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ObjectivesTo determine how the load of rilpivirine-resistant variants (mutational load) influences the virological response (VR) of HIV-1-infected patients to a rilpivirine-based first-line regimen.Patients and methodsFour hundred and eighty-nine patients infected with HIV-1 whose reverse transcriptase gene had been successfully resistance genotyped using next-generation sequencing were given a first-line regimen containing rilpivirine. Variables associated with the VR at 12 months were identified using a logistic model. The results were used to build a multivariate model for each mutational load threshold and the R2 variations were analysed to identify the mutational load threshold that best predicted the VR.ResultsThe mutational load at baseline was the only variable linked to the VR at 12 months (P  1700 copies/mL and to 50% when the mutational load was > 9000 copies/mL. The threshold of 9000 copies/mL was associated with the VR at 12 months with an OR of 36.7 (95% CI 4.7-285.1). The threshold of 1700 copies/mL was associated with the VR at 12 months with an OR of 7.2 (95% CI 1.4-36.8).ConclusionsThere is quantifiable evidence that determining a mutational load threshold can be used to identify those patients on a first-line regimen containing rilpivirine who are at risk of virological failure. The clinical management of HIV-infected patients can be improved by evaluating the frequency of mutant variants at a threshold of

ObjectivesThe objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir).Patients and methodsData were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).ResultsAmong the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P

OBJECTIVES: The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. METHODS: Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. RESULTS: On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P=0.0455) and T215Y (P=0.0455). CONCLUSIONS: In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performed.

Purpose: The purpose of this study was to assess in vitro Er:YAG laser efficacy for composite resin removal, as well as the thermal alterations occurring during laser irradiation.Materials and Methods: Cavity preparations (1.0 mm deep) in bovine teeth were restored with resin and divided into 2 groups: the control group, in which restorations were removed with a high-speed bur, and the experimental group, in which restorations were removed with Er:YAG laser at 250 mJ output energy, 80 J/cm2 energy density, and 6 Hz pulse repetition rate. The removal time was measured and the temperature alteration was checked. After the removal, the specimens were split in the middle, and the surrounding and deep walls were analyzed to check for the presence of restorative material.Results: The results revealed that the temperature rise during composite resin removal in both groups occurred on the substrate underneath the restoration. Although the temperature rose during composite filling removal, none of the groups presented a temperature increase higher than 5.6°C, which is considered the critical temperature increase above which there may be irreversible thermal damage to the pulp. Regarding the time for composite filling removal, it was observed that the laser group required more time than the control group for complete elimination of the material from the cavity walls.Conclusion: Although there was a greater temperature increase during composite resin removal with Er:YAG, it did not reach the critical temperature value above which there may be irreversible thermal damage to the pulp. [ABSTRACT FROM AUTHOR]

Under the scenario of the fourth industrial revolution, the adoption of Industry 4.0 in the day-to-day business of small and medium enterprises (SME) entails expected challenges. Focusing primarily on more advanced levels of maturity, the existing maturity models are inadequate for assessing companies with low maturity levels, such as most of existing SMEs. A framework for a maturity model tailored to SMEs is proposed in this paper, allowing for a comprehensive and high granularity assessment of these companies’ maturity levels, which then eases their integration into this industrial revolution. The proposed holistic model considers all Industry 4.0 dimensions while being detailed enough in its initial levels to properly assess SMEs at the same time.

Background and Aims: Chronic hepatitis D infection is the most severe form of viral hepatitis and can rapidly progress to cirrhosis or hepatocellular carcinoma. Despite recommendations for systematic screening of hepatitis B surface antigen (HBsAg)-positive individuals, data from real-world studies have reported a low frequency of hepatitis D (or delta) virus (HDV) screening. Our cross-sectional analysis evaluated the diagnostic cascade for hepatitis D infection in tertiary centres and described the characteristics of HDV-positive patients., Methods: A total of 6772 individuals who tested HBsAg positive for the first time between 2018 and 2022 were retrospectively included. Demographic, clinical and laboratory data were analysed., Results: A total of 5748 HBsAg-positive individuals (84.9%) were screened for HDV infection. The screening rate varied from 63% to 97% according to the screening strategy used in the centres including or not HDV reflex testing. The prevalence of HDV infection was 6.3%. HDV RNA levels were determined in 285 of the 364 (78.3%) HDV antibody screening-positive patients, and 167 (58.6%) had active HDV infection. 66.8% were males, with a mean age of 44.9 years. A total of 97.5% were born abroad, and 92.9% were HBeAg negative. At the time of diagnosis, HDV RNA levels were 6.0 Log UI/mL; 60.1% had alanine aminotransferase >40 U/L, and 56.3% had significant fibrosis (≥F2), including 41.6% with cirrhosis. The most common genotype was HDV-1 (75.4%). Coinfections were not uncommon: 7.4% were HIV positive, and 15.0% were HCV antibody positive., Conclusions: The present study highlights the need for increased screening and monitoring of HDV infection. Reflex testing helps to identify HDV-infected individuals., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background: Weekend surgical time is an underused asset. Concerns over a possible weekend effect (substandard care) may be a barrier., Methods: This study examined whether a weekend effect applies to elective colorectal surgery via a single-center retrospective analysis comparing outcomes between patients who underwent elective colorectal surgery on a weekend vs a weekday. Demographics, length of stay (LOS), operative and anesthesia time, the rate of reoperation within 30 days, and the rate of major complications were compared between patient groups., Results: Of the 2008 patients identified, 1721 (85.7%) underwent surgery on a weekday, and 287 (14.3%) underwent surgery on a weekend. The proportion of operations with an open approach was higher on weekends than weekdays (49.5% vs 41.8%, P = .017). Patients who underwent surgery on the weekend tended to have a shorter mean (SE) for LOS (4.2 [0.2] vs 6.1 [0.2], P < .001), anesthesia time (233.8 [6.5] vs 307.6 [3.3] minutes, P < .001), and operative time (225.4 [6.4] vs. 297.6 [3.3] minutes, P < .001). On multivariable analysis, patients who had an operation on a weekend had a 38% lower chance of having a prolonged LOS (>75th percentile of LOS) compared with those who had an operation on a weekday (adjusted odds ratio = 0.62; 95% CI 0.42-0.92). There were no differences in rates of complications or reoperation for patients undergoing surgery on a weekend compared with a weekday., Conclusion: At centers with experienced anesthesiologists, appropriately trained nursing staff, and expert surgeons, colorectal surgery performed on a weekend has similar safety outcomes as surgeries performed on a weekday., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Seronegative autoimmune hepatitis in children is a rare but potentially severe disease, sometimes requiring liver transplantation. This type of hepatitis may be associated with various immunological and hematological disorders, ranging from isolated lymphopenia to aplastic anemia. Precise pathophysiological mechanisms are still unknown, but the role of viruses cannot be excluded, either as directly pathogenic or as triggers, responsible for an inappropriate immune stimulation. Having the impression of an increasing number of seronegative autoimmune hepatitis since the beginning of SARS-CoV-2 pandemia period, we hypothesized that SARS-CoV-2 virus could be an infectious trigger., Methods: We conducted a retrospective, observational, descriptive study about children with seronegative autoimmune hepatitis, in a tertiary care center, between 2010 and 2022., Results: Thirty-two patients were included. The overall incidence of seronegative autoimmune hepatitis increased 3.3-fold in 2020-2022, during the SARS-CoV-2 pandemia period (16 patients in 2.8 years) compared with 2010-2019 the pre pandemia period (16 patients in 9 years). Patients' clinical and biochemical liver characteristics did not differ between the two periods. Hematological damages were less severe during the pandemia period. Immunological studies revealed a dysregulated immune response. The initiation of immunosuppressive therapy (corticosteroids ± cyclosporine) was earlier during the pandemia period than before., Conclusion: In cases of undetermined acute hepatitis, an immune-mediated origin should be considered, prompting a liver biopsy. If the histological aspect points to an immune origin, immunosuppressive treatment should be instituted even though autoimmune hepatitis antibodies are negative. Close hematological monitoring must be performed in all cases. The 3.3-fold increase of cases during the SARS-CoV-2 pandemia will need to be further analyzed to better understand the underlying immunological mechanisms, and to prove its potential involvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schmutz, Chartier, Leblanc, Mussini, Gardin, Gonzales, Roque-Afonso, Le Cam, Hery, Neven, Charbel, Vartanian, Jacquemin, Morelle and Almes.)

Introduction: Gabapentin has been used in enhanced recovery after surgery (ERAS) pathways for pain control for patients undergoing ambulatory uro-oncologic surgery; however, it may cause undesirable side effects. We studied the causal association between gabapentin and rapidity of recovery and perioperative pain management after minimally invasive uro-oncologic surgery., Methods: We identified 2397 patients ≤ 65 years undergoing prostatectomies or nephrectomies between 2018 and 2022; 131 (5.5%) did not receive gabapentin. We tested the effect of gabapentin use on time of discharge and perioperative opioid consumption, respectively, using multivariable linear regression adjusting for potential confounders including age, gender, BMI, American Society of Anesthesiologists score, and surgery type., Results: On adjusted analysis, we found no evidence of a difference in discharge time among those who did vs did not receive gabapentin (adjusted difference 0.07 hours shorter on gabapentin; 95% CI -0.17, 0.31; P = .6). There was no evidence of a difference in intraoperative opioid consumption by gabapentin receipt (adjusted difference -1.5 morphine milligram equivalents; 95% CI -4.2, 1.1; P = .3) or probability of being in the top quartile of postoperative opioid consumption within 24 hours (adjusted difference 4.2%; 95% CI -4.8%, 13%; P = .4). We saw no important differences in confounders by gabapentin receipt suggesting causal conclusions are justified., Conclusions: Our confidence intervals did not include clinically meaningful benefits from gabapentin, when used with an ERAS protocol, in terms of length of stay or perioperative opioid use. These results support the omission of gabapentin from ERAS protocols for minimally invasive uro-oncologic surgeries.

Objectives: Human herpesvirus-8 (HHV-8) can cause Kaposi's sarcoma or B lymphoproliferative disorders such as multicentric Castleman disease. Patient follow-up is based on assessing the HHV-8 viral load, which is usually achieved using real-time polymerase chain reaction (PCR). The HHV-8 Premix r-gene kit (BioMérieux) was used by some laboratories in the past, but BioMérieux ceased the production and distribution of this kit in 2021-2022. Other kits need to be tested so that they can be used for diagnostic purposes. Here we evaluated two commercial kits: HHV8 ELITe MGB Kit (ELITech) and Quanty HHV-8 (Clonit) and compared them with the HHV-8 Premix r-gene kit., Methods: We used whole blood samples that had previously been tested with the HHV-8 Premix r-gene kit for diagnostic purposes. Overall, 46 samples (37 HHV-8-positive and 9 HHV-8-negative) were tested with the ELITe MGB Kit and 37 (29 HHV-8-positive and 8 HHV-8-negative) with the Quanty HHV-8 kit. The different methods were compared using Bland-Altman and Passing-Bablok tests with Analyse-it software., Results: Qualitative results were concordant except for one HHV-8 low-positive sample that was found to be negative by the ELITe MGB Kit. The quantitative results were also concordant; both kits showed mean differences of 0.58 log 10 copies/ml and 0.73 log 10 copies/ml, respectively, compared to the Premix r-gene kit., Conclusions: Both the methods tested produced acceptable results and could be used for diagnostic purposes. It should be remembered that there is no international standard for HHV-8 quantification and that patients should always be followed using the same method., Competing Interests: The authors have no competing interests to declare., (© 2024 The Authors.)

Background: Anesthesiologists are experiencing unprecedented levels of workplace stress and staffing shortages. This analysis aims to assess how U.S. attending anesthesiologist burnout changed since the onset of the COVID-19 pandemic and target well-being efforts., Methods: The authors surveyed the American Society of Anesthesiologists' U.S. attending anesthesiologist members in November 2022. Burnout was assessed using the Maslach Burnout Inventory Human Services Survey with additional questions relating to workplace and demographic factors. Burnout was categorized as high risk for burnout (exhibiting emotional exhaustion and/or depersonalization) or burnout syndrome (demonstrating all three burnout dimensions concurrently). The association of burnout with U.S. attending anesthesiologist retention plans was analyzed, and associated factors were identified., Results: Of 24,680 individuals contacted, 2,698 (10.9%) completed the survey, with 67.7% (1,827 of 2,698) at high risk for burnout and 18.9% (510 of 2,698) with burnout syndrome. Most (78.4%, n = 2,115) respondents have experienced recent staffing shortages, and many (36.0%, n = 970) were likely to leave their job within the next 2 yr. Those likely to leave their job in the next 2 yr had higher prevalence of high risk for burnout (78.5% [760 of 970] vs. 55.7% [651 of 1,169], P < 0.001) and burnout syndrome (24.3% [236 of 970] vs. 13.3% [156 of 1,169], P < 0.001) compared to those unlikely to leave. On multivariable analysis, perceived lack of support at work (odds ratio, 9.2; 95% CI, 7.0 to 12.1), and staffing shortages (odds ratio, 1.96; 95% CI, 1.57 to 2.43) were most strongly associated with high risk for burnout. Perceived lack of support at work (odds ratio, 6.3; 95% CI, 3.81 to 10.4) was the factor most strongly associated with burnout syndrome., Conclusions: Burnout is more prevalent in anesthesiology since early 2020, with workplace factors of perceived support and staffing being the predominant associated variables. Interventions focused on the drivers of burnout are needed to improve well-being among U.S. attending anesthesiologists., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Direct-targeted next-generation sequencing (tNGS), with its undoubtedly superior diagnostic capacity over real-time PCR (RT-PCR), and direct-non-targeted NGS (ntNGS), with its higher capacity to identify and characterize multiple agents, are both likely to become diagnostic methods of choice in the future. tNGS is a rapid and sensitive method for precise characterization of suspected agents. ntNGS, also known as agnostic diagnosis, does not require a hypothesis and has been used to identify unsuspected infections in clinical samples. Implemented in the form of multiplexed total DNA metagenomics or as total RNA sequencing, the approach produces comprehensive and actionable reports that allow semi-quantitative identification of most of the agents present in respiratory, cloacal, and tissue samples. The diagnostic benefits of the use of direct tNGS and ntNGS are high specificity, compatibility with different types of clinical samples (fresh, frozen, FTA cards, and paraffin-embedded), production of nearly complete infection profiles (viruses, bacteria, fungus, and parasites), production of "semi-quantitative" information, direct agent genotyping, and infectious agent mutational information. The achievements of NGS in terms of diagnosing poultry problems are described here, along with future applications. Multiplexing, development of standard operating procedures, robotics, sequencing kits, automated bioinformatics, cloud computing, and artificial intelligence (AI) are disciplines converging toward the use of this technology for active surveillance in poultry farms. Other advances in human and veterinary NGS sequencing are likely to be adaptable to avian species in the future.

Background: The clinical outcome of COVID-19 pneumonia is highly variable. Few biological predictive factors have been identified. Genetic and immunological studies suggest that type 1 interferons (IFN) are essential to control SARS-CoV-2 infection., Objective: To study the link between change in blood IFN-α2 level and plasma SARS-Cov2 viral load over time and subsequent death in patients with severe and critical COVID-19., Methods: One hundred and forty patients from the CORIMUNO-19 cohort hospitalized with severe or critical COVID-19 pneumonia, all requiring oxygen or ventilation, were prospectively studied. Blood IFN-α2 was evaluated using the Single Molecule Array technology. Anti-IFN-α2 auto-Abs were determined with a reporter luciferase activity. Plasma SARS-Cov2 viral load was measured using droplet digital PCR targeting the Nucleocapsid gene of the SARS-CoV-2 positive-strand RNA genome., Results: Although the percentage of plasmacytoid dendritic cells was low, the blood IFN-α2 level was higher in patients than in healthy controls and was correlated to SARS-CoV-2 plasma viral load at entry. Neutralizing anti-IFN-α2 auto-antibodies were detected in 5% of patients, associated with a lower baseline level of blood IFN-α2. A longitudinal analysis found that a more rapid decline of blood IFN-α2 was observed in fatal versus surviving patients: mortality HR=3.15 (95% CI 1.14-8.66) in rapid versus slow decliners. Likewise, a high level of plasma SARS-CoV-2 RNA was associated with death risk in patients with severe COVID-19., Conclusion: These findings could suggest an interest in evaluating type 1 IFN treatment in patients with severe COVID-19 and type 1 IFN decline, eventually combined with anti-inflammatory drugs., Clinical Trial Registration: https://clinicaltrials.gov, identifiers NCT04324073, NCT04331808, NCT04341584., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Joly, Desjardins, Porcher, Péré, Bruneau, Zhang, Bastard, Cobat, Resmini, Lenoir, Savale, Lécuroux, Verstuyft, Roque-Afonso, Veyer, Baron, Resche-Rigon, Ravaud, Casanova, Le Grand, Hermine, Tharaux and Mariette.)

Background: There has been a recent focus among anesthesiologists on reducing the use of perioperative opioids in favor of multimodal analgesic regimens. Gabapentin has played an integral role in this evolution of practice. This comprehensive review assesses the current clinical evidence on the efficacy of perioperative gabapentin regarding postoperative pain and opioid requirements among the pediatric surgery population., Data Sources: Pubmed, CINAHL, Embase, Scopus, and Web of Science Review., Methods: This scoping review of the above databases includes all studies examining the use of gabapentin perioperatively in pediatric patients and its association with postoperative pain intensity and postoperative opioid consumption through July 2021. The inclusion criteria encompassed all studies evaluating gabapentin in the perioperative pediatric population through randomized controlled trials (RCTs) and retrospective studies. Relevant metadata from each study were abstracted and descriptive statistics were used to summarize the results., Results: Fifteen papers met the inclusion criteria for this review, including 11 RCTs and 4 retrospective studies. Sample sizes ranged from 20 to 144 patients. Administered doses varied widely, mainly between 5 and 20 mg/kg. The studies included primarily orthopedic (10) and neck surgery cases (3). Seven papers had gabapentin provided preoperatively only, two postoperative only, and six both pre- and postoperatively. Of the studies assessing postoperative pain, 6/11 studies saw a decrease in postoperative pain in at least one period for the gabapentin group. Of the studies considering opioid requirements, 6/10 reported a reduction, 1/10 an increase, and 3/10 no difference in opioid requirements for the gabapentin groups. Yet, most of these pain and opioid requirement findings were only significant at one to two time points in the study follow-up periods, and the actual decreases had minimal clinical significance., Conclusions: The current data on perioperative gabapentin in pediatric patients are insufficient to support the routine use of gabapentin in pediatric patients. Additional high-quality RCTs with more standardized protocols for gabapentin administration and outcome measures are necessary to provide more definitive conclusions., (© 2023 John Wiley & Sons Ltd.)

Background: Medical treatment of inflammatory bowel disease (IBD) has evolved significantly, and treatment with immunomodulators is recommended. These medications may alter the patient's immune response and increase the risk of opportunistic infections. Our aim was to evaluate the prevalence and the incidence of acute or chronic HEV infection in IBD patients under immunomodulatory treatment., Patients and Methods: We conducted a retrospective, multicenter, observational study between 2017 and 2018. IBD outpatients hospitalized for the infusion of immunomodulators were included in 16 French centers. During their daily hospitalization, blood samples were drawn for HEV serology (IgM and IgG) and HEV RNA detection., Results: A total of 488 patients were included, of which 327 (67%) patients had Crohn's disease and 161 (33%) ulcerative colitis. HEV IgM was detected in 3 patients, but HEV RNA was undetectable in all patients. The HEV IgG seroprevalence rate was 14.2%. IgG-positive patients were older at sampling ( p = 0.01) and IBD diagnosis ( p = 0.03), had higher seafood consumption ( p = 0.01) and higher doses of azathioprine ( p = 0.03). Ileal and upper digestive tract involvement was more frequent in IgG-positive patients ( p = 0.009), and ileocolic involvement was more frequent in IgG-negative patients ( p = 0.01). Under multivariate analysis, age > 50 years [OR: 2.21 (1.26, to 3.85), p = 0.004] was associated with previous HEV infection., Conclusion: Systematic screening for HEV infection is not needed among IBD patients on immunomodulatory medications. However, in the event of abnormal liver test findings, HEV should be part of the classic diagnostic assessment., Competing Interests: The authors declare no conflict of interest.

Vaccination against COVID-19 is the main public health approach to fight against the pandemic. The Spike (S) glycoprotein of SARS-CoV-2 is the principal target of the neutralizing humoral response. We evaluated the analytical and clinical performances of a surrogate virus neutralization test (sVNT) compared to conventional neutralization tests (cVNTs) and anti-S eCLIA assays in recovered and/or vaccinated healthcare workers. Our results indicate that sVNTs displayed high specificity and no cross-reactivity. Both eCLIA and sVNT immunoassays were good at identifying cVNT serum dilutions ≥1:16. The optimal thresholds when identifying cVNT titers ≥1:16, were 74.5 U/mL and 49.4 IU/mL for anti-S eCLIA and sVNT, respectively. Our data show that neutralizing antibody titers (Nab) differ from one individual to another and may diminish over time. Specific assays such as sVNTs could offer a reliable complementary tool to routine anti-S serological assays.

Background: Metastatic spine tumor surgery consists of palliative operations performed on frail patients with multiple medical comorbidities. Enhanced recovery after surgery (ERAS) programs involve an evidence-based, multidisciplinary approach to improve perioperative outcomes. This study presents clinical outcomes of a metastatic spine tumor ERAS pathway implemented at a tertiary cancer center., Methods: The metastatic spine tumor ERAS program launched in April 2019, and data from January 2018 to May 2020 were reviewed. Measured outcomes included the following: hospital length of stay (LOS), time to ambulation, urinary catheter duration, time to resumption of diet, intraoperative fluid intake, estimated blood loss (EBL), and intraoperative and postoperative day 0-5 cumulative opioid use (morphine milligram equivalent [MME])., Results: A total of 390 patients were included in the final analysis: 177 consecutive patients undergoing metastatic spine tumor surgery enrolled in the ERAS program and 213 consecutive pre-ERAS patients. Although the mean case durations were similar in the ERAS and pre-ERAS cohorts (265 vs. 274 min; p = .22), the ERAS cohort had decreased EBL (157 vs. 215 ml; p = .003), decreased postoperative day 0-5 cumulative mean opioid use (178 vs. 396 MME; p < .0001), earlier ambulation (mean, 34 vs. 57 h; p = .0001), earlier discontinuation of urinary catheters (mean, 36 vs. 56 h; p < .001), and shorter LOS (5.4 vs. 7.5 days; p < .0001)., Conclusions: The implementation of a multidisciplinary ERAS program designed for metastatic spine tumor surgery led to improved clinical quality metrics, including shorter hospitalizations and significant reductions in opioid consumption., (© 2022 American Cancer Society.)

Background: Coronavirus disease 2019 (COVID-19) has severely affected the elderly, who are expected to display decreased immune responses due to immunosenescence., Methods: This study retrospectively assesses neutralizing antibody (NAb) production up to 12 months after infection in long-term care patients. We used Roche Diagnostics immunoassay to quantify anti-spike (S) antibodies and a competitive immunoassay from YHLO as a surrogate test for NAb., Results: We included 91 patients (mean age, 86 years). There was no significant variation in anti-S titers over time. There was a significant decrease of NAb titers between month 3 and month 6 but no further significant change up to month 12. Overall, 75 of 91 (82%) and 52 of 91 (57%) patients had, at least once, anti-S titers >75 U/mL and NAb titers >50 AU/mL, respectively, corresponding to a significant neutralizing activity in vitro. All 68 patients studied at M12 had detectable anti-S antibodies and 60 (88%) had detectable NAb; 60 of 68 (88%) and 29 of 68 (42.6%) still had anti-S titers >75 U/mL and NAb titers >50 AU/mL. Higher NAb titers were correlated with severe infection, higher levels of C-reactive protein, and lower lymphocyte counts. No patient developed reinfection., Conclusions: Elderly people can display robust and persistent humoral response after severe acute respiratory syndrome coronavirus 2 infection, with NAb lasting up to 12 months., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: Research on the impact of various intraoperative haemodynamic variables on the incidence of postoperative ICU admission among older patients with cancer is limited. In this study, the relationship between intraoperative haemodynamic status and postoperative intensive care unit admission among older patients with cancer is explored., Methods: Patients aged ≥75 who underwent elective oncologic surgery lasting ≥120min were analysed. Chi-squared and t-tests were used to assess the associations between intraoperative variables with postoperative intensive care unit admission. Multivariable regressions were used to analyse potential predict risk factors for postoperative intensive care unit admission., Results: Out of 994 patients, 48 (4.8%) were admitted to the intensive care unit within 30 days following surgery. Intensive care unit admission was associated with the presence of ≥4 comorbid conditions, intraoperative blood loss ≥100mL, and intraoperative tachycardia and hypertensive urgency. On multivariable analysis, operation time ≥240min (Odds Ratio [OR] = 2.29, p = 0.01), and each minute spent with intraoperative hypertensive urgency (OR = 1.06, p = 0.01) or tachycardia (OR = 1.01, p = 0.002) were associated with postoperative intensive care unit admission., Conclusion: Intraoperative hypertensive urgency and tachycardia were associated with postoperative intensive care unit admission in older patients undergoing cancer surgery.

This study evaluated the performances of immunoassays (LFIA and ELISA) designed for SARS-CoV-2 Antigen (Ag)-detection in nasopharyngeal (NP) and serum samples in comparison to RT-PCR. NP samples from patients with respiratory symptoms (183 RT-PCR-positive and 74 RT-PCR-negative samples) were collected from March to April and November to December 2020. Seroconversion and antigen dynamics were assessed by symptom onset and day of RT-PCR diagnosis. Serum samples from 87 COVID-19 patients were used to investigate the added value of Ag quantification, at diagnosis and during follow-up. The sensitivity of COVID-VIRO-LFIA on samples with Ct ≤ 33, considered as the contagious threshold, was 86% on NPs (CI 95%: 79-90.5) and 76% on serum samples (CI 95%: 59.4-88), with a specificity of 100%. Serum N-Ag was detected during active infection as early as day two from symptom onset, with a diagnostic sensitivity of 81.5%. Within one week of symptom onset, diagnostic sensitivity and specificity reached 90.9% (95% CI, 85.1%-94.6%) and 98.3% (95% CI, 91.1%-99.9%), respectively. Serum N-Ag concentration closely correlated with disease severity. Longitudinal analysis revealed the simultaneous increase of antibodies and decrease of N-Ag. Sensitivities of COVID-VIRO-LFIA and COV-QUANTO-ELISA tests on NP and serum samples were close to 80%. They are suitable COVID-19-laboratory diagnostic tests, particularly when blood samples are available, thus reducing the requirement for NP sampling, and subsequent PCR analysis. ELISA titers may help to identify patients at risk of poor outcomes.

Cancer in patients with obesity has become increasingly common throughout much of the world. Based on our experiences in a specialized cancer center, we have developed a set of standards and expectations that should streamline the surgical journey for this patient population. These recommendations should inform the perioperative management of oncology patients with obesity and help raise awareness of this critical and under-discussed topic., Competing Interests: Disclosures Dr. Afonso is a consultant for Pacira and Merck. Dr. Tollinche serves as a paid consultant and has an advisory role for Merck and is a grant recipient through Merck Investigator Studies Program (MISP) to fund a clinical trial at MSKCC (NCT03808077). The remaining authors declare no conflicts of interest.

Epithelial tumors of the lacrimal gland are rare and usually develop in the orbital lobe. We report the exceedingly rare occurrence of a primary adenoid cystic carcinoma in the palpebral lobe of the lacrimal gland. A 26-year-old female was referred for evaluation of a gradually enlarging mass in the lateral upper eyelid, previously diagnosed as a chalazion. Computed tomography revealed a heterogeneous round lesion anterior to the orbital rim. Excisional biopsy was compatible with an adenoid cystic carcinoma. After excluding distant metastasis, and as the patient refused adjuvant radiotherapy, a second surgical procedure, with wide local excision, was indicated. Follow-up showed no recurrence. This case highlights the importance of performing a thorough clinical examination when diagnosing any lateral upper eyelid mass. A high index of suspicion for malignant tumors of the lacrimal gland should always be maintained, and a complete excision with histological analysis should be preferred whenever possible.

(1) Background: What is the role of serum CMV PCR in the diagnosis of recent primary infection (PI) in pregnant women when IgG avidity is uninformative? (2) Methods: Retrospective cohort study to compare serum versus whole blood CMV PCR. (a) Qualitative assessment: CMV PCR was performed on 123 serum samples and 74 whole blood samples collected from 132 pregnant women with recent CMV PI. PCR positivity rate was used to calculate sensitivity in serum and whole blood. (b) Quantitative assessment: CMV PCR was performed on 72 paired samples of serum and whole blood collected on the same day from 57 patients. (3) Results: In pregnant women, PCR positivity rate was 89% for serum samples versus 100% in whole blood in the case of very recent PI (<15 days), but only 27% in serum versus 68% in whole blood for PI occurring from 6 weeks to 3 months before. Comparing CMV viral loads between serum and whole blood, we determined the limit of CMV DNA detection in serum as 3 log copies/mL (whole blood equivalent). (4) Conclusions: Serum CMV PCR is reliable in confirming PI in cases when only IgM is detected. It is therefore a valuable tool in introducing valaciclovir treatment as early as possible to prevent mother-to-child CMV transmission.

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3-8] vs. 3 [2-4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.

We evaluated the performance of the QIAprep&amp Viral RNA UM Kit (Qiagen) for SARS-CoV-2 detection. It displayed specificity and sensitivity required for SARS-CoV-2 RNA detection from swab transport media without RNA extraction. This method identifies accurately patients at risk of transmission while saving time and cost of extraction., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

A 14-year-old patient underwent liver transplant. Three months after transplantation, EBV associated lymphoma was suspected. EBV serologies before and after transplantation were particularly discrepant. Eighteen months before transplantation, the serological profile suggested a recent EBV primary-infection, four months before transplantation, we had isolated anti-EBNA IgG and five days after transplantation, the serological profile suggested a past infection. All EBV PCR performed on whole blood were negative. Retrospectively, immunoblots anti-EBV IgG were performed. Blots showed no anti-EBV IgG before and until the day of liver transplantation. Five days after transplantation, slight bands of both IgG anti-p18 (VCA) and anti-EBNA-1 were found, without any other serological marker. These were probably due to passive transfers of IgG during surgery. There was therefore no argument for an immunization against EBV before or after liver transplant for this patient.

Objective: Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine., Methods: We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose. The specific T cell response was assessed in activated CD4 and CD8 T cells using intracellular flow cytometry staining of cytokines (interferon-γ, tumor necrosis factor, and interleukin-2) after stimulation with SARS-CoV-2 spike peptide pools., Results: A lower proportion of responders with neutralizing antibodies to the vaccine was observed in the RTX group (29%; n = 24) compared to the other immunosuppressants group (80%; n = 35) (P = 0.0001) and the healthy control group (92%; n = 26) (P < 0.0001). No patients treated with RTX in the last 6 months showed a response. Time since last infusion was the main factor influencing humoral response in RTX-treated patients. The functional CD4 and CD8 cellular responses to SARS-CoV-2 peptides for each single cytokine or polyfunctionality were not different in the RTX group compared to the other immunosuppressants group or the control group. In RTX-treated patients, the T cell response was not different between patients with and those without a humoral response., Conclusion: RTX induced a diminished antibody response to the mRNA COVID-19 vaccine, but the functional T cell response was not altered compared to healthy controls and autoimmune disease patients treated with other immunosuppressants. Further work is needed to assess the clinical protection granted by a functionally active T cell response in the absence of an anti-spike antibody response., (© 2021 American College of Rheumatology.)

Increasing attention is being paid to both anesthesiologist well-being and commitments to diversity, equity, and inclusion. Sexual minorities (ie, members of the lesbian, gay, bisexual, transgender, queer/questioning, intersex, and asexual [LGBTQIA] communities) face many challenges in society and the workplace, including mental health conditions, discrimination, and increased risk for burnout. In this review, we outline the current state of mental health conditions and burnout in sexual minority individuals, discrimination and harassment faced both in society and the workplace, and steps that workplaces can take to become more inclusive and welcoming., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: We reviewed internal data and the current literature to update our enhanced recovery protocol (ERP) for patients undergoing a total breast mastectomy. Following implementation, the protocol was audited by chart review and compliance reminders were sent through email., Objective: Our primary research aim was to examine the protocol compliance following the update. Our secondary aims were to examine the association between the change in protocol and the rates of postoperative nausea and vomiting (PONV) and hematoma formation requiring reoperation., Methods: We retrospectively obtained data extracted from the electronic medical record. To test for a difference in outcomes before versus after implementation of the protocol we used multivariable logistic regression with the primary comparisons excluding a ​± ​one-month window and secondary comparisons excluding a ​± ​three-month window from the date of implementation., Results: Our cohort included 5853 unique patients. Total intravenous anesthesia (TIVA) compliance increased by 17%-52% ( P  ​< ​0.001) and the use of intraoperative ketorolac dropped from 44% to nearly no utilization (0.7%; P  ​< ​0.001). The rate of reoperation due to bleeding decreased from 3.6% to 2.6% after implementation with the adjusted decrease being 1.0% (bootstrap 95% CI, 0.11%, 1.9%; P  ​= ​0.053) excluding a ​± ​1 month window and 1.2% (bootstrap 95% CI, 0.24%, 2.0%; P  ​= ​0.028) excluding a ​± ​3-month window. The rate of rescue antiemetics dropped by 6.4% (95% CI, 3.9%, 9.0%)., Conclusions: We were able to improve compliance for nearly all components of the protocol which translated to a meaningful change in an important patient outcome., Competing Interests: None declared., (© 2022 The Authors.)

Objective: Evaluation of relevance and feasibility of universal newborn congenital cytomegalovirus infection (cCMVI) screening in saliva., Design: Retrospective, population-based cohort study., Setting: Clamart, France, 2016-2020., Population: All neonates born consecutively in our level III maternity unit., Methods: CMV PCR in saliva for all neonates at birth, and, if positive, CMV PCR in urine to confirm or exclude cCMVI. Prospective and retrospective characterisation of maternal infections. ROC curve analysis to assess saliva PCR performances. Acceptability of screening among staff members evaluated by a survey., Main Outcome Measures: Number of cCMVI neonates; number of expected and unexpected cCMVI., Results: Among 15 341 tested neonates, 63 had cCMVI (birth prevalence of 0.4%, 95% CI 0.3-0.5). In 50% of cases, maternal infection was a non-primary infection (NPI) during pregnancy. cCMVI was expected or suspected (maternal primary infection [PI], antenatal or neonatal signs) in 24/63 neonates (38%), and unexpected in 39/63 neonates (62%). The best CMV saliva threshold to predict cCMVI was 356 (2.55 log) copies/ml [95% CI 2.52 log-3.18 log], with an area under the ROC curve of 0.97. Over 90% of the 72 surveyed staff members reported that the screening was easy and quick. No parent refused the screening., Conclusions: Universal screening for cCMVI with CMV PCR on saliva samples is feasible and highly acceptable to parents and healthcare providers. Over half (62%) of the cases had no prenatal/neonatal signs of cCMVI or a maternal history of CMV infection during pregnancy and would probably not have been diagnosed without universal screening., Tweetable Abstract: In 62% of congenital cytomegalovirus infection cases, only universal neonatal screening in saliva can detect infection., (© 2021 John Wiley & Sons Ltd.)

Background: Anti-hepatitis A virus (HAV) antibody titers at 20 IU/L are assumed to correlate with protection against HAV challenge., Methods: We examined the accuracy and precision of currently in use immunoassays for total or anti-HAV IgG determination, by repeated testing of dilutions of the international anti-HAV standard, within a 10-50 IU/mL concentration range., Results and Conclusion: Eight immunoassays were evaluated. All could confidently identify people who need to be vaccinated, or who might benefit from a booster vaccine: no positive interpretation for the 10 and 15 IU/mL concentrations. However, qualitative interpretation may differ from test to test in the 15-30 IU/mL range. This variation has to be taken into account when comparing seroprevalence data., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

We report a transfusion-transmitted hepatitis A virus infection in an immunocompromised patient in France, detected shortly after a transfusion of pathogen-reduced pooled platelets. This case raises questions about the efficacy of donor screening methods. Additional safety measures, such as routine donation screening, should be considered.

Background: Racial disparities are evident in multiple aspects of the perioperative care of breast cancer patients, but data examining whether such differences translate to clinical and patient-reported outcomes are limited. This study examined the impact of race on perioperative outcomes in autologous breast reconstruction., Methods: A retrospective cohort study including all breast cancer patients who underwent immediate autologous breast reconstruction at a single institution from 2010 to 2017 was conducted. Self-reported race was used to classify patients into three groups: white, African American, and other. The primary and secondary endpoints were occurrence of any major complications within 30 days of surgery and patient-reported outcomes (measured with the BREAST-Q), respectively. Regression models were constructed to identify factors associated with the outcomes., Results: Overall, 404 patients, including 259 white (64 percent), 63 African American (16 percent), and 82 patients from other minority groups (20 percent), were included. African American patients had a significantly higher proportion of preoperative comorbidities. Postoperatively, African American patients had a higher incidence of 30-day major complications (p = 0.004) and were more likely to return to the operating room (p = 0.006). Univariable analyses examining complications demonstrated that race was the only factor associated with 30-day major complications (p = 0.001). Patient-reported outcomes were not statistically different at each time point through 3 years postoperatively., Conclusions: African American patients continue to present with increased comorbidities and may be more likely to experience major complications following immediate autologous breast reconstruction. However, patient-reported satisfaction or physical well-being outcomes may not differ between groups., Clinical Question/level of Evidence: Risk, II., (Copyright © 2021 by the American Society of Plastic Surgeons.)