Percent Thrombus Predicts Popliteal Artery Aneurysm Related Limb Threatening Events.

OBJECTIVE: The objective of this study was to identify clinical and anatomic characteristics of Popliteal artery aneurysms (PAAs) associated with acutely limb threatening events. SUMMARY BACKGROUND DATA: Popliteal artery aneurysms (PAAs) are associated with high morbidity and mortality. Current guidelines recommend operative repair for PAAs with a diameter greater than 20 mm based on very limited evidence. METHODS: This retrospective cross-sectional cohort was derived from a multi-institutional database queried for all patients with a PAA from 2008 to 2022. Duplex ultrasound (DUS) characteristics of PAAs were abstracted by registered physicians in vascular interpretation. Symptom status at the time of DUS was divided into three categories: asymptomatic PAA, symptomatic PAA with claudication or chronic limb ischemia, and acutely limb threatening PAAs with a thromboembolic event, acute limb ischemia, or rupture. RESULTS: There were 470 PAAs identified in 331 patients. The mean age was 74 years at diagnosis, 94% of patients were white, and 97% of patients were male. In a univariate analysis, patient comorbidities and medications were not associated with symptom status. In a multivariate analysis including age, higher percent thrombus was significantly associated with symptomatic PAAs (RRR 15.2; CI 2.69-72.3; P<0.01) and PAAs with an acutely limb threatening event (RRR 17.9; CI 3.76-85.0; P<0.01). All other anatomic characteristics were not associated with symptom status. CONCLUSION: Percent thrombus was significantly associated with symptomatic PAAs and acutely limb threatening events, whereas diameter was not significantly associated with any symptom group. This analysis supports the use of percent thrombus in identifying high risk PAAs that warrant repair.

A Tracheostomy Support Device to Reduce Tracheostomy-Related Pressure Injury.

BACKGROUND: Tracheostomies provide many advantages for the care of patients who are critically ill but may also result in complications, including tracheostomy-related pressure injuries. Research efforts into the prevention of these pressure injuries has resulted in specialized clinical care teams and pathways. These solutions are expensive and labor intensive, and fail to target the root cause of these injuries; namely, pressure at the device-skin interface. Here we measure that pressure directly and introduce a novel medical device, the tracheostomy support system, to reduce it. METHODS: This was a cross-sectional study of 21 subjects in the ICU, each with a tracheostomy tube connected to a ventilator. A force-sensing resistor was used to measure baseline pressures at the device-skin interface along the inferior flange. This pressure was then measured again with the use of the tracheostomy support system in the inactive and active states. Resultant pressures and demographics were compared. RESULTS: Fifteen male and 6 female subjects, with an average age of 47 ± 14 (mean ± SD) years, were included in this study. Average pressures at the tracheostomy-skin interface at baseline in these 21 ICU subjects were 273 ± 115 (mean ± SD) mm Hg. Average pressures were reduced by 59% (median 62%, maximum 98%) with the active tracheostomy support system to 115 ± 83 mm Hg (P < .001). All the subjects tolerated the tracheostomy support system without issue. CONCLUSIONS: Despite best clinical practice, pressure at the tracheostomy-skin interface can remain quite high. Here we provide measures of this pressure directly and show that a tracheostomy support system can be highly effective at minimizing that pressure. There is room for improvement in tracheostomy care, and such improvement does not have to come at a great expense.

Organocatalyzed Hydroacylation of Enones by Photosensitization of Acyl Silanes.

A mild protocol for hydroacylation of enones through photosensitization of acyl silanes with thioxanthone under blue light (455 nm) irradiation is reported. A Brønsted acid is used as a cocatalyst in the reaction. The versatility of the method is demonstrated through inter- and intramolecular hydroacylation reaction. The hydroacylation product is applied for synthesizing an anti-HCV agent. Mechanistic insights are also provided through control experiments.

Giant Colonic Diverticulum: A Rare Type of Diverticular Disease.

Giant colonic diverticulum (GCD) is a well-recognized but infrequently encountered disease in clinical practice. GCD is its own unique entity and differs from commonly seen diverticular disease in both size and management. Initial clinical presentation is typically associated with diverticulitis and symptoms such as abdominal pain, fever, nausea, vomiting, rectal bleeding, or even a palpable abdominal mass. Surgery is the recommended treatment option largely due to the risk of associated complications including colonic perforation. We describe the case of a 56-year-old female diagnosed with a sigmoid GCD that was successfully stabilized medically and definitively treated surgically.

Survival and cancer recurrence after short-course perioperative probiotics in a randomized trial.

BACKGROUND & AIMS: The long-term impact of perioperative probiotics remains understudied while mounting evidence links microbiome and oncogenesis. Therefore, we analyzed overall survival and cancer recurrence among patients enrolled in a randomized trial of perioperative probiotics. METHODS: 6-year follow-up of surgical patients participating in a randomized trial evaluating short-course perioperative oral probiotic VSL#3 (n = 57) or placebo (n = 63). RESULTS: Study groups did not differ in age, preoperative hemoglobin, ASA status, and Charlson comorbidity index. There was a significant difference in preoperative serum albumin (placebo group 4.0 ± 0.1 vs. 3.7 ± 0.1 g/dL in the probiotic group, p = 0.030). Thirty-seven deaths (30.8 %) have occurred during a median follow-up of 6.2 years. Overall survival stratified on preoperative serum albumin and surgical specialty was similar between groups (p = 0.691). Age (aHR = 1.081, p = 0.001), serum albumin (aHR = 0.162, p = 0.001), and surgical specialty (aHR = 0.304, p < 0.001) were the only predictors of overall survival in the multivariate model, while the placebo/probiotic group (aHR = 0.808, p = 0.726) was not predictive. The progression rate among cancer patients was similar in the probiotic group (30.3 %, 10/33) compared to the placebo group (21.2 %, 7/33; p = 0.398). The progression-free survival was not significantly different (unstratified p = 0.270, stratified p = 0.317). CONCLUSIONS: Perioperative short-course use of VSL#3 probiotics does not influence overall or progression-free survival after complex surgery for visceral malignancy.

The impact of sex on platelet responses to aspirin in patients with peripheral artery disease.

Women with peripheral artery disease (PAD) have poorer limb salvage outcomes in spite of having lower risk factors for vascular disease than their male counterparts. Mono antiplatelet therapy with aspirin is the cornerstone of medical treatment for PAD to reduce the risk of arterial thrombosis, but platelets in women may have a variable response to this standard of care compared to men. Viscoelastic assays, such as thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's real-time coagulation profile and their response to specific antiplatelet medications. The aim of this prospective, observational study was to delineate the sex differences in platelet function using TEG-PM in patients with PAD on aspirin post-revascularization for PAD. All patients with PAD undergoing revascularization on aspirin monotherapy were prospectively enrolled between December 2020 and September 2023. The cohort was divided by sex, demographics, medications, procedure type, and outcomes were documented. Serial perioperative TEG-PM assays (1, 3, and 6 months) were performed up to 6 months postoperatively and platelet function was evaluated in both groups. Statistical analysis between women and men was performed to identify sex-specific differences in platelet function. Over the study period, a total of 303 patients were enrolled. Of this cohort, 149 patients met the study criteria and 266 samples were analyzed; 52 (34.89%) were women and 97 (65.11%) were men. In the platelet mapping assay, women showed significantly greater MAActF and MAAA, than men (16.66 vs. 14.94, p < .03 and 37.26 vs. 32.38, p < .01, respectively) indicating stronger thrombotic propensity. Additionally, platelet inhibition was significantly lower in women compared to men (52.95% vs. 61.65%, p < .05). In clinical outcomes reported as thrombotic events, women showed significantly higher occlusion in the area of intervention than men (4 vs. 1, p < .05). There is a growing awareness of the variations in the natural course, underlying mechanisms, and resulting outcomes of cardiovascular conditions, including PAD, in relation to sex. In this study, women did not achieve the same levels of platelet inhibition and displayed a procoagulant tendency in comparison to men when administered aspirin. Overall, aspirin monotherapy may be potentially sufficient for men, but women may require increased doses and/or additional antiplatelet medications to achieve an equivalent therapeutic effect.

Conducting Polymer Nanoparticles with Intrinsic Aqueous Dispersibility for Conductive Hydrogels.

Conductive hydrogels are promising materials with mixed ionic-electronic conduction to interface living tissue (ionic signal transmission) with medical devices (electronic signal transmission). The hydrogel form factor also uniquely bridges the wet/soft biological environment with the dry/hard environment of electronics. The synthesis of hydrogels for bioelectronics requires scalable, biocompatible fillers with high electronic conductivity and compatibility with common aqueous hydrogel formulations/resins. Despite significant advances in the processing of carbon nanomaterials, fillers that satisfy all these requirements are lacking. Herein, intrinsically dispersible acid-crystalized PEDOT:PSS nanoparticles (ncrys-PEDOTX ) are reported which are processed through a facile and scalable nonsolvent induced phase separation method from commercial PEDOT:PSS without complex instrumentation. The particles feature conductivities of up to 410 S cm-1 , and when compared to other common conductive fillers, display remarkable dispersibility, enabling homogeneous incorporation at relatively high loadings within diverse aqueous biomaterial solutions without additives or surfactants. The aqueous dispersibility of the ncrys-PEDOTX particles also allows simple incorporation into resins designed for microstereolithography without sonication or surfactant optimization; complex biomedical structures with fine features (< 150 µm) are printed with up to 10% particle loading . The ncrys-PEDOTX particles overcome the challenges of traditional conductive fillers, providing a scalable, biocompatible, plug-and-play platform for soft organic bioelectronic materials.

Clinical Utility of Infrapopliteal Calcium Score for the Evaluation of Severity of Peripheral Artery Disease.

PURPOSE: To identify associations between computed tomography (CT)-based lower-extremity calcium score (LECS) across different anatomic segments and the presence, severity, and clinical outcomes of peripheral artery disease (PAD). MATERIALS AND METHODS: In a mixed retrospective and prospective cohort study, 139 patients without prior lower-extremity intervention who underwent CT angiography of the aorta and lower extremities were identified. Subjects were classified as asymptomatic, claudicants, or having chronic limb-threatening ischemia (CLTI). LECS was measured using the Agatston method. Univariate and multivariate analyses were performed across categories of PAD severity. Receiver operating characteristic (ROC) analysis was performed, and an optimal cutoff point for LECS was identified. Claudicants were followed prospectively for CLTI and mortality. RESULTS: Higher infrapopliteal calcium score (CS) was independently associated with CLTI versus claudication (odds ratio [OR], 3.24 per unit increase in log10-transformed CS; P < .001) in addition to hemodialysis dependence and poor functional status. One hundred eighty-eight Agatston units was identified as the optimal cutoff for infrapopliteal CS in assessing the risk of CLTI versus claudication (area under the ROC curve, 0.84 [SD ± 0.049]). This cutoff was validated in an independent cohort to be associated with progression to CLTI (OR, 12.8; P = .0039). In the claudicant group followed prospectively, infrapopliteal CS ≥188 predicted increased risk of CLTI or death after adjusting for functional status and hemodialysis dependence (Cox hazard ratio, 4.92; P = .0202). CONCLUSIONS: Higher infrapopliteal CS was associated with CLTI among those with symptomatic PAD. An infrapopliteal CS cutoff of 188 Agatston units may serve as a useful tool to identify patients with increased risk of CLTI and mortality.

Popliteal artery aneurysm ultrasound criteria for reporting characteristics.

INTRODUCTION: Duplex ultrasound (DUS) is the modality of choice for surveillance of popliteal artery aneurysms (PAAs). However, noninvasive vascular laboratories have no standard guidelines for reporting results. This study assessed reports of PAA DUS for inclusion of information pertinent to operative decision-making and timing of surveillance. METHODS: This study was a retrospective review of a multi-institutional repository that was queried for all patients with a PAA from 2008 to 2022 and confirmed via manual chart review. DUS reports were abstracted and images were individually annotated for features of interest including dimensions, flow abnormalities, and percent thrombus burden. RESULTS: A total of 166 PAAs in 130 patients had at least one DUS available for viewing. Postoperative surveillance of PAAs was performed at several intervals: the first at 30 months (IQR 3.7-113, n = 44), the second at 64 months (IQR 20-172, n = 31), and the third at 152 months (IQR 46-217, n = 16) after the operation. The largest diameter of operative PAAs (median 27.5 mm, IQR 21.8-38.0) was significantly greater than nonoperative PAAs (median 20.9 mm, IQR 16.7-27.3); p < 0.01. Fewer than 33 (21%) reports commented on patency of distal runoff. We calculated an average percent thrombus of 60% (IQR 19-81) in nonoperative PAAs, which is significantly smaller than 75% (IQR 58-89) in operative PAAs; p < 0.01. CONCLUSION: In this multi-institutional retrospective study, PAAs are often not followed at intervals recommended by the Society for Vascular Surgery guidelines and do not include all measurements necessary for clinical decision-making in the multi-institutional repository studied. There should be standardization of PAA DUS protocols performed by all noninvasive vascular laboratories to ensure completeness of PAA DUS images and inclusion of characteristics pertinent to clinical decision-making in radiology reports.

Platelet function testing and clinical outcomes in peripheral arterial disease: Systematic review and narrative synthesis.

OBJECTIVE: This systematic review aims to comprehensively assess the contemporary literature on platelet function testing (PFT) in individuals undergoing revascularization therapy for peripheral arterial disease (PAD). The goal is to identify whether PFT can aid in detecting antiplatelet resistance, predicting post-procedural thrombotic complications, and informing tailored treatment strategies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature review was conducted using PubMed databases. Search terms included relevant medical subject headings (MeSH) terms. Eligible articles published in English between 1990 and 2023 were analyzed. Studies that examined PFT outcomes in patients with PAD after lower extremity revascularization were included. RESULTS: Ten studies met the inclusion criteria. Various PFT methods were used, including thromboelastography with platelet mapping, multiplate analyzer, Cytochrome P450 2C19 testing, VerifyNow, corrected whole blood aggregometry, platelet function analyzer-100, and light transmission aggregometry. PFT identified individuals who were resistant or non-sensitive to antiplatelet therapy, with such patients facing increased risks of graft/stent thrombosis, amputation, and reintervention. However, substantial heterogeneity in surgical procedures, drug regimens, and testing methods was observed among the studies. CONCLUSIONS: PFTs can play a crucial role in detecting resistance and non-sensitivity to antiplatelet drugs in patients with PAD post-revascularization. However, heterogeneity of data and methods underlines the need for standardized protocols and consensus-building among PFTs. Enhancing clinical utility and reliability could help optimize antiplatelet thromboprophylaxis, minimize thrombotic complications, and improve treatment strategies in vascular surgery. Further research is necessary to solidify the role of PFTs in guiding antiplatelet therapy post-revascularization in patients with PAD.

The cost of sympatry: spatio-temporal patterns in leopard dietary and physiological responses to tiger competition gradient in Rajaji Tiger Reserve, Uttarakhand, India.

Apex predators have critical roles in maintaining the structure of ecosystem functioning by controlling intraguild subordinate populations. Such dominant-subordinate interactions involve agonistic interactions including direct or indirect impacts on the subordinates. As these indirect effects are often mediated through physiological processes, it is important to quantify such responses to better understand population parameters. We used a large carnivore intraguild system involving tiger (Panthera tigris) and leopard (Panthera pardus) to understand the dietary and physiological responses under a spatio-temporal gradient of tiger competition pressures in Rajaji Tiger Reserve (RTR) between 2015 and 2020. We conducted systematic faecal sampling in the winters of 2015 and 2020 from the park to assess diet and physiological measures. Analyses of leopard-confirmed faeces suggest a dietary-niche separation as a consequence of tiger competition. In 2020, we found an increased occurrence of large-bodied prey species without tiger competition in western-RTR. Physiological measures followed the dietary responses where leopards with large-sized prey in the diet showed higher fT3M and lower fGCM measures in western-RTR. In contrast, eastern-RTR leopards showed lower levels of fT3M and fGCM in 2020, possibly due to intense competition from tigers. Overall, these patterns strongly indicate a physiological cost of sympatry where competition with dominant tigers resulted in elevated nutritional stress. We recommend expansion of leopard monitoring and population estimation efforts to buffers, developing appropriate plans for human-leopard conflict mitigation and intensive efforts to understand leopard population dynamics patterns to ensure their persistence during the ongoing Anthropocene.

Inhibition of Dopamine Neurons Prevents Incentive Value Encoding of a Reward Cue: With Revelations from Deep Phenotyping.

The survival of an organism is dependent on its ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the NAc is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats, it was found that, under baseline conditions, ∼84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCutTM revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient toward and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues.SIGNIFICANCE STATEMENT Activity of dopamine neurons in the ventral tegmental area (VTA) during cue presentation is necessary for the development of a sign-tracking, but not a goal-tracking, conditioned response in a Pavlovian task. We capitalized on the temporal precision of optogenetics to pair cue presentation with inhibition of VTA dopamine neurons. A detailed behavioral analysis with DeepLabCutTM revealed that cue-directed behaviors do not emerge without dopamine neuron activity in the VTA. Importantly, however, when optogenetic inhibition is lifted, cue-directed behaviors increase, and a sign-tracking response develops. These findings confirm the necessity of dopamine neuron activity in the VTA during cue presentation to encode the incentive value of reward cues.

Endotracheal tube forces exerted on the larynx and a novel support device to reduce it.

Objective: Endotracheal tubes (ETTs) are commonly associated with laryngeal injury that may be short lasting and temporary or more severe and life altering. Injury is believed to result from forces that these ETTs exert on the larynx. Here we quantify the forces of ETTs of various sizes on the laryngotracheal complex to gain a more quantitative understanding of these potential damaging forces. Here we also perform preclinical testing of a novel support device to offload these forces. Methods: Endotracheal intubation was performed on a fresh human cadaver using various ETT sizes. A strain-sensitive graphene nanosheet sensor and a commercially available force sensing resistor were secured behind the larynx, anterior to the prevertebral fascia. The forces exerted on the larynx were measured for each of the commonly used ETTs. A novel support device, ETT clip (Endo Clip), was attached to the ETTs and changes in these forces were observed. Results: Forces exerted on the laryngotracheal complex by various ETTs were observed to increase with increasing tube size. This pressure can be significantly reduced with a novel ETT clip. Conclusion: Here we demonstrate the first quantitative measurement of forces that ETTs exert on the larynx. We demonstrate a novel device that can easily clip onto an ETT reducing pressure on the laryngotracheal complex. This preclinical test paves the way for a human clinical trial. Level of evidence: 5.

Impacts of Anxiety and Depression on Clinical Hypertension in Low-Income US Adults.

INTRODUCTION: Depression and anxiety are common leading causes of disability and are associated with systemic effects including cardiovascular comorbidities. Low-income populations may experience higher frequencies of depressive or anxiety-related symptoms, and be at greater risk for developing hypertension. AIM: We performed a cross-sectional study of low-income participants who completed hypertension and disability questionnaires as part of the 2017-2018 cycle of the National Health and Nutrition Examination Survey (NHANES) to identify associations between depressive/anxiety-related symptoms and hypertension status. METHODS: Multivariable logistic regressions were performed to identify whether (1) frequency of depressive symptoms, (2) frequency of anxiety-related symptoms, (3) self-reported depression medication use, or (4) self-reported anxiety medication use predicted previous hypertension diagnosis. RESULTS: A total of 74,285,160 individuals were represented in our cohort. Participants that reported taking depression (OR 2.72; 95% CI 1.41-5.24; P = 0.009) and anxiety (OR 2.50; 95% CI 1.42-4.41; P = 0.006) medications had greater odds of hypertension. Individuals with depressive feelings daily, monthly, and few times per year were more likely to have hypertension. Respondents with daily (OR 2.28; 95% CI 1.22-4.24; P = 0.021) and weekly (OR 1.88; 95% CI 1.05-3.38; P = 0.040) anxiety symptoms were more likely to have hypertension. CONCLUSIONS: Low-income adults in the United States with symptoms of anxiety or depression have higher likelihood of hypertension than those with no symptoms. Respondents who indicated taking medication for anxiety disorders or depression were more likely to have been diagnosed with hypertension.

CT imaging of condyloma acuminata.

This case report shows the use of computed tomography (CT) imaging in evaluating a 53-year-old male patient presenting with anogenital wart like lesions. The patient was suspected of having condyloma acuminata. The significant extent of condyloma acuminata, as seen in this case, is a relatively uncommon finding. CT was ordered to help assess for local invasion and malignancy. This report also discusses Buschke-Lowenstein tumors, the rare malignant transformation of giant condyloma acuminata in the anogenital region. Invasion and malignancy in condyloma acuminata must be evaluated as they can have a poor and even fatal prognosis. Histological examination confirmed the diagnosis of condyloma acuminata and CT ruled out regional invasion, and metastatic disease. Additionally, the role of imaging in planning surgical excision is discussed. This case highlights the value of CT in the clinical diagnosis and management of condyloma acuminata.

Wall shear rate and energy loss coefficient measures using conventional Doppler ultrasound do not predict carotid plaque progression.

Background: The rate of carotid plaque progression is believed to be related to blood flow hemodynamics and shear stress. Our objective was to determine if wall shear rate (WSR) and the energy loss coefficient (ELC) measured by Doppler ultrasound could predict atherosclerotic carotid disease progression. Patients and methods: Patients at a large tertiary center with an initial ultrasound between 2016 and 2018 with a significant carotid plaque were included if they had at least one 6 months follow-up comparative study. Stenosis progression was assessed according to the NASCET (The North American Symptomatic Carotid Endarterectomy Trial) percentage criterion. Results: The average annual progression rate for the 74 plaques included was 5.7% NASCET per year. We identified 18 plaques with ≥10% NASCET progression and 56 plaques without significant progression <10% NASCET. Among the plaques with progression, only four plaques had progression greater than 20% NASCET. Median WSR was 6266 s-1 [5813-8974] in plaques with progression and 6564 s-1 [5285-8766] in stable plaques (p=0.643). Median ELC was 3.86 m2 [2.78-5.53] in plaque with progression and 4.32 m2 [3.42-6.81] in stable plaques (p=0.296). Conclusions: Although it is a widely accepted hypothesis that shear stress and hemodynamics of the carotid bifurcation contribute to plaque progression, we found that WSR and ELC estimated by Doppler ultrasound do not reliably predict atherosclerotic plaque progression in the carotid artery. Other ultrasound modalities, such as 3D imaging, may be used to assess the influence of plaque geometry and hemodynamics in plaque progression.

Inhibition of dopamine neurons prevents incentive value encoding of a reward cue: With revelations from deep phenotyping.

The survival of an organism is dependent on their ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the nucleus accumbens is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats it was found that, under baseline conditions, ∼84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCut revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient towards and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues. Significance Statement: Activity of dopamine neurons in the ventral tegmental area (VTA) during cue presentation is necessary for the development of a sign-tracking, but not a goal-tracking, conditioned response in a Pavlovian task. We capitalized on the temporal precision of optogenetics to pair cue presentation with inhibition of VTA dopamine neurons. A detailed behavioral analysis with DeepLabCut revealed that cue-directed behaviors do not emerge without VTA dopamine. Importantly, however, when optogenetic inhibition is lifted, cue-directed behaviors increase, and a sign-tracking response develops. These findings confirm the necessity of VTA dopamine during cue presentation to encode the incentive value of reward cues.

Dermatologic toxicities of anti-neoplastic immunotherapy in United States hospitalizations.

A major side effect of anti-neoplastic immunotherapy is the onset of dermatologic toxicities following the administration of several different immunotherapy drugs. We sought to assess the incidence and mortality of anti-neoplastic immunotherapy-associated dermatologic toxicities using a nationally representative sample of United States (US) adults. The National Inpatient Sample database was queried for encounters undergoing anti-neoplastic immunotherapy. Multiple logistic regression models were constructed to analyze incidence of dermatologic toxicity and associated mortality as well as calculate adjusted odds ratios (aOR) after controlling for age, race, sex, household income, and cancer type. Immunotherapy patients demonstrated greater odds of developing pruritus (aOR = 7.59; 95% CI 5.17-11.2; P < 0.001), rash (aOR = 2.81; 95% CI 2.00-3.94, P < 0.001), generalized (aOR = 5.32; 95% CI 3.35-8.43; P < 0.001) and localized (aOR = 2.67; 95% CI 1.01-7.05; P < 0.001) skin eruptions, and vitiligo (aOR = 13.3; 95% CI 5.15-34.4; P < 0.001) compared to patients who did not receive anti-neoplastic immunotherapy. There were no significant differences observed in incidence of non-scarring alopecia (P = 0.7), psoriasis (P = 0.094), and dermatitis (P = 0.9) between the two groups. Patients who underwent immunotherapy were more likely to develop dermatologic toxicity (aOR = 3.93; 95% CI 3.12-4.94; P < 0.001), however, no significant differences in mortality were observed. Patients undergoing anti-neoplastic immunotherapy have an increased risk of developing dermatologic toxicity compared to patients who did not receive anti-neoplastic immunotherapy.