Silver Nitrate Grade and Its Effect on Physical Developer Performance-A Validation Study.

Silver nitrate is a critical component of the physical developer (PD) reagent. Significant increases in the cost of silver nitrate in recent years have caused the United States Secret Service's Forensic Laboratory to look for a more economical way to produce physical developer. One possible solution to this dilemma is to use a lower grade of silver nitrate, which typically has a lower cost. This study compared the quality of fingerprints produced on various paper substrates by three physical developer working solutions, each prepared using either the American Chemical Society (ACS), U.S. Pharmacopeia (USP), or technical grade of silver nitrate. It was determined that the less pure grades of silver nitrate produced approximately the same quality of fingerprints as the ACS grade, which is currently used in the authors' laboratory for making PD working solutions. In the experiments comparing PD prepared using the ACS and USP grades of silver nitrate, the ACS grade was superior only 5% of the time, whereas the USP grade was chosen 27% of the time. In the experiments comparing PD prepared using the ACS and technical grades of silver nitrate, the ACS grade was superior only 10% of the time, whereas the technical grade was selected 17% of the time. For the majority of the sample comparisons, no difference in fingerprint quality was observed. The overall conclusion was that either USP or technical grade silver nitrate can be used in place of the current, and more expensive, ACS grade of silver nitrate.

Role of ADAM-17, p38 MAPK, cathepsins, and the proteasome pathway in the synthesis and shedding of fractalkine/CX3 CL1 in rheumatoid arthritis.

OBJECTIVE: To evaluate the mechanism of fractalkine (FKN)/CX3 CL1 synthesis and shedding in rheumatoid arthritis synovial fibroblasts (RASFs) and in rat adjuvant-induced arthritis (AIA). METHODS: The effect of tumor necrosis factor α (TNFα) and/or interferon-γ (IFNγ) on FKN synthesis and shedding in human RASFs was determined over time by immunostaining, quantitative reverse transcription-polymerase chain reaction, and Western blotting. The role of protease enzymes and signaling pathways was evaluated using chemical inhibitors and small interfering RNA (siRNA). The activity of 20S proteasome in the lysates and the DNA binding of NF-κB/p65 in the nuclear fractions were evaluated. The in vivo relevance of these findings was examined in rat AIA. RESULTS: In RASFs, stimulation with the combination of TNFα and IFNγ induced cellular expression of FKN within 24 hours. Activation of ADAM-17, but not ADAM-10, partly mediated the proteolytic shedding and release of soluble FKN (sFKN) following TNFα/IFNγ stimulation for 24-72 hours. Compared with control siRNA, ADAM-17 siRNA markedly inhibited TNFα/IFNγ-induced sFKN production (by ∼33%). TNFα/IFNγ-induced sFKN release was markedly suppressed by inhibitors of ADAM-17, p38 MAPK, proteasome, or cathepsin inhibitor but not by inhibitors of caspase 3 or calpain. TNFα/IFNγ-induced proteasome activity also correlated with rapid degradation of IκBα and p38 MAPK phosphorylation. In vivo findings showed increased FKN expression in the joints of rats with AIA, which correlated with increased expression of ADAM-17 and phospho-p38 MAPK. CONCLUSION: Our results provide new understanding of the role of ADAM-17, p38 MAPK, cathepsins, and the proteasome pathway in FKN expression and shedding. Regulating these pathways may suppress FKN-mediated inflammation and tissue destruction.

Challenges in the Multidisciplinary Management of Pediatric Patients with Intestinal Failure During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic had profound effects on the management of pediatric patients with intestinal failure. Limitations in personal protective equipment and other necessary supplies led to changes in home care of central venous catheters. Limitations for in-person clinic visits led to changes in care delivery systems and contributed to delays in care and delays in the progression toward enteral autonomy. The emotional strain of living with chronic illness during a pandemic caused hardships that are still being felt. Delays in surgical care also potentially delayed children weaning from parenteral nutrition. The global pandemic of COVID-19 and its far-reaching effects on society contributed to challenges and changes in the multidisciplinary care of pediatric patients with intestinal failure, of which the full effect is still unknown. [Pediatr Ann. 2022;51(7):e277-e280.].

Combined en bloc liver-double kidney transplantation in an infant with IVC thrombosis.

We report a case of a pediatric en bloc liver-double kidney transplant in a patient with IVC thrombosis below the renal veins. The patient is an 11-month-old girl diagnosed with congenital nephrotic syndrome at two months of age. Multifocal liver masses were identified on routine ultrasound at eight months of age. Alpha fetoprotein level was 55 319. Biopsy confirmed hepatoblastoma. CT scan confirmed multiple lesions in both lobes, which would require liver transplantation for resection. She was also found to have thrombosis of her infrarenal IVC secondary to multiple central lines. She was listed for combined liver-kidney transplant and began chemotherapy. After four cycles of chemotherapy, she underwent bilateral nephrectomies followed by a combined en bloc liver-double kidney transplant from a size matched donor. In order to provide adequate venous outflow from the kidneys in the absence of a recipient infrarenal IVC, the donor liver and kidneys were procured en bloc with a common arterial inflow via the infrarenal aorta and common outflow via the suprahepatic IVC. Kidney transplantation in the absence of adequate recipient venous drainage may require unusual vascular reconstruction techniques. This case demonstrates a novel approach in patients who may require combined liver-kidney transplantation.

Autologous intestinal reconstruction surgery for intestinal failure management.

PURPOSE OF REVIEW: Multidisciplinary management of intestinal failure has progressed over the past 30 years, facilitating the transition to enteral autonomy in many pediatric patients. However, there remains a select group of patients who reach a plateau in advancement of their enteral nutrition. Numerous surgical options have been pursued to attempt to slow intestinal transit, taper dilated bowel, and promote intestinal adaptation. This review highlights the current literature on autologous intestinal reconstruction surgery, focusing on the two most commonly performed procedures, the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP). RECENT FINDINGS: LILT and STEP remain viable options to treat medically refractory short bowel syndrome. There is over 20 years of experience with the LILT procedure in the literature, with one large series showing that 67% of patients eventually transitioned to full enteral nutrition. The International STEP Data Registry reported a weaning rate of 34% after median follow-up of 12.6 months. Repeat STEP has been described as a possible treatment for the redilation that occurs after both LILT and STEP. SUMMARY: LILT and STEP may facilitate enteral feeding advancement in patients with medically refractory short bowel syndrome.

Non-operative management of acute appendicitis in a pediatric patient with concomitant COVID-19 infection.

INTRODUCTION: In late December 2019, reports emerged from Wuhan, China of a novel corovonavirus SARS-CoV-2, which caused severe acute respiratory distress syndrome referred to as COVID-19. As the virus spread, reports of severe perioperative complications, including fatalities, began to emerge in the literature. We present a case of a previously healthy patient who developed classic symptoms of appendicitis. The patient was also found to be positive for COVID-19. Given the risks to both the patient and surgical team, we elected to pursue a non-operative management strategy for this patient with appendicitis. MATERIALS AND METHODS: A 13 year old female with COVID-19 presented with a day of right lower quadrant abdominal pain. A computerized tomography (CT) scan diagnosed uncomplicated appendicitis. The patient was successfully treated non-operatively with antibiotics and discharged home. CONCLUSION: To our knowledge, this case illustrates the first report of a pediatric patient with concomitant appendicitis and COVID-19 infection. We have been able to utilize a non-operative management strategy to effectively treat the patient's acute appendicitis, while protecting her from the risks of undergoing a general anesthetic as well as the operative team. We hope this report can provide others with a potential management strategy for similar patients.

Effect of high-temperature on high-performance liquid chromatography column stability and performance under temperature-programmed conditions.

Six commercially available analytical (4.1 or 4.6 mm i.d.) columns were evaluated under temperature-programmed high-temperature liquid chromatography (HTLC) conditions to access their stability and performance at extreme temperatures. Seven components consisting of acidic, basic and neutral compounds were analyzed under temperature-programmed conditions and solvent gradient conditions using three different mobile phase compositions (acidic, basic and neutral). Each column was checked with a two-component test mix at various stages of the evaluation to look for signs of stationary phase collapse. Three zirconia based stationary phases studied exhibited column bleed under temperature-programmed conditions. The other three columns, a polydentate silica column, a polystyrene-divinylbenzene (PS-DVB) polymeric column, and a graphitic carbon column performed well with no evidence of stationary phase degradation. The R.S.D. for the retention times and efficiencies were less than 10% for most conditions, and not more than 15% during the course of the evaluation for each column. The polydentate silica stationary phase was temperature programmed to 100 degrees C, the PS-DVB stationary phase was temperature programmed up to 150 degrees C, and the graphitic carbon column was used with temperature programming up to 200 degrees C. Comparable peak capacities and similar retention behaviors were observed under solvent gradient and temperature-programmed conditions. Temperature programming with dynamic mobile phase preheating can replace solvent gradient analysis without a loss of peak capacity when used with 4.1 or 4.6 mm columns.

Mortality associated with laparotomy-confirmed neonatal spontaneous intestinal perforation: a prospective 5-year multicenter analysis.

BACKGROUND: Spontaneous intestinal perforation (SIP) has been recognized as a distinct disease entity. This study sought to quantify mortality associated with laparotomy-confirmed SIP and to compare it to mortality of laparotomy-confirmed necrotizing enterocolitis (NEC). METHODS: Data were prospectively collected on 177,618 very-low-birth-weight (VLBW, 401-1500g) neonates born between January 2006 and December 2010 admitted to US hospitals participating in the Vermont Oxford Network (VON). SIP was defined at laparotomy as a focal perforation of the intestine without features suggestive of NEC or other intestinal abnormalities. The primary outcome was in-hospital mortality. RESULTS: At laparotomy, 2036 (1.1%) neonates were diagnosed with SIP and 4076 (2.3%) with NEC. Neonates with laparotomy-confirmed SIP had higher mortality (19%) than infants without NEC or SIP (5%, P=0.003). However, laparotomy-confirmed SIP patients had significantly lower mortality than those with confirmed NEC (38%, P<0.0001). Mortality in both NEC and SIP groups decreased with increasing birth weight and mortality was significantly higher for NEC than SIP in each birth weight category. Indomethacin and steroid exposure were more frequent in the SIP cohort than the other two groups (P<0.001). CONCLUSIONS: In VLBW infants, the presence of laparotomy-confirmed SIP increases mortality significantly. However, laparotomy-confirmed NEC mortality was double that of SIP. This relationship is evident regardless of birth weight. The variant mortality of laparotomy-confirmed SIP versus laparotomy-confirmed NEC highlights the importance of differentiating between these two diseases both for clinical and research purposes.

Citrulline levels following proximal versus distal small bowel resection.

PURPOSE: Citrulline, a nonprotein amino acid synthesized by enterocytes, is a biomarker of bowel length and the capacity to wean from parenteral nutrition. However, the potentially variant effect of jejunal versus ileal excision on plasma citrulline concentration [CIT] has not been studied. This investigation compared serial serum [CIT] and mucosal adaptive potential after proximal versus distal small bowel resection. METHODS: Enterally fed Sprague-Dawley rats underwent sham operation or 50% small bowel resection, either proximal (PR) or distal (DR). [CIT] was measured at operation and weekly for 8 weeks. At necropsy, histologic features reflecting bowel adaptation were evaluated. RESULTS: By weeks 6-7, [CIT] in both resection groups significantly decreased from baseline (P<0.05) and was significantly lower than the concentration in sham animals (P<0.05). There was no difference in [CIT] between PR and DR at any point. Villus height and crypt density were higher in the PR than in the DR group (P≤0.02). CONCLUSION: [CIT] effectively differentiates animals undergoing major bowel resection from those with preserved intestinal length. The region of intestinal resection was not a determinant of [CIT]. The remaining bowel in the PR group demonstrated greater adaptive potential histologically. [CIT] is a robust biomarker for intestinal length, irrespective of location of small intestine lost.

Mortality and management of surgical necrotizing enterocolitis in very low birth weight neonates: a prospective cohort study.

BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of death in very low birth weight (VLBW) neonates. The overall mortality of NEC is well documented. However, those requiring surgery appear to have increased mortality compared with those managed medically. The objective of this study was to establish national birth-weight-based benchmarks for the mortality of surgical NEC and describe the use and mortality of laparotomy vs peritoneal drainage. STUDY DESIGN: There were 655 US centers that prospectively evaluated 188,703 VLBW neonates (401 to 1,500 g) between 2006 and 2010. Survival was defined as living in-hospital at 1-year or hospital discharge. RESULTS: There were 17,159 (9%) patients who had NEC, with mortality of 28%; 8,224 patients did not receive operations (medical NEC, mortality 21%) and 8,935 were operated on (mortality 35%). On multivariable regression, lower birth weight, laparotomy, and peritoneal drainage were independent predictors of mortality (p < 0.0001). In surgical NEC, a plateau mortality of around 30% persisted despite birth weights >750 g; medical NEC mortality fell consistently with increasing birth weight. For example, in neonates weighing 1,251 to 1,500 g, mortality was 27% in surgical vs 6% in medical NEC (odds ratio [OR] 6.10, 95% CI 4.58 to 8.12). Of those treated surgically, 6,131 (69%) underwent laparotomy only (mortality 31%), 1,283 received peritoneal drainage and a laparotomy (mortality 34%), and 1,521 had peritoneal drainage alone (mortality 50%). CONCLUSIONS: Fifty-two percent of VLBW neonates with NEC underwent surgery, which was accompanied by a substantial increase in mortality. Regardless of birth weight, surgical NEC showed a plateau in mortality at approximately 30%. Laparotomy was the more frequent method of treatment (69%) and of those managed by drainage, 46% also had a laparotomy. The laparotomy alone and drainage with laparotomy groups had similar mortalities, while the drainage alone treatment cohort was associated with the highest mortality.

Report of 111 consecutive patients enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: a retrospective observational study.

BACKGROUND: The International Serial Transverse Enteroplasty (STEP) Data Registry is a voluntary online database created in 2004 to collect information on patients undergoing the STEP procedure. The aim of this study was to identify preoperative factors that are significantly associated with transplantation or death or attainment of enteral autonomy after STEP. STUDY DESIGN: Data were collected from September 2004 to January 2010. Univariate and multivariate logistic regression analyses were applied to determine the predictors of transplantation or death or enteral autonomy post-STEP. Time to reach full enteral nutrition was estimated using a Kaplan-Meier curve. RESULTS: Fourteen of the 111 patients in the Registry were excluded due to inadequate follow-up. Of the remaining 97 patients, 11 patients died and 5 progressed to intestinal transplantation. On multivariate analysis, higher direct bilirubin and shorter pre-STEP bowel length were independently predictive of progression to transplantation or death (p = 0.05 and p < 0.001, respectively). Of the 78 patients who were 7 days of age or older and required parenteral nutrition at the time of STEP, 37 (47%) achieved enteral autonomy after the first STEP. Longer pre-STEP bowel length was also independently associated with enteral autonomy (p = 0.002). Median time to reach enteral autonomy based on Kaplan-Meier analysis was 21 months (95% CI, 12-30). CONCLUSIONS: Overall mortality post-STEP was 11%. Pre-STEP risk factors for progressing to transplantation or death were higher direct bilirubin and shorter bowel length. Among patients who underwent STEP for short bowel syndrome, 47% attained full enteral nutrition post-STEP. Patients with longer pre-STEP bowel length were significantly more likely to achieve enteral autonomy.

Low serum citrulline concentration correlates with catheter-related bloodstream infections in children with intestinal failure.

BACKGROUND: Serum citrulline concentration is used as a biomarker of enterocyte mass and enteral tolerance, and low serum concentrations are correlated with bacteremia in immunosuppressed adults undergoing hematopoietic stem cell transplant. The authors sought to determine if citrulline was associated with the development of catheter-related bloodstream infections (CRBSIs) in children with intestinal failure. METHODS: Data were reviewed from 66 children treated in a multidisciplinary intestinal rehabilitation program, who had serum concentration citrulline measured between January 2007 and August 2009. All patients had a diagnosis of intestinal failure requiring parenteral nutrition (PN) support. Exclusion criteria included central venous catheter in situ <30 days, creatinine clearance <20 mL/minute, or a history of organ transplant/immunosuppression. RESULTS: A total of 15 patients were excluded because of the above criteria. In this cohort of 51 patients, 26 (51%) developed CRBSIs. Both groups were similar in terms of gestational age, diagnosis, nutrition status, and biochemical liver function tests. The mean (± standard deviation [SD]) minimum serum citrulline concentration was significantly lower in patients who developed CRBSIs (6.7 ± 4.6 µmol/L) than in those who did not (11.3 ± 6.4 µmol/L, P = .004). Multivariate logistic regression analysis identified lower minimum serum citrulline concentration and longer central venous catheter duration as independently associated with CRBSI (P = .003 and P = .038, respectively). CONCLUSIONS: Low serum citrulline concentration and longer central venous catheter time are independently associated with CRBSI in children with intestinal failure. Serum citrulline concentration may be a useful biomarker to identify patients with intestinal failure who are at high risk of developing a CRBSI.

Autologous intestinal reconstruction surgery.

Multidisciplinary management of intestinal failure has progressed over the last 30 years, facilitating the transition to enteral autonomy in many pediatric patients. However, there remains a select group of patients who reach a plateau in advancement of their enteral nutrition. Numerous surgical options have been pursued to attempt to slow intestinal transit, taper dilated bowel, and promote intestinal adaptation. The purpose of this chapter is to review the current literature on autologous intestinal reconstruction surgery, including a brief historical perspective, descriptions of procedures, and reported surgical outcomes.

Efficacy of ethanol locks in reducing central venous catheter infections in pediatric patients with intestinal failure.

PURPOSE: We sought to determine whether a regimen of 70% ethanol locks could reduce the rate of central venous catheter (CVC) infections in parenteral nutrition-dependent children with intestinal failure. METHODS: We performed a retrospective review of 23 parenteral nutrition-dependent children in our multidisciplinary intestinal rehabilitation clinic who started ethanol lock therapy between September 2007 and June 2009. The treatment regimen consisted of a 70% ethanol lock instilled 3 times per week in each catheter lumen. The rate of CVC infections before and after initiation of ethanol lock therapy was compared using the Wilcoxon signed ranks test with significance set at P < .05. RESULTS: The most common diagnoses leading to intestinal failure were necrotizing enterocolitis (26.1%), gastroschisis (21.7%), and intestinal atresia (14.3%). Ethanol locks were well tolerated with no reported adverse side effects. The infection rate decreased from 9.9 per 1000 catheter days prior to initiation of ethanol locks to 2.1 per 1000 catheter days during therapy (P = .03). CONCLUSIONS: A regimen of ethanol lock therapy administered three days per week appears to be a safe and effective means of reducing the rate of CVC infections in parenteral nutrition-dependent children with intestinal failure.

Relationship between biopsy-proven parenteralnutrition-associated liver fibrosis and biochemical cholestasis in children with short bowel syndrome.

PURPOSE: The aim of the study was to determine the frequency of biochemical cholestasis (direct bilirubin [DB] > or =2 mg/dL) in children with short bowel syndrome and biopsy-proven parenteral nutrition (PN)-associated liver disease and to define predictive factors for the occurrence and degree of hepatic fibrosis. METHODS: After institutional review board approval, a retrospective review was conducted of patients followed by 2 multidisciplinary intestinal rehabilitation programs between January 1, 2000, and September 30, 2008. Inclusion criteria were exposure to PN (>30 days) and having undergone a liver biopsy. Liver biopsy specimens were graded from 0 to 3 based upon degree of fibrosis in the pathology report. The most recent DB within 10 days before biopsy was recorded. RESULTS: A total of 66 children underwent 83 liver biopsy procedures. The most common diagnoses included necrotizing enterocolitis (NEC) (36.4%), gastroschisis (22.7%), and intestinal atresia (15.1%). Median age at biopsy was 6.1 months with a median duration of PN of 4.7 months. Of the patients, 70.3% had a history of exposure to parenteral omega-3 lipid emulsion. Of the liver biopsy specimens, 89% (74/83) demonstrated some degree of fibrosis (fibrosis scale 1-3), including 9.6% (8/83) with evidence of cirrhosis. 83% of biopsies without fibrosis and 55% of biopsies with fibrosis were obtained in patients without evidence of biochemical cholestasis (P = .20). Three (37%) of the 8 patients with cirrhosis on liver biopsy had no evidence of biochemical cholestasis. Univariate analysis identified only gestational age (GA) at birth as significantly associated with the degree of liver fibrosis (P = .03). A multivariate logistic regression model accounting for multiple biopsy procedures in patients revealed that GA was a predictor of fibrosis only in patients with a diagnosis other than NEC (P < .01). CONCLUSIONS: In children with short bowel syndrome, biochemical cholestasis does not reflect the presence or degree of histologically confirmed PN-associated liver fibrosis. Careful follow-up, combined with further refinement of diagnostic and hepatoprotective strategies, may be warranted in this patient population.

Persistent alanine aminotransferase elevations in children with parenteral nutrition-associated liver disease.

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) is a serious condition affecting many children with short bowel syndrome. The aim of this study was to longitudinally assess serum alanine aminotransferase (ALT), a marker for hepatocyte injury, in enterally fed children with PNALD. METHODS: Retrospective chart review of 31 patients treated from 1999 to 2006 by the Center for Advanced Intestinal Rehabilitation at Children's Hospital Boston (Mass). Inclusion criteria included PN duration of greater than 3 months with subsequent tolerance of full enteral nutrition and evidence of PN-associated liver injury. Time to normalize ALT and direct bilirubin were estimated using Kaplan-Meier and Cox proportional hazards methods. RESULTS: Mean age PN cessation was 6 months (range, 2-14 months). Median PN duration was 18 weeks (interquartile range [IQR], 13-33 weeks), and median follow-up was 24 weeks (IQR, 14-48 weeks). After transition to full enteral nutrition, 74% of children normalized direct bilirubin, whereas only 50% normalized ALT. Kaplan-Meier median time to direct bilirubin and ALT normalization were 13 weeks and 35 weeks, respectively (P = .001). CONCLUSION: Children with PNALD who have achieved PN independence have persistent ALT elevation despite normal direct bilirubin levels. This implies that hepatic injury may be ongoing beyond the time of bilirubin normalization in this cohort of patients.

Fcgamma receptor transmembrane domains: role in cell surface expression, gamma chain interaction, and phagocytosis.

We constructed chimeric receptors to dissect the role of the transmembrane (TM) domain in cell surface expression of and phagocytosis by the gamma chain-dependent Fcgamma receptors FcgammaRIIIA and FcgammaRI. FcgammaR chimeras containing the TM and cytoplasmic (CY) domains of the gamma chain were expressed on the cell surface and mediated an efficient phagocytic signal. In contrast, chimeras containing the FcgammaRIIIA TM were poorly expressed. Receptors containing the FcgammaRI TM and the gamma chain CY but lacking the gamma chain TM also were expressed efficiently and mediated phagocytosis, suggesting that a gamma chain dimer induced by the gamma chain TM is not required for efficient phagocytosis. Cotransfection of FcgammaRI or FcgammaRIIIA with the chimera CD8-gamma-gamma (EC-TM-CY) resulted in FcgammaR cell surface expression and phagocytosis, whereas CD8-CD8-gamma, whose TM does not associate with FcgammaR, allowed cell surface expression of (but not phagocytosis by) FcgammaRI. CD8-CD8-gamma also did not allow surface expression of FcgammaRIIIA. Exchanging FcgammaRI and CD8 TMs indicated that the C-terminal 11 amino acids of the FcgammaRI TM are essential for association of FcgammaRI with the gamma chain and phagocytosis. The data indicate that specific sequences in the FcgammaRIIIA and FcgammaRI TMs govern their different interactions with the gamma chain in cell surface expression and phagocytosis and that gamma chain TM sequences are not required for gamma chain-mediated phagocytosis. The data identify a specific region of the FcgammaRI TM and its asparagine as important for FcgammaRI cell surface expression in the absence of the gamma chain and for distinguishing the FcgammaRI and FcgammaRIIIA phenotypes.