Recent Follow-up Research Articles

NIMG-84. BELZUTIFAN REDUCTION OF CEREBRAL BLOOD FLOW IN VHL-ASSOCIATED HEMANGIOBLASTOMA PREDICTS RESPONSE TO TREATMENT

Abstract Hemangioblastoma (HMB) is a vascular-origin tumor occurring primarily in the cerebellum. Treatment typically involves surgical resection of the solid part of the tumor or stereotactic radiosurgery. An emerging treatment for hemangioblastoma is belzutifan (BZF), a hypoxia-inducible factor 2a (HIF2a) inhibitor. A recent trial found BZF to control hemangioblastoma in patients with von Hippel Lindau (vHL) syndrome. Perfusion MRI techniques including arterial spin labelling (ASL) and can be used to determine relative cerebral blood flow (rCBF). No prior studies have investigated rCBF in hemangioblastoma with relation to belzutifan, and the mechanism of action of belzutifan on hemangioblastoma is not well understood. Here, we aim to measure the response in rCBF in patients with vHL-associated hemangioblastoma treated with belzutifan. This retrospective cohort study constituted a group of seven patients with vHL-associated hemangioblastoma treated with Belzutifan at a daily oral dose of 120mg. Perfusion MRI with ASL sequences were acquired as part of the tumor imaging protocol. We quantified rCBF of the tumors prior to treatment, following intiation of BZF, and at most recent follow-up. Statistics were performed using R studio. The long axis diameter, volume of the solid tumor, rCBF mean, rCBF max, N mean, N max of lesions all decreased after Belzutifan treatment (p<0.001). While the long axis diameter of the cyst in cystic lesions did not show statistically significant change, the volume of cysts decreased significantly on Belzutifan (p=0.016). Spearman’s rank correlation analysis demonstrated association between change in rCBF mean, rCBF max, N mean and N max to % reduction in tumor volume. In addition, change in rCBF mean, change in rCBF max and change in N max all showed statistically significant association on multiple linear regression. Finally, early change in CBF and N predicted further volumetric response to treatment with belzutifan. We demonstrate that vHL-associated hemangioblastoma demonstrates decrease in rCBF in conjunction with and predictive of decreased volume following treatment with belzutifan.

Association of Oral Tobacco-Free Nicotine Delivery Product with Acute Renal Tubular Necrosis

Usage of novel non-tobacco oral nicotine delivery products (ONDPs) has been increasing among adolescents in the United States. It is presumed that they are less toxic than their tobacco-containing counterparts, but that has not been examined in controlled studies. Most of the studies have focused on non-renal manifestations of tobacco consumption via different means. The renal manifestations of non-tobacco ONDPs are not very well known, especially in immunocompromised patients. A 19-year-old male transplant recipient presented with flank pain and a few days’ history of intake of ZYNR pouches. Immunosuppression was with tacrolimus, mycophenolate, and steroids. Baseline serum creatinine was 1.1–1.3 mg/dL. Laboratory evaluation showed elevated C-reactive protein, increased serum creatinine and blood urea nitrogen, leukocytosis, neutrophilia, and increased lactate dehydrogenase (LDH). Infectious disease work-up was negative. A kidney transplant biopsy showed severe acute tubular injury/necrosis (ATN) without evidence of rejection. Donor-specific antibodies were negative. Other etiologies of hemolysis were negative. He did not require renal replacement therapy. Kidney function and LDH improved gradually. The most recent follow-up eight months after presentation showed a serum creatinine level of 2.6 mg/dL with stable electrolytes, with eGFR of 35 mL/min/1.73 m2. Here, we describe a 19-year-old adolescent with a kidney transplant who sustained ATN leading to advanced chronic disease apparently following the usage of non-tobacco ONDP. Further larger studies are needed to study ATN as a possible renal manifestation of these next-generation products to raise awareness among the public.

Resilience and spiritual well-being as resources for coping with radiotherapy and surviving in patients with glioblastoma.

The primary aims of this multicenter, prospective observational study were to investigate spiritual well-being, resilience, and psychosocial distress in an Italian sample of glioblastoma patients undergoing radiochemotherapy. The secondary aim was to explore the influence of demographic, clinical, and psychological characteristics on survival. The assessment was conducted only once, within the first week of radiochemotherapy treatment. Spiritual well-being was evaluated by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-Sp-12), and religious/spiritual beliefs and practices were evaluated by the System of Belief Inventory. Resilience was evaluated by the Connor-Davidson Resilience Scale (CD-RISC). Psychosocial distress was evaluated the by Distress Thermometer and Hospital Anxiety Depression Scale. We conducted an univariable analysis of overall survival (OS) using data from the most recent follow-up available, considering demographic and clinical variables that could influence survival. Follow-up was defined as either the time of death or the latest follow-up visit recorded. We recruited 104 patients, and the median follow-up time was 18.3 months. "Distressed" patients had lower scores than "not distressed" patients on the FACIT-Sp-12 and CD-RISC. While OS was not significant according to the FACIT-Sp-12 threshold, the Kaplan-Meier log-rank test was 0.05 according to the CD-RISC threshold. Among demographic variables, age showed significant associations with OS (p = 0.011). Resilience showed significant associations with OS (p = 0.025). Data showed that high spiritual well-being was associated with high resilience and an absence of psychosocial distress in our sample of glioblastoma patients undergoing radiochemotherapy. Patients with greater resilience survived longer than those with lesser resilience. Profiling spiritual well-being and resilience in glioblastoma patients undergoing radiochemotherapy can be seen as a resource to identify novel characteristics to improve clinical take-in-charge of glioblastoma patients.

Surgical Treatment and Outcomes of Trans-Ulnar Basal Coronoid Fracture-Dislocations

Trans-ulnar fracture-dislocations of the elbow are complex injuries that can be difficult to classify and treat. Trans-ulnar basal coronoid injuries, in which the coronoid is not attached to either the olecranon or the metaphysis, present substantial challenges to achieve anatomic reduction and stable internal fixation. The purpose of this study was to analyze the outcome of surgical treatment of trans-ulnar basal coronoid fracture-dislocations. Between 2002 and 2019, 32 consecutive trans-ulnar basal coronoid fracture-dislocations underwent open reduction and internal fixation (ORIF) at our institution. Four elbows were lost to follow-up within the first 6 months after surgery and were excluded. Among the 28 elbows remaining, there were 13 females and 15 males with a mean age of 56 (range 28-78) years at the time of injury. The mean clinical and radiographic follow-up times were 37 months and 29 months, respectively. Radiographs were reviewed to determine rates of union, Hastings and Graham heterotopic ossification (HO) grade, and Broberg and Morrey arthritis grade. Union occurred in 25 elbows. Union could not be determined for 1 elbow at most recent follow-up and the remaining 2 elbows developed nonunion of the coronoid. Complications occurred in 10 elbows (36%): deep infection (4), ulnar neuropathy (2), elbow contracture (2), and nonunion (2). There were reoperations in 11 elbows (39%): irrigation and débridement with hardware removal (4), hardware removal (2), ulnar nerve transposition (2), contracture release with HO removal (2), and revision ORIF with iliac crest autograft (1). At most recent follow-up, the mean flexion-extension arc was 106° (range 10-150°), and the mean pronation-supination arc was 137° (range 0-170°). The mean Quick Disabilities of Arm, Shoulder, and Hand score was 11 (range 0-39) points with a mean Single Assessment Numeric Evaluation-Elbow score of 81 (range 55-100) points. At final radiographic follow-up, 16 elbows (57%) had HO (8 class I and 8 class II), and 20 elbows (71%) had arthritis (8 grade 1, 6 grade 2, and 6 grade 3). Trans-ulnar basal coronoid fracture dislocations are severe injuries associated with high rates of reoperation, heterotopic ossification, and post-traumatic arthritis. However, the majority of elbows achieve union, a functional range of motion, and reasonable patient reported outcome measures. Over the study period, surgeons were more likely to utilize multiple deep approaches and separate fixation of the coronoid (either with lag screws or anteromedial plates) to ensure anatomic reduction.

Plate Osteosynthesis of Proximal Humerus Fracture is Associated with Significant Complications and Poor Functional Score for Patients Older than 45 Years Old: A Cohort Study

BackgroundDespite the introduction of new implants and biomechanical improvements for proximal humerus fractures (PHF), the complication rate remains significant, particularly in older adults. This study aimed to identify risk factors for complications and failure following plate osteosynthesis for PHF and discuss an age cut-off that surgeons should consider for complications. MethodsAdults with PHF treated with the proximal humerus internal locking system (PHILOS) at our large tertiary academic referral center between 2015 and 2020 were retrospectively identified. Univariate analysis was used to compare patients with and without complications. Then, a multivariate regression analysis was conducted to assess the possible complication risk factors. The receiver operating characteristic (ROC) curve of age was drawn to predict complication-free and favorable functional outcomes at the most recent follow-up. Oxford Shoulder Score (OSS) was considered favorable if OSS<10. ResultsA total of 135 patients were identified, with a mean age of 44 years (range 18-85 years) and a mean follow-up duration of 4.6 years (range 2-8 years). Complications were observed in 19 cases (14.1%), namely nonunion (n=5), avascular necrosis (n=1), infection (n=1), intra-articular screw perforation (n=1), arthritic changes (n=5), and superior humeral head migration (n=5). Eight patients (5.9%) needed revision surgery. Older age (OR=1.09) and Neer IV class (OR= 8.3) were associated with an increased likelihood of complication (P<0.001, P=0.02, respectively) in logistic multinominal regression analysis. The ROC curve for age in predicting complication-free cases had an area under the curve (AUC) of 0.829, indicating age as a significant predictor of ORIF outcomes in PHF (P<0.05). The optimalcut-off for age was 44 years, which yielded a sensitivity of 100% and a specificity of 65.7. The age ROC curve for predicting favorable OSS (OSS<10) had an of 0.829, indicating that age could predict the favorable OSS outcomes of ORIF in PHF. The optimal age cut-off was 46 years, yielding a sensitivity of 70.0% and a specificity of 78.6%. ConclusionThe outcomes of ORIF for PHF in patients older than 45 years are associated with significantly higher complication rates and poorer functional outcomes. Surgeons should possibly consider other treatment options for PHF in each older patient individually, especially with Neer type IV fractures.

Clean Intermittent Catheterisation via a Mitrofanoff is superior to long term Suprapubic Catheters for Bladder Drainage.

AimSome children require long-term drainage of the bladder but do not tolerate clean intermittent catheterisation (CIC) urethrally. We aimed to compare long term suprapubic catheter (SPC) drainage vs Mitrofanoff conduit (allowing CIC) by comparing the survival of the drainage methods and rates of urinary tract infection (UTI). MethodRetrospective review of a single surgeon’s experience (2007-2023). Data collection included diagnosis, age at procedures, date of surgery, date of most recent follow-up and date and reason for unplanned surgery. For SPCs, initial insertion of SPC and then conversion to a Foley catheter under GA was taken as normal (event free survival) and only further operations were counted as complication events. For Mitrofanoffs, any subsequent operation was counted as a complication.Data were given as a number (%) or median (interquartile range) as appropriate. Data analysed by Fisher exact and Mann-Whitney U-test. Kaplan Meier (KM) survival of drainage routes was compared, P<0.05 taken as significant. ResultsThere were 45 patients (n = 86 SPC episodes) compared to 108 patients (n = 110 Mitrofanoff procedures). Data were available in 73 SPC episodes and 109 Mitrofanoff episodes, including 3 redo procedures (one from another centre). There was no difference in gender (SPC group, 67% male vs. Mitrofanoff group, 77%; N.S.). There was no difference in age at procedure [7.5 (2.9 - 11.5) years vs 8.3 (5.9 - 11.4) years respectively; N.S.)KM comparison showed that Mitrofanoff have a better event-free survival than SPC (91% vs 52% at 1 year; 80% vs. 13% at 5 years; P<0.0001). Paired data showed a significant (86%) reduction in rate of UTI with conversion from SPC to Mitrofanoff drainage in 15 patients; SPC: 0.13 (0 - 0.46) UTIs/month vs subsequent Mitrofanoff: 0.02(0 - 0.08) UTI/month, P=0.04). ConclusionSPCs had a much higher rate of unplanned surgery than Mitrofanoffs, creating a considerable unplanned burden of care for families and clinical staff. For long-term bladder drainage CIC via a Mitrofanoff conduit should be considered in preference to SPC where urethral CIC is not possible.

Safety and efficacy of combined acetabular reconstruction and microwave ablation in the treatment of periacetabular metastatic disease: a retrospective clinical evaluation.

The periacetabular bone defects caused by metastatic disease often necessitate acetabular reconstruction and various techniques have been employed with varying degrees of success. The purpose of this study was to evaluate the efficacy and safety of acetabular reconstruction in conjunction with adjuvant microwave ablation as a surgical intervention for patients with periacetabular metastases. Between January 2019 and September 2023, 17 consecutive patients with different tumor subtypes required surgical intervention for periacetabular metastases. The acetabular reconstruction was performed by utilizing an acetabular reconstructive cage and cement total hip arthroplasty with microwave ablation. A retrospective review was performed to assess pain relief, intraoperative details and postoperative complications. Functional status following procedures was determined by the 1993 Musculoskeletal Tumor Society (MSTS) score and the overall survival of patients was estimated by Kaplan-Meier analysis. In total, 8 males and 9 females were included with an average age of 48.6 years (range 34-66). Patients reported a significant improvement in the level of pain and the mean VAS score declined from 7.7 preoperatively to 2.2 postoperatively. Of the 17 patients, 16 could ambulate either independently (6 patients) or using a walking aid (10 patients) with a mean MSTS score of 18.9. The median follow-up was 9.0 months. Nine patients were alive at the most recent follow-up with overall survival of 40.9% at 12 months and 30.7% at 36 months, respectively. In selected patients with periacetabular metastasis, the utilization of an acetabular cage and cement total hip arthroplasty presents a less invasive reconstruction technique. The incorporation of adjuvant microwave ablation has shown promise in providing long-lasting pain relief, reducing intraoperative bleeding, and improving local tumor control. However, further research and extended follow-up are necessary to establish the effectiveness of this procedure.

Radiographic Measurements of Pes Planovalgus Do Not Predict Clinical Outcomes in Tarsal Coalition Excision.

Many patients who undergo tarsal coalition excision have persistent postoperative pain. Most studies have utilized cat scan (CT) scan parameters of pes planovalgus and heel valgus but have found this to be an inconsistent predictor of outcomes. Plain radiographic parameters have been less utilized in trying to predict outcomes after coalition excision. Radiographic talonavicular coverage angle correlates with pain in patients with flexible pes planovalgus (PPV) but has not been studied in tarsal coalition population. Furthermore, foot alignment is not understood to change after simple coalition excision. The purpose of this study was to compare plain radiographic parameters, including talonavicular coverage angle, with pain after tarsal coalition excision, as well as compare preoperative and postoperative weight-bearing radiographs. Seventy-seven feet that underwent excision of the tarsal coalition had clinical outcomes and radiographic data collected >1 year postoperatively. Measures of PPV on preoperative and postoperative weight-bearing radiographs and CT scans were evaluated. Patients were an average of 13 years old at excision. Of the total, 65% had calcaneonavicular (CN) coalitions, whereas the remainder had talocalcaneal coalitions. All patients had significant postoperative improvement in clinical outcomes but 34% (13/38) had continued pain at the most recent follow-up, more so in talocalcaneal than CN coalitions (55% vs 26%, P < 0.001). The subset with CN coalitions had more severe preoperative PPV but greater postoperative PPV improvement. Except for a weak correlation between radiographic weight-bearing (anterior-posterior) talus-first metatarsal angle and pain with activity (r = -0.54), there were no other correlations between preoperative radiographic parameters and clinical outcomes. Heel valgus on CT did not correlate with radiographic measurements of PPV or pain. We did not find a correlation of radiographic PPV with persistent pain after tarsal coalition excision. We did find improvement in radiographic PPV in CN coalitions after treatment with simple excision. Heel valgus on CT was not a useful metric for evaluating PPV in the setting of a tarsal coalition. Level III-prognostic study.

Leadless pacemaker - lead parameters stability and battery longevity in the mid-term follow-up

Abstract Background A leadless pacemaker (L-PM) has been designed to avoid the need for a pacemaker pocket and transvenous lead. Long-term safety will largely depend on the need for replacements, mainly due to battery depletion (end-of-life). While the mean L-PM battery longevity predicted by the manufacturer is 12 years, real-world longevity data are still scarce. We aimed to describe L-PM parameters’ stability and battery longevity during the mid-term follow-up. Methods Single-center registry of consecutive patients undergoing L-PM implantation from May 2015 to November 2023. Procedural characteristics, lead parameters and battery longevity were collected immediately after implantation and during the most recent follow-up visit. Results Overall, 261 consecutive patients had a transcatheter L-PM implanted through a femoral vein (mean age 78±10 years; 66% male). Mean procedural duration was 44±28min and fluoroscopy time was 4,4±3,9min. The device was successfully implanted in all but one patient. The main indications for permanent pacing were high-degree atrioventricular block [N=130 (50%)], atrial fibrillation with pauses [N=78 (30%)], and sinus node disease [N=28 (11%)]. Immediately after implantation, three cases (1,2%) of pericardial effusion (one with tamponade) were reported. In one case (0,4%), a conventional pacemaker was implanted due to L-PM acute dysfunction. No other procedure-related complications, including dislodgment, were reported at discharge. After a mean follow-up of 2,8±1,7years, the pacing threshold and R-wave amplitude remained stable [0,67mV vs. 0,62mV (p=0,9); and 10,3mV vs. 16,1mV (p&amp;lt;0,001), respectively] and mean ventricular pacing was 54±38%. Expected battery longevity was &amp;gt;8 years (maximum value) in 84% of the patients. In the subgroup of patients with &amp;gt;5 years of follow-up (N=20; mean follow up of 6,3±1,8years), the expected battery longevity was &amp;gt;8 years in 85% (N=17) of the patients. In three cases, the L-PM was upgraded to cardiac resynchronization therapy or left bundle branch area pacing due to pacing-induced left ventricular dysfunction. There was one case of L-PM end-of-life 6 years after implant (pacing threshold 0,5mV; ventricular pacing 100%), in which a second L-PM was successfully implanted. Overall, 78 (31%) patients died, a mean of 2,2±1,9 years after L-PM implantation, none related to the device. Conclusion In this real-world cohort, L-PM maintained stable pacing parameters and, in the mid-term follow-up, only one battery depletion was observed while expected longevity remained above 8 years in the large majority of patients. Longer follow up will allow better understanding of both technical and clinical aspects relevant to manage end-of-life devices.Table 1Figure 1

Effect of a participatory whole-systems approach on mortality in children younger than 5 years in Jigawa state, Nigeria (INSPIRING trial): a community-based, parallel-arm, pragmatic, cluster randomised controlled trial and concurrent mixed-methods process evaluation

In 2019, Nigeria reported the highest mortality rate in children younger than 5 years globally. We aimed to assess a whole-systems approach to improving child mortality in northern Nigeria. We conducted a community-based, parallel-arm, pragmatic, cluster randomised controlled trial in Kiyawa local government area, Jigawa state, Nigeria, and a concurrent mixed-methods process evaluation using ethnography and quantitative implementation monitoring. Trial clusters were population catchment areas of 32 government primary health-care facilities. Compounds were randomly sampled, proportional to cluster size, and all women aged 16-49 years and children younger than 5 years who were permanent residents were eligible for inclusion and recruited as the evaluation population. Children younger than 7 days were recruited but excluded from analysis. Evaluation clusters were allocated to intervention or control via simple randomisation with a 1:1 ratio. Cluster names were written on paper, folded, and placed in a container by community representatives. Different community representatives took out names one by one, with the first half assigned to receive the intervention. The intervention consisted of three components: participatory learning and action (PLA) groups for men and women (including compound heads [ie, the member of the compound that residents deemed most senior]), partnership defined quality scorecard (PDQS), and health-care worker capacity building; it was delivered from March 1, 2021, to Dec 31, 2022. We could not mask participants, field staff, or intervention-delivery staff to cluster allocation but baseline, endline, and follow-up data excluded information on cluster allocation. PLA groups involved separate groups of up to 25 men or women from all villages in the intervention clusters. The primary outcome was all-cause mortality in children aged 7 days to 59 months between Oct 1, 2021, and Sept 20, 2022, referred to as the evaluation period. The trial was prospectively registered (ISRCTN 39213655) and the protocol has been published. We recruited 3800 compounds at baseline, with 12 893 children contributing to analysis of the primary outcome (7316 [56·8%] of 12 893 in the intervention group and 5577 [43·3%] in the control group). 6617 (51·3%) of 12 893 children were male, 6275 (48·7%) were female, and one (<0·1%) child had missing sex data. Sampled compounds randomly came from 388 (91·3%) of 425 villages in the 32 clusters. We conducted verbal autopsies for 1182 deaths, of which 369 (31·2%) were children aged 7 days to 59 months during the evaluation period. Of these 369, 91 (24·7%) were classified as pneumonia deaths. Children contributed a median 361 days (IQR 236-365) to the analysis, with 369 (2·9%) of 12 893 children censored on their date of death, 1545 (12·0%) on their 5th birthday, and 3392 (26·3%) on the date of the most recent follow-up in which their residence or survival status was known. We found no significant decrease in all-cause mortality (hazard ratio 0·95, 95% CI 0·68-1·33; p=0·79) or suspected pneumonia mortality (0·79, 0·43-1·46; p=0·46) in the intervention group. The process evaluation showed low coverage and issues in reach of the intervention, but qualitative data highlighted mechanisms for positive effects on health and relationships. Our intervention did not affect mortality. However, due to the high child mortality in this region, further efforts should be made to adapt our participatory whole-systems approach to use communities of action within compounds. GSK and Save the Children UK. For the Hausa translation of the abstract see Supplementary Materials section.

Auer rod-positive acute leukemia with predominantly lymphoid immunophenotype: Report on 11 cases and review of literature.

Auer rods (AuRs) are prominent intracellular structures found almost exclusively in myeloid cell malignancies, such as acute myeloid leukemia (AML), chronic and juvenile myelomonocytic leukemia and myelodysplastic syndrome. Extremely rare AuRs have been reported in patients with acute lymphoblastic leukemia (ALL) or among ambiguous lineage leukemia patients with a dominantly lymphoblastic immunophenotype. We report diagnostic and follow-up data of an international cohort of 11 children suffering from leukemias with AuRs and with significant presence of T and myeloid markers, majority of whom categorized as early T-cell precursor (ETP, n=7); or T-ALL (ETP status unknown, n=2), ALAL (acute leukemia of ambiguous lineage, n=1), and AML reclassified from ALAL (n=1). We described other diagnostic details and treatment types and responses. Moreover, we summarize previously published data. Among the four patients who started and remained on ALL-type therapy, all were in the first complete remission, whereas both patients who started and remained on AML-type therapy relapsed and died. Of the patients who followed either a combined ALL/AML protocol (Interfant 06) or who switched from one of the two types of therapy to the other, one patient died, and the remaining four were in first complete remission at the most recent follow-up. We also searched for similar cases in the literature and found only three additional children with nonmyeloid leukemia and AuRs and 10 adults with this type of leukemia. Briefly, ALL- or combined ALL/AML-type therapy may be effective for treating AuR-positive leukemia patients with a lymphoid immunophenotype.

Respiratory failure and rhabdomyolysis caused by severe hypokalemia in a young female with hypertension: a rare critical condition in primary aldosteronism

BackgroundThe two classic manifestations of primary aldosteronism are hypertension and hypokalemia. However, acute respiratory failure due to hypokalemia in primary hyperaldosteronism is rare.Case presentationThe patient was a 27-year-old female who presented with drowsiness and weakness in all extremities. She had been diagnosed with hypertension three years prior, with irregular follow-up, and had a history of preeclampsia one year later. She exhibited high blood pressure and severe hypokalemia (2 mEq/L), leading to respiratory depression and impending respiratory arrest. Consequently, the patient was intubated and transferred to the intensive care unit (ICU). She also developed rhabdomyolysis. Blood pressure tests, including hormonal tests (aldosterone: 13.2 ng/dL, plasma renin activity: 0.32 ng/mL/h), were conducted. Due to the high aldosterone-renin ratio, an abdominopelvic computed tomography (CT) scan was performed. The CT scan revealed a 14 × 12 mm round mass with a washout value above 60%, consistent with an adrenal adenoma, leading to a diagnosis of primary aldosteronism. The patient was discharged after stabilization, and one and a half months after ICU admission, a laparoscopic left adrenalectomy was successfully performed without post-operative complications. Histopathology showed encapsulated hypertrophy of the adrenal cortex with a predominance of large clear cells, confirming the diagnosis of adrenal adenoma. At the most recent follow-up, the patient had normal potassium levels, was normotensive without any medications, and exhibited no alarming signs or symptoms.ConclusionRespiratory depression to the extent of impending respiratory failure and rhabdomyolysis as a result of hypokalemia in primary aldosteronism are extremely rare. In this patient, who developed respiratory depression due to resistant hypokalemia, timely investigation of secondary causes and diagnosis of adrenal adenoma were crucial. The surgery provided definitive treatment for the patient’s blood pressure and prevented the recurrence of life-threatening complications.

Racial, Ethnic, and Socioeconomic Disparities in Pediatric Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder

BackgroundOnly 5% of aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) cases emerge during childhood. Poorer outcomes have been suggested in black/African American (AA) adults with NMOSD; however, conflicting and limited data exist for pediatric-onset NMOSD. This study evaluates racial, ethnic, and socioeconomic disparities in pediatric AQP4+ NMOSD outcomes. MethodsThirty-eight pediatric patients with AQP4+ NMOSD cared for at three pediatric tertiary care centers between 2009 and 2021 were identified. Patient addresses connected to socioeconomic measures available from the US Census. Demographic characteristics, pertinent clinical outcomes, and health care utilization in the two years following diagnosis were captured. ResultsCompared with non-Hispanic White children, Black/AA children had a significantly higher Expanded Disability Status Scale (EDSS) (2.46 vs 0.33, P = 0.003), 2.37 more hospital admissions (P = 0.002), and 28.40 additional inpatient days (P = 0.002) in the two years following their NMOSD diagnosis. Additionally, children with public insurance had higher relapse rates than those with private insurance (P = 0.046). At two years and at the most recent follow-up, a significantly higher EDSS was correlated with children living in census tracts with a lower median income, higher deprivation index, and higher proportion of population on assisted income, in poverty, and with vacant housing (all P < 0.05). ConclusionsWe identified racial, ethnic, and socioeconomic disparities in clinical outcomes and health care utilization in pediatric AQP4+ NMOSD. Further prospective and household-level data are needed to dissect the interplay of genetics, structural racism, and social determinants of health so that interventions to optimize care and outcomes for this population may be developed.

Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy

BackgroundCerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing ABCD1 complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy.MethodsIn a phase 2–3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI). The primary efficacy end point was survival without any of six major functional disabilities at month 24. The secondary end points included overall survival at month 24 and the change from baseline to month 24 in the total neurologic function score.ResultsA total of 32 patients received eli-cel; 29 patients (91%) completed the 24-month study and are being monitored in the long-term follow-up study. At month 24, none of these 29 patients had major functional disabilities; overall survival was 94%. At the most recent assessment (median follow-up, 6 years), the neurologic function score was stable as compared with the baseline score in 30 of 32 patients (94%); 26 patients (81%) had no major functional disabilities. Four patients had adverse events that were directly related to eli-cel. Myelodysplastic syndrome (MDS) with excess blasts developed in 1 patient at month 92; the patient underwent allogeneic hematopoietic stem-cell transplantation and did not have MDS at the most recent follow-up.ConclusionsAt a median follow-up of 6 years after lentiviral gene therapy, most patients with early cerebral adrenoleukodystrophy and MRI abnormalities had no major functional disabilities. However, insertional oncogenesis is an ongoing risk associated with the integration of viral vectors. (Funded by Bluebird Bio; ALD-102 and LTF-304 ClinicalTrials.gov numbers NCT01896102 and NCT02698579, respectively.)

Aberrant right subclavian artery intervention can provide relief of dysphagia.

An aberrant right subclavian artery represents the most common aortic arch vascular anomaly. Conventional wisdom states that these anomalies do not result in dysphagia, but rather serve as "red herrings". Clearly, in the vast majority of cases, this holds true. Nonetheless, one should never say never. Herein, we present a cohort of four children with debilitating dysphagia resulting from an aberrant right subclavian artery. Subclavian reimplantation via a right posterolateral thoracotomy was performed successfully in all cases. Dysphagia resolved postoperatively, and all patients were able to advance to a normal diet. They were able to gain appropriate weight postoperatively and continue to do well at most recent clinical follow-up. This case series suggests that aberrant right subclavian artery anatomy should be considered a potential aetiology of dysphagia, albeit rarely. Surgical intervention for select patients can provide dramatic resolution of symptoms.

7787 Primary Aldosteronism Medical Treatment Outcomes (PAMO): An International Consensus on Outcome Assessment Criteria and Multicentre Study

Abstract Disclosure: J. Yang: None. J. Burrello: None. J. Goi: None. T.A. Williams: None. W.F. Young: Consulting Fee; Self; Arena Pharmaceuticals, Inc.. Other; Self; Crinetics Pharmaceuticals. P.J. Fuller: None. P. Investigators: None. Primary aldosteronism (PA) is the most common endocrine cause of hypertension. Mineralocorticoid receptor antagonists, at adequate doses, lower blood pressure and cardiovascular risk in patients with PA. However, there is a lack of a standardized approach to medical therapy and subsequent outcomes assessment. We aimed to: 1) establish criteria for assessing outcomes of targeted medical treatment of PA, and 2) evaluate outcomes using these criteria across an international cohort. A panel of 31 PA experts from 31 centres across four continents used the Delphi method, including three rounds of online questionnaires, to reach consensus. Clinical data were then collected from consecutive patients with PA who started targeted medical treatment between 2016 and 2021 at the participating centres. Consensus was reached for six outcomes, including complete, partial, or absent biochemical response, and complete, partial, or absent clinical response. “Complete biochemical response” was defined as “correction of hypokalemia without potassium supplementation, and normalization of plasma renin activity or concentration”; while “absent biochemical response” was defined as “persistent hypokalemia and/or persistently suppressed or low plasma renin activity or concentration without change from baseline”. “Complete clinical response” was defined as “normal blood pressure without additional antihypertensive medications”; while “absent clinical response” was defined as “the same or increased blood pressure compared to before targeted treatment with same or more antihypertensive medications, not counting targeted therapy”. Of 1483 patients (mean age 52y, 48% female) from 28 centers, 232 (16%) had a complete clinical response, and 719 (49%) had a complete biochemical response at the most recent follow-up (median 29 months after treatment initiation). Compared to those with partial or absent clinical response, patients with complete clinical response had a significantly higher proportion of women and lower proportion with diabetes, stroke or left ventricular hypertrophy. They also had a significantly shorter duration of hypertension, lower BMI, higher eGFR and lower defined daily dose of antihypertensives at baseline. In contrast, these differences were not observed in those with a complete, partial or absent biochemical response. The defined daily dose of targeted therapy did not differ across the various response categories. In conclusion, we have established an international expert consensus for standardized criteria to evaluate the response to targeted medical treatment of PA, facilitate comparisons of outcome data and guide clinicians who manage PA. In a retrospective international cohort, less than half of medically-treated patients reached the established biochemical treatment targets. Further work is needed to increase the rate of complete response. Presentation: 6/3/2024

7202 CPP with Rapid Pubertal Progression in a 9-Year-Old Boy with Hypothalamic Teratoma

Abstract Disclosure: R. Robilliard: None. G. Tung: None. K. Svokos: None. R. Lulla: None. J.Q. Quintos: None. Background: Central Precocious Puberty (CPP) in males is rare, with incidence of 0.01-2/10,000. The most common identifiable cause of CPP in young children is hypothalamic hamartoma. No case hypothalamic teratoma has been reported to cause CPP in males. Clinical Case: At the age of 10-years and 5-months, a boy presented to the pediatric endocrinology with signs of precocious puberty including facial hair development, voice deepening, and increased growth velocity that began at 9 years old. There was no significant past medical history and he denied headache, blurry vision, or diplopia. Physical examination showed height of 140.4 cm (47%), Tanner 4 genitalia, Tanner 3 pubic hair, and testicular volumes of 15 cc (left) and 12-15cc (right). Bone age (BA) determined by radiography was 13.5 years with a predicted adult height (PAH) of 63 inches. The mid-parental target height was 67 +/- 4 inches. Evaluation including TSH, glucose, serum and CSF β-HCG, DHEA, CSF AFP was normal. Serum LH was 2.9 IU/L and testosterone level was 109 ng/dl, consistent with CPP. MRI of the pituitary showed a small, heterogeneous and fat-containing lesion extending inferiorly from the tuber cinereum consistent with teratoma. Treatment included GnRH agonist Lupron (30mg) every 3 months. Laboratory evaluation 8 months after initial presentation showed suppressed LH of 0.9 IU/L and FSH 0.5 mIU/mL, and testosterone of 57 ng/dL. Repeat radiography for BA one year after GnRHa suppression showed BA of 14 years at CA of 11 years 6 months and PAH of 64.4 inches. Growth velocity slowed to 5.3 cm/year. At the most recent follow-up visit at CA of 12 years, height was 151.5 cm (61%), growth velocity 6.3 cm/year (74% for age), Tanner 5 penis and pubic hair, left testicular volume of 15-20cc and right testicular volume of 15 cc. Most recent radiographic BA is14 years, and PAH is 65.9 inches. Given response to GnRH agonist injections every 3 months, the absence of CNS symptoms referable to the teratoma and no change in MR imaging, no surgical intervention is recommended. Conclusion: This is the first case of a hypothalamic teratoma reported in a male associated with CPP. Despite this rare cause, the patient has responded to standard treatment with GnRH agonist therapy alone. Presentation: 6/1/2024

Articular cartilage debridement results in short-term significant improvements in patient-reported outcomes for large areas of cartilage loss of the femur in the setting of mild to moderate knee osteoarthritis

PurposeThis study aims to evaluate patient-reported outcomes (PROs) following chondroplasty in patients with larger chondral defects (≥2 cm2) of the femur in the setting of osteoarthritis. Materials and methodsRetrospective review of patients who underwent chondroplasty of the femur. All patients were radiographically assessed to have Kellgren-Lawrence (KL) grades of 2 or 3 and had a minimum of 1-year postoperative follow-up. Areas of chondral loss were estimated by arthroscopic measurements and by MRI. PROs included the International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, and the Veterans Rand-12 Item. Statistical analysis was performed using paired t tests to compare baseline and follow-up data, as well as linear regressions to correlate lesion size with symptom improvement. ResultsA total of 39 patients were included. There were 20 KL grade 2 and 19 KL grade 3 knees. At both 1- and 2-year follow-ups, significant improvements were noted in International Knee Documentation Committee (34.9 ± 13.5 preoperative, 55.6 ± 18.8 at 2 years, P = .0025), Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (56.3 ± 14.7 preoperative, 64.5 ± 17.0 at 2 years, P = .0243), and Veterans Rand-12 Item Physical Component Scores (38.0 ± 12.7 preoperative, 43.8 ± 8.6 at 2 years, P = .0044). All increases exceed previously reported Minimal Clinically Important Differences. Four (10.3%) conversions to arthroplasty were noted at most recent follow-up. ConclusionsArticular cartilage debridement for large areas of cartilage loss of the femur in the setting of mild to moderate knee osteoarthritis results in significant improvements in physical function and knee-specific PROs at 1- and 2-year follow-ups.

Ten-year follow-up after face transplantation—A single-center retrospective cohort study

Face transplantation has emerged as reconstructive option for the most challenging facial deformities. A comprehensive analysis of functional outcomes, medical complications, incidence of malignancy, and chronic rejection in face transplantation recipients over an extended follow-up period has not yet been published leaving a notable gap in the literature. We retrospectively collected data of morbidity, rejection, vasculopathy, metabolic side effects, as well as functional outcome of sensory return, facial motor function, and speech from 9 patients who underwent face transplantation at Brigham and Women’s Hospital between 2009 and 2020. The median follow-up was 120 months (54 and 154 months). Four grafts (40%) developed signs of clinical and histopathologic chronic rejection without evidence of vasculopathy on computed tomography angiograms. Sensory return assessed with Weinstein enhanced sensory testing-monofilament showed an increase in 6 patients (66.7%), and facial expression analysis showed improvement throughout the whole cohort at their most recent follow-up. Speech intelligibility was stable or increasing for 5 patients (55.6%). In conclusion, the long-term outcomes reveal promising results in terms of overall graft retention and functional recovery. Metabolic, malignant, and infectious complications, as well as graft rejection episodes, are expected to occur in this population, and some may be related to patient’s age and lifestyle.

Choroid Involvement Secondary to Optic Disc Pit Maculopathy: OCT Analysis And Evolution After Surgical Treatment: Choroidal Involvement In Optic Pit Maculopathy

PurposeTo assess choroidal changes associated to optic disc pit maculopathy (ODP-M) and their evolution after surgical treatment. DesignMulticentric retrospective case series. MethodsAnalysis of 42 patients affected by unilateral ODP-M undergoing surgical treatment between 2013 and 2023. Optical coherence tomography (OCT) were performed at baseline and postoperative months 1, 6, 12, 24 and most recent follow-up. Subfoveal choroidal thickness (SFCT) and peripapillary choroidal thickness (PPCT) were measured in ODP-M and fellow eyes. The presence of retinal pigmented epithelium (RPE) atrophy was used to distinguish between “early” and “advanced” disease, and data regarding fluid localization were collected. ResultsBaseline SFCT in ODP-M eyes was significantly higher than fellow eyes (386.8±88.9 vs. 334.4±72.2 μm, p=0.002), differently from PPCT (192.6±47.8 vs. 181.2±45.7 μm, p=0.46). SFCT significantly decreased 1 month post-operatively (mean reduction 36.5 μm, p=0.009) and remained below pre-operative values throughout the follow-up, showed a mean reduction of 79.4 μm at final follow-up (p<0.001). Conversely, PPCT showed no changes between pre-operative and post-operative values (all p>0.05). Nine eyes (21.4%) showed submacular dilated choroidal vessels, correlated with the presence of subretinal fluid (p=0.008) and reducing in caliber after surgical treatment. The 10 eyes (23.8%) with “advanced” disease had lower baseline SFCT and worse BCVA compared to the “early” subgroup, and showed a delayed reduction of choroidal swelling post-operatively. ConclusionSubfoveal choroid may thicken and remodel in response to ODP-M, eventually returning to physiological values after surgical treatment. Moreover, the presence of RPE atrophy may influence retino-choroidal balance. Conversely, PPCT didn't show comparable modifications.