Global incidence of non-alcoholic fatty liver disease: A systematic review and meta-analysis of 63 studies and 1,201,807 persons.

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. We aimed to estimate the pooled global NAFLD incidence. METHODS: We performed a systematic review and meta-analysis of cohort studies of adults without NAFLD at baseline to evaluate the global incidence of ultrasound-diagnosed NAFLD. RESULTS: A total of 63 eligible studies (1,201,807 persons) were analyzed. Studies were from Mainland China/Hong Kong (n = 26), South Korea (n = 22), Japan (n = 14), other (n = 2, Sri Lanka, Israel); 63.8% were clinical center studies; median study year 2000 to 2016; 87% were good quality. Among the 1,201,807 persons at risk, 242,568 persons developed NAFLD, with an incidence rate of 4,612.8 (95% CI 3,931.5-5,294.2) per 100,000 person-years and no statistically significant differences by study sample size (p = 0.90) or study setting (p = 0.055). Males had higher incidence vs. females (5,943.8 vs. 3,671.7, p = 0.0013). Both the obese (vs. non-obese) and the overweight/obese groups (vs. normal weight) were about threefold more likely to develop NAFLD (8,669.6 vs. 2,963.9 and 8,416.6 vs. 3,358.2, respectively) (both p <0.0001). Smokers had higher incidence than non-smokers (8,043.2 vs. 4,689.7, p = 0.046). By meta-regression, adjusting for study year, study setting, and study location, study period of 2010 or after and study setting were associated with increased incidence (p = 0.010 and p = 0.055, respectively). By country, China had a higher NAFLD incidence compared to non-China regions (p = 0.012) and Japan a lower incidence compared to non-Japan regions (p = 0.005). CONCLUSIONS: NAFLD incidence is increasing with a current estimate of 4,613 new cases per 100,000 person-years. Males and overweight/obese individuals had significantly higher incidence rates compared to females and those of normal weight. Public health interventions for prevention of NAFLD are needed with a special emphasis on males, overweight/obese individuals, and higher risk regions. IMPACT AND IMPLICATIONS: Non-alcoholic fatty liver disease (NAFLD) affects approximately 30% of people worldwide and appears to be increasing, but data to estimate the incidence rate are limited. In this meta-analytic study of over 1.2 million people, we estimated an incidence rate of NAFLD of 46.13 per 1,000 person-years with significant differences by sex, BMI, geography, and time-period. As treatment options for NAFLD remain limited, prevention of NAFLD should remain the focus of public health strategies. Studies such as these can help policy makers in determining which and whether their interventions are impactful.

COMPARATIVE ANALYSIS OF OCT AND OCT ANGIOGRAPHY CHARACTERISTICS IN EARLY DIABETIC RETINOPATHY.

PURPOSE: To assess the quantitative characteristics of optical coherence tomography (OCT) and OCT angiography (OCTA) for the objective detection of early diabetic retinopathy (DR). METHODS: This was a retrospective and cross-sectional study, which was carried out at a tertiary academic practice with a subspecialty. Twenty control participants, 15 people with diabetics without retinopathy (NoDR), and 22 people with mild nonproliferative diabetic retinopathy (NPDR) were included in this study. Quantitative OCT characteristics were derived from the photoreceptor hyperreflective bands, i.e., inner segment ellipsoid (ISe) and retinal pigment epithelium (RPE). OCTA characteristics, including vessel diameter index (VDI), vessel perimeter index (VPI), and vessel skeleton density (VSD), were evaluated. RESULTS: Quantitative OCT analysis indicated that the ISe intensity was significantly trending downward with DR advancement. Comparative OCTA revealed VDI, VPI, and VSD as the most sensitive characteristics of DR. Correlation analysis of OCT and OCTA characteristics revealed weak variable correlation between the two imaging modalities. CONCLUSION: Quantitative OCT and OCTA analyses revealed photoreceptor and vascular distortions in early DR. Comparative analysis revealed that the OCT intensity ratio, ISe/RPE, has the best sensitivity for early DR detection. Weak variable correlation of the OCT and OCTA characteristics suggests that OCT and OCTA are providing supplementary information for DR detection and classification.

A Novel Distal Biceps Rupture Repair Technique Utilizing a Biocomposite Scaffold.

Distal biceps tendon ruptures are uncommon injuries that have a re-rupture rate of 1.2% - 6%. In severe traumatic injuries or chronic injuries, a distal biceps tendon repair may require augmentation due to insufficient tissue quality. Unsuccessful treatment of these injuries can result in the loss of approximately 40% of supination strength and 30% of elbow flexion strength. There has been a growing interest in biologic augmentation in orthopedic surgery, and its incorporation into distal biceps tendon repairs has increased as well. Established bio-inductive implants and dermal allografts have been shown to be of benefit; however, these biologics have drawbacks such as failure to incorporate at time of implantation, lack of structural strength, and technical difficulty of implantation. The BioBrace® (ConMed, New Haven, CT) is a bio-inductive, biocomposite scaffold that is composed of highly porous type I collagen and bio-resorbable poly (L-Lactide) (PLLA) microfilaments. It can be used in conjunction with distal biceps tendon repair or reconstruction. It has the advantage of providing strength to the augmented repair at time zero of implantation, while also demonstrating the ability to induce new organized tissue growth throughout its resorptive phase. We describe a technique to successfully augment a distal biceps tendon repair using the BioBrace®.

A fully automated algorithm for heart rate detection in post-dive precordial Doppler ultrasound.

Background: Doppler ultrasound is used currently in decompression research for the evaluation of venous gas emboli (VGE). Estimation of heart rate from post-dive Doppler ultrasound recordings can provide a tool for the evaluation of physiological changes from decompression stress, as well as aid in the development of automated VGE detection algorithms that relate VGE presence to cardiac activity. Method: An algorithm based on short-term autocorrelation was developed in MATLAB to estimate the heart rate in post-dive precordial Doppler ultrasound. The algorithm was evaluated on 21 previously acquired and labeled precordial recordings spanning Kisman-Masurel (KM) codes of 111-444 (KM I-IV) with manually derived instantaneous heart rates. Results: A window size of at least two seconds was necessary for robust and accurate instantaneous heart rate estimation with a mean error of 1.56 ± 7.10 bpm. Larger window sizes improved the algorithm performance, at the cost of beat-to-beat heart rate estimates. We also found that our algorithm provides good results for low KM grade Doppler recordings with and without flexion, and high KM grades without flexion. High KM grades observed after movement produced the greatest mean absolute error of 6.12 ± 8.40 bpm. Conclusion: We have developed a fully automated algorithm for the estimation of heart rate in post-dive precordial Doppler ultrasound recordings.

2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD. METHODS: Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence. RESULTS: We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% confidence interval [CI], 28.6%-31.1%); of these, 82.5% of included articles used ultrasound to diagnose NAFLD, with prevalence of 30.6% (95% CI, 29.2%-32.0%). South America (3 studies, 5716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI, 34.0%-37.5%) and 35.3% (95% CI, 25.4%-45.9%), respectively. From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to 37.3% (yearly increase of 0.7%, P < .0001), with South America showing the most rapid change of 2.7% per year, followed by Europe at 1.1%. CONCLUSIONS: Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work toward reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.

Proximal recolonization by self-renewing microglia re-establishes microglial homeostasis in the adult mouse brain.

Microglia are resident immune cells that play critical roles in maintaining the normal physiology of the central nervous system (CNS). Remarkably, microglia have an intrinsic capacity to repopulate themselves after acute ablation. However, the underlying mechanisms that drive such restoration remain elusive. Here, we characterized microglial repopulation both spatially and temporally following removal via treatment with the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622. We show that microglia were replenished via self-renewal, with no contribution from nonmicroglial lineages, including Nestin+ progenitors and the circulating myeloid population. Interestingly, spatial analyses with dual-color labeling revealed that newborn microglia recolonized the parenchyma by forming distinctive clusters that maintained stable territorial boundaries over time, indicating the proximal expansive nature of adult microgliogenesis and the stability of microglia tiling. Temporal transcriptome profiling at different repopulation stages revealed that adult newborn microglia gradually regain steady-state maturity from an immature state that is reminiscent of the neonatal stage and follow a series of maturation programs, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, interferon immune activation, and apoptosis. Importantly, we show that the restoration of microglial homeostatic density requires NF-κB signaling as well as apoptotic egress of excessive cells. In summary, our study reports key events that take place from microgliogenesis to homeostasis reestablishment.

QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY REVEALS ROD PHOTORECEPTOR DEGENERATION in EARLY DIABETIC RETINOPATHY.

PURPOSE: This study is to test the feasibility of optical coherence tomography (OCT) detection of photoreceptor abnormality and to verify that the photoreceptor abnormality is rod predominated in early diabetic retinopathy (DR). METHODS: OCT images were acquired from normal eyes, diabetic eyes with no DR, and mild nonproliferative DR (NPDR). Quantitative features, including thickness measurements quantifying band distances and reflectance intensity features among the external limiting membrane, inner segment ellipsoid, interdigitation zone, and retinal pigment epithelium were determined. Comparative OCT analysis of central fovea, parafovea, and perifovea were implemented to verify that the photoreceptor abnormality is rod predominated in early DR. RESULTS: Thickness abnormalities between the inner segment ellipsoid and interdigitation zone also showed a decreasing trend among cohorts. Reflectance abnormalities of the external limiting membrane, interdigitation zone, and inner segment ellipsoid were observed between healthy, no DR, and mild NPDR eyes. The normalized inner segment ellipsoid/retinal pigment epithelium intensity ratio revealed a significant decreasing trend in the perifovea, but no detectable difference in central fovea. CONCLUSION: Quantitative OCT analysis consistently revealed outer retina, i.e., photoreceptor changes in diabetic patients with no DR and mild NPDR. Comparative analysis of central fovea, parafovea, and perifovea confirmed that the photoreceptor abnormality is rod-predominated in early DR.

VASCULAR COMPLEXITY ANALYSIS IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF DIABETIC RETINOPATHY.

PURPOSE: This study aimed to verify the feasibility of using vascular complexity features for objective differentiation of controls and nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) patients. METHODS: This was a cross-sectional study conducted in a tertiary, subspecialty, academic practice. The cohort included 20 control subjects, 60 NPDR patients, and 56 PDR patients. Three vascular complexity features, including the vessel complexity index, fractal dimension, and blood vessel tortuosity, were derived from each optical coherence tomography angiography image. A shifting-window measurement was further implemented to identify local feature distortions due to localized neovascularization and mesh structures in PDR. RESULTS: With mean value analysis of the whole-image, only the vessel complexity index and blood vessel tortuosity were able to classify NPDR versus PDR patients. Comparative shifting-window measurement revealed increased sensitivity of complexity feature analysis, particularly for NPDR versus PDR classification. A multivariate regression model indicated that the combination of all three vascular complexity features with shifting-window measurement provided the best classification accuracy for controls versus NPDR versus PDR. CONCLUSION: Vessel complexity index and blood vessel tortuosity were the most sensitive in differentiating NPDR and PDR patients. A shifting-window measurement increased the sensitivity significantly for objective optical coherence tomography angiography classification of diabetic retinopathy.

Differential effects of partial and complete loss of TREM2 on microglial injury response and tauopathy.

Alzheimer's disease (AD), the most common form of dementia, is characterized by the abnormal accumulation of amyloid plaques and hyperphosphorylated tau aggregates, as well as microgliosis. Hemizygous missense variants in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) are associated with elevated risk for developing late-onset AD. These variants are hypothesized to result in loss of function, mimicking TREM2 haploinsufficiency. However, the consequences of TREM2 haploinsufficiency on tau pathology and microglial function remain unknown. We report the effects of partial and complete loss of TREM2 on microglial function and tau-associated deficits. In vivo imaging revealed that microglia from aged TREM2-haploinsufficient mice show a greater impairment in their injury response compared with microglia from aged TREM2-KO mice. In transgenic mice expressing mutant human tau, TREM2 haploinsufficiency, but not complete loss of TREM2, increased tau pathology. In addition, whereas complete TREM2 deficiency protected against tau-mediated microglial activation and atrophy, TREM2 haploinsufficiency elevated expression of proinflammatory markers and exacerbated atrophy at a late stage of disease. The differential effects of partial and complete loss of TREM2 on microglial function and tau pathology provide important insights into the critical role of TREM2 in AD pathogenesis.

Ultrasound in decompression research: fundamentals, considerations, and future technologies.

It is widely accepted that bubbles are a necessary but insufficient condition for the development of decompression sickness. However, open questions remain regarding the precise formation and behavior of these bubbles after an ambient pressure reduction (decompression), primarily due to the inherent difficulty of directly observing this phenomenon in vivo. In decompression research, information about these bubbles after a decompression is gathered via means of ultrasound acquisitions. The ability to draw conclusions regarding decompression research using ultrasound is highly influenced by the variability of the methodologies and equipment utilized by different research groups. These differences play a significant role in the quality of the data and thus the interpretation of the results. The purpose of this review is to provide a technical overview of the use of ultrasound in decompression research, particularly Doppler and brightness (B)-mode ultrasound. Further, we will discuss the strengths and limitations of these technologies and how new advancements are improving our ability to understand bubble behavior post-decompression.

A fully automated method for late ventricular diastole frame selection in post-dive echocardiography without ECG gating.

Venous gas emboli (VGE) are often quantified as a marker of decompression stress on echocardiograms. Bubble-counting has been proposed as an easy to learn method, but remains time-consuming, rendering large dataset analysis impractical. Computer automation of VGE counting following this method has therefore been suggested as a means to eliminate rater bias and save time. A necessary step for this automation relies on the selection of a frame during late ventricular diastole (LVD) for each cardiac cycle of the recording. Since electrocardiograms (ECG) are not always recorded in field experiments, here we propose a fully automated method for LVD frame selection based on regional intensity minimization. The algorithm is tested on 20 previously acquired echocardiography recordings (from the original bubble-counting publication), half of which were acquired at rest (Rest) and the other half after leg flexions (Flex). From the 7,140 frames analyzed, sensitivity was found to be 0.913 [95% CI: 0.875-0.940] and specificity 0.997 [95% CI: 0.996-0.998]. The method's performance is also compared to that of random chance selection and found to perform significantly better (p≺0.0001). No trend in algorithm performance was found with respect to VGE counts, and no significant difference was found between Flex and Rest (p>0.05). In conclusion, full automation of LVD frame selection for the purpose of bubble counting in post-dive echocardiography has been established with excellent accuracy, although we caution that high quality acquisitions remain paramount in retaining high reliability.

Microglial NFκB-TNFα hyperactivation induces obsessive-compulsive behavior in mouse models of progranulin-deficient frontotemporal dementia.

Frontotemporal dementia (FTD) is the second most common dementia before 65 years of age. Haploinsufficiency in the progranulin (GRN) gene accounts for 10% of all cases of familial FTD. GRN mutation carriers have an increased risk of autoimmune disorders, accompanied by elevated levels of tissue necrosis factor (TNF) α. We examined behavioral alterations related to obsessive-compulsive disorder (OCD) and the role of TNFα and related signaling pathways in FTD patients with GRN mutations and in mice lacking progranulin (PGRN). We found that patients and mice with GRN mutations displayed OCD and self-grooming (an OCD-like behavior in mice), respectively. Furthermore, medium spiny neurons in the nucleus accumbens, an area implicated in development of OCD, display hyperexcitability in PGRN knockout mice. Reducing levels of TNFα in PGRN knockout mice abolished excessive self-grooming and the associated hyperexcitability of medium spiny neurons of the nucleus accumbens. In the brain, PGRN is highly expressed in microglia, which are a major source of TNFα. We therefore deleted PGRN specifically in microglia and found that it was sufficient to induce excessive grooming. Importantly, excessive grooming in these mice was prevented by inactivating nuclear factor κB (NF-κB) in microglia/myeloid cells. Our findings suggest that PGRN deficiency leads to excessive NF-κB activation in microglia and elevated TNFα signaling, which in turn lead to hyperexcitability of medium spiny neurons and OCD-like behavior.

GIRK3 gates activation of the mesolimbic dopaminergic pathway by ethanol.

G protein-gated inwardly rectifying potassium (GIRK) channels are critical regulators of neuronal excitability and can be directly activated by ethanol. Constitutive deletion of the GIRK3 subunit has minimal phenotypic consequences, except in response to drugs of abuse. Here we investigated how the GIRK3 subunit contributes to the cellular and behavioral effects of ethanol, as well as to voluntary ethanol consumption. We found that constitutive deletion of GIRK3 in knockout (KO) mice selectively increased ethanol binge-like drinking, without affecting ethanol metabolism, sensitivity to ethanol intoxication, or continuous-access drinking. Virally mediated expression of GIRK3 in the ventral tegmental area (VTA) reversed the phenotype of GIRK3 KO mice and further decreased the intake of their wild-type counterparts. In addition, GIRK3 KO mice showed a blunted response of the mesolimbic dopaminergic (DA) pathway to ethanol, as assessed by ethanol-induced excitation of VTA neurons and DA release in the nucleus accumbens. These findings support the notion that the subunit composition of VTA GIRK channels is a critical determinant of DA neuron sensitivity to drugs of abuse. Furthermore, our study reveals the behavioral impact of this cellular effect, whereby the level of GIRK3 expression in the VTA tunes ethanol intake under binge-type conditions: the more GIRK3, the less ethanol drinking.

Non-invasive characterization of real-time bladder sensation using accelerated hydration and a novel sensation meter: An initial experience.

AIMS: The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. METHODS: Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade-G2® and recorded real-time sensation (0-100% scale) and standardized verbal sensory thresholds using a novel, touch-screen "sensation meter." 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. RESULTS: Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. ≥3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. CONCLUSIONS: This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity-sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way.

µ-Opioid receptors mediate the effects of chronic ethanol binge drinking on the hippocampal neurogenic niche.

Ethanol exposure and withdrawal alter the generation of new neurons in the adult hippocampus. The endogenous opioid system, particularly the µ-opioid receptor (MOR), can modulate neural progenitors and also plays a critical role in ethanol drinking and dependence. In the present study, we sought to determine whether MOR contributes to the effects of ethanol on the dentate gyrus (DG) neurogenic niche. MOR wild-type (WT), heterozygous (Het) and knockout (KO) littermates were subjected to voluntary ethanol drinking in repeated limited-access two-bottle choice (2BC) sessions. MOR deficiency did not alter progenitor proliferation, neuronal differentiation and maturation, apoptosis or microglia in ethanol-naïve mice. When exposed to five consecutive weeks of 2BC, MOR mutant mice exhibited a gene-dosage-dependent reduction of ethanol consumption compared with WT mice. Introducing a week of ethanol deprivation between each week of 2BC increased ethanol consumption in all genotypes and produced equivalent intakes in WT, Het and KO mice. Under the latter paradigm, ethanol drinking decreased progenitor proliferation and neuronal differentiation in the DG of WT mice. Interestingly, WT mice exhibited a strong negative correlation between ethanol intake and proliferation, which was disrupted in Het and KO mice. Moreover, MOR deficiency blocked the effect of ethanol on neuronal differentiation. MOR deficiency also protected against the neuroimmune response to ethanol drinking. Finally, chronic binge drinking induced a paradoxical decrease in apoptosis, which was independent of MOR. Altogether, our data suggest that MOR is implicated in some of the neuroplastic changes produced by chronic ethanol exposure in the DG.

Current modes of failure in TKA: infection, instability, and stiffness predominate.

BACKGROUND: Historically, polyethylene wear and its sequelae (osteolysis, late instability, aseptic loosening) were common causes for revision total knee arthroplasty (TKA). Recently, polyethylene manufacturing has become more consistent; furthermore, a clearer understanding of the importance of oxidation on polyethylene performance led to packaging of the polyethylene bearings in an inert environment. This improved the quality and consistency of polyethylene used in TKA, raising the question of whether different failure modes now predominate after TKA. QUESTIONS/PURPOSES: The purpose of this study was to determine the current reasons for (1) early and (2) late failures after TKA at one high-volume arthroplasty center. METHODS: We reviewed all first-time revision TKAs performed between 2001 and 2011 at one institution, yielding a group of 253 revision TKAs in 251 patients. Mean age at the time of revision was 64 years (SD 10 years). Mean time to revision was 35 months (SD 23 months). Preoperative evaluations, laboratory data, radiographs, and intraoperative findings were used to determine causes for revision. Early failure was defined as revision within 2 years of the index procedure. The primary failure mechanism was determined by the operating surgeon. RESULTS: Early failure accounted for 46% (116 of 253) of all revisions with infection (28 of 116 [24%]), instability (30 of 116 [26%]), and stiffness (21 of 116 [18%]) being the leading causes. Late failure accounted for 54% (137 of 253) of all revisions with the most common causes including infection (34 of 137 [25%]), instability (24 of 137 [18%]), and stiffness (19 of 253 [14%]). Polyethylene wear was implicated as the failure mechanism in 2% of early cases (two of 116) and 9% of late cases (13 of 137). CONCLUSIONS: In contrast to previous studies, wear-related implant failure in TKA was relatively uncommon in this series. Changes in polyethylene manufacturing, sterilization, and storage may have accounted for some of this difference; however, longer-term followup will be required to verify this finding. Infection, instability, and stiffness represent the most common causes of early and late failure. Strategies to improve outcomes in TKA should be aimed at infection prophylaxis and treatment, surgical technique, and patient selection. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Small Cell Cervical Carcinoma in Pregnancy: Therapeutic Options for an Aggressive Cancer Diagnosis.

Neuroendocrine small cell cervical carcinoma is an aggressive cancer which accounts for approximately 1 to 3% of all cervical neoplasms. Therapy must be altered in pregnancy to optimize maternal-fetal outcomes. A 39-year-old woman presented for a routine prenatal visit and was noted to have a grossly abnormal cervix. Cervical biopsies confirmed small cell carcinoma. At 19 weeks' gestation, chemotherapy was initiated. The patient delivered at 34 weeks' gestation to initiate radiation therapy. Six months later, she was diagnosed with metastatic disease and died from cancer complications. In pregnancy, treatment modalities for small cell cervical carcinoma are based on the patient's gestational age at diagnosis. While aggressive early treatment is preferred, platinum-based chemotherapy can be initiated in the second trimester and radiation therapy delayed until delivery. Small cell cervical carcinoma complicating pregnancy requires aggressive treatment. Chemotherapy in the second trimester with planned delayed radiation therapy, may optimize fetal outcomes.

Trends in functional outcome measures in orthopedic oncology.

The purpose of this study was to identify trends in the use of functional outcome measures within orthopedic oncology. The search engine, PubMed, was reviewed for all articles over an 11-year period from 2011 to 2021 from five major journals that publish in the field of orthopedic oncology. The functional outcome measures used in the articles were recorded along with study date, study design, clinical topic/pathology, and level of evidence. Out of 5968 musculoskeletal tumor-focused articles reviewed, 293 (4.9%) included at least one outcome measure. A total of 28 different outcome tools were identified. The most popular were Musculoskeletal Tumor Society (MSTS) score (61.1%) and Toronto Extremity Salvage (TESS) score (14.0%), followed by 36-Item Short Form Survey (SF-36) (4.1%) and Patient-Reported Outcomes Measurement Information System (PROMIS) (3.8%). The use of MSTS scores decreased by 0.7% each year, whereas PROMIS increased by 1.2% each year. Seventy-four articles used more than one outcome measure. Of these 74 articles, 61 had the MSTS as one of the outcome measures. Orthopedic oncology utilizes functional outcome measures less commonly in comparison to other orthopedic subspecialties. However, this may be due in large part to orthopedic oncologists putting more emphasis on outcomes such as local recurrence, implant failure, and mortality. MSTS score is the most widely used functional outcome measure, but the utilization of PROMIS has increased recently, and could be the next step in evaluating outcomes in orthopedic oncology as it is patient-derived rather than physician-derived.

Differential artery-vein analysis improves the OCTA classification of diabetic retinopathy.

This study investigates the impact of differential artery-vein (AV) analysis in optical coherence tomography angiography (OCTA) on machine learning classification of diabetic retinopathy (DR). Leveraging deep learning for arterial-venous area (AVA) segmentation, six quantitative features, including perfusion intensity density (PID), blood vessel density (BVD), vessel area flux (VAF), blood vessel caliber (BVC), blood vessel tortuosity (BVT), and vessel perimeter index (VPI) features, were derived from OCTA images before and after AV differentiation. A support vector machine (SVM) classifier was utilized to assess both binary and multiclass classifications of control, diabetic patients without DR (NoDR), mild DR, moderate DR, and severe DR groups. Initially, one-region features, i.e., quantitative features extracted from the entire OCTA, were evaluated for DR classification. Differential AV analysis improved classification accuracies from 78.86% to 87.63% and from 79.62% to 85.66% for binary and multiclass classifications, respectively. Additionally, three-region features derived from the entire image, parafovea, and perifovea, were incorporated for DR classification. Differential AV analysis further enhanced classification accuracies from 84.43% to 93.33% and from 83.40% to 89.25% for binary and multiclass classifications, respectively. These findings highlight the potential of differential AV analysis in augmenting disease diagnosis and treatment assessment using OCTA.

Colour fusion effect on deep learning classification of uveal melanoma.

BACKGROUND: Reliable differentiation of uveal melanoma and choroidal nevi is crucial to guide appropriate treatment, preventing unnecessary procedures for benign lesions and ensuring timely treatment for potentially malignant cases. The purpose of this study is to validate deep learning classification of uveal melanoma and choroidal nevi, and to evaluate the effect of colour fusion options on the classification performance. METHODS: A total of 798 ultra-widefield retinal images of 438 patients were included in this retrospective study, comprising 157 patients diagnosed with UM and 281 patients diagnosed with choroidal naevus. Colour fusion options, including early fusion, intermediate fusion and late fusion, were tested for deep learning image classification with a convolutional neural network (CNN). F1-score, accuracy and the area under the curve (AUC) of a receiver operating characteristic (ROC) were used to evaluate the classification performance. RESULTS: Colour fusion options were observed to affect the deep learning performance significantly. For single-colour learning, the red colour image was observed to have superior performance compared to green and blue channels. For multi-colour learning, the intermediate fusion is better than early and late fusion options. CONCLUSION: Deep learning is a promising approach for automated classification of uveal melanoma and choroidal nevi. Colour fusion options can significantly affect the classification performance.