Awareness and Practice of Patients with Helicobacter pylori Infection Toward their Disease in the Riyadh Region, Saudi Arabia.

Objective: This study aimed to study the awareness and practice of patients with Helicobacter pylori (H. pylori) toward their disease in the Riyadh region, Saudi Arabia. Material and Methods: This is a descriptive cross-sectional community-based study, in the central region of the kingdom. The target population of this study was adult patients with H. pylori infection, and a sample of 808 Saudi and non-Saudi male and female individuals were randomly selected using an online questionnaire. A consent form was obtained from all participants. Ethical approval was obtained from the university ethics committee. Results: There were a total of 808 responses. Most participants were female (89.4%) (n = 722) and between the ages of 35 and 60 years (60.8%), and most participants had a bachelor's degree (62.4%). 53.47% of the participants have good knowledge regarding their disease. Most of the participants knew it could cause gastric and duodenal ulcers (82.5%), but they did not know the infection might cause gastric cancer (48.6%). Conclusion: The study concluded that the majority of patients with H. pylori infection (53.47%) have good knowledge regarding their disease. Additionally, many participants were aware of the symptoms associated with H. pylori. Furthermore, many participants complained about their treatment.

A Hybrid Model of In-Person and Telemedicine Diabetes Education and Care for Management of Patients with Uncontrolled Type 2 Diabetes Mellitus: Findings and Implications from a Multicenter Prospective Study.

Background: Patients with uncontrolled type 2 diabetes mellitus (T2DM) require close follow-up, support, and education to achieve glycemic control, especially during the initiation or intensification of insulin therapy and self-care management. This study aimed to describe and evaluate the impact of implementing a hybrid model of in-person and telemedicine care and education on glycemic control for patients with uncontrolled T2DM (hemoglobin A1c [HbA1c] ≥9%) during the coronavirus disease pandemic. Methods: This prospective multicenter-cohort pre-/post-intervention study was conducted on patients with uncontrolled T2DM. This study included three chronic illness centers affiliated with the Family and Community Medicine Department at Prince Sultan Military Medical City in Riyadh, Saudi Arabia. A hybrid model of in-person (onsite) and telemedicine care and education was developed. This involved implementing initial in-person care at the physicians' clinic and initial in-person education at the diabetes education clinic, followed by telemedicine services of tele-follow-ups, support, and education for an average 4-month follow-up period. Results: Of the enrolled 181 patients, more than half of the participants were women (n = 103, 56.9%). The mean age of participants (standard deviation) was 58.64 ± 11.23 years and the mean duration of diabetes mellitus was 13.80 ± 8.55 years. The majority of the patients (n = 144; 79.6%) were on insulin therapy. Overall, in all three centers, the hybrid model had significantly reduced HbA1c from 10.47 ± 1.23% to 7.87 ± 1.59% (mean difference of reduction 2.59% [95% confidence interval (CI) = 2.34-2.85%], p < 0.001). At the level of each center, HbA1c was reduced significantly with mean differences of 3.17% (95% CI = 2.81-3.53%), 2.49% (95% CI = 1.92-3.06%), and 2.16% (95% CI = 1.76-2.57%) at centers A, B, and C, respectively (all p < 0.001). Conclusion: The findings showed that the hybrid model of in-person and telemedicine care and education effectively managed uncontrolled T2DM. Consequently, the role of telemedicine in diabetes management could be further expanded as part of routine diabetes care in primary settings to achieve better glycemic control and minimize nonessential in-person visits when appropriate.

Minimally invasive sacroiliac joint fusion using triangular titanium implants versus nonsurgical management for sacroiliac joint dysfunction: a systematic review and meta-analysis.

BACKGROUND: Minimally invasive sacroiliac joint (MISIJ) fusion is a surgical option to relieve SIJ pain. The aim of this systematic review and meta-analysis was to compare MISIJ fusion with triangular titanium implants (TTI) to nonoperative management of SIJ dysfunction. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. We included prospective clinical trials that compared MISIJ fusion to nonoperative management in individuals with chronic low back pain attributed to SIJ dysfunction. We evaluated pain on visual analogue scale, Oswestry Disability Index (ODI) score, health-related quality of life (HRQoL) using the 36-Item Short Form Health Survey (SF-36) physical component (PCS) and mental component summary (MCS) scores, patient satisfaction, and adverse events. RESULTS: A total of 8 articles representing 3 trials that enrolled 423 participants were deemed eligible. There was a significant reduction in pain score with MISIJ fusion compared with nonoperative management (standardized mean difference [SMD] -1.71, 95% confidence interval [CI] -2.03 to -1.39). Similarly, ODI scores (SMD -1.03, 95% CI -1.24 to -0.81), SF-36 PCS scores (SMD 1.01, 95% CI 0.83 to 1.19), SF-36 MCS scores (SMD 0.72, 95% CI 0.54 to 0.9), and patient satisfaction (odds ratio 6.87, 95% CI 3.73 to 12.64) were significantly improved with MISIJ fusion. No significant difference was found between the 2 groups with respect to adverse events (SMD -0.03, 95% CI -0.28 to 0.23). CONCLUSION: Our analysis showed that MISIJ fusion with TTI shows a clinically important and statistically significant improvement in pain, disability score, HRQoL, and patient satisfaction with a similar adverse event profile to nonoperative management in patients with chronic low back pain attributed to SIJ dysfunction.

Medical Interns' Knowledge, Attitude, and Practice Toward People Living with HIV: Multicenter Experience from Saudi Arabia.

Background: Discrimination by some healthcare providers toward people living with HIV/AIDS has been documented. Differences in cultural backgrounds make it harder for future doctors, who need a lot of knowledge and a positive attitude to treat patients. In conservative countries like Saudi Arabia, not enough is known about how much medical interns know about HIV and how they feel about people living with HIV/AIDS. Methods: From April to September 2021, this cross-sectional study use non-probability random sampling and utilized a self-administered questionnaire to collected the data from 346 medical interns who had graduated from five different medical schools. Results: Most of the subjects correctly identified the main transmission routes, such as unprotected sex (94.57%), blood and body fluid exchange (94.19%), and sharing needles or syringes (91.47%). But they did not know what the most common co-infections were for HIV patients or how to protect themselves after exposure. This paper showed that medical interns have some stigmatizing behaviors toward patients living with HIV, as 31.1% and 22.9% agreed, respectively, that they would feel more sympathetic toward people who get AIDS from blood transfusions compared to IV drug users (IDU). Conclusion: Medical interns also showed some positive attitudes, as more than half of the sample (56.2%) would not isolate beds for people living with HIV/AIDS. The study's conclusion is that HIV education and training programs should be added for medical interns, which might have a significant positive impact on their attitude.

The Efficacy and Safety of Intra-articular Low Molecular Weight Fraction of Human Serum Albumin for the Management of Moderate to Moderately Severe Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

Osteoarthritis is a chronic degenerative joint disease that affects weight-bearing joints. Low molecular weight fraction of 5% (LMWF-5A) human serum albumin is an intra-articular injection that emerged for the treatment of knee osteoarthritis. The aim of this review is to assess the efficacy and safety of LMWF-5A versus placebo through a systematic review and meta-analysis. The Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), EBSCO, and ClinicalTrials.gov registry databases were utilized to search for studies. Only randomized controlled trials (RCTs) that evaluated the efficacy of LMWF-5A versus placebo were included. Efficacy endpoints were represented by Western Ontario and McMaster Universities Arthritis Index (WOMAC) A and C scores for pain and function, respectively. Serious adverse events (SAEs), non-serious adverse events (NSAEs), and mortality rates were used to evaluate the safety of the drug. The revised Cochrane risk of bias tool was used for the risk of bias assessment. Seven RCTs (n=2939) that met the inclusion criteria were included. The meta-analysis did not find significant improvement in pain (WOMAC A) (standardized mean difference (SMD)= -0.01, 95% confidence interval (CI) -0.10 - 0.09, P=0.87, I²=30%). Additionally, no significant change in function was noted (WOMAC C) (SMD=0.01, 95% CI -0.08 - 0.10, P=0.87, I²=22%). The pooled analysis did not find a significant difference between LMWF-5A and placebo regarding the incidence of joint swelling (P=0.84), joint stiffness (P=0.53), arthralgia (P=0.53), extremity pain (P=0.45), NSAEs (P=0.21), SAEs (P=0.92), or mortality (P=1.00). However, the subgroup analysis showed a significant reduction of 42% in NSAEs upon administration of 10 mL of LMWF-5A (risk ratio (RR)=0.58, 95% CI 0.35-0.97, P=0.04). In summary, our meta-analysis did not find significant differences between LMWF-5A and placebo regarding the incidence of NSAEs, SAEs, or mortality. On the other hand, LMWF-5A did not demonstrate superiority over saline in terms of efficacy. Therefore, it is not an effective drug for managing knee osteoarthritis.

Factors that influence a patient's decision to engage in genetic research.

Introduction: The most challenging step in clinical research studies is patient recruitment. Many research studies do not reach their targets because of participant rejection. The purpose of this study was to assess patient as well as the community knowledge, motivation, and barriers to participate in genetic research. Methods: A cross-section study was conducted between September 2018 and February 2020 using face-to-face interviews with candidate patients from outpatient clinics at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia. Additionally, an online survey was conducted to assess the community's knowledge, motivation and barriers to participate in genetic research studies. Results: In total, 470 patients were interviewed for this study, with 341 being successfully recruited for the face to face interview, and the other patients being refused owing to time constraints. The majority percentage of the respondents were females. The respondents' mean age was 30, and 52.6% reported having a college degree. The survey results from 388 participants illustrated that around 90% of the participants, participated voluntarily due to a good understanding of genetics studies. The majority held positive attitudes toward being part of genetic research, which exceeded the reported motivation score of >75%. The survey indicated that >90% of individuals were willing to participate to acquire therapeutic benefits or to receive continued aftercare. However, 54.6% of survey participants were worried about the side effects and the risks involved in genetic testing. A higher proportion (71.4%) of respondents reported that lack of knowledge about genetic research was one of the barriers to rejecting participation. Conclusion: Respondents reported relatively high motivation and knowledge for participation in genetic research. However, study participants reported "do not know enough about genetic research" and "lack of time during clinic visit" as a barrier for participation in genetic research.

Liver Injury in Favipiravir-Treated COVID-19 Patients: Retrospective Single-Center Cohort Study.

(1) Background: Favipiravir (FVP) is a new antiviral drug used to treat COVID-19. It has been authorized to be used in the kingdom of Saudi Arabia in the treatment of COVID-19. The mechanism of action of FVP is working as a specific inhibitor for the RNA-dependent RNA polymerase of the RNA chain virus. FVP has the potential to be hepatotoxic because of the structure similarity with pyrazinamide. This retrospective study aimed to determine the prevalence of liver injury in FVP-treated COVID-19 patients in General East Jeddah Hospital, Saudi Arabia, during the COVID-19 pandemic. (2) Methods: A total of 6000 patients infected with COVID-19 and treated at the East Jeddah Hospital were included, with a sample size of 362 patients. The participants ranged from 18 to 70 years of age, both males and females, with normal hepatic and renal function and had a confirmed diagnosis of COVID-19 infection. Patients who had gouty arthritis, hepatic and renal dysfunction, dead patients, pregnant women, and breastfeeding mothers were all excluded from this study. A retrospective cohort study compared two groups of patients treated with and without FVP and who followed the Saudi Ministry of Health protocol to manage COVID-19 infection. (3) Results: An adverse effect of FVP on the liver was found that ranged from mild to severe. Stopping treatment with FVP was associated with an observed important increase in the levels of liver enzymes AST (p < 0.001), ALT (p < 0.001), alkaline phosphatase (p < 0.03), total bilirubin (p < 0.001), and direct bilirubin (p < 0.001) in the treated compared with the untreated group. (4) Conclusion: This study showed a significant difference between the treated and the untreated groups with FVP in liver injury. FVP influences the liver, increasing the blood levels of the liver function parameters.

LifeStyle and Exercise Relation to Neck and Back Pain in Saudi Arabia.

BACKGROUND: Personal anguish, incapacity, and a decline in work and life quality are all associated with neck and low back pain, making it a significant socioeconomic burden for individuals and society. It is well known that engaging in regular physical exercise has considerable health benefits. OBJECTIVE: The purpose of this research was to investigate the factors contributing to the high rates of musculoskeletal pain experienced by the Saudi Arabian population. METHODS: This population-based, cross-sectional study was done in Saudi Arabia with 2,717 participants aged 18 to 60. A questionnaire was provided online to assess neck, shoulder, and lower back discomfort, time spent in general or aerobic physical activity, time spent sitting, sleep problems, general health, work satisfaction, and nutrition. Using logistic regression, we observed potential risk factors for musculoskeletal pain. RESULTS: The prevalence of neck pain, shoulder pain, and lower back pain (LBP) were found to be 48.1%, 47.6%, and 63.8%, respectively. It was found that being a female (OR=1.78 [1.41-2.25], p<0.001), married (OR=1.58 [1.34-1.86], p<0.001), and having poor general health status (OR=3.78 [2.2-6.49], p<0.001), sleep disturbances (OR=2.46 [2.04-2.97], p<0.001) and poor job satisfaction (OR=1.29 [1.05-1.60], p=0.016) were independently associated with the prevalence of musculoskeletal pain. The diet of the individuals did not significantly influence the prevalence of MSPs. CONCLUSION: Good general health, good sleep, and good job satisfaction were associated with a reduced risk of experiencing neck or shoulder pain, but there was no association between physical activity and MSPs Longitudinal studies are required to acquire a better understanding of the relationship between MSP, aerobic activity, sleep, and diet.

Clinicopathologic and genomic characterizations of brain metastases using a comprehensive genomic panel.

Central nervous system (CNS) metastasis is the most common brain tumor type in adults. Compared to their primary tumors, these metastases undergo a variety of genetic changes to be able to survive and thrive in the complex tissue microenvironment of the brain. In clinical settings, the majority of traditional chemotherapies have shown limited efficacy against CNS metastases. However, the discovery of potential driver mutations, and the development of drugs specifically targeting affected signaling pathways, could change the treatment landscape of CNS metastasis. Genetic studies of brain tumors have so far focused mainly on common cancers in western populations. In this study, we performed Next Generation Sequencing (NGS) on 50 pairs of primary tumors, including but not limited to colorectal, breast, renal and thyroid tumors, along with their brain metastatic tumor tissue counterparts, from three different local tertiary centers in Saudi Arabia. We identified potentially clinically relevant mutations in brain metastases that were not detected in corresponding primary tumors, including mutations in the PI3K, CDK, and MAPK pathways. These data highlight the differences between primary cancers and brain metastases and the importance of acquiring and analyzing brain metastatic samples for further clinical management.

The impact of malocclusion on the oral health related quality of life of 11-14-year-old children.

BACKGROUND: The relationship between malocclusion and the oral health related quality of life (OHRQoL) of children needs to be explored further as existing literature presents conflicting evidence. This study aims to determine the association between malocclusion and OHRQoL of 11-14-year-old children. METHODS: This cross-sectional study was conducted among 250 caregiver/child dyads seeking orthodontic consultation at a tertiary care hospital. The OHRQoL was assessed using child perception questionnaire for 11-14-year-old children (CPQ11-14) and the severity of malocclusion was assessed using the Dental Aesthetic Index (DAI). CPQ11-14 scores ranged from 0 to 64, with lower scores representing better quality of life. Analysis of variance (ANOVA) was used to assess differences between domain and total CPQ11-14 scores. RESULTS: The mean CPQ11-14 score was 19.89 ± 9.8. Mean scores for the oral symptoms, functional limitations, emotional well-being, and social well-being domains were 5.26 ± 3.22, 3.67 ± 3.58, 3.98 ± 3.89 and 2.08 ± 2.98, respectively. Normal or slight malocclusion was seen in 37.6%, definite malocclusion was seen in 22.4%, severe malocclusion in 15.2% and handicapping malocclusion in 24.8% of the subjects. In comparisons by pairs, it was found that children with handicapping malocclusion had significantly (p < 0.05) higher scores for the social well-being domain as compared with children having normal/minor malocclusion, indicating a poorer quality of life. CONCLUSION: Handicapping malocclusion had a significant negative impact on the social well-being domain of OHRQoL among 11-14-year-old children in this population.

Landscape of somatic mutations in breast cancer: new opportunities for targeted therapies in Saudi Arabian patients.

Breast cancer (BCa) ranks first in incidence rate among cancers in Arab females. The association between genetic polymorphisms in tumor suppressor genes and the risk of BCa has been studied in many ethnic populations with conflicting conclusions while Arab females and Saudi Arabian studies are still lacking. We screened a cohort of Saudi BCa patients by NGS using a bespoke gene panel to clarify the genetic landscape of this population, correlating and assessing genetic findings with clinical outcomes. We identified a total of 263 mutations spanning 51 genes, including several frequently mutated. Among the genes analyzed, the highest mutation rates were found in PIK3CA (12.9%), BRCA2 (11.7%), BRCA1 (10.2%), TP53 (6.0%), MSH2 (3.8%), PMS2 (3.8%), BARD1 (3.8%), MLH1 (3.4%), CDH1 (3.0%), RAD50 (3.0%), MSH6 (3.0%), NF1 (2.6%), in addition to others. We identified multiple common recurrent variants and previously reported mutations. We also identified 46 novel variants in 22 genes that were predicted to have a pathogenic effect. Survival analysis according to the four most common mutations (BRCA1, BRCA2, TP53, and PIK3CA) showed reduced survival in BRCA1 and BRCA2-mutant patients compared to total patients. Moreover, BRCA2 was demonstrated as an independent predictor of reduced survival using independent Cox proportional hazard models. We reveal the landscape of the mutations associated with BCa in Saudi women, highlighting the importance of routine genetic sequencing in implementation of precision therapies in KSA.

Methylation Profiling of Medulloblastoma in a Clinical Setting Permits Sub-classification and Reveals New Outcome Predictions.

Medulloblastoma (MB) is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. DNA methylation profiling has rapidly advanced our understanding of MB pathogenesis at the molecular level, but assessments in Saudi Arabian (SA)-MB cases are sparse. MBs can be sub-grouped according to methylation patterns from FPPE samples into Wingless (WNT-MB), Sonic Hedgehog (SHH-MB), Group 3 (G3), and Group 4 (G4) tumors. The WNT-MB and SHH-MB subgroups are characterized by gain-of function mutations that activate oncogenic cell signaling, whilst G3/G4 tumors show recurrent chromosomal alterations. Given that each subgroup has distinct clinical outcomes, the ability to subgroup SA-FPPE samples holds significant prognostic and therapeutic value. Here, we performed the first assessment of MB-DNA methylation patterns in an SA cohort using archival biopsy material (FPPE n = 49). Of the 41 materials available for methylation assessments, 39 could be classified into the major DNA methylation subgroups (SHH, WNT, G3, and G4). Furthermore, methylation analysis was able to reclassify tumors that could not be sub-grouped through next-generation sequencing, highlighting its superior accuracy for MB molecular classifications. Independent assessments demonstrated known clinical relationships of the subgroups, exemplified by the high survival rates observed for WNT tumors. Surprisingly, the G4 subgroup did not conform to previously identified phenotypes, with a high prevalence in females, high metastatic rates, and a large number of tumor-associated deaths. Taking our results together, we demonstrate that DNA methylation profiling enables the robust sub-classification of four disease sub-groups in archival FFPE biopsy material from SA-MB patients. Moreover, we show that the incorporation of DNA methylation biomarkers can significantly improve current disease-risk stratification schemes, particularly concerning the identification of aggressive G4 tumors. These findings have important implications for future clinical disease management in MB cases across the Arab world.

Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia.

Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers and clinical outcomes. The treatment modality dictates the outcome and optimizing patient management can be challenging. In this study, we profiled a targeted panel of cancer-related genes in 37 Saudi Arabian patients with pLGGs to identify genetic abnormalities that can inform prognostic and therapeutic decision-making. We detected genetic alterations (GAs) in 97% (36/37) of cases, averaging 2.51 single nucleotide variations (SNVs) and 0.91 gene fusions per patient. The KIAA1549-BRAF fusion was the most common alteration (21/37 patients) followed by AFAP1-NTRK2 (2/37) and TBLXR-PI3KCA (2/37) fusions that were observed at much lower frequencies. The most frequently mutated) genes were NOTCH1-3 (7/37), ATM (4/37), RAD51C (3/37), RNF43 (3/37), SLX4 (3/37) and NF1 (3/37). Interestingly, we identified a GOPC-ROS1 fusion in an 8-year-old patient whose tumor lacked BRAF alterations and histologically classified as low grade glioma. The patient underwent gross total resection (GTR). The patient is currently disease free. To our knowledge this is the first report of GOPC-ROS1 fusion in PLGG. Taken together, we reveal the genetic characteristics of pLGG patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG.

New insights into the genomic landscape of meningiomas identified FGFR3 in a subset of patients with favorable prognoses.

Background: With a prevalence of 170 000 adults in the US alone, meningiomas are the most common primary intracranial tumors. The management of skull base meningiomas is challenging due to their complexity and proximity to crucial nearby structures. The identification of oncogenic mutations has provided further insights into the tumorigenesis of meningioma and the possibility of targeted therapy. This study aimed to further investigate the association of mutational profiles with anatomical distribution, histological subtype, WHO grade, and recurrence in patients with meningioma. Methods: Tissue samples were collected from 71 patients diagnosed with meningioma from 2008 to 2016. A total of 51 cases were skull based. Samples were subjected to targeted sequencing using a next generation customized cancer gene panel (n = 66 genes analyzed). Results: We detected genomic alterations (GAs) in 68 tumors, averaging 1.56 ± 1.07 genomic alterations (GAs) per sample. NF2 was the most frequently altered gene (36/71 cases). Interestingly, we identified a number of mutations in non-NF2 genes, including a hotspot TERTp c.-124: G > A mutation that may be related to poor prognosis and FGFR3 mutations that may represent biomarkers of a favorable prognosis as reported in other cancers. Conclusions: We demonstrate that comprehensive genomic profiling in our population can reveal a potential new prognostic biomarkers of skull base meningioma. These mutations can enhance diagnostic accuracy and clinical decision-making. Among our findings were the identification of a TERTp mutation and the first report of FGFR3 mutations that may represent biomarkers for the identification of skull base meningioma patients with a favorable prognosis.

Rare TP53 variant associated with Li-Fraumeni syndrome exhibits variable penetrance in a Saudi family.

Li-Fraumeni syndrome (LFS) is an inherited, autosomal-dominant condition that predisposes individuals to a wide-spectrum of tumors at an early age. Approximately 70% of families with classic LFS have pathogenic variants in the tumor suppressor gene TP53 that disrupt protein function or stability. While more than 70% of pathogenic variants in TP53 are missense variants, the vast majority occur very infrequently, and thus their clinical significance is uncertain or conflicting. Here, we report an extremely rare TP53 missense variant, c.799C > T (p.Arg267Trp), identified in a 2-year-old Saudi proband diagnosed with choroid plexus carcinoma (CPC) and six of his first- and second-degree relatives. CPC is frequently found in families with LFS, and this is the first detailed report of a family with this variant. Intriguingly, the proband's father is homozygous for TP53 c.799C > T and phenotypically normal at 39 years of age. While loss of TP53 heterozygosity is often observed in tumors from individuals with LFS, homozygous germline TP53 pathogenic variants are rare. Based on our analysis of this single family, we hypothesize that TP53 c.799C > T has low or variable penetrance for LFS, with predisposition to the development of CPC. The observations from this family have furthered our understanding of the phenotypic variability that may be caused by one variant of TP53, even in the same family, and suggest that other factors (genetic and/or environmental) may play a role in mechanism of disease manifestation in LFS.

Durable Response to Nivolumab in a Pediatric Patient with Refractory Glioblastoma and Constitutional Biallelic Mismatch Repair Deficiency.

Primary brain tumors are a leading cause of cancer-related morbidity and mortality in children. Glioblastoma (GBM) is a high-grade astrocytoma that occurs in both children and adults and is associated with a poor prognosis. Despite extensive study in recent years, the clinical management of these tumors has remained largely unchanged, consisting of surgical resection, conventional chemotherapy, and radiotherapy. Although the etiology and genomic drivers in GBM are diverse, constitutional mismatch repair-deficiency (CMMRD) syndrome is a rare, recessively inherited disease with a predisposition to gliomagenesis. CMMRD results from biallelic mutations in one of the mismatch repair genes including mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and post-meiotic segregation increased 2 (PMS2). In this report, we present the case of a 5-year-old female with GBM and CMMRD due to an MSH6 homozygous c.1883G>A mutation, who continues to experience an exceptional and durable response (9 months) to the immune checkpoint inhibitor (ICPI) nivolumab. Our patient presented with acute neurologic decline and increased intracranial pressure. Neuroimaging studies revealed a large left frontoparietal mass requiring neurosurgical decompression and resection. Histopathologic analyses resulted in a diagnosis of de novo GBM that was BRAF wild type and negative for programmed death-ligand 1 protein expression. She received standard-of-care treatment with surgery, radiation therapy, and temozolomide; however, the tumor recurred 3 months after the initial diagnosis. Molecular analyses of tumor and blood tissues revealed an MSH6 homozygous c.1883G>A mutation consistent with CMMRD. Given her CMMRD status, she was treated with nivolumab (3 mg/kg doses every 2 weeks for 36 weeks) and showed a 60% reduction in tumor size, improved clinical symptoms, and an ongoing durable response lasting 10 months to date. Our study highlights a durable response to the ICPI nivolumab in a pediatric patient with recurrent/refractory CMMRD-associated GBM. We show that incorporating genomic and/or molecular testing for CMMRD into routine pediatric oncology clinical care can identify a subset of patients likely to benefit from ICPI. KEY POINTS: Constitutional mismatch repair-deficiency (CMMRD) syndrome, alternatively known as biallelic mismatch repair deficiency syndrome, occurs in subset of pediatric cancer patients, including those with primary brain tumors.Patients from Arab and other developing countries are predicted to have higher incidence of CMMRD due to high prevalence of consanguinity.Integration of molecular and/or genomic testing into routine clinical care for pediatric cancer patients is important to identify patients with CMMRD syndrome.Patient with CMMRD-associated cancers may show increased responsiveness to immune checkpoint inhibitors.To the authors' knowledge, this is the first report in the Arab world of a durable response to immune checkpoint inhibitors in a pediatric glioblastoma patient.