Clinical Presentation of Small Intestinal Bacterial Overgrowth from Aerodigestive Tract Bacteria Versus Colonic-Type Bacteria: A Comparison Study.

BACKGROUND: Small Intestinal Bacterial Overgrowth (SIBO) is a heterogenous syndrome from excessive bacteria in the small intestine lumen. It is unknown if differences in type of bacterial overgrowth lead to differences in symptoms. METHODS: Patients with suspected SIBO were recruited prospectively. Exclusion criteria were probiotics, antibiotics, or bowel prep in preceding 30 days. Clinical characteristics, risk factors, and labs were collected. Proximal jejunal aspiration via upper enteroscopy was performed. Aerodigestive tract (ADT) SIBO was defined as > 105 CFU/mL of oropharyngeal and respiratory bacteria. Colonic-type SIBO was defined as > 104 CFU/mL of distal small bowel and colon bacteria. Aims were to compare symptom profiles, clinical complications, labs, and underlying risk factors between ADT and colonic-type SIBO. KEY RESULTS: We consented 166 subjects. Aspiration was not obtained in 22 and SIBO was found in 69 (49%) of 144 subjects. Daily abdominal distention trended towards more prevalent in ADT SIBO versus colonic-type SIBO (65.2% vs 39.1%, p = 0.09). Patient symptom scores were similar. Iron deficiency was more prevalent in ADT SIBO (33.3% vs 10.3%, p = 0.04). Subjects with colonic-type SIBO were more likely to have a risk factor for colonic bacteria colonization (60.9% vs 17.4%, p = 0.0006). Subjects with ADT SIBO were more likely to have a risk factor for diminished gastric acid (91.3% vs 67.4%, p = 0.02). CONCLUSIONS & INFERENCES: We found differences in iron deficiency and underlying risk factors between ADT and colonic-type SIBO. However, distinct clinical profiles remained elusive. Future research is needed to develop validated symptom assessment tools and distinguish cause from correlation.

The Utility of Corneal Cultures in Bacterial Keratitis.

OBJECTIVES: To determine the utility and use of corneal cultures in bacterial keratitis. METHODS: Retrospective single-center chart review of patients with bacterial keratitis who showed a positive corneal culture result from January 2017 to December 2021. RESULTS: Seventy-four cases of bacterial keratitis in 73 patients with positive cultures were identified. The most common organisms were Pseudomonas, Staphylococcus, and Streptococcus species. In total, 87.8% of cases were started on fortified antibiotics initially. All organisms isolated were susceptible to empiric antibiotics used (n=54). In 47.3% of cases, an antibiotic was discontinued once culture results became available, most often fortified vancomycin. Within the 27 Pseudomonas cases, consisting of predominantly contact lens wearers, at least one fortified antibiotic was discontinued in 66.7% of cases after a positive culture result. CONCLUSIONS: Multidrug resistance was infrequent in the study population. Empiric antibiotic therapy is still effective in bacterial corneal ulcers. Corneal cultures may have utility in antibiotic de-escalation.

Associations of Habitual Dietary Intake With Fecal Short-Chain Fatty Acids and Bowel Functions in Irritable Bowel Syndrome.

BACKGROUND GOALS: Diet may contribute to symptoms of irritable bowel syndrome (IBS) and luminal production of putative IBS biomarkers including short-chain fatty acids (SCFAs). Study aims were to to assess relationships of habitual fiber or starch intake with fecal SCFAs in patients with IBS and healthy volunteers (HVs). STUDY: In 18 HVs and 30 patients with IBS (13 constipation-predominant [IBS-C] and 17 diarrhea-predominant [IBS-D]), habitual diet using a food frequency questionnaire; bowel functions using a validated bowel diary; and fecal SCFAs by HPLC-mass spectrometry were assessed. Associations of fiber and starch with SCFAs were analyzed using Spearman (rs) and Pearson (R) correlations. Relationships between other dietary endpoints, SCFAs, and bowel functions were explored. RESULTS: Habitual fiber or starch intakes were not significantly correlated with SCFAs or bowel functions in all participants or HVs nor with SCFAs in IBS. Starch was negatively correlated (R=-0.53; P=0.04) with complete evacuation in IBS-D. Fiber (rs=0.65; P=0.02) and starch (rs=0.56; P=0.05) were correlated with ease of passage in IBS-C. Stool form, frequency, and ease of passage were positively correlated with total SCFAs (all P<0.05), acetate (all P<0.01), propionate (all P<0.05), and butyrate (form P=0.01; ease of passage P=0.05) among all participants, but not in IBS. Complete evacuation was negatively correlated with propionate (R=-0.34; P=0.04) in all participants. Total (P=0.04) and individual SCFAs (all P<0.05) were positively correlated with stool form in HVs. CONCLUSIONS: Habitual fiber and starch intake does not influence fecal SCFAs but may influence bowel functions in IBS. Fecal SCFAs correlate with bowel functions among all participants including HVs.

Morpho-physiological and demographic responses of three threatened Ilex species to changing climate aligned with species distribution models in future climate scenarios.

The success of a species in future climate change scenarios depends on its morphological, physiological, and demographic adaptive responses to changing climate. The existence of threatened species against climate adversaries is constrained due to their small population size, narrow genetic base, and narrow niche breadth. We examined if ecological niche model (ENM)-based distribution predictions of species align with their morpho-physiological and demographic responses to future climate change scenarios. We studied three threatened Ilex species, viz., Ilex khasiana Purkay., I. venulosa Hook. f., and I. embelioides Hook. F, with restricted distribution in Indo-Burma biodiversity hotspot. Demographic analysis of the natural populations of each species in Meghalaya, India revealed an upright pyramid suggesting a stable population under the present climate scenario. I. khasiana was confined to higher elevations only while I. venulosa and I. embelioides had wider altitudinal distribution ranges. The bio-climatic niche of I. khasiana was narrow, while the other two species had relatively broader niches. The ENM-predicted potential distribution areas under the current (2022) and future (2050) climatic scenarios (General Circulation Models (GCMs): IPSL-CM5A-LR and NIMR-HADGEM2-AO) revealed that the distribution of highly suitable areas for the most climate-sensitive I. khasiana got drastically reduced. In I. venulosa and I. embelioides, there was an increase in highly suitable areas under the future scenarios. The eco-physiological studies showed marked variation among the species, sites, and treatments (p < 0.05), indicating the differential responses of the three species to varied climate scenarios, but followed a similar trend in species performance aligning with the model predictions.

Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis: a prospective single-center experience with mid-term follow-up (with video).

BACKGROUND AND AIMS: Gastroparesis (GP) is a multifactorial disease associated with a large burden on the health care systems. Pyloric-directed therapies including gastric peroral endoscopic myotomy (G-POEM) can be effective in improving patient quality of life and symptom severity. We report on the safety and efficacy of G-POEM and its impact on the quality of life of patients managed at a large referral center. METHODS: Consecutive patients with confirmed GP referred for G-POEM due to failure of medical therapy were included. All patients were assessed at baseline and then at 1, 3, 6, and 12 and 24 months after G-POEM using validated symptom and quality of life instruments, including the Gastroparesis Cardinal Symptom Index (GCSI), Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), and 36-Item Short Form Survey (SF-36). Patients were evaluated before and 6 months after the procedure with EGD, 4-hour scintigraphy, and pyloric EndoFLIP. Technical success was defined as the ability to perform full-thickness pyloromyotomy. Clinical response was defined as an improvement of ≥1 point on GCSI. RESULTS: Fifty-two patients (median age, 48 years; range, 25-80 years, 88% female) underwent G-POEM between February 2018 and September 2020 for the following phenotypes: vomiting-predominant (n=30), dyspepsia-predominant (n=16), and regurgitation-predominant (n=6) GP. The technical success rate was 100%. Adverse events were noted in 3 of 52 patients (5.77%), and were all managed successfully endoscopically. Clinical response was achieved in 68%, 58%, and 48% of patients at 1-month, 6-month, and 12-month follow-up (P < .001, P < .001, and P < .01, respectively). When classified by the cause of GP, the clinical response rates were diabetic GP 64% (11 of 17), postsurgical GP 67% (6 of 9), and idiopathic GP 72% (13 of 18). A statistically significant improvement in PAGI-SYM scores was observed at 1, 3, 6, 12, and 24 months, in addition to significant improvement in several domains of SF-36. Mean 4-hour gastric emptying was reduced 6 months after G-POEM (10.2%) compared with baseline (36.5%, P < .001). We report a significant reduction in the number of emergency department visits and days spent in the hospital up to 24 months after G-POEM. CONCLUSIONS: G-POEM appears to be a safe and feasible treatment alternative for refractory GP with significant short-term and mid-term improvements in overall symptoms, quality of life scores, and health care utilization.

Extraction of Bionanomaterials from the Aqueous Bulk by Using Surface Active and Water-Soluble Magnetic Nanoparticles.

Surface active and water-soluble magnetic nanoparticles (NPs) were used to demonstrate the extraction of bionanomaterials from the aqueous bulk. Au NPs conjugated with different water-insoluble and water-soluble proteins were used as model bionanomaterials. UV-visible studies, zeta potential, and microscopic analyses were performed to quantify the extraction. Sodium dodecyl sulfate and dimethylene bis(dodecyldimethylammonium bromide) (12-2-12) stabilized surface active magnetic NPs were fully capable of extracting Au NPs conjugated with predominantly hydrophobic proteins from the aqueous bulk when placed at the aqueous-air interface. However, they were poor in extracting Au NPs from the aqueous bulk which were coated with predominantly hydrophilic water-soluble protein. On the other hand, water-soluble dodecyldimethyl-3-ammonio-1-propanesulfonate stabilized magnetic NPs proved to be fully capable of extracting all kinds of Au NPs conjugated with either water-soluble or water-insoluble proteins. The results highlight the remarkable ability of magnetic NPs in the extraction of bionanomaterials when placed at either biointerfaces or in the aqueous bulk of biological systems.

Status of mannose-binding lectin (MBL) and complement system in COVID-19 patients and therapeutic applications of antiviral plant MBLs.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a virus called "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)." In the majority of patients, infection with COVID-19 may be asymptomatic or may cause only mild symptoms. However, in some patients, there can also be immunological problems, such as macrophage activation syndrome (CSS) that results in cytokine storm syndrome (CSS) and acute respiratory distress syndrome (ARDS). Comprehension of host-microbe communications is the critical aspect in the advancement of new therapeutics against infectious illnesses. Endogenous animal lectins, a class of proteins, may perceive non-self glycans found on microorganisms. Serum mannose-binding lectin (sMBL), as a part of the innate immune framework, recognizes a wide range of microbial microorganisms and activates complement cascade via an antibody-independent pathway. Although the molecular basis for the intensity of SARS-CoV-2 infection is not generally understood, scientific literature indicates that COVID-19 is correlated with unregulated activation of the complement in terms of disease severity. Disseminated intravascular coagulation (DIC), inflammation, and immune paralysis contribute to unregulated complement activation. Pre-existing genetic defects in MBL and their association with complement play a major role in immune response dysregulation caused by SARS-CoV-2. In order to generate anti-complement-based therapies in Covid-19, an understanding of sMBL in immune response to SARS-CoV-2 and complement is therefore essential. This review highlights the role of endogenous sMBL and complement activation during SARS-CoV-2 infection and their therapeutic management by various agents, mainly plant lectins, since antiviral mannose-binding plant lectins (pMBLs) offer potential applications in the prevention and control of viral infections.

Delayed Gastric Emptying Is Not Associated with a Microbiological Diagnosis of Small Intestinal Bacterial Overgrowth.

BACKGROUND: Clinical symptoms of patients with small intestinal bacterial overgrowth (SIBO) may overlap with symptoms of gastroparesis. Prior studies suggest delayed small intestinal transit is associated with SIBO, but have not shown an association between delayed gastric emptying and SIBO. However, these studies have generally relied on the indirect method of breath testing to diagnose SIBO. AIMS: The aim of this study was to examine the association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. METHODS: In a single-center retrospective study of previous research participants who presented for small bowel enteroscopy for diagnostic evaluation of SIBO, we identified 73 participants who underwent gastric emptying study by scintigraphy. A microbiological diagnosis of SIBO was made in patients based on culture results of jejunal aspirates. Clinical symptoms were assessed using the total gastroparesis cardinal symptom index (GCSI) score. We compared delayed gastric emptying, 2- and 4-h gastric retention, and gastroparesis symptoms between patients with and without a microbiological diagnosis of SIBO. KEY RESULTS: Among 29 participants with SIBO and 44 without SIBO, 33 (45%) had evidence of delayed gastric emptying. There was no significant association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. Percent retained at 2 and 4 h, and total GCSI scores did not differ significantly between those with and without SIBO. CONCLUSIONS: Although delayed gastric emptying is common in patients with suspected SIBO, gastric emptying is not associated with a microbiological diagnosis of SIBO.

Risk Factors Associated With Upper Aerodigestive Tract or Coliform Bacterial Overgrowth of the Small Intestine in Symptomatic Patients.

INTRODUCTION: The clinical relevance of bacterial types identified in small bowel aspirate cultures during diagnostic evaluation of small intestinal bacterial overgrowth (SIBO) is unclear. AIM: The main purpose of this study was to assess associations between risk factors for upper aerodigestive tract (UAT) or coliform SIBO and SIBO diagnosis by culture. MATERIALS AND METHODS: Small bowel aspirates were cultured in patients with suspected SIBO, defined as ≥10 colony-forming units/mL coliform or ≥10 colony-forming units/mL UAT bacteria. History was reviewed for risk factors and potential SIBO complications. Symptoms, quality of life, psychological traits, and laboratory values were assessed. We compared groups by 2-sample t test, Wilcoxon rank sum test, and the Fisher exact test. Overall associations of primary and secondary endpoints with type of bacterial overgrowth were assessed by analysis of variance F-test, Kruskal-Wallis test, and the Fisher exact tests. Associations of risk factors with type of overgrowth were explored using multinomial logistic regression. RESULTS: Among 76 patients, 37 had SIBO (68% coliform, 33% UAT) and 39 did not. Conditions (P=0.02) and surgery (P<0.01) associated with decreased gastric acid were associated with SIBO. In multinomial logistic regression, conditions of decreased acid was associated with UAT SIBO [odds ratio (OR), 5.8; 95% confidence interval, 1.4-33.3]. Surgery causing decreased acid was associated with UAT [OR, 9.5 (1.4-106)] and coliform SIBO [OR, 8.4 (1.6-86.4)]. Three patients with discontinuous small bowel had coliform SIBO [OR, 17.4 (1.2-2515)]. There were no differences in complications, overall symptoms, quality of life, or psychological traits. CONCLUSIONS: Conditions or surgeries associated with decreased gastric acid are associated with SIBO diagnosis by culture.

Clinical heterogeneity of pediatric hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is often a chemoresistant neoplasm with a poor prognosis. Pediatric HCC may reflect unique biological and clinical heterogeneity. PROCEDURE: An IRB-approved retrospective institutional review of patients with HCC treated between 2004 and 2015 was undertaken. Clinical, radiographic, and histologic data were collected from all patients. RESULTS: Thirty-two patients with HCC, median age 11.5 years (range 1-20) were identified. Seventeen patients had a genetic or anatomic predisposition. Histology was conventional HCC (25) and fibrolamellar HCC (7). Evans staging was 1 (12); 2 (1); 3 (10); 4 (9). Sixteen patients underwent resection at diagnosis and five patients after neoadjuvant chemotherapy. Surgical procedures included liver transplantation (LT, 11), hemihepatectomy (9), and segmentectomy (1). Eighteen patients had medical therapy (13 neoadjuvant, 5 adjuvant). Most common initial medical therapy included sorafenib alone (7) and cisplatin/doxorubicin-based therapy (8). Overall, 14 (43.8%) patients survived with a median follow-up of 58.8 months (range 26.5-157.6). Cause of death was most often linked to lack of primary tumor surgery (11). Of the survivors, Evans stage was 1 (11), 2 (1), and 3 (2, both treated with LT). Four of 18 patients (22%) who received medical therapy, 8 of 17 patients with a predisposition (47%), and 14 of 21 patients (66%) who underwent surgery remain alive. CONCLUSIONS: Genetic and anatomic predisposing conditions were seen in over half of this cohort. Evans stage 1 or 2 disease was linked to improved survival. LT trended toward improved survival. Use of known chemotherapy agents may benefit a smaller group of pediatric HCC and warrants formal prospective study through cooperative group trials.

Congenital Portosystemic Shunts in Children: Associations, Complications, and Outcomes.

BACKGROUND: Congenital portosystemic shunt (CPSS) is a rare malformation in which splanchnic venous flow bypasses the liver. CPSS is associated with other congenital anomalies and syndromes and can be associated with life-threatening complications. CPSS and their management remain underreported in the literature. Here, we review the clinical characteristics, management, and outcomes of a cohort of children and young adults with CPSS from two pediatric centers. METHODS: Cases of CPSS from Cincinnati Children's Hospital Medical Center and C.S. Mott Children's Hospital were reviewed to define CPSS anatomy, associated anomalies, complications, interventions, and outcomes. The imaging features and histopathology of liver lesions were characterized in detail. RESULTS: A total of 11 cases were identified. Median age was 10 years (range 0-26); 8 (73%) cases were female. Associated anomalies included six patients with heterotaxy (55%), five patients with congenital heart disease (45%), three patients with Turner syndrome (27%), and two patients with omphalocele, exstrophy, imperforate anus, spinal defects (OEIS) complex (18%). Eight (73%) cases had hyperammonemia ± encephalopathy. A 4-month-old presented with hepatopulmonary syndrome, and 12-year-old presented with pulmonary hypertension. Eight patients (73%) had liver lesions including five with premalignant adenomas and three with well-differentiated hepatocellular carcinoma (HCC). Four children underwent successful CPSS occlusion/ligation. Three children underwent liver transplant (2) or resection (1) for HCC without recurrence at extended follow-up. CONCLUSIONS: CPSS is associated with multiple anomalies (heterotaxy, congenital heart disease) and syndromes (Turner syndrome). CPSS liver lesions should be very carefully evaluated due to risk of premalignant adenomas and HCC. Serious complications of CPSS can occur at a young age but can be managed endovascularly or with open surgery.

Two-dimensional ultrasound shear wave elastography for identifying and staging liver fibrosis in pediatric patients with known or suspected liver disease: a clinical effectiveness study.

BACKGROUND: Ultrasound shear wave elastography (SWE) measures liver stiffness noninvasively, but few studies have defined cutoff values for detecting liver fibrosis in pediatric patients using 2-D ultrasound SWE. OBJECTIVE: To evaluate the diagnostic performance of 2-D ultrasound SWE and define cutoff values for liver fibrosis in pediatric patients, using Canon (Toshiba) Aplio ultrasound systems. MATERIALS AND METHODS: This was an institutional review board-approved retrospective study of patients (≤18 years old) who had undergone both liver 2-D ultrasound SWE and percutaneous liver biopsy within 6 months. Liver biopsies were staged using the METAVIR (fibrosis) scoring system. Continuous data were compared using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance. RESULTS: Forty-six patients, with a median age of 11.5 years (interquartile range: 8.0-14.3 years), were included. Twenty-three patients were male (50%). Twenty-seven patients had a METAVIR fibrosis score of F0-1, and 19 patients had a score of F2-4. For differentiating METAVIR F0-1 from F2--4, the area under the ROC (AuROC) was 0.75 (95% confidence interval [CI]: 0.60-0.90). A cutoff of >1.89 m/s yielded sensitivity of 73.7% (95% CI: 51.2-88.2) and specificity of 77.8% (95% CI: 59.2-89.4). For the subset of patients without histological hepatic steatosis (n=35), the AuROC was 0.86 (95% CI: 0.71-1.0). The same cutoff of >1.89 m/s yielded a sensitivity of 80.0% (95% CI: 54.8-93.0) and specificity of 95.0% (95% CI 76.4-99.7). CONCLUSION: Two-dimensional ultrasound SWE distinguishes patients with no/mild fibrosis from those with moderate/severe fibrosis with good sensitivity and specificity. Diagnostic performance is comparable to that published for magnetic resonance elastography and is likely adversely impacted by steatosis.

Imaging of Fontan-associated liver disease.

The Fontan operation has dramatically altered the natural history of functionally single ventricle congenital heart disease. Patients who have undergone the Fontan operation are living longer and, thus, noncardiac morbidity resulting from the Fontan operation is increasingly being recognized. Fontan-associated liver disease (FALD), one of the chief morbidities following the Fontan operation, is believed to be a multifactorial process that manifests as hepatic congestion and fibrosis, portal hypertension, and development of focal liver lesions, including malignant tumors. This article reviews the imaging findings of FALD in the pediatric and young adult population, reviews the literature related to the imaging of FALD and discusses possible screening algorithms for this population. The need for further research to better understand the causes of FALD, to establish if early liver stiffness measurements (or their change over time) predict long-term outcomes and complications, and to define optimal liver screening procedures is highlighted.

Pediatric trichodysplasia spinulosa: A report of 2 cases and review of the literature.

Trichodysplasia spinulosa is a rare disorder caused by the ubiquitous trichodysplasia spinulosa-associated polyomavirus (TSPyV) and characterized clinically by predominately centrofacial, but often generalized, folliculocentric papules with protuberant keratinaceous spines. Although seroprevalence reaches up to 70% in adult populations, TSPyV causes clinical manifestations in a small percentage of patients who are immunosuppressed. Diagnosis can be made using typical clinical and histologic features, SV40T antibody immunostaining, and PCR of various tissues including the keratinaceous spine, skin, serum, urine, and CSF. Various topical and systemic medications have demonstrated variable success. Decreasing or discontinuing immunosuppression has also been shown to improve or alleviate clinical manifestations.

C/EBPα-dependent preneoplastic tumor foci are the origin of hepatocellular carcinoma and aggressive pediatric liver cancer.

Recent publications show that classic hepatoblastoma (HBL) is the result of failure of hepatic stem cells to differentiate into hepatocytes, while hepatocellular carcinoma (HCC) is caused by the dedifferentiation of hepatocytes into cancer stem cells. However, the mechanisms of aggressive HBL and the mechanisms that cause dedifferentiation of hepatocytes into cancer stem cells are unknown. We found that, similar to HCC but opposite to classic HBL, aggressive HBL is the result of dedifferentiation of hepatocytes into cancer stem cells. In both cases of liver cancer, the dephosphorylation of tumor suppressor protein CCAAT/enhancer binding protein α (C/EBPα) at Ser193 (Ser190 in human protein) or mutation of Ser193 to Ala results in a modified protein with oncogenic activities. We have investigated liver cancer in a mouse model C/EBPα-S193A, in a large cohort of human HBL samples, and in Pten/p53 double knockout mice and found that these cancers are characterized by elevation of C/EBPα that is dephosphorylated at Ser190/193. We found that dephosphorylated C/EBPα creates preneoplastic foci with cancer stem cells that give rise to HCC and aggressive HBL. C/EBPα-dependent dedifferentiation of hepatocytes into cancer stem cells includes increased proliferation of hepatocytes, followed by generation of multinucleated hepatocytes and subsequent appearance of hepatocytes with delta-like 1 homolog-positive intranuclear inclusions. We further isolated C/EBPα-dependent multinucleated hepatocytes and found that they possess characteristics of tumor-initiating cells, including elevation of stem cell markers. C/EBPα-dependent cancer stem cells are observed in patients with aggressive HBL and in patients with a predisposition for liver cancer. CONCLUSION: The earliest steps of adult HCC and aggressive pediatric liver cancer have identical features that include conversion of the tumor suppressor C/EBPα into an oncogenic isoform, which further creates preneoplastic foci where hepatocytes dedifferentiate into cancer cells, giving rise to liver cancer. (Hepatology 2018;67:1857-1871).

Applications of Molecular Structural Aspects of Gemini Surfactants in Reducing Nanoparticle-Nanoparticle Interactions.

Oppositely charged nanoparticle (NP)-nanoparticle (NP) interactions were studied by titrating sodium dodecyl sulfate (SDS) stabilized NPs with cetyltrimethylammonium bromide (CTAB) stabilized NPs at constant temperature with the help of UV-visible and dynamic light scattering measurements. CTAB stabilized NPs were systematically replaced with a series of cationic gemini surfactants to demonstrate the effect of head group and hydrocarbon tail modifications on the electrostatic interactions with SDS stabilized NPs. Introduction of the dimeric gemini head group (alkylammonium or imidazolium), spacer length, and double tail hydrocarbon length all significantly reduced the NP-NP interactions and delayed their salting-out process. They lead to the formation of stable colloidal aqueous solubilized NP-NP complexes. The results concluded that NP-NP interactions can be overcome if appropriately stabilized NPs are used to maintain their colloidal stability so as to achieve maximum applicability.

Transarterial radioembolization with yttrium-90 of unresectable primary hepatic malignancy in children.

BACKGROUND: Primary malignant liver tumors are rare, accounting for 1% to 2% of all childhood cancers. When chemotherapy fails, transarterial radioembolization with yttrium-90 (TARE-Y90) may offer an alternative therapy as a bridge to surgical resection or liver transplant or for palliation. METHODS: We conducted a retrospective review of 10 pediatric patients with histologically confirmed primary liver malignancy who received treatment with TARE-Y90. RESULTS: The median age at treatment was 5.5 years (range, 2-18 years). Median patient survival from initial diagnosis was 12.5 months (range, 10-28 months), and median patient survival after TARE-Y90 was 4 months (range, 2-20 months). Retreatment was well tolerated in three of 10 patients, with these patients demonstrating the longest survival times (range, 17-20 months). One patient was transplanted 6 weeks after TARE-Y90. By RECIST 1.1 criteria of all target lesions, eight of nine patients had stable disease, and one of nine had progressive disease. By mRECIST criteria (requiring postcontrast arterial phase imaging), two of seven patients had a partial response, four of seven had stable disease, and one of seven had progressive disease. CONCLUSION: TARE-Y90 of unresectable primary liver malignancy is both technically feasible and demonstrates an anticancer effect, and retreatment is well tolerated. TARE-Y90 could be considered as adjunctive therapy in pediatric patients with unresectable hepatic malignancies and could be used as a bridge to surgical resection or liver transplant. More research is required to determine the efficacy of this treatment in children and to define the clinical scenarios where benefit is likely to be optimized.

Acquired ornithine transcarbamylase deficiency in pediatric and adolescent patients with fibrolamellar hepatocellular carcinoma.

Ornithine transcarbamylase deficiency (OTCD) disrupts the metabolic pathway responsible for converting nitrogenous waste to urea, allowing for excretion. When impaired, ammonia levels accumulate in the blood resulting in severe, sometimes life-threatening toxicities. Abnormalities of the urea cycle are often inherited, though there are some rarer acquired forms. We describe two cases of acquired OTCD in pediatric patients with fibrolamellar hepatocellular carcinoma (FL-HCC). We detail its presentation and management, explore potential underlying pathophysiology, and propose a practice change to optimize care of FL-HCC patients.

Germline APC mutations in hepatoblastoma.

BACKGROUND: Conflicting reports on the frequency of germline adenomatous polyposis coli (APC) gene mutations in patients with hepatoblastoma (HB) have called into question the clinical value of APC mutation testing on apparently sporadic HB. METHODS: An Institutional Review Board approved retrospective review of clinical data collected from patients with HB who received APC testing at our institution was conducted. All HB patients seen at Cincinnati Children's Hospital Medical Center were eligible for testing. Potential genotype/phenotype correlations were assessed. RESULTS: As of July 2015, 29 patients with HB had received constitutional APC testing. Four (14%) were found to have APC pathogenic truncations of the APC protein and in addition two (7%) had APC missense variants of unknown clinical significance. Two patients (7%) had family histories indicative of familial adenomatous polyposis (FAP). Response to chemotherapy tracked differently in APC pathogenic cases, with a slower imaging response despite an equivalent or slightly faster α-fetoprotein (AFP) response. CONCLUSION: The prevalence of pathogenic APC variants in apparently sporadic HB may be higher than previously detected. Differences in time to imaging response, despite similar AFP response, may impact surgical planning. All patients with HB warrant germline APC mutation testing for underlying FAP.

Vascular anomaly cases for the pediatric hematologist oncologists-An interdisciplinary review.

Vascular anomalies (VAs) are classified as tumors or malformations depending on their clinical characteristics, pathological diagnosis, and genomic information. Diagnosis can be challenging because of the heterogeneity of clinical presentation; thus, the best diagnosis and care are provided by an interdisciplinary team of specialists. Over the past 10 years, an increasing number of pediatric hematologist/oncologists are caring for patients with VAs secondary to new medical therapy options and clinical trials. This paper focuses on complicated VA issues often seen by the pediatric hematologist/oncologist. The paper reviews clinical pearls on diagnosis, histology, radiology, and treatment options.