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OBJECTIVE: A condition known as ligamentum flavum (LF) hypertrophy occurs when the ligamentum flavum (LF) swells as a result of pressures applied to the spine. Among the elderly population, lumbar spinal stenosis is a major cause of pain and disabilities. Numerous studies indicate that lumbar spinal stenosis etiology involves the ligamentum flavum in a major way. This study looks into the relationship between low back pain and ligamentum flavum thickening. PATIENTS AND METHODS: The imaging tests and case histories of all patients with low back pain who had consecutive magnetic resonance imaging exams performed at the Prince Sattam University and King Khalid hospitals in Al Kharj City will serve as the basis for this retrospective observational study. A radiologist utilized the Pfirrmann grading system, which is based on spinal levels starting from the first lumbar to the first sacral vertebrae, to measure the thickness of the ligamentum flavum in all cases who underwent magnetic resonance imaging (MRI). A correlation between age, hypertrophy of LF, and low back pain was investigated. RESULTS: There were 79 participants in the study, ages ranging from 21 to 82, 49 of which were men. The patients' average age was 54 years, and 62% of them were men. We found no appreciable variations in LF thickness according to gender. At the L4-L5 and L5-S1 levels, the left LF was noticeably thicker than the right. Moreover, there was a significant difference (p < 0.05) in the bilateral LF thicknesses at L5-S1 compared to the comparable sides at L4-L5. CONCLUSIONS: By evaluating the thickness of LF on magnetic resonance images, we discovered that it may be closely associated with the etiology of pain processes in the spine.
Subject(s)
Hypertrophy , Ligamentum Flavum , Low Back Pain , Magnetic Resonance Imaging , Humans , Ligamentum Flavum/pathology , Ligamentum Flavum/diagnostic imaging , Low Back Pain/diagnostic imaging , Low Back Pain/pathology , Low Back Pain/etiology , Male , Middle Aged , Female , Aged , Retrospective Studies , Adult , Aged, 80 and over , Young Adult , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Spinal Stenosis/diagnostic imaging , Spinal Stenosis/pathologyABSTRACT
Background: This study aimed to assess the role of community pharmacists and their perception toward antimicrobial stewardship, in addition to identifying factors influencing their perception and practices in community pharmacy. Methods: A cross-sectional study was carried out among community pharmacists regarding antimicrobial stewardship. Convenience sampling was used to obtain the required sample from a community pharmacy in Baghdad. In total, 381 participants have completed the survey. Results: The majority of the participants (85.6%) strongly agreed/agreed that "antimicrobial stewardship programs reduce the problems of antibiotic resistance"; and 85.5% of them strongly agreed/agreed that community pharmacists required adequate training on antibiotics use. In addition, high percent of community pharmacists (88.4%) strongly agreed/agreed that pharmacists have a responsibility to take a prominent role in antimicrobial stewardship programs and infection-control programs in the health system. The total score of perception was significantly influenced by older age groups, postgraduate degrees, and experience of 6-10 years (p < 0.001). This study also showed that 65.4% of pharmacists always/often advise patients to continue the full course of antimicrobials, and 64.9% of them reported always/often considering clinical and safety parameters before dispensing antibiotics. The role of pharmacists was significantly influenced by the younger age group, females, higher degree in pharmacy, experience of 3-5 years, and medical complex pharmacy (p < 0.001). Conclusion: Community pharmacists have a good perception toward antimicrobial stewardship programs, but their role is still limited. More efforts are needed to design better strategies for antimicrobial stewardship in community pharmacy.
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Background: The transconjunctival approach paired with lateral canthotomy is a commonly used technique for widened exposure of the orbital floor and infraorbital rim. A major drawback of this approach is the severance of lateral canthal ligament fibers, which predisposes to potential postoperative eyelid malpositioning. To avoid these suboptimal aesthetic outcomes, a modification of this approach has been proposed in which the lower eyelid is mobilized with a paracanthal, trans-tarsal stair-step incision. In this pilot study, we describe our experience with the trans-tarsal stairstep incision for lateral extension of the transconjunctival incision and report its outcomes in a Western population. Methods: All patients who underwent facial fracture operative fixation at a single institution by a single senior surgeon were included. Clinical variables were extracted. Patients were stratified by incision type. Results: Compared with patients who underwent subtarsal incision (n = 20) and transconjunctival incision with lateral canthotomy (n = 4), patients who received the trans-tarsal stair-step incision (n = 10) had no incision-related complications or requirements for revision. The most common complications found in the comparison groups were ectropion and hypertrophic or irregular scarring, and 4 patients required revision. Conclusions: Our initial experience with the transconjunctival approach with the trans-tarsal stair-step incision shows promising outcomes. Further study may promote greater utilization of this technique in Western countries.
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In hand trauma, the uninjured forearm has been touted as the ideal site for ectopic banking in digit/hand amputations. Here, we describe the temporary ectopic implantation and subsequent replantation of a partially amputated hand and highlight the "Three R's" - Recovery, Rehabilitation, and Revision over the first year of recovery.
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Chronic kidney disease (CKD) is a global health issue of growing concern. According to projections from the Worldwide Health Observatory, it is currently one of the rapidly increasing contributors to global mortality. The prevalence of CKD and end-stage renal disease (ESRD) is increasing globally. The objective was to evaluate the prevalence and impact of clinical pharmacist intervention in resolving drug-related problems (DRPs) among patients with CKD. A single-arm, pre- and post-intervention study design was used, which was assessed to be suitable in testing for the feasibility of the implementation of an intervention in clinical practice. With this study pre- and post-intervention variables of interest were measured before and after an intervention in the same patients to evaluate the impact of clinical pharmacists on ambulatory patients with CKD. The findings of this study indicate a high prevalence of DRPs, with every patient experiencing at least one DRP. The mean DRP per patient was found to be 2.903 with STD ± 1.148. The study assessed the considerable influence of clinical pharmacist intervention on DRPs. The predominant form of DRP was drug interaction 167 (45.1%) which was reduced to 76 (20.5%) after intervention carried out by clinical pharmacists statistically significant (p = 0.032). Another common DRP was found to be poor compliance issues in pre-interventions (n = 144 (38.9%)) and was reduced to 80 (21.6%) at post-intervention significantly (p = 0.042). Untreated indications were noticed in 137 cases (37.0%), after pharmacist intervention, this number was significantly reduced to 27 cases (7.3%), with a statistically significant difference (p = 0.004). However, it is noteworthy that medication compliance among patients in our study was unsatisfactory and fell below expectations. As a clinical pharmacist played an important role in reducing the prevalence of poor medication adherence to lower levels in these CKD outpatients. This research emphasizes the vital role of clinical pharmacists in mitigating DRPs among CKD patients, resulting in improved medication management and potentially better health outcomes.
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DNA methylation is one of the most important epigenetic mark involved in many physiologic cellular processes and pathologies. During mitosis, the transmission of DNA methylation patterns from a mother to the daughter cells is ensured through the action of the Ubiquitin-like, containing PHD and RING domains, 1/DNA methyltransferase 1 (UHRF1/DNMT1) tandem. UHRF1 is involved in the silencing of many tumor suppressor genes (TSGs) via mechanisms that remain largely to be deciphered. The present study investigated the role and the regulation of UHRF1 poly-ubiquitination induced by thymoquinone, a natural anti-cancer drug, known to enhance or re-activate the expression of TSGs. We found that the auto-ubiquitination of UHRF1, induced by TQ, is mediated by reactive oxygen species, and occurs following DNA damage. We demonstrated that the poly-ubiquitinated form of UHRF1 is K63-linked and can still silence the tumor suppressor gene p16INK4A/CDKN2A. We further showed that TQ-induced auto-ubiquitination is mediated via the activity of Tip60. Since this latter is known as a nuclear receptor co-factor, we investigated if the glucocorticoid receptor (GR) might be involved in the regulation of UHRF1 ubiquitination. Activation of the GR, with dexamethasone, did not influence auto-ubiquitination of UHRF1. However, we could observe that TQ induced a K48-linked poly-ubiquitination of GR, probably involved in the proteosomal degradation pathway. Mass-spectrometry analysis of FLAG-HA-tagged UHRF1 identified UHRF1 partners involved in DNA repair and showed that TQ increased their association with UHRF1, suggesting that poly-ubiquitination of UHRF1 is involved in the DNA repair process. We propose that poly-ubiquitination of UHRF1 serves as a scaffold to recruit the DNA repair machinery at DNA damage sites.
Subject(s)
Benzoquinones , CCAAT-Enhancer-Binding Proteins , DNA Repair , Ubiquitin-Protein Ligases , Ubiquitination , Humans , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , Ubiquitination/drug effects , Benzoquinones/pharmacology , DNA Repair/drug effects , Antineoplastic Agents/pharmacology , DNA Damage/drug effectsABSTRACT
The development of resistance to carbapenems in Klebsiella pneumoniae due to the production of metallo-ß-lactamases (MBLs) is a critical public health problem because carbapenems are the last-resort drugs used for treating severe infections of extended-spectrum ß-lactamases (ESBLs) producing K. pneumoniae. Restoring the activity of carbapenems by the inhibition of metallo-ß-lactamases is a valuable approach to combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant K. pneumoniae isolates were used. The sub-inhibitory concentrations of pantoprazole and the well-reported metallo-ß-lactamase inhibitor captopril inhibited the hydrolytic activities of metallo-ß-lactamases, with pantoprazole having more inhibiting activities. Both drugs, when used in combination with meropenem, exhibited synergistic activities. Pantoprazole could also downregulate the expression of the metallo-ß-lactamase genes bla NDM and bla VIM. A docking study revealed that pantoprazole could bind to and chelate zinc ions of New Delhi and Verona integron-encoded MBL (VIM) enzymes with higher affinity than the control drug captopril and with comparable affinity to the natural ligand meropenem, indicating the significant inhibitory activity of pantoprazole against metallo-ß-lactamases. In conclusion, pantoprazole can be used in combination with meropenem as a new strategy for treating serious infections caused by metallo-ß-lactamases producing K. pneumoniae.
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In the original publication [...].
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BACKGROUND: Surgery in selected patients with locally advanced pancreatic cancer after induction chemotherapy may have drawbacks related to surgical risks and breaks or delays in oncological treatment, in particular when curative intent resection is not possible (that is non-therapeutic laparotomy). The aim of this study was to assess the incidence and oncological impact of a non-therapeutic laparotomy in patients with locally advanced pancreatic cancer treated with induction (m)FOLFIRINOX chemotherapy. METHODS: This was a retrospective international multicentre study including patients diagnosed with pathology-proven locally advanced pancreatic cancer treated with at least one cycle of (m)FOLFIRINOX (2012-2019). Patients undergoing a non-therapeutic laparotomy (group A) were compared with those not undergoing surgery (group B) and those undergoing resection (group C). RESULTS: Overall, 663 patients with locally advanced pancreatic cancer were included (67 patients (10.1%) in group A, 425 patients (64.1%) in group B, and 171 patients (25.8%) in group C). A non-therapeutic laparotomy occurred in 28.2% of all explorations (67 of 238), with occult metastases in 30 patients (30 of 67, 44.8%) and a 90-day mortality rate of 3.0% (2 of 67). Administration of palliative therapy (65.9% versus 73.1%; P = 0.307) and median overall survival (20.4 [95% c.i. 15.9 to 27.3] versus 20.2 [95% c.i. 19.1 to 22.7] months; P = 0.752) did not differ between group A and group B respectively. The median overall survival in group C was 36.1 (95% c.i. 30.5 to 41.2) months. The 5-year overall survival rates were 11.4%, 8.7%, and 24.7% in group A, group B, and group C, respectively. Compared with group B, non-therapeutic laparotomy (group A) was not associated with reduced overall survival (HR = 0.88 [95% c.i. 0.61 to 1.27]). CONCLUSION: More than a quarter of surgically explored patients with locally advanced pancreatic cancer after induction (m)FOLFIRINOX did not undergo a resection. Such non-therapeutic laparotomy does not appear to substantially impact oncological outcomes.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Pancreatic Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Laparotomy , Retrospective Studies , Fluorouracil , Leucovorin/therapeutic use , Neoadjuvant Therapy , Irinotecan , OxaliplatinABSTRACT
INTRODUCTION: Tyrosinase is a versatile, glycosylated copper-containing oxidase enzyme that mainly catalyzes the biosynthesis of melanin in mammals. Its overexpression leads to the formation of excess melanin, resulting in hyperpigmentary skin disorders, such as dark spots, melasma, freckles, etc. Therefore, inhibition of tyrosinase is a therapeutic approach for the treatment of hyperpigmentation. METHODS: The current study focused on evaluating tyrosinase inhibitory activities of triazole derivatives 1-20, bearing different substituents on the phenyl ring. 17 derivatives have shown a potent tyrosinase inhibition with IC50 values between 1.6 to 13 µM, as compared to the standard drug, i.e., kojic acid (IC50 = 24.1 ± 0.5 µM). Particularly, compounds 11 and 15 displayed 12 times more potent inhibitory effects than the kojic acid. RESULTS: The structure-activity relationship revealed that substituting halogens at the C-4 position of the benzene ring renders remarkable anti-tyrosinase activities. Compounds 1-3 and 8 showed a competitive type of inhibition, while compounds 5, 11, and 15 showed a non-competitive mode of inhibition. Next, we performed molecular docking analyses to study the binding modes and interactions between the ligands (inhibitors) and the active site of the tyrosinase enzyme (receptor). Besides this, we have assessed the toxicity profile of inhibitors on the BJ human fibroblast cell line. CONCLUSION: The majority of the newly identified tyrosinase inhibitors were found to be noncytotoxic. The results presented herein form the basis of further studies on triazole derivatives as potential drug leads against tyrosinase-related diseases.
Subject(s)
Enzyme Inhibitors , Hyperpigmentation , Monophenol Monooxygenase , Triazoles , Humans , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Hyperpigmentation/drug therapy , Molecular Docking Simulation , Molecular Structure , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Pyrones , Skin Diseases/drug therapy , Structure-Activity Relationship , Triazoles/chemistry , Triazoles/pharmacology , Triazoles/chemical synthesisABSTRACT
BACKGROUND: Minimally invasive surgery provides an unprecedented opportunity to review video for assessing surgical performance. Surgical video analysis is time-consuming and expensive. Deep learning provides an alternative for analysis. Robotic pancreaticoduodenectomy (RPD) is a complex and morbid operation. Surgeon technical performance of pancreaticojejunostomy (PJ) has been associated with postoperative pancreatic fistula. In this work, we aimed to utilize deep learning to automatically segment PJ RPD videos. METHODS: This was a retrospective review of prospectively collected videos from 2011 to 2022 that were in libraries at tertiary referral centers, including 111 PJ videos. Each frame of a robotic PJ video was categorized based on 6 tasks. A 3D convolutional neural network was trained for frame-level visual feature extraction and classification. All the videos were manually annotated for the start and end of each task. RESULTS: Of the 100 videos assessed, 60 videos were used for the training the model, 10 for hyperparameter optimization, and 30 for the testing of performance. All the frames were extracted (6 frames/second) and annotated. The accuracy and mean per-class F1 scores were 88.01% and 85.34% for tasks. CONCLUSION: The deep learning model performed well for automated segmentation of PJ videos. Future work will focus on skills assessment and outcome prediction.
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Deep Learning , Pancreaticojejunostomy , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/methods , Pancreaticojejunostomy/methods , Retrospective Studies , Pancreaticoduodenectomy/methods , Video RecordingABSTRACT
BACKGROUND: Pancreaticoduodenectomy (PD) remains the only curative option for patients with pancreatic adenocarcinoma (PDAC). Infectious complications (IC) can negatively impact patient outcomes and delay adjuvant therapy in most patients. This study aims to determine IC effect on overall survival (OS) following PD for PDAC. STUDY DESIGN: Patients who underwent PD for PDAC between 2010 and 2020 were identified from a single institutional database. Patients were categorized into two groups based on whether they experienced IC or not. The relationship between postoperative IC and OS was investigated using Kaplan-Meier and Cox-regression multivariate analysis. RESULTS: Among 655 patients who underwent PD for PDAC, 197 (30%) experienced a postoperative IC. Superficial wound infection was the most common type of infectious complication (n = 125, 63.4%). Patients with IC had significantly more minor complications (Clavien-Dindo [CD] < 3; [59.4% vs. 40.2%, p < 0.001]), major complications (CD ≥ 3; [37.6% vs. 18.8%, p < 0.001]), prolonged LOS (47.2% vs 20.3%, p < 0.001), biochemical leak (6.1% vs. 2.8%, p = 0.046), postoperative bleeding (4.1% vs. 1.3%, p = 0.026) and reoperation (9.6% vs. 2.2%, p < 0.001). Time to adjuvant chemotherapy was delayed in patients with IC versus those without (10 vs. 8 weeks, p < 0.001). Median OS for patients who experienced no complication, noninfectious complication, and infectious complication was 33.3 months, 29.06 months, and 27.58 months respectively (p = 0.023). On multivariate analysis, postoperative IC were an independent predictor of worse OS (HR 1.32, p = 0.049). CONCLUSIONS: IC following PD for PDAC independently predict worse oncologic outcomes. Thus, efforts to prevent and manage IC should be a priority in the care of patients undergoing PD for PDAC.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Pancreaticoduodenectomy , Postoperative Complications , Humans , Pancreaticoduodenectomy/adverse effects , Male , Female , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/mortality , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/mortality , Aged , Postoperative Complications/etiology , Postoperative Complications/mortality , Middle Aged , Retrospective Studies , Survival Rate , Surgical Wound Infection/etiology , Surgical Wound Infection/mortality , Follow-Up Studies , PrognosisABSTRACT
PURPOSE: Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA 19-9]) and conditional (C: performance status) factors should be considered when staging patients with localized pancreatic ductal adenocarcinoma (PDAC). The prognostic value of the combined ABC factors has not been quantitatively validated. METHODS: In this retrospective cohort study, we evaluated patients with localized PDAC treated with initial (modified) fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) at five high-volume pancreatic cancer centers in the United States and the Netherlands (2012-2019). Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS). RESULTS: Overall, 1,835 patients with localized PDAC were included. Tumor stage at diagnosis was potentially resectable in 346 (18.9%), BR in 531 (28.9%), and LA in 958 (52.2%) patients. The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). Performance status was ≥1 in 1,110 patients (60.7%). Independent poor prognostic factors for OS were BR disease (hazard ratio [HR], 1.26 [95% CI, 1.06 to 1.50]), LA disease (HR, 1.71 [95% CI, 1.45 to 2.02]), CA 19-9 >500 U/mL (HR, 1.36 [95% CI, 1.21 to 1.52]), and WHO performance status ≥1 (HR, 1.31 [95% CI, 1.16 to 1.47]). Patients were assigned 1 point for each poor ABC factor and 2 points for LA disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively. CONCLUSION: The ABC factors of tumor anatomy, CA 19-9, and performance status at diagnosis were independent prognostic factors for OS in patients with localized PDAC treated with initial (m)FOLFIRINOX. Staging of patients with localized PDAC at diagnosis should be based on anatomy, CA 19-9, and performance status.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Carcinoma, Pancreatic Ductal/drug therapy , Fluorouracil/therapeutic use , Leucovorin/therapeutic use , Prognosis , Neoadjuvant TherapyABSTRACT
BACKGROUND: Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends are understudied for colorectal peritoneal metastases (CRPM). PATIENTS AND METHODS: We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC. RESULTS: A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months, p = 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14, p < 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively, p < 0.001). CONCLUSIONS: Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.
Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Middle Aged , Neoadjuvant Therapy , Cytoreduction Surgical Procedures , Carcinoembryonic Antigen , Colorectal Neoplasms/pathology , Peritoneal Neoplasms/secondary , Retrospective Studies , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Survival RateABSTRACT
INTRODUCTION: About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of response to preoperative treatment. Serum carcinoembryonic antigen (CEA) is a potential alternative. METHODS: This retrospective cohort study from five referral centers included consecutive patients with localized pancreatic adenocarcinoma (2012-2019), treated with one or more cycles of (m)FOLFIRINOX, and non-elevated CA19-9 levels (i.e., < 37 U/mL) at baseline. Cox regression analyses were performed to assess prognostic factors for overall survival (OS), including CEA level at baseline, restaging, and dynamics. RESULTS: Overall, 277 patients were included in this study. CEA at baseline was elevated (≥5 ng/mL) in 53 patients (33%) and normalized following preoperative therapy in 14 patients (26%). In patients with elevated CEA at baseline, median OS in patients with CEA normalization following preoperative therapy was 33 months versus 19 months in patients without CEA normalization (p = 0.088). At time of baseline, only elevated CEA was independently associated with (worse) OS (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.04-1.98). At time of restaging, elevated CEA at baseline was still the only independent predictor for (worse) OS (HR 1.44, 95% CI 1.04-1.98), whereas elevated CEA at restaging (HR 1.16, 95% CI 0.77-1.77) was not. CONCLUSIONS: Serum CEA was elevated in one-third of patients with localized pancreatic adenocarcinoma having non-elevated CA19-9 at baseline. At both time of baseline and time of restaging, elevated serum CEA measured at baseline was the only predictor for (worse) OS. Therefore, serum CEA may be a useful tool for decision making at both initial staging and time of restaging in patients with non-elevated CA19-9.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/surgery , Carcinoembryonic Antigen , CA-19-9 Antigen , Antineoplastic Combined Chemotherapy Protocols , Biomarkers, Tumor , Prognosis , Retrospective Studies , Adenocarcinoma/surgery , Irinotecan , Oxaliplatin , Leucovorin , FluorouracilABSTRACT
Viruses are microscopic biological entities that can quickly invade and multiply in a living organism. Each year, over 36,000 people die and nearly 400 million are infected with the dengue virus (DENV). Despite dengue being an endemic disease, no targeted and effective antiviral peptide resource is available against the dengue species. Antiviral peptides (AVPs) have shown tremendous ability to fight against different viruses. Accelerating antiviral drug discovery is crucial, particularly for RNA viruses. DDX3X, a vital cell component, supports viral translation and interacts with TRPV4, regulating viral RNA metabolism and infectivity. Its diverse signaling pathway makes it a potential therapeutic target. Our study focuses on inhibiting viral RNA translation by blocking the activity of the target gene and the TRPV4-mediated Ca2+ cation channel. Six major proteins from camel milk were first extracted and split with the enzyme pepsin. The antiviral properties were then analyzed using online bioinformatics programs, including AVPpred, Meta-iAVP, AMPfun, and ENNAVIA. The stability of the complex was assessed using MD simulation, MM/GBSA, and principal component analysis. Cytotoxicity evaluations were conducted using COPid and ToxinPred. The top ten AVPs, determined by optimal scores, were selected and saved for docking studies with the GalaxyPepDock tools. Bioinformatics analyses revealed that the peptides had very short hydrogen bond distances (1.8 to 3.6 Å) near the active site of the target protein. Approximately 76% of the peptide residues were 5-11 amino acids long. Additionally, the identified peptide candidates exhibited desirable properties for potential therapeutic agents, including a net positive charge, moderate toxicity, hydrophilicity, and selectivity. In conclusion, this computational study provides promising insights for discovering peptide-based therapeutic agents against DENV.