Vascular endothelial growth factor response with propranolol therapy in patients with infantile hemangioma.

Vascular endothelial growth factor-A (VEGF-A) is a master regulator of angiogenesis, with higher levels in infantile hemangioma (IH). The effects of propranolol on IH are not fully understood and may involve vasoconstriction, angiogenesis inhibition, and apoptosis induction. Therefore, we examined the effects of propranolol therapy on levels of VEGF-A in patients with IH in the proliferative phase and compared the VEGF-A levels to those in untreated patients in the involuting or involuted phases, as well as studied the consistency between the clinical and VEGF responses in patients receiving treatment. In a prospective study, we compared 24 patients with IH in the proliferative phase to 9 patients with IH in the involuting or involuted phase, assessing clinical responses to therapy and changes in VEGF-A levels after 3 months. The median VEGF level before treatment was 275 pg/ml; however, after 3 months, the level significantly decreased to 100 pg/ml (P = 0.007). Median VEGF was significantly higher in patients in the proliferative phase after 3 months of treatment (100 pg/ml) as compared to those in the involuting phase (50 pg/ml). We found no significant correlation between VEGF level and IH size reduction. Propranolol therapy induced a significant decline in VEGF levels at the 3-month evaluation in patients in the proliferative phase; however, this did not reach the levels of IH in the involuting phase. VEGF response was not translated to a clinical response in some patients with IH. These results put in uncertainty the clinical benefit of targeting VEGF pathway in IH.

The interplay between vitamin D and COVID-19: protective or bystander?

The world is currently facing the COVID-19 pandemic, caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Due to a lack of specific treatment and prophylaxis, protective health measures that can reduce infection severity and COVID-19 mortality are urgently required. Clinical and epidemiological studies have shown that vitamin D deficiency can be linked to an increased risk of viral infection, including COVID-19. Therefore, in this review, we looked at various possible roles of vitamin D in reducing the risk of COVID-19 infection and severity. We describe in this article that individuals at high risk of vitamin D deficiency should consider taking vitamin D supplements to keep optimal concentrations. Moreover, we discuss different possible mechanisms by which vitamin D can efficiently reduce the risk of infections through modulation of innate and adaptive immunity against various types of infections. It is advisable to perform further studies addressing the observed influence of vitamin D levels to reduce the risk of COVID-19 infection and mortality.

Altered regulation of hepatic efflux transporters disrupts acetaminophen disposition in pediatric nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, representing a spectrum of liver pathologies that include simple hepatic steatosis and the more advanced nonalcoholic steatohepatitis (NASH). The current study was conducted to determine whether pediatric NASH also results in altered disposition of acetaminophen (APAP) and its two primary metabolites, APAP-sulfate and APAP-glucuronide. Pediatric patients with hepatic steatosis (n = 9) or NASH (n = 3) and healthy patients (n = 12) were recruited in a small pilot study design. All patients received a single 1000-mg dose of APAP. Blood and urine samples were collected at 1, 2, and 4 hours postdose, and APAP and APAP metabolites were determined by high-performance liquid chromatography. Moreover, human liver tissues from patients diagnosed with various stages of NAFLD were acquired from the Liver Tissue Cell Distribution System to investigate the regulation of the membrane transporters, multidrug resistance-associated protein 2 and 3 (MRP2 and MRP3, respectively). Patients with the more severe disease (i.e., NASH) had increased serum and urinary levels of APAP-glucuronide along with decreased serum levels of APAP-sulfate. Moreover, an induction of hepatic MRP3 and altered canalicular localization of the biliary efflux transporter, MRP2, describes the likely mechanism for the observed increase in plasma retention of APAP-glucuronide, whereas altered regulation of sulfur activation genes may explain decreased sulfonation activity in NASH. APAP-glucuronide and APAP-sulfate disposition is altered in NASH and is likely due to hepatic membrane transporter dysregulation as well as altered intracellular sulfur activation.

Nonalcoholic fatty liver disease: a comprehensive review of a growing epidemic.

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD.

Foreign body ingestion: children like to put objects in their mouth.

BACKGROUND: Foreign body ingestion is a common problem in the pediatric age group. Infants and young children explore objects by putting them in the mouth. DATA SOURCES: We reviewed the most recent literatures regarding the incidence, clinical presentation, as well as the most recent advances in the diagnostic and therapeutic modalities of foreign body ingestion in children. RESULTS: In 2007 more than 125 000 foreign body ingestions in patients of 19 years old and younger were reported to American Poison Control Centers in the USA. The majority of ingested foreign bodies pass spontaneously. CONCLUSIONS: Some foreign bodies can be harmful and require evaluation and intervention. The challenge in management is to distinguish the patients who require intervention from those who can be safely observed. In this review we suggest an algorithm for evaluation and management of children suspected to ingest a radiopaque foreign body.

Nonalcoholic fatty liver disease in children living in the obeseogenic society.

BACKGROUND: The problem of obesity in children has grown considerably in recent years in the United States as well as the rest of the world. This has resulted in a marked increase in the prevalence of nonalcoholic liver disease in the pediatric age group. Nonalcoholic fatty liver disease (NAFLD) is currently the most common hepatic disorder seen in pediatric hepatology practice. DATA SOURCES: We have reviewed the most recent literature regarding the prevalence, pathogenesis as well as the most recent advances in the diagnostic and therapeutic modalities of NAFLD in children. RESULTS: NAFLD affects a substantial portion of the population including children. CONCLUSIONS: The rising incidence of NAFLD, nonalcoholic steatohepatitis (NASH) and cirrhosis emphasizes the need for effective treatment options. The lack of complete understanding of the pathogenesis of NAFLD still limits our ability to develop novel therapeutic modalities that can target the metabolic derangements implicated in the development of the disorder.

The 11th Annual International Congress of Pediatric Hepatology, Gastroenterology and Nutrition.

The 11th Annual International Congress of Pediatric Hepatology, Gastroenterology and Nutrition, hosted by the Egyptian Pediatric Association in collaboration with the International Association for the Study of The Liver, provided a comprehensive review of different subjects related to pediatric hepatology, gastroenterology and nutrition. The meeting was chaired by Professor Mortada El-Shabrawi from Cairo University Children's Hospital and Professor Talal Abdel Aziz Farrag from the Military Medical Academy, Cairo, Egypt.

Production of low-background CuSn6-bronze for the CRESST dark-matter-search experiment.

One of the most intriguing open questions in modern particle physics is the nature of the dark matter in our universe. As hypothetical weakly interacting massive particles (WIMPs) do interact with ordinary matter extremely rarely, their observation requires a very low-background detector environment regarding radioactivity as well as an advanced detector technique that allows for active discrimination of the still present radioactive contaminations. The CRESST experiment uses detectors operating at milli-Kelvin temperature. Energy deposition in the detectors is recorded via the simultaneous measurement of a phonon-mediated signal and scintillation emitted by the CaWO(4) crystal targets. The entire setup is made of carefully selected materials. In this note we report on the development of ultra-pure bronze (CuSn(6)) wire in small quantities for springs and clamps that are currently being used in the CRESST II setup.

Postmastectomy radiotherapy reduces locoregional recurrence in elderly women with high-risk breast cancer.

AIMS: Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT). MATERIALS AND METHODS: Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out. RESULTS: Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival. CONCLUSIONS: In women aged 70 years or over with tumours greater than 5 cm or four or more positive nodes, significantly lower LRR was observed in women treated with radiotherapy compared with women treated without radiotherapy. PMRT should be considered in the management of elderly women with these high-risk characteristics.

Broken orthodontic trans-palatal archwire stuck to the throat of orthodontic patient: is it strange?

Trans-palatal arch wire is in common use in orthodontic practice. This case report of broken trans-palatal wire, swallowed and stuck to the throat of an orthodontic patient, is presented in the hope that it will stress the importance of careful examination of the appliance at each scheduled visit.

Plasma endothelin-1 concentrations in children with cirrhosis and their relationship to renal function and the severity of portal hypertension.

BACKGROUND: Plasma endothelin-1 (ET-1) is a potent vasoconstrictor peptide involved in the pathogenesis of several disorders. Endothelin-1 concentrations are increased in adult patients with cirrhosis. However, little is known about ET-1 concentrations in children with cirrhosis. METHODS: Radioimmune assay was used to measure plasma ET-1 concentrations in 19 children with cirrhosis (8 patients with ascites, and 11 without ascites), and 11 age- and sex-matched healthy children. The plasma ET-1 concentrations were correlated with the mean blood pressure, creatinine clearance, and severity of portal hypertension, as measured by portal flow volume and portal flow velocity. RESULTS: Patients with cirrhosis and ascites had increased plasma ET-1 concentrations compared with patients who did not have ascites (6.8 pg/mL +/- 0.62 pg/mL vs. 4.6 pg/mL +/- 0.35 pg/mL; mean +/- SEM; < 0.01) and controls (3.6 pg/mL +/- 0.27 pg/mL; mean +/- SEM; < 0.0005). Plasma ET-1 concentrations were higher in patients with cirrhosis who did not have ascites compared with controls ( < 0.005). No significant differences were observed between concentrations of the patients with cholestasis and those without cholestasis (5.4 pg/mL +/- 0.52 pg/mL vs. 5.2 +/- 0.32 pg/mL; mean +/- SEM; = 0.1). Plasma ET-1 concentrations correlated positively with the mean blood pressure ( = 0.58; < 0.05) and negatively with renal function, as measured by creatinine clearance ( = -0.7; <0.005). However, no correlation was detected between ET-1 concentrations and portal flow volume ( = -0.02; = 0.4) or portal flow velocity ( = -0.16; = 0.4). CONCLUSIONS: Plasma ET-1 concentrations are increased in children with cirrhosis, with or without ascites, compared with controls. Patients with cirrhosis and ascites have increased ET-1 concentrations compared with those without ascites. The degree of increase does not relate to the severity of portal hypertension. This increase tends to maintain systemic blood pressure but is associated with a decrease in renal function.

Evaluation of the triangular cord sign in the diagnosis of biliary atresia.

BACKGROUND: Infantile cholestasis continues to represent a diagnostic challenge. It is very important to diagnose surgically correctable disorders, such as biliary atresia, in a timely manner to prevent progressive damage to the liver. It has been recently suggested that the triangular cord (TC) sign is a simple and useful tool in the diagnosis of biliary atresia. METHODS: We prospectively studied 65 infants presenting with conjugated hyperbilirubinemia (age range: 32-161 days). All patients underwent ultrasonographic examination with a 7.0-MHz transducer (Acuson, Mountain View, CA). The TC was defined as a triangular, or tubular, echogenic density seen immediately cranial to the portal vein bifurcation. RESULTS: The TC sign was identified in 25 infants, and all of them had histologic features suggestive of biliary atresia; the diagnosis was confirmed at surgery by gross morphology of hepatobiliary system, and liver biopsy, with or without intraoperative cholangiogram. Among the 40 patients who did not have the TC sign, 6 had paucity of the intrahepatic bile ducts. Three had alph-1-antitrypsin deficiency, and 31 had neonatal hepatitis. None of the 40 patients who did not have the TC sign developed acholic stools. Seven patients with biliary atresia were followed by ultrasonographic examination for 6 months after the Kasai procedure. The TC sign disappeared in all patients after the surgery; however, the TC sign reappeared in 3 patients who developed progressive cholestasis after the procedure. CONCLUSION: The TC sign is a simple, timesaving, and reliable diagnostic tool in the evaluation of infants with infantile cholestasis. The TC sign may also prove to be helpful in following patients after hepatoportoenterostomy. We suggest a new diagnostic strategy for patients suspected to have biliary atresia. When the TC sign is visualized, the patient should undergo intraoperative cholangiogram to confirm the diagnosis of biliary atresia, reserving percutaneous liver biopsy for those patients in whom the TC sign could not be detected.

Tubular carcinoma of the breast: a population-based study of nodal metastases at presentation and of patterns of relapse.

Tubular carcinoma of the breast (TCB) is a recognized histologic variant of infiltrating ductal carcinoma (IDC) and has been considered to have a comparatively favorable prognosis. However, previous studies have been based on small numbers of cases, some pure TCB and some mixed histology, or have not employed an appropriate comparison group. In this study 171 pure TCB cases and a comparison group of 386 cases with grade I (well differentiated) IDC were identified in a population-based database maintained by the British Columbia Cancer Agency (BCCA). The proportion of cases with axillary nodal involvement at presentation was lower in TCB cases than in the grade I IDC comparison group (12.9% and 23.9%, respectively; p < 0.05). Low-risk tumors (T1 and without vascular lymphatic or perineural invasion) were more prevalent in the TCB patients than in the grade I IDC patients (66.7% and 60.0%; p < 0.05). Low-risk TCB cases had a significantly lower rate of nodal metastases at presentation than low-risk grade I IDC cases (7.0% and 13.2%; p < 0.05). Kaplan-Meier and log-rank analyses indicated a statistically significantly lower rate of local recurrence in TCB cases than among IDC cases (p < 0.05) and a trend toward a lower rate of systemic relapse in TCB cases (p = 0.07). However, no difference in disease-specific survival was observed between TCB cases and grade I IDC comparisons. We conclude that the biologic behavior of TCB was more favorable than that of a comparison group of IDC cases. In view of the low incidence of axillary node metastases at presentation in the low-risk TCB subset (7%), axillary dissection may be omitted as part of the initial surgical management in these patients.

Colonic inflammation found at diagnosis of juvenile retention polyps in pediatric patients.

OBJECTIVE: The finding of colonic inflammation concurrently with a juvenile retention polyp (JRP) may have prognostic value. However, the significance of abnormal mucosal histology with JRP has not been evaluated. We evaluated the significance of mucosal histology at the time of JRP removal with respect to future development of inflammatory bowel disease (IBD) and polyp recurrence. METHODS: The medical records of patients who had an endoscopic polypectomy performed at the Children's Hospital of Philadelphia (CHOP) from 1/1/87 through 4/30/98 were retrospectively reviewed. RESULTS: JRP was histologically identified in 96 patients. A total of 54 patients had colonic mucosal biopsies: 30 (55.6%) had normal histology and 24 (44.4%) had colitis. Of the 24 patients with colitis, 14 patients (58.3%) had inflammation at the polyp site. Twelve of these patients had additional inflammation elsewhere in the colon. Nine (37.5%) had inflammation elsewhere in the colon; however, biopsies around the polyp site were not obtained. One patient with inflammation did not have the location of the polyp documented. Four patients (16.7%) had IBD at the time of polypectomy; two were diagnosed prior and two coincident with JRP. None have subsequently been diagnosed with IBD. There was no difference in polyp recurrence between those with or without inflammation (16.7% [4/24] vs 10.0% [3/30]). The mean follow-up period was 72.4 months (range, 5-142 months). CONCLUSIONS: In our experience, histological mucosal inflammation is a common finding with JRP. This inflammation may be a precursor for the development of JRP but has no predictive value for polyp recurrence. This colitis does not seem to be associated with IBD.

Normal thiopurine methyltransferase levels do not eliminate 6-mercaptopurine or azathioprine toxicity in children with inflammatory bowel disease.

6-mercaptopurine (6-MP) and azathioprine (AZA) are used to treat inflammatory bowel disease (IBD). Side effects include infection, leukopenia, hepatitis, and pancreatitis. The level of thiopurine methyltransferase (TPMT), which metabolizes 6-MP to 6-methylmercaptopurine, may reflect the risk of side effects. We sought to evaluate the relationship between the side effects of these medications and the TPMT level of pediatric patients with IBD. The medical records of our patients who were diagnosed with IBD and who received 6-MP or AZA were reviewed for measured TPMT levels. All red blood cell (RBC) TPMT levels were determined at the Mayo Medical Laboratories, Rochester, MN. The occurrence of leukopenia, elevated aminotransferases, and pancreatitis was evaluated. Twenty-two patients, mean age 13.7 years, received 6-MP or AZA and had TPMT levels measured. The TPMT levels ranged 10.7-27.5 U/mL RBC with a mean of 17.2 +/- 3.2 U/mL RBC. Two children had levels below the accepted norm of 13.8 U/mL RBC. One of these patients (50%) developed both elevation of aminotransferases and leukopenia. Of all, 20 children had normal levels, 3 (15.0%) exhibited side effects: hepatitis (n = 2) and leukopenia (n = 1). We conclude that side effects of 6-MP or AZA occur despite normal TPMT levels.

The potential of digital dental radiography in recording the adductor sesamoid and the MP3 stages.

The current study was undertaken to evaluate the reliability of using a recent advance in clinical radiographic technique, digital dental radiography, in recording two growth indicators: the adductor sesamoid and MP3 stages. With an exposure time five times less than that used in the conventional approach, this method shows greatest flexibility in providing a high quality digitized radiographic images of the two growth indicators under investigation. Refereed Paper

Experiences with 6-mercaptopurine and azathioprine therapy in pediatric patients with severe ulcerative colitis.

BACKGROUND: The effectiveness of 6-mercaptopurine combined with azathioprine in treating severe ulcerative colitis has been shown in several adult studies. Reported pediatric experiences are rare. The purpose of this study was to investigate the safety and the potential efficacy of 6-mercaptopurine and azathioprine in the treatment of active ulcerative colitis in a pediatric population. METHODS: The medical records of patients with active ulcerative colitis who were under observation at The Children's Hospital of Philadelphia and its satellite clinics from January 1984 through December 1997 were retrospectively reviewed. Patients were included who had received a diagnosis of ulcerative colitis, who met no criteria for Crohn's colitis, and who had received treatment with 6-mercaptopurine and azathioprine. They were then analyzed for the development of side effects, the indication to use 6-mercaptopurine and azathioprine, and the ability to discontinue corticosteroid use in those patients taking 5-acetylsalicylic acid products who were corticosteroid-dependent or whose disease was refractory to treatment. Excluded from the corticosteroid analyses were patients who underwent surgery for their disease and patients treated with 5-acetylsalicylic acid only. Statistical analysis was performed by the Kaplan-Meier survival curve and paired Student's t-test. RESULTS: In a review of 200 medical records of patients with active ulcerative colitis, 20 patients met the criteria. The patients' average age at the initiation of treatment with 6-mercaptopurine and azathioprine was 13.8 years. Sixteen patients (80%) were corticosteroid dependent and 3 (15%) had ulcerative colitis refractory to corticosteroid treatment. One patient had severe colitis treated with 5-acetylsalicylic acid only. Discontinuation of corticosteroid was accomplished in 12 (75%) of 16 patients. The median time to discontinuation of corticosteroid after initiation of 6-mercaptopurine and azathioprine therapy was 8.4 months. Eight patients (67%), observed from 3 months to 65 months, have continued without corticosteroid therapy. Side effects included pancreatitis and shingles that resulted in discontinuation of 5-acetylsalicylic acid, leukopenia corrected by withholding 6-mercaptopurine, and self-resolved hepatitis. CONCLUSIONS: The data support the safety of 6-mercaptopurine and azathioprine use in the treatment of pediatric patients with ulcerative colitis; side effects were minimal and reversible. Eighteen (90%) of 20 patients tolerated the therapy well. The results also show that 12 (75%) of 16 pediatric patients with ulcerative colitis will benefit from the use of 6-mercaptopurine and azathioprine after initial discontinuation of corticosteroid therapy. Although 6-mercaptopurine and azathioprine may not prevent further relapses, medical management of these flares may be less intense and may not require long-term corticosteroid use. Prospective clinical trials in pediatric patients are necessary to delineate further the role of 6-mercaptopurine and azathioprine in pediatric ulcerative colitis.

Single toxin detection is inadequate to diagnose Clostridium difficile diarrhea in pediatric patients.

BACKGROUND & AIMS: Clostridium difficile is an important cause of symptomatic diarrhea in pediatric patients. The bacterium produces two toxins, although many laboratories assay for only one. We questioned this diagnostic approach when patients had positive results for C. difficile at our institution, but initially had tested negative at outside laboratories. METHODS: We retrospectively analyzed relative frequencies of C. difficile toxin A alone, toxin B alone, and toxins A and B from pediatric patients with diarrhea. Results were stratified according to toxin detection and patient age. RESULTS: Of 1061 specimens, 276 (26.8%) were positive for C. difficile toxin(s). Fifty-one (18.5%) were positive for toxin A alone, 133 (48.2%) for toxin B alone, and 92 (33.3%) for both toxins. Assaying for toxin B identified C. difficile infection more frequently than did assaying for toxin A (P < 0.0001). The frequency of toxin B detection was significantly higher for older children but not for infants. CONCLUSIONS: Testing for C. difficile toxin A or toxin B alone will result in more frequent misdiagnosis than testing for both toxins. This practice may lead to inappropriate further invasive investigations in children, although this finding may not be applicable to adults.