Prediction of Obliteration After the Gamma Knife Radiosurgery of Arteriovenous Malformations Using Hand-Crafted Radiomics and Deep-Learning Methods.

INTRODUCTION: Brain arteriovenous malformations (bAVMs) are vascular abnormalities that can be treated with embolization or radiotherapy to prevent the risk of future rupture. In this study, we use hand-crafted radiomics and deep learning techniques to predict favorable vs. unfavorable outcomes following Gamma Knife radiosurgery (GKRS) of bAVMs and compare their prediction performances. METHODS: One hundred twenty-six patients seen at one academic medical center for GKRS obliteration of bAVMs over 15 years were retrospectively reviewed. Forty-two patients met the inclusion criteria. Favorable outcomes were defined as complete nidus obliteration demonstrated on cerebral angiogram and asymptomatic recovery. Unfavorable outcomes were defined as incomplete obliteration or complications relating to the AVM that developed after GKRS. Outcome predictions were made using a random forest model with hand-crafted radiomic features and a fine-tuned ResNet-34 convolutional neural network (CNN) model. The performance was evaluated by using a ten-fold cross-validation technique. RESULTS: The average accuracy and area-under-curve (AUC) values of the Random Forest Classifier (RFC) with radiomics features were 68.5 ±9.80% and 0.705 ±0.086, whereas those of the ResNet-34 model were 60.0 ±11.9% and 0.694 ±0.124. Four radiomics features used with RFC discriminated unfavorable response cases from favorable response cases with statistical significance. When cropped images were used with ResNet-34, the accuracy and AUC decreased to 59.3 ± 14.2% and 55.4 ±10.4%, respectively. CONCLUSIONS: A hand-crafted radiomics model and a pre-trained CNN model can be fine-tuned on pre-treatment MRI scans to predict clinical outcomes of AVM patients undergoing GKRS with equivalent prediction performance. The outcome predictions are promising but require further external validation on more patients.

Decreased Posterior Tibial Slope and Its Association With Pediatric Posterior Cruciate Ligament Injury.

BACKGROUND: Recent adult studies have demonstrated that decreased posterior tibial slope angle (PTSA) may be a risk factor for posterior cruciate ligament (PCL) injury. However, there is no study investigating this phenomenon in a pediatric population. Understanding risk factors for PCL injuries among a pediatric population is important given the recent rise in athletic competition/specialization and sports-related injuries. HYPOTHESIS/PURPOSE: The purpose of this study was to compare PTSA between pediatric patients sustaining a primary PCL tear compared with age- and sex-matched controls. It was hypothesized that pediatric patients sustaining a PCL tear would have a decreased PTSA compared with controls, with decreased PTSA being associated with higher odds of PCL injury. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of all patients sustaining a PCL injury between 2006 and 2021 at a level 1 pediatric trauma center were reviewed. Patients aged ≤18 years with magnetic resonance imaging-confirmed PCL tear were included. Excluded were patients with concomitant anterior cruciate ligament tears, previous PCL reconstruction, or previous coronal plane realignment. A control cohort, with their ligament shown as intact on magnetic resonance imaging scans, was matched based on age and sex. PTSA was measured on lateral radiographs of the injured knee or tibia. The mean PTSA was compared between cohorts, and odds ratios were calculated based on the normal slope range (7°-10°) described in the literature, an upper range (>10°), and a lower range (<7°). Inter- and intrarater reliability were determined via calculation of an intraclass correlation coefficient. RESULTS: Of the 98 patients who sustained a PCL injury in this study period, 59 (60%) met inclusion criteria, and 59 healthy knee controls were matched. There were no differences between the cohorts for age (P = .90), sex (P > .99), or body mass index (P = .74). The PCL cohort had a lower mean ± SD PTSA compared with the control group (5.9°± 2.7° vs 7.3°± 4.3°; P = .03). PTSA <7° was associated with a 2.8 (95% CI, 1.3-6.0; P = .01) times risk of PCL tear. Conversely, PTSA >10° was associated with a 0.27 (95% CI, 0.09-0.81; P = .02) times risk of PCL tear. These PTSA measurements demonstrated acceptable intrarater and interrater reliability. CONCLUSION: PTSA <7° was associated with an increased odds of PCL injury, whereas a slope >10° was associated with a decreased odds of PCL injury in a pediatric population. These findings corroborate similar outcomes in adult studies; however, further studies are needed to elucidate PTSA as a risk factor for PCL injury.

DOTATATE PET/MR Imaging Differentiates Secondary-Progressive from de Novo World Health Organization Grade 3 Meningiomas.

BACKGROUND AND PURPOSE: WHO grade 3 meningiomas are rare and poorly understood and have a higher propensity for recurrence, metastasis, and worsened clinical outcomes compared with lower-grade meningiomas. The purpose of our study was to prospectively evaluate the molecular profile, PET characteristics, and outcomes of patients with World Health Organization grade 3 meningiomas who were imaged with gallium 68 (68Ga) DOTATATE PET/MR imaging. MATERIALS AND METHODS: Patients with World Health Organization grade 3 meningiomas enrolled in our prospective observational cohort evaluating the utility of (68Ga) DOTATATE PET/MR imaging in somatostatin receptor positive brain tumors were included. We stratified patients by de novo-versus-secondary-progressive status and evaluated the differences in the PET standard uptake value, molecular profiles, and clinical outcomes. RESULTS: Patients met the inclusion criteria (secondary-progressive: 7/14; de novo: 7/14). The secondary-progressive cohort had a significantly higher per-patient number of surgeries (4.1 versus 1.6; P = .011) and trended toward a higher number of radiation therapy courses (2.4 versus 1.6; P = .23) and cumulative radiation therapy doses (106Gy versus 68.3Gy; P = .31). The secondary-progressive cohort had a significantly lower progression-free survival compared with the de novo cohort (4.8 versus 37.7 months; P = .004). Secondary-progressive tumors had distinct molecular pathology profiles with higher numbers of mutations (3.5 versus 1.2; P = .024). Secondary-progressive tumors demonstrated higher PET standard uptake values (17.1 versus 12.4; P = .0021). CONCLUSIONS: Our study confirms prior work illustrating distinct clinical outcomes in secondary-progressive and de novo World Health Organization grade 3 meningiomas. Furthermore, our findings support (68Ga) DOTATATE PET/MR imaging as a useful management strategy in World Health Organization grade 3 meningiomas and provide insight into meningioma biology, as well as clinical management implications.

Cryptosporidium life cycle small molecule probing implicates translational repression and an Apetala 2 transcription factor in macrogamont differentiation.

The apicomplexan parasite Cryptosporidium is a leading cause of childhood diarrhea in developing countries. Current treatment options are inadequate and multiple preclinical compounds are being actively pursued as potential drugs for cryptosporidiosis. Unlike most apicomplexans, Cryptosporidium spp. sequentially replicate asexually and then sexually within a single host to complete their lifecycles. Anti-cryptosporidial compounds are generally identified or tested through in vitro phenotypic assays that only assess the asexual stages. Therefore, compounds that specifically target the sexual stages remain unexplored. In this study, we leveraged the ReFRAME drug repurposing library against a newly devised multi-readout imaging assay to identify small-molecule compounds that modulate macrogamont differentiation and maturation. RNA-seq studies confirmed selective modulation of macrogamont differentiation for 10 identified compounds (9 inhibitors and 1 accelerator). The collective transcriptomic profiles of these compounds indicates that translational repression accompanies Cryptosporidium sexual differentiation, which we validated experimentally. Additionally, cross comparison of the RNA-seq data with promoter sequence analysis for stage-specific genes converged on a key role for an Apetala 2 (AP2) transcription factor (cgd2_3490) in differentiation into macrogamonts. Finally, drug annotation for the ReFRAME hits indicates that an elevated supply of energy equivalence in the host cell is critical for macrogamont formation.

[Ga68] DOTATATE PET/MRI-Guided Radiosurgical Treatment Planning and Response Assessment in Meningiomas.

BACKGROUND: Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. METHODS: Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and PFS was evaluated using Cox regression. RESULTS: 27 patients with 64 tumors (26% WHO-1, 41% WHO-2, 26% WHO-3, 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) (mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (p < 0.0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort. CONCLUSIONS: DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant, however it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery.

Change in Posterior Tibial Slope Angle After Displaced Pediatric Tibial Tubercle Fracture: A Model for Growth Modulation in the ACL-Deficient Knee.

Background: Increased posterior tibial slope angle (PTSA) has been shown to be an important risk factor for anterior cruciate ligament (ACL) injury. PTSA modulation is not utilized routinely to reduce risk of primary rupture or graft failure. Displaced tibial tubercle (TT) fractures in the skeletally immature are associated with potential growth arrest and may be used as a model to study PTSA changes in this setting. Purpose/Hypothesis: To quantify the change in PTSA (ΔPTSA) after operative treatment of displaced TT fractures in skeletally immature patients. It was hypothesized that there would be a progressive decrease in PTSA after TT injury and that rate of ΔPTSA would be highest during peak growth velocity. Study Design: Case series; Level of evidence, 4. Methods: Included were 22 patients (n = 23 knees; mean chronological and bone age at injury, 14 years; 86% male) who underwent surgery for displaced TT fracture. PTSA was measured on lateral radiographs at time of surgery and subsequent follow-up, and bone age at the time of injury was determined using radiographic standards. The rate of ΔPTSA for individual patient, total cohort, and sex-based subgroup trends were determined via linear regression (degrees per month; positive value indicates relatively anterior). Individual patient regression coefficients were averaged into bone age cohorts. Results: Average follow-up was 17 months (range, 6-52 months). The mean PTSA was -12°± 2.4° at the time of injury, and the mean ΔPTSA for the cohort was 0.30°± 0.31° per month (range, -0.27° to 0.97° per month). Linear regression demonstrated a significant relationship between months postfixation and PTSA, demonstrating a ΔPTSA of 0.31° per month (95% confidence interval [CI], 0.24° to 0.38°; P < .001). The highest ΔPTSA was seen at bone age 14 years (mean, 0.58°± 0.44° per month). The mean absolute change in PTSA from injury to final follow-up was 4.1° (range, -3.4° to 21°). Conclusion: Our data suggested that PTSA becomes more anterior after operatively treated pediatric TT fractures and that ΔPTSA may be influenced by bone age. This concept may be useful in considering surgical modulation of excessive PTSA in the pediatric ACL-deficient knee.

Quantification of whole-organ individual and bilateral renal metabolic rate of oxygen.

PURPOSE: Renal metabolic rate of oxygen (rMRO2 ) is a potentially important biomarker of kidney function. The key parameters for rMRO2 quantification include blood flow rate (BFR) and venous oxygen saturation (SvO2 ) in a draining vessel. Previous approaches to quantify renal metabolism have focused on the single organ. Here, both kidneys are considered as one unit to quantify bilateral rMRO2 . A pulse sequence to facilitate bilateral rMRO2 quantification is introduced. METHODS: To quantify bilateral rMRO2 , measurements of BFR and SvO2 are made along the inferior vena cava (IVC) at suprarenal and infrarenal locations. From the continuity equation, these four parameters can be related to derive an expression for bilateral rMRO2 . The recently reported K-MOTIVE pulse sequence was implemented at four locations: left kidney, right kidney, suprarenal IVC, and infrarenal IVC. A dual-band variant of K-MOTIVE (db-K-MOTIVE) was developed by incorporating simultaneous-multi-slice imaging principles. The sequence simultaneously measures BFR and SvO2 at suprarenal and infrarenal locations in a single pass of 21 s, yielding bilateral rMRO2 . RESULTS: SvO2 and BFR are higher in suprarenal versus infrarenal IVC, and the renal veins are highly oxygenated (SvO2 >90%). Bilateral rMRO2 quantified in 10 healthy subjects (8 M, 30 ± 8 y) was found to be 291 ± 247 and 349 ± 300 (µmolO2 /min)/100 g, derived from K-MOTIVE and db-K-MOTIVE, respectively. In comparison, total rMRO2 from combining left and right was 329 ± 273 (µmolO2 /min)/100 g. CONCLUSION: The present work demonstrates that bilateral rMRO2 quantification is feasible with fair reproducibility and physiological plausibility. The indirect method is a promising approach to compute bilateral rMRO2 when individual rMRO2 quantification is difficult.

MRI-based quantification of whole-organ renal metabolic rate of oxygen.

During the early stages of diabetes, kidney oxygen utilization increases. The mismatch between oxygen demand and supply contributes to tissue hypoxia, a key driver of chronic kidney disease. Thus, whole-organ renal metabolic rate of oxygen (rMRO2 ) is a potentially valuable biomarker of kidney function. The key parameters required to determine rMRO2 include the renal blood flow rate (RBF) in the feeding artery and oxygen saturation in the draining renal vein (SvO2 ). However, there is currently no noninvasive method to quantify rMRO2 in absolute physiologic units. Here, a new MRI pulse sequence, Kidney Metabolism of Oxygen via T2 and Interleaved Velocity Encoding (K-MOTIVE), is described, along with evaluation of its performance in the human kidney in vivo. K-MOTIVE interleaves a phase-contrast module before a background-suppressed T2 -prepared balanced steady-state-free-precession (bSSFP) readout to measure RBF and SvO2 in a single breath-hold period of 22 s, yielding rMRO2 via Fick's principle. Variants of K-MOTIVE to evaluate alternative bSSFP readout strategies were studied. Kidney mass was manually determined from multislice gradient recalled echo images. Healthy subjects were recruited to quantify rMRO2 of the left kidney at 3-T field strength (N = 15). Assessments of repeat reproducibility and comparisons with individual measurements of RBF and SvO2 were performed, and the method's sensitivity was evaluated with a high-protein meal challenge (N = 8). K-MOTIVE yielded the following metabolic parameters: T2  = 157 ± 19 ms; SvO2  = 92% ± 6%; RBF = 400 ± 110 mL/min; and rMRO2  = 114 ± 117(µmol O2 /min)/100 g tissue. Reproducibility studies of T2 and RBF (parameters directly measured by K-MOTIVE) resulted in coefficients of variation less than 10% and intraclass correlation coefficients more than 0.75. The high-protein meal elicited an increase in rMRO2 , which was corroborated by serum biomarkers. The K-MOTIVE sequence measures SvO2 and RBF, the parameters necessary to quantify whole-organ rMRO2 , in a single breath-hold. The present work demonstrates that rMRO2 quantification is feasible with good reproducibility. rMRO2 is a potentially valuable physiological biomarker.

Phase-Specific Damage Tolerance of a Eutectic High Entropy Alloy.

Phase-specific damage tolerance was investigated for the AlCoCrFeNi2.1 high entropy alloy with a lamellar microstructure of L12 and B2 phases. A microcantilever bending technique was utilized with notches milled in each of the two phases as well as at the phase boundary. The L12 phase exhibited superior bending strength, strain hardening, and plastic deformation, while the B2 phase showed limited damage tolerance during bending due to micro-crack formation. The dimensionalized stiffness (DS) of the L12 phase cantilevers were relatively constant, indicating strain hardening followed by increase in stiffness at the later stages and, therefore, indicating plastic failure. In contrast, the B2 phase cantilevers showed a continuous drop in stiffness, indicating crack propagation. Distinct differences in micro-scale deformation mechanisms were reflected in post-compression fractography, with L12-phase cantilevers showing typical characteristics of ductile failure, including the activation of multiple slip planes, shear lips at the notch edge, and tearing inside the notch versus quasi-cleavage fracture with cleavage facets and a river pattern on the fracture surface for the B2-phase cantilevers.

Expression of transforming growth factor-ß in oral submucous fibrosis: A systematic review.

Oral submucous fibrosis (OSF) is a potentially malignant disorder characterised by inflammation and progressive fibrosis. Transforming growth factor-ß (TGF-ß) has been established as a master regulator of fibrosis in various organs; however, lack of systematic review on expression of TGF-ß and its isoforms in OSF restrict the understanding of their behaviour in its pathogenesis. Online electronic databases, such as PubMed Medline, Cochrane Library, Embase, and Scopus, were searched from their respective dates of inception till 31st March 2022. Human studies related to TGF-ß expression in histopathologically diagnosed OSF cases, with or without malignant transformation, were included and assessed using a Cochrane risk of bias assessment tool: For non randomised studies of interventions (ACROBAT NRSI). The electronic literature search yielded 394 articles. Of those, ten articles met the inclusion criteria and involved total of 579 OSF patients. The risk of bias (RoB) was low to moderate. These studies demonstrated a significant positive expression of TGF-ß and its isoforms in OSF compared to that in normal tissue samples. An increased pan TGF-ß expression was observed in the early stages of OSF, and an increased expression of TGF-ß1 and TGF-ß2 were seen in advanced stages of OSF. Stage wise expression of TGF-ß3 has not been discussed in the included studies. No significant relationship was observed between epithelial dysplasia and TGF-ß expression in OSF. The distinct pattern in the expression of pan TGF-ß, TGF-ß1 and TGF-ß2 in various stages of OSF indicates their different roles in OSF progression. We believe isoform targeted studies exploring stage wise expression of the marker will open new treatment avenues for OSF.

Long-Term Performance of Epicardial versus Transvenous Left Ventricular Leads for Cardiac Resynchronization Therapy.

Aims: to study the technical performance of epicardial left ventricular (LV) leads placed via video assisted thoracic surgery (VATS), compared to transvenously placed leads for cardiac resynchronization therapy (CRT). Methods: From 2001 until 2013, a total of 644 lead placement procedures were performed for CRT. In the case of unsuccessful transvenous LV lead placement, the patient received an epicardial LV lead. Study groups consist of 578 patients with a transvenous LV lead and 66 with an epicardial LV lead. The primary endpoint was LV-lead failure necessitating a replacement or deactivation. The secondary endpoint was energy consumption. Results: The mean follow up was 5.9 years (epicardial: 5.5 ± 3.1, transvenous: 5.9 ± 3.5). Transvenous leads failed significantly more frequently than epicardial leads with a total of 66 (11%) in the transvenous leads group vs. 2 (3%) in the epicardial lead group (p = 0.037). Lead energy consumption was not significantly different between groups. Conclusions: Epicardial lead placement is feasible, safe and shows excellent long-term performance compared to transvenous leads. Epicardial lead placement should be considered when primary transvenous lead placement fails or as a primary lead placement strategy in challenging cases.

Six-minute, in vivo MRI quantification of proximal femur trabecular bone 3D microstructure.

BACKGROUND: Assessment of proximal femur trabecular bone microstructure in vivo by magnetic resonance imaging has recently been validated for acquiring information independent of bone mineral density in osteoporotic patients. However, the requisite signal-to-noise ratio (SNR) and resolution for interrogation of the trabecular microstructure at this anatomical location prolongs the scan duration and renders the imaging protocol clinically infeasible. Parallel imaging and compressed sensing (PICS) techniques can reduce the scan duration of the imaging protocol without substantially compromising image quality. The present work investigates the limits of acceleration for a commonly used PICS technique, ℓ1-ESPIRiT, for the purpose of quantifying measures of trabecular bone microarchitecture. Based on a desired error tolerance, a six-minute, prospectively accelerated variant of the imaging protocol was developed and assessed for intersession reproducibility and agreement with the longer reference scan. PURPOSE: To investigate the limits of acceleration for MRI-based trabecular bone quantification by parallel imaging and compressed sensing reconstruction, and to develop a prototypical imaging protocol for assessing the proximal femur microstructure in a clinically practical scan time. METHODS: Healthy participants (n = 11) were scanned by a 3D balanced steady-state free precession (bSSFP) sequence satisfying the Nyquist criterion with a scan duration of about 18 min. The raw data were retrospectively undersampled and reconstructed to mimic various acceleration factors ranging from 2 to 6. Trabecular volumes-of-interest in four major femoral regions (greater trochanter, intertrochanteric region, femoral neck, and femoral head) were analyzed and six relevant measures of trabecular bone microarchitecture (bone volume fraction, surface-to-curve ratio, erosion index, elastic modulus, trabecular thickness, plates-to-rods ratio) were obtained for images of all accelerations. To assess agreement, median percent error and intraclass correlation coefficients (ICCs) were computed using the fully-sampled data as reference. Based on this analysis, a prospectively 3-fold accelerated sequence with a duration of about 6 min was developed and the analysis was repeated. RESULTS: A prospective acceleration factor of 3 demonstrated comparable performance in reproducibility and absolute agreement to the fully-sampled scan. The median CoV over all image-derived metrics was generally <6 % and ICCs >0.70. Also, measurements from prospectively 3-fold accelerated scans demonstrated in general median percent errors of <7 % and ICCs >0.70. CONCLUSION: The present work proposes a method to make in vivo quantitative assessment of proximal femur trabecular microstructure with a clinically practical scan duration of about 6 min.

Interplay of Transforming Growth Factor-Beta 1 and 3 in the Pathogenesis of Oral Submucous Fibrosis and Its Malignant Transformation: An Immunohistochemical Study.

Introduction Oral submucous fibrosis (OSF) is a chronic and potentially malignant oral condition that poses a significant public health issue due to its insidious nature. Transforming growth factor-beta (TGF-ß) is a key player in the pathogenesis of OSF and is responsible for fibrosis. This study aims to investigate the relationship between the expression of TGF-ß1 and TGF-ß3 in OSF and its malignant transformation by using immunohistochemistry. Materials and method The present study comprised of 120 formalin-fixed paraffin-embedded tissue samples, which included 20 normal oral mucosa (NOM), 80 OSF (20 each of stage 1- 4), and 20 oral squamous cell carcinoma (OSCC) (10 each of OSCC with and without OSF), and were stained for TGF-ß1 and TGF-ß3 by immunohistochemistry. Data were analyzed using R software version 4.1.2, GraphPad Prism 9.3.1 (GraphPad Software, San Diego, CA, USA) and Excel (Microsoft Corp., Redmond, WA). Results TGF-ß1 immunoexpression was negative in NOM with no significant difference among OSF and OSCC (with or without OSF). TGF-ß3 was significantly higher in OSCC (with or without OSF) than in OSF, and no significant difference was noted between OSF and NOM and between OSCC and NOM. A significant increase was seen in TGF-ß3 compared to TGF-ß1 in NOM, OSF (stage 1- 4), and OSCC with and without OSF. Conclusion TGF-ß3 has higher immunoexpression levels than TGF-ß1 in NOM, OSF, and OSCC. We speculate that quantitative or qualitative TGF- ß3 may be inadequate to prevent or attenuate fibrosis in OSF patients. There is also a modicum of probability that TGF-ß3 has a preventive rather than causative role in OSF pathogenesis. The role of TGF-ß3 in OSF needs further clarification.

Efficacy of anti-desmoglein 1 and anti-desmoglein 3 levels by enzyme-linked immunosorbent assay compared to biopsy of chronic oral ulcerative diseases with positive Nikolsky's sign to diagnose oral pemphigus vulgaris with or without skin involvement: a retrospective institutional observational pilot study.

OBJECTIVE: We assessed the efficacy of anti-desmoglein 1 (anti-DSG1) and anti-DSG3 levels by enzyme-linked immunosorbent assay (ELISA) as a preliminary diagnostic test in the diagnosis of oral pemphigus vulgaris (OPV) with or without skin involvement compared to biopsy. STUDY DESIGN: We retrospectively analyzed data collected from 23 patients (mean age 45.13 years) who had presented with chronic oral ulcerations, desquamative gingivitis, and a positive Nikolsky's sign. We performed ELISA, histopathologic examination, and direct immunofluorescence (DIF) and then calculated the sensitivity and specificity of the results of ELISA, histopathology, DIF, and the presence of a positive Nikolsky's sign in diagnosis. RESULTS: The ELISA results showed that 18 patients had elevated anti-DSG3 levels, of whom 8 also had elevated anti-DSG1 levels. The histopathology results indicated that 18 patients had OPV, of whom 4 had oral lichen planus, and 1 had sub-epithelial blistering disease confirmed to be mucous membrane pemphigoid MMP by DIF. ELISA, histopathology, and DIF had a 100% sensitivity and specificity, and the presence of a positive Nikolsky's sign had a sensitivity and specificity of 100% and 78.26%, respectively. CONCLUSIONS: Measurement of anti-DSG1 and anti-DSG3 levels by ELISA warrants consideration as a first-line diagnostic test for early detection of OPV with or without skin involvement over biopsy.

Allograft Anterior Cruciate Ligament Reconstruction in Adolescent Patients May Result in Acceptable Graft Failure Rate in Nonpivoting Sports Athletes.

BACKGROUND: Studies have demonstrated that pediatric patients have an increased risk of failure with allograft anterior cruciate ligament reconstruction (ACLR); however, there is no study investigating whether allograft ACLR may be safe in older adolescent patients who are not returning to competitive pivoting sports (ie, low risk). The purpose of this study was to assess outcomes for low-risk older adolescents selected for allograft ACLR. METHODS: We performed a retrospective chart review of patients younger than 18 years who received a bone-patellar-tendon-bone allograft or autograft ACLR by a single orthopaedic surgeon from 2012 to 2020. Patients were offered allograft ACLR if they did not intend to return to pivoting sports for 1 year. The autograft cohort was matched 1:1 based on age, sex, and follow-up. Patients were excluded for skeletal immaturity, multiligamentous injury, prior ipsilateral ACLR, or concomitant realignment procedure. Patients were contacted to obtain patient-reported outcomes at ≥2 years follow-up, including single assessment numerical evaluation, surgery satisfaction, pain scores, Tegner Activity Scale, and the Lysholm Knee Scoring Scale. Parametric and nonparametric tests were used as appropriate. RESULTS: Of the 68 allografts, 40 (59%) met inclusion and 28 (70%) were contacted. Among the 456 autografts, 40 (8.7%) were matched and 26 (65%) were contacted. Two allograft patients (2/40; 5%) failed at a median (interquartile range) follow-up of 36 (12, 60) months. There were 0/40 failures in the autograft cohort and 13/456 (2.9%) among the overall autografts; neither were significantly different from the allograft failure rate (both P > 0.05). Two (5.0%) patients in the autograft cohort required manipulation under anesthesia and arthroscopic lysis of adhesions. There were no significant differences between cohorts for single assessment numerical evaluation, Lysholm, Tegner, pain, and satisfaction scores (all P > 0.05). CONCLUSIONS: Although ACL allograft failure rates remain nearly two times higher than autograft failure rates in older adolescents, our study suggests that careful patient selection can potentially bring this failure rate down to an acceptable level. LEVEL OF EVIDENCE: Level III; retrospective matched cohort study.

Cyanotriazoles are selective topoisomerase II poisons that rapidly cure trypanosome infections.

Millions who live in Latin America and sub-Saharan Africa are at risk of trypanosomatid infections, which cause Chagas disease and human African trypanosomiasis (HAT). Improved HAT treatments are available, but Chagas disease therapies rely on two nitroheterocycles, which suffer from lengthy drug regimens and safety concerns that cause frequent treatment discontinuation. We performed phenotypic screening against trypanosomes and identified a class of cyanotriazoles (CTs) with potent trypanocidal activity both in vitro and in mouse models of Chagas disease and HAT. Cryo-electron microscopy approaches confirmed that CT compounds acted through selective, irreversible inhibition of trypanosomal topoisomerase II by stabilizing double-stranded DNA:enzyme cleavage complexes. These findings suggest a potential approach toward successful therapeutics for the treatment of Chagas disease.

Persistent Buccopharyngeal Membrane - A Systematic Review of Case Reports and Case Series.

OBJECTIVE: Persistent buccopharyngeal membrane (PBM) is a rare anomaly associated with failure of ecto-endodermal resorption of the buccopharyngeal membrane on the 26th day of intrauterine life. The current literature has insufficient information about PBM. DESIGN: Systematic Review. PATIENTS, PARTICIPANTS: Online electronic databases such as PubMed-MEDLINE, Embase, and Scopus were searched using appropriate keywords from the earliest available data until 30th August 2022, with no language restriction. Additional sources such as Google Scholar, major journals, gray literature, conference proceedings, and cross-referencing were also explored. MAIN OUTCOME MEASURES: The present systematic review evaluated and analysed the data available on PBM along with its treatment options and clinicopathological findings, prevalence, and prognosis of the patient. RESULTS: Thirty-four publications with 37 reported cases were included in this systematic review. The majority of patients had dyspnea (n = 18), followed by dysphagia (n = 10). Approximately 16 patients suffering from PBM reported orofacial abnormalities. Seventeen patients reported complete PBM, and 18 patients had partial PBM. The treatment modality followed by most patients (n = 15) was surgical excision of the membrane, along with stent placement in four patients. Oropharyngeal reconstruction was performed in four cases. The overall prognosis and survival rate of this rare condition is good. CONCLUSION: This review suggests that PBM is poorly understood, and the diagnosis of partial PBM is confirmed only when the patient complains of difficulty in breathing or eating. In-depth analysis and follow-up of the reported cases should be performed to diagnose the disease early so that clinicians can provide adequate treatment to the patients.

A Comparative Clinicopathological Study of Giant Cell Tumour (GCT), Central Giant Cell Granuloma (CGCG) and Peripheral Giant Cell Granuloma (PGCG).

Objective: To evaluate and compare the clinicopathological features of giant cell tumour (GCT), central giant cell granuloma (CGCG) and peripheral giant cell granuloma (PGCG). Material and methods: From 2006 to 2016, all histopathologically diagnosed cases of GCT were retrieved from the Department of Pathology, T.N.M.C, Mumbai and CGCG and PGCG were retrieved from the Department of Oral Pathology, Nair Hospital Dental College, Mumbai. Statistical analysis of the clinicopathological features was done using SPSS v 21.0, IBM. Intergroup comparison of all variables was done using t test for two groups, whereas, Kruskal-Wallis test and one-way ANOVA were done for more than two groups. Results: Twelve cases of GCT, 31 cases of CGCG and 39 cases of PGCG were reported over 11 years. The mean age of occurrence for GCT, CGCG and PGCG was 30.41 years, 27.69 years and 34.03 years, respectively. GCT was seen in long bones and CGCG and PGCG showed mandible predilection. Histologically, GCT showed evenly distributed giant cells with aggregated nuclei, whereas CGCG and PGCG showed aggregated giant cells with evenly distributed nuclei. The mean value of the number of giant cells and nuclei within giant cells was maximum in GCT (27.33, 33.50) followed by CGCG (23.56, 15.51) and PGCG (21.45, 11.32). Conclusion: The clinicopathological differences between GCT, CGCG and PGCG suggest that each one of these entities represent biologically different lesions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-022-01724-3.

Thermodynamics of Azo Dye Adsorption on a Newly Synthesized Titania-Doped Silica Aerogel by Cogelation: A Comparative Investigation with Silica Aerogels and Activated Charcoal.

The adsorption isotherms of azo dyes on a newly synthesized titania-doped silica (TdS) aerogel compared to silica aerogels and activated charcoal (AC) are systematically investigated. Monolithic TdS aerogels were synthesized by the cogelation process followed by supercritical drying of tetraethyl orthosilicate (TEOS) as a gel precursor and titanium(IV) isopropoxide (TTIP) as a metal complex precursor for co-polymerization in ethanol solvent. An acid-base catalyst was used for the hydrolysis and condensation of TEOS and TTIP. The effect of Ti4+ doping in a silica aerogel on the mesoporous structure and the adsorption capacity of methylene blue (MB) and crystal violet (CV) dyes were evaluated from the UV-vis absorption spectra. In order to compare the adsorption isotherms, the surface areas of silica and TdS aerogels were first normalized with respect to AC, as adsorption is a surface phenomenon. The azo dye equilibrium adsorption data were analyzed using different isotherm equations and found to follow the Langmuir adsorption isotherm. The maximum monolayer adsorption capacities for the adsorbent TdS aerogel normalized with the AC of the Langmuir isotherm are 131.58 and 159.89 mg/g for MB and CV dyes, respectively. From the Langmuir curve fitting, the Q max value of the TdS aerogel was found to increase by 1.22-fold compared to AC, while it increased 1.25-1.53-fold compared to the silica aerogel. After four cycles, regeneration efficiency values for MB and CV dyes are about 84 and 80%, respectively. The study demonstrates the excellent potential and recovery rate of silica and TdS aerogel adsorbents in removing dyes from wastewater. The pore volume and average pore size of the new aerogel, TdS, were found to be lower than those of the silica aerogel. Thus, a new TdS aerogel with a high capacity of adsorption of azo dyes is successfully achieved.