Clavulanic Acid Decreases Cocaine Cue Reactivity in Addiction-Related Brain Areas, a Randomized fMRI Pilot Study.

Background: Preclinical studies show that clavulanic acid (CLAV) inhibits cocaine self-administration. This study investigates the effect of CLAV on regions of brain activation in response to cocaine cues during functional magnetic resonance imaging (fMRI) in participants with cocaine use disorder (CUD). Methods: A double-masked, placebo-controlled clinical trial with thirteen individuals with severe CUD who were randomized to treatment with CLAV (N = 10, 9 completers) 500 mg/day or matched placebo (PBO) (N = 3) for 3 days. fMRI was used to assess brain reactivity to 18 alternating six-second video clips of cocaine or neutral scenes. In this paradigm, participants were exposed to three different stimulus conditions: NEUTRAL, WATCH (passive watching), and DOWN (actively inhibiting craving while watching). Results: Participants who received CLAV demonstrated a significant reduction in brain activity in the anterior cingulate gyrus (p = 0.009) and the caudate (p = 0.018) in response to DOWN cocaine cues. There was a trend toward lessened cue reactivity in other regions implicated in CUD. Conclusion: CLAV reduced the response of the brain regions associated with motivation and emotional response during the DOWN condition compared to PBO, suggesting CLAV may strengthen voluntary efforts to avoid cocaine use. This pilot data supports the use of CLAV for CUD. (Trial registered in ClinicalTrials.gov NCT04411914).

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.

Virtual Reality for the Management of Pain and Anxiety for IR Procedures: A Prospective, Randomized, Pilot Study on Digital Sedation.

PURPOSE: To assess the analgesic and anxiolytic effects of virtual reality (VR) augmentation in patients undergoing peripherally inserted central catheter (PICC) placement or fine-needle aspiration thyroid biopsy. MATERIALS AND METHODS: This is a prospective, single-center randomized controlled trial with 107 patients enrolled. Patients were randomly assigned to receive standard of care (SOC) or SOC+VR during PICC or thyroid biopsy procedures. Pain and anxiety were individually measured using the visual analog scale (VAS) before and after the procedure. Vital signs including heart rate and systolic and diastolic blood pressure were recorded. One-way analysis of variance test and Games-Howell post hoc analysis were used to assess effect size and statistical significance between SOC and SOC+VR measures. RESULTS: The PICC cohort consisted of 59 patients (33 in SOC+VR and 26 in SOC), with a median age of 53.1 years (interquartile range [IQR], 38.3-62.7 years). The thyroid biopsy cohort consisted of 48 patients (26 in SOC+VR and 22 in SOC), with a median age of 60.1 years (IQR, 49.0-67.2 years). One-way analysis of individuals undergoing thyroid biopsies with adjunctive VR revealed an effect size of -1.74 points (SE ± 0.71; P = .018) on VAS pain scale when compared with SOC. Analysis of individuals undergoing PICC placements revealed an effect size of -1.60 points (SE ± 0.81; P = .053) on VAS anxiety when compared with SOC. CONCLUSIONS: VR as a nonpharmacologic adjunct reduced some procedure-related pain and anxiety without increasing the procedural duration.

Fourier Phase Analysis of Dynamic Antral Contraction Scintigraphy: New Software, Reference Values, and Comparisons to Conventional Gastric Emptying.

Dynamic antral contraction scintigraphy (DACS) has been used to evaluate for gastric dysmotility by measuring antral contraction frequency and ejection fraction (EF). Fourier phase image analysis has the potential to assess gastric antral contractions for dyssynchrony as has been used for analyzing nuclear cardiology ventriculography (multigated acquisition studies) for cardiac dyssynchrony. The aims of this study were to determine whether Fourier phase analysis helps to characterize antral motility physiology, whether Fourier phase analysis correlates with conventional gastric emptying scintigraphy (GES), and which DACS parameters may aid in diagnosing gastric dysmotility, particularly delayed gastric emptying (GE). Methods: DACS and GES of healthy volunteers (n = 22) were compared with patients (n = 99) with symptoms of gastroparesis. New DACS Fourier phase analysis software was developed. Results: GE was delayed (n = 53) or normal (n = 46) in patients. There was a linear correlation between the time for the stomach to empty 50% of the meal and the percentage total proximal and distal in-phase antral pixels at 30 min (r = 0.37, P = 0.0001) and 60 min (r = 0.26, P = 0.007). In healthy volunteers, the mean proximal-to-distal ratio of in-phase antral pixels increased from 1.67 (30 min) to 2.65 (120 min) (P = 0.035), and EF increased from 23% (30 min) to 32% (120 min) (P = 0.022). Multivariable regressions of percentage total proximal and distal in-phase antral pixels (30 min) and EF (60 min) were the best predictors of abnormal GE (adjusted odds ratio, 3.30 [95% CI, 1.21-9.00] and 2.97 [95% CI, 1.08-8.21], respectively). Conclusion: This study used Fourier phase analysis to analyze DACS in healthy volunteers and patients with symptoms of gastroparesis. In addition to establishing reference values, new physiologic information on antral motility was obtained. In healthy volunteers, there was an increasing proximal-to-distal ratio of in-phase antral pixels and antral EF over time after meal ingestion. The percentage total proximal and distal in-phase antral pixels at both 30 and 60 min correlated well with GE values for the time for the stomach to empty 50% of the meal. For symptomatic patients, the percentage total proximal and distal in-phase antral pixels at 30 min and the EF at 60 min after meal ingestion correlated with delayed GE on conventional GES. Thus, Fourier phase analysis of DACS appears to have potential to further aid in diagnosing gastric dysmotility in GES.

Effects of maternal hypothyroidism on postnatal cardiomyocyte proliferation and cardiac disease responses of the progeny.

Maternal hypothyroidism (MH) could adversely affect the cardiac disease responses of the progeny. This study tested the hypothesis that MH reduces early postnatal cardiomyocyte (CM) proliferation so that the adult heart of MH progeny has a smaller number of larger cardiac myocytes, which imparts adverse cardiac disease responses following injury. Thyroidectomy (TX) was used to establish MH. The progeny from mice that underwent sham or TX surgery were termed Ctrl (control) or MH (maternal hypothyroidism) progeny, respectively. MH progeny had similar heart weight (HW) to body weight (BW) ratios and larger CM size consistent with fewer CMs at postnatal day 60 (P60) compared with Ctrl (control) progeny. MH progeny had lower numbers of EdU+, Ki67+, and phosphorylated histone H3 (PH3)+ CMs, which suggests they had a decreased CM proliferation in the postnatal timeframe. RNA-seq data showed that genes related to DNA replication were downregulated in P5 MH hearts, including bone morphogenetic protein 10 (Bmp10). Both in vivo and in vitro studies showed Bmp10 treatment increased CM proliferation. After transverse aortic constriction (TAC), the MH progeny had more severe cardiac pathological remodeling compared with the Ctrl progeny. Thyroid hormone (T4) treatment for MH mothers preserved their progeny's postnatal CM proliferation capacity and prevented excessive pathological remodeling after TAC. Our results suggest that CM proliferation during early postnatal development was significantly reduced in MH progeny, resulting in fewer CMs with hypertrophy in adulthood. These changes were associated with more severe cardiac disease responses after pressure overload.NEW & NOTEWORTHY Our study shows that compared with Ctrl (control) progeny, the adult progeny of mothers who have MH (MH progeny) had fewer CMs. This reduction of CM numbers was associated with decreased postnatal CM proliferation. Gene expression studies showed a reduced expression of Bmp10 in MH progeny. Bmp10 has been linked to myocyte proliferation. In vivo and in vitro studies showed that Bmp10 treatment of MH progeny and their myocytes could increase CM proliferation. Differences in CM number and size in adult hearts of MH progeny were linked to more severe cardiac structural and functional remodeling after pressure overload. T4 (synthetic thyroxine) treatment of MH mothers during their pregnancy, prevented the reduction in CM number in their progeny and the adverse response to disease stress.

Seasonal Variations and Factors that Influence Diverticular Bleeding in the United States of America.

BACKGROUND: Seasonal variation in hospitalizations for diverticulitis has a sinusoidal pattern, peaking in summer. Little is known about seasonal, regional trends, and risk factors associated with hospital admissions regarding diverticular bleeding in the United States. STUDY DESIGN: Cross-sectional population database review using the healthcare cost and utilization project's national inpatient sample. METHODS: Patients that had diagnoses of diverticulitis with bleeding or diverticulosis with bleeding admitted from January 1, 2015, through December 31, 2017, were identified and stratified by month and season. Then, the potential effects of region, age, gender, race, and patient risk factors on seasonal admissions for diverticular bleeding were explored, and data were analyzed in SAS and presented in Excel using chi-square and Kruskal-Wallis for categorical and continuous variables, respectively. RESULTS: Of the 54191 hospitalized cases for diverticular bleeding, the peak and the lowest seasons were spring and summer (25.5% vs. 24.2%, P<0.0001). A significant seasonal pattern in comorbidities was also identified, and those with diabetes (P<0.0001), hypertension (HTN) (P<0.0001), obesity (P<0.0001), and those on anticoagulants (P=0.016) all had more bleeding events in the spring. This was noted across US regions, gender, race, and age. Eventually, the southern region had the most admissions for diverticular bleeding at 40.9% (P<0.0001). CONCLUSION: A better understanding of these seasonal and regional trends may provide a mechanism to identify a potential trigger for diverticular bleeding events. This helps identify individuals at greatest risk for hospitalization, as well as prepare hospitals to allocate supplies appropriately during the seasons.

Understanding the Challenges Faced by Esophageal and Gastroesophageal Junction Cancer Survivors.

The primary aim of this study is to characterize long-term quality of life (QOL) in patients with esophageal and gastroesophageal junction (EGEJ) cancers who underwent curative intent treatment. EGEJ survivors were recruited to participate in a one-time cross-sectional survey study using validated questionnaires assessing QOL. Chart review was conducted for patient demographics and clinical characteristics. Spearman correlation coefficients, Wilcoxon signed-rank test, and Fisher's exact test were used to assess relationships between patient characteristics and long-term outcomes. QOL was relatively high in this sample, as evidenced by high median scores on the functional scales and low median scores in the symptom domains of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, with an overall median global health score of 75.0 (range 66.7-83.3). Patients using opiates at the time of survey reported lower role functioning (P = .004), social functioning (P = .052), and overall global health (P = .041). Younger patients had significantly higher rates of reflux (P = .019), odynophagia (P = .045), choking (P = .005), and cough (P = .007). Patients using opiates or of younger age had lower QOL and higher symptoms in this cohort of long-term EGEJ survivors.

Combining three independent pathological stressors induces a heart failure with preserved ejection fraction phenotype.

Heart failure (HF) with preserved ejection fraction (HFpEF) is defined as HF with an ejection fraction (EF) ≥ 50% and elevated cardiac diastolic filling pressures. The underlying causes of HFpEF are multifactorial and not well-defined. A transgenic mouse with low levels of cardiomyocyte (CM)-specific inducible Cavß2a expression (ß2a-Tg mice) showed increased cytosolic CM Ca2+, and modest levels of CM hypertrophy, and fibrosis. This study aimed to determine if ß2a-Tg mice develop an HFpEF phenotype when challenged with two additional stressors, high-fat diet (HFD) and Nω-nitro-l-arginine methyl ester (l-NAME, LN). Four-month-old wild-type (WT) and ß2a-Tg mice were given either normal chow (WT-N, ß2a-N) or HFD and/or l-NAME (WT-HFD, WT-LN, WT-HFD-LN, ß2a-HFD, ß2a-LN, and ß2a-HFD-LN). Some animals were treated with the histone deacetylase (HDAC) (hypertrophy regulators) inhibitor suberoylanilide hydroxamic acid (SAHA) (ß2a-HFD-LN-SAHA). Echocardiography was performed monthly. After 4 mo of treatment, terminal studies were performed including invasive hemodynamics and organs weight measurements. Cardiac tissue was collected. Four months of HFD plus l-NAME treatment did not induce a profound HFpEF phenotype in FVB WT mice. ß2a-HFD-LN (3-Hit) mice developed features of HFpEF, including increased atrial natriuretic peptide (ANP) levels, preserved EF, diastolic dysfunction, robust CM hypertrophy, increased M2-macrophage population, and myocardial fibrosis. SAHA reduced the HFpEF phenotype in the 3-Hit mouse model, by attenuating these effects. The 3-Hit mouse model induced a reliable HFpEF phenotype with CM hypertrophy, cardiac fibrosis, and increased M2-macrophage population. This model could be used for identifying and preclinical testing of novel therapeutic strategies.NEW & NOTEWORTHY Our study shows that three independent pathological stressors (increased Ca2+ influx, high-fat diet, and l-NAME) together produce a profound HFpEF phenotype. The primary mechanisms include HDAC-dependent-CM hypertrophy, necrosis, increased M2-macrophage population, fibroblast activation, and myocardial fibrosis. A role for HDAC activation in the HFpEF phenotype was shown in studies with SAHA treatment, which prevented the severe HFpEF phenotype. This "3-Hit" mouse model could be helpful in identifying novel therapeutic strategies to treat HFpEF.

Utility of the CANUKA Scoring System in the Risk Assessment of Upper GI Bleeding.

BACKGROUND: The Canada-United Kingdom-Adelaide (CANUKA) score was developed to stratify patients who experience upper gastrointestinal bleeding (UGIB) to predict who could be discharged from the emergency department. Our aim was to determine if the CANUKA score could be utilized for UGIB in-patients undergoing endoscopy in predicting adverse outcomes. We additionally sought to establish a CANUKA score cut point to predict adverse outcomes and in-hospital mortality and compare this to established scoring systems. METHODS: Between January 1, 2018 to June 30, 2019 all patients who underwent upper endoscopy after admission for UGIB were identified. We assigned a CANUKA score and compared the area under the receiver operating curve to established scoring systems. RESULTS: Our data set included 641 patients, with a mean age of 59.5±14.5 years. A CANUKA score ≥10 was associated with an adverse outcome [unadjusted odds ratio, 3.08 (1.79, 5.27)]. No patients experienced an adverse outcome with a CANUKA score <4. No patients died with a CANUKA score <6. Those with a CANUKA score of <10 had an in-hospital mortality of 2.1% compared with 6.8% for those with a score ≥10 ( P =0.008). AIMS65 had the best area under the receiver operating characteristic curve (0.809) for predicting mortality. CONCLUSIONS: The CANUKA score may serve utility as a predictor of adverse outcomes and mortality in patients admitted with UGIB undergoing endoscopy. Future studies, ideally prospective and multicenter, will be needed to validate its clinical utility.

A comparison of primary and secondary eye removal after open globe injury: A multi-centre study.

BACKGROUND/OBJECTIVES: Our goal was to compare the characteristics and surgical outcomes of patients who underwent primary eye removal surgery after open globe injury with those who underwent secondary eye removal surgery after open globe repair. SUBJECTS/METHODS: This was a retrospective review of subjects who underwent evisceration or enucleation within 3 months of an open globe injury, at three Level I trauma centres in three U.S. cities between July 2014 and July 2020. RESULTS: 19 patients underwent primary eye removal and 20 underwent secondary eye removal. The most common mechanism of trauma in patients who underwent primary eye removal was gunshot. Compared to the secondary eye removal group, patients who underwent primary eye removal were significantly more likely to be male; have longer hospital stays; be discharged to another care facility rather than home; have facial fractures; suffer intracranial injury; and be unable to consent themselves for surgery. Both groups had a low surgical complication rate with one case of socket contracture in each group. CONCLUSIONS: The standard of care for an open globe injury is prompt repair, but there are occasions when the globe is so damaged that it is deemed unrepairable. We found that globes that required primary eye removal were more often due to gunshot wounds, and that there was greater morbidity associated with these injuries. The authors' preferred surgical approach was evisceration with placement of a silicone sphere; patient outcomes demonstrate that this method was found to be safe, with a low complication and infection rate.

Gender and Racial Bias in Letters of Recommendation for Orthopedic Surgery Residency Positions.

OBJECTIVE: The primary purpose of this study was to retrospectively analyze letters of recommendation written for medical students applying to orthopedic residency for implicit race and gender bias. The secondary purpose was to determine if the presence of bias was influenced by the gender of the letter writer. DESIGN: This was a retrospective institutional review board (IRB) approved study. All letters of recommendation received in the years 2016 to 2018 were deidentified and analyzed using the Linguistics Inquiry and Word Count (LIWC) 2015 software. Independent variables in our analysis were applicant gender and applicant race. Dependent study variables included the summary and characteristic variables of a letter of recommendation, which are word count, analytic, clout, authenticity, tone, and positive and negative emotion word categories. Separate analyses were completed by gender of the letter writer as well. SETTING: Institution: Temple University Hospital, Philadelphia, Pennsylvania. PARTICIPANTS: Medical students applying to Temple University Hospital Orthopaedic Surgery Program from 2016 to 2018. A total of 2113 applicants were included in the study. RESULTS: Female, Asian and underrepresented minority applicants' letters were more likely to have a higher word count. In our subset analysis by gender of letter writer, when the letter writer was male, Asian applicants' letters were more likely to convey analytical thinking and authenticity. When the letter writer was male, male applicants scored higher for authenticity. Letters written by female attendings demonstrated no significant difference for male or female applicants in terms of composite variables or word categories. CONCLUSIONS: Our study shows that letters of recommendation for orthopedic surgery residency positions are likely to contain some degree of bias. Further studies are required to fully characterize the degree and magnitude of bias in letters of recommendation and whether the findings of our study are significant enough to contribute to the difference in socioeconomic demographics between orthopedic residents and society at large.

Seasonal and Geographic Variation in Peptic Ulcer Disease and Associated Complications in the United States of America.

BACKGROUND: Hospitalization for peptic ulcer disease (PUD) has been described outside of North America as peaking in the fall and winter. However, no recent literature has so far investigated the seasonal fluctuations and complications of PUD in the USA. Study Design: Cross-sectional population database review. METHODS: Patients with a diagnosis of either acute gastric or acute duodenal ulcers from January 1, 2015, through December 31, 2017, were identified in the Healthcare Cost and Utilization Project's National Inpatient Sample. The proportion of admissions with either hemorrhage or perforation was determined for each season and further subdivided into geographic regions. RESULTS: Of 18829 hospitalizations for PUD, admissions were the highest in the fall (25.9%) while being the lowest in the summer (23.9%). Complications, hemorrhage or perforation, were the highest and the lowest in the fall and spring, respectively (75.7% vs. 73.6%; P=0.060 for comparing all 4 seasons). Geographically, the West had the highest rate of peptic ulcer hemorrhage (64.5%, P=0.004), while the northeast had the highest rate of perforation (14.3%, P=0.003). Hemorrhage was more common in males, those who used aspirin, nonsteroidal anti-inflammatory drugs, or anticoagulants, and diabetics (P<0.05). Perforation was less common in males, those with diabetes, obesity, or hypertension (HTN), or those using aspirin or anticoagulants (P<0.05). Helicobacter pylori infection was more associated with perforation in the fall and winter months. CONCLUSION: Seasonal and regional trends in hospitalizations due to PUD may help identify modifiable risk factors, which can improve diagnostic and treatment outcomes for patients by allowing for more targeted identification of vulnerable populations.

Combination of STING and TLR 7/8 Agonists as Vaccine Adjuvants for Cancer Immunotherapy.

Immunostimulatory adjuvants that potently activate antigen-presenting cells and (in turn) prime cytotoxic T cells are a key component of anticancer vaccines. In this study, we investigated a multi-adjuvant approach combining a TLR 7/8 agonist (522) and a STING agonist (DMXAA) to promote enhanced antigen cross-presentation, stimulate specific antitumor T-cell responses, and provide improved anticancer efficacy. In vitro experiments using bone marrow-derived dendritic cells (BMDCs) confirmed enhanced activation with the 522-DMXAA combination based on both co-stimulatory molecule expression and pro-inflammatory cytokine secretion. The immunization of mice with vaccines comprising both 522 and DMXAA resulted in greater antitumor efficacy in B16F10 melanoma and MB49 bladder tumor models relative to mono-agonist vaccines. Flow cytometry-based analysis of immune cells from immunized mice revealed the significant activation of antigen-presenting cells, increased numbers of activated and Ag-specific CD8+ T cells in the spleen and lymph nodes, modest NK cell activation, and an overall reduction in CD206+ macrophages. These results were supported by an increase in the levels of IFN-γ and a reduction in IL-10 levels in the sera. Taken together, these findings demonstrate the potential of the TLR7/8 and STING agonist combination as vaccine adjuvants to activate both innate and adaptive immune responses.

Dog and human bladders have different neurogenic and nicotinic responses in inner versus outer detrusor muscle layers.

The aim of this study was to investigate layer and species variations in detrusor muscle strip responses to myogenic, neurogenic, and nicotinic, and muscarinic receptor stimulations. Strips from bladders of 9 dogs and 6 human organ transplant donors were dissected from inner and outer longitudinal muscle layers, at least 1 cm above urethral orifices. Strips were mounted in muscle baths and maximal responses to neurogenic stimulation using electrical field stimulation (EFS) and myogenic stimulation using potassium chloride (KCl, 120 mM) determined. After washing and re-equilibration was completed, responses to nicotinic receptor agonist epibatidine (10 µM) were determined followed by responses to EFS and muscarinic receptor agonist bethanechol (30 µM) in continued presence of epibatidine. Thereafter, strips and full-thickness bladder sections from four additional dogs and three human donors were examined for axonal density and intramural ganglia. In dog bladders, contractions to KCl, epibatidine, and bethanechol were 1.5- to 2-fold higher in the inner longitudinal muscle layer, whereas contractions to EFS were 1.5-fold higher in the outer (both pre- and post-epibatidine). Human bladders showed 1.2-fold greater contractions to epibatidine in the inner layer and to EFS in the outer, yet no layer differences to KCl or bethanechol were noted. In both species, axonal density was 2- to 2.5-fold greater in the outer layer. Dogs had more intramural ganglia in the adventitia/serosa layer, compared with more internal layers and to humans. These findings indicate several layer-dependent differences in receptor expression or distribution, and neurogenic responses in dog and human detrusor muscles, and myogenic/muscarinic differences between dog versus humans.

Safe perioperative tamoxifen use in autologous breast free flap reconstruction: systematic review and meta-analysis.

BACKGROUND: Perioperative tamoxifen remains a valuable therapeutic modality for breast cancer patients. Studies in the existing literature have suggested a potential increased risk of thrombotic complications in autologous breast free flap reconstruction patients exposed to tamoxifen perioperatively. However, several recent publications have questioned the validity of these associations. Therefore, we aim to perform a systematic appraisal of the existing literature to determine if perioperative tamoxifen exposure increases the risk of flap complications in autologous breast-free flap reconstruction patients. METHODS: A systematic literature search was performed using: PubMed, EMBASE, Cochrane Central, Web of Science, EBSCOHost, ClinicalTrials.gov, and TRIP databases from their inception up to April 2021. Articles analyzing the impact of perioperative tamoxifen in autologous breast free flap patients were included. The outcomes assessed were total flap loss, overall flap complications, thrombotic flap complications, which was defined as the sum of arterial and venous flap thrombi, and systemic venous thromboembolism (VTE). Pooled estimates and relative risk were calculated using a random effects model. RESULTS: 9294 Articles were screened and 7 were selected for analysis, which included 3669 flaps in 2759 patients. Compared to patients who did not receive tamoxifen perioperatively, those who received tamoxifen did not have an increased risk of thrombotic flap complications (pooled RR 1.06; 95% CI 0.61-1.84), total flap loss (pooled RR 2.17; 95% CI 0.79-5.95), overall flap complications (pooled RR 1.04; 95% CI 0.76-1.41), or systemic VTE (pooled RR 1.93; 95% CI 0.72-5.13). The heterogeneity of the studies was not significant for any of the outcomes. CONCLUSIONS: The purpose of this study was to update the current understanding of the impact of perioperative tamoxifen on autologous breast free flap reconstruction outcomes. The existing literature supports that the perioperative continuation of tamoxifen in breast free flap patients is not associated with an increased risk of thrombotic flap complications, total flap loss, overall flap complications, or systemic VTE.

Association of Retromer Deficiency and Tau Pathology in Down Syndrome.

Retromer deficiency is reported in Down syndrome and correlates with amyloidosis, however, its association with tau neuropathology remains unclear. Down syndrome and control brain tissues were evaluated for phosphorylated tau, tau modulators, and cathepsin-D activity. Several kinases and phosphatase PP2A were unchanged, but tau phosphorylation was elevated, and cathepsin-D activity decreased in aged patients with Down syndrome. Retromer proteins positively associated with soluble tau, whereas pathogenic tau negatively correlated with retromer proteins and cathepsin-D activity. Retromer deficiency and consequent reduction of cathepsin-D activity may contribute to pathogenic tau accumulation, thus, retromer represents a viable therapeutic target against tau pathology in Down syndrome. ANN NEUROL 2022;91:561-567.

A Comparison of Artificial Intelligence and Human Diabetic Retinal Image Interpretation in an Urban Health System.

INTRODUCTION: Artificial intelligence (AI) diabetic retinopathy (DR) software has the potential to decrease time spent by clinicians on image interpretation and expand the scope of DR screening. We performed a retrospective review to compare Eyenuk's EyeArt software (Woodland Hills, CA) to Temple Ophthalmology optometry grading using the International Classification of Diabetic Retinopathy scale. METHODS: Two hundred and sixty consecutive diabetic patients from the Temple Faculty Practice Internal Medicine clinic underwent 2-field retinal imaging. Classifications of the images by the software and optometrist were analyzed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and McNemar's test. Ungradable images were analyzed to identify relationships with HbA1c, age, and ethnicity. Disagreements and a sample of 20% of agreements were adjudicated by a retina specialist. RESULTS: On patient level comparison, sensitivity for the software was 100%, while specificity was 77.78%. PPV was 19.15%, and NPV was 100%. The 38 disagreements between software and optometrist occurred when the optometrist classified a patient's images as non-referable while the software classified them as referable. Of these disagreements, a retina specialist agreed with the optometrist 57.9% the time (22/38). Of the agreements, the retina specialist agreed with both the program and the optometrist 96.7% of the time (28/29). There was a significant difference in numbers of ungradable photos in older patients (≥60) vs younger patients (<60) (p=0.003). CONCLUSIONS: The AI program showed high sensitivity with acceptable specificity for a screening algorithm. The high NPV indicates that the software is unlikely to miss DR but may refer patients unnecessarily.

Sextus chest radiograph severity score correlates to clinical outcomes in patients with COVID-19: A cross-sectional study.

ABSTRACT: The value of chest radiography (CXR) in detection and as an outcome predictor in the management of patients with coronavirus disease-2019 (COVID-19) has not yet been fully understood.To validate a standardized CXR scoring system and assess its prognostic value in hospitalized patients found to have COVID-19 by imaging criteria and to compare it to computed tomography (CT).In this cross-sectional chart review study, patients aged 18-years or older who underwent chest CT at a single institution with an imaging-based diagnosis of COVID-19 between March 15, 2020 to April 15, 2020 were included. Each patient's CXR and coronal CT were analyzed for opacities in a 6-zonal assessment method and aggregated into a "Sextus score." Inter-reader variability and correlation between CXR and coronal CT images were investigated to validate this scoring system. Univariable and multiple logistic regression techniques were used to investigate relationships between CXR scores and clinical parameters in relation to patient outcomes.One hundred twenty-four patients (median [interquartile range] age 58.5 [47.5-69.0] years, 72 [58%] men, 58 [47%] Blacks, and 35 [28%] Hispanics) were included. The CXR Sextus score (range: 0-6) was reliable (inter-rater kappa = 0.76; 95% confidence interval [CI]: 0.69-0.83) and correlated strongly with the CT Sextus score (Spearman correlation coefficient = 0.75, P < .0001). Incremental increases of CXR Sextus scores of 2 points were found to be an independent predictor of intubation (adjusted odds ratio [95% CI]: 4.49 [1.98, 10.20], P = .0003) and prolonged hospitalization (≥10 days) (adjusted odds ratio [95% CI]: 4.06 [1.98, 8.32], P = .0001).The CXR Sextus score was found to be reproducible and CXR-CT severity scores were closely correlated. Increasing Sextus scores were associated with increased risks for intubation and prolonged hospitalization for patients with COVID-19 in a predominantly Black population. The CXR Sextus score may provide insight into identifying and monitoring high-risk patients with COVID-19.

Variation in Practice Patterns of Current Rhinoplasty Surgeons for Nasal Valve Compromise.

Background: To compare practice patterns of rhinoplasty surgeons with the 2010 clinical consensus statements (CCSs) on nasal valve compromise (NVC) and delineate what variables may affect such practice patterns and consensus. Methods: An online questionnaire pertaining to the 2010 CCS was administered at the Advances in Rhinoplasty meeting with responses based on a 9-point Likert scale. Results: Of 580 participants, 113 completed the survey with the majority of statements in accordance between panelists and surveyors. Less than 10% of responses met discordance criteria. Significant differences in practice patterns exist when stratified by specialty, years-in-practice, geographic location, type of practice, and annual number of rhinoplasties performed. Conclusion: There is a general concordance between practice patterns of active rhinoplasty surgeons and the 2010 CCS on NVC despite a decade of new studies in the interim. Significant differences, however, exist regarding the utility of diagnostic imaging, rhinoscopy, nasal endoscopy, and acoustic rhinomanometry in the evaluation of NVC. Furthermore, variables such as specialty, years in practice, annual number of rhinoplasties performed, practice setting, and geographic location significantly affect these perspectives and overall consensus.

Use of a new ALS specific respiratory questionnaire: the ARES score.

Objective: To develop an ALS respiratory symptom scale (ARES) and evaluate how ARES compares to Medical Research Council Modified Dyspnea Scale (MRC), Borg dyspnea scale, and respiratory subscores from ALSFRS-R (ALSFRS-Resp) in detecting respiratory symptoms, correlation with pulmonary function and ALSFRS-R, and deterioration of pulmonary function and ALSFRS-R over time.Methods: The ARES scale consists of 9 questions addressing dyspnea during activities and 3 questions addressing symptoms of worsening pulmonary function. 153 subjects with ALS completed MRC, Borg, ALSFRS-R, and ARES questionnaires at baseline, 16, 32, and 48 weeks, and spirometry at baseline. 73 of these subjects had spirometry, maximum inspiratory (MIP) and expiratory pressures (MEP), nasal inspiratory pressure (SNIP), and maximum voluntary ventilation (MVV) measured at each visit. Sensitivity of each scale and correlations between symptom scores, pulmonary function, and ALSFRS-R were evaluated at baseline and over the study duration.Results and conclusions: ARES was more sensitive than MRC, Borg and ALSFRS-Resp scales at baseline and for detecting changes at 16 and 32 weeks. ARES and ALSFRS-Resp correlated significantly with vital capacity at baseline, but Borg and MRC did not. Only ALSFRS-Resp correlated with respiratory pressures. Changes in ALSFRS-Resp and ARES both correlated with vital capacity decline; however, changes in ARES had superior correlation with respiratory pressure decline. Comparisons between telephone and in-person administration of ARES met criteria for satisfactory test-retest correlation in different settings one week apart. These findings suggest that the ARES may be more useful in monitoring symptom progression in ALS than other available scales.