Nevin Manimala

Endocrine. 2022 Dec 2. doi: 10.1007/s12020-022-03273-8. Online ahead of print.

ABSTRACT

PURPOSE: Thirty years into the genomic era, this study sought to explore events that helped transform the clinical landscape of hereditary medullary thyroid cancer (MTC).

METHOD: This retrospective analysis of prospectively collected data included all RET carriers referred to a tertiary center for neck surgery that was performed between 1986 and 2021, using descriptive statistics and Poisson regression analysis.

RESULTS: Altogether, 496 RET carriers were referred for thyroidectomy (388 carriers) or neck reoperation (108 carriers). Of these, 44 carriers had highest risk mutations (p.Met918Thr), 164 carriers high risk mutations (p.Cys634Arg/Gly/Phe/Ser/Trp/Tyr/insHisGluLeuCys), 116 carriers moderate-high risk mutations (p.Cys609/611/618/620/630Arg/Gly/Phe/Ser/Tyr) and 172 carriers low-moderate risk mutations (p.Glu768Asp, p.Leu790Phe, p.Val804Leu/Met, or p.Ser891Ala). Three event clusters drove referral numbers upward: a string of first reports of causative RET mutations between 1993 and 1998; the international consensus guidelines for diagnosis and therapy of MEN type 1 and type 2 in 2001; and the revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma in 2015. Referrals for neck reoperation declined sluggishly over 30 years, ending in 2018. Index patients continued to be referred into 2021. Referrals for thyroidectomy, grouped in 5-year increments, peaked in 1996-2000 for carriers of highest and high risk mutations, and in 2006-2010 for carriers of moderate-high and low-moderate risk mutations, some 10 years later.

CONCLUSION: International management guidelines are critical in building and increasing the pressure towards screening of sporadic-appearing disease and offspring of known gene families by encompassing the complete disease spectrum early on.

PMID:36456885 | DOI:10.1007/s12020-022-03273-8

Graefes Arch Clin Exp Ophthalmol. 2022 Dec 2. doi: 10.1007/s00417-022-05923-z. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate differences in acquisition time, peripheral extension, and chromaticity between 3 different commercialized ultra-wide-field (UWF) fundus cameras.

METHODS: Patients were prospectively enrolled from 07/2021 to 11/2021. Patients underwent fundus photography with the following scanning protocols: (1) single shot with Silverstone (Optos, California), two-shot montage with Clarus 500 (Carl Zeiss, Dublin, CA), and three-shot montage with iCare EIDON FA with UWF module (CenterVue Spa, a company of iCare Finland Oy; Vantaa, Finland). Acquisition time was calculated as the interval between the beginning and the end of the acquisition. Peripheral extension was quantified as the average ratio between the total retinal pixel area and the optic nerve head (ONH) pixel area. The average chromaticity of all pixels in the red-green-blue (RGB) space was calculated.

RESULTS: Twenty-three eyes of 13 prospectively enrolled healthy controls were included in the study. Optos Silverstone had a higher total retina area/ONH area ratio (509.1 [480.9;559.3]) compared to Zeiss Clarus (442.0 [431.9;510.5], p = 0.02) and iCare EIDON (369.7 [345.3;387.8], p < 0.0001). Silverstone demonstrated the shortest acquisition time (median [interquartile range]: 32 [20;58.5] s) compared to Zeiss Clarus (42 [28.5;53.5] s, p = 0.6733) and iCare EIDON (72 [68.5;78] s, p = 0.0003). iCare EIDON demonstrated the lowest variability of acquisition time (9.5 s), compared to Zeiss Clarus (25 s) and Optos Silverstone (38.5 s). A statistically significant difference was found in the RGB distribution between each of the 3 devices (p < 0.001). iCare EIDON demonstrated an average barycenter position (RGB = [0.412, 0.314, 0.275]) that represented the best color balance of the image. Zeiss Clarus had a noticeable red shift at the expense of the blue and green channels (RGB = [0.515, 0.294, 0.191]). Optos Silverstone showed an absence of the blue channel (RGB = [0.621, 0.372, 0.007]) which results in a distortion of the color of the image.

CONCLUSION: Optos Silverstone and Zeiss Clarus required less time than iCare EIDON to acquire a comparable size image and captured larger areas of the retina than iCare EIDON. iCare EIDON provided more color-balanced retinal images with greater richness of color content than the other two devices.

PMID:36456861 | DOI:10.1007/s00417-022-05923-z

J Immigr Minor Health. 2022 Dec 1. doi: 10.1007/s10903-022-01434-5. Online ahead of print.

ABSTRACT

This study explored factors that mediate the relationship between subjective wellbeing and depression in a sample of West Indian American immigrants. An intersectional theoretical framework was used to identify the relative contribution of psychological stressors-perceived discrimination, financial strain and acculturative stress-that mediate the relationship between subjective wellbeing and depression. A geographically diverse sample was recruited by an online survey (N = 255), consisting of 138 men, 115 women, 173 Indo-West Indians and 82 Afro-West Indians. Path analysis was used to identify the relative contribution of psychological stressors. Acculturative stress and financial strain were both statistically significant predictors of depression. Financial strain was identified as the major mediator between subjective wellbeing and depression in West Indian Americans. West Indian Americans are vulnerable to financial strain and acculturative stress. These sources of psychological stress are important contributors to depression in the community. More research is needed to clarify these relationships.

PMID:36456840 | DOI:10.1007/s10903-022-01434-5

J Digit Imaging. 2022 Dec 1. doi: 10.1007/s10278-022-00738-0. Online ahead of print.

ABSTRACT

Retinal fundus images are non-invasively acquired and faced with low contrast, noise, and uneven illumination. The low-contrast problem makes objects in the retinal fundus image indistinguishable and the segmentation of blood vessels very challenging. Retinal blood vessels are significant because of their diagnostic importance in ophthalmologic diseases. This paper proposes improved retinal fundus images for optimal segmentation of blood vessels using convolutional neural networks (CNNs). This study explores some robust contrast enhancement tools on the RGB and the green channel of the retinal fundus images. The improved images undergo quality evaluation using mean square error (MSE), peak signal to noise ratio (PSNR), Similar Structure Index Matrix (SSIM), histogram, correlation, and intersection distance measures for histogram comparison before segmentation in the CNN-based model. The simulation results analysis reveals that the improved RGB quality outperforms the improved green channel. This revelation implies that the choice of RGB to the green channel for contrast enhancement is adequate and effectively improves the quality of the fundus images. This improved contrast will, in turn, boost the predictive accuracy of the CNN-based model during the segmentation process. The evaluation of the proposed method on the DRIVE dataset achieves an accuracy of 94.47, sensitivity of 70.92, specificity of 98.20, and AUC (ROC) of 97.56.

PMID:36456839 | DOI:10.1007/s10278-022-00738-0

Atherosclerosis. 2022 Nov 9;363:48-56. doi: 10.1016/j.atherosclerosis.2022.11.006. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The association between rheumatoid arthritis (RA) and blood lipid levels has often been described as paradoxical, despite the strong association between RA and cardiovascular disease (CVD) risk. We aimed to clarify the genetic architecture that would explain the relationship between RA and blood-lipid levels, while considering inflammation as measured by C-reactive protein (CRP).

METHODS: Genome-wide association study (GWAS) summary statistics were collected from the CHARGE Consortium and Global Lipids Genetics Consortium. Blood-lipid levels includes HDL-C, LDL-C, triglycerides (TG), and total cholesterol (TC). Causality was examined by assessing Mendelian Randomization (MR) analysis. Pleiotropy, the identification of shared causal variants between traits, was assessed by conducting colocalization analyses.

RESULTS: Using the MR Egger method, RA did not appear to causally predict alterations in lipid factors, rather the MR Egger intercept revealed that the genetic relationship between RA and HDL-C, LDL-C and TC may be explained by horizontal pleiotropy (p=0.003, 0.006, and 0.018, respectively). MR was suggestive of a horizontally pleiotropic relationship between CRP and lipid factors, while a causal relationship could not be ruled out. Recurring genes arising from shared causal genetic variants between RA and varying lipid factors included NAT2/PSD3, FADS2/FADS1, SH2B3, and YDJC.

CONCLUSIONS: Horizontal pleiotropy appears to explain the genetic relationship between RA and blood-lipid levels. In addition, blood-lipid levels appear to suggest a horizontally pleiotropic relationship to CRP, if not mediated through RA as well. Consideration of the pleiotropic genes between RA and blood lipid levels may aid in enhancing diagnostic means to predict CVD.

PMID:36455308 | DOI:10.1016/j.atherosclerosis.2022.11.006

Atherosclerosis. 2022 Nov 23;363:22-29. doi: 10.1016/j.atherosclerosis.2022.11.018. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The susceptibility of low-density lipoprotein (LDL) to aggregation predicts atherosclerotic cardiovascular disease. However, causes of interindividual variation in LDL lipid composition and aggregation susceptibility remain unclear. We examined whether the lipid composition and aggregation susceptibility of LDL reflect the lipid composition of the human liver.

METHODS: Liver biopsies and blood samples for isolation of LDL particles were obtained from 40 obese subjects (BMI 45.9 ± 6.1 kg/m², age 43 ± 8 years). LDL was isolated using sequential ultracentrifugation and lipidomic analyses of liver and LDL samples were determined using ultra-high performance liquid chromatography-mass spectrometry. LDL aggregation susceptibility ex vivo was analyzed by inducing aggregation by human recombinant secretory sphingomyelinase and following aggregate formation.

RESULTS: The composition (acyl carbon number and double bond count) of hepatic triglycerides, phosphatidylcholines, and sphingomyelins (SMs) was closely associated with that of LDL particles. Hepatic dihydroceramides and ceramides were positively correlated with concentrations of the corresponding SM species in LDL as well with LDL aggregation. These relationships remained statistically significant after adjustment for age, sex, and body mass index.

CONCLUSIONS: Lipid composition of LDL reflects that of the human liver in obese patients. Changes in hepatic sphingolipid metabolism may contribute to interindividual variation of LDL lipid composition and susceptibility to aggregation.

PMID:36455305 | DOI:10.1016/j.atherosclerosis.2022.11.018

Clin Neurol Neurosurg. 2022 Nov 25;224:107544. doi: 10.1016/j.clineuro.2022.107544. Online ahead of print.

ABSTRACT

OBJECTIVE: Eagle syndrome or styloid process syndrome is a clinical condition of complex aetiology. Since, as a consequence of vascular compression,due to the length of the styloid process and its nearness to the internal carotid artery,it can lead to vertigo. Vertigo may be the only symptom of stylocarotid syndrome and it is extremely challenging diagnose.To the best of our knowledge, this is the first study that measures the lengths of styloid process on the Croatian population’s,and possible influence of styloid process length on isolated vertigo of unknown aetiology.

METHODS: This study included 829 subjects who were divided into two groups.The first group was the control group, consisting of 800 subjects.The second group, study group, consisted of 29 subjects who suffered from the vertigo of unknown aetiology.

RESULTS: The statistically significant difference between the study and the control group was observed in the length of the styloid process, and in the closest distance of the styloid process from the carotid artery.

CONCLUSIONS: The prolonged styloid process and its close association with the internal carotid artery may affect vertigo of unknown aetiology and should be clinically and radiographically investigated in cases of unexplained vertigo as an isolated and only symptom within stylocarotid syndrome.

PMID:36455302 | DOI:10.1016/j.clineuro.2022.107544

ACS Chem Neurosci. 2022 Dec 1. doi: 10.1021/acschemneuro.2c00478. Online ahead of print.

ABSTRACT

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder in the U.S. α-Synuclein (α-Syn) preformed fibrils (PFFs) have been shown to propagate PD pathology in neuronal populations. However, little work has directly characterized the morphological changes on membranes associated with α-Syn PFFs at a cellular level. Scanning ion conductance microscopy (SICM) is a noninvasive in situ cell imaging technique and therefore uniquely advantageous to investigate PFF-induced membrane changes in neuroblastoma cells. The present work used SICM to monitor cytoplasmic membrane changes of SH-SY5Y neuroblastoma cells after incubation with varying concentrations of α-Syn PFFs. Cell membrane roughness significantly increased as the concentration of α-Syn PFFs increased. Noticeable protrusions that assumed a more crystalline appearance at higher α-Syn PFF concentrations were also observed. Cell viability was only slightly reduced, though statistically significantly, to about 80% but independent of the dose. These observations indicate that within the 48 h treatment period, PFFs continue to accumulate on the cell membranes, leading to membrane roughness increase without causing prominent cell death. Since PFFs did not induce major cell death, these data suggest that early interventions targeting fibrils before further aggregation may prevent the progression of neuron loss in Parkinson’s disease.

PMID:36455298 | DOI:10.1021/acschemneuro.2c00478

Neurourol Urodyn. 2022 Dec 1. doi: 10.1002/nau.25107. Online ahead of print.

ABSTRACT

BACKGROUND: Intradetrusor onabotulinumtoxinA injection is an effective advanced treatment for overactive bladder. While the effective dosages have been well studied, very little data exist on treatment efficacy using differing injection techniques. The objective of this study was to determine whether the efficacy of a reduced injection technique of 5 injection sites was noninferior to the standard technique of 20 injection sites of intradetrusor onabotulinumtoxinA for treatment of overactive bladder.

METHODS: In this randomized noninferiority trial, men and women seeking treatment of overactive bladder with intradetrusor onabotulinumtoxinA injections were randomized to receive 100 units administered via either a reduced injection technique of 5 injection sites or a standard injection technique of 20 injection sites. Subjects completed a series of standardized questionnaires at baseline and at 4-12 weeks postprocedure to determine symptom severity and treatment efficacy. The primary outcome was treatment efficacy as determined by Overactive Bladder Questionnaire-Short Form with a noninferiority margin of 15 points. Secondary outcomes were incidence of urinary tract infection and urinary retention requiring catheterization.

RESULTS: Data from 77 subjects were available for analysis with 39 in the control arm (20 injections) and 38 in the study arm (5 injections). There was a significant improvement in both arms from baseline to follow-up in Overactive Bladder Questionnaire-Short Form and International Consultation on Incontinence Questionnaire scores (p < 0.001). Overall treatment success was 68% with no statistically significant difference between arms. A significant difference between arms was found on the Overactive Bladder Questionnaire-Short Form quality of life survey favoring the control arm (confidence interval [CI]: 0.36-20.5, p = 0.04). However, there were no significant differences between arms in the remaining validated questionnaires. The study arm did not demonstrate noninferiority to the control arm. Subjects in the study arm were significantly more likely to express a willingness to undergo the procedure again (odds ratio = 3.8, 95% CI: 1.42-10.67, p = 0.004). Adverse events did not differ between arms.

CONCLUSIONS: A reduced injection technique for administration of intradetrusor onabotulinumtoxinA demonstrates similar efficacy to the standard injection technique but did not demonstrate noninferiority. Subjects preferred the reduced injection technique over the standard technique. A reduced injection technique is a safe and effective alternative to the standard technique.

PMID:36455284 | DOI:10.1002/nau.25107

Neurosurg Focus. 2022 Dec;53(6):E9. doi: 10.3171/2022.9.FOCUS22402.

ABSTRACT

OBJECTIVE: Perioperative and/or postoperative cerebrovascular accidents (PCVAs) after intracranial tumor resection (ITR) are serious complications with devastating effects on quality of life and survival. Here, the authors retrospectively analyzed a prospectively maintained, multicenter surgical registry to design a risk model for PCVA after ITR to support efforts in neurosurgical personalized medicine to risk stratify patients and potentially mitigate poor outcomes.

METHODS: The National Surgical Quality Improvement Program database was queried for ITR cases (2015-2019, n = 30,951). Patients with and without PCVAs were compared on baseline demographics, preoperative clinical characteristics, and outcomes. Frailty (physiological reserve for surgery) was measured by the Revised Risk Analysis Index (RAI-rev). Logistic regression analysis was performed to identify independent associations between preoperative covariates and PCVA occurrence. The ITR-PCVA risk model was generated based on logit effect sizes and assessed in area under the receiver operating characteristic curve (AUROC) analysis.

RESULTS: The rate of PCVA was 1.7% (n = 532). Patients with PCVAs, on average, were older and frailer, and had increased rates of nonelective surgery, interhospital transfer status, diabetes, hypertension, unintentional weight loss, and elevated BUN. PCVA was associated with higher rates of postoperative reintubation, infection, thromboembolic events, prolonged length of stay, readmission, reoperation, nonhome discharge destination, and 30-day mortality (all p < 0.001). In multivariable analysis, predictors of PCVAs included RAI “frail” category (OR 1.7, 95% CI 1.2-2.4; p = 0.006), Black (vs White) race (OR 1.5, 95% CI 1.1-2.1; p = 0.009), nonelective surgery (OR 1.4, 95% CI 1.1-1.7; p = 0.003), diabetes mellitus (OR 1.5, 95% CI 1.1-1.9; p = 0.002), hypertension (OR 1.4, 95% CI 1.1-1.7; p = 0.006), and preoperative elevated blood urea nitrogen (OR 1.4, 95% CI 1.1-1.8; p = 0.014). The ITR-PCVA predictive model was proposed from the resultant multivariable analysis and performed with a modest C-statistic in AUROC analysis of 0.64 (95% CI 0.61-0.66). Multicollinearity diagnostics did not detect any correlation between RAI-rev parameters and other covariates (variance inflation factor = 1).

CONCLUSIONS: The current study proposes a novel preoperative risk model for PCVA in patients undergoing ITR. Patients with poor physiological reserve (measured by frailty), multiple comorbidities, abnormal preoperative laboratory values, and those admitted under high acuity were at highest risk. The ITR-PCVA risk model may support patient-centered counseling striving to respect goals of care and maximize quality of life. Future prospective studies are warranted to validate the ITR-PCVA risk model and evaluate its utility as a bedside clinical tool.

PMID:36455279 | DOI:10.3171/2022.9.FOCUS22402