Primary Medical Therapy Research Articles

7145 Enhanced Ability of the Small Peptide GH Receptor Antagonist, AZP-3813, to Decrease IGF1 When Combined with the Somatostatin Analog, Octreotide

Abstract Disclosure: G. Ravel: None. C. Berardet: Employee; Self; Amolyt Pharma. C. Chalmey: Employee; Self; Amolyt Pharma. H. Kurasaki: Employee; Self; Peptidream Inc. T. Tomiyama: Employee; Self; Peptidream Inc. P. Reid: Employee; Self; Peptidream Inc. D. Duracher: Employee; Self; Amolyt Pharma. R. Datta: Consulting Fee; Self; Amolyt Pharma. M. Aouadi: Employee; Self; Amolyt Pharma. M.D. Culler: Employee; Self; Amolyt Pharma. There is a strong rationale for combining a growth hormone (GH) receptor antagonist (GHRA) with somatostatin analog (SSA) therapy for acromegalic patients. While SSAs are the primary medical therapy for treatment of acromegaly, insulin-like growth factor 1 (IGF1) levels fail to normalize with SSA monotherapy in most patients. Even in patients with controlled IGF1, GH levels can remain elevated and induce symptoms by interacting with GH receptors throughout the body. In addition, while GHRAs have no significant effect on the causative pituitary tumor, SSAs can often induce tumor stabilization or shrinkage. AZP-3813 is a 16-amino acid, bicyclic peptide GHRA which has been demonstrated to potently decrease IGF1 in both rats and dogs. In order to examine the effect of combining AZP-3813 with a SSA in decreasing IGF1, 8-week old, male, Sprague Dawley rats were implanted subcutaneously with Alzet model 2002 minipumps containing either vehicle or the SSA, octreotide (OCT), at concentrations required to deliver either 20 or 40μg OCT/kg/day. Blood samples for IGF1 measurement were collected before, and 48 and 72 hours after pump implantation. Immediately following the 72-hour blood collection, rats from each infusion group were injected subcutaneously with either vehicle or AZP-3813 at 0.3, 1, 3, 10 or 30mg/kg (n=7/group). A subsequent blood sample was collected 24 hours after the injection of vehicle or AZP-3813, which also corresponded to 96 hours after pump implantation. Plasma levels of IGF1 were assessed by radioimmunoassay. In rats infused with vehicle, the 0.3mg/kg dose of AZP-3813 had no effect on IGF1 as compared with baseline; however, with higher doses a clear, dose-related decrease in IGF1 was observed ranging from -7 ± 3.0% with 1mg/kg AZP-3813 to -29 ± 2.0% with 30mg/kg. OCT infusion alone at 20μg/kg/day produced a -10 ± 3.6% decrease in IGF1, while injection of AZP-3813 into rats infused with 20μg/kg/day OCT, produced an enhanced, dose-related decrease, ranging from -7 ± 3.8% with 0.3mg/kg AZP-3813 to -38 ± 3.4% with 30mg/kg. A clear additive relationship was observed by focusing on the 3mg/kg dose of AZP-3813, which, alone, decreased IGF1 by -13 ± 2.8% in vehicle-infused rats. When injected into rats infused with OCT, which alone decreased IGF1 by -10 ± 3.6%, a combined decrease of -23 ± 3.3% was observed. The magnitude of the combined decrease was not statistically different from the decrease obtained with 30mg/kg AZP-3813 alone in vehicle-infused rats; thus, demonstrating a 10-fold increase in the effectiveness of AZP-3813 when combined with OCT. Similar results were observed with 40μg/kg/day OCT infusion. These results demonstrate the enhanced efficacy of AZP-3813 in decreasing IGF1 when combined with the SSA, OCT, and support the development of AZP-3813 as an add-on therapy in patients inadequately controlled with SSA treatment. Presentation: 6/3/2024

Ocular Surface Squamous Neoplasia: Changes in the Standard of Care 2003 to 2022.

The aim of this review was to elucidate treatment preferences for ocular surface squamous neoplasia and to examine the changes in treatment modalities over the past 2 decades. An electronic survey was distributed to members of The Cornea Society, Ocular Microbiology and Immunology Group, and 4 international corneal specialist listservs. Questions examined medical and surgical treatment preferences, and results were compared with surveys administered in 2003 and 2012. A total of 285 individuals responded to the survey; 90% of respondents were self-classified as corneal specialists. Seventy-three percent reported using primary topical monotherapy to treat ocular surface squamous neoplasia as compared with 58% in 2012 ( P = 0.008). Compared with 2003, the percentage use of topical interferon significantly increased ( P < 0.0001) from 14% to 55%, 5-fluorouracil increased ( P < 0.0001) from 5% to 23%, and mitomycin C decreased ( P < 0.0001) from 76% to 19% as a primary monotherapy. The frequency of performing excision without the use of postoperative adjunctive medical therapy decreased significantly ( P < 0.0001), from 66% to 26% for lesions <2 mm, 64% to 12% for lesions between 2 and 8 mm, and 47% to 5% for lesions >8 mm from 2003 to 2022. More clinicians initiated topical immuno/chemotherapy without performing a biopsy as compared to 2003 (31% vs. 11%, P < 0.0001). These results demonstrate a paradigm shift in the management of ocular surface squamous neoplasia. The use of primary medical therapy as a first approach has significantly increased, with a reduction in the frequency of performing surgical excision alone.

Efficacious Primary Pasireotide Therapy in a Case of a Large Invasive Adrenocorticotropin-secreting Pituitary Tumor

Abstract A 41-year-old woman presented with a headache, diplopia, weight gain, moon face, and central obesity. Her plasma adrenocorticotropin (ACTH) level was 25.5 pmol/L (116 pg/mL) (normal range, 1.6-13.9 pmol/L [7.2-63.3 pg/mL]), serum cortisol level was 397.3 nmol/L (14.4 µg/dL) (normal range, 195.1-540.7 nmol/L [7.1-19.6 µg/dL]), and urinary free cortisol was 413.9 nmol/day (150.3 µg/day) (normal range, &amp;lt;221.5 mmol/day [&amp;lt;80.3 µg/day]). ACTH-dependent hypercortisolism was present, with cortisol suppression using a high-dose dexamethasone suppression test. Cushing disease was diagnosed and a contrast-enhanced magnetic resonance imaging scan demonstrated a 36-mm pituitary tumor with right cavernous sinus invasion. Before surgery, 20 mg pasireotide long-acting-release was initiated, and her symptoms rapidly improved. After 1 month, obvious tumor shrinkage was observed, ACTH and cortisol levels decreased, and diplopia resolved; therefore, we continued medical therapy. After 11 months, her ACTH and cortisol levels normalized, and most of the tumor had disappeared. The clinical course in this case suggests that pasireotide may be useful for preoperative treatment and primary medical therapy, at least in some patients with Cushing disease caused by a large tumor predicted to have difficulty achieving remission by surgery.

Glaucoma Treatment Patterns in Sub-Saharan Africa.

Physicians were most likely to recommend primary medical therapy upon diagnosis of glaucoma. Laser therapy was underutilized where they were available. Physicians were more likely to recommend surgery in severe glaucoma, laser therapy in mild glaucoma, while recommendation of medical therapy did not depend on glaucoma severity. To characterize treatment patterns for newly diagnosed glaucoma in sub-Saharan Africa (SSA). This was a multicenter cross-sectional study of adults newly diagnosed with glaucoma at 27 eye care centers in 10 African countries. In addition to demographic and clinical data, physician treatment recommendations (medication, laser, surgery, or no treatment) were recorded. Statistical analyses were performed using STATA version 14.0. Data from 1201 patients were analyzed. Physicians were most likely to recommend primary medical therapy upon diagnosis of glaucoma (69.4%), with laser (13.2%), surgery (14.9%), and no treatment (2.5%) recommended to the remaining patients. All sites had medical therapy available and most (25/27, 92.6%) could provide surgical treatment; only 16/27 (59.3%) sites offered laser, and at these sites, 30.8% of eyes were recommended to undergo primary laser procedures. As glaucoma severity increased, the laser was recommended less, surgery more, and medications unchanged. Patient acceptance of medical therapy was 99.1%, laser 88.3%, and surgery 69.3%. Medical therapy for first-line glaucoma management is preferred by most physicians in SSA (69%). Laser therapy may be underutilized at centers where it is available. These findings underscore the need for comparative studies of glaucoma treatments in SSA to inform the development of evidence-based treatment guidelines and of programs to reduce glaucoma blindness in SSA. Strategic approaches to glaucoma therapy in SSA must address the question of whether medical therapy is the most optimal first-line approach in this setting.

D-7 | Outcomes of Patent Ductus Arteriosus Therapies in Patients

Presence of a hemodynamically significant PDA in premature infants, especially in <29 weeks is associated with complications like prolonged mechanical ventilation, NEC and IVH. Therapy with IV acetaminophen or NSAIDs for closure is effective in <50% and associated with many complications. Transcatheter PDA closure (TCPC) including Piccolo device approved for infants >700g has shown >95% success without significant complications. There is a lot of practice variability with no management consensus. We compared the outcomes between medical, surgical and device closure in patients of <2000g, including complications. Retrospective review of infants <29 week gestation, who underwent medical/interventional/surgical PDA closure at <2Kg at Nicklaus Children’s Hospital from 1/2010-11/2022. Patients with complex congenital heart defects, coarctation or pulmonary artery stenosis were excluded. TCPC device complications assessed included TV regurgitation, significant LPA or aortic obstruction, device embolization or erosion. Respiratory status calculated as respiratory severity score was also compared. Total of 86 infants born <29 weeks gestation and <2000g at procedure were included. 56% patients failed primary medical therapy and required either TCPC or surgical therapy (43% vs 57%). Medication use was associated with complications including NEC, pulmonary hemorrhage and AKI in 24% patients (n=15). The median gestational age of patients undergoing TCPC was 25+1 (22-28) wks, median weight 1260g (790-1930g), similar to surgical group for gestation and weight (1040g, 600-2000). 36 patients underwent TCPC with Piccolo, the remainder with MVP. Neonates with TCPC showed earlier improvement in respiratory status (RSS 3.6 vs 4.5, p 0.037 ) and earlier extubation (10 days vs. 26 days, p 0.01) compared to surgical ligation. TCPC use was safe and with no significant LPA or aortic stenosis seen with Piccolo device, one with MVP. Moderate TR was seen in one patient following Piccolo device. New NEC was seen in 1 patient after 10 days. TCPC is effective in patients <2000g with earlier improvement in respiratory status compared to surgical ligation, without any significant complications.

Medical management of retained products of conception: A prospective observational study

Objective(s)To measure the success rate of primary medical therapy in managing retained products of conception (RPOC) in women with secondary postpartum haemorrhage (PPH) and to identify factors associated with need for surgical management. Study designPostpartum patients presenting to a tertiary women’s hospital Emergency Department between July 2020 and December 2022 with secondary PPH and evidence of RPOC on ultrasound were recruited. Clinical information relating to the presentation was collected prospectively. Antenatal and intrapartum data were collected from medical record and Birthing Outcome System database review. The primary outcome was the success of medical management for RPOC, defined by the implementation of medical or expectant management without subsequent need for surgical intervention. ResultsForty-one patients with RPOC underwent primary medical or expectant management. Twelve patients (29%) were managed successfully with medical management, while twenty-nine (71%) proceeded to surgical management. Medical management involved antibiotics (n = 37, 90%), prostaglandin E1 analogue (n = 14, 34%) and other uterotonics (n = 3, 7%). A greater endometrial thickness on ultrasound was significantly associated with a requirement for secondary surgical intervention (p < 0.05). There was an association approaching statistical significance between a higher sonographic volume of RPOC and the failure of medical management (p = 0.07). There was no statistically significant association between the mode of delivery or the number of days postpartum with the success of medical management. Conclusion(s)For patients presenting with secondary PPH and sonographic RPOC, over two thirds required surgical management. Increased endometrial thickness was associated with an increased requirement for surgical management.

Cushing's disease: role of preoperative and primary medical therapy.

Transsphenoidal surgery is the first-line treatment for Cushing's disease. However, some situations may require the use of a primary medical treatment, such as in patients with severe life-threatening hypercortisolism, a situation which can be handled by fast-acting steroidogenesis inhibitors, instead of classical bilateral adrenalectomy. Primary medical treatment could also be considered in patients with non-severe hypercortisolism, but the evidence is far less convincing for its systematic use. The aim of this short review is to explain briefly the different circumstances in which primary medical therapy could be considered, the limits of this approach, and the way in which to initiate and monitor the treatment.

Medical management of secondary postpartum haemorrhage: A prospective cohort study.

Secondary postpartum haemorrhage (PPH) complicates ~1% of pregnancies and can cause serious maternal morbidity. However, evidence guiding optimal management is scarce and often based on case series and expert opinion. To measure the success of primary medical therapy in managing secondary PPH and to identify factors associated with need for surgical management. Postpartum patients presenting to a tertiary women's hospital emergency department between July 2020 and October 2021 with secondary PPH were recruited. Data from the acute presentation were prospectively collected. Antenatal and intrapartum data were collected from medical record review. The primary outcome was the success of medical management for secondary PPH, defined by the implementation of medical or expectant measures without subsequent need for surgical intervention. One-hundred and twenty patients underwent primary medical management for secondary PPH. Ninety-eight (82%) were managed successfully with medical management and 22 (18%) required surgery. Medical management involved misoprostol (n= 33; 27.5%), antibiotics (n= 108; 90%), and less commonly other uterotonics (n= 6; 5%). Factors associated with lower rates of successful medical management included: antecedent manual removal of placenta (MROP) (odds ratio (OR) 0.2, P= 0.047), primary PPH ≥500 mL (OR 0.39, P= 0.048) or ≥1 L (OR 0.24, P= 0.009), >200 mL blood loss at presentation (OR 0.17, P= 0.015), increasing time post-delivery (OR 0.84, P= 0.044), retained products of conception (RPOC) on ultrasound (OR 0.024, P= 0.001) and vaginal birth (OR 0.27, P= 0.027). Medical management was highly successful. Vaginal birth, MROP, primary PPH, RPOC on ultrasound and increasing time post-delivery were associated with increased need for surgical management.

Cholestatic liver diseases of genetic etiology: Advances and controversies.

With the application of modern investigative technologies, cholestatic liver diseases of genetic etiology are increasingly identified as the root cause of previously designated "idiopathic" adult and pediatric liver diseases. Here, we review advances in the field enhanced by a deeper understanding of the phenotypes associated with specific gene defects that lead to cholestatic liver diseases. There are evolving areas for clinicians in the current era specifically regarding the role for biopsy and opportunities for a "sequencing first" approach. Risk stratification based on the severity of the genetic defect holds promise to guide the decision to pursue primary liver transplantation versus medical therapy or nontransplant surgery, as well as early screening for HCC. In the present era, the expanding toolbox of recently approved therapies for hepatologists has real potential to help many of our patients with genetic causes of cholestasis. In addition, there are promising agents under study in the pipeline. Relevant to the current era, there are still gaps in knowledge of causation and pathogenesis and lack of fully accepted biomarkers of disease progression and pruritus. We discuss strategies to overcome the challenges of genotype-phenotype correlation and draw attention to the extrahepatic manifestations of these diseases. Finally, with attention to identifying causes and treatments of genetic cholestatic disorders, we anticipate a vibrant future of this dynamic field which builds upon current and future therapies, real-world evaluations of individual and combined therapeutics, and the potential incorporation of effective gene editing and gene additive technologies.

Corticotroph pituitary carcinoma with skeletal metastases masquerading as ectopic ACTH syndrome: a long and winding road to diagnosis.

SummaryPituitary carcinoma is a rare type of malignancy and only accounts for 0.1–0.2% of all pituitary tumours. Most pituitary carcinomas are hormonally active and they are mostly represented by corticotroph and lactotroph carcinomas. Corticotroph carcinoma can present as symptomatic Cushing’s disease or can evolve from silent corticotroph adenoma which is not associated with clinical or biochemical evidence of hypercortisolism. We hereby present a case of a bone-metastasized corticotroph pituitary carcinoma masquerading as an ectopic adrenocorticotropic hormone (ACTH) syndrome in a patient with a history of a non-functioning pituitary macro-adenoma. Our patient underwent two transsphenoidal resections of the primary pituitary tumour followed by external beam radiation therapy. Under hydrocortisone substitution therapy she developed ACTH-dependent hypercortisolism without arguments for recurrence on pituitary MRI and without central-to-peripheral ACTH-gradient on inferior petrosal sinus sampling, both suggesting ectopic production. Ultimately, she was diagnosed with an ACTH-secreting vertebral metastasis originating from the primary pituitary tumour. This case report demonstrates the complex pathophysiology of pituitary carcinoma and the long diagnostic work-up. Certain features in pituitary adenoma should raise the suspicion of malignancy.Learning pointsThe diagnosis of pituitary carcinoma can only be made based on documented metastasis, therefore, due to the often long latency period between the detection of the primary tumour and the occurrence of metastasis, the diagnostic work-up most often spans over multiple years.Pituitary carcinoma including corticotroph carcinoma is very rare in contrast to pituitary adenoma and only accounts for 0.1–0.2% of all pituitary tumours.Histopathology in pituitary adenoma should certainly accomplish the following goals: accurate tumour subtyping and assessment of tumoural proliferative potential.Repeated recurrence of pituitary adenoma after surgical resection, a discrepancy between biochemical and radiological findings, resistance to medical and radiation therapy, and silent tumours becoming functional are all hallmarks of pituitary carcinoma.Silent corticotroph adenomas are non-functioning pituitary adenomas that arise from T-PIT lineage adenohypophyseal cells and that can express adrenocorticotropic hormone on immunohistochemistry, but are not associated with biochemical or clinical evidence of hypercortisolism. Silent corticotroph adenomas exhibit a more aggressive clinical behaviour than other non-functioning adenomas.Treatment options for corticotroph carcinoma include primary tumour resection, radiation therapy, medical therapy, and chemotherapy. Sometimes bilateral adrenalectomy is necessary to achieve sufficient control of the cortisol excess.

Factors Associated with Revision Sinus Surgery in Patients with Chronic Rhinosinusitis.

Endoscopic sinus surgery (ESS) is performed in patients diagnosed with Chronic Rhinosinusitis (CRS) refractory to primary medical therapy to achieve adequate disease control. This study aimed to assess which factors and phenotypes of CRS are associated with revision surgery in patients undergoing ESS. This retrospective, single-center study included 667 patients undergoing ESS between 2012 and 2015. We performed group comparisons to detect differences between CRS patients undergoing primary or revision surgery and computed binary logistic regression models. Logistic regression analysis revealed higher odds for revision surgery in CRS patients with older age (p-value < 0.001), male gender (p-value = 0.011), diagnosis of AERD (p-value = 0.005), and presence of asthma (p-value < 0.001) or allergies (p-value = 0.031). Confirming previous studies, we found that the factors of age, CRSwNP, AERD, allergies, and asthma are associated with revision ESS and identified surgical techniques that were predominantly used in revision cases.

LONG TERM OUTCOMES OF PARTIAL ENTERAL NUTRITION THERAPY IN CHILDREN WITH CROHN’S DISEASE

Abstract BACKGROUND Partial enteral nutritional therapy (PEN, defined as 80% of daily caloric intake from formula) has shown similar efficacy in inducing remission for pediatric Crohn’s Disease (CD) in comparison to exclusive enteral nutrition (EEN, defined as 100% of daily caloric intake from formula). Long-term outcomes of PEN are not well defined in the literature We aimed to study the long-term outcomes of PEN as defined by the number of patients still on maintenance PEN at 1 and 2 years after initiation. METHODS This was a retrospective cohort study using electronic medical record data at a large pediatric academic center. Patients diagnosed with CD between ages 7-19 years at PEN initiation with available follow-up data were included. Exclusion criteria were diagnoses of ulcerative colitis or indeterminate colitis, concomitant treatment with systemic steroids (prednisone (or equivalent) dose &amp;gt; 20 mg daily), biologics, or immunomodulators. Data collected included demographic and IBD characteristics as well as details of PEN therapy. We calculated the one and two-year PEN persistence rates and used Kaplan-Meier methods to produce survival curves of PEN persistence with adjustment for censoring. RESULTS Between 2009 and 2021, forty-nine participants met inclusion criteria (out of 114 assessed for inclusion). Participants were mostly white (n = 38, 77%), and male (n = 30, 61%). The mean age at CD diagnosis was 11.4 years (standard deviation, SD: 2.9 years) and the mean age at PEN initiation was 12.1 years (SD: 2.6 years). The most common reasons for PEN initiation were primary induction (n = 30, 61%), family/patient preference to avoid other medications (n = 26, 53%), and failure of primary medical therapy (n = 10, 20%). The most chosen formula type for PEN therapy was partially hydrolyzed formulas (n = 30, 61%), followed by standard formulas with whole intact proteins (n = 16, 33%). The one-year PEN persistence rate was 51% (26/49) and the two-year persistence rate was 25% (12/49) (table1). The median time on PEN was 1.3 years (IQR: 0.6 – 2.2 years) (Figure 1). The most common reasons for discontinuation were disease relapse/progression (n=32/41,78%) and treatment non-adherence (n =8/41, 20%). A small number of individuals discontinued due to formula intolerance (n = 3/41,7%). The most common medical therapies escalated to were infliximab (n =21/41, 51%), and adalimumab (n = 8/41, 20%) when PEN was discontinued. DISCUSSION Our study suggests that PEN therapy can be used as potential long-term treatment strategy for mild pediatric Crohn’s disease while avoiding corticosteroids and side-effects common with other IBD therapies. Secondary analysis is underway to understand predictors of response or failure to PEN therapy such as disease location/ distribution, type of formula, and the amount of calories from food vs. formula.

How did the general surgeons intend to treat acute calculous cholecystitis during COVID-19 era?Results of online survey.

Acute calculous cholecystitis is one of the most encountered surgical pathologies. While early cholecystectomy is the first treatment choice during the first index hospitalization, it may change during COVID-19 era when hospital resources are restricted, and health-care personnel try to overcome pandemic difficulties. In this survey, our aim is to investigate surgeons' preferences and possible changing paradigms for acute cholecystitis therapy during COVID-19 pandemic. An online survey was conducted on an internet site through private invitation by social media sent to general surgeons. The survey consisted of 13 questions, including surgeons' hospital properties, and it questioned treatment preferences against acute calculous cholecystitis during the pandemic. After 3 months of data collection, responded answers were analyzed statistically. About 56% of the surgeons stated that their treatment strategy changed during the COVID-19 pandemic partially or totally. About 48.8% of surgeons preferred early cholecystectomy for cases with acute cholecystitis before COVID-19 era; when only 23.2% of the surgeons preferred early surgery during COVID-19 era. However, patients who had received antibiotics as primary medical therapy had medical therapy failure with a range of 40.2%. Percutaneous cholecystostomy rate was raised to 20.7% from 4.9% before the COVID era. Although 96.3% of the surgeons did not have seen any unusual complication related to the COVID-19 disease, more than half of the surgeons who preferred early cholecystectomy changed their treatment strategy during the COVID-19 pandemic. According to the survey results, although the medical therapy failure rate is high, 48.8% of the surgeons may persist in this non-operative approach after the pandemic.

Paediatric Pituitary Adenomas: Clinical Presentation, Biochemical Profile and Long-Term Prognosis.

Paediatric pituitary adenomas (PPAs) are uncommon, with evidence confined to small cohorts. We aimed to elucidate the baseline profile and outcomes of PPAs in a large, contemporary, monocentric cohort. Pituitary clinic at PGIMER over 8 years (2010-2018). PPAs in patients (≤20 years at diagnosis) were included. A retrospective review of their baseline clinico-biochemical and radiological profiles and outcomes post pituitary surgery/medical management was performed. There were a total of 74 patients, of which 42 were female. The median age was 15 (IQR 13-18) years. Corticotropinomas (32.4%) and somatotropinomas (25.7%) were common, with 1 case of TSHoma and pituitary blastoma. The most common presentation was headache (57%) overall and menstrual irregularities (64.2%) in girls. Most (78%) had macroadenomas. Prolactinomas showed an excellent response to primary medical therapy (83.3%). Transsphenoidal surgery was performed in 81% of patients. Diabetes insipidus (30%) and hyponatremia (26.7%) emerged as common postoperative complications. Adjuvant medical management was required in 25%, and radiotherapy in 18%. Remission rates in Cushing's and acromegaly were 62.5% and 57.8%, respectively, with long-term hormone deficits noted in one-third of patients. PPAs have unique features and management challenges, including effects on growth and puberty. Functional tumours and macroadenomas are common. Remission can be achieved in more than half of the patients, with endocrine deficits persisting in about a third of cases, needing long-term surveillance.

Impact of morphine use on mortality in STEMI patients treated with primary PCI – results from a new registry

Abstract Background Opioids decrease the effect of P2Y12 receptor inhibitors in vitro and observational reports suggest that morphine use may be associated with larger infarct size. Our research group showed previously, using a prospective single-centre registry, that periprocedural morphine use may have no impact on long-term mortality in STEMI patients treated with primary PCI and clopidogrel. Purpose We aimed to study this in vitro interaction on clinical outcomes in patients who were predominantly treated with the novel P2Y12 inhibitors prasugrel or ticagrelor, according to the current guidelines. Methods From May 2020 through February 2021, we collected demographic, anamnestic, procedural and laboratory data of 297 consecutive STEMI cases who were treated with primary PCI at our tertiary centre. Of them 126 patients (42.4%) received IV morphine during the periprocedural period. Outcome measure was time to all-cause mortality. The median follow-up time was 147 days (IQR 71–242 days), with 39 events. To adjust for confounding, a 1:1 propensity score-matching analysis (PSM) was performed using 186 cases. Absolute difference in survival was analysed using Kaplan-Meier survival curves and the logrank test, whereas the relative change was assessed by univariable Cox regression. Results An adequate balance on baseline covariates was achieved by the propensity score-matching. Kaplan-Meier analysis showed no statistically significant difference in all-cause mortality of the treatment groups neither in the original nor in the propensity score-matched population (p=0.220 and 0.762 respectively). In the matched population we found no difference in survival as the HR (Morphine/No Morphine) was 0.88 (95% confidence interval [CI]: 0.39–2.00), p=0.76. Conclusion Our preliminary data suggest that morphine may have no impact on mortality in STEMI patients treated with primary PCI and medical therapy according to the current guidelines including novel P2Y12 antagonists. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The research was supported by the Ministry of Innovation and Technology NRDI Office within the framework of the Artificial Intelligence National Laboratory Program. Kaplan-Meier curves: Original populationKaplan-Meier curves: PSM population

Pulmonary Vein Stenosis in Children: A Programmatic Approach Employing Primary and Anatomic Therapy.

Pulmonary vein stenosis (PVS) is a difficult condition to treat due to recurrence and progression. In 2017, we developed a comprehensive PVS Program at our center to address the multidisciplinary needs of these patients. We discuss the components of our program and our approach to these patients, using a combination of primary (medical) therapy in addition to anatomic therapy to preserve vessel patency. A multidisciplinary approach to treating these challenging patients is critical.

Systemic Sirolimus Therapy for Infants and Children With Pulmonary Vein Stenosis

BackgroundAnatomic interventions for pulmonary vein stenosis (PVS) in infants and children have been met with limited success. Sirolimus, a mammalian target of rapamycin inhibitor, has demonstrated promise as a primary medical therapy for PVS, but the impact on patient survival is unknown. ObjectivesThe authors sought to investigate whether mTOR inhibition with sirolimus as a primary medical therapy would improve outcomes in high-risk infants and children with PVS. MethodsIn this single-center study, patients with severe PVS were considered for systemic sirolimus therapy (SST) following a strict protocol while receiving standardized surveillance and anatomic therapies. The SST cohort was compared with a contemporary control group. The primary endpoint for this study was survival. The primary safety endpoint was adverse events (AEs) related to SST. ResultsBetween 2015 and 2020, our PVS program diagnosed and treated 67 patients with ≥moderate PVS. Of these, 15 patients were treated with sirolimus, whereas the remaining patients represent the control group. There was 100% survival in the SST group compared with 45% survival in the control group (log-rank p = 0.004). A sensitivity analysis was completed to address survival bias using median time from diagnosis of PVS to SST. A survival advantage persisted (log-rank p = 0.027). Two patients on sirolimus developed treatable AEs. Patients in the SST group underwent frequent transcatheter interventions with 3.7 catheterizations per person-year (25th to 75th percentile: 2.7 to 4.4 person-years). Median follow up time was 2.2 years (25th to 75th percentile: 1.2 to 2.9 years) in the SST group versus 0.9 years (25th to 75th percentile: 0.5 to 2.7 years) in the control group. ConclusionsThe authors found a survival benefit associated with SST in infants and children with moderate-to-severe PVS. This survival benefit persisted after adjusting the analysis for survival bias. There were 2 mild AEs associated with SST during the study period; both patients were able to resume therapy without recurrence.

P190 Ileo-caecal Crohn’s Disease; medical or surgical management. Cost and outcomes

Abstract Background An ileo-caecectomy is known to be an effective treatment for Crohn’s disease limited to the terminal ileum that can lead to a long term remission. ECCO guidelines recommend that patients with active inflammation should be treated medically. However the LIR!C trial suggested there are QOL benefits and reduced costs to performing primary surgery. Methods We aimed to compare the outcomes of patients treated with primary medical treatment to primary surgery for patients with Crohn’s disease limited to the terminal ileum. We reviewed our database to identify all these patients and analysed outcome data. Results 49 patients were identified: Mean age was 50 yrs (range 22 - 93). 23 were male. Mean length of follow-up was 96 months (range 3 - 404). 1st line treatment was: medical; 33 (67.3%), surgery; 16 (32.6%). Outcomes after medical treatment: 27 of 33 patients failed primary medical treatment, they required surgery at a mean of 38 months (range 1–900) after initiating medical treatment. Colonoscopy after surgery to assess for disease recurrence: Colonoscopic assessment or calprotectin post was undertaken ileo-caecectomy in 4 of 16 patients at a mean of 6.2 months (range 1–10) who underwent primary surgery; and in 25 of 27 patients who underwent surgery following failure of medical treatment. Outcomes after surgery: 4 of 16 patients who had primary surgical treatment had endoscopic recurrence, requiring medical treatment after a mean of 4.4 months (range 0–10). 8 of 27 patients who had surgery post-failure of medical treatment developed disease recurrence, requiring medical treatment after a mean of 40 months (range 7–136) Bile acid malabsorption (BAM): BAM occurred after surgery in 10 of 43 patients. No medically managed patient developed BAM. Conclusion These data suggest that in our population the vast majority of patients with ileo-caecal Crohn’s disease will fail medical treatment and require surgery. 25% of those who undergo surgery will develop BAM (requiring medication), and 40% of those treated surgically will require immunosuppressant treatment in the medium term. These outcomes should be discussed with patients so that they appreciate that ileo-caecectomy is unlikely to lead to long term drug free treatment, and medical treatment is unlikely to lead to the avoidance of surgery. From a health-economics point of view it could be argued there is little point in offering primary medical therapy and ileo-caecectomy should be the initial treatment of choice for patients with limited ileo-caecal Crohn’s disease. Unfortunately endoscopic/calprotectin assessment following primary surgery was often not performed in the majority of patients, and changes in our local practice need to be undertaken to correct this.

Impact of morphine use on mortality in STEMI patients treated with primary PCI - preliminary data from a new registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Opioids decrease the effect of P2Y12 receptor inhibitors in vitro and observational reports suggest that morphine use is associated with larger infarct size. Our research group presented previously, using a prospective single-center registry, that periprocedural morphine use may have no impact on long-term mortality in STEMI patients treated with primary PCI and clopidogrel. Purpose Our purpose is to check this interaction using a new registry of patients treated according to the current guidelines, including novel antiplatelet agents. Methods From May until November 2020, we collected 196 STEMI patients treated with primary PCI. 88 (44.9%) of them got morphine during the prehospital and periprocedural care. Baseline demographic, anamnestic, procedural, and laboratory data were collected. Survival data were analysed using Kaplan-Meier survival curves and the log-rank test. To adjust for confounding, a 1:1 propensity score-matching analysis was performed using 114 cases. Results An adequate balance on baseline covariates was achieved during propensity score-matching. Kaplan-Meier analysis showed no difference in 30-days mortality of the patients treated with or without morphine neither in the original nor in the propensity score-matched population (p = 0.094 and p = 0.309, respectively). Conclusion Our preliminary data suggest that morphine may have no impact on mortality in STEMI patients treated with primary PCI and medical therapy according to the current guidelines including novel P2Y12 antagonists. Abstract Figure. Kaplan-Meier curves

Impact of primary medical or surgical therapy on prolactinoma patients’ BMI and metabolic profile over the long-term

ObjectivesHigh prolactin levels have been associated with weight gain and impaired metabolic profiles. While treatment with dopamine agonists (DAs) has been shown to improve these parameters, there is a lack of surgical series on its comparative effect in prolactinoma patients. MethodsIn this retrospective, comparative study, consecutive patients with a prolactinoma were enrolled if treated with first-line transsphenoidal surgery (TSS) or with DAs. Patients with prolactinomas of Knosp grade >2 and those with a follow-up <24 months were excluded, as were patients with missing laboratory metabolic parameters at baseline and over the long-term. Effects of either treatment on BMI and the metabolic profile were analyzed, and independent risk factors for long-term obesity were calculated. ResultsPrimary treatment was TSS for 12 patients (40%) and DAs for 18 patients (60%). At diagnosis, no significant differences between the two cohorts were observed with regard to adenoma size, Knosp grading, baseline prolactin (PRL) levels, prevalence of hypogonadism, or laboratory metabolic parameters. Mean follow-up was 51.9 months (range, 24–158). Over the long-term, both TSS and DAs led to the control of hyperprolactinemia (92% vs. 72%) and hypogonadism (78% vs. 83%) in the majority of patients. While a significant decrease in patients’ BMI and fasting glucose were observed, changes in the lipid profile were marginal and independent of the treatment modality. At baseline, increased BMI—but not the primary treatment strategy—was an independent predictor of long-term obesity. ConclusionsOver the long-term, patients’ BMI and FG improve, but changes in the metabolic profile are marginal and independent of the primary treatment. It is presumable that not DAs per se, but rather the control of hyperprolactinemia plays a role in patients’ metabolic profile alterations.