Proteomic Analysis of Human Macrophages Overexpressing Angiotensin-Converting Enzyme.

Angiotensin converting enzyme (ACE) exerts strong modulation of myeloid cell function independently of its cardiovascular arm. The success of the ACE-overexpressing murine macrophage model, ACE 10/10, in treating microbial infections and cancer opens a new avenue into whether ACE overexpression in human macrophages shares these benefits. Additionally, as ACE inhibitors are a widely used antihypertensive medication, their impact on ACE expressing immune cells is of interest and currently understudied. In the present study, we utilized mass spectrometry to characterize and assess global proteomic changes in an ACE-overexpressing human THP-1 cell line. Additionally, proteomic changes and cellular uptake following treatment with an ACE C-domain selective inhibitor, lisinopril-tryptophan, were also assessed. ACE activity was significantly reduced following inhibitor treatment, despite limited uptake within the cell, and both RNA processing and immune pathways were significantly dysregulated with treatment. Also present were upregulated energy and TCA cycle proteins and dysregulated cytokine and interleukin signaling proteins with ACE overexpression. A novel, functionally enriched immune pathway that appeared both with ACE overexpression and inhibitor treatment was neutrophil degranulation. ACE overexpression within human macrophages showed similarities with ACE 10/10 murine macrophages, paving the way for mechanistic studies aimed at understanding the altered immune function.

COVID-19 infections among health care workers at a university hospital in Jeddah, Saudi Arabia.

BACKGROUND: The objective of this study was to describe the prevalence, characteristics, and risk factors of coronavirus disease-2019 (COVID-19) infection among health care workers (HCWs) at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. METHODS: A prospective cross-sectional study of HCWs confirmed to have COVID-19 infection from March 1, 2020 to December 31, 2022. RESULTS: A total of 746 HCWs were diagnosed with COVID-19. Patients' age ranged from 22 to 60 years with a mean ± standard deviation of 37.4 ± 8.7 years. The infection was community-acquired in 584 (78.3%) HCWs. The vast majority (82.6%) of the infected HCWs had no comorbidities. Nurses (400/746 or 53.6%) represented the largest professional group, followed by physicians (128/746 or 17.2%), administrative staff (125/746 or 16.8%), respiratory therapists (54/746 or 7.2%), and physiotherapists (39/746 or 5.2%). Symptoms included fever (64.1%), cough (55.6%), sore throat (44.6%), headache (22.9%), runny nose (19.6%), shortness of breath (19.0%), fatigue (12.7%), body aches (11.4%), diarrhea (10.9%), vomiting (4.4%), and abdominal pain (2.8%). Most (647 or 86.7%) patients were managed as outpatients. Four (0.5%) HCWs died. CONCLUSIONS: HCWs face a dual risk of SARS-CoV-2 infection, both from community exposure and within the hospital setting. Comprehensive infection control strategies are needed to protect HCWs both inside and outside the hospital environment.

Cardiotoxicity in Cancer Patients: The Prevalence, Risk Factors, and Cardioprotective Measures in a Cancer Centre in Saudi Arabia.

BACKGROUND: Chemotherapy-related cardiotoxicity can exhibit several patterns of functional, structural, and vascular complications. This study aims to identify the patterns and the factors associated with cardiotoxicity in cancer patients. METHOD: A retrospective cross-sectional analysis of 96 adult cancer patients undergoing anticancer therapy was investigated at King Khalid Hospital in Najran, Saudi Arabia, from May 2022 to April 2023. The data on patient and cancer characteristics, treatment, and outcomes were collected and analyzed. Factors associated with cardiotoxicity were investigated through univariate analyses using odds ratio (OR) and 95% confidence interval (CI). RESULTS:  Among the 96 cancer patients in the study, cardiotoxicity occurred in 12 individuals (12.5%). The mean age was 57.0 ± 13.3 years (range: 32-81 years), with 32 (33.3%) being above 65 years. The most common comorbidities were diabetes (n=48; 50%), followed by hypertension (n=32; 33.3%), and dyslipidemia (n=20; 20.8%). The most common cancers were gastrointestinal cancer (n=32; 33.3%), followed by breast cancer (n=22; 22.9%) and lymphoma (n=14; 14.6%). Females were disproportionately affected (64.6%), with 57.3% of them in the metastatic stage. The majority of patients (90.6%) had normal ejection fraction before chemotherapy initiation. In univariate analysis, current smoking (OR: 7.00; 95%CI: 1.94-25.25, p= 0.003), history of percutaneous cardiac intervention (OR: 40.24; 95%CI: 1.80-896.26, p= 0.019), diabetes (OR: 6.05; 95%CI: 1.24-29.32, p= 0.025), renal failure (OR: 8.20; 95%CI: 0.91-74.88, p= 0.046), dyslipidemia (OR: 5.00; 95 CI: 1.38-18.32, p=0.012), anthracycline use (OR: 18.33; 95%CI: 4.36-126.55, p <0.001), trastuzumab use (OR: 25.00; 95%CI: 6.25-129.86, p < 0.001), and increased chemotherapy cycles number (> 10 cycles) (OR: 73.00; 95%CI: 8.56- 622.36, p < 0.001) were associated with cardiotoxicity. Additionally, beta-blocker use was associated with lower rates of cardiotoxicity (OR: 0.17; 95%CI: 0.036-0.84, p= 0.029). CONCLUSIONS: The incidence of cardiotoxicity among cancer patients treated with chemotherapy is modest, difficult to predict, and independent of baseline cardiac systolic functions. Factors associated with cardiotoxicity include smoking, history of percutaneous cardiac intervention, diabetes, renal failure, dyslipidemia, anthracycline or trastuzumab use, and increased chemotherapy cycle numbers. A combination of various anticancer drugs and chemotherapy may dramatically raise the risk of cardiotoxicity in cancer patients. As a result, patients receiving high-risk cardiotoxic drugs should be monitored with caution to avoid drug-related cardiotoxicity. Furthermore, proactive treatment techniques aiming at reducing the possible cardiotoxic effects of anticancer therapy are critical.

Dorsal Root Ganglion Stimulation for the Management of Inflammatory Bowel Disease: A Case Report.

This case report presents the successful use of dorsal root ganglion stimulation (DRGS) in a 30-year-old female patient with Crohn's disease. Despite extensive treatments, the patient experienced chronic abdominal pain, diarrhea, bloating, cramping, fatigue, and other debilitating symptoms. After a successful DRGS trial with leads placed on the right T6 and T10, she was implanted with a permanent system. At 18 months she continues to experience significant improvement in symptoms, including reduced abdominal pain, decreased defecation frequency, better stool consistency, less pain with eating and bowel evacuation, and enhanced quality of life.

Prevalence, Clinical Characteristics and Determinants of Unsuccessful Treatment Outcomes Among Pulmonary Tuberculosis Patients: A 5-Year Registry-Based Retrospective Cohort Study.

Purpose: Despite the existence of effective medications, pulmonary tuberculosis (PTB) remains a significant global public health concern, The evaluation and feedback of national TB control programs are crucial, requiring diligent monitoring of TB treatment outcomes and analysis of the factors influencing these outcomes. This study aims to provide valuable insights into the challenges faced by TB patients, which can inform better strategies for treatment and management in the future. Patients and Methods: We conducted a study in King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia (KSA), from January 1, 2018 to December 31, 2023. The study was a registry-based retrospective cohort study. Patients' data were sourced from the National Tuberculosis Registry database of Saudi Arabia. Treatment outcomes were determined as either success or failure, considering clinical evaluation, changes in chest X-rays, and the results of subsequent sputum examinations during follow-up. To evaluate the data, SPSS version 28.0 was used. Results: A total of 427 PTB patients participated in the study. The results show successful treatment outcomes among 88.5% of patients. Among the patients, males exhibited a higher likelihood of treatment failure as compared to females (aOR 1.3; 95%Cl 1.2-1.5, p < 0.001). Patients with positive sputum smear (aOR 1.3; 95%Cl 1.1-1.3 p < 0.00) and the presence of cough were associated with an increased risk of treatment failure (aOR1.5; 95%Cl 1.1-1.4, p < 0.001). Conclusion: This study shows that the percentage of unsuccessful treatment outcomes is high, ie, 11.5%, due to patients' deaths and loss to follow-up. Enhanced supervision and treatment monitoring for tuberculosis patients at high risk of treatment failure can lead to improved treatment success rates in Saudi Arabia.

PRPS1-associated retinopathy: a diagnostic odyssey.

PURPOSE: This study describes how the diagnosis of Usher syndrome was revised to PRPS1-associated retinopathy and Charcot-Marie-Tooth disease type 5. CASE REPORT: A 38-year-old female with bilaterally subnormal vision and non-congenital hearing loss was initially diagnosed with Usher syndrome, based on finding variants in three genes (MYO7A, USH2A, and PCDH15), was re-evaluated at the inherited retinal disorders clinic. She had asymmetric retinopathy and right macular pseudocoloboma. She was also found to have myopathic facies, poor grip strength and atrophy of the calf muscles. Whole exome sequencing including variants in PRPS1 showed a variant (NM_002764.4:c.287 G > A; p.Arg96Gln), which was not detected by targeted Sanger sequencing of the DNA from her mother and sister. CONCLUSION: The constellation of asymmetric retinopathy and non-congenital hearing impairment should prompt the clinician to search for other diagnoses that may not be covered by an Usher syndrome next generation sequencing panel. Interpretation of genetic testing results should be correlated with a detailed clinical phenotype.

Deep learning-based identification of esophageal cancer subtypes through analysis of high-resolution histopathology images.

Esophageal cancer (EC) remains a significant health challenge globally, with increasing incidence and high mortality rates. Despite advances in treatment, there remains a need for improved diagnostic methods and understanding of disease progression. This study addresses the significant challenges in the automatic classification of EC, particularly in distinguishing its primary subtypes: adenocarcinoma and squamous cell carcinoma, using histopathology images. Traditional histopathological diagnosis, while being the gold standard, is subject to subjectivity and human error and imposes a substantial burden on pathologists. This study proposes a binary class classification system for detecting EC subtypes in response to these challenges. The system leverages deep learning techniques and tissue-level labels for enhanced accuracy. We utilized 59 high-resolution histopathological images from The Cancer Genome Atlas (TCGA) Esophageal Carcinoma dataset (TCGA-ESCA). These images were preprocessed, segmented into patches, and analyzed using a pre-trained ResNet101 model for feature extraction. For classification, we employed five machine learning classifiers: Support Vector Classifier (SVC), Logistic Regression (LR), Decision Tree (DT), AdaBoost (AD), Random Forest (RF), and a Feed-Forward Neural Network (FFNN). The classifiers were evaluated based on their prediction accuracy on the test dataset, yielding results of 0.88 (SVC and LR), 0.64 (DT and AD), 0.82 (RF), and 0.94 (FFNN). Notably, the FFNN classifier achieved the highest Area Under the Curve (AUC) score of 0.92, indicating its superior performance, followed closely by SVC and LR, with a score of 0.87. This suggested approach holds promising potential as a decision-support tool for pathologists, particularly in regions with limited resources and expertise. The timely and precise detection of EC subtypes through this system can substantially enhance the likelihood of successful treatment, ultimately leading to reduced mortality rates in patients with this aggressive cancer.

Evaluation of Washout Periods After Dorsal Root Ganglion Stimulation Trial.

OBJECTIVE: Dorsal root ganglion stimulation (DRG-S) is a novel therapy to treat chronic pain. It has shown efficacy when delivered intermittently, suggesting a delayed washout effect exists. To measure the washout period, and to determine whether there are differences in washout times among different types of treated pain, we measured the time for pain to return at the end of the patients' one-week DRG stimulation trials. MATERIALS AND METHODS: Patients who completed a successful DRG-S trial were included. The times until 25% (t25) and 90% (t90) of baseline pain level returned were recorded. The patients were divided into neuropathic, nociceptive, and mixed pain groups for subgroup comparison. t25 and t90 were plotted in the entire cohort and subgroups using reverse Kaplan-Meier plots (failure curves) and compared using a log-rank test. RESULTS: In total, 29 consecutive patients were included. Median t25 and t90 times were 7.1 and 19.5 hours, respectively. Median (interquartile range) times were longest for the nociceptive pain group (n = 17) and shortest for the neuropathic pain group (n = 6), with the mixed-pain group (n = 6) in between (t25: 7.1 [1.7-19.4], 3.40 [1.4-8.4], and 5.7 [0.8-17.6]; t90, 22.0 [10.7-71.0], 7.6 [3.6-19.8], and 20.9 [14.2-31.2], respectively). t90 times differed significantly by pain type (p = 0.040). CONCLUSIONS: This study showed a prolonged washout period after cessation of DRG-S therapy. Washout times vary according to pain type. The observed effects are possibly due to long-term depression of pain signaling and could allow the implementation of alternative stimulation strategies with DRG-S. Further investigations evaluating DRG-S washout times are warranted.

Perceptions and Understanding of Transgender Patient Care: A Survey of Practicing Facial Plastic Surgeons.

Transgender individuals face significant health disparities including deficiencies in physician education, knowledge, and comfort with care. The objective of this study was to determine the perceptions, practice patterns, and familiarity of facial plastic surgeons with transgender health care. An anonymous questionnaire was sent to facial plastic surgeons within the American Academy of Facial Plastic and Reconstructive Surgery list-serve. Primary datapoints included participant characteristics, transgender-related experience, and educational goals. Of the 66 facial plastic surgeons surveyed, 49% had treated 1 to 10 transgender patients during their career, and 70% were actively treating at least 1 transgender patient. The number of patients treated and surgeries performed was significantly associated with self-perceived competence, comfort counseling on gender-affirming surgeries, discussing gender identity, asking preferred pronouns, and a desire to learn more about transgender care. Most participants (61%) obtained transgender care training through real-world experience, with only 18% receiving formal training in residency or fellowship. In total, 50% of respondents believe transgender care training among facial plastic surgeons is inadequate and 60% support its incorporation into residency/fellowship curricula. Increased awareness is needed to address the disparities experienced by transgender patients. Many facial plastic surgeons desire to learn more and support incorporating transgender care into training. Understanding the current state of transgender care can assist the facial plastic community in promoting education that strengthens physicians' ability to deliver competent care that addresses the inequities faced by this diverse group.

Delayed Irreversible Fanconi Syndrome Associated With Vertebral Fracture After Tenofovir Discontinuation.

The use of tenofovir disoproxil fumarate (TDF) as an antiretroviral agent has been reported to adversely affect both renal tubules and bone health, leading to pathological fractures. While such an effect is largely reversible, substituting TDF with tenofovir alafenamide (TAF) might result in lower rates of adverse events with the preservation of tenofovir effectiveness. We report a case of a 40-year-old lady with HIV infection who had a vertebral fragility fracture secondary to TDF-associated Fanconi syndrome. The syndrome developed four years after TDF cessation and switching to TAF. Other etiologies for decreased bone mass were excluded, and the diagnosis of Fanconi syndrome was established based on her bone mineral density (BMD) and urine parameters. She was treated conservatively with active vitamin D, calcium, and progesterone/estrogen combination, but her phosphate wasting persisted despite switching to TAF; this likely represents a delayed irreversible effect of TDF on the patient's bone remodeling. This case report highlights the chronic sequelae of TDF therapy and the importance of monitoring for and early detection of renal tubulopathy and osteoporotic fractures in this patient population.

Clinicopathological study of ophthalmic cutaneous and mucocutaneous non-langerhans cell histiocytic lesions.

BACKGROUND: The "C group" of the histiocytic disorders is characterized by non-Langerhans-cell histiocytic lesions in the skin, mucosal surfaces, or both, out of which Juvenile xanthogranuloma (JXG) is the most common typically affecting the skin. The eye is the most common extra-cutaneous site of JXG., we aim at providing our clinical and histopathological experience with this group of diseases including the adult-onset xanthogranuloma (AXG). METHODS: This is a retrospective cohort study of all patients with the tissue diagnosis of ocular and periocular cutaneous and mucocutaneous non-LCH disorders who presented to us over a period of 25 years (January 1993 to December 2018). RESULTS: Twenty patients were diagnosed as "Group C" disease with an age range of 2 months-60.9 years. Eleven patients were females (55%) and nine were males (45%). The involvement was mostly unilateral in 80.9%. All cases fell into the xanthogranuloma family with 11 JXG patients, 8 AXG patients of skin and ocular surface, and one patient with solitary reticulohistiocytoma (SRH). The clinical site of involvement in JXG was primarily in the eyelid in 5 patients (45%), ocular surface lesions in 2 (18%), iris in 2 (18%), choroidal and bilateral orbital lesions in 1 patient each (9%). The group of AXG, presented equally with eyelid lesions in 4/8 and ocular surface lesions in 4/8. The non-Langerhans' histiocytic infiltrate showed supportive immunohistochemical staining properties (reactive to CD68 marker and negative to S-100 and langerin markers). CONCLUSION: Among the rare histiocytic disorders, xanthogranulomatosis is the commonest and has wide clinical manifestations. Accurate diagnosis needs to be supported by typical histopathological findings. JXG was the commonest in our study with relatively older mean age at presentation and frequent eyelid rather than iris involvement. AXG is often confused with xanthelasma when involving the eyelids with corneal limbal involvement is relatively frequent.

Drought priming reduces Calligonum mongolicum sensitivity to recurrent droughts via coordinated regulation of osmolytes, antioxidants, and hormones.

Pre-exposure of plants to abiotic stressors may induce stress memory and improve tolerance to subsequent stresses. Here, 3-month-old Calligonum mongolicum seedlings were exposed to drought (60 days) with (primed) or without (unprimed) early drought exposure of 50 days, to determine whether this enhances seedling resistance and investigate possible underlying mechanisms. Compared to unprimed, primed seedlings had higher biomass, shoot relative water content (15% and 22%), chlorophyll a, chlorophyll b, and carotenoids. They also had more superoxide anions (O2 -• ) and H2 O2 scavenging mechanisms through higher activity of SOD, CAT, APX, and dehydroascorbate reductase in assimilating shoots and roots, resulting in less ROS and oxidative stress damage. Plants also had higher ABA and JA but lower SA, likely reflecting an adaptive response to subsequent stress. Primed seedlings accumulated more IAA and brassinosteroids, which may account for their better growth. Accumulation of glycine betaine, pro, and total amino acids in assimilating shoots and roots of primed seedlings led to reduced osmotic stress. Drivers of responses of non-primed and primed seedlings to drought varied. Responses of primed seedlings were primarily characterized by more photosynthetic pigments, increased oxidative scavenging of O2 -• and H2 O2 , more phytohormones and osmolytes. Early drought priming of drought stress memory in C. mongolicum seedlings may provide a useful management approach to improve seedling establishment in vegetation restoration programs.

Fine mapping of a new common bean anthracnose resistance gene (Co-18) to the proximal end of Pv10 in Indian landrace KRC-5.

KEY MESSAGE: Mapping and fine mapping of bean anthracnose resistance genes is a continuous process. We report fine mapping of anthracnose resistance gene Co-18 which is the first anthracnose gene mapped to Pv10. The discovery of resistance gene is a major gain in the bean anthracnose pathosystem research. Among the Indian common bean landraces, KRC-5 exhibit high levels of resistance to the bean anthracnose pathogen Colletotrichum lindemuthianum. To precisely map the anthracnose resistance gene, we used a Recombinant Inbred Line (F2:9 RIL) population (KRC-5 × Jawala). The inheritance test revealed that KRC-5 carries a dominant resistance gene temporarily designated as Co-18. We discovered two RAPD markers linked to Co-18 among 287 RAPD markers. These RAPD markers were eventually developed into SCARs (Sc-OPR15 and Sc-OPF6) and flank Co-18 on chromosome Pv10 at a distance of 5.3 and 4.2 cM, respectively. At 4.0-4.1 Mb on Pv10, we detected a SNP (single-nucleotide polymorphism) signal. We synthesized 58 SSRs and 83 InDels from a pool of 135 SSRs and 1134 InDels, respectively. Five SSRs, four InDels, and two SCARs were used to generate the high-density linkage map, which led to the identification of two SSRs (SSR24 and SSR36) that are tightly linked to Co-18. These two SSRs flank the Co-18 to 178 kb genomic region with 13 candidate genes including five NLR (nucleotide-binding and leucine-rich repeat) genes. The closely linked markers SSR24 and SSR36 will be used in cloning and pyramiding of the Co-18 gene with other R genes to develop durable resistant bean varieties.

Phenotypic and genotypic features of POC1B-associated cone dystrophy.

PURPOSE: Patients with cone dystrophy (CD) can present with virtually normal retinal appearance, which may delay diagnosis. This study describes the inconspicuous clinical features of POC1B-associated CD in two Saudi families. METHODS: This is a retrospective case study. Clinical data analyzed included multimodal retinal imaging and electroretinography of the affected individuals. Genetic analysis was done for all probands. RESULTS: Three affected males from two Saudi families with POC1B-associated CD were included. The ages at presentation ranged from 18 to 34 years. Ophthalmic examination showed decreased Snellen visual acuities (range: 20/100-20/300) and color vision bilaterally. Fundus examination showed only mild vascular attenuation. Macular optical coherence tomography showed reduced reflectivity of the external limiting membrane, ellipsoid, and interdigitation zones. Full-field electroretinography demonstrated undetectable light-adapted responses and normal dark-adapted responses in all patients. Next-generation sequencing showed one proband to be homozygous for a previously unpublished nonsense variant in POC1B (NM_172240):c.672C>G; p(Tyr224*). Whole exome sequencing for the second proband showed a novel homozygous frameshifting variant in POC1B: c.991del; p(Arg331Glufs*13). CONCLUSION: We described two novel variants in POC1B and the associated subtle, yet significant retinal features. POC1B-associated CD is a rare cause of visual loss in patients with relatively normal fundus appearance. Deep phenotyping is necessary in formulating appropriate differential diagnosis.

Transition-Metal-Catalyzed Directed C-H Functionalization in/on Water.

Directing group assisted C-H bond functionalization using transition-metal-catalysis has emerged as a reliable synthetic tool for the construction of regioselective carbon-carbon/heteroatom bonds. Off late, "in/on water directed transition-metal-catalysis", though still underdeveloped, has appeared as one of the prominent themes in sustainable organic chemistry. This article covers the advancements, mechanistic insights and application of the sustainable directed C-H bond functionalization of (hetero)arenes in/on water in the presence of transition-metal-catalysis.

Does Reinforcement Learning Improve Outcomes for Critically Ill Patients? A Systematic Review and Level-of-Readiness Assessment.

OBJECTIVE: Reinforcement learning (RL) is a machine learning technique uniquely effective at sequential decision-making, which makes it potentially relevant to ICU treatment challenges. We set out to systematically review, assess level-of-readiness and meta-analyze the effect of RL on outcomes for critically ill patients. DATA SOURCES: A systematic search was performed in PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection, Elsevier/SCOPUS and the Institute of Electrical and Electronics Engineers Xplore Digital Library from inception to March 25, 2022, with subsequent citation tracking. DATA EXTRACTION: Journal articles that used an RL technique in an ICU population and reported on patient health-related outcomes were included for full analysis. Conference papers were included for level-of-readiness assessment only. Descriptive statistics, characteristics of the models, outcome compared with clinician's policy and level-of-readiness were collected. RL-health risk of bias and applicability assessment was performed. DATA SYNTHESIS: A total of 1,033 articles were screened, of which 18 journal articles and 18 conference papers, were included. Thirty of those were prototyping or modeling articles and six were validation articles. All articles reported RL algorithms to outperform clinical decision-making by ICU professionals, but only in retrospective data. The modeling techniques for the state-space, action-space, reward function, RL model training, and evaluation varied widely. The risk of bias was high in all articles, mainly due to the evaluation procedure. CONCLUSION: In this first systematic review on the application of RL in intensive care medicine we found no studies that demonstrated improved patient outcomes from RL-based technologies. All studies reported that RL-agent policies outperformed clinician policies, but such assessments were all based on retrospective off-policy evaluation.

Machine Learning-Based Prediction of COVID-19 Prognosis Using Clinical and Hematologic Data.

The coronavirus disease 2019 (COVID-19) pandemic is challenging healthcare systems worldwide. The prediction of disease prognosis has a critical role in confronting the burden of COVID-19. We aimed to investigate the feasibility of predicting COVID-19 patient outcomes and disease severity based on clinical and hematological parameters using machine learning techniques. This multicenter retrospective study analyzed records of 485 patients with COVID-19, including demographic information, symptoms, hematological variables, treatment information, and clinical outcomes. Different machine learning approaches, including random forest, multilayer perceptron, and support vector machine, were examined in this study. All models showed a comparable performance, yielding the best area under the curve of 0.96, in predicting the severity of disease and clinical outcome. We also identified the most relevant features in predicting COVID-19 patient outcomes, and we concluded that hematological parameters (neutrophils, lymphocytes, D-dimer, and monocytes) are the most predictive features of severity and patient outcome.

Endotype evaluation of Hispanic/Latinx-American patients with chronic rhinosinusitis with nasal polyps.

KEY POINTS: Hispanic-American patients with chronic rhinosinusitis with nasal polyps have a comparable level of tissue eosinophilia compared to their Caucasian counterparts in the United States. Mixed inflammation involving both neutrophils and eosinophils is more common in this population compared to Caucasians. Findings from this study may indicate that Hispanic-American patients have a unique endotype or endotypes that deserves further investigation.

Do alternative tobacco products induce less adverse respiratory risk than cigarettes?

RATIONALE: Due to the relatively short existence of alternative tobacco products, gaps exist in our current understanding of their long-term respiratory health effects. We therefore undertook the first-ever side-by-side comparison of the impact of chronic inhalation of aerosols emitted from electronic cigarettes (EC) and heated tobacco products (HTP), and combustible cigarettes (CC) smoke. OBJECTIVES: To evaluate the potential differential effects of alternative tobacco products on lung inflammatory responses and efficacy of vaccination in comparison to CC. METHODS: Mice were exposed to emissions from EC, HTP, CC, or air for 8 weeks. BAL and lung tissue were analyzed for markers of inflammation, lung damage, and oxidative stress. Another group was exposed for 12 weeks and vaccinated and challenged with a bacterial respiratory infection. Antibody titers in BAL and sera and pulmonary bacterial clearance were assessed. MAIN RESULTS: EC- and HTP-aerosols significantly augmented lung immune cell infiltrates equivalent to that achieved following CC-exposure. HTP and CC significantly increased neutrophil numbers compared to EC. All products augmented numbers of B cells, T cells, and pro-inflammatory IL17A+ T cells in the lungs. Decreased lung antioxidant activity and lung epithelial and endothelial damage was induced by all products. EC and HTP differentially augmented inflammatory cytokines/chemokines in the BAL. Generation of immunity following vaccination was impaired by EC and HTP but to a lesser extent than CC, with a CC > HTP > EC hierarchy of suppression of pulmonary bacterial clearance. CONCLUSIONS: HTP and EC-aerosols induced a proinflammatory pulmonary microenvironment, lung damage, and suppressed efficacy of vaccination.