Economics of primary healthcare: cost estimation of clinical services at primary care facilities in the six countries of the Gulf Cooperation Council.

OBJECTIVE: While the Gulf Cooperation Council (GCC) countries have demonstrated a strong commitment to strengthening primary healthcare (PHC), the costs of delivering these services in this region remain relatively unexplored. Understanding the costs of PHC delivery is essential for effective resource allocation and health system efficiency. DESIGN: We used an ingredient-based method to estimate the cost of delivering a selection of services at PHC facilities in the six GCC countries in 2019. Services were categorised into eight programmes: immunisation; non-communicable diseases (NCDs); oral and dental care; child health; nutrition; mental health; reproductive, maternal, neonatal and child health and general practice. The cost estimation focused on two key ingredients: the costs of drugs and supplies and the healthcare workforce cost. The coverage rates of specific types of health services, including screening and mental health services, were also estimated. Data for the analysis were obtained from ministries of health, health statistics reports, online databases, national surveys and scientific literature. RESULTS: The estimated costs of delivering the selected services at public PHC facilities in the six GCC countries totalled US$5.7 billion in 2019, representing 0.34% of the combined 2019 GDP. The per capita costs varied from US$69 to US$272. General practice and NCD programmes constituted 79% of the total costs modelled while mental health ranged between 0.0% and 0.3%. Over 8 million individuals did not receive NCD screening services, and over 30 million did not receive needed mental health services in public PHC facilities across the region. CONCLUSIONS: To our knowledge, this is the first study to estimate the costs of services delivered at PHC facilities in the GCC countries. Identifying the main cost drivers and the services which individuals did not receive can be used to help strengthen PHC to improve efficiency and scale up needed services for better health outcomes.

The portrayal of antimicrobial resistance in Bangladeshi newspapers during 2010-2021: Toward understanding the narrative.

BACKGROUND: Antimicrobial resistance (AMR) is a major global public health crisis and around the last decade, newspapers were one of the main sources of public dissemination of information for so. This study highlights how Bangladeshi mainstream newspapers represented AMR-related news and how they created the narrative of AMR in Bangladesh. METHODS: We conducted both quantitative and qualitative content analysis on 275 AMR-related news articles published in the twelve highest circulated dailies (January 2010 to September 2021). We divided the articles into report, opinion, and editorials and analyzed how their contents built the narrative of AMR in Bangladesh. RESULTS: Bangladeshi newspapers reported misuse of antibiotics by the consumers the most (32.2%), followed by selling without prescriptions (29%), and over-prescription by the health providers (26.1%). There were hardly any news reports describing the impact of pharmaceutical companies in prescribing and selling antibiotics. Around 45% of the news articles were event-oriented. Moreover, they suggested inadequate recommendations to battle AMR. CONCLUSION: Valid, consistent, and reliable AMR news coverage can play a crucial role in creating mass awareness, making providers accountable, and supporting national action plan in mitigating AMR threat. The Bangladeshi journalists interested in reporting AMR-issues should focus on disseminating more Bangla articles with scientific information, and reporting causes and recommendations responsibly.

Evaluating empathy level amongst the dental students using jefferson scale of physician empathy- health professional students.

BACKGROUND: Empathy is described as one's ability to perceive and apprehend another person's feelings, situation, emotions, and problems as their own. Empathetic behavior increases patients' satisfaction, reduces discomfort, and helps with patient's satisfaction. OBJECTIVE: To evaluate the psychometric properties of the Jefferson Empathy Scale and compare the measure of invariance within genders and amongst the public and private sector dental students. METHOD: This cross-sectional study utilized JSE-HPS version for research purpose. An exploratory factor analysis was performed to detect underlying factors. Reliability of the study tool was evaluated using Cronbach alpha test. Mann Whitney U test was used to compare the differences in scores between genders and among public and private university students while Student's t analysis compared the scores according to different domains. The level of significance was ≤ 0.05. RESULTS: Females demonstrated higher empathy levels (88.52 ± 14.19) along with private institute students (88.46 ± 13.98). Perspective taking and compassionate care domain was also scored highest by the females (31.73 ± 6.49 & 29.31 ± 6.22) and among second year students (33.30 ± 7.11 & 30.50 ± 7.16). PCA analysis extracted 4 factors namely (i) Health-care-provider's sense of humor contributed to improved outcome (ii) Health-care provider's understanding of patients' feelings and of their families influences treatment outcomes (iii) Understanding body language is as important as verbal communication and (iv) Patients feel better when their feelings are understood, which accounted for the 59.51% of the total variance. CONCLUSION: The findings revealed that students from private institute and females demonstrated higher empathy score. Moreover, the Jefferson Scale of Empathy (JSE) was found to be a reliable and validated tool for assessment of empathy in our sample population.

Vagus nerve stimulation alleviates cardiac dysfunction and inflammatory markers during heart failure in rats.

Vagus nerve stimulation (VNS) is under clinical investigation as a therapy for heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate its therapeutic effects on three main components of heart failure: cardiac function, cardiac remodeling and central neuroinflammation using a pressure overload (PO) rat model. Male Sprague-Dawley rats were divided into four groups: PO, PO + VNS, PO + VNS sham, and controls. All rats, except controls, underwent a PO surgery to constrict the thoracic aorta (~50 %) to induce HFrEF. Open loop VNS therapy was continuously administered to PO + VNS rats at 20 Hz, 1.0 mA for 60 days. Evaluation of cardiac function and structure via echocardiograms showed decreases in stroke volume and relative ejection fraction and increases in the internal diameter of the left ventricle during systole and diastole in PO rats (p < 0.05). However, these PO-induced adverse changes were alleviated with VNS therapy. Additionally, PO rats exhibited significant increases in myocyte cross sectional areas indicating hypertrophy, along with significant increases in myocardial fibrosis and apoptosis, all of which were reversed by VNS therapy (p < 0.05). Furthermore, VNS mitigated microglial activation in two central autonomic nuclei: the paraventricular nucleus of the hypothalamus and locus coeruleus. These findings demonstrate that when VNS therapy is initiated at an early stage of HFrEF progression (<10 % reduction in relative ejection fraction), the supplementation of vagal activity is effective in restoring multi organ homeostasis in a PO model.

Endoscopic sphincterotomy with balloon dilatation versus sphincterotomy alone for common bile duct stones removal: a randomised controlled trial.

INTRODUCTION: Endoscopic sphincterotomy (EST) plus endoscopic papillary large balloon dilatation (EPLBD) has been reported as a valid alternative to EST alone in removing common bile duct (CBD) stone. The aim of this study is to compare efficacy, and safety of these two groups of patients in removing CBD stone in Hospital Universiti Sains Malaysia (HUSM). MATERIALS AND METHODS: This is a prospective single centre randomised single blinded comparative study conducted in HUSM. The primary endpoints for this study are the overall complete stone clearance rate and complication rate, while the secondary outcome for this study are duration of procedure and rate of usage of adjunct methods. Objective data analysis is conducted using independent sample t-test and chi-squared test. RESULTS: A total of 66 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis which is CBD stone. 34 patients were allocated to EST plus EPLBD arm (n=34), and 32 patients were in EST alone arm (n=32) using randomisation method. For intention to treat, patients from EST alone arm that unable to achieve complete stone clearance will be switched to EST plus EPLBD arm. The overall complete stone removal rate for both groups were comparable (EST plus EPLDB: 100% versus EST alone: 93.8%; p= 0.139). The two patients from EST alone group (6.2%) that unable to achieve complete stone clearance were converted to EST plus EPLBD group for intention to treat and able to achieve complete stone clearance by EST plus EPLBD. For procedural time, both arms are comparable as well (EST plus EPLDB: 15.8 minutes vs EST alone: 15.5 minutes; p= 0.860). Complications such as pancreatitis occurred in one patient in EST plus EPLBD arm (EST plus EPLDB: 2.9 % vs EST alone: 0 %; p= 0.328), and bleeding occurred in one patient in EST alone arm (EST plus EPLDB: 0 % vs EST alone: 3.1 %; p= 0.299) , but it is not statistically significant. No perforation or cholangitis complication occurred in both groups. No adjunct usage was observed in both groups. CONCLUSION: In this study with limited sample size, both EST plus EPLBD and EST alone are effective and has comparable procedural time in removing CBD stone. Even though both methods are equally effective, EPLBD plus EST is an alternative solution if complete stone clearance is unable to achieve via EST alone.

Enhanced Electrochemical Performance of MWCNT-Assisted Molybdenum-Titanium Carbide MXene as a Potential Electrode Material for Energy Storage Application.

Two-dimensional (2D) materials such as MXenes have attracted considerable attention owing to their enormous potential for structural flexibility. Here, we prepared a Mo2TiC2Tx-layered structure from parent Mo2TiAlC2Tx MAX by chemically selective etching of the aluminum layer. The prepared MXene was employed in composite formation with CTAB-grafted multiwalled carbon nanotubes (MWCNTs) to have a structure with improved electrochemical performance. The samples were characterized to analyze the structure, morphology, elemental detection, vibrational modes, and surface chemistry, followed by an electrochemical performance of the Mo2TiC2Tx MXene and MWCNTs@Mo2TiC2Tx composite using the GAMRAY Potentiostat under a 1 M KOH electrolyte. The specific capacitance of pristine Mo2TiC2Tx was 425 F g-1, which was enhanced to 1740 F g-1 (almost 4 times) at 5 mV s-1 due to the increase in active surface area and conductive paths between the MXene sheets. The charge storage mechanism was studied by further resolving the cyclic voltammograms. MWCNTs@Mo2TiC2Tx showed much improved electrochemical performance and reaction kinetics, making it an ideal material candidate for supercapacitor applications.

Corrigendum to "Trends in decompensated cirrhosis and hepatocellular carcinoma among people with a hepatitis B notification in New South Wales" [JHEP Reports 4 (2022)].

[This corrects the article DOI: 10.1016/j.jhepr.2022.100552.].

Unearthing the role of septins in viral infections.

Septin proteins are a subfamily of closely related GTP-binding proteins conserved in all species except for higher plants and perform essential biological processes. Septins self-assemble into heptameric or octameric complexes and form higher-order structures such as filaments, rings, or gauzes by end-to-end binding. Their close association with cell membrane components makes them central in regulating critical cellular processes. Due to their organisation and properties, septins function as diffusion barriers and are integral in providing scaffolding to support the membrane's curvature and stability of its components. Septins are also involved in vesicle transport and exocytosis through the plasma membrane by co-localising with exocyst protein complexes. Recently, there have been emerging reports of several human and animal diseases linked to septins and abnormalities in their functions. Most of our understanding of the significance of septins during microbial diseases mainly pertains to their roles in bacterial infections but not viruses. This present review focuses on the known roles of septins in host-viral interactions as detailed by various studies.

Genetic diversity and forensic statistical support for the 12 X-STR markers in the Malaysian Indian population using Qiagen Investigator® Argus X-12 QS kit.

X-chromosome short tandem repeats (X-STRs) are useful for human identification, especially in complex kinship scenarios. Since forensic statistical parameters vary among populations and the X-STRs population data for the diverse population of Peninsular Malaysia's are unavailable, this attempt for Indians (n = 201) appears forensically relevant to support the 12 X-STRs markers' evidential value for human identification in Malaysia. The Qiagen Investigator® Argus X-12 QS kit showed that DXS10135 was the most polymorphic locus with high genetic diversity, polymorphism information richness, heterozygosity, and exclusion power. Based on allele frequencies, the strength of discrimination and mean exclusion chance (MECKrüger, MECKishida, MECDesmarais, and MECDesmaraisDuo) values for the Malaysian Indians were ≥0.999997790686228. As for haplotype frequencies, the overall discrimination power and mean exclusion probability (MECKrüger, MECKishida, MECDesmarais, and MECDesmaraisDuo) were ≥0.9999984801951. The genetic distance, neighbor-joining phylogenetic tree, and principal component analysis also supported the evidential value of the 12 X-STRs markers for forensic practical caseworks in Malaysia.

Bifunctional Inhibitor Reveals NEK2 as a Therapeutic Target and Regulator of Oncogenic Pathways in Lymphoma.

Expression of the serine/threonine kinase never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is essential for entry into mitosis via its role in facilitating centrosome separation. Its overactivity can lead to tumorigenesis and drug resistance through the activation of several oncogenic pathways, including AKT. Although the cancer-enabling activities of NEK2 are documented in many malignancies, including correlations with poor survival in myeloma, breast, and non-small cell lung cancer, little is known about the role of NEK2 in lymphoma. Here, in tumors from patients with diffuse large B-cell lymphoma (DLBCL), the most common, aggressive non-Hodgkin lymphoma, we found a high abundance of NEK2 mRNA and protein associated with an inferior overall survival. Using our recently developed NEK2 inhibitor, NBI-961, we discovered that DLBCL cell lines and patient-derived cells exhibit a dependency on NEK2 for their viability. This compromised cell fitness was directly attributable to efficient NEK2 inhibition and proteasomal degradation by NBI-961. In a subset of particularly sensitive DLBCL cells, NBI-961 induced G2/mitosis arrest and apoptosis. In contrast, an existing indirect NEK2 inhibitor, INH154, did not prevent NEK2 autophosphorylation, induce NEK2 proteasomal degradation, or affect cell viability. Global proteomics and phospho-proteomics revealed that NEK2 orchestrates cell-cycle and apoptotic pathways through regulation of both known and new signaling molecules. We show the loss of NEK2-sensitized DLBCL to the chemotherapy agents, doxorubicin and vincristine, and effectively suppressed tumor growth in mice. These studies establish the oncogenic activity of NEK2 in DLBCL and set the foundation for development of anti-NEK2 therapeutic strategies in this frequently refractory and relapse-prone cancer.

Socioeconomic characteristics and postoperative outcomes of patients undergoing prenatal vs. postnatal repair of myelomeningoceles.

PURPOSE: To investigate differences in sociodemographic characteristics and short-term outcomes between patients undergoing prenatal versus postnatal myelomeningocele repair. METHODS: Patients who underwent myelomeningocele repair at our institution were stratified based on prenatal or postnatal timing of repair. Baseline characteristics and outcomes were compared. Multivariate analysis was performed to identify whether prenatal repair was a predictor of outcomes independent of socioeconomic measures. RESULTS: 49 patients underwent postnatal repair, and 30 underwent prenatal repair. Patients who underwent prenatal repair were more likely to have private insurance (73.3% vs. 42.9%, p = 0.03) and live farther from the hospital where they received their repair (251.5 ± 447.4 vs. 72.5 ± 205.6 miles, p = 0.02). Patients who underwent prenatal repair had shorter hospital stays (14.3 ± 22.7 days vs. 25.3 ± 20.1 days, p = 0.03), fewer complications (13.8% vs. 42.9%, p = 0.01), fewer 30-day ED visits (0.0% vs. 34.0%, p < 0.001), lower CSF diversion rates (13.8% vs. 38.8%, p = 0.02), and better functional status at 3-months (13.3% vs. 57.1% delayed, p = 0.009), 6-months (20.0% vs. 56.7% delayed, p = 0.03), and 1-year (29.4% vs. 70.6% delayed, p = 0.007). On multivariate analysis, prenatal repair was an independent predictor of inpatient complication (OR(95%CI): 0.19(0.05-0.75), p = 0.02) and 3-month (OR(95%CI): 0.14(0.03-0.80) p = 0.03), 6-month (OR(95%CI): 0.12(0.02-0.73), p = 0.02), and 1-year (OR(95%CI): 0.19(0.05-0.80), p = 0.02) functional status. CONCLUSION: Prenatal repair for myelomeningocele is associated with better outcomes and developmental functional status. However, patients receiving prenatal closure are more likely to have private health insurance and live farther from the hospital, suggesting potential barriers to care.

Trends in substance-induced cardiomyopathy-related mortality among older adults in the United States from 1999 to 2020.

In this retrospective study, spanning from 1999 to 2020, we examined mortality trends related to SICM (substance-induced cardiomyopathy) among individuals aged 75 and older. A total of 473,408 SICM-related deaths were identified, with detailed data on the place of death available for 454,632 cases, revealing that a significant proportion occurred in medical facilities (45.43 %), nursing homes (24.67 %), hospices (4.21 %), and at home (25.69 %). Our analysis of age-adjusted mortality rates (AAMR) showed an overall decline from 1999 to 2020, decreasing from 14.5 to 7.7 per 10,000 population, with an initial increase from 1999 to 2001 followed by a subsequent decline. Gender-based analysis indicated consistently higher AAMRs for elderly men compared to elderly women. Moreover, we observed variations in AAMRs based on race and ethnicity, with NH Black or African American individuals having the highest AAMRs. Geographic disparities were notable, with states like Delaware having AAMRs twice as high as Utah. The Southern region consistently exhibited the highest AAMR, followed by the Midwestern, Northeastern, and Western regions. Furthermore, metropolitan areas consistently had higher AAMRs than nonmetropolitan areas, although both showed declining trends over the study period. These findings provide valuable insights into SICM-related mortality patterns among the elderly population, emphasizing the importance of considering demographic and geographic factors in public health planning and interventions.

Efficacy of Terbinafine and Itraconazole Combination Therapy Versus Terbinafine or Itraconazole Monotherapy in the Management of Fungal Diseases: A Systematic Review and Meta-Analysis.

Fungal infections constitute a common dermatological illness rampant in underdeveloped countries. Combination drug therapy is becoming increasingly well-established owing to drug resistance because of monotherapy. Different studies have been conducted previously to compare the medical regimens for the treatment of fungal infections. However, there is insufficient research on the difference in cure rates and recurrence rates with each regimen. To the best of our knowledge, this meta-analysis is the first to compare the effect of the most widely used oral antifungal medications and their combination usage. A meta-analysis of randomized controlled trials (RCTs) assesses the efficacy of terbinafine or itraconazole monotherapy versus combination therapy in fungal diseases. We queried PubMed and Cochrane Central from their inception to April 2022 for published studies, RCTs, and observational studies without any language restriction that compared itraconazole and terbinafine combination therapy with monotherapy in patients with fungal infections. The results from the studies were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and were pooled using a random-effects model, and a p-value of ≤0.05 was considered significant for the analysis. Endpoints of interest included cure rates and recurrence rates. Cure rates were increased significantly for combination therapy compared to terbinafine monotherapy (RR=2.01 (1.37, 2.94); p=0.0003; I2=67%). On sensitivity analysis, a significant association was observed between combination therapy and itraconazole monotherapy in terms of cure rates (RR=1.91 (1.41, 2.57); p<0.0001; I2=0%) and recurrence rates (RR=0.08 (0.02, 0.44); p=0.003; I2=0%). The findings of this meta-analysis suggest that itraconazole and terbinafine combination therapy has a better cure rate when compared to terbinafine monotherapy.

Comparing Low Volume Versus Conventional Volume of Polyethylene Glycol for Bowel Preparation during Colonoscopy: A Randomised Controlled Trial.

Background: Polyethylene glycol (PEG) solution is widely used as a colonoscopic bowel cleaning agent, although some patients are intolerant due to the need for ingesting large solution volumes and unpleasant taste. A low-volume solution may enhance patient tolerability and compliance in bowel preparation. Accordingly, this study compared the effectiveness of two difference PEG volumes for bowel preparation before colonoscopy in terms of bowel cleanliness, completeness of colonoscopy, patient tolerability and colonoscopy duration. Methods: Using a prospective randomised controlled single-blinded study design, 164 patients scheduled for colonoscopy were allocated to two groups (n = 82 patients in each) to receive either the conventional PEG volume (3 L, control group) or the low volume (2 L, intervention group). The Boston Bowel Preparation Scale (BBPS), a validated scale for assessing bowel cleanliness during colonoscopy, was used to score bowel cleanliness in three colon segments. Secondarily, colonoscopy completeness, tolerability to drinking PEG and the duration of colonoscopy were compared between the groups. Results: There were no statistically significant differences between the two intervention groups in terms of bowel cleanliness (P = 0.119), colonoscopy completion (P = 0.535), tolerability (P = 0.190) or the amount of sedation/analgesia required (midazolam, P = 0.162; pethidine, P = 0.708). Only the duration of colonoscopy differed between the two groups (longer duration in the control group, P = 0.039). Conclusion: Low-volume (2 L) PEG is as effective as the standard 3 L solution in bowel cleaning before colonoscopy; however, the superiority of either solution could not be established.

The effect of pre-endoscopy maltodextrin beverage on gastric residual volume and patient's well-being: a randomised controlled trial.

Prolonged fasting prior to oesophagogastroduodenoscopy (OGDS) could be noxious to patients' well-being. Strict fasting protocol has been used prior to OGDS with the concern of reduced visibility or suboptimal endoscopic assessment. Maltodextrin beverages were also commonly used as the pre-operative carbohydrate loading in enhanced recovery after surgery (ERAS) protocol. Our study aimed to look for the effects of maltodextrin beverage 2 h before OGDS on gastric residual volume and patient's well-being scores. This was a single-blinded, stratified randomised controlled trial, comparing control group (A, received 400 ml of plain water) and carbohydrate loading group (B, received 400 ml of Carborie). The primary objectives were to measure the gastric residual volume (GRV) and patient's well-being scores using visual analogue scale (VAS) scores for hunger, thirst, anxiety, tiredness and general discomfort. Of 80 randomised patients, 78 completed the study (38 received plain water and 40 Carborie). The median (IQR) GRV was not significantly different between group A and B (5.0 ml (20) vs 4.0 ml (19), p = 0.777). Both groups showed significant reduction in VAS scores in all five parameters (p ≤ 0.001). There were no complications attributed to endoscopy in either group. Pre-endoscopy maltodextrin beverage is as safe as clear water with improved patient's well-being in both groups.Clinical Trial Registration: NCT05106933.

Association between e-cigarette use and myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: The popularity of e-cigarettes has risen dramatically over the last few years, particularly among the younger population. Although the use of combustible cigarettes has established evidence to be associated with the development of several adverse cardiopulmonary diseases, the investigations regarding the prospective long-term effects of e-cigarette use on the cardiovascular system have just begun. We set to investigate if there is an association between the history of MI and e-cigarette use among smokers and non-smokers? METHODS: The current review aims to assess the association of myocardial infarction with e-cigarette consumption. PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) were queried up to October 2022 to identify articles assessing the incidence of myocardial infarction among e-cigarette users. Data were meta-analyzed using a random-effects model to derive odds ratios (OR) and 95% confidence intervals. RESULTS: Nine studies involving 984,764 patients were included. The mean age of e-cigarette smokers was less than the controls, and female participants dominated the sample size. E-cigarette users were associated with increased odds of MI than non-users [OR = 1.44; 95% CI (1.22, 1.74); P < 0.0001]. Dual users were also associated with increased odds of MI with large effect when compared to non-users [OR = 4.04; 95% CI (3.40, 4.81); P < 0.00001]. CONCLUSIONS: Dual use is associated with an increased risk of MI than e-cigarette use only. Similarly, dual and solely e-cigarette consumption patterns of nicotine delivery are at a higher risk of MI than non-smokers.

A comparative study of early functional outcomes in undisplaced neck of femur fracture treated with partially threaded and fully threaded cannulated screw fixation in patients above 60 years age.

Objective: To compare the partially threaded versus fully threaded cannulated screw fixation methods in stable neck of femur fracture in terms of early functional outcomes in patients of age 60 and above. Methods: A randomized controlled trial was conducted at Orthopedic Unit-II, Mayo Hospital Lahore, Pakistan from July 2021 to July 2022. A total of 82 (41 in each group) patients of both genders, aged 60 or above were included. All patients had garden Type-I or II and were mobile before they fractured the femoral neck were included. In Group-A, cannulated screw fixation (cancellous screws 6 mm) was done using partially threaded screws while fully threaded screws (cancellous screws 6 mm) were used in Group-B. Patients were followed up at six weeks, three months and six months interval for "Radiographic Union Scale for Hip (RUSH)" and "Harris Hip score". Results: In a total of 82 (41 in each group) patients, 66 (80.5%) we male. At 6th week (p=0540) and 3rd month (p=0.653) postoperatively, no significant differences were seen between groups for Hip Harris score. However, at 6th month, functional outcome of Group-B patients was significantly better as compared to Group-A (p=0.038). Mean RUSH score in Group-A and in Group-B at 6th month postoperative was 25.45±2.73 and 30.52±2.39 (p<0.001). Conclusion: Fully threaded cannulated screw fixation is better in treating undisplaced neck of femur fracture as compared to partially threaded cannulated screw fixation in terms of early functional outcomes among the age group of 60 years and above.RCT Registration number: NCT05587660.

Genomic profiling and sites of metastasis in non-small cell lung cancer.

Background: We investigated the biological predisposition to site of metastasis in patients with NSCLC based on their molecular profiling and program death ligand PD-L1 status. We sought to identify any association between metastatic site and molecular profile in NSCLC patients. Methods: This was a retrospective analysis of patients with stage IV NSCLC who were newly diagnosed from January 2014 to June 2022. Clinical characteristics, pathology, molecular reports, and imaging were retrieved and analyzed. Results: A total of 143 patients were included in the study. Median age was 65 years, with an equal number of men (n=71) and women (n=72). The most common histology was adenocarcinoma (81.8%). At least one genetic mutation was discovered in 100 patients. Mutations with a targetable drug were found in 86 patients. The most common mutations were TP53 (25.2%), EGFR (24.5%), KRAS/NRAS (20.3%), and CDKN2A/2B (7.7%). Patients with any mutation were significantly more likely to have metastatic disease to the brain (57% vs. 37%, p=0.03), but there was no difference in metastatic disease to bone (34% vs. 26%, p=0.32). Patients without a discoverable mutation were significantly more likely to have metastatic disease to other sites (e.g., adrenal gland 91% vs. liver 66%, p=0.002). There was no difference in progression-free survival (PFS) or overall survival (OS) between those with versus without mutations. Median PFS and OS were significantly longer in patients with an EGFR mutation than those with KRAS/NRAS or TP53 mutations. Patients with PD-L1 >1% or TP53 were significantly more likely to have metastatic disease to organs other than bone or brain (p=0.047 and p=0.023, respectively). We identified four prognostic groups in metastatic NSCLC. Patients with PD-L1 <1% and no actionable mutations have the poorest prognosis, with median survival of around 20 months. Conclusion: Patients with mutations discoverable on NGS are more likely to have metastatic disease to the brain. KRAS/NRAS in particular has a predilection to metastasize to the brain and bone. PD-L1 expression and a TP53 mutation, on the other hand, tend to lead to metastasis of NSCLC to organs other than brain or bone. These results need to be corroborated in larger prospective studies.