bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions
Authors: Henry Elia , Picou Frédéric , Barroca Vilma , Dechamps Nathalie , Sobrino Steicy , Six Emmanuelle , Gobeaux Camille , Auberger Patrick , Hérault Olivier , Pflumio Françoise , Arcangeli Marie-Laure
Published: August 2023

In a steady state, hematopoietic stem cells (HSC) exhibit very low levels of reactive oxygen species (ROS). Upon stress, HSC get activated and enter into proliferation and differentiation process to ensure blood cell regeneration. Once activated, their levels of ROS increase, as messengers to mediate their proliferation and differentiation programs. However, at the end of the stress episode, ROS levels need to return to normal to avoid HSC exhaustion. It was shown that antioxidants can prevent loss of HSC self-renewal potential in several contexts such as aging or after exposure to low doses of irradiation suggesting that antioxidants can be used to maintain HSC functional properties upon culture-induced stress. Indeed, in humans, HSC are increasingly used for cell and gene therapy approaches, requiring them to be cultured for several days. As expected, we show that a short culture period leads to drastic defects in HSC functional properties. Moreover, a switch of HSC transcriptional program from stemness to differentiation was evidenced in cultured HSC. Interestingly, cultured-HSC treated with 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (4-hydroxy-TEMPO or Tempol) exhibited a higher clonogenic potential in secondary colony forming unit cell (CFU-C) assay and higher reconstitution potential in xenograft model, compared to untreated cultured-HSC. By transcriptomic analyses combined with serial CFU-C assays, we show that Tempol, which mimics superoxide dismutase, protects HSC from culture-induced stress partly through VEGFα signaling. Thus, we demonstrate that adding Tempol leads to the protection of HSC functional properties during ex vivo culture.
Clinical and laboratory factors associated with splenic dysfunction among patients with sickle cell disease in a malaria endemic region
Authors: Ladu Adama I , Satumari Ngamarju A , Abba Aisha M , Abulfathi Fatima A , Jeffery Caroline , Adekile Adekunle , Bates Imelda
Published: August 2023

Background

Although loss of splenic function is the expected natural course for individuals with sickle cell disease (SCD), factors such as high HbF and coexistence of alpha thalassemia may ameliorate this process. We evaluated factors associated with two surrogate markers of spleen dysfunction, namely Howell–Jolly bodies (HJBs) and argyrophilic inclusion (AI) red cell counts, among patients with SCD.

Methods

Cross-sectional data of 182 patients with SCD (median age 11 y; 1–45 y) and 102 normal controls (median age 12 y; 1–32 y) were evaluated. Blood tests including full blood count, serum chemistry and high-performance liquid chromatography were performed. The HJB and AI red cell counts were performed on peripheral blood smears.

Results

The percentages of HJB and AI red cells rose significantly with increasing age in the SCD group. On regression analysis, the frequency of HJB red cells associated positively with mean corpuscular hemoglobin (MCH) (β=0.289; p=0.001) and negatively with HbF (β=−0.259; p=0.002). The AI red cell counts also associated positively with MCH (β=0.321; P=0.001) and negatively with HbF (β=−0.242; p=0.020).

Conclusions

Data from this study indicate that the negative association of HbF with both markers of splenic dysfunction among our patients with SCD residing in a malaria endemic region is similar to findings elsewhere of its ameliorating effect on splenic dysfunction.
Measuring Inequality Using Geospatial Data
Authors: Galimberti Jaqueson K , Pichler Stefan , Pleninger Regina
Published: August 2023

The main challenge in studying inequality is limited data availability, which is particularly problematic in developing countries. This study constructs a measure of light-based geospatial income inequality (LGII) for 234 countries/territories from 1992 to 2013 using satellite data on night-lights and gridded population data. Key methodological innovations include the use of varying levels of data aggregation, and a calibration of the lights–prosperity relationship to match traditional inequality measures based on income data. The new LGII measure is significantly correlated with cross-country variation in income inequality. Within countries, the light-based inequality measure is also correlated with measures of energy efficiency and the quality of population data. Two applications of the data are provided in the fields of health economics and international finance. The results show that light- and income-based inequality measures lead to similar results, but the geospatial data offer a significant expansion of the number of observations.
The role of zinc finger proteins in malignant tumors
Authors: Zhao Jia , Wen Doudou , Zhang Shubing , Jiang Hao , Di Xiaotang
Published: August 2023

Zinc finger proteins (ZNFs) are the largest family of transcriptional factors in mammalian cells. Recently, their role in the development, progression, and metastasis of malignant tumors via regulating gene transcription and translation processes has become evident. Besides, their possible involvement in drug resistance has also been found, indicating that ZNFs have the potential to become new biological markers and therapeutic targets. In this review, we summarize the oncogenic and suppressive roles of various ZNFs in malignant tumors, including lung, breast, liver, gastric, colorectal, pancreatic, and other cancers, highlighting their role as prognostic markers, and hopefully provide new ideas for the treatment of malignant tumors in the future.
Combining the Physical–Chemical Approach with Standard Base Excess to Understand the Compensation of Respiratory Acid–Base Derangements: An Individual Participant Meta-analysis Approach to Data from Multiple Canine and Human Experiments
Authors: Zadek Francesco , Danieli Andrea , Brusatori Serena , Giosa Lorenzo , Krbec Martin , Antolini Laura , Fumagalli Roberto , Langer Thomas
Published: August 2023

Background

Several studies explored the interdependence between Paco
2 and bicarbonate during respiratory acid–base derangements. The authors aimed to reframe the bicarbonate adaptation to respiratory disorders according to the physical–chemical approach, hypothesizing that (1) bicarbonate concentration during respiratory derangements is associated with strong ion difference; and (2) during acute respiratory disorders, strong ion difference changes are not associated with standard base excess.

Methods

This is an individual participant data meta-analysis from multiple canine and human experiments published up to April 29, 2021. Studies testing the effect of acute or chronic respiratory derangements and reporting the variations of Paco
2, bicarbonate, and electrolytes were analyzed. Strong ion difference and standard base excess were calculated.

Results

Eleven studies were included. Paco
2 ranged between 21 and 142 mmHg, while bicarbonate and strong ion difference ranged between 12.3 and 43.8 mM, and 32.6 and 60.0 mEq/l, respectively. Bicarbonate changes were linearly associated with the strong ion difference variation in acute and chronic respiratory derangement (β-coefficient, 1.2; 95% CI, 1.2 to 1.3; P < 0.001). In the acute setting, sodium variations justified approximately 80% of strong ion difference change, while a similar percentage of chloride variation was responsible for chronic adaptations. In the acute setting, strong ion difference variation was not associated with standard base excess changes (β-coefficient, –0.02; 95% CI, –0.11 to 0.07; P = 0.719), while a positive linear association was present in chronic studies (β-coefficient, 1.04; 95% CI, 0.84 to 1.24; P < 0.001).

Conclusions

The bicarbonate adaptation that follows primary respiratory alterations is associated with variations of strong ion difference. In the acute phase, the variation in strong ion difference is mainly due to sodium variations and is not paralleled by modifications of standard base excess. In the chronic setting, strong ion difference changes are due to chloride variations and are mirrored by standard base excess.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Differential Gene Expression Profiles and Pathways Highlight the Role of Osteoimmunology in Neurofibromatosis Type 1–Related Dystrophic Scoliosis With Osteopenia
Authors: Li Song , Wu Zhichong , Ma Yanyu , Zhu Yitong , Feng Zhenhua , Zhu Zezhang , Qiu Yong , Mao Saihu
Published: August 2023

Study Design.

Microarray approach and integrated gene network analysis.

Objective.

To explore the differential genetic expression profile, Gene Ontology terms, and Kyoto Encyclopedia of Genes and Genomes pathways in human trabecular bone (HTB)-derived cells of dystrophic scoliosis secondary to neurofibromatosis type 1 (DS-NF1) and compare these to normal controls.

Summary of Background Data.

The pathogenesis of DS-NF1 and the accompanying generalized osteopenia remain unclear. We hypothesized that HTBs may play a significant role in the etiology and pathogenesis of DS-NF1.

Materials and Methods.

Microarray analysis was used to identify differentially expressed genes of HTBs from patients with DS-NF1 compared with those from healthy individuals. Functional and pathway enrichment analysis were implemented through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway database. Then, the “search tool for the retrieval of interacting genes/proteins” database, Cytoscape, and “Molecular Complex Detection” were applied to construct the protein-protein interaction (PPI) network and screen hub genes. Pathway enrichment analysis was further performed for hub genes and gene clusters identified through module analysis. Six potential crucial genes were selected for validation by reverse transcription polymerase chain reaction.

Results.

Bioinformatic analysis revealed that there are 401 previously unrecognized differentially expressed genes (238 up and 163 downregulated genes) in HTBs from patients with DS-NF1, and they were mainly enriched in terms of immune response, type-I interferon (IFN) signaling, TNF signaling pathway and etinoic acid inducible gene I-like receptor signaling pathway. Five hub genes, including signal transducer and activator of transcription 1, 2’-5’-oligoadenylate synthetase-like, IFN induced with helicase C domain 1, IFN regulatory factor 7, and MX dynamin-like GTPase 1 were identified through PPI network, which were mainly enriched in terms of Jak-STAT and etinoic acid inducible gene I-like receptor signaling pathway. An independently dysregulated protein cluster containing CCL2, CXCL1, CXCL3, CX3CL1, TLR1, and CXCL12 was also identified through the PPI network. This indicated that the upper abnormally expressed genes may play essential roles in DS-NF1 pathogenesis and accompanied osteopenia.

Conclusion.

Six key genes were identified in the progression of DS-NF1–related osteopenia. Immune response might play a key role in the progression of osteopenia, whereas a CXCL12-mediated osteogenic effect might play a protective role.
M2 tumor-associated macrophage promoted DNA methylation in lung cancer metastasis via intensifying EZH2
Authors: Li Zheming , Luo Jing , Zhao Kaixiang , Xu Jingjing , Xia Lilong
Published: August 2023

This study aimed to explore the interaction between the tumor-associated macrophage (TAM) and enhancer of zeste homolog 2 (EZH2) in tumor microenvironment of lung cancer are obscure. M2 type of TAM was induced by interleukin-4 (IL-4) and interleukin-13 (IL-13) in RAW264.7 cells. Subsequently, the co-culture system of the M2 RAW264.7 treating LLC-1 cells were constructed to evaluate the cell proliferation, migration and invasion abilities. On top of that, the M2 RAW264.7 was injected into the LLC-1 cells-bearing mice. Tumor growth and the number of metastatic nodes were observed. Moreover, DNA methylation, EZH2 expression, target genes of EZH2 and the M2 type TAM-related markers were detected in vivo and in vitro. Further experiments of EZH2 function in lung cancer were carried out by the addition of EZH2 inhibitor (GSK126) and si-EZH2. M2 type of TAM was induced with IL-4 and IL-13 with increased expression of CD206, CD68, CD163 and Arg1. Following co-culture with M2 type TAM, the proliferative, invasive, migrative abilities, tumor growth and metastasis, and the DNA methylation, EZH2 level were strengthened whereas the target genes of EZH2, including p21, CDKN2A, CDKN2B were reduced in LLC-1 cells and LLC-1 cell-bearing mice. Of note, GSK126 and si-EZH2 offset the M2 type TAM’s effects, and inhibited the LLC-1 cell metastasis, DNA methylation and tumor growth. M2 type TAM promoted DNA methylation in LLC-1 cells and LLC-1 cell-bearing mice, which is related to the intensified EZH2.
Transcranial Color-Coded Sonography With Angle Correction As a Screening Tool for Raised Intracranial Pressure
Authors: Rajajee Venkatakrishna , Soroushmehr Reza , Williamson Craig A. , Najarian Kayvan , Ward Kevin , Tiba Hakam
Published: August 2023

OBJECTIVES:

Transcranial Doppler (TCD) has been evaluated as a noninvasive intracranial pressure (ICP) assessment tool. Correction for insonation angle, a potential source of error, with transcranial color-coded sonography (TCCS) has not previously been reported while evaluating ICP with TCD. Our objective was to study the accuracy of TCCS for detection of ICP elevation, with and without the use of angle correction.

DESIGN:

Prospective study of diagnostic accuracy.

SETTING:

Academic neurocritical care unit.

PATIENTS:

Consecutive adults with invasive ICP monitors.

INTERVENTIONS:

Ultrasound assessment with TCCS.

MEASUREMENTS AND MAIN RESULTS:

End-diastolic velocity (EDV), time-averaged peak velocity (TAPV), and pulsatility index (PI) were measured in the bilateral middle cerebral arteries with and without angle correction. Concomitant mean arterial pressure (MAP) and ICP were recorded. Estimated cerebral perfusion pressure (CPP) was calculated as estimated CPP (CPPe) = MAP × (EDV/TAPV) + 14, and estimated ICP (ICPe) = MAP–CPPe. Sixty patients were enrolled and 55 underwent TCCS. Receiver operating characteristic curve analysis of ICPe for detection of invasive ICP greater than 22 mm Hg revealed area under the curve (AUC) 0.51 (0.37–0.64) without angle correction and 0.73 (0.58–0.84) with angle correction. The optimal threshold without angle correction was ICPe greater than 18 mm Hg with sensitivity 71% (29–96%) and specificity 28% (16–43%). With angle correction, the optimal threshold was ICPe greater than 21 mm Hg with sensitivity 100% (54–100%) and specificity 30% (17–46%). The AUC for PI was 0.61 (0.47–0.74) without angle correction and 0.70 (0.55–0.92) with angle correction.

CONCLUSIONS:

Angle correction improved the accuracy of TCCS for detection of elevated ICP. Sensitivity was high, as appropriate for a screening tool, but specificity remained low.
Failure of First Transition to Pressure Support Ventilation After Spontaneous Awakening Trials in Hypoxemic Respiratory Failure: Influence of COVID-19
Authors: Pérez Joaquin , Accoce Matías , Dorado Javier H. , Gilgado Daniela I. , Navarro Emiliano , Cardoso Gimena P. , Telias Irene , Rodriguez Pablo O. , Brochard Laurent
Published: August 2023

OBJECTIVES:

To describe the rate of failure of the first transition to pressure support ventilation (PSV) after systematic spontaneous awakening trials (SATs) in patients with acute hypoxemic respiratory failure (AHRF) and to assess whether the failure is higher in COVID-19 compared with AHRF of other etiologies. To determine predictors and potential association of failure with outcomes.

DESIGN:

Retrospective cohort study.

SETTING:

Twenty-eight-bedded medical-surgical ICU in a private hospital (Argentina).

PATIENTS:

Subjects with arterial pressure of oxygen (AHRF to Fio
2 [Pao
2/Fio
2] < 300 mm Hg) of different etiologies under controlled mechanical ventilation (MV).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We collected data during controlled ventilation within 24 hours before SAT followed by the first PSV transition. Failure was defined as the need to return to fully controlled MV within 3 calendar days of PSV start. A total of 274 patients with AHRF (189 COVID-19 and 85 non-COVID-19) were included. The failure occurred in 120 of 274 subjects (43.7%) and was higher in COVID-19 versus non-COVID-19 (49.7% and 30.5%; p = 0.003). COVID-19 diagnosis (odds ratio [OR]: 2.22; 95% CI [1.15–4.43]; p = 0.020), previous neuromuscular blockers (OR: 2.16; 95% CI [1.15–4.11]; p = 0.017) and higher fentanyl dose (OR: 1.29; 95% CI [1.05–1.60]; p = 0.018) increased the failure chances. Higher BMI (OR: 0.95; 95% CI [0.91–0.99]; p = 0.029), Pao
2/Fio
2 (OR: 0.87; 95% CI [0.78–0.97]; p = 0.017), and pH (OR: 0.61; 95% CI [0.38–0.96]; p = 0.035) were protective. Failure groups had higher 60-day ventilator dependence (p < 0.001), MV duration (p < 0.0001), and ICU stay (p = 0.001). Patients who failed had higher mortality in COVID-19 group (p < 0.001) but not in the non-COVID-19 (p = 0.083).

CONCLUSIONS:

In patients with AHRF of different etiologies, the failure of the first PSV attempt was 43.7%, and at a higher rate in COVID-19. Independent risk factors included COVID-19 diagnosis, fentanyl dose, previous neuromuscular blockers, acidosis and hypoxemia preceding SAT, whereas higher BMI was protective. Failure was associated with worse outcomes.
Measurable residual disease in peripheral blood in myeloma: dream or reality
Authors: Kubicki Tadeusz , Derman Benjamin A. , Dytfeld Dominik , Jakubowiak Andrzej J.
Published: August 2023

Purpose of review

Therapeutic advancements in multiple myeloma have led to increasingly deeper and more durable responses, creating a need for highly sensitive and applicable techniques for measurable residual disease (MRD) assessment. Bone marrow assays can deeply assess for MRD, but it is not conducive to performing frequent and dynamic evaluations, which may be needed for MRD-adapted treatment approaches. Recently, numerous techniques for MRD assessment in peripheral blood have come under investigation, and their integration into routine clinical practice is eagerly anticipated.

Recent findings

The identification of circulating tumor cells (CTCs), evaluation of cell-free DNA, and measuring monoclonal protein concentration with mass spectrometry are promising research areas for assessing myeloma in peripheral blood. CTCs assessment and cell-free DNA may carry prognostic significance, but they lack the sensitivity of bone marrow-based techniques. Mass spectrometry has already been implemented in clinical practice in certain centers, but its full potential has yet to be fully realized. This review focuses on recent developments in these fields, emphasizing the potential future roles of these assessments.

MRD assessment in peripheral blood is still in the development stage but holds promise for not only complementing bone marrow based evaluations but also potential for improving sensitivity.
Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis
Authors: Liu Fangming , Wu Yuting , Zhang Baohui , Yang Shuhui , Shang Kezhuo , Li Jie , Zhang Pengju , Deng Weiwei , Chen Linlin , Zheng Liang , Gai Xiaochen , Zhang Hongbing
Published: August 2023

Background:

Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 (CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms.

Methods:

Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 (β-cateninΔ(ex3)/+
), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+
but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus (HBV); β-cateninlox(ex3)/+
mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer.

Results:

MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+
mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer.

Conclusion:

MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.
A Retrospective Review of Outcomes and Complications after Infant Ear Molding at a Single Institution
Authors: Sayadi Jamasb J. , Arora Jagmeet S. , Chattopadhyay Arhana , Hopkins Elena , Quiter Alison , Khosla Rohit K.
Published: August 2023

Background:

The purpose of this study was to evaluate outcomes and complications associated with infant ear molding at a single institution.

Methods:

We conducted a retrospective chart review of all infants who underwent ear molding using the EarWell Infant Ear Correction System with pediatric plastic surgery from October 2010 to March 2021. Types of ear anomalies, age at initiation, duration of treatment, gaps in treatment, comorbidities, and complications were extracted for included patients. The primary outcomes assessed were degree of ear anomaly correction and incidence of skin complications. Parents were also sent a questionnaire regarding their long-term satisfaction with the ear molding treatment process.

Results:

A total of 184 ears of 114 patients meeting inclusion criteria were treated during the study period. Mean age at treatment initiation was 21 days, and average duration of treatment was 40 days. Helical rim deformities (N = 50 ears) and lop ear (N = 40 ears) were the most common anomalies. A total of 181 ears (98.4%) achieved either a complete (N = 125 ears, 67.9%) or partial correction (N = 56 ears, 30.4%). The most common complications were eczematous dermatitis (N = 27 occurrences among 25 ears, 13.6%) and pressure ulcers (N = 23 occurrences among 21 ears, 12.5%). Infants who experienced a complication were 3.36 times more likely to achieve partial relative to complete correction (P < 0.001; 95% confidence interval 1.66–6.81).

Conclusion:

Ear molding is an effective treatment strategy for infant ear anomalies, with most patients achieving complete correction.
Posttraumatic Penile Replantation with Minimal Skin Necrosis
Authors: Veeramani Anamika , Hwang Charles D. , Gardenier Jason C. , Fruge Seth E. , Khouri Kimberly S. , Ehret Ashley L. , Vieira Brittany L. , Buta Martin R. , Cetrulo Curtis L.
Published: August 2023

Penile amputation is a surgical emergency where practical and timely perioperative management is crucial for ensuring a successful outcome. Tenuous viability of penile and scrotal skin has been well described in the literature, with a putative mechanism attributed to the transection of distal branches of the external pudendal artery. Although the perforasomes critical to penile replantation have been debated, this case report details a patient who successfully recovered sensation and function with minimal necrosis after penile replantation. Surgically, this was facilitated by intentional drain placement, aggressive debridement beyond the zone of injury, and planned redundancies with dorsal artery/vein anastomoses via interposition grafts of the dorsal penile vessels alone.
The Role of Radiology in Multidisciplinary Discussion of Patients With Interstitial Lung Diseases
Authors: Stowell Justin T. , Abril Andy , Khoor Andras , Lee Augustine S. , Baig Hassan Z.
Published: August 2023

Radiologists fulfill a vital role in the multidisciplinary care provided to patients with interstitial lung diseases and other diffuse parenchymal lung disorders. The diagnosis of interstitial lung diseases hinges on the consensus of clinical, radiology, and pathology medical subspecialists, but additional expertise from rheumatology, immunology, or hematology can be invaluable. The thin-section computed tomography (CT) features of lung involvement informs the diagnostic approach. Radiologists should be familiar with radiologic methods (including inspiratory/expiratory and prone imaging) and be well versed in the recognition of the CT features of fibrosis, assessment of the overall pattern of lung involvement, and classification according to the latest guidelines. We present a case-based review that highlights examples wherein CT features and subspecialist radiologist interpretation informed the multidisciplinary team consensus diagnosis and care pathways.
The Superficial Circumflex Iliac Artery Perforator Flap for Devastating Hand Injuries in Obese Patients
Authors: Jain Nirbhay S. , Bingham Elijah , Goldberg Mytien
Published: August 2023

Introduction

Blast injuries to the hand, such as those from fireworks, are debilitating and life altering. Often, because of the nature of the injury, there is a need for soft tissue and skin coverage. However, in the increasingly obese American population, free flaps often are too bulky for functional hand coverage. In this study, we present a series of 7 patients who underwent the superficial circumflex iliac artery perforator (SCIP) flap for upper extremity reconstruction with improvement in cosmesis, including a primarily repaired donor site, as well as an overwhelmingly high return to work with minimal revision surgery necessary.

Methods

All patients who underwent a SCIP for hand injuries from a blast were included. Flaps were harvested based on previously described methods. A single attending surgeon performed all surgeries. All patients were followed for at least 6 months. Preoperative and postoperative characteristics were described.

Results

A total of 7 patients were included in this study. Ages ranged from 16 to 58 years and body mass index from 19 to 48 kg/m2. More than half of the patients had a body mass index greater than 30 kg/m2. All donor sites were primarily closed. Five patients returned to their preinjury work. Three patients had neurotized flaps with return of protective sensation. Three patients required revision surgery; all 3 had liposuction, and 1 had additional flap advancement surgery.

Conclusion

The SCIP flap is a versatile flap that can be used in hand reconstruction in blast injuries with good functional outcome and improved cosmesis compared with other perforator flaps for the upper extremity.
A Pilot Randomized Trial of a Purposeful and Stimulating Volunteer Opportunity
Authors: Piette John D. , Hampstead Benjamin M. , Marinec Nicolle , Chen Jenny , Roberts J. Scott
Published: August 2023

Background:

Purposeful social interactions are important for healthy aging. We conducted a pilot trial of SPEAK! (Seniors Promoting English Acquisition and Knowledge), an intervention providing older volunteers with a safe, accessible opportunity to converse via webcam with English-language learners.

Methods:

A neurologically mixed sample of older adults was randomized to 8 weekly, webcam conversations with English-language learners or a waitlist control. Outcomes included the Cognitive Change Index (CCI) and surveys of program satisfaction. Here, we report on session completion, intervention satisfaction, and follow-up CCI scores. Exploratory analyses of CCI intervention effects controlled for baseline CCI scores and the interaction between group and baseline CCI.

Results:

Participants (N=38) were on average 70.8 years of age, 28/38 were White, and 16/38 demonstrated possible cognitive impairment on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Pairs completed 115/136 sessions (85%) and all volunteers said they would recommend the program. Controlling for the interaction between baseline CCI and randomization group, SPEAK! volunteers had better follow-up CCI scores than controls (P=0.018). Improvements in CCI were greater among participants with fewer baseline memory problems.

Conclusions:

SPEAK! was feasible and appreciated by older adults with and without cognitive impairment. Larger studies should confirm benefits for memory and other determinants of quality of life.
Multiple synchronous spinal dural arteriovenous fistulas: A systematic literature review
Authors: Ikeuchi Yusuke , Fujita Atsushi , Kohta Masaaki , Yamanishi Shunsuke , Tanaka Kazuhiro , Sasayama Takashi
Published: August 2023

Background

Multiple spinal dural arteriovenous fistulas (SDAVFs) are rare and account for only 1–2% of all SDAVF cases. The treatment for SDAVFs typically involves either direct surgy or endovascular treatment. Identifying the precise location of all fistulas is paramount for successful treatment procedures when multiple SDAVFs are present. They can be classified as synchronous (occurring simultaneously) or metachronous (occurring at different times), with each type differing with respect to etiology, diagnosis, and treatment. This study systematically reviewed the literature on multiple synchronous SDAVFs.

Methods

A comprehensive search was performed to identify all published multiple synchronous SDAVF cases. Overall, 23 patients with multiple SDAVFs were identified, including 21 from 19 articles and 2 from this study. Clinical presentation, lesion location, radiographic features, surgical treatment, and outcome were analyzed in each patient.

Results

All patients in this study were male individuals, and the duration from symptom onset to diagnosis in many of these patients was longer than that previously reported. Previous studies suggested that multiple SDAVFs typically occurred within three of fewer vertebral levels. However, >50% of examined patients had remote lesions separated by more than three vertebral levels. Patients with remote lesions had a significantly worse outcome (1/7 vs. 8/11, P=0.049). Therefore, accurate localization of fistulas before spinal angiography is critical for managing multiple remote SDAVFs.

Conclusions

Considering the possibility of multiple remote SDAVFs, careful interpretation of imaging findings is essential for accurate diagnosis and appropriate treatment planning.

KEY MESSAGES

What is already known on this topic

Multiple spinal dural arteriovenous fistulas (SDAVFs) can be classified as synchronous (occurring simultaneously) or metachronous (occurring at different times), and they differ in etiology, diagnosis, and treatment. However, the differences between two conditions need to be better clarified.

What this study adds

Patients with remote SDAVFs tended to receive more treatments and had worse prognosis than those with non-remote SDAVFs. Therefore, correct localization of fistulas before spinal angiography is essential for managing multiple remote SDAVFs.

How this study might affect research, practice or policy

Multiple remote SDAVFs may occur in patients; therefore, careful interpretation of imaging results is critical for accurate diagnosis and appropriate treatment planning.
Gamified Adaptive Approach Bias Modification in Individuals with Methamphetamine Use History from Communities in Sichuan: A Pilot RCT
Authors: Shen Danlin , Jiao Jianping , Zhang Liqun , Liu Yanru , Liu Xiang , Li Yuanhui , Zhang Tianjiao , Li Dai , Hao Wei
Published: August 2023

BACKGROUND

Cognitive bias modification (CBM) programs have shown promise in treating psychiatric conditions, but they can be perceived as boring and repetitive. Incorporating gamified designs and adaptive algorithms in CBM training may address this issue and enhance engagement and effectiveness.

OBJECTIVE

To gather preliminary data and assess the preliminary efficacy of an adaptive approach bias modification (A-ApBM) paradigm in reducing cue-induced craving in individuals with methamphetamine use history.

METHODS

A randomized controlled trial with three arms was conducted. Individuals aged 18-60 with methamphetamine dependence and at least one year of methamphetamine use were recruited from 12 community-based rehabilitation centers in Sichuan, China. Individuals with inability to fluently operate a smartphone and/or the presence of mental health conditions other than methamphetamine use disorder (MUD) were excluded. A-ApBM group engaged in ApBM training using a smartphone application for four weeks. A-ApBM used an adaptive algorithm to dynamically adjust the difficulty level based on individual performance. Cue-induced craving scores and relapse were assessed using a visual analog scale at baseline, post-intervention, and at week-16 follow-up.

RESULTS

A total of 136 participants were recruited and randomized: 48 were randomized to the A-ApBM group, 48 were randomized to the S-ApBM group, and 40 were randomized to the no-intervention control group. The A-ApBM group showed a significant reduction in cue-induced craving scores at post-intervention compared to baseline (Cohen’s d = 0.34, p < 0.01, 95% CI = [0.03,0.54]). The reduction remained significant at the week-16 follow-up (Cohen’s d = 0.40, p= 0.01, 95% CI = [0.18,0.57]). No significant changes were observed in the S-ApBM and control groups.

CONCLUSION

The adaptive ApBM paradigm with gamified designs and dynamic difficulty adjustments may be an effective intervention for reducing cue-induced craving in individuals with methamphetamine use history. This approach improves engagement and personalization, potentially enhancing the effectiveness of CBM programs. Further research is needed to validate these findings and explore the application of adaptive ApBM in other psychiatric conditions.

TRIAL REGISTRATION

Registered atclinicaltrials.gov(IDNCT05794438).
A Causal Inference of the Effect of Vaccination on COVID-19 Disease Severity and Need for Intensive Care Unit Admission Among Hospitalized Patients in an African Setting
Authors: Belayneh Eskedar Kebede , Leulseged Tigist Workneh , Teklu Blen Solomon , Tewodros Bersabel Hilawi , Megiso Muluken Zeleke , Weldesenbet Edengenet Solomon , Berhanu Mefthe Fikru , Shaweno Yohannes Shiferaw , Hailu Kirubel Tesfaye
Published: August 2023

Background

The COVID-19 pandemic is a respiratory illness that has spread to over 210 countries and killed over 6 million people. There is no specific treatment for COVID-19, but vaccines have been developed that can help prevent severe illness and death. A number of studies have investigated the effect of vaccination on disease severity and outcome, and the findings indicate that vaccination is linked to a significant reduction in the risk of hospitalization, intensive care unit admission, and death from the disease. However, there is a scarcity of evidence in Africa in general, and no similar study has been conducted in Ethiopia yet. Therefore, the study aimed to assess the effect of vaccination on COVID-19 disease severity and need for Intensive Care Unit (ICU) admission among hospitalized patients at a private specialty clinic in Ethiopia.

Methods

A retrospective cohort study was conducted among 126 patients with COVID-19, 41 vaccinated and 85 unvaccinated, who were hospitalized between September 2021 and May 2022. Data was summarized using frequency (percentage) and median (interquartile range). To compare the characteristics of the two groups, Chi-square/ Fisher’s Exact and Mann Whitney U tests at p-value of ≤ 0.05 were used. To identify the effect of vaccination on COVID-19 disease severity, Marginal Structural Model (MSM) with inverse probability weighting (IPW) approach using robust poisson regression model was fitted and adjusted relative risk (ARR) and 95% CI for ARR were used for interpreting the result.

Results

The cohort included groups that were fairly comparable in terms of their sociodemographic and clinical characteristics. More than half of the participants were older than 60 years (52.4%), were males (56.3%) and had one or more comorbid illness (52.4%). At admission 85 (67.5%) had severe disease and 11 (8.7%) progressed after hospitalization and required ICU admission, of which three unvaccinated cases died. From the final model, vaccination was found to be associated with a 62% decreased risk of developing severe COVID-19 disease if infected, compared to not getting vaccinated (ARR=0.38, 95% CI=0.23-0.65, p<0.0001).

Conclusions

The study’s findings support previous reports that vaccinated people are less likely to develop severe COVID-19 disease if infected with the virus, emphasizing the importance of continuing efforts to promote COVID-19 vaccination not only to safeguard individuals but also to confer community-level immunity.
Incidence of CKD and Death among Reproductive Age Women with Dialysis Requiring Acute Kidney Injury in Ethiopia: The Role of Obstetric Risk Factors
Authors: Lemma Ayantu Tesfaye , Leulseged Tigist Workneh , Lechebo Tsion Andrias , Osman Sisima kornelios , Mamo Delayehu Bekele
Published: August 2023

Background

Obstetric risk factors are among the leading preventable causes of Acute Kidney Injury (AKI) in hospitalized reproductive age women. Obstetric-related AKI (ORAKI) has been linked to a significant increase in the overall burden of AKI in resource-constrained settings, resulting in poor maternal and perinatal outcomes. As a result, understanding the impact of these factors on the progression of AKI is critical for a positive outcome. The study sought to determine the incidence of CKD and death, and the effect of obstetric risk factors on these outcomes among reproductive age women with dialysis requiring AKI at the national renal transplant center in Ethiopia.

Methods

A retrospective cohort study was conducted on 127 AKI cases (57 ORAKI and 70 None-ORAKI) who were on dialysis at the center from January 2018 to June 2020. A posthoc power analysis was calculated using G*Power 3.19.4. Data characterization and comparison was made using frequencies with percentages, median with interquartile range, chi-square test/ Fischer’s exact test and Mann-Whitney U test. A Robust Poisson regression model was used to identify factors that influence the progression of AKI to CKD and death, with Adjusted Relative Risk (ARR), 95% CIs for ARR, and P-values reported for result interpretation.

Results

The overall incidence rate (IR) of CKD was 5.4 per 1000 Person-days (PD) (ORAKI group=0 and None-ORAKI group= 9.7 per 1000 PD) and the overall incidence rate of death was 7.8 per 1000 PD (ORAKI group=5.5 per 1000 PD and None-ORAKI group= 9.7 per 1000 PD). According to the multivariable regression analysis, participants with ORAKI had a 22% lower risk of progression to CKD or death than those with None-ORAKI (ARR=0.78, 95%CI=0.67-0.90, p=0.001).

Conclusions

Although having obstetric related risk factors has been linked to an increased risk of developing AKI, once it occurs, those with ORAKI have a significantly better prognosis than those with None-ORAKI. Continued efforts to prevent AKI in pregnant women and to slow its progression once it has developed are critical for a better maternal and fetal outcome.
Prolonged Dual Antiplatelet Therapy in Acute Myocardial Infarction Patients without Revascularization: Results from a China Acute Myocardial Infarction (CAMI) registry study
Authors: Huang Cunrong , Yang Jingang , Li Ling , He Shenghu , Zhang Xuxia , Xu Haiyan , Wu Yuan , Zhang Jun , Qiao Shubin , Wu Yongjian , Zhao Yanyan , Wang Yang , Li Wei , Jin Chen , Gao Xiaojin , Yang Yuejin
Published: August 2023

Background

At least 12-month dual antiplatelet therapy (DAPT) is one of the standards of care following Percutaneous Coronary Intervention (PCI) in patients with acute coronary syndrome. However, study on prolonged DAPT for acute myocardial infarction (AMI) patients without revascularization is limited.

Methods

We studied 1744 AMI patients without revascularization from the China Acute Myocardial Infarction registry between January 2013 and September 2014. These patients were on DAPT and did not experience AMI, stroke, or bleeding events at 12-month follow-up. We divided them into two groups: 12-month DAPT group (DAPT for at least 12 months but less than 18 months) and 18-month DAPT group (DAPT for at least 18 months). The primary outcome is 24-month all-cause death.

Results

Overall, 1221 (70.0%) patients took DAPT for ≥12 months but <18 months, while 523 (30.0%) patients took DAPT for ≥18 months. The two groups had comparable proportions with high ischemic risk (27.0% vs. 25.6%, P = 0.5418), as well as high bleeding risk (29.0% vs. 28.5%, P = 0.8316). At 24 months, the all-cause mortality rate of 18-month DAPT group was significantly lower than that for 12-month DAPT group (3.7% vs 5.9%, P = 0.0471). Adjusted hazard ratio for all-cause death also showed statistical significance (0.59, 95% CI: 0.35-0.99, P = 0.0444).

Conclusions

DAPT for at least 18 months was associated with lower 24-month mortality for non-revascularization AMI patients without events within 12 months after onset.
TheLegionellaautoinducer LAI-1 is delivered by outer membrane vesicles to promote inter-bacterial and inter-kingdom signaling
Authors: Fan Mingzhen , Kiefer Patrick , Charki Paul , Hedberg Christian , Seibel Jürgen , Vorholt Julia A. , Hilbi Hubert
Published: August 2023

Legionella pneumophilais an environmental bacterium, which replicates in amoeba but also in macrophages, and causes a life-threatening pneumonia called Legionnaires’ disease. The opportunistic pathogen employs the α-hydroxyketone compound LAI-1 (Legionellaautoinducer-1) for intra-species and inter-kingdom signaling. LAI-1 is produced by the autoinducer synthase LqsA, but it is not known, how LAI-1 is released by the pathogen. Here, we use aV. choleraeluminescence reporter strain and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect bacteria-produced and synthetic LAI-1. Ectopic production of LqsA inE. coligenerated LAI-1, which partitions to outer membrane vesicles (OMVs), and slightly reduces OMV size. TheseE. coliOMVs trigger luminescence of theV. choleraereporter strain and inhibit the migration ofDictyostelium discoideumamoeba. Overexpression oflqsAinL. pneumophilaunder the control of strong stationary phase promoters (PflaAor P6SRNA), but not under control of its endogenous promoter (PlqsA), produces LAI-1, which is detected in purified OMVs. TheseL. pneumophilaOMVs trigger luminescence of theVibrioreporter strain and inhibitD. discoideummigration.L. pneumophilaOMVs are smaller upon overexpression oflqsAor upon addition of LAI-1 to growing bacteria, and therefore, LqsA affects OMV production. The overexpression oflqsAbut not a catalytically inactive mutant promotes intracellular replication ofL. pneumophilain macrophages, indicating that intracellularly produced LA1-1 modulates the interaction in favour of the pathogen. Taken together, we provide evidence thatL. pneumophilaLAI-1 is secreted through OMVs and promotes inter-bacterial communication as well as interactions with eukaryotic host cells.

Originality - Significance Statement

Inter-kingdom signaling involving low molecular weight bacterial compounds that are detected by eukaryotic cells represents an important, yet incompletely understood aspect of pathogen-host interactions. In many cases, the small signaling molecules are produced in only little amounts, their secretion mechanism is not known, and their effects on eukaryotic host cells are barely studied. Here, we reveal that the α-hydroxyketone compound LAI-1 ofL. pneumophilais released from the bacteria by outer membrane vesicles, which promote inter-bacterial communication as well as inter-kingdom signaling.
Urolithin A induces cardioprotection and enhanced mitochondrial quality during natural aging and heart failure
Authors: Liu S. , Faitg J. , Tissot C , Konstantopoulos D. , Laws R. , Bourdier G. , Andreux P.A. , Davey T. , Singh A. , Rinsch C. , Marcinek D.J. , D’Amico D.
Published: August 2023

Cardiovascular diseases remain the primary cause of global mortality, necessitating effective strategies to alleviate their burden. Mitochondrial dysfunction is a driving force behind aging and chronic conditions, including heart disease. Here, we investigate the potential of Urolithin A (UA), a gut microbiome-derived postbiotic that enhances mitophagy, to ameliorate both age-related decline in cardiac function and cardiac failure. We highlight the significance of targeting mitochondria, by comparing gene expression changes in aging human hearts and cardiomyopathies. UA oral administration successfully counteracts mitochondrial and cardiac dysfunctions in preclinical models of aging and heart failure. UA improves both systolic and diastolic heart functions, distinguishing it from other mitochondrial interventions. In cardiomyocytes, UA recovers mitochondrial ultrastructural defects and decline in mitochondrial biomarkers occurring with aging and disease. These findings extend UA’s benefits to heart health, making UA a promising nutritional intervention to evaluate in the clinic to promote healthy cardiovascular function as we age.
Real-World Experience of Deep Brain Stimulation Surgery in a Developing Southeast Asian Country
Authors: Dy Closas Alfand Marl F. , Tan Ai Huey , Tay Yi Wen , Hor Jia Wei , Toh Tzi Shin , Lim Jia Lun , Lew Choey Yee , Cham Chun Yoong , Yim Carolyn Chue Wai , Chee Kok Yoon , Ng Chong Guan , Lit Lei Cheng , Anuar Anis Nadhirah Khairul , Lange Lara M. , Fang Zih-Hua , Ciga Sara Bandres , Lohmann Katja , Klein Christine , Ahmad-Annuar Azlina , Muthusamy Kalai Arasu , Lim Shen-Yang
Published: August 2023

Background

The availability of deep brain stimulation (DBS), a highly efficacious treatment for several movement disorders, remains low in developing countries, with scarce data available on utilization and outcomes.

Objectives

We characterized the DBS cohort and outcomes at a Malaysian quaternary medical centre.

Methods

A retrospective chart review was done on DBS-related surgery at the University of Malaya, including clinico-demographic, genetics, and outcomes data focusing on post-operative medication reduction and complications.

Results

149 Parkinson’s disease (PD) patients underwent DBS targeting the subthalamic nucleus. Six had globus pallidus internus DBS (primarily for dystonia). Only 16.1% of cases were government-funded. Of the 133 PD patients operated in the past decade (2013-2022), 25 (18.8%) had disease duration <5 years. At 6-12 months post-DBS, median levodopa-equivalent daily dosage (LEDD) reduction was 440.5 [418.9] mg/day, corresponding to a reduction of ≥50% and ≥30% in 42.2% and 69.8% of patients, respectively. LEDD reductions were larger in the early-onset and short-duration subgroups. Three patients (1.9% of 155) had symptomatic intracranial hemorrhage, resulting in stroke in two. Pathogenic monogenic orGBA1variants were detected in 12/61 (19.7%) of patients tested, mostly comprising the “severe”GBA1variant p.L483P (14.8%).

Conclusion

This is the largest report on DBS from Southeast Asia. The procedures were effective, and complication rates on par with international norms. Our study found a high frequency ofGBA1-PD; and included a substantial number of patients with short-duration PD, who had good outcomes. It also highlights the inequity of access to device-aided therapy.