Dissociation of Hypertension and Renal Damage After Cessation of High-Salt Diet in Dahl Rats.

BACKGROUND: Every year, thousands of patients with hypertension reduce salt consumption in an effort to control their blood pressure. However, hypertension has a self-sustaining character in a significant part of the population. We hypothesized that chronic hypertension leads to irreversible renal damage that remains after removing the trigger, causing an elevation of the initial blood pressure. METHODS: Dahl salt-sensitive rat model was used for chronic, continuous observation of blood pressure. Rats were fed a high salt diet to induce hypertension, and then the diet was switched back to normal sodium content. RESULTS: We found that developed hypertension was irreversible by salt cessation: after a short period of reduction, blood pressure grew even higher than in the high-salt phase. Notably, the self-sustaining phase of hypertension was sensitive to benzamil treatment due to sustaining epithelial sodium channel hyperactivity, as shown with patch-clamp analysis. Glomerular damage and proteinuria were also irreversible. In contrast, some mechanisms, contributing to the development of salt-sensitive hypertension, normalized after salt restriction. Thus, flow cytometry demonstrated that dietary salt reduction in hypertensive animals decreased the number of total CD45+, CD3+CD4+, and CD3+CD8+ cells in renal tissues. Also, we found tubular recovery and improvement of glomerular filtration rate in the postsalt period versus a high-salt diet. CONCLUSIONS: Based on earlier publications and current data, poor response to salt restriction is due to the differential contribution of the factors recognized in the developmental phase of hypertension. We suggest that proteinuria or electrolyte transport can be prioritized over therapeutic targets of inflammatory response.

Biocompatible Cable Ties Are an Alternative to Metal Stabilizers for Bar Securement During Minimally Invasive Pectus Excavatum Repair.

Background: Bar stabilization during minimally invasive pectus excavatum repair (MIRPE) is critical to avoid dislodgement. Multiple techniques are described including stabilizers, wires, and sutures. This retrospective study compared bar movement and outcomes between existing techniques and ZipFix™, a biocompatible cable tie. Methods: Patients ≤20 years of age who underwent MIRPE with ZipFix between January 2021 and September 2022 were compared with historical controls who underwent repair by same surgeons between January 2018 and December 2020 using stabilizers or polydioxanone suture (PDS). Demographics, clinical details, and outcomes were compared using Kruskal-Wallis and chi-square tests. Results: Of the 116 patients who underwent repair, 45 had bars secured with ZipFix (39%) and 71 (61%) were historical controls (35 stabilizer, 36 PDS). Median (interquartile range) age was 15 (14-16) years and Haller index was 3.9 (3.6-4.5). Nine (8%) patients required two bars. Haller index and use of second bar were comparable between stabilization techniques (P > .05). In total, 49 patients (40%) reported any pain at 1 month and this was similar between stabilization techniques (P = .45). Median bar movement was greater for bars secured with PDS than with ZipFix or stabilizers at 1 month (5.5 versus 2.3 versus 3.3°, P = .010) and last follow-up (6.5 versus 2.1 versus 3.6°, P < .001). One patient whose bar was secured with PDS required revision for dislodgement. Conclusion: Pectus bar stabilization with ZipFix is a safe alternative to metal stabilizers and both techniques are superior to suture stabilization alone. The use of ZipFix may be preferred given its lower cost and ease of use.

Role of Alström syndrome 1 in the regulation of glomerular hemodynamics.

Inactivating mutations in the ALMS1 gene in humans cause Alström syndrome, characterized by the early onset of obesity, insulin resistance, and renal dysfunction. However, the role of ALMS1 in renal function and hemodynamics is unclear. We previously found that ALMS1 is expressed in thick ascending limbs, where it binds and decreases Na+-K+-2Cl- cotransporter activity. We hypothesized that ALMS1 is expressed in macula densa cells and that its deletion enhances tubuloglomerular feedback (TGF) and reduces glomerular filtration rate (GFR) in rats. To test this, homozygous ALMS1 knockout (KO) and littermate wild-type Dahl salt-sensitive rats were studied. TGF sensitivity was higher in ALMS1 KO rats as measured by in vivo renal micropuncture. Using confocal microscopy, we confirmed immunolabeling of ALMS1 in macula densa cells (nitric oxide synthase 1 positive), supporting a role for ALMS1 in TGF regulation. Baseline glomerular capillary pressure was higher in ALMS1 KO rats, as was mean arterial pressure. Renal interstitial hydrostatic pressure was lower in ALMS1 KO rats, which is linked to increased Na+ reabsorption and hypertension. GFR was reduced in ALMS1 KO rats. Seven-week-old ALMS1 KO rats were not proteinuric, but proteinuria was present in 18- to 22-wk-old ALMS1 KO rats. The glomerulosclerosis index was higher in 18-wk-old ALMS1 KO rats. In conclusion, ALMS1 is involved in the control of glomerular hemodynamics in part by enhancing TGF sensitivity, and this may contribute to decreased GFR. Increased TGF sensitivity, enhanced glomerular capillary pressure, and hypertension may lead to glomerular damage in ALMS1 KO rats. These are the first data supporting the role of ALMS1 in TGF and glomerular hemodynamics.NEW & NOTEWORTHY ALMS1 is a novel protein involved in regulating tubuloglomerular feedback (TGF) sensitivity, glomerular capillary pressure, and blood pressure, and its dysfunction may reduce renal function and cause glomerular damage.

Probenecid slows disease progression in a murine model of autosomal dominant polycystic kidney disease.

Development of autosomal dominant polycystic kidney disease (ADPKD) involves renal epithelial cell abnormalities. Cystic fluid contains a high level of ATP that, among other effects, leads to a reduced reabsorption of electrolytes in cyst-lining cells, and thus results in cystic fluid accumulation. Earlier, we demonstrated that Pkd1RC/RC mice, a hypomorphic model of ADPKD, exhibit increased expression of pannexin-1, a membrane channel capable of ATP release. In the current study, we found that human ADPKD cystic epithelia have higher pannexin-1 abundance than normal collecting ducts. We hypothesized that inhibition of pannexin-1 function with probenecid can be used to attenuate ADPKD development. Renal function in male and female Pkd1RC/RC and control mice was monitored between 9 and 20 months of age. To test the therapeutic effects of probenecid (a uricosuric agent and a pannexin-1 blocker), osmotic minipumps were implanted in male and female Pkd1RC/RC mice, and probenecid or vehicle was administered for 42 days until 1 year of age. Probenecid treatment improved glomerular filtration rates and slowed renal cyst formation in male mice (as shown in histopathology). The mechanistic effects of probenecid on sodium reabsorption and fluid transport were tested on polarized mpkCCDcl4 cells subjected to short-circuit current measurements, and in 3D cysts grown in Matrigel. In the mpkCCDcl4 epithelial cell line, probenecid elicited higher ENaC currents and attenuated in vitro cyst formation, indicating lower sodium and less fluid retention in the cysts. Our studies open new avenues of research into targeting pannexin-1 in ADPKD pathology.

Fellowships and defence engagement: from clinical niches to strategic impact.

Medical fellowships have traditionally developed the individual rather than furthering military or national strategic objectives. This paper describes a medical fellowship with the British Antarctic Survey to illustrate the benefits to the individual, to the military and to wider international defence engagement efforts.By rebranding such fellowships as Defence Healthcare Engagement and by treating international organisations on a par with partner nations, the humble fellowship can facilitate enduring, mutually beneficial healthcare engagement at low cost and with minimal additional resources.

Lack of direct bone effect of tofacitinib, a JAK inhibitor, in juvenile rats and evaluation of the association between offspring growth and femur length.

Bone has recently emerged as a target organ for some Janus kinase (JAK) inhibitors in adult and/or juvenile animal toxicity studies. Oral administration of tofacitinib, a JAK inhibitor, was not associated with clinical or macroscopic effects on bone growth and development in a rat juvenile animal study (JAS) with tofacitinib dosing starting on postnatal day (PND) 21. However, given that previous JAS did not include a targeted evaluation of bone, inclusive of microscopic examination, an additional rat JAS was conducted to further assess this risk. In this subsequent JAS, administration of tofacitinib from PND 7-49 or from PND 21-49 did not result in any direct effects on bone, with no histologic effects on developing bone. The only bone effect in this JAS was nonadverse shorter femur length, which was not considered to be a direct effect of tofacitinib, but rather an indicator of growth delay, as this was associated with lower body weights. There were no effects on femur length or body weight after a 2-month recovery period. To further explore the relationship between body weight and femur length, historical control data were analyzed from control rats in other JAS. This analysis clearly demonstrated that shorter femur length can occur as an indirect effect that is highly associated with lower body weight, consistent with what was observed in the JAS with tofacitinib. These analyses provide a robust and valuable data set to support the interpretation of such data in JAS, and further support the lack of direct effects of tofacitinib on bone growth and development. As with the previously conducted juvenile studies with tofacitinib, the additional JAS did not identify any special JAS-based concerns for use in pediatric patients as young as 2 years of age.

Decreased tubuloglomerular feedback response in high-fat diet-induced obesity.

Obesity increases the risk of renal damage, but the mechanisms are not clear. Normally, kidneys autoregulate to keep the glomerular capillary pressure (PGC), renal blood flow, and glomerular filtration rate in a steady state. However, in obesity, higher PGC, renal blood flow, and glomerular filtration rate are noted. Together, these may lead to glomerular damage. PGC is controlled mainly by afferent arteriole resistance, which, in turn, is regulated by tubuloglomerular feedback (TGF), a vasoconstrictor mechanism. High fat-induced obesity causes renal damage, and this may be related to increased PGC. However, there are no studies as to whether high-fat diet (HFD)-induced obesity affects TGF. We hypothesized that TGF would be attenuated in obesity caused by HFD feeding (60% fat) in Sprague-Dawley rats. Sprague-Dawley rats fed a normal-fat diet (NFD; 12% fat) served as the control. We studied 4 and 16 wk of HFD feeding using in vivo renal micropuncture of individual rat nephrons. We did not observe significant differences in body weight, TGF response, and mean arterial pressure at 4 wk of HFD feeding, but after 16 wk of HFD, rats were heavier and hypertensive. The maximal TGF response was smaller in HFD-fed rats than in NFD-fed rats, indicating an attenuation of TGF in HFD-induced obesity. Baseline PGC was higher in HFD-fed rats than in NFD-fed rats and was associated with higher glomerulosclerosis. We conclude that attenuated TGF and higher PGC along with hypertension in HFD-fed obese Sprague-Dawley rats could explain the higher propensity of glomerular damage observed in obesity.NEW & NOTEWORTHY Reduced tubuloglomerular feedback, higher glomerular capillary pressure, and hypertension in combination may explain the higher glomerular damage observed in high-fat diet-induced obesity.

Post-injury outcomes of children with behavioral health disorders.

BACKGROUND: The impact of Behavioral Health Disorders (BHDs) on pediatric injury is poorly understood. We investigated the relationship between BHDs and outcomes following pediatric trauma. METHODS: We analyzed injured children (age 5-15) from 2014 to 2016 using the Pediatric Trauma Quality Improvement Program. The primary outcome was in-hospital mortality. Univariable and multivariable analyses compared children with and without a comorbid BHD. RESULTS: Of 69,305 injured children, 3,448 (5%) had a BHD. These 3,448 children had a median of 1 [IQR: 1, 1] BHD diagnosis: ADHD (n = 2491), major psychiatric disorder (n = 1037), drug use disorder (n = 250), and alcohol use disorder (n = 29). A higher proportion of injured children with BHDs suffered intentional and penetrating injury. Firearm injuries were more common for BHD patients (3% vs 1%, p<0.001). Children with BHDs were more likely to have an ISS>25 compared to children without (5% vs 3%, p<0.001). While median LOS was longer for BHD patients (2 [1, 3] vs 2 [1, 4], p<0.001), mortality was similar (1% vs 1%, p = 0.76) and complications were less frequent (7% vs 8%, p = 0.002). BHD was associated with lower risk of mortality (OR 0.45, 95%CI [0.30, 0.69]) after controlling for age, sex, race, trauma type, and injury intent and severity. CONCLUSION: Children with BHDs experienced lower in-hospital mortality risk after traumatic injury despite more severe injury upon presentation. Intentional and penetrating injuries are particularly concerning, and future work should assess prevention efforts in this vulnerable group.

Thoracic paravertebral nerve catheter reduces postoperative opioid use for vertebral body tethering patients.

PURPOSE: Vertebral body tethering is increasingly being performed, yet postoperative pain management has not yet been optimized. We sought to determine whether the addition of a thoracic paravertebral block in addition to a standard multimodal postoperative pain management program could provide greater pain relief, reduced analgesic requirement, and reduced length of stay. METHODS: Patients who underwent VBT at a single tertiary referral center were retrospectively reviewed. All patients received a single-shot intrathecal (IT) injection at the completion of the procedure in addition to a standardized multimodal pain management program. 45 patients received a thoracic paravertebral catheter with lidocaine infusion (TPVB) which was left in place for 4-6 days, whereas 24 control patients did not have a TPVB. Length of stay, maximum postoperative Numeric Pain Intensity Scale (NPIS), and total dose of opioids, ibuprofen, ketorolac and acetaminophen administered during hospitalization were evaluated. RESULTS: 69 patients met inclusion criteria. The mean cumulative dose of opioids administered during hospitalization was 148 oral morphine milligram equivalent (MME) in the control group vs. 47 MME in the TPVB group (p < 0.0001). Severe postoperative NPIS of ≥ 7 was reported in 9 out of the 24 control patients (38%) and in 13 out of the 45 patients (29%) who received a TPVB in addition to the standardized care (p = 0.46). There was no significant difference in the mean cumulative dose of NSAIDs (ibuprofen, ketorolac) consumed by the control group compared to the TPVB group (2632 mg vs. 1630 mg, p = 0.77). Mean length of stay in the control group was 3.8 vs. 3.0 days in the TPVB group (p < 0.001). There were no major complications associated with use of the TPVB. CONCLUSION: In this series compared to controls, patients treated with a TPVB had reduced postoperative requirement of opioids and decreased length of hospital stay.

Concordance of 3 alternative teratogenicity assays with results from corresponding in vivo embryo-fetal development studies: Final report from the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) DruSafe working group 2.

An IQ DruSafe working group evaluated the concordance of 3 alternative teratogenicity assays (rat whole embryo culture, rWEC; zebrafish embryo culture, ZEC; and murine embryonic stem cells, mESC) with findings from rat or rabbit embryo-fetal development (EFD) studies. Data for 90 individual compounds from 9 companies were entered into a database. In vivo findings were deemed positive if malformations or embryo-fetal lethality were reported in either species. Each company used their own criteria for deciding whether the alternative assay predicted the in vivo findings. Standard concordance parameters were calculated, positive and negative predictive values (PPV and NPV) were adjusted for the aggregate portfolio prevalence of positive compounds (established by a survey of participating companies), and positive and negative likelihood ratios (LR+ and iLR-) were calculated. Of the 3 assays, only rWEC data were robustly predictive, particularly for negative predictions (NPVadj = 92%). However, both LR+ (4.92) and iLR- (4.72) were statistically significant for the rWEC assay. When analyzed separately for rats, the NPVadj and iLR-values for the rWEC assay increased to 96% and 9.75, respectively. These data suggest that a negative rWEC outcome could defer or replace a rat EFD study in certain regulatory settings.

Defining the learning curve in CT-guided navigated thoracoscopic vertebral body tethering.

Estimated blood loss (EBL), anesthesia time, operative time, and length of stay decreased over 67 navigated vertebral body tethering (VBT) surgeries performed in a 5-year period, indicating a steep learning curve. DESIGN: Retrospective review of prospectively collected data. HYPOTHESIS: There would be a significant improvement in the performance of VBT procedures over time at a single tertiary center in terms of perioperative and postoperative outcomes. PURPOSE: Learning a new procedure for surgeons takes time, and previous studies have described improved efficiency as experience grows. VBT procedures are increasingly being performed in the US, but there is limited data regarding the learning curve specifically regarding the use of CT-guided navigation. We sought to assess the learning curve of VBT with respect to estimated blood loss, anesthesia time, operative time, length of stay, percent correction of the major curve at first follow-up. We further sought to characterize change in rates of 90-day complications. METHODS: Pediatric scoliosis patients who underwent thoracic or lumbar CT-guided navigated VBT with a consistent surgical team at a single tertiary referral center between 2015 and 2020 were included. Student t-test was used to assess change in perioperative parameters over time, and also results between first and latest group of 20 patients were compared. RESULTS: 67 patients met inclusion criteria. Estimated blood loss (EBL), operative time, anesthesia time and length of stay significantly decreased over the 5-year study period. Specifically, on comparison of our first 20 patients with our last 20, the former had greater EBL (282 vs 116 ml, p = 0.0005; 8.5% vs 3.6%, p = 0.0024), operative time (4.8 h vs. 3.3 h, p < 0.001), anesthesia time (7.4 h vs. 5.7 h, p = 0.0001), and length of stay (3.7 days vs. 3.2 days, p = 0.019). We also found significant reduction in EBL, operative time, anesthesia time and LOS in patients who underwent VBT surgery after 2019. There was no significant change in the percent correction of the major Cobb angle at first erect imaging or 90-day complications over the 5-year study period or between the various cohorts. CONCLUSION: This series has demonstrated improvements in surgical efficiency for VBT including reduced EBL, operative time, anesthesia time and hospital stay over a 5-year period. This indicates improved surgical technique and outlines the significant learning curve for surgeons who wish to perform this procedure. Improved surgeon training programs and newer instrumentation may reduce this learning curve. TAKE HOME POINT: 67 cases in a 5-year period, VBT procedures performed at a single center had significantly decreased EBL, anesthesia time, operative time, and length of stay, indicating a steep learning curve.

Evolution of pediatric gastrointestinal ulcer disease: Is acute surgical intervention relevant?

BACKGROUND: There is a lack of contemporary data about pediatric gastrointestinal ulcer disease. We hypothesized that ulcers found in immunosuppressed children were more likely to require surgical intervention. METHODS: All children <21 years (n = 129) diagnosed with ulcers at a quaternary hospital from 1990 to 2019 were retrospectively reviewed. Clinical findings and pertinent information were collected. RESULTS: Of 129 cases, 19 (14.7%) were immunosuppressed. Eight were post-transplant; four were diagnosed with post-transplant lymphoproliferative disease (PTLD).  Eight were associated with cancer. Three were both.  Three of 19 immunosuppressed and 28/110 immunocompetent patients were taking acid suppression therapy. Nine immunosuppressed patients required surgical intervention, including all PTLD cases, compared to 14 immunocompetent (47.3% vs 16.4%, p < 0.01). Five patients had duodenal perforation, two had multiple small bowel perforations, and two had uncontrolled bleeding. Of 9/19 immunosuppressed patients, surgical complications included bleeding (n = 7), sepsis (n = 2), ostomy reoperation/readmissions (n = 2), and death within 30 days (n = 2). Two/eighteen immunocompetent patients had bleeding complications. CONCLUSION: Surgical treatment for ulcers remains relevant for pediatric patients. Immunosuppressed patients have more complications, longer hospital stays, and are more likely to need surgical intervention. Efforts should be made for ulcer prophylaxis with a low threshold to investigate epigastric pain in these complex patients. LEVEL OF EVIDENCE: Prognosis Study Level III Evidence.

Does preoperative and intraoperative imaging for anterior vertebral body tethering predict postoperative correction?

PURPOSE: Anterior vertebral body tethering (AVBT) is an emerging approach for idiopathic scoliosis. However, overcorrection and under-correction are common causes of revision surgery, and intraoperative tensioning of the cord is one key component to achieve appropriate curve correction. We sought to determine whether preoperative flexibility radiographs or intraoperative radiographs would predict correction at first erect imaging for scoliosis patients undergoing anterior vertebral body tethering (AVBT). METHODS: Single-center retrospective review. Fifty-one patients with a diagnosis of idiopathic scoliosis underwent anterior body tethering. Preoperative flexibility films and intraoperative radiographs were compared to first erect standing radiographs to determine if there was a correlation in Cobb angle. RESULTS: Preoperative major Cobb angle measured 52° ± 9°. Major Cobb angle on bending films was 24° ± 8°. Intraoperative imaging showed correction to a mean of 17° ± 8°. Postoperative first erect standing radiographs showed correction to a mean of 26° ± 10°. The mean difference in major Cobb angle between intraoperative radiograph and a first erect radiograph was 10° ± 4°, whereas the mean difference from preoperative bending radiograph at first erect was 2° ± 7°. Thus, correction on preoperative flexibility films correlated with the first erect radiograph. CONCLUSION: Preoperative bending radiographs provide a reasonable estimate of postoperative correction for patients undergoing AVBT with tensioning of the cord. Surgeons should expect the major Cobb angle to increase on first erect radiographs compared to intraoperative radiographs. These findings may guide patient selection and assist surgeons in achieving appropriate correction intraoperatively.

Initial experience with transanal proctectomy in children.

BACKGROUND: The use of transanal proctectomy may have particular advantages for pediatric patients with small pelvic working space. We report short-term outcomes of transanal completion proctectomy (taCP) during surgery for inflammatory bowel disease. METHODS: All patients (age≤19) underwent taCP from January 1, 2018 to December 31, 2019. Prior total abdominal colectomy (TAC) was performed using a single-incision technique. At operation, patients underwent single-incision laparoscopy with taCP. Patient demographics, pre and perioperative details, and postoperative complications were abstracted. RESULTS: Seven patients (n = 6) with a median age of 18 years [Range: 13-19] were included in this initial series. All patients had a prior TAC with end-ileostomy with taCP occurring a median of 6 [Range: 3-89] months after TAC. Six of 7 had a diagnosis of ulcerative colitis (UC) while 1 patient had Crohn's colitis. For patients with UC, taCP was part of an ileal pouch-anal anastomosis with the majority (n = 4) proceeding as a modified-two stage and the remaining (n = 2) a three-stage approach. Single-incision laparoscopy through the prior ileostomy site was used in all IPAA patients. Median operative time was 226 [Range: 150-264] minutes with no conversions to more invasive technique. Median hospital length of stay (LOS) was 5 [Range: 2-8] days. In-hospital complications occurred in two patients who had watery diarrhea that prolonged LOS but resolved postdischarge. One patient was readmitted for bowel obstruction that resolved with placement of red rubber catheter at the ileostomy site. Of the 4 patients with a functioning ileal pouch, 1 patient reported 6-10 bowel movements per day, while 3 others reported ≤5 bowel movements per day. Half (n = 2) reported 1-2 nocturnal bowel movements at their first postoperative visit. No patients reported soiling or leakage, though one patient had a single episode of incontinence. CONCLUSION: In this pilot series, transanal proctectomy was effective and safe. Future work should compare traditional MIS completion proctectomy to taCP for applications in pediatric inflammatory bowel disease. TYPE OF STUDY: Case series. LEVEL OF EVIDENCE: IV.

A Comparison of Single-Incision Versus Multiport Laparoscopic Splenectomy in Children.

Background: Although single-incision endoscopic splenectomy (SIES-Sp) has been shown to be feasible and safe, few have compared the SIES-Sp with multiport laparoscopic splenectomy (MPLS). The purpose of this study was to compare the two techniques in children undergoing total splenectomy. Materials and Methods: We reviewed all children (age <18 years) who underwent minimally invasive total splenectomy at a single tertiary referral center from January 1, 2000 to January 1, 2019. The primary outcome was complication rate 30 days after discharge defined by maximum Clavien-Dindo score. Secondary outcomes included conversion, operative time, hospital length of stay, postoperative pain scores, and readmission within 30 days of discharge. SIES-Sp and MPLS were compared using univariate analysis. Results: Of 48 children undergoing laparoscopic total splenectomy, 60% (n = 29) were SIES-Sp and 40% (n = 19) were MPLS. Subjects were 48% female (n = 23). Common diagnoses were idiopathic thrombocytopenic purpura (33% [n = 16]), hereditary spherocytosis (29% [n = 14]), and other congenital hemolytic anemias (23% [n = 11]). There were no differences in age, gender, or diagnosis between groups (all P > .05). One in three cases involved additional procedures. Spleens were smaller in both greatest dimension (13.0 cm versus 16.4 cm) and weight (156.5 g versus 240.0 g) in SIES-Sp compared with MPLS patients (both P < .05). Readmission and reoperation rates were similar (both P > .05). Complications occurred in 7% (n = 2) of SIES-Sp and in 11% (n = 2) of MPLS patients (P > .99). Severe complications included: cardiac arrest in 1 SIES-Sp patient and bleeding requiring reoperation in 1 MPLS patient. Conclusion: SIES-Sp is a safe alternative to the traditional MPLS for children. Additional procedures do not preclude a less invasive approach, but larger spleens may present a challenge.

The incidence of venous thromboembolism in children following colorectal resection for inflammatory bowel disease: A multi-center study.

BACKGROUND/PURPOSE: Children with inflammatory bowel disease (IBD) have increased risk for venous thromboembolism (VTE). We sought to determine incidence and risk factors for postoperative VTE in a multicenter cohort of pediatric patients undergoing colorectal resection for IBD. METHODS: Retrospective review of children ≤18 years who underwent colorectal resection for IBD from 2010 to 2016 was performed at four children's hospitals. Primary outcome was VTE that occurred between surgery and last follow-up. Factors associated with VTE were determined using univariable and multivariable analyses. RESULTS: Two hundred seventy-six patients were included with median age 15 years [13,17]. Forty-two children (15%) received perioperative VTE chemoprophylaxis, and 88 (32%) received mechanical prophylaxis. DVT occurred in 12 patients (4.3%) at a median of 14 days postoperatively [8,147]. Most were portomesenteric (n = 9, 75%) with the remaining catheter-associated DVTs in extremities (n = 3, 25%). There was no association with chemoprophylaxis (p > 0.99). On Cox regression, emergent procedure [HR 18.8, 95%CI: 3.18-111], perioperative plasma transfusion [HR 25.1, 95%CI: 2.4-259], and postoperative infectious complication [HR 10.5, 95%CI: 2.63-41.8] remained predictive of DVT. CONCLUSION: Less than 5% of pediatric IBD patients developed postoperative VTE. Chemoprophylaxis was not protective but rarely used. Patients with risk factors identified in this study should be monitored or given prophylaxis for VTE. LEVEL OF EVIDENCE: Treatment Study, Level III.

The effect of diversion on readmission following ileal pouch-anal anastomosis in children.

BACKGROUND: Readmission rates as high as 20% have been reported after ileal pouch-anal anastomosis (IPAA) in children, with obstruction and dehydration as the most commonly listed reasons. We hypothesized that a diverting ileostomy contributes to unplanned readmission after IPAA creation. METHODS: Children (age <18) who underwent IPAA creation from January 2007 to August 2018 at two affiliated institutions were reviewed. Patient demographics, operative details, and post-operative length of stay (LOS) were abstracted. Unplanned readmission within 30 days and details on patient readmission were reviewed. RESULTS: Ninety-three patients (57% female) with a median age of 15 years (range: 18 months-17 years) underwent IPAA. Indications for IPAA included ulcerative colitis (n = 63; 68%), familial adenomatous polyposis (n = 24; 26%), indeterminate colitis (n = 5; 5%), and total colonic Hirschsprung's (n = 1; 1%). Sixty-one (66%) patients were diverted at the time of IPAA creation. Fourteen patients (15%) were readmitted, and reasons for readmission included bowel obstruction (n = 9; 64%), dehydration (n = 2; 14%), anastomotic leak (n = 2; 14%), and gastrointestinal (GI) bleeding (n = 1; 6%). Patients with a diverting ileostomy at the time of IPAA were more often readmittted than patients who were not diverted (21% vs 3%, p = 0.03). Further, 10 (71%) of the readmitted patients had complications attributable to their ileostomy. In patients readmitted for obstructive symptoms, six (67%) required red rubber catheter insertion for resolution, two (22%) patients required reoperation for obstructions at the level of the stoma, and one (11%) resolved with bowel rest alone. CONCLUSION: Readmission following IPAA creation in children is often secondary to preventable issues related to diverting ileostomy. Surgeons should carefully consider the necessity of diversion. When it is necessary, particular attention to fascial aperture size and post-discharge initiatives to reduce dehydration may reduce readmission rates. LEVEL OF EVIDENCE: Level III.

Open versus thoracoscopic thymectomy for juvenile myasthenia gravis.

BACKGROUND: Juvenile myasthenia gravis (JMG) is an antibody mediated autoimmune disorder that manifests as progressive voluntary muscle weakness and fatigue. In medically refractory cases, thymectomy has been shown to abrogate symptoms and reduce glucocorticoid dependence. While transcervical or transsternal incisions have been the traditional approach, adult trends now favor thoracoscopic thymectomy. Little data exist to support this approach in children. METHODS: A retrospective review of all patients younger than 20 years of age who underwent a thymectomy for JMG at two pediatric institutions between 2001 and 2018 was performed. Children were divided into either an open (transcervical or transsternal) or thoracoscopic group and baseline characteristics, perioperative, and postoperative outcomes were compared. RESULTS: Thirty-four thymectomies were performed during the 18-year study period; 18 via an open and 16 via a thoracoscopic approach. The operative time was shorter for open procedures compared thoracoscopic ones (108 ±â€¯49 and 145 ±â€¯43 min, respectively, p = 0.025). Thoracoscopic thymectomy was associated with less intraoperative blood loss (5.5 ±â€¯6.0 vs 55 ±â€¯67 ml, p = 0.007), decreased duration of postoperative intravenous narcotic use (5.0 ±â€¯1.5 vs 20 ±â€¯23 h, p = 0.018), and a shorter length of hospitalization (1.7 ±â€¯1.0 vs 2.7 ±â€¯1.1 days, p = 0.009). No perioperative complication occurred in either group. Clinical improvement was reported in 94% of children in both groups. CONCLUSIONS: Thoracoscopic thymectomy in children is a safe and effective surgical technique for the treatment of JMG. Increased acceptance of this minimally invasive approach by children, families, and referring neurologists may enable earlier surgical intervention. TYPE OF STUDY: Clinical research paper. LEVEL OF EVIDENCE: III.