Nevin Manimala

Orthop Surg. 2024 Nov 23. doi: 10.1111/os.14304. Online ahead of print.

ABSTRACT

OBJECTIVE: Currently, there is no research that includes a comprehensive three-dimensional fracture mapping encompassing all types of Pilon fractures. Moreover, the existing classification systems for Pilon fractures exhibit only moderate to fair consistency and reproducibility. Additionally, some of these classification systems fail to accurately depict the morphological characteristics of the fractures. This study aimed to create a fracture map encompassing all types of Pilon fractures by three-dimensional fracture mapping. In addition, this study conducted a finite element analysis of the normal ankle joint, and based on the distribution of fracture lines and the stress distribution at the distal tibia, proposed a new classification for Pilon fractures.

METHODS: A retrospective analysis of Pilon fractures in our hospital from January 2018 to January 2024 was performed. A total of two hundred forty-four Pilon fractures were included, and their fracture lines were transcribed onto the tibia and fibula templates, and fracture maps and heat maps were created. A nonhomogeneous model of the ankle joint was constructed and verified, and the stress distribution on the distal tibia articular surface was measured and analyzed in three models (neutral, dorsiflexed, and plantarflexed model). Based on the fracture map and stress distribution, a five-column classification system for Pilon fractures was proposed, and the intraobserver and interobserver reliability was calculated using Cohen and Fleiss k statistics.

RESULT: The fracture line on the distal tibia articular surface showed a V-shaped distribution. One branch extended from the junction of the medial malleolar articular surface and the inferior tibial articular surface toward the medial malleolus. The other branch extended from the middle of the fibular notch to the posterior part of the medial ankle, toward the tibial shaft. The fibula fracture line mainly extended from the anterior and lower part of the lateral malleolus to the posterior and upper part. As evidenced by the neutral, dorsiflexed, and plantar flexion models, the stress on the posterolateral articular surface (posterolateral column) was low, while the majority of the stress was concentrated in the center. Three-column fractures were the most common, followed by two-column fractures. Using the five-column classification, the K-weighted values of interobserver and intraobserver analysis were 0.653 (p < 0.001) and 0.708 (p < 0.001), respectively.

CONCLUSIONS: In this study, the fracture line and morphological characteristics of Pilon fractures were analyzed in detail by three-dimensional mapping. In addition, this study conducted a finite element analysis of the stress distribution on the distal tibial joint surface of the normal ankle joint. Moreover, a novel classification system was proposed to reflect these findings. The new classification not only exhibits greater consistency, facilitating accurate communication of fracture characteristics among surgeons, but also aids in understanding the mechanisms of injury and formulating surgical strategies.

PMID:39579007 | DOI:10.1111/os.14304

Ophthalmic Physiol Opt. 2024 Nov 23. doi: 10.1111/opo.13393. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Associations between the occurrence of early age related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported, based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, we designed an omics-type approach for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole.

METHODS: A nested case-control study was designed with 200 early AMD cases and 200 healthy controls. For each participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At every position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first-order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for each descriptor at every graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini-Yekutieli procedure.

RESULTS: In terms of the amount and disparity of true discoveries, overall non-equivalence was found for early AMD and healthy groups. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise.

CONCLUSIONS: Between the retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoon and speckle bear essential parts of the total information. We pursued a constructive, completely documented, traceable and repeatable approach without invoking artificial intelligence methods.

PMID:39579005 | DOI:10.1111/opo.13393

Ophthalmic Physiol Opt. 2024 Nov 23. doi: 10.1111/opo.13392. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Associations between the occurrence of early age-related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, an omics-type approach was designed for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole.

METHODS: A nested case-control study was designed with 200 early AMD cases and 200 healthy controls. For every participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At each position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first-order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for every descriptor at each graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini-Yekutieli procedure.

RESULTS: In terms of the amount and disparity of true discoveries, overall non-equivalence of early AMD and healthy groups was found. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise.

CONCLUSIONS: Between retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within the OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but also the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoons and speckle bear essential parts of total information. A constructive, completely documented, traceable and repeatable approach was pursued without invoking artificial intelligence methods.

PMID:39579003 | DOI:10.1111/opo.13392

Biometrics. 2024 Oct 3;80(4):ujae138. doi: 10.1093/biomtc/ujae138.

ABSTRACT

With the advent of massive survival data with a cure fraction, large-scale regression for analyzing the effects of risk factors on a general population has become an emerging challenge. This article proposes a new probability-weighted method for estimation and inference for semiparametric cure regression models. We develop a flexible formulation of the mixture cure model consisting of the model-free incidence and the latency assumed by the semiparametric proportional hazards model. The susceptible probability assesses the concordance between the observations and the latency. With the susceptible probability as weight, we propose a weighted estimating equation method in a small-scale setting. Robust nonparametric estimation of the weight permits stable implementation of the estimation of regression parameters. A recursive probability-weighted estimation method based on data blocks with smaller sizes is further proposed, which achieves computational and memory efficiency in a large-scale or online setting. Asymptotic properties of the proposed estimators are established. We conduct simulation studies and a real data application to demonstrate the empirical performance of the proposed method.

PMID:39578979 | DOI:10.1093/biomtc/ujae138

Biometrics. 2024 Oct 3;80(4):ujae134. doi: 10.1093/biomtc/ujae134.

ABSTRACT

The development of sensors is opening new avenues in several fields of activity. Concerning agricultural crops, complex combinations of agri-environmental dynamics, such as soil and climate variables, are now commonly recorded. These new kinds of measurements are an opportunity to improve knowledge of the drivers of crop yield and crop quality at harvest. This involves renewing statistical approaches to account for the combined variations of these dynamic variables, here considered as temporal variables. The objective of the paper is to estimate an interpretable model to study the influence of the two combined inputs on a scalar output. A Sparse and Structured Procedure is proposed to Identify Combined Effects of Formatted temporal Predictors, hereafter denoted S piceFP. The method is based on the transformation of both temporal variables into categorical variables by defining joint modalities, from which a collection of multiple regression models is then derived. The regressors are the frequencies associated with joint class intervals. The class intervals and related regression coefficients are determined using a generalized fused lasso. S piceFP is a generic and exploratory approach. The simulations we performed show that it is flexible enough to select the non-null or influential modalities of values. A motivating example for grape quality is presented.

PMID:39578978 | DOI:10.1093/biomtc/ujae134

J Endovasc Ther. 2024 Nov 23:15266028241292954. doi: 10.1177/15266028241292954. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal endovascular method to treat infrapopliteal chronic limb-threatening ischemia (CLTI) remains to be determined, given the limitations of stent use in infrapopliteal artery disease. We performed a network meta-analysis (NWM) of randomized controlled trials (RCTs) to simultaneously compare the outcomes of different balloon angioplasty procedures for infrapopliteal artery lesions in CLTI patients.

METHODS: We searched the Cochrane Central Register of Controlled Trials, Embase, and PubMed. 8 eligible RCTs involving 3 endovascular modalities or combinations (plain old balloon angioplasty [POBA], drug-coated balloon [DCB], orbital atherectomy plus plain old balloon angioplasty [OA+POBA]) were included. Primary outcomes were efficacy (12-month clinically driven target lesion revascularization [CDTLR]) and safety (12-month major amputation and all-cause mortality). We used random-effects models based on the frequentist framework.

RESULTS: Plain old balloon angioplasty had a higher 12-month CDTLR rate than DCB (relative risk [RR]: 2.11, confidence interval [CI]: 1.33, 3.34) in the NWM and this result was still statistically significant (RR: 0.47, CI: 0.30, 0.75) in subgroup analyses. According to the SUCRA value, in terms of 12-month CDTLR, OA+POBA was considered the best treatment (SUCRA=72.2), while POBA was considered the worst treatment (SUCRA=8.9). In terms of 12-month all-cause mortality, OA+POBA was considered the best treatment (SUCRA=95.0), while DCB was considered the worst treatment (SUCRA=12.8). In terms of 12-month major amputation, POBA was considered the best treatment (SUCRA=72.0), while DCB was considered the worst treatment (SUCRA=23.0).

CONCLUSIONS: In infrapopliteal CLTI disease, DCB showed a significantly lower 12-month CDTLR in comparison to POBA. There is no statistically significant evidence to suggest that DCB raises safety concerns. The SUCRA values of OA+POBA indicate that it might offer a superior treatment option compared to DCB or POBA in terms of CDTLR and mortality. This advantage, however, was not sustained when major-amputation rates were analyzed. Consequently, further RCTs are required to examine the potential benefits of OA and other forms of atherectomy for managing infrapopliteal CLTI disease.

CLINICAL IMPACT: The findings of this study provide further evidence for the safety of DCB in the application of infrapopliteal CLTI disease and suggest preliminary benefits of atherectomy. These results are likely to encourage further research and application of these treatment modalities in managing infrapopliteal CLTI.POBA has been a traditional approach for treating infrapopliteal artery disease. The current evidence supports clinicians in exploring and utilizing DCB and atherectomy as better treatments.We focused on the performance of different balloon angioplasty procedures in infrapopliteal CLTI, considering the characteristics of infrapopliteal CLTI.

PMID:39578965 | DOI:10.1177/15266028241292954

Health Inf Manag. 2024 Nov 23:18333583241295717. doi: 10.1177/18333583241295717. Online ahead of print.

ABSTRACT

BACKGROUND: The transition of systems to the International Statistical Classification of Diseases 11th Version (ICD-11) allows access to comprehensive data that accurately portray the complexity of morbidity and mortality data in Malaysia.

OBJECTIVE: To demonstrate Malaysia’s experience in implementing ICD-11, from data collection to downstream data use applications.

METHOD AND IMPLEMENTATION: We describe improvements to existing data source systems and downstream data applications. For non-HIS and HIS (ICD-10) systems, data were manually entered into the health management information system equipped with ICD-11 or automatically mapped from ICD-10 to ICD-11. Following these system improvements, we collected and reported ICD-11 data from all hospitals nationwide, regardless of the individual systems’ status in ICD-11 use.

DISCUSSION: Lessons learnt related to legacy systems; ICD-11 releases and system updates; mapping; reporting; human resources and related applications.

CONCLUSION: With careful planning, standardisation of the collection and use of ICD-11 data can be accomplished with limited resources and in a complex environment with heterogeneous systems.

IMPLICATIONS: Use of ICD-11 data in downstream data applications improves data quality to answer specific business or research questions.

PMID:39578964 | DOI:10.1177/18333583241295717

J Cachexia Sarcopenia Muscle. 2024 Nov 23. doi: 10.1002/jcsm.13643. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) require complex management strategies. This study evaluated the prognostic significance of the perichemotherapy skeletal muscle index (SMI) and carbohydrate antigen 19-9 (CA 19-9) in patients with BRPC or LAPC treated with FOLFIRINOX.

METHODS: We retrospectively evaluated 227 patients with BR or LAPC who received at least four cycles of chemotherapy between 2015 and 2020. We analysed chemotherapy response, changes in SMI (ΔSMI, %) on computed tomography (CT) and CA19-9 to determine their impact on progression-free survival (PFS) and overall survival (OS). After the early application of loco-regional treatments (LRT) within 3 months after completing four cycles of chemotherapy, the outcomes were compared between ΔSMI and CA19-9 subgroups.

RESULTS: Among 227 patients (median age, 60 years; 124 [54.6%] male) with 97 BR and 130 LAPC, 50.7% showed partial response (PR) to chemotherapy, 44.5% showed stable disease and 4.8% showed progressive disease (PD). Post-chemotherapy CA19-9 levels were normalized in 41.0% of patients. The high and low ΔSMI groups (based on the gender-specific cut-off of -8.6% for males and -2.9% for females) comprised 114 (50.2%) and 113 (49.8%) patients, respectively. The high ΔSMI group had poorer survival rates than the low ΔSMI group in both PFS (HR = 1.32, p = 0.05) and OS (HR = 1.74, p = 0.001). Multivariable analysis showed that ΔSMI (high vs. low; PFS, HR = 1.39, p = 0.03; OS, HR = 1.82, p < 0.001) and post-chemotherapy response (PD vs. PR/SD; PFS, HR = 18.69, p < 0.001; OS, HR = 6.19, p < 0.001) were independently associated with both PFS and OS. Additionally, the post-chemotherapy CA19-9 (≥ 37 vs. < 37; HR = 1.48, p = 0.01) was an independent predictor for PFS. Early application of LRT after chemotherapy significantly improved PFS and OS in both ΔSMI groups (all p < 0.05). However, it was not beneficial in the group with high ΔSMI and post-chemotherapy CA19-9 ≥ 37 (PFS, p = 0.39 and OS, p = 0.33).

CONCLUSIONS: Progressive sarcopenic deterioration after four cycles of chemotherapy was associated with poor survival outcomes in patients with BR or LAPC after FOLFIRINOX. We also investigated the optimal clinical setting for the early application LRTs using the ΔSMI and post-chemotherapy CA 19-9.

PMID:39578950 | DOI:10.1002/jcsm.13643

Iran J Immunol. 2024 Nov 23;21(4). doi: 10.22034/iji.2024.103549.2846. Online ahead of print.

ABSTRACT

BACKGROUND: Gamma-delta (γδ) T cells are a distinct subset of T cells with a receptor composed of γ and δ chains. Their ability to directly recognize stress-induced molecules and non-peptide antigens expressed by cancer cells, along with their capacity to produce cytokines and interact with other immune cells, makes them potentially significant contributors to immune-based treatments.

OBJECTIVE: To investigate the presence and frequency of Tγδ cells in tumor-draining lymph nodes of patients with bladder cancer (BC), and to assess their association with prognostic parameters.

METHODS: Forty-nine fresh tumor-draining lymph nodes from untreated patients with BC were minced to obtain single cells. The cells were surface-stained with anti-CD3, anti-TCRγδ, and anti-HLA-DR antibodies, then acquired on a four-color FACSCalibur flow cytometer, and analyzed by FlowJo software.

RESULTS: On average, 2.07% ± 1.99% of CD3+ lymphocytes in regional nodes of BC exhibited a γδ T phenotype. A considerable percentage of these cells (37.90% ± 24.42%) expressed HLA-DR. Statistical analysis revealed that while the frequency of γδ T cells showed no variation among patients with different prognoses, the HLA-DR+ subset was higher in T4 patients than in T2 patients (p=0.031). These cells also tended to be increased in stage III compared to stage II (p=0.077).

CONCLUSION: The data collectively indicated an association of HLA-DR expressing γδ T cells with prognostic factors related to tumor progression (higher T-group and stage), suggesting their potential involvement in disease progression. However, future research, including longitudinal studies with larger cohorts, needs to validate these findings and elucidate the functional roles of γδ T cells in the immune response against BC.

PMID:39578946 | DOI:10.22034/iji.2024.103549.2846

Clin Oral Implants Res. 2024 Nov 23. doi: 10.1111/clr.14384. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the accuracy of CAD-CAM and conventional guides in the static computer-assisted implant surgery (sCAIS) placement of distal free-end implants.

MATERIAL AND METHODS: A prospective, controlled, and blinded quasi-experimental study was done involving 27 patients (76 implants) distributed into two groups according to the surgical guide manufacturing approach used: conventional (control group [CG]) or CAD-CAM (test group [TG]). The implants were planned in the software and the surgical guides were manufactured. Fully guided implant placement was carried out and the deviations were measured along with secondary variables as potential confounding factors. Descriptive analyses were performed on mean, standard deviation (SD), and interquartile range (IQR). In the comparative/inferential analysis hypothesis, contrasts were made of the quantitative and qualitative variables and multiple linear models were generated to adjust for the different confounding variables recorded.

RESULTS: Coronal horizontal deviation (CHD) was significantly greater in CG (1.52 mm) versus TG (1.04 mm) (p = 0.004). Apical horizontal deviation (AHD) in turn was 1.67 versus 1.46 mm, respectively; angular deviation was 2.87 versus 3.64; and vertical deviation was -0.1 versus -0.05 mm, with no significant differences between the groups (p > 0.05). A greater sleeve height, positioning in premolars versus molars, and the use of shorter implants, were associated with greater accuracy in relation to CHD and/or AHD (p < 0.05). The implant success rate at 1 year was 92.1%, 90.7% in TG, and 100% in CG, being statistically significant (p = 0.026) at the implant level, but not significant at the patient level.

CONCLUSIONS: The CAD-CAM surgical guides proved to be more accurate than the conventional guides in the sCAIS placement of distal free-end implants, with statistically significant differences being observed in terms of CHD. All implant failures occurred in TG (6 implants/3 patients).

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06404385.

PMID:39578942 | DOI:10.1111/clr.14384