Long-term Outcomes Research Articles

Impact of Race on Transplantation in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end-stage kidney disease (ESKD) and occurs without racial predilection. In general, non-White ESKD patients have less access to transplantation, especially living donor transplantation. We examined long-term outcomes of ADPKD-ESKD patients by self-reported race, with attention to the trajectory of Estimated Post-Transplant Survival (EPTS) scores over time. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to identify 32,611 ADPKD transplant recipients between 1/2000-12/2022. EPTS scores were calculated from the date of waitlisting until transplantation occurred. Cumulative incidences of living and deceased transplantation were calculated and plotted. Cox models were made for graft failure and death, and a sub-distribution hazards model for graft failure accounted for death as a competing outcome, with adjustment for patient, donor, and transplant factors. Compared to White ADPKD patients, all other groups had more dialysis years, more delayed graft function, and fewer living and pre-emptive transplants; mean EPTS scores were lower in African American (AA) and Hispanic patients at each timepoint on the waitlist. However, EPTS scores at the time of transplant was less likely to be <20% in AA and Hispanic patients, due to longer waiting time. AA patients had a significantly higher risk of graft failure with death as competing risk compared to White patients. Asian and Hispanic patients had similar graft survivals but better patient survival compared to White patients. Waitlist experience, allograft quality, and post-transplant outcomes of patients with ADPKD are influenced by patient race.

Parental Perceptions of Access to and Utilization of Services for Autistic Children in African American Families: An Exploratory Study.

Autism spectrum disorder (ASD) occurs within all racial, ethnic, and demographic pediatric groups. However, Black children with ASD are diagnosed at later stages of their development, and as a result may not receive or may age out of early intervention services, and demonstrate poorer long-term outcomes, across a range of factors. African American parent's perceptions regarding access to and utilization of healthcare services for their autistic children vary. Research examining autism spectrum disorder and parental perceptions of service utilization among African American (AA) families is limited. This qualitative study aimed to understand the challenges African American parents face when initiating healthcare services for their autistic children. Eleven AA mothers of autistic children participated in individual semi-structured interviews. Six themes related to pediatric treatment needs, interactions with providers, and parents' roles as experts and advocates were generated. Implications for pediatric treatment needs of autistic children and areas of opportunity for providers working with AA autistic children are discussed.

Efficacy and Safety of Mechanical Thrombectomy in Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients on Low-Dose Aspirin.

Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT. We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (mRS 0-2). Secondary outcomes included excellent functional outcome at 90 days (mRS 0-1), mortality, and day-one post-MT NIHSS score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH). Among 1,354 patients, 150 were on pre-stroke low-dose aspirin. After applying Inverse Probability of Treatment Weighting (IPTW), Aspirin use was associated with significantly better functional outcomes (mRS 0-2: OR =1.89 , 95% CI, 1.14 to 3.12 ) and lower 90-day mortality (OR = 0.56, 95% CI, 0.32 to 1.00). The aspirin group had lower NIHSS scores on day one (β = -1.5, 95% CI, -2.8 to - 0.27). The sICH rate was not significantly different between the groups (OR = 0.92, 95% CI, 0.60 to 1.43). Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.

Short- and Long-Term Outcomes of Patients Who Underwent the Arterial Switch Operation at Siriraj Hospital-Thailand's Largest National Tertiary Referral Center.

The aim of this study was to assess the short- and long-term outcomes of patients who underwent the arterial switch operation (ASO) at Siriraj Hospital in Thailand, and to identify postoperative complications and factors that significantly affect patient survival. We retrospectively studied all patients with dextro-transposition of the great arteries and anatomic variants who underwent the ASO from January 1995 to December 2020. Twenty-year overall survival and 15-year freedom from reoperation/reintervention were estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to identify factors independently associated with 30-day mortality. Of the 171 patients included, there were 116 males (67.84%). The median (minimum, maximum) age at operation was 33.5 (3-4,499) days, and the median (minimum, maximum) bodyweight was 3.4 (2.2-44.9) kg. Most patients (115/171, 67.25%) had an intact ventricular septum, whereas 48/171 (28.07%), had ventricular septal defects. The typical coronary anatomic pattern (1LCx-2R) was found in 120 patients (70.1%). Early mortality was 8.7% ± 4.4%, and there was no late death up to 20 years postoperatively with a median follow-up of five years. Fifteen-year freedom from reoperation or reintervention was 85.7%. Atypical coronary pattern was an independent factor for survival with an adjusted hazard ratio of 5.1 (95% confidence interval: 1.22-21.4; P = .026). The results of this study revealed excellent short- and long-term outcomes of the ASO at our center. Atypical coronary anatomy was found to be the only factor that independently predicted 30-day mortality.

Refining MR-guided thermal ablation for HCC within the Milan criteria: a decade of clinical outcomes and predictive modeling at a single institution

BackgroundThe appropriateness of ablation for liver cancer patients meeting the Milan criteria remains controversial.PurposeThis study aims to evaluate the long-term outcomes of MR-guided thermal ablation for HCC patients meeting the Milan criteria and develop a nomogram for predicting survival rates.MethodsA retrospective analysis was conducted from January 2009 to December 2021 at a single institution. Patients underwent MR-guided thermal ablation. Factors influencing progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate Cox regression and stepwise regression. A nomogram was developed for survival prediction, followed by risk stratification and internal validation. Adverse events (AEs) were also analyzed.ResultsA total of 181 patients were included, with a mean follow-up of 73.8 ± 31.7 months. The cumulative local tumor progression rates at 1, 3, and 5 years were 0.80%, 1.27%, and 1.86%, respectively. The 1-, 3-, and 5-year PFS rates were 81.8%, 57.4%, and 38.1%, and OS rates were 98.3%, 87.8%, and 62.9%. Poorer outcomes were associated with age ≤ 60 years, tumor size > 2 cm, multiple tumors, cirrhosis, proximity to major vessels, and narrow ablation margins (P < 0.05). The nomogram accurately predicted 3- and 5-year survival, and internal validation confirmed the results. AEs occurred in 33.7% of patients, with pain being the most common.ConclusionMR-guided ablation is effective for HCC patients within the Milan criteria, especially for those with smaller tumors and better liver function. The nomogram and risk stratification model are valuable tools for predicting patient outcomes and guiding treatment.

Epidemiology, diagnosis and treatment of anterior prostate cancer.

Anterior prostate cancers (APCs) are a group of impalpable neoplasms located in regions anterior to the urethra, which comprise the transition zone, apical peripheral zone and anterior fibromuscular stroma. These regions are typically undersampled using conventional biopsy schemes, leading to a low detection rate for APC and a high rate of false negatives. Radical prostatectomy series suggest prevalence rates of at least 10-30%, but transperineal systematic biopsy is ideal for diagnosis, particularly where multiparametric MRI is unavailable. Combined MRI-targeted and systematic biopsies demonstrate high concordance with final histopathology and lead to the fewest incidences of upgrading and upstaging at radical prostatectomy. Thus, the use of combined biopsy techniques has important implications for preoperative work-up and surgical planning, as APCs are associated with larger cancer volumes and a higher rate of positive surgical margins than posterior prostate cancer. Nevertheless, anterior tumour location might confer a relative resistance to stage progression, as APCs exhibit lower rates of extraprostatic extension, seminal vesical invasion and lymph node metastases than the more commonly seen posterior neoplasms. Few studies have examined the long-term outcomes of partial gland approaches to APCs, but MRI-targeted techniques have the potential to provide real-time intraoperative guidance and maximize the oncological safety of anterior focal treatment options in patients with APC.

A plain language summary of a study of long-term outcomes in patients with IgA nephropathy from the UK National Registry of Rare Kidney Diseases (RaDaR)

A plain language summary of a study of long-term outcomes in patients with IgA nephropathy from the UK National Registry of Rare Kidney Diseases (RaDaR)

Precision oncology: The role of minimally-invasive ablation therapy in the management of solid organ tumors.

Solid organ tumors present a significant healthcare challenge, both economically and logistically, due to their high incidence and treatment complexity. In 2023, out of the 1.9 million new cancer cases in the United States, over 73% were solid organ tumors. Ablative therapies offer minimally invasive solutions for malignant tissue destruction in situ, often with reduced cost and morbidity compared to surgical resection. This review examines the current Food and Drug Administration-approved locoregional ablative therapies (radiofrequency, microwave, cryogenic, high-intensity focused ultrasound, histotripsy) and their evolving role in cancer care. Data were collected through a comprehensive survey of the PubMed-indexed literature on tumor ablation techniques, their clinical indications, and outcomes. Over time, emerging clinical data will help establish these therapies as the standard of care in solid organ tumor treatment, supported by improved long-term outcomes and progression-free survival.

Proximal humerus fracture dislocations: outcomes of management.

Proximal humerus fracture dislocations are amongst the most severe proximal humerus injuries, presenting a challenging management problem. The aim of this study was to report on long-term outcomes of management of proximal humerus fracture dislocations. Patients with a proximal humerus fracture dislocation managed at a Level 1 trauma centre from January 2010 to December 2018 were included. Patients with isolated tuberosity fracture dislocations or pathological fractures were excluded. Outcome measures were the Oxford Shoulder Score (OSS), EQ-5D-5L, return to work and radiological outcomes. Complications recorded included further surgery, loss of position/fixation, non-union/malunion and avascular necrosis. Sixty-nine patients were included with a proximal humerus fracture dislocation in the study period; 48 underwent surgical management and 21 were managed successfully with closed reduction alone. The mean (SD) age of the cohort was 59.7 (±20.4), and 54% were male. Overall patients reported a mean OSS of 39.8 (±10.3), a mean EQ-5D utility score of 0.73 (±0.20), and 78% were able to return to work at a median of 1.2 months. There was a high prevalence of complications in both patients managed operatively or with closed reduction (25% and 38% respectively). In patients undergoing surgical management, 21% required subsequent surgery. Patient reported outcome measures post proximal humerus fracture dislocations do not return to normal population levels. Further, these injuries are associated with a high prevalence of complications. Appropriate patient counselling should be undertaken before embarking on definitive management.

Role of Statins in Reducing Cardiovascular Mortality: A Systematic Review of Long-Term Outcomes

Role of Statins in Reducing Cardiovascular Mortality: A Systematic Review of Long-Term Outcomes

Validation of a New Classification for Severe Bronchopulmonary Dysplasia in Extremely Preterm Infants: Insights from a Large Japanese Cohort.

A recent scoping review identified histological chorioamnionitis (HCA), small for gestational age (SGA), and bubbly/cystic appearance on chest X-ray (bubbly/cystic CXR) as risk factors for severe bronchopulmonary dysplasia (BPD). To further validate these results, a large-scale database was analyzed. This retrospective multicenter cohort study included infants born at <28 weeks' gestational age between 2003 and 2016. The validated risk factors identified from the scoping review were analyzed for independent associations with severe BPD using multivariable logistic regression. Additionally, the association of these factors with long-term outcomes at 3 years, including home oxygen therapy (HOT) and neurodevelopmental impairments (NDIs), were analyzed. Among 15,834 extremely preterm infants, HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were significantly and independently associated with severe BPD (adjusted odds ratio, 1.20; 95% confidence interval, 1.06-1.36) (1.73; 1.51-1.98) (1.79; 1.60-2.01), respectively. These three factors were also linked to HOT at 3 years (1.54; 1.14-2.08) (1.70; 1.21-2.39) (2.63; 1.94-3.56), respectively. Their combination significantly increased the prevalence of severe BPD and HOT at 3 years, particularly with bubbly/cystic CXR. Only SGA was independently associated with NDIs in BPD infants (1.55; 1.32-1.83). HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were identified as important risk factors for severe BPD and long-term respiratory outcomes. While further research is needed to validate their role in endotype-specific classification of BPD, these findings may contribute to early prognostic strategies and targeted interventions before 36 weeks' postmenstrual age.

Long-term surgical outcomes of esotropic duane retraction syndrome type 1

Duane retraction syndrome (DRS) is complicated to treat due to its wide spectrum of clinical presentations and the treatment of choice varies among surgeons. To provide insight into this challenging condition, we evaluated the long-term surgical outcomes of esotropic DRS type 1. The surgical motor success, defined as a horizontal deviation of 8 prism diopters (PD) or less, was found in 77.3% of patients after an average follow-up of 5.6 ± 3.4 years. After surgery, a gradual shift towards exotropia was observed at an average rate of 1.3 ± 3.7 PD exodrift per year. In this study, the long-term surgical outcomes were generally favorable in esotropic DRS type 1. However, due to the nature of exodrift over time following medial rectus recession, it is crucial to educate the patient about the potential long-term overcorrection, and to carefully calculate the appropriate surgical dosage.

Cerebral injury and long-term neurodevelopment impairment in children following severe fetomaternal transfusion: a retrospective cohort study

ObjectiveFetomaternal transfusion (FMT) is associated with increased perinatal mortality and morbidity, but data on postnatal outcomes are scarce. Our aim was to determine the incidence of adverse short-termand long-term sequelae...

Long-Term Outcomes in Radioiodine-Resistant Follicular Cell-Derived Thyroid Cancers Treated with [177Lu]Lu-DOTAGA.FAPi Dimer Therapy.

Aim: The study aimed to analyze the long-term outcomes of [177Lu]Lu-DOTAGA.FAPi dimer therapy in individuals diagnosed with radioiodine-resistant (RAI-R) follicular cell-derived thyroid cancer. Materials and Methods: In this retrospective study, 73 patients with RAI-R follicular thyroid carcinoma who had undergone multiple lines of previous treatments were included. Following [68Ga]Ga-DOTA.SA.FAPi positron emission tomography-computed tomography scan, among the 73 patients, 65 received [177Lu]Lu-DOTAGA.FAPi dimer monotherapy with a median activity of 5.5 GBq per cycle at 8-week intervals. The remaining eight patients underwent tandem [177Lu]Lu/[225Ac]Ac-DOTAGA.FAPi dimer therapy, consisting of a median of two cycles of [177Lu]Lu-DOTAGA.FAPi dimer followed by one cycle of [225Ac]Ac-DOTAGA.FAPi dimer, also at 8-week intervals. The primary endpoint included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included PERCIST criteria response assessment and safety assessment according to Common Terminology Criteria for Adverse Events (V5.0). Results: We enrolled 37 female and 36 male patients, with a mean age of 54.3 years (range: 27 - 80 years). The patients received a median cumulative activity of 22.2 GBq (range, 4 GBq-55.5 GBq) of [177Lu]Lu-DOTAGA-FAPi dimer over one to nine cycles, with a median of three cycles. Among 73 patients, 20 died and 16 deaths were due to thyroid cancer. Nineteen patients experienced disease progression, with an estimated median PFS of 29 months [CI 14-34 months]. The estimated median OS was 32 months [CI 21-40 months]. Four patients (5.4%) encountered grade III anemia, primarily linked to bone metastasis in three cases and neck tumor mass bleed in one. Grade III thrombocytopenia occurred in three patients (4%). No grade III renal or hepatotoxicity was observed. Conclusion: In this study, [177Lu]Lu-DOTAGA.FAPi dimer therapy showed promising safety and efficacy in aggressive, radioiodine-resistant thyroid cancer, achieving a median PFS and OS of 29 and 32 months, respectively, with manageable adverse events. Confirmation of our findings is needed from prospective clinical trials comparing [177Lu]Lu-DOTAGA.FAPi dimer therapy to other treatments.

Patients With Chronic Lateral Ankle Instability and Small Osteochondral Lesions of the Talus Obtain Good Postoperative Results: A Minimum 10-Year Follow-up With Radiographic Evidence.

Few studies reported the long-term clinical outcomes and joint degeneration of patients with chronic lateral ankle instability (CLAI) and small osteochondral lesions of the talus (OLTs) following simultaneous open modified Broström-Gould (MBG) surgery and arthroscopic bone marrow stimulation (BMS). The purpose of this study was to study the long-term results of patients after BMS and BMG surgery, and to further evaluate the potential effect of OLT size on postoperative results. In this retrospective study, 110 CLAI patients were divided into 57 patients with OLTs (including 24 patients having combined small osteochondral lesions of the tibial plafond) receiving simultaneous BMS and MBG surgeries (BMS+MBG group), and 53 patients without OLTs receiving isolated open MBG surgery (MBG group). The OLT size and pre- and postoperative Kellgren-Lawrence grade were assessed. The subjective scores (visual analog scale pain score, Tegner activity, and Karlsson-Peterson scores), surgical complications, and return to sports were also compared pre- and postoperatively. Patients were followed up at a mean of 144.2 ± 14.9 and 145.6 ± 11.4 months for the BMS+MBG and MBG groups, respectively. Subjective scores were significantly improved (P < .001), and no difference was found in subjective scores or surgical complications between the 2 groups (P > .05). Both groups showed progression of osteoarthritis grade (P < .001), but with no significant difference of changes from the preoperative to the final follow-up (BMS+MBG group: 0.84 ± 0.75 to 1.32 ± 0.80; MBG group: 0.32 ± 0.48 to 0.86 ± 0.56, changes: 0.48 ± 0.59 vs 0.55 ± 0.51, P = .575). For sports function, both groups had similar results in Tegner scores (5.8 ± 1.3 vs 6.2 ± 1.3, P = .081). However, in a subgroup analysis, we found that in the BMS+MBG group, patients exceeding the mean size of OLTs (50 mm2) were associated with an average lower postoperative Karlsson-Peterson score (P = .025) and higher postoperative osteoarthritis grade (P = .037), with more changes (P = .017) than those with OLTs <50 mm2. Patients with CLAI and small OLTs following simultaneous open MBG surgery and arthroscopic BMS showed good long-term outcomes and only mild progression of joint degeneration-overall similar to patients treated for CLAI with MBG surgery. Moreover, as OLT size increased, good outcomes were less predictable.

Chronic pain after colorectal cancer treatment: A population-based cross-sectional study.

With the recently validated tool for estimating chronic pain after colorectal cancer surgery, the aims of this study were to calculate the prevalence and to identifypredictive risk factors for chronic pain after colorectal cancer treatment. Clinical data from colorectal cancer patients treated between 2001 and 2014 were obtained from the Danish Colorectal Cancer Group database. In 2016, all survivors were invited to participate in a national cross-sectional questionnaire study on long-term functional outcomes, including the chronic pain questionnaire. The prevalence of chronic pain was analysed in groups based on demographic data and treatment-related factors. Multivariate logistic regression analysis was performed to determine significant predictors of chronic pain, displayed as odds ratios (OR) and 95% confidence intervals. The response rate was 63.8%, representing 11 600 patients (7127 colon and 4473 rectal cancer patients). The overall prevalence of pain was 41.5%, with 15.4% having major pain. Major pain was more prevalent in rectal cancer patients than colon cancer patients (16.7% vs. 14.5%, p < 0.001). Predictors for major pain were: young age <60 years [OR 1.7 (95% CI 1.51-1.91)]; female sex [OR 1.63 (95% CI 1.46-1.82)]; an open surgical approach [OR 1.18 (95% CI 1.05-1.33)]; chemotherapy [OR 1.32 (95% CI 1.18-1.49)]; radiotherapy [OR 1.39 (95% CI 1.17-1.65)]; permanent stoma [1.56 (95% CI 1.31-1.86)]; comorbidity [OR 1.69 (95% CI 1.5-1.9)]; anastomotic leakage [OR 1.31 (95% CI 1.05-1.64)]. Chronic pain is prevalent after colorectal cancer surgery. All patients should be informed about the risks before cancer treatment, particularly those who are at an increased risk of developing major pain.

Clinical evaluation of endoscopic biliary stenting in treatment of malignant obstructive jaundice.

Malignant obstructive jaundice (MOJ) is characterized by the presence of malignant tumors infiltrating or compressing the bile duct, causing poor bile drainage, generalized yellowing, pain, itching, and malaise. MOJ is burdensome for both the society and the families of affected patients and should be taken seriously. To evaluate the clinical effect of stent placement during endoscopic retrograde cholangiopancreatography for relieving MOJ and the efficacy of percutaneous transhepatic biliary drainage in terms of liver function improvement, complication rates, and long-term patient outcomes. The clinical data of 59 patients with MOJ who were admitted to our hospital between March 2018 and August 2019 were retrospectively analyzed. According to the treatment method, the patients were divided into an observation group (29 patients) and a control group (30 patients). General data, liver function indices, complications, adverse effects, and 3-year survival rates after different surgical treatments were recorded for the two groups. There were no significant differences in baseline information (sex, age, tumor type, or tumor diameter) between the two groups (P > 0.05). Alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels were significantly better in both groups after surgery than before surgery (P < 0.05). The overall incidence of biliary bleeding, gastrointestinal bleeding, pancreatitis, and cholangitis was 6.9% in the observation group and 30% in the control group (P < 0.05). No significant differences in the rates of blood transfusion, intensive care unit admission, or death within 3 years were observed between the two groups at the 1-month follow-up (P > 0.05). The 3-year survival rates were 46.06% and 39.71% in the observation and control groups, respectively. Endoscopic biliary stenting effectively relieves MOJ and significantly improves liver function, with minimal complications. This technique is a promising palliative approach for patients ineligible for radical surgery. However, further research is needed to optimize current treatment strategies and to explore their potential in treating nonmalignant cases of obstructive jaundice.

Impact of time in tight range on all-cause and cardiovascular mortality in type 2 diabetes: A prospective cohort study.

Currently, there is a lack of evidence regarding time in tight range (TITR) and long-term adverse outcomes. We aimed to investigate the association between TITR and the risk of all-cause and cardiovascular mortality among patients with type 2 diabetes. A total of 6061 patients with type 2 diabetes were prospectively recruited in a single centre. TITR was measured with continuous glucose monitoring (CGM) at baseline and was defined as the percentage of time in the target glucose range of 3.9-7.8 mmol/L (70-140 mg/dL) during a 24-h period. Cox proportion hazard regression models were used to examine the association between TITR and the risk of all-cause and cardiovascular mortality. During a median follow-up period of 10.9 years, 1898 (31.3%) death events were confirmed, with 689 (11.4%) due to cardiovascular mortality. The restricted cubic spline revealed significant linear relationships between lower TITR and higher risks of all-cause and cardiovascular mortality (p for linearity <0.01). In the fully adjusted model including glycated haemoglobin A1c, each 10% decrease in TITR was associated with 4% (95% confidence interval, 1.01-1.06) increased risk of all-cause mortality and 4% (95% confidence interval, 1.00-1.08) increased risk of cardiovascular mortality. Subgroup analyses showed that the linear relationship between TITR and all-cause mortality risk was sustained in patients with haemoglobin A1c <7.0% and patients with fasting plasma glucose <7.0 mmol/L. Lower TITR is associated with an increased risk of all-cause and cardiovascular mortality in patients with type 2 diabetes, indicating that tight glycaemic control within the physiological range may be crucial for reducing long-term mortality risk, especially in those with seemingly well-controlled diabetes.

Long-Term Cognitive Outcomes of Esketamine Nasal Spray in Treatment-Resistant Depression: A Preliminary Report

Background/Objectives: Ketamine/esketamine has a rapid/robust antidepressant effect on treatment-resistant depression (TRD). However, its long-term cognitive effects remain unclear. In this study, we investigated the potential cognitive effects of an esketamine spray on a series of TRD patients. Methods: We evaluated the cognitive performance of eight TRD patients subjected to an esketamine nasal spray as an adjunct treatment for six months. Cognitive assessments were performed before treatment initiation (T0) and at three (T3) and six (T6) months by an experienced neuropsychologist using a comprehensive neuropsychological battery. Depression severity was assessed by the Montgomery–Åsberg Depression Rating Scale. Changes in cognitive performance were analyzed by determining the bias between time points. To investigate the association between the severity of depression and performance on cognitive tests, we used correlation with correction for repeated measures and regression analysis with a general linear mixed model. We used the Tukey method to compare three estimates and the Dunnett method to compare two estimates. Results: Improvements in at least one test from T0 to T6 were found for attention, memory, and the executive functions of working memory, set-shifting, and inhibitory control. Most of the improvements had occurred by T3, but working memory and set-shifting improvements were significant only at T6. The severity of depression decreased significantly from T0 to T6, and most cognitive improvements were correlated with an improvement in depression severity. No test indicated a worsening of cognitive performance from T0 to T6. Conclusions: Our results suggest that the cognitive performance of TRD patients improved with long-term adjunct treatment with an esketamine nasal spray. Confirmatory studies are necessary.

P-20 EARLY ZOLEDRONIC ACID TREATMENT IN A PEDIATRIC CASE OF OSTEOGENESIS IMPERFECTA TYPE V: CLINICAL OUTCOMES AND THE ROLE OF IFITM5 (BRIL) MUTATION

Abstract Introduction Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility, low bone mass, and frequent fractures. OI is typically associated with mutations in the COL1A1 and COL1A2 genes, but a subset of cases, such as OI type V, is linked to mutations in the IFITM5 gene, also known as BRIL (bone-restricted IFITM-like). Clinical Case This report presents a case of a 2-year-old boy diagnosed with OI type V, a rare form of the disease caused by a mutation in BRIL. The patient exhibited multiple recurrent bone fractures beginning in infancy, though there was no family history of bone disease or consanguineous marriage. Physical examination revealed that the patient was of normal weight and height for his age, with neurodevelopmental milestones met. Laboratory tests showed elevated alkaline phosphatase (ALP) levels, indicative of increased bone turnover, while other values were within normal ranges. Radiological evaluations confirmed an active fracture in the left tibia but showed no additional pathological involvement. Genetic testing identified a de novo C&amp;gt;T variant in the IFITM5 gene, confirming the diagnosis of OI type V. The patient was treated with intravenous zoledronic acid (ZA), a bisphosphonate therapy, which is currently being tested in infants and toddlers for OI treatment. The treatment led to a significant reduction in fracture recurrence and a decrease in ALP levels, demonstrating its efficacy in managing the disease. Despite these positive outcomes, certain hallmark features of OI type V, such as hyperplastic callus formation and new periosteal bone growth, were not observed during follow-up, possibly due to the early initiation of ZA therapy. OI type V is distinguished from other forms of OI by hyperplastic callus formation and increased osteoblast activity, often accompanied by elevated ALP levels. Radiographic and histological findings specific to this type include periosteal bone growth and a reticular lamellation pattern in the bone matrix. Although ZA has shown promise in reducing fracture risk and improving clinical outcomes, its long-term efficacy in preventing other disease manifestations, such as intramembranous ossification, remains uncertain. The underlying pathological mechanisms of OI type V, particularly the role of BRIL, are not yet fully understood. Further research into the activation of BRIL in osteoblasts could lead to the development of targeted therapies that address the root cause of the disease. While ZA therapy has been effective in managing the immediate symptoms of OI type V, a deeper understanding of the disease's genetic and molecular basis is crucial for improving long-term treatment outcomes. In conclusion, the IFITM5 (BRIL) mutation is recognized as the genetic cause of OI type V. Early intervention with ZA has shown positive effects in managing the disease, but further research is needed to fully understand the pathological mechanisms and to develop treatments that can address all aspects of the disease.Table 1:Lab workout (age 2)ALP = alkaline phosphatase; AST = aspartate transaminase; BUN = blood urea nitrogen; GGT = gamma-glutamyl transferase; CBC: complete blood count