Fetal malrotation with midgut volvulus: Prenatal diagnosis and planning.

Introduction: Malrotation of the intestinal tract is a congenital malformation commonly found either incidentally or after affected individuals develop signs and symptoms of intestinal obstruction. Malrotation is prone to midgut volvulus that can cause intestinal obstruction and lead to ischemia and necrosis requiring emergent surgical intervention. Rare instances of in utero midgut volvulus have been reported in the literature and carry a high mortality given the difficulty in establishing a diagnosis prior to development of signs of intestinal ischemia and necrosis. Advancements in imaging have made it possible to diagnose in utero malrotation earlier, raising the question of optimal timing of delivery, especially in cases of prenatally diagnosed midgut volvulus. In these cases, the risks of premature birth must be weighed against the risks of fetal intestinal ischemia and potential fetal demise. Case presentation: This case report details an interesting presentation of intestinal malrotation with suspected midgut volvulus found on prenatal imaging at 33 weeks and 4 days' gestation. This prompted delivery of the infant at 34 weeks and 2 days' gestation with urgent operative management, within 3 hours of life, after diagnosis was confirmed postnatally. Intraoperatively, the infant was confirmed to have midgut volvulus without bowel ischemia, the intestines were reduced, and a Ladd procedure was performed without incident. The infant recovered postoperatively without complication, tolerated advancement to full volume feeds and was discharged on day of life 18. Conclusion: Successful management of fetal malrotation with midgut volvulus may be accomplished by early access to a multi-disciplinary team of professionals, prompt postnatal confirmation of diagnosis, and urgent correction to minimize the risk of complications.

Association of Intercostal Nerve Cryoablation During Nuss Procedure With Complications and Costs.

BACKGROUND: Intercostal nerve cryoablation with the Nuss procedure has been shown to decrease opioid requirements and hospital length of stay; however, few studies have evaluated the impact on complications and hospital costs. METHODS: A retrospective cohort study was performed for all Nuss procedures at our institution from 2016 through 2020. Outcomes were compared across 4 pain modalities: cryoablation with standardized pain regimen (n = 98), patient-controlled analgesia (PCA; n = 96), epidural (n = 36), and PCA with peripheral nerve block (PNB; n = 35). Outcomes collected included length of stay, opioid use, variable direct costs, and postoperative complications. Univariate and multivariate hierarchical regression analysis was used to compare outcomes between the pain modalities. RESULTS: Cryoablation was associated with increased total hospital cost compared with PCA (cryoablation, $11 145; PCA, $8975; P < .01), but not when compared with epidural ($9678) or PCA with PNB ($10 303). The primary driver for increased costs was operating room supplies (PCA, $2741; epidural, $2767; PCA with PNB, $3157; and cryoablation, $5938; P < .01). With multivariate analysis, cryoablation was associated with decreased length of stay (-1.94; 95% CI, -2.30 to -1.57), opioid use during hospitalization (-3.54; 95% CI, -4.81 to -2.28), and urinary retention (0.13; 95% CI, 0.05-0.35). CONCLUSIONS: Cryoablation significantly reduces opioid requirements and length of stay relative to alternative modalities, but it was associated with an increase in total hospital costs relative to PCA, but not epidural or PCA with PNB. Cryoablation was not associated with allodynia or slipped bars requiring reoperation.

Variations in Nuss Procedure Operative Techniques and Complications: A Retrospective Review.

INTRODUCTION: The Nuss procedure is the most common and preferred operative correction of pectus excavatum. Surgeon preference and patient factors can result in variations in Nuss procedure technique. We hypothesize that certain techniques are associated with increased risk of complications. MATERIALS AND METHODS: We performed a single-center retrospective review of Nuss operations from 2016 to 2020. Variations in intraoperative techniques included sternal elevator (SE) use, number of bars placed, and usage of bilateral stabilizing sutures. Patient demographics, intraoperative data, and postoperative outcomes were reported as median with interquartile ranges or percentages. Statistical significance (p < 0.05) was determined with Wilcoxon's rank-sum and chi-square tests. Multivariate analysis was performed to control for introduction of intercostal nerve cryoablation and surgeon volume, and reported as odds ratio with 95% confidence interval. RESULTS: Two hundred and sixty-five patients were identified. Patients repaired with two bars were older with a larger Haller index (HI). Patient demographics were not significantly different for SE or stabilizing suture use. Placement of two bars was associated with significantly increased risk of readmission. Similarly, SE use was associated with increased risk of pleural effusion and readmission. Finally, the use of bilateral stabilizing sutures resulted in less frequent slipped bars without statistical significance. CONCLUSION: Older patients with a larger HI were more likely to need two bars placed to repair pectus excavatum. Placement of multiple bars and SE use are associated with significantly higher odds of certain complications.

Thoracoscopic Resection of Thoracic Inlet Neuroblastic Tumors in Young Children.

Background: Thoracic inlet (TI) tumors are rare, and can be particularly challenging to resect due to proximity to mediastinal vessels and nerves. Traditional resection is typically performed through "trapdoor" or sternoclavicular incisions. The purpose of our study was to evaluate the feasibility and effectiveness of thoracoscopic resection of this group of tumors. Methods: We performed a single-center retrospective chart review for children who presented with TI neuroblastic tumors between 2011 and 2020. Demographics, tumor characteristics, treatment, operative complications, and outcomes were collected and analyzed. Results: Eight patients were identified. The median age at diagnosis was 13 months (interquartile range [IQR] 6-32) with median tumor size at diagnosis of 4.1 cm (IQR 3.6-4.4). Neoadjuvant chemotherapy was given in 50% (4/8) with 38% (3/8) undergoing upfront surgery; 1 patient was observed without chemotherapy or surgery. Ultimately, 6 patients had thoracoscopic resection. For thoracoscopic resections, median intraoperative estimated blood loss was 15 mL (IQR 10-28), median operative room time was 199 minutes (IQR 152-259), and median hospital length of stay was 2 days (IQR 2-3). There were two complications: one recurrent laryngeal nerve injury and one new-onset Horner's syndrome. Complete gross total resection was achieved for all children and there were no recurrences or mortalities with a median follow-up of 3 years. Conclusion: Thoracoscopic resection for TI neuroblastic tumors is feasible with minimal morbidity and can lead to adequate oncological resection.

Intercostal cryoablation during Nuss procedure: A large volume single surgeon's experience and outcomes.

BACKGROUND: Recent studies have shown intercostal cryoablation(IC) during the Nuss procedure decreases hospital length of stay(LOS) and opioid administration. However, few studies have also evaluated the risk of postoperative complications related to IC. METHODS: We performed a single center retrospective analysis of all patients who underwent Nuss procedure by one surgeon from 2/2016 to 2/2020, comparing intraoperative IC to other pain management modalities(non-IC). Primary outcomes were postoperative complications, hospital LOS, and opioid administration. Multivariate analysis was performed with outcomes reported as regression coefficients(RC) or odds ratios(OR) with 95% confidence interval. RESULTS: IC was associated with decreased hospital LOS (RC -1.91[-2.29 to -1.54], less hospital opioid administration (RC -4.28[-5.13 to -3.43]), and less discharge opioid administration (RC -3.82[-5.23 to -2.41]). With respect to postoperative complications, IC decreased the odds of urinary retention (OR 0.16[0.06 to 0.44]); however, increased the odds of slipped bars requiring reoperation (OR 36.65[5.04-266.39]). CONCLUSIONS: Our single surgeon experience controls for surgeon variability and demonstrates intraoperative IC for the Nuss procedure is an effective pain management modality that decreases hospital LOS and opioid use during hospitalization and at discharge; however, it is associated with increased odds of slipped bars requiring reoperation. LEVEL OF EVIDENCE: III.

Preoperative resource utilization prior to minimally invasive repair of pectus excavatum.

BACKGROUND: Preoperative testing to assess the physiologic impact of pectus excavatum is sometimes ordered to meet third-party payor preauthorization requirements. This study describes the utility of physiologic testing prior to minimally invasive repair of pectus excavatum (MIRPE). METHODS: We retrospectively reviewed patients that underwent MIRPE from 1/2012-7/2016 at two academic children's hospitals. Data collected included demographics, insurance, Haller Index (HI), pulmonary function tests (PFTs) and echocardiograms (ECHO) obtained, and preauthorization denials. RESULTS: A total of 360 patients (mean age 15.7 ± 2.0 years; mean HI 4.5 ± 1.5) underwent MIRPE (Hospital 1: 189, Hospital 2: 171). Commercial insurers covered 84% of patients. Hospital 1 obtained more frequent preoperative testing (PFTs: 73% vs 6%, p < 0.0001). Overall, 72% of PFTs were normal with abnormal studies limited to mild findings. Similarly, 85% of ECHOs were normal. Third-party payors more frequently denied preauthorization for MIRPE at Hospital 2 (11% vs. 5%, p = 0.03). CONCLUSIONS: More frequent preoperative testing may decrease initial preauthorization denials for MIRPE; however, this increased utilization of resources may not be necessary as the majority of test results are normal.

Quantifying the effect of resident education on outcomes in pediatric appendicitis.

BACKGROUND/PURPOSE: Surgical residents are involved in the care of patients in a climate where quality of care is an important outcome measure. The purpose of this study was to evaluate the effect of resident involvement on appendectomy outcomes. METHODS: We retrospectively reviewed appendectomies, ages 0-18, from January 2016 to December 2018. Operative time, operative charges, and postoperative outcomes were evaluated for cases with and without a resident. Data were analyzed using Wilcoxon rank and Fisher's exact tests. RESULTS: Of 1842 appendectomies (1267 resident present and 575 no resident present), there was no difference in postoperative stay, abscess formation, readmission, or emergency room visits for simple or complex appendicitis. Operative time was significantly longer for cases of simple appendicitis by 10 min (p = <0.0001) and charges significantly higher by $600 (p = <0.0001) when a resident was involved in the case. These differences held true for complex appendicitis (time longer by 9 min, p = <0.0001 and charges higher by $500, p = 0.03). CONCLUSION: Resident involvement results in an increase in operative time and charges, with no difference in length of stay or complications. These results highlight the cost of resident involvement, without an increase in complications experienced by patients. LEVEL OF EVIDENCE: Level III evidence.

Same Anesthesia Endoscopic Retrograde Cholangiopancreatography and Laparoscopic Cholecystectomy: The Pediatric ERCP Database Intiative Experience.

BACKGROUND: Successful combined Laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) in the Same Session (LESS) has been reported in several studies in adult patients with choledocholithiasis. METHODS: This was a retrospective analysis of data collected prospectively in the Pediatric ERCP Database Initiative using REDCAP. Adverse events were recorded separately and were reviewed for this study. The primary outcome was the hospitalization days. Secondary outcomes included total duration of anesthesia, morbidity, time from diagnosis to procedure. RESULTS: Twenty-five patients underwent LESS, and 42 underwent the traditional ERCP followed by laparoscopic cholecystectomy. The groups were similar in age, weight, ASA. The median length of stay in the LESS group was 3 days, compared with 4 days (P = .32). Total procedure time was similar between the 2 groups, but anesthesia time was shorter in the LESS group (P = .0401). Morbidity was similarly low between the 2 groups. CONCLUSIONS: Relative to 2 interventions, a single session combining ERCP and laparoscopic cholecystectomy in pediatric patients is effective with a similar adverse event rate and length of stay. The use of a single sedation and reduced total anesthesia time are potential benefits of this approach. This modality may be considered for pediatric patients with choledocholithiasis with or without hemolytic disease.

Repetitive Imaging following Minimally Invasive Repair of Pectus Excavatum Is Unnecessary.

INTRODUCTION: The objective of this study was to evaluate the necessity of repeat imaging after an initial chest radiograph (CXR) following minimally invasive repair of pectus excavatum (MIRPE). MATERIALS AND METHODS: A retrospective review was performed on patients who underwent MIRPE from January 2012 to July 2016 at two academic children's hospitals. Data collected included demographics, severity of pectus defect (Haller index [HI]), utilization of CXRs, outpatient follow-up, and clinical outcomes. RESULTS: A total of 360 patients (171 at Hospital 1 and 189 at Hospital 2) underwent MIRPE. Median age was 15.6 years and 84% were males. The median HI was 4.0. Median postoperative hospital length of stay was 4.2 days and median time to bar removal was 34 months. There was significant variation in postoperative imaging between the hospitals, including frequency of immediate postoperative CXR, total number of CXRs during hospitalization, and number of postoperative outpatient CXRs prior to bar removal. However, there was no significant difference in outcomes between the hospitals, including postoperative pneumothorax, postoperative chest tube placement, and complications. CONCLUSION: These data suggest that increased repetitive imaging after an initial postoperative CXR does not affect clinical outcomes and may not be necessary after MIRPE.

Are Foley catheters needed after minimally invasive repair of pectus excavatum?

BACKGROUND: High narcotic requirements after minimally invasive repair of pectus excavatum (MIRPE) can increase the risk of urinary retention. Placement of intraoperative Foley catheters to minimize this risk is variable. This study determines the rate of urinary retention in this population to guide future practice. MATERIALS AND METHODS: We reviewed retrospectively all patients who underwent MIRPE from January 2012 to July 2016 at 2 academic children's hospitals. Data collected included demographics, BMI, severity of the pectus defect, postoperative pain management, and the incidence of urinary retention and urinary tract infection (UTI). RESULTS: Of 360 total patients who underwent MIRPE, 218 had an intraoperative Foley catheter. Patients with epidural pain control were more likely to receive a Foley catheter. The urinary retention rate was 34% for patients without an intraoperative Foley, and 1% in patients after removal of an intraoperatively placed Foley. Urinary retention was greater with an epidural compared with patient-controlled anesthesia (55% vs 26%, P = .002) in the no intraoperative Foley group. No urinary tract infections were identified. Epidural pain control was the only risk factor on multivariate analysis for retention in patients without an intraoperatively Foley catheter. CONCLUSION: Intraoperative Foley catheters obviate urinary retention without increasing the risk of urinary tract infection after MIRPE. These results will allow surgeons to better counsel patients regarding Foley placement.

Collaborations with Pediatric Hospitalists: National Surveys of Pediatric Surgeons and Orthopedic Surgeons.

To understand characteristics of pediatric hospitalist (PH) involvement in the care of children admitted to surgical services and explore surgeons' perspectives of PH effectiveness, we conducted a cross-sectional, web-based survey of pediatric surgical (PS) and pediatric orthopedic subspecialists (OS) from professional organizations. We used basic analyses to compare responses between the 2 surgical groups. The initial response rate was 48% (291/606) for PS and 59% (415/706) for OS. Among 185 PS and 212 OS unique programs, PH were routinely engaged (69% and 75%) in the care of surgical patients, particularly in patients with medical complexity (64% PS vs 81% OS; P = .003). PS and OS perceived positive PH impact on care coordination and comorbidity management but little on pain management or length of stay. OS were more likely than PS to view PH involvement positively (64% vs 42%; P < .001). Further research on care models, especially for children with medical complexity, is needed.

Postoperative Feeding Regimens After Laparoscopic Gastrostomy Placement.

PURPOSE: The objective of this study was to evaluate postoperative feeding regimens after laparoscopic gastrostomy placement and their effect on outcomes. METHODS: Children 18 years of age or younger, who underwent laparoscopic gastrostomy placement at a tertiary-care academic children's hospital between January 2014 and October 2016, were reviewed. Data collected included patient characteristics, postoperative feeding regimen, and clinical outcomes. Statistical analysis was performed using Chi-square, Fisher's exact, and Wilcoxon Rank-Sum tests. RESULTS: We reviewed the medical records of 270 children that underwent laparoscopic gastrostomy placement by 15 pediatric surgeons. The median age was 2.7 (interquartile range [IQR], 0.7-9.6) years, and 50% (n = 136) were male. The median body mass index was 15.5 (IQR, 14.0-17.5). Complications within 90 days included: granulation tissue (34%), leakage (17%), dislodgement (14%), and skin and soft-tissue infection (9%). Two patients returned to the operating room, 1 for a dislodged tube, and another for a volvulus within 10 days of gastrostomy tube placement. A subset analysis of outpatients that underwent elective laparoscopic gastrostomy placement showed variation in the day of initial feeds (0-2 postoperative days [POD]), method of initial feeds (continuous versus bolus) and choice of initial feeds (Pedialyte versus formula/breast milk). There was a significant difference in median hospital length of stay for early versus late initiation of feeds (POD 0: 2.1 days versus POD ≥1: 3.1 days, P < .01) without a difference in postoperative complications. CONCLUSION: There is substantial variation in the postoperative feeding regimen after laparoscopic gastrostomy. Initiation of early postoperative feeds may result in decreased length of stay without increasing complications.

Endoscopic retrograde cholangiography for pediatric choledocholithiasis: Assessing the need for endoscopic intervention.

AIM: To assess pediatric patients for choledocholithiasis. We applied current adult guidelines to identify predictive factors in children. METHODS: A single-center retrospective analysis was performed at a tertiary children's hospital. We evaluated 44 consecutive pediatric patients who underwent endoscopic retrograde cholangiography (ERCP) for suspected choledocholithiasis. Patients were stratified into those with common bile duct stones (CBDS) at ERCP vs those that did not using the American Society of Gastrointestinal Endoscopy (ASGE) guidelines (Very Strong and Strong criteria) for suspected CBDS. RESULTS: CBDS were identified in 84% at the time of ERCP. Abdominal ultrasound identified CBDS in 36% of patients. Conjugated bilirubin ≥ 0.5 mg/dL was an independent risk factor for CBDS (P = 0.003). The Very Strong (59.5%) and Strong (48.6%) ASGE criteria identified the majority of patients (P = 0.0001). A modified score using conjugated bilirubin had a higher sensitivity (81.2% vs 59.5%) and more likely to identify a stone than the standard criteria, odds ratio of 25.7 compared to 8.8. Alanine aminotransferase and gamma-glutamyl transferase values identified significant differences in a subset of patients with odds ratio of 4.1 and 3.25, respectively. CONCLUSION: Current adult guidelines identified the majority of pediatric patients with CBDS, but specific pediatric guidelines may improve detection, thus decreasing risks and unnecessary procedures.

Spontaneous pneumomediastinum in the pediatric patient.

BACKGROUND: Spontaneous pneumomediastinum (SPM) data in children are limited. We investigated the management of SPM at our institution. METHODS: We reviewed children with pneumomediastinum treated from January 2011 to October 2014. Primary (no precipitating factors) and secondary (underlying respiratory disease) SPM patients were included. Admission data and clinical outcomes were recorded. RESULTS: A total of 129 patients were included. Average age was 11.6 ± 4.6 years; 90 males (70%). Frequent presenting symptoms were chest pain (n = 76) and dyspnea (n = 51). Of the total, 89 patients (69%) were admitted. No patient required additional interventions. Of those, 85 patients (65.9%) had follow-up. Patients with secondary SPM (n = 58) were more likely than primary (n = 71) to be admitted (84% vs 56%, P = .001), receive oxygen (69% vs 35%, P = .04), and have longer stays (2 days [interquartile range, 1 to 3] vs 1 day [interquartile range, 0 to 1], P < .001). Readmission rates were equivalent. CONCLUSIONS: Differentiating types of SPM is important as clinical course differs. Secondary SPM patients are more frequently admitted than primary SPM patients.

Persistent cat scratch disease requiring surgical excision in a patient with MPGN.

We present the case of a 13-year-old immunosuppressed patient with unrelenting cat scratch disease despite 9 months of antibiotic therapy. The patient was being treated with mycophenolate and prednisone for membranoproliferative glomerulonephritis (type 1) diagnosed 13 months before the onset of cat scratch disease. Cat scratch disease was suspected due to epitrochlear lymphadenitis and an inoculation papule on the ipsilateral thumb, and the diagnosis was confirmed by the use of acute and convalescent titers positive for Bartonella henselae. The patient experienced prolonged lymphadenitis despite azithromycin and rifampin therapy, and she developed a draining sinus tract ∼4 months after initial inoculation while receiving antibiotics. Acute exacerbation of the primary supratrochlear node prompted incision and drainage of the area, with no improvement in the disease course. Ultimately, excision of all affected nodes and the sinus tract 9 months after the initial diagnosis was required to achieve resolution. Bartonella was detected at a high level according to a polymerase chain reaction assay in the excised nodes. Persistent treatment with oral antibiotics may have prevented disseminated infection in this immunosuppressed patient. Surgical excision of affected nodes should be considered in patients with cat scratch disease that persists beyond 16 weeks.

Analysis of submitted abstracts for the American Academy of Pediatrics, Section on Surgery, National Conference (AAP SoSU).

PURPOSE: In this study, we characterized the topics and type of research performed for abstracts submitted to the AAP SoSU national conferences from 2010-2013. METHODS: All abstracts submitted to the AAP SoSU Program Committee from 2010-2013 were analyzed. Abstracts were classified as basic science, clinical, domestic, international, as well as by disease processes, single, multicenter, retrospective, prospective, registry data, or other. RESULTS: From 2010-2013, 709 abstracts were submitted (2010 - 163, 2011 - 166, 2012 - 208, 2013 - 172), of which 349 were accepted (49% total acceptance rate (AR)). 17% represented basic science studies (74% AR), while 592 (84%) were clinical studies (44% AR). By disease state, CDH (57 abstracts, 70.2% AR), appendicitis (53 abstracts, 43% AR), and NEC (39 abstracts, 56% AR) were the most common. Most clinical abstracts (63%) were single-center retrospective reviews, 13% were large data registries, <5% were prospective studies, and only 5 abstracts were randomized controlled trials. CONCLUSIONS: The AAP SoSU abstract submission data demonstrate a wide variety of research studies spanning the entirety of our field. Basic science studies have a higher AR than clinical studies, and the topics of CDH, appendicitis, and NEC continue to be the most popular areas of study.

Management of the pediatric spontaneous pneumothorax: is primary surgery the treatment of choice?

BACKGROUND: Surgery as the primary management strategy for pediatric primary spontaneous pneumothorax is controversial. This study aims to evaluate the outcomes and effectiveness of management approaches for pediatric spontaneous pneumothorax. METHODS: Outcomes of pediatric patients undergoing initial nonoperative treatment versus video-assisted thoracoscopic surgery with blebectomy and mechanical pleurodesis were compared via a retrospective review. RESULTS: We identified 96 patients with 108 pneumothoraces. Of 98 pneumothoraces with initial nonoperative management, 37% had surgery during their initial hospitalization for persistent air leak. Of those discharged home without video-assisted thoracoscopic surgery, 40% recurred. Initial nonoperative management resulted in more total hospital days (median: 11 vs 5 days, P < .001). No significant predictors of recurrence were identified on multivariate analysis. Sixty-three percent of all patients ultimately required surgery. CONCLUSIONS: Fewer than 40% of primary spontaneous pneumothorax patients are definitively treated with nonoperative management. A prospective study is needed to determine whether primary surgery with blebectomy/mechanical pleurodesis is a more effective treatment strategy.

Complications related to the Nuss procedure: minimizing risk with operative technique.

INTRODUCTION: Pectus Excavatum (PEx) is the most frequent congenital chest wall deformity; surgical correction has a complication rate of 10%-50%. The purpose of this study was to evaluate outcomes in a recent cohort of pediatric patients from a single institution and investigate factors associated with complications. METHODS: A review of all patients with PEx treated with a Nuss procedure from 2003 to 2011 was performed. Complications included hemo/pneumothorax, infection, bar migration, and operative injury. Chi-square, Student's t-test, and logistic regression were performed. RESULTS: The study included 127 Nuss patients with a the median age of 15.2 years (5.4-18.7) and a mean Haller index of 4.2 (+1.6). The total complication rate was 26% and bar migration rate was 18%. The use of a stabilizer was associated with fewer overall complications (17% vs 41%,p=0.006), decreased reoperation (16% vs 41%,p=0.003), decreased readmission (15% vs 39%,p=0.004), and decreased bar migration rate (9% vs 36%,p=0.001) compared to patients without a stabilizer. On multivariate analysis, the use of a stabilizer (OR 0.18,p=0.011,95% CI 0.049-0.68) and the use of a pericostal suture (OR 0.19,p=0.03,95% CI 0.41-0.85) were associated with decreased rates of bar migration. CONCLUSION: The use of a lateral stabilizer and pericostal sutures decreased complication and reoperation rates for the Nuss procedure.

Duodenum inversum: a report and review of the literature.

Duodenum inversum is a rare congenital malformation defined by a duodenum which travels superiorly and then posteriorly prior to crossing the midline above the pancreas. It is often confused with other, more common, anomalies of intestinal rotation. We present a case of duodenum inversum diagnosed incidentally in a one-month old infant with Trisomy 21 during evaluation for reflux disease. Due to an inability to definitively rule out malrotation, the diagnosis was confirmed with a diagnostic laparoscopy. We discuss available literature concerning this rare anatomic anomaly as well as provide recommendations for diagnosis and treatment.