bluuebunny/crossref_metadata_2025 huggingface dataset:
Daptomycin synergistic properties from in vitro and in vivo studies: a systematic review
Authors: Antonello Roberta Maria , Canetti Diana , Riccardi Niccolò
Published: September 2022

Introduction

Daptomycin is a bactericidal lipopeptide antibiotic approved for the treatment of systemic infections (i.e. skin and soft tissue infections, bloodstream infections, infective endocarditis) caused by Gram-positive cocci. It is often prescribed in association with a partner drug to increase its bactericidal effect and to prevent the emergence of resistant strains during treatment; however, its synergistic properties are still under evaluation.

Methods

We performed a systematic review to offer clinicians an updated overview of daptomycin synergistic properties from in vitro and in vivo studies. Moreover, we reported all in vitro and in vivo data evaluating daptomycin in combination with other antibiotic agents, subdivided by antibiotic classes, and a summary graph presenting the most favourable combinations at a glance.

Results

A total of 92 studies and 1087 isolates (723 Staphylococcus aureus, 68 Staphylococcus epidermidis, 179 Enterococcus faecium, 105 Enterococcus faecalis, 12 Enterococcus durans) were included. Synergism accounted for 30.9% of total interactions, while indifferent effect was the most frequently observed interaction (41.9%). Antagonistic effect accounted for 0.7% of total interactions. The highest synergistic rates against S. aureus were observed with daptomycin in combination with fosfomycin (55.6%). For S. epidermidis and Enterococcus spp., the most effective combinations were daptomycin plus ceftobiprole (50%) and daptomycin plus fosfomycin (63.6%) or rifampicin (62.8%), respectively.

Future perspectives

We believe this systematic review could be useful for the future updates of guidelines on systemic infections where daptomycin plays a key role.
Successful endovascular exclusion of Mycobacterium bovis mycotic aneurysm following intravesical bacille Calmette–Guerin therapy
Authors: Cook Victoria , Singla Animesh A , Herlihy David , Mohabbat Walid , Fisher Charles , Puttaswamy Vikram
Published: September 2022

Bacille Calmette–Guerin (BCG) is a live-attenuated strain of Mycobacterium bovis. It is routinely used in the treatment of early-stage transitional cell carcinoma. The development of mycotic aneurysm in the context of prior intra-vesical BCG treatment has not been reported. This case demonstrates a rare but potentially catastrophic vascular complication of BCG. A high index of suspicion is required for any patient presenting with new aneurysmal disease in the context of previous BCG therapy. The value of endovascular surgery as a bridge to definitive surgical repair and diagnostic considerations is discussed.
The association between job quality and the incidence of PTSD amongst police personnel
Authors: Burchell Brendan , Miller Jessica , Brewin Chris , Soffia Magdalena , Wang Senhu
Published: September 2022

It has been widely reported that surveys have found high levels of ICD-11 complex post-traumatic stress disorder (CPTSD) (12.6%) among police personnel, and a further 8.0% with PTSD. Until now, there has been little research linking PTSD to working conditions. This report examines how the prevalence of CPTSD varies with measures of job quality. Positive indicators of job quality (for instance, the feeling of doing meaningful work, support from colleagues and managers, work–life balance, job security, and promotion prospects) typically predict half the rate of CPTSD. Negative indicators of poor job quality (such as having to deal with sexual harassment or extreme time pressures) are associated with CPTSD rates twice as high as the policing average. Additional evidence shows that police forces with better working conditions tend to have markedly lower rates of PTSD. These analyses cannot prove the direct causal relationship from job quality to PTSD but do provide unequivocal evidence of an association. Improving job quality may greatly reduce the level of this most debilitating psychological disorder, CPTSD, in the policing population.
Regulation of wakefulness by GABAergic dorsal raphe nucleus-ventral tegmental area pathway
Authors: Cai Ping , Wang Fu-Dan , Yao Jing , Wang Wen-Feng , Hu Yu-Duan , Liu Ren-Fu , Li Zhang-Shu , Zhu Zhong-Hua , Cai Yu-Tong , Lin Zhi-Hui , Tang Wei-Tao , Zhuang Cong-Wen , Xiao Wen-Hao , Zeng Yu-Hang , Huang Sheng-Nan , Fu Zhifei , Wang Wen-Xiang , Chen Li
Published: September 2022

The dorsal raphe nucleus (DRN) has previously been proved to be involved in the regulation of the sleep–wake behavior. DRN contains several neuron types, such as 5-HTergic and GABAergic neurons. GABAergic neurons, which are the second largest cell subtype in the DRN, participate in a variety of neurophysiological functions. However, their role in sleep–wake regulation and the underlying neural circuitry remains unclear. Herein, we used fiber photometry and synchronous electroencephalogram (EEG)/electromyography (EMG) recording to demonstrate that DRN GABAergic neurons exhibit high activities during wakefulness and low activities during NREM sleep. Short-term optogenetic activation of DRN GABAergic neurons reduced the latency of NREM-to-wake transition and increased the probability of wakefulness, while long-term optogenetic activation of these neurons significantly increased the amount of wakefulness. Chemogenetic activation of DRN GABAergic neurons increased wakefulness for almost 2 h and maintained long-lasting arousal. In addition, inhibition of DRN GABAergic neurons with chemogenetics caused a reduction in the amount of wakefulness. Finally, similar to the effects of activating the soma of DRN GABAergic neurons, optogenetic stimulation of their terminals in the ventral tegmental area (VTA) induced instant arousal and promoted wakefulness. Taken together, our results illustrated that DRN GABAergic neurons are vital to the induction and maintenance of wakefulness, which promote wakefulness through the GABAergic DRN-VTA pathway.
1,8-Dihydroxynaphthalene Melanin Biosynthesis in Colletotrichum fructicola Is Developmentally Regulated and Requires the Cooperative Function of Two Putative Zinc Finger Transcription Factors
Authors: Liang Xiaofei , Li Bingxuan , Zhao Xuemei , Yao Liqiang , Kong Yuanyuan , Liu Wenkui , Zhang Rong , Sun Guangyu
Published: September 2022

In ascomycetes, 1,8-dihydroxynaphthalene (DHN) melanin plays important protective functions and its production is usually coupled with development and environmental stress responses. The regulation of melanin biosynthesis, however, remains obscure. Colletotrichum fructicola is a phytopathogen with a broad host range that produces melanized appressoria and perithecia. In this study, we annotated melanin genes in a high-quality C. fructicola genome and characterized two zinc finger transcription factors (TFs) ( cmr1 and cmr2) that form a loosely organized gene cluster with several melanin biosynthesis genes. Deleting either TF abolished melanization in both mycelia and perithecia but did not affect appressoria. The deletion mutants also showed perithecial development defects. Overexpressing cmr1 in Δ cmr2 strongly activated the expression of melanin biosynthesis genes including pks1, scd1, t4hr1, and thr1 and caused hyper-accumulation of charcoal to black pigment(s). On the other hand, overexpressing cmr2 in Δ cmr1 activated pks1, t4hr1, and thr1, but not scd1. We conclude that proper DHN melanin accumulation in C. fructicola requires the cooperative function of two in-cluster TFs that also regulate perithecial development. The study clarifies DHN melanin regulations in C. fructicola and expands the function of melanin in-cluster TFs to sex regulation.
Preoperative exercise and prehabilitation
Authors: Esser Tobias , Zimmer Philipp , Schier Robert
Published: September 2022

Purpose of review

The purpose of this narrative review is to give an overview about the effects of multimodal prehabilitation and current existing and prospectively planned studies. The potential efficacy of exercise in the context of prehabilitation ranges from preoperatively improving patients’ functional capacity to inducing cellular mechanisms that affect organ perfusion via endothelial regeneration, anti-inflammatory processes and tumour defense.

Recent findings

Current studies show that prehabilitation is capable of reducing certain postoperative complications and length of hospital stay in certain patient populations. These findings are based on small to mid-size trials with large heterogeneity, lacking generalizability and evidence that prehabilitation has positive effects on long term survival.

The concept of prehabilitation contains the features, namely preoperative exercise, nutritional intervention and psychological support. Preoperative exercise holds potential molecular effects that can be utilized in the perioperative period in order to improve patients’ postoperative outcome. Future multimodal prehabilitation trials must specifically clarify the clinical impact of this concept on patients’ quality of life after major cancer surgery and cancer-specific survival.
A new noninvasive finger sensor (NICCI system) for continuous blood pressure and pulse pressure variation monitoring
Authors: Flick Moritz , Bergholz Alina , Kouz Karim , Breitfeld Philipp , Nitzschke Rainer , Flotzinger Doris , Saugel Bernd
Published: September 2022

BACKGROUND

The NICCI system (Getinge, Gothenburg, Sweden) is a new noninvasive haemodynamic monitoring system using a finger sensor.

OBJECTIVE(S)

We aimed to investigate the performance of the NICCI system to measure blood pressure and pulse pressure variation compared with intra-arterial measurements.

DESIGN

A prospective method comparison study

SETTING

University Medical Center Hamburg-Eppendorf, Hamburg, Germany

PATIENTS

Forty-seven neurosurgery patients

MAIN OUTCOME MEASURES

We performed a method comparison study in 47 neurosurgery patients to compare NICCI blood pressure measurements (BPNICCI) with intra-arterial blood pressure measurements (BPART) (Bland–Altman analysis, four-quadrant plot, error grid analysis) and NICCI pulse pressure variation measurements (PPVNICCI) with pulse pressure variation calculated manually from the intra-arterial blood pressure waveform (PPVART) (Bland–Altman analysis, predictive agreement, Cohen's kappa).

RESULTS

The mean of the differences ± standard deviation (95% limits of agreement) between BPNICCI and BPART was 11 ± 10 mmHg (-8 to 30 mmHg) for mean blood pressure (MBP), 3 ± 12 mmHg (-21 to 26 mmHg) for systolic blood pressure (SBP) and 12 ± 10 mmHg (-8 to 31 mmHg) for diastolic blood pressure (DBP). In error grid analysis, 54% of BPNICCI and BPART MBP measurement pairs were classified as ‘no risk’, 43% as ‘low risk’, 3% as ‘moderate risk’ and 0% as ‘significant risk’ or ‘dangerous risk’. The mean of the differences between PPVNICCI and PPVART was 1 ± 3% (-4 to 6%). The predictive agreement between PPVNICCI and PPVART was 80% and Cohen's kappa was 0.55.

CONCLUSIONS

The absolute agreement between BPNICCI and BPART was not clinically acceptable. We recommend not using the current version of the NICCI system for blood pressure monitoring during surgery. The absolute agreement between PPVNICCI and PPVART was clinically acceptable with moderate predictive agreement regarding pulse pressure variation categories. The NICCI system needs to be further developed and re-evaluated when an improved version is available.

TRIAL REGISTRATION

The study was registered in the German Clinical Trials Register (DRKS00023188) on 2 October 2020.
Treatment of Arrhythmias During Pregnancy
Authors: Pacheco Luis D. , Eyada Mostafa , Saade George R.
Published: September 2022

Cardiac disease is the most common cause of maternal mortality in developed nations. Cardiac arrhythmias are frequent among patients with structural heart disease and may require immediate treatment to prevent hemodynamic instability leading to acute maternal and fetal decompensation. Antiarrhythmic therapy during pregnancy should follow the same principles recommended for nonpregnant individuals. Although multidisciplinary management is recommended, obstetricians, and maternal-fetal medicine specialists may sometimes need to emergently recognize and treat rhythm anomalies before support services become available.
Obstetrical Readiness: Preparing Rural Emergency Departments Without Hospital-Based Obstetrical Services
Authors: FORMAN JEANA , HENKLE JILL
Published: September 2022

In rural states, hospitals that provide birthing services are closing at an alarming rate, increasing the distance birthing people are traveling, rural Emergency Departments play a vital role in reducing maternal morbidity and mortality. An interdisciplinary education and simulation with debriefing program was created to improve the care by non-obstetric providers for routine and emergent obstetrical care. The program includes monthly lectures, hands on skills training, and in-situ interdisciplinary simulations with debriefings to build a foundation of knowledge and skill for rural Emergency Department staff statewide.
Symptoms associated with nucleic acid turning-negative-time in COVID-19 patients?
Authors: Li Qiang , Zhang Lei , Feng Limin , Sun Hongyuan , Ma Yan , Liu Xiaoya , Shi Cunzhong , Luo Mingchi
Published: September 2022

Objective:

To explore on the association between nucleic acid turning-negative-time and traditional Chinese medicine (TCM) symptoms in coronavirus disease 2019 (COVID-19) patients with the Omicron variant.

Method:

For this retrospective cross-sectional study, we enrolled 189 patients with COVID-19 (age 20–90 years) were included. multiple linear regression models were used to investigate the TCM symptoms affecting the nucleic acid turning-negative-time of COVID-19 patients, during the process of data analysis, taking with nucleic acid turning-negative-time as the dependent variable, and TCM symptoms as independent variables, and at the same time, sex, age, hypertension, diabetes, and coronary heart disease were as confounding variables.

Results:

The study found that the most common TCM symptoms of COVID-19 patients with Omicron were cough, dry throat, expectoration, fever, sore throat, pharyngeal itching, running nose, and nasal congestion. Regression analysis showed that the fit regressive equation showed a significant difference (F = 4.286, P < 0.001), R = 0.400, the adjusted R 2 = 0.123, and three variables in the regression equation showed significant difference (P < 0. 05). The results showed that nucleic acid turning-negative-time was mostly related to constipation, fever, and expectoration. If the patients had the symptoms of constipation, fever, and expectoration; that is, if patients showed these symptoms, the turning-negative-time of nucleic acid in patients with Omicron will be prolonged.

Conclusions:

Treatment based on symptoms for patients with constipation, fever, and expectoration may have important clinical significance for the COVID-19 patients with Omicron.
Traditional Chinese Medicine for promoting Mental Health of Patients with COVID-19: A Scoping Review
Authors: Ji Zhaochen , Hu Haiyin , Wang Danlei , Di Nitto Marco , Fauci Alice Josephine , Okada Masayoshi , Li Kai , Wang Hui
Published: September 2022

Objective:

This study aimed to systematically review and depict the current studies of traditional Chinese medicine for the mental health of patients with COVID-19.

Methods:

A scoping review was conducted by searching PubMed, Web of Science, CNKI, Wanfang database, VIP database, and SinoMed, with the retrieval time being from the establishment of the database to April 18, 2022. The basic information of the included studies, objective, design, types of patients, interventions, outcomes, etc. was reviewed and summarised narratively. Methodological quality was assessed using the Cochrane Risk of Bias assessment tool, the Methodological Index for Non-Randomized Studies or the Newcastle-Ottawa Scale.

Results:

We identified 30 TCM studies from 6 databases. Among them, finished randomised controlled trials (n = 16) accounted for most of the studies, followed by single-arm studies (n = 9). In terms of study theme, 20 studies defined the mental health of patients with COVID-19 as the research theme. Psychological assessment was included in the inclusion criteria (performed before participation) of 9 studies, whereas the other studies only mentioned the mental outcomes. TCM interventions included TCM exercises (Yijinjing, Baduanjin, Liuzijue, Taichi), acupoint stimulation (auricular and body points), moxibustion, decoction or granules based on TCM syndrome differentiation, decoction or granules with fixed formulae (Baidu-Jieduan granules, Xuanfei-Baidu decoction, and Qingfei-Paidu decoction), Chinese patent medicine (Jinhua-Qinggan granules), TCM psychological therapy (TCM ideological therapy, TCM five-tone therapy, and TCM psychological sand table), and TCM nursing (dialectical care, dialectical diet, and psychological counselling). Anxiety and depression were the main outcomes evaluated in regard to mental health in patients with COVID-19. The limitations of methodological quality were predominantly from follow-up, blinding, and registration. Positive results were reported by 27 studies (90%, n = 30).

Conclusion:

We summarised the existing literature about the impact of TCM on mental health in patients with COVID-19. The number of studies evaluating the impact of TCM on mental health is encouraging, but overall methodological quality was low. Several TCM interventions warrant further evaluation, particularly among populations outside of China, for the purpose of establishing supporting evidence. More importantly, researches with stronger methodological quality need to be developed.
Double-Needle Haptic Repositioning: A Troubleshooting Technique for Flanged Intraocular Lens Fixation
Authors: Hung Jia-Horung , Wang Li-An , Hsu Shu-Hsien , Hsu Sheng-Min , Yamane Shin
Published: September 2022

Purpose:

Haptic repositioning during flanged intraocular lens (IOL) fixation can be difficult, and the haptic requiring repositioning may be at increased risk of excessive bending or breakage. This study aimed to report double-needle haptic repositioning technique outcomes for the aforementioned difficulty during flanged IOL fixation.

Methods:

This retrospective case series included seven eyes requiring haptic repositioning during flanged IOL fixation. The method features reinsertion of an already externalized haptic into the needle lumen followed by a needle–haptic complex internalized through the original tract into the eyeball. Thus, an adequate configuration for contralateral haptic can be achieved for insertion into the needle lumen to create a double-needle condition before both haptics are successfully externalized.

Results:

The median follow-up duration was 24 months (range, 4–24 months). Postoperatively, the IOL was well-centered, and corrected distance visual acuity improved from 20/320 (20/4,000–20/70) to 20/50 (20/250–20/20). No intraoperative or postoperative complications were noted.

Conclusion:

The technique produced encouraging results in patients undergoing haptic repositioning during flanged IOL fixation. This technique could potentially reduce haptic overbending risk and facilitate haptic adjustment. Further studies are needed to confirm the feasibility of the technique.
A Comparative Study of Two Extended Depth of Focus Intraocular Lenses
Authors: Song Mi Yeon , Kang Kyoung Hae , Lee Hun , Kim Tae-im , Koh Kyungmin
Published: September 2022

Objective:

To assess and compare the visual performance of two extended depth-of-focus intraocular lenses (IOLs), Tecnis Symfony (Symfony; Johnson & Johnson Vision, Santa Ana, CA) and Acrysof IQ Vivity (Vivity; Alcon Inc, Fort Worth, TX).

Methods:

The medical records of patients undergoing cataract surgery with Symfony or Vivity implantation from May 2021 to September 2021 and the data available for the 3-month follow-up were reviewed. The main measures of the findings were uncorrected and corrected distance (4 m) visual acuity (VA), uncorrected intermediate (66 cm) VA (UIVA) and uncorrected near (40 and 33 cm) VA (UNVA), refractive error (RE), defocus profiles analysis, optical quality parameters, and patient-reported quality of vision questionnaire results.

Results:

Of the 40 patients, 19 patients (31 eyes) were treated with the Symfony IOL and 21 (32 eyes) with the Vivity IOL. The mean age of the patients was 63.4±7.8 (range, 40–76) years in the Symfony group and 61.8±9.7 (range, 40–77) years in the Vivity group. There was no meaningful difference between the two groups in the preoperative parameters, except that the Vivity group had a better CDVA. Among the main measures of results, there was no statistically significant difference, except for the UNVA (33 cm). The Symfony group also showed a smoother defocus curve at 3 months postoperatively.

Conclusion:

There was no significant difference between the two groups regarding uncorrected/corrected distance VA, UIVA, UNVA (40 cm), RE, optical quality parameters, and patient-reported quality of vision questionnaire results. The Symfony group demonstrated a significantly superior UNVA (33 cm) and a smoother defocus curve with a broad landing zone.
Descemet Membrane Endothelial Keratoplasty–Induced Refractive Shift and Descemet Membrane Endothelial Keratoplasty–Induced Intraocular Lens Calculation Error
Authors: Debellemanière Guillaume , Ghazal Wassim , Dubois Mathieu , Rampat Radhika , Fabre Laura , Panthier Christophe , Courtin Romain , Mazharian Adrien , Zeboulon Pierre , Rouger Hélène , Saad Alain , Gatinel Damien
Published: September 2022

Purpose:

The aim of this study was to determine the mechanisms leading to the refractive shift and intraocular lens calculation error induced by Descemet membrane endothelial keratoplasty (DMEK), using ocular biometry and corneal elevation tomography data.

Methods:

This is a retrospective, monocentric cohort study. Eyes which underwent uncomplicated DMEK surgery with available pre-DMEK and post-DMEK Scheimpflug rotating camera data (Pentacam, Oculus, Wetzlar, Germany) were considered for inclusion with an age-matched control group of healthy corneas. Cataract surgery data were collected for triple-DMEK cases. DMEK-induced refractive shift (DIRS) and intraocular lens calculation error (DICE) were calculated. Pearson r correlation coefficient was calculated between each corneal parameter variation and both DIRS and DICE.

Results:

DIRS was calculable for 49 eyes from 43 patients. It was 30.61% neutral, 53.06% hyperopic (36.73% > 1D), and 16.32% myopic (6.12% > 1 D). DICE was calculable for 30 eyes of 26 patients: It was 46.67% neutral, 40.00% hyperopic (10.00% > 1D), and 13.33% myopic (3.33% > 1D). DIRS and DICE were mainly associated with variations in PRC/ARC ratio, anterior average radii of curvature (ARC), posterior average radii of curvature (PRC), and posterior Q.

Conclusions:

Our results suggest that ARC variations, PRC/ARC ratio variations, PRC variations, and posterior Q variations are the most influential parameters for both DIRS and DICE. We suggest that a distinction between those different phenomenons, both currently described as “hyperopic shift” in the literature, should be made by researchers and clinicians.
Refractive Corneal Lenticule Extraction With the CLEAR Femtosecond Laser Application
Authors: Leccisotti Antonio , Fields Stefania V. , De Bartolo Giuseppe
Published: September 2022

Purpose:

The aim of this study was to evaluate a new femtosecond laser application for refractive corneal lenticule extraction with suction control and computerized regulation of centration and alignment (Ziemer CLEAR).

Methods:

This was a retrospective, consecutive, noncomparative case series study. Patients undergoing CLEAR for spherical equivalent (SE) between −3 and −10 D, evaluating SE, defocus equivalent, refractive astigmatism, visual acuity, and centration at 10 months were evaluated in the study.

Results:

Fifty-three eyes of 42 patients (mean age 40.4 ± 8.6 years) were included, with preoperative SE −5.99 ± 1.49 D and mean corrected distance visual acuity (CDVA) of 0.05 ± 0.07 logMAR. With no suction losses, an intact lenticule was extracted in all eyes. In 6 eyes, peripheral adhesion was resolved by lenticulerrhexis, and in 1 eye, the incision was opened by a crescent blade. Moderate interface inflammation occurred in 3 eyes. At day 1, in the 42 eyes with uneventful surgery, the mean CDVA was 20/27, whereas in the 11 eyes with extra surgical manipulations, it was 20/36 (P= 0.04). At 10 months, for the 53 eyes, the mean uncorrected distance visual acuity was 0.05 ± 0.09 logMAR; in 37 eyes (70%), it was 20/25 or better; and the mean CDVA was 0.04 ± 0.06 logMAR. Eight eyes (15%) lost 1 logMAR line. The mean SE was −0.13 ± 0.15 D. The mean defocus equivalent was 0.33 ± 0.32 D, with 46 eyes (87%) ≤0.50 D and 52 eyes (98%) ≤1 D. Refractive astigmatism was ≤0.50 D in 48 eyes (90%). The efficacy index was 1.00, and the safety index was 0.98. The mean decentration from the corneal vertex was 0.28 ± 0.07 mm.

Conclusions:

The application yielded good predictability, efficacy, and safety. Slower visual recovery was observed after extra surgical manipulations.
Accelerated Corneal Collagen Cross-Linking Protocols for Progressive Keratoconus: Systematic Review and Meta-analysis
Authors: Karam Mohammad , Alsaif Abdulmalik , Aldubaikhi Ahmed , Aljebreen Meshaal , Alazaz Rand , Alkhowaiter Nahlaa , Almudhaiyan Tariq , Aljassar Faisal
Published: September 2022

Purpose:

The aim of this study was to compare the outcomes of 18 mW/cm2 (5 minutes) versus 9 mW/cm2 (10 minutes) accelerated corneal collagen cross-linking protocols in patients with progressive keratoconus.

Methods:

A systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and electronic information was searched to identify studies comparing the outcomes of 5- versus 10-minute protocols in patients with progressive keratoconus. Mean changes in uncorrected visual acuity, best-corrected visual acuity, cylinder (diopters), thinnest corneal thickness, corneal keratometry values (K1 and K2), corneal high-order aberration (HOA), spherical aberration, coma, and trefoil were the primary outcome measures. Secondary outcome measures included the mean change in central corneal thickness and postoperative complications. Random effects modeling was used for the analysis.

Results:

Four studies that enrolled 329 eyes were included. The 10-minute protocol had significantly improved outcomes compared with the 5-minute protocol for the mean changes in K1 and K2 (P < 0.00001), corneal total HOA (P = 0.0002), and corneal coma (P = 0.00001). However, no statistically significant differences were found between the 2 protocols in uncorrected visual acuity, best-corrected visual acuity, cylinder, thinnest corneal thickness, spherical aberration, or trefoil. The 5-minute protocol was associated with a significantly lower mean change in the central corneal thickness for secondary outcomes. In addition, no significant differences were found between the 2 protocols for postoperative complications.

Conclusions:

The 10-minute protocol had better K1, K2, and HOA outcomes than the 5-minute protocol, but no statistically significant differences in the other outcomes.
Risk of Gastrointestinal Infections After Initiating Vedolizumab and Anti-TNFα Agents for Ulcerative Colitis
Authors: Dalal Rahul S. , Mitri Jennifer , Goodrick Hannah , Allegretti Jessica R.
Published: September 2022

Goals:

Characterize and compare the risk of Clostridioides difficile infection (CDI) and cytomegalovirus colitis (CMVC) after initiation of vedolizumab or anti-tumor necrosis factor (TNF)α agents for ulcerative colitis (UC).

Background:

Immunosuppression is a risk factor for gastrointestinal infections including CDI and CMVC among patients with UC; however, the risk according to the biological class is poorly understood.

Study:

A retrospective cohort study of adults with UC involving the initiation of vedolizumab or anti-TNFα agents during June 1, 2014 to December 31, 2020 was conducted at a large academic health system. The primary outcomes for both CDI and CMVC analyses were first CDI or CMVC after biological initiation. The secondary outcome for the CDI analysis was severe CDI (>10,000 white blood cells or serum creatinine >1.5 mg/dL). Independent variables included demographics and UC history/severity factors. Inverse probability of treatment weighted Cox regression was performed to assess the hazard of CDI by biological group. Due to few outcomes, CMVC was reported descriptively.

Results:

A total of 805 UC patients initiated vedolizumab (n=195) or anti-TNFα agents (n=610). There were 43 CDIs and 11 severe CDIs over 1436 patient-years. The inverse probability of treatment weighted Cox regression demonstrated no association between CDI and vedolizumab versus anti-TNFα (hazard ratio 0.33, 95% confidence interval 0.05-2.03), but identified a significantly lower hazard of severe CDI for vedolizumab versus anti-TNFα (hazard ratio 0.10, 95% confidence interval 0.01-0.76). There were 5 cases of CMVC, all in the anti-TNFα group.

Conclusions:

There was a lower adjusted risk of severe CDI but not total CDI associated with vedolizumab. CMVC was not observed after initiating vedolizumab. These findings may provide reassurance regarding the use of vedolizumab when also considering the risk of gastrointestinal infections.
The Potential for Selective Cyclin-Dependent Kinase 4/6 Inhibition in the Therapy for Head and Neck Squamous Cell Carcinoma
Authors: Adkins Douglas , Ley Jessica , Cohen Jared , Oppelt Peter
Published: September 2022

Preclinical data support investigation of selective CDK4/6 inhibition as a therapeutic strategy for human papillomavirus (HPV)–unrelated head and neck squamous cell carcinoma (HNSCC). Phase 1 clinical trials established the feasibility of combining palbociclib with cetuximab in patients with recurrent or metastatic HNSCC. Nonrandomized phase II trials showed that palbociclib plus cetuximab resulted in efficacy outcomes better than cetuximab in biomarker-unselected, platinum-resistant or cetuximab-resistant, HPV-unrelated HNSCC. A double-blind, randomized phase II trial (PALATINUS) evaluated the efficacy of palbociclib or placebo and cetuximab in patients with biomarker-unselected, platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC. Palbociclib and cetuximab did not significantly prolong overall survival compared with placebo and cetuximab. However, correlative biomarker analyses identified that trends for better overall survival with palbociclib and cetuximab were observed in certain prespecified subsets; the largest reduction in risk of death with palbociclib versus placebo and cetuximab occurred in the subset with CDKN2A mutations. Several phase II–III trials are underway investigating palbociclib in biomarker-selected patients with HPV-unrelated locally advanced or recurrent or metastatic HNSCC.
HER2 and HER3 as Therapeutic Targets in Head and Neck Cancer
Authors: Saddawi-Konefka Robert , Schokrpur Shiruyeh , Lui Asona J. , Gutkind J. Silvio
Published: September 2022

Work over the past several decades has identified that aberrations in the ErbB signaling pathways are key drivers of oncogenesis, and concurrent efforts to discover targetable vulnerabilities to counter this aberrant oncogenic signaling offer tremendous promise in treating a host of human cancers. These efforts have been centered primarily on EGFR (also known as HER1), leading to the discovery of the first targeted therapies approved for head and neck cancer. More recently, HER2 and HER3 signaling pathways have been identified as highly dysregulated in head and neck cancer. This review highlights the HER2 and HER3 signaling pathways and clinical efforts to target these receptors and their aberrant signaling to treat head and neck squamous cell carcinomas and other head and neck malignancies, including salivary gland carcinomas. This includes the use of small molecule inhibitors and blocking antibodies, both as single agents or as part of multimodal precision targeted and immunotherapies.
Cross-sectional Analysis of Instagram Use in American Plastic Surgery Practices
Authors: Sultan Darren L. , Nazarian Sheila S. , Furnas Heather J. , Amalfi Ashley N. , Perrotti John , Clappier Mona , Siddiqui Sabrina , Suydam Rebecca , Barnett Sarah , Tanna Neil
Published: September 2022

Background:

The growth of social media has transformed advertising within plastic surgery. While recent studies have characterized these developments, objective analysis is needed.

Methods:

This is a cross-sectional analysis of online media use by American Society of Plastic Surgeons (ASPS) members who received board-certification in 2000, 2005, 2010, 2015 and 2019. Online searches and StatShow revealed social media and website metrics. Metropolitan-based practices were determined using the Department of Agriculture’s continuum codes. Descriptive and quantitative analyses were used to make inferences regarding study aims.

Results:

This study included 811 surgeons. 58.6% had practice websites and 43.9% had professional Instagram accounts. Instagram use was widespread across subspecialties, and there was no significant difference in the number of followers by subspecialty (p = 0.34). Year of certification had no significant effect on the number of followers (p = 0.12); however, recently certified and seasoned members had the fewest. Collectively, the top 1% of surgeons had more followers than the remaining 99% combined. Those with metropolitan-based practices had significantly higher website traffic (p = 0.01) but no difference in the number of followers (p = 0.88). There was no evidence that the number of followers or posts per month correlated with website traffic (R2 = 0.004 and 0.036, respectively).

Conclusions:

The study demonstrates findings from a cross-sectional analysis of plastic surgeons from different training backgrounds, regions, and tenure. The use of Instagram in professional practice is widespread, but there is no correlation between its use and increased website traffic.
USP25 UPREGULATION BOOSTS GSDMD-MEDIATED PYROPTOSIS OF ACINAR CELLS IN ACUTE PANCREATITIS
Authors: Lv Hui , Liu Xuejin , Zhou Hongtao
Published: September 2022

Acute pancreatitis (AP) is an inflammation-associated disorder in the digestive system. Ubiquitin-specific peptidase 25 (USP25) can modulate inflammation in diseases. This study expounded on the role of USP25 in pyroptosis of acinar cells in AP. Acinar cells were treated with lipopolysaccharide (LPS) and caerulein (CRE) to induce AP. Afterward, the expression patterns of USP25, microRNA (miR)-10a-5p, and Krüppel-like factor 4 (KLF4) in acinar cells were examined. Then, acinar cell viability and levels of NLR family pyrin-domain containing 3 (NLRP3), cleaved caspase-1, cleaved N-terminal gasdermin D (GSDMD-N), interleukin (IL)-1β, and IL-18 were determined. We observed that USP25 was highly expressed in AP models, and silencing USP25 increased cell viability and inhibited pyroptosis of AP acinar cells. The bindings of USP25 to KLF4 and miR-10a-5p to KLF4 and the GSDMD 3′UTR sequence were validated. We found that USP25 binding to KLF4 inhibited ubiquitination degradation of KLF4, KLF4 transcriptionally decreased miR-10a-5p expression, and miR-10a-5p targeted GSDMD expression. Finally, rescue experiments proved that KLF4 overexpression or miR-10a-5p suppression enhanced pyroptosis of AP acinar cells. Overall, USP25 stabilized KLF4 expression through deubiquitination, limited miR-10a-5p expression, and increased GSDMD expression, finally promoting pyroptosis of acinar cells in AP.
Lipopolysaccharide-Preconditioned Mesenchymal Stem Cell Transplantation Attenuates Critical Persistent Inflammation Immune Suppression and Catabolism Syndrome in Mice
Authors: Chen Xiancheng , Chen Ming , Yang Yang , Xu Can , Lu Huimin , Xu Yali , Li Xiaojing , Wei Yu , Zhu Zhanghua , Ding Yitao , Yu Wenkui
Published: September 2022

Background

Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is associated with high mortality and high health care costs, and there is currently no effective target treatment. Mesenchymal stem cells (MSCs) possess multipotent immunomodulatory properties. Lipopolysaccharide (LPS)-preconditioned type 1 MSCs (MSC1s) are potentially beneficial for PIICS treatment because of their pro-inflammatory, anti-infective, and healing properties. Here, we investigated the therapeutic efficacy and mechanisms of action of MSC1s in PIICS.

Methods

We previously optimized a reaggravated PIICS mouse model, which was employed in this study. PIICS mice were subjected to cecal ligation and puncture (CLP) on day 1 and LPS injection on day 11. Subsequently, the mice were treated with or without MSC1s. Animal survival and phenotypes, along with the levels of catabolism, inflammation, and immunosuppression, were evaluated. MSC1s were co-cultured with CD8+ T cells in vitro, and inflammatory cytokine levels and CD8+ T cell function were assessed.

Results

MSC1 transplantation alleviated weight loss and muscle wasting, inhibited catabolism and inflammation, and considerably improved the proportion and function of CD8+ T cells in the PIICS mice. After co-culture with MSC1s, the expression levels of CD107a and interferon gamma increased, whereas the expression level of programmed death 1 (PD-1) decreased significantly in CD8+ T cells. MSC1s also promoted pro-inflammatory cytokine secretion and reduced the concentration of soluble PD-L1 in vitro.

Conclusions

MSC1s can protect mice against critical PIICS, partly by enhancing CD8+ T cell function. Therefore, MSC1 transplantation is a novel therapeutic candidate for PIICS.
Infrared thermography-based body-surface thermal inhomogeneity monitoring to assess the severity of hypoperfusion in critically ill patients
Authors: Luo Jing-chao , Zhang Jia-dong , Zhao Qin-yu , Wang Huan , Tu Guo-wei , Luo Ming-hao , Huang Dan-lei , Zhang Ji-yang , Lu Wei , Gao Fei , Luo Zhe
Published: September 2022

Background

Uneven body-surface thermal distribution is a manifestation of hypoperfusion and can be quantified by infrared thermography. Our aim was to investigate whether body-surface thermal inhomogeneity could accurately evaluate the severity of patients at risk of hypoperfusion.

Methods

This was a prospective cohort study in which infrared thermography images were taken from unilateral legs of critically ill patients at high-risk of hypoperfusion in a cardiac surgical intensive care unit. For each patient, five body-surface thermal inhomogeneity parameters, including standard deviation (SD), kurtosis, skewness, entropy and low temperature area rate (LTAR), were calculated. Demographic, clinical, and thermal characteristics of deceased and living patients were compared. The risk of mortality and capillary refill time (CRT) were chosen as the primary outcome and benchmarking parameter for hypoperfusion, respectively. The area under the receiver operating characteristic curve (AUROC) was used to evaluate predictive accuracy.

Results

373 patients were included and 55 (14.7%) died during hospital stay. Of inhomogeneity parameters, SD (0.738) and LTAR (0.768), had similar AUROC to CRT (0.757) for assessing mortality risk. Besides, there was a tendency for LTAR (1 to 3 to 7%) and SD (0.81 to 0.88 to 0.94 °C) to increase in normotensive, hypotensive, and shock patients. These thermal parameters are associated with CRT, lactate, and blood pressure. The AUROC of a combined prediction incorporating three thermal inhomogeneity parameters (SD, kurtosis and entropy) was considerably higher at 0.866.

Conclusions

Body-surface thermal inhomogeneity provided a non-invasive and accurate assessment of the severity of critically ill patients at high-risk of hypoperfusion.
BACTERIAL PATHOGEN–ASSOCIATED MOLECULAR PATTERNS UPREGULATE HUMAN GLUCOCORTICOID RECEPTOR EXPRESSION IN PERIPHERAL BLOOD MONONUCLEAR CELLS
Authors: Greenhalgh David G. , Green Tajia L. , Lim Debora , Cho Kiho
Published: September 2022

It is well known that bacterial components (pathogen-associated molecular patterns [PAMPs]) induce a proinflammatory response through pattern recognition receptor signaling. What is not known, however, is how the inflammatory response is downregulated. We hypothesize that bacterial products initiate compensatory anti-inflammatory responses by inducing expression of the human glucocorticoid receptor (hGR). Peripheral blood mononuclear cells (PBMCs) were isolated from leukocytes concentrated from single human donors (Leukopaks). PBMCs were treated with a gram-negative bacterial component, LPS, or gram-positive bacterial components, lipoteichoic acid (LTA) or peptidoglycan (PGN), for 1, 3, or 13 h. Protein expression of hGR was evaluated by Western blot analysis. RNA was extracted from similarly treated cells for reverse transcription-polymerase chain reaction analysis of hGR and cytokine expression. At 13 h after LPS treatment, there was an increase in the reference hGR protein (hGRα) expressed within some but not all PBMCs isolated from Leukopaks. There was also a dose-dependent increase in hGRα expression with increasing concentrations of PGN (10 and 50 μg/mL). LTA, however, did not affect hGRα expression. PGN also increased the mRNA expression of an hGR splice variant, hGR-B(54). The mRNA expression changes for the inflammatory cytokines were Leukopak specific. We found that cell wall components of both gram-positive and gram-negative bacteria can increase the expression of hGRα. Although these PAMPs augment the inflammatory response, it seems that there is a simultaneous upregulation of hGRα expression. Because binding of cortisol to hGRα typically induces anti-inflammatory proteins, the same PAMPs that induce an inflammatory response seem to also initiate a negative feedback system by inducing hGRα expression in PBMCs.
The Association Between Extravascular Lung Water and Critical Care Outcomes Following Bilateral Lung Transplantation
Authors: Munshi Laveena , Cypel Marcelo , Mohamed Alaa , Elhazmi Alyaa , Fan Eddy , Scales Damon , Tikkanen Jussi , Del Sorbo Lorenzo , Ferguson Niall D. , Keshavjee Shaf , Granton John
Published: September 2022

Background.

Primary graft dysfunction (PGD) is a form of acute respiratory failure that complicates 30% of bilateral lung transplants. Higher grades of PGD correlate with higher severity of respiratory failure and unfavorable outcomes. Immediate PGD determination posttransplant‚ however, is not always predictive of PGD over subsequent days or intensive care unit outcomes. We aimed to evaluate whether extravascular lung water index (ELWI) measured immediately post bilateral lung transplant was associated with higher severity of PGD at 72 h and duration of mechanical ventilation.

Methods.

We conducted a prospective, observational study of bilateral lung transplant patients admitted to the intensive care unit. ELWI measurements were performed at admission, 6, 12, 24, 36, 48, 60, and 72 h following transplant or until extubation. We evaluated the association between admission ELWI and 72-h PGD grade and duration of mechanical ventilation.

Results.

Across 56 patients enrolled, 268 transpulmonary thermodilution measurements were conducted. At admission, median ELWI increased with PGD grade (grade 1: 9 mL/kg [interquartile range (IQR), 8–11 mL/kg]‚ grade 2 [10 mL/kg (IQR, 8–12 mL/kg)]‚ and grade 3 [17 mL/kg (IQR, 14–19 mL/kg); P < 0.001]). Using multivariable Poisson regression analysis adjusting for confounders, admission ELWI elevation was associated with higher severity of PGD at 72 h (incidence rate ratio [IRR], 1.06; 95% confidence interval, 1.01-1.12) and duration of mechanical ventilation (IRR, 1.62; 95% confidence interval, 1.23-2.14). The combination of an ELWI of ≥13 mL/kg and partial pressure of oxygen/fraction of inspired oxygen ≤ 100 within 6 h of admission had high sensitivity (75%) and specificity (100%) for grade 3 PGD at 72 h (area under the curve, 0.95) and performed better than ELWI or partial pressure of oxygen/fraction of inspired oxygen alone.

Conclusions.

Our exploratory study demonstrates an association between admission ELWI and high grades of PGD at 72 h and longer duration of ventilation. These results provide the impetus to study whether goal-directed ELWI algorithms can improve transplant outcomes.
JMM Profile: Brachyspira species: the causative agent of Avian Intestinal Spirochaetosis
Authors: Passey Jade L. , La Ragione Roberto M.
Published: September 2022

The genus

Brachyspira

includes nine officially recognised species, several of which are pathogenic to mammals and birds. B. pilosicoli, B. intermedia, and

B. alvinipulli

are the causative agents of avian intestinal spirochaetosis (AIS), a gastrointestinal disease in poultry caused by the colonisation of the caeca and/ or colo-rectum by

Brachyspira

. AIS primarily affects layer hens and broiler breeders over the age of 15 weeks. The severity of symptoms can vary but typically presents as reduced growth rates, delayed onset of lay, reduced egg production, faecally stained eggs, and diarrhoea. This disease is estimated to cost the UK laying industry £18 million per annum.

Brachyspira

colonisation in humans is common in populations from developing countries and HIV-positive patients; however, it is rarely investigated as a human pathogen.
Extended genomic analyses of the broad-host-range phages vB_KmiM-2Di and vB_KmiM-4Dii reveal slopekviruses have highly conserved genomes
Authors: Smith-Zaitlik Thomas , Shibu Preetha , McCartney Anne L. , Foster Geoffrey , Hoyles Lesley , Negus David
Published: September 2022

High levels of antimicrobial resistance among members of the

Klebsiella oxytoca

complex (KoC) have led to renewed interest in the use of bacteriophage (phage) therapy to tackle infections caused by these bacteria. In this study we characterized two lytic phages, vB_KmiM-2Di and vB_KmiM-4Dii, that were isolated from sewage water against two GES-5-positive

Klebsiella michiganensis

strains (PS_Koxy2 and PS_Koxy4, respectively). ViPTree analysis showed both phages belonged to the genus Slopekvirus. rpoB gene-based sequence analysis of 108 presumptive

K. oxytoca

isolates (n=59 clinical, n=49 veterinary) found

K. michiganensis

to be more prevalent (46 % clinical and 43 % veterinary, respectively) than

K. oxytoca

(40 % clinical and 6 % veterinary, respectively). Host range analysis against these 108 isolates found both vB_KmiM-2Di and vB_KmiM-4Dii showed broad lytic activity against KoC species. Several hypothetical homing endonuclease genes were encoded within the genomes of both phages, which may contribute to their broad host range. Differences in the tail fibre protein may explain the non-identical host range of the two phages. Pangenome analysis of 24 slopekviruses found that genomes within this genus are highly conserved, with more than 50 % of all predicted coding sequences representing core genes at ≥95 % identity and ≥70 % coverage. Given their broad host ranges, our results suggest vB_KmiM-2Di and vB_KmiM-4Dii represent attractive potential therapeutics. In addition, current recommendations for phage-based pangenome analyses may require revision.