Identification of a clinically efficacious CAR T cell subset in diffuse large B cell lymphoma by dynamic multidimensional single-cell profiling.

Chimeric antigen receptor (CAR) T cells used for the treatment of B cell malignancies can identify T cell subsets with superior clinical activity. Here, using infusion products of individuals with large B cell lymphoma, we integrated functional profiling using timelapse imaging microscopy in nanowell grids with subcellular profiling and single-cell RNA sequencing to identify a signature of multifunctional CD8+ T cells (CD8-fit T cells). CD8-fit T cells are capable of migration and serial killing and harbor balanced mitochondrial and lysosomal volumes. Using independent datasets, we validate that CD8-fit T cells (1) are present premanufacture and are associated with clinical responses in individuals treated with axicabtagene ciloleucel, (2) longitudinally persist in individuals after treatment with CAR T cells and (3) are tumor migrating cytolytic cells capable of intratumoral expansion in solid tumors. Our results demonstrate the power of multimodal integration of single-cell functional assessments for the discovery and application of CD8-fit T cells as a T cell subset with optimal fitness in cell therapy.

Protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of brain tumors.

Here, we present a protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of primary, metastatic, and recurrent brain tumors. We provide instructions for isolating peripheral blood mononuclear cells (PBMCs), producing CAR T cells in conjunction with locoregional delivery, and preclinical trial design and analysis involving CAR T cells. Additionally, we describe comprehensive preclinical readouts and guidelines for critical endpoint sample collections. In line with clinical trial procedures, our protocol broadens available treatment modalities for direct clinical translation. For complete details on the use and execution of this protocol, please refer to Donovan et al.1.

TurboID-Based IRE1 Interactome Reveals Participants of the Endoplasmic Reticulum-Associated Protein Degradation Machinery in the Human Mast Cell Leukemia Cell Line HMC-1.2.

The unfolded protein response is an intricate system of sensor proteins in the endoplasmic reticulum (ER) that recognizes misfolded proteins and transmits information via transcription factors to either regain proteostasis or, depending on the severity, to induce apoptosis. The main transmembrane sensor is IRE1α, which contains cytoplasmic kinase and RNase domains relevant for its activation and the mRNA splicing of the transcription factor XBP1. Mast cell leukemia (MCL) is a severe form of systemic mastocytosis. The inhibition of IRE1α in the MCL cell line HMC-1.2 has anti-proliferative and pro-apoptotic effects, motivating us to elucidate the IRE1α interactors/regulators in HMC-1.2 cells. Therefore, the TurboID proximity labeling technique combined with MS analysis was applied. Gene Ontology and pathway enrichment analyses revealed that the majority of the enriched proteins are involved in vesicle-mediated transport, protein stabilization, and ubiquitin-dependent ER-associated protein degradation pathways. In particular, the AAA ATPase VCP and the oncoprotein MTDH as IRE1α-interacting proteins caught our interest for further analyses. The pharmacological inhibition of VCP activity resulted in the increased stability of IRE1α and MTDH as well as the activation of IRE1α. The interaction of VCP with both IRE1α and MTDH was dependent on ubiquitination. Moreover, MTDH stability was reduced in IRE1α-knockout cells. Hence, pharmacological manipulation of IRE1α-MTDH-VCP complex(es) might enable the treatment of MCL.

Prediction of Reproductive Outcomes of Intracytoplasmic Sperm Injection Cycles Using a Multivariate Scoring System.

Background: Prediction of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) success is crucial in counselling patients about their real chance of getting a live birth before commencing treatment. A multivariate scoring system proposed by Younis et al., 2010, was amongst the predictive models used to evaluate IVF/ICSI success. The score entitles basal endocrine, clinical and sonographic parameters. Aims: The objective of this study is to assess the predictability of the Younis multivariate score for pregnancy outcomes in ICSI cycles. Settings and Design: This prospective observational cohort study (NCT03846388) included patients who pursued IVF or ICSI in a tertiary infertility unit between February 2019 and December 2021. Materials and Methods: The score variables were age, body mass index, antral follicle count, basal follicle-stimulating hormone (FSH), basal FSH/luteinising hormone ratio, infertility duration, number of previous cancellations and mean ovarian volume. For each woman included in the study, Younis multivariate score was calculated. Then, we correlate the different reproductive outcomes with score levels to validate the score predictability. A score of ≤14 was defined as a low score based on the previous study's results. Statistical Analysis Used: The student's t-test and Mann-Whitney test were used to compare numerical variables, whereas categorical variables were analysed using the Chi-square test. A receiver operating curve (ROC) and a multivariate logistic regression model were used to investigate the predictability of the Younis scoring model for cycle outcomes. Results: Two hundred ninety-two ICSI-ET cycles were analysed. Of the total cohort, 143 (48.97%) women included showed a low score (≤14), whereas 149 (51.03%) women showed a high score (>14). Women with low scores had significantly higher pregnancy and live birth rates compared to women with high scores (60.1% vs. 7.4%, respectively, P < 0.001; 44.7% vs. 6.7%, respectively, P < 0.001). The area under the curve (AUC) in the ROC curve analysis showed a higher predictability for the scoring system for live birth rate with an AUC of 0.796, with a sensitivity of 86.5% and specificity of 63.8% when using a cut-off level of ≤14. For pregnancy prediction, the AUC was 0.829, with a sensitivity of 88.66% and a specificity of 70.77% when using the same cut-off. Women who have a low score have a high chance of having frozen embryos. Likewise, women who have a high score have a very high chance of cycle cancellation. Conclusions: The Younis multivariate score can be used for the prediction of ICSI cycle outcomes and to calculate the chance of cycle cancellation, pregnancy and take-home baby before ICSI.

Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.

In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 108 T cells per m2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 108 CAR+ T cells per m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 .

Outcomes of Endoscopic Stapedectomy: Systematic Review.

Introduction Stapes surgery was traditionally performed with the use of microscopy either through postauricular, endaural or transcanal approaches. Endoscopic stapedectomy ushered a revolution as a new technique with less complications. Objective To review the outcomes of endoscopic stapes surgery with an emphasis on intraoperative and postoperative clinical and audiological results. Data Synthesis A literature review on the PubMed, Web of Science, Scopus, the Cochrane Library, and Embase databases was conducted. Endoscopic stapes surgery or stapedotomy were the main keywords used, and we searched for studies and research published from January 2015 to October 2021. Articles on endoscopic stapes surgery were included, and qualitative and descriptive analyses of the studies and outcomes data regarding audiometric changes and postoperative complications were conducted. Articles including patients with cholesteatoma were excluded. A total of 122 studies were retrieved for qualitative and descriptive analyses and to measure the outcomes of endoscopic stapedotomy; only 12 studies met the inclusion criteria, and the rest was excluded. The meta-analysis revealed a statistically significant difference in hearing improvement. The gain in air-bone gap ranged from 9 dB to 16 dB. A low rate of operative and postoperative complications was reported. Conclusions Endoscopic stapes surgery appears to be a reasonable alternative to microscopic stapes surgery, with shorter operative times, low complication rate, and significant hearing improvement. The endoscopic technique enabled a better visualization and less scutum drilling, which was confirmed by all included studies.

Tobacco Use and Uptake of COVID-19 Vaccinations in Finland: A Population-Based Study.

INTRODUCTION: People who smoke are at higher risk of Coronavirus Disease-2019 (COVID-19) hospitalizations and deaths and might benefit greatly from high COVID-19 vaccination coverage. Studies on tobacco use and COVID-19 vaccine uptake in the general population are lacking. AIMS AND METHODS: We conducted a cohort study utilizing linked data from 42 935 participants from two national surveys in Finland (FinSote 2018 and 2020). Exposures were smoking and smokeless tobacco (snus) use. The primary outcome was the uptake of two COVID-19 vaccine doses. Secondary outcomes were the uptake of one COVID-19 vaccine dose; three COVID-19 vaccine doses; time between the first and second dose; and time between the second and third dose. We examined the association between tobacco use and COVID-19 vaccine uptake and between-dose spacing in Finland. RESULTS: People who smoke had a 7% lower risk of receiving two COVID-19 vaccine doses (95% confidence interval [CI] = 0.91; 0.96) and a 14% lower risk of receiving three doses (95% CI = 0.78; 0.94) compared to never smokers. People who smoked occasionally had a lower risk of receiving three vaccine doses. People who currently used snus had a 28% lower uptake of three doses (95% CI = 0.56; 0.93) compared to never users but we did not find evidence of an association for one or two doses. We did not find evidence of an association between tobacco use and spacing between COVID-19 vaccine doses. CONCLUSIONS: People who smoke tobacco products daily, occasionally, and use snus had a lower uptake of COVID-19 vaccines. Our findings support a growing body of literature on lower vaccination uptake among people who use tobacco products. IMPLICATIONS: People who smoke or use snus might be a crucial target group of public health efforts to increase COVID-19 vaccinations and plan future vaccination campaigns. CLINICAL TRIALS REGISTRATION NUMBER: NCT05479383.

Different techniques of adenoidectomy and its impact on middle ear pressure: a randomized controlled study.

OBJECTIVES: The aim of this work is to compare between different techniques of adenoidectomy: endoscopic microdebrider-assisted, coblation and conventional adenoidectomy and its effect on middle ear pressure. BACKGROUND: Adenoidectomy, either alone or with tonsillectomy, is considered among the most performed procedures in pediatric otorhinolaryngology. This procedure usually related to the Eustachian tube function and middle ear status. Eustachian tube dysfunction is mainly caused by mechanical obstruction of the tubal orifice, insufficient swallowing and inflammation in the nasopharyngeal mucosa. METHODS: This prospective randomized study was conducted on 90 patients with symptomatic adenoid hypertrophy confirmed by nasopharyngeal X-ray and endoscopic grading preoperatively. Patients were admitted at Otorhinolaryngology department of our institute during the period from January 2022 to January 2023. They were divided into three groups that were operated either by conventional (Group I), endoscopic microdebrider (Group II), or coblation technique (Group III). Each group was assessed through the audiometric parameters plus postoperative bleeding, and VAS results for pain score and postoperative endoscopic grading for adenoid recurrence. RESULTS: Mean age in group A was 9.03 years and in group B was 8.99 years and was 8.99 years in group C with insignificant differences between three groups. There is significant improvement of tympanographic results comparing all groups of the patients at 6 months postoperatively. There is significant relation between the mean VAS comparing preoperative and postoperative results. CONCLUSION: There are better results in tympanographic data at conventional adenoidectomy versus other techniques. However, there are also better postoperative results after either coblation or endoscopic microdebrider adenoidectomy over the conventional technique.

Preoperative Magnetic Resonance Elastography (MRE) of Skull Base Tumours: A Review.

Conventional magnetic resonance imaging (MRI) can detect tumors consistency, but it can't predict tumor stiffness or adherence of the tumor to nearby structures. Magnetic resonance elastography (MRE) is a known non-invasive MRI based imaging technique used to assess the viscoelasticity of the tissues particularly liver fibrosis. This study discussed the importance of preoperative MRE in skull base tumors and the future implications of this new imaging modality. We did review of the English literature (by searching PubMed) regarding the use of MRE in preoperative assessment of skull base tumours stiffness and adherence to surrounding tissues. Recent research demonstrated that MRE can detect the stiffness and adherence of skull base tumors to surrounding structures by recording the spread of mechanical waves in the different tissues. In addition to non-radiation exposure, this technique is fast and can be incorporated into the conventional (MRI) study. MRE can palpate skull base tumours by imaging, allowing the stiffness of the tumour to be assessed. Preoperative assessment of brain tumours consistency, stiffness, and adherence to surrounding tissues is critical to avoid injury of important nearby structures and better preoperative patient counselling regarding surgical approach (endoscopic or open), operative time, and suspected surgical complications. However, the accuracy of MRE is less in small and highly vascular tumors. Also, MRE can't accurately detect tumour-brain adherence, but the new modality (slip-interface imaging) can. Hence, adding MRE to the conventional MRI study may help in preoperative diagnosis and treatment of skull base tumours.

A simple home test to differentiate habitual from pathological mouth breathing.

BACKGROUND: Mouth breathing (MB) is defined as breathing through the mouth alone or the mouth and the nose for more than six months. Unfortunately, after managing its mechanical causes, MB may continue due to habit, obscuring the results of surgical correction of nasal breathing and misleading to unnecessary or aggressive maneuvers. OBJECTIVE: to develop and evaluate a new test to define children of habitual MB. MATERIALS AND METHODS: Design: a prospective observational study conducted from May 2022 to February 2023. SETTING: multicenter; outpatient university clinics and a private ENT center. PARTICIPANTS: 577 children aged 2-12 years and complaining of MB during sleep (±daytime) for ≥6 months were assessed for eligibility, 340 were excluded due to a lack of inclusion criteria, 29 declined or discontinued participation, and 208 were enrolled. Of these, 180 gave reliable data. THE TEST: After about 1 h of the child's sleep, the parent applies one warmed hand to close the child's open mouth recording his awakeness time (AT) for a maximum of 3 min for three nights. On the next visit, the child's examination started for obstruction causes, including endoscopy, and the test results were collected. MAIN OUTCOME AND MEASURES: The AT was compared to examination results aiming to find a significant diagnostic relation. Children with no abnormality in the clinical and endoscopic examination were considered habitual mouth breathers. RESULTS: Among 94 males and 86 females aged 2-12 years, MB duration ranged from 6 to 42 months, with a mean of 15.9. The home test results were presented by the mean AT in seconds. The awakeness time (AT) could discriminate patients' abnormalities at a cut-off level of <133 s, with 98.5% sensitivity and 89.7% specificity. Results <133 s are considered positive. Positive results mean the presence of a cause of obstruction. Negative results suggest no reason could be detected by endoscope or clinical examination. True positive children were 120 (66.7%), and 12 (6.7%) were false positive. True negative children were 43 (23.9%), and 5 (2.8%) were false negative. CONCLUSIONS: Test results ≥133 s are associated with habitual MB. We recommend the test for the initial assessment of night MB.

Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models.

BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM. MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated in vivo via single i.v. injection (1 × 1011 viral particle) with or without fractionated (2 Gy/day x 5 days) radiation followed by analysis of animal survival times, viral infection, and DNA damage. RESULTS: PDOX formation was confirmed in 17/23 (73.9%) GBMs while maintaining key histopathological features and diffuse invasion of the patient tumors. Using differentially expressed genes, we subclassified PDOX models into proneural, classic and mesenchymal groups. Animal survival times were inversely correlated with the implanted tumor cells. SVV-001 was active in vitro by killing primary monolayer culture (4/13 models), 3D neurospheres (7/13 models) and glioma stem cells. In 2/2 models, SVV-001 infected PDOX cells in vivo without harming normal brain cells and significantly prolonged survival times in 2/2 models. When combined with radiation, SVV-001 enhanced DNA damages and further prolonged animal survival times. CONCLUSION: A panel of 17 clinically relevant and molecularly annotated PDOX modes of GBM is developed, and SVV-001 exhibited strong anti-tumor activities in vitro and in vivo.

Risk factors of sudden cardiac death in Egyptian patients younger than 40 years.

BACKGROUND: Sudden cardiac death in young people is a major problem. The causes are well known; however, they may not be discovered before the episode of sudden death. A challenge for the future is identifying patients at risk before an episode of sudden cardiac death. Development of preventive and educational programs is required to identify sudden cardiac death/sudden cardiac arrest (SCD/SCA) risk factors, causes and characteristics. We aimed to study the characteristics of SCD/SCA in a cohort of young Egyptian population. Our retrospective cohort study included 246 patients of SCD/SCA who were collected from 5000 records of arrhythmia patients from January 2010 till January 2020. The records of the specialized arrhythmia clinic were reviewed to collect the families of SCD/SCA. All patients and/or their first-degree relatives were subjected to thorough history taking and clinical evaluation and investigations. Comparisons were done regarding age group and presence of positive family history of SCD. RESULTS: Males constituted 56.9% of the study population. Mean age was 26.6 ± 12.73 years. Positive family history was present in 202 (82.1%) cases. Sixty-one percent of the cases had history of syncopal attacks. SCD/SCA during non-exertion or sleep occurred in 50.4% of cases. Hypertrophic cardiomyopathy was the most common cause of SCD/SCA (20.3%), followed by dilated cardiomyopathy (19.1%), long QT Syndrome (11.4%), complete heart block (8.5%), and Brugada syndrome (6.8%). In the older age group of 18-40 years, hypertrophic cardiomyopathy was responsible for SCD in 44 patients (25.3%) versus 6 patients (8.3%) in younger age group (p-value: 0.003). DCM was also dominant in older age group (42 patients; 24.1%) versus 5 patients (6.9%) in younger age group. Hypertrophic cardiomyopathy was more prevalent in positive family history group (46 patients; 22.8%) versus 4 patients (9.1%) in negative family history group (p-value: 0.041). CONCLUSION: Family history of SCD was the most common risk factor of SCD. The most common cause of SCD in young Egyptian patients below 40 years was hypertrophic cardiomyopathy, followed by dilated cardiomyopathy. Both diseases were more common in the age group between 18 and 40 years. Hypertrophic cardiomyopathy was more common in patients with positive family history of SCD/SCA.

Current tobacco use and SARS-CoV-2 infection in two Norwegian population-based cohorts.

BACKGROUND: Clear evidence of an increased risk for SARS-CoV-2 infection among smokers has not been established. We aimed to investigate associations between cigarette smoking or use of snus (snuff) and other nicotine-containing products and a positive SARS-CoV-2 test, taking test behavior into account. METHODS: Current tobacco use and testing behavior during the pandemic were recorded by adult participants from the Norwegian Mother, Father and Child Cohort Study and The Norwegian Influenza Pregnancy Cohort. SARS-CoV-2 infection status was obtained from The Norwegian Surveillance System for Communicable Diseases (MSIS) in May 2021 (n = 78,860) and antibody measurements (n = 5581). We used logistic regression models stratified by gender and adjusted for age, education, region, number of household members, and work situation. RESULTS: Snus use was more common among men (26%) than women (9%) and more prevalent than cigarette smoking. We found no clear associations between cigarette smoking or snus and a COVID-19 diagnosis among men. Associations among women were conflicting, indicating that cigarette smoke was negatively associated with a diagnosis (OR 0.51, 95% CI 0.35, 0.75), while no association was found for snus use (OR 1.07, 95% CI 0.86, 1.34). Compared with non-users of tobacco, both cigarette smokers and snus users had increased odds of being tested for SARS-CoV-2. CONCLUSIONS: Cigarette smoking, but not snus use, was negatively associated with SARS-CoV-2 infection in women. The lack of an association between snus use and SARS-CoV-2 infection in this population with prevalent snus use does not support the hypothesis of a protective effect of nicotine.

Cord blood transplantation for nonmalignant disorders: early functional immunity and high survival.

There is no consensus on the best donor for children with nonmalignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We evaluated the 2-year overall survival (OS) after umbilical cord blood transplantation (UCBT) in patients with nonmalignant disorders from 2009 to 2020 enrolled in a prospective clinical trial using either 5/6 or 6/6 UCB as the cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. Fifty-five children were enrolled, median age 5 months (range, 1-111 months); primary immune deficiency (45), metabolic (5), hemophagocytic lymphohistiocytosis (1), and hematologic disorders (4). Twenty-six patients had persistent infections before transplant. Nineteen of them (34%) were 6/6 matched, and 36 (66%) were 5/6 human leukocyte antigen-matched. The OS at 2 years was 91% (95% cumulative incidence, 79-96), with a median follow-up of 4.3 years. The median time to neutrophil and platelet recovery were 17 days (range, 5-39 days) and 37 days (range, 20-92 days), respectively. All but one evaluable patient achieved full donor chimerism. The cumulative incidence of acute GVHD grades 2-4 on day 100 was 16% (n = 9). All patients with viral infections at the time of transplant cleared the infection at a median time of 54 days (range, 44-91 days). All evaluable patients underwent correction of their immune or metabolic defects. We conclude that in the absence of MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in young children with nonmalignant disorders. This trial has been registered at www.clinicaltrials.gov as NCT00950846.

Nasal sinuses cholesteatoma: case series and review of the English literature.

BACKGROUND: Nasal sinus cholesteatomas are uncommon slow-growing lesions that are frequently misdiagnosed preoperatively. They can develop due to embryologic remnants or iatrogenic factors (surgical trauma or nasal sinus trauma). In addition, they can cause bone destruction resulting in intracranial or intraorbital complications as well as malignant change if neglected. Complete surgical removal is a must with strict postoperative follow-up. MATERIALS AND METHODS: Three cases of nasal sinus cholesteatoma are reported. The first case was found inside the ethmoidal sinus, the second in the frontal sinus, and the third was found inside a concha bullosa. In all three cases, a wide endoscopic surgical excision was performed. Due to the lateral extension of the lesion, frontal sinus trephine was also used in the case of frontal sinus nasal cholesteatoma. In addition, a review of the English literature for the reported cases of nasal sinus cholesteatomas was conducted. RESULTS: There were no reported recurrence or residual during strict postoperative follow-up for 2 years (by endoscopic examination and diffusion-weighted MRI with delayed postcontrast T1 images). A review of the English literature revealed 42 cases of nasal sinuses cholesteatomas (including the present three cases) (17 in the frontal sinus, 15 in the maxillary sinus, 5 in the ethmoid sinus, 3 in the sphenoid sinus, and 2 in a concha bullosa). CONCLUSIONS: Although nasal sinus cholesteatomas are uncommon, they must be considered in the differential diagnosis of slow-growing nasal sinuses lesions. Preoperative CT scan and diffusion-weighted MRI are essential for proper diagnosis and to exclude other similar lesions, such as nasal sinus mucoceles, cholesterol granuloma, or neoplastic lesions. Wide complete surgical excision is necessary to avoid recurrence and facilitate postoperative follow-up. As with ear cholesteatoma, strict postoperative follow-up is required to detect recurrence or residual early and is performed by endoscopic examination, diffusion-weighted MRI, and delayed post-gadolinium T1 images.

Tobacco use and risk of COVID-19 infection in the Finnish general population.

Empirical evidence, primarily based on hospital-based or voluntary samples, suggests that current smokers have a lower risk of COVID-19 infection than never smokers. In this study, we used nationally representative data to examine the association between tobacco use and the risk of having a confirmed COVID-19 case. We explored several forms of tobacco use, contributing to separate the role of nicotine from smoking. We used data from 44,199 participants from three pooled national health surveys in Finland (FinSote 2018-2020). The primary outcome was a confirmed COVID-19 case. We examined current smoking, moist smokeless tobacco (snus), e-cigarettes with and without nicotine and nicotine replacement therapy products. Current daily smokers had a relative risk of 1.12 of a confirmed COVID-19 case (95% CI 0.65; 1.94) in fully adjusted models compared with never smokers. Current snus use was associated with a 68% higher risk of a confirmed COVID-19 case (RR 1.68, 95% CI 1.02; 2.75) than never users. We did not find conclusive evidence of associations between e-cigarettes with and without nicotine and nicotine replacement therapy products and the risk of confirmed COVID-19 cases. Our findings suggest that nicotine might not have a protective role in the risk of COVID-19 as previously hypothesized.

Successful use of venous graft from native liver with hepatocellular carcinoma during living donor liver transplantation with no impact on recurrence rate: A retrospective cohort study.

Introduction: There are still debates regarding using portal vein (PV) from liver with hepatocellular carcinoma (HCC) for vascular reconstruction. This study aimed to assess the feasibility and patency of PV venous graft from an explanted liver with HCC for the reconstruction of the hepatic veins tributaries or PV in living donor liver transplantation (LDLT) and to see if it has any risk on recurrence of HCC. Patient and methods: We conducted a retrospective study on 81 patients with HCC who underwent LDLT from April 2004 to July 2022. Results: Venous graft from native liver PV was used for vascular reconstruction in 31 patients as follows; reconstruction of V5 in 7 patients, V8 in 4 patients, V6 in 3 patients, combined V5 and V8 in 4 patients, V6 with V5/V8 in 5 patients, and as Y shape venous graft for 2 PV reconstruction in 8 patients. The implantation of the new conduit PV graft after reconstruction of the anterior sector tributaries was direct to the IVC in 8 patients, and to the common orifice of the left and middle hepatic veins in 12 patients. The 1 month, 3 months, and 1-year overall patency of the venous graft was 93.5%, 90.3%, and 84%, respectively. Nine patients had recurrent HCC. In multivariate analysis, the independent risk factors for HCC recurrence were AFP >400 ng/mL (HR = 1.47, 95% CI: 1.69-2.31, P = 0.01), moderate/poor differentiated tumor (HR = 3.06, 95% CI: 2.58-6.29, P = 0.02), and microvascular invasion (HR = 2.51, 95% CI: 1.05-1.93, P = 0.01). Using a PV venous graft had no risk factor for HCC recurrence (P = 0.9). Conclusion: The use of PV venous graft of native liver with HCC for venous reconstruction is a feasible and valuable option in LDLT with good patency rates and no risk of HCC recurrence.

Impact of right ventricular lead position on left ventricular functions and early remodeling in permanent single- and dual-chamber pacemakers.

BACKGROUND: Right ventricular (RV) apical pacing can induce both interventricular dyssynchrony and intraventricular dyssynchrony. Mechanical dyssynchrony after long-term RV apical pacing is associated with reduced left ventricular (LV) systolic function and deterioration in functional capacity. AIM: We aimed to identify the short-term effects of the pacemaker RV lead position on remodeling of LV systolic functions. PATIENTS AND METHODS: The study included 30 patients who presented with an indication of permanent pacing and who underwent permanent single- or dual-chamber pacemaker insertion: 15 patients with RV apical pacing (RV apex), and 15 patients with non-apical pacing (mid-septal). The two-dimensional (2D) speckle tracking imaging technique was used for quantification of global longitudinal function of the left ventricle and dyssynchrony evaluation before pacemaker implantation and after a 3-month follow-up. RESULTS: At the 3­month follow-up, post-pacing 2D speckle tracking echocardiography revealed impairment of global longitudinal strain in all patients and intraventricular dyssynchrony was significantly increased in the apical location compared with the non-apical location (radial dyssynchrony: 108.67 ± 11.68 ms vs. 80.53 ± 8.17 ms, p < 0.001) with a greater difference (50.53 ± 13.30 ms) in the apical location than in the non-apical location (29.87 ± 6.64 ms, p < 0.001). CONCLUSION: In the short-term follow-up, 2D speckle tracking echocardiography showed more radial dyssynchrony in the apical location than in the non-apical location of RV lead. The RV septal pacing is a better alternative in terms of less dyssynchrony compared to RV apical pacing. Older age, higher percentage of pacing, and device type are prognostic factors for development of pacemaker-induced cardiomyopathy.

Factors associated with self-perceived health status in Portugal: Results from the National Health Survey 2014.

Background: Self-perceived health is an important indicator of illness and mortality. This study aims at identifying a wide range of factors that can influence self-perceived health status among a representative sample in Portugal. Methods: We used the 2014 National Health Survey (n = 17,057), whereby participants were required to assess their health status from "Very good," "Good," "Fair," "Poor" to "Very poor." We grouped the answers "Very good" and "Good," and "Poor" and "Very poor," respectively. Multinomial logistic regression was used to compare participants' characteristics across groups by computing odds ratio and corresponding 95% confidence intervals. Models included Socioeconomic/demographic characteristics, objective health status, healthcare use, functional disability, barriers to healthcare services utilization, lifestyle variables, mental health status, social support, and satisfaction with life as potential factors that can affect self-perceived health. Models were adjusted for sex, age, educational level, degree of urbanization, and presence of chronic diseases. Results: About 45% of participants reported good/very good, 39% reported fair, while ~16% reported poor/very poor health perception. Poor/very poor health was more reported by women when compared to men (19.1 vs. 11.4%, respectively, p < 0.001). A higher prevalence of poor/very poor health status was reported by participants living in thinly populated areas or among older populations. Lower educational levels, lower income, as well as unemployment, were found to increase the risk of reporting poor/very poor health status. Utilizing healthcare services more frequently, experiencing barriers to access healthcare services, having depressive symptoms or activity limitations, or lacking social support were found to be significantly associated with poor/very poor self-perceived health. Conclusion: Subjects living in Portugal tend to report less good/very good health status and more poor/very poor health when compared to the rest of Europe. This study stresses the importance of socioeconomic factors, chronic illness, barriers to access healthcare services, social isolation, and mental health status in influencing self-perceived health and highlights the urgent need for social-informed policies, strategies, and interventions to reduce health inequalities in Portugal.