Hemoglobin A1c Levels Are Related to Patency and Adverse Limb Events in Diabetics After Revascularization.

OBJECTIVE: Poor glycemic control in the perioperative period has been reported to be associated with early and late major adverse limb events (MALE). However, these studies were mostly from large databases or lacked long-term outcomes. We examined the long-term effects of high hemoglobin A1c (HbA1c) level on patency, MALE, limb salvage (LS) and survival after lower extremity revascularization procedures in diabetic patients. METHODS: Patients with diabetes who had revascularization for Rutherford class 3-6 ischemia between May 2002 and December 2018 were identified. Patients with HbA1c≤7% were compared to HbA1c>7% for patency, MALE, survival, LS and amputation-free survival (AFS). RESULTS: Of 706 patients, 699 had HbA1c data (775 limbs), with 311 (357 limbs) in HbA1c≤7%, and 388 (418 limbs) in HbA1c>7% groups. Patients with HbA1c>7% were younger (69.9±10.2 vs 71.7±9.5, P=0.011), had higher lipid levels, insulin use (70% vs 49%, P<0.01), ASA 4, and had lower prevalence of chronic kidney disease (CKD) (32%vs41%, P=0.023). HbA1c>7% patients were more likely to present with chronic limb-threatening ischemia (CLTI) (79% vs 72%,P=0.019) and undergo infrapopliteal interventions (49% vs 42%, P=0.005), with no difference in anatomic complexity (TASC C/D, 75% vs 77%, p=0.72) or type of revascularization (24% vs 18% Open, 66% vs 70% EV, 10% vs 12% Hybrid, p=0.236). Patency and freedom from MALE were significantly lower in patients with HbA1c>7% for infra-inguinal revascularizations, whereas AFS and overall survival were similar. In patients with CLTI, LS rates at five years were significantly lower in patients undergoing open revascularization (HbA1c>7%: 64%±6%vs HbA1c<7%:86%±5%, P=0.020), whereas it was similar after endovascular interventions (HbA1c>7%:79%±4% vs HbA1c<7%:77%±3%, p=0.631). Seventy patients with HbA1c>7% lost limbs vs 38 patients with HbA1c≤7% (P=0.007). In multivariate analysis, HbA1c was significantly associated with primary patency. HbA1c, insulin use, level of intervention, and ACEI use were associated with MALE. CONCLUSIONS: Perioperative HbA1c>7% is associated with poorer patency rates, and increased MALE especially at the infra-inguinal level revascularization in diabetics, with no significant impact on survival. Limb salvage is impacted after open, but not after endovascular revascularization.

Atypical Presentation of Ziprasidone-Induced Neuroleptic Malignant Syndrome: A Case Report.

Neuroleptic malignant syndrome (NMS) is a severe adverse reaction associated with neuroleptic or antipsychotic drugs. This case report discusses a 43-year-old man with a history of bipolar disorder and polysubstance abuse who presented with altered mental status, autonomic dysfunction, and muscular rigidity. The patient had recently started on ziprasidone, a second-generation antipsychotic, leading to an atypical presentation of NMS. Unlike classic findings associated with NMS induced by first-generation antipsychotics, this case lacked high fever, lead pipe rigidity, or elevated creatine kinase levels greater than 1000 on initial presentation. The delay in diagnosis was attributed to the milder symptoms and absence of typical findings, resulting in extensive diagnostic workup and interventions. The patient responded positively to treatment with lorazepam based on the Woodbury severity stage guidelines. This case underscores the complexity of diagnosing NMS induced by second-generation antipsychotics and highlights the need for awareness and tailored treatment approaches for atypical presentations.

Medicinal and chemosensing applications of chitosan based material: A review.

Chitosan (CTS), has emerged as a highly intriguing biopolymer with widespread applications, drawing significant attention in various fields ranging from medicinal to chemosensing. Key characteristics of chitosan include solubility, biocompatibility, biodegradability and reactivity, making it versatile in numerous sectors. Several derivatives have been documented for their diverse therapeutic properties, such as antibacterial, antifungal, anti-diabetic, anti-inflammatory, anticancer and antioxidant activities. Furthermore, these compounds serve as highly sensitive and selective chemosensor for the detection of various analytes such as heavy metal ions, anions and various other species in agricultural, environmental and biological matrixes. CTS derivatives interacting with these species and give analytical signals. In this review, we embark on an exploration of the latest advancements in CTS-based materials, emphasizing their noteworthy contributions to medicinal chemistry spanning the years from 2021 to 2023. The intrinsic biological and physiological properties of CTS make it an ideal platform for designing materials that interact seamlessly with biological systems. The review also explores the utilization of chitosan-based materials for the development of colorimetric and fluorimetric chemosensors capable of detecting metal ions, anions and various other species, contributing to advancements in environmental monitoring, healthcare diagnostics, and industrial processes.

CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology.

BACKGROUND: Human cell division cycle-associated protein 8 (CDCA8), a critical regulator of mitosis, has been identified as a prospective prognostic biomarker in several cancer types, including breast, colon, and lung cancers. This study analyzed the diagnostic/prognostic potential and clinical implications of CDCA8 across diverse cancers. METHODS: Bioinformatics and molecular experiments. RESULTS: Analyzing TCGA data via TIMER2 and GEPIA2 databases revealed significant up-regulation of CDCA8 in 23 cancer types compared to normal tissues. Prognostically, elevated CDCA8 expression correlated with poorer overall survival in KIRC, LUAD, and SKCM, emphasizing its potential as a prognostic marker. UALCAN analysis demonstrated CDCA8 up-regulation based on clinical variables, such as cancer stage, race, and gender, in these cancers. Epigenetic exploration indicated reduced CDCA8 promoter methylation levels in Kidney Renal Clear Cell Carcinoma (KIRC), Lung Adenocarcinoma (LUAD), and Skin Cutaneous Melanoma (SKCM) tissues compared to normal controls. Promoter methylation and mutational analyses showcased a hypomethylation and low mutation rate for CDCA8 in these cancers. Correlation analysis revealed positive associations between CDCA8 expression and infiltrating immune cells, particularly CD8+ and CD4+ T cells. Protein-protein interaction (PPI) network analysis unveiled key interacting proteins, while gene enrichment analysis highlighted their involvement in crucial cellular processes and pathways. Additionally, exploration of CDCA8-associated drugs through DrugBank presented potential therapeutic options for KIRC, LUAD, and SKCM. In vitro validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) confirmed elevated CDCA8 expression in LUAD cell lines (A549 and H1299) compared to control cell lines (Beas-2B and NL-20). CONCLUSION: This study provides concise insights into CDCA8's multifaceted role in KIRC, LUAD, and SKCM, covering expression patterns, diagnostic and prognostic relevance, epigenetic regulation, mutational landscape, immune infiltration, and therapeutic implications.

Comparison of success and cost after retrieval of two inferior vena cava filters.

OBJECTIVE: The objective of this study was to help guide inferior vena cava (IVC) filter choices by better understanding the retrieval characteristics, complications, and total costs between two commonly used IVC filters. METHODS: All patients who underwent retrieval or attempted retrieval of Denali (Bard Peripheral Vascular) or Option (Argon Medical Devices) IVC filters were identified between March 2016 and October 2021 at a single tertiary care center. Those with imaging studies that permitted evaluation of filter placement, presence or degree of tilt, and/or hooking of the filter into the IVC wall were included in the present study. Filter retrieval success, number of attempts, use of advanced techniques, and fluoroscopy and procedural times were recorded and compared between the two filters. RESULTS: A total of 87 patients presented for retrieval of 52 Denali and 35 Option Elite filters during the study period. Denali filters were more likely to be successfully retrieved at the first attempt (94% vs 77%; P = .019). The procedural and fluoroscopy times were shorter for Denali filters (29 minutes vs 63 minutes [P < .001] and 7 minutes vs 25 minutes [P < .001], respectively). Denali filters were less likely to be significantly tilted (≥15○) at retrieval (12% vs 29%; P < .001) or to have the filter hook embedded in the IVC wall (6% vs 40%; P < .001). Tilting of the filter of ≥15○ had no significant effects on the retrieval success rate (no tilt or tilt <15○ vs tilt of ≥15○: 98% vs 100%; P = .58). In contrast, filter hook penetration into the IVC wall significantly reduced successful recovery (41% vs 99%; P < .001). CONCLUSIONS: The findings from this study suggest that although the filter designs are similar, a benefit exists in the ease of retrievability of the Denali over the Option filter. We found that tilting and hooking of the filter in the IVC wall occurred significantly more with the Option filter. These factors likely made retrieval more difficult and contributed to the longer procedure and fluoroscopy times.

Serum proteomic analysis in esophagectomy patients with postoperative delirium: A case-control study.

BACKGROUND: Postoperative delirium occurs in up to 80% of patients undergoing esophagectomy. We performed an exploratory proteomic analysis to identify protein pathways that may be associated with delirium post-esophagectomy. OBJECTIVES: Identify proteins associated with delirium and delirium severity in a younger and higher-risk surgical population. METHODS: We performed a case-control study using blood samples collected from patients enrolled in a negative, randomized, double-blind clinical trial. English speaking adults aged 18 years or older, undergoing esophagectomy, who had blood samples obtained were included. Cases were defined by a positive delirium screen after surgery while controls were patients with negative delirium assessments. Delirium was assessed using Richmond Agitation Sedation Scale and Confusion Assessment Method for the Intensive Care Unit, and delirium severity was assessed by Delirium Rating Scale-Revised-98. Blood samples were collected pre-operatively and on post-operative day 1, and discovery proteomic analysis was performed. Between-group differences in median abundance ratios were reported using Wilcoxon-Mann-Whitney Odds (WMWodds1) test. RESULTS: 52 (26 cases, 26 controls) patients were included in the study with a mean age of 64 (SD 9.6) years, 1.9% were females and 25% were African American. The median duration of delirium was 1 day (IQR: 1-2), and the median delirium/coma duration was 2.5 days (IQR: 2-4). Two proteins with greater relative abundance ratio in patients with delirium were: Coagulation factor IX (WMWodds: 1.89 95%CI: 1.0-4.2) and mannosyl-oligosaccharide 1,2-alpha-mannosidase (WMWodds: 2.4 95%CI: 1.03-9.9). Protein abundance ratios associated with mean delirium severity at postoperative day 1 were Complement C2 (Spearman rs = -0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (rs = 0.61, 95%CI = [0.29, 0.81]). CONCLUSIONS: We identified changes in proteins associated with coagulation, inflammation, and protein handling; larger, follow-up studies are needed to confirm our hypothesis-generating findings.

Retrospective study of efficacy and adverse events of immune checkpoint inhibitors in 22 xeroderma pigmentosum patients with metastatic or unresectable cancers.

Background: Xeroderma pigmentosum (XP), a rare disease with defects in DNA repair genes, has >1,000-fold increased risk of ultraviolet-induced skin cancers. Immune checkpoint inhibitors (ICIs) are used for treating cancers with large numbers of mutations but may also promote adverse events (AEs). Deficient DNA repair in XP patients may lead to increased numbers of mutations, leading to enhanced efficacy of cancer response or, alternatively, to increased AE in response to ICI. We sought to compare the efficacy and AE of ICI in XP patients with metastatic or unresectable cancers to that of ICI-treated patients in the general population. Methods: In this retrospective study, we reviewed medical records of XP patients treated in the United States and in London (UK). We also reviewed published reports of ICI-treated XP patients and patients in the general population. Results: Metastatic or unresectable cancers in all 22 (100%) XP patients showed regression or remission in response to ICI. The types and frequencies of AE in XP patients were similar to those reported among ICI-treated patients in the general population. However, two XP patients had concurrent additional cancers that did not respond to ICI, two XP patients had cancer recurrence or progression after initial response, and eight XP patients developed new skin cancers during or after ICI treatment. Conclusion: In this retrospective study with small sample size, XP patients demonstrated positive responses to ICI and the treatment was well tolerated but some patients developed new skin cancers while being treated. ICIs can be considered in treating metastatic or unresectable cancers in XP patients.

Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study.

OBJECTIVE: In critically ill adults with delirium, biomarkers of systemic inflammation, astrocyte activation, neuroprotection, and systemic inflammation measured at one week of critical illness may be associated with mortality. DESIGN: Prospective observational study. SETTING: Intensive care unit (ICU). PATIENTS: 178 ICU patients with delirium, alive and remaining in ICU at one week. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples collected for a pair of previously published, negative, clinical trials were utilized. Samples were collected at study enrollment/ICU admission (Day 1 sample) and one week later (Day 8 sample), and analyzed for interleukins (IL)-6, 8, 10, Insulin-like Growth Factor (IGF), S100 Binding Protein (S100B), Tumor Necrosis Factor Alpha (TNF-A) and C-Reactive Protein (CRP). Delirium, delirium severity, and coma were assessed twice daily using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), CAM-ICU-7, and Richmond Agitation-Sedation Scale (RASS), respectively. Mortality was assessed until discharge using the electronic medical record. Logistic regression models adjusting for age, sex, severity of illness, comorbidities, sepsis, and randomization status, were used to assess the relationship among biomarkers and mortality. Higher IL-10 quartiles at day 8 were associated with increased odds of hospital mortality (IL-10: OR 2.00 95%CI: 1.1-3.65, p = 0.023). There was a significant interaction between day 1 and day 8 biomarker quartiles only for IL-6. Patients with IL-6 values in the first three quartiles on admission to the ICU that transitioned to higher IL-6 quartiles at day 8 had increased probability of hospital mortality. CONCLUSION: In this hypothesis-generating study, higher IL-6 and IL-10 quartiles at one week, and increase in IL-6 from day 1 to day 8 were associated with increased hospital mortality. Studies with larger sample sizes are needed to confirm the mechanisms for these observations.

Collaborative Team Training in Virtual Reality is Superior to Individual Learning For Performing Complex Open Surgery: A Randomized Controlled Trial.

OBJECTIVE: To assess whether multiplayer immersive Virtual Reality (iVR) training was superior to single-player training for the acquisition of both technical and nontechnical skills in learning complex surgery. BACKGROUND: Superior teamwork in the operating room (OR) is associated with improved technical performance and clinical outcomes. iVR can successfully train OR staff individually; however, iVR team training has yet to be investigated. METHODS: Forty participants were randomized to individual or team iVR training. Individually trained participants practiced alongside virtual avatar counterparts, whereas teams trained live in pairs. Both groups underwent 5 iVR training sessions over 6 weeks. Subsequently, they completed a real-life assessment in which they performed anterior approach total hip arthroplasty surgery on a high-fidelity model with real equipment in a simulated OR. Teams performed together, and individually trained participants were randomly paired up. Videos were marked by 2 blinded assessors recording the 'Non-Operative Technical Skills for Surgeons, Oxford NOn-TECHnical Skills II and Scrub Practitioners' List of Intraoperative Non-Technical Skills' scores. Secondary outcomes were procedure duration and the number of technical errors. RESULTS: Teams outperformed individually trained participants for nontechnical skills in the real-world assessment (Non-Operative Technical Skills for Surgeons: 13.1±1.5 vs 10.6±1.6, P = 0.002, Non-TECHnical Skills II score: 51.7 ± 5.5 vs 42.3 ± 5.6, P = 0.001 and Scrub Practitioners' List of Intraoperative Non-Technical Skills: 10 ± 1.2 vs 7.9 ± 1.6, P = 0.004). They completed the assessment 33% faster (28.2 minutes ± 5.5 vs 41.8 ± 8.9, P < 0.001), and made fewer than half the number of technical errors (10.4 ± 6.1 vs 22.6 ± 5.4, P < 0.001). CONCLUSIONS: Multiplayer training leads to faster surgery with fewer technical errors and the development of superior nontechnical skills.

Optimal medical management in patients undergoing peripheral vascular interventions for chronic limb-threatening ischemia is associated with improved outcomes.

OBJECTIVE: Optimizing medical management and risk factor modification are underused strategies in patients with chronic limb-threatening ischemia (CLTI), despite evidence of improved outcomes. The Vascular Quality Initiative (VQI) registry is a tool to improve quality of vascular care. In this study, we used the VQI to evaluate trends in medical management in patients with CLTI undergoing peripheral vascular interventions (PVI), and the impact of changes in management on overall survival (OS), amputation-free survival (AFS), and limb salvage (LS). METHODS: Patients undergoing index PVI for CLTI between 2012 and 2016, with ≥24 months of follow-up were identified from the national VQI registry. Patient details including smoking status and medication use, OS, LS, and AFS were analyzed with linear-by-linear association, t test, and logistic regression. RESULTS: There were 12,370 PVI completed in 11,466 patients. There was a significant increase in infrapopliteal interventions (from 29.8% to 39.0%; P < .001) and PVI performed for tissue loss (from 59.1% to 66.5%; P < .001). The percentage of current smokers at time of PVI decreased (from 36.2% to 30.7%; P = .036). At discharge, statins were initiated in 25%, aspirin in 45%, and P2Y12 therapy in 58% of patients not receiving these medications before PVI. Over the course of follow-up, dual antiplatelet therapy (DAPT) (from 41.1% to 48.0%; P < .001), angiotensin-converting enzyme (ACE) inhibitor (from 46.2% to 51.3%; P < .001), and statin (from 70.4% to 77.5%; P < .001) use increased. Combined DAPT, ACE inhibitor and statin use increased from 33.6% to 39.6% (P ≤ .001). Significant improvement in 24-month OS and AFS was noted (OS, from 90.9% to 93.7% [P = .002]: AFS, from 81.2% to 83.1% [P = .046]), but not LS (from 89.6% to 89.0%; P = .83). Combined therapy with P2Y12 inhibitors, statins and ACE inhibitors was an independent predictor of improved OS (hazard ratio, 0.61; 95% confidence interval, 0.39-0.96; P = .034). DAPT was independent predictor of improved LS (hazard ratio, 0.83; 95% confidence interval, 0.79-0.87; P < .007). CONCLUSIONS: Antiplatelet, ACE inhibitor, and statin use increased over the study period and was associated with improved OS and AFS. LS trends did not change significantly over time, possibly owing to the inclusion of patients with a greater disease burden or inadequate medical management. Medical management, although improved, remained far from optimal and represents an area for continued development.

Heterocyclic Organic Compounds as a Fluorescent Chemosensor for Cell Imaging Applications: A Review.

Fluorometric determination of different biologically, industrially, and environmentally important analytes is a powerful technique because this technique has excellent selectivity, high sensitivity, rapid photoluminescence response, low cost, applicability to bioimaging, and low detection limit. Fluorescence imaging is a powerful technique for screening different analytes in the living system. Heterocyclic organic compounds have been extensively used as a fluorescence chemosensor for the determination of different biologically important cations like Co2+, Zn2+, Cu2+, Hg2+, Ag+, Ni2+, Cr3+, Al3+, Pd2+, Fe3+ Pt2+, Mn2+, Sn2+, Pd2+, Au3+, Pd2+, Cd2+, Pb2+ and other ions in biological and environmental systems. These compounds also showed significant biological applications such as anti-cancer, anti-ulcerogenic, antifungal, anti-inflammatory, anti neuropathic, antihistaminic, antihypertensive, analgesic, antitubercular, antioxidant, antimalarial, antiparasitic, antiglycation, antiviral anti-obesity, and antibacterial potency. In this review, we summarize the heterocyclic organic compounds based on fluorescent chemosensors and their applications in bioimaging studies for the recognition of different biologically important metal ions.

Prostate cancer cell-platelet bidirectional signaling promotes calcium mobilization, invasion and apoptotic resistance via distinct receptor-ligand pairs.

Platelets play a crucial role in cancer and thrombosis. However, the receptor-ligand repertoire mediating prostate cancer (PCa) cell-platelet interactions and ensuing consequences have not been fully elucidated. Microvilli emanating from the plasma membrane of PCa cell lines (RC77 T/E, MDA PCa 2b) directly contacted individual platelets and platelet aggregates. PCa cell-platelet interactions were associated with calcium mobilization in platelets, and translocation of P-selectin and integrin αIIbß3 onto the platelet surface. PCa cell-platelet interactions reciprocally promoted PCa cell invasion and apoptotic resistance, and these events were insensitive to androgen receptor blockade by bicalutamide. PCa cells were exceedingly sensitive to activation by platelets in vitro, occurring at a PCa cell:platelet coculture ratio as low as 1:10 (whereas PCa patient blood contains 1:2,000,000 per ml). Conditioned medium from cocultures stimulated PCa cell invasion but not apoptotic resistance nor platelet aggregation. Candidate transmembrane signaling proteins responsible for PCa cell-platelet oncogenic events were identified by RNA-Seq and broadly divided into 4 major categories: (1) integrin-ligand, (2) EPH receptor-ephrin, (3) immune checkpoint receptor-ligand, and (4) miscellaneous receptor-ligand interactions. Based on antibody neutralization and small molecule inhibitor assays, PCa cell-stimulated calcium mobilization in platelets was found to be mediated by a fibronectin1 (FN1)-αIIbß3 signaling axis. Platelet-stimulated PCa cell invasion was facilitated by a CD55-adhesion G protein coupled receptor E5 (ADGRE5) axis, with contribution from platelet cytokines CCL3L1 and IL32. Platelet-stimulated PCa cell apoptotic resistance relied on ephrin-EPH receptor and lysophosphatidic acid (LPA)-LPA receptor (LPAR) signaling. Of participating signaling partners, FN1 and LPAR3 overexpression was observed in PCa specimens compared to normal prostate, while high expression of CCR1 (CCL3L1 receptor), EPHA1 and LPAR5 in PCa was associated with poor patient survival. These findings emphasize that non-overlapping receptor-ligand pairs participate in oncogenesis and thrombosis, highlighting the complexity of any contemplated clinical intervention strategy.

Comparison of outcomes for balloon angioplasty, atherectomy, and stenting in the treatment of infrapopliteal disease for chronic limb-threatening ischemia.

OBJECTIVE: We evaluated limb salvage (LS), amputation-free survival (AFS), and target extremity reintervention (TER) after plain old balloon angioplasty (POBA), stenting, and atherectomy for treatment of infrapopliteal disease (IPD) with chronic limb-threatening ischemia (CLTI). METHODS: All index peripheral vascular interventions for IPD and CLTI were identified from the Vascular Quality Initiative registry. Of the multilevel procedures, the peripheral vascular intervention type was indexed to the infrapopliteal segment. Propensity score matching was used to control for baseline differences between groups. Kaplan-Meier and Cox regression were used to calculate and compare LS and AFS. RESULTS: The 3-year LS for stenting vs POBA was 87.6% vs 81.9% (P = .006) but was not significant on Cox regression analysis (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.56-0.76; P = .08). AFS was superior for stenting vs POBA (78.1% vs 69.5%; P = .001; HR, 0.73; 95% CI, 0.60-0.90; P = .003). LS was similar for POBA and atherectomy (81.9% vs 84.8%; P = .11) and for stenting and atherectomy (87.6% vs 84.8%; P = .23). The LS rate after propensity score matching for POBA vs stenting was 83.4% vs 88.2% (P = .07; HR, 0.71; 95% CI, 0.50-1.017; P = .062). The AFS rate for stenting vs POBA was 78.8% vs 69.4% (P = .005; HR, 0.69; 95% CI, 0.54-0.89; P = .005). No significant differences were found between stenting and atherectomy (P = .21 for atherectomy; and P = .34 for POBA). The need for TER did not differ across the groups but the interval to TER was significantly longer for stenting than for POBA or atherectomy (stenting vs POBA, 12.8 months vs 7.7 months; P = .001; stenting vs atherectomy, 13.5 months vs 6.8 months; P < .001). CONCLUSIONS: Stenting and atherectomy had comparable LS and AFS for patients with IPD and CLTI. However, stenting conferred significant benefits for AFS compared with POBA but atherectomy did not. Furthermore, the interval to TER was nearly double for stenting compared with POBA or atherectomy. These factors should be considered when determining the treatment strategy for this challenging anatomic segment.

Impact of Statins on Survival and Limb Salvage in Patients Undergoing Peripheral Endovascular Intervention for Chronic Limb-Threatening Ischemia.

BACKGROUND: Statin therapy is recommended in all patients with peripheral arterial disease (PAD). Its impact on reduction in mortality has been well-documented, yet effect on limb-specific outcomes has been less conclusive. Differences among PAD subgroups or variability of statin use may contribute to the inconsistent findings. We evaluated statin use in patients who underwent peripheral endovascular intervention (PVI) for chronic limb-threatening ischemia (CLTI) and its impact on overall survival (OS), amputation-free survival (AFS) and limb salvage (LS). METHODS: The national Vascular Quality Initiative was queried for the index PVI for CLTI during the period 2010-2016; follow-up (FU) through 2020. Demographics, comorbidities, operative details, and FU status were recorded. Patients were categorized as E-Statin: statin use pre-PVI through discharge (D/C) and FU or N-Statin: No statins pre-PVI, at D/C or any time during FU. The propensity score matched model (PSM) was constructed. Groups were compared using chi-square, Kaplan-Meier survival and Cox regression analysis. RESULTS: There were 9,089 index PVI in 8,402 patients; E-Statin: 7149 index PVI in 6,591 patients; and N-Statin: 1940 index PVI in 1811 patients. The mean age was 69 ± 12 years and 58% were male. Statin use was associated with improved 3-year OS-E Statin: 92.9% ± 0.9 versus N Statin: 91.1% ± 2.2%; P = 0.003; hazard ratio (HR): Exp (B) (95% confidence interval): 0.66 (0.44-0.99); P = 0.047 and remained significant following PSM: E Statin: 95.1% ± 0.2% versus 90.8% ± 0.3%; P = 0.02; HR: 0.50 (0.27-0.92); P = 0.025. No significant differences in 3-year LS or AFS were noted between the prematched groups; LS: E Statin: 83.7% ± 0.8 versus N Statin: 84.0% ± 1.7%; P = 0.89; HR: 1.09 (0.88-1.35); P = 0.44; AFS-E Statin: 77.2% ± 1.1% versus 76.1% ± 2.5%; P = 0.17; HR: 0.97 (0.79-1.18); P = 0.74. or following PSM: AFS: 80.2% ± 2.8% vs. 74.7% ± 3.9%; P = 0.53, HR: 0.92 (0.72-1.19); P = 0.54; LS 85.3% ± 1.9% vs. 83.5% ± 2.6%; P = 0.51, HR: 1.08 (0.83-1.4); P = 0.57. Statins significantly improved LS among those with renal failure: 67.8% ± 2.6% vs. 59.7% ± 4.4%; P = 0.003; HR: 56 (0.40-0.79); P = 0.001. CONCLUSIONS: Statins are independently associated with improved OS in patients who undergo PVI for CLTI and should be considered for all barring intolerance. Statin use was associated with improved LS in patients with end-stage renal disease. Additional research is needed in this area, particularly, the impact of statin therapy in high-risk CLTI subgroups.

Understanding radiation exposure and improving safety for vascular surgery trainees.

OBJECTIVE: Despite having robust radiation safety education procedures and policies in place, we discovered that the trainees at our Accreditation Council for Graduate Medical Education-approved integrated vascular surgery residency and fellowship program were exceeding the annual radiation exposure limits. In the present report, we have described our quality improvement project to identify the root causes and implement policies to improve radiation safety education, oversite, and, ultimately, the exposure levels of our trainees. METHODS: A committee of faculty, fellows, radiology nurses, and radiation safety officers from each of the programs affiliated hospitals convened to identify the potential root causes of the increased radiation exposure and potential modifiable actions. The radiation exposure reports for postgraduate year 4 to 7 trainees were evaluated before and after the interventions. RESULTS: Excessive radiation exposure was found to be more prevalent than anticipated, with multiple trainees surpassing the annual exposure limits. The committee classified the factors at play and interventions into four categories: policies and procedures, curriculum, environment, resources, and equipment. The multisite status of our program was a key factor associated with the increased radiation exposure. In addition, we found that excessive radiation levels were occurring primarily at a single hospital site. After the interventions, the monthly average levels at this site had decreased considerably from 936 mrem to 272 mrem. CONCLUSIONS: We found it alarming that the safety policies in place at vascular residency and fellowship programs were inadequate in securing the safety of their trainees. We found interventions such as inventorying and ensuring the availability of safety equipment, hands-on instruction to complement traditional didactics, lowering the default frame rates, and converting to real-time dosimetry to be effective measures for reducing radiation exposure.

Designing Highly Efficient Temperature Controller for Nanoparticles Hyperthermia.

This paper presents various control system design techniques for temperature control of Magnetic Fluid hyperthermia. The purpose of this research is to design a cost-effective, efficient, and practically implementable temperature controller for Magnetic Fluid hyperthermia, which is presently under research as a substitute to the radiation and chemotherapy treatment of cancer. The principle of this phenomenon centers on the greater sensitivity of tumor cells to changes in temperature in comparison to healthy cells. Once the nanoparticles reach the desired tissue, it can then be placed in a varying magnetic field to dissipate the heat locally by raising the temperature to 45 °C in order to kill cancerous cells. One of the challenging tasks is to maintain the temperature strictly at desired point i.e., 45 °C. Temperature controller for magnetic fluid hyperthermia provides the tight control of temperature in order to avoid folding of proteins and save the tissues around the cancerous tissue from getting destroyed. In contrast with most of the existing research on this topic, which are based on linear control strategies or their improved versions, the novelty of this research lies in applying nonlinear control technique like Sliding Mode Control (SMC) to accurately control the temperature at desired value. A comparison of the control techniques is presented in this paper, based on reliability, robustness, precision and the ability of the controller to handle the non-linearities that are faced during the treatment of cancer. SMC showed promising results in terms of settling time and rise time. Steady state error was also reduced to zero using this technique.

Cancer: Can CRISPR Become a Game Changer?

Recent development in CRISPR technologies has emerged as a powerful tool for genome editing, which can become a powerful diagnostic and therapeutic option for cancer patients. While literature search demonstrates some successes in this dimension in animal models and phase-I human trials, still the promised panacea has shortcomings in terms of off-target mutations (OTMs), minimal efficiency, and tailoring individualised interventions. While there is a promise for the future, although the CRISPR technology still has to climb up the ladder in terms of improvements with more enhanced efficiency tools for delivering the payload into cell and reducing the off-target mutations. Key Words: CRISPR, Oncology, Off-target mutations (OTMs), Genome editing, 3-D cell cultures.

Vitamin D status and its correlation to depression.

BACKGROUND: Vitamin D can influence more than 200 genes in various tissues showing its credibility among the fat-soluble vitamins. Vitamin D deficiency is directly proportional to major clinical conditions such as cardiovascular diseases, diabetes, malignancy, and multiple sclerosis. This study was conducted to determine the vitamin D level of individuals and its association with depression. METHODS: Vitamin D levels of 100 healthy and 100 depressed subjects were determined. The isolated subjects were screened on the Beck Depression Inventory (BDI) scale and divided into three groups according to their age. Group-I comprised subjects of age 20 years and below, Group-II included subjects of age 21 to 60, and Group-III comprised subjects of ≥ 61 years of age. A sufficient level of vitamin D in normal subjects was noted, while mild deficiency of vitamin D status was observed in depressed subjects. RESULTS: Our study has reported a higher percentage of vitamin D deficiency in the Peshawar region. The results of our study indicated that depression was common in individuals having vitamin D deficiency. CONCLUSIONS: The study showed a very high frequency of vitamin D deficiency in subjects with depression in Peshawar, Pakistan. The deficiency of vitamin D was observed more in females as compared to males. Further studies should explicate whether the highly widespread vitamin D deficiency could be cost-effectively treated as part of preventive or treatment interventions for depression.

Potential clinical complications of Orise™ gel use, a new submucosal lifting agent: experience from a tertiary care center and review of the literature.

Background: Endoscopic mucosal resection (EMR) involves forming a fluid cushion in the submucosal area with a lifting agent, followed by superficial resection. Orise™ gel is one of the commonly used lifting agents for EMR. We present a case series and literature review that analyzes the characteristic histopathological findings and clinical implications observed where Orise™ gel was used before EMR. Methods: Colon resection specimens and prior EMR specimens where Orise™ gel was used were reviewed for patients undergoing EMR between January 2018 and December 2020. The literature review included relevant studies from the Medline and Cochrane databases from January 2018 to December 2020. Results: A total of 12 colon polyp EMRs using Orise gel were performed during the study period. Seven patients (58.34%) underwent surgical resection. Histological examination revealed that, after the EMR procedure, the Orise™ gel material changed its morphological characteristics over time from a basophilic (bluish) non-inflamed pattern to an eosinophilic (pink) type pattern, eliciting a foreign body reaction. The endoscopic appearance and examination of the excised specimens weeks after injection gave the impression of a mass in some cases. The material was also present transmurally and in some cases in the peri-intestinal adipose tissue. Conclusions: It was observed that Orise™ gel use elicits a foreign body-type granulomatous reaction. This potential side effect may lead to overdiagnosis of a mass/lesion and unnecessary surgical interventions. This case series and review of the literature aims to increase awareness of the changes caused by Orise™ gel in the gastrointestinal tract.

Pyrolysis and Oxidation of Waste Tire Oil: Analysis of Evolved Gases.

Valorization of waste such as waste tires offers a way to manage and reduce urban waste while deriving economic benefits. The rubber portion of waste tires has high potential to produce pyrolysis fuels that can be used for energy production or further upgraded for use as blend fuel with diesel. In the preset work, waste tire oil (WTO) was produced from the pyrolysis of waste tires in an electric heating furnace at 500-550 °C in the absence of oxygen. Pyrolysis (in nitrogen) and oxidation (in air) of the obtained WTO sample were then performed in a thermogravimetric (TG) furnace that was connected to a Fourier transform infrared cell where the evolved gases were analyzed. The WTO sample was heated up to 800 °C in the TG furnace where the temperature of the sample was ramped up at three heating rates, namely, 5, 10, and 20 °C/min. The TG mass loss and differential thermogravimetric mass loss plots were used to analyze the thermal degradation pathways. Kinetic analysis was performed using the distributed activation energy model to estimate the activation energies along the various stages of the reaction. The pollutant gases, namely, CO2, CO, NO, and H2O, formed during WTO oxidation were evaluated by means of the characteristic infrared absorbance. The functional groups evolved during pyrolysis, namely, alkanes, alkenes, aromatics, and carbonyl groups, were also analyzed. The obtained information can be used for the better design of gasifiers and combustors, to ensure the formation of high-value gaseous products while reducing the emissions. The utilization of waste tires by producing pyrolysis oils thus offers a way of tackling the menace of waste tires while acting as a potential energy source.