COVID-19 shifted antibiotic stewardship program resources and changed antibiotic use (AU). Shifts in patient populations with COVID surges, including pauses to surgical procedures, and dynamic practice changes makes temporal associations difficult to interpret. Our analysis aimed to address the impact of COVID on AU after adjusting for other practice shifts.We performed a longitudinal analysis of AU data from 30 Southeast US hospitals. Three pandemic phases  were compared to baseline (1/2018–1/2020). AU (days of therapy (DOT)/1000 patient days (PD)) was collected for all antimicrobial agents and specific subgroups: broad spectrum , CAP , and antifungal. Monthly COVID burden was defined as all PD attributed to a COVID admission. We fit negative binomial GEE models to AU including phase and interaction terms between COVID burden and phase to test the hypothesis that AU changes during the phases were related to COVID burden. Models included adjustment for Charlson comorbidity, surgical volume, time since 12/2017 and seasonality.Observed AU rates by subgroup varied over time; peaks were observed for different subgroups during distinct pandemic phases . Compared to baseline, we observed a significant increase in overall, broad spectrum, and CAP groups during phase 1 (Table). In phase 2, overall and CAP AU was significantly higher than baseline, but in phase 3, AU was similar to baseline. These phase changes were separate from effects of COVID burden, except in phase 1 where we observed significant effects on antifungal (increased) and CAP (decreased) AU (Table).Changes in hospital AU observed during early phases of the COVID pandemic appeared unrelated to COVID burden and may have been due to indirect pandemic effects . By pandemic phase 3, these disruptive effects were not as apparent, potentially related to shifts in non-COVID patient populations or ASP resources, availability of COVID treatments, or increased learning, diagnostic certainty, and provider comfort with avoiding antibacterials in patients with suspected COVID over time.Melissa D. Johnson, PharmD, Biomeme: Licensed Transcriptional Signature for Candidemia|Charles River Laboratories: Grant/Research Support|Entasis Therapeutics: Advisor/Consultant|Merck & Co. Inc: Advisor/Consultant|Merck & Co. Inc: Grant/Research Support|Pfizer, Inc.: Advisor/Consultant|Scynexis Inc.: Grant/Research Support|Theratechnologies: Advisor/Consultant Angelina Davis, PharmD, M.S., Merck & Co.: Honoraria Sonali D. Advani, MBBS, MPH, FIDSA, Locus Biosciences: Advisor/Consultant|Locus Biosciences: Honoraria|Sysmex America: Advisor/Consultant Ibukun Kalu, MD, Pfizer, Inc.: Institutional support for clinical trial Rebekah W. Moehring, MD, MPH, FIDSA, FSHEA, UpToDate, Inc.: Author Royalties.


The first long-acting (LA) antiretroviral therapy (ART) regimen, cabotegravir+rilpivirine (CAB+RPV) injection, was approved by the FDA in January 2021 for ART-experienced, people with HIV (PWH) with undetectable viral load (VL< 50 copies/mL). We assessed clinical effectiveness of CAB+RPV LA in the first year of use in the United States (US).Using electronic health record data from the OPERA® cohort, all ART-experienced adults who received ≥1 CAB+RPV LA prescriptions for the first time between 21Jan2021 and 28Feb2022 were followed until 13Mar2022. Discontinuation was defined as an ART switch or > 2 consecutive missed doses. VL were monitored from first injection until end of follow-up or discontinuation. Confirmed virologic failure was defined as 2 consecutive VLs > 200 copies/mL or 1 VL > 200 copies/mL + discontinuation. Results were stratified by VL at first prescription .Of 994 PWH prescribed CAB+RPV, all were ART-experienced and 85% had undetectable VL (< 50 copies/mL), 90% were suppressed (< 200 copies/mL), and the remainder had VL ≥200/mL (6%) or missing baseline VL (4%). Of those prescribed, 344 (38%) received CAB+RPV LA injections over a median 53  days; 14% were women, 36% were Black, 29% were Hispanic, 25% had a BMI of ≥30, and the median age was 40  years (Table 1). At the end of observation, 62% had not yet received CAB+RPV injections as they were in the process of approval, were on oral lead-in, or had been denied. At study end, 310 (90%) of the 344 remained on CAB+RPV LA with median follow-up of 3.4  months. Among those with VLs after first injection, the last VL was < 200 copies/mL in 99% and < 50 copies/mL in 94% (Table 2); all follow-up VLs were < 200 copies/mL in 97%, and < 50 copies/mL in 88%. Thirty viremic PWH received CAB+RPV LA injections (Table) with a median VL at first prescription of 4.2  log copies/mL. Five or fewer PWH experienced confirmed virologic failure in each of the suppressed and viremic groups.In this real-world cohort of PWH who received CAB+RPV LA injections in the US, observations from the first year suggest that this regimen is effective among virologically suppressed individuals.Michael G. Sension, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Honoraria Ricky K. Hsu, MD, Gilead: Honoraria|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employment Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds Andrew Zolopa, MD, ViiV Healthcare: full time employee|ViiV Healthcare: Stocks/Bonds Jean A. van Wyk, MB,ChB; MFPM, ViiV Healthcare Limited: I am an employee of ViiV Healthcare|ViiV Healthcare Limited: Stocks/Bonds Gregory P. Fusco, MD, MPH, AIDS Healthcare Foundation: Client of employer|EMD: Grant/Research Support|Gilead Sciences: Client of employer|Janssen: Client of employer|Merck & Co.: Client of employer|Theratechnologies: Client of employer|ViiV Healthcare: Client of employer.


Corrigendum on:Effectiveness of mobile applications to quit smoking: Systematic review and meta-analysisBy Raquel Cobos-Campos, Arantza Sáez de Lafuente, Antxon Apiñaniz, Naiara Parraza, Iraida Pérez Llanos, Gorka OriveTobacco Prevention and Cessation, Volume 6, Issue November, Pages 1-11Publish date: 10 November 2020https://doi.org/10.18332/tpc/127770DOI: An error in data entry occurred during the production tables 2 and 3 in the manuscript, as the authors accidentally omitted the confidence interval dashes in the tables.Table 2. Comparison of smartphone app versus other intervention The table is the following:The correct table should be:Table 3. Comparison of smartphone app versus other intervention: Sensitivity analysisThe table is the following:The correct table should be:


Background: Weight loss and physical activity (PA) are recommended for arthritis management. The Group Lifestyle Balance (GLB) Program(TM) is an evidence-based, lifestyle change program for weight loss in individuals with prediabetes, but hasn’t been evaluated in people with arthritis. Purpose: The purpose of this study was to evaluate the effectiveness of an adapted version of the GLB program on PA and psychosocial outcomes related to weight loss among overweight (Body Mass Index >27) individuals with arthritis. Methods: A single-group, quasi-experimental design was used to examine the effects of the adapted GLB program on measures of PA and psychosocial outcomes. All participants (N=15) received the GLB program and completed the following surveys: CHAMPS PA, Self-Efficacy for PA (SE), Social Support for PA (SS), Weight Loss Efficacy (WEL) and Barriers to Healthy Eating (BHE) at baseline, 12-weeks, 6 months, and 12 months. Repeated measures ANOVA and the Friedman Test were used to examine changes over time. Results: Participants (aged 53-79 years) were primarily female (82%), white (94%), and college educated (94%). Significant improvements were found in BHE subsections of self-control and motivation (p=0.002), daily mechanics (p=0.042), and WEL subsections of availability (p=0.049), social pressure (p=0.010), physical discomfort (p=0.011), and positive activities (p=0.007). Weekly caloric expenditure (p=0.004), metabolic equivalent minutes (p=0.022) for all activities, and moderate-intensity activities (p=0.019) also showed significant improvements. However, most improvements were seen in the short-term. Conclusions: The GLB program should be further evaluated for its effectiveness in people with arthritis.


The correct name is: Fabrizio Tediosi. The correct citation is: Akweongo P, Chatio ST, Owusu R, Salari P, Tediosi F, Aikins M (2021) How does it affect service delivery under the National Health Insurance Scheme in Ghana? Health providers and insurance managers perspective on submission and reimbursement of claims. PLoS ONE 16(3): e0247397.


Corrigendum on:https://doi.org/10.18332/tid/140824Association of heated tobacco product use and secondhand smoke exposure with suicidal ideation, suicide plans, and suicide attempts among Korean adolescents: A 2019 national survey By Soyoon Park, Kang-Sook Lee Tobacco Induced Diseases, Volume 19, Issue September, Pages 1–11, Publish date: 21 September 2021 DOI: The manuscript type is ‘Research Paper’ instead of ‘Review Paper’.


Immunocompromised (IC) patients (pts) can have prolonged SARS-CoV-2 PCR positivity, even after resolution of COVID-19 symptoms. This study aimed to determine if viable virus could be detected in samples collected > 21 days after an initial positive (pos) SARS-CoV-2 PCR in IC pts. We obtained 20 remnant SARS-CoV-2 PCR pos nasopharyngeal swabs from IC pts  with a pos repeat PCR within the previous 30 days. The repeat specimens were cultured on Vero-hACE2-TMPRSS2 cells and incubated for 96 hours to assess viral viability. Viable RNA and infectious virus in the cultured cells were measured by qPCR and infectious plaque assays. RNA sequencing was performed on a HiSeq platform (Illumina). Samples also underwent SARS-CoV-2 antigen (Ag) testing (BD Veritor). Clinical data were extracted from the electronic health record by chart review. Pt characteristics are in Table 1. Viral cultures from the repeat specimen were negative (neg) for 18 pts and pos for 2 (Table 2). Pt 1 is a 60M treated with obinatuzumab 19 days prior to his first pos PCR test, with repeat specimen collected 21 days later (cycle threshold (Ct) not available). Pt 1 had a low viral titer (27 PFU/mL) & a D614G mutation on sequencing. Pt 2 is a 75M treated with rituximab 10 days prior to his first pos PCR test, with repeat specimen collected 23 days later (Ct 27.56/27.74). Pt 2 had a high viral titer (2e6 PFU/mL) and D614G, S98F, and S813I mutations.Demographics of Study Population (N=20)Characteristics of patients with a positive SARS-CoV-2 viral culture90% of specimens collected > 21 days after an initial pos SARS-CoV-2 PCR did not have viable virus detected on their repeat specimen. The 2 pts with pos viral cultures had active hematologic malignancies treated with an anti-CD20 mAb at the time of COVID-19 diagnosis. One pt had a high concentration of active, viable virus. No known variants of concern were noted in this cohort, collected in Q2 2020, though prolonged replication is a risk for variant development. Further data are needed about risk factors for persistent viable viral shedding & methods to prevent transmission of viable virus from IC hosts. Victoria J. Fraser, MD, CDC Epicenters (Grant/Research Support)Cigna/Express Scripts Doris Duke Fund to Retain Clinical Scientists Foundation for Barnes-Jewish Hospital NIH  Victoria J. Fraser, MD, Centers for Disease Control and Prevention  Involved: Self): Grant/Research Support, Research Grant or Support; Cigna/Express Scripts  Involved: Spouse/Partner): Employee; Doris Duke Charitable Foundation  Involved: Self): Grant/Research Support, Research Grant or Support; National Institutes of Health  Involved: Self): Grant/Research Support, Research Grant or Support; The Foundation for Barnes-Jewish Hospital  Involved: Self): Grant/Research Support, Research Grant or Support Michael S. Diamond, MD, PhD, Carnival Corporation (Consultant)Emergent BioSolutions (Grant/Research Support)Fortress Biotech (Consultant)Immunome (Advisor or Review Panel member)Inbios (Consultant)Moderna Vir Biotechnology  Carey-Ann Burnham, PhD, BioFire bioMerieux (Grant/Research Support)Cepheid Luminex (Grant/Research Support)Roche  Carey-Ann Burnham, PhD, BioFire  Involved: Self): Grant/Research Support; bioMerieux  Involved: Self): Grant/Research Support, Scientific Research Study Investigator, Speakers’ bureau; Cepheid  Involved: Self): Consultant, Grant/Research Support, Scientific Research Study Investigator; Luminex  Involved: Self): Scientific Research Study Investigator Hilary Babcock, MD, MPH, FIDSA, FSHEA, Nothing to disclose


Small hospitals in the US may lack access to infectious diseases (ID) expertise despite similar rates of antimicrobial use and drug-resistant bacteria as larger hospitals. A tele-antimicrobial stewardship program (TASP) is a force multiplier, expanding access to specialty care, training, and guidance on appropriate resource utilization. Data on the impact of TASPs in community or rural inpatient settings is limited.We established a TASP at a 160-bed hospital in Armstrong County, PA (population < 5000) in September 2020. Tele-ID consult services were already being used . A non-local ID pharmacist or ID physician performed prospective audits and provided feedback with 1 local pharmacist on a 30-minute video conference call daily. At TASP implementation, all patients receiving intravenous (IV) fluoroquinolones, metronidazole, and azithromycin were reviewed. Figure 1 shows the additional support following TASP implementation, including addition of ceftriaxone, carbapenems, IV vancomycin, and tocilizumab to daily reviews. A patient monitoring form was developed to track interventions and the local pharmacists were trained in documentation. Table 1 lists other TASP features implemented.Figure 1. TASP TimelineTable 1. TASP AccomplishmentsFrom 09/01/2020 to 04/30/2021, 304 stewardship opportunities were identified and 77% of interventions were accepted. Recommending a duration of therapy was accepted most frequently (93.5%) and de-escalation of therapy least frequently (69.6%) (Table 2). Recommending an ID consultation or diagnostic testing was always accepted but only comprised 6.2% of all interventions. Daily calls involved an average of 5 patient reviews. Monthly antimicrobial use declined on average from 673 DOT (days of therapy)/1000 PD (patient days) to 638 DOT/1000 PD . Daily calls were cancelled on 31/166 weekdays (18.7%) due to staffing shortages.Table 2. TASP Interventions (9/2020 - 4/2021)Figure 2. Monthly Antimicrobial Use in Days of Therapy (DOT) per 1000 Patient Days (4/2019 - 5/2021)Implementation of TASP in a community hospital resulted in a high percentage of accepted stewardship interventions and lower antimicrobial usage. Success is dependent on robust educational efforts, establishing strong relationships with local providers, and involvement of key stakeholders. Lack of dedicated stewardship time for local pharmacists is a very significant barrier.Erin K. McCreary, PharmD, BCPS, BCIDP, AbbVie (Consultant)Cidara (Consultant)Entasis (Consultant)Ferring (Consultant)Infectious Disease Connect, Inc Merck (Consultant)Shionogi (Consultant)Summit (Consultant) Erin K. McCreary, PharmD, BCPS, BCIDP, AbbVie  Involved: Self): Consultant; Cidara  Involved: Self): Consultant; Entasis  Involved: Self): Consultant; Ferring  Involved: Self): Consultant; Infectious Disease Connect, Inc  Involved: Self): Director of Stewardship Innovation, Other Financial or Material Support; Merck  Involved: Self): Consultant; Shionogi  Involved: Self): Consultant; Summit  Involved: Self): Consultant Tina Khadem, PharmD, Infectious Disease Connect, Inc. (Employee) Nancy Zimmerman, RN, BSN, I’d connect (Employee) John Mellors, MD, Abound Bio, Inc. (Shareholder)Accelevir (Consultant)Co-Crystal Pharma, Inc. Gilead Sciences, Inc. Infectious DIseases Connect Janssen (Consultant)Merck (Consultant) Rima Abdel-Massih, MD, Infectious Disease Connect  Rima Abdel-Massih, MD, Infectious Disease Connect  Involved: Self): Chief Medical Officer, Other Financial or Material Support, Other Financial or Material Support, Shareholder J Ryan. Bariola, MD, Infectious Disease Connect


Reference to original study: Antoszyk AN, Glassman AR, Beaulieu WT, Jampol LM, Jhaveri CD, Punjabi OS, et al.; DRCR Retina Network. Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2020 Dec 15;324(23):2383–2395.


Tocilizumab is an interleukin-6 monoclonal antibody with widespread use in rheumatologic conditions. Observational studies have shown a promising role of Tocilizumab in severe COVID-19 patients with cytokine storm syndrome. Data about tocilizumab use in pregnant patients is limited. We report two outcomes of two pregnant patients with COVID-19 in the second trimester who received tocilizumabA 24-year-old 20 weeks pregnant lady with a history of asthma and gestational diabetes mellitus presented with three days history of fever, cough and shortness of breath . She was clinically stable but later developed ARDS and developed increased oxygen demand up to 10 liters/min. She received Tocilizumab on. Patient was observed in a high dependency unit but did not require mechanical ventilation. Patient was discharged home with full recovery and later delivered a healthy baby. Timeline of medicines used during hospital . Case 2: 39-year-old 23 weeks pregnant lady presented with seven days history of fever cough and shortness of breath . On presentation, she had progressive worsening hypoxic respiratory failure and was intubated. Patient had her nasopharyngeal swab for CODI-19 RT PCR was positive. The patient had severe ARDS requiring ECMO  for respiratory support. Tocilizumab 400 mg was given on the presentation, along with other medications . Patient had regular monitoring of fetus; however, she had intrauterine fetal demise on day 14. Patient It is unclear if IUFD was due to using of tocilizumab or severity of COVID19 itself. The patient stayed in ICU for 20 days and was discharged after full recovery.Figure 1. Case 1 treatment timeline. Abberviations: Azithro: Azithromycin, HCQ: Hydroxychloroquine, CQ: Chloroquine, LPV/r: lopinavir/Ritonavir, Osel: Oseltamivir, MP: Methylprednisolone, Ampi-sulb: Ampicillin-sulbactam, TCZ: tocilizumabFigure 2. Case 2 treatment timelineLearning points: Tocilizumab use in pregnant patients with severe COVID-19 pneumonia during the second trimester improved maternal outcomes in our cases. Tocilizumab use may be associated with worse fetal outcomes, including intrauterine fetal demise (IUFD).Figure 3. Table of clinical characteristics, pregnant outcomes. Abbreviations: LRTI: lower respiratory tract infection, HCQ: Hydroxychloroquine, CQ: chloroquine, Osel: Oseltamivir, Cef: Ceftrixone, Ampi-Sulb: ampicillin-sulbactam, Azithro: Azithromycin, TCZ: tocilizumab, MP: methylpredinisolone, H/O: History of, LSCS: C-section, NA: not available. Pip-tazo: Piperacillin-tazobactam, Mero: Meropenem, Sulfa-trim: Sulfamethoxazole-Trimethoprim, IUFD: Intrauterine fetal death.The pharmacological management of pregnant patients with severe COVID-19 pneumonia poses significant challenges. The use of Tocilizumab may improve maternal outcomes but may also increase the risk of worse fetal outcomes. Caution should be exercised in using this agent, and risks and benefits should be discussed with the patients.All Authors: No reported disclosures


Klebsiellae are Gram-negative pathogens responsible for serious nosocomial and community-acquired infections. Carbapenem resistance, both intrinsic and acquired, complicates therapy. Taniborbactam  is a bicyclic boronate β-lactamase inhibitor (BLI) that inhibits all four Ambler classes of β-lactamase enzymes, both serine- and metallo-, with the notable exception of class B IMP β-lactamases. Taniborbactam is currently undergoing phase 3 clinical trials in combination with cefepime  as part of the β-lactam-BLI (BL-BLI) combination FEP-taniborbactam (FTB).Figure 1. Structures of taniborbactam and cefepime. The β-lactamase inhibitor is in red and the β-lactam antibiotic is in black.Klebsiellae (CRK) strains collected as part of the Antibiotic Resistance Leadership Group (ARLG) Consortium on Resistance against Carbapenems in Klebsiella (CRACKLE) study. Among these strains, 193 expressed class A KPCs, one expressed a class B NDM, and six expressed class D OXA-48 or variants. Broth microdilution minimum inhibitory concentrations (MIC)s were determined using the ThermoFisher Sensititre system with custom assay panels. American Type Culture Collection strains were used for quality control. The susceptible-dose-dependent breakpoint for FEP was provisionally used for FTB, where taniborbactam was fixed at 4 µg/mL.We determined the activity of FTB against 200 carbapenem-resistant Klebsiella strains tested, susceptibility for β-lactams alone ranged from 1% for ceftazidime (CAZ), 2.5% for meropenem, and 13.5% for FEP (Table 1). The addition of BLIs increased % susceptibility compared to BL alone to: 98% for CAZ-avibactam (CZA); 95.5% for MEM-vaborbactam (MVB); and 99.0% for FTB. MIC50 and MIC90 were in the susceptible and provisionally susceptible range for CZA and MVB, and in the provisionally susceptible range for FTB. Analyzing the CZA and MVB non-susceptible strains, 7 of 9 MVB non-susceptible strains and 2 of 4 CZA-resistant strains were provisionally susceptible to FTB.Among the 200 Table 1. MIC50 and MIC90 values (μg/mL) and percent susceptibility for Klebsiella pneumoniae strains (n=200). AMK, amikacin; CST, colistin; CAZ, ceftazidime; CZA, ceftazidime-avibactam; FEP, cefepime; FTB, cefepime-taniborbactam; MEM, meropenem; MVB, meropenem-vaborbactam; TGC, tigecycline. * The breakpoint for CST is intermediate, as no susceptible breakpoint is available. ** The susceptible-dose-dependent breakpoint for FEP alone was provisionally applied to FTB, where taniborbactam was fixed at 4 μg/mL. Breakpoints from CLSI M100, 31st ed, 2021.The addition of taniborbactam restored susceptibility to FEP in 99.0% of CRACKLE isolates studied, comparable to CZA and MVB. Taniborbactam also restored FEP activity against some MVB- and CZA-resistant strains. FTB may provide a promising therapy for CRK infections.Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA Infectious Diseases Board Review Course Mammoth Biosciences (Consultant)NBME Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date  Robin Patel, MD, BioFire  Involved: Self): Grant/Research Support; Contrafect  Involved: Self): Grant/Research Support; IDSA  Involved: Self): Editor’s stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course  Involved: Self): Honoraria; Netflix  Involved: Self): Consultant; TenNor Therapeutics Limited  Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella  Involved: Self): Consultant David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck Pfizer Qpex (Advisor or Review Panel member)Shionogi Utility (Advisor or Review Panel member) Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea Bayer (Consultant)C3J (Consultant)Cerexa Contrafect Debiopharm Destiny (Consultant)Durata Genentech Green Cross Integrated Biotherapeutics (Consultant)Janssen Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis Pfizer (Grant/Research Support)Regeneron sepsis diagnostics Tetraphase (Consultant)Theravance Trius (Consultant)UpToDate Valanbio xBiotech (Consultant) Daniel D. Rhoads, MD, Becton, Dickinson and Company (Grant/Research Support) Michael Jacobs, MBBS, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) Focco van den Akker, PhD, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) David A. Six, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Greg Moeck, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Krisztina M. Papp-Wallace, Ph.D., Merck & Co., Inc. (Grant/Research Support)Spero Therapeutics, Inc. (Grant/Research Support)Venatorx Pharmaceuticals, Inc. (Grant/Research Support)Wockhardt Ltd.  Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)


The data on CAPA in the U.S. are limited to date and clinical characteristics unique to this phenomenon have not been widely reported.This retrospective observational study was conducted at multiple VA hospitals across southern California and Arizona. CAPA cases were identified in inpatients with laboratory-confirmed COVID-19 based on microbiologic or serologic evidence of aspergillosis and pulmonary abnormalities on imaging, and were classified according to ECMM/ISHAM consensus definitions. Characteristics of interest included immunosuppressive/modulatory agents used prior to onset of CAPA, COVID-19 disease course, length of hospitalization, and mortality.2. Baseline comorbidities included diabetes mellitus (47%), cardiovascular disease (65%), and pulmonary disease (71%). Evidence of aspergillosis was mostly based on respiratory culture, with mainly A. fumigatus (75%). Systemic corticosteroids were used in 14 patients, with a total dose of 400 mg prednisone equivalents starting 10 days prior to Aspergillus detection. Patients also received tocilizumab (18%), leflunomide (6%), tacrolimus (6%), mycophenolate (6%), and investigational agent LSALT or placebo (6%); 2 patients (12%) did not receive any immunosuppression/modulation. Length of hospitalization for COVID-19 was 22 days. Death occurred in 12 patients (71%), including all patients with probable CAPA, at 34 days after COVID-19 diagnosis and 16 days after CAPA diagnosis. Eight patients (47%) were treated for aspergillosis; mortality did not appear to differ with treatment (75% vs. 67%).Seventeen patients with probable (18%) or possible (82%) CAPA were identified from April 2020 to March 2021. Values below reported as medians. All patients were male and 13 (76%) were white, with age 74 years and BMI 26 kg/mTable 1. COVID-19 Inpatient CharacteristicsTable 2. Incidence of Aspergillus Growth on Respiratory CultureAspergillus spp. increased compared to previous years. Future work will attempt to identify risk factors for CAPA and attributable mortality via comparison to inpatients with COVID-19 without CAPA.This case series reports high mortality among patients with CAPA; the primary contributor to this outcome is unclear. Frequency of lower respiratory tract sampling in patients with COVID-19 may have limited diagnosis of CAPA. Interestingly, inpatient respiratory cultures with Matthew B. Goetz, MD, Nothing to disclose Martin Hoenigl, MD, Astellas (Grant/Research Support)Gilead (Grant/Research Support)Pfizer (Grant/Research Support) Martin Hoenigl, MD, Astellas  Involved: Self): Grant/Research Support; F2G  Involved: Self): Grant/Research Support; Gilead  Involved: Self): Grant/Research Support; Pfiyer  Involved: Self): Grant/Research Support; Scýnexis  Involved: Self): Grant/Research Support Sanjay Mehta, MD, D(ABMM), DTM&H, MedialEarlySign (Consultant)ZibdyHealth


Scientific Reportshttps://doi.org/10.1038/srep19578, published online 27 January 2016Correction to: The original PDF of this article contains an error in the footer, where the volume number "5:19578" should read "6:19578".


Sharp declines in influenza and respiratory syncytial virus (RSV) circulation across the U.S. have been described during the pandemic in temporal association with community mitigation for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to determine relative frequencies of rhinovirus/enterovirus (RV/EV) and other respiratory viruses in children presenting to emergency departments or hospitalized with acute respiratory illness (ARI) prior to and during the COVID-19 pandemic. We conducted a multi-center active prospective ARI surveillance study in children as part of the New Vaccine Surveillance Network (NVSN) from December 2016 through January 2021. Molecular testing for RV/EV, RSV, influenza, and other respiratory viruses  were performed on specimens collected from children enrolled children. Cumulative percent positivity of each virus type during March 2020–January 2021 was compared from March-January in the prior seasons  using Pearson’s chi-squared. Data are provisional.Among 69,403 eligible children, 37,676 (54%) were enrolled and tested for respiratory viruses. The number of both eligible and enrolled children declined in early 2020 , but 4,691 children (52% of eligible) were enrolled and tested during March 2020-January 2021. From March 2020-January 2021, the overall percentage of enrolled children with respiratory testing who had detectable RV/EV was similar compared to the same time period in 2017-2018 and 2019-2020 . In contrast, the percent positivity of RSV, influenza, and other respiratory viruses combined declined compared to prior years, .Figure 1. Percentage of Viral Detection Among Enrolled Children Who Received Respiratory Testing, New Vaccine Surveillance Network (NVSN), United States, December 2016 – January 2021Table 1. Percent of Respiratory Viruses Circulating in March 2020– January 2021, compared to March-January in Prior Years, New Vaccine Surveillance Network (NVSN), United States, March 2017 – January 2021During 2020, RV/EV continued to circulate among children receiving care for ARI despite abrupt declines in other respiratory viruses within this population. These findings warrant further studies to understand virologic, behavioral, biological, and/or environmental factors associated with this continued RV/EV circulation.Jennifer E. Schuster, MD, Merck, Sharpe, and Dohme  Involved: Self): Grant/Research Support Marian G. Michaels, MD, MPH, Viracor  John V. Williams, MD, GlaxoSmithKline Quidel  Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer  Janet A. Englund, MD, AstraZeneca GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Claire Midgley, PhD, Nothing to disclose Natasha B. Halasa, MD, MPH, Genentech Quidel Sanofi  Natasha B. Halasa, MD, MPH, Genentech  Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi  Involved: Self): Grant/Research Support, Research Grant or Support


Journal of the Brazilian Society of Tropical MedicineRevista da Sociedade Brasileira de Medicina Tropical/Title: Natural infection of triatomines (Hemiptera: Reduviidae) by trypanosomatids in two different environments in the municipality of Ouro Preto do Oeste, State of Rondônia, BrazilVol. 45(3): 2012 - Page: 395-398, - doi: 10.1590/S0037-86822012000300023In regard to the triatomines collected in the present study, where we cite: Rhodnius prolixus and R. prolixus.Should read:Rhodnius montenegrensis and R. montenegrensis.


Conservation Physiology, Volume 9(1): coab028, doi: 10.1093/conphys/coab028An earlier version of this manuscript, which had not been approved by the authors, was inadvertently published. As a result, the manuscript contained several grammatical and formatting errors. The following references were also included in error:Oncorhynchus kisutch: isit better to be cool? J Fish Biol 95: 793–801.Elsner RA, Shrimpton JM (2019) Behavioural changes during theparr–smolt transformation in Coho salmon Percafluviatilis populations originating from different salinity habitats.Conserv Physiol 7: 1–5.Christensen EAF, Grosell M, Steffensen JF (2019) Maximum salinitytolerance and osmoregulatory capabilities of European perch Procambarus clarkii) and rusty crayfish (Faxoniusrusticus). MBI 11: 259–278.Fredricks K, Tix J, Smerud J, Cupp A (2020) Laboratory trials to evaluatecarbon dioxide as a potential behavioral control method forinvasive red swamp  Behavioral thermoregulation in twospecies of Antarctic fish. Salmo salar smolts in relationto behavioural salinity preferences and thresholds. J Fish Biol 88:595–617.Stich DS, Zydlewski GB, Zydlewski JD (2016) Physiological preparednessand performance of Atlantic salmon Mustelus canis. Fed Proc 37: 427–427.Reynolds WW, Casterlin ME (1978a) Thermoregulatory behavior insmooth dogfish shark, Petromyzon marinus) in anelectronic shuttlebox. Hydrobiologia 61: 145–147.Reynolds WW, Casterlin ME (1978b) Behavioral thermoregulation byAmmocoete larvae of the sea lamprey  Thermoregulatory behaviour ofthe primitive arthropod J Fish Biol 50:1166–1180.Schurmann H, Steffensen JF (1997) Effects of temperature, hypoxiaand activity on the metabolism of juvenile Atlantic cod. The final version of this manuscript has now replaced this earlier version, and so these errors are no longer present. The publisher apologizes for this mistake and regrets any confusion caused.


Solitary pulmonary capillary haemangioma (SPCH) is a benign lung tumour that presents as ground-glass nodules on computed tomography (CT) images and mimics lepidic-predominant adenocarcinoma. This study aimed to establish a discriminant model using a radiomic feature analysis to distinguish SPCH from lepidic-predominant adenocarcinoma.In the adenocarcinoma group, all tumours were of the lepidic-predominant subtype with high purity (>70%). A classification model was proposed based on a two-level decision tree and 26 radiomic features extracted from each segmented lesion. For comparison, a baseline model was built with the same 26 features using a support vector machine as the classifier. Both models were assessed by the leave-one-out cross-validation method.P < 0.05).This study included 13 and 49 patients who underwent complete resection for SPCH and adenocarcinoma, respectively. Two sets of features were identified for discrimination between the 2 different histology types. The first set included 2 principal components corresponding to the 2 largest eigenvalues for the root node of the two-level decision tree. The second set comprised 4 selected radiomic features. The area under the receiver operating characteristic curve, accuracy, sensitivity, specificity were 0.954, 91.9%, 92.3% and 91.8% in the proposed classification model, and were 0.805, 85.5%, 61.5% and 91.8% in the baseline model, respectively. The proposed classification model significantly outperformed the baseline model  is a primary benign lung tumour that exhibits proliferation of capillaries in the alveolar septa [1]. Solitary pulmonary capillary haemangioma (SPCH) is a primary benign lung tumour that exhibits proliferation of capillaries in the alveolar septa . This unet al.  and the National Taiwan University Hospital, Taipei, Taiwan .Conflict of interest: none declared.Hao-Jen Wang: Data curation; Formal analysis; Investigation; Methodology; Writing—original draft. Mong-Wei Lin: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Writing—original draft. Yi-Chang Chen: Investigation; Methodology; Writing—review & editing. Li-Wei Chen: Formal analysis; Investigation; Writing—original draft. Min-Shu Hsieh: Conceptualization; Data curation; Methodology; Writing—original draft. Shun-Mao Yang: Data curation; Methodology; Writing—review & editing. Ho-Feng Chen: Data curation; Formal analysis; Writing—review & editing. Chuan-Wei Wang: Data curation; Formal analysis; Writing—review & editing. Jin-Shing Chen: Conceptualization; Supervision; Writing—review & editing. Yeun-Chung Chang: Conceptualization; Data curation; Supervision; Validation; Writing—review & editing. Chung-Ming Chen: Conceptualization; Data curation; Supervision; Validation; Writing—original draft.Interactive CardioVascular and Thoracic Surgery thanks Giuseppe Cardillo, Georges Decker, Marcelo F. Jimenez and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.ivab271_Supplementary_DataClick here for additional data file.


Leptonetidae Simon, 1890 includes 20 genera and 366 species from North America, the Mediterranean Region and Asia. Currently, 132 species belonging to six genera have been recorded in China.The spider family Yueleptonetadongxing gen. et sp. n., is described from Guangdong Province, China. Yueleptoneta gen. n. is distinct from the other genera in the chelicerae having the stridulatory file on the lateral margin and the male palp having a tarsal spur, lacking strong spines or apophyses on the femur and tibia.A new genus and species of leptonetid spiders,  Leptonetidae Simon, 1890 are tiny (1–3 mm) and typically have six eyes, with posterior median eyes displaced behind the anterior lateral eyes and posterior lateral eyes, anterior median eyes lost. Most species live in moist habitats, such as leaf litter, under rocks and especially in caves , Jingneta Wang & Li, 2020 (9 spp.), Leptonetela Kratochvíl, 1978 (105 spp.), Longileptoneta Seo, 2015 (6 spp.), Masirana Kishida, 1942 (1 sp.) and Rhyssoleptoneta Tong & Li, 2007 (2 spp.) ((2 spp.) .In this paper, a new genus and species of leptonetid spiders, collected from the leaf litter in Guangdong Provnice of China, is described and illustrated.The specimens were examined using a Leica M205C stereomicroscope. Details were studied under an Olympus BX51 compound microscope. Photomicroscope images were made with a Canon EOS 750D zoom digital camera (18 megapixels) mounted on an Olympus BX51 compound microscope. Photos were stacked with Helicon Focus 6.7.1 and processed in Adobe Photoshop CC 2020. For scanning electron microscopy (SEM), specimens were air-dried, sputter-coated using IXRF SYSTEMS and imaged with a Hitachi TM3030 SEM. Leg measurements are shown as: total length  and, when missing, was coded as "–". Palp measurements are shown as: total length . All measurements were taken using an Olympus BX51 compound microscope and are in millimetres.All specimens are preserved in 75% ethanol. The type material is deposited in the College of Life Science, Shenyang Normal University (SYNU) in Liaoning, China.The following abbreviations are used in the text and figures: AER = anterior eye row; ALE = anterior lateral eyes; ALE–PME = distance between ALE and PME; At = atrium; Co = conductor; Em = embolus; PER = posterior eye row; PLE = posterior lateral eyes; PLE–PLE = distance between PLE and PLE; PLE–PME = distance between PLE and PME; PME = posterior median eyes; Sd = sperm duct; Ser = serrula; Sp = spermathecae; Str = stridulatory file; Ts = tarsal spur.Tonggen. n.670671CA-C5FC-5904-9D1B-E6FE8014652948D97727-253F-49F3-B682-63811BDE1C9DYueleptonetaYueleptonetadongxing Yang, Tong & Bian Status: new species described in this paper.Carapace brown and median groove needle-shaped, distinct. Six-eyed Fig. A. ALE anYueleptoneta gen. n. is similar to Leptonetela Kratochvíl, 1978 and Longileptoneta Seo, 2015 in having a strong palpal tarsal spur , where the material has been collected and the genus name China (Guangdong).Yang, Tong & Biansp. n.DACD4A80-4151-5CA4-958A-A20CD121A0AB1149790B-DC13-4697-AF09-15E761E573E8Type status:Holotype. Occurrence: individualCount: 1; sex: male; lifeStage: adult; Taxon: scientificName: Yueleptonetadongxing; order: Araneae; family: Leptonetidae; genus: Yueleptoneta; scientificNameAuthorship: Yang, Tong & Bian; Location: country: China; stateProvince: Guangdong; county: Heyuan City; locality: Xinhuilong Town, Dongxing Village, Wanlvgu Resort Area; verbatimElevation: 160 m a.s.l.; verbatimCoordinates: 23°42'44"N, 114°38'5"E; Event: samplingProtocol: sifting leaf litter; eventDate: 24 April 2021Type status:Paratype. Occurrence: individualCount: 4; sex: female; lifeStage: adult; Taxon: scientificName: Yueleptonetadongxing; order: Araneae; family: Leptonetidae; genus: Yueleptoneta; scientificNameAuthorship: Yang, Tong & Bian; Location: country: China; stateProvince: Guangdong; county: Qingyuan City, Yingde City; locality: Donghua Temple; verbatimElevation: 157 m a.s.l.; verbatimCoordinates: 24°9'15"N, 113°26'36"E; Event: samplingProtocol: sifting leaf litter; eventDate: 5 April 2021Male. Total length 1.81 Fig. F. EnditeFemale. Similar to male in general features Fig. A–C. TotaYueleptonetadongxing sp. n. are distinguished by the characters discussed in the genus diagnosis section.Specimens of The specific name is a noun in apposition and refers to the type locality.


HSV recurrences are usually managed effectively with existing antiviral drugs . However, in immunocompromised patients , if lesions persist or recur while receiving antiviral treatment, acyclovir resistance should be suspected. In this population, there are limited treatment options. The helicase-primase inhibitor pritelivir is a novel oral antiviral, with a new mode of action and is active against both HSV-1 and HSV-2, including acyclovir and foscarnet-resistant strains. In this case series, we report the first clinical experiences with pritelivir in the treatment of immunocompromised patients with acyclovir resistant HSV infection.All patient reported in this case series received pritelivir in a Phase 2 study. There were treated in an open-label design with a 400 mg pritelivir oral loading dose followed by a 100 mg oral maintenance dose daily for up to 28 days.Of the 23 patients, 11 had HIV infection and 12 had malignancy, transplant or an autoimmune disease. Of this cohort, 19 patients showed full resolution of their HSV-related lesions during the 28 day treatment period, while in 4 subjects lesions improved but did not completely heal during the observation period. Pritelivir was well tolerated without significant adverse effects.Reasons for incomplete lesion resolution during the 28 day treatment period, were extensive lesions in one patient, one patient with resistance development, and one patient with lesions in the oral cavity. Three patients subsequently experienced full resolution, while one patient required foscarnet due to CMV reactivation, necessitating early discontinuation.Pritelivir is a promising novel treatment option for patients with severe mucocutaneous HSV-1/2 infections that are resistant to acyclovir and foscarnet. An international Phase 3 study is underway to evaluate pritelivir efficacy in immunocompromised patients.Joerg Albrecht, MD/PhD, Biogen (Scientific Research Study Investigator)Investigator for AiCuris (Scientific Research Study Investigator) Robin K. Avery, MD, Aicuris (Grant/Research Support)Astellas (Grant/Research Support)Chimerix (Research Grant or Support)Merck (Grant/Research Support)Oxford Immunotec (Grant/Research Support)Qiagen (Grant/Research Support)Takeda/Shire (Grant/Research Support) Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma Chimerix Clinigen (Consultant)Genentech Janssen Karius (Grant/Research Support)Merck Molecular Partners Novartis (Grant/Research Support)Oxford Immunotec Partner Therapeutics (Consultant)Pulmotec Shire/Takeda Viracor (Grant/Research Support)Xenex (Grant/Research Support) Nicolas C. Issa, MD, AiCuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)GSK (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator) Camille Kotton, MD, Shire/Takeda (Advisor or Review Panel member) Camille Kotton, MD, UpToDate  Involved: Self): I write chapters on zoonoses for UpToDate., Independent Contractor Princy N. Kumar, MD, AMGEN Eli Lilly (Grant/Research Support)Gilead GSK Merck & Co., Inc.  Moti Ramgopal, MD FACP FIDSA, Abbvie Gilead Janssen Merck ViiV  Anna Wald, MD, MPH, Aicuris (Consultant)Crozet (Consultant)GSK (Scientific Research Study Investigator)Merck Sanofi (Scientific Research Study Investigator)X-Vax (Consultant) Michael G. Ison, MD, MS, Celltrion, Inc. (Consultant)


Adult studies have demonstrated intra-season declines in influenza vaccine effectiveness (VE) with increasing time since vaccination; however, data in children are limited. We conducted a prospective, test-negative study of children ages 6 months through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers each season in the New Vaccine Surveillance Network during the 2015-2016 through 2019-2020 influenza seasons. Cases were children with an influenza-positive molecular test; controls were influenza-negative children. Controls were matched to cases by illness onset date using 3:1 nearest neighbor matching. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥ 1 dose of influenza vaccine ≥ 14 days before the onset of illness that resulted in hospitalization among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date during each season were estimated using multivariable logistic regression models.Of 8,430 hospitalized children , 4,653 (55%) received ≥ 1 dose of influenza vaccine. On average, 48% and 85% of children were vaccinated by the end of October and December, respectively. Influenza-positive cases  were less likely to be vaccinated than influenza-negative controls  and overall VE against hospitalization was 53% . Pooling data across 5 seasons, the odds of any influenza-associated hospitalization increased 0.96%  per week with a corresponding weekly decrease in VE of 0.45% (p=0.275). Odds of hospitalization with time since vaccination increased 0.66%  per week in children ≤ 8 years  and 2.16%  per week in children 9-17 years (n=771). No significant differences were observed by virus subtype or lineage.Figure 1. Declines in influenza VE over time from 2015-2016 through 2019-2020, overall (a) and by age group We observed minimal intra-season declines in VE against influenza-associated hospitalization in U.S. children. Vaccination following Advisory Committee on Immunization Practices guidelines and current timing of vaccine receipt is the best strategy for prevention of influenza-associated hospitalization in children. Marian G. Michaels, MD, MPH, Viracor  John V. Williams, MD, GlaxoSmithKline Quidel  Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Natasha B. Halasa, MD, MPH, Genentech Quidel Sanofi  Natasha B. Halasa, MD, MPH, Genentech  Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi  Involved: Self): Grant/Research Support, Research Grant or Support Janet A. Englund, MD, AstraZeneca GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer  Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa Moderna Pfizer Virometix


Carbapenem-resistant gram-negative bacilli (CRGNB) are increasingly reported around the world as a cause of serious infections. However, the epidemiology and clinical course of patients with CRGNB in Japan is not well understood.Enterobacterales, CR nonfermenting gram-negative bacilli (NFGNB) and CR Aeromonas sp. isolation were included. Carbapenem resistance was tested by agar dilution method and defined based on the CLSI criteria for each species. Infections were determined by NHSN protocols.We prospectively collected CR cases from 4/2019 to 9/2020 in Multi-Drug Resistant organisms clinical research network (MDRnet) consisting of 5 tertiary care facilities in Japan. We looked for all CRGNB, and all unique patients with CR Enterobacterales, 119 NFGNB, 7 Aeromonas spp.) were included . Acinetobacter sp. was not detected. Isolation sites were sputum (n = 12) and urine (n = 7) in Enterobacterales, sputum (n = 62) and blood (n = 18) in NFGNB, and blood (n = 6) in Aeromonas spp. The median age and male ratio of the patients were 68 years [IQR: 53-74] and 19 (63.3%) in Enterobacterales, 72 years [IQR: 60-79] and 70 (58.8%) in NFGNB and 78 years [IQR: 54-83] and 2 (28.6%) in Aeromonas spp. Ten (33.3%) patients with Enterobacterales, 55 (46.2%) patients with NFGNB, and 6 (85.7%) patients with Aeromonas spp. were infected cases. The others were considered as colonized. There were no patients with ICU stay or intubation in Enterobacterales, while 5 (4.2%) and 4 (3.4%) patients were in ICU and intubated in NFGNB, and 2 patients were in ICU and intubated in Aeromonas spp., respectively. All-cause 30-day mortality rates were 10% in Enterobacterales, 16.8 % in NFGNB and 28.6% in Aeromonas spp. In the infected patients, 3 patients (30%) with Enterobacterales, 12 patients (21.8%) with NFGNB and 1 patient (16.7%) with Aeromonas spp. died within 30 days after isolation. In total, 156 patients  David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck Pfizer Qpex (Advisor or Review Panel member)Shionogi Utility (Advisor or Review Panel member) Yohei Doi, MD, PhD, AstraZeneca (Speaker's Bureau)bioMerieux (Consultant)FujiFilm Gilead (Consultant)GSK (Consultant)Meiji (Consultant)MSD (Consultant)Shionogi (Consultant) Yohei Doi, MD, PhD, Astellas  Involved: Self): Grant/Research Support; AstraZeneca  Involved: Self): Speakers' bureau; bioMerieux  Involved: Self): Consultant, Speakers' bureau; Chugai  Involved: Self): Consultant; Entasis  Involved: Self): Consultant; FujiFilm  Involved: Self): Advisor or Review Panel member; Gilead  Involved: Self): Consultant; GSK  Involved: Self): Consultant; Kanto Chemical  Involved: Self): Grant/Research Support; MSD  Involved: Self): Speaking Fee; Pfizer  Involved: Self): Grant/Research Support; Shionogi  Involved: Self): Grant/Research Support, Speakers' bureau; Teijin Healthcare  Involved: Self): Speakers' bureau; VenatoRx  Involved: Self): Consultant


Treponema parvum is a spirochete associated with human and animal oral/nonoral soft tissue infections. Here, we report the complete genome sequences of three human oral isolates of T. parvum, namely, ATCC 700770T (OMZ 833T), ATCC 700773 (OMZ 842), and OMZ 843, which possess circular chromosomes of a median size of 2.63 Mb. Treponema parvum is a small, obligately anaerobic, strictly carbohydrate-dependent spirochete , OMZ 842 (ATCC 700773), and OMZ 843, obtained directly from Chris Wyss, whose group isolated and characterized these strains  at 37°C in supplemented tryptone-yeast extract-gelatin-volatile fatty acids-serum (TYGVS) medium  medium , followe) medium , with se) medium  and Pilo) medium . Reads w) medium  to confi) medium . DefaultT. parvum genomes lack identifiable homologues of several key T. denticola virulence-related factors, including sialidase (TDE0471)  (T. parvum. The T. parvum type strain (ATCC 700770) genome possesses homologues of the T. denticola DNA methyltransferase (TDE0909) and restriction endonuclease (TDE0911) proteins (The three TDE0471)  and the TDE0471) , which iTDE0405) , factor TDE0405) , and proTDE0405)  are simiproteins , differeT. parvum genome sequences and raw sequencing data were deposited in DDB/ENA/GenBank under the accession numbers CP054142 (ATCC 700770T), CP054257 (ATCC 700773), and CP058315 (OMZ 843) (PRJNA284866.The complete OMZ 843)  and unde


Candida species are a major cause of invasive and mucocutaneouls infections. There are limited oral treatment options available for patients with Candida infections who are unresponsive to or who are intolerant of currently available antifungals. Oral ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor antifungal with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp  is ongoing for the treatment of patients intolerant of or with fungal disease refractory to standard antifungal therapy. We present an analysis of patient outcomes from the FURI study by fungal disease type. Table 1: FURI Outcomes by Fungal DiseaseFURI patients were eligible for enrollment if they have proven or probable, severe mucocutaneous candidiasis, invasive candidiasis or invasive aspergillosis,other fungal diseases and evidence of failure to, intolerance to, or toxicity related to a currently approved standard-of-care antifungal treatment or can not receive approved oral antifungal options  and a continued IV antifungal therapy is clinically undesirable or unfeasible. An independent Data Review Committee (DRC) provided an assessment of treatment response for 74 patients enrolled in the FURI study from 22 centers in US, UK and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016- 2020. A total of 39 (52.7%) patients had invasive candidiasis, 32 (43.2%) had mucocutaneous candidiasis and 3 (4.5%) patients had invasive aspergillosis. The percent of patients who were determined to have a complete response (CR), partial response (PR), clinical improvement (CI) was 63.5%, stable disease (SD) was 23.0%, patients with progression of disease 6.8% and 4 patients were indeterminate. Additionally, there was 1 death in the FURI study that was not related to fungal disease. Table 1 shows outcomes by fungal disease type as determined by the DRC. Analysis of 74 patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal disease and limited treatment options. Peter G. Pappas, MD, Astellas (Research Grant or Support)Cidara (Research Grant or Support)F2G (Consultant)Matinas Mayne Pharma (Research Grant or Support)Scynexis (Research Grant or Support) Oliver Cornely, Prof., Actelion Al-Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Consultant)Amplyx Astellas Basilea Biocon (Consultant)Biosys (Consultant)Cidara CoRe Consulting (Consultant)Da Volterra DFG (German Research Foundation) (Grant/Research Support)Entasis (Consultant)F2G German Federal Ministry of Research and Education (Grant/Research Support)Gilead Grupo Biotoscana (Consultant)Immunic (Grant/Research Support)IQVIA (Consultant)Janssen (Grant/Research Support)Matinas (Consultant)Medicines Company (Grant/Research Support)MedPace Melinta Therapeutics (Grant/Research Support)Menarini (Consultant)Merck/MSD Molecular Partners (Consultant)MSG-ERC (Consultant)Mylan (Consultant)Nabriva (Consultant)Noxxon (Consultant)Octapharma (Consultant)Paratek (Consultant)Pfizer PSI (Consultant)Roche Diagnostics (Consultant)Scynexis Seres (Consultant)Shionogi (Consultant)Wiley (Blackwell)  Philipp Koehler, MD, Ambu GmbH Astellas Pharma (Speaker's Bureau)Euopean Confederation of Medical Mycology (Speaker's Bureau)German Federal Ministry of Research and Education (Grant/Research Support)Gilead MSD (Speaker's Bureau)Noxxon N.V. (Consultant)Pfizer (Speaker's Bureau)State of North Rhine-Westphalia, Germany (Grant/Research Support) Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark T2 Biosystems (Consultant) Barbara D. Alexander, MD, MHS, SCYNEXIS, Inc. (Consultant) Rachel Miller, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Caryn Morse, MD, Chimerix (Scientific Research Study Investigator)Covis Pharma (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator)Ridgeback Biotherapeutics (Scientific Research Study Investigator)Roche (Scientific Research Study Investigator)SCYNEXIS, Inc. (Scientific Research Study Investigator)Theratechnologies (Advisor or Review Panel member)Viiv (Advisor or Review Panel member) Luis Ostrosky-Zeichner, MD, Amplyx (Consultant)Cidara (Consultant)F2G (Consultant)Gilead Pfizer Scynexis Viracor (Consultant) Jürgen Prattes, Dr, AbbVie Inc. (Shareholder)Gilead (Speaker's Bureau)MSD (Grant/Research Support)Novo Nordisk (Shareholder)Pfizer (Advisor or Review Panel member)Stryker (Shareholder) Andrej Spec, MD, MSCI, Mayne Pharma (Grant/Research Support) Riina Rautemaa-Richardson, DDS, PhD, FRCPath, SCYNEXIS, Inc. (Scientific Research Study Investigator) Thomas J. Walsh, MD, PhD (hon), Scynexis Shionogi  Francisco M. Marty, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Marisa Miceli, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) Martin Hoenigl, MD, Astellas (Grant/Research Support)Gilead (Grant/Research Support)Pfizer (Grant/Research Support) Martin Hoenigl, MD, Astellas  Involved: Self): Grant/Research Support; F2G  Involved: Self): Grant/Research Support; Gilead  Involved: Self): Grant/Research Support; Pfiyer  Involved: Self): Grant/Research Support; Scýnexis  Involved: Self): Grant/Research Support Thomas F. Patterson, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) Nkechi Azie, MD, SCYNEXIS, Inc.  David A. Angulo, MD, SCYNEXIS, Inc.


A large number of microbes exist in the gut and they have the ability to process and utilize ingested food. It has been reported that their products are involved in colorectal cancer development. The molecular mechanisms which underlie the relationship between gut microbial products and CRC are still not fully understood. The role of some microbial products in CRC is particularly controversial. Elucidating the effects of gut microbiota products on CRC and their possible mechanisms is vital for CRC prevention and treatment. In this review, recent studies are examined in order to describe the contribution metabolites and toxicants which are produced by gut microbes make to CRC, primarily focusing on the involved molecular mechanisms.Abbreviations: CRC: colorectal cancer; SCFAs: short chain fatty acids; HDAC: histone deacetylase; TCA cycle: tricarboxylic acid cycle; CoA: cytosolic acyl coenzyme A; SCAD: short chain acyl CoA dehydrogenase; HDAC: histone deacetylase; MiR-92a: microRNA-92a; KLF4: kruppel-like factor; PTEN: phosphatase and tensin homolog; PI3K: phosphoinositide 3-kinase; PIP2: phosphatidylinositol 4, 5-biphosphate; PIP3: phosphatidylinositol-3,4,5-triphosphate; Akt1: protein kinase B subtype α; ERK1/2: extracellular signal–regulated kinases 1/2; EMT: epithelial-to-mesenchymal transition; NEDD9: neural precursor cell expressed developmentally down-regulated9; CAS: Crk-associated substrate; JNK: c-Jun N-terminal kinase; PRMT1: protein arginine methyltransferase 1; UDCA: ursodeoxycholic acid; BA: bile acids; CA: cholic acid; CDCA: chenodeoxycholic acid; DCA: deoxycholic acid; LCA: lithocholic acid; CSCs: cancer stem cells; MHC: major histocompatibility; NF-κB: NF-kappaB; GPR: G protein-coupled receptors; ROS: reactive oxygen species; RNS: reactive nitrogen substances; BER: base excision repair; DNA: deoxyribonucleic acid; EGFR: epidermal growth factor receptor; MAPK: mitogen activated protein kinase; ERKs: extracellular signal regulated kinases; AKT: protein kinase B; PA: phosphatidic acid; TMAO: trimethylamine n-oxide; TMA: trimethylamine; FMO3: flavin-containing monooxygenase 3; H2S: Hydrogen sulfide; SRB: sulfate-reducing bacteria; IBDs: inflammatory bowel diseases; NSAID: non-steroidal anti-inflammatory drugs; BFT: fragile bacteroides toxin; ETBF: enterotoxigenic fragile bacteroides; E-cadherin: extracellular domain of intercellular adhesive protein; CEC: colonic epithelial cells; SMOX: spermine oxidase; SMO: smoothened; Stat3: signal transducer and activator of transcription 3; Th17: T helper cell 17; IL17: interleukin 17; AA: amino acid; TCF: transcription factor; CDT: cytolethal distending toxin; PD-L1: programmed cell death 1 ligand 1 Althougstridium . As wellstridium ,10.2S, and bacterial toxins, contribute to CRC’s development and progression [It is commonly believed that intestinal microbiota products, including butyrate, Hgression . Butyratgression . However2.2.1.Colon bacteria break down indigested dietary fibers and starches and produce short-chain fatty acids (SCFA), such as acetic acid, propionic acid, and butyric acid . The aerButyrate is the most studied short-chain fatty acid and it is mostly synthesized by glycolysis from hydrocarbons by two families of the firmicutes of the human colon, ruminococcaceae and lachnospiraceae . As a hiThe overexpression of microRNA-92a (MiR-92a) in CRC  facilitaMiR-203 expression levels are significantly reduced in CRC tissues and carcinoma cell lines, and this low expression relates to tumor size and pathologic staging (pTNM) . PreviouPropionibacterium, which is found in fibrous foods and dairy products, creates SCFAs, mainly propionates and acetate. Acetate inhibits CRC cell multiplication and triggers CRC cell apoptosis in a dose-dependent manner. However, the precise mechanism by which it transports across the CRC cell membrane is not completely understood [The bacterium derstood ,37. Studderstood . Acetatederstood ,40. It iderstood . Further2.2.Clostridium, Enterococcus, Bifidobacterium, and Lactobacillus, convert unabsorbed BAs into hydrophobic secondary bile salts. For example, gut bacteria transform CA into deoxycholic acid (DCA), and CDCA into lithocholic acid (LCA) [Bile acids (BAs) are made in the liver from cholesterol and are then transported into the intestine by bile which promotes the intestine’s uptake of fat. Two main BAs, cholic acid (CA) and chenodeoxycholic acid (CDCA), are produced in the human liver by the ‘classical’ pathway . More thid (LCA) .Clostridium species, including Clostridium absonum, and Clostridium baratii. It has a chemical structure that is quite similar to that of DCA, but unlike the hydrophobic bile acid DCA, UDCA has been proven to impede colon cancer occurrence [UDCA is a secondary bile acid which is produced by currence ,48. Paticurrence . UDCA cacurrence . UDCA cacurrence , and regcurrence . Furthercurrence , supprescurrence , and inhcurrence . Howevercurrence . In addicurrence . The imp2.3.Lactobacillus acidophilus. Niacin, which is also called nicotinic acid or vitamin B3, acts as a precursor to coenzymes, including nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), and its presence is indispensable for viable cells [In addition to being obtained from food, vitamin B is produced by the intestinal microbiota, for example, le cells . In addile cells . Niacin le cells . Some exle cells ; whereasle cells . CSC intle cells . Niacin le cells . However3.3.1.Those who follow high-fat diets generate a greater amount of secondary BA, mostly DCA and LCA, and have a higher incidence of CRC ,65. CholEpidermal growth factor receptor (EGFR) is a tyrosine kinase receptor, an ErbB family protein which promotes proliferation , invasio3.2.Trimethylamine N – oxide is a Trimethylamine (TMA) oxidation product, belonging to the amine oxide family . TMA con3.3.2S is created by Sulfate-reducing bacteria (SRB) metabolizing sulfates in food, and other sulfur-containing compounds, including taurine [2S in CRC subjects’ feces is higher than in the control group without tumors [2S levels in patients with colon tumors and sigmoid surgery compared to healthy individuals of a similar age [2S is also reduced in colon cancer patients [2S will likely work in the pathogenesis of intestinal diseases, inflammatory bowel diseases  and CRC [2S in CRC have reached different conclusions. Some studies believe that H2S promotes CRC due to its ability to promote inflammation and genotoxicity at physiological concentrations [2S appears to be related to the disruption of disulfide bonds in the double layer of mucus in the colonic wall by H2S, which leads to the epithelium being exposed to bacteria and toxins [2S can protect the mucus layer and reconstitute the already disrupted mucus layer, thereby preventing inflammation [2S [2S-releasing compounds exhibit potent anticancer effects through inhibition of the proliferation and/or inducing apoptosis in several types of cancer cell, including CRC, but the mechanism that is involved remains unknown and could be related to H2S inhibiting nuclear factor-κB (NF-κB) signaling and increasing intracellular Ca2+ concentration, which leads to cell cycle arrest [H taurine . There it tumors . Anotherilar age , meaningpatients . It can  and CRC . Studiestrations ,94, in atrations ,96. The d toxins . Interesammation ,99. Sevetion [2S ,101. H2Se arrest ,103. Gen3.4.In addition to transforming nutrients, bacteria also affect CRC by producing carcinogenic metabolites or toxic factors. These toxins can be characterized by genotoxicity, pro-inflammatory, and epithelial infiltration, and can induce and promote CRC occurrence. The commonly held belief is that there is a complex interaction between bacterial toxins and CRC occurrence.Enterotoxigenic bacteria fragilis (ETBF) produces, is a 20kDa zinc-dependent metalloproteinase toxin with three isotypes , all of which demonstrate similar biological activity [B.fragilis toxin (BFT), which is the main virulence factor activity . BFT indactivity , while tactivity . BFT alsactivity . Bacteriactivity , and SMOactivity .Stat3 is a multifunctional transcription factor in which affects the pathogenesis of autoimmunity by binding to numerous genes that are associated with Th17 cell division, activation, and multiplication, while mediating expression and epigenetic alterations . BFT canfusobacterium nucleatum (Fn), regulating the adhesion and invasions of bacteria. The expression of FadA gene was obviously increased in CRC patient specimens in comparison to normal tissues [The cell surface protein FadA is a key poison factor for  tissues . It exis tissues . Intrins tissues . The bin tissues . FadA ca tissues . FadAc s tissues .Escherichia coli (E. coli) and other gram-negative bacteria in the large intestine and directly damage DNA [E. coli, actinomycetes, shigella dysentery, and helicobacter pylori [campylobacter jejuni induces. CDT-derived campylobacter jejuni cause injury to host cell DNA, and promote colorectal tumorigenesis by triggering cell multiplication and the enhancing of nuclear translocation of β-catenin protein [The main toxins that intestinal bacteria produce are colistin and CDT , which are made by mage DNA ,122,123.mage DNA . Certainmage DNA ,126. Colmage DNA . Bacterimage DNA . CDT arer pylori . The genr pylori . CdtA anr pylori . CDT canr pylori . CDT has protein .4.bifidobacterium long and bifidobacterium short can improve cancer control, significantly reduce tumor progression and enhance the PD-L1 blocking antibody’s anticancer effect [Colorectal cancer is a multifactorial disease and microbial dysbiosis in the human gut that has been identified as a danger factor for CRC . Althougr effect . It has r effect . AlthougTo summarize, gut microbes’ products can play an important role in the prevention of CRC  or the p


Several treatments are available for treatment of early and very early-stage Hepatocellular Carcinoma, also known as small Hepatocellular Carcinoma (SHCC). However, there is no consensus with regards to the efficacies of these methods. We aimed at identifying the most effective initial treatment strategy for SHCC through Bayesian network meta-analyses.Studies published between January, 2010, and February, 2021 were searched in EMBASE, Cochrane Library, PubMed and Web of science databases, and conference proceedings for trials. The included studies reported the survival outcomes of very early and early Hepatocellular Carcinoma patients subjected to radiofrequency ablation (RFA), microwave ablation (MWA), surgical resection (SR), transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), minimally invasive liver surgery (MIS), stereotactic body radiotherapy (SBRT) and cryoablation (CA). Then, data were extracted from studies that met the inclusion criteria. Patient survival data were retrieved from the published Kaplan–Meier curves and pooled. A Bayesian random-effects model was used to combine direct and indirect evidence.A total of 2058 articles were retrieved and screened, from which 45 studies assessing the efficacies of 8 different treatments in 11,364 patients were selected. The included studies had high methodological quality. Recurrence free survival*  and overall survival (OS) outcomes were highest in MIS-treated patients , followed by SR-treated patients . TACE was highly efficacious (58.9%) at decreasing the rates of major complications. Similar findings were obtained through sensitivity analysis, and in most of the prognostic subgroups.MIS and SR exhibited the highest clinical efficacies, however, they were associated with higher rates of complications. Ablation is effective in small tumors, whereas SBRT is a relatively promising treatment option for SHCC. More well-designed, large-scale randomized controlled trials should be performed to validate our findings.The online version contains supplementary material available at 10.1186/s12935-021-02365-1. Globally, hepatocellular carcinoma (HCC) is the sixth most prevalent tumor and the fourth leading cause of cancer-related deaths . Due to The most common therapeutic strategies for SHCC include surgery ), ablation (such as radiofrequency ablation (RFA)), microwave ablation (MWA), cryotherapy ablation (CRA), percutaneous ethanol injection (PEI), non-catheter based therapies, such as stereotactic body radiotherapy (SBRT) and catheter based embolic therapies such as transarterial chemoembolization (TACE). Liver transplantation is the most effective treatment option for SHCC  . HoweverAblation induces the necrosis of neoplastic cells by modifying the local temperature. This strategy is associated with several advantages, including minimal invasiveness, high safety, cost-effectiveness, and reproducibility. RFA is the most common ablative technique and, in selected patients, it has been shown to exhibit comparable efficacies to surgery. It is an effective replacement therapy for SHCC . In receTherefore, there is no consensus on optimal treatment options for very early or early-stage HCC. In cases where large clinical trials with multiple comparator arms are not available, bayesian network meta-analysis can be used to compare different treatment methods to identify the most effective approach . A randoAll procedures in this meta-analysis were performed in accordance with PRISMA  guidelines . RelevanEligibility criteria included the study population, intervention, comparison, outcome, and study design (PICOS) . i. The The exclusion criteria were: i. Case reports, letters to the editor, editorials and reviews were excluded; ii. Studies that focused on large HCC, intrahepatic recurrent small HCC, small HCC with extrahepatic metastases or vascular invasions, as well as those that focused on Child–Pugh classification of C or above; iii. Studies that did not report the relevant outcomes, and iv. Studies whose reported data were replicated in already included studies were excluded.Duplicates were excluded and titles as well as abstracts of the retrieved articles independently screened by two investigators (SY and HPL) using Endnote 7X  to determine if they met the inclusion criteria. Full texts of the selected articles were reviewed to determine if they were eligible for inclusion in the analysis. Two authors (SY and JNS) extracted and summarized the data from included studies, including first author names, publication dates, study settings, study designs, mean duration of follow-up, general characteristics, disease characteristics, OS, RFS, DFS and major complication rates. Any disagreements were resolved by consultations with senior authors.The quality of non-randomized trials was independently evaluated by two investigators using the Newcastle Ottawa Scale . Each stIn this meta-analysis, RFS, PFS, DFS and TFS were combined and redefined as RFS*. DFS was the time from randomization to tumor recurrence or death. PFS was the time between randomization and death or progression  . TFS wasNetwork meta-analysis (NMA) was performed using natural log transformations of Hazard ratios (HRs) and their 95% confidence intervals (CIs) to estimate standard errors (SEs), which consider the number and time of events. Hazard ratios (HRs) with 95% CI were used to determine effect sizes for OS, RFS and DFS. Odds ratios (ORs) with 95% CI were calculated to determine the effect sizes of major complication rates.2 value > 50% indicated a significant level of heterogeneity, therefore, sensitivity analyses were conducted by omitting one study at a time to identify heterogeneity sources [A network-node plot of comparisons was generated to indicate the number of trials that formed direct comparisons between treatment groups. RFA was used as the common parameter for comparisons in order to include all trials within 1 framework. It was assumed that efficacy would not vary based on dosages or schemes. Results were validated using “gemtc” (version 0.8–8) in R (version 4.0.3) and JAGS (version 4.3.0) softwares with identical parameter settings. A random-effects consistency model was used for each outcome measure. Three independent Markov chains were established for running 100 000 interactions with 10 000 burn-in samples and 10 thinning rates. The process was conducted to obtain a posterior distribution. Model convergence of iterations was evaluated and visualized using trace plots and Brooks-Gelman-Rubin diagnostics. Global inconsistencies were not present, therefore, NMA was performed following the consistency framework . Node-sp sources . MultivaA total of 2058 potentially relevant articles were identified from database searches. Then, after removal of duplicates at the initial stage of title and abstract reviews, 1208 articles were excluded because they did not meet the inclusion criteria. Full-texts for 259 articles were retrieved for detailed reviews and assessments. Notably, a total of 214 records were excluded, and 45 articles –85 involThe included studies showed a high methodological quality. Analysis using the Cochrane Collaboration tool showed a low risk of bias for the 10 randomized trials. The 35 non-randomized studies were of high quality . Details on quality assessments of randomized and non-randomized studies are presented in Additional file The NMA of interventional techniques for very early or early-stage HCC was conducted using the R-software Fig. . The resOS was reported in 43 trials. The HR and the corresponding 95% CI of OS were calculated after different treatments. Pooling of HRs for OS revealed a significant advantage for surgery, including SR and MIS, compared to RFA in network meta-analysis . Pooling of HRs for OS showed a statistically significant advantage for SR, compared to MWA , TACE  and RFA . Pooling of HRs for OS showed a statistically significant advantage for MIS compared to MWA , TACE  and RFA . Analysis of OS for patients subjected to ablative electrochemical therapies and non-ablative treatment revealed a high efficacy for MWA, PEI, CRA and SBRT, while the effectiveness of TACE was low, relative to that of RFA. However, differences in OS outcomes after treatment with these therapeutic approaches were not significant. Compared to SR, MIS was associated with better OS outcomes , however differences were not significant  and 0.48 (95% CI 0.36–0.64), respectively, indicating a significant advantage compared to RFA. It was established that SBRT and CRA had better efficacies, whereas TACE was associated with poor RFS*, compared to RFA, however, the differences were not significant. Notably, RFA and MWA exhibited the same RFS. Pooling of HRs for RFS* revealed a significant advantage for SR, compared to MWA  and TACE . In addition, pooling of HRs for RFS revealed a statistically significant advantage for MIS, compared to MWA , TACE  and CRA . All other treatments exhibited significant advantages, relative to TACE  was significantly associated with more severe complications, compared to RFA- and MWA-associated complications. Moreover, TACE  and SBRT  were associated with significantly less severe complications, compared to TACE. Furthermore, pooled RR revealed a significant advantage for TACE, compared to MWA   and study designs (RCT and Non-RCT) with RFS as the endpoint. Moreover, subgroup analyses were conducted according to tumor sizes (HCCs ≤ 3 cm and ≤ 5 cm) and study designs (RCT and Non-RCT) with OS as the endpoint. Studies that reported on OS outcomes were assigned into ≤ 3 cm (10 studies) and ≤ 5 cm (20 studies) subgroups. Pooled data showed significant benefits for SR, compared to RFA  for HCC ≤ 5 cm  and MIS   staging system. Bayesian network meta-analysis showed that MIS and SR exhibited better OS and RFS outcomes, relative to the other non-surgical treatment methods. In addition, MIS was associated with better outcomes, compared to SR while SBRT was more effective at increasing RFS outcomes, relative to the other non-surgical treatment approaches, whereas TACE was associated with significantly poor RFS* outcomes, compared to the other six treatment methods. Subgroup analysis revealed that RFA was more effective in patients with small nodules (< 2 cm or 3 cm in diameter). Notably, tumor nodule sizes were the main causes of heterogeneity. Borderline observations were made between MIS and CRA for OS , and between MIS and SR for RFS* . Studies with larger sample sizes should be conducted to verify these findings. Findings from RCT and non-RCT subgroups were consistent with these findings. Subgroup analyses based on liver status (Child–Pugh score) , AFP, vaEORTC developed clinical practice guidelines that recommend SR and MIS as first line treatment options for SHCC , 90. SurA network meta-analysis by Lin et al.  analyzedThis study has several strengths and a few limitations. i. The strength of this study is that cumulative OS and RFS were compared by calculating HRs (hazard rates), which are the most appropriate parameters for determining time-dependent outcomes , 111. HoThe findings of this network meta-analysis indicated that MIS and SR exhibit high clinical efficacies, however, these two approaches are correlated with a high number of complications. Ablation is highly effective for small tumors, whereas SBRT is more effective when compared to other ablation treatments in some cases. This indicates that SBRT is a relatively promising treatment for HCC. Subgroup analysis indicated that further studies should explore indications for different treatments. Moreover, well-designed, large-scale randomized controlled trials should be conducted to validate the findings of this study.Additional file 1: Figure S1: Quality assessment of included RCTs using Cochrane risk of bias assessment tool. RCTs: randomized controlled trials.Additional file 2: Figure S2. Funnel plot showing standard error by RR for major complication rates. RR: risk ratio.Additional file 3: Figure S3. Results on convergence of Gelman Rubin diagnostics. A: Results on OS; B: Results on RFS* ; C: Results on major complications rate. 1: RFA, 2: MWA, 3: SR, 4: TACE, 5: PEI, 6: MIS, 7: SBRT, 8: CRA. The level of adequacy of convergence of Gelman Rubin diagnostics approached 1 for all the three outcome parameters, indicating good convergence. OS: Overall Survival, RFS: recurrence-free survival, PFS: progression-free survival, DFS: disease free survival, TFS, tumor-free survival, RFA: radiofrequency ablation, MWA: microwave ablation, SR: surgical resection, TACE: transarterial chemoembolization, PEI: percutaneous ethanol injection, MIS: Minimally invasive liver surgery, SBRT: stereotactic body radiotherapy, CRA: cryotherapy ablation.Additional file 4: Figure S4. Forest plots showing relationships between different interventional methods and OS for subgroup analyses (HCCs tumor size ≤ 5 cm), compared to RFA and MWA. HR values and 95% CI were used. 1: RFA, 2: MWA, 3: SR, 6: MIS, 7: SBRT, 8: CRA. OS: Overall Survival, HCC: Hepatocellular Carcinoma, RFA: radiofrequency ablation, MWA: microwave ablation, HR: Hazard ratio, SR: surgical resection, MIS: Minimally invasive liver surgery, SBRT: stereotactic body radiotherapy, CRA: cryotherapy ablation.Additional file 5: Figure S5. Forest plots showing the relationship between different interventional methods and OS for subgroup analyses (HCCs tumor size ≤ 3 cm) compared to RFA. HR values and 95% CI were used for comparisons. 1: RFA, 3: SR, 4: TACE, 5: PEI, 6: MIS, 7: SBRT. OS: Overall Survival, HCC: Hepatocellular carcinoma, RFA: radiofrequency ablation, HR: Hazard ratio, SR: surgical resection, TACE: transarterial chemoembolization, PEI: percutaneous ethanol injection, MIS: Minimally invasive liver surgery, SBRT: stereotactic body radiotherapy.Additional file 6: Figure S6. Forest plots showing the relationship between different interventional methods and OS for subgroup analyses (RCTs) compared to RFA. HR values and 95% CI were used for comparisons. 1: RFA, 2: MWA, 3: SR, 5: PEI, 8: CRA. OS: Overall Survival, RCTs: randomized controlled trials, RFA: radiofrequency ablation, HR: Hazard ratio, MWA: microwave ablation, SR: surgical resection, PEI: percutaneous ethanol injection, CRA: cryotherapy ablation.Additional file 7: Figure S7. Forest plots showing the relationship between different interventional approaches and OS for subgroup analyses (non-RCTs), compared to RFA and MWA. HR values and 95% CI were used for comparisons. 1: RFA, 2: MWA, 3: SR, 4: TACE, 6: MIS, 7: SBRT, 8: CRA. OS: Overall Survival, non-RCTs: non-randomized controlled trials, RFA: radiofrequency ablation, MWA: microwave ablation, HR: Hazard ratio, SR: surgical resection, TACE: transarterial chemoembolization, MIS: Minimally invasive liver surgery, SBRT: stereotactic body radiotherapy, CRA: cryotherapy ablation.Additional file 8: Figure S8. Forest plots showing the relationship between different interventional methods and DFS, compared to RFA and MWA. HR values and 95% CI were used for comparisons. 1: RFA, 2: MWA, 3: SR, 6: MIS, 7: SBRT. DFS: disease free survival, RFA: radiofrequency ablation, MWA: microwave ablation, HR: Hazard ratio, CI: confidence interval, SR: surgical resection, MIS: Minimally invasive liver surgery, SBRT: stereotactic body radiotherapy.Additional file 9: Figure S9. Forest plots showing the relationship between different interventional methods and RFS, compared to RFA, MWA and CRA. HR values and 95% CI were used for comparisons. 1: RFA, 2: MWA, 3: SR, 4: TACE, 6: MIS, 7: SBRT, 8: CRA. RFS: recurrence-free survival, RFA: radiofrequency ablation, MWA: microwave ablation, HR: Hazard ratio, CI: confidence interval, SR: surgical resection, TACE: transarterial chemoembolization, MIS: Minimally invasive liver surgery, SBRT: stereotactic body radiotherapy.Additional file 10: Figure S10. Forest plots showing the association between different interventional methods and RFS*  for subgroup analyses (RCTs), compared to RFA. HR values and 95% CI were used for comparisons. 1: RFA, 2: MWA, 3: SR, 8: CRA. RFS: recurrence-free survival, PFS: progression-free survival, DFS: disease free survival, TFS, tumor-free survival, RCTs: randomized controlled trials, RFA: radiofrequency ablation, HR: Hazard ratio, CI: confidence interval, MWA: microwave ablation, SR: surgical resection, CRA: cryotherapy ablation.Additional file 11: Figure S11. Forest plots showing the association between different interventional methods and RFS*  for subgroup analyses (non-RCTs), compared to RFA and MWA. HR values and 95% CI were used for comparisons. 1: RFA, 2: MWA, 3: SR, 4: TACE, 6: MIS, 7: SBRT, 8: CRA. RFS: recurrence-free survival, PFS: progression-free survival, DFS: disease free survival, TFS, tumor-free survival, non-RCTs: non-randomized controlled trials, RFA: radiofrequency ablation, MWA: microwave ablation, HR: Hazard ratio, CI: confidence interval, SR: surgical resection, TACE: transarterial chemoembolization, MIS: Minimally invasive liver surgery, SBRT: stereotactic body radiotherapy, CRA: cryotherapy ablation.Additional file 12: Figure S12. Forest plots showing the association between different interventional arms and RFS*  for subgroup analyses (HCCs tumor size ≤ 5 cm), compared to RFA and MWA. HR values and 95% CI were used for comparisons. 1: RFA, 2: MWA, 3: SR, 6: MIS, 7: SBRT, 8: CRA. RFS: recurrence-free survival, PFS: progression-free survival, DFS: disease free survival, TFS, tumor-free survival, HCC: Hepatocellular Carcinoma, RFA: radiofrequency ablation, MWA: microwave ablation, HR: Hazard ratio, CI: confidence interval, SR: surgical resection, MIS: Minimally invasive liver surgery, SBRT: stereotactic body radiotherapy, CRA: cryotherapy ablation.Additional file 13: Figure S13. Forest plots showing the association between different interventional approaches and RFS*  for subgroup analyses (HCCs tumor size ≤ 3 cm), compared to TACE. HR values and 95% CI were used for comparisons. 1: RFA, 3: SR, 4: TACE, 6: MIS. RFS: recurrence-free survival, PFS: progression-free survival, DFS: disease free survival, TFS, tumor-free survival, HCC: Hepatocellular Carcinoma, TACE: transarterial chemoembolization, HR: Hazard ratio, CI: confidence interval, RFA: radiofrequency ablation, SR: surgical resection, MIS: Minimally invasive liver surgery.Additional file 14: Figure S14. Forest plots showing the association between different interventional methods and major complication rates in subgroup analyses (RCTs), compared to RFA. RR values and 95% CI were used for comparisons. 1: RFA, 2: MWA, 3: SR, 5: PEI, 8: CRA. RCTs: randomized controlled trials, RFA: radiofrequency ablation, RR: risk ratio, MWA: microwave ablation, SR: surgical resection, PEI: percutaneous ethanol injection, CRA: cryotherapy ablation.Additional file 15: Figure S15. Forest plots showing the association between different interventional approaches and major complications rate for subgroup analyses (non-RCTs), compared to RFA. RR values and 95% CI were used for comparisons. 1: RFA, 2: MWA, 3: SR, 4: TACE, 6: MIS, 7: SBRT, 8: CRA. non-RCTs: non-randomized controlled trials, RFA: radiofrequency ablation, RR: risk ratio, MWA: microwave ablation, SR: surgical resection, TACE: transarterial chemoembolization, MIS: Minimally invasive liver surgery, SBRT: stereotactic body radiotherapy, CRA: cryotherapy ablation.Additional file 15: Table S1. The inconsistent loops P-value for different comparisons.


Calotesmystaceus Duméril & Bibron, 1837 complex. Of the three new species, C.vindumbarbatus Wagner, Ihlow, Hartmann, Flecks, Schmitz & Böhme, 2021 was known only from northern Myanmar.Three new species were recently described from the Calotesvindumbarbatus from Myanmar with strong support and showed inappreciable genetic divergence from the type specimens of C.vindumbarbatus. We report the first country record of C.vindumbarbatus from China. In addition, a supplementary description, based on the newly-collected specimens and revised diagnosis of this species, was provided.Seven specimens of lizard were collected from Tongbiguan Nature Reserve, western Yunnan, China. Phylogenetically, these specimens clustered with the type specimens of  Calotesmystaceus, originally described from “Pays de Birmans” (= Myanmar), was previously considered to be widely distributed from India, Myanmar, China, Laos, Cambodia, Thailand and Vietnam  which was measured using a string and a ruler. Morphological terminology followed Total genomic DNA was extracted from liver tissues with the universal protocol of DNA extraction . A regioSequences were aligned using ClustalW  with defWagner, Ihlow, Hartmann, Flecks, Schmitz & Böhme, 2021A540C62E-C105-57B7-A108-C0F7E17E15C5Type status:Other material. Occurrence: catalogNumber: KIZ 059299; individualCount: 1; sex: male; lifeStage: adult; Location: country: China; stateProvince: Yunnan; locality: Nabang Town, Yingjiang County, Dehong Prefecture; verbatimElevation: 320 m; verbatimCoordinates: 24°45'47"N 97°34'15"E; Event: eventRemarks: collected by Shuo Liu on 5 September 2018; Record Level: basisOfRecord: preserved specimeType status:Other material. Occurrence: catalogNumber: KIZ 059176; individualCount: 1; sex: female; lifeStage: adult; Location: country: China; stateProvince: Yunnan; locality: Nabang Town, Yingjiang County, Dehong Prefecture; verbatimElevation: 320 m; verbatimCoordinates: 24°45'47"N 97°34'15"E; Event: eventRemarks: collected by Shuo Liu on 5 September 2018; Record Level: basisOfRecord: preserved specimeType status:Other material. Occurrence: catalogNumber: KIZ20209131; individualCount: 1; lifeStage: juvenile; Location: country: China; stateProvince: Yunnan; locality: Xueli Village, Taiping Town, Yingjiang County, Dehong Prefecture; verbatimElevation: 350 m; verbatimCoordinates: 24°26'32"N, 97°33'4"E; Event: eventRemarks: collected by Shuo Liu on 13 September 2020; Record Level: basisOfRecord: preserved specimeType status:Other material. Occurrence: catalogNumber: KIZ20209132; individualCount: 1; lifeStage: juvenile; Location: country: China; stateProvince: Yunnan; locality: Xueli Village, Taiping Town, Yingjiang County, Dehong Prefecture; verbatimElevation: 350 m; verbatimCoordinates: 24°26'32"N, 97°33'4"E; Event: eventRemarks: collected by Shuo Liu on 13 September 2020; Record Level: basisOfRecord: preserved specimeType status:Other material. Occurrence: catalogNumber: KIZ20209133; individualCount: 1; lifeStage: juvenile; Location: country: China; stateProvince: Yunnan; locality: Xueli Village, Taiping Town, Yingjiang County, Dehong Prefecture; verbatimElevation: 350 m; verbatimCoordinates: 24°26'32"N, 97°33'4"E; Event: eventRemarks: collected by Shuo Liu on 13 September 2020; Record Level: basisOfRecord: preserved specimeType status:Other material. Occurrence: catalogNumber: KIZ20209134; individualCount: 1; lifeStage: juvenile; Location: country: China; stateProvince: Yunnan; locality: Xueli Village, Taiping Town, Yingjiang County, Dehong Prefecture; verbatimElevation: 350 m; verbatimCoordinates: 24°26'32"N, 97°33'4"E; Event: eventRemarks: collected by Shuo Liu on 13 September 2020; Record Level: basisOfRecord: preserved specimeType status:Other material. Occurrence: catalogNumber: KIZ20209135; individualCount: 1; lifeStage: juvenile; Location: country: China; stateProvince: Yunnan; locality: Xueli Village, Taiping Town, Yingjiang County, Dehong Prefecture; verbatimElevation: 350 m; verbatimCoordinates: 24°26'32"N, 97°33'4"E; Event: eventRemarks: collected by Shuo Liu on 13 September 2020; Record Level: basisOfRecord: preserved specimeMorphometric and meristic data are presented in Table This species has a very strong ability to change the body colouration Fig. . UsuallyThe colourations of adult females are relatively dim. Usually, the ground colour of females is purple brown, there are dark longitudinal stripes on the chin region and dark reticulate stripes on the back and there are radial dark stripes around the eyes, the white stripe along the upper lip and the dorsolateral blotches are more indistinct. However, the females can also change their body colouration. The stripes on the back, chin region and around the eyes may become indistinct. The head, forelimbs and anterior half of the body may become bluish, the white stripe and dorsolateral blotches may become more distinct. However, the colourations of females are still not as bright as those of males.Calotes species of the complex, males with a known maximum SVL of 116.4 mm, females with a SVL of 97.2 mm. Tail length short, approximately twice the length of SVL. It can be distinguished from the other species of the complex by the combination of the following characters: 1) head and body robust, posterior parts of jaw angle slightly swollen in adult males, not swollen in female; 2) dorsal scales large, feebly keeled, pointing upwards and backwards, ventral scales small, parallel and strongly keeled; 3) body scales arranged in 50–56 rows around mid-body; 4) 18–22 lamellae on the fourth finger and 22–27 lamellae on the fourth toe; 5) 40–49 vertebral scales, nuchal crest developed in adults, dorsal crest developed in adult males, but undeveloped in females; 6) two short separated spines on each side above the tympanum and two shorter spines beside each of them; 7) oblique fold of skin in front of forelimb insertion distinct, covered with small granular dark scales; 8) the head, forelimbs and anterior half of the body blue in adult males, white stripe along the upper lip present, the posterior half of the body, hindlimbs and tail almost uniform brown; 9) 4–5 white blotches on each side of lateral body, gradually increasing brown blotches are present just on each white blotch, the first two are smaller than the white blotches and the rest almost covering the whole of the white blotches; 10) the colourations of adult females similar to those of males, but relatively dim; 11) nuchal and dorsal crest undeveloped in juveniles, the white stripe along the upper lip distinct, but the dorsolateral blotches indistinct and dark reticulate pattern present on the back in juveniles.A medium-sized Calotes, C.irawadi Zug, Brown, Schulte & Vindum, 2006 and C.emma Gray, 1845 were observed to be sympatric with this species.The specimens were found on the trunks beside roads during the day Fig.  and wereCalotesvindumbarbatus from Myanmar with strong support. The genetic distance (uncorrected p-distance) between the specimens from China and the type specimens of C.vindumbarbatus from Myanmar was only 0.9% , low nuchal and dorsal crest, no brownish dorsolateral blotches. Some of the newly-collected specimens of C.vindumbarbatus from western Yunnan agree well with these diagnoses; however, some of the newly-collected specimens of C.vindumbarbatus from western Yunnan have much larger body sizes (maximum SVL 116.4 mm), much longer nuchal and dorsal crest and obvious brown dorsolateral blotches. Therefore, we consider that the specimens of C.vindumbarbatus in According to Calotesvindumbarbatus was known previously only from northern Myanmar  to parts of southern and eastern India. Therefore, C.versicolor is also not distributed in China. C.irawadi in China. In conclusion, there are seven species of Calotes distributed in China to date, namely: C.emma Gray, 1845; C.goetzi Wagner, Ihlow, Hartmann, Flecks, Schmitz & Böhme, 2021; C.irawadi Zug, Brown, Schulte & Vindum, 2006; C.jerdoni Günther, 1870; C.medogensis Zhao & Li, 1984; C.paulus ; and C.vindumbarbatus Wagner, Ihlow, Hartmann, Flecks, Schmitz & Böhme, 2021.Oriocalotes Günther, 1864 was abolished and Diploderma Hallowell, 1861 was resurrected; therefore, the agamids in China still consist of 12 genera (The fauna of the agamids in China was analysed 10 years ago . Thereaf2 genera . In the 2 genera . However


JAMIA Open, Volume 5, Issue 1, April 2022, ooab119,https://doi.org/10.1093/jamiaopen/ooab119In the originally published version of this manuscript, the title was incorrect.The incorrect title read:ATRI EDC: a novel cloud-native remote data capture system for large multicenter Alzheimer’s disease and Alzheimer’s disease-related dementias clinical trailsThis has now been corrected to:ATRI EDC: a novel cloud-native remote data capture system for large multicenter Alzheimer’s disease and Alzheimer’s disease-related dementias clinical trials