A Predefined Rule-Based Multi-Factor Risk Stratification Is Associated With Improved Outcomes at a Rural Primary Care Practice.

This study built a predefined rule-based risk stratification paradigm using 19 factors in a primary care setting that works with rural communities. The factors include medical and nonmedical variables. The nonmedical variables represent 3 demographic attributes and one other factor represents transportation availability. Medical variables represent major clinical variables such as blood pressure and BMI. Many risk stratification models are found in the literature but few integrate medical and nonmedical variables, and to our knowledge, no such model is designed specifically for rural communities. The data used in this study contain the associated variables of all medical visits in 2021. Data from 2022 were used to evaluate the model. After our risk stratification model and several interventions were adopted in 2022, the percentage of patients with high or medium risk of deteriorating health outcomes dropped from 34.9% to 24.4%, which is a reduction of 30%. The medium-complex patient population size, which had been 29% of all patients, decreased by about 4% to 5.7%. According to the analysis, the total risk score showed a strong correlation with 3 risk factors: dual diagnoses, the number of seen providers, and PHQ9 (0.63, 0.54, and 0.45 correlation coefficients, respectively).

Outcomes of balloon-expandable versus self-expandable stent graft for endovascular repair of iliac aneurysms using iliac branch endoprosthesis.

PURPOSE: The purpose of this study was to compare outcomes of internal iliac artery (IIA) stenting using balloon-expandable (BESG) or self-expandable stent grafts (SESG) during endovascular repair of aortoiliac aneurysms with iliac branch endoprosthesis (IBE; W. L. Gore, Flagstaff, Ariz). METHODS: We retrospectively reviewed all consecutive patients treated for aortoiliac aneurysms using IBE between 2014 and 2020. IIA stenting was performed using either the IIA side branch SESG or a Gore VBX BESG (W. L. Gore). Indications for use of BESGs were "up-and-over" IBE technique for type IB endoleak after prior endovascular aortic aneurysm repair (EVAR), short IIA length, and need for IIA extension into divisional branches (outside instructions for use). End points included technical success, freedom from buttock claudication, primary IIA patency, and freedom from IIA branch instability (eg, branch-related death or rupture, occlusion, disconnection, or reintervention for stenosis, kink, or endoleak), freedom from type IC/IIIC endoleak, and freedom from secondary interventions. RESULTS: There were 90 patients (86 males and 4 females) with a mean age of 74 ± 7 years treated by EVAR with 108 IBEs. Choice of stent was BESG in 43 and SESG in 65 targeted IIAs. BESGs were used more frequently in patients with prior EVAR (22% vs 2%; P = .003,), isolated IBEs (31% vs 2%; P < .001), and in patients with IIA aneurysms requiring stenting into divisional branches (36% vs 5%; P < .001). Technical success was similar for BESGs and SESGs (97% vs 100%; P = .40), respectively. The mean follow-up was 25 ± 16 months (range, 11-34 months). At 2 years, freedom from buttock claudication was 100% for BESG and 95 ± 3% for SESG (Log-rank 0.26), with no difference in primary patency (BESG, 100% vs SESG, 94 ± 4%; Log-rank 0.94). There were four (9%) IIA-related endoleaks in the BESG group and one (2%) in the SESG group (P = .08). Freedom from IIA branch instability was 87 ± 6% for BESG and 96 ± 3% for SESG at 2 years (Log-rank 0.043). Freedom from type IC/IIIC endoleak was 87 ± 7% for BESG and 98 ± 2% for SESG at the same interval (Log-rank 0.06). There was no difference in freedom from reinterventions for BESG and SESG (92 ± 6% vs 98 ± 2%; Log-rank 0.34), respectively. CONCLUSIONS: BESGs were used more frequently during IBE procedures indicated for failed EVAR, isolated common iliac aneurysms, and IIA aneurysms requiring extension into divisional branches. Despite these differences and BESG being used outside instructions for use, both stent types had similar primary patency, freedom from buttock claudication, and freedom from reinterventions. However, BESGs were associated with higher rates of IIA-related branch instability.

Staged total arch replacement, followed by fenestrated-branched endovascular aortic repair, for patients with mega aortic syndrome.

OBJECTIVE: The aim of the present study was to review the clinical outcomes of a staged approach using total arch replacement (TAR) with an elephant trunk or a frozen elephant trunk, followed by fenestrated-branched endovascular aortic repair (F-BEVAR) for patients with mega aortic syndrome. METHODS: We reviewed the clinical data and outcomes of 11 consecutive patients (8 men; mean age, 71 ± 7 years) treated by staged TAR and F-BEVAR from January 2014 to December 2018. The F-BEVAR procedures were performed under a prospective, nonrandomized, physician-sponsored investigational device exemption protocol. All patients had had mega aortic syndrome, defined by an ascending aorta, arch, and extent I-II thoracoabdominal aortic aneurysm. The endpoints were 30-day mortality, major adverse events (MAE), patient survival, freedom from reintervention, and freedom from target vessel instability. RESULTS: Of the 11 patients, 6 had developed chronic postdissection aneurysms after previous Stanford A (three A11, two A10, one A9) dissection repair and 5 had had degenerative aneurysms with no suitable landing zone in the aortic arch. The thoracoabdominal aortic aneurysms were classified as extent I in four patients and extent II in seven. One patient had died within 30 days after TAR (9.0%). However, none of the remaining 10 patients who had undergone F-BEVAR had died. First-stage TAR resulted in MAE in three patients (27%), including one spinal cord injury. The mean length of stay was 12 ± 6 days. The mean interval between TAR and F-BEVAR was 245 ± 138 days with no aneurysm rupture during the interval. Second-stage F-BEVAR was associated with MAE in two patients (20%), including spinal cord injury in one patient from spinal hematoma due to placement of a cerebrospinal fluid drain. The mean follow-up period was 14 ± 10 months. At 2 years postoperatively, patient survival, primary patency, secondary patency, and freedom from renal-mesenteric target vessel instability was 80% ± 9%, 94% ± 6%, 100%, and 86% ± 8%, respectively. No aortic-related deaths occurred during the follow-up period. Four patients had required reintervention, all performed using an endovascular approach. CONCLUSIONS: A staged approach to treatment of mega aortic syndrome using TAR and F-BEVAR is a feasible alternative for selected high-risk patients. Larger clinical experience and longer follow-up are needed.

Evaluation of physician's knowledge in Jordan about the ACC/AHA blood cholesterol guidelines.

BACKGROUND: Elevated levels of blood lipids are considered a major modifiable risk factor for the development of cardiovascular diseases. The optimal management of dyslipidaemia remains inadequate worldwide. Accordingly, there is an increasing need to evaluate the basis that health care providers are using to control dyslipidaemia. AIM: To evaluate the awareness of Jordanian physicians about the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for dyslipidaemia management. METHOD: A written questionnaire was distributed to 250 physicians from different areas of Jordan during 7 months period (from February 2018 until the end of August 2018). The target population is composed of the following categories: juniors, residents, fellows and consultants who were recruited from private, government and military practice settings. The validated developed questionnaire was distributed by trained medical personnel. RESULTS: A total of 207 physicians filled and handed back the questionnaire. The response rate was 82.8%. Generally, there was a difference in the level of knowledge between physicians (juniors/ residents/ consultants) while there was no difference between genders or practice settings (private or government). The current study showed that the awareness of physicians in different areas of Jordan regarding the 2013 (ACC/AHA) dyslipidaemia guidelines is suboptimal. CONCLUSION: Results indicated low levels of knowledge of 2013 ACC/AHA guidelines for the management of dyslipidaemia among physicians in Jordan. Hence, multiple interventions are needed to be implemented in order to increase the level of awareness among Jordanian physicians.

Advancing evidence-based healthcare facility design: a systematic literature review.

Healthcare facility design is a complex process that brings together diverse stakeholders and ideally aligns operational, environmental, experiential, clinical, and organizational objectives. The challenges inherent in facility design arise from the dynamic and complex nature of healthcare itself, and the growing accountability to the quadruple aims of enhancing patient experience, improving population health, reducing costs, and improving staff work life. Many healthcare systems and design practitioners are adopting an evidence-based approach to facility design, defined broadly as basing decisions about the built environment on credible and rigorous research and linking facility design to quality outcomes. Studies focused on architectural options and concepts in the evidence-based design literature have largely employed observation, surveys, post-occupancy study, space syntax analysis, or have been retrospective in nature. Fewer studies have explored layout optimization frameworks, healthcare layout modeling, applications of artificial intelligence, and layout robustness. These operations research/operations management approaches are highly valuable methods to inform healthcare facility design process in its earliest stages and measure performance in quantitative terms, yet they are currently underutilized. A primary objective of this paper is to begin to bridge this gap. This systematic review summarizes 65 evidence-based research studies related to facility layout and planning concepts published from 2008 through 2018, and categorizes them by methodology, area of focus, typology, and metrics of interest. The review identifies gaps in the existing literature and proposes solutions to advance evidence-based healthcare facility design. This work is the first of its kind to review the facility design literature across the disciplines of evidence-based healthcare design research, healthcare systems engineering, and operations research/operations management. The review suggests areas for future study that will enhance evidence-based healthcare facility designs through the integration of operations research and management science methods.

Outcomes after splenectomy in children: a 48-year population-based study.

PURPOSE: In children who have undergone splenectomy, there may be impaired immunologic function and an increased risk of infection. We aimed to define the long-term rate of and risk factors for post-splenectomy infection using a population-based cohort study. METHODS: All children (< 18 years) who underwent splenectomy from 1966 to 2011 in Olmsted County, MN were identified using the Rochester Epidemiology Project (REP). Descriptive statistics, Kaplan-Meier estimates, and Cox Proportional hazard ratios were performed to evaluate for risk factors associated with developing infection. RESULTS: Ninety patients underwent splenectomy and 46% were female. Indications included trauma (42%), benign hematologic disease (33%), malignancy (13%), and other (11%). Most were performed open. Vaccination was completed in (72%) for pneumococcal, H. influenza, and meningococcal vectors. Nineteen patients developed infection, and associated factors included non-traumatic, non-malignant disease [HR 4.83 (1.18-19.85)], and performance of multiple surgical procedures [HR 2.80 (1.09-7.21)]. Estimated survival free of infection rates at 15 and 20 years following surgery was both 97%. CONCLUSIONS: After splenectomy in children, most patients do not develop infection. Nearly three-quarters of patients were vaccinated with the lowest rates in patients that underwent a splenectomy for trauma. In patients who received multiple procedures during a splenectomy, the infection risk was higher.

Profiled absorber design illuminated uniformly by parabolic reflectors.

In this paper, a general method is proposed in order to develop a special absorber profile that receives sunlight from parabolic reflectors uniformly. Different parameters were taken into consideration while performing the simulation including reflector focal length, collector length, and concentration ratio. The total power reflected to the absorber was calculated by accounting for the Fresnel angular dependency and the shadowing effect by the absorber. Furthermore, a verification method based on the ray tracing technique was also developed in order to verify that uniform illumination was achieved. The uniformity of the sunlight flux onto the absorber is expected to improve solar system efficiency and extend its life service. Therefore, the validated absorber profile design in this theoretical work can be useful for applications which employ parabolic concentrators with the concern of reaching higher performance by achieving a uniform concentration ratio on the absorber.

Prehospital Transfusion for Gastrointestinal Bleeding.

OBJECTIVE: Gastrointestinal (GI) bleeding is a common medical emergency with significant morbidity and mortality. Many patients are coagulopathic, which may perpetuate bleeding. Remote damage control resuscitation, including early correction of coagulopathy and anemia, may benefit exsanguinating patients with GI bleeding. METHODS: We conducted a retrospective review of patients with acute GI bleeding who received packed red blood cells (pRBC) and/or plasma during transportation to our institution between 2010 and 2014. A comparison group of patients who were not transfused en route was selected, and demographics, outcomes, and response to resuscitation were compared. RESULTS: A total of 112 patients with GI bleeding received pRBC (82%, n = 92 pRBC, mean 1.7 ± 0.9 units), plasma (62%, n = 69, mean 1.7 ± 0.8 units) or both (44%, n = 49) en-route. The comparison group comprised 49 patients transported by helicopter who were not transfused en-route. Demographics, crystalloid resuscitation, transfusion prior to transfer, rate of intervention, ICU days, length of stay, and mortality were similar between groups. Patients transfused en route had a significant increase in hemoglobin from 8.3 ± 2.2 to 8.9 ± 2.1 (P = .03) and decrease in INR from 2.0 ± 1.0 to 1.6 ± 1.4 (P = .01), whereas those not transfused en route experienced stable hemoglobin (8.7 ± 2.8 to 9.4 ± 2.5; P = .21) and INR values (1.9 ± 1.0 to 1.6 ± 1.4; P = .32). Both groups had a significant improvement in hemodynamic parameters with resuscitation. CONCLUSION: Prehospital damage control resuscitation with pRBC and/or plasma resulted in the improvement of hemodynamic instability, coagulopathy and anemia in patients with acute GI bleeding. Almost all patients required additional inpatient interventions and/or transfusions, suggesting that pre-hospital transfusion is being utilized for appropriately selected patients.

Impact of BMI on Ability to Successfully Create an IPAA.

BACKGROUND: IPAA is the surgical treatment of choice for patients with ulcerative colitis. Limited data exist on how obesity impacts the ability of the surgeon to successfully create an IPAA. OBJECTIVE: We aimed to determine how BMI affects the ability to successfully complete the operation. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: We included all of the patients undergoing an IPAA for ulcerative colitis between January 2002 and August 2013 at our institution. A total of 1175 patients underwent proctocolectomy for ulcerative colitis during the study period; 129 were not offered IPAA (reasons included patient preference (n = 53), advanced age/comorbidity (n = 28), obesity (n = 23), incontinence (n = 8), suspicion of Crohn's disease (n = 8), rectal cancer (n = 3), and other (n = 6)). Twenty-six patients had a concurrent cancer diagnosis, and 5 had a polyposis syndrome. MAIN OUTCOME MEASURES: We used logistic regression modeling to estimate the association between BMI and unsuccessful pouch attempts. RESULTS: Of the 1046 patients offered IPAA, 19 (1.82%) could not be technically completed at the time of surgery. Increasing BMI was associated with a higher risk of not being able to technically perform IPAA (OR = 1.26 (95% CI, 1.17-1.34)). The chance of an unsuccessful pouch rose from 2.0% at a BMI of 30 to 5.7% at a BMI of 35 and 15.0% at a BMI of 40 (p < 0.01). The area under the receiver operator characteristics curve was 0.82. BMI explained 21% of the variation in pouch success rate. LIMITATIONS: This study is limited in its generalizability. Also, the verbosity within the operative dictations varied among surgeons, making it impossible to be certain which maneuvers were performed to gain length in each patient. In addition, we were limited to BMI as a surrogate for visceral obesity, and we did not include medical therapy at the time of IPAA attempt. CONCLUSIONS: There is a strong association between increasing BMI and the ability to technically perform IPAA. Obese patients should be counseled to lose weight preoperatively to increase the probability of successful IPAA construction at the time of operation.

Long-term outcomes of gastrografin in small bowel obstruction.

BACKGROUND: The gastrografin (GG) challenge is a diagnostic and therapeutic tool used to treat patients with small bowel obstruction (SBO); however, long-term data on SBO recurrence after the GG challenge remain limited. We hypothesized that patients treated with GG would have the same long-term recurrence as those treated before the implementation of the GG challenge protocol. METHODS: Patients ≥18 years who were treated for SBO between July 2009 and December 2012 were identified. We excluded patients with contraindications to the GG challenge (i.e., signs of strangulation), patients having SBO within 6-wk of previous abdominal or pelvic surgery and patients with malignant SBO. All patients had been followed a minimum of 1 y or until death. Kaplan-Meier method and Cox regression models were used to describe the time-dependent outcomes. RESULTS: A total of 202 patients were identified of whom 114 (56%) received the challenge. Mean patients age was 66 y (range, 19-99 y) with 110 being female (54%). A total of 184 patients (91%) were followed minimum of 1 year or death (18 patients lost to follow-up). Median follow-up of living patients was 3 y (range, 1-5 y). During follow-up, 50 patients (25%) experienced SBO recurrences, and 24 (12%) had exploration for SBO recurrence. The 3-year cumulative rate of SBO recurrence in patients who received the GG was 30% (95% confidence interval [CI], 21%-42%) compared to 27% (95% CI, 18%-38%) for those who did not (P = 0.4). The 3-year cumulative rate of exploration for SBO recurrence in patients who received the GG was 15% (95% CI, 8%-26%) compared to 12 % (95% CI, 6%-22%) for those who did not (P = 0.6). CONCLUSIONS: The GG challenge is a clinically useful tool in treating SBO patients with comparable long-term recurrence rates compared to traditional management of SBO.

Validation of the anatomic severity score developed by the American Association for the Surgery of Trauma in small bowel obstruction.

BACKGROUND: The anatomic severity schema for small bowel obstruction (SBO) has been described by the American Association for the Surgery of Trauma (AAST). Although acknowledging the importance of physiological and comorbid parameters, these factors were not included in the developed system. Thus, we sought to validate the AAST-SBO scoring system and evaluate the effect of adding patient's physiology and comorbidity on the prediction for the proposed system. METHODS: Patients aged ≥18 y who were treated for SBO at our institution between 2009 and 2012 were identified. The physiology and comorbidity as well as the AAST anatomic scores were determined, squared, and added to calculate the score that we termed Acute General Emergency Surgical Severity-Small Bowel Obstruction (AGESS-SBO). The area under the receiver operating characteristic (AUROC) curve analyses were performed for the AAST anatomic score and compared with the AGESS-SBO score as a predictor for inhospital mortality, extended hospital stay, and inhospital complications. RESULTS: A total of 351 patients with mean age of 66 ± 17 years were identified, of whom 145 (41%) underwent operation to treat bowel obstruction. Extended hospital stay (>9 d) occurred in 86 patients (25%), inhospital complications in 73 (21%), and inhospital mortality in eight patients (2%). The median (interquartile range [IQR]) AAST anatomic score was 1 point (IQR: 1-2), physiology score was 0 point (IQR: 0-1), and comorbidity score was 1 point (IQR: 1-3); for overall median AGESS-SBO score of 5 points (IQR: 3-13). The AUROC curve analyses demonstrated that the AGESS-SBO system with measures of presenting physiology, comorbidities in addition to AAST anatomic criteria could be beneficial in predicting key outcomes including inhospital mortality (AUROC curve: 0.80 versus 0.54, P = 0.03). CONCLUSIONS: The AAST anatomic score is a reliable system, which assists care providers to categorize SBO. Adding physiology and comorbidity parameters to the described anatomic criteria can be helpful in predicting the outcomes including mortality. Further studies evaluating its usefulness in research and quality improvement purposes across institutions are still required.

Low tissue oxygen saturation is associated with requirements for transfusion in the rural trauma population.

BACKGROUND: Tissue O2 saturation (StO2) is a measure of tissue perfusion and should decrease during active hemorrhage. An initial StO2 value upon trauma center arrival measured concurrently with or prior to vitals, may predict hemorrhagic shock, requiring early blood product transfusion. Our aim was to identify the early StO2 threshold associated with a greater volume of packed red blood cell (PRBC) transfusion 24 h after injury. METHODS: All highest tier triage trauma patients from January 2011 to July 2012 were included in this study. The initial StO2 value upon arrival was used for comparison. RESULTS: A total of 632 patients were considered, 74% of them male with a mean age of 46 years. Initial StO2 values were available for 325 patients. An StO2 value of 65% was determined as the cutoff due to the marked increase in PRBC consumption in 24 h. There were 23 patients (7%) with an StO2 reading <65% compared to 302 patients with values ≥65%. Both groups had similar systolic blood pressure (118 vs. 126) and heart rate (99 vs. 95) in the trauma bay. In addition, there was no difference in the initial hemoglobin, pH, or base deficit. An early StO2 value <65% also led to a greater number of PRBC transfused in 24 h (6.4 vs. 1.7). Regression analysis demonstrated that an StO2 <65% was the only variable associated with a higher PRBC transfusion volume in 24 h (p = 0.01). CONCLUSIONS: An StO2 value <65% correlates with greater requirement for PRBC transfusion 24 h after injury. This suggests that StO2 can be used as an early marker of hemorrhage which may be superior to traditional vital signs in the trauma population.

Innovate and Validate: Design-Led Simulation Optimization to Test Centralized Registration Feasibility in a Multispecialty Clinic.

OBJECTIVE: This study utilizes a design-led simulation-optimization process (DLSO) to refine a hybrid registration model for a free-standing outpatient clinic. The goal is to assess the viability of employing DLSO for innovation support and highlight key factors influencing resource requirements. BACKGROUND: Manual registration in healthcare causes delays, impacting patient services and resource allocation. This study addresses these challenges by optimizing a hybrid centralized registration and adopting technology for efficiency. METHOD: An iterative methodology with simulation optimization was designed to test a proof of concept. Configurations of four and five registration options within a hybrid centralized system were explored under preregistration adoption rates of 30% and 50%. Three self-service kiosks served as a baseline during concept design and test fits. RESULTS: Centralized registration accommodated a daily throughput of 2,000 people with a 30% baseline preregistration rate. Assessing preregistration impact on seating capacity showed significant reductions in demand and floor census. For four check-in stations, a 30%-50% preregistration increase led to a 32% seating demand reduction and a 26% decrease in maximum floor census. With five stations, a 50% preregistration reduced seating demand by 23% and maximum floor census by 20%. CONCLUSION: Innovating introduces complexity and uncertainties requiring buy-in from diverse stakeholders. DLSO experimentation proves beneficial for validating novel concepts during design.

Treatment of Internal Mammary Nodes is Associated With Improved Overall Survival in Breast Cancer: A Meta-Analysis.

INTRODUCTION: The role of internal mammary nodal irradiation (IMNI) as a component of regional nodal radiotherapy is a controversial issue in breast radiation oncology with conflicting results presented in recent landmark trials. We thus created a meta-analysis of available data to better ascertain the potential benefit of IMNI. We hypothesize that with the increased power available within a meta-analysis, IMNI will prove to improve overall survival (OS) in breast cancer. METHODS: Literature search was conducted for prospective studies comparing IMNI to no IMNI. Primary endpoint was OS and secondary endpoints included local recurrence, regional recurrence, disease-free survival (DFS), breast cancer mortality (BCM), distant metastasis-free survival (DMFS), grade 2+ skin toxicity, cardiac events, and pneumonitis events. Subgroup analyses were performed for tumor location (medial/central vs. lateral), and nodal status (pN+ vs. pN0). Fixed-effect model was used if there was no heterogeneity, random-effects model otherwise. RESULTS: Four studies with a total of 5258 patients (IMNI: n=2592; control: n=2666) were included in the study. Pooled results showed IMNI significantly improved OS for all-comers (hazard ratio [HR]=0.89; 95% CI 0.81-0.97; P =0.008), as well as subgroups of pN+ with medial/central tumor location (HR=0.84; 95% CI 0.73-0.96; P =0.01) and pN+ with lateral tumor location (HR=0.87; 95% CI 0.77-0.99; P =0.04). There was no significant difference in OS for subgroups of pN0 and medial/central tumor location. There was no difference in local recurrence, but regional recurrence was significantly improved ( P =0.04). Endpoints of DFS (HR 0.91, 95% CI 0.84-0.99 P =0.03), BCM (HR 0.87, 95% CI 0.77-0.98, P =0.03), and DMFS (HR=0.87; 95% CI, 0.78-0.98; P =0.02) were all improved with IMNI. Grade 2+ skin toxicity, cardiac events and pneumonitis events were not significantly different between patient in the IMNI and no IMNI groups. CONCLUSION: Inclusion of IMN irradiation improves OS, DFS, BCM, and DMFS in breast cancer. Largest effect on OS was noted in the subgroup of patients with pN+ and medial/central tumor location.

A systematic review on Nb2O5-based photocatalysts: Crystallography, synthetic methods, design strategies, and photocatalytic mechanisms.

With the increasing popularity of photocatalytic technology and the highly growing issues of energy scarcity and environmental pollution, there is an increasing interest in extremely efficient photocatalytic systems. The widespread immense attention and applicability of Nb2O5 photocatalysts can be attributed to their multiple benefits, including strong redox potentials, non-toxicity, earth abundance, corrosion resistance, and efficient thermal and chemical stability. However, the large-scale application of Nb2O5 is currently impeded by the barriers of rapid recombination loss of photo-activated electron/hole pairs and the inadequacy of visible light absorption. To overcome these constraints, plentiful design strategies have been directed at modulating the morphology, electronic band structure, and optical properties of Nb2O5. The current review offers an extensive analysis of Nb2O5-based photocatalysts, with a particular emphasis on crystallography, synthetic methods, design strategies, and photocatalytic mechanisms. Finally, an outline of future research directions and challenges in developing Nb2O5-based materials with excellent photocatalytic performance is presented.

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.

Purpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results:  Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1ß Signaling Pathways.

Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Outcomes of chemical component paralysis using botulinum toxin for incisional hernia repairs.

BACKGROUND: Botulinum toxin A (BTX) confers flaccid paralysis and pain modulation when injected into a muscle. We hypothesized that long-term paralysis of the abdominal wall musculature (i.e., chemical component paralysis, CCP) would benefit incisional hernia repair (IHR) by decreasing postoperative pain, the use of opioid analgesia, and thus opioid-related side effects. METHODS: Adult patients who underwent elective IHR with preoperative CCP (n = 22) were compared to concurrent matched controls (n = 66, 1:3 ratio) based on age (±5 years), sex, body mass index (±5 kg/m(2)), history of hernia recurrence (0 vs. ≥1), and type of repair (open vs. laparoscopic). BTX was injected under ultrasonographic guidance into the transversus abdominis and internal and external oblique muscles at three sites bilaterally (300 units total). RESULTS: Patients who underwent IHR with CCP used significantly less opioid analgesia (mean ± SD morphine equivalents) when compared to controls on hospital days (HDs) 2 and 5: HD2, 48 ± 27 versus 87 ± 41; HD5, 17 ± 16 versus 48 ± 45. Likewise, CCP patients reported significantly less pain (visual analogue scale 1-10) when compared to controls on HD2 (5.2 ± 1.5 vs. 6.8 ± 2) and HD4 (3.6 ± 1.2 vs. 5.2 ± 1.9): all p < 0.007 (Bonferroni adjusted). There was no difference in postoperative complications (surgical site, 9 vs. 14 %), opioid-related adverse events (ileus 5 vs. 5 %), hospital stay (4 ± 3 vs. 3 ± 2 days), or hernia recurrence (18 months mean follow-up: 9 vs. 9 %). CONCLUSIONS: Despite similar multimodality treatment of postoperative pain after IHR, patients who underwent CCP required significantly less opioid analgesia and reported less pain.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Explainable Artificial Intelligence to Identify Dosimetric Predictors of Toxicity in Patients with Locally Advanced Non-Small Cell Lung Cancer: A Secondary Analysis of RTOG 0617.

PURPOSE: Dosimetric predictors of toxicity in patients treated with definitive chemoradiation for locally advanced non-small cell lung cancer are often identified through trial and error. This study used machine learning (ML) and explainable artificial intelligence to empirically characterize dosimetric predictors of toxicity in patients treated as part of a prospective clinical trial. METHODS AND MATERIALS: A secondary analysis of the Radiation Therapy Oncology Group (RTOG) 0617 trial was performed. Multiple ML models were trained to predict grade ≥3 pulmonary, cardiac, and esophageal toxicities using clinical and dosimetric features. Model performance was evaluated using the area under the curve (AUC). The best performing model for each toxicity was explained using the Shapley Additive Explanation (SHAP) framework; SHAP values were used to identify relevant dosimetric thresholds and were converted to odds ratios (ORs) with confidence intervals (CIs) generated using bootstrapping to obtain quantitative measures of risk. Thresholds were validated using logistic regression. RESULTS: The best-performing models for pulmonary, cardiac, and esophageal toxicities, outperforming logistic regression, were extreme gradient boosting (AUC, 0.739), random forest (AUC, 0.706), and naive Bayes (AUC, 0.721), respectively. For pulmonary toxicity, thresholds of a mean dose >18 Gy (OR, 2.467; 95% CI, 1.049-5.800; P = .038) and lung volume receiving ≥20 Gy (V20) > 37% (OR, 2.722; 95% CI, 1.034-7.163; P = .043) were identified. For esophageal toxicity, thresholds of a mean dose >34 Gy (OR, 4.006; 95% CI, 2.183-7.354; P < .001) and V20 > 37% (OR, 3.725; 95% CI, 1.308-10.603; P = .014) were identified. No significant thresholds were identified for cardiac toxicity. CONCLUSIONS: In this data set, ML approaches validated known dosimetric thresholds and outperformed logistic regression at predicting toxicity. Furthermore, using explainable artificial intelligence, clinically useful dosimetric thresholds might be identified and subsequently externally validated.