Citations

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

BACKGROUND AND OBJECTIVES: The lateral transorbital approach (LTOA) has gained increased recognition, but there is still a paucity of data on its effectiveness and advantages compared with the LTOA with lateral orbitotomy, herein denoted as the lateral orbital wall approach (LOWA). The aim of this study was to provide an anatomical reappraisal and the authors' clinical experience to compare the 2 approaches to the orbit and middle cranial fossa (MCF). METHODS: Eight latex-injected cadaveric specimens were used to perform LTOA and LOWA. The operative depth of each approach to key anatomical landmarks was measured. Fifty high-resolution computed tomography studies were reviewed to calculate the operative angles. We reviewed 40 consecutive cases treated with LTOA and LOWA at our institution. RESULTS: Compared with the LTOA, the LOWA provided shorter operative depths to the optic foramen ( P < .05), foramen ovale ( P < .05), and to the junction eyeball-cranial nerve II ( P = .13). It also offered better access to the anterior aspect of the orbit with less orbital content retraction. The LTOA and LOWA provided different operative angles to key anatomical landmarks in the orbit and MCF ( P < .05). In our chart review, 31 patients underwent the LTOA, whereas 9 underwent the LOWA to treat orbital and MCF lesions. Patients undergoing LOWA experienced postoperative complications related to periorbital nerves, such as frontalis palsy (n = 1) and supraorbital neuralgia (n = 1). Patients undergoing LTOA were more prone to complications associated with intraorbital manipulation (n = 4), including diplopia and ptosis. CONCLUSION: Our data suggest that the LTOA can be an effective surgical strategy for addressing orbital apex and MCF lesions. Although the LOWA provides access to the aforementioned areas, it may be more suitable for anterior orbital lesions that require direct access with wider entry exposure and extensive orbital content manipulation.

Abstract Context Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels. Objective Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism. Design Phase 3 trial with a 26-week, double-blind, placebo-controlled period followed by a 156-week, open-label extension (OLE). Setting Twenty-one sites across North America and Europe. Participants A total of 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52. Intervention(s) All OLE participants received TransCon PTH administered once daily. Main Outcome Measure(s) Multicomponent efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes and bone mineral density. Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events. Results At week 52, 81% (63/78) met the multicomponent efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. Patient-reported outcomes showed sustained improvements in quality of life, physical functioning, and well-being. Mean bone mineral density Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most treatment-emergent adverse events were mild or moderate and none led to trial discontinuation during the OLE. Conclusion At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.

Abstract Disclosure: S.W. Ing: Advisory Board Member; Self; Ultragenyx, Amolyt. Grant Recipient; Self; Alexion Pharmaceuticals, Inc.. Research Investigator; Self; BridgeBio Pharma, Takeda, Amolyt, Radius Health, Inc, Ultragenyx. P. Harmatz: Research Investigator; Self; BridgeBio Pharma. S. Mora: Research Investigator; Self; BridgeBio Pharma. E.A. Imel: Research Investigator; Self; BridgeBio Pharma. P.J. Tebben: Research Investigator; Self; BridgeBio Pharma. M.L. Warren: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt. Speaker; Self; Ascendis. N. Ma: Research Investigator; Self; Calcilytix Therapeutics, Ultragenyx, Inozyme. Other; Self; Up To Date. A.A. Khan: Research Investigator; Self; BridgeBio Pharma, Ascendis. A. Palermo: Research Investigator; Self; BridgeBio Pharma. B. Decallonne: Research Investigator; Self; BridgeBio Pharma. S. Lemoine: Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. G. Mantovani: Research Investigator; Self; BridgeBio Pharma. A. Linglart: Consulting Fee; Self; Alexion, Novo Nordisk, Merck, Pfizer, Inc.. Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. H. Wasserman: Research Investigator; Self; BridgeBio Pharma. A.P. Barbosa: Research Investigator; Self; BridgeBio Pharma. C. Cardot-bauters: Research Investigator; Self; BridgeBio Pharma. M. Roberts: Employee; Self; BridgeBio Pharma. A. Mathew: Employee; Self; BridgeBio Pharma. S. Adler: Employee; Self; BridgeBio Pharma. M.C. Zillikens: Research Investigator; Self; BridgeBio Pharma. R.J. Clifton-Bligh: Consulting Fee; Self; Ipsen, Kyowa Kirin, Amgen Inc, Eisai. Research Investigator; Self; BridgeBio Pharma. L. Rejnmark: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt, Takeda, Kyowa Kirin. Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR) variants, is characterized by low parathyroid hormone (PTH) concentrations, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. While a rare disease, ADH1 is one of the more frequently identified causes of genetic hypoparathyroidism. Conventional therapy includes calcium (Ca) and/or active vitamin D, but this regimen incompletely corrects the hypocalcemia and is associated with persistent hypercalciuria, which may result in renal complications including nephrocalcinosis (NC), nephrolithiasis (NL), and chronic kidney disease (CKD). The CLARIFY disease monitoring study [NCT05227287] is a global, multicenter, longitudinal study to understand disease burden, management, and progression in children and adults with ADH1 over a 5-year period. Here we report data on the characteristics of adult participants at study entry. As of November 2023, 45 adults (≥18 years) with ADH1 were enrolled, with a mean±SD age of 42.1±16.5 years (range 18-80). The mean±SD age of a hypocalcemia diagnosis was 19.1±19.1 years, while the mean±SD age for a diagnosis of ADH1 was 28.2±20.6 years. As reported on medical history, in decreasing order of prevalence, 36% (16) had NC, 22% (10) had intracranial calcifications, 11% (5) had history of seizures, 11% (5) had CKD, 9% (4) had cataracts, 7% (3) had NL, and 4% (2) had undergone renal transplant. Treatment data were available for 43 participants and included the following: 74% (32) Ca and active vitamin D, 9% (4) Ca alone, 9% (4) active vitamin D alone, 37% (16) magnesium, 33% (14) thiazide diuretics, 26% (11) potassium, 7% (3) phosphate binder, 7% (3) PTH, and 5% (2) no treatment. Mean±SD fasting values collected prior to conventional therapy dose are presented. PTH concentrations (10.1±8.2 pg/mL [nl 15-65]) and albumin-corrected calcium ([cCa]=7.5±1.0 mg/dL [nl 8.5-10.5]) were low. Despite the low mean cCa, the mean 24-hr urine calcium was elevated (268±183 mg/d, [nl &lt;250 women, &lt;300 men]). Blood phosphate was 4.8±0.8 mg/dL [nl 2.5-4.8] while blood magnesium was 1.8±0.2 mg/dL [nl 1.8-2.4]. 25-OH vitamin D was 35.0±13.5 ng/mL [nl 30-80]. Renal function as assessed by CKD-EPIcr_R showed eGFR of 86±23 mL/min/1.73m² (range 36-123). This study represents the largest cohort of adults with ADH1 described to date. These data highlight variability in therapeutic approaches in a real-world setting with some participants receiving up to 6 different medications/supplements. Despite being followed in expert centers, and treated with available therapies, patients on average have low cCa with relatively high 24-hr urine calcium excretion. The CLARIFY study provides an opportunity to better understand the progression and burden of disease in participants with ADH1. Presentation: 6/3/2024

Abstract Disclosure: S.W. Ing: Research Investigator; Self; BridgeBio Pharma. P. Harmatz: Research Investigator; Self; BridgeBio Pharma. S. Mora: Research Investigator; Self; BridgeBio Pharma. E.A. Imel: Research Investigator; Self; BridgeBio Pharma. P.J. Tebben: Research Investigator; Self; BridgeBio Pharma. M.L. Warren: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt. Speaker; Self; Ascendis. N. Ma: Research Investigator; Self; Calcilytix Therapeutics, Ultragenyx, Inozyme. Other; Self; Up To Date. A.A. Khan: Research Investigator; Self; BridgeBio Pharma, Ascendis. A. Palermo: Research Investigator; Self; BridgeBio Pharma. B. Decallonne: Research Investigator; Self; BridgeBio Pharma. S. Lemoine: Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. G. Mantovani: Research Investigator; Self; BridgeBio Pharma. A. Linglart: Consulting Fee; Self; Alexion, Novo Nordisk, Merck, Pfizer, Inc.. Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. H. Wasserman: Research Investigator; Self; BridgeBio Pharma. A.P. Barbosa: Research Investigator; Self; BridgeBio Pharma. C. Cardot-bauters: Research Investigator; Self; BridgeBio Pharma. M. Roberts: Employee; Self; BridgeBio Pharma. A. Mathew: Employee; Self; BridgeBio Pharma. S. Adler: Employee; Self; BridgeBio Pharma. M.C. Zillikens: Research Investigator; Self; BridgeBio Pharma. R.J. Clifton-Bligh: Consulting Fee; Self; Ipsen, Kyowa Kirin, Amgen Inc, Eisai. Research Investigator; Self; BridgeBio Pharma. L. Rejnmark: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt, Takeda, Kyowa Kirin. Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR) variants, is characterized by low parathyroid hormone (PTH) concentrations, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. While a rare disease, ADH1 is one of the more frequently identified causes of genetic hypoparathyroidism. Conventional therapy includes calcium (Ca) and/or active vitamin D, but this regimen incompletely corrects the hypocalcemia and is associated with persistent hypercalciuria, which may result in renal complications including nephrocalcinosis (NC), nephrolithiasis (NL), and chronic kidney disease (CKD). The CLARIFY disease monitoring study [NCT05227287] is a global, multicenter, longitudinal study to understand disease burden, management, and progression in children and adults with ADH1 over a 5-year period. Here we report data on the characteristics of adult participants at study entry. As of November 2023, 45 adults (≥18 years) with ADH1 were enrolled, with a mean±SD age of 42.1±16.5 years (range 18-80). The mean±SD age of a hypocalcemia diagnosis was 19.1±19.1 years, while the mean±SD age for a diagnosis of ADH1 was 28.2±20.6 years. As reported on medical history, in decreasing order of prevalence, 36% (16) had NC, 22% (10) had intracranial calcifications, 11% (5) had history of seizures, 11% (5) had CKD, 9% (4) had cataracts, 7% (3) had NL, and 4% (2) had undergone renal transplant. Treatment data were available for 43 participants and included the following: 74% (32) Ca and active vitamin D, 9% (4) Ca alone, 9% (4) active vitamin D alone, 37% (16) magnesium, 33% (14) thiazide diuretics, 26% (11) potassium, 7% (3) phosphate binder, 7% (3) PTH, and 5% (2) no treatment. Mean±SD fasting values collected prior to conventional therapy dose are presented. PTH concentrations (10.1±8.2 pg/mL [nl 15-65]) and albumin-corrected calcium ([cCa]=7.5±1.0 mg/dL [nl 8.5-10.5]) were low. Despite the low mean cCa, the mean 24-hr urine calcium was elevated (268±183 mg/d, [nl &lt;250 women, &lt;300 men]). Blood phosphate was 4.8±0.8 mg/dL [nl 2.5-4.8] while blood magnesium was 1.8±0.2 mg/dL [nl 1.8-2.4]. 25-OH vitamin D was 35.0±13.5 ng/mL [nl 30-80]. Renal function as assessed by CKD-EPIcr_R showed eGFR of 86±23 mL/min/1.73m² (range 36-123). This study represents the largest cohort of adults with ADH1 described to date. These data highlight variability in therapeutic approaches in a real-world setting with some participants receiving up to 6 different medications/supplements. Despite being followed in expert centers, and treated with available therapies, patients on average have low cCa with relatively high 24-hr urine calcium excretion. The CLARIFY study provides an opportunity to better understand the progression and burden of disease in participants with ADH1. Presentation: 6/3/2024

OBJECTIVE Advances in surgical technology and microneurosurgery have led to increased utilization of so-called minimally invasive approaches, including the supraorbital eyebrow (SE) and minipterional (MPT) approaches for lesions involving the interpeduncular region. This study aimed to describe and compare anatomical landmarks, along with highlighting the advantages and disadvantages of the SE and MPT approaches to the interpeduncular region. METHODS Ten formalin-fixed, latex-injected cadaveric specimens were used to perform bilateral SE and MPT approaches to the interpeduncular region. The operative depth of each approach to key anatomical landmarks was measured. Forty-five axial thin-slice computed tomography studies were reviewed to calculate the operative angles, with consideration of the midline as a reference. A 3D interactive anatomical model generated through the photogrammetry scanning technique was described. RESULTS The depths of the operative corridors of the SE and MPT approaches to the interpeduncular fossa were 83.4 ± 1.8 mm and 67.7 ± 3.2 mm, respectively (p < 0.001). The mean angle of the MPT approach to the interpeduncular fossa was significantly wider than the one provided by the SE approach (39.9° ± 5.1° vs 28.4° ± 3.6°, p < 0.001). The interpeduncular region can consistently be accessed through the carotid-oculomotor triangle with the SE approach, as well as with the MPT approach. Furthermore, the SE route offered adequate access to the interpeduncular fossa through the opticocarotid triangle. The MPT route provided direct access to the upper prepontine cistern and anterior mesencephalic zone (AMZ). CONCLUSIONS The MPT approach provides a wider and shorter operative corridor and can be employed for lesions in the interpeduncular region with extension to the prepontine cistern and ventrolateral midbrain lesions requiring access through the AMZ. The SE approach is better suited for ventromedial midbrain lesions requiring access via the interpeduncular fossa safe entry zone. Additional studies analyzing these approaches in a clinical setting will help to delineate their reliability and efficacy.

Abstract Study question What does the collaborative document on adenomyosis terminology, classification, and diagnosis by ESGE, ESHRE, and WES provides? Summary answer This good practice recommendations paper offers guidance on the technical aspects, terminology, classification, and diagnosis of adenomyosis in women of reproductive age. What is known already The existing literature on adenomyosis terminology is heterogeneous and confusing. Various classification systems based on ultrasound and MRI have been proposed, yet none have gained international acceptance or clinical validation. The contradictory data on the diagnostic accuracy of these modalities further complicate adenomyosis diagnosis in reproductive-age women. Study design, size, duration A working group from ESGE, ESHRE, and WES has collaborated to write recommendations concerning the terminology, classification, and diagnosis of adenomyosis. Participants/materials, setting, methods Focusing on terminology, classification, and diagnosis, this good practice paper paves the way for further recommendations on the management and surgical treatment of adenomyosis in reproductive-age women. Main results and the role of chance The document overviews adenomyosis terminology and reviews proposed classification systems based on histology, ultrasound, and MRI, concluding with diagnostic recommendations. Limitations, reason for caution Owing the scarcity of evidence, these recommendations predominantly rely on clinical expertise. Wider implications of the findings The recommendations aim to enhance existing adenomyosis guidelines. Study funding/Competing interests All costs were covered by ESHRE funds, with no external funding for the development process or manuscript production.