Comparison of Intubating Conditions with Succinylcholine Versus Rocuronium in the Prehospital Setting.

OBJECTIVE: Rapid sequence intubation (RSI) is frequently performed by emergency medical services (EMS). We investigated the relationship between succinylcholine and rocuronium use and time until first laryngoscopy attempt, first-pass success, and Cormack-Lehane (CL) grades. METHODS: We included adult patients for whom prehospital RSI was attempted from July 2015 through June 2022 in a retrospective, observational study with pre-post analysis. Timing was verified using recorded defibrillator audio in addition to review of continuous ECG, pulse oximetry, and end-tidal carbon dioxide waveforms. Our primary exposure was neuromuscular blocking agent (NMBA) used, either rocuronium or succinylcholine. Our prespecified primary outcome was the first attempt Cormack-Lehane view. Key secondary outcomes were first laryngoscopy attempt success rate, timing from NMBA administration to first attempt, number of attempts, and hypoxemic events. RESULTS: Of 5,179 patients in the EMS airway registry, 1,475 adults received an NMBA while not in cardiac arrest. Cormack-Lehane grades for succinylcholine and rocuronium were similar: grade I (64%, 59% [95% CI 0.64-1.09]), grade II (16%, 21%), grade III (18%, 16%), grade IV (3%, 3%). The median interval from NMBA administration to start of the first attempt was 57 s for succinylcholine and 83 s for rocuronium (mean difference 28 [95% CI 20-36] seconds). First attempt success was 84% for succinylcholine and 83% for rocuronium. Hypoxemic events were present in 25% of succinylcholine cases and 23% of rocuronium cases. CONCLUSIONS: Prehospital use of either rocuronium or succinylcholine is associated with similar Cormack-Lehane grades, first-pass success rates, and rates of peri-intubation hypoxemia.

Analysis of the CD8+ T cell anti-HIV activity in heterologous cell co-cultures reveals the benefit of multiple HLA class I matches.

CD8+ T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4+ T cells by cytotoxic and non-cytotoxic mechanisms. To investigate the involvement of human leukocyte antigen (HLA) class I compatibility in anti-HIV responses, we co-cultured primary CD8+ T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4+ T cells. Altogether, CD8+ T cell anti-HIV activity was evaluated in more than 200 co-cultures. Marked heterogeneity in HIV-1 replication levels was observed among the co-cultures sharing a common CD8+ T cell source. The co-cultures that exhibited greater than 50% reduction in HIV production were found to have significantly increased numbers of matching HLA class I alleles (Yates chi-square = 54.21; p < 0.001). With CD8+ T cells from HIV controllers and asymptomatic viremic individuals, matching HLA-B and/or HLA-C alleles were more predictive of strong anti-HIV activity than matching HLA-A alleles. Overall, HLA class I genotype matches were more closely associated with CD8+ T cell anti-HIV activity than supertype pairings. Antibodies against HLA class I and CD3 reduced the CD8+ T cell anti-HIV activity. Stimulated CD8+ T cells exhibited increased anti-HIV activity and reduced dependency on HLA compatibility. These findings provide evidence that the maximal suppression of HIV replication by CD8+ T cells requires the recognition of multiple epitopes. These studies provide insight for HIV vaccine development, and the analytic approach can be useful for the functional characterization of HLA class I alleles and tentative HLA class I supertypes.

Novel endoscopic visualization techniques for bladder cancer detection: a review of the contemporary literature.

PURPOSE OF REVIEW: To describe the principles of photodynamic diagnosis (PDD), narrow-band imaging (NBI) and Storz Professional Image Enhancement System (SPIES) techniques for the endoscopic management of nonmuscle-invasive bladder cancer (BCa) and to report their impact on clinical practice. RECENT FINDINGS: PDD is associated with an increased sensitivity for detecting BCa specifically carcinoma in situ (CIS). Moreover, PDD has been shown to lower recurrence rate in comparison with white-light cystoscopy. The impact on progression-free survival is still unclear yet. NBI and, more recently, SPIES are two novel imaging techniques that do not require preoperative instillation of photosensitizing agents. NBI seems to be associated with lower recurrence rates. Nevertheless, further trials are necessary to confirm these results, in particular in high-risk lesions and CIS. Randomized clinical trials addressing the clinical impact of SPIES are ongoing. SUMMARY: Novel endoscopic imaging techniques are useful diagnostic tools for evaluating BCa during cystoscopic diagnostic surveillance as well as during transurethral resection of the bladder. Although the standard of care remains white-light cystoscopy, these techniques provide higher sensitivity in detecting BCa especially CIS. The continued evidence also suggests that this increased detection leads to lower recurrence rates. The impact on progression and the cost-efficacy as well as selection remains to be refined.

Recovery and assessment of leukocytes from LR Express filters.

Leukocytes, or white blood cells, are used for a variety of investigational purposes and they offer advantages over laboratory-adapted cell lines. Leukocytes that are typically discarded by blood banks during the collection of red blood cells, platelets, and plasma can often be obtained for research use. However, the available leukocytes are frequently contained within a blood filtration device, such as the Terumo LR Express (TLRE) filter. In this study, procedures were evaluated for the ability to elute viable leukocytes from TLRE filters. The recovered leukocytes were assessed for composition, growth, and functionality. The large majority (>70%) of leukocytes were eluted with a single reverse-elution procedure and the recovered cells contained representative populations of the major leukocyte subsets. Purified T cells exhibited diverse T cell receptor repertoires, characteristic growth upon mitogen stimulation, and CD4+ T cells were able to support HIV-1 propagation. Purified monocytes were able to be differentiated into phenotypically characteristic populations of macrophages and dendritic cells. Overall, TLRE filters offer an attractive source of primary human cells for research and possibly clinical purposes.

Vaccine hesitancy among general practitioners: evaluation and comparison of their immunisation practice for themselves, their patients and their children.

To gain knowledge about vaccine hesitancy among general practitioners (GPs), we conducted a survey to compare their vaccination attitudes for themselves, their children and their patients. A questionnaire survey was sent to GPs working in private practice in the Rhône-Alpes region, France, between October 2013 and January 2014. GPs' immunisation practices for diphtheria-tetanus-poliomyelitis (DTP), measles-mumps-rubella (MMR), pneumococcal, pertussis, hepatitis B (hepB), human papillomavirus (HPV), seasonal and H1N1 influenza and meningococcal C (menC) vaccines were considered. Divergence was defined by the presence of at least one different immunisation practice between their patients and their children. A total of 693 GPs answered the questionnaire. When considering all investigated vaccines, 45.7 % of divergence was found. Individually, divergence was highest for the newest and more controversial, i.e. HPV (11.8 %), hepB (13.1 %), menC (23.7 %) and pneumococcal (19.8 %) vaccines. Only 73.9 % of GPs declared that they recommended HPV vaccine for their daughters. After multivariate analysis, older age was associated with higher risk of divergence. According to the French 2012 recommendations, GPs were insufficiently immunised, with 88 % for DTP and 72 % for pertussis. GPs declared to recommend vaccination against DTP, pertussis and MMR for their patients and their children in more than 95 % of cases. The declared rates of recommendation were lower than 90 % for other vaccines. These results bring new insight about vaccine hesitancy. GPs have divergent immunisation attitudes toward their relatives and their patients, especially when considering the newest and most controversial vaccines, with HPV vaccine being the main focus of controversies.

Mechanistic Rationale for Ketene Formation during Dabbing and Vaping.

Ketene is one of the most toxic vaping emissions identified to date. However, its high reactivity renders it relatively challenging to identify. In addition, certain theoretical studies have shown that realistic vaping temperature settings may betoo low to produce ketene. Each of these issues is addressed herein. First, an isotopically labeled acetate precursor is used for the identification of ketene with enhanced rigor in vaped aerosols. Second, discrepancies between theoretical and experimental findings are explained by accounting for the effects of aerobic (experimental) versus anaerobic (simulated and theoretical) pyrolysis conditions. This finding is also relevant to explaining the relatively low-temperature production of aerosol toxicants beyond ketene. Moreover, the study presented herein shows that ketene formation during vaping is not limited to molecules possessing a phenyl acetate substructure. This means that ketene emission during vaping, including from popular flavorants such as ethyl acetate, may be more prevalent than is currently known.

CD8+ Lymphocytes from Healthy Blood Donors Secrete Antiviral Levels of Interferon-Alpha.

The adaptive immune response to viral infections features the antigen-driven expansion of CD8+ T cells. These cells are widely recognized for their cytolytic activity that is mediated through the secretion of cytokines such as perforin and granzymes. Less appreciated is their ability to secrete soluble factors that restrict virus replication without killing the infected cells. In this study we measured the ability of primary anti-CD3/28-stimulated CD8+ T cells from healthy blood donors to secrete interferon-alpha. Supernatants collected from CD8+ T cell cultures were screened for their ability to suppress HIV-1 replication in vitro and their interferon-alpha concentrations were measured by ELISA. Interferon-alpha concentrations in the CD8+ T cell culture supernatants ranged from undetectable to 28.6 pg/mL. The anti-HIV-1 activity of the cell culture supernatants was observed to be dependent on the presence of interferon-alpha. Appreciable increases in the expression levels of type 1 interferon transcripts were observed following T cell receptor stimulation, suggesting that the secretion of interferon-alpha by CD8+ T cells is an antigen-driven response. In 42-plex cytokine assays, the cultures containing interferon-alpha were also found to contain elevated levels of GM-CSF, IL-10, IL-13, and TNF-alpha. Together, these results demonstrate that the secretion of anti-viral levels of interferon-alpha is a common function of CD8+ T cells. Furthermore, this CD8+ T cell function likely plays broader roles in health and disease.

HIV/AIDS: 30 years of progress and future challenges.

Acquired immune deficiency syndrome (AIDS) was first described 30 years ago in a report from the US Centers for Disease Control. Two years later the causative virus was identified and afterwards named the human immunodeficiency virus (HIV). This article reviews the progress made in the three decades since the recognition of AIDS and the discovery of HIV, with respect to the virus, the infected cell, and the host, as well as directions for future studies.

Natural suppression of human immunodeficiency virus type 1 replication is mediated by transitional memory CD8+ T cells.

HIV replication is suppressed in vitro by a CD8(+) cell noncytotoxic antiviral response (CNAR). This activity directly correlates with an asymptomatic clinical state. The objective of this study was to identify the phenotype of CD8(+) cell subsets having strong CNAR activity. CD8(+) cell subset frequencies and CNAR levels were measured for human immunodeficiency virus (HIV)-uninfected individuals and three groups of HIV type 1 (HIV-1)-infected individuals: asymptomatic individuals with low-level viremia (vHIV), antiretroviral-drug-treated subjects with undetectable virus levels (TxHIV), and therapy-naïve aviremic elite controllers (EC). CD8(+) cells from the vHIV individuals exhibited the highest HIV-suppressing activity and had elevated frequencies of CD45RA(-) CD27(+) and PD-1(+) (CD279(+)) cells. Functional assessments of CD8(+) cells sorted into distinct subsets established that maximal CNAR activity was mediated by CD45RA(-) CCR7(-) CD27(+) and PD-1(+) CD8(+) cells. T cell receptor (TCR) repertoire profiles of CD8(+) cell subsets having strong CNAR activity exhibited increased perturbations in comparison to those of inactive subsets. Together, these studies suggest that CNAR is driven by HIV replication and that this antiviral activity is associated with oligoclonally expanded activated CD8(+) cells expressing PD-1 and having a transitional memory cell phenotype. The findings better describe the identity of CD8(+) cells showing CNAR and should facilitate the evaluation of this important immune response in studies of HIV pathogenesis, resistance to infection, and vaccine development.

A methyl-deviator epigenotype of estrogen receptor-positive breast carcinoma is associated with malignant biology.

We broadly profiled DNA methylation in breast cancers (n = 351) and benign parenchyma (n = 47) for correspondence with disease phenotype, using FFPE diagnostic surgical pathology specimens. Exploratory analysis revealed a distinctive primary invasive carcinoma subclass featuring extreme global methylation deviation. Subsequently, we tested the correlation between methylation remodeling pervasiveness and malignant biological features. A methyl deviation index (MDI) was calculated for each lesion relative to terminal ductal-lobular unit baseline, and group comparisons revealed that high-grade and short-survival estrogen receptor-positive (ER(+)) cancers manifest a significantly higher MDI than low-grade and long-survival ER(+) cancers. In contrast, ER(-) cancers display a significantly lower MDI, revealing a striking epigenomic distinction between cancer hormone receptor subtypes. Kaplan-Meier survival curves of MDI-based risk classes showed significant divergence between low- and high-risk groups. MDI showed superior prognostic performance to crude methylation levels, and MDI retained prognostic significance (P < 0.01) in Cox multivariate analysis, including clinical stage and pathological grade. Most MDI targets individually are significant markers of ER(+) cancer survival. Lymphoid and mesenchymal indexes were not substantially different between ER(+) and ER(-) groups and do not explain MDI dichotomy. However, the mesenchymal index was associated with ER(+) cancer survival, and a high lymphoid index was associated with medullary carcinoma. Finally, a comparison between metastases and primary tumors suggests methylation patterns are established early and maintained through disease progression for both ER(+) and ER(-) tumors.

Prevention of group B streptococcal neonatal disease revisited. The DEVANI European project.

The purpose of this paper was to present the current knowledge on the prevention of group B streptococcus (GBS) neonatal infections and the status of prevention policies in European countries and to present the DEVANI pan-European program, launched in 2008. The aim of this program was to assess the GBS neonatal infection burden in Europe, to design a new vaccine to immunize neonates against GBS infections, to improve the laboratory performance for the diagnosis of GBS colonization and infection, and to improve the methods for the typing of GBS strains. The current guidelines for GBS prevention in different countries were ascertained and a picture of the burden before and after the instauration of prevention policies has been drawn. After the issue of the Centers for Disease Control and Prevention (CDC) guidelines, many European countries have adopted universal screening for the GBS colonization of pregnant women and intrapartum prophylaxis to colonized mothers. Nevertheless, some European countries continue advocating the risk factor approach to GBS prevention. Most European countries have implemented policies to prevent GBS neonatal infections and the burden of the disease has decreased during the last several years. Nevertheless, further steps are necessary in order to develop new strategies of prevention, to improve microbiological techniques to detect GBS colonization and infection, and to coordinate the prevention policies in the EU.

Dual role of autophagy in HIV-1 replication and pathogenesis.

Autophagy, the major mechanism for degrading long-lived intracellular proteins and organelles, is essential for eukaryotic cell homeostasis. Autophagy also defends the cell against invasion by microorganisms and has important roles in innate and adaptive immunity. Increasingly evident is that HIV-1 replication is dependent on select components of autophagy. Fittingly, HIV-1 proteins are able to modulate autophagy to maximize virus production. At the same time, HIV-1 proteins appear to disrupt autophagy in uninfected cells, thereby contributing to CD4+ cell death and HIV-1 pathogenesis. These observations allow for new approaches for the treatment and possibly the prevention of HIV-1 infection. This review focuses on the relationship between autophagy and HIV-1 infection. Discussed is how autophagy plays dual roles in HIV-1 replication and HIV-1 disease progression.

Derivation of non-infectious envelope proteins from virions isolated from plasma negative for HIV antibodies.

Natural membrane-bound HIV-1 envelope proteins (mHIVenv) could be used to produce an effective subunit vaccine against HIV infection, akin to effective vaccination against HBV infection using the hepatitis B surface antigen. The quaternary structure of mHIVenv is postulated to elicit broadly neutralizing antibodies protective against HIV-1 transmission. The founder virus transmitted to infected individuals during acute HIV-1 infection is genetically homogeneous and restricted to CCR5-tropic phenotype. Therefore, isolates of plasma-derived HIV-1 (PHIV) from infected blood donors while negative for antibodies to HIV proteins were selected for expansion in primary lymphocytes as an optimized cell substrate (OCS). Virions in the culture supernatants were purified by removing contaminating microvesicles using immunomagnetic beads coated with anti-CD45. Membrane cholesterol was extracted from purified virions with beta-cyclodextrin to permeabilize them and expel p24, RT and viral RNA, and permit protease-free Benzonase to hydrolyze the residual viral/host DNA/RNA without loss of gp120. The resultant mHIVenv, containing gp120 bound to native gp41 in immunoreactive form, was free from infectivity in vitro in co-cultures with OCS and in vivo after inoculating SCID-hu Thy/Liv mice. These data should help development of mHIVenv as a virally safe immunogen and enable preparation of polyclonal hyper-immune globulins for immunoprophylaxis against HIV-1 infection.

Acute compartment syndrome of the leg caused by cocaine use, creatine supplementation and vigorous exercise.

Delayed diagnosis of acute compartment syndrome (ACS) can be catastrophic. Reporting abnormal presentations to facilitate timely diagnosis and treatment is vital. We present a case of ACS in the deep posterior compartment of the leg with an unusual presentation and cause. The patient presented to the emergency department complaining of numbness on the plantar aspect of his left foot, and described a history of cocaine use, increased exercise and creatine supplementation. The patient was diagnosed with acute deep posterior compartment syndrome of the left leg and underwent a lower extremity fasciotomy. There are case reports demonstrating that strenuous activity, drug use and creatine supplementation cause increased compartment pressures and ACS. Rare in the literature is a case where these activities occur concurrently with the abnormal presentation of symptoms seen in this case. We hope this case brings awareness of atraumatic risk factors and uncommon presentations to the medical community.

Anti-infective DNase I coatings on polydopamine functionalized titanium surfaces by alternating current electrophoretic deposition.

Implant-associated infections (IAIs) can cause serious problems due to the difficult-to-treat nature of the biofilms formed on the implant surface. In mature biofilms, the matrix, which consists of polysaccharides, proteins, lipids and extracellular DNA (eDNA), forms a protective environment for the residing bacteria, shielding them from antibiotics and host defenses. Recently, the indirect prevention of biofilm growth through the degradation of eDNA using an enzyme, such as deoxyribonuclease (DNase) I, has gained attention and is regarded as a promising strategy in the battle against IAIs. In this study, coatings of DNase I were applied on titanium implant materials and their anti-infective properties were investigated. First, the effectiveness of alternating current electrophoretic deposition (AC-EPD) as a novel processing route to apply DNase I on titanium was examined and compared with the commonly applied diffusion methodology (i.e. classic dipping). For the same processing time, the use of AC-EPD in combination with a polydopamine (PDA) coupling chemistry on the titanium electrode surface significantly increased the protein deposition yield as compared to classic dipping, thereby yielding homogeneous coatings with a thickness of 12.8 nm and an average surface roughness, Sa, of ∼20 nm. X-ray photoelectron spectroscopy confirmed the presence of peptide bonds on all DNase-coated substrates. Time-of-flight secondary ion mass spectrometry detected a more dense DNase I layer in the case of AC-EPD for electrodes coupled as anode during the high-amplitude half cycle of the AC signal. The enzyme activity, release kinetics, and shelf life of DNase I coatings were monitored in real-time using a quantitative qDNase assay. The activity of DNase I coatings produced using AC-EPD was three time higher than for coatings prepared by classic dipping. For both deposition methods, a high initial burst release was observed within the first 2 h, while some activity was still retained at the surface after 7 days. This can be explained by the stable attachment of a small fraction of DNase to the surface through covalent bonding to the PDA layer, while superimposing DNase deposits were only loosely bound and therefore released rapidly upon immersion in the medium. Interestingly, coatings prepared with AC-EPD exhibited a prolonged, gradual release of DNase activity. The AC-EPD DNase coatings significantly reduced biofilm formation of both Staphylococcus epidermidis and Pseudomonas aeruginosa up to 20 h, whereas DNase coatings prepared by short classic dipping only reduce S. epidermidis biofilm formation, and this to a lesser extent as compared to AC-EPD DNase coatings. Overall, this study indicates that AC-EPD allows to rapidly concentrate DNase I on PDA-functionalized titanium, while maintaining the enzyme activity and anti-infective ability. This highlights the potential of AC-EPD as a time-efficient coating strategy (as opposed to the much slower dip-coating methodologies) for bioactive molecules in a wide variety of biomedical applications.

["Long-haul COVID": An opportunity to address the complexity of post-infectious functional syndromes]. / « COVID long ¼ : une opportunité pour approcher la complexité des syndromes fonctionnels post-infectieux.

In this work, we address the issue of prolonged symptoms following an infection by SARS-CoV-2, labeled "long COVID". This clinically unspecific syndrome must be put in perspective with the post-infectious syndromes known for a long time but ultimately poorly understood and little studied, qualified, for lack of convincing arguments for a unambiguous pathophysiology and better terms, as functional somatic syndromes. The clinical implications for clinical care ("holistic" work-up and care of patients), for research (need for truly "bio-psycho-social" investigations), and the social implications of "long COVID" (social construction of the syndrome through the experiences of patients exposed on social networks, inequalities in the face of the disease and its socioeconomic consequences) are considered. "Long COVID" must be view, because of its expected prevalence, as an opportunity to address the complexity of post-infectious (functional) syndromes, their risk factors, and the biological, psychological and social mechanisms underlying them.

[Rituximab immunomonitoring in autoimmune diseases: a support tool in clinical practice?] / Immunomonitoring du rituximab appliqué aux maladies auto-immunes : une aide pour la pratique clinique ?

INTRODUCTION: Immune monitoring of monoclonal antibodies is a helpful tool in optimizing the management of patients treated with TNF blockers, especially in gastroenterology. In contrast, studies evaluating the interest of such monitoring are lacking for other monoclonal antibodies used in autoimmune diseases, including rituximab despite its widespread use in the field for almost 15 years. Hence, we conducted a study whose goal was to describe the clinical and biological characteristics of all patients who had a rituximab immune monitoring. METHODS: All the clinical, biological and therapeutic data attached to the demands (from 2015 onwards) we received for immune monitoring of rituximab (measurements of rituximab serum levels and anti-rituximab antibodies using the drug-sensitive assay LISA-TRACKER Duo Rituximab®), were retrospectively reviewed. Suspected cases of hypersensitivity and secondary non-response were included. RESULTS: Several medical specialities (nephrology, haematology, neurology, rheumatology, internal medicine) were represented among the 18 records included in the study (out of 23 demands), 10 being suspected cases of hypersensitivity and 8 secondary non-responders. All 6 patients whose symptoms were consistent with the classical presentation of serum sickness, as well as half of the secondary non-responders, were positive for antirituximab antibodies. CONCLUSION: This detailed real world case study illustrates the potential benefits of rituximab immune monitoring (especially anti-rituximab antibodies) in autoimmune diseases, suggesting it could be helpful in suspected cases of serum sickness, as well as secondary non-response (B-cell non-depletion being an early red flag). Larger and disease-specific studies are warranted to support these findings.

[Myelofibrosis: A review]. / Les myélofibroses.

Myelofibrosis is a BCR-ABL1-negative chronic myeloproliferative neoplasm that includes primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. It is characterized by stem cell-derived clonal proliferation that is often, but not always, accompanied by somatic mutations, which are classified into driver mutations (JAK2, CALR, or MPL), subclonal mutations and fibrosis on bone marrow biopsy. Myelofibrosis commonly demonstrates splenomegaly, constitutional symptoms, anemia, thrombocytosis, or thrombocytopenia. Patients may also be asymptomatic. Complications as thromboembolic or hemorrhagic events can reveal the disease. Primary myelofibrosis is the least common myeloproliferative neoplasm but is associated with poor survival and acute leukemic transformation. In contrast to the significant progress made in understanding the disease's pathogenesis, treatment for myelofibrosis remains largely palliative. The JAK2 inhibitor, ruxolitinib is not sufficient in eliminating the underlying myeloid progenitor clone, as disease inevitably returns with therapy discontinuation. Allogeneic hematopoietic stem cell transplantation is the only therapeutic option that offers potential cure. The development of novel treatment strategies aimed at slowing or even reversing disease progression, prolonging patient survival and preventing evolution to blast-phase are still lacking.

Comparative Effectiveness in Perioperative Outcomes of Robotic versus Open Radical Cystectomy: Results from a Multicenter Contemporary Retrospective Cohort Study.

BACKGROUND: The comparative effectiveness of robotic-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) in terms of perioperative outcomes is still a matter of debate affecting payors, physicians, and patients. OBJECTIVE: To evaluate comparative perioperative and longer-term morbidity of RARC versus ORC in a multicenter contemporary retrospective cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter study included patients with bladder cancer treated with radical cystectomy at 10 academic centers between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Intraoperative outcomes including blood loss and operative time as well as postoperative outcomes including time to discharge, complication, readmission, reoperation, and mortality rates at 30 and 90 d were assessed. Multiple imputation and inverse probability of treatment weighting (IPTW) were used. IPTW-multivariable-adjusted regression and logistic analyses were performed to evaluate the associations of RARC versus ORC with perioperative outcomes at 30 and 90 d. RESULTS AND LIMITATIONS: Overall, 1887 patients (1197 RARC and 690 ORC) were included in the study. After IPTW-adjusted analysis, no differences between the groups in terms of preoperative characteristics were observed. RARC was associated with lower blood loss (p<0.001), shorter length of stay (p<0.001), and longer operative time (p=0.007). On IPTW-adjusted multivariable logistic regression analyses, no differences in terms of 30- and 90-d complications, reoperation, and mortality rates were observed. RARC was independently associated with a higher readmission rate at both 30 and 90 d. Limitations are mainly related to the retrospective nature of the study. CONCLUSIONS: While RARC was associated with less blood loss and shorter hospital stay, it also led to longer operation times and more readmissions. There were no differences in 30- and 90-d complications. Because there are no apparent differences in safety between ORC and RARC in expert centers, differences in oncologic and cost-effectiveness outcomes are likely to drive decision making regarding RARC utilization. PATIENT SUMMARY: In this study we investigated the differences between RARC and ORC in terms of perioperative outcomes. We found no difference in early and late complications. We concluded that, to date, differences in oncologic and cost-effectiveness outcomes should drive decision making regarding RARC utilization.

CD8+ cell anti-HIV activity rapidly increases upon discontinuation of early antiretroviral therapy.

INTRODUCTION: CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course. MATERIALS AND METHODS: In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment. RESULTS AND DISCUSSION: CD8+ lymphocytes from subjects with untreated primary HIV-1 infection strongly suppressed HIV replication. Initiation of antiretroviral therapy during primary HIV-1 infection caused a marked decline in this CNAR. CD8+ cells from these subjects regained anti-HIV activity when early therapy was discontinued. The timing of the appearance of CD8+ cell anti-HIV activity directly correlated with the emergence of detectable virus levels. Maximal CNAR activity coincided with a decay in the kinetics of HIV replication. In addition, peak viral loads during treatment interruption were lower than pre-treatment virus levels (median reduction = 0.8 logs, p = 0.005) and CD4+ T cell counts were maintained for a 24-week period of follow-up. CONCLUSION: These results suggest that CNAR plays an important role in suppressing HIV replication in the setting of antiretroviral treatment interruption in HIV-infected individuals.