Case Report: Three cases of clinically suspected viral myocarditis with recovery of left ventricular dysfunction.

Viral myocarditis is an important cause of non-ischemic cardiomyopathy. Multiple clinical manifestations have been reported, including acute heart failure, cardiogenic shock, and ventricular arrhythmias. We present three patients with clinically suspected viral myocarditis causing acute heart failure. Serum coxsackievirus B antibodies were positive in all three patients. Each case resulted in significant clinical improvement with hemodynamic support and acute recovery of left ventricular ejection fraction. Despite an initial critical presentation concerning for cardiogenic shock, we highlight three cases of clinically suspected coxsackie myocarditis with an excellent short-term prognosis.

Prevalence of H. pylori and gastric intestinal metaplasia in BRCA1 and BRCA2 carriers.

BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer (GC), however the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of GC risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the pathogenesis of GC in this population. 100 unselected BRCA1/2 carriers undergoing endoscopic ultrasound from 3/2022-3/2023 underwent concomitant upper endoscopy with non-targeted gastric antrum and body biopsies. The study population (70% women; mean age: 60.1) included 66% BRCA2 carriers. H. pylori was detected in one (1%) individual, 7 (7%) had GIM, 2 (2%) had autoimmune atrophic gastritis, and no GCs were diagnosed. Among BRCA1/2 carriers, H. pylori prevalence was low and GIM prevalence was similar to the general population, however identification of H. pylori or GIM may help inform future GC risk management strategies in BRCA1/2 carriers.

MRI white matter hyperintensities and neuropsychological performance in a clinical sample.

OBJECTIVE: White-matter hyperintensities (WMH) are commonly observed on MRI of non-demented patients. Findings are mixed regarding their association with neuropsychological test performance. The purpose of this study is to investigate the association of white-matter hyperintensities on routine clinical MRI and neuropsychological test performance in non-demented outpatients. METHOD: Two groups were selected based on MRI results: (1) normal (n = 62, Mage = 50.21, Medu = 14.89) and (2) WMH without other MRI abnormality (n = 56, Mage = 55.43, Medu = 14.04). Neuropsychological tests assessed five cognitive domains for which index scores were calculated and categorized in the following clinical ranges: well below average, below average, low average, average, and above average. RESULTS: Likelihood ratios comparing base rates for the WMH and normal groups across these clinical ranges revealed significant base rate differences only for attention/processing speed (Lχ2 = 16.47, df = 4, p < .01), with more WMH patients in the below average range and fewer above average. Odds ratios were calculated using two z-score cutoffs: -1.67 and -1.00. While patients with WMH were significantly more likely to have an index z-score ≤ -1.00 on attention/processing speed tests (OR = 3.62, 95% CI: 1.08-12.19) and an executive function test of reasoning (OR = 4.63, 95% CI: 1.18-18.19), there was no difference in the likelihood the groups would have a z-score ≤ -1.67 in any cognitive domain. CONCLUSIONS: Taken together, these findings indicate that among referred outpatients without dementia, WMH on routine clinical MRI are associated with relatively mild decreased attention and processing speed.

Assessment of bladder filling during prostate cancer radiation therapy with ultrasound and cone-beam CT.

Prostate cancer patients undergoing external beam radiation therapy (EBRT) benefit from a full bladder to decrease bowel and bladder toxicity. Ultrasound may offer a proxy metric for evaluation, sparing CBCT dosing. Patients were prospectively enrolled pre-simulation from January 2017 to February 2018. Bladder volume was evaluated prior to RT using US daily and CBCT for three daily treatments and then weekly unless otherwise indicated. 29 patients completed median 40 days of RT, resulting in 478 CBCT and 1,099 US bladder volumes. 21 patients were treated to intact glands and 8 to the post-prostatectomy bed. Median patient age was 70 years. Bladder volume on CBCT and US positively correlated (r = 0.85), with average bladder volume for all patients of 162 mL versus 149 mL, respectively. Bladder volume during treatment was consistently lower than the volume at CT simulation (153 mL vs 194 mL, p<0.01) and progressively declined during treatment. Patients older than 70 years presented with lower average bladder volumes than those < 70 years (122 mL vs 208 mL, respectively, p<0.01). Patients with the highest agreement between CBCT and US (<10% variability) had higher average bladder volumes (192 mL vs 120 mL, p=0.01). US was found to be an accurate measure of bladder volume and may be used to monitor daily bladder volumes in patients being treated with radiation for prostate cancer.

US regulatory considerations for low field magnetic resonance imaging systems.

Although there has been a resurgence of interest in low field magnetic resonance imaging (MRI) systems in recent years, low field MRI is not a new concept. FDA has a long history of evaluating the safety and effectiveness of MRI systems encompassing a wide range of field strengths. Many systems seeking marketing authorization today include new technological features (such as artificial intelligence), but this does not fundamentally change the regulatory paradigm for MR systems. In this review, we discuss some of the US regulatory considerations for low field magnetic resonance imaging (MRI) systems, including applicability of existing laws and regulations and how the U.S. Food and Drug Administration (FDA) evaluates low field MRI systems for market authorization. We also discuss regulatory considerations in the review of low field MRI systems incorporating novel AI technology. We foresee that MRI systems of all field strengths intended for general diagnostic use will continue to be evaluated for marketing clearance by the metric of substantial equivalence set forth in the premarket notification pathway.

"There is No One Way to Be Transgender and to Live Sex": Transgender and Non-Binary Individuals' Experiences with Pornography.

Transgender or non-binary (TGNB) people are often present as protagonists of pornographic material. This study is the first to consider TGNB people as critical consumers of sexually explicit material. The sample included 212 self-identified TGNB individuals: 47.2% trans man/transmasculine, 15.6% trans woman/transfeminine and 37.3% non-binary. The online questionnaire consisted of a sociodemographic data collection, multiple-choice questions about preferences and habits concerning pornography, and open-ended questions about the sensations experienced when watching pornography, opinions on the representation of TGNB people in pornography, and their experience in watching pornographic videos with cisgender or TGNB protagonists. The answers were analyzed using the qualitative method of thematic analysis. We identified four themes that appeared across the responses: 1) heteronormativity and cisnormativity in pornography: the need for deconstructing the current cis-het-patriarchial normative and binary system, which dominates pornography except for the ethical porn industry, 2) cisgender pornography compared to TGNB pornography, 3) pleasurable sensations (e.g., identification and empowerment) associated with TGNB pornography, and 4) negative sensations (e.g., objectification and dysphoria) associated with TGNB pornography. Results are discussed in light of the objectification framework and the minority stress model.

Accuracy of Caudocranial Canine Femoral Radiographs Compared to Computed Tomography Multiplanar Reconstructions for Measurement of Anatomic Lateral Distal Femoral Angle.

OBJECTIVE: This study aimed to compare the accuracy of sternal recumbency caudocranially obtained radiographs of canine femora to computed tomographic (CT) frontal plane reconstructions of the same femora for assessing anatomic distal lateral femoral angles (aLDFA). STUDY DESIGN: Multicentre, retrospective study utilizing 81 matched radiographic and CT studies of clinical patients undergoing assessment for various issues were reviewed. Anatomic lateral distal femoral angles were measured, and accuracy assessed with descriptive statistics and Bland-Altman plot analysis, with CT considered the reference standard. Sensitivity and specificity of a cut-off for measured aLDFA (102 degrees) were determined to assess radiography as a screening tool for significant deformity. RESULTS: Radiographs on average overestimated aLDFA by 1.8 degrees compared to CT. Bland-Altman analysis identified a 15.4 degrees 95% limit of agreement range and a tendency for greater overestimation at higher average measured value. Radiographic measurement of aLDFA of 102 degrees or less had a 90% sensitivity, 71.83% specificity, and 98.08% negative predictive value for the CT measurement being less than 102 degrees. CONCLUSION: Accuracy of aLDFA measurement by caudocranial radiographs does not demonstrate sufficient accuracy when compared to CT frontal plane reconstructions with unpredictable differences. Radiographic assessment is a useful screening tool to exclude animals with a true aLDFA of greater than 102 degrees with a high degree of certainty.

PASCAL repair system for patients with mitral regurgitation: A systematic review.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) of the mitral valve has emerged as the standard treatment for patients with mitral regurgitation (MR) with high surgical risk. Even though MitraClip is widely used, the novel PASCAL device system offers distinct technical features. We aim to study the safety and efficacy of the PASCAL repair system in clinically significant MR. METHODS: PubMed, Medline, Cochrane Central Register of Controlled Trials, and EMBASE were searched for articles published from August 2016 until June 2022 to identify studies that investigated the safety and efficacy of PASCAL for patients with degenerative, functional and mixed MR. Primary performance endpoints were technical, device, and procedural successes. Primary safety endpoint was composite 30 day major adverse events (MAE). Secondary endpoints were MR grade at discharge and 30 days, 30 day postprocedural NYHA functional class, left ventricular ejection fraction (LVEF), change in 6-min walk distance (6MWD), 30-day and 12-month all-cause mortality. RESULTS: We included twelve retrospective and prospective observational studies and one randomized controlled study consisting of 1028 patients with severe, symptomatic MR (NYHA III-IV: 84.0%, MR ≥ 3+: 99.7%) and high surgical risk (mean logistic EuroSCORE of 16.4).Technical success was 95.7%, procedural success was 95.2%, and device success was 86.1% relative to the weighted average. MR grade was ≤2+ in 94.7% of patients at discharge and 94.0% patients at 30-day follow-up. Mean 30-day and 12-month mortality after device implantation were 4.54% and 12.2%. CONCLUSION: The PASCAL repair system appears to be a safe and effective therapeutic option to treat severe, symptomatic MR in high surgical risk patients.

Secular trends in the utility of SGLT-2 inhibitors in heart failure patients with type 2 diabetes mellitus across Metro South Health hospitals in South-East Queensland.

BACKGROUND: The 2018 Australian Heart Failure (HF) guidelines strongly recommended commencing sodium-glucose co-transporter-2 inhibitors (SGLT-2is) in HF patients with type 2 diabetes mellitus (T2DM). The uptake of SGLT-2is for HF patients with T2DM in our health service is unknown. AIMS: To determine the adoption of the 2018 HF guidelines by assessing the temporal trends of SGLT-2is' usage in HF patients with T2DM at Metro South Health (MSH) hospitals, in South-East Queensland. METHODS: Retrospective analysis of all HF patients (ejection fraction (EF) < 50%) with T2DM who were managed within MSH hospitals between June 2018 and June 2021. RESULTS: A total of 666 patients met the inclusion criteria with 918 HF encounters. Mean age was 72 years and 71% were male (473/666). Mean EF was 30% (SD ± 11%), and mean estimated glomerular filtration rate was 48 mL/min/1.73 m2 (SD ± 25). Fifty-four per cent (362/666) had contraindications to SGLT-2is. Among those without contraindications, there was a five-fold increase in the utility of SGLT-2is, 7% (2/29) before versus 38% (103/275) after implementation of the HF guidelines (P < 0.001). Patients on SGLT-2is were younger (64 years vs 69 years, P = 0.002) and had a lower number of HF hospitalisations (1.1 vs 2.1, P = 0.01). CONCLUSIONS: During the study period, 54% of our HF patients with T2DM were not on SGLT-2is due to prescribing guidelines/limitations in the Australian context. We observed a five-fold significant increase in the uptake of SGLT-2is before and after implementation of HF guidelines among patients without contraindications to SGLT-2is. There were significantly fewer HF hospitalisations among patients on SGLT-2is compared to those without.

The World-Wide Adaptations of Diabetic Management in the Face of COVID-19 and Socioeconomic Disparities: A Scoping Review.

Diabetes is an increasingly prevalent chronic disease throughout the world. It is imperative for patients to have access to reliable treatment and resources in order to avoid long-term complications. Economic and social factors contribute to the accessibility of these resources and have a direct impact on diabetes management. Socioeconomic status (SES) presents challenges to diabetic management due to financial and geographical access to care, medications, educational resources, healthy food options, and physical activity. The coronavirus (COVID-19) pandemic exacerbated these challenges, especially during the height of lockdowns. Therefore, it is important to gain insight into how the pandemic challenged diabetes management, taking into consideration socioeconomic disparities. The objective is to assess how the COVID-19 pandemic has impacted the care of chronic diabetic patients internationally and determine how these outcomes vary between patients of different socioeconomic classes. The following study was designed as a scoping review and utilized PubMed, EMBASE, CINAHL, and Web of Science. A Boolean search strategy combined search terms as follows: (((COVID-19) AND (diabetes)) AND ((socioeconomic factors) OR (social inequality OR standard of living))) AND (treatment OR management). Inclusion criteria included studies addressing diabetic patients, socioeconomic variables (income, occupation, level of education, and ethnicity), glycemic control, and degree of access to quality healthcare. Studies exploring the pathophysiology of COVID-19 or diabetes mellitus were excluded. In addition, studies were chosen between the years 2020 and 2022. The search resulted in 214 articles. The full-text assessment was then conducted on the remaining 67 articles. After screening for eligibility and relevance, 19 articles were retained for this review. The results of this study indicate that 8 out of the 18 studies revealed worse outcomes for those with diabetes mellitus and concomitant COVID-19 infection. Patients with diabetes were more likely to be hospitalized and represent a larger percentage of COVID-19 fatalities. In addition, patients with diabetes and co-morbid COVID-19 infection were more likely to have a higher hemoglobin A1c (HbA1c), belong to a lower SES, and have worse glycemic control due to pandemic-associated lockdown. In order to combat the effects of the pandemic, many countries created novel and innovative management strategies. Overall, there are positive and negative effects from the pandemic on diabetic management strategies. This scoping review identified successes in diabetic treatment under pandemic conditions and areas that need optimization. The successful adaptations of many nations convey the capacity for new policy implementation to care for diabetic patients regardless of SES.

Glottalized lateral in Rikvani Andi: an acoustic study.

Glottalized sonorants are a rare sound type that has been under scrutiny for a number of reasons of general relevance to the phonetic theory. It has been claimed that the timing of glottalization of glottalized sonorants may shift in accordance with the position in the syllable onset (pre-glottalization) or coda (post-glottalization), to provide a cue for its place of articulation; other studies argued against this claim. The paper investigates acoustic properties of the glottalized lateral in Rikvani Andi, a one-village dialect of Andi (East Caucasian). Based on the data from elicitations and free narratives, we consider the acoustic correlates that have been argued in the literature to differentiate glottalized sonorants from their modal counterparts, including aperiodicity, intensity, duration and spectral tilt. In Rikvani Andi, all of the correlates prove to be statistically significant in recordings of isolated words, but the differences tend to decrease in free narratives. The timing of glottalization does not support the existing generalizations - while the glottalized lateral only occurs in Rikvani Andi in the syllable onset, it tends to be mid- to post-glottalized. We discuss two possible explanations of why the Rikvani Andi glottalized sonorant fails to comply with typological expectations.

Analysis of variation in pre-procedural fasting duration for common inpatient gastrointestinal procedures.

Background: Gastrointestinal procedures generally require pre-procedural fasting to optimize sedation safety. While the American Society of Anesthesiologists (ASA) recommends no intake of clear liquids and solid food 2-4 and 6-8 hours respectively prior to endoscopic procedures, the actual nil per os (NPO) duration for these procedures in practice is unknown. Our objective was to analyze NPO duration for patients undergoing these procedures and to determine its association with clinical and administrative variables. Methods: Inpatient data from 2016-2018 for the three procedures was extracted from electronic medical records and administrative data at a single-center tertiary academic medical center. Various statistical tests (Kruskal-Wallis, Wilcoxon, Pearson) were employed depending on the outcome type and data distribution. Results: One thousand three hundred and twenty-five esophagogastroduodenoscopies (EGDs), 753 colonoscopies, and 550 endoscopic retrograde cholangiopancreatographies (ERCPs) were included. The median NPO time for all procedures was 12.6 hours (IQR, 9.6-16.1 hours). The median NPO times were 12.6, 11.9, and 13.1 hours for EGD, colonoscopy, and ERCP respectively. NPO duration was greater for Hispanic than non-Hispanic patients (median 13.9 vs. 12.4, P=0.018). NPO duration was also associated with increased age (r=0.041, P=0.027) and inversely related to hospital occupancy (r=-0.08, P<0.0001). There were no statistically significant associations with provider type, hospital location or service, length of stay, and total number of comorbidities. Conclusions: NPO times for common inpatient gastroenterology (GI) procedures generally exceeded 12 hours, suggesting there is an opportunity to adopt changes to decrease NPO duration for low-risk patients while maintaining adherence to guidelines and best practice.

Geography and language divergence: The case of Andic languages.

We study the correlation between phylogenetic and geographic distances for the languages of the Andic branch of the East Caucasian (Nakh-Daghestanian) language family. For several alternative phylogenies, we find that geographic distances correlate with linguistic divergence. Notably, qualitative classifications show a better fit with geography than cognacy-based phylogenies. We interpret this result as follows: The better fit may be due to implicit geographic bias in qualitative classifications. We conclude that approaches to classification other than those based on cognacy run a risk to implicitly include geography and geography-related factors as one basis of genealogical classifications.

Targeted exon skipping of NF1 exon 17 as a therapeutic for neurofibromatosis type I.

We investigated the feasibility of utilizing an exon-skipping approach as a genotype-dependent therapeutic for neurofibromatosis type 1 (NF1) by determining which NF1 exons might be skipped while maintaining neurofibromin protein expression and GTPase activating protein (GAP)-related domain (GRD) function. Initial in silico analysis predicted exons that can be skipped with minimal loss of neurofibromin function, which was confirmed by in vitro assessments utilizing an Nf1 cDNA-based functional screening system. Skipping of exons 17 or 52 fit our criteria, as minimal effects on protein expression and GRD activity were noted. Antisense phosphorodiamidate morpholino oligomers (PMOs) were utilized to skip exon 17 in human cell lines with patient-specific pathogenic variants in exon 17, c.1885G>A, and c.1929delG. PMOs restored functional neurofibromin expression. To determine the in vivo significance of exon 17 skipping, we generated a homozygous deletion of exon 17 in a novel mouse model. Mice were viable and exhibited a normal lifespan. Initial studies did not reveal the presence of tumor development; however, altered nesting behavior and systemic lymphoid hyperplasia was noted in peripheral lymphoid organs. Alterations in T and B cell frequencies in the thymus and spleen were identified. Hence, exon skipping should be further investigated as a therapeutic approach for NF1 patients with pathogenic variants in exon 17, as homozygous deletion of exon 17 is consistent with at least partial function of neurofibromin.

Brief visuospatial memory test-revised normative data and form equivalency for adults ages 80-89.

Objective: To provide normative data and examine form equivalency of the Brief Visuospatial Memory Test-Revised (BVMT-R) in a sample of 9th decade adults. Method: The sample was comprised of 90 healthy individuals ages 80-84 (n = 42) and 85-89 (n = 48). The average years of education was 14.8 (2.4). The BVMT-R Forms 1 and 4 were administered in a counterbalanced order, one week apart. Form equivalency was conducted utilizing Analysis of Variance (ANOVA). Results: There were no significant gender, education, or MMSE differences between the two age groups or between the counterbalanced subgroups. There were no significant differences between Forms 1 and 4 for the 80-84 age group. However, BVMT-R Form 1 Trial 1 and Total Recall raw scores were significantly higher than those for Form 4 in the 85-89 age group. Conclusions: Individuals in their early 80s obtained comparable scores on Forms 1 and 4 of the BVMT-R; however, individuals in their late 80 s showed more difficulty learning and recalling information presented in Form 4 compared to Form 1. It is recommended that clinicians consider form-specific normative data with this population.

Analysis of patient-specific NF1 variants leads to functional insights for Ras signaling that can impact personalized medicine.

We have created a panel of 29 NF1 variant complementary DNAs (cDNAs) representing missense variants, many with clinically relevant phenotypes, in-frame deletions, splice variants, and nonsense variants. We have determined the functional consequences of the variants, assessing their ability to produce mature neurofibromin and restore Ras signaling activity in NF1 null (-/-) cells. cDNAs demonstrate variant-specific differences in neurofibromin protein levels, suggesting that some variants lead to neurofibromatosis type 1 (NF1) gene or protein instability or enhanced degradation. When expressed at high levels, some variant proteins are still able to repress Ras activity, indicating that the NF1 phenotype may be due to low protein abundance. In contrast, other variant proteins are incapable of repressing Ras activity, indicating that some do not functionally engage Ras and stimulate GTPase activity. We observed that effects on protein abundance and Ras activity can be mutually exclusive. These assays allow us to categorize variants by functional effects, may help to classify variants of unknown significance, and may have future implications for more directed therapeutics.

Frequency of neurological manifestations in COVID-19: a systematic review and meta-analysis of 350 studies

ObjectiveTo summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality. DesignSystematic review and meta-analysis Eligibility criteriaStudies enrolling consecutive COVID-19 patients (probable or confirmed) presenting with neurological manifestations. Data sourcesPubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31st December 2019 to 15th December 2020. Data extraction and analysisTwo authors independently screened titles and abstracts retrieved by literature search. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2. ResultsOf 2,455 citations, 350 studies were included in this review, providing data on 145,634 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence-2%). In COVID-19 patients aged >60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91). ConclusionsUp to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias. Systematic review registrationPROSPERO CRD42020181867. What is already known on this topicThe frequency of neurological manifestations including fatigue, myalgia, taste and smell impairments, headache and dizziness in COVID-19 patients has been reported in a few systematic reviews and meta-analyses. However, considerable heterogeneity has been observed in terms of methodological quality of the studies, severity of the disease, mean age and hospitalization status of the patients. The evidence regarding the frequency of neurological diagnoses including stroke, encephalitis, Guillain Barre syndrome (GBS) is also limited to case reports and case series and no data exists thus far on the pooled prevalence estimates for neurological diagnoses in COVID-19 patients. What this study addsTo the best of the authors knowledge, this is the largest systematic review and meta-analysis to date (including 350 studies with data on 145,634 cases) summarizing the evidence on the frequency of the full spectrum of neurological manifestations in COVID-19 patients in the overall, young and elderly populations. For the first time, our review reports the pooled prevalence of stroke in COVID-19 patients. Risk of bias, old age and disease severity were potential determinants of the frequency and nature of neurological manifestations as well as its association with mortality. Our review also highlights the need to develop reporting standards for studies describing the frequency of clinical features. Moreover, we note that this will be the first systematic review and meta-analysis on this subject to include studies reported in all languages.