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Positron Emission Tomography (PET) ligands have advanced Alzheimers disease (AD) diagnosis and treatment. Using autoradiography and cryo-EM, we identify AD brain tissue with elevated tau burden, purify filaments, and determine the structure of second-generation high avidity PET ligand MK-6240 at 2.31 Å resolution, which bound at a 1:1 ratio within the cleft of tau paired-helical filament (PHF), engaging with glutamine 351, lysine 353, and isoleucine 360. This information elucidates the basis of MK-6240 PET in quantifying PHF deposits in AD and may facilitate the structure-based design of superior ligands against tau amyloids.

ObjectiveEvaluate whether total elbow replacement (TER) through a lateral approach is accurate and stable.Animals12 skeletally mature large-breed dog cadavers were used.MethodsLimb alignment, elbow joint motion, and collateral ligament laxity were evaluated preoperatively. The order of surgery (left or right) and the approach (lateral or medial) were randomly selected for TER in each dog. The other approach was used in the contralateral elbow. Intraoperative technical difficulties, duration of surgery, and anatomic complications were recorded. Limb alignment, elbow joint motion, collateral ligament laxity, and prosthetic component alignment were evaluated after surgery. Data were collected from June 11 to 15, 2023.ResultsThe duration of surgery using a lateral or medial approach did not differ (P = .499). Anatomic complications were not observed. The lateral approach resulted in 8° more elbow extension (P = .003), 1.58° less lateral collateral ligament constraint (P = .033), 2.80° less medial collateral ligament constraint (P = .002), 4.38° less frontal plane constraint (P = .004), 8° greater humeral component inclination (P = .033), and 5.6° greater radioulnar component varus (P = .001) than the medial approach. Varus of the radius, mechanical axis deviation, limb supination, elbow flexion, mediolateral humeral component and craniocaudal radioulnar component orientation did not differ among joints operated using a lateral or medial approach. In normal cadaveric elbows, a lateral approach for TER appears feasible, producing equivalent limb alignment, joint laxity, and joint motion to normal elbows and to TER placed using a medial approach.Clinical relevanceIn dogs, TER can be performed using a lateral surgical approach.

BACKGROUND: Detection and treatment of anal histologic high-grade squamous intraepithelial lesions (hHSIL) prevents anal cancer. However, anal hHSIL incidence among women with human immunodeficiency virus (HIV, WHIV) remains unknown. Performance of anal high-risk human papillomavirus ([hr]HPV), anal cytology (anal-cyt), and both for hHSIL detection longitudinally over 2 years also remains undetermined. METHODS: We determined 2-year incidence and cumulative risk estimates (2-y-CR) of anal hHSIL among WHIV using prevalence and incidence (per 100 person-years [py]) observations stratified by baseline hrHPV and/or anal-cyt results. RESULTS: In total, 229 WHIV with complete baseline data were included in the analysis; 114 women without prevalent anal hHSIL were followed with 2 annual evaluations. Median age was 51, 63% were Black, and 23% were Hispanic. Anal hrHPV or abnormal anal-cyt was associated with an increased risk of incident anal hHSIL at 2 years (18.9/100py [95% confidence interval {CI} 11.4-31.3] and 13.4/100py [95% CI 8.0-22.7], respectively) compared with no detection of anal HPV or negative cytology (2.8/100py [95% CI 1.1-7.4] and 4.2 [95% CI, 1.8-10.2]) The presence of anal hrHPV with abnormal cytology was associated with 2-y-CR of anal hHSIL of 65.6% (95% CI 55.4%-75%); negative hrHPV with negative cytology was associated with 2-y-CR of anal hHSIL of 9.2% (95% CI 7.0-16.0). CONCLUSIONS: Detection of anal hrHPV or abnormal anal cytology are comparable predictors for 2-y-CR of anal hHSIL. The absence of anal hrHPV combined with negative cytology was predictive of a lower (but measurable) risk of developing anal hHSIL. These findings provide important data to inform anal cancer screening guidelines for WHIV.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Abstract Positron Emission Tomography (PET) ligands have advanced Alzheimer’s disease (AD) diagnosis and treatment. Using autoradiography and cryo-EM, we identify AD brain tissue with elevated tau burden, purify filaments, and determine the structure of second-generation high avidity PET ligand MK-6240 at 2.31 Å resolution, which bound at a 1:1 ratio within the cleft of tau paired-helical filament (PHF), engaging with glutamine 351, lysine 353, and isoleucine 360. This information elucidates the basis of MK-6240 PET in quantifying PHF deposits in AD and may facilitate the structure-based design of superior ligands against tau amyloids.

Background: COVID-19 has put a huge strain on the healthcare systems worldwide, requiring unprecedented intensive care resources. There is still an unmet clinical need for easily available biomarkers capable of predicting the risk for severe disease. The main goal of this prospective multicenter study was to identify biomarkers that could predict ICU admission and in-hospital mortality. Methods: We prospectively recruited COVID-19 PCR positive patients in two hospitals, in Belgium and Italy. Blood samples were collected at hospital admission and 20 potential biomarkers were measured with the Luminex technology. Logistic regression models were performed to identify the biomarkers that, alone or together, were associated with patient disease severity. Results: Our study demonstrates that elevated levels of circulating inflammatory cytokines were associated with disease severity in COVID-19 hospitalized patients. CXCL10, IL-4, IL-6 and MCP-1 values were predictive of ICU admission. Elevated levels of IL-6 and MCP-1 were also associated with in hospital death in COVID-19 hospitalized patients. Conclusion: Altogether, elevated and correlated inflammatory cytokines in the blood of COVID-19 patients at hospital admission are predictive of disease severity and suggest a dysregulated inflammation induced by SARS-CoV-2 infection.

Abstract Safe and effective brain tumor surgery aims to remove tumor tissue, not non-tumoral brain. This is a challenge since tumor cells are often not visually distinguishable from peritumoral brain during surgery. To address this, we conducted a multicenter study testing whether the Sentry System could distinguish the three most common types of brain tumors from brain tissue in a label-free manner. The Sentry System is a new real time, in situ brain tumor detection device that merges Raman spectroscopy with machine learning tissue classifiers. Nine hundred and seventy-six in situ spectroscopy measurements and colocalized tissue specimens were acquired from 67 patients undergoing surgery for glioblastoma, brain metastases, or meningioma to assess tumor classification. The device achieved diagnostic accuracies of 91% for glioblastoma, 97% for brain metastases, and 96% for meningiomas. These data show that the Sentry System discriminated tumor containing tissue from non-tumoral brain in real time and prior to resection.

Abstract We discuss the upper limit, k max, of the transverse-momentum integration performed in the k t -factorization formula. Based on explicit calculations in the Yukawa theory and the study of seminal papers, we argue that k max is equal to the factorization scale μ F used to factorize the cross section into an off-shell hard coefficient and a universal factor. There is consequently a relation between k max and the definition of unintegrated parton densities (UPDFs). The use of an inconsistent relation leads potentially to the overestimation of the cross section, which has been observed, e.g., in D-meson production [1]. One of our conclusions is that UPDFs related to collinear PDFs by an integration up to μ ∼ Q, where Q is the hard scale and μ the scale in the collinear PDFs, imply that k max 2 $$ {k}_{\textrm{max}}^2 $$ ∼ Q 2. Integrating the transverse-momentum significantly above may result in the overestimation of the cross section. On the opposite, for UPDFs related to the collinear ones by an integration of the transverse momentum up to infinity, any k max 2 $$ {k}_{\textrm{max}}^2 $$ > Q 2 is fine.

Objective: This study aimed to assess the association of body mass index (BMI) with anal high-risk human papillomavirus (HR-HPV) and biopsy-confirmed histologic anal high-grade squamous intraepithelial lesions (HSIL) among a clinic-based sample of Hispanics in Puerto Rico. Methods: This cross-sectional study evaluated medical records of adults who received services at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center between October 2014 and December 2022. The study included 543 records with complete clinical information regarding anal HR-HPV and anal HSIL status. Chi-square and logistic regression analyses were performed. Results: Mean age of participants was 44.10 ± 13.24 years, 65.2% were men, 71.7% were HIV-infected, 74.4% had anal HR-HPV infection, and 37.9% had biopsy-confirmed HSIL. Regarding BMI, 2.4% were underweight, 31.9% normal weight, and 39.0 % overweight; while 17.3 % had class I, 5.2% class II, and 4.2% class III obesity. No significant association was observed between BMI and anal HR-HPV infection in adjusted analyses. Lower odds of anal HSIL were observed among overweight individuals (OR: 0.63, 95% CI: 0.41 – 0.99) and those with class II/III obesity (OR: 0.48, 95% CI: 0.22 – 1.01) compared to adults with underweight/normal BMI, after adjusting for potential confounders. No significant association was observed for class I obesity. Conclusion: BMI was not associated with anal HR-HPV infection. Overweight and obese individuals had lower odds of having anal HSIL than adults with underweight/normal BMI. This finding could suggest underdiagnosis of HSIL among overweight/obese individuals, or reduced risk in this group.

Metabolic rewiring is essential for tumor growth and progression to metastatic disease, yet little is known regarding how cancer cells modify their acquired metabolic programs in response to different metastatic microenvironments. We have previously shown that liver-metastatic breast cancer cells adopt an intrinsic metabolic program characterized by increased HIF-1α activity and dependence on glycolysis. Here, we confirm by in vivo stable isotope tracing analysis (SITA) that liver-metastatic breast cancer cells retain a glycolytic profile when grown as mammary tumors or liver metastases. However, hepatic metastases exhibit unique metabolic adaptations including elevated expression of genes involved in glutathione (GSH) biosynthesis and reactive oxygen species (ROS) detoxification when compared to mammary tumors. Accordingly, breast-cancer-liver-metastases exhibited enhanced de novo GSH synthesis. Confirming their increased capacity to mitigate ROS-mediated damage, liver metastases display reduced levels of 8-Oxo-2′-deoxyguanosine. Depletion of the catalytic subunit of the rate-limiting enzyme in glutathione biosynthesis, glutamate-cysteine ligase (GCLC), strongly reduced the capacity of breast cancer cells to form liver metastases, supporting the importance of these distinct metabolic adaptations.Loss of GCLC also affected the early steps of the metastatic cascade, leading to decreased numbers of circulating tumor cells (CTCs) and impaired metastasis to the liver and the lungs. Altogether, our results indicate that GSH metabolism could be targeted to prevent the dissemination of breast cancer cells.

Abstract The one-loop contribution of scalar and vector leptoquarks (LQs) to the electromagnetic properties (NEPs) of massive Dirac neutrinos is presented via an effective Lagrangian approach. For the contribution of gauge LQs to the effective neutrino charge radius defined in Bernabeu et al. (Phys Rev Lett 89:101802, 2002. https://doi.org/10.1103/PhysRevLett.89.101802 [Erratum: Phys Rev Lett 89:229902 (2002)]), we considered a Yang–Mills scenario and used the background field method for the calculation. Analytical results for nonzero neutrino mass are presented, which can be useful to obtain the NEPs of heavy neutrinos, out of which approximate expressions are obtained for light neutrinos. For the numerical analysis we concentrate on the only renormalizable scalar and vector LQ representations that do not need extra symmetries to forbid tree-level proton decay. Constraints on the parameter space consistent with current experimental data are then discussed and it is found that the scalar $${\widetilde{R}}_2$$ R ~ 2 and the vector $$U_1$$ U 1 representations could yield the largest LQ contributions to the NEPs: for LQ couplings to both left- and right handed neutrinos of the order of O(1) and a LQ mass of 1.5-2 TeV, the magnetic dipole moment (MDM) of a Dirac neutrino with a mass in the eV scale can be of the order of $$10^{-9}$$ 10 - 9 – $$10^{-10}$$ 10 - 10 $$\mu _B$$ μ B , whereas its neutrino electric dipole moment (EDM) can reach values as high as $$10^{-20}$$ 10 - 20 – $$10^{-19}$$ 10 - 19 ecm. On the other hand, the effective NCR can reach values up to $$10^{-35}$$ 10 - 35 cm $$^2$$ 2 even if LQs do not couple to right-handed neutrinos, in which case the EDM vanishes and the contribution to the MDM would be negligible.

Abstract Efficacy of the human epidermal growth factor receptor (HER)2-targeting trastuzumab emtansine (T-DM1) in breast cancer (BC) relies on HER2 status determined by immunohistochemistry or fluorescence in-situ hybridization. Heterogeneity in HER2 expression, however, generates interest in “whole-body” assessment of HER2 status using molecular imaging. We evaluated the role of HER2-targeted molecular imaging in detecting HER2-positive BC lesions and patients unlikely to respond to T-DM1. Patients underwent zirconium-89 (89Zr) trastuzumab (HER2) PET/CT and [18F]-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT before T-DM1 initiation. Based on 89Zr-trastuzumab uptake, lesions were visually classified as HER2-positive (visible/high uptake) or HER2-negative (background/close to background activity). According to proportion of FDG-avid tumor load showing 89Zr-trastuzumab uptake (entire/dominant part or minor/no part), patients were classified as HER2-positive and HER2-negative, respectively. Out of 265 measurable lesions, 93 (35%) were HER2-negative, distributed among 42 of the 90 included patients. Of these, 18 (19%) lesions belonging to 11 patients responded anatomically (>30% decrease in axial diameter from baseline) after three T-DM1 cycles, resulting in an 81% negative predictive value (NPV) of the HER2 PET/CT. In combination with early metabolic response assessment on FDG PET/CT performed before the second T-DM1 cycle, NPVs of 91% and 100% were reached in predicting lesion-based and patient-based (RECIST1.1) response, respectively. Therefore, HER2 PET/CT, alone or in combination with early FDG PET/CT, can successfully identify BC lesions and patients with a low probability of clinical benefit from T-DM1.

Summary: The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. Analysis of The Cancer Genome Atlas data shows recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a panel of 23 primary tumor/patient-derived xenograft basal breast cancers reveals early evolution of chr4p deletion. Mechanistically we show that chr4p loss is associated with enhanced proliferation. Gene function studies identify an unknown gene, C4orf19, within chr4p, which suppresses proliferation when overexpressed—a member of the PDCD10-GCKIII kinase module we name PGCKA1. Genome-wide pooled overexpression screens using a barcoded library of human open reading frames identify chromosomal regions, including chr4p, that suppress proliferation when overexpressed in a context-dependent manner, implicating network interactions. Together, these results shed light on the early emergence of complex aneuploid karyotypes involving chr4p and adaptive landscapes shaping breast cancer genomes.

Several studies have been conducted that show the crucial role of active participation in music in health promotion (e.g. Dingle et al., 2021; Sheppard & Broughton, 2020); however, little research has focused on the biopsychosocial effects of choral singing. The present study aims to evaluate the effectiveness, in terms of improving physiological and psychosocial factors, of a choral program for middle-aged and older individuals. We integrated our study with qualitative observations of the atmosphere and flow state experienced by the choristers. The data were collected before and after 12 weeks of training, with 23 participants took part in the study. They experienced significant improvements in weight, oxygen saturation, heart rate, and satisfaction of psychological needs. A beneficial trend, although not statistically significant, were observed for blood pressure, cholesterol, triglycerides, stress, psychological needs, and mental health. The observations progressively revealed a more cohesive and focused group. Our findings support the potential for cross-disciplinary collaboration between healthcare and arts policy to promote and enhance health and well-being throughout the lifespan.

Summary: The existence of neural stem cells (NSCs) in adult human brain neurogenic regions remains unresolved. To address this, we created a cell atlas of the adult human subventricular zone (SVZ) derived from fresh neurosurgical samples using single-cell transcriptomics. We discovered 2 adult radial glia (RG)-like populations, aRG1 and aRG2. aRG1 shared features with fetal early RG (eRG) and aRG2 were transcriptomically similar to fetal outer RG (oRG). We also captured early neuronal and oligodendrocytic NSC states. We found that the biological programs driven by their transcriptomes support their roles as early lineage NSCs. Finally, we show that these NSCs have the potential to transition between states and along lineage trajectories. These data reveal that multipotent NSCs reside in the adult human SVZ.

Abstract Systemic sclerosis (SSc) is a rare autoimmune disease in which interstitial lung disease (ILD) is the leading cause of morbidity and mortality. Clinical management of the lung disease is mainly based on pulmonary function testing (PFT) and their changes over time. Little is known about the reproducibility of PFT testing in SSc patients. The aim of this study was to assess the test–retest reliability and reproducibility of PFTs in SSc patients with or without ILD over 30 days in order determine the potential physiologic variation over the time. We performed prospective observational study of SSc patients. The FVC, FEV1/FVC ratio, DLCO and KCO parameters were assessed in this population at four different timepoints; T0 (time 0) and H3 (T0 + 3 h) defined test–retest reliability, D15 (T0 + 15 days) and D30 (T0 + 30 days) for reproducibility. A mixed linear model was used to test the effect of time (and therefore reproducibility) on patients and we looked for an interaction. We included 25 SSc patients divided in two groups, 14 with ILD and 11 non-ILD. Interactions between time and group were not significant and were not reported. Time and group did not significantly influence the different measures of the PFT: FVC [p values time and group effect respectively (0.33; 0.34)], FEV1/FVC ratio (0.093; 0.056) and DLCO (0.99; 0.13) in the ILD and non ILD group (Table S2). The analyse with interactions between time and group were not significant and are not reported. We also used a Bland Altman test to assess reproducibility for FVC (L) and DLCO (mMKpa/min/L), Figs. 1 and 2 respectively. The measurements were therefore reproducible over time and in each group. PFT parameters are reproducible over time in a clinically stable population of SSc (no significant effect of the time T0, H3, D15 and D30) and there is no significant distinction between patients with ILD and no ILD. These respiratory functional data can further underline their use in clinical practice.

Background: L. Australis is one of the most prevalent Leptospira strains infecting dogs, leading, in natural conditions, to severe life-threatening cases. Objective: The objective was to evaluate the onset and duration of immunity (OOI and DOI) induced by a new licensed quadrivalent antileptospiral vaccine (EURICAN® L4) including four Leptospira components (Canicola, Icterohaemorrhagiae, Grippotyphosa and Australis) against L. Australis. To this end, a severe L. Australis challenge model was developed, using a canine strain recently isolated from the field. Material and Methods: Seven- to ten-week-old puppies received two doses of the vaccine four weeks apart and were challenged with an L. Australis isolate two weeks (OOI) and 12 months (DOI) later. Mortality, clinical signs, leptospiremia, leptospiruria, renal carriage, and renal lesions were assessed after challenge. Results: The challenge induced multiple severe clinical signs in controls, leading to the death or euthanasia of 83% of puppies and 57% of adults. In controls, leptospiremia was detected in all dogs, leptospiruria in 67% of puppies and 86% of adults, kidneys tested positive for Leptospira in 83% of puppies and 71% of adults, and kidney lesions were observed in 100% of puppies and 86% of adults. In addition, thrombocytopenia associated with increased concentrations of urea, creatinine, and aspartate aminotransferase was recorded in controls displaying severe clinical signs. In both OOI and DOI studies, none of the vaccinates had clinical signs, no Leptospira was detected in blood, urine, and kidney samples, and no kidney lesions were observed in vaccinates. No significant changes in hematological and biochemical parameters in vaccinates were recorded. Conclusion: EURICAN® L4 was shown to induce quick and long-lasting protection against a severe L. Australis infectious challenge, preventing mortality, clinical signs, infection, bacterial excretion, renal lesions, and renal carriage.

Background: Interstitial lung diseases (ILDs) are an heterogeneous group of infiltrating lung pathologies, for which prompt diagnosis and continuous assessment are of paramount importance. While chest CT is an established diagnostic tool for ILDs, there are no formal guidelines on the follow-up regimen, leaving the frequency and modality of follow-up largely at the clinician’s discretion. Methods: The study retrospectively evaluated the indication of chest CT in a cohort of 129 ILD patients selected from the ambulatory care polyclinic at University Hospital of Liège. The aim was to determine whether the imagining acquisition had a true impact on clinical course and follow-up. We accepted three different situations for justifying the indication of the CTs: clinical deterioration, a decrease in pulmonary function tests (at least a 10% drop in a parameter), and monitoring for oncological purposes. The other indications, mainly routine follow-up, were classified as “non-justified”. Radiation dose output was evaluated with Computed Tomography Dose Index (CTDI) and Dose Length Product (DLP). Results: The mean number of CT scans per patient per year was 1.7 ± 0.4, determining irradiation in CTDI (mGy)/year of 34.9 ± 64.9 and DLP in (mGy*cm)/year of 1095 ± 1971. The percentage of justified CT scans was 57 ± 32%, while the scans justified a posteriori were 60 ± 34%. Around 40% of the prescribed monitoring CT scans had no impact on the management of ILD and direct patient care. Conclusions: Our study identifies a trend of overuse in chest CT scans at follow-up (up to 40%), outside those performed for clinical exacerbation or oncological investigation. In the particular case of ILD exacerbation, CT scan value remains high, underlying the benefit of this strategy.

The unprecedented precision of satellite laser altimetry data from the NASA ICESat-2 mission and the increasing availability of high-resolution elevation datasets open new opportunities to measure snow depth in mountains, a critical variable for ecosystem and water resource monitoring. We retrieved snow depth over the upper Tuolumne basin (California, USA) for 3 years by differencing ICESat-2 ATL06 snow-on elevations and various snow-off digital elevation models. Snow depth derived from ATL06 data only (snow-on and snow-off) offers a poor temporal and spatial coverage, limiting its potential utility. However, using a digital terrain model from airborne lidar surveys as the snow-off elevation source yielded a snow depth accuracy of ∼ 0.2 m (bias) and precision of ∼ 1 m (random error) across the basin, with an improved precision of 0.5 m for low slopes (< 10∘), compared to eight reference airborne lidar snow depth maps. Snow depths derived from ICESat-2 ATL06 and a satellite photogrammetry digital elevation model have a larger bias and reduced precision, partly induced by increased errors in forested areas. These various combinations of repeated ICESat-2 snow surface elevation measurements with satellite or airborne products will enable tailored approaches to map snow depth and estimate water resource availability in mountainous areas with limited snow depth observations.

Pulmonary vascular diseases such as pulmonary embolism and pulmonary hypertension are important and frequently under-recognised conditions. This article provides an overview of key highlights in pulmonary vascular diseases from the European Respiratory Society International Congress 2023. This includes insights into disease modification in pulmonary arterial hypertension and novel therapies such as sotatercept and seralutinib. Exciting developments in our understanding of the mechanisms underpinning pulmonary hypertension associated with interstitial lung disease are also explored. A comprehensive overview of the complex relationship between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) is provided along with our current understanding of the molecular determinants of CTEPH. The importance of multidisciplinary and holistic care cannot be understated, and this article also addresses advances beyond medication, with a special focus on exercise training and rehabilitation.

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.

Background: Limited research exists regarding the association between smoking and anal warts. In this study, we evaluated this association among a clinic-based Hispanic population in Puerto Rico. Methods: Cross-sectional study among eligible patients seen at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center (2016–2023) (n = 920). Sociodemographic and clinical variables were collected from medical records. Patients underwent a high-resolution anoscopy (HRA) during the clinical visit; physicians assessed anal condylomas on HRA. Poisson regression models with robust standard errors were used to evaluate the association between smoking and anal warts. Demographic and clinical factors were also assessed. Results: The mean age of participants was 45.8 ± 13.1 years, 66.4 % were men, and 21.6 % were current smokers. While 10.8 % self-reported a history of anogenital condylomas, 18.9 % had anal condylomas on clinical evaluation. A higher prevalence of anal condylomas was observed among current smokers (PR = 1.28, 95 % CI: 0.94–1.75) in comparison to non-smokers in adjusted analysis, but this was not statistically significant. However, a higher prevalence of anal condylomas was observed among younger individuals (PR = 0.96, 95 % CI: 0.96–0.98) and individuals with anal high-grade squamous intraepithelial lesions (HSIL) as compared to those with benign histology (PR = 1.74. 95 % CI: 1.09–2.77). Conclusions: Although current smoking seemed to be positively associated with anal condylomas in this high-risk Hispanic population, this finding was not statistically significant as the power to detect an association was limited. However, younger age and HSIL diagnosis were associated with a higher prevalence of anal condylomas.