bluuebunny/crossref_metadata_2025 huggingface dataset:
An independent hybrid imaging of Sgr A* from the data in EHT 2017 observations
Authors: Miyoshi Makoto , Kato Yoshiaki , Makino Junichiro
Published: May 2024

We propose that the ring structure found by the Event Horizon Telescope Collaboration (EHTC) as the black hole shadow of Sgr A* is an artefact caused by the bumpy point spread function (PSF) of the EHT 2017 data. The imaging using sparse u-v data requires detailed scrutiny of the PSF. The estimated shadow diameter ($\mathrm{48.7\pm 7~\mu \rm as}$) is equal to the spacing between the main beam and the first sidelobe of the PSF ($\mathrm{49.09~\mu \rm as}$), which immediately suggests a potential problem in the deconvolution of the PSF. We show that the ring image can be derived from non-ring simulated data sets (noise only; point source) with a narrow field-of-view (FOV) and an assumed self-calibration, suggesting that the EHT 2017 u-v coverage is insufficient for reliable imaging. The EHTC analysis, based on calibrations with assumptions about the source's size and properties, selected the final image by prioritizing the appearance rate of a similar structure from a large imaging parameter space over data consistency. Our independent analysis with conventional hybrid mapping reveals an elongated east–west structure, consistent with previous observations. We believe it to be more reliable than the EHTC image, owing to half the residuals in normalized visibility amplitude. The eastern half is brighter, possibly due to a Doppler boost from the rapidly rotating disc. We hypothesize that our image shows a portion of the accretion disc from about 2 to a few RS (where RS is the Schwarzschild radius) away from the black hole, rotating with nearly $\mathrm{60~{{\ \rm per\ cent}}}$ of the speed of light and viewed from an angle of 40°−45°.
Non-Poissonian Bursts in the Arrival of Phenotypic Variation Can Strongly Affect the Dynamics of Adaptation
Authors: Martin Nora S , Schaper Steffen , Camargo Chico Q , Louis Ard A
Published: May 2024

Modeling the rate at which adaptive phenotypes appear in a population is a key to predicting evolutionary processes. Given random mutations, should this rate be modeled by a simple Poisson process, or is a more complex dynamics needed? Here we use analytic calculations and simulations of evolving populations on explicit genotype–phenotype maps to show that the introduction of novel phenotypes can be “bursty” or overdispersed. In other words, a novel phenotype either appears multiple times in quick succession or not at all for many generations. These bursts are fundamentally caused by statistical fluctuations and other structure in the map from genotypes to phenotypes. Their strength depends on population parameters, being highest for “monomorphic” populations with low mutation rates. They can also be enhanced by additional inhomogeneities in the mapping from genotypes to phenotypes. We mainly investigate the effect of bursts using the well-studied genotype–phenotype map for RNA secondary structure, but find similar behavior in a lattice protein model and in Richard Dawkins’s biomorphs model of morphological development. Bursts can profoundly affect adaptive dynamics. Most notably, they imply that fitness differences play a smaller role in determining which phenotype fixes than would be the case for a Poisson process without bursts.
Relative Vaccine Effectiveness of Cell- vs Egg-Based Quadrivalent Influenza Vaccine Against Test-Confirmed Influenza Over 3 Seasons Between 2017 and 2020 in the United States
Authors: Stein Alicia N , Mills Carrie W , McGovern Ian , McDermott Kimberly W , Dean Alex , Bogdanov Alina N , Sullivan Sheena G , Haag Mendel D M
Published: May 2024

Background

Influenza vaccine viruses grown in eggs may acquire egg-adaptive mutations that may reduce antigenic similarity between vaccine and circulating influenza viruses and decrease vaccine effectiveness. We compared cell- and egg-based quadrivalent influenza vaccines (QIVc and QIVe, respectively) for preventing test-confirmed influenza over 3 US influenza seasons (2017–2020).

Methods

Using a retrospective test-negative design, we estimated the relative vaccine effectiveness (rVE) of QIVc vs QIVe among individuals aged 4 to 64 years who had an acute respiratory or febrile illness and were tested for influenza in routine outpatient care. Exposure, outcome, and covariate data were obtained from electronic health records linked to pharmacy and medical claims. Season-specific rVE was estimated by comparing the odds of testing positive for influenza among QIVc vs QIVe recipients. Models were adjusted for age, sex, geographic region, influenza test date, and additional unbalanced covariates. A doubly robust approach was used combining inverse probability of treatment weights with multivariable regression.

Results

The study included 31 824, 33 388, and 34 398 patients in the 2017–2018, 2018–2019, and 2019–2020 seasons, respectively; ∼10% received QIVc and ∼90% received QIVe. QIVc demonstrated superior effectiveness vs QIVe in prevention of test-confirmed influenza: rVEs were 14.8% (95% CI, 7.0%–22.0%) in 2017–2018, 12.5% (95% CI, 4.7%–19.6%) in 2018–2019, and 10.0% (95% CI, 2.7%–16.7%) in 2019–2020.

Conclusions

This study demonstrated consistently superior effectiveness of QIVc vs QIVe in preventing test-confirmed influenza over 3 seasons characterized by different circulating viruses and degrees of egg adaptation.
Xpert-Ultra Assay in Stool and Urine Samples to Improve Tuberculosis Diagnosis in Children: The Médecins Sans Frontières Experience in Guinea-Bissau and South Sudan
Authors: Moretó-Planas Laura , Mahajan Raman , Fidelle Nyikayo Lazro , Ajack Yoanis Bedpinj Peter , Tut Chol Buai , Osman Eltigani , Sangma Mitchell , Tobi Apal , Gallo Jonathan , Biague Evelize , Gonçalves Ramiro , Rocaspana Mercè , Medina Cándida , Camará Miguel , Flevaud Laurence , Ruby Lisa C , Bélard Sabine , Sagrado María José , Molina Israel , Llosa Augusto E
Published: May 2024

Background

More than half of childhood tuberculosis cases remain undiagnosed yearly. The World Health Organization recommends the Xpert-Ultra assay as a first pediatric diagnosis test, but microbiological confirmation remains low. We aimed to determine the diagnostic performance of Xpert-Ultra with stool and urine samples in presumptive pediatric tuberculosis cases in 2 high-tuberculosis-burden settings.

Methods

This Médecins Sans Frontières cross-sectional multicentric study took place at Simão Mendes Hospital, Guinea-Bissau (July 2019 to April 2020) and in Malakal Hospital, South Sudan (April 2021 to June 2023). Children aged 6 months to 15 years with presumptive tuberculosis underwent clinical and laboratory assessment, with 1 respiratory and/or extrapulmonary sample (reference standard [RS]), 1 stool, and 1 urine specimen analyzed with Xpert-Ultra.

Results

A total of 563 children were enrolled in the study, 133 from Bissau and 400 from Malakal; 30 were excluded. Confirmation of tuberculosis was achieved in 75 (14.1%), while 248 (46.5%) had unconfirmed tuberculosis. Of 553 with an RS specimen, the overall diagnostic yield was 12.4% (66 of 533). A total of 493 stool and 524 urine samples were used to evaluate the performance of Xpert-Ultra with these samples. Compared with the RS, the sensitivity and specificity of Xpert-Ultra were 62.5% (95% confidence interval, 49.4%–74%) and 98.3% (96.7%–99.2%), respectively, with stool samples, and 13.9% (7.5%–24.3%) and 99.4% (98.1%–99.8%) with urine samples. Nine patients were positive with stool and/or urine samples but negative with the RS.

Conclusions

Xpert-Ultra in stool samples showed moderate to high sensitivity and high specificity compared with the RS and an added diagnostic yield when RS results were negative. Xpert-Ultra in stool samples was useful in extrapulmonary cases. Xpert-Ultra in urine samples showed low test performance.

Clinical Trials Registration

NCT06239337
Blood Money: Selling Plasma to Avoid High-Interest Loans
Authors: Dooley John M , Gallagher Emily A
Published: May 2024

Little is known about the motivations and outcomes of sellers in remunerated markets for human materials. We exploit dramatic growth in the U.S. blood plasma industry to shed light on the sellers of plasma. Sellers tend to be young and liquidity-constrained with low incomes and limited access to traditional credit. Plasma centers absorb demand for nontraditional credit. After a plasma center opens nearby, demand for payday loans falls by over 13% among young borrowers. Meanwhile, foot traffic increases by over 4% at nearby stores, suggesting that constrained households use plasma markets to smooth consumption without appealing to high-cost debt.
At the Forefront: Social Workers’ Role in Psilocybin Treatment for Depression and Substance Misuse
Authors: Parker Claire , Wood Bethany Marie
Published: May 2024

This article underscores the critical role of social workers in harnessing the potential therapeutic benefits of psilocybin for treating major depressive disorder (MDD) and substance use disorder (SUD). Contemporary treatments for MDD often have side effects, and the success rate for SUD treatments remains low. The pervasiveness of MDD, combined with the challenges in treating SUD, highlights a need for innovative treatments. This article provides an overview of the resurgence of literature over the past two decades that illuminates the therapeutic promise of psilocybin for mental health treatment; clinical trials elucidate the efficacy of psilocybin-assisted therapy in mitigating MDD and demonstrate great promise in reducing SUD symptoms. The long-lasting posttreatment effect emphasizes its potential as a novel treatment modality. Furthermore, psilocybin’s recognition as a “breakthrough therapy” by the U.S. Food and Drug Administration (FDA) and the accelerating pace of psychedelic reform bills indicate growing acceptance and interest in its therapeutic capacities. Psilocybin-assisted therapy emerges as a potent treatment option, showcasing remarkable effectiveness even after a single dose. Recommendations and pathways for social workers to be involved in psilocybin-assisted therapy investigation, advocacy, and implementation are provided.
The Gendered Impact of Digital Jobs Platforms: Experimental Evidence from Mozambique
Authors: Jones Sam , Sen Kunal
Published: May 2024

This study examines the impact of digital labor-market platforms on jobs outcomes using a randomized encouragement design embedded in a longitudinal survey of Mozambican technical-vocational college graduates. We differentiate between platforms targeting formal jobs, where jobseekers direct their search, and informal tasks, where clients seek workers. Our analysis reveals statistically insignificant intent-to-treat and complier-average treatment effects for headline employment outcomes in the full sample. Notably, while the average male moderately benefits from platform usage, women do not. Rather, they are less responsive to the encouragement nudge, and female treatment compliers report higher reservation wages and lower job search. This suggests digital platforms can inadvertently perpetuate gender disparities in labor markets.
Thinking small: miniaturization might have facilitated adaptation to new niches in tarantulas
Authors: Biswas Aritra , Karanth K Praveen
Published: May 2024

The interplay between ecology and morphology holds significant importance in the field of evolutionary ecology. Miniaturization, a prevalent trend across diverse branches of the tree of life, often emerges as a consequence of adaptation to specific ecological niches. However, the causes and outcomes of miniaturization can vary significantly among different taxa. In our study, we utilized tarantulas as a model system to explore whether microhabitat choices are linked to morphological characteristics. Specifically, we examined whether the transition to a non-burrowing, ground-dwelling lifestyle is associated with miniaturization. Our findings indicate that the evolution of morphological traits in tarantulas has primarily been influenced by stabilizing selection, with no discernible difference in morphotypes associated with fossorial or arboreal habits. Nevertheless, we observed that whenever tarantulas opportunistically transitioned to a non-burrowing, ground-dwelling lifestyle—such as living under rocks, logs, or within crevices—they seem to have undergone body-form miniaturization and a reduction in the ratio of forelimb to hindlimb length. This study underscores the potential for repeated shifts to unique ecological niches to disrupt the conventional trajectory of morphological evolution, resulting in the emergence of novel phenotypes.
Unraveling the ultrastructure and dynamics of autophagic vesicles: Insights from advanced imaging techniques
Authors: Jiang Ting , Ma Chaoye , Chen Hao
Published: May 2024

Autophagy, an intracellular self‐degradation process, is governed by a complex interplay of signaling pathways and interactions between proteins and organelles. Its fundamental purpose is to efficiently clear and recycle cellular components that are damaged or redundant. Central to this process are autophagic vesicles, specialized structures that encapsulate targeted cellular elements, playing a pivotal role in autophagy. Despite growing interest in the molecular components of autophagic machinery and their regulatory mechanisms, capturing the detailed ultrastructural dynamics of autophagosome formation continues to present significant challenges. However, recent advancements in microscopy, particularly in electron microscopy, have begun to illuminate the dynamic regulatory processes underpinning autophagy. This review endeavors to provide an exhaustive overview of contemporary research on the ultrastructure of autophagic processes. By synthesizing observations from diverse technological methodologies, this review seeks to deepen our understanding of the genesis of autophagic vesicles, their membrane origins, and the dynamic alterations that transpire during the autophagy process. The aim is to bridge gaps in current knowledge and foster a more comprehensive comprehension of this crucial cellular mechanism.
Health Care Utilization by Patients With Chronic Pelvic Pain
Authors: Green Isabel , Briggs Morgan , Encalada Soto Diana , Cole Kristin , Wygant Jenna , Burnett Tatnai , Zhu Xuan , Chen Innie , Sangaralingam Lindsey R. , Thao Viengneesee
Published: May 2024

OBJECTIVE:

To describe the patterns of health care utilization among patients with chronic pelvic pain.

METHODS:

Deidentified administrative claims data from the OptumLabs Data Warehouse were used. Adult female patients who had their first medical claim for chronic pelvic pain between January 1, 2016, and December 31, 2019, were included. Utilization was examined for 12 months after the index diagnosis. The greedy nearest neighbor matching method was used to identify a control group of individuals without chronic pelvic pain. Comparisons were made between those with and those without chronic pelvic pain using χ2 tests for categorical data and Wilcoxon rank-sum tests for continuous data.

RESULTS:

In total, 18,400 patients were analyzed in the chronic pelvic pain cohort. Patients with chronic pelvic pain had a higher rate of chronic overlapping pain conditions. Patients with chronic pelvic pain had higher rates of health care utilization across all queried indices. They had more outpatient office visits; 55.5% had 10 or more office visits. Patients with chronic pelvic pain showed higher utilization of the emergency department (ED) (6.3 visits vs 1.9 visits; P<.001). Urine culture and pelvic ultrasonography were the most utilized tests. One-third of patients with chronic pelvic pain utilized physical therapy (PT), and 13% utilized psychological or behavioral therapy. Patients with chronic pelvic pain had higher rates of hysterectomy (8.9% vs 0.6%). The average total health care costs per patient with chronic pelvic pain per year was $12,254.

CONCLUSION:

Patients with chronic pelvic pain have higher rates of chronic overlapping pain conditions and undergo more ED visits, imaging tests, and hysterectomies than patients without chronic pelvic pain. Improving access to multidisciplinary care, increasing utilization of interventions such as PT and psychological or behavioral therapy, and reducing ED utilization may be possible targets to help reduce overall health care costs and improve patient care.
Patient with mediastinal carcinoma of unknown primary with RET fusion achieves durable response with RET inhibition
Authors: Barsouk Adam , Elghawy Omar , Stone Sara , Singh Aditi
Published: May 2024

Selective RET inhibitors have shown promise in thyroid cancer (TC) and nonsmall cell lung cancer (NSCLC) harboring RET fusions on next-generation sequencing (NGS), although rarity of the rearrangement has led to limited data for certain tumor types, such as carcinoma of unknown primary. We present a 65-year-old female with no history of malignancy, smoking or radiation exposure, who was found to have an anterior mediastinum malignancy of unknown primary, with metastases to supraclavicular lymph nodes. Core biopsy of the mediastinum revealed poorly differentiated carcinoma, while a biopsy of the thyroid revealed atypia of indeterminate significance (Bethesda III). PD-L1 immunohistochemistry was positive (90%), and liquid NGS revealed mutations in TP53 and the TERT promoter (c.-124C>T), as well as a CCDC6-RET fusion. This genetic profile resembled an anaplastic TC vs. NSCLC primary, although thymic primary and poorly differentiated TC remained on the differential. The patient was initiated on selpercatinib, which was held after 3 weeks due to thrombocytopenia and hypertension. At a reduced dosage, patient developed transaminitis, and selpercatinib was switched to pralsetinib. Brain MRI showed a nonenhancing temporal lobe signal abnormality, which on biopsy proved to be glioblastoma (GBM) with TERT promoter c.-124C>T mutation and FGFR3-TACC3 fusion by NGS. Pralsetinib was held during adjuvant chemoradiation for the GBM, and again for 4 weeks due to pneumonitis that resolved with steroids, and pralsetinib was restarted at a reduced dose. The patient has since demonstrated a stable reduction of the mediastinal mass for >15 months with RET inhibition therapy, despite several treatment interruptions.
GPR75: A Newly Identified Receptor for Targeted Intervention in the Treatment of Obesity and Metabolic Syndrome
Authors: Fragner Michael L. , Parikh Manish A. , Jackson Kaedrea A. , Schwartzman Michal Laniado , Frishman William H. , Peterson Stephen J.
Published: May 2024

Metabolic syndrome increases the risk of stroke, cardiovascular disease, and diabetes. The morbidity and mortality associated with this constellation of risk factors are equally alarming when considering the economic and global significance that this epidemic has on an institutional and patient level. Despite several current treatments available, there needs to be a continuous effort to explore more specific and effective druggable entities for preventative and therapeutic interventions. Within this context, the G-protein coupled receptor, GPR75, is an attractive pharmacological target. GPR75 and its association with its ligand, 20-hydroxyeicosatetraenoic acid, have been shown to promote hypertension, inflammation, obesity, and insulin resistance. This review will help shed light on this novel signaling pathway and offer a perspective on a promising new direction of targeting different aspects of the metabolic syndrome involving GPR75. Gene targeting of GPR75 is more effective than current pharmacologic therapies without the known side effects.
Inhibition of the transmembrane transporter ABCB1 overcomes resistance to doxorubicin in patient-derived organoid models of HCC
Authors: Blukacz Lauriane , Nuciforo Sandro , Fucile Geoffrey , Trulsson Fredrik , Duthaler Urs , Wieland Stefan , Heim Markus H.
Published: May 2024

Background:

Transarterial chemoembolization is the first-line treatment for intermediate-stage HCC. However, the response rate to transarterial chemoembolization varies, and the molecular mechanisms underlying variable responses are poorly understood. Patient-derived hepatocellular carcinoma organoids (HCCOs) offer a novel platform to investigate the molecular mechanisms underlying doxorubicin resistance.

Methods:

We evaluated the effects of hypoxia and doxorubicin on cell viability and cell cycle distribution in 20 patient-derived HCCO lines. The determinants of doxorubicin response were identified by comparing the transcriptomes of sensitive to resistant HCCOs. Candidate genes were validated by pharmacological inhibition.

Results:

Hypoxia reduced the proliferation of HCCOs and increased the number of cells in the G0/G1 phase of the cell cycle, while decreasing the number in the S phase. The IC50s of the doxorubicin response varied widely, from 29nM to >1µM. Doxorubicin and hypoxia did not exhibit synergistic effects but were additive in some HCCOs. Doxorubicin reduced the number of cells in the G0/G1 and S phases and increased the number in the G2 phase under both normoxia and hypoxia. Genes related to drug metabolism and export, most notably ABCB1, were differentially expressed between doxorubicin-resistant and doxorubicin-sensitive HCCOs. Small molecule inhibition of ABCB1 increased intracellular doxorubicin levels and decreased drug tolerance in resistant HCCOs.

Conclusions:

The inhibitory effects of doxorubicin treatment and hypoxia on HCCO proliferation are variable, suggesting an important role of tumor-cell intrinsic properties in doxorubicin resistance. ABCB1 is a determinant of doxorubicin response in HCCOs. Combination treatment of doxorubicin and ABCB1 inhibition may increase the response rate to transarterial chemoembolization.
Efficacy and Safety of Amenamevir, a Helicase-Primase Inhibitor for the Treatment of Acyclovir-Resistant Herpes Simplex Virus 1 Keratitis
Authors: Boucher Rafael , Boutolleau David , Burrel Sonia , Haigh Oscar , Fernandez José , Vauloup-Fellous Christelle , Barreau Emmanuel , Rousseau Antoine , Labetoulle Marc
Published: May 2024

Purpose:

The purpose of this study was to describe the efficacy and tolerance of amenamevir (AMNV), an inhibitor of the viral helicase-primase, for the treatment of recalcitrant herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACVR) herpes simplex virus 1 strains.

Methods:

In this retrospective case series, 6 consecutive patients with HSK caused by an ACVR herpes simplex virus 1 strain with a failure of conventional antiviral therapy were included after having been treated with AMNV (there was no control group of comparable patients for whom previous treatment would have been continued despite its inefficacy). Medical files were assessed for clinical data including reason(s) for AMNV introduction (frequent recurrences despite appropriate preventive antiviral treatment and/or clinical resistance to suppressive antiviral treatment of an ongoing clinical relapse), genotypical resistance to herpes simplex virus 1 documentation, immune status, clinical types and number of HSK episodes before and during AMNV treatment, adverse effects observed during AMNV treatment, and best corrected visual acuity.

Results:

Of 6 patients, 4 (66%) did not experience a single recurrence during AMNV therapy while 2 others had recurrences (1 over 24 months of treatment and 2 over 23 months, ie two-fold less frequently than with conventional preventive treatment). On the overall history of these 6 patients, AMNV appeared to be associated with a reduction in HSK recurrences, with a mean of only 0.02 ± 0.04 episodes/month during follow-up under AMNV as compared to 0.14 ± 0.04 episodes/month in the year preceding AMNV introduction (P = 0.03). Improvement in vision acuity was also observed (mean best corrected visual acuity 0.17 ± 0.12 logarithm of the minimum angle of resolution at the end of follow-up vs. 0.30 ± 0.35 before AMNV onset), albeit nonsignificant probably due to the limited number of patients (P = 0.38). Neither clinical nor biological adverse effects were observed while under AMNV during the follow-up (16.5 ± 5.8 months).

Conclusions:

Although there was no control group, AMNV may be a valuable option to reduce ACVR HSK recurrences.
Implementing Behavioral Optimization and Outcomes Support Team in a Medical/Surgical Telemetry Unit
Authors: Kay Chikaodi , Miller Marilyn , Buckingham Brandon
Published: May 2024

Background:

A community hospital reported 21 staff assaults with injuries and 242 emergency response code green (CG) calls for violent behaviors, resulting in a loss of time in the 2022 fiscal year. Evidence has shown that exposure to violent behavior can compromise effective patient care and lead to job dissatisfaction, high turnover, and higher healthcare costs.

Purpose:

This quality improvement project aims to develop and implement behavioral optimization and outcome support team (BOOST) in a medical–surgical telemetry unit to reduce patient-to-staff assaults/injuries.

Methods:

BOOST was piloted for 15 weeks; process data included staff knowledge and satisfaction with BOOST; outcome data included the number of BOOST and CG calls and staff assaults/injuries. The team members included registered psychiatric nurses, nursing supervisors, and security officers. Data were collected and analyzed weekly using a run chart.

Results:

The survey data demonstrated increased staff knowledge of the behavioral response team and staff satisfaction with the BOOST implementation. No staff injuries or assaults were reported during the BOOST implementation.

Conclusions:

Behavioral optimization and outcome support team was effective in de-escalating patients and the team provided support to nursing staff. BOOST utilization can effectively reduce assaults and injuries in the workplace.
General Surgery Resuscitation Preference Documentation: A Quality Improvement Initiative
Authors: Jin Helen Jingshu , Koichopolos Jennifer , Moffat Bradley , Colquhoun Patrick , Morgan Bronagh , Elliot Launa , Sibbald Robert , Zwiep Terry
Published: May 2024

Background/Purpose:

Documentation of resuscitation preferences is crucial for patients undergoing surgery. Unfortunately, this remains an area for improvement at many institutions. We conducted a quality improvement initiative to enhance documentation percentages by integrating perioperative resuscitation checks into the surgical workflow. Specifically, we aimed to increase the percentage of general surgery patients with documented resuscitation statuses from 82% to 90% within a 1-year period.

Methods:

Three key change ideas were developed. First, surgical consent forms were modified to include the patient’s resuscitation status. Second, the resuscitation status was added to the routinely used perioperative surgical checklist. Finally, patient resources on resuscitation processes and options were updated with support from patient partners. An audit survey was distributed mid-way through the interventions to evaluate process measures.

Results:

The initiatives were successful in reaching our study aim of 90% documentation rate for all general surgery patients. The audit revealed a high uptake of the new consent forms, moderate use of the surgical checklist, and only a few patients for whom additional resuscitation details were added to their clinical note.

Conclusions:

We successfully increased the documentation percentage of resuscitation statuses within our large tertiary care center by incorporating checks into routine forms to prompt the conversation with patients early.
Return to Sport at Preinjury Level is Common After Surgical Treatment of SLAP Lesions: A Systematic Review and a Meta-analysis
Authors: Gregori Pietro , Maffulli Nicola , Abboud Joseph , Za Pierangelo , Giurazza Giancarlo , Papalia Giuseppe Francesco , Ferrini Augusto , Franceschetti Edoardo
Published: May 2024

Background:

Patients undergoing surgery for Superior-Labrum-anterior-to-posterior (SLAP) lesions are often worried about their return to sport performance. This systematic review determined the rate of return to sport and return to sport at the previous level (RTSP) after surgery for SLAP lesion.

Materials and Methods:

The PRISMA guidelines were followed. Meta-analysis of data through forest plot projections was conducted. Studies were divided and analyzed according to the type of interventions (isolated slap repair or SLAP repair with rotator cuff debridement and biceps tenodesis).

Results:

The mean overall rate of return to sport after the procedures was 90.6% and the mean overall rate of return to sport at the previous level after the procedures was 71.7%. RTSP rates of the whole population were 71% (95% CI: 60%–80%), 66% (95% CI: 49%–79%), and 78% (95% CI: 67%–87%) for isolated SLAP repair, SLAP repair with the rotator cuff debridement and biceps tenodesis, respectively. A lack of subgroup analysis for the specific performance demand or type of lesion related to the surgical technique used might induce a high risk of bias.

Discussion:

Return to sports at the previous level after surgically treated superior labrum anterior to posterior lesion is possible and highly frequent, with the highest rates of RTSP in patients treated with biceps tenodesis. More studies and better-designed trials are needed to enrich the evidence on indications of SLAP surgical treatment in relation to specific sports-level demand.

Level of Evidence:

Level—IV.
The Fate of the Shoulder Post Rotator Cuff Repair: Biomechanical Properties of the Supraspinatus Tendon and Surrounding Structures
Authors: Solari Hannah E. , Hackett Lisa M. , Lam Patrick , Murrell George A.C.
Published: May 2024

The study aimed to describe the changes in biomechanical properties of the supraspinatus tendon, deltoid muscle, and humeral head post arthroscopic rotator cuff repair using shear wave elastography. Shear wave velocity of the tendon, deltoid, and humeral head of 48 patients was measured at predetermined sites at 1 week, 6 weeks, 12 weeks, 6 months, and 12 months post repair. One-way ANOVA with Tukey’s correction and Spearman’s correlation were performed. Mean±SEM healing tendon stiffness, adjacent to tendon footprint, increased from 1 week (6.2±0.2 m/s) to 6 months (7.5±0.3 m/s) and 12 months (7.8±0.3 m/s) (P<0.001). Mean±SEM deltoid muscle stiffness was higher at 12 months (4.1±0.2 m/s) compared to 1 week (3.4±0.1 m/s) and 12 weeks (3.5±0.1 m/s) (P<0.05). Humeral head stiffness did not change. Following arthroscopic rotator cuff repair, supraspinatus tendon stiffness increased in a curvilinear fashion over 6 months. From 6 months, deltoid muscle stiffness increased, corresponding to when patients were instructed to return to normal activities.
Critical Shoulder Angle in Patients With Cuff Tears
Authors: Cerciello Simone , Mocini Fabrizio , Proietti Lorenzo , Candura Dario , Corona Korona
Published: May 2024

Objective:

The pathogenesis of rotator cuff tears (RCTs) is multifactorial. Critical shoulder angle (CSA), which represents the lateral extension of the acromion over the cuff, has been proposed as an extrinsic risk factor. The aim of the present systematic review and meta-analysis was to analyze the available literature regarding the correlation between RCT and CSA.

Methods:

A review was carried out in accordance with the “Preferred Reporting Items for Systematic reviews and Meta-Analyses” guidelines on July 17, 2023, using the following databases: PubMed, Ovid, and Cochrane Reviews. The following keywords were used: “critical shoulder angle,” “rotator cuff tears,” and “rotator cuff lesions.” The methodological quality of the studies was assessed with the MINORS SCORE.

Results:

Twenty-eight studies were included. The average CSA among the 2110 patients with full-thickness RCT was 36.7 degrees, whereas the same value among the 2972 controls was 33.1 degrees. The average CSA in the 348 patients with partial-thickness RCT was 34.6 degrees, whereas it was 38.1 degrees in the 132 patients with massive RCT. The average MINORS score was 15.6.

Conclusions:

CSA values were significantly higher in patients with RCT compared with the asymptomatic population. In addition, it appears that CSA values increase with the severity of rotator cuff involvement.
Regenerative Medicine Solutions for Rotator Cuff Injuries in Athletes: Indications and Outcomes
Authors: Foti Calogero , Vellucci Claudia , Santoro Antonio
Published: May 2024

Rotator cuff (RC) injuries include a wide range of pathologic states. Athletes are perhaps the most susceptible to RC injuries ranging from tendinopathy to partial or full-thickness tears, due to functional overload and repetitive movements, causing abstention from sports for long periods. Regenerative medicine keeps giving us multiple choices to fight the disability caused by these pathologies. A literature search was performed, and findings related to the structure-function of rotator cuff units, pathophysiology of injuries, regenerative medicine treatments, and future strategies were outlined. Platelet-rich plasma (PRP) has a greater number of articles and clinical trials, accompanied by stem cells progenitor, prolotherapy, and new approaches such as microfragmented adipose tissue and exosomes. RC injuries in athletes can cause pain, functional impotence, and the risk of recurrence, and can lead them to stop playing sports. Regenerative medicine offers a range of treatments, but some of them need further studies to underline their actual validity.
Audiologic Outcomes After Vestibulotomy in Patients With Congenital Absence of the Oval Window
Authors: Song Bokhyun , Koh Sung Min , Kim Junyoung , Cho Yang-Sun
Published: May 2024

Objective

To examine the clinical features and surgical outcomes in patients with congenital absence of the oval window (CAOW), and to investigate the potential factors that affect audiologic results.

Study Design

A retrospective chart review.

Setting

A tertiary academic center.

Patients and Intervention

A total of 17 ears among 16 patients were confirmed to have CAOW. Among them, 13 ears underwent vestibulotomy for hearing reconstruction. Clinical parameters associated with the hearing outcomes were analyzed.

Main Outcome Measures

A mean air-bone gap (ABG) after 6-month and long-term follow-up was compared with preoperative measurements.

Results

Intraoperative findings showed that anomalies of the malleus or incus were observed in 11 ears (64.7%), stapes anomalies were present in all ears (100%), and facial nerve anomalies were present in 10 ears (58.8%). Because of unfavorable facial nerve anomalies, hearing reconstruction was aborted in four cases (23.5%). In the hearing reconstruction group, the mean ABG at 6 months postoperation was significantly reduced after compared with the preoperative value (44.0 ± 8.4 dB versus 58.8 ± 9.1 dB, p = 0.006). After dividing ears into a success subgroup (ABG ≤ 30 dB, seven ears) and non-success subgroup (ABG > 30 dB, six ears), the use of a drill during vestibulotomy was significantly related to a poor hearing outcome (100% versus 16.7%, p = 0.015). The long-term follow-up result (mean, 60 mo) revealed no deterioration compared with the 6-month postoperative result. Five ears (29.4%) underwent revision surgery, and three of them showed ABG improvements. No serious complications were reported.

Conclusion

Vestibulotomy is an effective and safe option for hearing restoration in patients with CAOW, particularly when the use of a drill is not required. The long-term audiologic outcome is also reliable.
The Role of Gut Microbiota and Innate Immune Response in an Autoimmune Pancreatitis Model
Authors: Ito Suguru , Higashiyama Masaaki , Nishimura Hiroyuki , Tomioka Akira , Tanemoto Rina , Nishii Shin , Mizoguchi Akinori , Akita Yoshihiro , Okada Yoshikiyo , Kurihara Chie , Narimatsu Kazuyuki , Komoto Shunsuke , Tomita Kengo , Hokari Ryota
Published: May 2024

Background

Although the involvement of intestinal microbiota in innate immunity has been reported recently, the pathogenicity of autoimmune pancreatitis (AIP) remains unclear. This study aimed to investigate whether probiotics ameliorate inflammation in AIP through interactions with innate immunity.

Materials and Methods

The AIP mouse model was generated by intraperitoneal administration of Escherichia coli to C56BL/6 female mice. Alterations in the intestinal microbiota in the AIP group were evaluated using high-throughput sequencing. Peritoneal macrophages (PMs) were collected and cocultured in vitro with Lactobacillus gasseri (LG) or ligands of Toll-like receptors (TLRs). LG was administered intraperitoneally to AIP model mice, and pancreatitis activity was evaluated to examine the ameliorative effects of LG.

Results

In the AIP model mice, inflammation was significantly induced in the pancreas, and the intestinal microbiota was altered with decreased LG. Antimicrobial treatment suppressed pancreatitis. In vitro, E. coli stimulation increased inflammatory cytokine expression, which was significantly decreased when the LG or TLR7 ligand was cocultured with PMs. Intraperitoneal administration of LG to AIP model mice significantly suppressed pancreatitis.

Conclusion

The mouse model demonstrated the involvement of intestinal microbiota in pancreatitis, and LG administration suppressed pancreatitis, possibly through TLR7 signaling in PMs. LG may be a helpful probiotic for treating AIP.
Certolizumab Has Favorable Efficacy on Preventing Pancreas and Target Organs Damage in Acute Pancreatitis
Authors: Cirak Zafer , Tanoglu Alpaslan , Yeniceri Murat , Tanoglu Esra Guzel , Kaplan Mustafa , Sade Ayşe Gökcen
Published: May 2024

Objective

It was targeted to assess the efficacy of certolizumab on pancreas and target organs via biochemical parameters and histopathologic scores in experimental acute pancreatitis (AP).

Materials and Methods

Forty male Sprague Dawley rats were divided into the following 5 equal groups: group 1 (sham group), group 2 (AP group), group 3 (AP + low-dose certolizumab group), group 4 (AP + high-dose certolizumab group), and group 5 (placebo group). Rats in all groups were sacrificed 24 hours after the last injection and amylase, tumor necrosis factor α, transforming growth factor β, interleukin 1β, malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were studied in blood samples. Histopathological investigation of both the pancreas and target organs (lungs, liver, heart, kidneys) was performed by a pathologist blind to the groups. In silico analysis were also accomplished.

Results

The biochemical results in the certolizumab treatment groups were identified to be significantly favorable compared to the AP group (P < 0.001). The difference between the high-dose group (group 4) and low-dose treatment group (group 3) was found to be significant in terms of biochemical parameters and histopathological scores (P < 0.001). In terms of the effect of certolizumab treatment on the target organs (especially on lung tissue), the differences between the low-dose treatment group (group 3) and high-dose treatment group (group 4) with the AP group (group 2) were significant.

Conclusions

Certolizumab has favorable protective effects on pancreas and target organs in AP. It may be a beneficial agent for AP treatment and may prevent target organ damage.
Early Hypophosphatemia as a Prognostic Marker in Acute Pancreatitis
Authors: Stewart Connor F. , Adeniran Esther A. , Yadav Dhiraj , Gorelick Fred S. , Liddle Rodger A. , Wu Bechien , Pandol Stephen J. , Jeon Christie Y.
Published: May 2024

Objectives

Acute pancreatitis (AP) is a complex disease representing a significant portion of gastrointestinal-related hospitalizations in the U.S. Understanding risk factors of AP might provide attractive therapeutic targets. We evaluated hypophosphatemia a prognostic marker in AP.

Methods

We performed a retrospective review of electronic health records of patients with AP from 01/ 01/2012–12/31/2021 at Cedars-Sinai Medical Center with serum phosphate measured within 48 hours of admission. Multivariable logistic regression modeling was used to evaluate associations with ICU admission and AP severity. Multivariable log-linear modeling was employed to examine associations with length of stay (LOS).

Results

Of 1526 patients admitted for AP, 33% (499) had a serum phosphate level measured within 48 hours. Patients with hypophosphatemia were more likely to have ICU admission (adjusted odds ratio (AOR) = 4.57; 95% confidence interval (CI): 2.75–7.62; P < 0.001), have a longer hospital stay (log-LOS = 0.34; SE; 0.09; 95% CI: 0.17–0.52; P < 0.001), and have moderate or severe AP (AOR = 1.80; 95% CI: 1.16–2.80; P < 0.001) compared with those without hypophosphatemia.

Conclusion

Serum phosphate is infrequently measured in patients with AP and shows promise as an early prognostic marker for outcomes of AP.
Lipase-to-Amylase Ratio for the Prediction of Clinically Relevant Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy
Authors: Chui Juanita N. , Ziaziaris William A. , Nahm Christopher B. , Fuchs Talia , Sahni Sumit , Lim Christopher S.H. , Gill Anthony J. , Samra Jaswinder S. , Mittal Anubhav
Published: May 2024

Objective

Postoperative pancreatic fistula (POPF) represents a leading cause of morbidity and mortality following major pancreatic resections. This study aimed to evaluate the use of postoperative drain fluid lipase-to-amylase ratio (LAR) for the prediction of clinically relevant fistulae (CR-POPF).

Methods

Consecutive patients undergoing pancreaticoduodenectomy between 2017 and 2021 at a tertiary centre were retrospectively reviewed. Univariable and multivariable analyses were performed to identify predictors for CR-POPF (ISGPS grade B/C). Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the performance of LAR and determine optimum prediction thresholds.

Results

Among 130 patients, 28 (21.5%) developed CR-POPF. Variables positively associated with CR-POPF included soft gland texture, acinar cell density, diagnosis other than PDAC or chronic pancreatitis, resection without neoadjuvant therapy, and postoperative drain fluid lipase, amylase, and LAR (all P<0.05). Multivariable regression analysis identified LAR as an independent predictor of CR-POPF (P<0.05). ROC curve analysis showed that LAR had moderate ability to predict CR-POPF on POD1 (AUC,0.64; 95%CI,0.54–0.74) and excellent ability on POD3 (AUC,0.85; 95%CI,0.78–0.92) and POD 5 (AUC,0.86; 95%CI,0.79–0.92). Optimum thresholds were consistent over PODs 1 to 5 (ratio>2.6) and associated with 92% sensitivity and 46% to 71% specificity.

Conclusions

Postoperative drain fluid LAR represents a reliable predictor for the development of CR-POPF. With early prognostication, the postoperative care of patients at risk of developing high-grade fistulas may be optimized.
Cancer-Derived Small Extracellular Vesicles Affect Vascular Endothelial Cells and Promote Adhesiveness of Pancreatic Cancer Cells
Authors: Furuke Hirotaka , Arita Tomohiro , Konishi Hirotaka , Kataoka Satoshi , Shibamoto Jun , Takabatake Kazuya , Takaki Wataru , Shimizu Hiroki , Yamamoto Yusuke , Morimura Ryo , Komatsu Shuhei , Shiozaki Atsushi , Ikoma Hisashi , Otsuji Eigo
Published: May 2024

Objectives

Pancreatic cancer (PC) is one of the most aggressive malignancies due to the high rate of metastasis. The mechanisms underlying metastasis need to be elucidated. Small extracellular vesicles (sEVs) mediate cell-to-cell communication, and cancer-derived sEVs contribute to the formation of premetastatic niches. The present study examined changes in adhesiveness by the internalization of PC-derived sEVs into vascular endothelial cells, and investigated the molecular mechanisms underlying metastasis.

Materials and Methods

Pancreatic cancer-derived sEVs were internalized into vascular endothelial cells, and changes in adhesiveness were evaluated. We evaluated the effects of sEVs on the formation of liver metastasis in vivo. We also assessed molecular changes in vascular endothelial cells by the internalization of PC-derived sEVs.

Results

The internalization of PC-derived sEVs into vascular endothelial cells promoted the adhesiveness of vascular endothelial cells and PC cells. Pancreatic cancer-derived sEVs contained high levels of transforming growth factor β1 mRNA and acted as its transporter. Once PC-derived sEVs were internalized into vascular endothelial cells, the expression of fibronectin 1 increased on the cell surface, and the adhesiveness of vascular endothelial cells was enhanced.

Conclusions

We investigated association between PC-derived sEVs and adhesiveness. Regulation of PC-derived sEVs has potential as a therapeutic modality to suppress the metastasis of PC.
Severity of Gallstone-, Sludge-, or Microlithiasis-Induced Pancreatitis—All of the Same?
Authors: Sirtl Simon , Bretthauer Katharina , Ahmad Mahmood , Hohmann Eric , Schmidt Vanessa F. , Allawadhi Prince , Vornhülz Marlies , Klauss Sarah , Goni Elisabetta , Vielhauer Jakob , Orgler Elisabeth , Saka Didem , Knoblauch Mathilda , Hofmann Felix O. , Schirra Jörg , Schulz Christian , Beyer Georg , Mahajan Ujjwal M. , Mayerle Julia , Zorniak Michal
Published: May 2024

Background/Aim

Severity of microlithiasis- and sludge-induced pancreatitis in comparison to gallstone-induced pancreatitis has never been studied for a lack of definition.

Materials and Methods

In this retrospective cohort study, 263 patients with acute biliary pancreatitis treated at a tertiary care center from 2005 to 2021 were stratified according to the recent consensus definition for microlithiasis and sludge. The gallstone-pancreatitis cohort was compared to microlithiasis, sludge, and suspected stone passage pancreatitis cohorts in terms of pancreatitis outcome, liver function, and endosonography/endoscopic retrograde cholangiopancreatography results using one-way analysis of variance and χ2 test. Multinomial logistic regression analysis was performed to correct for bias.

Results

Microlithiasis- and sludge-induced pancreatitis, classified according to the revised Atlanta classification, did not present with a milder course than gallstone-induced pancreatitis (P = 0.62). Microlithiasis and sludge showed an increase in bilirubin on the day of admission to hospital, which was not significantly different from gallstone-induced pancreatitis (P = 0.36). The likelihood of detecting biliary disease on endosonography resulting in bile duct clearance was highest on the day of admission and day 1, respectively.

Conclusions

Microlithiasis and sludge induce gallstone-equivalent impaired liver function tests and induce pancreatitis with similar severity compared with gallstone-induced acute biliary pancreatitis.
Screening of Amino Acids as a Safe Energy Source for Isolated Rat Pancreatic Acini
Authors: Zub Anastasiia M. , Manko Bohdan O. , Manko Volodymyr V.
Published: May 2024

Objectives

Amino acids play an essential role in protein synthesis, metabolism, and survival of pancreatic acini. Adequate nutritional support is important for acute pancreatitis treatment. However, high concentrations of arginine and lysine may induce acute pancreatitis. The study aimed to identify the most suitable l-amino acids as safe energy sources for pancreatic acinar cells.

Materials and Methods

Pancreatic acini were isolated from male Wistar rats. Effects of amino acids (0.1–20 mM) on uncoupled respiration of isolated acini were studied with a Clark electrode. Cell death was evaluated with fluorescent microscopy and DNA gel electrophoresis.

Results

Among the tested amino acids, glutamate, glutamine, alanine, lysine, and aspartate were able to stimulate the uncoupled respiration rate of isolated pancreatic acini, whereas arginine, histidine, and asparagine were not. Lysine, arginine, and glutamine (20 mM) caused complete loss of plasma membrane integrity of acinar cells after 24 hours of incubation. Glutamine also caused early (2–4 hours) cell swelling and blebbing. Aspartate, asparagine, and glutamate only moderately decreased the number of viable cells, whereas alanine and histidine were not toxic. DNA fragmentation assay and microscopic analysis of nuclei showed no evidence of apoptosis in cells treated with amino acids.

Conclusions

Alanine and glutamate are safe and effective energy sources for mitochondria of pancreatic acinar cells.