Botulinum Toxin Enhanced Foker Process for Long Gap Esophageal Atresia.

BACKGROUND: The traction-induced esophageal growth (Foker) process for the treatment of long gap esophageal atresia (LGEA) relies on applying progressive tension to the esophagus to induce growth. Due to its anti-fibrotic and muscle-relaxing properties, we hypothesize that Botulinum Toxin A (BTX) can enhance traction-induced esophageal growth. METHODS: A retrospective two-center cohort study was conducted on children who underwent a BTX-enhanced Foker process for LGEA repair from 2021 to 2023. BTX (10 units/ml, 2 units/kg, per esophageal pouch) was applied at the time of traction initiation. Time on traction, complications, and anastomotic outcomes were compared against historical controls (Foker process without BTX) from 2014 to 2021. RESULTS: Twenty infants (LGEA type A:12, B:4, C:4; 35% reoperative; median [IQR] age 3 [2-5] months), underwent BTX-enhanced Foker process (thoracotomy with external traction: 9; minimally invasive [MIS] multi-staged internal traction: 11). Mean gap lengths were similar between BTX-enhanced external and external traction control patients (mean [SD], 50.6 mm [12.6] vs. 44.5 mm [11.9], p = 0.21). When compared to controls, the BTX-enhanced external traction process was significantly faster (mean [SD], 12.1 [1.6] days vs. 16.6 [13.2] without BTX, p = 0.04) despite similar preoperative gap lengths. There was no difference in time on traction for those undergoing a minimally invasive process. There were no significant differences in complications or anastomotic outcomes in either cohort. CONCLUSION: Botulinum toxin may play a role in accelerating the traction-induced esophageal growth process for LGEA repair. Minimizing time on traction can decrease sedation and paralysis burden while on external traction. Further studies are needed to elucidate the effects of BTX on the esophagus. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective, Two-center, Cohort study.

Effect of citizenship status on access to pediatric liver and kidney transplantation.

Transplantation of non-US citizen residents remains controversial. We evaluate national trends in transplant activity among pediatric noncitizen residents (PNCR). Pediatric liver and kidney transplant data were obtained from the Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients. Data on transplanted organs, region, waitlist additions, procedures, and citizenship status were analyzed from 2012-2022. Rates of PNCR transplantation activity were compared with population rates from the US Census Bureau. On average, 713 ± 47 pediatric liver and 1039 ± 51 kidney patients were added to the waitlist, with 544 ± 32 liver and 742 ± 33 kidney transplants performed annually. Of these, PNCR comprised 1.5% and 3.3% of liver and kidney waitlist additions and 1.5% and 2.9% of liver and kidney transplant procedures, respectively. There were no significant changes in waitlist or transplant activity nationwide over the study period. There was a significant geographic variation in the percentage of waitlist additions and transplants across the United Network for Organ Sharing regions among the PNCR for liver and kidney transplantation. This is the first study to evaluate national trends in transplantation activity among PNCRs. The significant regional variation in transplantation activity for PNCR may suggest multilevel structural and systemic barriers to transplant accessibility.

A simple solid media assay for detection of synergy between bacteriophages and antibiotics.

The emergence of antibiotic-resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. Although phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation, and purification have enabled a reevaluation of their utility in contemporary clinical medicine. In most phage therapy cases, phages are administered in combination with antibiotics to ensure that patients receive the standard-of-care treatment. Some phages may work cooperatively with antibiotics to eradicate ARB, as often determined using non-standardized broth assays. We sought to develop a solid media-based assay to assess cooperativity between antibiotics and phages to offer a standardized platform for such testing. We modeled the interactions that occur between antibiotics and phages on solid medium to measure additive, antagonistic, and synergistic interactions. We then tested the method using different bacterial isolates and identified a number of isolates where synergistic interactions were identified. These interactions were not dependent on the specific organism, phage family, or antibiotic used. A priori susceptibility to the antibiotic or the specific phage were not requirements to observe synergistic interactions. Our data also confirm the potential for the restoration of vancomycin to treat vancomycin-resistant Enterococcus (VRE) when used in combination with phages. Solid media assays for the detection of cooperative interactions between antibiotics and phages can be an accessible technique adopted by clinical laboratories to evaluate antibiotic and phage choices in phage therapy.IMPORTANCEBacteriophages have become an important alternative treatment for individuals with life-threatening antibiotic-resistant bacteria (ARB) infections. Because antibiotics represent the standard-of-care for treatment of ARB, antibiotics and phages often are delivered together without evidence that they work cooperatively. Testing for cooperativity can be difficult due to the equipment necessary and a lack of standardized means for performing the testing in liquid medium. We developed an assay using solid medium to identify interactions between antibiotics and phages for gram-positive and gram-negative bacteria. We modeled the interactions between antibiotics and phages on solid medium, and then tested multiple replicates of vancomycin-resistant Enterococcus (VRE) and Stenotrophomonas in the assay. For each organism, we identified synergy between different phage and antibiotic combinations. The development of this solid media assay for assessing synergy between phages and antibiotics will better inform the use of these combinations in the treatment of ARB infections.

Association of LDL-cholesterol <1.8 mmol/L and statin use with the recurrence of intracerebral hemorrhage.

BACKGROUND: Recent intensive low-density lipoprotein cholesterol (LDL-C) lowering trials, including FOURIER, ODYSSEY OUTCOMES, and Treat Stroke to Target (TST) trials, have mostly refuted the concern surrounding statin use, LDL-C lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than 10 times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking. AIMS: We aim to investigate the association between LDL-C levels and statin use with ICH risk among ICH survivors, and to determine whether the risk differed with patients' characteristics, especially ICH etiology. METHODS: Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ⩾1.8 mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models. RESULTS: In 502 ICH survivors (mean age = 64.2 ± 13.5 years, mean follow-up LDL-C = 2.2 ± 0.6 mmol/L, 28% with LDL-C <1.8 mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9 ± 2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio (AHR) = 1.07, 95% confidence interval (CI) = 0.57-2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8 mmol/L (AHR = 1.99, 95% CI = 1.06-3.73). This association was predominantly observed in ICH attributable to CAA (AHR = 2.52, 95% CI = 1.06-5.99) and non-statin users (AHR = 2.91, 95% CI = 1.08-7.86). CONCLUSION: The association between post-ICH LDL-C <1.8 mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.

Metastatic pulmonary calcifications after pediatric liver transplantation.

BACKGROUND: Pulmonary calcification (PC) is a rare clinical entity observed following liver transplantation (LT). Most often identified in adults or in patients with concomitant renal failure, PC is rarely reported in children. While the clinical course of PC is largely benign, cases of progressive respiratory failure and death have been reported. Additionally, PC may mimic several other disease processes making diagnosis and management challenging. Currently, little is reported regarding the diagnosis, management, and long-term outcomes of children with PC following LT. METHODS: We performed a retrospective chart review of patients undergoing LT at our institution between 2006 and 2023. We identified two patients who developed PC following LT. Their diagnosis, clinical course, and long-term outcomes are reported. A literature review of the presentation, diagnosis, management, and outcomes of adult and pediatric patients with PC post-LT was also performed. CONCLUSIONS: Pulmonary calcifications are a rare but notable complication after pediatric liver transplantation. Our case series adds to the limited literature on this clinical entity in children but also highlights the fact that effective diagnosis and treatment may be safely accomplished without the use of lung biopsy.

Universal Digital High-Resolution Melt Analysis for the Diagnosis of Bacteremia.

Fast and accurate diagnosis of bloodstream infection is necessary to inform treatment decisions for septic patients, who face hourly increases in mortality risk. Blood culture remains the gold standard test but typically requires approximately 15 hours to detect the presence of a pathogen. We, therefore, assessed the potential for universal digital high-resolution melt (U-dHRM) analysis to accomplish faster broad-based bacterial detection, load quantification, and species-level identification directly from whole blood. Analytical validation studies demonstrated strong agreement between U-dHRM load measurement and quantitative blood culture, indicating that U-dHRM detection is highly specific to intact organisms. In a pilot clinical study of 17 whole blood samples from pediatric patients undergoing simultaneous blood culture testing, U-dHRM achieved 100% concordance when compared with blood culture and 88% concordance when compared with clinical adjudication. Moreover, U-dHRM identified the causative pathogen to the species level in all cases where the organism was represented in the melt curve database. These results were achieved with a 1-mL sample input and sample-to-answer time of 6 hours. Overall, this pilot study suggests that U-dHRM may be a promising method to address the challenges of quickly and accurately diagnosing a bloodstream infection.