Nevin Manimala

Ann Biomed Eng. 2023 Nov 9. doi: 10.1007/s10439-023-03394-9. Online ahead of print.

ABSTRACT

As datasets increase in size and complexity, biomechanists have turned to artificial intelligence (AI) to aid their analyses. This paper explores how explainable AI (XAI) can enhance the interpretability of biomechanics data derived from musculoskeletal simulations. We use machine learning to classify the simulated lateral pinch data as belonging to models with healthy or one of two types of surgically altered wrists. This simulation-based classification task is analogous to using biomechanical movement and force data to clinically diagnose a pathological state. The XAI describes which musculoskeletal features best explain the classifications and, in turn, the pathological states, at both the local (individual decision) level and global (entire algorithm) level. We demonstrate that these descriptions agree with assessments in the literature and additionally identify the blind spots that can be missed with traditional statistical techniques.

PMID:37943340 | DOI:10.1007/s10439-023-03394-9

Eur J Orthop Surg Traumatol. 2023 Nov 9. doi: 10.1007/s00590-023-03773-x. Online ahead of print.

ABSTRACT

PURPOSE: This study’s objective is to assess the effectiveness of supramalleolar osteotomies (SMOT) in the treatment of asymmetrical ankle osteoarthritis in terms of the improvement in alignment assessed radiographically and its impact on symptoms measured by the American Orthopedic Foot and Ankle Society ankle-hindfoot score (AOFAS ankle-hindfoot score).

METHODS: Twelve patients participated in this prospective observational case series study. Standing anteroposterior, true lateral, and mortise views radiographs were taken. For preoperative planning, the lateral distal tibial angle (LDTA), talar tilt (TT), talocrural angle (TCA), and anterior distal tibial angle (ADTA) were all measured. A medial opening wedge osteotomy mainly was used to treat the varus arthritis ankle. A further oblique fibular osteotomy is frequently necessary.

RESULTS: The male-to-female ratio was 3:1, and the mean age of the patients was 26.25 ± 13.032 years. There were highly statistically significant differences between pre-and post-operative AOFAS ankle-hindfoot score (p < 0.001). Statistically significant differences concerning ankle range of motion (p = 0.002, < 0.001) of dorsiflexion and planter flexion were detected. Comparison between pre-and post-operative patients’ radiology characteristics shows statistically significant differences concerning TT (p = 0.016) and LDTA (p = 0.046).

CONCLUSION: SMOT is very effective in the treatment of post-traumatic ankle osteoarthritis and postpones ankle fusion or total ankle replacements. This surgery significantly improves functional and radiological outcomes as well as the range of motion in the ankle. Meticulous preoperative planning by radiological measurements of different angles around the ankle is considered the crucial factor in success of that operation.

PMID:37943337 | DOI:10.1007/s00590-023-03773-x

JNCI Cancer Spectr. 2023 Oct 31;7(6):pkad049. doi: 10.1093/jncics/pkad049.

ABSTRACT

BACKGROUND: Patients with cancer experience significant symptom burden. We investigated symptom severity in adolescents and young adults (18- to 39-year-olds) during the year following a cancer diagnosis and made comparisons with older adult (those older than 40 years of age) patients with cancer.

METHODS: All Albertan residents diagnosed with a first primary neoplasm at 18 years of age or older between April 1, 2018, and December 31, 2019, and who completed at least 1 electronic patient-reported outcome questionnaire were included. Symptom severity was assessed using the Edmonton Symptom Assessment System-revised. Descriptive statistics, multivariable logistic modeling, and mixed logistic regression modeling were used to describe symptom severity, identify risk factors, and assess symptom trajectories, respectively.

RESULTS: In total, 473 and 322 adolescents and young adults completed a patient-reported outcomes questionnaire at diagnosis and 1 year after diagnosis, respectively. Adolescent and young adult patients with cancer reported high levels of tiredness, poor well-being, and anxiety. Important risk factors included metastatic disease, female sex, treatment types received, and age at diagnosis. Symptom severity varied by clinical tumor group, with those diagnosed with sarcoma having the worst scores for all symptoms at diagnosis and patients with intrathoracic or endocrine tumors having the worst scores for all symptoms at 1 year after diagnosis. Statistically significant differences in symptom severity over the 1-year period were observed between adolescents and young adults and older adults-specifically, the odds of having moderate to severe symptoms were statistically significantly greater among adolescents and young adults with respect to pain, tiredness, nausea, depression, anxiety, and poor well-being (all P < .01).

CONCLUSIONS: A substantial proportion of adolescents and young adults experience moderate to severe symptoms during the year following diagnosis. Modifying existing supportive services and developing interventions based on the needs of adolescent and young adult patients with cancer could aid symptom control.

PMID:37943323 | DOI:10.1093/jncics/pkad049

Eur J Gastroenterol Hepatol. 2023 Dec 1;35(12):1349-1353. doi: 10.1097/MEG.0000000000002657. Epub 2023 Oct 6.

ABSTRACT

BACKGROUND AND AIMS: Epidemiologic evidence suggests that Hodgkin lymphoma (HL) and multiple sclerosis (MS) share a common set of risk factors with Crohn’s disease (CD) and ulcerative colitis (UC). It was hypothesized that such shared risk factors would lead to clustering of the 4 diagnoses in the same patients.

METHODS: All patients with HL, MS, CD, or UC were identified in the veterans population from 2016-2020 and the Medicare population from 1986 to 1989. In a case-control study, the observed concurrences amongst these 4 diagnoses were compared with their expected frequencies in the overall veterans or Medicare population during the same time period by calculating odds ratios (OR) with their 95% confidence intervals (CI).

RESULTS: The study included 6 million veterans and 35 million Medicare patients. In the veterans population, inflammatory bowel disease (IBD) was significantly associated with a concurrent diagnosis of HL (OR: 1.40, 95% CI: 1.15-1.71) and MS (1.34, 1.19-1.50). In the Medicare population, IBD was also significantly associated with HL (1.84, 1.07-3.17) and MS (2.31, 1.59-3.35). Similar trends were observed in CD or UC when analyzed separately in both datasets. In the veterans population, adjustment for the potentially confounding influence of ethnicity, sex, and age left all OR values largely unaffected and statistically significant.

CONCLUSION: The concurrence of IBD with HL or MS could reflect on a common pathway in the etiology or pathogenesis of these 4 diseases.

PMID:37942756 | DOI:10.1097/MEG.0000000000002657

Am J Mens Health. 2023 Nov-Dec;17(6):15579883231204120. doi: 10.1177/15579883231204120.

ABSTRACT

Incarceration can lead to different risk behaviors often due to increased distress and disruption of social networks. It is not well known, however, how these associations may differ by age. In this study, we measure age differences in longitudinal associations between incarceration and substance use, sex risk, and sexually transmitted infection (STI) among Black sexual minority men and Black transgender women (BSMM/BTW). We recruited BSMM/BTW from 2009 to 2011 that were part of the HIV Prevention Trials Network 061 study. We compared those less than 30 years old (n = 375) to those 30 years old or greater (n = 794) examining substance use, sex risk, and STI infection stratified by age. Logistic regression with inverse probability weighting was used for the statistical analysis. Approximately 59% of the sample reported incarceration history. In adjusted analysis, incarceration was more strongly associated with alcohol use and stimulant use among older individuals as was sexual risk behaviors including buying and selling sex. Concurrent partnerships were associated with the younger age groups. STI incidence was associated with younger individuals while associations with HIV infection were similar for the two age groups. Understanding differences in substance use and STI risk among age cohorts is imperative to the design and implementation of re-entry programs. Younger BSMM/BTW participating in re-entry support programs may benefit in particular from HIV/STI prevention and care efforts, while post-release substance abuse treatment and harm reduction programs should target older individuals with continued substance abuse.

PMID:37942721 | DOI:10.1177/15579883231204120

Demography. 2023 Nov 9:11054960. doi: 10.1215/00703370-11054960. Online ahead of print.

ABSTRACT

This research note reinvestigates Abdellaoui et al.’s (2019) findings that genetically selective migration may lead to persistent and accumulating socioeconomic and health inequalities between types (coal mining or non-coal mining) of places in the United Kingdom. Their migration measure classified migrants who moved to the same type of place (coal mining to coal mining or non-coal mining to non-coal mining) into “stay” categories, preventing them from distinguishing migrants from nonmigrants. We reinvestigate the question of genetically selective migration by examining migration patterns between places rather than place types and find genetic selectivity in whether people migrate and where. For example, we find evidence of positive selection: people with genetic variants correlated with better education moved from non-coal mining to coal mining places with our measure of migration. Such findings were obscured in earlier work that could not distinguish nonmigrants from migrants.

PMID:37942709 | DOI:10.1215/00703370-11054960

Prostate. 2023 Nov 9. doi: 10.1002/pros.24648. Online ahead of print.

ABSTRACT

BACKGROUND: Neuropilin 2 (NRP2) expression in tissue is an independent prognostic factor for aggressive prostate cancer. Since the NRP2 pathway activation is thought to occur in part through secondary resistance, quantification of NRP2 in initial tissue biopsy specimens collected at diagnosis may have limited utility in identifying patients at highest risk for morbidity and mortality. Given that metastatic tissue is only occasionally obtained for analysis, there is a need for development of a plasma biomarker indicative of NRP2 pathway activation to potentially inform prostate cancer prognosis. Therefore, we investigated if plasma levels of NRP2 or vascular endothelial growth factor C (VEGF-C), a known soluble ligand of NRP2, are prognostic for prostate cancer. We hypothesized that plasma NRP2 and VEGF-C would be associated with more advanced disease or relapsed disease.

METHODS: NRP2 and VEGF-C levels were quantified by enzyme-linked immunoassay in plasma samples obtained from 145 prostate cancer patients in an opportunistic biobank. These patients were either (1) newly diagnosed (N = 28), (2) in remission (N = 56), or (3) relapsed disease (N = 61). Plasma samples from 15 adult males without known malignancy served as a comparator cohort. Statistical analysis was performed to investigate the association of plasma NRP2/VEGF-C with patient outcomes, adjusting for age, race, prostate-specific antigen (PSA), Gleason score, and tumor stage at diagnosis.

RESULTS: Neither NRP2 nor VEGF-C levels were significantly different in cancer patients compared to noncancer controls. We observed no clear association between plasma NRP2 and disease severity. Increased plasma VEGF-C was significantly associated with disease remission and correlated with Stage I/II and intermediate-risk Gleason score. Neither NRP2 nor VEGF-C correlated with PSA level.

CONCLUSIONS: Although tissue NRP2 expression correlates with severe disease, this was not observed for plasma NRP2. Plasma NRP2 levels did not correlate with disease severity or relapse. VEGF-C was highest in patients in remission and with less severe disease. Future investigation is needed to identify noninvasive methods to assess tumor NRP2 status.

PMID:37942701 | DOI:10.1002/pros.24648

J Neuroimaging. 2023 Nov 9. doi: 10.1111/jon.13170. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Thalamic hypometabolism is a consistent finding in brain PET with F-18 fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). However, the pathophysiology of this metabolic alteration is unknown. We hypothesized that it might be secondary to disturbance of peripheral input to the thalamus by NF1-characteristic peripheral nerve sheath tumors (PNSTs). To test this hypothesis, we investigated the relationship between thalamic FDG uptake and the number, volume, and localization of PNSTs.

METHODS: This retrospective study included 22 adult NF1 patients (41% women, 36.2 ± 13.0 years) referred to whole-body FDG-PET/contrast-enhanced CT for suspected malignant transformation of PNSTs and 22 sex- and age-matched controls. Brain FDG uptake was scaled voxelwise to the individual median uptake in cerebellar gray matter. Bilateral mean and left-right asymmetry of thalamic FDG uptake were determined using a left-right symmetric anatomical thalamus mask. PNSTs were manually segmented in contrast-enhanced CT.

RESULTS: Thalamic FDG uptake was reduced in NF1 patients by 2.0 standard deviations (p < .0005) compared to controls. Left-right asymmetry was increased by 1.3 standard deviations (p = .013). Thalamic hypometabolism was higher in NF1 patients with ≥3 PNSTs than in patients with ≤2 PNSTs (2.6 vs. 1.6 standard deviations, p = .032). The impact of the occurrence of paraspinal/paravertebral PNSTs and of the mean PNST volume on thalamic FDG uptake did not reach statistical significance (p = .098 and p = .189). Left-right asymmetry of thalamic FDG uptake was not associated with left-right asymmetry of PNST burden (p = .658).

CONCLUSIONS: This study provides first evidence of left-right asymmetry of thalamic hypometabolism in NF1 and that it might be mediated by NF1-associated peripheral tumors.

PMID:37942683 | DOI:10.1111/jon.13170

Pediatr Transplant. 2023 Nov 9:e14638. doi: 10.1111/petr.14638. Online ahead of print.

ABSTRACT

BACKGROUND: The study purpose was to add to limited literature assessing anti-HLA donor-specific antibody (DSA) appearance, clearance, specificity, and impact in intestinal/multivisceral (MV) transplant as well as the value of serial monitoring following an institutional protocol shift implementing serial monitoring.

METHODS: This single-center retrospective review included intestinal/MV recipients transplanted 1/1/15-9/31/17 with completed DSA testing. Patients were divided into groups based on DSA presence post-transplant. The primary outcome was biopsy-proven acute rejection (BPAR). Secondary outcomes included graft loss and death. Descriptive analysis of DSA was completed.

RESULTS: Of the 35 intestinal/MV recipients (60% pediatric) with DSA testing, 24 patients had post-transplant DSA. Fifteen patients in the DSA(+) group had T-cell-mediated BPAR versus five in the DSA(-) group (63% vs 45%, p = .47). Days to BPAR were 25 [IQR 19-165] (DSA(+) group) versus 232 [IQR 25.5-632.5] (DSA(-) group) (p = .066). There were no differences between groups for graft loss or death. One hundred and five DSA were identified in the DSA(+) group with 63% being class II, and 54% cleared during follow-up. DSA were directed against 50 different HLA alleles, with the most common being directed against HLA- DQ (35%). Time to first DSA and to clearance did not differ between class I and II.

CONCLUSION: Findings confirm previous data that suggest post-transplant DSA in this population may lead to increased BPAR or shorter time to BPAR, although not statistically significant. Most DSA were identified within the first month after transplant, and ahead of rejection identification on biopsy. DSA therefore may have utility as an early rejection biomarker and use may be considered in place of early protocol biopsies, particularly in pediatric patients. We identified novel findings of DSA directed against a large breadth of HLA in intestinal/MV patients.

PMID:37942670 | DOI:10.1111/petr.14638

Expert Rev Med Devices. 2023 Nov 9. doi: 10.1080/17434440.2023.2280685. Online ahead of print.

ABSTRACT

AIM: To evaluate the relevance of Incidental prostate [¹⁸F]FDG uptake (IPU) and to explore the potential of radiomics and machine learning (ML) to predict prostate cancer (PCa).

METHODS: We retrieved [¹⁸F]FDG PET/CT scans with evidence of IPU performed in 2 institutions between 2015-2021. Patients were divided in PCa and non-PCa, according to biopsy. Clinical and PET/CT derived information (comprehensive of radiomic analysis) were acquired. 5 ML models were developed and their performance in discriminating PCa vs non-PCa IPU was evaluated. Radiomic analysis was investigated to predict ISUP Grade.

RESULTS: Overall 56 IPU were identified and 31 patients performed prostate biopsy. Eighteen of those were diagnosed as PCa. Only PSA and radiomic features (8 from CT and 9 from PET images, respectively) showed statistically significant difference between PCa/non-PCa patients. Eight features resulted robust between the two institutions. CT-based ML models showed a good performance, especially in terms of negative predictive value (NPV 0.733-0.867). PET-derived ML models resulted less accurate except the Random Forest model (NPV = 0.933). Radiomics could not accurately predict ISUP grade.

CONCLUSIONS: Paired with PSA, radiomic analysis seems to be promising to discriminate PCa/non-PCa IPU. ML could be a useful tool to identify non-PCa IPU, avoiding further investigations.

PMID:37942630 | DOI:10.1080/17434440.2023.2280685