Rabies is a neglected viral disease that kills nearly 70 000 humans annually, majorly in Africa and Asia. Ingress of compromised counterfeit anti-rabies vaccine raises global concern. Counterfeit vaccine has formulation, packaging, labelling, and supply-chain discrepancies. The sales and purchase of vaccines may need due vigilance through market surveillance to identify and seize to protect from potential harms. Strict regulations and improved monitoring systems may be implemented to counter cold chain failures and illegal activities. Consistent community engagement programs and patient advocacy on rabies to share knowledge and gaps toward sustainable outcomes was needed. “Block-chain” could revamp the existing system to support and enable supply chain management and eliminate illegal activities. To meet the vision of zero human rabies deaths by 2030, issues on strong intervention and collaborative response from all stakeholders could be considered on priority.
Iatrogenic bile duct injury remains one of the most critical complications of laparoscopic cholecystectomy, associated with significant morbidity, mortality, diminished long-term survival, impaired quality of life, and an increased incidence of legal actions. Prompt identification and early diagnosis followed by a multidisciplinary management approach led by a hepatobiliary surgeon, have been demonstrated to reduce complication rates and improve postoperative outcomes. Despite this, no consensus guidelines currently exist regarding the optimal timing for surgical reconstruction. Hepaticojejunostomy remains the standard of care for severe bile duct injuries. A retrospective review was conducted on patients who underwent surgery for intraoperative bile duct injuries from January 2009 to January 2022. The analysis included demographic data, the type of bile duct injury classified according to the Strasberg system, clinical symptoms, diagnostic investigations, timing of referral, post-referral management, and associated morbidity. A total of 24 patients underwent surgical repair for post-cholecystectomy bile duct injury over 13 years. Most cases (92%) were referred from other institutions, and delayed reconstruction (>21 days) was performed in 74% of patients. Roux-en-Y hepaticojejunostomy was the main procedure (71%). Postoperative morbidity occurred in 16.6%, with 2 patients requiring reoperation, and no mortality was observed. After a median follow-up of 6.2 years, anastomotic patency was maintained in 91.6% of patients, and 2 patients (8.3%) required redo reconstruction for stricture. Surgical reconstruction generally leads to favorable outcomes for most patients with intraoperative bile duct injury. Referral to specialized centers is crucial for optimal management due to the complexities involved. These centers should offer multidisciplinary services, including hepatobiliary surgeons, endoscopists, and interventional radiologists. This collaborative expertise is essential for accurate injury identification and enhances the likelihood of successful treatment outcomes.
Caused by viruses and/or bacteria (such as seasonal influenza virus, respiratory syncytial virus, Mycoplasma pneumoniae , and human metapneumovirus), the mild and self-limiting acute respiratory infection (ARIs) may sometimes entail medical attention. Seasonal influenza, rhinovirus, RSV and hMPV were increasingly detected as ARI infections increased in China. Divided into two major subgroups A and B, hMPV (human Metapneumovirus ) is enveloped with non-segmented, ~13 kb negative-strand RNA genome coding for N, P and L proteins forming a helical ribonucleoprotein complex (RNP) of ~13–14 nm diameter. Efforts to develop vaccines and drugs to treat hMPV are warranted. hMPV proteins (SH, P, G, and M2-2) are good vaccine targets. Little progress is seen thus far in developing hMPV vaccine via the traditional route. Sophisticated computational tools ensure the safety and efficacy of a designed vaccine, and advanced modeling techniques are used to test its structural stability and functionality. Multi-epitope-based mRNA vaccine seems feasible. Multi-epitope mRNA vaccine is developed using advanced immunoinformatics, engaging the F protein and few G, M1, M2, and SH proteins epitopes. The designed and optimized mRNA sequence is inserted into bacterial plasmid to mass produce. Some vaccines were promising during initial clinical trials. This strategy demonstrates the adaptability of mRNA technology and its potential to treat a variety of infectious diseases in coming days. Developing multi-epitope-based vaccine targeting many respiratory viral pathogens seems more promising and practical. Effective multi-epitope mRNA vaccine could offer safeguard to hMPV-vulnerable groups, revolutionizing the strategies to counter hMPV. Studies have also evaluated T cell-based therapies.
This study aimed to investigate the predictive diagnostic role of thyroglobulin (Tg) as a preoperative tumor marker among patients at the National Cancer Center in Yemen. Analysis of 323 cases (141 malignant, 182 benign) demonstrated high diagnostic accuracy with an area under the curve (AUC) of 0.913 (95% CI: 0.879–0.946, P < 0.001). Various threshold values were evaluated, with optimal diagnostic performance observed at different cutoff points, suggesting Tg’s potential as a valuable preoperative screening tool. A prospective study of 323 patients of thyroid nodule was conducted between January 2013 and March 2025. A diagnostic accuracy study was performed to analyzing the high level of preoperative Tg in 323 patients presenting with thyroid nodules in comparison with post total thyroidectomy histopathological results, where 141 patients subsequently confirmed had malignant nodule and 182 cases confirmed as benign nodule Of all results of preoperative Tg level of 323 cases, we were performed the receiver operating characteristic (ROC) curve analysis to evaluate the diagnostic accuracy Tg. Multiple cutoff points were analyzed to determine optimal threshold values for clinical application. Statistical significance was set at P < 0.001. The result of The ROC curve analysis revealed excellent discriminatory power with an AUC of 0.913 (95% CI: 0.879–0.946, SE: 0.017, P < 0.001). This indicates strong diagnostic capability of Tg as a preoperative marker. This study demonstrates that preoperative serum Tg is a highly effective biomarker for differentiating malignant from benign thyroid nodules, supported by an AUC of 0.913 in 323 histopathological confirmed cases. While Tg’s adaptability across cutoff thresholds enhances its diagnostic utility, optimal values require context specific validation. The findings advocate integrating Tg into preoperative screening to improve risk stratification and reduce unnecessary interventions. However, broader multicenter studies are needed to confirm generalizability and establish standardized thresholds, particularly beyond the studied Yemeni cohort, to refine thyroid cancer management globally.
Children’s Oncology Group (COG) has set one of the two internationally recognized guidelines for the treatment of children with Wilms tumors (WTs). Their guidelines recommend upfront radical nephrectomy without preoperative chemotherapy. The study assessed the risk of intraoperative tumor spillage in correlation with the tumor’s size and laterality. A prospective case series study was conducted during the period from April 2018 to April 2024 and included all children with unilateral WTs who were candidate for upfront radical nephrectomy. Exclusion criteria included those patients who were not candidate for this therapeutic option as per the guidelines of COG. Recorded data included age and sex at time of presentation, tumor size and laterality, and any incident of intraoperative spillage. Patients were grouped according to tumor’s maximum diameter (TMD); into those with TMD ≥12 cm, and those with TMD <12 cm, and according to tumor laterality into those with right-sided lesions, and those with left-sided lesions. A total of 17 patients were enrolled, of whom 8 (47.1%) had right-sided lesions. TMD was ≥12 cm in 14 (82.4%) patients. Radical nephrectomy with the tumor capsule intact was achieved in 16 (94.1%) patients. Intraoperative spillage, which represents rupture of the tumor capsule during resection, was reported in only 1 (5.9%) patient. There was no statistical significance correlating the risk of intraoperative spillage with the tumor size or laterality in the studied patients. Based on the results of this study, there is no statistical significance correlating the risk of intraoperative spillage with the tumor size or laterality. However, surgeons should be careful when resecting large tumors of ≥20 cm in their maximum diameter as the risk of spillage is more in such cases.
Recurrent gestational trophoblastic neoplasia (GTN) is rare but can manifest as uterine rupture-related bleeding. A 27-year-old woman with a history of perivaginal bleeding during pregnancy experienced recurrent lower abdominal pain and internal bleeding two years after initial remission with methotrexate chemotherapy. Imaging and elevated beta-hCG levels led to a diagnosis of GTN recurrence with suspected uterine rupture. Surgical intervention included cornuectomy and hysterorrhaphy, preserving fertility. Histopathology suggested choriocarcinoma. The patient received four sessions of EMACO chemotherapy over three months. Serial beta-hCG levels showed remission. Long-term beta-hCG monitoring is crucial for early intervention and recurrence detection. Fertility-sparing surgical management, although associated with higher recurrence risks compared to definitive hysterectomy, provides an important therapeutic option for women of reproductive age. Conservative treatment preserves fertility while cautioning against the risk of secondary recurrence. Long-term monitoring is essential.
Recurrence of gastrointestinal stromal tumors (GISTs) can manifest as local recurrence or distant metastases. Various prognostic factors have been identified as significant predictors of the risk of recurrence. We report the case of an ileal stromal tumor resected 11 years ago, which recurred locally and was managed surgically at our institution. This study has been reported in line with the SCARE 2025 criteria. Surgical resection remains the cornerstone of treatment for localized recurrent GISTs, often complemented by neoadjuvant or adjuvant targeted therapy. Decisions regarding the surgical indications in cases of recurrence should be judiciously deliberated within a multidisciplinary forum.
In Latin America, research on soft tissue sarcomas (STS) has been predominantly descriptive, focusing on epidemiological and clinical-pathological characteristics. To evaluate long-term survival outcomes and identify prognostic factors in patients with extremity STS (eSTS). This was a retrospective cohort study analyzing 140 patient records diagnosed with eSTS at a Social Security Hospital in Ecuador between 1986 and 2020. Clinical, pathological, and treatment data were extracted from medical records. Survival rates were estimated using Kaplan–Meier methods. Univariate and multivariate Cox regression analyses were used to identify factors associated with overall survival (OS). Among the 140 patients, the most common histological subtypes were liposarcoma, fibrosarcoma, and undifferentiated pleomorphic sarcoma. At diagnosis, 45% of tumors were clinical stage IA or IB. Upfront surgery was performed in 36% of patients; 31% required re-excision due to inadequate initial surgery, and 33% underwent resection for recurrent disease. At the end of follow-up, 116 patients (82.9%) were alive, and 24 (17.1%) had died. Estimated OS rates at 5, 10, 15, and 20 years were 71.3%, 61.9%, 41.3%, and 41.3%, respectively. In univariate analysis, clinical stage (P = 0.002), histological grade (P = 0.014), lymph node involvement (P = 0.018), surgical margins (P = 0.027), and adjuvant therapy (P = 0.041) were significantly associated with OS. However, no independent prognostic factor was identified in multivariate analysis. This is the first long-term survival analysis of eSTS patients in Ecuador. Although several variables were associated with improved survival in univariate analysis, none remained significant in multivariate analysis. These findings highlight the importance of early-stage diagnosis and appropriate surgical management, while also underscoring the need for larger, prospective studies to validate prognostic indicators in this population.
This study is the first to report on the initial experience of surgeons using ultrasound guidance to implant central venous chemotherapy ports in cancer patients, addressing a lack of data in the Nepalese region. This is a retrospective descriptive study conducted among patients who underwent ultrasonography-guided central chemoport insertion by the same team of surgeons at a tertiary-level hospital. The procedure was performed under local anesthesia in the operating theater. A total of 41 patients with ages ranging from 38 to 82 years and a median age of 59 years were included in the study. Cannulation was successful in 100% of cases. The right internal jugular vein was cannulated in 40 patients (97.6%). The indications were neoadjuvant, adjuvant, and palliative chemotherapy in 30%, 58%, and 12% of cases, respectively. Successful cannulation was achieved in a single attempt in 28 patients (68.3%), while 12 patients (29.3%) required a double attempt. Nine patients (22.0%) had skin infections, two patients (4.9%) developed kinking of the catheter, one patient (2.4%) experienced a blockage of the catheter, and one patient (2.4%) had a catheter tip fracture that migrated to the right atrium. Ultrasound-guided chemoport insertion by experienced surgeons has favorable outcomes. Complications can range from minor to severe, even life-threatening. Early identification of complications and appropriate management are recommended.
The advent of immune checkpoint inhibitors has significantly advanced oncology, presenting new therapeutic avenues for a variety of cancers. Despite their success in managing melanoma, lung cancer, renal cell carcinoma, colorectal cancer, and hepatocellular carcinoma, their efficacy in pancreatic ductal adenocarcinoma (PDAC), particularly microsatellite stable (MSS) cases, is notably limited. This report delineates an extraordinary case of a patient with metastatic PDAC concomitant with autoimmune pancreatitis (AIP), which exhibited a partial response to an innovative treatment regimen comprising a PD-1 inhibitor, chemotherapy, and anlotinib. This regimen was well-tolerated, and next-generation sequencing analysis affirmed MSS status. The pronounced therapeutic response observed in this metastatic pancreatic cancer scenario is exceptionally uncommon. We reported an old female with metastatic MSS PDAC. The patient achieved a partial response and exhibited good tolerance to a treatment regimen that included a PD-1 inhibitor, chemotherapy, and anti-vascular agents and extended overall survival of over 25 months. Our findings suggest that certain patients with metastatic MSS PDAC, particularly those with AIP, may demonstrate enhanced sensitivity to and benefit from immunotherapy. These observations underscore the potential for personalized immunotherapy approaches in this patient subgroup, warranting further investigation.
Multiple myeloma (MM) is a prevalent hematologic malignancy, and bortezomib (BTZ), as the first proteasome inhibitor, has significant effects in the treatment of MM. However, BTZ suffers from low water solubility, poor in vivo stability, and toxic side effects, which limit its application in clinical treatment. To address these issues, BTZ polymeric micelles (BTZ/PM) based on poly(ethylene glycol)-distearoylphosphatidylethanolamine (mPEG-DSPE) were developed in this study to enhance the therapeutic effect and safety of the drug. By optimizing the preparation process, BTZ/PM micelles with a high encapsulation rate (83.1%) and small particle size (~14 nm) were successfully prepared. In a tumor-bearing mouse model, BTZ/PM micelles demonstrated a significant tumor-suppressing effect. Compared with the commercially available BTZ preparation, BTZ/PM micelles exhibited a stronger tumor-suppressing effect at the same dose and had less impact on the mortality rate and body weight change of the mice, indicating a better safety profile.
Purpose: This study assessed the long-term impact of bile leak complications on the pediatric hepatoblastoma (HB) patients post-surgery. With HB predominantly affecting children under five, the increased survival rates necessitate a focus on the post-surgical complications, particularly concerning the effects of bile leaks. Methods: A retrospective analysis was conducted on patients treated for HB at our institution from 1980 to 2022. The diagnosis, operative procedure, complications, mortality, and prognosis were retrospectively analyzed to examine the incidence and long-term effects of surgical complications, especially bile leaks. The study involved detailed statistical analyses, including assessments of the Kaplan–Meier survival rates and comparisons of complication incidences using log-rank tests. Results: Of the 53 reviewed cases, 43 were analyzed. Bile leaks occurred in 20% of liver resection patients, markedly impacting their long-term QOL through severe complications like gastric obstructions, portal vein occlusion, and bile duct stricture. Nonetheless, the overall 5-year survival rate was high at 87.8%. The prognosis did not differ significantly between patients with and without short-term complications. Conclusion: In patients with HB, postoperative bile leaks occasionally lead to long-term complications. Even if the complications do not influence their prognosis, surgeons must be alert for the possibility of long-term complications after surgery for HB.
Introduction: Colorectal cancers (CRCs) are the second cause of malignancy-related deaths and over half of CRCs become metastatic. Genetics plays a critical role in understanding metastatic colorectal cancers (MCRCs), as various genetic mutations influence progression and treatment responses. While there exists plenty of research on genetic mutations in CRCs, few studies have focused on mutations in MCRC patients. The present study aims to provide an overview of the prevalence of KRAS, NRAS, BRAF, and MMR mutations in Iranian MCRC patients. Methods: The present study is a descriptive cross-sectional study on patients with MCRCs referred to a tertiary medical center in Iran from March 2015 to March 2022. Ethics approval was obtained from the ethics committee of the University of Medical Sciences. The patient's MCRC was confirmed by pathology and Genotyping Assessments of tissue for KRAS, NRAS, BRAF, and MMR mutations. Results: A total of 136 MCRC patients were included in this study; 44 patients (40.7%) had KRAS mutations in their lesions. KRAS mutation status was not significantly related to age or gender (P > 0.05). Only one NRAS mutation was found in one patient. There were no cases of BRAF mutation identified. Among 48 patients assessed for MMRs deficiency, 8 cases (16.7%) were positive, 7 cases (14.6%) were MSI-H, and 1 case (2.1%) was MSI-L. Conclusion: Although no significant relation was found between the KRAS mutation pattern and gender, age, or tumor primary location, the MSI-H mutation-positive tumors were significantly more prevalent in younger patients.
Background: This study examines alternative splicing (AS) events in genes linked to chromatin accessibility in various cancers and their relation to the tumor immune microenvironment. Methods: Data from the Cancer Genome Atlas Database (TCGA) were used to identify independent prognostic factors for pan-cancer. We explored the correlation between differentially expressed genes and tumor immunity, including immune checkpoint genes, tumor development, and immune cells. A regulatory network diagram of alternative splicing-splicing factors (AS-SFs) was constructed to find potential immunotherapy targets. Results: IRF5 and E2F8 genes showed significant differential expression in pan-cancer. Age, cancer grade, primary tumor, cancer lymph nodes, and distant metastasis were independent prognostic factors. The risk model achieved good predictive performance, with AUC values of 0.705, 0.746, 0.743, and 0.743 for 1-year, 3-year, 5-year, and 10-year survival predictions, respectively. Positive correlations were found between IRF5/E2F8 and CD274/CTLA4 in certain cancers using TIMER and CIBERSORT software. Conclusions: AS events in chromatin accessibility genes (IRF5 and E2F8) have significant predictive value in pan-cancer prognosis. Our model assesses patient survival probability and highlights the synergistic impact of immune checkpoints and the AS-SF regulatory network on tumor immunotherapy.
Background: Radiotherapy is an effective method for esophageal squamous cell carcinoma (ESCC) treatment show reduced effectiveness in long-term due to reduced sensitivity of cancer cells to radiotherapy. Niraparib tosylate, a poly ADP-ribose polymerase (PARP) inhibitor may enhance the radiosensitivity of these cells. Hence, the present study was aimed to study the effects of niraparib tosylate on ESCC proliferation, apoptosis and cell cycle along with radiosensitivity enhancement efficiency. Materials and methods: ESCC cell lines, KYSE-30 were subjected to niraparib tosylate or irradiation treatments or combination of both. CCK8 and colony formation assays were performed to monitor cell growth status. Cell cycle and apoptosis level were investigated through flow cytometry. The expressions of targeted genes were detected at protein levels by western blot. Besides, xenografts were successfully established in immunocompromised mice. Student’s t-test was used to compare data and P < 0.05 was considered statistically significant. Results: Treatment with niraparib tosylate showed G2/M cycle arrest and apoptosis in KYSE-30 cells and the rate was observed to be more significant with combination therapy. These effects were further strengthened when cells were cultured under hypoxia and high atmospheric pressure. An enhanced susceptibility to radiotherapy was observed with niraparib tosylate combination. The homologous recombination related regulator, Rad51, showed remarkable upregulation in cancer cells exposed to combination of drug-radiation treatment. The tumor burden was also relieved in xenograft mouse models with combination of drug-radiation treatment, indicating the potential of niraparib tosylate use clinical cancer therapy. Conclusion: From the results, a novel function of niraparib tosylate can be established, impairing DNA damage repair efficiency to increase the susceptibility of ESCC to radiotherapy, resulting in cell apoptosis and G2/M cycle arrest in vitro and in vivo.
