had a lower threshold for transfusion (Hct

Background We sought to examine the effect of routine antithrombin III (AT3) infusion on hemorrhagic and thrombotic complications, blood product utilization, and circuit lifespan in neonatal extracorporeal membrane oxygenation (ECMO). Methods We performed a retrospective cohort study of 162 infants placed on ECMO for hypoxic respiratory failure. Infants requiring ECMO for primary cardiac support were excluded. Demographic data, time on ECMO, blood product usage, coagulation profile, and complications were compared between 90 control patients and 72 patients treated with AT3. Results Infants receiving AT3 during ECMO had less thrombotic and similar bleeding complications as compared to infants receiving standard anticoagulation therapy. Total blood product infusion during ECMO was decreased (54.7±20.1 vs. 67.4±34.9mL/kg per day, p =0.001) in infants receiving AT3 during ECMO. Tighter control of activated clotting time and higher serum heparin anti-Xa levels were observed in the AT3 cohort during the first days of ECMO support. 1st ECMO circuit lifespan did not differ between groups. Conclusions Routine administration of AT3 in neonates receiving ECMO therapy was associated with tighter control of anticoagulation and a reduction in thrombotic events without increasing unwanted bleeding. However, circuit lifespan was unaffected. Level of evidence Level III.

Preterm infants, especially very low birth weight (VLBW

Background Neurologic complications including hemorrhage, ischemia, and infarction are often identified in neonates undergoing extracorporeal membrane oxygenation (ECMO) and may contribute to the high morbidity observed in ECMO survivors. Screening for intracranial complications is reliant on bedside transcranial ultrasound (CUS) prior to and during ECMO therapy, and advanced imaging [i.e. computed tomography (CT)/magnetic resonance imaging (MRI)] is recommended after completion of ECMO support. The goal of this study is to describe the correlation of intracranial complications identified on CUS during ECMO and MRI after completion of ECMO. Methods Fifty-five neonates underwent ECMO support at the Children’s Hospital of Georgia at Augusta University from January 1, 2012 to December 31, 2017. Forty-four (80%) had a brain MRI performed prior to transfer or discharge. Ultrasound studies were reviewed by a single blinded pediatric radiologist and MRIs were reviewed by a single blinded neuro-radiologist. Results Of the 44 neonates with post-ECMO MRI, CUS during ECMO identified intracranial lesions in nine neonates, which were all confirmed on post-ECMO MRI. Sixteen subjects (46%) with unremarkable CUS during ECMO had identifiable lesions on post-ECMO MRI, yielding a sensitivity of 36% and a specificity of 100% for CUS in the detection of intracranial lesions. Despite the lack of correlation between CUS and MR, 84.6% of survivors exhibited normal development at 24 months of age. Conclusion While necessary for the identification of intracranial lesions during neonatal ECMO, CUS demonstrated low correlation with post-ECMO MRI in the identification of intracranial lesions, which supports Extracorporeal Life Support Organization (ELSO) recommendations.

Objective: To determine if umbilical cord milking performed on a cut umbilical cord segment increased the hemoglobin/hematocrit, with a reduction in the incidence of intraventricular hemorrhage, need for blood transfusions, and pressor requirement in infants with

This study concerns with the optimisation of a fibre-reinforced composite material ply book and application to an aeronautical component. The presented material solution is a recyclable FML (Fibre Metal Laminate). Recyclable and structural PMCs (Polymeric Matrix Composites) developed up-to now in ENEA had to be improved to satisfy the high-demanding fire characteristics requirements in aeronautics, particularly for the case considered in ongoing project FireMat (www.firemat.it), namely a turbine-bonnet production. FireMat project objective is the combination of weight reduction and fire resistance, maximizing the use C2C recyclable, secondary and biomass derived raw materials. Aluminium layers were introduced inside the lamination, to act as oxygen barriers and improve fire-retardancy. FML were obtained starting from a fire-retardant biobased resin, which was associated with aeronautical grade basalt-derived mineral fabric, processed in the form of a prepreg and then coupled with aluminium foils. FE modelling was based on performed mechanical characterization of the single layers and inter- layer adhesive strength of the ply stack: a composite sandwich structure (including aluminium honeycomb) was optimised.

Treatment of gastroschisis often requires multiple surgical procedures to re-establish abdominal domain, reduce abdominal contents, and eventually close the abdominal wall. In patients who have concomitant respiratory failure requiring extracorporeal membrane oxygenation (ECMO), this process becomes further complicated. This situation is rare and only five such cases have been reported in the ECMO registry database. Management of three of the five patients along with results and implications for future care of similar patients is discussed here. Two patients had respiratory failure due to meconium aspiration syndrome and one patient had persistent acidosis as well as worsening pulmonary hypertension leading to the decision of ECMO. The abdominal contents were placed in a spring-loaded silastic silo while on ECMO and primary closure was performed three to six days after the decannulation. All three patients survived and are developmentally appropriate. We recommend avoiding aggressively reducing the abdominal contents and using a silo to conservatively reducing the gastroschisis while the patient is on ECMO therapy. Keeping the intra-abdominal pressure below 20 mm Hg can possibly reduce ECMO days and ventilator time and has been shown to decrease morbidity and mortality. Patients with gastroschisis and respiratory failure requiring ECMO can have good outcomes despite the complexity of required care.

Background Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated with a high risk of death and neurodevelopmental impairment. Prevention of IC has become a major focus in very low birth weight infants, with fluconazole increasingly used as prophylaxis. Methods We identified all randomized, placebo-controlled trials evaluating fluconazole prophylaxis in premature infants conducted in the United States. We obtained patient-level data from the study investigators and performed an aggregated analysis. The occurrence of each endpoint in infants who received prophylaxis with fluconazole vs placebo was compared. Endpoints evaluated were IC or death, IC, death, Candida colonization, and fluconazole resistance among tested isolates. Safety endpoints evaluated included clinical and laboratory parameters. Results Fluconazole prophylaxis reduced the odds of IC or death, IC, and Candida colonization during the drug exposure period compared with infants given placebo: odds ratios of 0.48 (95% confidence interval [CI], .30-.78), 0.20 (95% CI, .08-.51), and 0.28 (95% CI, .18-.41), respectively. The incidence of clinical and laboratory adverse events was similar for infants who received fluconazole compared with placebo. There was no statistically significant difference in the proportion of tested isolates that were resistant to fluconazole between the fluconazole and placebo groups. Conclusions Fluconazole prophylaxis is effective and safe in reducing IC and Candida colonization in premature infants, and has no impact on resistance.

Background: Fruits and vegetables are key to a healthy diet, particularly in children; however, parents may be concerned about contaminants found in fruits and vegetables. Making informed food choices for children requires understanding and balancing the risks of contaminant exposure with the importance of providing a healthy diet. The objective of this work is to identify fruits and vegetables commonly consumed by infants and toddlers; identify potential contaminants in fruits and vegetables; and outline considerations in assessing contaminant risks in food categories with a critical role in a healthy diet. Method: Commonly consumed fruits and vegetables were obtained from the Feeding Infants & Toddlers Study (FITS 2016). The US Food and Drug Administration Total Diet Study was reviewed for contaminant occurrence, and multiple experts were consulted on considerations in assessing risk of certain contaminants. Results: FITS data show eight fruits and nine vegetables account for over 80% of consumption in infants and toddlers. Several contaminants have been detected in fruits and vegetables. Questions to be addressed prior to establishing contaminant guidance were identified. Conclusion: Contaminant guidance for fruits and vegetables consumed by infants and toddlers raises several challenges. Expertise from multiple disciplines is required to find an approach that maximizes public health benefit.

Many important events occur at birth. The fetus is suddenly removed from a protected intra-uterine environment that is aquatic, warm, and nearly sterile, to the dry, cold external world laden with microbes. To survive, the neonate must interact with many organisms, making use of some, while vigorously defending against the others like a nation conducting trade with friendly countries and guarding against hostile ones from invading it, waging wars if necessary. Although, the neonatal immune system is plastic, however, it is highly tolerant which is due to both the fetal development during gestation as well as significant sudden changes in fetal environment and enormous exposure to the new antigens and intestinal bacteria and their products. This "quiescent mode" of innate immune system is part of a highly regulated process to fulfill all requirements of multi-layered process of early life, implemented effectively through the cells of innate immune system. While, most of the neonatal innate immune cells (e.g., neutrophils and monocytes) present contained activity and lower frequencies compared to their adult counterparts, innate lymphoid cells (ILCs), a distinct cellular component of innate immunity, show higher level of activity and presence during period of infancy compared to later stages of life and adulthood, which may suggest a role for ILCs in variable susceptibility to certain conditions during life time. In this review, while we focus on the characteristics and status of ILCs in neonatal immune system, we also draw an analogy from a national defense perspective because of the great similarities between that and the immune system by providing the known biological counterparts of all five core operational elements, the five Ds of defense, detection, discrimination, deployment, destruction, and de-escalation, with special focus on innate immunity, maternal support, and influence during the neonatal and infancy periods.

The use of point-of-care sonography in clinical settings such as emergency medicine and intensive care units has increased, but adoption in neonatology has been slow. Unlike the focused assessment with sonography for trauma scan used in adults, a quick bedside scan to rapidly evaluate an acutely deteriorating neonate does not exist. The objective of our article is to introduce a focused bedside ultrasound scan that is easy to learn, rapidly performed, and relatively inexpensive.© 2018 by the American Institute of Ultrasound in Medicine.

Brain metastasis in solid organ cancers is associated with adverse prognosis, which is further aggravated by limited systemic treatment options. Such patients are also often excluded from clinical trials since their poor prognosis is perceived to unfavorably impact trial outcomes and misrepresent efficacy data. We retrospectively evaluated the efficacy of treatment guided by Encyclopedic Tumor Analysis (ETA) in patients with advanced refractory malignancies and brain metastases to determine the impact on outcomes. Freshly biopsied tumor tissue (primary / lymph node / liver) and peripheral blood of patients were used for integrational multi-analyte investigations as part of ETA, which included gene mutations, gene expression, and in vitro chemosensitivity profiling of viable tumor cells. Based on ETA, patients received individualized therapy recommendations. All patients underwent a PET-CT scan as well as MRI scan prior to treatment start to determine extent of disease. All patients underwent follow-up PET-CT scans and brain MRI scans every 6–8 weeks. Of the ten patients with brain metastases, which were evaluated after receiving ETA-guided treatment, the median follow-up duration was 97 days (range 79 – 180 days) during which all ten patients remained progression-free. Median time to progression for these patients on the last (failed) line of treatment was 91 days (range 30 - 176 days). Five patients showed partial response and five patients showed stable disease while on ETA-guided treatment. During the follow-up period, all brain metastases were either stable (n=7) or had regressed (n=3), and none of the patients reported new brain lesions. Personalized ETA guided treatments imparted clinical benefit by halting disease progression in this cohort of high-risk patients who would have otherwise been considered for palliative regimens due to perceived unfavorable prognosis.

This paper is devoted to the theoretical study of rubber-metal friction with particular reference to a lip seal for large high-speed rotor applications. The paper, starting from previously published mathematical models related to friction estimations, presents a semi-analytical mathematical model to estimate friction loss induced by rubber lip seals. The sliding friction model is formulated on the basis of rubber and metal surface properties. Viscoelastic and hysteretic properties of the rubber are considered as function of temperature and excitation frequency. The metal surface profile is modelled as a superimposition of base ideal peak profiles. Finally, the friction coefficient is modelled as a function of temperature, frequency and contact pressure. A preliminary validation of the model is achieved by comparing the estimated friction torque provided by the model with the friction torque measured on an actual rotor-stator system at different operating temperatures.

Sales of raw or unpasteurized milk and milk products are still legal in at least 30 states in the United States. Raw milk and milk products from cows, goats, and sheep continue to be a source of bacterial infections attributable to a number of virulent pathogens, including Listeria monocytogenes, Campylobacter jejuni, Salmonella species, Brucella species, and Escherichia coli O157. These infections can occur in both healthy and immunocompromised individuals, including older adults, infants, young children, and pregnant women and their unborn fetuses, in whom life-threatening infections and fetal miscarriage can occur. Efforts to limit the sale of raw milk products have met with opposition from those who are proponents of the purported health benefits of consuming raw milk products, which contain natural or unprocessed factors not inactivated by pasteurization. However, the benefits of these natural factors have not been clearly demonstrated in evidence-based studies and, therefore, do not outweigh the risks of raw milk consumption. Substantial data suggest that pasteurized milk confers equivalent health benefits compared with raw milk, without the additional risk of bacterial infections. The purpose of this policy statement was to review the risks of raw milk consumption in the United States and to provide evidence of the risks of infectious complications associated with consumption of unpasteurized milk and milk products, especially among pregnant women, infants, and children.

Survival of high-grade glioma patients remains dismal due to onset of resistance to even the limited systemic treatment option currently available. Except for indirect prediction of alkylating agent Temozolomide response through MGMT promotor methylation and NTRK fusions for larotrectinib, there are no biomarkers available for drug response prediction. Cell based, in vitro chemosensitivity assays can interrogate the efficacy of an array of cytotoxic drugs. However, the unavailability of live tumor cells for such assays pose challenges in clinical practice. Repeat biopsies are neither advisable nor feasible. Access to Circulating Glial Cells (CGCs) can provide real time insight into the chemo dynamics of the tumor. In this study, we show for the first time that CGCs can be harvested from peripheral blood of glioma patients for chemo response and resistance profiles (CRR) of cytotoxic drugs. CGCs were harvested from 15 ml of peripheral blood from high grade GBM patients (n=9) out of whom cells derived from surgically excised tumor tissue were also available for comparison in 2 patients. CellWizard™ process was adopted for enrichment of CGCs which is based upon epigenetically active media with paradoxical chemo-toxicity that selectively induces lethality in normal cells. This paradoxical cytotoxicity of the medium leads to selective elimination of most leukocytes thus facilitating a label free negative enrichment of CGCs. In vitro chemo sensitivity assay performed on live CGCs and cell death events were determined to evaluate response to different class of chemotherapy drugs. Evaluation of drug response showed very high concordance between tumor derived cells and CGCs in both patients where live tissue was available. In 7 patients where CGCs alone could be evaluated, the response showed replication between in vitro profile compared to treatment antecedents in 5 patients. 2 patients were treatment naïve and the response reflected high sensitivity to Temozolomide.

Invasive procedures for diagnosis of CNS malignancies carry inherent risks of high morbidity and mortality. Although circulating biomarkers such as cell free DNA (cfDNA) and microvesicle (MV) borne nucleic acids have been proposed as potential diagnostic aids, their stand-alone utility has inherent limitations. However, Circulating Glial Cells (CGCs) combined with cfDNA could offer a viable alternative to invasive biopsies for diagnosis of CNS malignancies; yet the technological challenge in the detection of CGCs in glioma patients presents a formidable challenge. In this study, we evaluated the feasibility of harvesting CGCs from suspected cases of Glioma. From a cohort of 23 suspected cases of CNS malignancies, we used 15ml of peripheral blood and used the CellWizard™ process and related protocol for isolation of CGCs. CellWizard™ is an epigenetically active media with paradoxical chemo-toxicity that selectively induces lethality in normal cells which have a functionally responsive cell death (apoptosis) mechanism, while simultaneously conferring survival privilege on apoptosis resistant cells typically released from a malignant tumor. This paradoxical cytotoxicity of the medium leads to selective elimination of most leukocytes thus facilitating a label free negative enrichment of CGCs, which can be harvested and further characterized. Patients included 11 Glioblastoma, 3 Anaplastic astrocytoma, 2 Medulloblastoma, 5 Oligodendroglioma, 1 Gliosarcoma and 1 meningioma patient. Characterization of CGCs was performed using GFAP, S100 and CD45 markers. CGCs were detected in 16 out of 23 (69.6 %) patients and could be stained positively for both GFAP and S100 and negatively for CD45. Detection of viable CGCs in cases of CNS malignancies can be used for characterization of markers related to the diagnosis.

Newborns with ABO blood group incompatibility can have a spectrum of clinical presentations from remaining asymptomatic to severe hemolytic anemia with jaundice. This case presentation discusses dizygotic twins who demonstrated both ends of the clinical spectrum. Similar cases in which there is such extreme variation between twins were not attainable in the current literature, which prompted the authors to present it as a rare occurrence and one that was unexpected based on their past experience with ABO incompatibility both in singletons and in twins.

Background: Zinc and copper are essential for preterm infants, but recommended requirements from different groups vary widely. Recommended zinc intakes have steadily increased over the years. Although this would be expected to impair copper absorption, recommended copper intakes have not risen in parallel. Objectives: To systematically review the literature on zinc and copper retention in preterm infants; to examine the effect on zinc intake on copper retention; and to estimate the zinc and copper intakes required to meet the levels of zinc and copper retention required for normal growth. Design: Studies reporting zinc and/or copper retention in preterm infants (

Requirements for optimal nutrition, especially for micronutrients, are not well defined for premature infants. The "reference fetus," developed by Ziegler et al,(1) has served as a model to define nutritional needs and studies designed to determine nutrient requirements. Revision of nutrient requirements and provision of optimal nutrition may lead to improved outcomes in preterm infants. Appropriate provision of nutrients also may help prevent nutritional disorders, such as metabolic bone disease and anemia. In this review, we discuss calcium, phosphorus, magnesium, vitamin D, iron, and copper, and define optimal intakes based on the available published data.

Human milk is the preferred feeding for both term and preterm infants. While being considered optimal for term infants, human milk, even from mothers delivering preterm infants, is lacking in protein, energy, sodium, calcium, and phosphorus, resulting in poorer growth and nutrient deficiencies when compared to formulas designed for these high-risk infants. Further, the lack of growth is associated with long-term adverse consequences. Since human milk has unique properties in promoting gastrointestinal maturation and immunological benefits, it is prudent to implement strategies to fortify it appropriately to realize its benefits which include reduced rates of necrotizing enterocolitis, fewer episodes of sepsis and urinary tract infections, and improved visual and neurocognitive development. Donor human milk is being widely used when mothers' own milk is not available or is in short supply. While it retains some of the biological properties and clinical benefits of mothers' own milk, it requires additional care in fortification, especially if the donor milk is from a pool of term human milk. As nutritional strategies improve, the ultimate goal is to minimize extrauterine growth restriction and promote appropriate growth after regaining birth weight.

Treatment of gastroschisis often requires multiple surgical procedures to re-establish abdominal domain, reduce abdominal contents, and eventually close the abdominal wall. In patients who have concomitant respiratory failure requiring extracorporeal membrane oxygenation (ECMO), this process becomes further complicated. This situation is rare and only five such cases have been reported in the ECMO registry database. Management of three of the five patients along with results and implications for future care of similar patients is discussed here. Two patients had respiratory failure due to meconium aspiration syndrome and one patient had persistent acidosis as well as worsening pulmonary hypertension leading to the decision of ECMO. The abdominal contents were placed in a spring-loaded silastic silo while on ECMO and primary closure was performed three to six days after the decannulation. All three patients survived and are developmentally appropriate. We recommend avoiding aggressively reducing the abdominal contents and using a silo to conservatively reducing the gastroschisis while the patient is on ECMO therapy. Keeping the intra-abdominal pressure below 20 mm Hg can possibly reduce ECMO days and ventilator time and has been shown to decrease morbidity and mortality. Patients with gastroschisis and respiratory failure requiring ECMO can have good outcomes despite the complexity of required care.

Conventional treatment of respiratory failure involves positive pressure ventilation that can worsen lung damage. Extracorporeal membrane oxygenation (ECMO) is typically used when conventional therapy fails. In this study, we evaluated the use of venovenous (VV)-ECMO for the treatment of severe pediatric respiratory failure at our institution. A retrospective analysis of pediatric patients (age 1-18) placed on ECMO in the last 15 years (1999-2014) by the pediatric surgery team for respiratory failure was performed. Five pediatric patients underwent ECMO (mean age 10 years; range, 2-16). All underwent VV-ECMO. Diagnoses were status asthmaticus (2), acute respiratory distress syndrome due to septic shock (1), aspergillus pneumonia (1), and respiratory failure due to parainfluenza (1). Two patients had severe barotrauma prior to ECMO initiation. Average oxygenation index (OI) prior to cannulation was 74 (range 23-122). No patients required conversion to VA-ECMO. The average ECMO run time was 4.4 days (range 2-6). The average number of days on the ventilator was 15 (range 4-27). There were no major complications due to the procedure. Survival to discharge was 100%. Average follow up is 4.4 years (range 1-15). A short run of VV-ECMO can be lifesaving for pediatric patients in respiratory failure. Survival is excellent despite severely elevated oxygen indices. VV-ECMO may be well tolerated and can be considered for severe pediatric respiratory failure.

Breastfeeding is universally accepted as the preferred feeding for all newborn infants, including premature infants. The World Health Organization, American Academy of Pediatrics, Canadian Pediatric Society and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, among others, recommend exclusive breastfeeding for the first 6 months in term infants, while complementary feeding is introduced over the next several months. However, for preterm infants, fortification is recommended to meet requirements. Human milk composition varies with the duration of lactation, within a day and even during one expression, and composition may be altered by method of storage and pasteurization. In this monograph, the use of human milk for premature infants, its limitations, strategies to overcome said limitations and follow-up studies will be reviewed.

Breastfeeding is universally accepted as the preferred feeding for all newborn infants, including premature infants. The World Health Organization, American Academy of Pediatrics, Canadian Pediatric Society and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, among others, recommend exclusive breastfeeding for the first 6 months in term infants, while complementary feeding is introduced over the next several months. However, for preterm infants, fortification is recommended to meet requirements. Human milk composition varies with the duration of lactation, within a day and even during one expression, and composition may be altered by method of storage and pasteurization. In this monograph, the use of human milk for premature infants, its limitations, strategies to overcome said limitations and follow-up studies will be reviewed.

The US market for organic foods has grown from $3.5 billion in 1996 to $28.6 billion in 2010, according to the Organic Trade Association. Organic products are now sold in specialty stores and conventional supermarkets. Organic products contain numerous marketing claims and terms, only some of which are standardized and regulated. In terms of health advantages, organic diets have been convincingly demonstrated to expose consumers to fewer pesticides associated with human disease. Organic farming has been demonstrated to have less environmental impact than conventional approaches. However, current evidence does not support any meaningful nutritional benefits or deficits from eating organic compared with conventionally grown foods, and there are no well-powered human studies that directly demonstrate health benefits or disease protection as a result of consuming an organic diet. Studies also have not demonstrated any detrimental or disease-promoting effects from an organic diet. Although organic foods regularly command a significant price premium, well-designed farming studies demonstrate that costs can be competitive and yields comparable to those of conventional farming techniques. Pediatricians should incorporate this evidence when discussing the health and environmental impact of organic foods and organic farming while continuing to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agriculture’s MyPlate recommendations. This clinical report reviews the health and environmental issues related to organic food production and consumption. It defines the term “organic,” reviews organic food-labeling standards, describes organic and conventional farming practices, and explores the cost and environmental implications of organic production techniques. It examines the evidence available on nutritional quality and production contaminants in conventionally produced and organic foods. Finally, this report provides guidance for pediatricians to assist them in advising their patients regarding organic and conventionally produced food choices.

We would like to thank Dr Cummings for giving us the opportunity to explain our study results. Results from nine randomized, controlled, trials (RCTs),1, 2, 3, 4, 5, 6, 7, 8, 9 including the one that has been just published (e-pub ahead of print) by Dizdar et al.9 and meta-analyses10, 11, 12 comparing animal-derived surfactants, namely, poractant alfa (PA), beractant (BE), bovactant (BO) and/or calfactant (CA), have consistently shown faster weaning of oxygen and mean airway pressure, less need for redosing, fewer days on oxygen and mechanical ventilation, shorter length of stay (LOS) as well as survival advantage in babies treated with PA. These advantages with PA over BE, CA or BO are likely related to major biological and/or biochemical differences between these animal-derived surfactant preparations. PA contains the highest amount of phospholipids when compared with BE or CA. Higher amount of phospholipids has been shown to downregulate oxidative functions in monocytes and confer better anti-inflammatory properties.13 In addition, bacterial growth in different surfactant preparations is influenced by microbial species and the composition and dose of the surfactant. PA was bactericidal in a dose-dependent fashion and differed from BE and BO, a surfactant preparation similar to CA.14 PA contains the highest amount of plasmalogens (PL) when compared with BE.15 BO contains the lowest amount of PL.15 PL are anti-oxidant phospholipids and presence of higher amounts of PL in the tracheal aspirates from pre-term infants has been shown to be associated with a lower risk for bronchopulmonary dysplasia (BPD).16 Also, the amount of surfactant-associated protein B (SP-B) is highest in PA when compared with BE or CA. SP-B is the most important SP in helping the phospholipids to rapidly adsorb at the air–liquid interphase and in decreasing surface tension. Furthermore, the phospholipid molecular species of PA is much closer to that of human surfactant.17, 18

To compare the effect of early extubation to nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) on the need for mechanical ventilation via endotracheal tube (MVET) at 7 days of age in preterm infants30 weeks' gestation requiring intubation and surfactant for respiratory distress syndrome (RDS) within 60 min of delivery.Multicenter, randomized, controlled trial. A total of 57 infants were randomized within 120 min of birth to NCPAP (BW 1099 g and GA 27.8 weeks) and 53 infants to NIPPV (BW 1052 g, and GA 27.8 weeks). Infants were stabilized on NCPAP at birth and were given poractant alfa combined with MVET within 60 min of age. When stabilized on MVET, they were extubated within the next hours or days to NCPAP or NIPPV.A total of 42% [corrected] of infants needed MVET at 7 days of age in the NCPAP group compared with 17% in the NIPPV group (OR: 3.6; 95% CI: 1.5, 8.7). Days on MVET were 12 ± 11 days in NCPAP group compared with 7.5 ± 12 days in the NIPPV group (median 1 vs 7 days; P=0.006). Clinical bronchopulmonary dysplasia (BPD) was 39% in the NCPAP group compared to 21% in the NIPPV group (OR: 2.4; 95% CI: 1.02, 5.6). Physiological BPD was 46% in the NCPAP group compared with 11% in the NIPPV group (OR: 6.6, 95% CI: 2.4, 17.8; P=0.001). There were no differences in any other outcomes between the two groups.NIPPV compared with NCPAP reduced the need for MVET in the first week, duration of MVET, and clinical as well as physiological BPD in preterm infants receiving early surfactant for RDS.

Objective: The objective of this study is to compare all-cause in-hospital mortality in preterm infants with respiratory distress syndrome (RDS) treated with poractant alfa, calfactant or beractant. Study Design: A retrospective cohort study of 14 173 preterm infants with RDS, treated with one of three surfactants between 2005 and 2009, using the Premier Database was done. Multilevel, multivariable logistic regression modeling, adjusting for patient- and hospital-level factors was performed. Result: Calfactant treatment was associated with a 49.6% greater likelihood of death than poractant alfa (odds ratio (OR): 1.496, 95% confidence interval (CI): 1.014–2.209, P=0.043). Beractant treatment was associated with a non-significant 37% increase in mortality, compared with poractant alfa (OR: 1.370, 95% CI: 0.996–1.885, P=0.053). No differences in mortality were observed between calfactant and beractant treatment (OR: 1.092, 95% CI: 0.765–1.559, P=0.626). Conclusion: Poractant alfa treatment for RDS was associated with a significantly reduced likelihood of death when compared with calfactant and a trend toward reduced mortality when compared with beractant.

We report a rare case of a newborn with complete monosomy 21 prenatally diagnosed in the amniotic fluid and subsequently confirmed in other tissues. Patient presented with multiple osseous, cardiac, and vascular anomalies. Cardiac anomalies included large atrial septal defect, ventricular septal defect, aneurysm of the left pulmonary artery and patent ductus arteriosus with large bidirectional shunt. Interruption of the inferior vena cava was noted. Although interrupted inferior vena cava associated with cardiac anomalies was previously reported, it has not been reported in association with monosomy 21.

The provision of appropriate nutritional support is an essential part of the primary and adjunctive management of many gastrointestinal (GI) disorders in neonatology and pediatrics. Few conditions in neonatology pose as great a challenge as intestinal failure or short bowel syndrome (SBS). The latter, SBS, is a complex disorder affecting normal intestinal physiology with nutritional, metabolic and infectious consequences. It is a result of the alteration of intestinal digestion and absorption following extensive bowel resection. Medical management of SBS is a very labor-intensive problem. Nutritional support and monitoring are of paramount importance, and long-term morbidity and mortality will depend on recognition and careful management of associated complications. With the increased use of intestine or intestine-liver transplant, maintaining these infants in good 'health' to allow transplantation will go a long way in achieving good long-term outcomes.

This in vivo study examines innate lymphoid cells in breast milk.