Using energy to go downhill-a genoprotective role for ATPase activity in DNA topoisomerase II.

Type II topoisomerases effect topological changes in DNA by cutting a single duplex, passing a second duplex through the break, and resealing the broken strand in an ATP-coupled reaction cycle. Curiously, most type II topoisomerases (topos II, IV and VI) catalyze DNA transformations that are energetically favorable, such as the removal of superhelical strain; why ATP is required for such reactions is unknown. Here, using human topoisomerase IIß (hTOP2ß) as a model, we show that the ATPase domains of the enzyme are not required for DNA strand passage, but that their loss elevates the enzyme's propensity for DNA damage. The unstructured C-terminal domains (CTDs) of hTOP2ß strongly potentiate strand passage activity in ATPase-less enzymes, as do cleavage-prone mutations that confer hypersensitivity to the chemotherapeutic agent etoposide. The presence of either the CTD or the mutations lead ATPase-less enzymes to promote even greater levels of DNA cleavage in vitro, as well as in vivo. By contrast, aberrant cleavage phenotypes of these topo II variants is significantly repressed when the ATPase domains are present. Our findings are consistent with the proposal that type II topoisomerases acquired ATPase function to maintain high levels of catalytic activity while minimizing inappropriate DNA damage.

Recurrent mutations in topoisomerase IIα cause a previously undescribed mutator phenotype in human cancers.

Topoisomerases nick and reseal DNA to relieve torsional stress associated with transcription and replication and to resolve structures such as knots and catenanes. Stabilization of the yeast Top2 cleavage intermediates is mutagenic in yeast, but whether this extends to higher eukaryotes is less clear. Chemotherapeutic topoisomerase poisons also elevate cleavage, resulting in mutagenesis. Here, we describe p.K743N mutations in human topoisomerase hTOP2α and link them to a previously undescribed mutator phenotype in cancer. Overexpression of the orthologous mutant protein in yeast generated a characteristic pattern of 2- to 4-base pair (bp) duplications resembling those in tumors with p.K743N. Using mutant strains and biochemical analysis, we determined the genetic requirements of this mutagenic process and showed that it results from trapping of the mutant yeast yTop2 cleavage complex. In addition to 2- to 4-bp duplications, hTOP2α p.K743N is also associated with deletions that are absent in yeast. We call the combined pattern of duplications and deletions ID_TOP2α. All seven tumors carrying the hTOP2α p.K743N mutation showed ID_TOP2α, while it was absent from all other tumors examined (n = 12,269). Each tumor with the ID_TOP2α signature had indels in several known cancer genes, which included frameshift mutations in tumor suppressors PTEN and TP53 and an activating insertion in BRAF. Sequence motifs found at ID_TOP2α mutations were present at 80% of indels in cancer-driver genes, suggesting that ID_TOP2α mutagenesis may contribute to tumorigenesis. The results reported here shed further light on the role of topoisomerase II in genome instability.

Association between Acute and Chronic Inflammatory States: A Case-Control Study.

BACKGROUND: Fever is the hallmark of efficient acute inflammatory response, which may be disrupted in chronic inflammatory conditions. The "continuum theory" proposes that the return of acute inflammatory states with high fever predicts improvement in chronic diseases during treatment. Our objective was to investigate the observation made, during classical homeopathic treatment, that such an association exists between chronic inflammation and efficient acute inflammation. METHODS: In a case-control study, the reports of patients diagnosed with chronic inflammatory conditions with at least 6 months of follow-up under homeopathic treatment were retrospectively sampled from homeopathic medical practices from Greece, India, Romania and Russia. Twenty patients who improved under homeopathic treatment and 20 age-matched controls of those who did not improve were selected. The occurrence of common acute infectious diseases with fever during the follow-up period was investigated. RESULTS: The average age of the cases and controls was 28.4 (SD: 16.64) and 27.9 (SD: 17.19) years respectively. 18/20 cases and 4/20 controls developed common infectious diseases with fever. Cramer's V co-efficient value was found to be 0.551 (p < 0.01), indicating that improvement was more in patients with fever than without. Odds ratio of improving with respect to development of acute infectious diseases was 36.0 (95% CI: 5.8 to 223.5). The binary logistic regression model indicated significant contribution of occurrence of acute infections with fever as a predictor for improvement in chronic inflammatory disease. CONCLUSIONS: Classical homeopathic clinical observations indicate an association between chronic inflammatory status in the body and the ability to mount efficient acute inflammation. In this case-control study, the occurrence of common infections with fever during treatment heralded improvement in chronic inflammatory disease. Further powered studies are necessary to substantiate this finding.

Prognostic value of mitral regurgitation in patients undergoing left ventricular assist device deployment: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) represent an important therapeutic option for patients progressing to end-stage heart failure. LVAD has previously been shown to have a promising role in improving mitral regurgitation (MR). Nevertheless, the prognostic value of preoperative uncorrected MR in this population remains unclear. METHODS: A systematic database search with meta-analysis was conducted of comparative original articles of patients with preoperative mild MR (Grade 0-I) versus moderate-severe MR (Grade II-III) undergoing LVAD implantation, in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to June 2022. Primary outcomes were overall and operative mortality. Secondary outcomes were neurological dysfunction, gastrointestinal bleeding, right heart failure, LVAD thrombosis, and driveline infection. RESULTS: Our search yielded 2228 relevant studies. A total of 19 studies met the inclusion criteria with a total of 11 873 patients. LVAD caused a statistically significant decrease of 35.9% in the number of patients with moderate-severe MR (grade II-III) postoperatively. No significant difference was observed in terms of overall mortality, operative mortality, GI bleeding, LVAD thrombosis, and driveline infection rates between mild and moderate-severe MR. An increased rate of right heart failure was seen among patients with moderate-severe MR, while lower rates of neurological events were also observed. CONCLUSION: LVAD improves the haemodynamics of the left ventricle, to promote resolution of MR. Nevertheless, the severity of preoperative mitral regurgitation in patients undergoing LVAD deployment does not seem to affect mortality.

Leading Transformation in Medical Education Through Extended Reality.

Extended reality (XR) has exponentially developed over the past decades to incorporate technology whereby users can visualise, explore, and interact with 3-dimensional-generated computer environments, and superimpose virtual reality (VR) onto real-world environments, thus displaying information and data on various levels of the reality-virtuality continuum. In the context of medicine, VR tools allow for anatomical assessment and diagnosis, surgical training through lifelike procedural simulations, planning of surgeries and biopsies, intraprocedural guidance, and medical education. The following chapter aims to provide an overview of the currently available evidence and perspectives on the application of XR within medical education. It will focus on undergraduate and postgraduate teaching, medical education within Low-Middle Income Countries, key practical steps in implementing a successful XR programme, and the limitations and future of extended reality within medical education.

Utilization of computed tomography in pediatric temporal fractures: A dose reduction approach.

OBJECTIVES: METHODS: Retrospective chart review was performed of pediatric patients who underwent CT brain as part of a trauma pan-scan and dedicated temporal bone CT in the setting of head trauma. The original CT images were re-reviewed by two board certified Neuroradiologists in a blinded manner to determine the presence or absence of temporal bone fracture and if present, fracture line involvement of the 5 critical temporal bone anatomic structures. The dose length product (DLP), a measure of approximate total radiation dose delivered during CT scan (mGy-cm), was noted from the data available. RESULTS: There were 24 temporal bone fractures in a total of 29 patients (4 with bilateral fractures). There were 21 of 24 fractures that were correctly identified on trauma pan-scan CT with dedicated temporal bone CT considered as the diagnostic gold standard. There was a combined sensitivity and specificity of 91 % and 100 % respectively. The sensitivity and specificity in identifying involvement of critical structures were as follows: carotid canal (100 % and 100 %); ossicular chain (75 % and 100 %); tegmen tympani (60 % and 97.9 %); facial nerve canal (25 % and 100 %); otic capsule (N/A and 98.5 %). The median DLP for trauma pan-scan CT and temporal bone CT were 627 mGy-cm and 267 mGy-cm respectively. CONCLUSION: Dedicated TBCT is not required to accurately diagnose and characterize temporal bone fractures seen on trauma pan-scan CT. The radiation exposure of concurrent or subsequent dedicated temporal bone imaging is equal to approximately one half of the original trauma pan-scan CT.

Planetary health and sustainability teaching in UK medical education: A review of medical school curricula.

BACKGROUND: The doctors of the future need to be empowered to deliver healthcare sustainably while protecting their patients' health in the context of a degrading environment. This study aimed to objectively review the extent and nature of the teaching of planetary health and sustainability topics in UK medical education. METHODS: A multi-centre national review of the timetabled teaching sessions in medical courses in the UK during the academic year 2020/2021 against the General Medical Council's adopted 'Educating for Sustainable Healthcare - Priority Learning Outcomes'. Medical students were recruited and reviewed the entirety of their own institution's online teaching materials associated with core teaching sessions using a standardised data collection tool. Learning outcome coverage and estimated teaching time were calculated and used to rank participating medical schools. RESULTS: 45% of eligible UK medical schools were included in the study. The extent of teaching varied considerably amongst courses. Mean coverage of the 13 learning outcomes was 9.9 (SD:2.5) with a mean estimated teaching time of 140 min (SD:139). Courses with dedicated planetary health and sustainability sessions ranked best. CONCLUSION: There is large disparity in the education that medical students receive on these topics. Teaching may not adequately prioritise sustainability or reflect advances in planetary health knowledge.[Box: see text].

Medical student perceptions of mental illness: a cross-sectional transnational study in two medical schools.

BACKGROUND: Despite shifting global attitudes, mental illness remains highly stigmatised amongst practicing doctors. This has wider implications on doctors' training to care for patients with mental illness. There is need for exploration of the presence and mitigation of stigma in early medical education to prevent such attitudes propagating into clinical practice. Thus, this study explores whether stigmatising attitudes are detectable amongst medical students in London and Singapore and examines whether they are ameliorated by specific curricular and welfare features of formal medical education, utilising the Mental Illness Stigma Framework (MISF). METHODS: A mixed-methods approach was adopted. Medical students at Imperial College London (UK; n = 211) and Nanyang Technological University (Singapore; n = 141) completed a validated scale (the OMS-HC-15) to assess attitudes towards mental illness. Semi-structured interviews were conducted (Imperial: n = 12, NTU: n = 8) until theoretical saturation was reached. Quantitative data were analysed descriptively and comparatively using SPSS and interview data subjected to inductive thematic analysis. RESULTS: Total OMS-HC-15 scores ranged from 19-51 for Imperial (n = 211) and 16-53 for NTU (n = 141). No significant differences in overall stigma scores were found between the two schools (p = 0.24), nor when comparing year groups within each school. Four themes were identified across interview data: student perceptions, impacts of medical school culture, university support, and curricular impacts on mental illness perceptions. Themes allowed identification of aspects of medical school that were well-received and warranted further emphasis by students, alongside areas for improvement. CONCLUSION: Mental health stigma was identified in two medical schools, with differing cultures. Mean stigma scores obtained were comparable between both UK and Singaporean medical students. Nuanced differences were identified via subgroup analysis, and the MISF identified both shared and country-specific drivers for this stigma across the qualitative data. Actionable recommendations to mitigate this were hypothesised. Curricular improvements such as earlier psychiatric teaching and sharing of personal stories may improve future stigma scores as students' progress through the course. Specific welfare-based changes to formal support systems were also deemed to be beneficial by students. The impacts of welfare and curricular redesign in relation to societal influence on students' attitudes warrants further investigation, as does medical students' self-stigma.

In Silico Identification of Potential Quadruplex Forming Sequences in LncRNAs of Cervical Cancer.

Long non-coding RNAs (lncRNAs) have emerged as auxiliary regulators of gene expression influencing tumor microenvironment, metastasis and radio-resistance in cancer. The presence of lncRNA in extracellular fluids makes them promising diagnostic markers. LncRNAs deploy higher-order structures to facilitate a complex range of functions. Among such structures, G-quadruplexes (G4s) can be detected or targeted by small molecular probes to drive theranostic applications. The in vitro identification of G4 formation in lncRNAs can be a tedious and expensive proposition. Bioinformatics-driven strategies can provide comprehensive and economic alternatives in conjunction with suitable experimental validation. We propose a pipeline to identify G4-forming sequences, protein partners and biological functions associated with dysregulated lncRNAs in cervical cancer. We identified 17 lncRNA clusters which possess transcripts that can fold into a G4 structure. We confirmed in vitro G4 formation in the four biologically active isoforms of SNHG20, MEG3, CRNDE and LINP1 by Circular Dichroism spectroscopy and Thioflavin-T-assisted fluorescence spectroscopy and reverse-transcriptase stop assay. Gene expression data demonstrated that these four lncRNAs can be potential prognostic biomarkers of cervical cancer. Two approaches were employed for identifying G4 specific protein partners for these lncRNAs and FMR2 was a potential interacting partner for all four clusters. We report a detailed investigation of G4 formation in lncRNAs that are dysregulated in cervical cancer. LncRNAs MEG3, CRNDE, LINP1 and SNHG20 are shown to influence cervical cancer progression and we report G4 specific protein partners for these lncRNAs. The protein partners and G4s predicted in lncRNAs can be exploited for theranostic objectives.

Present and future of machine learning in breast surgery: systematic review.

BACKGROUND: Machine learning is a set of models and methods that can automatically detect patterns in vast amounts of data, extract information, and use it to perform decision-making under uncertain conditions. The potential of machine learning is significant, and breast surgeons must strive to be informed with up-to-date knowledge and its applications. METHODS: A systematic database search of Embase, MEDLINE, the Cochrane database, and Google Scholar, from inception to December 2021, was conducted of original articles that explored the use of machine learning and/or artificial intelligence in breast surgery in EMBASE, MEDLINE, Cochrane database and Google Scholar. RESULTS: The search yielded 477 articles, of which 14 studies were included in this review, featuring 73 847 patients. Four main areas of machine learning application were identified: predictive modelling of surgical outcomes; breast imaging-based context; screening and triaging of patients with breast cancer; and as network utility for detection. There is evident value of machine learning in preoperative planning and in providing information for surgery both in a cancer and an aesthetic context. Machine learning outperformed traditional statistical modelling in all studies for predicting mortality, morbidity, and quality of life outcomes. Machine learning patterns and associations could support planning, anatomical visualization, and surgical navigation. CONCLUSION: Machine learning demonstrated promising applications for improving breast surgery outcomes and patient-centred care. Neveretheless, there remain important limitations and ethical concerns relating to implementing artificial intelligence into everyday surgical practices.

Formulation, Device, and Clinical Factors Influencing the Targeted Delivery of COVID-19 Vaccines to the Lungs.

The COVID-19 pandemic has proven to be an unprecedented health crisis in the human history with more than 5 million deaths worldwide caused to the SARS-CoV-2 and its variants ( https://www.who.int/emergencies/diseases/novel-coronavirus-2019 ). The currently authorized lipid nanoparticle (LNP)-encapsulated mRNA vaccines have been shown to have more than 90% vaccine efficacy at preventing COVID-19 illness (Baden et al. New England J Med 384(5):403-416, 2021; Thomas et al., 2021). In addition to vaccines, other small molecules belonging to the class of anti-viral and anti-inflammatory compounds have also been prescribed to reduce the viral proliferation and the associated cytokine storm. These anti-viral and anti-inflammatory compounds have also been shown to be effective in reducing COVID-19 exacerbations especially in reducing the host inflammatory response to SARS-CoV-2. However, all of the currently FDA-authorized vaccines for COVID-19 are meant for intramuscular injection directly into the systemic circulation. Also, most of the small molecules investigated for their anti-COVID-19 efficacy have also been explored using the intravenous route with a few of them explored for the inhalation route (Ramakrishnan et al. Lancet Respir Med 9:763-772, 2021; Horby et al. N Engl J Med 384(8):693-704, 2021). The fact that the SARS-CoV-2 enters the human body mainly via the nasal and airway route resulting in the lungs being the primary organs of infection as characterized by acute respiratory distress syndrome (ARDS)-mediated cytokine storm in the alveolar region has made the inhalation route gain significant attention for the purposes of targeting both vaccines and small molecules to the lungs (Mitchell et al., J Aerosol Med Pulm Drug Deliv 33(4):235-8, 2020). While there have been many studies reporting the safety and efficacy of targeting various therapeutics to the lungs to treat COVID-19, there is still a need to match the choice of inhalation formulation and the delivery device platform itself with the patient-related factors like breathing pattern and respiratory rate as seen in a clinical setting. In that perspective, this review aims to describe the various formulation and patient-related clinical factors that can play an important role in the judicious choice of the inhalation delivery platforms or devices for the development of inhaled COVID-19 vaccines.

Assessing G4-Binding Ligands In Vitro and in Cellulo Using Dimeric Carbocyanine Dye Displacement Assay.

G-quadruplexes (G4) are the most actively studied non-canonical secondary structures formed by contiguous repeats of guanines in DNA or RNA strands. Small molecule mediated targeting of G-quadruplexes has emerged as an attractive tool for visualization and stabilization of these structures inside the cell. Limited number of DNA and RNA G4-selective assays have been reported for primary ligand screening. A combination of fluorescence spectroscopy, AFM, CD, PAGE, and confocal microscopy have been used to assess a dimeric carbocyanine dye B6,5 for screening G4-binding ligands in vitro and in cellulo. The dye B6,5 interacts with physiologically relevant DNA and RNA G4 structures, resulting in fluorescence enhancement of the molecule as an in vitro readout for G4 selectivity. Interaction of the dye with G4 is accompanied by quadruplex stabilization that extends its use in primary screening of G4 specific ligands. The molecule is cell permeable and enables visualization of quadruplex dominated cellular regions of nucleoli using confocal microscopy. The dye is displaced by quarfloxin in live cells. The dye B6,5 shows remarkable duplex to quadruplex selectivity in vitro along with ligand-like stabilization of DNA G4 structures. Cell permeability and response to RNA G4 structures project the dye with interesting theranostic potential. Our results validate that B6,5 can serve the dual purpose of visualization of DNA and RNA G4 structures and screening of G4 specific ligands, and adds to the limited number of probes with such potential.

Role of Invasive Mechanical Ventilation and ECMO in the Management of COVID-19: A Systematic Review.

OBJECTIVES: This systematic review aims to provide insight into the outcome of extracorporeal membrane oxygenation (ECMO) and invasive mechanical ventilation use in critically ill COVID-19 patients. DATA SOURCES: Electronic databases PubMed Central and PubMed were searched from January 2020 to June 2020 for published studies about ECMO and/or invasive mechanical ventilation use in COVID-19 patients. Data Extraction and Study Selection: The search strategy retrieved 766 articles, of which 19 studies consisting of 204 patients fulfilled the inclusion criteria and were included in the analysis. DATA SYNTHESIS: Primary outcomes evaluated were discharge and/or clinical improvement and mortality rate. Secondary outcomes evaluated included reported complications and the mean number of days of hospitalization for survivors. Weighted averages of included studies were calculated, and data were pooled in forest plots. Nearly, 68.1% of the patients received invasive mechanical ventilation without ECMO support, and 31.9% were placed on ECMO. Also, 22.5% of the patients were discharged and/or clinically improved and 51.5% died. Twenty-six percent of the study population deteriorated but remained alive or experienced no improvement in clinical condition. And 75.2% of those who died belonged to the non-ECMO group and 24.8% to the ECMO group. The mortality rate in the non-ECMO group was 56.8% compared to 40% in the ECMO group. CONCLUSION: The utility of ECMO during a pandemic is uncertain as it is a resource-intensive modality, especially when the mortality rate in severely ill patients infected with COVID-19 virus is already known to be high. HOW TO CITE THIS ARTICLE: Nagraj S, Karia R, Hassanain S, Ghosh P, Shah VR, Thomas A. Role of Invasive Mechanical Ventilation and ECMO in the Management of COVID-19: A Systematic Review. Indian J Crit Care Med 2021;25(6):691-698.

A cost-effectiveness analysis of the use of oral ibrexafungerp versus fluconazole for acute vulvovaginal candidiasis in the UK NHS primary care service.

BACKGROUND: Vulvovaginal Candidiasis (VVC) is a fungal infection causing inflammation of the vagina and/or the vulva. Symptoms include itching, irritation, and discharge. VVC presents commonly across primary care and, despite its mild symptoms, carries psychological burden and has a significant impact on women's quality of life. UK guidelines support treatment via oral or topical azole antifungal agents. Recent evidence attests to the superiority of novel non-azole antifungals. Thus, rigorous financial assessment of both antifungals is necessary for optimal VVC treatment allocation in UK primary care. AIM: To evaluate the cost-effectiveness of ibrexafungerp against the gold standard fluconazole as first-line treatment of VVC within the NHS. METHOD: A systematic review on the efficacy of ibrexafungerp and fluconazole in acute VVC was conducted. Cost-effectiveness analysis was initiated using health outcome data from the DOVE trial, a Phase 2 RCT. Costs in pound sterling were ascertained in monetary units, and effectiveness determined as reduced need for follow-up medication. RESULTS: An incremental cost-effectiveness ratio of £2185.74 was determined. This suggests oral ibrexafungerp being largely more costly yet slightly more effective than fluconazole, and thus has unfavourable net benefit. Two sensitivity analyses were conducted considering follow-up medication combination and market price, which provided confidence in the calculated cost-effectiveness ratio. CONCLUSION: This analysis highlights fluconazole's cost-effectiveness in current UK guidelines and favourability.

PLAstic Surgery Teaching In the Undergraduate Curriculum of Medical Students-United Kingdom (PLASTICS-UK): A UK national collaborative survey of plastic surgery in the undergraduate medical curriculum.

OBJECTIVE: To undertake a United Kingdom national medical student survey investigating undergraduate plastic surgery exposure and specialty perceptions. BACKGROUND: Plastic surgery incorporates all anatomical regions, age groups and tissue types; clinical challenges vary from trauma and burns to congenital defects and cancer and although around 50% of the workload is trauma, it is often misperceived to revolve around cosmetic surgery. METHOD: Following ethical approval, a national survey was conducted across 27 included UK medical schools (31/03/23-07/07/23). Trends were analysed, with comparisons made between surgical and non-surgical aspirants. RESULTS: Data were included from 2513 students; 29.2% had surgical career aspirations. Students perceived plastic surgery as challenging, competitive, and impacting quality of life; however, most had no formal teaching (56.3%); merely 6.2% had clinical exposure and 30.4% had an undergraduate plastic surgery placement available. Breast reconstruction was the most frequently correctly identified surgery (91.8%), with head and neck cancer surgery the least (35.9%). Surgical aspirants were less likely to overestimate private practice (p < 0.001) but demonstrated greater self-confidence in plastic surgery understanding (p < 0.001) and their future ability to make plastic surgery referrals (p < 0.001), being more likely to pursue it (p < 0.001). Surgical aspirants were 17.3% more likely to obtain non-curricular plastic surgery experience (p < 0.001), and 5.6% more self-confident dressing basic wounds (p < 0.001). CONCLUSION: A greater need for undergraduate plastic surgery teaching was determined. Significant heterogeneity across medical schools was identified. Formation of a national undergraduate plastic surgery curriculum, led by professional bodies, may tackle disparities among medical schools, improve accessibility and facilitate knowledge acquisition.

Gender-Affirming Surgery in Low- and Middle-Income Countries: A Systematic Review.

Objectives: Fewer than one-fifth of all studies on gender-affirming care originate from low- and middle-income countries (LMICs). This is the first systematic review to examine surgical demographics and outcomes following gender-affirming surgery (GAS) in LMICs. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, five databases were systematically searched for original studies and case series on GAS within LMIC settings. Excluded reports included animal studies, non-English language studies, secondary studies including reviews, individual case reports and conference abstracts. Results: This review includes 34 studies involving n = 5064 TGNB individuals. Most studies (22, 64.7%) were from upper-middle-income countries, followed by lower-middle-income countries (12, 35.3%). A total of 31 studies (91.2%) reported on post-operative outcomes. Of n = 5013 patients who underwent GAS, 71.5% (n = 3584) underwent masculinizing and 29.5% (n = 1480) underwent feminizing procedures. The predominant procedures were metoidioplasty (n = 2270/3584, 63.3%) and vaginoplasty (n = 1103/1480, 74.5%). Mean follow-up was 47.7 months. In patients who underwent metoidioplasty, 6.8% (n = 155) of patients experienced a complication and 6.3% (n = 144) underwent revision surgery. In patients who underwent vaginoplasty, 11.5% (n = 127) of patients experienced a complication and 8.5% (n = 94) underwent revision surgery. Of the studies (25/34, 73.5%) that reported on quality of life and post-operative satisfaction, the majority showed marked improvements in psychosocial and functional outcomes. Notably, no post-surgical regret was reported among the surveyed patients. Conclusions: Existing literature on GAS in LMICs remains scarce and is concentrated in select institutions that drive specific procedures. Our review highlights the low reported volumes of GAS, variability in surgical outcomes and quality of life.

Readout-Segmented Echoplanar (RESOLVE) Diffusion-Weighted Imaging on 3T MRI in Detection of Cholesteatoma-Our Experience.

Background Several research studies have demonstrated the utility of diffusion-weighted imaging (DWI) in detecting middle ear cholesteatomas, especially with the non-echoplanar imaging (non-EPI) DWI technique. REadout Segmentation Of Long Variable Echo trains (RESOLVE), a multishot-EPI DWI, has better spatial resolution at a thinner section acquisition with reduced image distortion compared to the single-shot-EPI DWI technique. Purpose In this study, we evaluated the diagnostic ability of RESOLVE -DWI in middle ear cholesteatomas with surgical and histopathological support. Patients and Methods Fifty patients with clinical suspicion of primary cholesteatoma or postoperative recurrence were subjected to routine sequences and RESOLVE-DWI on magnetic resonance imaging (MRI). Thirty-eight patients had unilateral disease, while 12 patients had bilateral disease. The bilateral temporal bones of 50 patients were evaluated on MRI. The results attained by RESOLVE-DWI were correlated with intraoperative and histopathological findings. Results RESOLVE-DWI truly detected 55 of the 58 surgically proven cholesteatomas. RESOLVE-DWI could not detect three cholesteatoma lesions due to their small size and falsely diagnosed one case each of impacted wax and non-cholesteatomatous otitis media as cholesteatoma. With a 95% confidence interval, RESOLVE-DWI showed 94.8% sensitivity, 95.2% specificity, 96% positive predictive value, 93% negative predictive value, and 95% diagnostic accuracy in cholesteatoma detection. Conclusion RESOLVE-DWI is a sensitive and specific DWI technique for detecting middle ear cholesteatoma. However, RESOLVE-DWI has limitations in the diagnosis of small (<3 mm) cholesteatomas.

Machine learning algorithms for the prognostication of abdominal aortic aneurysm progression: a systematic review.

INTRODUCTION: Abdominal aortic aneurysm (AAA), often characterized by an abdominal aortic diameter over 3.0 cm, is managed through screening, surveillance, and surgical intervention. AAA growth can be heterogeneous and rupture carries a high mortality rate, with size and certain risk factors influencing rupture risk. Research is ongoing to accurately predict individual AAA growth rates for personalized management. Machine learning, a subset of artificial intelligence, has shown promise in various medical fields, including endoleak detection post-EVAR. However, its application for predicting AAA growth remains insufficiently explored, thus necessitating further investigation. Subsequently, this paper aims to summarize the current status of machine learning in predicting AAA growth. EVIDENCE ACQUISITION: A systematic database search of Embase, MEDLINE, Cochrane, PubMed and Google Scholar from inception till December 2022 was conducted of original articles that discussed the use of machine learning in predicting AAA growth using the aforementioned databases. EVIDENCE SYNTHESIS: Overall, 2742 articles were extracted, of which seven retrospective studies involving 410 patients were included using a predetermined criteria. Six out of seven studies applied a supervised learning approach for their machine learning (ML) models, with considerable diversity observed within specific ML models. The majority of the studies concluded that machine learning models perform better in predicting AAA growth in comparison to reference models. All studies focused on predicting AAA growth over specified durations. Maximal luminal diameter was the most frequently used indicator, with alternative predictors being AAA volume, ILT (intraluminal thrombus) and flow-medicated diameter (FMD). CONCLUSIONS: The nascent field of applying machine learning (ML) for Abdominal Aortic Aneurysm (AAA) expansion prediction exhibits potential to enhance predictive accuracy across diverse parameters. Future studies must emphasize evidencing clinical utility in a healthcare system context, thereby ensuring patient outcome improvement. This will necessitate addressing key ethical implications in establishing prospective studies related to this topic and collaboration among pivotal stakeholders within the AI field.

The Presence of Chronic Total Occlusion in Noninfarct-Related Arteries Is Associated With Higher Mortality and Worse Patient Outcomes Following Percutaneous Coronary Intervention for STEMI: A Systematic Review, Meta-Analysis and Meta-Regression.

Reperfusion therapy with percutaneous coronary intervention improves outcomes in patients with ST-elevation myocardial infarction. We conducted a meta-analysis to assess the impact of chronic total occlusion (CTO) in noninfarct-related artery on the outcomes of these patients. Comprehensive searches were performed using PubMed, Google Scholar, and EMBASE. The primary endpoint was the 30-day mortality rate, with secondary endpoints including all-cause mortality, repeat myocardial infarction, and stroke. Forest plots were created for the pooled analysis of the results, with statistical significance set at P < 0.05. A total of 19 studies were included in this meta-analysis, with 23,989 patients (3589 in CTO group and 20,400 in no-CTO group). The presence of CTO was associated with significantly higher odds of 30-day mortality [18.38% vs 5.74%; relative risk (RR), 3.69; 95% confidence intervals (CI), 2.68-5.07; P < 0.00001], all-cause mortality (31.00% vs 13.40%; RR, 2.79; 95% CI, 2.31-3.37; P < 0.00001), cardiovascular-related deaths (12.61% vs 4.1%; RR, 2.61; 95% CI, 1.99-3.44; P < 0.00001), and major adverse cardiovascular events (13.64% vs 9.88%; RR, 2.08; 95% CI, 1.52-2.86; P < 0.00001) than the non-CTO group. No significant differences in repeated myocardial infarction or stroke were observed between the CTO and non-CTO groups. Our findings underscore the need for further research on the benefits and risks of performing staged or simultaneous percutaneous coronary intervention for CTO in the noninfarct-related artery in patients with ST-elevation myocardial infarction.

Autologous breast reconstruction in low- and middle-income countries (LMICs): a systematic review of current practices and challenges.

INTRODUCTION: Efforts to improve global healthcare persist, yet LMICs face challenges accessing surgical care, especially breast reconstruction amidst rising breast cancer cases. This review evaluates the present state and challenges of autologous breast reconstruction in low- and middle-income countries (LMICs). EVIDENCE ACQUISITION: Utilizing the PRISMA guidelines and the Cochrane Collaboration's standards, databases such as EMBASE, MEDLINE, Cochrane, PubMed, and Google Scholar were examined for studies on breast reconstruction in LMICs (based on the World Bank's 2022-2023 definitions) up to August 2022. Articles and case reports focusing on autologous reconstruction following breast cancer surgery in these regions were incorporated. EVIDENCE SYNTHESIS: From an initial 288 articles, 19 met the criteria after thorough assessment. These articles documented 4899 patient cases from LMICs, with the breakdown being: 11 on LD flaps, nine on TRAM flaps, eight on DIEP flaps, two on TDAP flaps, and one on TMG flap. Flap necrosis emerged as the prevalent complication in four studies. CONCLUSIONS: While autologous breast reconstruction presents superior aesthetic benefits without notable long-term economic setbacks, its adoption in LMICs is limited. This is partly due to the domination of implant-based methods among patients and surgeons, selected due to convenience. The scarcity of concrete evidence and standardized metrics in LMICs clouds the understanding of this procedure. Despite its advantages, awareness is low, necessitating more training and awareness campaigns. Uniform reporting, quality data, and financial analysis can provide a comprehensive LMIC understanding, aiding future research.