First-line Management Research Articles

Chinese expert consensus on treatment of malignant pleural effusion (2023 Edition)

Malignant pleural effusion (MPE) is a pleural effusion that is caused by a malignant tumor originating in the pleura or by a metastatic malignant tumor from another site that has invaded the pleura. MPE is associated with poor prognosis. Members of the Pleural and Mediastinal Diseases Working Group (preparatory) of Chinese Thoracic Society and some external experts selected clinical issues related to the management of MPE and conducted rigorous evidence retrieval and evaluation. After several meetings and revisions of the manuscript, recommendations were made. This consensus applies to patients aged≥18 years old with MPE caused by various malignancies except for pleural mesothelioma. It included four chapters: pathogenesis of MPE, prognostic evaluation of MPE, local thoracic treatment, and systemic anticancer therapy for MPE.The main recommendations of this consensus are as follows:1. Prognosis evaluation of MPE was valuable in formulating treatment options. It is suggested to comprehensively evaluate the patient's prognosis by combining the patient's performance status, tumor type, and laboratory examination.2. It is recommended that in patients with symptomatic MPE, therapeutic thoracentesis could be used as the initial therapeutic option. Evaluate whether the lung is expandable after thoracentesis and drainage, and then develop a therapeutic regimen.3. In patients with MPE and known expandable or nonexpandable lung, an indwelling pleural catheter (IPC) is recommended as a first-line pleural management. Daily IPC drainages are recommended. In patients with MPE and expandable lung, talc pleurodesis by talc poudrage or talc slurry is recommended if the drug is accessible. Other pleurodesis agents include povidone iodine, bleomycin, and doxycycline.4. After drainage, it is suggested to consider the option of intrapleural use of recombinant human endostatin or bevacizumab alone or in combination with intrapleural chemotherapy. Intrapleural intervention including electrocautery, argon knife, cryotherapy, laser and radiofrequency ablation, is recommended for use in patients who have undergone rigorous evaluation in eligible hospitals. The use of intrapleural urokinase or streptokinase via pleural catheter is recommended for patients with symptomatic MPE and loculated effusion.5. For patients with good performance status and metastatic malignancies, systemic anti-cancer treatment is recommended as standard of care.

Application of Light Therapy in Dementia Care

Patients with dementia often display related sleep disturbance, depression, and behavioral and psychological symptoms, which are traditionally managed through the use of antipsychotic medications or physical restraint. However, these management interventions can have negative effects on the physical and psychological health of patients. The results of several meta-analyses suggest non-pharmacological interventions, including light therapy, should be used for the first-line management of these dementia symptoms. Light therapy uses artificial light to compensate for insufficient light exposure during the daytime and to help patients with dementia properly regulate their circadian rhythms. Sleep disturbance and depression in those with dementia may be effectively relieved through the application of light therapy. Nurses should assess the needs and symptoms of patients with dementia and consider applying light therapy as a complementary care intervention to improve quality of care.

A Phase 3 Study of Eltrombopag Vs. Standard First-Line Management for Newly Diagnosed Immune Thrombocytopenia in Children: Trial in Progress Update

Background: Immune thrombocytopenia (ITP) causes low platelet counts, variable bleeding symptoms, and reductions in health-related quality of life (HRQoL). Despite this, novel therapies for newly diagnosed ITP have not been introduced in over 30 years. Eltrombopag, a thrombopoietin receptor agonist (TPO-RA), was FDA approved for children with chronic ITP in 2015. The use of eltrombopag for adults with newly diagnosed ITP has been described in two small single-center trials (Tripathi et al, Int J Hematol, 2014; Gόmez-Almaguer et al, Blood, 2014), and pediatric hematologists do use TPO-RAs off-label in some cases of newly diagnosed ITP (Neunert et al, Pediatr Blood Cancer, 2016). TPO-RAs may be an efficacious and more durable first-line therapy for children with newly diagnosed ITP who require treatment. This abstract provides a 4-year interval update on the Pediatric ITP Newly diagnosed patients Eltrombopag vs Standard therapy (PINES) trial in progress. Study Design and Methods: The PINES trial, NCT03939637, is an investigator-initiated prospective, open label, randomized, multi-center trial sponsored by the ITP Consortium of North America (ICON) and funded by Novartis. The primary objective is to determine if the proportion of patients with a platelet response, defined as ≥3 of 4 platelet counts >50 x10 9/L during weeks 6-12 without rescue treatment, is significantly greater in patients with newly diagnosed ITP treated with eltrombopag compared to those treated with standard first-line therapy. Patients (n=162) from 30 ICON centers (Figure) are randomized 2:1, stratified by age and treatment status, to receive the experimental treatment, eltrombopag, or investigator's choice of 3 standard first-line therapies: prednisone, intravenous immune globulin or anti-D globulin at standardized doses. Eligible patients are ages 1 to <18 with primary ITP, within 3 months of diagnosis, with platelet count <30 x10 9/L who require pharmacologic treatment from the perspective of the treating clinician. Baseline treatment status is 1) upfront treatment, or patients within 10 days of ITP diagnosis with no prior treatment, and 2) treatment failure, or patients previously managed with observation or a first-line standard agent. Patients are ineligible if they can be observed without medication or have severe bleeding. A one-sided z-test, at alpha=0.025, will be used to compare the proportion of patients who have a platelet response between the two treatment arms. All randomized patients will be analyzed in the intention-to-treat analysis. Secondary objectives include treatment arm comparison of bleeding scores (WHO Bleeding Scale and Modified Buchanan Score), changes in HRQoL (measured by the Kids ITP Tool, Hockenberry Fatigue Scale, PROMIS, and Global Change Scale), and changes in percentage of CD4 +25 +Foxp3 + regulatory T (Treg) cells. Due to challenges related to recruitment and the logistics and safety of obtaining frequent assessments during the COVID-19 pandemic, the primary endpoint was re-defined in 2021 to what is considered a clinically equivalent definition of response, from ≥6 of 8 weekly to ≥3 of 4 biweekly platelet counts >50 x10 9/L during weeks 6-12. Baseline Characteristics: Since first site activation in 2019, 100 patients have been enrolled (Table). Subjects include 42 patients aged 1-<6 years, 34 patients aged 6-<12 years, and 24 patients aged 12-<18 years. Thirty-six patients received upfront treatment and 64 patients had treatment failure prior to enrollment. Median baseline platelet count at enrollment was 5 x10 9/L (range 1 - 28 x10 9/L). Median WHO Bleeding Scale at enrollment was 1 (range 0 - 3) and median modified Buchanan Overall Score was 3 (range 0 - 3). Baseline HRQoL surveys have been obtained for >80% of eligible subjects. Treg samples have been obtained for 95% of subjects, and 74% of subjects have consented to optional biology studies. Conclusion: Despite historical difficulty completing interventional trials in pediatric ITP and pandemic-related enrollment challenges, PINES trial enrollment is progressing successfully and will ultimately provide definitive data regarding the efficacy of eltrombopag in children with newly diagnosed ITP. There are no current data supporting the use of TPO-RAs for newly diagnosed ITP in children, or as monotherapy for newly diagnosed ITP in adults. Results from this trial therefore carry the potential to change management practices in ITP.

Post-Transplant Lymphoproliferative Disorders (PTLD) in Real Life: Data from the French K-Virogref Registry on 525 Adult Patients

Introduction Post-transplant lymphoproliferative disorders (PTLD) are rare and severe complications of organ or allogeneic stem cell transplants (AST), often linked to EBV. The recommended first-line management of systemic PTLD, in addition to lowering immunosuppression, currently consists of response-tailored treatment (RTT): monotherapy with rituximab (R) and, in case of CR, a continuation of rituximab as monotherapy (RM), otherwise 4 courses of R-CHOP. The data in the literature are limited to a few very rare prospective studies and limited series, generally monocentric. Patients and methods The French national K-virogref database, supported by the French Institute against Cancer (INCa), started in September 2013, gathers data from PTLDs confirmed by biopsy and re-reading in the Lymphopath network. Data from 10 years of this registry have been analyzed. Results A total of 525 adult patients are analyzed, the median age of transplant is 44 years, that of diagnosis of PTLD 58 years, 63% are men. Transplants are 61% kidneys, 17% livers, 6% lungs, 6% hearts, 8% stem cells. The median time from transplant to diagnosis of PTLD is 97 months, with 16% of diagnosis within the first year. The histology is of early lesion type in 4.6%, polymorphic in 12% and of lymphoma type in 83.3%, 46.7% are linked to EBV. Of the total 435 are systemic and 90 (17%) are localized to the central nervous system (CNS); predictors of CNS PTLD are later age at transplant (52 years vs 43 years), male gender ( p=1.10-3), a kidney transplant (69% vs 60%), CNS PTLDs are more often late after the transplant, more often of the lymphoma type and almost always linked to EBV (97.8%). The EBV status of the recipient at the time of transplantation was known in 242 cases, of which 50 were EBV negative; the negative EBV status is linked to an earlier age at diagnosis (43 years vs 58 years), a shorter time between transplant and diagnosis (11.5 months vs 66.5), more often early forms, more frequent localization in the graft (24% vs 9%), better survival. The median overall survival (OS) of all patients is 2700 days, tumor EBV status has no influence on OS, progression-free survival (PFS) is 1500 days. Median survivals are 2600 days for AST, 4600 for hearts, 5400 for lungs and not reached (NR) for livers and kidneys. Among the classic prognostic criteria, the IPI is not discriminating between 0 and 2, whereas the personal status is clearly discriminating (cf figure). Of the patients CD20+ without CNS localization nor Burkitt, treatment data were known for 274 patients: 27% received only immuno-chemotherapy (IC), 38% had RM and 35% R then R-CHOP. Survival is identical between IC and R then R-CHOP, with less chemotherapy in the sequential treatment, and is significantly higher (p=0.011) for RM, the RTT has a trend to a better OS than IC (p=0.062). In the event of chemotherapy, the use of an anthracycline has a better OS (median NR vs 750 days). Conclusion To our knowledge, this is the largest series of PTLD presented to date. The results of OS are similar to those presented in the prospective studies with selected patients and our data confirm the interest of RTT, with in case of chemotherapy, the need to use an anthracycline. The most discriminating and simplest prognostic criterion is PS. However, this very large series only concerns adult patients and cannot describe real-life pediatric PTLD.

Bronchial Artery Embolization: IS NBCA/LIPIODOL Better Than PVA?

Introduction: Bronchial artery embolization (BAE) is a minimally invasive interventional procedure, which is now considered the first-line management strategy and an alternative to surgery for massive and recurrent haemoptysis. The advances in embolic agents have led to a significant improvement in the success rates of the procedure, however, there has been no significant change in the recurrence rate of haemoptysis. Methods: This retrospective study was conducted at a tertiary care center from January 2012 to December 2020. The final analysis was performed on 123 patients [NBCA(n= 37) and PVA(n= 86)]. Technical and clinical success rates, complications and recurrence rates were compared between the two groups. Results: A total of 248 arteries were embolized. In the PVA group, clinical success was achieved in 84 out of 86 cases (97.6%) and with NBCA in 36 out of 37 patients (97.3%) (p >0.05). Of the 120 patients in whom BAE was clinically successful, recurrence was observed in 43 patients within the 12-month follow-up period. The study showed a statistically significant association between the embolizing agent used for BAE and the recurrence of hemoptysis (χ2 = 4.80, df = 1, p = 0.028). The use of PVA particles for BAE was found to have2.62 times higher odds (95% CI 1.10 - 6.81) of recurrence of hemoptysis as compared to the use of NBCA glue. Conclusions: BAE with NBCA provided higher hemoptysis-free survival rates compared with PVA particles without increasing complication rates.

ERCP for the initial management of malignant biliary obstruction – real world data on 596 procedures

Aims To evaluate outcomes of ERCP as first-line management in patients with malignant biliary obstruction (MBO) of all causes and stages, reflecting a real-life setting. Methods Retrospective observational study of patients with ERCP as the first-line management of MBO at Oslo University Hospital between 2015 and 2021. Primary outcome measure was a ≥ 50% decrease from the pre-procedural bilirubin within 30 days after ERCP. Secondary outcome measures were technical success of ERCP, complications and overall mortality. Results A total of 596 patients were included, median age 70 years. ASA score was ≥ III in 67% of patients. The most common cancers causing MBO were pancreatic cancer (52%), metastatic lesions (20%) and cholangiocarcinoma (16%). The primary outcome measure was achieved in 62% of patients. With endoscopic access, overall technical success was 80% with 85% for the distal extrahepatic group, 71% for the perihilar, 40% for the intrahepatic and 53% for multiple level MBOs. Reinterventions were performed in 27% of the patients. Complications occurred in 15% of the patients, including post-ERCP pancreatitis in 9%. Most complications were of minor/moderate severity (81%). Overall mortality was 33% within the first 90 days. Patients deceased by the end of the study period (83%) had median survival of 146 days (range 1–2,582 days). Conclusions ERCP has a high rate of clinical effect and technical success in the management of both distal extrahepatic and perihilar MBO. Our data indicate that ERCP is a valid option in the first-line management of MBO.

The screening and management of sleep disturbances in people living with HIV: Delphi consensus.

Sleep disturbances in people living with HIV (PLHIV) are frequent but their management remains insufficient. In the absence of specific recommendations, a DELPHI consensus research project was conducted in France to establish best practice. A multidisciplinary Steering Committee (STC) undertook a literature review and used it with clinical expertise to create statements that were voted on. Two profiles of healthcare professionals with significant experience in monitoring PLHIV were selected for the voting: physicians and nurses/psychologists. Votes were collected electronically, independently, and anonymously. The STC created 27 statements covering six areas: Screening of sleep disturbances, Investigation, First-line management, Referral to a specialist, Antiretroviral treatment (ARV), and Prevention. Two rounds of votes included 42 physicians and 32 nurses/psychologists. Consensus was reached for 24 out of 27 statements (89%) including: to assess quantity and quality of sleep among PLHIV at least annually, ideally using a common methodology within the medical department; to consider the temporary addition of a hypnotic treatment in cases of acute insomnia not improved by the rules of sleep hygiene, with full awareness of potential drug-drug interactions and risk of dependence; to correct ferritinaemia if <100 ng/mL before referral to a specialist when restless legs syndrome is suspected; to consider changing the time of ARV administration or an ARV switch within the same class when sleep disturbances are caused by an ARV. This DELPHI Consensus provides best practice for screening and managing sleep disturbances in PLHIV and optimising their quality of life.

ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats.

Seizure emergencies (ie, status epilepticus [SE] and cluster seizures [CS]), are common challenging disorders with complex pathophysiology, rapidly progressive drug-resistant and self-sustaining character, and high morbidity and mortality. Current treatment approaches are characterized by considerable variations, but official guidelines are lacking. To establish evidence-based guidelines and an agreement among board-certified specialists for the appropriate management of SE and CS in dogs and cats. None. A panel of 5 specialists was formed to assess and summarize evidence in the peer-reviewed literature with the aim to establish consensus clinical recommendations. Evidence from veterinary pharmacokinetic studies, basic research, and human medicine also was used to support the panel's recommendations, especially for the interventions where veterinary clinical evidence was lacking. The majority of the evidence was on the first-line management (ie, benzodiazepines and their various administration routes) in both species. Overall, there was less evidence available on the management of emergency seizure disorders in cats in contrast to dogs. Most recommendations made by the panel were supported by a combination of a moderate level of veterinary clinical evidence and pharmacokinetic data as well as studies in humans and basic research studies. Successful management of seizure emergencies should include an early, rapid, and stage-based treatment approach consisting of interventions with moderate to preferably high ACVIM recommendations; management of complications and underlying causes related to seizure emergencies should accompany antiseizure medications.

What is a tibial pilon fracture and how should they be acutely managed? A survey of consultant British Orthopaedic Foot and Ankle Society members and non-members.

Controversy exists around which distal tibial fractures are pilon fractures. We evaluated views to define a pilon fracture and support the development of standards of care. Views regarding the characteristics of a pilon fracture and acute soft tissue management were determined through a questionnaire. This was trialled, approved by the British Orthopaedic Foot and Ankle Society and distributed to its members. This was also distributed nationally as part of the ENFORCE study. In total, 282 consultants from 27 units responded, of whom 24% (69/282) were foot and ankle specialists. Some 58% (163/282) agreed that a pilon fracture is primarily a soft tissue injury, 81% (228/282) that pilon fractures occur though high-energy transfer, 81% (228/282) that pilon fractures are sustained through an axial compression mechanism and 93% (265/282) that they are a potentially limb-threatening injury. Overall, 83% (234/282) agreed that in a length-unstable pilon fracture it is not possible to maintain the talus near anatomically under the tibial plafond without rigid fixation to control length - with 87% (246/282) agreeing that the acute first-line management should be a spanning external fixator. Opinions were that the time frame between diagnosis and intervention should be: less than 6h (63%; 154/246), 6-12h (31%; 77/246) and 12-24h (6%; 15/246). Consensus supports defining a pilon fracture as a potentially limb-threatening high-energy axial compression injury, and a spanning external fixator as the first-line management of a length-unstable injury less than 12h from diagnosis.

Resolution of Stroke-Related Hemichorea-Hemiballismus with Haloperidol

Hemichorea-hemiballismus (HC-HB) is a hyperkinetic disorder characterized by violent, unilateral jerking movements which usually improve to choreoathetosis with time. Etiology of HC-HB has been demonstrated in case reports and series, with acute stroke being one of the known etiologies. Among the rare post-stroke hyperkinetic syndromes, HC-HB is the most common. However, there is limited data on management and long term follow up of this debilitating condition when related to acute stroke. Here we describe a 79-year-old gentleman with acute caudate stroke, with resulting HC-HB, whose symptoms were managed with haloperidol while hospitalized. Resolution of HC-HB and subsequent discontinuation of haloperidol yielded an optimal patient outcome. Long term follow-up for this patient has demonstrated lack of symptom recurrence at 1 year. This case further supports the use of neuroleptics such as haloperidol as first line for management of HC-HB.

Should IUI replace IVF as first-line treatment for unexplained infertility? A literature review

BackgroundUnexplained infertility accounts for 25% of infertility causes in the UK. Active intervention methods, such as intrauterine insemination (IUI) or in vitro fertilisation (IVF), are often sought. Despite the National Institute for Health and Care Excellence (NICE) recommending IVF for unexplained infertility, this recommendation has generated an ongoing debate, with few fertility clinics discontinuing the use of IUI as the first-line management of choice. In contrast to NICE, recent guidance released from the European Society for Human Reproduction and Embryology (ESHRE) in August 2023 supports the use of IUI as first-line. High-quality evidence behind such interventions is lacking, with current literature providing conflicting results.AimsThis review aims to provide a literature overview exploring whether IUI or IVF should be used as first-line treatment for couples with unexplained infertility, in the context of current guidelines.MethodsThe primary outcome used to assess efficacy of both treatment methods is live birth (LB) rates. Secondary outcomes used are clinical pregnancy (CP) and ongoing pregnancy (OP) rates. A comprehensive literature search of 4 databases: Ovid MEDLINE, EMBASE, Maternity & Infant Care and the Cochrane Library were searched in January 2022. Upon removal of duplications, abstract screening, and full-text screening, a total of 34 papers were selected.Discussion/conclusionThis review highlights a large discrepancy in the literature when examining pregnancy outcomes of IUI and IVF treatments. Evidence shows IUI increases LB and CP rates 3-fold compared to expectant management. Literature comparing IUI to IVF is less certain. The review finds the literature implies IVF should be used for first-line management but the paucity of high-quality randomised controlled trials (RCTs), coupled with heterogeneity of the identified studies and a lack of research amongst women > 40 years warrants the need for further large RCTs. The decision to offer IUI with ovarian stimulation (IUI-OS) or IVF should be based upon patient prognostic factors. We suggest that IUI-OS could be offered as first-line treatment for unexplained infertility for women < 38 years, with good prognosis, and IVF could be offered first to those > 38 years. Patients should be appropriately counselled to enable informed decision making.

Management of Persistent, Post-adenotonsillectomy Obstructive Sleep Apnea in Children: An Official American Thoracic Society Clinical Practice Guideline.

Background: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. Although adenotonsillectomy is first-line management for pediatric OSA, up to 40% of children may have persistent OSA. This document provides an evidence-based clinical practice guideline on the management of children with persistent OSA. The target audience is clinicians, including physicians, dentists, and allied health professionals, caring for children with OSA. Methods: A multidisciplinary international panel of experts was convened to determine key unanswered questions regarding the management of persistent pediatric OSA. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Results: Recommendations were developed for six management options for persistent OSA. Conclusions: The panel developed recommendations for the management of persistent pediatric OSA based on limited evidence and expert opinion. Important areas for future research were identified for each recommendation.

The success of ultrasound-guided hydrostatic reduction in managing delayed presentation of childhood intussusception: A single center experience

BackgroundChildhood intussusception is a common surgical emergency. The current practice for non-operative management in Sri Lanka is ultrasound-guided hydrostatic reduction (USGHR). This retrospective study aims to demonstrate the efficacy and safety of this procedure even in a setting of delayed presentation. MethodWe explore outcomes of USGHR in the management of intussusception in children presenting to a single tertiary care center in Sri Lanka, between November 2019 and March 2021. Hydrostatic reduction was performed in patients with radiologically confirmed intussusception in the absence of contraindications. In failed attempts or early recurrences, USGHR was repeated for a maximum of 2 more attempts. ResultsOur study included 135 participants. Of the patients for which data on symptom duration was available 31.5% (n = 41) presented delayed (t>48 hrs). Hydrostatic reduction showed an overall success rate of 86.4%. No association was seen between time since onset of symptoms and success of USGHR (p<0.05). In 19 patients (14.1%) operative intervention was required. The rates of operative intervention were comparable between those presenting within (12.4%) and after 48 h (12.2%). One case (0.7%) of bowel perforation and 1 case of peritonitis (0.7%) occurred in those presenting within and after 48 h respectively. ConclusionThe success rate of USGHR was high despite delays in patient presentation. Thus, hydrostatic reduction is a safe, effective procedure to be performed as the first-line management option in childhood intussusception even in a setting of delayed presentation. Overall success increases with repeat reduction. Level of evidenceRetrospective study comparative – level III

The correlation between transient osteoporosis of the hip and pregnancy: A review.

Transient osteoporosis of the hip is indubitably a comparatively infrequent entity affecting both men and women worldwide. Its occurrence in the course of pregnancy, specifically in the third trimester, and lactation are of paramount concernment. The exact association between transient hip osteoporosis and pregnancy is precarious. Etiology and potential pathophysiological mechanisms behind this correlation are still to be utterly defined. Magnetic resonance imaging is highly regarded as the gold standard imaging method for assiduous assessment of this disorder. Physicians of copious medical specialties should practice scrupulous techniques for early and pertinent diagnosis when pregnant women are presented with persistent hip pain, as differential diagnosis with femoral head avascular necrosis can be exceedingly arduous. Treatment is predominantly conservative with protected weight-bearing and analgesic medication in the first line of management. In terms of prognosis, the disease ordinarily resolves spontaneously after a few months. Further research is required in order to elucidate the ambiguity surrounding the establishment of globally approved diagnosis and treatment guidelines for pregnancy-associated transient hip osteoporosis. This paper aims to accentuate the significance of this particular disorder by providing a succinct review of the existing literature, augmenting clinicians' knowledge about the features of pregnancy-related transient proximal femur osteoporosis.

FRI321 Aggressive Prolactinoma Empirically Treated With Cabergoline Leading To Rapid CSF Leak

Abstract Disclosure: A. Yau: None. T. Reisman: None. Over two-thirds of pituitary tumors are prolactinomas. These are discovered as a result of symptoms of hypogonadism, menstrual irregularities, infertility or galactorrhea, as well as symptoms of mass effects including visual field deficit or acute severe headaches.1 A more rare subgroup, aggressive prolactinomas, in which the tumors are radiographically invasive and show resistance to dopamine agonist treatment as well as surgery, account for 10% of all hypophyseal neoplasia. 2 During medical treatment of prolactinomas, there is a known rare complication of CSF rhinorrhea; recorded time of onset of leak following treatment ranges from 14 days to 5 years.3 We present a case in which a patient with an aggressive prolactinoma rapidly developed a CSF leak within 48 hours of starting cabergoline treatment. Case: A 36-year-old male with type 2 diabetes, erectile dysfunction and infertility presents to Endocrine clinic after initial evaluation by Urology revealed elevated prolactin. He reported headaches, gynecomastia associated with liquid discharge from nipples, and minor issues with peripheral vision. He was started empirically on cabergoline for probable prolactinoma and within 48 hours developed worsening frontal headache, cough and clear fluid leakage from his right nostril. Labs revealed prolactin over 2600 ng/ml. MRI pituitary showed evidence of pituitary adenoma as well as likely CSF leak. Cabergoline was stopped and the patient was sent to the emergency room. The patient was underwent urgent neurosurgical transsphenoidal endoscopic surgery and CSF leak repair with resolution of rhinorrhea and cough. Post-operative MRI was consistent with minimal residual tumor. He was monitored in the NICU with no obvious post-operative pituitary hormone imbalance, diabetes insipidus, adrenal insufficiency or syndrome of inappropriate ADH. Months after discharge, the patient’s prolactin remained elevated to the 600’s ng/ml and repeat MRI showed a mass occupying the entire sella and suprasellar cistern, compressing the optic chiasm. Conclusion: In this case of a patient with the subtype of aggressive prolactinoma, there seems to be a more rapid presentation of complications. When treating these rare subtypes, physicians need to stay vigilant of developing complications or even consider nonstandard therapies as first-line management. 1. Molitch ME, Drummond J, Korbonits M. Prolactinoma Management. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; January 6, 2022.2. Lasolle H, Ilie MD, Raverot G. Aggressive prolactinomas: how to manage?. Pituitary. 2020;23(1):70-77. doi:10.1007/s11102-019-01000-73. Arimappamagan A, Sadashiva N, Kandregula S, Shukla D, Somanna S. CSF Rhinorrhea Following Medical Treatment for Prolactinoma: Management and Challenges. J Neurol Surg B Skull Base. 2019;80(6):620-625. doi:10.1055/s-0039-1677686 Presentation: Friday, June 16, 2023

Role of Insole Material in Treatment of Plantar Fasciitis: A Randomized Clinical Trial

Category: Hindfoot; Other Introduction/Purpose: Plantar fasciitis (PF), a leading cause of persistent heel pain, results in almost a million physician visits annually. Conservative treatment is often the first line of management with insoles being frequently prescribed. While multiple studies have compared insoles based on the degree of customization to foot contour, the literature is lacking in data comparing insoles based on their material. In this randomized clinical trial, we compared the early effects of foam, polyurethane, and carbon fiber insoles in the treatment of PF, using a robust set of PROMS. Methods: A randomized clinical trial was designed at the foot and ankle research center of a tertiary care hospital in Massachusetts. Adult patients diagnosed with PF who had not received injectable or surgical treatment for it were included. Participants who consented were randomly allocated one of the three prefabricated insoles – carbon fiber insole (Group 1, n=13), polyurethane insole (Group 2, n=13), or foam insole (Group 3, n=9) for regular use. Their response was recorded using PROMIS 3a (for pain intensity), PROMIS 4a (for pain interference), FAOS (Foot and Ankle Outcome Score), and VAS for pain at baseline (T0), two (T2), six (T6) and twelve weeks (T12). A per-proto analysis was undertaken using Kruskal Wallis and Friedman tests. P&lt; 0.05 was set as the level of significance. Results: Among groups 1, 2 and 3, the mean age of participants was 51.9±13.2, 51±12.5, and 47.9±13.5 years respectively and baseline weight varied as 211.6±32.7 lbs, 193.6±59.3 lbs, and 180.7±33 lbs respectively (p&gt;0.05 for both). The group-wise distribution of participants based on sex and laterality of the affected foot showed no difference. Participants in each group reported similar intensity of the pain (VAS) at baseline and at all follow-up time points (p&gt;0.05). A comparison of outcomes between baseline and subsequent timepoints showed significant improvement in quality of life (FAOS) at T12 (p=0.047) for carbon fibre insole users (Figure 1), significant pain relief on PROMIS Pain intensity and Pain Interference questionnaires for foam insoles at T3 and T12 (p=0.0003, 0.036 respectively). Conclusion: Carbon fiber insoles offered slightly better pain relief as early as six weeks into treatment and improved quality of life after twelve weeks of use. A possible link between the material of insole used and effective treatment of PF may exist. Conducting further analyses on the position of the foot during gait while using insoles and designing the insoles based on patient-specific criteria should be considered for future research.

Role of 99mTc-sestamibi Scintimammography in Predicting Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Prospective Study.

Neoadjuvant chemotherapy (NACT) is the first line of management for locally advanced breast cancer (LABC). However, chemoresistance is prevalent in 18%-50% of the cases. One of the important and most studied causes of chemoresistance is P-glycoprotein (Pgp) expression. 99mTc-sestamibi scintimammography may serve as a useful imaging tool to predict Pgp expression, thereby response to NACT. The aim was to study the role of 99mTc-sestamibi scintimammography in predicting response to NACT in treatment-naive, biopsy-proven LABC patients. 99mTc-sestamibi scintimammography (early and delayed images) was performed on a total of 34 patients. Eight patients were lost to follow-up, and only 26 (25 females and 1 male) patients were available for final analysis, with a mean age of 49.7 ± 10.7 years. 99mTc-sestamibi washout rate (WOR) (%) and T/B buildup were calculated. Pre-NACT and Post-NACT tumor sizes were measured clinically, and a % decrease in tumor size was calculated. The WOR and T/B buildup values were correlated with the % decrease in tumor size. We found a statistically significant negative correlation between WOR (%) and % decrease in tumor size and a statistically significant positive correlation between T/B buildup and % decrease in tumor size. Furthermore, we found a positive correlation between the early T/B ratio and the Ki-67 index (P = 0.22). Early categorization of responders and nonresponders can help in optimal therapy planning. 99mTc-sestamibi scintimammography can serve as an imaging marker for Pgp expression, thereby predicting clinical response to NACT in LABC patients. Further studies with larger sample sizes are warranted to consolidate the above findings.

Conservative and operative management of spontaneous pneumothorax in children and adolescents: Are we abusing of CT?

No age-specific pediatric guidelines exist for the management of spontaneous pneumothorax (SP) in children and adolescents. Treatment remains heterogeneous and center dependent. The role of computed tomography (CT) has yet to be defined. Review the management of SP in children and adolescents, with emphasis on conservative management and role of CT. Retrospective analysis of 61 consecutive patients with SP at single tertiary center. Clinical, radiological, surgical data, follow-up, and outcomes were revised. First-line management was conservative for 32 (53%) patients and operative for 29 (47%). Asymptomatic/paucisymptomatic patients managed conservatively experienced less first-line treatment failure. Furthermore, the patients needing at least a chest drain or surgery during the follow-up were significantly lower in the conservative group. Conservative and operative patients showed no significant differences regarding ipsilateral recurrences or contralateral occurrences. Of the 61 overall CTs performed, 14 (23%) had an impact on management. Forty-three (70%) patients had at least a CT, in 22 (51%) the CT was positive for blebs. For 10 of these patients (45%) the presence of blebs had an impact on management. Patients with and without blebs showed no differences regarding ipsilateral recurrence, contralateral occurrences, or the need for at least a chest drain or surgery during the follow-up. First-line conservative management had a significantly shorter hospitalization and better outcome, with a similar incidence of recurrences. The presence of blebs at CT does not predict the risk of recurrence. The CT scan should be reserved for a small number of selected patients who have post-VATS refractory or recurrent pneumothorax.

OA11 Osteoporosis, denosumab, and hypocalcaemia in multimorbid renal impairment

Abstract Introduction Osteoporosis affects approximately 30% of patients with chronic kidney disease (CKD) at stages 3-5, with 10% of women and 5% of men experiencing a fragility fracture within a given three-year follow up period. First-line management of osteoporosis with bisphosphonates is often precluded in CKD, with alendronate and zoledronate being contraindicated in creatinine clearances of &amp;lt; 35mL/min, and risedronate if &amp;lt; 30mL/min. Denosumab, a RANK-ligand inhibiting monoclonal antibody, can be used in cases of poorer renal function, however causes hypocalcaemia more commonly than bisphosphonates. Concomitant CKD compounds this risk if creatinine clearance falls below 30mL/min, presenting additional challenges for management. Case description A 75-year old woman with known osteoporosis and chronic kidney disease secondary to hypertension and a pauci-immune necrotising glomerulonephritis was found to have a serum calcium of 2.08mmol/L approximately three months after commencing six-monthly denosumab. Her lumbar spine T-score on dual x-ray absorptiometry showed severe osteoporosis at −2.9, with a fragility fracture of the humerus sustained four years prior. Her baseline eGFR was 23mL/min/1.73m2, and creatinine clearance was 22mL/min. Her past medical history was extensive and included secondary hyperparathyroidism due to CKD and resulting vitamin D deficiency, with a PTH of 23.0pmol/L, serum calcium of 2.26mmol/L, and a serum 25-OH vitamin D3 level of 33.5nmol/L four months prior to denosumab therapy. The history also included Sjögren’s syndrome on long-term daily prednisolone 7.5mg, alternate-day hydroxychloroquine 200mg, and daily leflunomide 10mg for accompanying synovitis of the hands, hypothyroidism controlled with daily levothyroxine 50mcg, hypertension controlled with daily 2.5mg bisoprolol, peripheral neuropathy secondary to vitamin B12 deficiency on three-monthly hydroxocobalamin, myocardial infarction with percutaneous coronary intervention to three arteries, diverticular disease with abscess perforation requiring laparotomy and intensive care admission, and a previous deep vein thrombosis on long-term anticoagulation with apixaban. The patient had received risedronate in the past while her creatinine clearance still permitted this. Her vitamin D deficiency had been managed orally with Adcal-D3 and colecalciferol 800IU once daily, which was uptitrated to 1600IU once daily prior to commencing denosumab. However, despite the patient’s serum vitamin D levels rising from 33.5 to 37.2nmol/L in the months preceding her first denosumab infusion, serum calcium had fallen below normal range on post-infusion blood tests. Serum phosphate returned at 0.91mmol/L, and vitamin D had fallen to 23.1nmol/L in the three months following denosumab treatment. Consequently, the patient was commenced on longer term intensive vitamin D supplementation. Discussion This case raises the issue of multifactorial hypocalcaemia against a backdrop of osteoporosis, persistent vitamin D deficiency, and medical comorbidity limiting management options. The significance of CKD in this case highlights the importance of monitoring and replacing vitamin D. While the hypocalcaemia detected at three months post-infusion may have occurred in part due to the direct effect of denosumab, the patient’s vitamin D deficiency no doubt also played a role in this, and failing to detect the deficiency may have resulted in premature termination of denosumab treatment. This case also highlights the extended timeframe in which such hypocalcaemia may present. Case-series literature describes hypocalcaemia manifesting at, on average, eight days post-infusion in patients with CKD-associated hyperparathyroidism. However we demonstrate here that extended lag times up to twelve weeks are possible; the patient was symptomatic with leg cramping at the time of clinic follow up. Future practice may benefit from establishing monitoring regimes for those with CKD and osteoporosis receiving denosumab, or bisphosphonates toward the lower end of permitted renal function. Key learning points Chronic kidney disease both limits available management options in osteoporosis, and increases the likelihood of complications from the remaining available agents – illustrated here with hypocalcaemia. Hypocalcaemia in a patient with chronic kidney disease and osteoporosis may be driven by several factors: hyperphosphataemia, vitamin D deficiency, and the effect of denosumab to prevent mobilisation of calcium from bone to serum can all be culprits. Calcium, phosphate, and vitamin D all need to be tightly monitored in medically complex patients on treatment for osteoporosis.

Treatment of Ovarian Cancer Beyond PARP Inhibition: Current and Future Options.

Ovarian cancer is the leading cause of gynecological cancer death. Improved understanding of the biologic pathways and introduction of poly (ADP-ribose) polymerase inhibitors (PARPi) during the last decade have changed the treatment landscape. This has improved outcomes, but unfortunately half the women with ovarian cancer still succumb to the disease within 5years of diagnosis. Pathways of resistance to PARPi and chemotherapy have been studied extensively, but there is an unmet need to overcome treatment failure and improve outcome. Major mechanisms of PARPi resistance include restoration of homologous recombination repair activity, alteration of PARP function, stabilization of the replication fork, drug efflux, and activation of alternate pathways. These resistant mechanisms can be targeted to sensitize the resistant ovarian cancer cells either by rechallenging with PARPi, overcoming resistance mechanism or bypassing resistance pathways. Augmenting the PARPi activity by combining it with other targets in the DNA damage response pathway, antiangiogenic agents and immune checkpoint inhibitors can potentially overcome the resistance mechanisms. Methods to bypass resistance include targeting non-cross-resistant pathways acting independent of homologous recombination repair(HRR), modulating tumour microenvironment, and enhancing drug delivery systems such as antibody drug conjugates. In this review, we will discuss the first-line management of ovarian cancer, resistance mechanisms and potential strategies to overcome these.