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Infection, Genetics and Evolution :... Jun 2024Chronic leg ulcers are hard to treat and can be a burden, particularly in resource-limited settings where diagnosis is a challenge. Staphylococcus aureus is among the...
BACKGROUND
Chronic leg ulcers are hard to treat and can be a burden, particularly in resource-limited settings where diagnosis is a challenge. Staphylococcus aureus is among the common bacteria isolated from chronic wounds with a great impact on wound healing, particularly in patients with co-morbidities. Antimicrobial resistance genes and virulence factors in Staphylococcus aureus isolates were assessed to support healthcare professionals to make better therapeutic choices, and importantly to curb the development and spread of antibiotic resistance.
METHODS
A cross-sectional study involved both inpatients and outpatients with chronic leg ulcers was conducted from August 2022 to April 2023 in 2 health facilities in Kilimanjaro region in Tanzania. Antimicrobial susceptibility testing was done using the disc diffusion method. Further, whole genome sequencing was performed to study the genotypic characteristics of the isolates.
RESULTS
A total of 92 participants were recruited in which 9 participants were only positive for 10 Staphylococcus aureus isolates upon culture. Five STs among 9 isolates were identified. Most of them belonged to ST8 (44%), with 1 isolate does not belong to any ST. Additionally, 50% of the isolates were methicillin-resistant Staphylococcus aureus (MRSA). All S. aureus isolates had almost similar virulence factors such as hemolysin, proteases and evasions that promote toxin production, protease production and host immune evasion respectively. Moreover, all mecA positive S. aureus isolates were phenotypically susceptible to cefoxitin.
CONCLUSION
Presence of mecA positive S. aureus isolates which are also phenotypically susceptible to cefoxitin implies the possibility of classifying MRSA as MSSA. This may result in the possible emergence of highly cefoxitin - resistant strains in health care and community settings when subsequently exposed to beta-lactam agents. Therefore, combination of whole genome sequencing and conventional methods is important in assessing bacterial resistance and virulence to improve management of patients.
PubMed: 38945421
DOI: 10.1016/j.meegid.2024.105631 -
Journal of Stroke and Cerebrovascular... Jun 2024Cerebral Vasomotor Reactivity (VMR) is a property of cerebral hemodynamics that protects from cerebrovascular disease. We aimed to explore the VMR longitudinal changes...
BACKGROUND AND AIM
Cerebral Vasomotor Reactivity (VMR) is a property of cerebral hemodynamics that protects from cerebrovascular disease. We aimed to explore the VMR longitudinal changes in patients with acute non-disabling stroke/Transient Ischemic Attack (TIA) to understand its implication in stroke ethiopatogenesis.
METHODS
VMR by Transcranial Doppler Breath Holding test was performed at 48-72 h from stroke onset (T1) and after 6 months (T2) on MCA of the non-affected hemisphere and PCA of the affected hemisphere.
RESULTS
We consecutively enrolled 124 patients with a median age of 66.0 (IQR 54.75-74.25) years with a median NIHSS 2 (IQR 1-3). Both MCA (1.38 %/s SD 0.58) and PCA (1.35 %/s SD 0.75) BHI at T1 did not differ among different stroke subtypes (p=0.067 and p=0.350; N=124). MCA and PCA BHI decreased from T1 to T2 (respectively 1.39 %/s SD 0.56 vs 1.18%/s SD 0.44 and 1.30 %/s SD 0.69 vs 1.20 %/s SD 0.51; N=109) regardless of ethiopatogenesis (respectively p<0.0001 and p=0.111).
CONCLUSION
the VMR is higher in acute phase than at 6 months in patients with non-disabling stroke/TIA, regardless of etiopathogenesis. The higher VMR in acute phase could be sustained by an increased Cerebral Blood Flow due to collateral circulation activation supporting the ischemic zone.
PubMed: 38945417
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107841 -
Journal of Affective Disorders Jun 2024Disrupted cellular communication, inflammatory responses and mitochondrial dysfunction are consistently observed in late-life depression (LLD). Exosomes (EXs) mediate...
BACKGROUND
Disrupted cellular communication, inflammatory responses and mitochondrial dysfunction are consistently observed in late-life depression (LLD). Exosomes (EXs) mediate cellular communication by transporting molecules, including mitochondrial DNA (EX-mtDNA), playing critical role in immunoregulation alongside tumor necrosis factor (TNF). Changes in EX-mtDNA are indicators of impaired mitochondrial function and might increase vulnerability to adverse health outcomes. Our study examined EX-mtDNA levels and integrity, exploring their associations with levels of TNF receptors I and II (TNFRI and TNFRII), and clinical outcomes in LLD.
METHODS
Ninety older adults (50 LLD and 40 controls (HC)) participated in the study. Blood was collected and exosomes were isolated using size-exclusion chromatography. DNA was extracted and EX-mtDNA levels and deletion were assessed using qPCR. Plasma TNFRI and TNFRII levels were quantified by multiplex immunoassay. Correlation analysis explored relationships between EX-mtDNA, clinical outcomes, and inflammatory markers.
RESULTS
Although no differences were observed in EX-mtDNA levels between groups, elevated levels correlated with poorer cognitive performance (r = -0.328, p = 0.002) and increased TNFRII levels (r = 0.367, p = 0.004). LLD exhibited higher deletion rates (F = 4.402, p = 0.039), with a trend remaining after adjusting for covariates (p = 0.084). Deletion correlated with poorer cognitive performance (r = -0.335, p = 0.002). No other associations were found.
LIMITATION
Cross-sectional study with a small number of participants from a specialized geriatric psychiatry treatment center.
CONCLUSION
Our findings suggest that EX-mtDNA holds promise as an indicator of cognitive outcomes in LLD. Additional research is needed to further comprehend the role of EX-mtDNA levels/integrity in LLD, paving the way for its clinical application in the future.
PubMed: 38945405
DOI: 10.1016/j.jad.2024.06.092 -
Journal of ISAKOS : Joint Disorders &... Jun 2024Patients with excessive posterior tibial slope (PTS) may have higher risks of anterior cruciate ligament (ACL) reconstruction (ACL-R) failure, and clinical outcomes... (Review)
Review
IMPORTANCE
Patients with excessive posterior tibial slope (PTS) may have higher risks of anterior cruciate ligament (ACL) reconstruction (ACL-R) failure, and clinical outcomes after revision ACL-R procedures are typically poor.
OBJECTIVE
To perform a systematic review of the literature summarizing the clinical and radiological outcomes of the surgical treatment of ACL insufficiency in the setting of excessive PTS using a tibial deflexion osteotomy combined with ACL-R.
EVIDENCE REVIEW
A systematic review of the literature was performed using PubMed, Cochrane Library, and OVID Medline databases from 1990 to present. Inclusion criteria were: studies of outcomes of isolated tibial deflexion osteotomies performed with primary or revision ACL-R in the English language. Data extracted included study demographic information, type of tibial deflexion osteotomy and concomitant procedures, radiological outcomes, patient reported outcome scores, and postoperative complications FINDINGS: Six studies, with 133 knees were identified. All included studies were retrospective case series, with a weighted mean follow-up of 3.39 years. In 106 of 133 (79.7%) knees, tibial deflexion osteotomy was performed concomitantly with an ACL-R, whereas in 27 of 133 (20.3%) knees the procedures were staged. 22, 45, and 66 of 133 knees (16.5%, 33.8%, and 49.6%) underwent primary, 1 revision, and 2 or greater revision ACL-R, respectively. 3 of 133 (2.25%) knees demonstrated recurrent ACL graft failure at final follow-up. On average, PTS decreased from 15.2 degrees preoperatively to 7.1 degrees postoperatively. Mean International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores increased from 42.5, 46.4, and 4.2 preoperatively to 71.8, 89.0, and 6.7 postoperatively.
CONCLUSIONS
The results of this review suggest that combined ACL-R and tibial deflexion osteotomy may be effective in decreasing PTS and improving knee function and stability.
STUDY DESIGN
Systematic Review; Level of evidence 4.
PubMed: 38945397
DOI: 10.1016/j.jisako.2024.06.010 -
Biological Psychiatry Jun 2024Diverse antidepressants were recently described to bind to TrkB and drive a positive allosteric modulation of endogenous BDNF. Although neurotrophins such as BDNF can...
BACKGROUND
Diverse antidepressants were recently described to bind to TrkB and drive a positive allosteric modulation of endogenous BDNF. Although neurotrophins such as BDNF can bind to the p75 neurotrophin receptor (p75NTR), their precursors are the high affinity p75NTR ligands. While part of an unrelated receptor family capable of inducing completely opposite physiological changes, TrkB and p75NTR feature a cross-like conformation dimer and carry a cholesterol-recognition and alignment consensus in the transmembrane domain. Since such qualities were found crucial for antidepressants to bind to TrkB and drive behavioral and neuroplasticity effects, we hypothesized that their effects might also depend on p75NTR.
METHODS
ELISA-based binding assay and NMR spectroscopy were accomplished to assess whether antidepressants would bind to p75NTR. HEK293T cells and a variety of in vitro assays were used to address whether fluoxetine (FLX) or ketamine (KET) would trigger any α- and γ-secretase-dependent p75NTR proteolysis, and lead to p75NTR nuclear localization. Ocular dominance shift was performed with male and female p75KO mice to study the effects of KET and FLX on brain plasticity, in addition to pharmacological interventions to verifying how p75NTR signaling is important for the effects of KET and FLX in enhancing extinction memory in male WT mice and rats.
RESULTS
Antidepressants were found binding to p75NTR, FLX and KET triggered the p75NTR proteolytic pathway and induced p75NTR-dependent behavioral/neuroplasticity changes.
CONCLUSION
We thus hypothesize that antidepressants co-opt both BDNF/TrkB and proBDNF/p75NTR systems to induce a more efficient activity-dependent synaptic competition, thereby boosting the brain ability for remodeling.
PubMed: 38945387
DOI: 10.1016/j.biopsych.2024.06.021 -
Biological Psychiatry Jun 2024Fragile X syndrome (FXS) is a genetic condition associated with increased risk for social anxiety and avoidance. Using functional near-infrared spectroscopy (fNIRS), we...
BACKGROUND
Fragile X syndrome (FXS) is a genetic condition associated with increased risk for social anxiety and avoidance. Using functional near-infrared spectroscopy (fNIRS), we previously demonstrated aberrant neural activity responding to faces in young girls with FXS cross-sectionally. Here, we tested the hypothesis that abnormalities in neural activation and sensitization would increase with age in 65 girls with FXS, ages 5-16 years, relative to an age-matched control group of 52 girls who had comparable cognitive function and clinical symptoms.
METHODS
Functional NIRS data were collected at two time points, 2.8±0.6 years apart during a face-processing task. Linear mixed-effects models examined longitudinal neural profiles in girls with FXS and control. Correlational analysis was performed to examine associations between neural sensitization (increasing neural response to repeated stimuli), and clinical ratings.
RESULTS
In girls with FXS, 32 participants had one, and 24 had two fNIRS scans. In controls, 21 had one, and 29 had two fNIRS scans. Brain activations in the right middle and superior frontal gyri were higher in FXS than controls at both time points. Neural sensitization also increased in FXS at a higher rate than controls in the superior frontal gyrus when responding to upright faces. For the FXS group, sensitization in the superior frontal gyrus positively correlated with longitudinal increases in anxiety and social avoidance scores.
CONCLUSION
Girls with FXS show increasingly abnormal neural activation and sensitization responding to faces over time. Aberrant neural sensitization in girls with FXS is associated with longitudinal changes in anxiety and social skills.
PubMed: 38945386
DOI: 10.1016/j.biopsych.2024.06.020 -
The French Journal of Urology Jun 2024Compare scoring systems using Fournier gangrene severity index (FGSI), Uludag Fournier gangrene severity index (UFGSI), Laboratory Risk Indicator for Necrotizing...
INTRODUCTION
Compare scoring systems using Fournier gangrene severity index (FGSI), Uludag Fournier gangrene severity index (UFGSI), Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), and neutrophil-lymphocyte ratio (NLR) to predict the outcome of patients with Fournier gangrene Materials and Methods: This is a retrospective cohort study that includes FG patients from 2012 to 2021. NLR, FGSI, UFGSI, and LRINEC values were calculated and analyzed. Each scoring system was analyzed using a receiver operating curve (ROC) analysis to determine its sensitivity, specificity, and area under the curve (AUC). Statistical analysis was performed using SPSS version 25.
RESULTS
A total of 158 patients were included in this study. Regarding the mortality outcome, FGSI comprised the highest value of AUC with 80.9, with a sensitivity of 91.7% and specificity of 68.5%. LRINEC comprised the AUC value of 61.1, with 79.2% sensitivity and 64.2% specificity. NLR comprised an AUC value of 63.7, 91.7% of sensitivity, and 98.1% of specificity. In terms of length of stay, LRINEC and NLR were associated as significant predictor.
CONCLUSION
FGSI, UFGSI, and NLR are significant predictors associated with mortality in patients with Fournier gangrene. FGSI and UFGSI comprised the highest sensitivity and specificity value in predicting mortality prognosis. Moreover, this study highlighted the role of NLR and LRINEC as significant predictors for the length of hospitalization. This study shows that FGSI is still a reliable scoring system for predicting mortality in patients with Fournier Gangrene.
PubMed: 38945366
DOI: 10.1016/j.fjurol.2024.102673 -
Journal of Vascular Surgery. Venous and... Jun 2024We evaluated the impact of completion intraoperative venography on clinical outcomes for axillosubclavian vein (AxSCV) thrombosis due to venous thoracic outlet syndrome...
INTRODUCTION
We evaluated the impact of completion intraoperative venography on clinical outcomes for axillosubclavian vein (AxSCV) thrombosis due to venous thoracic outlet syndrome (vTOS).
METHODS
We performed a retrospective, single-center review of all patients with vTOS treated with First Rib Resection and intraoperative venography from 2011 - 2023. We reviewed intraoperative venographic films to classify findings, collected demographics, clinical and perioperative variables, and clinical outcomes. Primary endpoints were symptomatic relief and primary patency at 3 months and 1 year. Secondary endpoints were time free from symptoms, reintervention rate, perioperative complications, and mortality.
RESULTS
Fifty-one AxSCVs (49 patients, mean age of 31.3 ± 12.6, 52.9% female) were treated for vTOS with first rib resection and external venolysis followed by completion intraoperative venography with a mean follow up of 15.5 ± 13.5 months. Prior to FRR, 32 underwent catheter-directed thrombolysis (62.7%). Completion intraoperative venography identified 16 patients with No Stenosis (Group 1, 31.3%), 17 with No Stenosis after Angioplasty (Group 2, 33.3%), 10 with Residual Stenosis after Angioplasty (Group 3, 19.7%), and 8 with Complete Occlusion (Group 4, 15.7%). The overall symptomatic relief was 44 of 51 (86.3%) and did not differ between venographic classifications (Group 1: 14 of 16, Group 2: 13 of 17, Group 3: 10 of 10, and Group 4: 7 of 8; Log-Rank Test, p = 0.5). The overall 3-month and 1-year primary patency was 42 of 43 (97.7%) and 32 of 33 (97.0%), respectively (Group 1: 16 of 16 and 9 of 9; Group 2: 16 of 17 and 12 of 13; Group 3: 10 of 10, 5 of 5; Group 4: primary patency not obtained). There was one asymptomatic re-thrombosis that resolved with anticoagulation, and three patients underwent reintervention with venous angioplasty for significant symptom recurrence an average 2.89 ± 1.7 months after FRR.
CONCLUSION
Our single-center retrospective study demonstrates that FRR with completion intraoperative venography has excellent symptomatic relief, short- and mid-term patency despite residual venous stenosis and complete occlusion. While completion intraoperative venographic classification did not correlate with adverse outcomes, this protocol yielded excellent results and provides important clinical data for postoperative management. Our results also support a conservative approach to AxSCV occlusion identified after FRR.
PubMed: 38945363
DOI: 10.1016/j.jvsv.2024.101936 -
Contraception Jun 2024To evaluate the method of immediate postpartum IUD (ppIUD) insertion (manual versus ring forceps) and expulsion rate within 6-weeks postpartum.
OBJECTIVE
To evaluate the method of immediate postpartum IUD (ppIUD) insertion (manual versus ring forceps) and expulsion rate within 6-weeks postpartum.
STUDY DESIGN
We performed a retrospective cohort study of patients who had a singleton vaginal delivery and an immediate ppIUD inserted at Rush University from January 2014 to September 2023. The primary outcome was rate of expulsion within 6-weeks postpartum. We compared the rate of expulsion by method of insertion, either using a manual technique versus using ring forceps. We performed univariable analysis for the association between baseline maternal characteristics and the primary outcome and we performed multivariable logistic regression to determine the independent association of the method of insertion and the primary outcome.
RESULTS
Two hundred nineteen patients met eligibility with 117 immediate ppIUDs inserted manually and 102 inserted with ring forceps. Baseline maternal demographics were similar across study groups. After adjusting for factors selected a priori (estimated blood loss, body mass index, gestational age at delivery, nulliparity, type of IUD), use of ring forceps was more likely to result in expulsion compared to manual insertion (30.4% vs 16.2% respectively; adjusted OR 2.49, 95% confidence interval 1.28-4.90).
CONCLUSION
In this retrospective analysis, insertion of immediate ppIUD with ring forceps was independently associated with an increased rate of expulsion within 6 weeks postpartum when compared to manual insertion.
IMPLICATIONS
In this setting, ring forceps was associated with high rates of immediate postpartum IUD expulsion compared to manual technique. Studies disagree, suggesting need for additional work.
PubMed: 38945350
DOI: 10.1016/j.contraception.2024.110532 -
The American Journal of Cardiology Jun 2024Radial artery (RA) access has been increasingly utilized for coronary procedures due to lower rates of access-site complications and improved patient satisfaction....
Radial artery (RA) access has been increasingly utilized for coronary procedures due to lower rates of access-site complications and improved patient satisfaction. However, limited data are available for RA access for peripheral vascular intervention (PVI). We performed a retrospective review of 143 patients who underwent PVI via RA access from February 2020 to September 2022 at a single institution. Baseline characteristics and follow-up data were ascertained from a prospectively maintained institutional database. Of 491 PVI, 156 (31.8%) were performed through the RA. Anatomical location for intervention were the femoral (44.8%), iliac (31.1%), popliteal (9.6%) peroneal (2.7%), tibial (9.9%), and subclavian (1.9%) arteries. Procedural access was obtained through the right RA (92.9%), left RA (4.5%), or right ulnar artery (2.6%) using the 6 French R2P Destination Slender sheath in 85 cm, 105 cm, and 119 cm lengths. Atherectomy was used in 34.7%. Mean contrast volume was 105.5 mL and the average fluoroscopy time was 18.5 minutes. Conversion to femoral access occurred in 3 cases (1.9%) due to arterial spasm and non-crossable lesions. Concomitant pedal access occurred in 2 cases (1.3%). Periprocedural complication rate was 3.84%, of which access-site hematoma was most common (3.2%); none required blood transfusion, surgical intervention, or additional hospital stay. There was 1 case (0.64%) of in-hospital stroke. The mortality rate at 30-day, 6-month, and 1-year was 1.4%, 2.8%, and 4.2%, respectively. In conclusion, RA access is feasible for diverse PVI, and future studies are needed to assess safety and benefit compared to femoral artery access.
PubMed: 38945347
DOI: 10.1016/j.amjcard.2024.06.025