Investigating and Practicing Orthopedics at the Intersection of Sex and Gender: Understanding the Physiological Basis, Pathology, and Treatment Response of Orthopedic Conditions by Adopting a Gender Lens: A Narrative Overview.

In the biomedical field, the differentiation between sex and gender is crucial for enhancing the understanding of human health and personalizing medical treatments, particularly within the domain of orthopedics. This distinction, often overlooked or misunderstood, is vital for dissecting and treating musculoskeletal conditions effectively. This review delves into the sex- and gender-specific physiology of bones, cartilage, ligaments, and tendons, highlighting how hormonal differences impact the musculoskeletal system's structure and function, and exploring the physiopathology of orthopedic conditions from an epidemiological, molecular, and clinical perspective, shedding light on the discrepancies in disease manifestation across sexes. Examples such as the higher rates of deformities (adolescent idiopathic and adult degenerative scoliosis and hallux valgus) in females and osteoporosis in postmenopausal women illustrate the critical role of sex and gender in orthopedic health. Additionally, the review addresses the morbidity-mortality paradox, where women, despite appearing less healthy on frailty indexes, show lower mortality rates, highlighting the complex interplay between biological and social determinants of health. Injuries and chronic orthopedic conditions such osteoarthritis exhibit gender- and sex-specific prevalence and progression patterns, necessitating a nuanced approach to treatment that considers these differences to optimize outcomes. Moreover, the review underscores the importance of recognizing the unique needs of sexual minority and gender-diverse individuals in orthopedic care, emphasizing the impact of gender-affirming hormone therapy on aspects like bone health and perioperative risks. To foster advancements in sex- and gender-specific orthopedics, we advocate for the strategic disaggregation of data by sex and gender and the inclusion of "Sexual Orientation and Gender Identity" (SOGI) data in research and clinical practice. Such measures can enrich clinical insights, ensure tailored patient care, and promote inclusivity within orthopedic treatments, ultimately enhancing the precision and effectiveness of care for diverse patient populations. Integrating sex and gender considerations into orthopedic research and practice is paramount for addressing the complex and varied needs of patients. By embracing this comprehensive approach, orthopedic medicine can move towards more personalized, effective, and inclusive treatment strategies, thereby improving patient outcomes and advancing the field.

Diagnostic Yield of head Computed Tomography in Patients with Syncope: Sex Differences.

BACKGROUND: Syncope is responsible for approximately 1-3% of all emergency department (ED) visits and up to 6% of all hospital admissions in the United States. Although often of no long-term consequence, syncope can be the first presentation of a range of serious conditions such as strokes, tumors, or subarachnoid hemorrhages. Head computed tomography (CT) scanning is therefore commonly ordered in the ED for patients presenting with syncope to rule out any of these conditions, which may present without other associated physical or neurological findings on initial examination. However, the diagnostic yield of head CTs in patients presenting with syncope is unclear. OBJECTIVES: To determine the diagnostic yield of head CT in the ED in patients with syncope. METHODS: We conducted an observational analytical retrospective cross-sectional study on 360 patients diagnosed with syncope who underwent a head CT to determine the diagnostic yield of syncope to determine whether head CT is necessary for every patient presenting with syncope to the ED. RESULTS: The total of new CT findings was 11.4%. Percentages varied between men (12.8%) and women (9.7%), P = 0.353. There were no significant differences between sexes regarding the findings in head CT, yet the incidence increased, especially among elderly males. CONCLUSIONS: Age had a more significant impact on diagnostic yield of syncope than head CT. The use of a head CT scan as a routine diagnosis tool in patients with syncope is unjustifiable unless there is an indication based on medical history or physical examination.

Volume Measurement of the Cavum Septi Pellucidi: Normative Values Between 20 and 40 Weeks of Gestation.

BACKGROUND: The cavum septi pellucidi (CSP) is a brain-enclosed cavity located on the midline between the two leaflets of the septum pellucidum that separates the lateral ventricles. This structure develops in the fetus from week 18 and can be seen up to week 37 in almost all cases and then begins to disappear. OBJECTIVES: To measure and determine the normative values of the CSP volume in fetuses between 20 to 40 weeks of gestation. METHODS: The study comprised 161 consecutive pregnant women between 20 to 40 weeks of gestation with single viable fetuses. All patients had normal, disease-free pregnancies. Transvaginal or transabdominal ultrasound was used according to the fetal presentation. The fetal head was assessed in mid-sagittal sections. Once the CSP was visualized, its volume was measured using three-dimensional ultrasound with Virtual Organ Computer-aided Analysis software. The width of the CSP was also measured at the biparietal diameter (BPD) plane. RESULTS: Of the 161 fetuses, the CSP volume was measured in 158. In three patients the CSP was not identified. The CSP volume correlated poorly with gestational age (r=0.229) and with the BPD (r=0.295). The mean CSP volume was 0.508 ± 0.372 ml (range: 0.03-1.78 ml). The simple measurement of the CSP width correlated better with gestational age (r=0.535) and the BPD (r=0.484). CONCLUSIONS: The CSP volume had a poor correlation with gestational age; however, the volume did not exceed 2 ml regardless of gestational age. This information can be used to assess pathologies involving the CSP.

Epidemiological and Clinical Characteristics of Mpox in Cisgender and Transgender Women and Non-Binary Individuals Assigned to the Female Sex at Birth: A Comprehensive, Critical Global Perspective.

The 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes the scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Argentina, Brazil, Colombia, Nigeria, Europe, Vietnam, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam, linked to a new Mpox sub-lineage in women, emphasized the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of this disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

The role of the neutrophil-lymphocyte ratio in predicting poor outcomes in COVID-19 patients.

BACKGROUND: This study examines how the neutrophil-lymphocyte ratio (NLR) predicts coronavirus disease 2019 (COVID-19) hospitalization, severity, length, and mortality in adult patients. METHODS: A study was done using a retrospective, single-center, observational design. A total of 400 patients who were admitted to the Ziv Medical Center (Safed, Israel) from April 2020 to December 2021 with a confirmed diagnosis of COVID-19 through RT-PCR testing were included in the analysis. Two complete blood count laboratory tests were conducted for each patient. The first test was administered upon admission to the hospital, while the second test was conducted prior to the patient's discharge from the hospital or a few days before their death. RESULTS: Four hundred patients were included in the study, 206 males (51.5%) and 194 females (48.5%). The mean age was 64.5 ± 17.1 years. In the group of cases, there were 102 deaths, and 296 survivors were recorded, with a fatality rate of 25.5%. The median NLR was 6.9 ± 5.8 at the beginning of hospitalization and 15.1 ± 32.9 at the end of hospitalization (p < 0.001). The median length of hospital stay was 9.4 ± 8.8 days. NLR in the fatality group was 34.0 ± 49.9 compared to 8.4 ± 20.4 in the survivor group (p < 0.001). Comparison between the NLR at the time of admission of the patient and before discharge/death was 6.9 ± 5.8 vs. 15.1 ± 32.9 (p < 0.001). CONCLUSIONS: The analyses conducted revealed a statistically significant correlation between the NLR and the severity, mortality rates, and the duration of hospitalization. The consideration of NLR should commence during the initial phases of the disease when assessing individuals afflicted with COVID-19.

The Impact of Generative Conversational Artificial Intelligence on the Lesbian, Gay, Bisexual, Transgender, and Queer Community: Scoping Review.

BACKGROUND: Despite recent significant strides toward acceptance, inclusion, and equality, members of the lesbian, gay, bisexual, transgender, and queer (LGBTQ) community still face alarming mental health disparities, being almost 3 times more likely to experience depression, anxiety, and suicidal thoughts than their heterosexual counterparts. These unique psychological challenges are due to discrimination, stigmatization, and identity-related struggles and can potentially benefit from generative conversational artificial intelligence (AI). As the latest advancement in AI, conversational agents and chatbots can imitate human conversation and support mental health, fostering diversity and inclusivity, combating stigma, and countering discrimination. In contrast, if not properly designed, they can perpetuate exclusion and inequities. OBJECTIVE: This study aims to examine the impact of generative conversational AI on the LGBTQ community. METHODS: This study was designed as a scoping review. Four electronic scholarly databases (Scopus, Embase, Web of Science, and MEDLINE via PubMed) and gray literature (Google Scholar) were consulted from inception without any language restrictions. Original studies focusing on the LGBTQ community or counselors working with this community exposed to chatbots and AI-enhanced internet-based platforms and exploring the feasibility, acceptance, or effectiveness of AI-enhanced tools were deemed eligible. The findings were reported in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). RESULTS: Seven applications (HIVST-Chatbot, TelePrEP Navigator, Amanda Selfie, Crisis Contact Simulator, REALbot, Tough Talks, and Queer AI) were included and reviewed. The chatbots and internet-based assistants identified served various purposes: (1) to identify LGBTQ individuals at risk of suicide or contracting HIV or other sexually transmitted infections, (2) to provide resources to LGBTQ youth from underserved areas, (3) facilitate HIV status disclosure to sex partners, and (4) develop training role-play personas encompassing the diverse experiences and intersecting identities of LGBTQ youth to educate counselors. The use of generative conversational AI for the LGBTQ community is still in its early stages. Initial studies have found that deploying chatbots is feasible and well received, with high ratings for usability and user satisfaction. However, there is room for improvement in terms of the content provided and making conversations more engaging and interactive. Many of these studies used small sample sizes and short-term interventions measuring limited outcomes. CONCLUSIONS: Generative conversational AI holds promise, but further development and formal evaluation are needed, including studies with larger samples, longer interventions, and randomized trials to compare different content, delivery methods, and dissemination platforms. In addition, a focus on engagement with behavioral objectives is essential to advance this field. The findings have broad practical implications, highlighting that AI's impact spans various aspects of people's lives. Assessing AI's impact on diverse communities and adopting diversity-aware and intersectional approaches can help shape AI's positive impact on society as a whole.

Probing the genomic landscape of human sexuality: a critical systematic review of the literature.

Whether human sexuality is the result of nature or nurture (or their complex interplay) represents a hot, often ideologically driven, and highly polarized debate with political and social ramifications, and with varying, conflicting findings reported in the literature. A number of heritability and behavioral genetics studies, including pedigree-based investigations, have hypothesized inheritance patterns of human sexual behaviors. On the other hand, in most twin, adoption, and nuclear family studies, it was not possible to disentangle between underlying genetic and shared environmental sources. Furthermore, these studies were not able to estimate the precise extent of genetic loading and to shed light both on the number and nature of the putative inherited factors, which remained largely unknown. Molecular genetic studies offer an unprecedented opportunity to overcome these drawbacks, by dissecting the molecular basis of human sexuality and allowing a better understanding of its biological roots if any. However, there exists no systematic review of the molecular genetics of human sexuality. Therefore, we undertook this critical systematic review and appraisal of the literature, with the ambitious aims of filling in these gaps of knowledge, especially from the methodological standpoint, and providing guidance to future studies. Sixteen studies were finally retained and overviewed in the present systematic review study. Seven studies were linkage studies, four studies utilized the candidate gene approach, and five studies were GWAS investigations. Limitations of these studies and implications for further research are discussed.

Knowledge of Human Papillomavirus (HPV), Attitudes, and Practices Towards Anti-HPV Vaccination Among Israeli Nurses.

Human papillomavirus (HPV) is a small, non-enveloped, double-stranded DNA virus, belonging to the family of Papillomaviridae. It is a highly common infectious agent, which causes one of the most widespread sexually transmitted infections (STIs), involving approximately 20% of sexually active female adolescents and up to 80% of female adults aged 50 years. There exist two major preventative strategies: namely, anti-HPV vaccination and cervical screening. Healthcare providers, including nurses, can play a crucial role in HPV immunization campaigns, counteracting vaccine hesitancy and doing advocacy and counseling. To explore the overall knowledge of HPV and HPV-related issues, as well as the attitudes and practices of Israeli nurses, a modified and adapted, previously validated knowledge, attitudes, and practices (KAP) questionnaire was administered to a sample of 565 participants, 481 female (85.1%) and 84 male (14.9%). Most of them were married (n = 428, 75.8%), with more than 5 years of experience (n = 405, 71.7%), working in the general/internal medicine ward (n = 432, 76.5%), and Jewish (n = 352, 62.3%). Only 87 nurses (15.4%) got vaccinated against HPV. Forty-four (9.1%) of the female nurses never underwent a Pap smear. Higher percentages of right replies were reported only for the item related to available preventative strategies for cervical cancer (82.1% versus 17.9%). Higher percentages of wrong replies were reported for items related to body regions that can be infected by HPV (60.5% versus 39.5%), percentage of girls aged 15-18 years being sexually active (68.0% versus 32.0%). Similar percentages of right and wrong replies were reported for items related to whom the Pap test is recommended (52.7% versus 47.3%), Israeli Ministry of Health's guidelines for anti-HPV vaccination (50.4% versus 49.6%), and percentage of boys aged 15-18 years being sexually active (44.4% versus 55.6%). Concerning the reliability of the third section of the questionnaire, Cronbach's alpha was deemed to be acceptable (α = 0.64). Statistically significant determinants of reporting lower scores in HPV-related attitudes and practices were religion (OR 1.44 [95%CI 1.02-2.04]), and male offspring (OR 1.22 [1.03-1.44]). This study has important implications for policy- and decision-makers in that they should be aware of the overall poor and unsatisfactory level of HPV-related knowledge among Israeli nurses and implement multipronged HPV vaccine promotion programs, taking into account the challenges of a multicultural and diverse society like Israel.

Epidemiological trends and clinical features of the ongoing monkeypox epidemic: A preliminary pooled data analysis and literature review.

An emerging outbreak of monkeypox infection is quickly spreading worldwide, being currently reported in more than 30 countries, with slightly less than 1000 cases. In the present preliminary report, we collected and synthesized early data concerning epidemiological trends and clinical features of the ongoing outbreak and we compared them with those of previous outbreaks. Data were pooled from six clusters in Italy, Australia, the Czech Republic, Portugal, and the United Kingdom, totaling 124 cases (for 35 of which it was possible to retrieve detailed information). The ongoing epidemic differs from previous outbreaks in terms of age (54.29% of individuals in their thirties), sex/gender (most cases being males), risk factors, and transmission route, with sexual transmission being highly likely. Also, the clinical presentation is atypical and unusual, being characterized by anogenital lesions and rashes that relatively spare the face and extremities. The most prevalent sign/symptom reported was fever (in 54.29% of cases) followed by inguinal lymphadenopathy (45.71%) and exanthema (40.00%). Asthenia, fatigue, and headache were described in 22.86% and 25.71% of the subjects, respectively. Myalgia was present in 17.14% of the cases. Both genital and anal lesions (ulcers and vesicles) were reported in 31.43% of the cases. Finally, cervical lymphadenopathy was described in 11.43% of the sample, while the least commonly reported symptoms were diarrhea and axillary lymphadenopathy (5.71% of the case series for both symptoms). Some preliminary risk factors can be identified (being a young male, having sex with other men, engaging in risky behaviors and activities, including condomless sex, human immunodeficiency virus positivity (54.29% of the sample analyzed), and a story of previous sexually transmitted infections, including syphilis). On the other hand, being fully virally suppressed and undetectable may protect against a more severe infectious course. However, further research in the field is urgently needed.

Ensuring equitable, inclusive and meaningful gender identity- and sexual orientation-related data collection in the healthcare sector: insights from a critical, pragmatic systematic review of the literature.

In several countries, no gender identity- and sexual orientation-related data is routinely collected, if not for specific health or administrative/social purposes. Implementing and ensuring equitable and inclusive socio-demographic data collection is of paramount importance, given that the LGBTI community suffers from a disproportionate burden in terms of both communicable and non-communicable diseases. To the best of the authors' knowledge, there exists no systematic review addressing the methods that can be implemented in capturing gender identity- and sexual orientation-related data in the healthcare sector. A systematic literature review was conducted for filling in this gap of knowledge. Twenty-three articles were retained and analysed: two focussed on self-reported data, two on structured/semi-structured data, seven on text-mining, natural language processing, and other emerging artificial intelligence-based techniques, two on challenges in capturing sexual and gender-diverse populations, eight on the willingness to disclose gender identity and sexual orientation, and, finally, two on integrating structured and unstructured data. Our systematic literature review found that, despite the importance of collecting gender identity- and sexual orientation-related data and its increasing societal acceptance from the LGBTI community, several issues have to be addressed yet. Transgender, non-binary identities, and also intersex individuals remain often invisible and marginalized. In the last decades, there has been an increasing adoption of structured data. However, exploiting unstructured data seems to overperform in identifying LGBTI members, especially integrating structured and unstructured data. Self-declared/self-perceived/self-disclosed definitions, while being respectful of one's perception, may not completely be aligned with sexual behaviours and activities. Incorporating different levels of information (biological, socio-demographic, behavioural, and clinical) would enable overcoming this pitfall. A shift from a rigid/static nomenclature towards a more nuanced, dynamic, 'fuzzy' concept of a 'computable phenotype' has been proposed in the literature to capture the complexity of sexual identities and trajectories. On the other hand, excessive fragmentation has to be avoided considering that: (i) a full list of options including all gender identities and sexual orientations will never be available; (ii) these options should be easily understood by the general population, and (iii) these options should be consistent in such a way that can be compared among various studies and surveys. Only in this way, data collection can be clinically meaningful: that is to say, to impact clinical outcomes at the individual and population level, and to promote further research in the field.

HIV Pre-exposure Prophylaxis and Its Impact on the Gut Microbiome in Men Having Sex With Men.

HIV/AIDS still imposes a high epidemiological and societal burden. Together with antiretroviral therapy, pre-exposure prophylaxis (PrEP) represents a fundamental tool in the fight against HIV/AIDS. PrEP is considered effective and safe, even though it may affect organs like the kidney, bone, and liver, as shown by randomized clinical trials (RCTs). These side effects may be mediated by alterations of the gut microbiome. Whilst the impact of the human rectal and vaginal microbiome on HIV prevention has been highly investigated among women, less is known about its effect among men having sex with men (MSM), a vulnerable population at high risk for HIV and disproportionately affected by HIV/AIDS. In the present paper, we will overview the effects of PrEP on the gut microbiota in MSM. Mining PubMed/MEDLINE, we identified three studies that have found significant changes affecting the gut microbiota. However, these shifts in the gut microbiome composition are variable, probably due to methodological differences, even though all studies reviewed in the present overview consistently report aberrations at the level of the gut microbiota. More data are needed, especially concerning the long-term side effects of PrEP: despite the studies included being a high-quality RCT, and two well-designed cross-sectional studies, evidence related to the impact of HIV PrEP on the gut microbiome in MSM is scarce and based on small populations. A better understanding of the interactions between the gut microbiota, sexual orientation/identity, and HIV prevention is expected to improve PrEP adherence and devise strategies to counteract PrEP-related side effects.

How to Integrate Sex and Gender Medicine into Medical and Allied Health Profession Undergraduate, Graduate, and Post-Graduate Education: Insights from a Rapid Systematic Literature Review and a Thematic Meta-Synthesis.

Sex and gender are concepts that are often misunderstood and misused, being utilized in a biased, preconceived, interchangeable way. Sex and gender medicine is generally overlooked, despite the profound impact of sex and gender on health outcomes. The aims of the present rapid systematic literature review were (i) to assess the extent to which sex- and gender-sensitive topics are covered in medical courses; (ii) to assess the need for and willingness toward integrating/incorporating sex and gender medicine into health-related education; (iii) to identify barriers and facilitators of the process of implementation of sex and gender medicine in medical teaching, mentoring, and training; and (iv) to evaluate the effectiveness of interventional projects targeting curriculum building and improvement for future gender-sensitive physicians. Seven themes were identified by means of a thematic analysis, namely, (i) how much sex- and gender-based medicine is covered by medical courses and integrated into current medical curricula, (ii) the knowledge of sex and gender medicine among medical and allied health profession students, (iii) the need for and willingness toward acquiring sex- and gender-sensitive skills, (iv) how to integrate sex- and gender-based medicine into medical curricula in terms of barriers and facilitators, (v) existing platforms and tools to share knowledge related to sex and gender medicine, (vi) sex- and gender-based medicine aspects in the post-medical education, and (vii) the impact of sex- and gender-sensitive topics integrated into medical curricula. Based on the identified gaps in knowledge, further high-quality, randomized trials with larger samples are urgently warranted to fill these gaps in the field of implementation of gender medicine in educating and training future gender-sensitive physicians.

Inflammatory Markers in the Diagnosis of Fibromyalgia.

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain accompanied by various additional symptoms. The prevalence of FMS ranges between 2-8% of the population. The exact pathophysiology of the disease remains unknown, and under certain circumstances it is difficult for the physician to diagnose. Previous studies have shown a correlation between inflammatory biomarkers such as C-reactive protein (CRP) and FMS activity, suggesting that an inflammatory component may play a role in this disease pathogenesis. OBJECTIVES: To investigate the role of certain new inflammatory biomarkers in the diagnosis of patients with FMS. METHODS: In this study data were collected from FMS patients who were admitted to Ziv Medical Center during the period 2013 to 2019 in an attempt to find a connection between inflammatory markers detectable by a traditional complete blood count (CBC) tests such as neutrophil-lymphocytes ratio (NLR), platelet-lymphocyte ratio (PLR), mean platelet value (MPV), red cell distribution width (RDW), and C-reactive protein (CRP) and FMS. RESULTS: We found significantly higher CRP levels, MPV, and PLR and lower lymphocyte count in the FMS group compared to the control group. CONCLUSIONS: FMS has certain inflammatory components that may be useful in disease diagnosis.

Fertility-Sparing Treatment of Patients with Endometrial Cancer: A Review of the Literature.

Endometrial cancer (EC) is currently the most common malignancy of the female genital tract in developed countries. Although it is more common in postmenopausal women, it may affect up to 25% in the premenopausal age and 3-5% under the age of 40 years. Furthermore, in the last decades a significant shift to pregnancy at older maternal ages, particularly in resource-rich countries, has been observed. Therefore, in this scenario fertility-sparing alternatives should be discussed with patients affected by EC. This study summarizes available literature on fertility-sparing management of patients affected by EC, focusing on the oncologic and reproductive outcomes. A systematic computerized search of the literature was performed in two electronic databases (PubMed and MEDLINE) in order to identify relevant articles to be included for the purpose of this systematic review. On the basis of available evidence, fertility-sparing alternatives are oral progestins alone or in combination with other drugs, levonorgestrel intrauterine system and hysteroscopic resection in association with progestin therapies. These strategies seem feasible and safe for young patients with G1 endometrioid EC limited to the endometrium. However, there is a lack of high-quality evidence on the efficacy and safety of fertility-sparing treatments and future well-designed studies are required.

Big Data for Biomedical Education with a Focus on the COVID-19 Era: An Integrative Review of the Literature.

Medical education refers to education and training delivered to medical students in order to become a practitioner. In recent decades, medicine has been radically transformed by scientific and computational/digital advances-including the introduction of new information and communication technologies, the discovery of DNA, and the birth of genomics and post-genomics super-specialties (transcriptomics, proteomics, interactomics, and metabolomics/metabonomics, among others)-which contribute to the generation of an unprecedented amount of data, so-called 'big data'. While these are well-studied in fields such as medical research and methodology, translational medicine, and clinical practice, they remain overlooked and understudied in the field of medical education. For this purpose, we carried out an integrative review of the literature. Twenty-nine studies were retrieved and synthesized in the present review. Included studies were published between 2012 and 2021. Eleven studies were performed in North America: specifically, nine were conducted in the USA and two studies in Canada. Six studies were carried out in Europe: two in France, two in Germany, one in Italy, and one in several European countries. One additional study was conducted in China. Eight papers were commentaries/theoretical or perspective articles, while five were designed as a case study. Five investigations exploited large databases and datasets, while five additional studies were surveys. Two papers employed visual data analytical/data mining techniques. Finally, other two papers were technical papers, describing the development of software, computational tools and/or learning environments/platforms, while two additional studies were literature reviews (one of which being systematic and bibliometric).The following nine sub-topics could be identified: (I) knowledge and awareness of big data among medical students; (II) difficulties and challenges in integrating and implementing big data teaching into the medical syllabus; (III) exploiting big data to review, improve and enhance medical school curriculum; (IV) exploiting big data to monitor the effectiveness of web-based learning environments among medical students; (V) exploiting big data to capture the determinants and signatures of successful academic performance and counteract/prevent drop-out; (VI) exploiting big data to promote equity, inclusion, and diversity; (VII) exploiting big data to enhance integrity and ethics, avoiding plagiarism and duplication rate; (VIII) empowering medical students, improving and enhancing medical practice; and, (IX) exploiting big data in continuous medical education and learning. These sub-themes were subsequently grouped in the following four major themes/topics: namely, (I) big data and medical curricula; (II) big data and medical academic performance; (III) big data and societal/bioethical issues in biomedical education; and (IV) big data and medical career. Despite the increasing importance of big data in biomedicine, current medical curricula and syllabuses appear inadequate to prepare future medical professionals and practitioners that can leverage on big data in their daily clinical practice. Challenges in integrating, incorporating, and implementing big data teaching into medical school need to be overcome to facilitate the training of the next generation of medical professionals. Finally, in the present integrative review, state-of-art and future potential uses of big data in the field of biomedical discussion are envisaged, with a focus on the still ongoing "Coronavirus Disease 2019" (COVID-19) pandemic, which has been acting as a catalyst for innovation and digitalization.

Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic.

BACKGROUND: Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called "cytokine storm" related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic. METHODS: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed. RESULTS: Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates (n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55-1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53-9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38-37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38-0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06-0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36-0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34-1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001-5.54], p = 0.050; based on unadjusted estimates). CONCLUSION: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19.

Gynecology Meets Big Data in the Disruptive Innovation Medical Era: State-of-Art and Future Prospects.

Tremendous scientific and technological achievements have been revolutionizing the current medical era, changing the way in which physicians practice their profession and deliver healthcare provisions. This is due to the convergence of various advancements related to digitalization and the use of information and communication technologies (ICTs)-ranging from the internet of things (IoT) and the internet of medical things (IoMT) to the fields of robotics, virtual and augmented reality, and massively parallel and cloud computing. Further progress has been made in the fields of addictive manufacturing and three-dimensional (3D) printing, sophisticated statistical tools such as big data visualization and analytics (BDVA) and artificial intelligence (AI), the use of mobile and smartphone applications (apps), remote monitoring and wearable sensors, and e-learning, among others. Within this new conceptual framework, big data represents a massive set of data characterized by different properties and features. These can be categorized both from a quantitative and qualitative standpoint, and include data generated from wet-lab and microarrays (molecular big data), databases and registries (clinical/computational big data), imaging techniques (such as radiomics, imaging big data) and web searches (the so-called infodemiology, digital big data). The present review aims to show how big and smart data can revolutionize gynecology by shedding light on female reproductive health, both in terms of physiology and pathophysiology. More specifically, they appear to have potential uses in the field of gynecology to increase its accuracy and precision, stratify patients, provide opportunities for personalized treatment options rather than delivering a package of "one-size-fits-it-all" healthcare management provisions, and enhance its effectiveness at each stage (health promotion, prevention, diagnosis, prognosis, and therapeutics).