Kaplan-Meier Survival Estimates Research Articles

Prognostic role of ECG patterns in Anderson Fabry disease

Abstract Background Anderson Fabry disease (AFD) is an X-linked lysosomal storage disorder leading to a deficiency in α-galactosidase A and globotriasylceramide (Gb3) deposition in different organs. Cardiac involvement is extremely common. It has been shown that the ECG abnormalities are directly correlated with the progressive accumulation of glycosphingolipids in the myocardium and cardiac conduction system. However, it is still unclear whether the ECG alterations are correlated with clinical events. Purpose To evaluate the prognostic role of ECG patterns in an unselected population of patients with AFD. Methods We conducted a retrospective multicenter study enrolling 215 consecutive patients. Based on the baseline ECG the study population was divided into the following five groups: 1) normal ECG or minimal alterations; 2) left ventricular hypertrophy (LVH) without signs of overload; 3) isolated negative T waves in the inferior and/or lateral leads; 4) LVH with signs of overload with or without incomplete right bundle branch block (RBBB); 5) complete RBBB. The primary endpoint was the composite of sudden cardiac death, resuscitated cardiac arrest, sustained ventricular tachycardia, and heart failure. Results Median age of study population was 45 years (32-57), and 86 patients (40%) were men. The rate of classic phenotype was 68%. Patients with ECG patterns 3 and 4 were older at baseline, more frequently affected by arterial hypertension, mostly male and showed greater left ventricular thickening, At a median follow up of 60 months (25-83) the overall Kaplan-Meier survival free from the primary endpoint was 57%: the Kaplan-Meier survival estimates of ECG groups were 66%, 75%, 68%, 27% e 52% respectively (log Rank 0.0026). On multivariable analysis patients belonging to either 3 or 4 group showed an increased risk of primary endpoint (HR= 2.45; 95% CI 1.04-5.78, p=0.040) compared to other groups. Conclusion ECG at baseline may be a useful tool to predict the risk of cardiovascular events in Anderson-Fabry Disease. Future studies should investigate if ECG may be useful also to evaluate the clinical response to specific therapy.

One-year outcomes of patients with hypertrophic cardiomyopathy according to levels of inflammatory biomarkers

Abstract Background Hypertrophic cardiomyopathy (HCM) is a vastly heterogeneous sarcomere disorder unified by maximal left ventricular (LV) thickness increases. The lifetime relative risk of morbidity in HCM is four-fold higher than in the general population, primarily driven by arrhythmias and heart failure (HF). Numerous prognostic features have been identified, but our ability to identify high-risk patients of progression remains rudimentary. Small retrospective studies have shown that systemic inflammation is associated with adverse outcomes in patients with HF; others, small and single-center, have also shown associations between adverse outcomes and inflammation in HCM. Purpose We aimed to determine whether elevated levels of inflammatory biomarkers are associated with an increased risk of acute heart failure (AHF) and mortality at 1 year in a large cohort of patients with HCM across multiple centers in the United States (US). Methods In this retrospective study, using the US cohort of 60 healthcare organizations in the TriNetX database, we included more than 85,000 adult patients with HCM (ICD-10-CM codes I42.1 and I42.2) between 2004 and 2024. Patients were divided according to predetermined cut-offs of different inflammatory biomarkers (C-reactive protein [CRP], <2 mg/L vs. 2-100 mg/L; white blood cells [WBC], < vs. ≥ the median [8x10^3/µL]; neutrophils [Neu], < vs. ≥ the median [5x10^3/µL]). These cohorts were then 1:1 propensity score matched (PSM) for age, sex, and race. We used Kaplan-Meier survival curves to derive cumulative incidence curves (as 1 minus Kaplan-Meier survival estimates) for AHF (ICD-10-CM codes I50.21, I50.23, I50.31, I50.33, I50.41, I50.43) or death, and we compared them with the Log-rank (Mantel-Cox) test. We also derived Hazard Ratios (HR) with 95% Confidence Interval (CI) from Cox regression analysis to compare the outcomes within the groups at 1-year. Results After PSM, patients with HCM and CRP levels between 2-100 mg/L experienced higher rates of the composite outcome (19.6% vs. 12.2%, Log-rank p<0.001; HR 1.67, 95% CI [1.29-2.16]), as well as the separate outcomes of death (14.7% vs. 6.8%, Log-rank p<0.001; HR 2.23, 95% CI [1.68-2.98]) and AHF (10.9% vs. 7.5%, Log-rank p<0.001; HR 1.49, 95% CI [1.07-2.07]), compared to those with CRP <2 mg/L (Table 1)(Figure 1). Similarly, patients with Neu ≥5x10^3/µL reported higher incidences of the composite outcome (20.3% vs. 13.2%, Log-rank p<0.001; HR 1.62, 95% CI [1.55-1.68]) and the separates outcomes, compared to those with Neu <5x10^3/µL (Table 1) (Figure 1). Patients with WBC ≥8x10^3/µL also had increased rates of the composite outcome (19.4% vs. 14.1%, Log-rank p<0.001; HR 1.43, 95% CI [1.38-1.48]) and the separate outcomes, compared to those with WBC <8x10^3/µL (Table 1)(Figure 1). Conclusions In the first large 'real world' analysis of patients with HCM, elevated levels of inflammatory biomarkers were associated with worse outcomes of death and acute heart failure.

Determinants of Length of Stay for Medical Inpatients Using Survival Analysis

With the increase in insured patients and an aging population, managing the length of stay (LOS) for inpatients has become crucial for controlling medical costs. Analyzing the factors influencing LOS is necessary for effective management. Previous studies often used multiple or logistic regression analyses, which have limitations such as unmet assumptions and the inability to handle time-dependent variables. To address these issues, this study applied survival analysis to examine the factors affecting LOS using the National Health Insurance Service (NHIS) sample cohort data from 2016 to 2019, covering over 4 million records. We used Kaplan–Meier survival estimation to assess LOS probabilities based on sociodemographic, patient, health checkup, and institutional characteristics. Additionally, the Cox proportional hazards model controlled for confounding factors, providing more robust validation. Key findings include the influence of age, gender, type of insurance, and hospital type on LOS. For instance, older patients and medical aid recipients had longer LOS, while general hospitals showed shorter stays. This study is the first in Korea to use survival analysis with a large cohort database to identify LOS determinants. The results provide valuable insights for shaping healthcare policies aimed at optimizing inpatient care and managing hospital resources more efficiently.

A Comparative Study of Hospitalization Mortality Rates between General and Emergency Hospitalized Patients Using Survival Analysis

Background/Objectives: In Korea’s emergency medical system, when an emergency patient arises, patients receive on-site treatment and care during transport at the pre-hospital stage, followed by inpatient treatment upon hospitalization. From the perspective of emergency patient management, it is critical to identify the high death rate of patients with certain conditions in the emergency room. Therefore, it is necessary to compare and analyze the determinants of the death rate of patients admitted via the emergency room and generally hospitalized patients. In fact, previous studies investigating determinants of survival periods or length of stay (LOS) primarily used multiple or logistic regression analyses as their main research methodology. Although medical data often exhibit censored characteristics, which are crucial for analyzing survival periods, the aforementioned methods of analysis fail to accommodate these characteristics, presenting a significant limitation. Methods:Therefore, in this study, survival analyses were performed to investigate factors affecting the dying risk of general inpatients as well as patients admitted through the emergency room. For this purpose, this study collected and analyzed the sample cohort DB for a total of four years from 2016 to 2019 provided by the Korean National Health Insurance Services (NHIS). After data preprocessing, the survival probability was estimated according to sociodemographic, patient, health checkup records, and institutional features through the Kaplan–Meier survival estimation. Then, the Cox proportional hazards models were additionally utilized for further econometric validation. Results: As a result of the analysis, in terms of the ‘city’ feature among the sociodemographic characteristics, the small and medium-sized cities exert the most influence on the death rate of general inpatients, whereas the metropolitan cities exert the most influence on the death rate of inpatients admitted through the emergency room. In terms of institution characteristics, it was found that there is a difference in determinants affecting the death rate of the two groups of study, such as the number of doctors per 100 hospital beds, the number of nurses per 100 hospital beds, the number of hospital beds, the number of surgical beds, and the number of emergency beds. Conclusions: Based on the study results, it is expected that an efficient plan for distributing limited medical resources can be established based on inpatients’ LOS.

Assessment of Outcomes by Intention-to-Treat Comparison for Locally Advanced Pancreatic Cancer: A Population-Derived Cohort Study.

The overall treatment response among patients with locally advanced pancreatic cancer (LAPC) is poorly understood as most studies report solely on resected patients. We aimed to investigate the outcomes in patients with LAPC as an intention-to-treat-analysis from the time of diagnosis from a complete source population. An observational cohort study in a population-defined region within a universal healthcare system. All consecutive patients discussed at multi-disciplinary tumour board (MDT), aged ≥ 18 years and diagnosed with LAPC were included. Exposure was set as recommended treatment by MDT (i.e. upfront surgery, neoadjuvant therapy, palliative treatment or best supportive care). Outcome measures were overall survival analysed by Kaplan-Meier survival estimates and multivariable analyses using logistic regression for odds ratios (OR) and Cox proportional hazard analysis for hazard ratios (HR). In total, 8803 MDT events (6055 unique patients) with pancreatic disease were held during the study period. Some 1436 (24%) had pancreatic cancer, of which 162 (11%) had LAPC and 134 met the population-defined criteria. In overall survival analyses, the patients who were recommended neoadjuvant therapy (± surgery) demonstrated no significant difference to palliative chemotherapy (median 11.0 months vs. 11.8 months; p = 0.226). In multivariable analysis, adjusted OR for overall survival comparing the treatment groups was 0.27 (95% CI 0.02-3.29, p = 0.306) and Cox proportional HR 0.96 (95% CI 0.58-1.59, p = 0.865). In patients with LAPC, survival was not statistically different between those recommended for attempt at neoadjuvant (± surgery) compared with those recommended palliative chemotherapy. The findings suggest that conversion/downstaging chemotherapy is successful in only a select few.

Comparing optimum prosthesis combinations of total stemmed, stemless and reverse shoulder arthroplasty revision rates for men and women with glenohumeral osteoarthritis

BackgroundThis study investigated prostheses from a large national arthroplasty registry with the lowest rates of revision, defined as optimum. We compared optimum shoulder arthroplasty revision rates for osteoarthritis (OA) to determine the most suitable/effective procedure for men and women. MethodsThere were three cohort groups of optimum primary shoulder arthroplasties for OA undertaken between 1st January 2008 and 31 December 2022: stemless shoulder arthroplasty with cemented polyethylene glenoids (slTSA), stemmed shoulder arthroplasty with modified central peg polyethylene glenoids (stTSA), and cementless reverse shoulder arthroplasty (rTSA). The cumulative percent revision (CPR) was determined using Kaplan-Meier estimates of survivorship and hazard ratios (HR) from Cox proportional hazard models adjusted for age, gender, humeral head/glenosphere size, polyethylene type, and surgeon volume. Possible interactions were examined. A sub-analysis from 1 January 2017 captured additional patient demographics, ASA score, BMI and glenoid morphology. ResultsThe CPR at 7 years was 4.0%(95% confidence interval (CI) 3.1, 5.1) for slTSA (n=3,041), 3.8%(95%CI 2.7, 5.5) for stTSA (n=1,259) and 4.1%(95%CI 3.7, 4.6) for rTSA (n=12,341). slTSA had a higher rate of revision compared to rTSA after the first 9 months (p<0.001). rTSA had a lower revision rate compared to stTSA from 3 months on (p=0.004). After adjusting for other confounders, prosthesis type and gender were associated with revision rates (p<0.001) whereas surgeon volume was not. Additionally, gender and prosthesis type strongly interacted (p=0.013) and the combined model exhibited greater predictive performance when including this interaction. Women had lower rates of revision than men for both stTSA and rTSA, but not slTSA. Most revisions were for infection in men, especially rTSA. After 3 months, the rate of revision for slTSA vs rTSA for women was increased (p<0.001) and revision rates for men did not significantly differ. However, in a sub-analysis of procedures in males since 2017 with additional adjustments, slTSA had a lower revision rate than stTSA (p=0.010). ConclusionsThe optimum shoulder arthroplasty revision rates vary for both the gender and implant type for the diagnosis of OA. A model combining optimum prostheses and gender predicted revision better than optimum implants alone. After 3 months, rTSA was associated with lower revision rates compared to slTSA in women, whereas there were no significant differences between optimum prostheses in men. However, surgeons may also consider lower revision risk of optimum slTSA at sub analysis and increased cumulative incidence of infection for rTSA requiring revision to resolve decision making for male patients.

Long-term outcomes of mitral valve repair in children.

Mitral Valve Disease in children presents unique challenges due to the wide range of associated pathologies and the complexities of pediatric cardiac anatomy. Mitral valve repair in this demographic is preferred over replacement due to the drawbacks associated with prosthetic valves in young patients, such as the need for long-term anticoagulation and issues with prosthetic size and growth. This retrospective study reviewed pediatric patients under 18 years who underwent mitral valve repair between January 2002 and December 2023. Exclusion criteria included patients with atrioventricular septal defects or single-ventricle physiology. Surgical outcomes were assessed using preoperative and postoperative transthoracic echocardiography, with follow-up data analyzed via Kaplan-Meier survival estimates. The study included 47 patients with a median age of 4 years. Surgical techniques varied based on the specific mitral valve pathology. The overall early mortality was 6.3%, and the one and ten-year survival rates were 93.6 ± 3.6% and 91.4 ± 4.1%, respectively. Most patients showed improved or stable postoperative cardiac function during a median follow-up of 105 months. Notably, the rate of freedom from re-operation at ten years was 85.1 ± 6.9%, highlighting the durability of the surgical interventions. Mitral valve repair in children demonstrates favorable long-term outcomes with low mortality and reoperation rates, particularly when performed at an older age to accommodate growth and avoid the complexities of smaller, more delicate cardiac structures. These findings suggest that mitral valve repair should be considered a viable and effective option for managing pediatric MVD, with a personalized approach essential for optimizing outcomes.

Distal endovascular extension after FET: short and mid-term outcome in a high-volume single-center experience

ObjectivesThis study aims to investigate results and outcomes of distal endovascular extensions after FET procedure. MethodsBetween September 2018 and December 2022, all consecutive patients who underwent thoracic endovascular aortic repair (TEVAR) or complex thoraco-abdominal repair (TAA-EVAR) after FET were included in the study. Patients were assigned to “Aneurysm” group or to “Dissection” group according to underlying patology before FET repair. The primary endpoints were overall technical success and early re-intervention rate. Secondary endpoints included 30-day and mid-term overall survival. ResultsA total of 29 patients were included in the study and divided as follows, n=12 in the aneurysm group and n=17 in the dissection group. The mean age of the population was 64.6±10.2 years, 69% were male. All patients received TEVAR as primary extension while 9 of them underwent further extension to a subsequent TAA-EVAR in a second stage. Among the dissection group, 7 patients experienced a distal stent-graft induced new entries (dSINE) caused by the stent-graft portion of the FET. Technical success of the first stage (TEVAR) was fully achieved as well as for the second stage (TAA-EVAR). Within the first 30 days, no patient expired or required early reinterventions. Freedom-from-reintervention at 36 months was 72% and 64% in the aneurysm and dissection group, respectively. Overall, 1 major adverse event (MAE) (3,4%) and 3 access-related complication (10.3%) occurred among the entire cohort. The Kaplan-Meier survival estimation showed a non-significant log-rank value (p=.248) with a survival rate of 91.7% and 100% at 12, 24 and 36 months each for aneurysm and dissection group, respectively. ConclusionDistal endovascular extensions after FET repair is feasible with low perioperative morbidity and mortality regardless of the underlying pathology. Technical success rate of endovascular extension is high but aortic-related re-intervention rate remains quite consistent over time. Thus, a close surveillance is advocated for such patients.

Adaptation of a modified Elixhauser comorbidity index to isolate the impact of body mass index on survival outcomes in patients with cancer in a large integrated healthcare system.

124 Background: Variable impacts of body mass index (BMI) on overall survival (OS) and cancer-specific survival (CSS) have been described in patients with cancer, with existing data highlighting both detrimental effects and malignancy-specific benefits. Real-world data derived from integrated healthcare systems are underexplored in this context, and tight control of confounding using validated tools such as the Elixhauser Comorbidity Index (ECI) is rarely employed in pre-existing studies. Herein, we offer a highly refined description of the impact of BMI on cancer-specific outcomes in a large patient cohort using a targeted ECI model. Methods: 153,270 patient records were abstracted from an integrated healthcare system from 2010-2018, including descriptors of age, race/ethnicity, income, disease stage, and treatment regimens. Standardized derivation of BMI within one year prior to diagnosis was performed and categorized by World Health Organization definitions. A custom ECI was designed to exclude ICD codes for obesity to effectively isolate the impact of BMI on downstream analyses. Kaplan-Meier survival estimates of OS and CSS were constructed, and univariate and multivariate Cox proportional hazard (PH) modeling was performed to determine hazard ratios (HR). Results: When normalized to healthy BMI in multivariate modeling, we found a favorable dose-dependent relationship of overweight and obese BMI on OS and CSS independent of age, race/ethnicity, income, modified ECI score, cancer stage, or therapeutic regimen (Table). This advantage to OS and CSS was not as strongly reflected in severely obese patients, though still significant compared to healthy BMI counterparts. Being underweight was a negative prognostic indicator for OS and CSS in all patients compared to a healthy BMI. Conclusions: We demonstrate a beneficial impact of increased BMI on OS and CSS in a large cohort of patients treated in an integrated healthcare model independent of tightly controlled confounding. Specifically, we highlight the utility of isolating obesity using a targeted ECI model for comorbidity adjustment, which may provide a more robust measure of the influence of BMI on survival. Our findings raise questions regarding attention to adequate control of confounding in prior studies, as well as the potential benefit of removing variation in healthcare delivery in understanding these outcomes. Adjusted HR of OS and CSS stratified by BMI category (*95% Confidence Interval). BMI Category Adjusted OS Adjusted CSS Normal Weight(18.5 – 24.9) 1 (reference) 1 (reference) Underweight(&lt; 18.5) 1.35 (1.25 – 1.45*) 1.28 (1.15 – 1.41) Overweight(25 – 29.9) 0.83 (0.81 – 0.85) 0.84 (0.81 – 0.87) Obese(30 – 39.9) 0.81 (0.79 – 0.83) 0.81 (0.78 – 0.84) Severe Obesity(≥ 40) 0.86 (0.82 – 0.90) 0.82 (0.77 – 0.87) Unknown 1.33 (1.24 – 1.43) 1.19 (1.07 – 1.31)

TERT Expression and Clinical Outcome in Pulmonary Carcinoids.

The clinical course of pulmonary carcinoids ranges from indolent to fatal disease, suggesting that specific molecular alterations drive progression toward the fully malignant state. A similar spectrum of clinical phenotypes occurs in pediatric neuroblastoma, in which activation of telomerase reverse transcriptase (TERT) is decisive in determining the course of disease. We therefore investigated whether TERT expression defines the clinical fate of patients with pulmonary carcinoid. TERT expression was examined by RNA sequencing in a test cohort and a validation cohort of pulmonary carcinoids (n = 88 and n = 105, respectively). A natural TERT expression cutoff was determined in the test cohort on the basis of the distribution of TERT expression, and its prognostic value was assessed by Kaplan-Meier survival estimates and multivariable analyses. Telomerase activity was validated by telomere repeat amplification protocol assay. Similar to neuroblastoma, TERT expression exhibited a bimodal distribution in pulmonary carcinoids, separating tumors into TERT-high and TERT-low subgroups. A natural TERT cutoff discriminated unfavorable from favorable clinical courses with high accuracy both in the test cohort (5-year overall survival [OS], 0.547 ± 0.132 v 1.0; P < .001) and the validation cohort (5-year OS, 0.788 ± 0.063 v 0.913 ± 0.048; P < .001). In line with these findings, telomerase activity was largely absent in TERT-low tumors, whereas it was readily detectable in TERT-high carcinoids. In multivariable analysis considering TERT expression, histology (typical v atypical carcinoid), and stage (≤IIA v ≥IIB), high TERT expression was an independent prognostic marker for poor survival, with a hazard ratio of 5.243 (95% CI, 1.943 to 14.148; P = .001). Our data demonstrate that high TERT expression defines clinically aggressive pulmonary carcinoids with fatal outcome, similar to neuroblastoma, indicating that activation of TERT may be a defining feature of lethal cancers.

The impact of the tumor microenvironment on the survival of penile cancer patients

PeCa is a rare entity with rising incidence rates due to increased infections with human papillomaviruses (HPV). The distinct subtypes of PeCa with an individual pathogenesis demand biomarkers for a precise patient risk assessment regarding disease progression and therapeutic susceptibility. We recently identified promising candidates associated with an HPV-instructed tumor microenvironment (TME) using HPV-positive PeCa cell lines and tissue microarrays (TMA). The capacity of HPV + p63 + PeCa cells to release neutrophil-attracting CXCL-8 provided a molecular link explaining the infiltration of CD15 + myeloid cells in PeCa specimens. The candidate biomarkers HPV, p63, CD15, DKK1, and CD147 linked a tumor-promoting TME with a higher TNM classification reflecting more aggressive and metastasizing cancers. Based on immune-reactive scores (IRS) from TMA staining for these biomarkers, we calculated correlations and conducted association analyses to assess the degree of relationship between all biomarkers. We then conducted Kaplan–Meier survival estimates and Cox regression analyses to delineate the impact on PeCa patient survival. There is a notable predictive potential regarding the survival of patients with biomarker profiles beyond the potency of the individual biomarker. From all candidate biomarkers and biomarker profiles, the combination of CD147 and infiltrating CD15 + cells linked to an active HPV-driven transformation displayed cancer-immune dynamics with dismal prognosis for patients. After deciphering relevant interdependencies, the HPV + CD147 + CD15 + status was the most potent profile predicting metastasis-free survival of PeCa patients. The results of this report underscore the need for analysis of the TME and the development of multi-parameter composite scores that reflect fundamental cancer-immune relationships to tailor therapeutic interventions based on actual cancer immune dynamics.

Survival, technical and biological outcome of fixed tooth- and implant-supported restorations: A retrospective analysis of a patient cohort treated in an undergraduate dental education program

ObjectivesThere is a paucity of data on the outcome of fixed tooth- and implant-supported porcelain-fused-to-metal (PFM) and ceramic-based (CB) restorations fabricated during undergraduate dental education. Therefore, this retrospective study examined the outcome of fixed restorations placed in patients participating in an undergraduate program. MethodsPatient records were searched for data on fixed PFM and CB restorations. For these restorations, the functional period in situ and technical and biological complications, namely restoration fracture, decementation, screw loosening, secondary caries, and loss of vitality, were recorded. Periodontal parameters were also documented. Kaplan-Meier survival and complication estimates after 1 and 5 years were calculated for restoration types, materials, designs (veneered/non-veneered), cementation/retention modes and localizations with group sizes ≥ 15. Regression models were used to analyze the influence of demographic data and abovementioned restoration characteristics on restoration survival, technical and biological outcome. Results1196 restorations with a mean observation time of 5 years were included in the analysis. The different restoration types exhibited survival rates of > 90.8% after 5 years, accompanied by a favorable biological outcome. However, monolithic resin-matrix or feldspathic ceramic restorations were found to have a higher fracture rate than lithium disilicate or zirconium dioxide ceramic restorations resulting in lower survival rates for these restorations. Additionally, resin-matrix ceramic restorations showed a higher decementation rate than lithium disilicate restorations. ConclusionsFixed tooth- and implant-supported CB restorations fabricated from lithium disilicate and zirconium dioxide ceramics demonstrated better survival and lower complication rates than restorations fabricated from resin-matrix or feldspathic ceramics in an undergraduate dental education program. Clinical significanceDue to the more favorable outcome of CB restorations fabricated from lithium disilicate or zirconium dioxide ceramics, undergraduate dental education should focus on the application of these ceramics to increase restoration survival by reducing technical complications.

Long-Term Outcomes of Primary Cemented Total Hip Arthroplasty with Acetabular Bone Graft for Protrusio Acetabuli: Minimum 10-Year Follow-Up.

Background: This study reports the long-term survivorship of primary total hip arthroplasty (THA) for protrusio acetabuli. Methods: Patients undergoing THA utilising cement and bone graft acetabular reconstruction for protrusio acetabuli in a university teaching hospital during the period 2003 to 2014 were included. Kaplan-Meier survival estimates were calculated with 95% confidence intervals (CI) up to 15 years following surgery. PROMs were collected pre- and post-operatively for hip-specific function (Oxford Hip Score [OHS]) and health-related quality of life (HRQoL) using the EQ-5D-3L. Results: 129 consecutive THAs (96 patients) performed for protrusio acetabuli were identified (median age 69, IQR 61-75; female 115 [89.1%]; 38 [29.5%] inflammatory arthritis) with a mean follow-up of 15.7 years (range: 10.1-20.1 years). At the final follow-up, fifty-six (43.4%) patients had died and there were eleven (8.5%) reoperations, of which eight (6.2%) involved the revision of the acetabular component. The fifteen-year Kaplan-Meier any-reoperation survival estimate was 91.3% (95% CI 85.9-97.0). When considering all-cause acetabular revision only, the 15-year survival estimate was 93.1% (95% CI 88.2-98.3). The median pre-operative OHS improved significantly from baseline to 1 year post-THA, beyond the minimal important change (mean difference 28, 95% CI 25-30, p < 0.001). Similarly, there were clinically relevant improvements in HRQoL at 1 year post surgery (mean difference 0.10, 95% CI 0.06-0.15, p < 0.001). Conclusions: This study demonstrates that primary cemented THA utilising acetabular bone graft for reconstruction in patients with protrusio acetabuli was associated with 15-year survival rates of 93.1% and clinically relevant improvements in hip-specific function and HRQoL.

What Are the Factors Associated With Revision Surgery on the Residual Limb and Functional Results in Patients With Posttraumatic Lower Limb Amputations?

Lower limb amputations performed after trauma are associated with a high risk of revision surgery. While the factors influencing revision surgery in the upper limbs have been studied, no studies have analyzed these factors in the lower limbs. Existing explanations for these revision surgeries are unclear, often leaving patients uninformed. Surgeons also lack the tools to explain the factors that influence repeat operations to patients. Therefore, the aim of this study was to provide surgeons with some answers so they can inform their patients undergoing posttraumatic lower limb amputation, whether military or civilian. (1) What was the survivorship of the initial amputation free from any revision surgery? (2) What patient- and injury-related factors were associated with revision amputation? (3) Do these factors influence functional outcomes in these patients? A single-center, retrospective study was conducted between January 2010 and February 2020 on patients who had undergone traumatic lower limb amputation. Between January 2010 and February 2020, 322 patients underwent amputation or were followed up at Percy Military University Hospital. Thirty-one patients had undergone amputation at another center, 178 had undergone amputation for nontraumatic reasons, and 27 patients had only upper limb amputations. Of those remaining, 1 died before 6 months, and 6% (5 of 86) were not fitted with a prosthesis, leaving 99% (85 of 86) for survivorship free from revision analysis and 93% (80 of 86) for functional endpoints analysis in this retrospective study at a median of 6.5 years (IQR 5 to 9) following the index amputation. The median age at the time of amputation was 31 years (IQR 26 to 52), 85% (72 of 85) of patients were men, and 31% (26 of 85) were military personnel. Revision surgery was defined as surgery performed at or after 6 months to ensure that the residual limb was healed and fitted with a prosthesis. Revision procedures performed before 6 months (median 2 [IQR 0 to 7]) were considered as part of the initial residual limb formation surgery. We performed Kaplan-Meier survivorship analysis for the time free from revision amputation from 6 months after amputation. We considered the competitive risk of death using a Fine-Gray model by an ascending stepwise procedure. To answer our third research question, we performed a chart review and assessed patients' use of prostheses and assistive devices and the percentage of patients who returned to work. An ordinal logistic regression was used to analyze the factors influencing functional outcome using an ascending stepwise procedure. A total of 85 patients (94 limbs) were included, of whom 25 (27 limbs) underwent a revision surgery on the residual limb > 6 months after amputation. Kaplan-Meier survival estimates indicated that 5 years after the initial amputation 64% (95% confidence interval 53% to 77%) of the patients remained free from revision surgery on their residual limb. Factors associated with increased odds of revision amputation were smoking (subdistribution HR 2.6 [95% CI 1.2 to 5.8]; p = 0.02) and an age of > 50 years (subdistribution HR 0.3 [95% CI 0.1 to 0.8]; p = 0.01). Ninety-four percent (80 of 85) of patients were fitted with prostheses, and 40% (32 of 80) of patients used material or human assistance for simple activities of daily living. Seventy-one percent of patients (57 of 80) had returned to work. Ordinal logistic regression revealed an association between preinjury sports activity and the absence of need for assistance in daily activities (OR 9 [95% CI 2.9 to 31.8]; p < 0.001). Smoking appeared to be an associated risk factor for residual limb revision surgery in posttraumatic lower limb amputations and is potentially modifiable. Being at least 50 years of age seemed to be associated with a lower incidence of revision surgery, which is probably linked to lower functional demands made on limbs beyond this age. Our study showed a remarkable rate of fitting with a prosthetic device, with an improved functional result if the patient was athletic before the trauma. These results provide more precise information on the care pathway to be considered for each patient. A study with a much larger sample would make it possible to assess the risk factors for the occurrence of each complication involving revision surgery. Level III, therapeutic study.

Tumour-associated macrophages in diffuse large B-cell lymphoma: the prognostic and therapeutic impact in a South African centre with high HIV seroprevalence.

Diffuse large B-cell lymphoma (DLBCL) is a common malignancy among people living with HIV. Macrophage enrichment of the tumour microenvironment (TME) is a prognostic factor in DLBCL among immunocompetent people, with some studies reporting that macrophage enrichment predicts a superior response to rituximab therapy. The macrophage phenotype is also important, with reportedly poorer outcomes with enrichment of anti-inflammatory (M2) macrophages. To date, the relationship between the type/number of tumour macrophages and outcomes in HIV-associated DLBCL (HIV-DLBCL) has been poorly explored. In this study, we assessed tumour macrophage numbers in a South African cohort of patients with DLBCL and a high HIV-seropositivity rate. Immunohistochemistry for CD68 and CD163 was performed on the diagnostic biopsies of 79 patients with DLBCL. Relevant information was documented from the clinical records, including disease stage, international-prognostic index score, HIV-related parameters, C-reactive protein, ferritin levels and immune cell numbers (monocytes, lymphocytes and neutrophils). Survival analysis was performed using Kaplan-Meier survival estimates, and the correlation between tumour macrophage numbers and a variety of immunological parameters was assessed using Spearman's rho. Of the 79 patients included, 87.2% were living with HIV, and rituximab therapy was used in 46.9%. Tumour macrophage numbers were not related to HIV status, but low pro-inflammatory (M1) macrophage numbers (CD68 + CD163 -) were significantly associated with poorer outcomes (HR 2.02, p = 0.03). M2 macrophage (CD68 + CD163 +) enrichment was not predictive of survival but was associated with improved response to rituximab therapy (HR 0.19; p = 0.002). Macrophage numbers were marginally correlated with ferritin levels, which showed modest performance as a peripheral blood biomarker of the TME macrophage status (AUC 0.6 at a level of 374µg/L), and high ferritin levels were associated with a superior response to rituximab-therapy (HR 0.28, p = 0.034). Pro-inflammatory macrophages are important in tumour control in HIV-DLBCL, while M2 macrophage enrichment improves the response to rituximab therapy. Ferritin shows promise as a biomarker for identifying patients more likely to benefit from rituximab therapy.

Consensus molecular subtyping of metastatic colorectal cancer expands biomarker-directed therapeutic benefit for patients with CMS1 and CMS2 tumors.

We developed a whole transcriptome sequencing (WTS)-based Consensus Molecular Subtypes (CMS) classifier using FFPE tissue and investigated its prognostic and predictive utility in a large clinico-genomic database of CRC patients (n = 24,939). The classifier was trained against the original CMS datasets using an SVM model and validated in an independent blinded TCGA dataset (88.0% accuracy). Kaplan-Meier estimates of overall survival (OS) and time-on-treatment (TOT) were calculated for each CMS (p < 0.05 considered significant). CMS2 tumors were enriched on left-side of colon and conferred the longest median OS. In RAS-wildtype mCRC, left-sided tumors and CMS2 classification were associated with longer TOT with anti-EGFR antibodies (cetuximab and panitumumab). When restricting to only CMS2, there was no significant difference in TOT between right- versus left-sided tumors. CMS1 tumors were associated with a longer median TOT with pembrolizumab relative to other CMS groups, even when analyzing only microsatellite stable (MSS) tumors. A WTS-based CMS classifier allowed investigation of a large multi-institutional clinico-genomic mCRC cohort, suggesting anti-EGFR therapy benefit for right-sided RAS-WT CMS2 tumors and immune checkpoint inhibitor benefit for MSS CMS1. Routine CMS classification of CRC provides important treatment associations that should be further investigated.

Survivorship of Primary NexGen Knee Replacement: Comparing Cementless Trabecular Metal to Other Designs of Tibial Component.

The impact of cementless trabecular metal (TM) implants on implant survivorship are not well delineated. This study compares primary total knee arthroplasty (TKA) revision rates of cemented knee replacements with two cementless knee replacement designs-cementless TM and a non-TM cementless design. Data from a national registry queried TKA procedures performed for osteoarthritis from 1999 to 2020. The risk of revision of Zimmer NexGen TKA using cementless TM, cementless non-TM, and cemented non-TM were compared. Analyses included Kaplan-Meier estimates of survivorship and Cox hazard ratios (HR), stratified by age and gender. Cementless TM components had higher risks of revision compared with cementless non-TM implants (HR = 1.49; p ≤ 0.001). Cementless TM implants showed higher risks of revision compared with cemented non-TM prostheses for the first 2 years (HR = 1.75, p < 0.001). Non-TM prostheses posed equal risk of revision for cementless and cemented fixations (HR = 0.95, p = 0.522). Patients aged 55 to 64 years and 65 to 74 years had a higher risk of revision for cementless TM compared with cementless non-TM (HR = 1.40, p = 0.033 and HR = 1.79, p < 0.001, respectively) and cemented non-TM implants (HR = 1.51, p < 0.001 and HR = 1.54, p < 0.001, respectively). The study shows there is an increased risk of revision with TM cementless implants for patients aged 55 to 74 years. These results do not support the use of TM tibial implants for patients of this age group for primary TKA.

Craniospinal irradiation and/or intraventricular radioimmunotherapy after high-dose chemotherapy and autologous stem cell rescue in patients with CNS retinoblastoma-Safety and outcomes.

The prognosis for patients with central nervous system (CNS) retinoblastoma (RB) (trilateral or stage 4b metastatic RB) treated with high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) remains poor. The impact of irradiation when administered as part of upfront therapy post HDC-ASCT on treatment outcomes and survival is unknown. We performed a retrospective review of all patients with CNS RB (seven stage 4b, eight trilateral, one pineal lesion belonging to methylation group RB) who underwent induction chemotherapy with an intent to proceed to HDC-ASCT at two institutions. Twelve of 16 patients (n=75%) achieved an objective response to induction chemotherapy, while four patients had progressive/refractory disease; two patients responded to subsequent therapy and proceeded to ASCT, and two patients did not. Seven of 14 patients who underwent HDC-ASCT, received radiotherapy as part of upfront therapy post HDC-ASCT in the form of craniospinal irradiation (CSI) (n=3), intraventricular radioimmunotherapy (n=3), or both CSI and intraventricular radioimmunotherapy (n=1). The Kaplan-Meier estimate of overall survival for these patients was 62.5% at 5years; no patients developed second malignant neoplasms within the radiation fields. For the seven patients who did not receive radiotherapy, the overall survival was 28.6% at 5years. CSI (23.4Gy) alone or in conjunction with intraventricular RIT may have clinical utility in eliminating persistent MRD post HDC-ASCT, contributing to improved disease-free survival in patients with CNS RB. This treatment strategy merits evaluation in a prospective, multicenter clinical trial for patients with CNS metastatic RB.

Influence of design features and brand of reverse shoulder arthroplasties on survivorship and reasons for revision surgery: results of 5,494 arthroplasties with up to 15 years' follow-up reported to the Norwegian Arthroplasty Register 2007-2022.

We aimed to report the survival of different reverse shoulder arthroplasty (RSA) designs and brands, and factors associated with revision. The secondary aim was to evaluate the reasons for revision. We included 4,696 inlay and 798 onlay RSAs reported to the Norwegian Arthroplasty Register (NAR) 2007-2022. Kaplan-Meier estimates of survivorship and Cox models adjusted for age, sex, diagnosis, implant design, humeral fixation, and previous surgery were investigated to assess revision risks. The reasons for revision were compared using competing risk analysis. Overall, the 10-year survival rate was 94% (confidence interval [CI] 93-95). At 5 years all brands exceeded 90%. Compared with Delta Xtend (n = 3,865), Aequalis Ascend Flex (HR 2.8, CI 1.7-4.6), Aequalis Reversed II (HR 2.2, CI 1.2-4.2), SMR (HR 2.5, CI 1.3-4.7), and Promos (HR 2.2, CI 1.0-4.9) had increased risk of revision. Onlay and inlay RSAs had similar risk of revision (HR 1.2, CI 0.8-1.8). Instability and deep infection were the most frequent revision causes. Male sex (HR 2.3, CI 1.7-3.1), fracture sequelae (HR 3.1, CI 2.1-5.0), and fractures operated on with uncemented humeral stems had increased risk of revision (HR 3.5, CI 1.6-7.3). We found similar risk of revision with inlay and onlay designs. Some prosthesis brands had a higher rate of revision than the most common implant, but numbers were low.

Comparison of treatment strategies based on clinical and pathological nodal status in resectable gastric adenocarcinoma.

To determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status. In this retrospective analysis, the National Cancer Database was used to identify resected non-metastatic GC (2006-2016). Patients were stratified by clinical nodal status-negative (cLN-) and positive (cLN+). In patients with cLN- disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN- and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan-Meier survival estimate, log-rank test, and multivariable Cox proportional hazards analysis were performed. We identified 7827 patients (cLN- 4828; cLN+ 2999). On multivariable analysis in patients with cLN- disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70-0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88-1.40, p = 0.39) and POC (n = 341) in patients with pLN- disease. On multivariable analysis in all patients with cLN- disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75-0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70-1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677). Postoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node-negative disease to pathologically node-positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease.