Efficacy of Inclisiran in Patients Having Familial Hypercholesterolemia: Heterozygous Compared to Homozygous Trait, a Systematic Review and Meta-analysis.

OBJECTIVE: To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. METHODS: We conducted the systematic review and meta-analysis of ORION clinical trials. PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atheroscalerotic parameters considered for our objective were low-density lipoprotein cholesterol, total cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B, and nonhigh-density lipoprotein cholesterol. Primary outcomes were the percentage difference in atheroscalerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by the Cochrane risk of bias tool. Meta-analysis was performed when at least 2 studies reported on the same variable. RESULTS: Four ORION clinical trials provided the data related to the mean difference in the atheroscalerotic parameters at follow-up relative to baseline, of HeFH and HoFH patient populations, after administration of 300 mg inclisiran subcutaneously. We pooled together these mean differences for each group and applied a statistical test to analyze if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in low-density lipoprotein cholesterol (HeFH: -48.62%; HoFH: -9.12%; P < 0.05), total cholesterol (HeFH: -30.31%; HoFH: -11.50%; P < 0.05), apolipoprotein (HeFH: -39.97%; HoFH: -14.68%; P < 0.05), and nonhigh-density lipoprotein (HeFH: -44.51%; HoFH: -12.22%; P < 0.05) between HeFH and HoFH groups. However, the difference in pooled mean difference in PCSK9 values (HeFH: -68.41%; HoFH: -56.25%; P = 0.2) between HeFH and HoFH groups was statistically insignificant. Studies were of high quality. CONCLUSIONS: There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.

Unmasking the long-term effects: unravelling neuropsychiatric and neurological consequences of COVID-19.

The COVID-19 pandemic has not only burdened healthcare systems but has also led to a new emerging medical enigma that is post-COVID-19 syndrome or "long COVID." Characterized by persistent symptoms that extend beyond the acute phase of the illness, long COVID has rapidly become a public health concern with ambiguous neurological and neuropsychiatric dimensions. This narrative review aims at synthesizing available research to decode the long-term impacts of COVID-19 on neurological and mental health. Drawing from a multitude of studies, this review synthesizes evidence on various neuropsychiatric and neurological symptoms, including cognitive deficits, mood disorders, and more. The narrative delves into potential pathogenic mechanisms, hoping to fill existing research gaps and offering directions for future inquiry. The objective is not just academic; it has immediate real-world implications. Understanding these long-term effects is crucial for developing effective treatments and interventions, thereby better serving the millions of individuals living with these lingering symptoms. As healthcare systems continue to grapple with the fallout from the pandemic, this review provides much-needed context and insights into an area that demands urgent research and action.

Can Artificial Intelligence Beat Humans in Detecting Breast Malignancy on Mammograms?

BACKGROUND: The study was aimed at identifying how useful Computer-Aided Detection (CAD) could be in reducing false-negative reporting in mammography and early detection of breast cancer at an early stage as the best protection is early detection. MATERIALS AND METHODS: This retrospective study was conducted in a tertiary care setup of Atomic Energy Cancer Hospital, Nuclear Medicine, Oncology and Radiotherapy Institute (AECH-NORI), where 33 patients with suspicious findings on mammography and subsequent biopsy-proven malignancy were included. The findings of mammography including the lesion type, breast parenchymal density, and sensitivity of CAD detection, as well as the final biopsy results, were recorded. A second group of 40 normal screening mammograms was also included who had no symptoms, had Breast Imaging-Reporting and Data System category I(BI-RADS I) mammograms, and had no pathology identified on correlative sonomammography as well. RESULTS: A total of 35 masses, 11 pleomorphic clusters of microcalcification, five clustered foci of macrocalcification, and nine lesions with pleomorphic clusters of microcalcification and two with pleomorphic clusters of microcalcification only were included. The CAD system was able to identify 26 masses (74%), eight lesions with pleomorphic clusters of microcalcification (72%), five foci of macrocalcification (100%), six lesions with pleomorphic clusters of microcalcification (66%), and two pleomorphic clusters of microcalcification without formed mass (100%). The overall sensitivity of the CAD system was 75.8%. CAD was able to identify 13 out of 16 masses with invasive ductal carcinoma (81.3%), eight out of nine lesions proven as invasive ductal carcinoma with ductal carcinoma in situ (DCIS) (88.9%), two out of five masses with invasive lobular carcinoma (40%), four out of four masses with invasive mammary carcinoma (100%), and zero out of one lesion identified as medullary carcinoma (0%). There was 100% detection for pleomorphic clusters of microcalcification without formed mass with CAD marking two out of two mammograms. CONCLUSION: CAD performed better with combined lesions, accurately marked pleomorphic clusters of microcalcification, and identified small lesions in predominant fibrofatty parenchymal density but was not reliable in dense breast, areas of asymmetric increased density, summation artifacts, edematous breast parenchyma, and retroareolar lesions. It also performed poorly with ill-defined lesions of invasive lobular carcinoma. Human intelligence hence beats CAD for the diagnosis of breast malignancy in mammograms as per our experience.

Unveiling the Mysteries of Long COVID Syndrome: Exploring the Distinct Tissue and Organ Pathologies Linked to Prolonged COVID-19 Symptoms.

The ongoing battle against the coronavirus disease 2019 (COVID-19) pandemic has encountered a complex aspect with the emergence of long COVID syndrome. There has been a growing prevalence of COVID-19-affected individuals experiencing persistent and diverse symptoms that extend beyond the initial infection phase. The phenomenon known as long COVID syndrome raises significant questions about the underlying mechanisms driving these enduring symptoms. This comprehensive analysis explores the complex domain of long COVID syndrome with a view to shed light on the specific tissue and organ pathologies contributing to its intricate nature. This review aims to analyze the various clinical manifestations of this condition across different bodily systems and explore potential mechanisms such as viral persistence, immune dysregulation, autoimmunity, and molecular mimicry. The goal is to gain a better understanding of the intricate network of pathologies contributing to long COVID syndrome. Understanding these distinct pathological indicators provides valuable insights into comprehending the complexities of long COVID and presents opportunities for developing more accurate diagnostic and therapeutic strategies, thereby improving the quality of patient care by effectively addressing the ever-changing medical challenge in a more focused manner.

Public Perception of Ideal Areola Proportions.

BACKGROUND: In breast reconstruction, mastopexy, and breast reduction procedures, surgeons make decisions about the resulting areola size, and this significantly impacts the overall aesthetic result. Despite the importance of these decisions, little is known about the general population's preferences for areola size. The objective of this study was to survey the global population to better understand the public's perceptions of ideal areola dimensions. METHODS: A survey was developed with 9 different composite diagrams of a female torso (every combination of 3 breast widths and 3 waist widths). In each composite diagram, 6 different areola sizes were shown (areola-to-breast diameter ranging from 1:12 to 6:12). The survey was distributed via the Amazon Mechanical Turk digital platform, and respondents' demographics (sex, age, race/ethnicity, country, and state if located in the United States) and preferences for the most aesthetically pleasing size in each composite diagram were recorded. RESULTS: Among 2259 participants, with 1283 male (56.8%) and 976 female (43.2%), most participants were between 25 and 34 years old (1012, 44.8%), were from the United States (1669, 73.9%), and identified as White (1430, 63.3%). With 9 breast width and waist width combinations, the respondents were most likely to prefer the 2:12 (32.9%) areola-to-breast ratio ( P < 0.0001). The second most commonly preferred ratio was 3:12 (30.6%) ( P < 0.0001). Gender subgroup analysis showed that women preferred middle-range ratios, such as 2:12, 3:12, and 4:12 ( P < 0.0001). Meanwhile, men were more likely to prefer extreme ratios of 1:12 or 6:12 ( P < 0.0001). Across almost all races/ethnicities, 2:12 was significantly the most popular, except among American Indian/Alaskan Native and Middle Eastern where 3:12 was the most preferred ( P < 0.0001). Within the top 6 countries (United States, India, Brazil, Italy, Canada, United Kingdom), the United States, India, and Italy preferred 2:12, and Brazil, Canada, and the United Kingdom preferred 3:12 ( P < 0.0001). CONCLUSIONS: This study provides the first objective data on public impressions of the ideal areola proportions and can serve as a guide for surgical decision making in breast reconstruction and reshaping procedures.

Previous Emergency Department Admission Is Associated With Increased 90-Day Readmission Following Cervical Spine Surgery: Evidenced Using Propensity Score Matching.

STUDY DESIGN: This was a retrospective case-control study. OBJECTIVE: The objective of this study was to evaluate whether prior emergency department admission was associated with an increased risk for 90-day readmission following elective cervical spinal fusion. SUMMARY OF BACKGROUND DATA: The incidence of cervical spine fusion reoperations has increased, necessitating the improvement of patient outcomes following surgery. Currently, there are no studies assessing the impact of emergency department visits before surgery on the risk of 90-day readmission following elective cervical spine surgery. This study aimed to fill this gap and identify a novel risk factor for readmission following elective cervical fusion. METHODS: The 2016-2018 Nationwide Readmissions Database was queried for patients aged 18 years and older who underwent an elective cervical fusion. Prior emergency admissions were defined using the variable HCUP_ED in the Nationwide Readmissions Database database. Univariate analysis of patient demographic details, comorbidities, discharge disposition, and perioperative complication was evaluated using a χ 2 test followed by multivariate logistic regression. RESULTS: In all, 2766 patients fit the inclusion criteria, and 18.62% of patients were readmitted within 90 days. Intraoperative complications, gastrointestinal complications, valvular, uncomplicated hypertension, peripheral vascular disorders, chronic obstructive pulmonary disease, cancer, and experiencing less than 3 Charlson comorbidities were identified as independent predictors of 90-day readmission. Patients with greater than 3 Charlson comorbidities (OR=0.04, 95% CI 0.01-0.12, P <0.001) and neurological complications (OR=0.29, 95% CI 0.10-0.86, P =0.026) had decreased odds for 90-day readmission. Importantly, previous emergency department visits within the calendar year before surgery were a new independent predictor of 90-day readmission (OR=9.74, 95% CI 6.86-13.83, P <0.001). CONCLUSIONS: A positive association exists between emergency department admission history and 90-day readmission following elective cervical fusion. Screening cervical fusion patients for this history and optimizing outcomes in those patients may reduce 90-day readmission rates.

An Assessment of Risk Factors of Delayed Speech and Language in Children: A Cross-Sectional Study.

Introduction Communication is the exchange of information through speaking, writing, and other mediums. Speech is the expression of thoughts in spoken words. Language is the principal method that humans use for relaying information; consisting of words conveyed by speech, writing, or gestures. Language is the conceptual processing of communication. Problems in communication or oral motor function are called speech and language disorders. Developmental delay is diagnosed when a child does not attain normal developmental milestones at the expected age. Speech and/or language disorders are amongst the most common developmental difficulties in childhood. Such difficulties are termed 'primary' if they have no known etiology, and 'secondary' if they are caused by another condition such as hearing and neurological impairment, and developmental, behavioral, or emotional difficulties. Objectives The objective of our study was to observe the risk factors for speech and language delay in the children presenting to the speech therapy clinic of a tertiary care hospital in a large urban center. Methodology A cross-sectional study was conducted on 150 children presenting at the speech therapy clinic of Lahore General Hospital from July to August 2021. A well-designed questionnaire was used to collect data about the sociodemographic profile, and biological, developmental, and environmental risk factors of speech and language delay in children. SPSS, version 25 (IBM Corp., Armonk, NY) was used to enter and analyze the data. Results Parents or caretakers of a total of 98 male and 52 female children took part in this study aged 2-11 years. The average age of speech and language delay among the children was 5.65 years, 66.7% of which went to normal school while 31.3% went to special school; 66.7% were from urban areas. Around 60% had middle ear infections, and 34.7% were found to have oropharyngeal anomalies. A history of intrapartum complications was found in 68.4% of children; 46.7% of children had a history of use of a pacifier and 38% had a history of thumb sucking. Nearly 39% of children belonged to a multilingual family environment and 66.7% had a family history of screen viewing for more than two hours. Conclusion The major risk factors contributing to speech and language delay in children are family history of speech and language delay, prolonged sucking habits, male gender, oropharyngeal anomalies, hearing problems, and middle ear infections. Measures should be taken to educate people regarding risk factors, courses, and management of speech and language delay in children.

Retroperitoneal Spindle Cell Rhabdomyosarcoma With Compression Features in a 48-Year-Old Male: A Case Report.

Spindle cell rhabdomyosarcoma (SC-RMS) is an unprecedented version of embryonal rhabdomyosarcomas (RMSs) that emerges from the mesenchyme with the capacity to differentiate into skeletal muscle cells. Retroperitoneal RMS is extremely rare in the adult population. We present the case of a primary spindle cell retroperitoneal RMS with compression features. Investigation-based diagnosis of RMS is difficult due to the lack of specificity of clinical findings. Radiology does not help in making an accurate diagnosis. Surgical removal of the tumor followed by chemotherapy and radiotherapy is the best possible treatment for RMS in adults. SC-RMS has a poor long-term prognosis. To our knowledge, such cases of retroperitoneal SC-RMS compressing the abdominal viscera and resulting in hydroureteronephrosis have never been reported before.

Medicine as constraint: Assessing the barriers to gender-affirming care.

In this commentary, we describe the way in which science has been used to constrain transgender peoples' access to gender-affirming care. The required diagnosis of gender dysphoria is rooted in both the historical assumption that psychological distress is an inherent aspect of being transgender and the incorrect notion that gender-affirming care is a panacea for the mental health issues that transgender people may experience, regardless of whether these mental health issues are related to their being transgender. We provide recommendations for how to address these barriers to care moving forward.

Gender-Affirming Surgery: Perioperative Medical Care.

OBJECTIVE: Gender-affirming surgeries are becoming increasingly common in the United States. For many transgender and gender-diverse patients, gender-affirming surgery is a critical aspect of their overall health and wellness and has a significant impact on their social functioning. Although often the role of the primary care provider, endocrinology specialists may also need to counsel their patients and collaborate with surgical teams. METHODS: This narrative review provides an overview of the preoperative assessment and perioperative management for the most common gender-affirming surgeries. RESULTS: Preoperative assessment prior to gender-affirming surgeries can resemble assessment for other surgeries. CONCLUSION: In the absence of data specific to gender-affirming surgeries, risk stratification and amelioration must use surrogate data from other populations.

An integrated literature review on sustainable food supply chains: Exploring research themes and future directions.

The sustainable food supply chain (SFSC) is a research area of global significance. The increasing number of research articles in SFSC justifies this. With 80% of publications in SFSC coming up in the last 7 years, this field is expanding and diversifying at a rapid rate. The research on sustainable food supply chain (SFSC) covers a wide variety of areas and has a wide range of research themes in FSC. To facilitate the theoretical understanding of SFSC, we have conducted a review of the literature on SFSC. With the aim to define prominent research themes in SFSC, we follow an integrated review approach of structured literature review (SLR), bibliometric analysis, and thematic analysis. Bibliometric analysis was conducted using the vosviewer software version 1.6.16. The thematic analysis identified- "Waste management", "SC sustainability and impact assessment", "Decision support", "Operations management and optimization", "Food quality and safety", "Sustainable business models", "Innovation and technological solution", "SC strategy", and "Social sustainability" as the key emergent themes. We discuss the conceptual and theoretical basis of each of these themes. "SC sustainability and impact assessment" is identified as the most dominant theme in SFSC. Innovation and technological solution is an emerging theme with many new publications related to disruptive technologies coming up. Research in collaboration and decision theory-based approaches is important to enable sustainability in FSC. Quantifying waste streams, identifying hotspots are important future directions of research in SFSCM. Circular economy, AFSC, and the use of advanced technologies to enable circularity and sustainability also have great scope. The review aims to help researchers and academicians understand the boundaries and domain of SFSC and the future scope of these themes about how they can enhance the sustainability in SFSC.

Thoracoscopic (hybrid) complex chest wall resection in pediatric Ewing sarcoma.

Askin tumor (a Ewing sarcoma variant) is the most common tumor of the chest wall in the pediatric age group. Multimodal treatment is required, with complete resection being the cornerstone of effective management. We describe the case of a 13-year boy with a left paraspinal Ewing sarcoma with intraspinal extension and spinal cord compression with neurological weakness. He underwent complex surgical resection using thoracoscopic resection of multiple ribs along with vertebral resection and reconstruction, after neoadjuvant therapy.

Development of in-bore magnetostrictive transducer for ultrasonic guided wave based-inspection of steam generator tubes of PFBR.

An in-bore magnetostrictive transducer is designed for the steam generator tubes of Prototype fast breeder reactor for the generation of L(0,2) modes of frequencies in the range of 250-350 kHz. Towards this, axi-symmetric finite element models are developed to optimize the coil parameters. The optimized length of the transmitter and the receiver coils turns out to be 10 mm (~half the wavelength) for the frequency of 300 kHz. The optimized width of the coils turns out to be 0.46 mm. FE models also show the generation, propagation and reception of L(0,2) modes in the frequency range of 250-350 kHz. The role of skin effect in the magnetostrictive based-generation of L(0,2) modes with frequency is also discussed. A transducer is designed based on the FE results. The transducer is tested for the generation of L(0,2) mode in the frequency range of 250-350 kHz in a 1 m long steam generator tube segment. A good agreement is observed between FE and experimental normalized amplitudes and the times of flight for different frequencies. L(0,2) modes are found to generate and propagate and received, as predicted by the finite element simulations. An excellent agreement is observed between the experimentally measured group velocities with those obtained from the dispersion curves in this frequency range. Experiments show the signal to noise ratio to be better than 15 dB. To ascertain the utility of the transducer in steam generator tubes for the long range testing, L(0,2) mode at 300 kHz frequency is propagated in a 1.5 m long tube. The resulted multiple end reflections amount to the propagation of 51 m distance. To check the capability of detection of defects, a short tube with a full circumferential defect of depth 0.46 mm (20%WT) and a short tube with a pin hole of 1.5 mm diameter are considered. Further, FE results for the case of the axi-symmetric circumferential defect are validated experimentally. For the case of the pinhole (non-axi-symmetric), the experimental signal to noise ratio turns out to be 6 dB, which is only 6 dB lower as compared to that obtained using a piezo based ultrasonic transducer of frequency 300 kHz coupled to the end of the tube.

From dangerous branches to urban banyan: Facilitating aerial root growth of Ficus rubiginosa.

Large urban trees have many benefits. However, falling branches pose a serious hazard to both people and infrastructure. In several tree species, aerial roots grow down from branches to the ground. These roots are capable of thickening to support the branches, lessening the risk of tree failure. Unfortunately, in urban environments most aerial roots die before reaching the ground. Here, we report a new method for encouraging aerial roots to reach the ground, developed by the second-year botany class at UNSW Sydney. Our class tested three experimental treatments on aerial roots of Ficus rubiginosa Desf. ex Vent. (Port Jackson Fig)-PVC pipes filled with sphagnum moss, PVC pipes filled with potting mix, and PVC pipes filled with sphagnum moss and topped with funnels to catch extra rainwater. All three treatments significantly improved aerial root growth, with 26 of the 30 (87%) treatment roots reaching the ground after one year compared to 0 of the 10 control roots. Our method was successful for roots up to 3 m above the ground, suggesting the potential growth rate of aerial roots is substantial when conditions are favourable. Our novel approach is an attractive and cost-effective alternative to slings and other artificial supports. This project is an example of using undergraduate practical classes to teach science while simultaneously addressing important real-world problems.

Development of ultrasonic guided wave inspection methodology for steam generator tubes of prototype fast breeder reactor.

An ultrasonic guided wave based methodology is developed for inspection of steam generator tubes of the prototype fast breeder reactor. To this aim, axisymmetric longitudinal mode (L(0,2)) at the frequency of 250 kHz is optimized using 3D-finite element simulation and experiments. The group velocity of mode L(0,2) at 250 kHz is found to be 5387 m/s. First, the long range propagation of the L(0,2) mode at 250 kHz is examined and the mode is found to propagate over a distance of 45.6 m with a sufficiently good SNR. Secondly, the detection of multiple defects such as circumferential, axial, partial-pinholes and tapered defects lying in the same line of sight is investigated using 3D-finite element simulation and the results obtained are validated experimentally for the first three cases. The sensitivities achieved are 0.23 mm depth (10%WT) for circumferential, axial and tapered defects and for partial-pinholes: 1 mm diameter and 1.38 mm depth (60%WT). Thirdly, 3D-FE simulations with ID and OD pinhole defects are performed which show that the ID and OD defects are detected by L(0,2) with a fairly similar sensitivity. Finally, study on the thermal expansion bend (with three successive bends) shows that the bend does not have much influence on the mode and the multiple circumferential defects considered in the bend are detected with good sensitivity.

Signal noise based transfer function approach for reliability estimation of ultrasonic inspection.

In recent years several methods for reducing the burden of experimentation for obtaining Probability of Detection (PoD) curves have been proposed, especially involving the use of numerical simulation. In particular, there is much interest in being able to estimate the PoD capabilities of a given NDE method, target embodiment and material, provided this is known for some canonical material for the same combination of method/embodiment. Ultrasonic experiments on materials with low signal to noise ratio (SNR) are often difficult and time consuming since the higher signal noise causes serious complications. Set in this context, this paper proposes an approach for transferring PoD curves among materials with different SNR values. The classical transfer function PoD approach is based on the hypothesis that the ratio of signals in related quadrants is equal, which requires large datasets for multiple quadrants. The approach proposed here directly deals with SNR instead of the ratio of signals, and thus requires only the experimental data of the parent application. The new approach is illustrated through example cases involving the prediction of PoD curves for ultrasonic inspection of an aluminium plate using the empirical PoD data for the same in austenitic stainless steel and mild steel. The approach is also demonstrated in each of the possible combinations among these three materials.

Bayesian synthesis for simulation-based generation of probability of detection (PoD) curves.

This paper examines the feasibility of using Bayesian synthesis to reduce the number of experimental cases and trials required for generation of probability of detection (PoD) curves. A Bayesian framework is developed for the data-level combination of experimental and simulated datasets, in the context of the inspection of back-wall breaking notches in metallic samples by bulk ultrasonic shear waves. PoD curves generated using the proposed approach, where results from a reduced number of experimental defect cases and trials are used in combination with simulated datasets, are shown to compare well with those from the conventional approach using a large number of experiments. Finally, the framework is also shown to be versatile for generating PoD curves for complex defects (illustrated through the example of an inclined notch) using simulations for canonical defects (vertical notches).