bluuebunny/crossref_metadata_2025 huggingface dataset:
Fundamental scaling relationships revealed in the optical light curves of tidal disruption events
Authors: Mummery Andrew , van Velzen Sjoert , Nathan Edward , Ingram Adam , Hammerstein Erica , Fraser-Taliente Ludovic , Balbus Steven
Published: October 2023

We present fundamental scaling relationships between properties of the optical/UV light curves of tidal disruption events (TDEs) and the mass of the black hole that disrupted the star. We have uncovered these relations from the late-time emission of TDEs. Using a sample of 63 optically selected TDEs, the latest catalogue to date, we observed flattening of the early-time emission into a near-constant late-time plateau for at least two-thirds of our sources. Compared to other properties of the TDE light curves (e.g. peak luminosity or decay rate) the plateau luminosity shows the tightest correlation with the total mass of host galaxy (p-value of 2 × 10−6, with a residual scatter of 0.3 dex). Physically this plateau stems from the presence of an accretion flow. We demonstrate theoretically and numerically that the amplitude of this plateau emission is strongly correlated with black hole mass. By simulating a large population (N = 106) of TDEs, we determine a plateau luminosity-black hole mass scaling relationship well described by $\log _{10} \left({{M_{\bullet }}/M_\odot }\right) = 1.50 \log _{10} \left({ L_{\rm plat}}/10^{43} \, {\rm erg\, s^{-1}}\right) + 9.0$ (here Lplat is measured at 6 × 1014 Hz in the rest frame). The observed plateau luminosities of TDEs and black hole masses in our large sample are in excellent agreement with this simulation. Using the black hole mass predicted from the observed TDE plateau luminosity, we reproduce the well-known scaling relations between black hole mass and galaxy velocity dispersion. The large black hole masses of 10 of the TDEs in our sample allow us to provide constraints on their black hole spins, favouring rapidly rotating black holes. Finally, we also discover two significant correlations between early time properties of optical TDE light curves (the g-band peak luminosity and radiated energy) and the TDEs black hole mass.
Galaxy cluster optical mass proxies from probabilistic memberships
Authors: Doubrawa Lia , Cypriano Eduardo S , Finoguenov Alexis , Lopes Paulo A A , Maturi Matteo , Gonzalez Anthony H , Dupke Renato
Published: October 2023

Robust galaxy cluster mass estimates are fundamental for constraining cosmological parameters from counts. For this reason, it is essential to search for tracers that, independent of the cluster’s dynamical state, have a small intrinsic scatter and can be easily inferred from observations. This work uses a simulated data set to focus on photometric properties and explores different optical mass proxies including richness, optical luminosity, and total stellar mass. We have developed a probabilistic membership assignment that makes minimal assumptions about the galaxy cluster properties, limited to a characteristic radius, velocity dispersion, and spatial distribution. Applying the estimator to over 919 galaxy clusters with zphot < 0.45 within a mass range of 1012.8–1015 M⊙, we obtain robust richness estimates that deviate from the median true value (from simulations) by −0.01 ± 0.12. The scatter in the mass–observable relations is $\sigma _{log_{10}(M|\mathcal {R})}=0.181 \pm 0.009$ dex for richness, $\sigma _{log_{10}(M|L_\lambda)}=0.151 \pm 0.007$ dex for optical luminosity, and $\sigma _{log_{10}(M|M_\lambda ^{*})}=0.097 \pm 0.005$ dex for stellar mass. We also discuss membership assignment, completeness and purity, and the consequences of small centre and redshift offsets. We conclude that the application of our method for photometric surveys delivers competitive cluster mass proxies.
Combining chirp mass, luminosity distance, and sky localization from gravitational wave events to detect the cosmic dipole
Authors: Grimm N , Pijnenburg M , Mastrogiovanni S , Bonvin C , Foffa S , Cusin G
Published: October 2023

A key test of the isotropy of the Universe on large scales consists in comparing the dipole in the cosmic microwave background (CMB) temperature with the dipole in the distribution of sources at low redshift. Current analyses find a dipole in the number counts of quasars and radio sources that is 2–5 times larger than expected from the CMB, leading to a tension reaching 5σ. In this paper, we derive a consistent framework to measure the dipole independently from gravitational wave (GW) detections. We exploit the fact that the observer velocity does not only change the distribution of events in the sky, but also the luminosity distance and redshifted chirp mass, which can be extracted from the GW waveform. We show that the estimator with higher signal-to-noise ratio is the dipole in the chirp mass measured from a population of binary neutron stars. Combining all estimators (accounting for their covariance) improves the detectability of the dipole by 30–50 per cent compared to number counting of binary black holes alone. We find that a few 106 events are necessary to detect a dipole consistent with the CMB one, whereas if the dipole is as large as predicted by radio sources, it will already be detectable with 105 events, which would correspond to a single year of observation with next-generation GW detectors. GW sources provide therefore a robust and independent way of testing the isotropy of the Universe.
Identify main-sequence binaries from the Chinese Space Station Telescope Survey with machine learning
Authors: Li Jia-jia , Wang Jin-liang , Ji Kai-fan , Liu Chao , Chen Hai-liang , Han Zhan-wen , Chen Xue-fei
Published: October 2023

The statistical properties of double main sequence (MS) binaries are very important for binary evolution and binary population synthesis. To obtain these properties, we need to identify these MS binaries. In this paper, we have developed a method to differentiate single MS stars from double MS binaries from the Chinese Space Station Telescope (CSST) Survey with machine learning. This method is reliable and efficient to identify binaries with mass ratios between 0.20 and 0.80, which is independent of the mass ratio distribution. But the number of binaries identified with this method is not a good approximation to the number of binaries in the original sample due to the low detection efficiency of binaries with mass ratios smaller than 0.20 or larger than 0.80. Therefore, we have improved this point by using the detection efficiencies of our method and an empirical mass ratio distribution and then can infer the binary fraction in the sample. Once the CSST data are available, we can identify MS binaries with our trained multi-layer perceptron model and derive the binary fraction of the sample.
A case of dupilumab combination therapy for exacerbation of atopic dermatitis in a patient with eosinophilic granulomatosis with polyangiitis treated with mepolizumab
Authors: Iwadate Yosuke , Arinuma Yoshiyuki , Matsueda Yu , Tanaka Tomoki , Wada Tatuhiko , Tanaka Sumiaki , Oku Kenji , Yamaoka Kunihiro
Published: October 2023

We report a 60-year-old male with eosinophilic granulomatosis with polyangiitis (EGPA) complicated with atopic dermatitis (AD). The patient was initially treated with prednisolone, cyclosporine A, and mepolizumab (MEPO). Due to worsening skin symptoms after prednisolone tapering, dupilumab (DUP) was added as an adjunctive therapy for AD confirmed by skin biopsy. The combination therapy of MEPO and DUP resulted in rapid improvement of skin symptoms, suggesting it may be an effective therapeutic option for patients with EGPA and AD. This case report emphasises the importance of a multidisciplinary approach in treating complex diseases such as EGPA and AD.
Antibiotic Use Among Hospitalized Patients With COVID-19 in the United States, March 2020–June 2022
Authors: Kim Christine , Wolford Hannah , Baggs James , Reddy Sujan , Hicks Lauri A , Neuhauser Melinda M , Kabbani Sarah
Published: October 2023

We conducted a retrospective study to describe antibiotic use among US adults hospitalized with a COVID-19 diagnosis. Despite a decrease in overall antibiotic use, most patients hospitalized with COVID-19 received antibiotics on admission (88.1%) regardless of critical care status, highlighting that more efforts are needed to optimize antibiotic therapy.
Does Slow and Steady Win the Race? Rates of Antipsychotic Discontinuation, Antipsychotic Dose, and Risk of Psychotic Relapse
Authors: McCutcheon Robert A , Taylor David , Rubio Jose , Nour Joseph , Pillinger Toby , Murray Robin M , Jauhar Sameer
Published: October 2023

Background

Antipsychotics are recommended for prevention of relapse in schizophrenia. It is unclear whether increased risk of relapse following antipsychotic discontinuation is predominantly associated with an absolute magnitude of dose reduction or rate of antipsychotic reduction. Establishing the responsible mechanism is important because prolonged withdrawal schedules have been suggested to reduce risk of relapse.

Study Design

Individual patient data from antipsychotic discontinuation studies were obtained. We estimated the occupancy of receptors over time using half-lives and median effective dose ED50 values obtained from pharmacokinetic and receptor occupancy studies. Hazard ratios for relapse events were calculated using Cox proportional hazards models to assess the influence of formulation (oral, 1-monthly, and 3-monthly injections). The change in hazard ratio over time was estimated, and the effect of time-varying covariates was calculated, including rate of occupancy reduction and absolute receptor occupancy.

Study Results

Five studies including 1388 participants with schizophrenia were identified (k = 2: oral, k = 2: 1-monthly injection, k = 1: 3-monthly injection). Withdrawal of long-acting injectable medication did not lead to a lower hazard ratio compared with withdrawal of oral medication, and this included the period immediately following randomization. Hazard ratios were not associated with the rate of decline of receptor occupancy; however, they were associated with reduced absolute occupancy in trials of long-acting injections (P = .038).

Conclusions

Antipsychotic discontinuation is associated with an increased risk of psychotic relapse, related to receptor occupancy. Although relapse does not appear to be related to the rate of discontinuation, gradual discontinuation strategies may allow for easier antipsychotic reinstatement in case of symptomatic worsening.
Sampling for the Early Detection of Peronospora sparsa in Blackberry Nursery Stock Plants
Authors: Ivey Melanie L. Lewis , Madrid Alejandra M. Jimenez
Published: October 2023

Downy mildew, caused by Peronospora sparsa, is a systemic disease of blackberry that can cause significant production losses worldwide. P. sparsa is disseminated through asymptomatic infected blackberry plants. Currently, there is no clean plant certification program for blackberry downy mildew. The objective of this research was to determine the detection frequency of P. sparsa in blackberry roots, stems, and leaves for the development of sampling guidelines for asymptomatic nursery plants. Stems, emerging leaves, and fully expanded leaves collected from commercial ‘Natchez’, ‘Ouachita’, and ‘Caddo’ nursery stock were tested by nested PCR using published primers at the early bud sprouting, vegetative, and flowering to green berry phenological stages for the presence of P. sparsa. Initially, 90, 40, and 100% of Caddo, Natchez, and Ouachita, respectively, tested positive for  P. sparsa. Detection of P. sparsa was inconsistent across cultivar, tissue type, plant, and phenological stage. Except for Natchez plants, P. sparsa was detected most frequently in leaves at all three phenological stages. Overall, detection of P. sparsa in Natchez was low, with the highest frequency of detection occurring at the vegetative stage. For Caddo and Ouachita, newly emerging leaves at the bud sprouting stage yielded a slightly higher frequency of detection than fully expanded leaves. The detection frequency in stem or root tissue ranged from 0 to 50% depending on the cultivar and phenological stage. In this study, we demonstrated that sampling newly emerging leaves at early bud break will result in an 80 to 90% detection frequency in cultivars that are susceptible to P. sparsa.
Pathotype Characterization of Fusarium oxysporum f. sp. lentis (Fol) Isolates in North America
Authors: Bugingo Collins , Brelsford Monica , McPhee Kevin , Burrows Mary
Published: October 2023

Fusarium wilt caused by Fusarium oxysporum f. sp. lentis ( Fol) is a devastating disease of lentils impacting yield in the Northern Great Plains. Characterizing the different pathotypes of Fol and their distribution is an essential part of breeding for resistant cultivars. To date, there has been no characterization of Fol pathotypes in North America. Using a lentil differential set from the International Center for Agriculture Research in Dry Areas, 51 pathogenic isolates of Fol from Canada, Montana, Washington, and North Dakota were characterized based on virulence assessed on foliar wilt symptoms using a disease index. Nine pathotypes were identified; pathotype 7 was highly virulent on all the differential sets and the most predominant at 55%. Pathotypes 1 and 6 were the second most predominant at 10 and 11%, respectively. This study identified for the first time Fol pathotypes present in North America. These findings will help in future efforts for Fusarium wilt management in lentils.
Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness
Authors: Koutsogiannis Zisis , Mina John G. , Albus Christin A. , Kol Matthijs A. , Holthuis Joost C. M. , Pohl Ehmke , Denny Paul W.
Published: October 2023

Toxoplasma gondii is an obligate, intracellular apicomplexan protozoan parasite of both humans and animals that can cause fetal damage and abortion and severe disease in the immunosuppressed. Sphingolipids have indispensable functions as signaling molecules and are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Ceramide is the precursor for all sphingolipids, and here we report the identification, localization and analyses of the Toxoplasma ceramide synthases TgCerS1 and TgCerS2. Interestingly, we observed that while TgCerS1 was a fully functional orthologue of the yeast ceramide synthase (Lag1p) capable of catalyzing the conversion of sphinganine to ceramide, in contrast TgCerS2 was catalytically inactive. Furthermore, genomic deletion of TgCerS1 using CRISPR/Cas‐9 led to viable but slow‐growing parasites indicating its importance but not indispensability. In contrast, genomic knock out of TgCerS2 was only accessible utilizing the rapamycin‐inducible Cre recombinase system. Surprisingly, the results demonstrated that this “pseudo” ceramide synthase, TgCerS2, has a considerably greater role in parasite fitness than its catalytically active orthologue (TgCerS1). Phylogenetic analyses indicated that, as in humans and plants, the ceramide synthase isoforms found in Toxoplasma and other Apicomplexa may have arisen through gene duplication. However, in the Apicomplexa the duplicated copy is hypothesized to have subsequently evolved into a non‐functional “pseudo” ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the unusual biology that characterize these protozoan parasites.
Botulinum Toxin for the Management of Pelvic Floor Tension Myalgia and Persistent Pelvic Pain
Authors: Knapman Blake Lawson , Li Fiona G. , Deans Rebecca , Nesbitt-Hawes Erin , Maheux-Lacroix Sarah , Abbott Jason
Published: October 2023

OBJECTIVE:

To systematically review the literature on use of botulinum toxin to treat pelvic floor tension myalgia and persistent pelvic pain.

DATA SOURCES:

The ClinicalTrials.gov, PubMed, EMBASE, and Scopus databases were searched from inception to November 2022 by two independent assessors (B.L.K. and F.G.L.). Identified studies were screened by title and abstract and included after full-text review. Data extraction was subsequently performed and recorded in Microsoft Excel.

METHODS:

This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines after registration in PROSPERO (CRD42022289132). All randomized studies, prospective studies with more than five participants, and retrospective studies with more than 10 participants published in English or French and assessing the use of botulinum toxin for the treatment of pelvic floor tension myalgia and persistent pelvic pain in women were included. Meta-analyses were performed on randomized data.

TABULATION, INTEGRATION, AND RESULTS:

Of 4,722 articles identified, 24 satisfied inclusion criteria. A meta-analysis of five randomized controlled trials totaling 329 participants demonstrated no differences in patient- and clinician-reported outcome measures, including pain, dyspareunia, sexual function, and vaginal manometry. Mean duration of follow-up was 6 months. A qualitative analysis of 14 prospective and four retrospective studies including 804 participants is supportive of botulinum toxin; however, the quality of data is low, and there is marked heterogeneity between studies.

CONCLUSION:

Meta-analyses of randomized data do not support the use of botulinum toxin to treat pelvic floor tension myalgia and persistent pelvic pain. Failure of these data to confirm the findings of nonrandomized prospective studies that suggest a treatment benefit may be attributable to the absence of placebo control and confounding outcomes obtained from an active comparator group. Further randomized controlled trials with true placebo are strongly recommended.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42022289132.
Caprini Model Integration into an Electronic Medical Record to Improve Perioperative Venous Thromboembolism Prophylaxis
Authors: Akella Sraavya , Russo Douglas , Bradley Catherine S. , Kowalski Joseph T.
Published: October 2023

This quality-improvement retrospective cohort study of patients undergoing major elective nononcologic gynecologic surgery compares the proportion of patients receiving appropriate perioperative venous thromboembolism (VTE) chemoprophylaxis before and after a novel integration of the Caprini risk-assessment model (RAM) into the electronic medical record (EMR). A sample size of 83 patients in each group (166 total) was calculated to provide 80% power and show a 20% increase in appropriate administration of VTE prophylaxis, with an alpha of 0.05. Heparin was appropriately used in 24 patients (28.9%) in the pre–Caprini-RAM group and 39 patients (47.0%) in the post–Caprini-RAM group (P=.016). There were no differences in bleeding events, transfusions, or other secondary outcomes. Integrating the Caprini-RAM into an EMR for patients undergoing nononcologic gynecologic surgery significantly improved appropriate use of VTE chemoprophylaxis.
Management of Femoral Neck Fractures in Patients Age ≥50 Years by American Board of Orthopaedic Surgery Part II Examination Candidates
Authors: Patterson Joseph T. , Heckmann Nathanael , Garvin Kevin L. , Nelson Charles L. , Jacobs Joshua J. , Lieberman Jay R.
Published: October 2023

Objective:

Assess associations between fellowship training, procedure, and performance in femoral neck fracture (FNF) surgery on adults by American Board of Orthopaedic Surgery (ABOS) Part II Examination candidates.

Setting:

ABOS SCRIBE database exam years 2007-2020.

Participants:

6,777 candidates performing 39,283 FNF surgeries on adults age ≥ 50 years.

Intervention:

Fellowship training.

Main Outcome Measurements:

Case volume; procedure performed: internal fixation (IF), hemiarthroplasty (HA), or total hip arthroplasty (THA); complications; readmission; reoperation.

Results:

Over the observation period, fewer candidates reported FNF surgery (68% overall, -0.6%/year, R2=0.80) while more candidates reported fellowship training (87% overall, +1.4%/year, R2=0.81). The rate of any complication was significantly associated with fellowship training (32% overall, p<0.001). Readmission (12%, p=0.080) and reoperation (5%, p=0.531) were not significantly associated with fellowship training. The odds of any complication (odds ratio [OR]=-0.03 [95% CI -0.07 to -0.001] per 10 cases) and surgical complication (OR=-0.12 [95% CI -0.17 to -0.07] per 10 cases) were negatively associated with candidate FNF case volume. 3,396 THA for FNF were performed (8% of cases). THA use increased 25 cases/year (R2=0.83) and was associated with adult reconstruction (p<0.001) and oncology (p<0.001) fellowship training. Any complication of THA for FNF (32%, p=0.261), readmission (9% overall, p=0.321), and reoperation (5%, p=0.200) were not significantly associated with fellowship training.

Conclusions:

Between 2007-2020, femoral neck fracture surgery was performed by fewer ABOS Part II Examination candidates and there was greater use of THA. Over this time period there was a greater prevalence of fellowship training but complications were not associated with fellowship training. Complications were associated with FNF case volume.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Examining the Role of Paraspinal Musculature in Postoperative Disability After Lumbar Fusion Surgery for Degenerative Spondylolisthesis
Authors: Schönnagel Lukas , Guven Ali E. , Camino-Willhuber Gaston , Caffard Thomas , Tani Soji , Zhu Jiaqi , Haffer Henryk , Muellner Maximilian , Zadeh Arman , Sanchez Leonardo A. , Shue Jennifer , Duculan Roland , Schömig Friederike , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Mancuso Carol A. , Hughes Alexander P.
Published: October 2023

Study Design.

Retrospective analysis of prospectively enrolled patients.

Objective.

To evaluate the relationship between paraspinal muscle (PM) atrophy and Oswestry Disability Index (ODI) improvement after spinal fusion surgery for degenerative lumbar spondylolisthesis.

Background.

Atrophy of the PM is linked to multiple spinal conditions, sagittal malalignment, and increased postoperative complications. However, only limited evidence for the effect on patient-reported outcomes exists.

Methods.

Patients with degenerative lumbar spondylolisthesis undergoing decompression and fusion surgery were analyzed. Patients with missing follow-up, no imaging, or inadequate image quality were excluded. The ODI was assessed preoperatively and two years postoperatively. A cross-sectional area of the PM was measured on a T2-weighted magnetic resonance imaging sequence at the upper endplate of L4. On the basis of the literature, a 10-point improvement cutoff was defined as the minimum clinically important difference. Patients with a baseline ODI below the minimum clinically important difference were excluded. Logistic regression was used to calculate the association between fatty infiltration (FI) of the PM and improvement in ODI, adjusted for age, sex, and body mass index.

Results.

A total of 133 patients were included in the final analysis, with only two lost to follow-up. The median age was 68 years (IQR 62–73). The median preoperative ODI was 23 (IQR 17–28), and 76.7% of patients showed improvement in their ODI score by at least 10 points. In the multivariable regression, FI of the erector spinae and multifidus increased the risk of not achieving clinically relevant ODI improvement (P=0.01 and <0.001, respectively). No significant association was found for the psoas muscle (P=0.158).

Conclusions.

This study demonstrates that FI of the erector spinae and multifidus is significantly associated with less likelihood of clinically relevant ODI improvement after decompression and fusion. Further research is needed to assess the effect of interventions.
Association Between Osteoarthritis Burden and Intervertebral Disk Degeneration in Patients Undergoing Lumbar Spine Surgery for Degenerative Lumbar Spondylolisthesis
Authors: Schönnagel Lukas , Camino-Willhuber Gaston , Braun Sebastian , Zhu Jiaqi , Tani Soji , Guven Ali E. , Caffard Thomas , Chiapparelli Erika , Arzani Artine , Haffer Henryk , Muellner Maximilian , Shue Jennifer , Duculan Roland , Bendersky Mariana , Cammisa Frank P. , Girardi Federico P. , Sama Andrew A. , Mancuso Carol A. , Hughes Alexander P.
Published: October 2023

Study Design.

A retrospective analysis of prospectively collected data.

Objective.

To assess the association between intervertebral disk degeneration and hip and knee osteoarthritis (OA) in patients with degenerative lumbar spondylolisthesis.

Background.

The co-occurrence of hip OA and degenerative spinal pathologies was first described as the “hip-spine syndrome” and has also been observed in knee OA. It remains unclear whether both pathologies share an underlying connection beyond demographic factors.

Materials and Methods.

Intervertebral disk degeneration was classified by the Pfirrmann Classification and intervertebral vacuum phenomenon. Intervertebral vacuum phenomenon was classified into mild (1 point), moderate (2 points), and severe (3 points) at each level and combined into a lumbar vacuum score (0–15 points). Similarly, a lumbar Pfirrmann grade was calculated (5–25 points). Patients with previous hip or knee replacement surgery were classified as having an OA burden. We used multivariable regression to assess the association between OA and disk degeneration, adjusted for age, body mass index, and sex.

Results.

A total of 246 patients (58.9% female) were included in the final analysis. Of these, 22.3% had OA burden. The multivariable linear regression showed an independent association between OA burden and lumbar vacuum (β = 2.1, P<0.001) and Pfirrmann grade (β = 2.6, P<0.001). Representing a 2.1 points higher lumbar vacuum and 2.6 points higher lumbar Pfirrmann grade after accounting for demographic differences.

Conclusions.

Our study showed that OA burden was independently associated with the severity of the intervertebral disk degeneration of the lumbar spine. These findings give further weight to a shared pathology of OA of large joints and degenerative processes of the lumbar spine.

Level of Evidence:

3.
Use of Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction After Cardiac Transplantation: Results of an A Priori Ventless Approach
Authors: Jorde Ulrich P. , Arfaras-Melainis Angelos , Wan Ningxin , Uehara Mayuko , Castagna Francesco , Vukelic Sasa , Rochlani Yogita M. , Madan Shivank A. , Murthy Sandhya , Patel Snehal R. , Sims Daniel B. , Borgi Jamil , Goldstein Daniel J. , Forest Stephen J. , Jakobleff William A. , Saeed Omar
Published: October 2023

Primary graft dysfunction (PGD) after cardiac transplantation is a devastating complication with increasing frequency lately in the setting of donation after circulatory death (DCD). Severe PGD is commonly treated with extracorporeal membrane oxygenation (ECMO) using central or peripheral cannulation. We retrospectively reviewed the outcomes of PGD after cardiac transplantation requiring ECMO support at our center from 2015 to 2020, focused on our now preferential approach using peripheral cannulation withouta prioriventing. During the study period, 255 patients underwent heart transplantation at our center and 26 (10.2%) of them required ECMO for PGD. Of 24 patients cannulated peripherally 19 (79%) were alive at 30 days and 17 (71%) 1 year after transplant; two additional patients underwent central ECMO cannulation due to unfavorable size of femoral vessels and concern for limb ischemia. Successful decannulation with full graft function recovery occurred in 22 of 24 (92%) patients cannulated peripherally. Six of them had an indwelling intra-aortic balloon pump placed before the transplantation. None of the other 18 patients received a ventricular vent. In conclusion, the use of ana prioriperipheral and ventless ECMO approach in patients with PGD after heart transplant is an effective strategy associated with high rates of graft recovery and survival.
Idiopathic bilateral occlusion of Foramen of Monro treated by septostomy with unilateral foraminoplasty: a rare case report
Authors: Sattout Ghaith Izz Aldeen , Wardeh Abdulkareem Muhammad , Alhassoun Alia , Zain Aldain Rami Naji , Alshraikey Ahmad Mohammed
Published: October 2023

Introduction:

Idiopathic occlusion of the Foramen of Monro is extremely rare in adults. The occlusion is classified into four types, with the first being the most infrequent. This condition induces noncommunicating hydrocephalus with the ensuing increased intracranial pressure symptoms. Headache is usually the chief complaint.

Presentation of the case:

The authors present a case of a 28-year-old female who presented with a chronic headache that was unresponsive to analgesics. No other neurological deficits were present. Fundoscopic examination revealed the presence of bilateral papillary edema. Computed tomography scan results showed bilateral enlargement of the lateral ventricles of the brain. A subsequent MRI scan ruled out secondary causes of occlusion, such as colloid cysts, meningiomas, or choroid plexus tumors, which entailed an idiopathic etiology.

Treatment options include ventriculoperitoneal shunt insertion and septostomy with foraminoplasty. The former option is currently the treatment of choice, yet it is notorious for its ramifications, including foreign body reaction, breakage, and mechanical problems. The latter option is free of these risks; however, it requires meticulousness and precision to avoid damaging the fornix, which leads to impaired memory function.

Conclusion:

Septostomy with unilateral foraminoplasty could yield better outcomes if it is performed fastidiously.
Evaluation of the Prognostic Role of Liver Metastases on Patient Outcomes
Authors: Waninger Jessica J. , Ma Vincent T. , Chopra Zoey , Pearson Ashley N. , Green Michael D.
Published: October 2023

The liver is a common site of metastasis for many primary malignancies, but the quantitative impact on survival is unknown. We performed a systematic review and meta-analysis of 83 studies (604,853 patients) assessing the overall hazard associated with liver metastases by primary tumor type and treatment regimen. The pooled overall survival hazard ratio (HR) for all included studies was 1.77 (95% confidence interval [CI], 1.62–1.93). Patients with breast cancer primaries fared the worst (HR, 2.37; 95% CI, 1.64–3.44), as did patients treated with immunotherapies (HR, 1.86; 95% CI, 1.42–2.42). Liver metastases negatively impact survival, necessitating new approaches to disease management.
What Role Does Radiotherapy Play in the Molecular Era for Intrahepatic Cholangiocarcinoma?
Authors: Koay Eugene J. , Javle Milind , Belknap Madeline , Derasari Shrey , Roach Millicent , Ludmir Ethan B.
Published: October 2023

Intrahepatic cholangiocarcinoma is a rare disease, yet with rising incidence globally. Most patients are not eligible for potentially curative surgical resection, and many patients with unresectable disease die within 12 months of diagnosis, primarily due to liver failure from the primary tumor. Recent prospective and retrospective studies indicate that local control of the primary tumor can be achieved with hypofractionated radiotherapy in patients with unresectable disease, translating into prolonged survival of these patients. During the time that these encouraging reports for radiotherapy have been published, numerous concurrent studies have also shown that intrahepatic cholangiocarcinoma is a molecularly diverse disease with multiple targetable genetic alterations and a complex tumor microenvironment. These biological insights have translated into new drug approvals for subsets of patients. We review the current knowledge about the biology and targeted treatment of intrahepatic cholangiocarcinoma and describe these developments in the context of modern radiotherapy.
Early Experience of Direct-to-Implant Breast Reconstruction Using Acellular Dermal Matrix after Robot-Assisted Nipple-Sparing Mastectomy
Authors: Kim Shin Hyun , Park Seonghyuk , Lee Dong Won , Park Hyung Seok , Lew Dae Hyun , Song Seung Yong
Published: October 2023

Background:

The authors performed a retrospective review to analyze operative outcomes of breast mound reconstruction after robot-assisted mastectomy.

Methods:

Patients who underwent nipple-sparing mastectomy (NSM) with a robotic device (Da Vinci Xi) and immediate prepectoral prosthetic reconstruction by lateral incision from June of 2018 to July of 2019 were enrolled. Patient characteristics, complications, and satisfaction rates as assessed by BREAST-Q were analyzed. The surgical technique was described in detail.

Results:

Thirty-nine cases, including 7 bilateral cases (total 46 breasts), underwent robot-assisted NSM followed by immediate prepectoral prosthetic implant reconstruction. The median patient age was 46.63 years (range, 21 to 63 years). The mean operation time for each prepectoral breast mound reconstruction using the direct-to-implant technique was 126.55 minutes. Robot-assisted reconstruction resulted in superior BREAST-Q scores compared with the conventional reconstruction method. Major infection occurred in 7 cases (15.2%), and complete nipple loss occurred in 3 cases (6.6%). Severe complications requiring breast implant removal occurred in 4 breasts (8.7%). Two cases were due to the coexistence of infection and skin necrosis; in 1 case, the skin flap became congested on postoperative day 3 and required additional surgery to change the expander. Other complications were resolved with conservative care or minor revision.

Conclusions:

This report is the first concerning robot-assisted NSM followed by prepectoral acellular dermal matrix–wrapped prosthetic reconstruction. This procedure was not inferior to other methods. Further prospective research to evaluate oncologic outcomes is warranted.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Septal Extension Graft in Cleft Rhinoplasty: Patients with Secondary Unilateral Cleft Lip Nasal Deformity
Authors: Saito Takafumi , Lonic Daniel , Lo Chi-Chin , Tu Junior Chun-Yu , Hattori Yoshitsugu , Lo Lun-Jou
Published: October 2023

Background:

Tip refinement procedures are still controversial in secondary unilateral cleft rhinoplasty. The aim of this study was to assess whether the septal extension graft improved nasal and tip deformity and achieved a normal profile with clinical and three-dimensional morphometric analyses.

Methods:

A consecutive series of 194 skeletally mature patients with unilateral cleft were included and analyzed. All had undergone secondary open rhinoplasty, performed by a single surgeon, with the use of the septal extension graft between 2013 and 2021. Clinical data were collected, and three-dimensional morphometric measurements were performed. An age-, sex-, and ethnicity-matched normal group was included for comparisons.

Results:

The authors’ standard procedures included open approach combining reverse-U incision, septal extension graft, dorsal augmentation, lip revision, and vermilion augmentation. The postoperative outcome showed significantly increased numerical values (nasal bridge length, nasal height, nasal tip projection, nasal dorsum angle, columellar angle, columellar-lobule angle, nostril height ratio, nasal surface area, nasal volume) and decreased numerical values (alar width, tip/middle deviation, nasal tip angle, labial-columellar angle) compared with the preoperative morphology. The postoperative measurement showed significantly higher numerical values (nasal protrusion, tip/middle deviation, nasal dorsum angle) and lower numerical values (columellar-lobule angle, nostril height ratio, alar width ratio) compared with the control group.

Conclusions:

This study revealed that the authors’ secondary cleft rhinoplasty significantly improved the underprojected, up-rotated, deviated, and poorly defined tip and short nasal bridge deformities. The technique could result in the nose of the patients with cleft lip nasal deformity being closer to that of the normative profile.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The Nature, Causes, and Clinical Impact of Errors in the Clinical Laboratory Testing Process Leading to Diagnostic Error: A Voluntary Incident Report Analysis
Authors: van Moll Christel , Egberts Toine , Wagner Cordula , Zwaan Laura , ten Berg Maarten
Published: October 2023

Objectives

Diagnostic errors, that is, missed, delayed, or wrong diagnoses, are a common type of medical errors and preventable iatrogenic harm. Errors in the laboratory testing process can lead to diagnostic errors. This retrospective analysis of voluntary incident reports aimed to investigate the nature, causes, and clinical impact of errors, including diagnostic errors, in the clinical laboratory testing process.

Methods

We used a sample of 600 voluntary incident reports concerning diagnostic testing selected from all incident reports filed at the University Medical Center Utrecht in 2017–2018. From these incident reports, we included all reports concerning the clinical laboratory testing process. For these incidents, we determined the following: nature: in which phase of the testing process the error occurred; cause: human, technical, organizational; and clinical impact: the type and severity of the harm to the patient, including diagnostic error.

Results

Three hundred twenty-seven reports were included in the analysis. In 77.1%, the error occurred in the preanalytical phase, 13.5% in the analytical phase and 8.0% in the postanalytical phase (1.5% undetermined). Human factors were the most frequent cause (58.7%). Severe clinical impact occurred relatively more often in the analytical and postanalytical phase, 32% and 28%, respectively, compared with the preanalytical phase (40%). In 195 cases (60%), there was a potential diagnostic error as consequence, mainly a potential delay in the diagnostic process (50.5%).

Conclusions

Errors in the laboratory testing process often lead to potential diagnostic errors. Although prone to incomplete information on causes and clinical impact, voluntary incident reports are a valuable source for research on diagnostic error related to errors in the clinical laboratory testing process.
68Ga-FAPI and 18F-FDG PET/CT in Intravenous Leiomyomatosis
Authors: Li Zhuoyuan , Su Dan , Chen Yue
Published: October 2023

Intravenous (IV) leiomyomatosis is a rare IV disease. Our case presents 68Ga-FAPI and 18F-FDG PET/CT findings of IV leiomyomatosis in a 37-year-old woman. Intravenous leiomyomatosis shows only mild FDG but intense 68Ga-FAPI activity on PET/CT studies. In this case, 68Ga-FAPI was superior to 18F-FDG PET/CT in detecting IV leiomyomatosis.
Skin and Subcutaneous Tissue Metastases of the Pulmonary Carcinoid Tumor on 68Ga-DOTATATE PET/CT
Authors: Filizoglu Nuh , Ozguven Salih
Published: October 2023

Pulmonary carcinoid tumors are a very rare type of neuroendocrine tumor, accounting for only 1% to 2% of all primary lung cancers. Pulmonary carcinoids most commonly metastasize to the mediastinal lymph nodes, liver, and bones. Metastasis of pulmonary carcinoids to the skin and subcutaneous tissue is extremely rare and has been reported in only a small number of cases. We presented 68Ga-DOTATATE PET/CT findings of an exceptional case of a pulmonary carcinoid tumor with extensive skin, subcutaneous, thyroid, and intramuscular metastases.
Defining Standards for Hepatopancreatobiliary Cancer Surgery in Ontario, Canada: A Population-Based Cohort Study of Clinical Outcomes
Authors: Hirpara Dhruvin H , Irish Jonathan , Rashid Mohammed , Martin Tharsiya , Zhu Alice , Hunter Amber , Jayaraman Shiva , Wei Alice C , Coburn Natalie G , Wright Frances C
Published: October 2023

BACKGROUND:

In 2006, Cancer Care Ontario created Surgical Oncology Standards for the delivery of hepatopancreatobiliary (HPB) surgery including hepatectomy and pancreaticoduodenectomy (PD). Our objective was to identify the impact of standardization on outcomes after HPB surgery in Ontario, Canada.

STUDY DESIGN:

This study was a population-level analysis of patients undergoing hepatectomy or PD (2003 to 2019). Logistic regression models were used to compare 30- and 90-day mortality and length of stay (LOS) before (2003 to 2006), during (2007 to 2011), and after (2012 to 2019) standardization. Interrupted time series models were used to co-analyze secular trends.

RESULTS:

A total of 7,904 hepatectomies and 5,238 PDs were performed. More than 80% of all cases were performed at a designated center (DC) before standardization. This increased to >98% in the poststandardization era. Median volumes at DCs increased from 55 to 67 hepatectomies/year and from 22 to 50 PDs/year over time. In addition, 30-day mortality after hepatectomy was 2.6% before standardization and 2.3% after standardization (p = 0.9); 30-day mortality after PD was 3.6% before standardization and 2.4% after standardization (p = 0.1). Multivariable analyses revealed a significant difference in 90-day mortality following PD poststandardization (4.3% vs 6.3%; adjusted odds ratio, 0.7; p = 0.03). Median LOS was shorter for hepatectomy (6 days vs 8 days) and PD (9 days vs 14 days; p < 0.0001) after standardization. Immediate and late effects on mortality and LOS were likely attributable to secular trends, which predated standardization.

CONCLUSIONS:

Standardization was associated with a higher volume of hepatectomy and PDs with further concentration of care at DCs. Pre-existing quality initiatives may have attenuated the effect of standardization on quality outcomes. Our data highlight the merits of a multifaceted provincial system for enabling consistent access to high quality HPB care throughout a region of 15 million people over a 16-year period.
GLUD1 dictates muscle stem cell differentiation by controlling mitochondrial glutamate levels
Authors: Soro-Arnáiz Inés , Cherkaoui Sarah , Fitzgerald Gillian , Zhang Jing , Gilardoni Paola , Ghosh Adhideb , Bar-Nur Ori , Masschelein Evi , Maechler Pierre , Zamboni Nicola , Poms Martin , Cremonesi Alessio , García Cañaveras Juan Carlos , De Bock Katrien , Morscher Raphael J.
Published: October 2023

Muscle stem cells (MuSCs) enable muscle growth and regeneration after exercise or injury. Upon activation MuSCs metabolically rewire to meet the changing demands of proliferation. Here we describe that primary changes in metabolism itself can dictate MuSC fate decisions to control differentiation and fusion. We found that glutamine anaplerosis into the TCA cycle decreases during MuSC differentiation and coincides with decreased expression of the mitochondrial glutamate deaminase GLUD1. Genetic deletion ofGlud1in proliferating MuSCs resulted in precocious differentiation and imbalanced fusion combined with loss of self-renewalin vitroandin vivo. Mechanistically, deletingGlud1caused mitochondrial glutamate accumulation in proliferating MuSCs and inhibited the malate-aspartate shuttle (MAS). Restoring MAS activity by supplementation of alanine normalized differentiation. In conclusion, high GLUD1 activity in proliferating MuSCs prevents deleterious mitochondrial glutamate accumulation and inactivation of the MAS. It thereby acts as a compartment specific metabolic brake on MuSC differentiation.

Graphical Abstract

Highlights

Glutamine is the major TCA cycle substrate in MuSCs with decreasing contribution upon differentiation.

Loss ofGlud1impairs MuSC self-renewal capacity and causes imbalanced fusionin vitroandin vivo.

Glud1deletion leads to mitochondrial glutamate trapping and malate-aspartate shuttle (MAS) dysfunction.

Restoration of MAS activity inGlud1deficient MuSCs reverses precocious differentiation and imbalanced fusion.
Analysis of the Diverse Antigenic Landscape of the Malaria Invasion Protein RH5 Identifies a Potent Vaccine-Induced Human Public Antibody Clonotype
Authors: Barrett Jordan R. , Pipini Dimitra , Wright Nathan D. , Cooper Andrew J. R. , Gorini Giacomo , Quinkert Doris , Lias Amelia M. , Davies Hannah , Rigby Cassandra , Aleshnick Maya , Williams Barnabas G. , Bradshaw William J. , Paterson Neil G. , Martinson Thomas , Kirtley Payton , Picard Luc , Wiggins Christine D. , Donnellan Francesca R. , King Lloyd D. W. , Wang Lawrence T. , Popplewell Jonathan F. , Silk Sarah E. , Swain Jed de Ruiter , Skinner Katherine , Kotraiah Vinayaka , Noe Amy R. , MacGill Randall S. , King C. Richter , Birkett Ashley J. , Soisson Lorraine A. , Minassian Angela M. , Lauffenburger Douglas A. , Miura Kazutoyo , Long Carole A. , Wilder Brandon K. , Koekemoer Lizbé , Tan Joshua , Nielsen Carolyn M. , McHugh Kirsty , Draper Simon J.
Published: October 2023

The highly conserved and essentialPlasmodium falciparumreticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines that seek to protect against the disease-causing blood-stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here we characterize over 200 human IgG monoclonal antibodies induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule, and establish epitope specificity, antibody association rate and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect againstP. falciparumparasite challengein vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria.
PROTOSPACEJAM: AN OPEN-SOURCE, CUSTOMIZABLE AND WEB-ACCESSIBLE DESIGN PLATFORM FOR CRISPR/CAS9 INSERTIONAL KNOCK-IN
Authors: Peng Duo , Vangipuram Madhuri , Wong Joan , Leonetti Manuel D.
Published: October 2023

CRISPR/Cas9-mediated knock-in of DNA sequences enables precise genome engineering for research and therapeutic applications. However, designing effective guide RNAs (gRNAs) and homology-directed repair (HDR) donors remains a bottleneck. Here, we present protoSpaceJAM, an open-source algorithm to automate and optimize gRNA and HDR donor design for CRISPR/Cas9 insertional knock-in experiments. protoSpaceJAM utilizes biological rules to rank gRNAs based on specificity, distance to insertion site, and position relative to regulatory regions. protoSpaceJAM can introduce recoding mutations (silent mutations and mutations in non-coding sequences) in HDR donors to prevent re-cutting and increase knock-in efficiency. Users can customize parameters and design double-stranded or single-stranded donors. We validated protoSpaceJAM’s design rules by demonstrating increased knock-in efficiency with recoding mutations and optimal strand selection for single-stranded donors. An additional module enables the design of genotyping primers for next-generation sequencing of edited alleles. Overall, protoSpaceJAM streamlines and optimizes CRISPR knock-in experimental design in a flexible and modular manner to benefit diverse research and therapeutic applications. protoSpaceJAM is available open-source as an interactive web tool atprotospacejam.czbiohub.orgor as a standalone Python package atgithub.com/czbiohub-sf/protoSpaceJAM.