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Abdulmajeed Alshowair,1 Abdullah M Assiri,2 Abdullah Hussein Balfas,3 Rakan Alkhattabi,3 Tilal Abdalla Eltegani,3 Sara Altowairib,3 Abdullah Hamed Almalki,3 Eman Ahmed Alharbi,3 Suad Alotai,3 Fahad Alobaid,3 Najeeb Saud S Altowiher3 1Community Health Excellence, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia; 2Preventive Health, Ministry of Health, Riyadh, Saudi Arabia; 3Public Health Directorate, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi ArabiaCorrespondence: Abdulmajeed Alshowair, Community Health Excellence, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia, Tel +966547135224, Email dr.a.majeed@gmail.comPurpose: To estimate the prevalence and determinants of latent tuberculosis (LTBI) among inmates of four correctional facilities in Saudi Arabia.Methods: This is a retrospective review of health records. All inmates of four correctional facilities in Saudi Arabia were screened for tuberculosis in 2022. Their LTBI status was defined as more than 10mm Mantoux test result and negative X-ray chest result. The prevalence of LTBI and their determinants like age, gender, country of origin, location of the prison, and human immunodeficiency viruses (HIV) status were studied.Results: We reviewed screening data of 10,042 inmates in four Saudi prisons. The prevalence of LTBI was 7.4%. The risk difference of LTBI was significantly higher in males compared to female inmates (P < 0.001). The highest prevalence of LTBI was noticed among males (7.7%), those older than 60 years old (26.9%), and African expatriates (12.1%). None of the female inmates or those with HIV had LTBI. The binomial regression analysis revealed a highly significant effect of older age on the risk of having LTBI.Conclusion: The prevalence of LTBI was low among inmates at Saudi correctional facilities. The males, old age, and persons from African and Asian countries had a higher risk of LTBI. The prevalence of LTBI among inmates of Saudi prisons could be predicted by knowing their age group.Keywords: tuberculosis, latent tuberculosis, inmate screening

Abdulaziz M Al-Garni,1 Hasan S Alamri,1 Waddah M Alalmaei Asiri,1 Abdulaziz Muflih Abudasser,1 Amal Saad Alawashiz,2 Fatima Ahmed Badawi,2 Ghaidaa Abdulrahman Alqahtani,2 Sultan Saad Ali Alnasser,2 Abdulwahab Mufareh Assiri,2 Khalid Talab Salem Alshahrani,2 Osama Ayed Saleh Asiri,2 Ohoud Hussain Moalwi,2 Manar Saeed Alqahtani,2 Reema S Alqhatani2 1Department of Internal Medicine, College of Medicine, King Khalid University, Abha, 61421, Saudi Arabia; 2College of Medicine, King Khalid University, Abha, Saudi ArabiaCorrespondence: Abdulaziz M Al-Garni, Department of Internal Medicine, College of Medicine, King Khalid University, Abha, 61421, Saudi Arabia, Email amoalqarni@kku.edu.saBackground: Use of different social media platforms has increased radically over the past decade, emerging as an important part of adolescents and young people’s everyday life. This might exert potential adverse effects on sleep quality and daytime performance of young adults.Aim of Study: To assess the relation between use of social media platforms and sleep quality among public secondary school students.Methods: A cross-sectional study was conducted on 961 students in Aseer region, Saudi Arabia. Students were asked to fill in a structured interview questionnaire covering personal data, pattern of social media use, sleep quality using The Pittsburgh Sleep Quality Index (PSQI) and their mental health status using the depression, anxiety and stress scale (DASS-21).Results: Students’ ages ranged from 15 to 20 years with a mean age of 16.7 ± 2.1 years old. A total of 570 (59.3%) students were females. Tiktok (80%), Snapchat (77.9%), Instagram (63.8%) and YouTube (58.8%) were the most reported platforms used. Regarding their sleep quality, 34.7% of students were poor sleepers. TikTok use (OR 1.33, 95% CI 1.01– 1.77), hours spent on social media (OR 1.26, 95% CI 1.16– 1.37) and having moderate to severe depressive symptoms (OR 1.69, 95% CI 1.19– 2.40) were significant independent predictors of poor sleep among the studied sample.Conclusion: The present study emphasized the association between prolonged use of social media and poor sleep quality among Saudi adolescents. Awareness and behavioral change strategies and activities concerning the drawbacks of poor sleep and proper use of social media are urgently called for to control mental and physical health consequences of poor sleep and social media addiction.Keywords: adolescents, mental health, Saudi Arabia, screen time, sleep quality, snapchat, social media, students, tiktok

Abdullah M Assiri,1 Abdullah Alhelali,2 Ibrahim AL-Benhassan,3 Saeed Abo Hamed,3 Assaf Alkathiri,2 Elhadi Miskeen,4 Mohammed Alqarny5 1Department of Surgery, College of Medicine, Najran University, Najran, Saudi Arabia; 2Otolaryngology Department, Abha Children Hospital & Aseer Central Hospital, Abha, Saudi Arabia; 3Pediatric Critical Care Unit, Abha Maternity and Children Hospital, Abha, Saudi Arabia; 4Department of Obstetrics and Gynecology, College of Medicine, University of Bisha, Bisha, Saudi Arabia; 5Otolaryngology Head and Neck Surgery, Department of Surgery, College of Medicine, University of Bisha, Bisha, Saudi ArabiaCorrespondence: Mohammed Alqarny, Department of Surgery, College of Medicine, University of Bisha, P.O. Box 0011, Bisha, Asir, 61922, Saudi Arabia, Email maalgarni@ub.edu.saAbstract: Endotracheal intubation is common in the emergency department, intensive care units, and operating rooms. It involves the insertion of an endotracheal tube (ETT) through the mouth or nose into the trachea to maintain a patent airway and facilitate mechanical ventilation. Using a stylet during intubation can guide the ETT through the vocal cords. However, complications can arise when the stylet is not removed after successful intubation. Herewith, we reported a patient who was two years old and suffered from respiratory failure. However, in the first 12 hours, we observed a foreign body in the trachea, a small end of a metal stylet immediately removed by bronchoscope. This case demonstrates that multiple uses of a stylet, especially by a single user, can result in impaction of the stylet in the ETT during intubation, requiring force when the stylet is withdrawn after intubation, which can result in breakage, shearing, and retention of the stylet or plastic sheath in the lumen of the ETT.Keywords: stylet, foreign body, Saudi Arabia

Sumaya N Almohareb,1– 3 Majed S Al Yami,1– 3 Ahmed M Assiri,4 Omar A Almohammed5,6 1Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Department of Clinical Pharmacy, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 3King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; 4Health Volunteering Center, Ministry of Health, Riyadh, Saudi Arabia; 5Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 6Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Omar A Almohammed, Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia, Tel +966 555104065, Email oalmohammed@ksu.edu.saPurpose: Venous thromboembolism (VTE), a major complication that has been reported in patients with COVID-19, is associated with an increased risk of mortality. The purpose of this study was to compare in-hospital mortality among hospitalized patients with COVID-19 who received high-intensity versus standard-intensity thromboprophylactic anticoagulation.Patients and Methods: A secondary database analysis was conducted using data for adult patients who were hospitalized for COVID-19 in Saudi Arabia and received enoxaparin for thromboprophylaxis during their hospitalization. While enoxaparin 40 mg daily is considered the standard-intensity, doses higher than the standard but not to reach the therapeutic dose were considered as high-intensity. The primary outcome in the study was in-hospital mortality, and the secondary outcomes included intensive care unit (ICU) and hospital length of stay. Chi-square and t-tests were used to assess the difference between the two independent groups, and propensity score matching was performed to adjust for baseline characteristics.Results: From 3508 patients who received high- or standard-intensity enoxaparin, 1422 patients, 711 in each group, were included in the analyses after propensity score matching. The mean age of the participants was 57.2 years, and around 30% of them were female. About 72% of the patients were admitted to the ICU. No difference was observed between the two groups in the in-hospital mortality outcome (36% vs 33.5% in the high-intensity and the standard group, respectively; RR=1.06, 95% CI 0.95– 1.18). However, patients who received high-intensity thromboprophylaxis had a significantly longer duration of hospitalization (15.6 days vs 13.6 days; p=0.003) and ICU stay (12.3 days vs 10.8 days; p=0.039) compared to patients who received the standard dose.Conclusion: The use of high-intensity thromboprophylaxis was not associated with a reduction in mortality. Therefore, our results do not support the routine use of high-intensity prophylactic anticoagulation in both ICU and non-ICU patients with COVID-19.Graphical Abstract: Keywords: COVID-19, venous thromboembolism, anticoagulation, thromboprophylaxis, mortality

Anas Khan, 1, 2 Ahmed Alahmari, 2 Yasir Almuzaini, 2 Nada Alturki, 2 Alhanouf Aburas, 3 Fahad A Alamri, 2 Mohammed Albagami, 4 Mashael Alzaid, 4 Turki Alharbi, 4 Rahaf Alomar, 4 Muath Abu Tayli, 4 Abdullah M Assiri, 5 Hani A Jokhdar 6 1Department of Emergency Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Global Center of Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia; 3Health Sciences Department, College of Health and Rehabilitation Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 4Saudi Data and Artificial Intelligence Authority, Riyadh, Saudi Arabia; 5Ministry of Health, Riyadh, Saudi Arabia; 6Deputyship of Public Health, Ministry of Health, Riyadh, Saudi ArabiaCorrespondence: Alhanouf AburasHealth Sciences Department, College of Health and Rehabilitation Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi ArabiaEmail Alhanoufaburas@gmail.comIntroduction: The novel coronavirus (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-chain ribonucleic acid (RNA) virus. As of March 25, 2021, the total number of positive cases and fatalities in the Kingdom of Saudi Arabia (KSA) had reached 386,300 and 6624, respectively, with a case fatality rate of 1.71%. The KSA was among the leading nations to heed the advice of WHO officials and put strict precautionary and preventive measures in place to curb the early spread of COVID-19 before it was declared a global pandemic.Methodology: This was an uncontrolled before–after study following a mixed-method approach for data collection. National and regional data were extracted from the Health Electronic Surveillance Network (HESN), a centralized public health collection system for quantitative and statistical data. Quantitative and qualitative methods have been utilized in studying data derived from tech media.Results: The Saudi authorities utilized different technological tools to aid in managing and combating the COVID-19 pandemic. In the case of Al Madinah Al Mounawarah, after the implementation of several technologies, the most important being Tawakkalna, the number of active daily cases decreased by 61%.Conclusion: The use of the Tawakkalna application was proven to be a successful method in fighting the COVID-19 pandemic in the KSA. This vital and essential experience warrants the use of different digital technology that offers a personalized profile displaying the person’s status (affected, vaccinated, or no history of infection). This application played and will continue to play a crucial and effective role in pandemic containment in Saudi Arabia.Keywords: digital technology, risk management, Saudi Arabia, applications

Amani Almeharish,1 Abdullah M Assiri,2 Areej Alfattani,1 Edward De Vol1 1Department of Biostatics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 2Department of Comparative Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaCorrespondence: Amani AlmeharishDepartment of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Kingdom of Saudi ArabiaEmail aalmeharish26@kfshrc.edu.saAbstract: The spread of COVID-19 has become a significant threat to economic activity throughout the world, and it has made life particularly difficult for research institutions. According to a report published by Spain’s largest public research body, Cybermetrics Labs, King Faisal Specialist Hospital and Research Centre (KFSH&RC) is ranked first among the leading hospitals in the Arab world, and it has instituted a wide range of policy changes to accommodate researchers by providing them with additional flexibility. The aim of this project was to highlight the most prevalent COVID-related global challenges facing research institutions and describe how research protocol at KFSH&RC has been adjusted to minimize the disruption experienced by its researchers.Keywords: SARS-CoV-2, COVID-19, healthcare, disease, research, virus

Abdullatif Taha Babakr,1 Osman Mohamed Elsheikh,2 Abdullah A Almarzouki,3 Adel Mohamed Assiri,1 Badr Eldin Elsonni Abdalla,4 Hani Yousif Zaki,5 Samir H Fatani,1 EssamEldin Mohamed NourEldin11Department of Medical Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia; 2Department of Biochemistry, Faculty of Medicine, International University of Africa, Khartoum, Sudan; 3Department of Internal Medicine, Faculty of Medicine, Umm Al-Qura University, Makkah, 4Department of Biochemistry, Sciences Faculty for Girls, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 5Department of Biochemistry and Nutrition, Faculty of Medicine, University of Gezira, Sudan Background: Autoantibodies to oxidized low-density lipoprotein (oxLDL) are a heterogeneous group of antibodies that are controversially discussed to be either pathogenic or protective. Biochemical and anthropometric measurements correlated with increased levels of these antibodies are also controversial, especially in conditions of impaired glucose tolerance and type 2 diabetes mellitus. The present study was conducted to evaluate levels of oxLDL antibodies and their correlation with obesity in different glycemic situations. Methods: Two hundred and seventy-four adult males were classified into three subgroups: group 1 (n=125), comprising a control group of nondiabetic subjects; group 2 (n=77), comprising subjects with impaired glucose tolerance; and group 3 (n=72), comprising patients with type 2 diabetes mellitus. Body mass index was calculated, and measurement of oxLDL and oxLDL antibodies was performed. Results: Higher mean concentrations of oxLDL were found in the type 2 diabetes mellitus and impaired glucose tolerance groups (143.5±21.9 U/L and 108.7±23.7 U/L, respectively). The mean value for the control group was 73.5±27.5 U/L (P

The 2017–2027 National Academies' Decadal Survey, Thriving on Our Changing Planet, recommended Surface Biology and Geology (SBG) as a “Designated Targeted Observable” (DO). The SBG DO is based on the need for capabilities to acquire global, high spatial resolution, visible to shortwave infrared (VSWIR; 380–2500 nm; ~30 m pixel resolution) hyperspectral (imaging spectroscopy) and multispectral midwave and thermal infrared (MWIR: 3–5 μm; TIR: 8–12 μm; ~60 m pixel resolution) measurements with sub-monthly temporal revisits over terrestrial, freshwater, and coastal marine habitats. To address the various mission design needs, an SBG Algorithms Working Group of multidisciplinary researchers has been formed to review and evaluate the algorithms applicable to the SBG DO across a wide range of Earth science disciplines, including terrestrial and aquatic ecology, atmospheric science, geology, and hydrology. Here, we summarize current state-of-the-practice VSWIR and TIR algorithms that use airborne or orbital spectral imaging observations to address the SBG DO priorities identified by the Decadal Survey: (i) terrestrial vegetation physiology, functional traits, and health; (ii) inland and coastal aquatic ecosystems physiology, functional traits, and health; (iii) snow and ice accumulation, melting, and albedo; (iv) active surface composition (eruptions, landslides, evolving landscapes, hazard risks); (v) effects of changing land use on surface energy, water, momentum, and carbon fluxes; and (vi) managing agriculture, natural habitats, water use/quality, and urban development. We review existing algorithms in the following categories: snow/ice, aquatic environments, geology, and terrestrial vegetation, and summarize the community-state-of-practice in each category. This effort synthesizes the findings of more than 130 scientists.

Objective: To systematically assess the effect of the adjunctive administration of corticosteroids in the treatment of acute bacterial meningitis.Methods: We performed a systematic review and meta-analysis by searching several databases for reports (published from January 1966 through February 2008) of placebo-controlled randomized trials of corticosteroid use in the treatment of adolescents and adults with acute bacterial meningitis. We used random-effects models. Sources of heterogeneity were explored by preplanned subgroup analyses.Results: The 4 eligible trials (published between 1999 and 2007) were of high methodological quality and included 1261 adult patients. Overall, the short-term mortality rate associated with corticosteroid administration was not significantly lower than that associated with placebo (relative risk [RR], 0.81; 95% confidence interval [CI], 0.54-1.20; I(2)=54%). A significant interaction was found between the effect of corticosteroids and the income status of the country (P=.02) and the prevalence of infection with human immunodeficiency virus (HIV) among study populations (P=.03). The administration of corticosteroids resulted in a lower short-term mortality rate than did the administration of placebo in high-income countries (pooled RR, 0.5; 95% CI, 0.27-0.92; I(2)=0%) and in the studies with a low prevalence of infection with HIV (RR, 0.66; 95% CI, 0.44-0.99; I(2)=0%). In studies from high-income countries, the number needed to treat with corticosteriods to prevent 1 death and 1 neurologic sequela was 12.5 (95% CI, 7.1-100.0) and 11.0 (95% CI, 5.6-100.0), respectively.Conclusion: Our meta-analysis suggests that the adjunctive administration of corticosteroids is beneficial in the treatment of adolescents and adults with bacterial meningitis in patient populations similar to those seen in high-income countries and in areas with a low prevalence of HIV infection. [ABSTRACT FROM AUTHOR]

With the evident increased prevalence of respiratory tract infections (RTIs) such as Respiratory Syncytial Virus (RSV), influenza, Group A Streptococcus (GAS), and COVID-19, the conventional diagnostic methods are considered sub-optimal in providing timely management to patients in the Kingdom of Saudi Arabia (KSA). Gaps in current diagnostics are magnified by the Kingdom's unique demographic composition, comprising 11.9 million foreign workers, and the annual influx of over 10 million pilgrims. Current gaps in timely diagnosis leads to delays in treatment, misuse of antibiotics, and protracted hospital stays, subsequently compromising patient care, and escalating healthcare costs. KSA healthcare stakeholders suggest that the integration of rapid molecular Point-of-Care Testing (POCT) into the Kingdom's healthcare infrastructure is an absolute necessity. This publication serves as an urgent call for action aimed at healthcare policymakers in Saudi Arabia, to review the existing diagnostic challenges and include rapid POCTs in the Saudi healthcare strategy for respiratory infections., Competing Interests: Declaration of competing interest AM Assiri received honoraria for roundtable discussions from IQVIA. HS is the IRB chairman at King Fahad Medical City (KFMC) and a board member of the Saudi Association for Pulmonary Hypertension (SAPH). HS, LD, and RV are employees of IQVIA., (Copyright © 2024. Published by Elsevier Inc.)

Human-to-human transmission of the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) is currently inefficient. However, there is concern that the virus might mutate and thereby increase its transmissibility and thus pandemic potential. The pandemic SARS-CoV-2 depends on a highly cleavable furin motif at the S1/S2 site of the viral spike (S) protein for efficient lung cell entry, transmission, and pathogenicity. Here, by employing pseudotyped particles, we investigated whether augmented cleavage at the S1/S2 site also increases MERS-CoV entry into Calu-3 human lung cells. We report that polymorphism T746K at the S1/S2 cleavage site or optimization of the furin motif increases S protein cleavage but not lung cell entry. These findings suggest that, unlike what has been reported for SARS-CoV-2, a highly cleavable S1/S2 site might not augment MERS-CoV infectivity for human lung cells.IMPORTANCEThe highly cleavable furin motif in the spike protein is required for robust lung cell entry, transmission, and pathogenicity of SARS-CoV-2. In contrast, it is unknown whether optimization of the furin motif in the spike protein of the pre-pandemic MERS-CoV increases lung cell entry and allows for robust human-human transmission. The present study indicates that this might not be the case. Thus, neither a naturally occurring polymorphism that increased MERS-CoV spike protein cleavage nor artificial optimization of the cleavage site allowed for increased spike-protein-driven entry into Calu-3 human lung cells., Competing Interests: The authors declare no conflict of interest.

Background: Team-based learning (TBL) and problem-based learning (PBL) are two effective educational approaches used in medical education for increasing knowledge acquisition, learning motivation, and collaborative and communication skills among students. Few studies have been conducted in Saudi Arabia to evaluate medical students' perceptions of these approaches., Aim of the Study: The present study aimed to evaluate the perceptions of current or previous preclinical students at the College of Medicine, Najran University (NU) about the effectiveness of PBL and TBL and to assess students' perceptions regarding the strengths and limitations of both educational approaches and their preferences., Methods: A cross-sectional survey was conducted on 106 preclinical students at NU, Saudi Arabia. The survey questionnaire was validated by a pilot study and designed based on Kirkpatrick's evaluation model. Descriptive statistics was used to analyze the collected data through IBM SPSS Statistics 2.0., Results: 73.6% of participants enjoyed PBL and found it motivating compared to TBL and classic lectures. PBL was reported as more effective for knowledge acquisition (50%), teamwork (62.3%), and high academic performance (58%)., Conclusion: It is concluded that PBL was more favored by the students regarding the learning outcomes. TBL was reported to need more individual preparation and effort and require lecturer involvement, suggesting the need for structured facilitation in this learning approach and potentially indicating the challenges associated with coordinating team-based activities., (© 2024. The Author(s).)

Background: Eczema is a common inflammatory skin disease with a significant global health burden. Eczema has a significant impact on quality of life., Objective: We aimed to estimate the prevalence, severity, and risk factors associated with eczema among schoolchildren in Saudi Arabia., Methods: The standardized Global Asthma Network questionnaires and methodology were used to conduct a nationwide cross-sectional study across 20 regions in Saudi Arabia between March and April 2019. Data were collected from 137 primary schools and 140 intermediate schools by using a multistage stratified cluster sampling method., Results: The study included 3614 young children aged 6 to 7 years and 4068 adolescents aged 13 to 14 years. Current eczema was prevalent among 4.5% of the children and 5.1% of the adolescents. Severe eczema was reported in 0.8% and 0.9% of the young children and adolescents, respectively. Several factors showed significant association with eczema. Among the children, eczema was linked positively to having a history of chest infections and wheezing in early life, as well as to ever attending day care and current exposure to cats. Among the adolescents, the main potential risk factors included paracetamol use in the previous year, adherence to a lifestyle of vigorous physical activity, and current exposure to cats. Conversely, high consumption of nuts was found to be negatively associated with eczema., Conclusion: The prevalence of eczema in schoolchildren in Saudi Arabia is lower than the global average but within the average range for the Eastern Mediterranean region. Further studies in Saudi Arabia should be conducted to identify variation among different regions., Competing Interests: Supported by the Saudi Ministry of Health. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. Data availability statement: The data set used in the current study is managed and maintained by the Asthma Control Program at the General Directorate of Health Programs and Chronic Diseases, Ministry of Health, Saudi Arabia. On reasonable request and with permission from the data owners, interested individuals may obtain the data sets used in this study from the corresponding author., (© 2024 The Authors.)

The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic drug-induced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Abady, Jeong, Kwon, Assiri, Cho and Saadeldin.)

The prevalence of consanguineous marriages (CMs) varies worldwide from one country to another. However, the Middle East stands out as a region with a notably high rate of CMs. CM is particularly widespread in Saudi Arabia, where the prevalence of autosomal recessive genetic diseases has increased. This study aims to identify the Saudi population's awareness of genetic diseases and premarital screening tests (PMSTs). It also seeks to understand couples' perceptions of genetic diseases before and after marriage and their attitudes towards PMSTs and genetic counselling (GC) in reducing the risk of CM. Through the administration of online questionnaires, this cross-sectional study surveyed 2,057 participants to assess their awareness of genetic diseases and their understanding of testing and preventive measures for inherited diseases. Descriptive analysis, nonparametric chi-square tests and logistic regressions were performed to assess the association of categorical responses. This study included 2,035 Saudi Arabian respondents. A significant correlation was found between positive family history and partner selection (p = 0.001), as well as between partnering within the same tribe (p = 0.000139), with a different tribe (p = 0.000138) and from another family (p = 0.000489). About 91.3% of participants expressed agreement regarding the need to enhance public awareness and knowledge concerning genetic disorders, while 87% agreed that increased government regulations are required to prevent the spread of genetic diseases in affected families. Despite increased awareness of genetic diseases and PMSTs, there appears to be a lack of understanding regarding the limitations of PMSTs. The persistently high rate of CM underscores the challenge of altering marriage customs. Further governmental efforts are required to promote awareness of alternative reproductive options, establish new regulations and expand screening programmes., (© 2024. The Author(s).)

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Jay Lucidarme, Stephen A. Clark, and Ray Borrow report performing contract research on behalf of the UK Health Security Agency (UKHSA) for GSK, Pfizer, and Sanofi. Muhamed-Kheir Taha reports performing contract research on behalf of the Institut Pasteur for GSK, Pfizer, and Sanofi. Shamez N. Ladhani reports performing contract research on behalf of the UKHSA and St. George’s University of London for GSK, Pfizer, Merck Sharp & Dohme, and Sanofi. Helen Campbell and Mary Ramsay report receipt of a recovery charge by the Immunisation and Vaccine Preventable Diseases Division at UKHSA for provision to vaccine manufacturers (GSK, Pfizer, and Sanofi) of postmarketing surveillance reports on meningococcal, Haemophilus influenzae, and pneumococcal infections, which are required by the U.K. Licensing Authority in compliance with their risk management strategy. Jennifer Zipprich reports that her spouse is employed by Pfizer. No other potential conflicts of interest were disclosed.

Study Question: Are sperm phospholipase C zeta (PLCζ) profiles linked to the quality of embryogenesis and pregnancy?, Summary Answer: Sperm PLCζ levels in both mouse and humans correlate with measures of ideal embryogenesis whereby minimal levels seem to be required to result in successful pregnancy., What Is Known Already: While causative factors underlying male infertility are multivariable, cases are increasingly associated with the efficacy of oocyte activation, which in mammals occurs in response to specific profiles of calcium (Ca2+) oscillations driven by sperm-specific PLCζ. Although sperm PLCζ abrogation is extensively linked with human male infertility where oocyte activation is deficient, less is clear as to whether sperm PLCζ levels or localization underlies cases of defective embryogenesis and failed pregnancy following fertility treatment., Study Design, Size, Duration: A cohort of 54 couples undergoing fertility treatment were recruited at the assisted reproductive technology laboratory at the King Faisal Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. The recruitment criteria for males was a minimum sperm concentration of 5×106 sperm/ml, while all female patients had to have at least five oocytes. Sperm PLCζ analysis was performed in research laboratories, while semen assessments were performed, and time-lapse morphokinetic data were obtained, in the fertility clinic as part of routine treatment. The CRISPR/Cas9 system was concurrently used to induce indels and single-nucleotide mutations within the Plcζ gene to generate strains of Plcζ mutant mice. Sperm PLCζ was evaluated using immunofluorescence and immunoblotting with an antibody of confirmed consistent specificity against PLCζ., Participants/materials, Setting, Methods: We evaluated PLCζ profiles in sperm samples from 54 human couples undergoing fertility treatment in the context of time-lapse morphokinetic analysis of resultant embryos, correlating such profiles to pregnancy status. Concurrently, we generated two strains of mutant Plcζ mice using CRISPR/Cas9, and performed IVF with wild type (WT) oocytes and using WT or mutant Plcζ sperm to generate embryos. We also assessed PLCζ status in WT and mutant mice sperm in the context of time-lapse morphokinetic analysis and breeding outcomes., Main Results and the Role of Chance: A significant (P ≤ 0.05) positive relationship was observed between both PLCζ relative fluorescence and relative density with the times taken for both the second cell division (CC2) (r = 0.26 and r = 0.43, respectively) and the third cell division (S2) (r = 0.26). Examination of localization patterns also indicated significant correlations between the presence or absence of sperm PLCζ and CC2 (r = 0.27 and r = -0.27, respectively; P ≤ 0.025). Human sperm PLCζ levels were at their highest in the ideal times of CC2 (8-12 h) compared to time ranges outside the ideal timeframe (<8 and >12 h) where levels of human sperm PLCζ were lower. Following assignment of PLCζ level thresholds, quantification revealed a significantly higher (P ≤ 0.05) rate of successful pregnancy in values larger than the assigned cut-off for both relative fluorescence (19% vs 40%, respectively) and relative density (8% vs 54%, respectively). Immunoblotting indicated a single band for PLCζ at 74 kDa in sperm from WT mice, while a single band was also observed in sperm from heterozygous of Plcζ mutant mouse sperm, but at a diminished intensity. Immunofluorescent analysis indicated the previously reported (Kashir et al., 2021) fluorescence patterns in WT sperm, while sperm from Plcζ mutant mice exhibited a significantly diminished and dispersed pattern at the acrosomal region of the sperm head. Breeding experiments indicated a significantly reduced litter size of mutant Plcζ male mice compared to WT mice, while IVF-generated embryos using sperm from mutant Plcζ mice exhibited high rates of polyspermy, and resulted in significantly reduced numbers of these embryos reaching developmental milestones., Limitations, Reasons for Caution: The human population examined was relatively small, and should be expanded to examine a larger multi-centre cohort. Infertility conditions are often multivariable, and it was not possible to evaluate all these in human patients. However, our mutant Plcζ mouse experiments do suggest that PLCζ plays a significant role in early embryo development., Wider Implications of the Findings: We found that minimal levels of PLCζ within a specific range were required for optimal early embryogenesis, correlating with increased pregnancy. Levels of sperm PLCζ below specific thresholds were associated with ineffective embryogenesis and lower pregnancy rates, despite eliciting successful fertilization in both mice and humans. To our knowledge, this represents the first time that PLCζ levels in sperm have been correlated to prognostic measures of embryogenic efficacy and pregnancy rates in humans. Our data suggest for the first time that the clinical utilization of PLCζ may stand to benefit not just a specific population of male infertility where oocyte activation is completely deficient (wherein PLCζ is completely defective/abrogated), but also perhaps the larger population of couples seeking fertility treatment., Study Funding/competing Interest(s): J.K. is supported by a faculty start up grant awarded by Khalifa University (FSU-2023-015). This study was also supported by a Healthcare Research Fellowship Award (HF-14-16) from Health and Care Research Wales (HCRW) to J.K., alongside a National Science, Technology, and Innovation plan (NSTIP) project grant (15-MED4186-20) awarded by the King Abdulaziz City for Science and Technology (KACST) for J.K. and A.M.A. The authors declare no conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Epistaxis is one of the most common ear, nose, and throat (ENT) emergencies that present to the emergency or primary care centers., Study Aim: This study aimed to assess the knowledge of the Saudi general public toward epistaxis., Methods: This study adopted a cross-sectional analytical study design. The questionnaire link was distributed using social media channels. The participants were adult Saudi nationals that live in Saudi Arabia. The data was collected using a self-administered questionnaire that assessed knowledge related to epistaxis. The knowledge score was calculated using the 10 knowledge evaluation questions. Each correct response was assigned a value of "one." The scores ranged from "zero" to "ten," with higher scores signifying greater knowledge. A percentage score was computed, and the participants' knowledge was classified as poor (% score: ≤50%), moderate (% score: 51 to 70%), and good (% score: 71 to 100%). Statistical Package for Social Sciences (SPSS) version 26 was used for statistical analysis., Results: The study included 452 participants of whom 70.1% were females. Married individuals comprised 60.8% of the sample. The prevalence of self-reported epistaxis was 43.6% in the last 6 months. Among the participants, 42.9%, had "Poor" knowledge score, followed by 39.6% who had "moderate" score, and 17.5% had "Good" score. These results show that most participants had poor to moderate knowledge, with a minority demonstrating a good level of knowledge. All demographic variables have significantly influenced the adequacy of knowledge about epistaxis. Furthermore, participants who believed that the general public has insufficient knowledge on epistaxis had a significantly lower knowledge score ( p  = 0.001)., Conclusion: The present study found a non-satisfactory, low-to-moderate knowledge level of the Saudi general public toward epistaxis. We propose emphasizing public knowledge and education about first aid for epistaxis because proper first aid can minimize significant complications when done properly., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Assiri.)

Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and underlying liver diseases, including chronic hepatitis B or C infections, excessive alcohol consumption, nonalcoholic fatty liver disease (NAFLD), and exposure to chemical carcinogens. It is crucial to detect this disease early on before it metastasizes to adjoining parts of the body, worsening the prognosis. Serum biomarkers have proven to be a more accurate diagnostic tool compared to imaging. Among various markers such as nucleic acids, circulating genetic material, proteins, enzymes, and other metabolites, alpha-fetoprotein (AFP) is a protein marker primarily used to diagnose HCC. However, current methods need a large sample and carry a high cost, among other challenges, which can be improved using biosensing technology. Early and accurate detection of AFP can prevent severe progression of the disease and ensure better management of HCC patients. This review sheds light on HCC development in the human body. Afterward, we outline various types of biosensors (optical, electrochemical, and mass-based), as well as the most relevant studies of biosensing modalities for non-invasive monitoring of AFP. The review also explains these sensing platforms, detection substrates, surface modification agents, and fluorescent probes used to develop such biosensors. Finally, the challenges and future trends in routine clinical analysis are discussed to motivate further developments.

Hepatic cancer is widely regarded as the leading cause of cancer-related mortality worldwide. Despite recent advances in treatment options, the prognosis of liver cancer remains poor. Therefore, there is an urgent need to develop more representative in vitro models of liver cancer for pathophysiology and drug screening studies. Fortunately, an exciting new development for generating liver models in recent years has been the advent of organoid technology. Organoid models hold huge potential as an in vitro research tool because they can recapitulate the spatial architecture of primary liver cancers and maintain the molecular and functional variations of the native tissue counterparts during long-term culture in vitro. This review provides a comprehensive overview and discussion of the establishment and application of liver organoid models in vitro. Bioengineering strategies used to construct organoid models are also discussed. In addition, the clinical potential and other relevant applications of liver organoid models in different functional states are explored. In the end, this review discusses current limitations and future prospects to encourage further development.

Objectives: There are limited data on the clinical and epidemiological aspects of mpox in Saudi Arabia. This study investigates the characteristics of Mpox cases from May to September 2023., Methods: A total of 381 cases of Mpox were included in this study, diagnosed based on a combination of clinical symptoms and laboratory testing., Results: The majority of mpox cases were males (91.1%), with a mean age of (±SD) of 32.4 (±8.3) years; 356 (93.4%) did not report travel, 277 (72.7%) denied engaging in extra-marital sex, and 379 (99.5%) were not linked to secondary cases. Fever was reported in 371 (97.4%), whereas headache was present in 314 (82.4%). Cough (1.3%) and conjunctivitis (0.5%) were rare. The most commonly affected areas in terms of lesions were the palms and soles (297 cases, 78%), followed by the genitals (206 cases, 54%), face (198 cases, 52%), and mouth (160 cases, 42%). Of the 1325 identified contacts, 1134 (85.5%) were hospital contacts, and 191 (14.5%) were community contacts, and 393 (29.6%) were high-risk contact. Of the high-risk contacts, 284 (72.3%) accepted post-exposure vaccination. The genotyped samples were all subclade IIb (formerly the West Africa clade)., Conclusions: This study provides valuable insights into mpox characteristics in Saudi Arabia. The genome of monkeypox virus belonged to subclade IIb of the West Africa clade. Further analysis of the global tree sublineage is needed., Competing Interests: All authors have no competing interests to declare., (© 2024 The Author(s).)

Background: Functional constipation (FC) is a common condition in children, and information on the clinical characteristics of FC in Saudi children is scarce., Objective: Describe the clinical profile of FC in Saudi children., Design: Retrospective., Setting: Hospital that provides primary, intermediate and tertiary care., Patients and Methods: All children diagnosed with FC according to the Rome IV criteria were included and had at least one follow-up clinic visit. Demographic and clinical data collected from medical records included the age at onset, duration of constipation, clinical features, treatment modalities, and factors associated with clinical response. Descriptive statistics and Pearson's chi-squared test were used in the statistical analysis to see how categorical study variables were linked to clinical response. A P value of ≤.05 was used to report statistical significance., Main Outcome Measure: Compliance and clinical response to polyethylene glycol (PEG) compared with lactulose., Sample Size: 370 children from 0.1 to 13 years of age., Results: The median (IQR) age of onset was 4 (5) years and less than one year in 14%. The median (IQR) duration of constipation was 4 months (11) and less than two months in 93/370 (25%). Abdominal pain was the most commonly associated feature (44%). Screening for celiac disease and hypothyroidism was negative. A Fleet enema was the most common disimpaction method (54%) and PEG was the most common maintenance medication (63.4%). PEG was significantly better tolerated ( P =.0008) and more effective than lactulose ( P <.0001). Compliance was the only variable significantly associated with clinical response., Conclusions: PEG was better tolerated and more effective than lactulose in our study, a finding in agreement with the literature. Therefore, PEG should be the drug of choice in the initial management of FC in Saudi children. Prospective studies on the causes of noncompliance are needed to improve the response to treatment., Limitations: The limitations of retrospective design are missing data, recall bias, and hospital-based limitation, such as missing milder cases treated at the outpatient level. However, the sample size of 370 may have minimized these limitations., Competing Interests: CONFLICT OF INTEREST: None.

Liver organoids take advantage of several important features of pluripotent stem cells that self-assemble in a three-dimensional culture matrix and reproduce many aspects of the complex organization found within their native tissue or organ counterparts. Compared to other 2D or 3D in vitro models, organoids are widely believed to be genetically stable or docile structures that can be programmed to virtually recapitulate certain biological, physiological, or pathophysiological features of original tissues or organs in vitro. Therefore, organoids can be exploited as effective substitutes or miniaturized models for the study of the developmental mechanisms of rare liver diseases, drug discovery, the accurate evaluation of personalized drug responses, and regenerative medicine applications. However, the bioengineering of organoids currently faces many groundbreaking challenges, including a need for a reasonable tissue size, structured organization, vascularization, functional maturity, and reproducibility. In this review, we outlined basic methodologies and supplements to establish organoids and summarized recent technological advances for experimental liver biology. Finally, we discussed the therapeutic applications and current limitations.

SARS-CoV-2 caused the pandemic of the rapidly evolving COVID-19. As of December 6, 2023, there were 765,152,854 COVID-19-recovering cases. Long-term consequences known as "long COVID" and "post-COVID-19 conditions" (PCCs) or "post-acute COVID-19 syndrome" are being reported more frequently in a subset of recovering patients. Systemic, neuropsychiatric, cardio-respiratory, and gastrointestinal symptoms are the most prevalent. The management of PCCs poses unique challenges due to the lack of official guidelines and the complex nature of the illness. This abstract highlights key principles derived from recent reviews and expert recommendations to provide healthcare professionals with a comprehensive approach to manage post-COVID-19 patients. Preventive medicine plays a crucial role in managing PCCs. While no specific medications are available for treatment, preventive measures such as COVID-19 vaccination, adherence to precautionary measures, regular consultations with medical professionals, monitoring symptoms and progress, and seeking information on symptom management are essential to assist patients in their recovery and improve their quality of life. Medical management requires transparent goal-setting and collaborative decision-making based on the patient's symptoms, comorbidities, and treatment objectives. Treatment plans for post-COVID-19 patients should focus on patient education, using registries and calendars to track symptoms and triggers, providing support and reassurance, and offering holistic support through peer networks and supportive psychotherapy techniques. Symptomatic and rehabilitative care, including well-established symptom management techniques, physical rehabilitation programs, and addressing mental health and well-being, are vital components of post-COVID-19 management. Lifestyle factors such as stress reduction, nutrition, and sleep should be incorporated into managing underlying medical conditions in post-COVID-19 patients. Regular follow-up visits and referrals to specialists are recommended to monitor the patient's progress and address specific organ system involvement or additional care needs. In summary, for the effective management of PCCs, a holistic approach should include preventive measures, patient education, supportive psychotherapy, symptomatic and rehabilitative care, medical management, counseling on lifestyle elements, and appropriate follow-up plans. However, it is crucial to stay updated with evolving guidelines and recommendations from healthcare authorities to provide the most effective and evidence-based care to post-COVID-19 patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Assiri et al.)

Introduction: Changing population demographics places a premium on optimizing older adult health. Vaccine-preventable diseases represent a substantial clinical and economic burden in older adults (≥65 years)., Areas Covered: This narrative review summarizes the adult immunization landscape in three countries; Saudi Arabia, the United Arab Emirates and Türkiye, informed by literature searches; PubMed (23-27 September 2023) supplemented by citation tracking via Google Scholar). Existing vaccination recommendations and published data were reviewed to evaluate vaccine uptake, chiefly focusing on core adult vaccines (seasonal influenza, pneumococcal, and herpes zoster). Barriers to vaccine access and uptake were reviewed, and initiatives to improve recommended vaccine uptake in older (≥65 years) or otherwise high-risk adults are described., Expert Opinion: Uptake of recommended adult vaccines is low in all three countries. Receipt of annual seasonal influenza vaccine is typically below 50% in both older and at-risk younger adults; pneumococcal vaccination rates are even lower in eligible adults (<15% and often far lower), as is herpes zoster vaccine uptake (typically <5%). Low coverage is driven chiefly by low awareness of vaccine benefits, inconsistent recommendations, and vaccine hesitancy, together with often complex adult vaccine access pathways. Initiatives and remedies aimed at augmenting adult vaccination rates are warranted.

Objectives: To analyze the evolution of tuberculosis (TB) epidemiology in Saudi Arabia in the 5 years following the implementation of the end-TB Strategy., Methods: A retrospective analysis of surveillance data, reported by the national tuberculosis control program from 2015-2019, was carried out. The annual incidence and the percentage of yearly changes were calculated and compared to the World Health Organization (WHO) milestones, which anticipate a 4-5% annual decline. Additionally, various other epidemiological indicators of TB were examined., Results: The national TB incidence declined from 10.55% per 100,000 in 2015 to 8.76% per 100,000 in 2019, aligning with the WHO's 2019 milestone estimated between 8.59-8.96% per 100,000. While Makkah Region (40.3%) and Riyadh (24.6%) accounted for the majority of cases, Jazan region consistently exhibited the highest incidence throughout the study period. Demographic features shifted towards a younger age category, male, and native dominance. There was a consistent decrease in resistance and intermediate sensitivity to all first-line anti-TB drugs, associated with a substantial decrease in both polydrug resistance (from 4.7-1.9%; p <0.001) and multidrug resistance (from 4.4-2.4%; p =0.008)., Conclusion: The figures of TB incidence TB in Saudi Arabia between 2015-2019 has met the WHO end-TB milestones, predicting successful progress toward the 2035 goal., (Copyright: © Saudi Medical Journal.)

Objective:  The objective of this study was to evaluate the awareness and practice of Najran University students toward common problems related to the ear, nose, and throat., Methods:  A cross-sectional study was utilized in this research, employing data from a sample of 429 students at Najran University. The participants completed a self-administered questionnaire and ensured anonymity. The questionnaire used in this study had been previously validated., Results:  The sample for the current study primarily consisted of students aged more than 20 years (84.1%; n = 361), with a predominance of females (69.0%; n = 296). The majority of them were in health colleges (45.2%; n=194). The study results show that 37.8% (n = 162) had a good knowledge level, while 62.2% (n = 267) had poor knowledge about problems related to ENT. The vast majority, 87.2% (n = 374), believed that going to the hospital was the appropriate action to take in cases of acute ENT problems. The results established a statistically significant association between age, gender, health college, college, and department with p-values <0.005 (0.002*, 0.001*, 0.003*, and 0.005*), respectively, and the level of knowledge about problems related to ENT. There was no statistically significant association between nationality, clinical history of the participants, and the level of knowledge about problems related to ENT (p > 0.005)., Conclusion:  The study revealed that 37.8% of the participants had good knowledge about problems related to the ears, nose, and throat. The participants older than 20 years had better knowledge of common ENT problems than those younger than 20 years. Female participants showed a higher level of knowledge and awareness of problems related to the ears, nose, and throat. The study noted that the participants in Health College, the faculty of medicine, and the third academic level had good knowledge about problems related to ENT. The study established that going to the hospital was the appropriate action to be taken in case of a sudden ENT problem. Therefore, we recommend concerted efforts be made among the medical community to increase knowledge about common ENT problems., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Assiri et al.)

Objectives: The authors conducted a study to estimate the rising disease and economic burden of viral severe acute respiratory infections and their management, including COVID-19, respiratory syncytial virus, and influenza types A and B, in early and delayed diagnosis scenarios in the Kingdom of Saudi Arabia from a national perspective., Methods: This cross-sectional study was conducted in May 2022 using a de novo Excel-based universal cost-of-illness calculator model. The study used primary data, such as expert interviews, as well as secondary data from a thorough literature search., Results: The total economic burden of viral severe acute respiratory infections in patients with an early diagnosis was lower than those with a delayed diagnosis among patients with complications, both from the payer's (United States dollar [USD] 3846 million vs USD 4726 million) and societal (USD 4048 million vs USD 5020 million, respectively) perspectives. The major cost driver of the total economic burden for both early and delayed diagnosis was disease management costs: 49% (USD 1880 million) and 58% (USD 2730 million), respectively., Conclusions: In the Kingdom of Saudi Arabia, the total economic burden for COVID-19, influenza (epidemic phase), and respiratory syncytial virus was higher with a delayed diagnosis vs an early diagnosis, emphasizing the importance of using a broader diagnostic method., Competing Interests: The authors have no competing interests to declare., (© 2023 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.)

Biomaterial templates play a critical role in establishing and bioinstructing three-dimensional cellular growth, proliferation and spatial morphogenetic processes that culminate in the development of physiologically relevant in vitro liver models. Various natural and synthetic polymeric biomaterials are currently available to construct biomimetic cell culture environments to investigate hepatic cell-matrix interactions, drug response assessment, toxicity, and disease mechanisms. One specific class of natural biomaterials consists of the decellularized liver extracellular matrix (dECM) derived from xenogeneic or allogeneic sources, which is rich in bioconstituents essential for the ultrastructural stability, function, repair, and regeneration of tissues/organs. Considering the significance of the key design blueprints of organ-specific acellular substrates for physiologically active graft reconstruction, herein we showcased the latest updates in the field of liver decellularization-recellularization technologies. Overall, this review highlights the potential of acellular matrix as a promising biomaterial in light of recent advances in the preparation of liver-specific whole organ scaffolds. The review concludes with a discussion of the challenges and future prospects of liver-specific decellularized materials in the direction of translational research.

Background and Aim: Access to adequate healthcare systems is seen as a fundamental human right. Therefore, healthcare services must be distributed and accessible in the most efficient way possible to those who need them the most. Primary healthcare centers are the backbone of any healthcare system as they provide essential healthcare services to the general population. Inequalities in the distribution of primary healthcare centers can lead to disparities in healthcare access and outcomes. This study aimed to assess the equity of primary healthcare centers distribution, we analyzed and evaluated the allocation of primary healthcare centers in Saudi Arabia from 2017 to 2021., Method: This cross-sectional study utilized data from the Health Statistical Yearbook published by the Ministry of Health, Saudi Arabia, during the period of 2017-2021. The number of primary healthcare centers per 10,000 population was calculated for the 20 health regions. We used the Gini index to measure inequality in the distribution of primary healthcare centers. The Pearson coefficient was calculated to assess the correlation between the number of primary healthcare centers and the population in each health region., Result:  The overall ratio of primary healthcare centers to population decreased from 0.72 to 0.62 between 2017 and 2021. The Gini index showed relative equality in the distribution of primary healthcare centers from 2017 to 2021 with values between 0.2 and 0.3. There was a positive correlation between the population and the primary healthcare centers in Jeddah, Tabouk, and the Northern Region. However, in Riyadh, Makkah, Taif, Madinah, Qaseem, Eastern Region, Al-Ahsa, Aseer, Hail, Jazan, Najran, Al-Baha, and Al-Jouf, the correlation was found to be negative., Conclusion:  From 2017 to 2021, primary healthcare facilities are distributed fairly throughout 20 health regions of Saudi Arabia. However, there are still some disparities between provinces, and efforts must be made to ensure that primary healthcare centers are distributed equitably across the country to improve healthcare access and outcomes for all., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Al-Sheddi et al.)

Introduction Trauma and injuries are common among pilgrims during Hajj, the biggest mass gathering event. Trauma and injury causes vary from falling and pressing in crowds to being burned by boiled water and road traffic accidents (RTA). Time to reach the hospital during highly condensed areas in Hajj are challenges for the public health authorities and the healthcare system to achieve optimum control, management, and outcome. This study aims to explore the pattern of trauma and injuries during Hajj as it is crucial to improve future preventive measures and care quality. Methods A cross-sectional questionnaire-based study was conducted in one hospital in each of the Mena and Arafat (Al-Mashaar's areas) in Makkah City, Saudi Arabia, from July 8 to 10, 2022. Data was collected through interviews with patients who visit the hospitals or enter the emergency department and are diagnosed with trauma or injury during the Hajj season of 1443 Hijri date (2022). Results A total of 264 people volunteered to participate in the survey. The mean age by years was 43.5 ± 10.7, and the majority (56%) were between 41 and 64. There were multiple nationalities - the most common nationality was Egyptian (25%), followed by Saudi (10%). The commonest type of trauma was cutting wounds (50%), and the commonest cause was falling (39%), followed by foot twisting (31%). There were 142 cases in Arafat and 122 cases in Mena in the study duration. Tissue contusions are higher in Arafat. Fractures (5%) were in both areas but higher in Mena with burns and sprains. Friction blister injuries were only in Mena and were statistically associated with walking barefoot (p<0.01), which was associated with Egyptians (p<0.05). Also, thigh chafing is only in Mena, while eye traumas and abrasion are only in Arafat. There were four causes of injury that are statistically significantly associated with the area (p<0.05): foot twisting in Arafat, pressing in overcrowding, stoning, and burning in Mena. Moreover, all the RTA cases (n=4) were in Arafat, and all the stoning and burning by boiling water were in Mena. Admission was only for burning (n=2) and falling (n=2) cases and only in Mena emergency hospital; otherwise, all trauma cases were discharged after receiving management - no deaths among the study sample. Injuries in Mena are likely to happen in the evening and night (n=91), while in Arafat, it is more likely in two periods (n=113), in the early morning and afternoon. This difference is statistically significant between the two areas (p<0.05). Most pilgrims (n=129/253) reach the hospital in 16 to 30 minutes. A statistically significant association exists between the duration and the area (p<0.05). Most patients in Arafat (88%) reach the hospital in less than 30 minutes, while only 50% take the same duration in Mena. Conclusion The Hajj season of 1443 H (2022) has a similar trauma pattern and improved outcomes compared to previous seasons. Discovering and digging into the causes of traumas and injuries should be optimized in future research for better control and customized prevention measures. Establishing new and remodeling current prevention measures is recommended for more control., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Al-Hayani et al.)

Introduction: BRAF V600E mutations frequently occur in papillary thyroid cancer (PTC). β-catenin, encoded by CTNNB1 , is a key downstream component of the canonical Wnt signaling pathway and is often overexpressed in PTC. BRAF V600E -driven PTC tumors rely on Wnt/β-catenin signaling to sustain growth and progression., Methods: In the present study, we investigated the tumorigenicity of thyroid cancer cells derived from BRAF V600E PTC mice following Ctnnb1 ablation (BVE- Ctnnb1 null )., Results: Remarkably, the tumorigenic potential of BVE- Ctnnb1 null tumor cells was lost in nude mice. Global gene expression analysis of BVE- Ctnnb1 null tumor cells showed up-regulation of NKG2D receptor activating ligands (H60a, H60b, H60c, Raet1a, Raet1b, Raet1c, Raet1d, Raet1e, and Ulbp1) and down-regulation of inhibitory MHC class I molecules H-2L and H-2K2 in BVE- Ctnnb1 null tumor cells. In vitro cytotoxicity assay demonstrated that BVE- Ctnnb1 wt tumor cells were resistant to NK cell-mediated cytotoxicity, whereas BVE- Ctnnb1 null tumor cells were sensitive to NK cell-mediated killing. Furthermore, the overexpression of any one of these NKG2D ligands in the BVE- Ctnnb1 wt cell line resulted in a significant reduction of tumor growth in nude mice., Conclusions: Our results indicate that active β-catenin signaling inhibits NK cell-mediated immune responses against thyroid cancer cells. Targeting the β-catenin signaling pathway may have significant therapeutic benefits for BRAF -mutant thyroid cancer by not only inhibiting tumor growth but also enhancing host immune surveillance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zou, Al-Yahya, Al-Alwan, BinEssa, Khabar, Almohanna, Assiri, Altaweel, Qattan, Meyer, Alzahrani and Shi.)

Introduction: Severe acute respiratory illness (SARI) among pilgrims continues to be an important healthcare issue. The aim of this study was to describe the viral aetiology of patients admitted to hospitals in the holy cities of Makkah and Madinah during the 2022 peri-Hajj period., Methods: This is a retrospective analysis of patients admitted to hospitals with SARI. Patients were tested with multiplex polymerase chain reaction for the most common viral aetiologies., Results: In total, 179 cases of SARI were identified during the study period. Of these, 101 (56.4%) were males, 78 (43.6%) were females, and 78 (43.6%) were Saudi. The mean age was 58.60 years (standard deviation 20.5) years. The most common age group was ≥65 years ( n =68, 36%), followed by 55-59 years ( n =37, 19%). The most common comorbidities were diabetes mellitus ( n =67, 36%), hypertension ( n =65, 35%) and chronic lung disease ( n =34, 18%). Eighty-five (47.5%) patients tested negative and 94 (42.5%) tested positive for various viral aetiologies. The most frequently detected viruses were severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) ( n =28, 15%) and influenza ( n =22, 12%); of the influenza cases, 16 were influenza A (6 (43%) were H3N2), and six were influenza B. The only case of Middle East respiratory syndrome coronavirus (MERS-CoV) was in a citizen, and none of the visitors or residents had MERS-CoV. Of the total cases, 27 (14%) died during the follow-up period. In a binary regression analysis, only age was associated with mortality ( P =0.002)., Conclusion: The most commonly detected viruses among patients admitted to hospital with SARI were SARS-CoV-2 and influenza. It is important to continue surveillance of admitted and non-admitted patients in different Hajj periods to identify any shift in the aetiologic agents., Competing Interests: None declared., (© 2023 The Author(s).)

There has been a notable increase in rhino-orbito-cerebral mucormycosis (ROCM) post-coronavirus disease 2019 (COVID-19), which is an invasive fungal infection with a fatal outcome. Magnetic resonance imaging (MRI) is a valuable tool for early diagnosis of ROCM and assists in the proper management of these cases. This study aimed to describe the characteristic MRI findings of ROCM in post-COVID-19 patients to help in the early diagnosis and management of these patients. This retrospective descriptive study was conducted at a single hospital and included 52 patients with COVID-19 and a histopathologically proven ROCM infection who were referred for an MRI of the paranasal sinuses (PNS) due to sino-orbital manifestations. Two radiologists reviewed all the MR images in consensus. The diagnosis was confirmed by histopathological examination. The maxillary sinus was the most commonly affected PNS (96.2%). In most patients (57.7%), multiple sinuses were involved with the black turbinate sign on postcontrast images. Extrasinus was evident in 43 patients with orbital involvement. The pterygopalatine fossa was involved in four patients. Three patients had cavernous sinus extension, two had pachymeningeal enhancement, and one had epidural collection. The alveolar margin was affected in two patients, and five patients had an extension to the cheek. The awareness of radiologists by the characteristic MRI features of ROCM in post-COVID-19 patients helps in early detection, early proper management, and prevention of morbid complications.

Purpose: The purpose of this study was to evaluate the effectiveness of either hydroxychloroquine, triple combination therapy (TCT), favipiravir, dexamethasone, remdesivir, or COVID-19 convalescent plasma (CCP) in comparison with standard-of-care for hospitalized patients with COVID-19 using real-world data from Saudi Arabia., Patients and Methods: A secondary database analysis was conducted using the Saudi Ministry of Health database for patients with COVID-19. Adult (≥18 years) hospitalized patients with COVID-19 between March 2020 and January 2021 were included in the analysis. A propensity score matching technique was used to establish comparable groups for each therapeutic approach. Lastly, an independent t -test and chi-square test were used to compare the matching groups in the aspects of the duration of hospitalization, length of stay (LOS) in intensive care units (ICU), in-hospital mortality, and composite poor outcome. Multilevel logistic regression model was used to assess the association between the severity stage of COVID-19 and the outcomes while using the medication or intervention used as a grouping variable in the model., Results: The mean duration of hospitalization was significantly longer for patients who received TCT, favipiravir, dexamethasone, or CCP compared to patients who did not receive these therapies, with a mean difference ranging between 2.2 and 4.9 days for dexamethasone and CCP, respectively. Furthermore, the use of favipiravir or CCP was associated with a longer stay in ICU. Remdesivir was the only agent associated with in-hospital mortality benefit. A higher risk of mortality and poorer composite outcome were associated with the use of favipiravir or dexamethasone. However, the logistic regression model reveled that the difference between the two matched cohorts was due to the severity stage not the medication. Additionally, the use of hydroxychloroquine, TCT, or CCP had no impact on the incidence of in-hospital mortality or composite poor outcomes., Conclusion: Remdesivir was the only agent associated with in-hospital mortality benefit. The observed worsened treatment outcomes associated with the use of dexamethasone or FPV shall be attributed to the severity stage rather than the medication use. In light of these varied results, additional studies are needed to continue evaluating the actual benefits of these therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto-Abs) to type I IFNs were reported as a risk factor for life-threatening COVID-19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS)., Methods: We evaluated the prevalence of type I IFN auto-Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo-controlled clinical trial for treatment with IFN-β1b and lopinavir-ritonavir (MIRACLE trial). Samples were tested for type I IFN auto-Abs using a multiplex particle-based assay., Results: Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto-Abs for at least one subtype of type I IFNs. Auto-Abs positive patients were not different from auto-Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto-Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto-Abs negative patients. The effect of treatment with IFN-β1b and lopinavir-ritonavir did not significantly differ between the two groups., Conclusion: This study demonstrates the presence of type I IFN auto-Abs in hospitalized patients with MERS., Competing Interests: YA provided nonpaid consultations on therapeutics for MERS for Gilead Sciences and SAB Biotherapeutics, and he is a board member of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). All other authors declare no financial or commercial conflict of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Saudi Arabia (SA) reported its first case of COVID-19 on 2 March 2020. Mortality varied nationwide; by April 14, 2020, Medina had 16% of SA's total COVID-19 cases and 40% of all COVID-19 deaths. A team of epidemiologists investigated to identify factors impacting survival., Methods: We reviewed medical records from two hospitals: Hospital A in Medina and Hospital B in Dammam. All patients with a registered COVID-related death between March and May 1, 2020, were included. We collected data on demographics, chronic health conditions, clinical presentation, and treatment. We analyzed data using SPSS., Results: We identified 76 cases: 38 cases from each hospital. More fatalities were among non-Saudis at Hospital A (89%) versus Hospital B (82%, p  < 0.001). Hypertension prevalence was higher among cases at Hospital B (42%) versus Hospital A (21%) ( p  < 0.05). We found statistically significant differences ( p  < 0.05) in symptoms at initial presentation among cases at Hospital B versus Hospital A, including body temperature (38°C vs. 37°C), heart rate (104 bpm vs. 89 bpm), and regular breathing rhythms (61% vs. 55%). Fewer cases (50%) at Hospital A received heparin versus Hospital B (97%, p -value < 0.001)., Conclusion: Patients who died typically presented with more severe illnesses and were more likely to have underlying health conditions. Migrant workers may be at increased risk due to poorer baseline health and reluctance to seek care. This highlights the importance of cross-cultural outreach to prevent deaths. Health education efforts should be multilingual and accommodate all literacy levels., Competing Interests: The authors report no conflict of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

The absolute shortage of compatible liver donors and the growing number of potential recipients have led scientists to explore alternative approaches to providing tissue/ organ substitutes from bioengineered sources. Bioartificial regeneration of a fully functional tissue/organ replacement is highly dependent on the right combination of engineering tools, biological principles, and materiobiology horizons. Over the past two decades, remarkable achievements have been made in hepatic tissue engineering by converging various advanced interdisciplinary research approaches. Three-dimensional (3D) bioprinting has arisen as a promising state-of-the-art tool with strong potential to fabricate volumetric liver tissue/organ equivalents using viscosity- and degradation-controlled printable bioinks composed of hydrous microenvironments, and formulations containing living cells and associated supplements. Source of origin, biophysiochemical, or thermomechanical properties and crosslinking reaction kinetics are prerequisites for ideal bioink formulation and realizing the bioprinting process. In this review, we delve into the forecast of the potential future utility of bioprinting technology and the promise of tissue/organ- specific decellularized biomaterials as bioink substrates. Afterward, we outline various methods of decellularization, and the most relevant studies applying decellularized bioinks toward the bioengineering of in vitro liver models. Finally, the challenges and future prospects of decellularized material-based bioprinting in the direction of clinical regenerative medicine are presented to motivate further developments., Competing Interests: The authors declare no conflict of interest., (Copyright:© 2023, Mir TA, Nakamura M, Sakai S, et al.)

Background Workplace safety has increased in many developed nations, but work-related injuries (WRIs) are on the rise. Globally, approximately 2.9 million fatal work-related injuries and diseases occurred in 2021, up from 1.1 million in 1999. Method This work employs a cross-sectional study using the open data published by the General Organization for Social Insurance (GOSI) on an annual basis for the years 2016 to 2021. The data from one year in each category were compared with a reference year by using the index value method and simple linear regression. Additionally, the researchers calculated the injury-to-worker ratio for each year. Aim The aim of this study is to assess the trending epidemiology of work-related injuries in Saudi Arabia from 2016 to 2021 among insured workers and compare this trend to previous studies. Result A total of 1,009 work-related deaths wererecorded over the study period, averaging 168 per year. In comparison with non-Saudi workers, the Saudi workers' shares of injuries rose from 5.3% in 2016 to 10% in 2021. Injuries in the construction sector comprised 42%-48% of all injuries, followed by the commerce sector. In 2021, the highest percentage of injuries involved service occupations (47.5%), followed by the engineering sector. Between 2016 and 2018, the most common injury cause was falls (28.5% in 2018), and from 2020 to 2021, exposure to inanimate mechanical forces caused the most injuries (46%). Conclusion The study revealed that the trend of work-related injuries had decreased during the study period, consistent with the results of similar previous studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Asiri et al.)

Background: The 2022 Monkeypox virus (Mpox) outbreak had involved multiple countries around the globe. Here, we report clinical features and outcome of human Mpox of the first cases in Saudi Arabia., Methods: We obtained records of confirmed Mpox cases in Saudi Arabia from the public electronic health information system, Health Electronic Surveillance Network (HESN) and the healthcare providers completed a de-identified structured clinical data collection form., Results: The reported seven cases were travel-related and all were males between 24 and 41 years of age (mean age + SD) was 30.14 (+ 6.69) years. Of the cases, three (43 %) had heterosexual contact and the others had other intimate encounters while traveling abroad. They presented with skin lesions (100 %), fever (86 %), and lymphadenopathy (71 %). The illness was mild to moderate, did not require antiviral medications, and lasted 7-15 days. The mean duration of skin rash (+ SD) was 10 (+ 2.68) days. Routine laboratory tests (CBC, BUN, serum electrolytes, and liver enzymes) were within normal limits, and initial screening for HIV was negative. Expanded contact tracing did not reveal secondary cases of Mpox in the community or the healthcare setting., Conclusion: The current study showed heterosexual transmission of Mpox and the clinical course was mild and non-complicated. Therefore, clinicians and public health professionals should consider Mpox among individuals presenting with skin rash especially in the context of the investigation of HIV and other sexually transmitted diseases., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Mammalian oocyte activation is initiated by intracellular calcium (Ca 2+ ) oscillations, driven by the testis-specific phospholipase C zeta (PLCζ). Sperm PLCζ analysis represents a diagnostic measure of sperm fertilisation capacity. The application of antigen unmasking/retrieval (AUM) generally enhanced the visualisation efficacy of PLCζ in mammalian sperm, but differentially affected the PLCζ profiles in sperm from different human males. It is unclear whether AUM affects the diagnosis of PLCζ in human sperm. Herein, we examined whether the application of AUM affected the correlation of PLCζ profiles with sperm parameters and fertilisation capacity. PLCζ fluorescence levels and localisation patterns were examined within the sperm of males undergoing fertility treatment (55 patients aged 29-53) using immunofluorescence in the absence/presence of AUM. The changes in PLCζ profiles following AUM were examined in relation to sperm health and fertilisation outcome. AUM enhanced the observable levels and specific localisation patterns of PLCζ in relation to both optimal sperm parameters and fertilisation outcome, without which significant differences were not observed. The extent of the change in levels and localisation ratios of PLCζ was also affected to a larger degree in terms of the optimal parameters of sperm fertility and fertilisation capacity by AUM. Collectively, AUM was essential to accurately assesses PLCζ in human sperm in both scientific and clinical contexts.

During mammalian spermatogenesis, the ubiquitin proteasome system maintains protein homoeostasis (proteastasis) and spermatogenic cellular functions. DCAF17 is a substrate receptor in the ubiquitin CRL4 E3 Ligase complex, absence of which causes oligoasthenoteratozoospermia in mice resulting in male infertility. To determine the molecular phenomenon underlying the infertility phenotype caused by disrupting Dcaf17, we performed RNA-sequencing-based gene expression profiling of 3-weeks and 8-weeks old Dcaf17 wild type and Dcaf17 disrupted mutant mice testes. At three weeks, 44% and 56% differentially expressed genes (DEGs) were up- and down-regulated, respectively, with 32% and 68% DEGs were up- and down-regulated, respectively at 8 weeks. DEGs include protein coding genes and lncRNAs distributed across all autosomes and the X chromosome. Gene ontology analysis revealed major biological processes including proteolysis, regulation of transcription and chromatin remodelling are affected due to Dcaf17 disruption. We found that Dcaf17 disruption up-regulated several somatic genes, while germline-associated genes were down-regulated. Up to 10% of upregulated, and 12% of downregulated, genes were implicated in male reproductive phenotypes. Moreover, a large proportion of the up-regulated genes were highly expressed in spermatogonia and spermatocytes, while the majority of downregulated genes were predominantly expressed in round spermatids. Collectively, these data show that the Dcaf17 disruption affects directly or indirectly testicular proteastasis and transcriptional signature in mouse., (© 2022. The Author(s).)

Purpose: After the impressive results of the 2020 Hajj management, Saudi authorities decided to expand the quota to 60,000 pilgrims in 2021, which resulted in a convenient and successful experience., Patients and Methods: This was a retrospective pre and post-study study conducted on all pilgrims attending the 2021 Hajj using the polymerase chain reaction (PCR) test surveillance with paired-swab samples (pre-Hajj and post-Hajj) to evaluate the risk potential of COVID-19 among Hajj pilgrims, the effectiveness of preventive measures and the potential effect of the Hajj ritual as a huge mass gathering on the epidemiological situation of the Saudi Arabian population., Result: Forty-one cases had positive COVID-19 infections out of a total of 58,428 pilgrims who attended the 2021 Hajj season, as detected by nonmandatory pre- and post-Hajj PCR. Notably, the 2021 Hajj season achieved a decreasing leg of the COVID-19 pandemic curve. The adjusted incidence rate in KSA from July 11th to August 7th ranged from 19 to 24 cases per 100,000 population. In contrast, the incidence rate for the same duration in Hajj ranged from 3 to 7 cases per 100,000 pilgrims., Conclusion: The Saudi mitigation plan ensured the safety of pilgrims and healthcare workers for Hajj, successfully limited the risk of COVID-19 transmission inside and contributed to global health security. The success story of Hajj in 2020 and 2021 during the pandemic represents a successful model for planning, achieving and managing future mass gatherings by integrating technology with global and national health policies and public health measures., Competing Interests: Conflicts of Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Animal and human data indicate variable effects of interferons in treating coronavirus infections according to inflammatory status and timing of therapy. In this sub-study of the MIRACLE trial (MERS-CoV Infection Treated with a Combination of Lopinavir-Ritonavir and Interferon β-1b), we evaluated the heterogeneity of treatment effect of interferon-β1b and lopinavir-ritonavir versus placebo among hospitalized patients with MERS on 90-day mortality, according to cytokine levels and timing of therapy. We measured plasma levels of 17 cytokines at enrollment and tested the treatment effect on 90-day mortality according to cytokine levels (higher versus lower levels using the upper tertile (67%) as a cutoff point) and time to treatment (≤ 7 days versus > 7 days of symptom onset) using interaction tests. Among 70 included patients, 32 received interferon-β1b and lopinavir-ritonavir and 38 received placebo. Interferon-β1b and lopinavir-ritonavir reduced mortality in patients with lower IL-2, IL-8 and IL-13 plasma concentrations but not in patients with higher levels (p-value for interaction = 0.09, 0.07, and 0.05, respectively) and with early but not late therapy (p = 0.002). There was no statistically significant heterogeneity of treatment effect according to other cytokine levels. Further work is needed to evaluate whether the assessment of inflammatory status can help in identifying patients with MERS who may benefit from interferon-β1b and lopinavir-ritonavir. Trial registration: This is a sub-study of the MIRACLE trial (ClinicalTrials.gov number, NCT02845843)., (© 2022. The Author(s).)