Treatment Patterns and Recommendations for Improving the Management of Hepatocellular Carcinoma in Saudi Arabia.

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer in the world associated with high morbidity and mortality. Despite being a significant healthcare burden there is limited information on the unmet needs and current treatment practices for intermediate and advanced-stage HCC in Saudi Arabia. This article analyzes the gaps and provides expert consensus on the management strategies for unresectable HCC in Saudi Arabia. A pre-meeting online questionnaire, comprising 20 objective questions about the treatment landscape and diagnosis of HCC in Saudi Arabia, was distributed to experts in the field of HCC management. An advisory board meeting including a panel of 13 experts was held in September 2022 where the responses to the survey questionnaire were reviewed and discussed. The survey results and experts' discussion highlighted the growing incidence of liver cancer in Saudi Arabia. HCC comprised the majority of all liver cancer cases due to rising rates of chronic viral infections and lifestyle-related risk factors. Most physicians in Saudi Arabia follow the Barcelona Clinic Liver Cancer guidelines as a prognostic tool for the detection and staging of patients with HCC. Most of the patients with HCC in Saudi Arabia are diagnosed in the intermediate or advanced stages with poor prognoses and limited therapeutic options. Establishing evidence-based surveillance techniques, a multidisciplinary approach to diagnosis, and better accessibility of treatment options is vital for the management of HCC in Saudi Arabia.

ACE2-Fc and DPP4-Fc decoy receptors against SARS-CoV-2 and MERS-CoV variants: a quick therapeutic option for current and future coronaviruses outbreaks.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the Middle East respiratory syndrome coronavirus (MERS-CoV) are highly pathogenic human coronaviruses (CoVs). Anti-CoVs mAbs and vaccines may be effective, but the emergence of neutralization escape variants is inevitable. Angiotensin-converting enzyme 2 and dipeptidyl peptidase 4 enzyme are the getaway receptors for SARS-CoV-2 and MERS-CoV, respectively. Thus, we reformatted these receptors as Fc-fusion decoy receptors. Then, we tested them in parallel with anti-SARS-CoV (ab1-IgG) and anti-MERS-CoV (M336-IgG) mAbs against several variants using pseudovirus neutralization assay. The generated Fc-based decoy receptors exhibited a strong inhibitory effect against all pseudotyped CoVs. Results showed that although mAbs can be effective antiviral drugs, they might rapidly lose their efficacy against highly mutated viruses. We suggest that receptor traps can be engineered as Fc-fusion proteins for highly mutating viruses with known entry receptors, for a faster and effective therapeutic response even against virus harboring antibodies escape mutations.

Vaccines and therapeutics for immunocompromised patients with COVID-19.

The COVID-19 pandemic has disproportionately impacted immunocompromised patients. This diverse group is at increased risk for impaired vaccine responses, progression to severe disease, prolonged hospitalizations and deaths. At particular risk are people with deficiencies in lymphocyte number or function such as transplant recipients and those with hematologic malignancies. Such patients' immune responses to vaccination and infection are frequently impaired leaving them more vulnerable to prolonged high viral loads and severe complications of COVID-19. Those in turn, have implications for disease progression and persistence, development of immune escape variants and transmission of infection. Data to guide vaccination and treatment approaches in immunocompromised people are generally lacking and extrapolated from other populations. The large clinical trials leading to authorisation and approval of SARS-CoV-2 vaccines and therapeutics included very few immunocompromised participants. While experience is accumulating, studies focused on the special circumstances of immunocompromised patients are needed to inform prevention and treatment approaches.

SARS-CoV-2 Reinfection Rate and Outcomes in Saudi Arabia: A National Retrospective Study.

BACKGROUND: The characterization of reinfection with SARS-CoV-2 has been a subject of concern and controversy, especially with the surge of infections with highly transmissible variants worldwide. METHODS: This retrospective national study used comorbidities, vaccination status, SARS-CoV-2 variants of concern, and demographics data to profile participants who were reinfected with SARS-CoV-2, defined as having two reverse transcriptase-polymerase chain reaction-positive SARS-CoV-2 tests within at least 90 days apart. A multivariate logistic regression model assessed the risk factors associated with reinfection . Two control groups were selected: nonreinfected participants reporting a positive test (control group one) and those reporting a negative test (control group two). RESULTS: Between March 2020 and December 2021, 4454 reinfected participants were identified in Saudi Arabia (0.8%, 95% confidence interval [CI] 0.7-0.8). The majority (67.3%) were unvaccinated (95% CI 65.9-68.7) and 0.8% (95% CI 0.6-1.1) had severe or fatal SARS-CoV-2 disease. COVID-19 vaccines were 100% effective against mortality in reinfected individuals who received at least one dose, whereas it conferred 61% (odds ratio [OR] 0.4, 95% CI 0.1-1.0) additional protection against severe disease after the first dose and 100% after the second dose. In the risk factor analysis, reinfection was highly associated with comorbidities, such as HIV (OR 2.5, 95% CI 1.3-5.2; P = 0.009), obesity (OR 2.3, 95% CI 1.3-3.9; P = 0.003), pregnancy (OR 3.2, 95% CI 1.4-7.4; P = 0.005), and working in health care facilities (OR 6.1, 95% CI 3.1-12.9; P <0.0001). The delta variant (B.1.617.2) was the most frequent variant of concern among the reinfected cohort. CONCLUSION: This in-depth study of the reinfection profile identified risk factors and highlighted the associated SARS-CoV-2 variants. Results showed that naturally acquired immunity to SARS-CoV-2 through multiple reinfections together with vaccine-induced immunity provided substantial protection against severe SARS-CoV-2 disease and mortality.

Achieving global equity for COVID-19 vaccines: Stronger international partnerships and greater advocacy and solidarity are needed.

Peter Figueroa and co-authors advocate for equity in the worldwide provision of COVID-19 vaccines.

Synthetic SARS-CoV-2 Spike-Based DNA Vaccine Elicits Robust and Long-Lasting Th1 Humoral and Cellular Immunity in Mice.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) calls for an urgent development of effective and safe prophylactic and therapeutic measures. The spike (S) glycoprotein of severe acute respiratory syndrome-coronavirus (SARS-CoV-2) is a major immunogenic and protective protein and plays a crucial role in viral pathogenesis. In this study, we successfully constructed a synthetic codon-optimized DNA-based vaccine as a countermeasure against SARS-CoV-2, denoted VIU-1005. The design was based on a codon-optimized coding sequence of a consensus full-length S glycoprotein. The immunogenicity of the vaccine was tested in two mouse models (BALB/c and C57BL/6J). Th1-skewed systemic S-specific IgG antibodies and neutralizing antibodies (nAbs) were significantly induced in both models 4 weeks after three injections with 100 µg of the VIU-1005 vaccine via intramuscular needle injection but not intradermal or subcutaneous routes. Such immunization induced long-lasting IgG and memory T cell responses in mice that lasted for at least 6 months. Interestingly, using a needle-free system, we showed an enhanced immunogenicity of VIU-1005 in which lower or fewer doses were able to elicit significantly high levels of Th1-biased systemic S-specific immune responses, as demonstrated by the significant levels of binding IgG antibodies, nAbs and IFN-γ, TNF and IL-2 cytokine production from memory CD8+ and CD4+ T cells in BALB/c mice. Furthermore, compared to intradermal needle injection, which failed to induce any significant immune response, intradermal needle-free immunization elicited a robust Th1-biased humoral response similar to that observed with intramuscular immunization. Together, our results demonstrate that the synthetic VIU-1005 candidate DNA vaccine is highly immunogenic and capable of inducing long-lasting Th1-skewed humoral and cellular immunity in mice. Furthermore, we show that the use of a needle-free system could enhance the immunogenicity and minimize doses needed to induce protective immunity in mice, supporting further preclinical and clinical testing of this candidate vaccine.

Global public health security and justice for vaccines and therapeutics in the COVID-19 pandemic.

A Lancet Commission for COVID-19 task force is shaping recommendations to achieve vaccine and therapeutics access, justice, and equity. This includes ensuring safety and effectiveness harmonized through robust systems of global pharmacovigilance and surveillance. Global production requires expanding support for development, manufacture, testing, and distribution of vaccines and therapeutics to low- and middle-income countries (LMICs). Global intellectual property rules must not stand in the way of research, production, technology transfer, or equitable access to essential health tools, and in context of pandemics to achieve increased manufacturing without discouraging innovation. Global governance around product quality requires channelling widely distributed vaccines through WHO prequalification (PQ)/emergency use listing (EUL) mechanisms and greater use of national regulatory authorities. A World Health Assembly (WHA) resolution would facilitate improvements and consistency in quality control and assurances. Global health systems require implementing steps to strengthen national systems for controlling COVID-19 and for influenza vaccinations for adults including pregnant and lactating women. A collaborative research network should strive to establish open access databases for bioinformatic analyses, together with programs directed at human capacity utilization and strengthening. Combating anti-science recognizes the urgency for countermeasures to address a global-wide disinformation movement dominating the internet and infiltrating parliaments and local governments.

Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1.

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

Epidemiology of Pancreatic Cancer in Saudi Arabia: A Retrospective Analysis of Pancreatic Cancer Diagnosed in Saudi Arabia Between 2004 and 2015.

PURPOSE: Over the last decades, the incidence of pancreatic cancer has increased, particularly in countries with a higher socioeconomic status. The present work aimed to provide detailed epidemiological data on the incidence of pancreatic cancer in Saudi Arabia. PATIENTS AND METHODS: In this retrospective descriptive study, the epidemiological data on pancreatic cancer cases diagnosed in 13 administrative regions of Saudi Arabia between January 2004 and December 2015 were extracted from the Saudi Cancer Registry. The frequency, the crude incidence rate (CIR), and the age-standardized incidence rate (ASIR), stratified by geographical region, gender, and the year of diagnosis, were analyzed. RESULTS: From January 2004 to December 2015, a total of 2338 cases of pancreatic cancer were registered, including 1443 males and 895 females. The overall CIR was 1.28/100,000 among males and 0.80/100,000 in females, with an overall ASIR of 2.26 and 1.41/100,000 for males and females, respectively. Higher ASIR and CIR were observed among males than females (ratio 1.6). In both genders, the ASIR of pancreatic cancer increased with increasing age, with the highest incidence in patients aged 70 years or more. The ASIR in the Eastern Region (3.2/100,000) and the regions of Riyadh (3.0/100,000) and Tabuk (2.6/100,000) proved to be significantly higher than in the other regions of the country. Among women, the ASIR was significantly higher in Riyadh (2.3/100,000), the northern region (2.2/100,000), and Tabuk (2.0/100,000). CONCLUSION: This study revealed a slight increase of the CIR and ASIR of pancreatic cancer among males and females of the Saudi population. Eastern region, Riyadh, and Tabuk had the highest overall ASIRs of pancreatic cancer among males, Riyadh, Northern region, and Tabuk among Saudi females. The area least affected by pancreatic cancer was observed in Jazan among male and female Saudis. The rates of pancreatic cancer in Saudi Arabia were significantly higher among males compared with female Saudis. Further analytical studies are needed to identify the potential risk factors for pancreatic cancer among the Saudi population.

Validating candidate biomarkers for different stages of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic condition caused by the accumulation of fat in the liver. NAFLD may range from simple steatosis to advanced cirrhosis, and affects more than 1 billion people around the world. To date, there has been no effective treatment for NAFLD. In this study, we evaluated the expression of 4 candidate NAFLD biomarkers to assess their possible applicability in the classification and treatment of the disease.Twenty-six obese subjects, who underwent bariatric surgery, were recruited and their liver biopsies obtained. Expression of 4 candidate biomarker genes, PNPLA3, COL1A1, PPP1R3B, and KLF6 were evaluated at gene and protein levels by RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively.A significant increase in the levels of COL1A1 protein (P = .03) and PNPLA3 protein (P = .03) were observed in patients with fibrosis-stage NAFLD compared to that in patients with steatosis-stage NAFLD. However, no significant differences were found in abundance of PPP1R3B and KLF6 proteins or at the gene level for any of the candidate.This is the first study, to our knowledge, to report on the expression levels of candidate biomarker genes for NAFLD in the Saudi population. Although PNPLA3 and PPP1R3B had been previously suggested as biomarkers for steatosis and KLF6 as a possible marker for the fibrosis stage of NAFLD, our results did not support these findings. However, other studies that had linked PNPLA3 to fibrosis in advanced NAFLD supported our current finding of high PNPLA3 protein in patients with fibrosis. Additionally, our results support COL1A1 protein as a potential biomarker for the fibrosis stage of NAFLD, and indicate its use in the screening of patients with NAFLD. Further studies are required to validate the use of COL1A1 as a biomarker for advanced NAFLD in a larger cohort.

Preparedness and response to COVID-19 in Saudi Arabia: Building on MERS experience.

Nearly four months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 2.3 million confirmed cases and more than 160,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In Saudi Arabia, unprecedented precautionary strict measures were applied to prevent virus entry to the country or to mitigate its impact when it arrives. Here, we review the response of Saudi Arabia to COVID-19 pandemic and how did the experience learned from the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic since 2012 has helped the country to be better prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.

Prevalence of biopsy-proven nonalcoholic fatty liver among patients with gallstone disease.

BACKGROUND/AIM: Gallstone disease (GD) and nonalcoholic fatty liver disease (NAFLD) are associated with metabolic syndrome. Despite the benign nature of NAFLD, 10% of patients may develop advanced fibrosis and cirrhosis. We aimed to identify the prevalence and factors associated with NAFLD among GD patients in the Saudi population. PATIENTS AND METHODS: This is a single-center, observational cohort study that included patients seen in general surgery clinics at our institution from 2011 to 2017. All liver biopsies were taken at the same time as the cholecystectomy. Demographical and clinical data were prospectively collected from the study population. RESULTS: Of the 301 GD patients in the study, 15% had a normal body mass index (BMI), 29% were overweight, and 56% were obese. There were 143 (47.8%) patients with NAFLD, of which 125 (41.8%) showed steatosis and 18 (6%) had nonalcoholic steatohepatitis. There was a significant positive correlation between NAFLD and age (r = 0.243; P < 0.0001), and BMI (r = 0.242; P < 0.0001). Obese patients with BMI 30-40 kg/m[2] were 2.403 (P = 0.039) more likely to have NAFLD compared with normal BMI patients, and this value increased to 6.145 (P = 0.002) in patients with BMI >40 kg/m[2]. Additionally, patients with T2DM were 2.839 times (P = 0.015) more likely to have NAFLD compared with those who did not. CONCLUSIONS: The prevalence of NAFLD among GD patients is high. High BMI and diabetes are independent factors associated with NAFLD in GD patients. The results suggest that there may be a need for routine liver biopsy in selected patients during cholecystectomy.

Pancreatic tuberculosis in immunocompetent patients. At the University Hospital in Kingdom of Saudi Arabia.

OBJECTIVES: To raise awareness of practitioners on benign treatable conditions such as pancreatic tuberculosis (TB). Methods: A retrospective study at King Khaled University Hospital, Riyadh, Saudi Arabia of all patient charts presented with pancreatic mass for a period of 10 years (2007-2017) with a study duration of 4 years between 2013 and 2017. Patients with confirmed diagnosis of pancreatic cancer were excluded. A written ethical approval was obtained accordingly. Results: All adult patient charts were retrospectively reviewed with a pancreatic mass for a period of 10 years (2007-2017). Nine patients were identified with proven diagnosis of TB. The data were obtained based on demographic features, sign and symptoms, duration of illness, imaging, ultrasound, contrast enhanced computed tomography scan, cytology or histopathology, polymerase chain reaction, culture and follow up with anti-tuberculous therapy and samples for cytology or histology. The histological findings of granuloma with caseation or positive culture were used confirming the diagnosis of TB. All patients were immunocompetent and screened for human immunodeficiency viruses before starting anti-TB treatment. Results were negative. All patients who underwent fine needle aspiration (FNA) and endoscopic ultrasound (EUS) for suspicious pancreatic mass were provided trial of antibiotics as cases of pancreatic tuberculosis showed dramatic improvement during follow up and cured from the disease. Conclusion: The EUS and FNA are good tools to confirm malignancy and rule out benign treatable conditions like TB for any patient with a pancreatic mass suspicious for carcinoma.

Comparison study between open and laparoscopic liver resection in a Saudi tertiary center.

OBJECTIVES: To compare King Saud University Medical City experience in laparoscopic liver resection with our previously established database for open resections. METHODS: A retrospective study was conducted at King Saud University Medical City, Riyadh, Saudi Arabia. All adult patients who underwent liver resection from 2006 to 2017 were included. Patients who had their procedure converted to open were excluded. RESULTS: Among the 111 liver resections included, 22 (19.8%) were performed laparoscopically and 89 (80.1%) were performed using the open technique. Malignancy was the most common indication in both groups (78.5%). The mean operative time was 275 min (SD 92.2) in the laparoscopic group versus 315 min (SD 104.3) in the open group. Intraoperative blood transfusion was required in the laparoscopic (9%) and open groups (31.4%). The morbidity rate was 13.6% in the laparoscopic group and 31.4% in the open group, and the mortality rate was 0% in the laparoscopic group and 5.6% in the open group. CONCLUSION: Laparoscopic liver resection appears to be a safe technique and can be performed in various benign and malignant cases.

Transient liver dysfunction increases surgical site infections after coronary surgery.

Background Surgical site infections can have a significant impact on cardiac surgical outcome. The liver plays an important role in infection prevention. This study aimed to retrospectively determine whether transient postoperative liver dysfunction after coronary bypass surgery increased surgical site infections. Methods A modified version of the Schindl scoring scale for liver dysfunction was adapted to objectively quantify transient liver dysfunction in the first 7 days after on-pump coronary artery bypass grafting. A retrospective analysis of clinical outcomes at 30 months postoperatively was performed on data of 575 patients who underwent coronary artery bypass between 2014 and 2016. The patients were categorized into a liver dysfunction group (Schindl score ≥ 4) and a non-liver dysfunction group (Schindl score < 4). Results The liver dysfunction group (47.3%) had significantly more patients who were obese, current smokers, and had diabetes, renal impairment, and peripheral vascular disease. Surgical site infections occurred predominantly in the liver dysfunction group (12.1% vs. 0.3%, p < 0.001). The independent predictors of surgical site infection were liver dysfunction, body mass index > 30 kg m-2, and coronary bypass surgery combined with other cardiac procedures. Conclusions Surgical wound infections can be precipitated by multiple factors before, during, and after coronary bypass surgery. Transient liver dysfunction in the perioperative period is associated with an increased rate of surgical infections even after adjusting for known risk factors. Considering this factor as well as other known risks may help to identify and stratify patients with a potentially higher risk of surgical site infections.