bluuebunny/crossref_metadata_2025 huggingface dataset:
The Human Blood Fluke, Schistosoma mansoni, Harbors Bacteria Throughout the Parasite's Life Cycle
Authors: Formenti Fabio , Cortés Alba , Deiana Michela , Salter Susannah , Parkhill Julian , Berriman Matt , Rinaldi Gabriel , Cantacessi Cinzia
Published: July 2023

While symbiotic relationships between invertebrates and bacteria have been extensively described, studies of microbial communities inhabiting parasitic worms remain scarce. Exploring the microbiota associated with helminths responsible for major infectious diseases will inform on parasite biology, host-pathogen interactions, and disease pathophysiology. We investigated the presence of microorganisms inhabiting tissues of the human parasite Schistosoma mansoni. In situ hybridization using a pan-bacterial 16S rRNA gene probe revealed bacteria colonizing key developmental stages that were successfully removed after antibiotic treatment of live parasites. Understanding the composition and function of the S. mansoni-associated microbiota may lead to the development of novel microbiome-targeting control strategies
Fungal brain abscess in a severely burned patient
Authors: Stevens Audrey , Waldrop Caitlyn , Mandell Samuel , Abdelfattah Kareem , Arnoldo Brett , Akarichi Chiaka O , Clark Audra T
Published: July 2023

Burn patients are particularly susceptible to atypical and opportunistic infections. Here we report an unusual case of a 40-year-old previously healthy man with a 74% TBSA burn injury who developed a presumed Fusarium brain abscess. This patient had a complicated infectious course including ESBL E. coli and Elizabethkingia bacteremia and pneumonia, MRSA ventilator-associated pneumonia, Mycobacterium abscessus bacteremia, and Fusarium fungemia. After diagnosis with a fungal abscess on magnetic resonance imaging of the brain, the patient was treated with aspiration and appropriate antifungal therapies. The patient was eventually transitioned to comfort care and died on hospital day 167. This is the first published report of a Fusarium-related brain abscess since it was first reported in a case report of a burned child in 1974.
Dose-escalation part of Phase I study of single-agent mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma
Authors: Munakata Wataru , Izutsu Koji , Mishima Yuko , Nagai Hirokazu , Ishihara Yuko , Suzumiya Junji , Kanakura Yuzuru , Nanki Toshihiro , Miyake Takeshi , Kawasaki Atsuko , Yoshinaga Tatsuya , Ishizawa Kenichi
Published: July 2023

Objective

This dose-escalation part of an ongoing Phase I study assessed the tolerability, safety and pharmacokinetics of mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

Methods

Mosunetuzumab was administered intravenously, with step-up dosing in a 3 + 3 design, on Days 1, 8 and 15 of Cycle 1, and Day 1 of each subsequent 21-day cycle for up to 17 cycles to patients across five cohorts with different target doses (2.8, 6.0, 13.5, 27.0 or 60.0 mg).

Results

As of 5 July 2022, 23 patients had received mosunetuzumab. The median patient age was 63.0 years, 56.5% of patients were male, and 69.6% of patients had diffuse large B-cell lymphoma, 17.4% had transformed follicular lymphoma (FL) and 13.0% had FL. The median number of prior lines of therapy was 4. Mosunetuzumab was well tolerated and there were no deaths. The most common adverse events (any grade) were neutropenia/neutrophil count decreased (47.8%) and cytokine release syndrome (34.8%). Most cytokine release syndrome events were Grade 1/2 (one Grade 3), and most occurred within 24 hours of the first dose of mosunetuzumab. The apparent half-life of mosunetuzumab was 4.1–5.0 days. Two patients achieved a complete response, and 11 patients achieved a partial response.

Conclusions

This study demonstrated that mosunetuzumab has an acceptable safety profile and antitumor activity in Japanese patients with relapsed/refractory B-cell NHL. The recommended Phase II dose of 1.0/2.0/60.0/60.0/30.0 mg was tolerable and there were no new or different safety signals compared with the global Phase I study.
Mitracarpus frigidus reduces lipid metabolism and PGE2 levels in inflammatory cells
Authors: Lemos Ari Sérgio de O , Campos Lara M , Granato Juliana da T , Goliatt Priscila V Z C , Dib Paula R B , Hottz Eugenio D , Glanzmann Nícolas , Campos Laíris C , Bizarro Heloisa D S , Chedier Luciana M , Coimbra Elaine S , Fabri Rodrigo L
Published: July 2023

Objectives

To evaluate the ability of the aqueous extract of Mitracarpus frigidus (MFAq) to inhibit lipid body formation and inflammatory mediator production in macrophages stimulated with lipopolysaccharide (LPS) and interferon gamma (IFN-γ).

Methods

MFAq was chemically characterized by ultrafast liquid chromatography/quadruple time-of-flight tandem mass spectrometry. The macrophages obtained from mice were incubated with MFAq. Cell viability and membrane integrity were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and propidium iodide assays, respectively. Moreover, NO, reactive oxygen species (ROS), transforming growth factor beta (TGF-β), prostaglandin E2 (PGE2) levels and lipid bodies (LBs) were examined in macrophages that were stimulated with LPS and IFN-γ and treated with MFAq. Finally, molecular docking analysis was conducted to investigate the interaction of MFAq with the cyclooxygenase 2 (COX-2) enzyme.

Key findings

Chlorogenic acid, clarinoside, harounoside, rutin, kaempferol-3O-rutinoside and 2-azaanthraquinone were identified in MFAq. MFAq significantly inhibited NO, ROS and LBs, and did not affect the membrane integrity of macrophages. MFAq-treated cells showed significantly lower levels of TGF-β and PGE2. Molecular docking demonstrated that the compounds found in MFAq are able to inhibit COX-2 by binding to important residues in the catalytic site.

Conclusions

MFAq interferes with lipid metabolism in stimulated macrophages, leading to the reduction of important inflammatory mediators. Furthermore, MFAq can directly inhibit the COX-2 enzyme or inhibit its expression owing to its ability to reduce NO production.
ECHO: A hierarchical combination of classical and multi-agent epistemic planning problems
Authors: Soldà Davide , Fabiano Francesco , Dovier Agostino
Published: July 2023

The continuous interest in Artificial Intelligence (AI) has brought, among other things, the development of several scenarios where multiple artificial entities interact with each other. As for all the other autonomous settings, these multi-agent systems require orchestration. This is, generally, achieved through techniques derived from the vast field of Automated Planning. Notably, arbitration in multi-agent domains is not only tasked with regulating how the agents act, but must also consider the interactions between the agents’ information flows and must, therefore, reason on an epistemic level. This brings a substantial overhead that often diminishes the reasoning process’s usability in real-world situations. To address this problem, we present ECHO, a hierarchical framework that embeds classical and multi-agent epistemic (epistemic, for brevity) planners in a single architecture. The idea is to combine (i) classical; and(ii) epistemic solvers to model efficiently the agents’ interactions with the (i) ‘physical world’; and(ii) information flows, respectively. In particular, the presented architecture starts by planning on the ‘epistemic level’, with a high level of abstraction, focusing only on the information flows. Then it refines the planning process, due to the classical planner, to fully characterize the interactions with the ‘physical’ world. To further optimize the solving process, we introduced the concept of macros in epistemic planning and enriched the ‘classical’ part of the domain with goal-networks.

Finally, we evaluated our approach in an actual robotic environment showing that our architecture indeed reduces the overall computational time.
Real-World Effectiveness of Palbociclib Plus Aromatase Inhibitors in African American Patients With Metastatic Breast Cancer
Authors: Rugo Hope S , Liu Xianchen , Li Benjamin , McRoy Lynn , Chen Connie , Layman Rachel M , Brufsky Adam
Published: July 2023

Background

Disparities in survival and clinical outcomes between African American and White patients with breast cancer (BC) are well documented, but African American patients have not been well represented in randomized clinical trials of CDK4/6 inhibitors. Real-world studies can provide evidence for effective treatment strategies for underreported patient populations.

Patients and Methods

This retrospective analysis of African American patients with HR+/HER2− metastatic breast cancer (mBC) from the Flatiron Health longitudinal database evaluated treatments for patients with BC in routine clinical practice in the US. Patients initiated first-line therapy with palbociclib plus an aromatase inhibitor (AI) or AI alone between February 2015 and March 2020. Outcomes assessed included overall survival (OS) and real-world progression-free survival (rwPFS) until September 2020.

Results

Of 270 eligible patients, 127 (median age 64 years) were treated with palbociclib + AI, and 143 (median age 68 years) were treated with an AI. Median follow-up was 24.0 months for palbociclib + AI and 18.2 months for AI-treated patients. Median OS was not reached (NR; 95% CI, 38.2-NR) in the palbociclib + AI group versus 28.2 months (95% CI, 19.2-52.8) in the AI group (adjusted HR, 0.56; 95% CI, 0.36-0.89; P = .013). Median rwPFS was 18.0 months (95% CI, 12.4-26.7) in the palbociclib + AI group and 10.5 months (95% CI, 7.0-13.4) in the AI group (adjusted HR, 0.74; 95% CI, 0.47-1.17; P = .199).

Conclusion

This comparative analysis of palbociclib + AI versus AI alone indicates that palbociclib combined with endocrine therapy in the first line is associated with improved effectiveness for African American patients with HR+/HER2− mBC in real-world settings.

Trial number

NCT05361655
Allelic compatibility in plant immune receptors facilitates engineering of new effector recognition specificities
Authors: Bentham Adam R , De la Concepcion Juan Carlos , Benjumea Javier Vega , Kourelis Jiorgos , Jones Sally , Mendel Melanie , Stubbs Jack , Stevenson Clare E M , Maidment Josephine H R , Youles Mark , Zdrzałek Rafał , Kamoun Sophien , Banfield Mark J
Published: July 2023

Engineering the plant immune system offers genetic solutions to mitigate crop diseases caused by diverse agriculturally significant pathogens and pests. Modification of intracellular plant immune receptors of the nucleotide-binding leucine-rich repeat (NLR) receptor superfamily for expanded recognition of pathogen virulence proteins (effectors) is a promising approach for engineering disease resistance. However, engineering can cause NLR autoactivation, resulting in constitutive defense responses that are deleterious to the plant. This may be due to plant NLRs associating in highly complex signaling networks that coevolve together, and changes through breeding or genetic modification can generate incompatible combinations, resulting in autoimmune phenotypes. The sensor and helper NLRs of the rice (Oryza sativa) NLR pair Pik have coevolved, and mismatching between noncoevolved alleles triggers constitutive activation and cell death. This limits the extent to which protein modifications can be used to engineer pathogen recognition and enhance disease resistance mediated by these NLRs. Here, we dissected incompatibility determinants in the Pik pair in Nicotiana benthamiana and found that heavy metal–associated (HMA) domains integrated in Pik-1 not only evolved to bind pathogen effectors but also likely coevolved with other NLR domains to maintain immune homeostasis. This explains why changes in integrated domains can lead to autoactivation. We then used this knowledge to facilitate engineering of new effector recognition specificities, overcoming initial autoimmune penalties. We show that by mismatching alleles of the rice sensor and helper NLRs Pik-1 and Pik-2, we can enable the integration of synthetic domains with novel and enhanced recognition specificities. Taken together, our results reveal a strategy for engineering NLRs, which has the potential to allow an expanded set of integrations and therefore new disease resistance specificities in plants.
Export Controls and the Junction of Economics and National Security: A Review Article
Authors: Pillar Paul R
Published: July 2023

Mario Daniels and John Krige's Knowledge Regulation and National Security in Postwar America is a detailed history of the U.S. use of export controls and domestic debates over that use. Their account describes how issues of trade and commerce increasingly have been viewed in terms of security. Their history, which ends in 2020, does not directly address the current use of export controls and other measures to restrict the transfer of knowledge but is highly relevant to issues surrounding that use. Such controls represent a retreat from globalization and raise questions about their economic costs to the United States, their ultimate political impact on the targeted country, and their consequences for scientific inquiry.
Neural Cells for Neurodegenerative Diseases in Clinical Trials
Authors: Fan Yiping , Goh Eyleen L K , Chan Jerry Kok Yen
Published: July 2023

Neurodegenerative diseases (ND) are an entire spectrum of clinical conditions that affect the central and peripheral nervous system. There is no cure currently, with treatment focusing mainly on slowing down progression or symptomatic relief. Cellular therapies with various cell types from different sources are being conducted as clinical trials for several ND diseases. They include neural, mesenchymal and hemopoietic stem cells, and neural cells derived from embryonic stem cells and induced pluripotent stem cells. In this review, we present the list of cellular therapies for ND comprising 33 trials that used neural stem progenitors, 8 that used differentiated neural cells ,and 109 trials that involved non-neural cells in the 7 ND. Encouraging results have been shown in a few early-phase clinical trials that require further investigations in a randomized setting. However, such definitive trials may not be possible given the relative cost of the trials, and in the setting of rare diseases.
A disfiguring neglected tropical disease sweeps war-torn Yemen: a community-based study of prevalence and risk factors of cutaneous leishmaniasis among rural communities in the western highlands
Authors: Al-Ashwal Manal A , Atroosh Wahib M , Al-Adhroey Abdulelah H , Al-Subbary Assia A , Yee-Ling Lau , Al-Mekhlafi Hesham M
Published: July 2023

Background

Cutaneous leishmaniasis (CL) is a major health problem in Yemen and is endemic in many rural areas across the country.

Methods

A community-based cross-sectional survey followed by unmatched case–control comparisons was conducted among 612 participants in Utmah district, western Yemen. A total of 223 participants were included in the case–control analysis to identify the significant risk factors. Skin scrapping samples were examined by microscopy and internal transcribed spacer 1 nested polymerase chain reaction.

Results

Overall, 33% (202/612) of the participants had active skin lesions and/or scars that met the clinical criteria for CL. A total of 90 (14.7%) participants had suspected active CL lesions; however, a prevalence of 8.7% (53/612) was obtained based on molecular and parasitological examination, with Leishmania tropica being the only causative agent identified. Multivariable logistic regression analyses showed that being ≤10 y old, being female, living in houses with cracked walls, living in the presence of other family members with typical ulcerating skin diseases and sleeping outside were factors significantly associated with an increased likelihood of having CL. Moreover, keeping livestock on the ground floor of the house was significantly associated with a decreased likelihood of having CL.

Conclusion

The study reveals an alarmingly high prevalence of CL among the studied population. Therefore there is an urgent need for effective control measures and improved treatment efforts against this devastating disease.
Occurrence and Chemical Control Strategy of Wheat Brown Foot Rot Caused by Microdochium majus
Authors: Mao Yushuai , Wu Jian , Song Wen , Zhao Baoquan , Zhao Huahua , Cai Yiqiang , Wang Jianxin , Zhou Mingguo , Duan Yabing
Published: July 2023

Wheat brown foot rot (WBFR), caused by a variety of phytopathogenic fungi, is an important soilborne and seedborne disease of wheat. WBFR causes wheat lodging and seedling dieback, which seriously affect the yield and quality of wheat. In this study, 64 isolates of WBFR were isolated from different wheat fields in Yancheng city, Jiangsu Province, China. The internal transcribed spacer, elongation factor 1α, and RNA polymerase II subunit were amplified and the sequencing results of the fragments were analyzed with BLAST in NCBI. Through morphological and molecular identification, all of the isolates were identified as Microdochium majus. Verification by Koch’s postulates confirmed that M. majus was the pathogen causing WBFR. The antifungal activities of fludioxonil and prochloraz against 64 isolates of M. majus were determined based on mycelial growth inhibition method. The results showed that fludioxonil and prochloraz had good antifungal activity against M. majus. The mean 50% effective concentration values of fludioxonil and prochloraz against M. majus were 0.2956 ± 0.1285 μg/ml and 0.0422 ± 0.0157 μg/ml, respectively. Control efficacy for seed-coating treatments conducted in a greenhouse indicated that M. majus severely damaged the normal growth of wheat, while seed coating with fludioxonil or prochloraz significantly reduced the disease incidence and improved the seedling survival rates. At fludioxonil doses of 7.5 g per 100 kg and prochloraz doses of 15 g per 100 kg, the incidence was reduced by 22.26 and 25.33%, seedling survival rates increased by 25.37 and 22.66%, and control efficacy reached 70.02 and 72.30%, respectively. These findings provide vital information for the accurate diagnosis and effective management of WBFR.
CRISPR/Cas, Multiomics, and RNA Interference in Virus Disease Management
Authors: Kasi Viswanath Kotapati , Hamid Aflaq , Ateka Elijah , Pappu Hanu R.
Published: July 2023

Plant viruses infect a wide range of commercially important crop plants and cause significant crop production losses worldwide. Numerous alterations in plant physiology related to the reprogramming of gene expression may result from viral infections. Although conventional integrated pest management-based strategies have been effective in reducing the impact of several viral diseases, continued emergence of new viruses and strains, expanding host ranges, and emergence of resistance-breaking strains necessitate a sustained effort toward the development and application of new approaches for virus management that would complement existing tactics. RNA interference-based techniques, and more recently, clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing technologies have paved the way for precise targeting of viral transcripts and manipulation of viral genomes and host factors. In-depth knowledge of the molecular mechanisms underlying the development of disease would further expand the applicability of these recent methods. Advances in next-generation/high-throughput sequencing have made possible more intensive studies into host−virus interactions. Utilizing the omics data and its application has the potential to expedite fast-tracking traditional plant breeding methods, as well as applying modern molecular tools for trait enhancement, including virus resistance. Here, we summarize the recent developments in the CRISPR/Cas system, transcriptomics, endogenous RNA interference, and exogenous application of dsRNA in virus disease management.
Phenylpropanoids Following Wounding and Infection of Sweet Sorghum Lines Differing in Responses to Stalk Pathogens
Authors: Khasin Maya , Bernhardson Lois F. , O'Neill Patrick M. , Palmer Nathan A. , Scully Erin D. , Sattler Scott E. , Sarath Gautam , Funnell-Harris Deanna L.
Published: July 2023

Sweet sorghum ( Sorghum bicolor) lines M81-E and Colman were previously shown to differ in responses to Fusarium thapsinum and Macrophomina phaseolina, stalk rot pathogens that can reduce the yields and quality of biomass and extracted sugars. Inoculated tissues were compared for transcriptomic, phenolic metabolite, and enzymatic activity during disease development 3 and 13 days after inoculation (DAI). At 13 DAI, M81-E had shorter mean lesion lengths than Colman when inoculated with either pathogen. Transcripts encoding monolignol biosynthetic and modification enzymes were associated with transcriptional wound (control) responses of both lines at 3 DAI. Monolignol biosynthetic genes were differentially coexpressed with transcriptional activator SbMyb76 in all Colman inoculations, but only following M. phaseolina inoculation in M81-E, suggesting that SbMyb76 is associated with lignin biosynthesis during pathogen responses. In control inoculations, defense-related genes were expressed at higher levels in M81-E than Colman. Line, treatment, and timepoint differences observed in phenolic metabolite and enzyme activities did not account for observed differences in lesions. However, generalized additive models were able to relate metabolites, but not enzyme activities, to lesion length for quantitatively modeling disease progression: in M81-E, but not Colman, sinapic acid levels positively predicted lesion length at 3 DAI when cell wall-bound syringic acid was low, soluble caffeic acid was high, and lactic acid was high, suggesting that sinapic acid may contribute to responses at 3 DAI. These results provide potential gene targets for development of sweet sorghum varieties with increased stalk rot resistance to ensure biomass and sugar quality.
Gla‐domain mediated targeting of externalized phosphatidylserine for intracellular delivery
Authors: Hardy Jonathan , Bauzon Maxine , Chan Charles Kwok Fai , Makela Ashley V. , Kanada Masamitsu , Schneider Doug , Blankenberg Francis , Contag Christopher H. , Hermiston Terry
Published: July 2023

Phosphatidylserine (PS) is a negatively charged phospholipid normally localized to the inner leaflet of the plasma membrane of cells but is externalized onto the cell surface during apoptosis as well as in malignant and infected cells. Consequently, PS may comprise an important molecular target in diagnostics, imaging, and targeted delivery of therapeutic agents. While an array of PS‐binding molecules exist, their utility has been limited by their inability to internalize diagnostic or therapeutic payloads. We describe the generation, isolation, characterization, and utility of a PS‐binding motif comprised of a carboxylated glutamic acid (GLA) residue domain that both recognizes and binds cell surface‐exposed PS, and then unlike other PS‐binding molecules is internalized into these cells. Internalization is independent of the traditional endosomal–lysosomal pathway, directly entering the cytosol of the target cell rapidly. We demonstrate that this PS recognition extends to stem cells and that GLA‐domain‐conjugated probes can be detected upon intravenous administration in animal models of infectious disease and cancer. GLA domain binding and internalization offer new opportunities for specifically targeting cells with surface‐exposed PS for imaging and delivery of therapeutics.
Suicide among men
Authors: Scrandis Debra A. , Arnow Deborah
Published: July 2023

In the US each year, 80% of suicide deaths occur among men. As primary care is often the front door to identification and treatment of mental health problems, NPs in this setting are poised, with training in appropriate skills and tools, to recognize warning signs and risk factors in these patients as well as deliver necessary care and interventions to them. By being aware of known risk factors, identifying warning signs, communicating in a therapeutic manner, screening with standardized tools, assessing lethal means, developing safety plans, and making treatment referrals, primary care NPs can mitigate suicidal behaviors among men and save lives.
Lumbar Pedicle Subtraction Osteotomy (PSO)
Authors: Scheer Justin K. , Clark Aaron J. , Mitsunaga Kyle , Tan Lee A , Theologis Alekos A.
Published: July 2023

Study Design:

Operative video and supplemental manuscript.

Objective:

To present a novel step-by-step approach to performing a lumbar pedicle subtraction osteotomy (PSO) using laterally based satellite rods.

Summary of Background Data:

Multi-rod constructs have demonstrated paramount for decreasing rates of pseudarthrosis after PSOs. Multi-rods constructs can be achieved using either “satellite” rods (rods not connected to the primary rods) and/or “accessory rods” (rods connected to the primary rods).

Methods:

A step-by-step approach to performing a lumbar PSO using a laterally based satellite rod configuration is provided through a case example and surgical technique video.

Results:

Lateral satellite rods can be particularly useful from a surgical perspective, as they provide temporary stabilization while the PSO is being performed, facilitate closure of the osteotomy site (symmetric and/or asymmetric), and serve as the final fixation rods across the PSO without needing to be exchanged.

Conclusions:

Use of laterally based satellite rods is a useful technique for lumbar PSOs, as they provide temporary stabilization while the PSO is being performed, facilitate closure of the osteotomy site, and serve as the final fixation rods across the PSO without needing to be exchanged.
Coronavirus Disease 2019 Shutdown Did Not Affect Mental Health Scores in Lumbar Decompression Patients in a Large Metropolitan Region
Authors: Hartman Timothy J. , Nie James W. , MacGregor Keith R. , Oyetayo Omolabake O. , Zheng Eileen , Singh Kern
Published: July 2023

Study Design:

Retrospective study.

Objective:

To evaluate the effect of the coronavirus disease 2019 (COVID-19) shutdown in a large metropolitan area on mental health scores of spine patients undergoing lumbar decompression in the preoperative and early postoperative phases.

Summary of Background Data:

Global mental health has been demonstrated to be negatively affected by COVID-19 shutdowns. Preoperative mental health affects outcomes in spine patients, and the effect of COVID-19 shutdowns on mental health in this population is unclear.

Patients and Methods:

Patients were retrospectively identified from a single orthopedic spine surgeon registry. Patients were divided into 2 cohorts, separated by the date of surgery on or after March 20, 2020, the date of local shutdown due to COVID-19. After division, patients were propensity score matched for age, sex, ethnicity, common comorbidities, body mass index, preoperative visual analog scale back and leg pain scores, and preoperative Oswestry Disability Index. Perioperative characteristics were observed and recorded. Mental health scores, 12-item Short Form Mental Component Score, and 9-item Patient Health Questionnaire 9 were collected preoperatively, at 6 weeks, and at 12 weeks and compared between cohorts through Student t tests.

Results:

Three hundred thirty-four patients were identified, with 184 patients remaining after propensity score matching. Of the remaining 184 patients, 119 patients were identified as having surgery within the 2 years before the shutdown (“Pre-Shutdown”), whereas 65 patients had surgery within the 2 years after shutdown (“Post-Shutdown”). There were no significant differences between Pre-Shutdown and Post-Shutdown cohorts with regard to either Short Form Mental Component Score or Patient Health Questionnaire-9 at any time period evaluated (P > 0.050, all).

Conclusion:

The COVID-19 shutdown in a large metropolitan area did not affect preoperative or early postoperative mental health in patients undergoing lumbar decompression. However, each cohort was matched for preoperative pain and disability scores, which may have adversely been affected by the shutdown.
Are Clinical or Surgical Outcomes Different Based on Whether the Same Surgeon or Hospital System Performs the Spine Revision?
Authors: Issa Tariq Z. , Toci Gregory R. , Lambrechts Mark J. , Lee Yunsoo , Sherman Matthew , Brush Parker L. , Siegel Nicholas , Trenchfield Delano , Lambo Dominic , Parson Jory , Kim Erin , Canseco Jose A. , Hilibrand Alan S. , Vaccaro Alexander R. , Kepler Christopher K. , Schroeder Gregory D.
Published: July 2023

Study Design:

Retrospective cohort study.

Objective:

To determine the effects of discontinuity in care by changing surgeons, health systems, or increased time to revision surgery on revision spine fusion surgical outcomes and patient-reported outcomes.

Summary of Background Information:

Patients undergoing revision spine fusion experience worse outcomes than those undergoing primary lumbar surgery. Those requiring complex revisions are often transferred to tertiary or quaternary referral centers under the assumption that those institutions may be more accustomed at performing those procedures. However, there remains a paucity of literature assessing the impact of discontinuity of care in revision spinal fusions.

Methods:

Patients who underwent revision 1–3 level lumbar spine fusion 2011–2021 were grouped based on (1) revision performed by the index surgeon versus a different surgeon, (2) revision performed within the same versus different hospital system as the index procedure, and (3) length of time from index procedure. Multivariate regression for outcomes controlled for confounding differences.

Results:

A total of 776 revision surgeries were included. An increased time interval between the index procedure and the revision surgery was predictive of a lower risk for subsequent revision procedure (odds ratio: 0.57, P=0.022). Revision surgeries performed by the same surgeon predicted a reduced length of hospital stay (β: −0.14, P=0.001). Neither time to revision nor undergoing by the same surgeon or same practice predicted 90-day readmission rates. Patients are less likely to report meaningful improvement in Mental Component Score-12 or Physical Component Score-12 if revision surgery was performed at a different hospital system.

Conclusions:

Patients who have revision lumbar fusions have similar clinical outcomes regardless of whether their surgeon performed the index procedure. However, continuity of care with the same surgeon may reduce hospital length of stay and associated health care costs. The length of time between primary and revision surgery does not significantly impact patient-reported outcomes.

Level of Evidence:

Level III.
Spinal Cord Stimulators and Intrathecal Pain Pump Removal Versus Retention During Posterior Lumbar Fusion
Authors: McDonald Christopher L. , Alsoof Daniel , Anderson George , Johnson Keir , Daniels Alan H.
Published: July 2023

Study Design:

Retrospective cohort study.

Objective:

To determine risks associated with posterior lumbar arthrodesis after spinal cord stimulator (SCS) and intrathecal pain pump (IPP) insertion.

Summary of Background Data:

SCS and IPPs aid in the management of chronic back and radicular pain. Little is known regarding the risks of subsequent fusion with these devices in place.

Methods:

The PearlDiver Mariner database was queried for spinal fusion between 2010 and 2020. Study groups were created for indwelling SCS or IPP and matched to a separate cohort without SCS or IPP. Subgroups were created for those who had their device removed and those who retained their device at the time of surgery. Complications up to 2 years postoperatively were reviewed and confounding variables were controlled using multivariable logistic regression.

Results:

Four thousand five hundred three patients had an indwelling SCS/IPP and underwent posterior lumbar fusion. Compared with patients without history of an SCS/IPP, patients undergoing a lumbar fusion with an SCS/IPP which was removed or retained had higher rates of revision surgery at 1 year [7.3% vs. 5.0%, odds ratio (OR) =1.48, P<0.001] and 2 year (10.8% vs. 7.0%, OR =1.59, P<0.001). For all time intervals, there were higher odds of instrumentation failure (2 y: OR =1.65, P<0.001), and pulmonary complications (2 y: OR =1.18, P<0.001). At 2 years, there were higher odds of surgical site complications (OR 1.15, P=0.02) and urinary complications (OR=1.07, P=0.04). There were no differences in complications up to 2 years postoperatively in patients with an SCS/IPP who had their devices retained or removed (P>0.05).

Conclusions:

Patients with a history of spinal cord stimulators and intrathecal pain pumps are at increased risk of mechanical complications and revision fusion compared with patients without these devices. Patients with an SCS or IPP have similar rates of complications during lumbar fusion whether the device is removed or retained.
Epigenetic deregulation of MLF1 drives intrahepatic cholangiocarcinoma progression through EGFR/AKT and Wnt/β-catenin signaling
Authors: Tang Zengwei , Yang Yuan , Chen Wen , Liang Tingbo
Published: July 2023

Background:

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy with multiple etiologies and is largely refractory to current treatment strategies. Myeloid leukemia factor 1 (MLF1) is associated with human cancer progression. Nevertheless, the function of MLF1 in iCCA remains unknown.

Methods:

We performed expression analyses of MLF1 in human iCCA. In vitro and in vivo experiments were conducted to investigate the role of MLF1 in iCCA progression. The upstream regulatory mechanism of MLF1 upregulation in iCCA was deciphered by luciferase and DNA methylation analyses.

Results:

MLF1 was significantly upregulated in clinical iCCA tissue specimens and human iCCA cell lines. MLF1 was positively correlated with KRT19 and MUC1 expression and epithelial-mesenchymal transition (EMT) gene set enrichment score in clinical iCCA. High MLF1 expression was independently associated with worse prognoses in iCCA patients after curative resection. In addition, experimental knockdown of MLF1 attenuated, while overexpression of MLF1 promoted the proliferation, invasiveness, and growth of iCCA cells in vitro and in vivo. Mechanically, MLF1 comodulated EGFR/AKT and Wnt/β-catenin signalings through regulating EGFR, AKT, WNT3, and p-GSK3β expression. Promoter CpG sites’ hypermethylation-induced downregulation of miR-29c-3p contributed to MLF1 upregulation in iCCA patients. The upregulation of DNA methyltransferase (DNMT)1, 3A, and 3B downregulated miR-29c-3p by dictating promoter DNA methylation pattern. MiR-29c-3p showed therapeutic potential by targeting MLF1 in iCCA.

Conclusions:

Our results demonstrated that hypermethylation-mediated miR-29c-3p downregulation contributes to MLF1 upregulation in iCCA, which resulted in tumor cells’ proliferation and metastasis through comodulating EGFR/AKT and Wnt/β-catenin signalings.
THE HAIRY PHOENIX
Authors: Shakha  , Panigrahi Arnav , Gupta Shikha , Chawla Rohan , Gupta Viney
Published: July 2023

Purpose:

To report a case of a patient of anterior uveitis, iris neovascularization, high intraocular pressure and vasculitis in a patient with subconjunctival and intra ocular caterpillar hair.

Methods:

Case report.

Results:

A 30-year-old man complaining of episodes of blurring of vision and colored haloes in his left eye was referred for high intraocular pressure that was uncontrolled despite maximum tolerable medication in the left eye. He was diagnosed as a case of Posner-Schlossman syndrome in view of signs of anterior uveitis. He was also noted to have retinal hemorrhages in the peripheral fundus with peripheral vasculitis and capillary non perfusion areas. He underwent an uneventful trabeculectomy. During surgery, caterpillar hair were noted in his inferior conjunctiva that were removed. Later, a seta was also found in the vitreous in supertemporal quadrant.

Conclusion:

The case is an unusual presentation of caterpillar hair masquerading as a Posner-Schlossman syndrome.
What’s gut got to do with it? The role of the microbiota and inflammation in the development of adiposity and obesity
Authors: Jennings Travis , Janquart Mallory , Washak Catherine , Duddleston Khrystyne , Kurtz Courtney
Published: July 2023

Obesity is a complex and heterogeneous disease characterized by increased adiposity, ie, the accumulation of lipids and the growth of adipose tissue. In this mini-review, we explore the important role of the gut microbiota and immune system in the development of adiposity. Dysbiosis of the microbiota leads to increased permeability of the gut barrier and bacterial products in the bloodstream, which triggers metabolic inflammation of adipose tissue, muscle, and liver. Inflammation in these highly metabolic organs exacerbates adiposity and contributes to the development of comorbidities associated with obesity. Studies in animal models that manipulate the microbiota and/or inflammation have shown promise in the treatment of obesity.
Long-term trifocal toric intraocular lens outcomes in Asian eyes after cataract surgery
Authors: Ang Robert Edward T.
Published: July 2023

Purpose:

To determine the visual and refractive outcomes of trifocal toric intraocular lens (IOL) implantation in Asian eyes with cataract and astigmatism.

Setting:

Asian Eye Institute, Makati City, Philippines.

Design:

Prospective study.

Methods:

187 eyes were implanted with the FineVision POD FT IOL and followed for 2 years. The measurements included subjective refraction, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), distance-corrected intermediate visual acuity (DCIVA), uncorrected near visual acuity (UNVA), distance-corrected near visual acuity (DCNVA), defocus curve, photopic and mesopic contrast sensitivity, and rotational stability.

Results:

The mean spherical equivalent and cylinder values were, respectively, −0.07 ± 0.34 diopters (D) and −0.48 ± 0.31 D at the 2-year follow-up. At this same follow-up, 69.4% of patients had monocular CDVA and 79.3% had binocular UDVA ≤0.0 logMAR. For intermediate vision, monocular DCIVA reached 74.1%, while binocular UIVA was 86.2% ≤ 0.1 logMAR. Near vision showed 63% for monocular DCNVA and 70.7% for binocular UNVA ≤0.1 logMAR. The mean values at this follow-up were 0.02 ± 0.08, 0.08 ± 0.10, and 0.10 ± 0.12 logMAR for CDVA, DCIVA, and DCNVA, respectively. At the visual acuity threshold of ≤0.20 logMAR, the binocular defocus curve extended up to −3.75 D. Stable contrast sensitivity values were obtained at the different follow-ups. The mean IOL rotation was ≤2 degrees.

Conclusions:

The FineVision POD FT IOL yielded good visual outcomes at far, near, and intermediate distances with accurate refractive outcomes and good rotational stability in Asian eyes.
Nashville Qi? Chinese Medicine in an American Heartland
Authors: Rogaski Ruth
Published: July 2023

This article shares preliminary results from current research on Chinese medicine in Nashville, Tennessee, a city in the American South known both as “Music City, USA” and “The Buckle of the Bible Belt.” The author has interviewed dozens of patients and practitioners in Nashville to understand how Chinese medicine came to the city, what styles of practice are present, and whether or not new understandings of Chinese medicine’s fundamental concept of qi might emerge from the unique cultural setting of the American South. While Chinese medicine is flourishing in the city, because of complexities at the intersection of religion, science, and the experience of healing, the clinical encounter between patients and practitioners is not typically characterized by a mutual embrace of a language of qi.
An Autopsy Case of Abdominal Aortic Aneurysm in a Pediatric Decedent With Tuberous Sclerosis Complex
Authors: Auen Thomas , Linde Erin
Published: July 2023

Vascular involvement in tuberous sclerosis complex (TSC) is uncommon and even more so in pediatric patients. When asymptomatic, these vascular abnormalities carry increased risk of rupture with increased morbidity and mortality. Here, we describe a case of a ruptured unrecognized abdominal aortic aneurysm in an 11-month-old patient with a history of TSC. The abdominal aortic aneurysm was discovered at autopsy and highlights the rarity of abdominal aortic aneurysm in pediatric patients diagnosed with TSC and the importance of screening for associated aneurysmal disease in the pediatric population with TSC. Furthermore, the extensive retroperitoneal hemorrhage seen in this case also highlights a rare but potential mimic of abuse in the pediatric population.
Parents' Experiences on Therapeutic Hypothermia for Neonates With Hypoxic-Ischemic Encephalopathy (HIE): A Single-Center Cross-Sectional Study
Authors: Grass Beate , Erlach Melanie , Rathke Verena , Cippa Giuditta , Hagmann Cornelia , Brotschi Barbara
Published: July 2023

Background and Objectives:

The purpose of the study is to assess parental experiences of therapeutic hypothermia for moderate to severe hypoxic-ischemic encephalopathy with the goal of improving local clinical practice guidelines and fostering family-integrated care in neonates with hypoxic-ischemic encephalopathy.

Methods:

This single-center retrospective cross-sectional study included neonates and their parents registered in the Swiss National Asphyxia and Cooling Register between 2011 and 2021. Based on a literature review, an anonymous survey of parents of neonates with hypoxic-ischemic encephalopathy was developed and conducted using an online survey tool. Descriptive statistics were used to analyze the survey results.

Results:

The overall response rate to this survey was 64% (46/72). Sufficient information about hypoxic-ischemic encephalopathy was reported by 78% (36/46) of parents and sufficient information about the process of therapeutic hypothermia by 87% (40/46) of parents. The majority of parents indicated the need for, and at least a satisfactory perception of, professional (91%; 42/46) and emotional (87%; 40/46) support. Parents identified fostering family involvement and regular family communication that focuses on family integrated care as areas for improvement.

Conclusions:

There is still an unmet need for multidisciplinary teams to provide professional, empathetic, high quality, and family-integrated care to families with a neonate receiving therapeutic hypothermia for moderate or severe hypoxic-ischemic encephalopathy.
Improving Resident Hospital Discharge Communication by Changing Electronic Health Record Templates to Enhance Primary Care Provider Satisfaction
Authors: Lynch Kimberly A. , Baron Sarah W. , Rikin Sharon , Kanevsky Julie , Kelly Carol B. , Carrozzi Gianni , Wey Ginger , Yang Karen
Published: July 2023

Background and Objectives:

Despite use of standardized electronic health record templates, the structure of discharge summaries may hinder communication from inpatient settings to primary care providers (PCPs). We developed an enhanced electronic discharge summary template to improve PCP satisfaction with written discharge summaries targeting diagnoses, medication reconciliation, laboratory test results, specialist follow-up, and recommendations.

Methods:

Resident template usage was measured using statistical process control charts. PCP reviewers' discharge summary satisfaction was surveyed using 5-point Likert scales analyzed using the Mann-Whitney U test. Residents were surveyed for satisfaction.

Results:

Resident template usage increased from 61% initially to 72% of discharge summaries at 6 months. The PCP reviewers reported increased satisfaction for summaries using the template compared with those without (4.3 vs 3.9, P = .003). Surveyed residents desired template inclusion in the default electronic discharge summary (93%).

Conclusions:

This system-level resident-initiated quality improvement initiative created a novel discharge summary template that achieved widespread usage among residents and significantly increased outpatient PCP satisfaction.
Transformed Giant Congenital Melanocytic Nevus on 18F-FDG PET/CT
Authors: Feng Chengtao , Li Ke , Wang Chun , Zhao Sheng , Chen Long
Published: July 2023

A 50-year-old man experienced cough and bloody sputum for 1 month. CT detected a mass in the right lung. Staging 18F-FDG PET/CT revealed multiple hypermetabolic lesions in the lung, mediastinum, liver, and bones. Further physical examination revealed black patches in the skin covering most parts of the body, which presented at his birth and were growing very slowly, consistent with giant congenital melanocytic nevus. Pathology examination after biopsy of the lung demonstrated metastatic melanoma.
Evaluation of Alveolar Bone Reconstruction In Clefts With Early Or Late Secondary Bone Grafting: Use Of The 3d Kamperos score
Authors: Mattei Romane , Maggiulli Federica , Baumler Caroline , Torres Jacques-Henri , Captier Guillaume
Published: July 2023

There is still no consensus on the optimal age for alveolar grafting. In order to decide on the success of this graft, the best known radiographic assessments lacks precision. Kamperos recently proposed a 3D CBCT score that simultaneously assesses alveolar bone height and thickness, as well as the nasal floor level. The aim of this study was to apply this new score and compare it between an early secondary alveolar grafting « ESAG » (4-7 y) and a late secondary alveolar grafting « LSAG » (8-11 y) surgery group. A total of 32 cases of ESAG and 17 of LSAG were analysed. On 3D imaging, the median age of ESAGs was 10 years and 15 years for LSAGs. In the ESAGs, 78% of the permanents canines were not on the arch compared to 18% in the LSAGs. In both groups, the reconstruction of the nasal floor was very adequate but the height and thickness appeared less good in the ESAGs. The final score was higher in LSAG (Chi2, P < 0.005). The analysis of the alveolar bone with the Kamperos score is accurate and relevant but it should preferably be performed in the permanent dentition phase. This is because the area of rhizalysis of the primary teeth and the follicular sac of the erupting permanent teeth influence the presence of effective bone.
Minor Suture Fusion is Associated With Chiari Malformation in Nonsyndromic Craniosynostosis
Authors: Mizutani Kosuke , Kurimoto Michihiro , Nagakura Masamune , Nawashiro Tomoki , Nagai Toshiya , Aoki Kosuke , Kato Mihoko , Saito Ryuta
Published: July 2023

Here, we focused on the association between minor suture fusion and Chiari malformation (CM) occurrence in nonsyndromic craniosynostosis (NSC), and evaluated how the minor suture affects the posterior cranial fossa by measuring the posterior fossa deflection angle (PFA). In this retrospective study, the clinical records of 137 patients who underwent surgery for NSC at Aichi Children’s Health and Medical Center between April 2010 and May 2022 were analyzed. Clinical data from Aichi Developmental Disability Center Central Hospital was collected for 23 patients as the external validation set. Among the 137 patients, 123 were diagnosed with NSC and the remaining 14 with syndromic craniosynostosis. Of the 123 NSC patients, 23 patients presented with CM. Multivariate analysis showed that occipito-mastoid fusion was the only significant risk factor for CM (P=0.0218). Within the NSC group, CM patients had a significantly increased PFA (6.33±8.10 deg) compared with those without CM (2.76±3.29 deg, P=0.0487). Nonsyndromic craniosynostosis patients with occipito-mastoid suture fusion had a significantly increased PFA (6.50±7.60 deg) compared with those without occipito-mastoid fusion (2.60±3.23 deg, P=0.0164). In the validation cohort, occipito-mastoid suture fusion was validated as an independent risk factor for CM in univariate analysis. Minor suture fusion may cause CM associated with NSC. Chiari malformation could develop due to an increased PFA due to minor suture fusion, which causes growth disturbance in the affected side and compensatory dilation in the contralateral side within the posterior cranial fossa.