Seasonal Betacoronavirus Antibodies' Expansion Post-BNT161b2 Vaccination Associates with Reduced SARS-CoV-2 VoC Neutralization.

SARS-CoV-2 vaccination is known to induce antibodies that recognize also variants of concerns (VoCs) of the virus. However, epidemiological and laboratory evidences indicate that these antibodies have a reduced neutralization ability against VoCs. We studied binding and neutralizing antibodies against the Spike protein domains and subunits of the Wuhan-Hu-1 virus and its alpha, beta, delta VoCs and of seasonal betacoronaviruses (HKU1 and OC43) in a cohort of 31 health care workers prospectively followed post-vaccination with BNT162b2-Comirnaty. The study of sequential samples collected up to 64 days post-vaccination showed that serological assays measuring IgG against Wuhan-Hu-1 antigens were a poor proxy for VoC neutralization. In addition, in subjects who had asymptomatic or mild COVID-19 prior to vaccination, the loss of nAbs following disease could be rapid and accompanied by post-vaccination antibody levels similar to those of naïve vaccinees. Interestingly, in health care workers naïve for SARS-CoV-2 infection, vaccination induced a rapid and transient reactivation of pre-existing seasonal coronaviruses IgG responses that was associated with a subsequent reduced ability to neutralize alpha and beta VoCs.

A high susceptibility to redox imbalance of the transmissible stages of Plasmodium falciparum revealed with a luciferase-based mature gametocyte assay.

The goal to prevent Plasmodium falciparum transmission from humans to mosquitoes requires the identification of targetable metabolic processes in the mature (stage V) gametocytes, the sexual stages circulating in the bloodstream. This task is complicated by the apparently low metabolism of these cells, which renders them refractory to most antimalarial inhibitors and constrains the development of specific and sensitive cell-based assays. Here, we identify and functionally characterize the regulatory regions of the P. falciparum gene PF3D7_1234700, encoding a CPW-WPC protein and named here Upregulated in Late Gametocytes (ULG8), which we have leveraged to express reporter genes in mature male and female gametocytes. Using transgenic parasites containing a pfULG8-luciferase cassette, we investigated the susceptibility of stage V gametocytes to compounds specifically affecting redox metabolism. Our results reveal a high sensitivity of mature gametocytes to the glutathione reductase inhibitor and redox cycler drug methylene blue (MB). Using isobologram analysis, we find that a concomitant inhibition of the parasite enzyme glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase, a key component of NADPH synthesis, potently synergizes MB activity. These data suggest that redox metabolism and detoxification activity play an unsuspected yet vital role in stage V gametocytes, rendering these cells exquisitely sensitive to decreases in NADPH concentration.

Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques.

The design of an effective HIV-1 vaccine remains a major challenge. Several vaccine strategies based on viral vectors have been evaluated in preclinical and clinical trials, with largely disappointing results. Integrase defective lentiviral vectors (IDLV) represent a promising vaccine candidate given their ability to induce durable and protective immune responses in mice after a single immunization. Here, we evaluated the immunogenicity of a SIV-based IDLV in nonhuman primates. Six rhesus monkeys were primed intramuscularly with IDLV-Env and boosted with the same vector after 1 year. A single immunization with IDLV-Env induced broad humoral and cellular immune responses that waned over time but were still detectable at 1 year postprime. The boost with IDLV-Env performed at 1 year from the prime induced a remarkable increase in both antibodies and T-cell responses. Antibody binding specificity showed a predominant cross-clade gp120-directed response. Monkeys' sera efficiently blocked anti-V2 and anti-CD4 binding site antibodies, neutralized the tier 1 MW965.26 pseudovirus and mediated antibody-dependent cellular cytotoxicity (ADCC). Durable polyfunctional Env-specific T-cell responses were also elicited. Our study demonstrates that an IDLV-Env-based vaccine induces functional, comprehensive, and durable immune responses in Rhesus macaques. These results support further evaluation of IDLV as a new HIV-1 vaccine delivery platform.

HIV-1 DNA dynamics and variations in HIV-1 DNA protease and reverse transcriptase sequences in multidrug-resistant patients during successful raltegravir-based therapy.

There is limited information on the variations of HIV-1 DNA mutation profile in reverse transcriptase (RT) and protease (PR) genes during suppressive antiretroviral treatment (plasma HIV-1 RNA continuously <50 copies/ml) with raltegravir (RAL)-based regimens in patients with baseline RT/PR resistant HIV. Twelve multidrug resistant (RT: 12/12, PR: 8/12) HIV-infected patients were followed during effectively suppressive RAL-based therapy. Total and integrated HIV-1 DNA were assessed by real time PCR at baseline and every 6 months. Ultrasensitive (threshold: 2.5 copies/ml) plasma HIV-1 RNA and genotypic analysis of RT and PR in proviral DNA were performed at baseline and at 24 months. Half of the patients had full viral suppression (plasma HIV-RNA < 2.5 copies/ml) at month 12. Total HIV-1 DNA declined significantly after 12 months of therapy (from 249.2 to 145.7 copies/106 cells, P = 0.023), and remained stable until 24 months, when total HIV-1 DNA levels raised, concomitantly with a less stringent suppression of HIV-1 RNA (81.8% of patients with >2.5 copies/ml). Integrated HIV-1 DNA did not show fluctuations during the study period. Sequencing of the PR and RT regions from HIV-1 DNA revealed changes in the resistance mutation profile in five patients. Total HIV-1 DNA declined after the introduction of RAL-based therapy, with a rebound after 2 years. No changes were observed in levels of integrated DNA, suggesting limited effect on archived HIV. The RT and PR sequence changes in archived HIV-1 DNA suggest that variation of the mutation profile can occur even in the absence of detectable HIV-1 RNA. J. Med. Virol. 88:2115-2124, 2016. © 2016 Wiley Periodicals, Inc.

Endogenous CCL2 neutralization restricts HIV-1 replication in primary human macrophages by inhibiting viral DNA accumulation.

BACKGROUND: Macrophages are key targets of HIV-1 infection. We have previously described that the expression of CC chemokine ligand 2 (CCL2) increases during monocyte differentiation to macrophages and it is further up-modulated by HIV-1 exposure. Moreover, CCL2 acts as an autocrine factor that promotes viral replication in infected macrophages. In this study, we dissected the molecular mechanisms by which CCL2 neutralization inhibits HIV-1 replication in monocyte-derived macrophages (MDM), and the potential involvement of the innate restriction factors protein sterile alpha motif (SAM) histidine/aspartic acid (HD) domain containing 1 (SAMHD1) and apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3) family members. RESULTS: CCL2 neutralization potently reduced the number of p24 Gag+ cells during the course of either productive or single cycle infection with HIV-1. In contrast, CCL2 blocking did not modify entry of HIV-1 based Virus Like Particles, thus demonstrating that the restriction involves post-entry steps of the viral life cycle. Notably, the accumulation of viral DNA, both total, integrated and 2-LTR circles, was strongly impaired by neutralization of CCL2. Looking for correlates of HIV-1 DNA accumulation inhibition, we found that the antiviral effect of CCL2 neutralization was independent of the modulation of SAMHD1 expression or function. Conversely, a strong and selective induction of APOBEC3A expression, to levels comparable to those of freshly isolated monocytes, was associated with the inhibition of HIV-1 replication mediated by CCL2 blocking. Interestingly, the CCL2 neutralization mediated increase of APOBEC3A expression was type I IFN independent. Moreover, the transcriptome analysis of the effect of CCL2 blocking on global gene expression revealed that the neutralization of this chemokine resulted in the upmodulation of additional genes involved in the defence response to viruses. CONCLUSIONS: Neutralization of endogenous CCL2 determines a profound restriction of HIV-1 replication in primary MDM affecting post-entry steps of the viral life cycle with a mechanism independent of SAMHD1. In addition, CCL2 blocking is associated with induction of APOBEC3A expression, thus unravelling a novel mechanism which might contribute to regulate the expression of innate intracellular viral antagonists in vivo. Thus, our study may potentially lead to the development of new therapeutic strategies for enhancing innate cellular defences against HIV-1 and protecting macrophages from infection.

Multicolor bioluminescence boosts malaria research: quantitative dual-color assay and single-cell imaging in Plasmodium falciparum parasites.

New reliable and cost-effective antimalarial drug screening assays are urgently needed to identify drugs acting on different stages of the parasite Plasmodium falciparum, and particularly those responsible for human-to-mosquito transmission, that is, the P. falciparum gametocytes. Low Z' factors, narrow dynamic ranges, and/or extended assay times are commonly reported in current gametocyte assays measuring gametocyte-expressed fluorescent or luciferase reporters, endogenous ATP levels, activity of gametocyte enzymes, or redox-dependent dye fluorescence. We hereby report on a dual-luciferase gametocyte assay with immature and mature P. falciparum gametocyte stages expressing red and green-emitting luciferases from Pyrophorus plagiophthalamus under the control of the parasite sexual stage-specific pfs16 gene promoter. The assay was validated with reference antimalarial drugs and allowed to quantitatively and simultaneously measure stage-specific drug effects on parasites at different developmental stages. The optimized assay, requiring only 48 h incubation with drugs and using a cost-effective luminogenic substrate, significantly reduces assay cost and time in comparison to state-of-the-art analogous assays. The assay had a Z' factor of 0.71 ± 0.03, and it is suitable for implementation in 96- and 384-well microplate formats. Moreover, the use of a nonlysing D-luciferin substrate significantly improved the reliability of the assay and allowed one to perform, for the first time, P. falciparum bioluminescence imaging at single-cell level.

Real-World Experience on Why Research Flatlines: A Review of Trials From the Coordinator's Perspective.

INTRODUCTION: Investigator-initiated research trial failure is a national concern that hinders the dissemination of information while wasting resources, time, and funding. The goal of this analysis was to provide an objective review of points to consider increasing an investigator's chances of success. METHODS: The included trials were divided into two groups based on whether they were successful or unsuccessful in meeting enrollment goals. Common issues were noted for each trial to identify prevalent issues and compare their quantity within each group. RESULTS: Unsuccessful trials averaged twice as many issues as trials in the successful group. The most common problems identified in unsuccessful studies involved study planning, whereas the most common problems identified in successful studies revolved around study staff. CONCLUSIONS: There is no single definitive indicator for trial failure; however, awareness of these issues in a trial's planning phase can help prevent their occurrence and aid in overall completion and publication.

The role of the surgical volume for clinical outcomes in VATS lobectomy for lung cancer: a national large database multicenter analysis.

Improving the quality of lung cancer care at a cost that can be sustained is a hotly debated issue. High-risk, low-volume procedures (such as lung resections) are believed to improve significantly when centralised in high-volume centres. However, limited evidence exists to support volume requirements in lung cancer surgery. On the other hand, there was no evidence that the number of lung resections affected either the short-term perioperative results or the long-term cost. Using data from an extensive nationwide registry, this study investigated the correlations between surgical volumes and selected perioperative outcomes. A retrospective analysis of a prospectively filled national registry that follows stringent quality assurance and security procedures was conducted to ensure data accuracy and security. Patients who underwent VATS lobectomy from 2014 to 2019 at the participating centres were included. Selected perioperative outcomes were reported. Total direct hospital cost is measured at discharge for hospitalisations with a primary diagnosis of lung cancer, hospital stay costs, and postoperative length of hospital stay after lobectomy. After the propensity score matched, centres were divided into three groups according to the surgical volume of the unit where VATS lobectomies were performed (high-volume centre: > 500 lobectomies; medium-volume centre: 200-500 lobectomies; low-volume centre: < 200 lobectomies). 11,347 patients were included and matched (low-volume center = 2890; medium-volume center = 3147; high-volume center = 2907). The mean operative time density plot (Fig. 1A) showed no statistically significant difference (p = 0.67). In contrast, the density plot of the harvested lymph nodes (Fig. 1B) showed significantly higher values in the high-volume centres (p = 0.045), albeit without being clinically significant. The adjusted rates of any and significant complications were higher in the low-volume centre (p = 0.034) without significantly affecting the length of hospital stay (p = 0.57). VATS lobectomies for lung cancer in higher-volume centres seem associated with a statistically significantly higher number of harvested lymph nodes and lower perioperative complications, yet without any significant impact in terms of costs and resource consumption. These findings may advise the investigation of the learning curve effect in a complete economic evaluation of VATS lobectomy in lung cancer. Fig. 1 The mean operative time density plot showed no statistically significant difference (p = 0.67).

The Role of Sublobar Resection in Early-Stage Non-Small-Cell Lung Cancer.

The results of a prospective, multi-institutional randomized trial developed to assess the equality of sublobar resection versus standard lobectomy were first published in 1995. They concluded that, compared with lobectomy, sublobar resections did not show any significant improvement either in terms of postoperative morbidity and mortality nor in terms of late post-resectional cardiorespiratory function. Moreover, due to the higher mortality and local recurrence rate related to sublobar resection, lobectomy had to be judged as the best surgical option for patients diagnosed with peripheral early-stage non-small-cell lung cancer. Since then, lobectomy has been considered the best surgical option for fit patients suffering from early-stage non-small cell lung cancer. In 2022 and 2023, three non-inferiority randomized trials were published, comparing lobectomy with the sublobar resection in T1a N0 patients whose tumors were up to 2 cm in size. Although presenting some important differences, all three trials met their primary endpoints, disclosing the non-inferiority of sublobar resections in terms of overall and disease-free survival. This narrative review aims to compare the newly published results of these trials as well as to report results from recent non-randomized studies on this topic.

1000 Robotic-assisted lobectomies for primary lung cancer: 16 years single center experience.

OBJECTIVE: This study aimed at describing our high-volume single center experience in robotic-assisted thoracic surgery (RATS) to evaluate short outcome and feasibility of the technique, the adequacy of oncological results, and the learning curve. METHODS: We retrospectively analyzed data from 1000 consecutive patients who underwent lobectomy and systematic lymphadenectomy for primary lung cancer using RATS approach between May 2007 and May 2023. RESULTS: Nine-hundred ninety-seven patients (99.7 %) underwent lobectomy, whereas 3 (0.03 %) patients bilobectomy. Conversion rate to open surgery was 3.7 %. Minor complications occurred in 213 (21.3 %) patients, major complications in 29 patients (2.9 %). The 30-day and 90-day operative mortality was 0 % and 0.1 %, respectively. The median number of N1 + N2 stations resected was 5 (range 0-9), with a median number of 17 of N1 + N2 lymph nodes resected (range 0-55). The oncological outcome was evaluated only on the subgroup of patients (n = 895) with non-small cell lung cancer. Pathological lymph node upstaging from cN0 to pN1/pN2 was evident in 147 patients (17.3 %): 9 % from cN0 to pN1 and 7.1 % from cN0 to pN2. With a median follow-up of 3.9, 5-year OS and DFS were respectively 89.3 % and 83.6 % for stage I, 74 % and 66.5 % for stage II, and 61 % and 36.4 % for stage IIIA. CONCLUSIONS: Better vision and excellent instrument maneuverability of the robotic surgical system allowed excellent results in terms of early, adequate oncological outcome comparable to open surgery literature data, and acceptable learning curve. ULTRAMINI ABSTRACT: 1000 consecutive patients who underwent lobectomy and systematic lymphadenectomy for primary lung cancer using RATS approach have been analyzed with the aim to describe our high-volume single center experience, and to evaluate short outcome and feasibility of the technique, the adequacy of oncological results, and the learning curve.

The Role of Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Thoracic Tumors.

Pleural mesothelioma (PM) is a rare but aggressive thoracic tumor with a poor prognosis. Multimodal treatment-including induction chemotherapy, aggressive surgical resection, radiotherapy and immunotherapy in selected cases-currently represents the best therapeutic option. Single-center studies advocate hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection as an additional therapeutic option, although its impact on post-operative morbidity and survival has not yet been evaluated on a larger scale. HITHOC can be applied not only in the case of mesothelioma, but also in the case of thymoma with pleural involvement or-in very selected cases-in patients with secondary pleural metastases. Despite favorable outcomes and reduced clinical risks, there is no uniform approach to HITHOC, and a wide variety of indications and technical applications are still reported. Based on available data, HITHOC seems to offer a clear benefit in regard to overall survival of all mesothelioma patients; however, multicenter randomized controlled trials are required to validate and standardize this approach. The aim of this review is to focus on the present role of HITHOC in thoracic tumors with pleural involvement as well as on future challenges, particularly in the light of possible combined therapy of thoracic tumors still presenting poor prognoses.

Functional diversification of innate and inflammatory immune responses mediated by antibody fragment crystallizable activities against SARS-CoV-2.

Monoclonal antibodies (mAb) targeting the SARS-CoV-2 Spike (S) glycoprotein have been exploited for the treatment of severe COVID-19. In this study, we evaluated the immune-regulatory features of two neutralizing anti-S mAbs (nAbs), named J08 and F05, with wild-type (WT) conformation or silenced Fc functions. In the presence of D614G SARS-CoV-2, WT nAbs enhance intracellular viral uptake in immune cells and amplify antiviral type I Interferon and inflammatory cytokine and chemokine production without viral replication, promoting the differentiation of CD16+ inflammatory monocytes and innate/adaptive PD-L1+ and PD-L1+CD80+ plasmacytoid Dendritic Cells. In spite of a reduced neutralizing property, WT J08 nAb still promotes the IL-6 production and differentiation of CD16+ monocytes once binding Omicron BA.1 variant. Fc-mediated regulation of antiviral and inflammatory responses, in the absence of viral replication, highlighted in this study, might positively tune immune response during SARS-CoV-2 infection and be exploited also in mAb-based therapeutic and prophylactic strategies against viral infections.

Colorectal Cancer Pulmonary Metastasectomy: When, Why and How.

Colorectal cancer is the third-most-diagnosed cancer in males and in females, representing 8% of estimated new cases, and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9-12% are eligible for local treatments with radical intent, including surgical resection, SBRT (stereotactic body radiation therapy) and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.

Diagnostic and Therapeutic Approach to Thoracic Outlet Syndrome.

Thoracic outlet syndrome (TOS) is a group of symptoms caused by the compression of neurovascular structures of the superior thoracic outlet. The knowledge of its clinical presentation with specific symptoms, as well as proper imaging examinations, ranging from plain radiographs to ultrasound, computed tomography and magnetic resonance imaging, may help achieve a precise diagnosis. Once TOS is recognized, proper treatment may comprise a conservative or a surgical approach.

B cell immunofocusing and repriming in two HIV-1 Env immunization regimens.

Diverse and rapidly mutating viruses pose challenges to immunogen and vaccine design. In this study, we evaluated the ability of memory B-cells obtained from two independent NHP trials to cross-react with individual HIV-1 vaccine components of two different multivalent immunization strategies. We demonstrated that while an HIV-1 Env multiclade, multivalent immunization regimen resulted in a dominant memory B-cell response that converged toward shared epitopes, in a sequential immunization with clonally-related non-stabilized gp140 HIV-1 Envs followed by SOSIP-stabilized gp140 trimers, the change in immunogen format resulted in repriming of the B-cell response.

Multicentre retrospective analysis on pulmonary metastasectomy: an European perspective.

OBJECTIVES: To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS: Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS: A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25-75% = 1-2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS: Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice.

Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein.

Persistent infection with high risk genotypes of human papillomavirus (HPV) is the cause of cervical cancer, one of most common cancer among woman worldwide, and represents an important risk factor associated with other anogenital and oropharyngeal cancers in men and women. Here, we designed a therapeutic vaccine based on integrase defective lentiviral vector (IDLV) to deliver a mutated nononcogenic form of HPV16 E7 protein, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer, fused to calreticulin (CRT), a protein able to enhance major histocompatibility complex class I antigen presentation (IDLV-CRT/E7). Vaccination with IDLV-CRT/E7 induced a potent and persistent E7-specific T cell response up to 1 year after a single immunization. Importantly, a single immunization with IDLV-CRT/E7 was able to prevent growth of E7-expressing TC-1 tumor cells and to eradicate established tumors in mice. The strong therapeutic effect induced by the IDLV-based vaccine in this preclinical model suggests that this strategy may be further exploited as a safe and attractive anticancer immunotherapeutic vaccine in humans.

Artificial Neural Networks in Lung Cancer Research: A Narrative Review.

BACKGROUND: Artificial neural networks are statistical methods that mimic complex neural connections, simulating the learning dynamics of the human brain. They play a fundamental role in clinical decision-making, although their success depends on good integration with clinical protocols. When applied to lung cancer research, artificial neural networks do not aim to be biologically realistic, but rather to provide efficient models for nonlinear regression or classification. METHODS: We conducted a comprehensive search of EMBASE (via Ovid), MEDLINE (via PubMed), Cochrane CENTRAL, and Google Scholar from April 2018 to December 2022, using a combination of keywords and related terms for "artificial neural network", "lung cancer", "non-small cell lung cancer", "diagnosis", and "treatment". RESULTS: Artificial neural networks have shown excellent aptitude in learning the relationships between the input/output mapping from a given dataset, without any prior information or assumptions about the statistical distribution of the data. They can simultaneously process numerous variables, managing complexity; hence, they have found broad application in tasks requiring attention. CONCLUSIONS: Lung cancer is the most common and lethal form of tumor, with limited diagnostic and treatment methods. The advances in tailored medicine have led to the development of novel tools for diagnosis and treatment. Artificial neural networks can provide valuable support for both basic research and clinical decision-making. Therefore, tight cooperation among surgeons, oncologists, and biostatisticians appears mandatory.

Differences in selected postoperative outcomes between simple and complex segmentectomies for lung cancer: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to synthesize the evidence on the preoperative characteristics, operative outcomes, and postoperative complications of simple and complex segmentectomy for lung cancer. METHODS: A systematic review of EMBASE (through Ovid), MEDLINE (via PubMed), and Cochrane CENTRAL (January 1990 - January 2023) was done. We included studies to compare simple versus complex segmentectomies for lung cancer in terms of characteristics and operative and postoperative outcomes. RESULTS: There was a statistically significant difference regarding higher operative time in favor of simple segmentectomies (Mean Difference, MD = 15.76, 95% Confidence Interval, CI: 2.46 - 29.07, p = 0.02). The incidence of postoperative complications did not change between the two groups (Risk Ratio, RR = 0.86, 95% CI: 0.66 - 1.13, p = 0.27). There were no significant differences regarding postoperative length of hospital stay between simple or complex segmentectomies (MD = -0.02, 95% CI: 0.56 - 0.51, p = 0.93). CONCLUSIONS: Simple and complex segmentectomies have comparable postoperative outcomes; in particular, postoperative complication rates and length of hospital stay were similar. Complex segmentectomies were associated with a longer operative time.

Integrase Defective Lentiviral Vector Promoter Impacts Transgene Expression in Target Cells and Magnitude of Vector-Induced Immune Responses.

Integrase defective lentiviral vectors (IDLVs) are a promising vaccine delivery platform given their ability to induce high magnitude and durable antigen-specific immune responses. IDLVs based on the simian immunodeficiency virus (SIV) are significantly more efficient at transducing human and simian dendritic cells (DCs) compared to HIV-based vectors, resulting in a higher expansion of antigen-specific CD8+ T cells. Additionally, IDLV persistence and continuous antigen expression in muscle cells at the injection site contributes to the durability of the vaccine-induced immune responses. Here, to further optimize transgene expression levels in both DCs and muscle cells, we generated ten novel lentiviral vectors (LVs) expressing green fluorescent protein (GFP) under different hybrid promoters. Our data show that three of the tested hybrid promoters resulted in the highest transgene expression levels in mouse DCs, monkey DCs and monkey muscle cells. We then used the three LVs with the highest in vitro transgene expression levels to immunize BALB/c mice and observed high magnitude T cell responses at 3 months post-prime. Our study demonstrates that the choice of the vector promoter influences antigen expression levels in target cells and the ensuing magnitude of T cell responses in vivo.