Predictive Value of C-reactive Protein in the Spontaneous Passage of Lower Ureteric Stones: A Prospective Single-Centre Study.

INTRODUCTION: Ureteric stones, characterised by their presence in the ureter, present a common yet often painful urological condition requiring timely intervention. As C-reactive protein (CRP) emerges as a potential biomarker, its correlation with the spontaneous stone passage (SSP) offers valuable insights into patient management and treatment strategies. The present study aimed to assess if CRP levels can predict SSP in symptomatic lower ureteric calculi of size 5 mm-10 mm. MATERIALS AND METHODS: This prospective observational study, conducted at the Indira Gandhi Institute of Medical Sciences in Patna, India, from July 2022 to June 2023, focused on individuals aged 13 to 60 years presenting with ureteric colic and single distal ureteral stones (5 mm-10 mm). Patients underwent comprehensive initial assessment and monitoring, including diagnostic procedures such as a complete blood count, urinalysis, CRP levels, and renal function evaluations. Treatment consisted of hydration encouragement, tamsulosin (0.4 mg) daily administration, and diclofenac (50 mg) as needed. Follow-up assessments at one-month post-treatment involved clinical examination and imaging studies to evaluate treatment efficacy. RESULTS: This study analysed 157 patients with ureteric stones, finding that 76% experienced SSP. Lower CRP levels (≤6 mg/L), along with other laboratory parameters like low white blood cell counts, low neutrophil levels, absence of leukocyturia, absence of hematuria, and lower urine specific gravity, were associated with higher SSP rates. C-reactive protein levels ≤6 mg/L emerged as a strong predictor of SSP in multiple regression analysis. CONCLUSION: The findings underscore the potential utility of CRP as a predictive biomarker in guiding the management and treatment strategies for ureteric stones.

Multidisciplinary Care for Moebius Syndrome and Related Disorders: Building a Management Protocol.

Moebius syndrome is a collection of orofacial anomalies with highly variable features affecting many different systems but characterised by bilateral facial palsy and absent eye abduction. We largely regard Moebius syndrome as a diagnosis of exclusion. Lack of awareness and knowledge means that children often fall between services, leading to treatment delays and difficulty interfacing with social care and schools, with long-term impact on physical health and psychosocial development. We developed a multidisciplinary team comprising core clinicians (lead physician, geneticist, speech and language therapist, psychologist and specialist nurse) and an expanded group to encompass the other affected systems. The interactions between our specialties lead to the development of a treatment protocol, which we present. The protocol harnesses the aspects of care of children with a range of other rare diseases at a specialised paediatric centre and synthesises them into a holistic approach for MBS and related conditions. Management is sequenced on an "ABC-style" basis, with airway, feeding, vision and speech taking priority in the early years. We define management priorities as airway stabilisation with swallow assessment, ocular surface protection and maintenance of nutritional support. Management principles for issues such as speech, reflux, drooling and sleep issues are outlined. In later years, psychological support has a prominent role geared towards monitoring and interventions for low mood, self-esteem and bullying.

Genomic surveillance of SARS-CoV-2 and emergence of XBB.1.16 variant in Rajasthan.

PURPOSE: Genomic surveillance of positive SARS-CoV-2 samples is important to monitor the genetic changes occurring in virus, this was enhanced after the WHO designation of XBB.1.16 as a variant under monitoring in March 2023. From 5th February till May 6, 2023 all positive SARS-CoV-2 samples were monitored for genetic changes. METHODS: A total of 1757 samples having Ct value <25 (for E and ORF gene) from different districts of Rajasthan were processed for Next Generation Sequencing (NGS). The FASTA files obtained on sequencing were used for lineage determination using Nextclade and phylogenetic tree construction. RESULTS AND CONCLUSIONS: Sequencing and lineage identification was done in 1624 samples. XBB.1.16 was the predominant lineage in 1413 (87.0%) cases while rest was other XBB (207, 12.74%) and other lineages (4, 0.2%). Of the 1413 XBB.1.16 cases, 57.47% were males and 42.53% were females. Majority (66.53%) belonged to 19-59 year age. 84.15% of XBB.1.16 cases were infected for the first time. Hospitalization was required in only 2.2% cases and death was reported in 5 (0.35%) patients. Most of the cases were symptomatic and the commonest symptoms were fever, cough and rhinorrhea. Co-morbidities were present in 414 (29.3%) cases. Enhanced genomic surveillance helped to rapidly identify the spread of XBB variant in Rajasthan. This in turn helped to take control measures to prevent spread of virus and estimate public health risks of the new variant relative to the previously circulating lineages. XBB variant was found to spread rapidly but produced milder disease.

Beyond Traditional Training: Exploring the Benefits of Virtual Reality Simulator in Lumbar Pedicle Screw Insertion - A Randomized Controlled Trial.

INTRODUCTION: This study compares the effectiveness of virtual reality simulators (VRS) and a saw bone model for learning lumbar pedicle screw insertion (LPSI) in neurosurgery. METHODS: A single-center, cross-sectional, randomized controlled laboratory investigation was conducted involving residents and fellows from a tertiary care referral hospital. Participants were divided into two groups (A and B). Group A performed 3 LPSI tasks: the first on a saw bone model, the second on VRS, and the third on another saw bone model. Group B completed 2 LPSI tasks: the first on a saw bone model and the second on another saw bone model. The accuracy of LPSI was evaluated through noncontrast computed tomography scans for the saw bone models, while the in-built application of VRS was utilized to check for accuracy of screw placement using the simulator. RESULTS: The study included 38 participants (19 in each group). Group A participants showed reduced mean entry point error (0.11 mm, P 0.024), increased mean purchase length (4.66 cm, P 0.007), and no cortical breaches (P 0.031) when placing the second saw bone model screw. Similar improvements were observed among group A participants in PGY 1-3 while placing the second saw bone model screws. CONCLUSIONS: Virtual reality simulators (VRS) prove to be an invaluable tool for teaching complex neurosurgical skills, such as LPSI, to trainees. This technology investment can enhance the learning curve while maintaining patient safety.

Re-Admissions of 'Unknown' Traumatic Brain Injury Patients - Inadequacy of Rehabilitative Services in a Developing Country.

BACKGROUND: In neurosurgical practice, continuous care after discharge and the ability to detect subtle indicators of clinical deterioration are mandatory to prevent the progression of a disease. The care of 'unknown' patients discharged to rehabilitation homes may not have this privilege, especially in resource-poor countries such as India. OBJECTIVE: We have attempted to study the causes and outcomes of re-admissions of 'unknown' patients with previous traumatic brain injury (TBI) to estimate the quality of nursing care in our rehabilitation centers. MATERIAL AND METHODS: The electronic hospital records of all consecutive 'unknown' TBI patients with unplanned re-admissions at our institute from January 2014 to December 2018 were retrospectively reviewed and analyzed for the factors determining the risk and outcomes of re-admission. RESULTS: Out of 245 patients sent to rehabilitation homes at discharge, 47 patients (19.18%) were re-admitted. A total of 33 patients (70%) were re-admitted between 1 month and 1 year. Out of these, 38 patients (80.9%) were re-admitted because of preventable causes. Fifteen patients (31.9%) died during the hospital stay. The rest of the 32 (68%) patients were discharged after the management of the concerned condition with an average hospital stay of 9 ± 11.1 days. The average Glasgow coma scale (GCS) at re-admission of the patients who died was 6 (range 3-11). Two patients were brought in the brain dead status, whereas 20 patients (42.6%) had a GCS of 5 or below at the time of re-admission. The risk of mortality among patients with non-preventable causes was 88.9% (8/9) compared to preventable causes 18.4% (7/38). However, preventable causes for re-admission are much more common, resulting in nearly a similar overall contribution to mortality. CONCLUSIONS: There is a high rate of mortality and morbidity in 'unknown' patients with TBI because of poor post-discharge care in developing countries. Because preventable causes are the major contributor to re-admissions, the re-admission rate is a good indicator of a lack of adequate rehabilitative services. The need for improving the post-discharge management of 'unknown' patients with TBI in resource-poor countries cannot be over-emphasized.

Rathke's Cleft Cyst and Craniopharyngioma: A Continuum of the Same Spectrum? Insights from an Interesting Case and Previous Literature.

Rathke's Cleft Cysts (RCCs) and Craniopharyngiomas (CPs) may represent disease entities on the same etio-pathological spectrum. We report the case of a 36-year-old female presenting with vision loss and menstrual irregularities, imaging shows a predominantly cystic lesion in the sellar region with suprasellar extension. She underwent a microscopic transnasal resection of the lesion. She later presented with recurrent symptoms and increased residual lesion size on imaging, a transcranial excision of the lesion was performed. Histopathology from the initial operative specimen revealed RCC with squamous metaplasia which was BRAF negative, while the specimen from the second surgery revealed BRAF positive papillary stratified squamous architecture suggestive of Papillary CP. This case adds to the evidence that both RCCs and papillary CPs may be the spectrum of the same disease. Further, papillary CPs may be an evolution from the RCCs.

Hyposalivation in patients with psoriasis: Association with severity, inflammatory, and anti-inflammatory cytokine biomarkers of the disease.

The aim of the study is to expound the effect of psoriasis on salivary glands by evaluating the secretion of saliva and salivary cytokine biomarkers in patients with psoriasis. This study was conducted by recruiting 120 subjects that included 60 patients diagnosed clinically with active psoriasis and 60 healthy controls who were age and gender matched to psoriatic subjects. Unstimulated whole saliva was collected from all the subjects by spitting method, and levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-2 (IL-2), and IL-10 (IL-10) were determined via enzyme-linked immunosorbent assay (BT Lab, Shanghai, China). Secretion of saliva in psoriasis patients was considerably reduced than in healthy controls. The concentrations of pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-2) were significantly increased, whereas level of anti-inflammatory cytokine (IL-10) was markedly decreased in the saliva of psoriasis patients with hyposalivation compared to healthy subjects. Our results demonstrated significant negative correlation of salivary flow rates with the disease severity. No significant correlations were obtained between salivary levels of tested cytokines and salivary flow rates in our study. Findings of the study reflect inflammation of salivary glands with reduced salivary flow rates in psoriasis patients. The inflammatory responses in salivary gland tissues by virtue of increased pro-inflammatory cytokines concentrations together with lower anti-inflammatory cytokine levels may have a role in affecting the saliva secretion in psoriasis patients. Secretion of unstimulated saliva in psoriasis patients decreases with the severity and duration of the disease.

Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.

OBJECTIVE: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. METHODS: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. RESULTS: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). CONCLUSION: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Engineered nanomicelles inhibit the tumour progression via abrogating the prostaglandin-mediated immunosuppression.

Cancer treatment is challenged due to immunosuppressive inflammatory tumour microenvironment (TME) caused by infiltration of tumour-promoting and inhibition of tumour-inhibiting immune cells. Here, we report the engineering of chimeric nanomicelles (NMs) targeting the cell proliferation using docetaxel (DTX) and inflammation using dexamethasone (DEX) that alters the immunosuppressive TME. We show that a combination of phospholipid-DTX conjugate and PEGylated-lipid-DEX conjugate can self-assemble to form sub-100 nm chimeric NMs (DTX-DEX NMs). Anti-cancer activities against syngeneic and xenograft mouse models showed that the DTX-DEX NMs are more effective in tumour regression, enhance the survival of mice over other treatment modes, and alter the tumour stroma. DTX-DEX NMs cause a significant reduction in myeloid-derived suppressor cells, alter the polarization of macrophages, and enhance the accumulation of cytotoxic CD4+ and CD8+ T cells in tumour tissues, along with alterations in cytokine expression. We further demonstrated that these DTX-DEX NMs inhibit the synthesis of prostaglandins, especially PGE2, by targeting the cyclooxygenase 2 that is partly responsible for immunosuppressive TME. Therefore, this study presents, for the first time, the engineering of lithocholic acid-derived chimeric NMs that affect the prostaglandin pathway, alter the TME, and mitigate tumour progression with enhanced mice survival.

Thermal performance enhancement of lauric acid using nanomaterials as composite phase change material.

In the present work, lauric acid was taken as a phase change material (PCM), and different nanoparticles (NPs) such as SiO2, TiO2, CuO, and ZnO were taken as the supporting materials. CuO NPs were prepared through the co-precipitation technique; SiO2, TiO2, and ZnO NPs were synthesized via the sol-gel technique. These NPs with different weight fractions were dispersed into molten lauric acid, individually. The variations in thermal properties (phase change temperature and latent heat for solid and liquid) of the prepared composite PCMs due to the dispersion of NPs were observed by DSC analyses. An increase in thermal conductivity of the composite PCMs was observed with the increasing weight fraction of NPs. In order to ascertain the long-term utility, a thermal reliability test was conducted on the composite PCMs with repeated heating and cooling cycles. Also, the specific heats of the pure PCM and the composite PCMs were determined as a function of temperature. Further, the experimental investigation was performed on the pure PCM and the prepared composite PCMs to assess their phase change behavior, and the test results clearly proved that the time required for the complete melting and freezing process of the composite PCMs was less when compared to pure PCM. By considering the above facts, the newly prepared composite PCMs can be recommended as a potential candidate for low-temperature solar heating applications.

Innovations in craniovertebral junction training: harnessing the power of mixed reality and head-mounted displays.

OBJECTIVE: The objective of this study was to analyze the potential and convenience of using mixed reality as a teaching tool for craniovertebral junction (CVJ) anomaly pathoanatomy. METHODS: CT and CT angiography images of 2 patients with CVJ anomalies were used to construct mixed reality models in the HoloMedicine application on the HoloLens 2 headset, resulting in four viewing stations. Twenty-two participants were randomly allocated into two groups, with each participant rotating through all stations for 90 seconds, each in a different order based on their group. At every station, objective questions evaluating the understanding of CVJ pathoanatomy were answered. At the end, subjective opinion on the user experience of mixed reality was provided using a 5-point Likert scale. The objective performance of the two viewing modes was compared, and a correlation between performance and participant experience was sought. Subjective feedback was compiled and correlated with experience. RESULTS: In both groups, there was a significant improvement in median (interquartile range [IQR]) objective performance with mixed reality compared with DICOM: 1) group A: case 1, median 6 (IQR 6-7) versus 5 (IQR 3-6), p = 0.009; case 2, median 6 (IQR 6-7) versus 5 (IQR 3-6), p = 0.02; 2) group B: case 1, median 6 (IQR 5-7) versus 4 (IQR 2-5), p = 0.04; case 2, median 6 (IQR 6-7) versus 5 (IQR 3-7), p = 0.03. There was significantly higher improvement in less experienced participants in both groups for both cases: 1) group A: case 1, r = -0.8665, p = 0.0005; case 2, r = -0.8002, p = 0.03; 2) group B: case 1, r = -0.6977, p = 0.01; case 2, r = -0.7417, p = 0.009. Subjectively, mixed reality was easy to use, with less disorientation due to the visible background, and it was believed to be a useful teaching tool. CONCLUSIONS: Mixed reality is an effective teaching tool for CVJ pathoanatomy, particularly for young neurosurgeons and trainees. The versatility of mixed reality and the intuitiveness of the user experience offer many potential applications, including training, intraoperative guidance, patient counseling, and individualized medicine; consequently, mixed reality has the potential to transform neurosurgery.

Laparoscopic choledochal cyst excision and biliary reconstruction in patients with previous surgery/ intervention: Feasibility and outcome.

INTRODUCTION: The aim of the study was to evaluate the feasibility and outcome of laparoscopic surgery in complicated choledochal cyst (CDC) with previous interventions (laparotomy or biliary drainage). PATIENTS AND METHODS: Patients with CDC who underwent surgery from July 2014 to July 2019 were evaluated. CDC without previous interventions (Group A) was compared with CDC that had previous interventions (Group B) to assess the feasibility and outcome of laparoscopic surgery. RESULTS: In 5 years' period, 38 patients were operated for CDC. The mean age was similar in both groups (3.78 ± 2.27 in Group A and 4.08 ± 2.73 in Group B). Out of six CDC with previous intervention (Group B), five patients were previously managed at other institutions as follows: (1) Laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) stenting. (2) Laparotomy for biliary peritonitis and ERCP. (3) Percutaneous drainage of the large cyst. (4) Laparoscopic cholecystectomy. (5) ERCP stenting. (6) Percutaneous drainage for biliary ascites. All patients underwent laparoscopic CDC excision and hepatico-duodenostomy. The mean duration of surgery was 160.3 ± 17.22 in Group A and 169.2 ± 17.5 in Group B ( P = 0.258). None required intraoperative blood transfusion. None had a bile leak. Drain was removed at 4.47 ± 0.98 in Group A, while at 4.17 ± 0.75 days in Group B ( P = 0.481). There was statistically no significant difference in feed starting time or length of stay. In follow-up of 6 months-3 years, all patients are asymptomatic. CONCLUSIONS: Laparoscopy in complicated CDC with previous intervention is technically tedious but is feasible. The procedure is safe and delivers a good outcome.

Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics. METHODS: This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings. RESULTS: Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS. CONCLUSIONS: Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.

Towards detection of early response in neoadjuvant chemotherapy of breast cancer using Bayesian intravoxel incoherent motion.

Introduction: The early identification of good responders to neoadjuvant chemotherapy (NACT) holds a significant potential in the optimal treatment of breast cancer. A recent Bayesian approach has been postulated to improve the accuracy of the intravoxel incoherent motion (IVIM) model for clinical translation. This study examined the prediction and early sensitivity of Bayesian IVIM to NACT response. Materials and methods: Seventeen female patients with breast cancer were scanned at baseline and 16 patients were scanned after Cycle 1. Tissue diffusion and perfusion from Bayesian IVIM were calculated at baseline with percentage change at Cycle 1 computed with reference to baseline. Cellular proliferative activity marker Ki-67 was obtained semi-quantitatively with percentage change at excision computed with reference to core biopsy. Results: The perfusion fraction showed a significant difference (p = 0.042) in percentage change between responder groups at Cycle 1, with a decrease in good responders [-7.98% (-19.47-1.73), n = 7] and an increase in poor responders [10.04% (5.09-28.93), n = 9]. There was a significant correlation between percentage change in perfusion fraction and percentage change in Ki-67 (p = 0.042). Tissue diffusion and pseudodiffusion showed no significant difference in percentage change between groups at Cycle 1, nor was there a significant correlation against percentage change in Ki-67. Perfusion fraction, tissue diffusion, and pseudodiffusion showed no significant difference between groups at baseline, nor was there a significant correlation against Ki-67 from core biopsy. Conclusion: The alteration in tumour perfusion fraction from the Bayesian IVIM model, in association with cellular proliferation, showed early sensitivity to good responders in NACT. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03501394, identifier NCT03501394.

Role of Cavernous Sinus Extension and MRI T2 Hypointensity in the Extent of Resection following Trans-Sphenoidal Surgery for Giant Pituitary Adenomas.

Background: Giant pituitary adenomas (GPA) pose a significant neurosurgical challenge. In this study, we present an experience of 60 consecutive patients with GPA operated by trans-sphenoidal surgery (microscopic/endoscopic). Objective: The aim of this study was to elucidate preoperative factors predicting extent of resection (EOR) following transsphenoidal surgery for GPA. Materials and Methods: The study was a retrospective evaluation of 60 adult patients (>18 years) with GPA operated over a decade. The patients were analyzed for their clinical presentation, EOR, radiology, visual outcome, endocrinological outcome, and complications. Results: The mean age of the cohort was 41.5 ± 13.3 years, mean tumor volume was 38.2 ± 19.1 cm3, and mean follow-up was 30.6 ± 21.7 months. Improvement in vision was seen in forty patients (66.7%), while another 16 (26.7%) had stable vision as prior to surgery. Duration of visual symptoms was found to be statistically significantly associated with postoperative improvement of vision (P = 0.001). Twenty-four patients (40.0%) underwent subtotal resection (STR), while the remaining 36 patients (60.0%) underwent either gross total or near-total resection. Factors associated with STR were retrosellar (P = 0.04), subfrontal (P = 0.02), Knosp 3,4 cavernous sinus extension (P = 0.03), and MRI T2 hypointensity (P = 0.02). During follow-up, eight patients (13.3%) had radiological evidence of growth of residual tumor. Conclusions: Most cases of GPA can be adequately handled by trans-sphenoidal surgery. The presence of retrosellar, subfrontal, cavernous sinus extensions, and T2 hypointensity should alert the surgeon for likelihood of STR, postoperative residual tumor hemorrhage and need for second-stage endonasal or transcranial surgery. However, utilization of extended endoscopic route has allowed good debulking of tumors having subfrontal and parasellar extensions, which was not possible previously using traditional microscopic transsphenoidal surgery.

AI and Blockchain-Based Secure Data Dissemination Architecture for IoT-Enabled Critical Infrastructure.

The Internet of Things (IoT) is the most abundant technology in the fields of manufacturing, automation, transportation, robotics, and agriculture, utilizing the IoT's sensors-sensing capability. It plays a vital role in digital transformation and smart revolutions in critical infrastructure environments. However, handling heterogeneous data from different IoT devices is challenging from the perspective of security and privacy issues. The attacker targets the sensor communication between two IoT devices to jeopardize the regular operations of IoT-based critical infrastructure. In this paper, we propose an artificial intelligence (AI) and blockchain-driven secure data dissemination architecture to deal with critical infrastructure security and privacy issues. First, we reduced dimensionality using principal component analysis (PCA) and explainable AI (XAI) approaches. Furthermore, we applied different AI classifiers such as random forest (RF), decision tree (DT), support vector machine (SVM), perceptron, and Gaussian Naive Bayes (GaussianNB) that classify the data, i.e., malicious or non-malicious. Furthermore, we employ an interplanetary file system (IPFS)-driven blockchain network that offers security to the non-malicious data. In addition, to strengthen the security of AI classifiers, we analyze data poisoning attacks on the dataset that manipulate sensitive data and mislead the classifier, resulting in inaccurate results from the classifiers. To overcome this issue, we provide an anomaly detection approach that identifies malicious instances and removes the poisoned data from the dataset. The proposed architecture is evaluated using performance evaluation metrics such as accuracy, precision, recall, F1 score, and receiver operating characteristic curve (ROC curve). The findings show that the RF classifier transcends other AI classifiers in terms of accuracy, i.e., 98.46%.

Echocardiographic and Clinical Outcomes in Symptomatic Patients With Less Than Severe Aortic Stenosis After Supra-Annular Self-Expanding Transcatheter Aortic Valve Replacement.

Optimal timing for aortic valve replacement in symptomatic patients with less than severe aortic stenosis (AS) is not well defined. There is limited information on the benefit of valve replacement in these patients. Symptomatic patients with less than severe AS, defined as a mean aortic gradient ≥20 and <40 mm Hg, peak aortic velocity >3 and <4 m/s, and aortic valve area >1.0 and <1.5 cm2, enrolled in the Society for Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry and who underwent attempted supra-annular, self-expanding transcatheter aortic valve replacement (TAVR) were reviewed. Site-reported valve hemodynamics, clinical events, and quality of life metrics were analyzed at 30 days and 1 year after the procedure. A total of 1,067 patients with attempted TAVR (mean age 78.4 ± 8.4 years; Society for Thoracic Surgery score 4.7 ± 3.4%) were found to have symptoms but less than severe AS. From baseline to postprocedure, mean gradient decreased (29.9 ± 4.9 vs 8.4 ± 4.8 mm Hg, p <0.001), and aortic valve area increased (1.2 ± 0.1 vs 2.2 ± 0.7 cm2, p <0.001). Clinical events included 30-day and 1-year all-cause mortality (1.5% and 9.6%), stroke (2.2% and 3.3%), and new pacemaker implantation (18.1% and 20.9%). There were statistically significant improvements in the New York Heart Association functional class and Kansas City Cardiomyopathy Questionnaire at 30 days and 1 year. In conclusion, patients with symptomatic but less than severe AS who underwent supra-annular, self-expanding TAVR experienced improved valve hemodynamics and quality of life measures 1 year after the procedure. Randomized studies of TAVR versus a control arm in symptomatic patients with less than severe AS are ongoing.

Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer.

BACKGROUND: Anthracycline-related cardiac toxicity is a recognized consequence of cancer therapies. We assess resting cardiac and skeletal muscle energetics and myocyte, sarcomere, and mitochondrial integrity in patients with breast cancer receiving epirubicin. METHODS: In a prospective, mechanistic, observational, longitudinal study, we investigated chemotherapy-naive patients with breast cancer receiving epirubicin versus sex- and age-matched healthy controls. Resting energetic status of cardiac and skeletal muscle (phosphocreatine/gamma ATP and inorganic phosphate [Pi]/phosphocreatine, respectively) was assessed with 31P-magnetic resonance spectroscopy. Cardiac function and tissue characterization (magnetic resonance imaging and 2D-echocardiography), cardiac biomarkers (serum NT-pro-BNP and high-sensitivity troponin I), and structural assessments of skeletal muscle biopsies were obtained. All study assessments were performed before and after chemotherapy. RESULTS: Twenty-five female patients with breast cancer (median age, 53 years) received a mean epirubicin dose of 304 mg/m2, and 25 age/sex-matched controls were recruited. Despite comparable baseline cardiac and skeletal muscle energetics with the healthy controls, after chemotherapy, patients with breast cancer showed a reduction in cardiac phosphocreatine/gamma ATP ratio (2.0±0.7 versus 1.1±0.5; P=0.001) and an increase in skeletal muscle Pi/phosphocreatine ratio (0.1±0.1 versus 0.2±0.1; P=0.022). This occurred in the context of increases in left ventricular end-systolic and end-diastolic volumes (P=0.009 and P=0.008, respectively), T1 and T2 mapping (P=0.001 and P=0.028, respectively) but with preserved left ventricular ejection fraction, mass and global longitudinal strain, and no change in cardiac biomarkers. There was preservation of the mitochondrial copy number in skeletal muscle biopsies but a significant increase in areas of skeletal muscle degradation (P=0.001) in patients with breast cancer following chemotherapy. Patients with breast cancer demonstrated a reduction in skeletal muscle sarcomere number from the prechemotherapy stage compared with healthy controls (P=0.013). CONCLUSIONS: Contemporary doses of epirubicin for breast cancer treatment result in a significant reduction of cardiac and skeletal muscle high-energy 31P-metabolism alongside structural skeletal muscle changes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04467411.