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Medicine Jun 2024Musculoskeletal symptoms, such as neck pain and low back pain (LBP) are common after a traffic accident (TA). While motion-style acupuncture treatment (MSAT) is... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness and safety of motion-style acupuncture treatment using traction for inpatients with acute low back pain caused by a traffic accident: A randomized controlled trial.
BACKGROUND
Musculoskeletal symptoms, such as neck pain and low back pain (LBP) are common after a traffic accident (TA). While motion-style acupuncture treatment (MSAT) is effective in relieving pain, MSAT using traction (T-MSAT) has rarely been studied, and evidence for its efficacy and safety is lacking. To address this gap, this study aimed to assess the effectiveness and safety of T-MSAT for pain and functional disturbances in patients with acute LBP caused by a TA.
METHODS
This two-armed, parallel, assessor blinded randomized controlled trial, conducted at Jaseng Hospital of Korean Medicine, included 100 patients with acute LBP occurring within 1 week of a TA. The participants were randomly allocated (1:1 ratio) to receive either combined T-MSAT and integrative Korean medicine treatment (IKMT) or only conventional IKMT, applied for 3 consecutive days after admission. The primary outcome was the difference between numerical rating scale (NRS) scores for LBP at baseline and after treatment completion on day 4 after admission.
RESULTS
At the primary endpoint, the difference in NRS scores for LBP between the T-MSAT and control groups was 0.94 (95% confidence interval [CI] 0.40-1.48). The T-MSAT group showed a significantly lower NRS score for LBP than the control group. Differences in visual analogue scale (VAS) scores between the T-MSAT and control groups were significant at baseline and discharge. The area under the curve of the VAS score showed a significant difference (-46.86 [95% CI -85.13 to -8.59]), indicating faster pain reduction in the T-MSAT group than in the control group. Recovery (30% pain reduction) was achieved more rapidly in the T-MSAT group than in the control group (log-rank test P = .005). Meanwhile, the NRS, VAS, Oswestry disability index, and quality of life scores at discharge or at the 12-week follow-up showed no significant difference. The rates of mild adverse events (AEs) were comparable between the groups. No severe AEs were reported, and none of the AEs were associated with the clinical trial.
CONCLUSIONS
T-MSAT combined with IKMT is a safe treatment that can effectively and quickly reduce initial pain in patients with LBP.
Topics: Humans; Low Back Pain; Male; Female; Acupuncture Therapy; Middle Aged; Traction; Accidents, Traffic; Adult; Treatment Outcome; Pain Measurement; Single-Blind Method
PubMed: 38905412
DOI: 10.1097/MD.0000000000038590 -
PloS One 2024As new and improved antigen-detecting rapid diagnostic tests for SARS-CoV-2 infection (Ag-RDT) continue to be developed, assessing their diagnostic performance is...
BACKGROUND
As new and improved antigen-detecting rapid diagnostic tests for SARS-CoV-2 infection (Ag-RDT) continue to be developed, assessing their diagnostic performance is necessary to increase test options with accurate and rapid diagnostic capacity especially in resource-constrained settings. This study aimed to assess the performance of two Ag-RDTs in a population-based study.
METHODS
We conducted a diagnostic accuracy study in neighborhoods with high socioeconomic vulnerability in Salvador-Brazil, including individuals aged ≥12 years old who attended primary health services, between July and December 2022, with COVID-19 symptoms or who had been in contact with a confirmed case. Two Ag-RDTs were compared in parallel using reverse transcription polymerase chain reaction (RT-PCR) as reference standard, the PanbioTM COVID-19 Ag test (Abbott®) and Immuno-Rapid COVID-19 Ag (WAMA Diagnostic®). Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated.
RESULTS
For the Abbott test the sensitivity was 52.7% (95% CI: 44.3% - 61.0%), specificity 100% (95% CI: 98.7% - 100%), PPV 100% (95% CI: 95.4% - 100%) and NPV 80.4% (95% CI: 75.9% - 84.4%). For the WAMA test, the sensitivity was 53.4% (95% CI: 45.0% - 61.6%), specificity 100% (95% CI: 98.7% - 100%), PPV 100% (95% CI: 95.4% - 100%) and NPV 80.7% (95% CI: 76.2% - 84.6%). Sensitivity for the group with Cycle Threshold (CT) <24 was 82.3% (95%CI: 72.1-90.0, n = 83) for PanbioTM COVID-19 Ag test and 87.3% (95%CI: 77.9-93.8, n = 83) for Immuno-Rapid COVID-19 Ag test.
CONCLUSION
Sensitivity for both Ag-RDT was lower than reported by manufacturers. In the stratified analysis, sensitivity was higher among those with lower CT values <24. Specificity was high for both rapid antigen tests. Both Ag-RDT showed to be useful for rapid diagnostic of potential cases of COVID-19. Negative results must be assessed carefully according to clinical and epidemiological information.
Topics: Humans; COVID-19; Male; SARS-CoV-2; Adult; Female; Middle Aged; Sensitivity and Specificity; Brazil; Child; COVID-19 Serological Testing; Adolescent; Antigens, Viral; Young Adult; Aged; Socioeconomic Factors
PubMed: 38905178
DOI: 10.1371/journal.pone.0298579 -
JAMA Network Open Jun 2024An intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake per week and meal replacement diet (5:2 MR) could provide... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
An intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake per week and meal replacement diet (5:2 MR) could provide additional benefits to patients with type 2 diabetes.
OBJECTIVE
To evaluate the effect of the 5:2 MR on glycemic control among patients with early type 2 diabetes compared with metformin and empagliflozin.
DESIGN, SETTING, AND PARTICIPANTS
The EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study is a randomized, open-label, active parallel-controlled clinical trial conducted between November 13, 2020, and December 29, 2022, in 9 centers across China. A total of 509 eligible patients underwent screening, out of which 405 were randomly assigned to 3 groups and included in the intention-to-treat analysis.
INTERVENTIONS
Patients were randomly allocated in a 1:1:1 ratio to receive either metformin, empagliflozin, or 5:2 MR. The treatment was 16 weeks, with an 8-week follow-up.
MAIN OUTCOMES AND MEASURES
The primary end point was the change in hemoglobin A1c (HbA1c) level from baseline to 16 weeks. Secondary end points included changes in body weight, anthropometric measurements, and biochemical parameters.
RESULTS
Of the 405 randomized participants (265 men [65.4%]; mean [SD] age, 45.5 [11.0] years; mean [SD] body mass index, 29.5 [4.1]; and mean [SD] HbA1c level, 7.9% [0.6%]), 332 completed the 16-week treatment. From baseline to week 16, participants in the 5:2 MR group showed the greatest reduction in HbA1c (least-squares mean [LSM], -1.9% [SE, 0.2%]), significantly greater than patients receiving metformin (LSM, -1.6% [SE, 0.2%]; adjusted LSM difference, -0.3% [95% CI, -0.4% to -0.1%]) and empagliflozin (LSM, -1.5% [SE, 0.2%]; adjusted LSM difference, -0.4% [95% CI, -0.6% to -0.2%]). At week 16, the mean weight loss in the 5:2 MR group (LSM, -9.7 kg [SE, 2.2 kg]) was greater than that in the metformin group (LSM, -5.5 kg [SE, 2.3 kg]) and empagliflozin group (LSM, -5.8 kg [SE, 2.3 kg]).
CONCLUSIONS AND RELEVANCE
This randomized clinical trial of Chinese adults with overweight or obesity and with early type 2 diabetes found that 5:2 MR could improve glycemic outcomes and weight loss in the short term compared with metformin or empagliflozin, making it a promising initial intervention and early management for type 2 diabetes.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Identifier: ChiCTR2000040656.
Topics: Humans; Male; Female; Middle Aged; Diabetes Mellitus, Type 2; Fasting; Metformin; Glucosides; Benzhydryl Compounds; Glycemic Control; Adult; Glycated Hemoglobin; Hypoglycemic Agents; China; Blood Glucose; Intermittent Fasting
PubMed: 38904963
DOI: 10.1001/jamanetworkopen.2024.16786 -
Microbiology Spectrum Jun 2024Carbapenem-resistant Enterobacterales represent a major health threat and have few approved therapeutic options. Enterobacterales isolates were collected from...
UNLABELLED
Carbapenem-resistant Enterobacterales represent a major health threat and have few approved therapeutic options. Enterobacterales isolates were collected from hospitalized inpatients from 49 sites in six European countries (1 January-31 December 2020) and underwent susceptibility testing to cefiderocol and β-lactam/β-lactamase inhibitor combinations. Meropenem-resistant (MIC >8 mg/L) and cefiderocol-susceptible isolates were analyzed by PCR, and cefiderocol-resistant isolates by whole-genome sequencing, to identify resistance mechanisms. Overall, 1,909 isolates (including 970 spp., 382 , and 244 spp.) were collected, commonly from bloodstream infections (43.6%). Cefiderocol susceptibility was higher than approved β-lactam/β-lactamase inhibitor combinations and largely comparable to cefepime-taniborbactam and aztreonam-avibactam against all Enterobacterales (98.1% vs 78.1%-97.4% and 98.7%-99.1%, respectively) and Enterobacterales resistant to meropenem ( = 148, including 125 spp.; 87.8% vs 0%-71.6% and 93.2%-98.6%, respectively), β-lactam/β-lactamase inhibitor combinations (66.7%-92.1% vs 0%-88.1% and 66.7%-97.9%, respectively), and to both meropenem and β-lactam/β-lactamase inhibitor combinations (61.9%-65.9% vs 0%-20.5% and 76.2%-97.7%, respectively). Susceptibilities to approved and developmental β-lactam/β-lactamase inhibitor combinations against cefiderocol-resistant Enterobacterales ( = 37) were 10.8%-56.8% and 78.4%-94.6%, respectively. Most meropenem-resistant Enterobacterales harbored carbapenemase (110/148) genes, although metallo-β-lactamase (35/148) and oxacillinase (OXA) carbapenemase (6/148) genes were less common; cefiderocol susceptibility was retained in β-lactamase producers, other than NDM, AmpC, and non-carbapenemase OXA producers. Most cefiderocol-resistant Enterobacterales had multiple resistance mechanisms, including ≥1 iron uptake-related mutation (37/37), carbapenemase gene (33/37), and mutation (24/37). The susceptibility to cefiderocol was higher than approved β-lactam/β-lactamase inhibitor combinations against European Enterobacterales, including meropenem- and β-lactam/β-lactamase inhibitor combination-resistant isolates.
IMPORTANCE
This study collected a notably large number of Enterobacterales isolates from Europe, including meropenem- and β-lactam/β-lactamase inhibitor combination-resistant isolates against which the activities of cefiderocol and developmental β-lactam/β-lactamase inhibitor combinations were directly compared for the first time. The MIC breakpoint for high-dose meropenem was used to define meropenem resistance, so isolates that would remain meropenem resistant with doses clinically available to patients were included in the data. Susceptibility to cefiderocol, as a single active compound, was high against Enterobacterales and was higher than or comparable to available β-lactam/β-lactamase inhibitor combinations. These results provide insights into the treatment options for infections due to Enterobacterales with resistant phenotypes. Early susceptibility testing of cefiderocol in parallel with β-lactam/β-lactamase inhibitor combinations will allow patients to receive the most appropriate treatment option(s) available in a timely manner. This is particularly important when options are more limited, such as against metallo-β-lactamase-producing Enterobacterales.
PubMed: 38904361
DOI: 10.1128/spectrum.04181-23 -
International Journal of Biological... 2024Shear stress-induced Dickkopf-1 (DKK1) secretion by endothelial cells (ECs) promotes EC dysfunction and accelerates atherosclerosis (AS). However, the paracrine role of...
Shear stress-induced Dickkopf-1 (DKK1) secretion by endothelial cells (ECs) promotes EC dysfunction and accelerates atherosclerosis (AS). However, the paracrine role of endothelial DKK1 in modulating adjacent smooth muscle cells (SMCs) in atherosclerosis remains unclear. This study investigated the role of EC-secreted DKK1 in SMC-derived foam cell formation under shear stress, and . Parallel-plate co-culture flow system was used to explore the cellular communication between ECs and SMCs under shear stress . Endothelium-specific knockout of DKK1 (DKK1/APOE) and endothelium-specific overexpression of DKK1 (DKK1) mice were constructed to investigate the role of endothelial DKK1 in atherosclerosis and SMC-derived foam cell formation . RNA sequencing (RNA-seq) was used to identify the downstream targets of DKK1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot, coimmunoprecipitation (Co-IP) assays and chromatin immunoprecipitation (ChIP) experiments were conducted to explore the underlying regulatory mechanisms. DKK1 is transcriptionally upregulated in ECs under conditions of low shear stress, but not in co-cultured SMCs. However, DKK1 protein in co-cultured SMCs is increased via uptake of low shear stress-induced endothelial DKK1, thereby promoting lipid uptake and foam cell formation in co-cultured SMCs via the post-translational upregulation of scavenger receptor-A (SR-A) verified in parallel-plate co-culture flow system, DKK1 and DKK1 mice. RNA sequencing revealed that DKK1-induced SR-A upregulation in SMCs is dependent on Ubiquitin-specific Protease 53 (USP53), which bound to SR-A via its USP domain and cysteine at position 41, exerting deubiquitination to maintain the stability of the SR-A protein by removing the K48 ubiquitin chain and preventing proteasomal pathway degradation, thereby mediating the effect of DKK1 on lipid uptake in SMCs. Moreover, DKK1 regulates the transcription of USP53 by facilitating the binding of transcription factor CREB to the USP53 promoter. SMC-specific overexpression of USP53 via adeno-associated virus serotype 2 vectors in DKK1/APOE mice reversed the alleviation of atherosclerotic plaque burden, SR-A expression and lipid accumulation in SMCs within plaques resulting from DKK1 deficiency. Our findings demonstrate that, endothelial DKK1, induced by pathological low shear stress, acts as an intercellular mediator, promoted the foam cell formation of SMCs. These results suggest that targeted intervention with endothelial DKK1 may confer beneficial effects on atherosclerosis.
Topics: Animals; Atherosclerosis; Mice; Intercellular Signaling Peptides and Proteins; Foam Cells; Myocytes, Smooth Muscle; Endothelial Cells; Humans; Ubiquitination; Male; Coculture Techniques; Mice, Knockout; Ubiquitin-Specific Proteases; Mice, Inbred C57BL
PubMed: 38904030
DOI: 10.7150/ijbs.91957 -
Frontiers in Medicine 2024This study aimed to investigate the influence of potential placebo and nocebo effects on pain perception of percutaneous needle electrolysis (PNE) in individuals with...
Placebo and nocebo effects of percutaneous needle electrolysis and dry-needling: an intra and inter-treatment sessions analysis of a three-arm randomized double-blinded controlled trial in patients with patellar tendinopathy.
OBJECTIVE
This study aimed to investigate the influence of potential placebo and nocebo effects on pain perception of percutaneous needle electrolysis (PNE) in individuals with patellar tendinopathy.
METHODS
In this secondary analysis of a three-arm randomized double-blinded controlled trial, intra and inter-session pain perception data from 48 sporting participants with patellar tendinopathy between 18 and 45 years were investigated. Participants were divided into 3 parallel groups: "no-sham group" [PNE intervention], "single-sham group" [sham PNE by using dry needling], and "double-sham group" [sham PNE by using sham needles]. Every group received 4 sessions of the needling therapies targeting the patellar tendon over 8 weeks and was instructed to perform a unilateral eccentric exercise program of the quadriceps muscle on the affected side. Clinical and needle-related pain was assessed before, during, and after each treatment session using a visual analog scale.
RESULTS
No differences were found between groups intra- or inter-session in terms of pain reduction ( = 0.424) despite clinical pain decreased in all groups since the first treatment session ( < 0.001). Furthermore, although the double-sham group showed a lower percentage of participants reporting needle-related pain during needle intervention ( = 0.005), the needle-related pain intensity after needle intervention was similar between groups ( = 0.682). Moreover, there were no group differences for the duration of pain sensation after any needle intervention ( = 0.184), extending in many cases beyond 24 h.
CONCLUSION
Needling therapies for individuals with patellar tendinopathy are prone to elicit placebo effects regarding clinical pain and nocebo effects regarding needling-related pain. Clinicians and physical therapists treating musculoskeletal pain conditions should consider the added value and potential mechanisms of action before routinely using needle techniques.
PubMed: 38903823
DOI: 10.3389/fmed.2024.1381515 -
Frontiers in Genetics 2024Kinship analysis is a crucial aspect of forensic genetics. This study analyzed 1,222 publications on kinship analysis from 1960 to 2023 using bibliometric analysis...
Kinship analysis is a crucial aspect of forensic genetics. This study analyzed 1,222 publications on kinship analysis from 1960 to 2023 using bibliometric analysis techniques, investigating the annual publication and citation patterns, most productive countries, organizations, authors and journals, most cited documents and co-occurrence of keywords. The initial publication in this field occurred in 1960. Since 2007, there has been a significant increase in publications, with over 30 published annually except for 2010. China had the most publications ( = 213, 17.43%), followed by the United States ( = 175, 14.32%) and Germany ( = 89, 7.28%). The United States also had the highest citation count. Sichuan University in China has the largest number of published articles. The University of Leipzig and the University of Cologne in Germany exhibit the highest total citation count and average citation, respectively. Budowle B was the most prolific author and Kayser M was the most cited author. In terms of publications, , , and were the most prolific journals. Among them, boasted the highest h-index, citation count, and average citation rate. The most frequently cited publication was "Van Oven M, 2009, Hum Mutat", with a total of 1,361 citations. The most frequent co-occurrence keyword included "DNA", "Loci", "Paternity testing", "Population", "Markers", and "Identification", with recent interest focusing on "Kinship analysis", "SNP" and "Inference". The current research is centered around microhaplotypes, forensic genetic genealogy, and massively parallel sequencing. The field advanced with new DNA analysis methods, tools, and genetic markers. Collaborative research among nations, organizations, and authors benefits idea exchange, problem-solving efficiency, and high-quality results.
PubMed: 38903754
DOI: 10.3389/fgene.2024.1401898 -
Sleep Advances : a Journal of the Sleep... 2024Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However,...
STUDY OBJECTIVES
Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However, neuroimaging modalities are unable to show any consistent markers in obstructive sleep apnea (OSA) patients. We hypothesized that, compared with those of the control cohort, advanced diffusion MRI metrics could show subtle microstructural alterations in the brains of patients with OSA.
METHODS
Sixteen newly diagnosed patients with moderate to severe OSA and 15 healthy volunteers of the same age and sex were considered healthy controls. Multishell diffusion MRI data of the brain, along with anatomical data (T1 and T2 images), were obtained on a 3T MRI system (Siemens, Germany) after a polysomnography (PSG) test for sleep abnormalities and a behavioral test battery to evaluate cognitive and executive brain functions. Diffusion MRI data were used to compute diffusion tensor imaging and diffusion kurtosis imaging (DKI) parameters along with white-matter tract integrity (WMTI) metrics for only parallel white-matter fibers.
RESULTS
OSA was diagnosed when the patient's apnea-hypopnea index was ≥ 15. No significant changes in cognitive or executive functions were observed in the OSA cohort. DKI parameters can show significant microstructural alterations in the white-matter region, while the WMTI metric, the axonal-water-fraction (fp), reveals a significant decrease in OSA patients concerning the control cohort.
CONCLUSIONS
Advanced diffusion MRI-based microstructural alterations in the white-matter region of the brain suggest that white-matter tracts are more sensitive to OSA-induced intermittent hypoxia.
PubMed: 38903701
DOI: 10.1093/sleepadvances/zpae031 -
Frontiers in Psychology 2024Head movements that are synchronized with musical rhythms often emerge during musical activities, such as hip hop dance. Although such movements are known to affect the...
Head movements that are synchronized with musical rhythms often emerge during musical activities, such as hip hop dance. Although such movements are known to affect the meter and pulse perception of complex auditory rhythms, no studies have investigated their contribution to the performance of sensorimotor synchronization (SMS). In the present study, participants listened to syncopated auditory rhythms and flexed their dominant hand index finger in time with the perceived pulses (4/4 meters). In the first experiment (Exp. 1), the participants moved their heads via voluntary neck flexion to the pulses in parallel with finger SMS (Nodding condition, ND). This performance was compared with finger SMS without nodding (Without Nodding condition, WN). In the second experiment (Exp. 2), we investigated the specificity of the effect of head SMS on finger SMS confirmed in Exp. 1 by asking participants to flex their bilateral index fingers to the pulses (Bimanual condition, BM). We compared the performance of dominant hand finger SMS between the BM and ND conditions. In Exp. 1, we found that dominant hand finger SMS was significantly more stable (smaller standard deviation of asynchrony) in the ND versus WN condition ( < 0.001). In Exp. 2, dominant hand finger SMS was significantly more accurate (smaller absolute value of asynchrony) in the ND versus BM condition ( = 0.037). In addition, the stability of dominant hand finger SMS was significantly correlated with the index of phase locking between the pulses and head SMS across participants in the ND condition ( = -0.85, < 0.001). In contrast, the stability of dominant hand finger SMS was not significantly correlated with the index of phase locking between pulses and non-dominant hand finger SMS in the BM condition ( = -0.25, = 0.86 after multiple comparison correction). These findings suggest that SMS modulation depends on the motor effectors simultaneously involved in synchronization: simultaneous head SMS stabilizes the timing of dominant hand finger SMS, while simultaneous non-dominant hand finger SMS deteriorates the timing accuracy of dominant hand finger SMS. The present study emphasizes the unique and crucial role of head movements in rhythmic behavior.
PubMed: 38903467
DOI: 10.3389/fpsyg.2024.1335050 -
Cureus May 2024When planning esthetic dental treatments, understanding smile preferences is important for dental professionals. This study aimed to evaluate the impact of selected...
INTRODUCTION
When planning esthetic dental treatments, understanding smile preferences is important for dental professionals. This study aimed to evaluate the impact of selected smile characteristics on the attractiveness of young Saudis as assessed by Saudi laypersons and explore gender-preferred changes in smile attractiveness.
METHODOLOGY
This observational study assessed the dynamic smile attractiveness of 168 Saudi individuals (84 males and 84 females), selected through non-probability convenience sampling. Dynamic smiles were elicited by viewing comedic content and captured with a camera standardized for consistent positioning. Videos were edited and adjusted to images, and the frames with the most pronounced smiles were chosen. The intra-rater reliability was assessed using intra-class correlation coefficients (ICCs) and Cohen's kappa tests (κ). The highest and lowest 25th percentiles were categorized as attractive and unattractive smiles, respectively, on the visual analog scale (VAS) by laypersons. Six smile characteristics - anterior smile line, smile arc, upper lip curvature, posterior teeth displayed, smile index, and smile symmetry - were quantitatively evaluated from these images for each participant and classified into attractive and unattractive groups based on laypersons' VAS evaluations. Continuous variables were tested with the Mann-Whitney U test, and for the categorical variables, the Chi-square test was applied. The significance was set at 5%.
RESULTS
The four randomly selected out of the 22 raters had good VAS reliability; ICCs varied from 0.661 to 0.94, with an average of 0.737, and Cohen's kappa tests for smile characteristics showed values from 0.617 to 0.89. Good agreement was also found with the smile index, with ICCs of 0.775, and dynamic smile symmetry, with ICCs of 0.872. Laypersons rated female smiles as more attractive compared to male smiles ( = 0.004). Low or average anterior smile lines ( = 0.001 for males; = 0.03 for females), parallel smile arcs ( = 0.001 for males; = 0.02 for females), and higher smile indexes ( = 0.001 for males; = 0.004 for females) were significantly attractive, showing no significant gender differences. Conclusions: Laypersons reliably rated the young Saudis' dynamic smiles as attractive. Of the rated smile characteristics, those with a low or average anterior smile line, parallel smile arcs, and a larger smile index were deemed more attractive. This study's findings show no significant gender differences in the impact of the studied smile characteristics on attractiveness. This study's findings can help dental professionals customize treatment plans that meet patients' expectations.
PubMed: 38903316
DOI: 10.7759/cureus.60726