Impact of routine surveillance duplex ultrasound and subsequent reintervention after superficial femoral artery stenting.

OBJECTIVE: Superficial femoral artery (SFA) stenting is a common treatment for peripheral artery disease. It is effective in the short term; however, in-stent restenosis (ISR) limits long-term success. Surveillance with duplex ultrasound (DUS) can identify patients who develop ISR leading to early reintervention, but data to support this practice is sparce. The purpose of this study was to evaluate whether surveillance and subsequent reintervention improves outcomes in patients with SFA stents. METHODS: A single-center, retrospective study was performed with patients undergoing SFA stenting between 2005 and 2020 who had a follow-up with DUS. Five groups were identified based on the presence of ISR on DUS (ISR vs no ISR [NISR]), recurrence of symptoms (symptomatic [SX] vs asymptomatic [ASX]), and if any reintervention was performed (reintervention [R] vs no reintervention [NR]): (1) ISR+SX+R; (2) ISR+SX+NR; (3) ISR+ASX+R; (4) ISR+ASX+NR; and (5) NISR+NR. The primary endpoint was amputation-free survival, and the secondary endpoint was patency. Predictors of mortality and surveillance were identified by multivariable logistic regressions and Cox multivariate regression models. Survival curves were presented as Kaplan-Meier plots using log-rank test for subgroup comparison. RESULTS: Two hundred fifty-seven patients were included in the analysis. The indication for intervention was claudication in 28% and chronic limb-threatening ischemia in 72%. A total of 161 patients (63%) underwent reintervention for ISR. Of patients who had restenosis on DUS, those who were symptomatic and did not undergo reintervention (ISR+SX+NR) did the worst, with 50% amputation rate. In contrast, those who were asymptomatic but did undergo reintervention (ISR+ASX+R) had the lowest amputation rate of 13%. Active smoking was a predictor of both loss of patency and amputation (1.72; 95% confidence interval [CI], 1.00-2.98; P = .050; 3.55; 95% CI, 1.53-8.25; P = .003). Post procedure dual antiplatelet therapy had a positive association with limb salvage (hazard ratio [HR], 0.23; 95% CI, 0.09-0.58; P = .001), whereas diabetes (HR, 2.61; 95% CI, 1.21-6.01; P = .019), stent occlusion (HR, 17.0; 95% CI, 5.93-63.1; P < .001), and chronic limb-threatening ischemia presentations (HR, 4.31; 95% CI, 1.86-11.7; P=.002) were negatively associated with limb salvage. CONCLUSIONS: Routine surveillance DUS and subsequent reintervention on ISR after SFA stenting is associated with improved patency and amputation-free survival. Surveillance DUS should be routine for patients after stenting, with reintervention strongly considered if ISR is identified for both symptomatic and asymptomatic.

Long-term outcomes of staged iliofemoral endoconduits prior to complex endovascular aortic aneurysm repair.

OBJECTIVE: Adverse iliofemoral anatomy may preclude complex endovascular aortic aneurysm repair (EVAR). In our practice, staged iliofemoral endoconduits (ECs) are planned prior to complex EVAR to improve vascular access and decrease operative time while allowing the stented vessel to heal. This study describes the long-term results of iliofemoral ECs prior to complex EVAR. METHODS: Between 2012 and 2023, 59 patients (44% male; median age, 75 ± 6 years) underwent ECs before complex EVAR using self-expanding covered stents (Viabahn). For common femoral artery (CFA) disease, ECs were delivered percutaneously from contralateral femoral access and extended into the CFA to preserve the future access site for stent graft delivery. Internal iliac artery patency was maintained when feasible. During complex EVAR, the EC extended into the CFA was directly accessed and sequentially dilated until it could accommodate the endograft. Technical success was defined as successful access, closure, and delivery of the endograft during complex EVAR. Endpoints were vascular injury or EC disruption, secondary interventions, and EC patency. RESULTS: Unilateral EC was performed in 45 patients (76%). ECs were extended into the CFA in 21 patients (35%). Median diameters of the native common iliac, external iliac, and CFA were 7 mm (interquartile range [IQR], 6-8 mm), 6 mm (IQR, 5-7 mm), and 6 mm (IQR, 6-7 mm), respectively. Internal iliac artery was inadvertently excluded in 10 patients (17%). Six patients (10%) had an intraoperative vascular injury during the EC procedure, and six patients (10%) had EC disruption during complex EVAR, including five EC collapses requiring re-stenting and one EC fracture requiring open cut-down and reconstruction with patch angioplasty. In 23 patients (39%), 22 Fr OD devices were used; 20 Fr were used in 22 patients (37%), and 18 Fr in 14 patients (24%). Technical success for accessing EC was 89%. There was no difference in major adverse events at 30 days between the iliac ECs and iliofemoral ECs. Primary patency by Kaplan-Meier estimates at 1, 3, and 5 years were 97.5%, 89%, and 82%, respectively. There was no difference in primary patency between iliac and iliofemoral ECs. Six secondary interventions (10%) were required. The mean follow-up was 34 ± 27 months; no limb loss or amputations occurred during the follow-up. CONCLUSIONS: ECs improve vascular access, and their use prior to complex EVAR is associated with low rates of vascular injury, high technical success, and optimal long-term patency. Complex EVAR procedures can be performed percutaneously by accessing the EC directly under ultrasound guidance and using sequential dilation to avoid EC disruption.

Early experience with patient-specific unibody bifurcated fenestrated-branched devices for complex endovascular aortic aneurysm repair.

OBJECTIVE: Short distances between the lowest visceral/renal artery and the aortic bifurcation are technically challenging during complex endovascular aortic aneurysm repair (EVAR), particularly after previous infrarenal repair. Traditionally, inverted limb bifurcated devices have been used in addition to fenestrated-branched (FB) endografts, but short overlap, difficult cannulation, and potential crushing of bridging stents are limitations for their use. This study reviews the early experience of patient-specific company manufactured devices (PS-CMDs) with a unibody bifurcated FB design for complex EVAR. METHODS: Consecutive complex EVAR procedures over a 34-month period with unibody bifurcated FB-devices as part of physician-sponsored investigational device exemption studies at two institutions were reviewed. Unibody bifurcated FB designs included FB bifurcated or fenestrated inverted limb devices. End points included technical success, survival, frequency of type I or III endoleaks, limb occlusion, and secondary interventions. RESULTS: Among 168 patients undergoing complex EVAR, 33 patients (19.6%; 78.7% male; mean age, 77 years) received unibody bifurcated FB PS-CMDs. FB bifurcated and fenestrated inverted limb devices were used in 31 (93.9%) and 2 (6.06%) patients, respectively. The median maximum aneurysm diameter was 61 mm (interquartile range [IQR], 55-69 mm). Prior EVAR was reported by 29 patients (87.9%), of whom 2 (6.06%) had suprarenal stents. A short distance between the lowest renal artery and aortic bifurcation was demonstrated in 30 patients (90.9%), with median distance of 47 mm (IQR, 38-54 mm). Preloaded devices were used in 23 patients (69.7%). A total of 128 fenestrations were planned; 22 (17.2%) were preloaded with guidewires and 5 (3.9%) with catheters. The median operative time was 238 minutes (226-300 minutes), with a median fluoroscopy time of 65.5 minutes (IQR, 56.0-77.7 minutes) and a median dose area product of 147 mGy∗cm2 (IQR, 105-194 mGy∗cm2). Exclusive femoral access was used in 14 procedures (42.4%). Technical success was 100%. Target vessel primary patency was 100% at a median follow-up time of 11.7 months (IQR, 3.5-18.6 months). Two patients (6.06%) required reintervention for iliac occlusion; one patient required stenting and the other a femoral-femoral bypass. No aortic-related deaths occurred after the procedure. During follow-up, 11 type II endoleaks (33.3%) and 1 type Ib endoleak (3.03%) were detected; the latter was treated with leg extension. No type Ia or III endoleaks occurred. CONCLUSIONS: Complex EVAR using unibody bifurcated FB-PS-CMDs is a simple, safe, and cost-effective alternative for the treatment of patients with short distances between the renal arteries and the aortic bifurcation. Further studies are required to assess benefits and durability of unibody bifurcated FB devices.

Flavonoids and Alzheimer's disease: reviewing the evidence for neuroprotective potential.

Neurodegeneration, which manifests as several chronic and incurable diseases, is an age-related condition that affects the central nervous system (CNS) and poses a significant threat to the public's health for the elderly. Recent decades have experienced an alarming increase in the incidence of neurodegenerative disorders (NDDs), a severe public health issue due to the ongoing development of people living in modern civilizations. Alzheimer's disease (AD) is a leading trigger of age-related dementia. Currently, there are no efficient therapeutics to delay, stop, or reverse the disease's course development. Several studies found that dietary bioactive phytochemicals, primarily flavonoids, influence the pathophysiological processes underlying AD. Flavonoids work well as a supplement to manufactured therapies for NDDs. Flavonoids are effective in complementing synthetic approaches to treat NDDs. They are biologically active phytochemicals with promising pharmacological activities, for instance, antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor, anti-apoptotic, and antioxidant effects. The production of nitric oxide (NO), tumor necrosis factor (TNF-α), and oxidative stress (OS) are downregulated by flavonoids, which slow the course of AD. Hence, this research turned from preclinical evidence to feasible clinical applications to develop newer therapeutics, focusing on the therapeutic potential of flavonoids against AD.

Relationship of neutrophil lymphocyte ratio, monocyte lymphocyte ratio and neutrophil monocyte ratio with treatment response in pulmonary tuberculosis patients during intensive phase treatment.

OBJECTIVE: To determine the relationship of Neutrophil Lymphocyte Ratio (NLR), Monocyte Lymphocyte Ratio (MLR), and Neutrophil Monocyte Ratio (NMR) with treatment response in Pulmonary Tuberculosis (PTB) patients during intensive phase treatment (IPT). METHODS: This analytical cross-sectional study was conducted at Ojha Institute of Chest Diseases (OICD), Dow University of Health Sciences, from February to December 2021. 100 patients were enrolled using purposive sampling technique. Both male and female of age 18 and above, rifampicin sensitive newly diagnosed cases of PTB by Acid Fast Bacilli (AFB) microscopy and Gene Xpert MTB/RIF were included. SPSS version 26 was used to analyze data. Numerical data was expressed in median and interquartile range and categorical data was expressed in frequencies and percentages. RESULTS: Out of total 100 patients, 81% (n = 81) showed treatment response with negative AFB Sputum Smear Microscopy (SSM) after 2nd month. Out of 81% (n = 81) of the patients who achieved treatment response, 83.9% (n = 68) also had decreased NLR, 85.2% (n = 69) had decreased MLR and 83.9% (n = 68) had decreased NMR from baseline. However 19% (n = 19) did not achieved treatment response with positive AFB SSM after 2nd month of ATT (Anti tuberculosis treatment), among them 10.52% (n = 2) were INH resistant with no decrease in all the ratios after 2nd month. CONCLUSION: Leukocyte ratios decreased significantly from baseline as PTB was treated in patients who achieved treatment response with negative AFB SSM after two months of ATT and hence these ratios could be used as markers to monitor the treatment response.

Letter to editor : optimizing surgical approaches for anterior communicating artery aneurysms: development and internal validation of a novel surgical scoring system.

The recent publication titled "Optimizing Surgical Approaches for Anterior Communicating Artery Aneurysms: Development and Internal Validation of a Novel Surgical Scoring System" presents a groundbreaking study in neurosurgery. This critique examines both the positive and negative impacts of the research. Positive aspects include the potential to improve patient outcomes through personalized surgical approaches guided by a standardized scoring system. Internal validation enhances the credibility of the scoring system. However, challenges such as the need for external validation and additional surgeon training are acknowledged. Overall, while the study offers promising advancements, further research and validation are essential for widespread implementation in clinical practice.

Letter to the editor: "A nomogram based on radiomics and clinical information to predict prognosis in percutaneous balloon compression for the treatment of trigeminal neuralgia: a retrospective cohort study of published cases".

This critique evaluates a recent study on a nomogram based on radiomics and clinical data to predict the prognosis of percutaneous balloon compression (PBC) for trigeminal neuralgia (TN), focusing on its strengths, weaknesses, and suggestions for future research. It acknowledges the innovative approach's potential to personalize treatment and improve outcomes, but raises concerns about the study's retrospective nature, sample size limitations, and challenges in implementing radiomics in clinical practice. Overall, although the nomogram offers promise, further validation in larger cohorts is essential to confirm its utility and reliability. Future research should prioritize prospective multicenter studies with standardized protocols, collaborative efforts among institutions, and innovative techniques to advance our understanding and management.

Effect of connector height and retainer occlusal thickness on the fracture resistance of posterior 4-unit monolithic 5Y-TZP fixed partial dentures after thermomechanical aging.

STATEMENT OF PROBLEM: The connector height and retainer occlusal thickness of fixed partial dentures (FPDs) may affect restoration longevity. PURPOSE: The purpose of this in vitro study was to determine and compare the fracture resistance of 4-unit monolithic 5% yttria tetragonal zirconia polycrystal (5Y-TZP) FPDs made with different connector heights and retainer occlusal thicknesses after thermomechanical aging. MATERIAL AND METHODS: Forty test metal dies were duplicated from a master metal die containing 2 anatomic abutment preparations of the mandibular right first premolar and second molar for a 4-unit FPD. The dies were divided into 2 groups of 20 each for the fabrication of 4-unit FPDs, with 2-mm and 4-mm uniform connector heights at all 3 connectors, resulting in 6.3-mm2 and 12.6-mm2 connector areas. Each of these groups was further divided into 2 subgroups based on the occlusal thickness of the 2 retainers of 1 mm and 2 mm (n=10). Polyvinyl siloxane impressions of the test metal dies were made and poured in Type V dental stone. Laboratory scans were performed on all the stone dies, and 40 5Y-TZP FPDs (Ceramill Zolid FX) were designed and fabricated. Subsequently, all the FPDs were luted on to the metal dies with a self-adhesive resin cement. The FPDs were preloaded (400 000 mechanical cycles; 4000 thermocycles) using a mastication simulator and tested for axial compressive strength. Two-way analysis of variance (ANOVA) was used to examine the effect of connector and occlusal thicknesses on the fracture load (α=.05). The data were further assessed using the post hoc Tukey HSD multiple comparison test (α=.05). RESULTS: The mean fracture load values were between 737 N and 1563 N. Significant differences in the mean fracture load were found between the connector heights (601 N; P<.001) and occlusal thicknesses (225 N; P=.002), but the interaction of the 2 factors was not significant (P=.132) The Tukey post hoc analysis showed significant differences between the connector thicknesses groups (P<.01), but the occlusal thicknesses were found to be similar for the same connector height (P=.609) CONCLUSIONS: Connector height and occlusal retainer thickness influenced the fracture load of 4-unit monolithic 5Y-TZP FPDs after thermomechanical aging.

Synthesis and characterizations of conocarpus- and azadirachta-derived activated carbons as wastewater recycling material.

Water being the most important fluid supporting the life as well as industry is getting sparse and polluted day by day. Activated carbon (AC) can be utilized in various applications of significant environmental impact and sustainable living such as carbon dioxide sensing and capturing, air purification, and water recycling. However, in the wake of the recent corona pandemic which resulted in global lockdown and took the entire world by shock, a cost-effective and simple synthesis of such a useful material remains dire need of time. Therefore, this paper describes a simple and cost-effective synthesis of activated carbon (AC) of high porosity and surface area derived from the pruning of conocarpus and azadirachta trees. In reference to the study under consideration, alongside numerous others, a furnace was employed to synthesize activated carbon. However, our approach utilized a more conventional methodology wherein the environmental parameters were not optimized. In furnace-based procedures, factors such as temperature, pressure, and humidity are meticulously regulated, contrasting with the conventional methodologies where such parameters lack optimal control. Consequently, employing a furnace does not constitute a cost-effective approach for the physical activation of organic samples thus proving a furnace is not imperative for physical activation. The synthesis was carried out by physical activation in the form of carbonization followed by chemical activation with potassium hydroxide (KOH). The influence of activated carbon from each pruning over filtration of water containing industrial dye was investigated. Activation temperature and impregnation ratio of 600-800 °C and 1:5 were selected respectively. X-ray diffraction patterns (XRD) for all AC samples indicted the appearance of broad peaks at 2θ value of 20-30° which confirms the presence of carbon in the sample. The physical morphology arrangement by SEM analysis showed uneven arrangement of pores of conocarpus which indicated higher iodine number and hence higher adsorption capacity of 442.13 mg/g.

Frequency of neuro-imaging in the emergency room in patients with vertigo: A cross-sectional study at a tertiary care hospital in Karachi, Pakistan.

Objective: To determine the frequency of neuro-imaging and the prevalence of positive findings in patients with vertigo visiting an emergency room of a low-middle-income-country, Pakistan. Methods: This is a retrospective cross-sectional study conducted in the emergency room of the Aga Khan University Hospital, a 550 bedded tertiary care teaching facility located in Karachi, Pakistan. The frequency of neuro-imaging in patients visiting emergency room with vertigo during 20 years (2000-2020), their findings and disposition was calculated in percentages. A cost-analysis was performed in Pakistani Rupees & US Dollars to estimate the financial burden. Results: During the emergency room visits for vertigo, neuro-imaging (CT scans, MRIs, or both) was conducted for 159 patients, accounting for 70.98% of the cases. Out of these, 64 individuals (40.25%) received a positive diagnosis, which included acute infarcts, hemorrhages, metastases, space-occupying lesions, and meningeal enhancements. Interestingly, among those with negative findings, the 98 patients faced significantly higher costs, amounting to Rs.4,108,000 ($22,449), in contrast to the positive cases, which incurred Rs.2,496,600 ($13,642). Conclusion: The frequency of obtaining neuro-imaging tests in patients with vertigo were significantly high in our study. In addition, there was a significant financial burden associated with neuro-imaging especially for our low-middle-income country.

Base Editing Landscape Extends to Perform Transversion Mutation.

Base editors have drawn considerable academic and industrial attention in recent years because of their ability to alter single DNA bases with precision. However, the existing cytosine and adenine base editors can only install transition mutations. Three recent studies (Kurt et al.,Zhao et al., and Chen et al.) expand the base editing toolbox by developing cytosine transversion base editors.

Outcomes of Elective and Non-elective Fenestrated-branched Endovascular Aortic Repair for Treatment of Thoracoabdominal Aortic Aneurysms.

OBJECTIVE: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs). BACKGROUND: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described. METHODS: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006-2021) were reviewed. Endpoints including early mortality and major adverse events (MAEs), all-cause mortality, and aortic-related mortality (ARM), were analyzed and compared in patients who had non-elective versus elective repair. RESULTS: A total of 2603 patients (69% males; mean age 72±10 year old) underwent FB-EVAR for TAAAs. Elective repair was performed in 2187 patients (84%) and non-elective repair in 416 patients [16%; 268 (64%) symptomatic, 148 (36%) ruptured]. Non-elective FB-EVAR was associated with higher early mortality (17% vs 5%, P <0.001) and rates of MAEs (34% vs 20%, P <0.001). Median follow-up was 15 months (interquartile range, 7-37 months). Survival and cumulative incidence of ARM at 3 years were both lower for non-elective versus elective patients (50±4% vs 70±1% and 21±3% vs 7±1%, P <0.001). On multivariable analysis, non-elective repair was associated with increased risk of all-cause mortality (hazard ratio, 1.92; 95% CI] 1.50-2.44; P <0.001) and ARM (hazard ratio, 2.43; 95% CI, 1.63-3.62; P <0.001). CONCLUSIONS: Non-elective FB-EVAR of symptomatic or ruptured TAAAs is feasible, but carries higher incidence of early MAEs and increased all-cause mortality and ARM than elective repair. Long-term follow-up is warranted to justify the treatment.

Early Results and Feasibility of Total Endovascular Aortic Arch Repair Using 3-Vessel Company-Manufactured and Physician-Modified Stent-Grafts.

OBJECTIVE: Total endovascular repair of aortic arch aneurysms is feasible in select patients. This study aims to evaluate the feasibility and early outcomes of total endovascular arch repair using 3-vessel company-manufactured devices (CMDs) and physician-modified endo grafts (PMEGs). METHODS: Patients unfit for open repair who underwent 3-vessel total arch repair at a single institution from 2018 to 2021 were reviewed. Patients received either 3-vessel inner-branch CMDs or PMEGs. Three-vessel designs were used to incorporate the innominate, left common carotid, and left subclavian arteries. The antegrade inner branches in both devices were accessed via right brachial or carotid approach. The left carotid was accessed via carotid cutdown or femoral approach. The left subclavian artery was accessed via transfemoral approach. The study endpoints included procedural technical success, patient survival, neurologic events, cardiac complications, reinterventions, and target artery patency. RESULTS: Nine patients underwent treatment. Four patients were treated with PMEGs, and 5 with CMDs. Procedural technical success was 100%. There were no in-hospital deaths. There were no strokes, transient ischemic attacks, myocardial infarction, or spinal ischemia in the perioperative period. Major adverse events occurred in 3 patients (33%). Two (22%) vascular access complications and one (11%) acute kidney injury occurred. One (11%) patient required early reintervention for an access complication. The median follow-up period was 358 days (CMD, 392 days; PMEG, 198 days). There was a late reintervention and conversion to open repair at 142 days of follow-up in a patient with a PMEG that developed an aortic infection, leading to death on postoperative day 239. The mean length of stay was 7±4 days. Computed tomography imaging obtained during the immediate postoperative period revealed endoleak in 6 (66%) patients, out of which 5 resolved spontaneously and 1 required reintervention via left subclavian artery stenting. Target artery patency was 100% at the end of the follow-up period. CONCLUSIONS: Three-vessel total endovascular aortic arch repair using a CMD or PMEG is feasible with optimal early outcomes. Physician-modified stent-grafts are a feasible option for patients who do not meet anatomic criteria for CMDs. CLINICAL IMPACT: Management of aortic arch disease remains a significant challenge in vascular surgery. This study showcases the feasibility and safety of using a total endovascular approach to repair the aortic arch, which could potentially reduce morbidity and mortality associated with traditional surgical approaches. The results suggest that this minimally invasive technique could be an alternative treatment option for high-risk patients and could significantly improve outcomes for those requiring aortic arch repair. Overall, this study represents a promising development in the field of endovascular surgery and highlights the potential to improve patient outcomes.

Redo Fenestrated-Branched Endovascular Aortic Repair (F-BEVAR) for Failed F-BEVAR.

Failed fenestrated-branched endovascular aortic repair (F-BEVAR) requiring a redo F-BEVAR is a rare event. In this study, we report 2 cases of a failed F-BEVAR secondary to a type IIIb endoleak from tears on the fabric graft successfully treated with redo F-BEVAR. This is a technically challenging procedure that requires meticulous planning, advanced imaging technologies and experienced operators. Redo F-BEVAR appears to be a feasible and safe treatment option. However, larger series and long-term follow-up are needed to confirm effectiveness and durability.

Investigating theobromine as a potential anti-human coronaviral agent.

Coronaviruses (CoVs) have long been known to infect humans, mainly alpha-CoV and beta-CoV. The vaccines developed for SARS-CoV-2 are likely not effective against other coronavirus species, whereas the risk of the emergence of new strains that may cause the next epidemic/pandemic is high. The development of antiviral drugs that are effective across different CoVs represents a viable strategy for improving pandemic preparedness. In this study, we aim to identify pan-coronaviral agents by targeting the conserved main protease (Mpro). For drug screening, the catalytic dyad of four human CoVs (HCoVs: SARS-CoV-2, and seasonal CoV NL63, OC43, and 229E) was targeted by molecular docking. The identified leading candidate theobromine, a xanthine derivative, was further tested in cell culture models of coronavirus infection. Theobromine binds strongly with the catalytic dyad (His41 and Cys144/145) of SARS-CoV-2 and HCoV-NL63 Mpro, mildly with HCoV-OC43, but not with HCoV-229E. However, theobromine only shows dose-dependent inhibition in Calu3 cells inoculated with SARS-CoV-2, but not in cells inoculated with seasonal CoVs. Theobromine exerts antiviral activity against coronavirus infections potentially through targeting Mpro. However, the antiviral potency is distinct among different CoVs.

Evaluation of interleukin-33 & sST2 levels in type-2 diabetic mellitus patients with or without metabolic syndrome.

Background & objectives: Diabetes mellitus (DM) is characterized by increase in blood glucose levels due to defective insulin secretion or insulin sensitivity. Interleukins (ILs) are known to play an important role in the pathogenesis of DM. The aim of this study was to investigate the serum concentration of IL-33 and its receptor soluble ST2 (sST2) in patients with diabetes and draw a correlation between their serum levels and different standard glycaemic indices of patients affected with type-2 diabetes with or without metabolic syndrome. Methods: Thirty type-2 diabetic individuals and 30 healthy controls were recruited for this study. Serum and plasma were separated by centrifugation of blood for quantitative measurement of IL-33, sST2 and other biochemical parameters. Results: It was observed that serum IL-33 levels were significantly less and sST2 levels were significantly high in type-2 diabetic individuals as compared to healthy controls. A significant correlation between the serum IL-33 concentration and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also found. Additionally, data also elucidated that serum levels of high-density lipoprotein, low-density lipoprotein or triglyceride in type-2 diabetics did not influence the serum levels of IL-33 and sST2, thereby excluding these factors as the major drivers of changes in serum IL-33 and sST2 concentration. Interpretation & conclusions: This study demonstrated alteration in serum levels of IL-33 and sST2 in type-2 diabetic individuals. Further mechanistic studies, focusing on the progression of type-2 diabetes could elucidate the involvement of IL-33 in the cellular acquisition of insulin resistance as observed in type-2 diabetics.

H3 G34-mutant high-grade gliomas: integrated clinical, imaging and pathological characterisation of a single-centre case series.

BACKGROUND: Diffuse hemispheric glioma, H3 G34-mutant, is a novel paediatric tumour type in the fifth edition of the WHO classification of CNS tumours associated with an invariably poor outcome. We present a comprehensive clinical, imaging and pathological review of this entity. METHODS: Patients with confirmed H3 G34R-mutant high-grade glioma were included in a single-centre retrospective cohort study and examined for clinical, radiological and histo-molecular data. RESULTS: Twelve patients were enrolled in the study - 7 males/5 females; the mean age was 17.5 years (10-57 years). Most patients presented with signs of raised intracranial pressure (8/12). The frontal lobe (60%) was the prevalent location, with a mixed cystic-nodular appearance (10/12) and presence of vascular flow voids coursing through/being encased by the mass (8/12), and all tumours showed cortical invasion. Nine patients had subtotal resection limited by functional margins, two patients underwent supra-total resection, and one patient had biopsy only. 5-ALA was administered to 6 patients, all of whom showed positive fluorescence. Histologically, the tumours showed a marked heterogeneity and aggressive spread along pre-existing brain structures and leptomeninges. In addition to the diagnostic H3 G34R/V mutation, pathogenic variants in TP53 and ATRX genes were found in most cases. Potential targetable mutations in PDGFRA and PIK3CA genes were detected in five cases. The MGMT promoter was highly methylated in half of the samples. Methylation profiling was a useful diagnostic tool and highlighted recurrent structural chromosome abnormalities, such as PDGFRA amplification, CDKN2A/B deletion, PTEN loss and various copy number changes in the cyclin D-CDK4/Rb pathway. Radiochemotherapy was the most common adjuvant treatment (9/12), and the average survival was 19.3 months. CONCLUSIONS: H3 G34R-mutant hemispheric glioma is a distinct entity with characteristic imaging and pathological features. Genomic landscaping of individual tumours can offer an opportunity to adapt individual therapies and improve patient management.

Relationship Between Mental Health Disorders and Readmissions Following Total Joint Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: There is limited evidence exploring the relationship between mental health disorders and the readmissions following total joint arthroplasty (TJA). Therefore, we conducted a meta-analysis to evaluate the relationship between mental health disorders and the risk of readmission following TJA. METHODS: We searched PubMed, Cochrane, and Google Scholar from their inception till April 19, 2022. Studies exploring the association of mental health disorders and readmission risk following TJA were selected. The outcomes were divided into 30-day readmission, 90-day readmission, and readmission after 90 days. We also performed subgroup analyses based on the type of arthroplasty: total hip arthroplasty (THA) and total knee arthroplasty (TKA). A total of 12 studies were selected, of which 11 were included in quantitative analysis. A total of 1,345,893 patients were evaluated, of which 73,953 patients suffered from mental health disorders. RESULTS: The risk of 30-day readmission (odds ratio = 1.43, 95% CI 1.14-1.80, P = .002, I2 = 87%) and 90-day readmission (OR = 1.35, 95% CI 1.22-1.49, P < .00001, I2 = 89%) was significantly associated with mental health disorders. On subgroup analyses, 30-day readmission was significantly associated with THA (OR = 1.29, 95% CI 1.04-1.60, P = .02), but not with TKA (OR = 1.44, 95% CI 0.51-4.06, P = .50). Similarly, 90-day readmission was significantly associated with both THA (OR = 1.21, 95% CI 1.14-1.29, P < .00001) and TKA (OR = 1.33, 95% CI 1.17-1.51, P < .0001). CONCLUSION: Mental health disorders are significantly associated with increased 30-day and 90-day readmissions. Increasing awareness regarding mental health disorders and readmission in arthroplasty will help in efficient preoperative risk stratification and better postoperative management in these patients.

Nanomedicines: intervention in inflammatory pathways of cancer.

Inflammation is a complex defense process that maintains tissue homeostasis. However, this complex cascade, if lasts long, may contribute to pathogenesis of several diseases. Chronic inflammation has been exhaustively studied in the last few decades, for its contribution in development and progression of cancer. The intrinsic limitations of conventional anti-inflammatory and anti-cancer therapies triggered the development of nanomedicines for more effective and safer therapies. Targeting inflammation and tumor cells by nanoparticles, encapsulated with active therapeutic agents, offers a promising outcome with patient survival. Considerable technological success has been achieved in this field through exploitation of tumor microenvironment, and recognition of molecules overexpressed on endothelial cells or macrophages, through enhanced vascular permeability, or by rendering biomimetic approach to nanoparticles. This review focusses on the inflammatory pathways in progression of a tumor, and advancement in nanotechnologies targeting these pathways. We also aim to identify the gaps that hinder the successful clinical translation of nanotherapeutics with further clinical studies that will allow oncologist to precisely identify the patients who may be benefited from nanotherapy at time when promotion or progression of tumor initiates. It is postulated that the nanomedicines, in near future, will shift the paradigm of cancer treatment and improve patient survival.

Double Crown-Retained Removable Prostheses Supported by Implants or Teeth and Implants: A Long-Term Clinical Retrospective Evaluation.

OBJECTIVES: The objective of this retrospective clinical study was to investigate the survival rates and complications of implant (I)-retained or tooth-implant (TI)-retained prostheses and abutments (teeth, implants) over a mean observation period of 11.26 years. The study also aimed to analyze the differences and complication rates between implant-retained double crown removable dental prostheses (I-DC-RDPs) versus tooth-implant-retained double crown removable dental prostheses (TI-DC-RDPs). MATERIAL AND METHODS: We reviewed the clinical data of 110 nonsmokers (mean age = 53.9 years) who received DC-RDPs in maxillary or mandibular arches. 153 teeth and 508 implants were used to restore partially edentulous (PE; TI-DC-RDPs; n = 53) and completely edentulous (CE; TI-DC-RDPs; n = 57) arches. Two designs of the distal extension were used: cantilevers (CANs) and saddles (SADs). Restorations were examined for abutment survival, mechanical, or biological complications. RESULTS: The 10-year survival rates were 99.3% (95% CI: 95.4-99.9%) for teeth and 99.3% (95% CI: 97.5-99.7%) for implants. The cumulative rates of TI- and I-RDPs free of technical complications were 77% and 86%, respectively. The risk of complications was not significantly different between the CAN and SAD subgroups of I-RDPs (p > 0.05). However, for TI-RDPs, technical complication risk was significantly higher in SAD type compared with CAN restorations (p = 0.02). CONCLUSIONS: I- and TI-DC-RDPs seem to be recommendable for restoration of CE or PE arches. The technical and biological complication rates were lower for I-DC-RDPs in the CE arches than for TI-DC-RDPs in the PE arches. Regarding the RDP design, CAN prostheses produced significantly fewer technical complications than did SAD prostheses.