Amputation surgery associated with shortened survival in patients with localized extremity bone sarcoma.

Background: This study assesses survival rates among patients with localized extremity bone sarcoma who have undergone amputation, pinpointing subpopulations that are disproportionately affected by amputation-related survival disparities. Methods: Examination of data was conducted using the Surveillance, Epidemiology, and End Results (SEER) program, analyzing records of 3765 patients diagnosed with localized extremity bone sarcoma between 2000 and 2019. Of these, 857 received amputations (Amputation cohort), and 2908 underwent limb-sparing surgeries. Propensity score matching, considering demographic and clinical features, was utilized to ensure a fair comparison. Results: Following propensity score matching, the study focused on 1714 cases. The Amputation cohort was observed to have significantly poorer survival rates (Cancer-Specific Survival [CSS]: Hazard Ratio [HR] = 1.28, 95% Confidence Interval [CI]: 1.05-1.55; Overall Survival [OS]: HR = 1.37, 95% CI: 1.15-1.63). Subsequent subgroup analysis indicated that individuals with tumors exceeding 8 cm in size or those located in the lower limbs were notably at a higher risk of shortened survival (for tumors >8 cm - CSS: HR = 1.32, 95% CI: 1.02-1.71; OS: HR = 1.39, 95% CI: 1.09-1.76; for lower limb tumors - CSS: HR = 1.25, 95% CI: 1.01-1.54; OS: HR = 1.33, 95% CI: 1.11-1.61). Conclusions: Our findings demonstrate that patients diagnosed with localized extremity bone sarcoma undergoing amputation exhibit lower survival rates, especially in cases involving tumors of greater size or those situated in the lower limbs. In patient groups where amputation is inevitable, careful follow-up is required after surgical intervention.

Long-Term Outcomes of High-Flexion Design Total Knee Arthroplasty with a Short Posterior Flange.

Background: The purpose of this study was to evaluate the clinical and radiological outcomes of high-flexion total knee arthroplasty (TKA) using Vega Knee System (B. Braun, Aesculap) at a long-term follow-up and to analyze the implant survivorship. Methods: We enrolled 165 patients (232 knees) with a minimum 7-year follow-up after TKA (VEGA Knee System). For clinical assessment, range of motion (ROM), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were used. For radiologic assessment, hip-knee-ankle angle, component position, and the existence of radiolucent lines and loosening were used. Survival analysis was conducted using the Kaplan-Meier method. Results: The mean follow-up period was 9.8 years. The mean ROM increased from 124.4° to 131.4° at the final follow-up. The WOMAC score decreased from 38.5 to 17.4 at the final follow-up (p < 0.001). All 5 subscales of the KOOS improved at the final follow-up (all subscales, p < 0.001). Revision TKA was performed in 10 cases (4.3%), which included 9 cases of aseptic loosing and 1 case of periprostatic joint infection. Of the 9 aseptic loosening cases (3.9%), 8 cases (3.4%) were loosening of the femoral component and 1 case (0.4%) was loosening of the tibial component. When revision for any reason was considered an endpoint, the 10-year survivorship was 96.2% (95% confidence interval [CI], 93.9%-98.5%). On the other hand, when revision for aseptic loosening was considered the endpoint, the 10-year survivorship was 96.6% (95% CI, 94.4%-98.8%). Conclusions: The Vega Knee System provided good clinical results in the long-term follow-up period. Although the VEGA Knee System showed acceptable implant survivorship, loosening of the femoral component occurred in about 3.4% of the patients. For more accurate evaluation of the survivorship of high-flexion design TKA with a short posterior flange, it is necessary to conduct more long-term follow-up studies targeting diverse races, especially Asians who frequently perform high-flexion activities.

Predictors of persistent opioid use in bladder cancer patients undergoing radical cystectomy: A SEER-Medicare analysis.

PURPOSE: To evaluate patient and provider characteristics that predict persistent opioid use following radical cystectomy for bladder cancer including non-opioid naïve patients. METHODS: Patients undergoing cystectomy between July 2007 and December 2015 were identified using the SEER-Medicare database. Opioid exposure was identified before and after cystectomy using Medicare Part D data. Multivariable analyses were used to identify predictors of the primary outcomes: persistent opioid use (prescription 3-6 months after surgery) and postoperative opioid prescriptions (within 30 days of surgery). Secondary outcomes included physician prescribing practices and rates of persistent opioid use in their patient cohorts. RESULTS: A total of 1,774 patients were included; 29% had prior opioid exposure. Compared to opioid-naïve patients, non-opioid naïve patients were more frequently younger, Black, and living in less educated communities. The percentage of persistent postoperative use was 10% overall and 24% in non-opioid naïve patients. Adjusting for patient factors, opioid naïve individuals were less likely to develop persistent use (OR 0.23) while a 50-unit increase in oral morphine equivalent per day prescribed following surgery nearly doubled the likelihood of persistent use (OR 1.98). Practice factors such as hospital size, teaching affiliation, and hospital ownership failed to predict persistent use. 29% of patients filled an opioid prescription postoperatively. Opioid naïve patients (OR 0.13) and those cared for at government hospitals (OR 0.59) were less likely to fill an opioid script along with those residing in the Northeast. Variability between physicians was seen in prescribing practices and rates of persistent use. CONCLUSIONS: Non-opioid naïve patients have higher rates of post-operative opioid prescription than opioid-naïve patients. Physician prescribing practices play a role in persistent use, as initial prescription amount predicts persistent use even in non-opioid naïve patients. Significant physician variation in both prescribing practices and rates of persistent use suggest a role for standardizing practices.

Compound heterozygous mutations in three Chinese patients of Segawa syndrome and their treatment outcomes.

Segawa syndrome is a rare autosomal recessive form of dopa-responsive dystonia resulting from TH gene dysfunction. Patients typically exhibit symptoms such as generalized dystonia, rigidity, tremors, infantile Parkinsonism, and pseudo-spastic paraplegia. Levodopa is often an effective treatment. Due to its rarity, high heterogeneity, and poorly understood pathological mutation and phenotype spectrums, as well as genotype-phenotype and genotype-treatment outcome correlations, Segawa syndrome poses diagnostic and therapeutic challenges. In our study, through clinical and molecular analyses of three Chinese Segawa patients, we re-evaluated the pathogenicity of a TH mutation (c.880G>C;p.G294R) previously categorized as "Conflicting classifications of pathogenicity" in ClinVar. Also, we summarized the clinical phenotypes of all reported Segawa syndrome cases until 2023 and compared them with our patients. We identified a novel phenotype, "cafe-au-lait macules," not previously observed in Segawa patients. Additionally, we discussed the correlation between specific genotypes and phenotypes, as well as genotypes and treatment outcomes of our three cases. Our findings aim to enhance the understanding of Segawa syndrome, contributing to improved diagnosis and treatment approaches in the future.

Rehabilitative goals for patients undergoing lung retransplantation.

Lung retransplantation (LRT) involves a second or subsequent lung transplant (LT) in a patient whose first transplanted graft has failed. LRT is the only treatment option for irreversible lung allograft failure caused by acute graft failure, chronic lung allograft dysfunction, or postoperative complications of bronchial anastomosis. Prehabilitation (rehabilitation before LT), while patients are on the waiting list, is recognized as an essential component of the therapeutic regimen and should be offered throughout the waiting period from the moment of listing until transplantation. LRT is particularly fraught with challenges, and prehabilitation to reduce frailty is one of the few opportunities to address modifiable risk factors (such as functional and motor impairments) in a patient population in which there is clearly room to improve outcomes. Although rehabilitative outcomes and quality of life in patients receiving or awaiting LT have gained increased interest, there is a paucity of data on rehabilitation in patients undergoing LRT. Frailty is one of the few modifiable risk factors of retransplantation that is potentially preventable. As such, it is imperative that professionals involved in the field of retransplantation conduct research specifically exploring rehabilitative techniques and outcomes of value for patients receiving LRT, because this area remains unexplored.

Corrigendum: Comorbidities and outcomes of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a real-world, nationwide, retrospective study from Hungary.

[This corrects the article DOI: 10.3389/pore.2024.1611497.].

Minimally invasive pancreatoduodenectomy by junior surgeon: Initial experience of the next generation.

BACKGROUND: Several guidelines exist for minimally invasive pancreatoduodenectomy (MIPD) regarding its prerequisites and learning curve. However, these guidelines are based on the experience of the pioneers of MIPD; minimal data exist on the experience of the next generation of surgeons. The aim of this study was to compare the two surgeon types (veteran and junior) for MIPD in terms of immediate postoperative outcomes. METHODS: The postoperative outcomes of 22 patients who underwent robot-assisted pancreatoduodenectomy (RAPD) by a junior surgeon from July 2021 to December 2022 were retrospectively reviewed. The outcomes were compared with the initial postoperative outcomes and the contemporary postoperative outcomes of RAPD by a veteran surgeon. RESULTS: In comparing the initial outcomes between the two surgeon types, the veteran surgeons showed a shorter operation time (junior surgeon vs. veteran surgeon: 606 ± 89 vs. 467 ± 77 min, p < 0.001). However, there was no significant difference in terms of postoperative outcomes, such as blood loss (300 [200-600] ml. vs. 200 [100-500] ml, p = 0.208), major complications (≥CDC IIIa: 4 (18.2%) vs. 4 (18.2%), p = 1.000), postoperative pancreatic fistula (POPF; ≥ISGPF Grade B: 2 (9.1%) vs. 3 (13.6%), p > 0.999), and length of hospital stay (18.0 ± 8.9 days vs. 18.3 ± 7.9 days, p = 0.915), between the two surgeon types. In addition, in a comparison of the contemporary outcomes, there was no significant difference in terms of postoperative outcome (complications: 4 (18.2%) vs 11 (11.1%), p = 0.580; POPF: 2 (9.1%) vs. 3 (3.0%), p = 0.484; length of hospital stay: 18.0 ± 8.9 vs. 15.0 ± 6.5 days, p = 0.065). CONCLUSION: The initial outcomes of MIPD by a well-trained junior surgeon were found to be comparable to those of MIPD by a veteran surgeon.

Use of Endodontic Procedures in Young Permanent Teeth.

Background: Regenerative endodontic procedures (REPs) have emerged as a promising treatment option for young permanent teeth with pulp necrosis, offering the potential for tissue repair and preservation. Materials and Methods: A retrospective analysis was conducted on a cohort of 30 patients aged 8 to 16 years with pulp necrosis in young permanent teeth. The patients underwent REPs, including disinfection, triple antibiotic paste application, and a coronal barrier. Clinical and radiographic data were collected at baseline and follow-up appointments at 6, 12, and 24 months. Radiographs were analyzed for root lengthening, apical closure, and resolution of periapical lesions. Results: The mean increase in root length after 24 months was 3.42 mm (SD ± 1.12 mm), and 90% of cases demonstrated complete apical closure. The overall success rate, defined as the absence of clinical symptoms and radiographic evidence of pathology, was 80. Conclusion: REPs show promising outcomes in young permanent teeth with pulp necrosis, promoting root development, and apical closure.

Assessment of AI Models in Predicting Treatment Outcomes in Orthodontics.

Background: In the realm of orthodontics, the evaluation of treatment outcomes is a pivotal aspect. In recent times, artificial intelligence (AI) models have garnered attention as potential tools for predicting these outcomes. These AI models have the potential to enhance treatment planning and decision-making processes. However, a comprehensive assessment of their effectiveness and accuracy is essential before their widespread integration. Materials and Methods: In this study, we assessed the capability of AI models to predict treatment outcomes in orthodontics. A sample of 30 patients undergoing orthodontic treatment was selected. Various patient-specific parameters, including age, initial malocclusion severity, and treatment approach, were collected. The AI model was trained using a dataset comprising historical treatment cases and their respective outcomes. Subsequently, the trained AI model was applied to predict the treatment outcomes for the selected patients. Results: The results of this study indicated a moderate level of accuracy in the predictions made by the AI model. Out of the 30 patients, the model accurately predicted treatment outcomes for 22 patients, yielding a success rate of approximately 73%. However, the model exhibited limitations in accurately predicting outcomes for cases involving complex malocclusions or those requiring non-standard treatment approaches. Conclusion: In conclusion, this study underscores the potential of AI models in predicting treatment outcomes in orthodontics. While the AI model demonstrated promising accuracy in the majority of cases, its efficacy was diminished in complex and non-standard cases. Therefore, while AI models can serve as valuable tools to aid orthodontists in treatment planning, they should be utilized in conjunction with clinical expertise to ensure optimal decision-making and patient care.

Trends in the characteristics and outcomes of older patients with non-traumatic spinal cord injury treated in inpatient rehabilitation facilities: 2013-2018.

OBJECTIVE: To describe the characteristics and outcomes of older (≥ 65 years of age) patients with a non-traumatic spinal cord injury (NTSCI) treated in inpatient rehabilitation facilities (IRFs) between 2013 and 2018. DESIGN: Observational study. SETTING: IRFs in the United States. PARTICIPANTS: 93,631 IRF Medicare stays for patients with NTSCI. INTERVENTIONS: Not Applicable. MAIN OUTCOME MEASURES: Length of stay, self-care and mobility function, discharge destination. RESULTS: Between 2013 and 2018, the number of older (≥ 65 years of age) Medicare patients with a NTSCI treated in IRFs increased about 22.1 percent, from 14,149 to 17,275. In addition to the increase, patients' sociodemographic characteristics shifted to have a slightly higher percentage of patients aged 65-74 years, a slightly higher percentage of males, and slightly fewer patients who identified as Hispanic. There was also a trend of more patients in the higher acuity case-mix groups and comorbidities tiers, but the median length of stay remained 12 days across all years. The percent of patients discharged home or to a community-based setting varied from 73.7 to 75.2 without a trend, although discharge self-care and mobility function increased slightly across the years. CONCLUSIONS: Between 2013 and 2018, the number of Medicare patients with NTSCI treated in IRFs increased by more than 22 percent. While patient complexity increased, the median length of stay remained 12 days across the years. Discharge self-care and mobility function increased slightly, and the percent of patients discharged home ranged from 73.7 to 75.2 across the years.

Internal mammary node abnormality in imaging studies and treatment outcomes in patients with breast cancer.

The clinical significance of mild internal mammary node (IMN) enlargement (Mild-IMN) is uncertain. This study aimed to evaluate the relationship between treatment outcomes and IMN status in patients with breast cancer who underwent postmastectomy radiation therapy between January 2010 and December 2018. Overall, 250 patients were categorized based on IMN status: Clinically normal IMN (Normal-IMN; n=172), Mild-IMN (n=39) and clinically metastatic IMN (cMet-IMN; n=39). None of the patients in the Normal- or Mild-IMN groups received IMN irradiation. In the cMet-IMN group, 25 patients underwent IMN irradiation with an IMN boost (10 Gy in 5 fractions), while 14 patients did not. The median follow-up time was 80.0 months (range, 7.2-147.6 months). The 7-year overall survival (OS), disease-free survival (DFS) and IMN recurrence-free survival (IRF) rates were 80.2, 73.0 and 93.4%, respectively. Multivariate analyses indicated that only cMet-IMN had a significant impact on OS [hazard ratio (HR), 1.66; 95% CI, 1.01-3.68; P=0.05] and DFS (HR, 1.91; 95% CI, 1.08-3.39; P=0.03), while cMet-IMN did not have a significant impact on IRF (HR, 1.66; 95% CI, 0.41-6.78; P=0.48). Additionally, receiving an IMN boost had no influence on OS (HR, 1.11; 95% CI, 0.37-2.34; P=0.84), DFS (HR, 1.28; 95% CI, 0.51-3.22; P=0.60) or IRF (HR, 1.94; 95% CI, 0.22-17.47; P=0.55). In conclusion, the impact of Mild-IMN on clinical outcomes was small. Although irradiation for cMet-IMN is important, the impact of the cMet-IMN boost with 10 Gy in 5 fractions on clinical outcomes may also be limited.

Correlation between serum isoniazid concentration and therapeutic response in patients of pulmonary tuberculosis in Central India: A prospective observational study.

BACKGROUND: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis is one of the top ten causes of death worldwide. Isoniazid (INH) is an important component of anti-tuberculosis therapy (ATT). Low isoniazid levels can serve as a risk factor for the development of treatment failure, relapse of disease and acquired secondary resistance. Hence, serum level of isoniazid becomes a critical factor in determining the treatment outcome of patients on ATT. This study aimed to evaluate the correlation between serum isoniazid concentration and therapeutic response in patients of pulmonary tuberculosis in Central India. METHODS: This was a prospective single cohort observational study conducted at a tertiary care hospital. Therapeutic response in newly diagnosed patients of pulmonary TB was determined based the microbiological, clinical and radiological parameters. Serum INH levels were estimated based on a spectrophotometric method using nano-spectrophotometer. RESULTS: In this study, patients had a significant improvement in treatment outcome as evident by a significant decrease in the TB score I at end of IP (p = 0.001) and a significant decline in the Timika score at end of CP (p = 0.001). Although all patients converted to sputum negative at end of CP, 20% remained positive at end of IP. Lower INH levels were seen in 13.3% of the study population. Higher INH levels were observed in sputum converters, patients with low TB score I and low Timika score, although no statistically significant difference was noted (p > 0.05). CONCLUSION: In this study, we could not find any statistically significant association between serum INH levels and therapeutic outcome of the patients. Further studies on a larger population could provide better understanding about the prevalence of low serum isoniazid levels among the Indian population and establish its relationship with therapeutic outcome. Also, the usage of a comparatively less expensive spectrophotometric method of analysis makes this feasible in almost every district hospital without the need of high-performance liquid chromatography which is costlier and needs more expertise.

Predictors for long-term relapse of orthodontic treatment in patients with cleft lip and palate. A clinical follow-up study.

OBJECTIVES: To identify predictors for long-term relapse of orthodontic therapy in patients with cleft lip and palate (CLP). MATERIALS AND METHODS: Patients with uni- and bilateral non-syndromal CLP were followed up at least two years after completion of their orthodontic therapy. Plaster casts of the start of treatment (T1), after completion of treatment (T2), and at follow-up (T3) were measured using the modified Huddart Bodenham Index. Characteristics of multidisciplinary therapy were taken from the patient files. Potentially influencing factors of relapse were investigated using logistic regression analyses and Spearman correlations. RESULTS: In total 58.07% of the included 31 patients showed a stable treatment outcome at follow-up after an average of 6.9 years. Even if relapse occurred, 61.54% of these patients still showed improvement regarding their occlusion compared to baseline. Predictors for the occurrence of relapse were the severity of dysgnathia at baseline (p = 0.039) and the extent of therapeutic change (p = 0.041). The extent of therapeutic change was additionally a predictor for the extent of post-therapeutic relapse (ρ = 0.425; p = 0.019). CONCLUSIONS: Patients with CLP benefit from their orthodontic therapy in the long term despite an increased tendency to relapse. CLINICAL RELEVANCE: Results of this long-term study could be used to adapt the treatment concept for patients with CLP and reinforce the significance of a patient-centered orthodontic treatment concept for affected patients.

Clinical and Imaging Characteristics of SARS-CoV-2 Breakthrough Infection in Hospitalized Immunocompromised Patients.

OBJECTIVE: To evaluate the clinical and imaging characteristics of SARS-CoV-2 breakthrough infection in hospitalized immunocompromised patients in comparison with immunocompetent patients. MATERIALS AND METHODS: This retrospective study analyzed consecutive adult patients hospitalized for COVID-19 who received at least one dose of the SARS-CoV-2 vaccine at two academic medical centers between June 2021 and December 2022. Immunocompromised patients (with active solid organ cancer, active hematologic cancer, active immune-mediated inflammatory disease, status post solid organ transplantation, or acquired immune deficiency syndrome) were compared with immunocompetent patients. Multivariable logistic regression analysis was performed to evaluate the effect of immune status on severe clinical outcomes (in-hospital death, mechanical ventilation, or intensive care unit admission), severe radiologic pneumonia (≥ 25% of lung involvement), and typical CT pneumonia. RESULTS: Of 2218 patients (mean age, 69.5 ± 16.1 years), 274 (12.4%), and 1944 (87.6%) were immunocompromised an immunocompetent, respectively. Patients with active solid organ cancer and patients status post solid organ transplantation had significantly higher risks for severe clinical outcomes (adjusted odds ratio = 1.58 [95% confidence interval {CI}, 1.01-2.47], P = 0.042; and 3.12 [95% CI, 1.47-6.60], P = 0.003, respectively). Patient status post solid organ transplantation and patients with active hematologic cancer were associated with increased risks for severe pneumonia based on chest radiographs (2.96 [95% CI, 1.54-5.67], P = 0.001; and 2.87 [95% CI, 1.50-5.49], P = 0.001, respectively) and for typical CT pneumonia (9.03 [95% CI, 2.49-32.66], P < 0.001; and 4.18 [95% CI, 1.70-10.25], P = 0.002, respectively). CONCLUSION: Immunocompromised patients with COVID-19 breakthrough infection showed an increased risk of severe clinical outcome, severe pneumonia based on chest radiographs, and typical CT pneumonia. In particular, patients status post solid organ transplantation was specifically found to be associated with a higher risk of all three outcomes than hospitalized immunocompetent patients.

Hemophagocytic lymphohistiocytosis in Egyptian children: diagnosis, treatment challenges, and outcome.

BACKGROUND: Hemophagocyticlymphohistiocytosis (HLH) is a spectrum of immune activation which could be genetically determined, or secondary to an underlying illness. Our aim was to present the clinico-genetic aspects of HLH among Egyptian children and to evaluate the patterns of reactivation and outcome with illustrations of overlap manifestations. RESEARCH DESIGNAND METHODS: We retrospectively collected the data of 55 patients with HLH, registered at Ain Shams University Children's Hospital,Cairo, Egypt. RESULTS: Median age at diagnosis was 19 months (range 2-180), 33 patients (60%) fulfilled the diagnostic HLH criteria at presentation. Fourteen (25.45%) patients had secondary HLH, 15 (27.27%) patients had genetically documented familial HLH (11 had variants in UNC13D gene and one in PRF1 gene), 3 had Griscelli and Chediak-Higashi syndromes. Sixteen patients (29.1%) had reactivations, 8 (50%) of them had molecularly confirmed HLH. We report the death of 40 patients, the median duration from the diagnosis to death of 5 months mostly due to disease activity. CONCLUSIONS: This study confirms that the nonspecific signs and symptoms of HLH are challenging. Genetic testing, though expensive and sophisticated, is integral for the diagnosis. The difficulty in finding non-related donors for stem cell transplantation and the early reactivations are the causes of the inferior outcome.

Updated guidelines for prescribing opioids to treat patients with chronic non-cancer pain in Korea: developed by committee on hospice and palliative care of the Korean Pain Society.

There are growing concerns regarding the safety of long-term treatment with opioids of patients with chronic non-cancer pain. In 2017, the Korean Pain Society (KPS) developed guidelines for opioid prescriptions for chronic non-cancer pain to guide physicians to prescribe opioids effectively and safely. Since then, investigations have provided updated data regarding opioid therapy for chronic non-cancer pain and have focused on initial dosing schedules, reassessment follow-ups, recommended dosage thresholds considering the risk-benefit ratio, dose-reducing schedules for tapering and discontinuation, adverse effects, and inadvertent problems resulting from inappropriate application of the previous guidelines. Herein, we have updated the previous KPS guidelines based on a comprehensive literature review and consensus development following discussions among experts affiliated with the Committee on Hospice and Palliative Care in the KPS. These guidelines may assist physicians in prescribing opioids for chronic non-cancer pain in adult outpatient settings, but should not to be regarded as an inflexible standard. Clinical judgements by the attending physician and patient-centered decisions should always be prioritized.

Clinicopathologic characteristics and treatment outcomes of pancreatic cancer patients at a tertiary referral hospital in Kenya.

The global incidence of pancreatic cancer (PC) continues to steadily increase whereas its prognosis remains poor. Previous studies have suggested worse outcomes among individuals of African descent. The characteristics of patients with PC in Kenya, and their contemporary management and survival outcomes remain largely unknown. This study aimed to describe the clinical and pathologic characteristics, management, and outcomes of patients diagnosed with PC at Kenyatta National Hospital (KNH), a tertiary referral hospital in Kenya. Records of 242 patients diagnosed with PC at KNH between 1st January 2014 and 30th September 2021 were assessed in this retrospective cohort study. Data on their clinical, histopathologic, and treatment characteristics was presented as mean (± standard deviation) and/or median (interquartile range) for continuous variables and frequency (percentage) for categorical variables. Kaplan-Meier and Cox proportional hazard ratios were used for survival analysis. PC occurred in a young population, the median age being 58.5 years (inter-quartile range 35-88). The majority of tumours (54%) were metastatic at diagnosis, while 28% and 14% were stage III and stage I/II, respectively. Surgical resections with curative intent were performed on 7% overall and 44% of stage I/II cases. The majority of patients with stage I/II disease (52.9%) received chemotherapy whereas the majority with stage III and IV disease received the best supportive care only (62.7% and 64.9%, respectively). Patients who underwent surgical resection (HR for mortality 0.20, 95% CI 0.05-0.83, p = 0.021) and chemotherapy (HR for mortality 0.15, 95% CI 0.08-0.29, p < 0.001) had significantly improved survival, reflecting a more favourable stage of the disease more amenable to aggressive therapies. The median survival time was 3 months and the 1-year survival rate was 32%.

SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension.

BACKGROUND: This study aims to assess the impact of sotatercept on exercise tolerance, exercise capacity, and right ventricular function in pulmonary arterial hypertension. METHODS: SPECTRA (Sotatercept Phase 2 Exploratory Clinical Trial in PAH) was a phase 2a, single-arm, open-label, multicenter exploratory study that evaluated the effects of sotatercept by invasive cardiopulmonary exercise testing in participants with pulmonary arterial hypertension and World Health Organization functional class III on combination background therapy. The primary end point was the change in peak oxygen uptake from baseline to week 24. Cardiac magnetic resonance imaging was performed to assess right ventricular function. RESULTS: Among the 21 participants completing 24 weeks of treatment, there was a significant improvement from baseline in peak oxygen uptake, with a mean change of 102.74 mL/min ([95% CIs, 27.72-177.76]; P=0.0097). Sotatercept demonstrated improvements in secondary end points, including resting and peak exercise hemodynamics, and 6-minute walk distance versus baseline measures. Cardiac magnetic resonance imaging showed improvements from baseline at week 24 in right ventricular function. CONCLUSIONS: The clinical efficacy and safety of sotatercept demonstrated in the SPECTRA study emphasize the potential of this therapy as a new treatment option for patients with pulmonary arterial hypertension. Improvements in right ventricular structure and function underscore the potential for sotatercept as a disease-modifying agent with reverse-remodeling capabilities. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03738150.