bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Safety and Efficacy of a Water-Free Cyclosporine 0.1% Ophthalmic Solution for Treatment of Dry Eye Disease: ESSENCE-2 OLE
Authors: Wirta David L. , Galor Anat , Aune Carol A. , Vollmer Patrick M. , Liang Eva , Meides Alice S. , Krösser Sonja
Published: May 2024

Purpose:

The ESSENCE-2 Open-Label Extension study aimed to demonstrate long-term safety, tolerability, and efficacy of a novel water-free, nonpreserved topical cyclosporine 0.1% ophthalmic solution (US brand name VEVYE) for patients with dry eye disease (DED).

Methods:

This was a Phase 3, prospective, multicenter, open-label, clinical study. All patients received cyclosporine 0.1% ophthalmic solution and dosed each eye twice a day for 52 weeks. Primary safety end points were ocular and nonocular adverse events (AEs). Secondary safety end points included visual acuity, biomicroscopy, intraocular pressure, and dilated fundoscopy. Efficacy end points, such as total corneal fluorescein staining (tCFS) score (National Eye Institute [NEI] Scale), ocular symptoms (visual analog scale [VAS]), and Schirmer tear test, were also assessed.

Results:

A total of 202 patients were enrolled from the ESSENCE-2 study. At week 52, 175 patients (86.6%) completed ESSENCE-2 open-label extension. A total of 55 patients (27.5%) reported 74 ocular treatment-emergent adverse events (TEAEs). The most common ocular AE was instillation site pain (6.5%), which was of mild intensity in all cases. Patients showed statistically significant improvements in all prespecified efficacy end points compared with baseline at each visit. Corneal staining improvements were early and stabilized over time while tear production improved continuously. Symptomatology improvement followed these effects with scores reaching a minimum after 1 year of treatment.

Conclusions:

The water-free cyclosporine 0.1% ophthalmic solution was safe and well tolerated during long-term use. The results demonstrated sustained 1-year efficacy, in both signs and symptoms of DED, and may help understand short and long-term healing dynamics in a predominant inflammatory DED population.
Triglyceride Glucose Index: A Potential Indicator in the Evaluation of Graves Ophthalmopathy
Authors: Gundogan Ali Osman , Belviranli Selman , Tezcan Ali , Zengin Nazmi
Published: May 2024

Purpose:

To determine the relationship between Graves ophthalmopathy (GO) and triglyceride glucose index (TGI) and to evaluate the predictive importance of this index in terms of GO activity.

Methods:

This retrospective study included 20 inactive GO patients, 20 active GO patients, and 20 healthy controls. TGI was calculated using fasting plasma triglyceride and fasting plasma glucose levels and values were compared between the groups. The receiver operating characteristics curve was used to calculate the optimal TGI cutoff value and the sensitivity and specificity of this value between active and inactive GO groups.

Results:

No significant difference was detected between the groups in terms of age and gender (p = 0.561 and p = 0.762, respectively). TGI value was 8.49 (8.41, 8.67) in the control group, 8.76 (8.74, 8.87) in the inactive GO group, and 9.06 (8.87, 9.08) in the active GO group (p < 0.001 for control group vs. inactive GO group; p < 0.001 for control group vs. active GO group; p = 0.001 for inactive GO group vs. active GO group). The optimal receiver operating characteristics cutoff value of TGI between active and inactive GO groups was 8.86 with 85% sensitivity and 75% specificity (area under curve: 0.837, p < 0.001, 95% confidence interval: 0.711–0.964).

Conclusion:

TGI was higher in both inactive and active GO patients compared with controls. It also appears that TGI may be used as a predictive marker indicating GO activity. This cheap and easily accessible parameter may be beneficial in detecting the disease and monitoring its activity in clinical practice.
Influence of the Phenylephrine Test in Outcomes of External Levator Advancement for Involutional Ptosis
Authors: Chaneac Livia , Bertrand Baptiste , Schmid Amaury , Guyot Laurent , David Thierry , Dalmas Florian
Published: May 2024

Purpose:

This study aims to evaluate the influence of preoperative phenylephrine testing on the surgical outcome of patients undergoing surgery for involutional ptosis by external levator advancement.

Methods:

This was an observational, monocentric, retrospective study. Fifty-one eyelids from 32 patients, who had surgery between January 2018 and May 2023, were included for analysis. Preoperative clinical examination data were collected. Evaluation was performed at 1 month postoperatively. Surgical success was defined by a postoperative margin reflex distance between 3 and 5 mm inclusive. Symmetry success was defined by a difference in margin reflex distance between the 2 upper eyelids of no more than 1 mm.

Results:

The surgical success rate was 86%. A positive preoperative phenylephrine test was significantly associated with a better surgical success rate (p = 0.01), including on symmetry (p = 0.01). The secondary outcomes, namely preoperative margin reflex distance, function of the upper eyelid levator muscle, and unilaterality of surgery, were not statistically associated with surgical outcome.

Conclusions:

The phenylephrine test is a predictive factor of surgical success in patients undergoing external levator advancement. Our study suggests that patients with a negative phenylephrine test should be overcorrected intraoperatively.
Isolated Superior Ophthalmic Vein Thrombosis
Authors: Yi Richard , Gabbard Ryan , Pratt James , Chang Kenneth , Patel Rakesh M. , Robinson Mark
Published: May 2024

The purpose of this article is to report a rare case of isolated superior ophthalmic vein thrombosis. A 74-year-old female presented to the emergency department with a sudden onset of eye pain and bulging. Ophthalmological examination was remarkable for proptosis and ptosis with chemosis of the OS. Neuroimaging demonstrated an isolated superior ophthalmic vein thrombosis secondary to presumed thrombosis of the superior vein varix. Hypercoagulable, infectious, and autoimmune lab workups were unremarkable. The patient was initiated on anticoagulation with the eventual resolution of her symptoms. Isolated superior ophthalmic vein thrombosis is an uncommon diagnosis that requires urgent evaluation to prevent vision loss. Risk factors are multifactorial with infectious being the most common etiology. Our case is unique in that there was no identifiable risk factor.
A Qualitative Study of A Health Center-Based Mobile Produce Market
Authors: Rudel Rebecca K. , Byhoff Elena , Fielman Sarah B. , Strombotne Kiersten L. , Drainoni Mari-Lynn , Greece Jacey A.
Published: May 2024

Healthcare-based food assistance programs have the potential to improve patients’ food security, but are underutilized. We conducted a qualitative study of user and staff perceptions of an on-site mobile market at a federally-qualified health center (FQHC). Five themes were identified: 1) financial need drives the decision to use the market, 2) people attend specifically to receive healthy food, 3) users feel a connection to the FQHC, which increases participation, 4) social networks increase usage of the program, and 5) long lines, inclement weather, inaccessibility, and inconsistent marketing and communication are attendance barriers. Findings should inform implementation of future healthcare-based food assistance programs.
Impact of metabolic bariatric surgery on outcomes and the 10-year risk of major adverse cardiovascular events during a 7-year period: a retrospective cohort study
Authors: Pan Hsin-Mei , Lee Wei-Jei , Ser Kong-Han , Soong Tien-Chou , Lee Ming-Hsien , Lin Chien-Hua , Hsu Kuo-Feng
Published: May 2024

Background:

Metabolic bariatric surgery offers enduring weight reduction and alleviation of obesity-related comorbidities, including dyslipidemia, diabetes, hypertension, and major adverse cardiovascular events (MACE). Long-term data on one-anastomosis gastric bypass (OAGB) and single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy (SADJB-SG) is lacking, necessitating this investigation.

Materials and Methods:

In this multicenter prospectively-collected retrospective observational study, 830 adult Taiwanese patients (682 OAGB, 148 SADJB-SG) who underwent surgery from 1 January 2011 to 31 December 2017, were initially identified. Following protocol, 224 patients (177 OAGB, 47 SADJB-SG) with complete follow-up data at various intervals up to 3 years after surgery were included in the final analysis. The study’s primary focus is to evaluate the long-term safety, efficacy, and durability of OAGB and SADJB-SG in promoting weight loss and diabetes remission. Additionally, changes in 10-year and lifetime risks of MACE before and 3-year after surgery are assessed using Taiwan MACE risk prediction model and the China-PAR project model.

Results:

SADJB-SG patients exhibit higher diabetes prevalence, lower BMI, and more severe diabetes compared to OAGB. Both groups demonstrate significant improvements in BMI, diabetes, hypertension, and dyslipidemia three years after surgery, with the most substantial improvements occurring in the second year. The Taiwan MACE risk model reveals a significant reduction in 10-year MACE and stroke risks for both groups. The China-PAR project model indicates a synchronized reduction in atherosclerotic cardiovascular disease 10-year and lifetime risk in both OAGB and SADJB-SG groups.

Conclusions:

OAGB and SADJB-SG exhibit sustained improvements in weight reduction and obesity-related comorbidities over 3 years after surgery. Notably, both procedures contribute to a substantial reduction in 10-year MACE, stroke, and atherosclerotic cardiovascular disease risks. These findings underscore the efficacy of OAGB and SADJB-SG in the context of metabolic bariatric surgery.
A Randomized Crossover Study in Single-Sided Deafness Comparing a Cartilage Conduction CROS System and an Air-Conduction CROS System
Authors: Takaki Ken , Kashio Akinori , Nozaki Etsushi , Kanai Tomomi , Kamogashira Teru , Saze Fumikazu , Uranaka Tsukasa , Urata Shinji , Koyama Hajime , Kawahara Yoshihiro , Yamasoba Tatsuya
Published: May 2024

Objective

To investigate if cartilage conduction (CC) rerouting devices are noninferior to air-conduction (AC) rerouting devices for single-sided deafness (SSD) patients by measuring objective and subjective performance using speech-in-noise tests that resemble a realistic hearing environment, sound localization tests, and standardized questionnaires.

Study Design

Prospective, single-subject randomized, crossover study.

Setting

Anechoic room inside a university.

Patients

Nine adults between 21 and 58 years of age with severe or profound unilateral sensorineural hearing loss.

Interventions

Patients’ baseline hearing was assessed; they then used both the cartilage conduction contralateral routing of signals device (CC-CROS) and an air-conduction CROS hearing aid (AC-CROS). Patients wore each device for 2 weeks in a randomly assigned order.

Main Outcome Measures

Three main outcome measures were 1) speech-in-noise tests, measuring speech reception thresholds; 2) proportion of correct sound localization responses; and 3) scores on the questionnaires, “Abbreviated Profile of Hearing Aid Benefit” (APHAB) and “Speech, Spatial, and Qualities of Hearing Scale” with 12 questions (SSQ-12).

Results

Speech reception threshold improved significantly when noise was ambient, and speech was presented from the front or the poor-ear side with both CC-CROS and AC-CROS. When speech was delivered from the better-ear side, AC-CROS significantly improved performance, whereas CC-CROS had no significant effect. Both devices mainly worsened sound localization, whereas the APHAB and SSQ-12 scores showed benefits.

Conclusion

CC-CROS has noninferior hearing-in-noise performance except when the speech was presented to the better ear under ambient noise. Subjective measures showed that the patients realized the effectiveness of both devices.
Quality of Life for Patients with Sporadic Small Vestibular Schwannomas Following Middle Fossa Craniotomy
Authors: Jiramongkolchai Pawina , Vacaru Alexandra , La Monte Olivia , Lee Joshua , Schwartz Marc S. , Friedman Rick A.
Published: May 2024

Objective

To evaluate quality-of-life outcomes for patients with vestibular schwannomas (VS) undergoing a middle cranial fossa (MCF) approach.

Study Design

Prospective study from 2018 to 2023.

Setting

Tertiary academic institution.

Patients

Adults with sporadic VS.

Interventions

MCF

Main Outcome Measures

The primary outcome measure was the change in preoperative and 1-year postoperative Penn Acoustic Neuroma Quality-of-life (PANQOL) scores. Secondary outcome measures included hearing preservation and facial nerve function.

Results

Of the 164 patients who underwent MCF for sporadic VS, 78 patients elected to voluntarily complete preoperative PANQOL assessments prior to surgery. Seventy-one (91%) of those 78 patients completed postoperative PANQOL surveys. Fifty (70%) of the respondents were female and the median age was 48 years (range, 27–71 years). Overall, at 1-year postsurgery, a minimal clinically important difference (MCID) was obtained in the hearing (mean difference, 10.5; 95% confidence interval [CI], 4.3–16.7) and anxiety (mean difference, 18.8; 95% CI, 11.7–25.9) domains. For patients with hearing preservation (n = 48, 68%), MCIDs were reached in the hearing (mean difference, 13.4; 95% CI, 6.3–20.6), anxiety (mean difference, 20.8; 95% CI, 11.8–29.9), energy (mean difference, 13.7; 95% CI, 3.6–23.8), pain (mean difference, 13.7; 95% CI, 3.6–23.8) domains, and overall PANQOL scores (mean difference, 12.7; 95% CI, 7.1–18.3). Postoperatively, 64 (90%) patients maintained a House-Brackmann I.

Conclusions

To our knowledge, this is the largest study examining disease-specific QOL for VS patients undergoing MCF. Based on our institution's experience, MCF approach for small VS is associated with clinically meaningful improvements in QOL, hearing preservation, and excellent facial nerve outcomes.
Comparison of the benefits and risks of hemihepatic inflow occlusion: a systematic review and meta-analysis
Authors: Guo Lianming , Gong Weiqiang
Published: May 2024

Background:

Application of hemihepatic inflow occlusion (HIO) and total hepatic inflow occlusion (TIO) are two common approaches for hepatectomy. However, their efficacy and safety remain controversial.

Methods:

Randomized control trials (RCTs) published before 15t January 2023 were included by a systematic literature search, which compared the clinical outcomes between HIO and TIO. The primary outcome was the estimated blood loss (EBL). Three independent authors screened and extracted the data and resolved disagreements by consensus. The ROB2.0 tool was used for evaluating the risk of bias.

Results:

A total of 1026 patients (511 TIO and 515 HIO) from 9 studies were analyzed in the meta-analyses. The EBL between TIO and HIO group was similar, while HIO was associated with a lower proportion of patients required transfusion (P=0.002), less units of blood transferred (P<0.001) and a lower overall complication rate (P=0.008). There were no significant differences between TIO and HIO in mortality (P=0.37), length of stay (P=0.97), bile leak rate (P=0.58), liver failure rate (P=0.96), reoperation rate (P=0.48), postoperative haemorrhage rate (P=0.93) and incidence of postoperative ascites (P=0.96). The operative time of HIO was usually no more than 15 min longer than that of TIO (P<0.001).

Conclusions:

Comparing with the TIO, HIO increased the operative time and failed to further reduce the EBL in patients with liver surgery. However, despite the complexity of the operation, HIO was recommended due to the similar effect on the consumption of blood products and the postoperative complications.
Safety of Monoclonal Antibodies as Treatment for Coronavirus Disease 2019 (COVID-19) During Pregnancy
Authors: Bugaighis Mona , Milosh Brooke , Cervia Joseph
Published: May 2024

OBJECTIVE:

Pregnant patients are at increased risk of severe illness, in-hospital mortality, and preterm birth in the setting of coronavirus disease 2019 (COVID-19); however, they often are excluded from clinical trials that analyze improved therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thus, there are relatively few available data that examine the safety of monoclonal antibodies (mAbs) in pregnant patients with COVID-19, which we aimed to explore in this systematic review.

DATA SOURCES:

We searched PubMed, Cochrane, EMBASE, and Google Scholar on September 30, 2022. Included studies encompassed English-language case reports with at least five participants, cross-sectional studies, case–control studies, cohort studies, retrospective or prospective chart reviews, and randomized controlled trials that enrolled pregnant women who received SARS-CoV-2–targeted mAbs. Studies were screened for eligibility using Covidence according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines and were subsequently evaluated for risk of bias with the JBI critical appraisal checklist.

TABULATION, INTEGRATION, AND RESULTS:

Initial search yielded 616 studies; 13 publications were ultimately eligible. Pregnant patients were treated with SARS-CoV-2–neutralizing mAbs casirivimab-imdevimab, bamlanivimab, or bamlanivimab-etesevimab. A total of 365 patients were treated with casirivimab-imdevimab, 13 were treated with bamlanivimab, and 11 were treated with bamlanivimab-etesevimab. There were no cases of maternal mortality. Eighteen of the 389 patients had adverse effects related to mAb administration—all resolved. Of the patients treated with casirivimab-imdevimab, there were 35 preterm deliveries, two fetal deaths, one neonatal death due to sepsis, five cases of preterm prelabor rupture of membranes (PROM), one case of PROM, and 24 neonatal intensive care unit (NICU) admissions. Of the patients treated with bamlanivimab, there was one case of preterm PROM and one preterm delivery. There were no NICU admissions in the bamlanivimab or bamlanivimab-etesevimab cohorts.

CONCLUSION:

Preliminary data suggest that neutralizing mAb treatment for COVID-19 in pregnant patients is safe. However, treatment-associated events support the importance of clinical trials to determine the statistical significance of maternal and fetal outcomes in pregnant patients treated with SARS-CoV-2–targeted mAbs.
Patient Outcomes Compared Between Admissions Coordinated by the Transfer Center and Emergency Department at a U.S. Tertiary Care Hospital
Authors: Pagali Sandeep R. , Ryu Alexander J. , Fischer Karen M. , Parikh Riddhi S. , Newman James S. , Burton M. Caroline
Published: May 2024

Background

Patient admissions at a U.S. tertiary care hospital occur via the emergency department (ED), or transfer center. We aim to compare the clinical outcomes of patients admitted from the ED to admissions coordinated by the transfer center.

Methods

Admissions to Mayo Clinic Hospital, Rochester, MN, between July 2019 to June 2021 were identified in this retrospective study and categorized into two cohorts—transfer center and ED. The two cohorts were then matched for age, sex, admitting service, and Charlson Comorbidity Index. Univariate and multivariate analyses were performed to compare hospital length of stay (LOS), mortality, 30-day mortality, and 30-day readmissions between the two cohorts.

Results

73,685 admissions were identified, of which 24,262 (33%) were transfer center admissions. In the matched cohorts (n = 19,093, each), in-hospital mortality (2.4% versus 1.9%), 30-day mortality (5.4% versus 3.9%), 30-day readmission (12.7% versus 7.2%), and LOS (6.4 days versus 5.1 days) were significantly higher (P < 0.001) among the admissions coordinated by transfer center. A higher palliative care consultation rate (9.4% versus 6.2%, P < 0.001), and a lower proportion of home discharges home (76.2% versus 82.5%, P < 0.001) among transfer center admissions was observed. Similar findings were noted in multivariate analysis, even when adjusting for LOS.

Conclusions

Transfer center admissions had higher in-hospital mortality, LOS, 30-day mortality, and 30-day readmission compared to ED admissions. This study also highlights new considerations for palliative care consultation before transfer acceptance, especially to avoid futile transfers. Additional studies analyzing factors behind the outcomes of transfer center admissions are required.
Telehealth and Telemedicine
Authors: Bonica Gina M. , Johns Richard W. , Jadvar Hossein
Published: May 2024

Telehealth and telemedicine experienced remarkable growth during and after the recent COVID-19 pandemic. Telehealth is generally defined as nonclinical services that employ telecommunication technology. Telemedicine refers more specifically to remote clinical services including diagnosis, monitoring, and treatment. Nuclear medicine is no exception in employing telemedicine increasingly in clinical practice for image interpretation and treatment consultation and care delivery supervision. There is no doubt that soon, the use of tele-nuclear medicine will increase, comparable to the employment of telecommunication in other fields of medicine. We review the medicolegal and regulatory aspects of the evolution in the clinical practice of medicine through telehealth and telemedicine.
A Review of Socioeconomic Disparities in Submucous Cleft Diagnosis and Outcomes
Authors: Trotter Collean , Choi Dylan G. , Stoneburner Jacqueline , Roohani Idean , Alfeerawi Sarah , Fahradyan Artur , Lee Jessica A. , Magee William P. , Urata Mark M. , Hammoudeh Jeffrey A.
Published: May 2024

Submucous cleft palate (SMCP) is a common congenital anomaly characterized by a diastasis of the levator veli palitini muscle. The subtlety of SMCP on physical examination can contribute to diagnostic delays. This study aims to analyze the factors contributing to delays in care and subsequent postoperative outcomes in patients with SMCP. All patients with surgical indications for SMCP who underwent palatoplasty at an urban academic children’s hospital were included. Patient socioeconomic characteristics, medical history, and postoperative outcomes were collected. Patients were compared based on insurance type and government assistance utilization. Statistical analyses including independent t-test, Wilcoxon ranked sum test, χ2 analyses, Fisher’s exact test, and stepwise logistic regression were performed. Among the 105 patients with SMCP, 69.5% (n=73) had public insurance and 30.5% (n=32) private. Patients with public insurance were diagnosed later (5.5±4.6 versus 2.6±2.4 years old; p<0.001) and underwent palatoplasty later (7.3±4.1 versus 4.4±3.4 years old; p<0.001) than those with private insurance. Patients receiving government assistance experienced higher rates of post-surgical persistent velopharyngeal insufficiency (74.5% versus 44.8%; p=0.006). The authors’ results suggest a disparity in the recognition and treatment of surgical SMCP. Hence, financially vulnerable populations may experience an increased risk of inferior speech outcomes and subsequent therapies and procedures.
Intraductal Papillomas From the Parotid Gland
Authors: Mao Lei , Lin Rong-Zhi , Fan Da-Ge
Published: May 2024

Intraductal papillomas have been mostly described in minor salivary glands but are extremely rare in the parotid gland. Consequently, limited information is available to guide otolaryngologists and pathologists in managing intraductal papillomas, specifically in the parotid gland. Diagnosing intraductal papillomas in this location poses significant challenges. In this report, the authors present a new case and first conduct a systematic literature review of the intraductal papillomas originating from the parotid gland. This study contributes valuable insights that can improve diagnostic accuracy, providing more precise treatments, and patient outcomes in cases of intraductal papillomas in the parotid gland.
The Effects of Sustained Immunosuppression Withdrawal After Liver Transplantation on Metabolic Syndrome
Authors: Angelico Roberta , Sensi Bruno , Toti Luca , Campanella Elisa , Lenci Ilaria , Baiocchi Leonardo , Tisone Giuseppe , Manzia Tommaso Maria
Published: May 2024

Background.

Liver transplant (LT) recipients often experience adverse effects of immunosuppressive (IS) drugs, especially on metabolic profiles. Selected LT recipients can achieve successful IS withdrawal; however, its effects on metabolic syndrome (MS) are unknown.

Methods.

This is a retrospective single-center study investigating the incidence and/or regression of MS in 75 selected LT recipients who were previously enrolled in prospective IS withdrawal trials between 1999 and 2017. Patients who were transplanted due to nonalcoholic steatohepatitis/metabolic-associated fatty liver disease were excluded, as well as those with a follow-up <3 y after IS weaning.

Results.

Forty-four patients (58.7%) achieved sustained withdrawal or minimization of immunosuppression (WMIS) and 31 patients (41.3%) required reintroduction of immunosuppression (no-WMIS). Among LT recipients who were metabolically healthy (n = 52, 69.3%) before the start of IS weaning, there was a significantly lower rate of de novo MS in WMIS patients compared with no-WMIS patients after 5 y (8.3% and 47.8%, respectively, P = 0.034). Of 23 LT recipients (30.7%) who had MS at the time of commencing IS withdrawal, complete regression of MS was observed in 47.1% of WMIS patients and in none (0%) of the no-WMIS patients after 5 y (P = 0.054). Furthermore, individual components of MS were better controlled in IS-weaned patients, such as arterial hypertension and abnormal serum lipids.

Conclusions.

Achievement of sustained IS withdrawal reduces the incidence of de novo MS development in metabolically healthy patients and increases the likelihood of MS regression in patients with established MS. The foreseeable long-term beneficial effects of these favorable metabolic changes on morbidity and mortality of LT recipients require further investigation.
Outpatient and Ambulatory Extended Recovery Robotic Hepatectomy: Multinational Study of 307 Cases
Authors: Park James O , Lafaro Kelly , Hagendoorn Jeroen , Melstrom Laleh , Gerhards Michael F , Görgec Burak , Marsman Hendrik A , Thornblade Lucas W , Pilz da Cunha Gabriela , Yang Frank F , Labadie Kevin P , Sham Jonathan G , Swijnenburg Rutger-Jan , He Jin , Fong Yuman
Published: May 2024

BACKGROUND:

For open minor hepatectomy, morbidity and recovery are dominated by the incision. The robotic approach may transform this “incision dominant procedure” into a safe outpatient procedure.

STUDY DESIGN:

We audited outpatient (less than 2 midnights) robotic hepatectomy at 6 hepatobiliary centers in 2 nations to test the hypothesis that the robotic approach can be a safe and effective short-stay procedure. Establishing early recovery after surgery programs were active at all sites, and home digital monitoring was available at 1 of the institutions.

RESULTS:

A total of 307 outpatient (26 same-day and 281 next-day discharge) robotic hepatectomies were identified (2013 to 2023). Most were minor hepatectomies (194 single segments, 90 bi-segmentectomies, 14 three segments, and 8 four segments). Thirty-nine (13%) were for benign histology, whereas 268 were for cancer (33 hepatocellular carcinoma, 27 biliary, and 208 metastatic disease). Patient characteristics were a median age of 60 years (18 to 93 years), 55% male, and a median BMI of 26 kg/m2 (14 to 63 kg/m2). Thirty (10%) patients had cirrhosis. One hundred eighty-seven (61%) had previous abdominal operation. Median operative time was 163 minutes (30 to 433 minutes), with a median blood loss of 50 mL (10 to 900 mL). There were no deaths and 6 complications (2%): 2 wound infections, 1 failure to thrive, and 3 perihepatic abscesses. Readmission was required in 5 (1.6%) patients. Of the 268 malignancy cases, 25 (9%) were R1 resections. Of the 128 with superior segment resections (segments 7, 8, 4A, 2, and 1), there were 12 positive margins (9%) and 2 readmissions for abscess.

CONCLUSIONS:

Outpatient robotic hepatectomy in well-selected cases is safe (0 mortality, 2% complication, and 1.6% readmission), including resection in the superior or posterior portions of the liver that is challenging with nonarticulating laparoscopic instruments.
Systemic Inflammatory Effect of Hypobaria During Aeromedical Evacuation after Porcine Traumatic Brain Injury
Authors: Price Adam D , Baucom Matthew R , Becker Ellen R , Archdeacon Chad M , Smith Maia P , Caskey Chelsea , Schuster Rebecca , Blakeman Thomas C , Strilka Richard J , Pritts Timothy A , Goodman Michael D
Published: May 2024

BACKGROUND:

Traumatic brain injury (TBI)-related morbidity is caused largely by secondary injury resulting from hypoxia, excessive sympathetic drive, and uncontrolled inflammation. Aeromedical evacuation (AE) is used by the military for transport of wounded soldiers to higher levels of care. We hypothesized that the hypobaric, hypoxic conditions of AE may exacerbate uncontrolled inflammation after TBI that could contribute to more severe TBI-related secondary injury.

STUDY DESIGN:

Thirty-six female pigs were used to test TBI vs Sham TBI, hypoxia vs normoxia, and hypobaria vs ground conditions. TBI was induced by controlled cortical injury, hypobaric conditions of 12,000 ft were established in an altitude chamber, and hypoxic exposure was titrated to 85% SpO2 while at altitude. Serum cytokines, ubiquitin C-terminal hydrolase L1, and TBI biomarkers were analyzed via ELISA. Gross analysis and staining of cortex and hippocampus tissue was completed for glial fibrillary acidic protein and phosphorylated tau.

RESULTS:

Serum interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly elevated after TBI in pigs exposed to altitude-induced hypobaria/hypoxia, as well as hypobaria alone, compared with ground level/normoxia. No difference in TBI biomarkers after TBI or hypobaric, hypoxic exposure was noted. No difference in brain tissue glial fibrillary acidic protein or phosphorylated tau when comparing the most different conditions of Sham TBI + ground or normoxia with the TBI + hypobaria/hypoxia group was noted.

CONCLUSIONS:

The hypobaric environment of AE induces systemic inflammation after TBI. Severe inflammation may play a role in exacerbating secondary injury associated with TBI and contribute to worse neurocognitive outcomes. Measures should be taken to minimize barometric and oxygenation changes during AE after TBI.
Timing-specific parental effects of ocean warming in a coral reef fish
Authors: Bonzi L. C. , Spinks R. K. , Donelson J. M. , Munday P. L. , Ravasi T. , Schunter C.
Published: May 2024

Population and species persistence in a rapidly warming world will be determined by an organism’s ability to acclimate to warmer conditions, especially across generations. There is potential for transgenerational acclimation but the importance of ontogenetic timing in the transmission of environmentally induced parental effects remains mostly unknown. We aimed to disentangle the effects of two critical ontogenetic stages (juvenile development and reproduction) to the new-generation acclimation potential, by exposing the spiny chromis damselfish
Acanthochromis polyacanthus
to simulated ocean warming across two generations. By using hepatic transcriptomics, we discovered that the post-hatching developmental environment of the offspring themselves had little effect on their acclimation potential at 2.5 months of life. Instead, the developmental experience of parents increased regulatory RNA production and protein synthesis, which could improve the offspring’s response to warming. Conversely, parental reproduction and offspring embryogenesis in warmer water elicited stress response mechanisms in the offspring, with suppression of translation and mitochondrial respiration. Mismatches between parental developmental and reproductive temperatures deeply affected offspring gene expression profiles, and detrimental effects were evident when warming occurred both during parents’ development and reproduction. This study reveals that the previous generation’s developmental temperature contributes substantially to thermal acclimation potential during early life; however, exposure at reproduction as well as prolonged heat stress will likely have adverse effects on the species’ persistence.
Pervasive relaxed selection in termite genomes
Authors: Ewart Kyle M. , Ho Simon Y. W. , Chowdhury Al-Aabid , Jaya Frederick R. , Kinjo Yukihiro , Bennett Juno , Bourguignon Thomas , Rose Harley A. , Lo Nathan
Published: May 2024

Genetic changes that enabled the evolution of eusociality have long captivated biologists. More recently, attention has focussed on the consequences of eusociality on genome evolution. Studies have reported higher molecular evolutionary rates in eusocial hymenopteran insects compared with their solitary relatives. To investigate the genomic consequences of eusociality in termites, we analysed nine genomes, including newly sequenced genomes from three non-eusocial cockroaches. Using a phylogenomic approach, we found that termite genomes have experienced lower rates of synonymous substitutions than those of cockroaches, possibly as a result of longer generation times. We identified higher rates of non-synonymous substitutions in termite genomes than in cockroach genomes, and identified pervasive relaxed selection in the former (24–31% of the genes analysed) compared with the latter (2–4%). We infer that this is due to reductions in effective population size, rather than gene-specific effects (e.g. indirect selection of caste-biased genes). We found no obvious signature of increased genetic load in termites, and postulate efficient purging of deleterious alleles at the colony level. Additionally, we identified genomic adaptations that may underpin caste differentiation, such as genes involved in post-translational modifications. Our results provide insights into the evolution of termites and the genomic consequences of eusociality more broadly.
Local and landscape factors shape alpha and beta trophic interaction diversity in urban gardens
Authors: Martínez-Núñez Carlos , Casanelles Abella Joan , Frey David , Zanetta Andrea , Moretti Marco
Published: May 2024

Promoting urban green spaces is an effective strategy to increase biodiversity in cities. However, our understanding of how local and landscape factors influence trophic interactions in these urban contexts remains limited. Here, we sampled cavity-nesting bees and wasps and their natural enemies within 85 urban gardens in Zurich (Switzerland) to identify factors associated with the diversity and dissimilarity of antagonistic interactions in these communities. The proportions of built-up area and urban green area at small landscape scales (50 m radius), as well as the management intensity, sun exposure, plant richness and proportion of agricultural land at the landscape scale (250 m radius), were key drivers of interaction diversity. This increased interaction diversity resulted not only from the higher richness of host and natural enemy species, but also from species participating in more interactions. Furthermore, dissimilarity in community structure and interactions across gardens (beta-diversity) were primarily influenced by differences in built-up areas and urban green areas at the landscape scale, as well as by management intensity. Our study offers crucial insights for urban planning and conservation strategies, supporting sustainability goals by helping to understand the factors that shape insect communities and their trophic interactions in urban gardens.
Comparison of the physicochemical properties of native and
cultivated Artemisia fukudo Makino
Authors: Kang Bo Ra , Kim Eun Hee , Kim Yeon Kyoung , Kim Ah Hhyun , Oh Gyu Yeon , Park Yoo Min , Jo Ah Hyeon , Na Hwan Sik , Shin Mi Yeong , An Yang Joon , Cho Jeong Yong , Lee So Hyeon
Published: May 2024

Artemisia fukudo Makino belongs to the
Asteraceae family, is a halophyte that can grow in salinity
soils and is known for its various physiological activities. However, few
studies were comparing it according to the growth environment. Therefore, in
this study, we analyzed the antioxidant activity, functional ingredients, and
safety of Artemisia fukudo Makino according to the growth
environment. Total polyphenol content was the highest in native mature leaves,
but 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic
acid) and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity was higher
in cultivated leaves than in native leaves. The total mineral content, excluding
sodium, was higher in cultivated than in native leaves. The content of potassium
and calcium was higher in cultivated leaves than in native leaves. In addition,
heavy metal analysis showed that cultivated leaves were generally lower than
those of native leaves. Residual pesticides were not detected in all samples. In
conclusion, since there is no significant difference in cultivated leaves
compared to native leaves, it was judged that cultivated leaves could be used as
a variety to be grown and mass-produced.
Quantifying Differential Rhythmicity based on Effect Sizes with LimoRhyde2
Authors: Obodo Dora , Asiaee Amir
Published: May 2024

Current methods for assessing differential rhythmicity in genomic data focus on hypothesis testing and model selection, often assuming sinusoidal rhythms. A more appropriate approach is to estimate differences in rhythmic properties between two or more conditions using effect sizes. To address this gap, we extend LimoRhyde2, a method for quantifying rhythm-related effect sizes and their uncertainty in genome-scale data, to enable differential rhythmicity analyses. Through extensive testing, we validate the method for differential rhythmicity analysis and showcase how it improves biological interpretation for circadian systems biology.
ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis
Authors: Zhu Junji , Liu Guan Qun , Goins Christopher M. , Stauffer Shaun R. , Gack Michaela U.
Published: May 2024

Interferon (IFN)-stimulated gene 15 (ISG15), a ubiquitin-like protein, is covalently conjugated to host (immune) proteins such as MDA5 and IRF3 in a process called ISGylation, thereby limiting the replication of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, whether SARS-CoV-2 proteins can be directly targeted for ISGylation remains elusive. In this study, we identified the nucleocapsid (N) protein of SARS-CoV-2 as a major substrate of ISGylation catalyzed by the host E3 ligase HERC5; however, N ISGylation is readily removed through de-ISGylation by the papain-like protease (PLpro) activity of NSP3. Mass spectrometry analysis identified that the N protein undergoes ISGylation at four lysine residues (K266, K355, K387 and K388), and mutational analysis of these sites in the context of a SARS-CoV-2 replicon (N-4KR) abolished N ISGylation and alleviated ISGylation-mediated inhibition of viral RNA synthesis. Furthermore, our results indicated that HERC5 targets preferentially phosphorylated N protein for ISGylation to regulate its oligomeric assembly. These findings reveal a novel mechanism by which the host ISGylation machinery directly targets SARS-CoV-2 proteins to restrict viral replication and illuminate how an intricate interplay of host (HERC5) and viral (PLpro) enzymes coordinates viral protein ISGylation and thereby regulates virus replication.
The roles of an extended N-terminal region and ETD motif in a pump-like cation channelrhodopsin discovered in a lake microbiome
Authors: Takaramoto Shunki , Fainsod Shai , Nagata Takashi , Rozenberg Andrey , Béjà Oded , Inoue Keiichi
Published: May 2024

Channelrhodopsins are light-gated ion channels consisting of seven-transmembrane helices and a retinal chromophore, which are used as popular optogenetic tools for modulating neuronal activity. Cation channelrhodopsins (CCRs), first recognized as the photoreceptors in the chlorophyteChlamydomonas reinhardtii, have since been identified in diverse species of green algae, as well in other unicellular eukaryotes. The CCRs from non-chlorophyte species are commonly referred to as bacteriorhodopsin-like channelrhodopsins, or BCCRs, as most of them feature the three characteristic amino acid residues of the “DTD motif” in the third transmembrane helix (TM3 or helix C) matching the canonical DTD motif of the well-studied archaeal light-driven proton pump bacteriorhodopsin. Here, we report characterization of HulaCCR1, a novel BCCR identified through metatranscriptomic analysis of a unicellular eukaryotic community in Lake Hula, Israel. Interestingly, HulaCCR1 has an ETD motif in which the first residue of the canonical motif is substituted for glutamate. Electrophysiological measurements of the wild-type and a mutant with a DTD motif of HulaCCR1 suggest the critical role of the first glutamate in spectral tuning and channel gating. Additionally, HulaCCR1 exhibits long extensions at the N– and C-termini. Photocurrents recorded from a truncated variant without the signal peptide predicted at the N-terminus were diminished, and membrane localization of the truncated variant significantly decreased, indicating that the signal peptide is important for membrane trafficking of HulaCCR1. These characteristics of HulaCCR1 would be related to a new biological significance in the original unidentified species, distinct from those known for other BCCRs.
A Novel GeneARHGAP44for Longitudinal Changes in Glycated Hemoglobin (HbA1c) in Subjects without Type 2 Diabetes: Evidence from the Long Life Family Study (LLFS) and the Framingham Offspring Study (FOS)
Authors: Wang Siyu , Lenzini Petra , Thygarajan Bharat , Lee Joseph H. , Vardarajan Badri N. , Yashin Anatoli , Miljkovic Iva , Daw E. Warwick , Lin Shiow J. , Patti Gary , Brent Michael , Zmuda Joseph M. , Perls Thomas T. , Christensen Kaare , Province Michael A. , An Ping
Published: May 2024

Glycated hemoglobin (HbA1c) indicates average glucose levels over three months and is associated with insulin resistance and type 2 diabetes (T2D). Longitudinal changes in HbA1c (ΔHbA1c) are also associated with aging processes, cognitive performance, and mortality. We analyzed ΔHbA1c in 1,886 non-diabetic Europeans from the Long Life Family Study to uncover gene variants influencing ΔHbA1c. Using growth curve modeling adjusted for multiple covariates, we derived ΔHbA1c and conducted linkage-guided sequence analysis. Our genome-wide linkage scan identified a significant locus on17p12. In-depth analysis of this locus revealed a variant rs56340929 (explaining 27% of the linkage peak) in theARHGAP44gene that was significantly associated with ΔHbA1c. RNA transcription ofARHGAP44was associated with ΔHbA1c. The Framingham Offspring Study data further supported these findings on the gene level. Together, we found a novel geneARHGAP44for ΔHbA1c in family members without T2D. Follow-up studies using longitudinal omics data in large independent cohorts are warranted.
IL-23 drives uveitis by acting on a novel population of tissue-resident entheseal T cells
Authors: Hedley Robert , Ward Amy , Chu Colin J , Coupland Sarah E , Kiriakidis Serafim , Taylor Peter C , Dakin Stephanie G ,   The ORBIT consortium, Buckley Christopher D , Sherlock Jonathan , Dick Andrew D , Copland David A
Published: May 2024

Recurrent acute anterior uveitis is a frequent extra-articular manifestation of the axial spondyloarthropathies (AxSpA); chronic inflammatory diseases affecting the spine, enthesis, peripheral joints, skin, and gastrointestinal tract. Pathology in AxSpA has been associated with local tissue-resident populations of interleukin (IL)-23 responsive lymphoid cells. Here we reveal a novel population of ocular T cells defined by CD3+CD4-CD8-γδTCR+IL-23R+ that reside within the anterior uvea as an ocular entheseal analogue of the mouse eye. Localised cytokine expression demonstrates that uveal IL-23R+ IL-17A-producing cells are both necessary and sufficient to drive uveitis in response to IL-23. This T cell population is also present in humans, occupying extravascular tissues of the anterior uveal compartment. Consistent with the concept of IL-23 as a unifying mediator in AxSpA, we present evidence that IL-23 can also act locally on tissue resident T cells in the anterior compartment of the eye at sites analogous to the enthesis to drive ocular inflammation.
A Mechanically Resilient Soft Hydrogel Improves Drug Delivery for Treating Post-Traumatic Osteoarthritis in Physically Active Joints
Authors: Joshi Nitin , Yan Jing , Dang Mickael , Slaughter Kai , Wang Yufeng , Wu Dana , Ung Trevor , Pandya Virja , Chen Mu Xian , Kaur Shahdeep , Bhagchandani Sachin , Alfassam Haya A , Joseph John , Gao Jingjing , Dewani Mahima , Yip Ryan Chak Sang , Weldon Eli , Shah Purna , Shukla Chetan , Sherman Nicholas E , Luo James N , Conway Thomas , Eickhoff James P. , Botelho Luis , Alhasan Ali H , Karp Jeffrey M , Ermann Joerg
Published: May 2024

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel’s potential for PTOA treatment in active patients.