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Diabetes Research and Clinical Practice Jun 2024Continuous glucose monitoring (CGM)-derived metrics have been used to accurately assess glycemic variability (GV) to facilitate management of diabetes mellitus, yet... (Review)
Review
Continuous glucose monitoring (CGM)-derived metrics have been used to accurately assess glycemic variability (GV) to facilitate management of diabetes mellitus, yet their relationship with diabetic peripheral neuropathy (DPN) is not fully understood. We performed a systematic review and meta-analysis to evaluate the association between GV metrics and the risk of developing DPN. Nine studies totaling 3,649 patients with type 1 and type 2 diabetes mellitus were included. A significant association was found between increased GV, as indicated by metrics including standard deviation (SD) with OR and 95% CI of 2.58 (1.45-4.57), mean amplitude of glycemic excursions (MAGE) with OR and 95% CI of 1.90 (1.01-3.58), mean of daily difference (MODD) with OR and 95% CI of 2.88 (2.17-3.81) and the incidence of DPN. Our findings support a link between higher GV and an increased risk of DPN in patients with diabetes. These findings highlight the potential of GV metrics as indicators for the development of DPN, advocating for their inclusion in diabetes management strategies to potentially mitigate neuropathy risk. Longitudinal studies with longer observation periods and larger sample sizes are necessary to validate these associations across diverse populations.
PubMed: 38944250
DOI: 10.1016/j.diabres.2024.111757 -
Clinical Medicine (London, England) Jun 2024We aimed to assess the appropriateness of penicillin allergy (PenA) assessment conducted by clinical teams and to review the safety of subsequent exposure of these...
OBJECTIVES
We aimed to assess the appropriateness of penicillin allergy (PenA) assessment conducted by clinical teams and to review the safety of subsequent exposure of these patients to penicillin.
METHODS
Opportunistic, prospective observational study of usual clinical care, between 16/05/23 and 14/08/23, of inpatients with a PenA and requiring antibiotics, in a 750-bed hospital in England. To assess the appropriateness of management, PenA patients prescribed penicillins were grouped into risk categories using a validated antibiotic allergy assessment tool: eligible for de-label on history alone (direct de-label; DDL), eligible for direct oral challenge (DOC), high risk or unable to obtain history.
RESULTS
Of the 123 patients admitted with a PenA (or sensitivity record) and exposed to a penicillin, data were collected for 50. Their PenA records were grouped follows: eligible for DDL 34 (68%), eligible for DOC 11 (22%), high risk 4 (8%) and unable to obtain history 1 (2%). In 14/50 (28%) patients there was no evidence of a current PenA assessment in the medical notes.
CONCLUSIONS
Using the allergy risk tool, most patients with penA records were exposed to penicillin appropriately. However, patients meeting high risk criteria were also exposed to penicillin when the tool excluded them. PenA assessment needs to be carried out with appropriate training and governance structures in place.
PubMed: 38944245
DOI: 10.1016/j.clinme.2024.100225 -
Journal of Thrombosis and Haemostasis :... Jun 2024There is no established risk score for anticoagulant-related bleeding during the acute phase in patients with pulmonary embolism (PE). The Syncope, Anemia, Renal...
BACKGROUND
There is no established risk score for anticoagulant-related bleeding during the acute phase in patients with pulmonary embolism (PE). The Syncope, Anemia, Renal Dysfunction (PE-SARD) bleeding score was developed to predict early major bleeding, but has not yet been fully externally validated.
OBJECTIVES
To externally validate the PE-SARD bleeding score.
PATIENTS/METHODS
Using the COMMAND VTE Registry-2 database, which enrolled 5197 consecutive acute symptomatic venous thromboembolism patients among 31 centers in Japan between January 2015 and August 2020, we identified acute PE patients. We divided those into 3 groups by the score: high-risk (>2.5 points), intermediate-risk (1-2.5 points), and low-risk (0 points). The discriminating and calibration performances of the score for 30-day major bleeding were assessed. Subgroup analyses based on active cancer were also performed.
RESULTS
Of 2781 eligible patients, the high-risk group accounted for 557 patients (20%), intermediate-risk group for 1412 (51%), and low-risk group for 812 (29%). Major bleeding occurred in 121 patients within 30 days. The cumulative 30-day incidence of major bleeding substantially increased in the higher risk categories by the score (high-risk group: 8.2% [95%CI, 5.9%-10.5%], intermediate-risk group: 4.6% [95%CI, 3.5%-5.7%], and low-risk group: 1.8% [95%CI, 0.8%-2.7%]). The discriminating power of the score was modest with a C-statistic of 0.65 (95%CI, 0.61-0.70) with a good calibration performance with a score of <4 points except for in active cancer patients.
CONCLUSIONS
The PE-SARD bleeding score had a modest discriminating performance with a limited calibration performance in acute PE patients without active cancer.
PubMed: 38944241
DOI: 10.1016/j.jtha.2024.06.011 -
Kidney International Jun 2024
PubMed: 38944240
DOI: 10.1016/j.kint.2024.05.029 -
The Journal of Foot and Ankle Surgery :... Jun 2024Ankle arthrodesis is an effective surgical intervention for end-stage arthritis or severe ankle joint deformity. Both internal (IF) and external fixation (EF) techniques... (Review)
Review
Ankle arthrodesis is an effective surgical intervention for end-stage arthritis or severe ankle joint deformity. Both internal (IF) and external fixation (EF) techniques are valid options, but there is controversy regarding the most effective technique. This study compares the safety and efficacy of EF and IF fixation techniques for ankle arthrodesis. A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines. A literature search of electronic databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL), was performed to identify all studies directly comparing the two techniques. Both fixed and random effects models of analysis were used depending on heterogeneity. Odds of union in the EF and IF groups were comparable (OR=0.60, CI 0.36-1.02, p=0.06) however, EF was associated with greater odds of deep hardware infections (OR=3.67, 1.97-6.83, p <0.05) and amputations (OR=3.17, CI 1.06-9.54, p =0.04). Odds of revision surgery and superficial wound complications were similar between groups. EF techniques had significantly longer operation times (MD=31.23, CI-25.11-37.34, p <0.05) and intraoperative blood loss (MD=46.31, CI-24.93-67.69, p <0.05). No significant difference was noted in pain and functionality scores. IF and EF techniques have reasonable union rates with similar postoperative outcomes. However, IF patients are more likely to achieve primary union and less likely to have deep infections, being mindful that EF techniques were usually indicated for more complex cases. LEVEL OF EVIDENCE: IV.
PubMed: 38944233
DOI: 10.1053/j.jfas.2024.05.010 -
The Journal of Foot and Ankle Surgery :... Jun 2024The modified Lapidus procedure has emerged as a versatile solution for various pedal pathologies, particularly hallux abducto valgus. There have been numerous...
The modified Lapidus procedure has emerged as a versatile solution for various pedal pathologies, particularly hallux abducto valgus. There have been numerous modifications over time regarding fixation techniques, joint preparation methods, graft utilization, and weightbearing protocols. However, concerns persist regarding prolonged non-weightbearing postoperatively, prompting the need for alternative approaches. This retrospective descriptive cohort analysis assessed the outcomes of 40 feet from 34 patients who underwent the modified Lapidus procedure with a medial plating system, aimed to evaluate immediate weightbearing outcomes on union rate, fixation-related complications, and functional outcomes. Among the 40 feet, findings showed a 95% (38/40) union rate within 6 months, with 2.5% (1/40) experiencing delayed union and 2.5% (1/40) facing fixation-related complications. There is a single case of malunion in the cohort. Additionally, statistically significant improvements were observed across all domains of the Manchester-Oxford Foot Questionnaire at p < .001. These findings suggest immediate weightbearing as a potential alternative to traditional non-weightbearing protocols. However, the study's retrospective nature and lack of a comparative group warrant cautious interpretation. Further research is essential to validate these findings and refine postoperative care protocols. By challenging conventional practices, this study underscores the complexity of optimizing patient outcomes in modified Lapidus procedure management. Tailored approaches and prospective investigations are imperative for establishing definitive guidelines and enhancing surgical techniques in this domain.
PubMed: 38944232
DOI: 10.1053/j.jfas.2024.06.004 -
Environmental Pollution (Barking, Essex... Jun 2024Accurate interpretation of mercury (Hg) isotopic data requires the consideration of several biotic factors such as age, diet, geographical range, and tissue metabolic...
Accurate interpretation of mercury (Hg) isotopic data requires the consideration of several biotic factors such as age, diet, geographical range, and tissue metabolic turnover. A priori knowledge of prey-predator isotopic incorporation rates and Hg biomagnification is essential. This study aims to assess Hg stable isotopes incorporation in an Arctic species of Phocidae, the hooded seal Cystophora cristata, kept in human care for 24 months (2012 - 2014) and fed on a constant diet of Norwegian Spring Spawning herring Clupea harengus. We measured THg, MMHg and iHg levels, as well as Hg stable isotope composition with both mass dependent (MDF) and mass independent (MIF) fractionation (e.g. δHg and Hg) in hooded seal kidney, liver, hair and muscle, in addition to herring muscle. We then calculated Hg MDF and MIF isotopic fractionation between hooded seals and their prey. We found a significant shift in δHg between hooded seal hair (+0.80‰) and kidney (-0.78‰), and herring muscle. In hooded seals tissues δHg correlated positively with MMHg percentage. These findings suggest that tissue-specific Hg speciation is the major driver of changes in Hg isotopic fractionation rates in this Arctic predator. ΔHg, ΔHg, ΔHg and ΔHg values did not vary between herring and hooded seal tissues, confirming their utility as tracers of Hg marine and atmospheric sources in top predators. To our knowledge, this represents the first attempt to assess complex Hg isotope dynamics in the internal system of Arctic Phocidae, controlling the effects of age, diet, and distribution. Our results confirm the validity of Hg stable isotopes as tracers of environmental Hg sources even in top predators, but emphasize the importance of animal age and tissue selection for inter-study and inter-species comparisons.
PubMed: 38944182
DOI: 10.1016/j.envpol.2024.124450 -
European Journal of Pharmacology Jun 2024Malignant renal rhabdoid tumor (MRTK) is an aggressive and rare malignancy primarily affecting infants and young children. The intricate interactions within the Tumor...
Malignant renal rhabdoid tumor (MRTK) is an aggressive and rare malignancy primarily affecting infants and young children. The intricate interactions within the Tumor Microenvironment (TME) are crucial in shaping MRTK's progression. This study elucidates the significance of tumor-associated macrophages(TAMs) within this milieu and their interplay with eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) in tumor cells, collectively contributing to MRTK's malignant advancement. Through comprehensive analysis of clinical samples and the TARGET database, EIF4EBP1 emerges as a central macrophage-associated gene with robust prognostic implications. Elevated EIF4EBP1 expression correlates with poor prognosis and heightened infiltration of TAMs. Functional validation demonstrates that EIF4EBP1 knockdown in G401 cells significantly attenuates self-proliferation, migration, and invasion. Moreover, EIF4EBP1 regulates macrophage recruitment and M2 polarization through the ERK/P38 MAPK-MIF axis. Notably, M2 macrophages reciprocally foster the malignant behavior of MRTK tumor cells. This study unveils the pivotal role of EIF4EBP1 in propelling MRTK's malignant progression, unraveling a complex regulatory network involving EIF4EBP1 and TAMs. These findings underscore EIF4EBP1 as a promising biomarker and highlight its therapeutic potential in MRTK management.
PubMed: 38944176
DOI: 10.1016/j.ejphar.2024.176787 -
Biological Psychiatry Jun 2024Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently...
OBJECTIVE
Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure detection of involved brain circuits. The present study investigated whether structural brain connectivity deviations differ between recently discovered and validated insomnia subtypes.
METHODS
Structural and diffusion weighted 3-Tesla MRI data of four independent studies were harmonized. The sample consisted of 73 controls without sleep complaints and 204 participants with insomnia grouped into five subtypes based on their fingerprint of mood and personality traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age and sex evaluated group differences in structural connectivity strength, indicated by fractional anisotropy, streamline volume density and mean diffusivity, and evaluated within three different atlases.
RESULTS
Insomnia subtypes showed differentiating profiles of deviating structural connectivity which concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in four of the five subtypes: highly distressed, moderately distressed reward sensitive, slightly distressed low reactive and slightly distressed high reactive. Connectivity deviation profile significance ranged from p= 0.001 to p=0.049 for different resolutions of brain parcellation and connectivity weight.
CONCLUSIONS
Our results provide a first indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping of insomnia could be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.
PubMed: 38944140
DOI: 10.1016/j.biopsych.2024.06.014 -
American Journal of Ophthalmology Jun 2024The association between the total macular burden of hyperreflective foci (HRF) in eyes with intermediate AMD (iAMD) and the onset of persistent choroidal...
PURPOSE
The association between the total macular burden of hyperreflective foci (HRF) in eyes with intermediate AMD (iAMD) and the onset of persistent choroidal hypertransmission defects (hyperTDs) was studied using swept-source optical coherence tomography (SS-OCT).
DESIGN
Post hoc subgroup analysis of a prospective study.
METHODS
A retrospective review of iAMD eyes from subjects enrolled in a prospective SS-OCT study was performed. All eyes underwent 6×6 mm SS-OCT angiography (SS-OCTA) imaging at baseline and follow-up visits. En face sub-retinal pigment epithelium (subRPE) slabs with segmentation boundaries positioned 64-400 µm beneath Bruch's membrane (BM) were used to identify persistent choroidal hyperTDs. None of the eyes had persistent hyperTDs at baseline. The same subRPE slab was used to identify choroidal hypotransmission defects (hypoTDs) attributable to HRF located either intraretinally (iHRF) or along the RPE (rpeHRF) based on corresponding B-scans. A semiautomated algorithm was used by two independent graders to validate and refine the HRF outlines. The HRF area and the drusen volume within a 5mm fovea-centered circle were measured at each visit.
RESULTS
The median follow-up time for the 171 eyes from 121 patients included in this study was 59.1 months (95%CI: 52.0-67.8 months). Of these, 149 eyes (87%) had HRF, and 82 (48%) developed at least one persistent hyperTD during the follow-up. Although univariable Cox regression analyses showed that both drusen volume and total HRF area were associated with the onset of the first persistent hyperTD, multivariable analysis showed that the area of total HRF was the sole significant predictor for the onset of hyperTDs (P<0.001). ROC analysis identified an HRF area ≥ 0.07 mm² to predict the onset of persistent hyperTDs within one year with an area under the curve (AUC) of 0.661 (0.570-0.753), corresponding to a sensitivity of 55% and a specificity of 74% (P<0.001).
CONCLUSIONS
The total macular burden of HRF, which includes both the HRF along the RPE and within the retina, is an important predictor of disease progression from iAMD to the onset of persistent hyperTDs and should serve as a key OCT biomarker to select iAMD patients at high-risk for disease progression in future clinical trials.
PubMed: 38944135
DOI: 10.1016/j.ajo.2024.06.023