Background: Mice are useful small animal models to study the pathogenesis of SARS-CoV-2 infection. As the ancestral SARS-CoV-2 strains did not utilize murine Ace2 as a receptor, wild-type mice were not susceptible to the SARS-CoV-2 infection. Infection of human ACE2-expressing transgenic mice with SARS-CoV-2 induces fatal encephalitis, which is not commonly observed in humans. We and others have previously demonstrated the ability of the SARS-CoV-2 Beta variant to productively infect wild-type mice. Herein, we employed RNA-seq to investigate the transcriptomic landscapes in the lungs after the infection of wild-type mice with SARS-CoV-2 Beta variant. Methods: We intranasally infected 6-week-old wild-type C57BL/6J mice with the SARS-CoV-2 (B.1.351 strain) and collected lungs at 3- and 6-days post-infection for RNA-sequencing. We used the Limma-Voom package to identify differentially expressed genes (DEGs) and the fgsea package for pathway enrichment analysis. We used Cytoscape to identify hub genes and gene networks. Lastly, we employed RT-qPCR and multiplex assay to validate the RNA-seq data. Results: Using a cutoff of an adjusted p-value below 0.05 and an absolute log2 fold change value greater than 0.75, we identified 285 DEGs on day 3 and 46 DEGs on day 6. The canonical pathways analysis showed that several key pathways such as apoptosis and cytokine response were upregulated in the infected lungs. Protein-protein interaction analyses identified innovative target genes such as if11, Ccna2, and Aurkb. We also identified the top 10 hub genes that included Prc1, Ube2c, Ccnb2, Ncapg, Aurkb, Cep55, Mki67, Dlgap5, Ccna2, and Kif11. RT-qPCR analysis for Tnfa, Il6, Ccl2, and Ccl3 further validated the RNA-seq analysis. Consistent with gene expression results, we detected significantly increased protein levels of various inflammatory mediators such as IL-6, CCL2, CXCL2, and CXCL10 in the infected lungs. Conclusions This is the first transcriptomic analysis of the lungs of wild-type mice infected with a clinical isolate of SARS-CoV-2. Our findings provide a further understanding of the pathogenic events that occur in this mouse model of SARS-CoV-2 infection.

Background: Post-liver transplant biliary strictures are a common cause of morbidity among patients who have undergone living donor liver transplantation (LDLT). Limited data are available concerning the response rates to various treatment modalities and the long-term outcomes for these individuals. Methods: This study was a retrospective analysis of a prospectively collected database, including adult patients aged 18 years or older who underwent LDLT between 2006 and 2022. Results: Between 2006 and 2022, a total of 3,550 patients underwent liver transplantation. After applying exclusion criteria, 2,956 patients were included in the analysis.During the study period, 344 patients (11.6%) developed biliary strictures. Of these, 77.0% underwent endoscopic retrograde cholangiopancreatography as the primary treatment for biliary strictures, while the remainder received percutaneous transhepatic biliary drainage. Identified risk factors for post-liver transplant biliary strictures included the presence of multiple biliary anastomoses, bile leak, and older donor and recipient ages. The overall graft and patient survival rates were comparable between patients with and without biliary strictures, at both 1 year (93.0% vs. 96.3%) and 5 years (82.3% vs. 79.2%). Conclusions Biliary strictures are observed in approximately 11% of recipients following LDLT. While the presence of biliary strictures is associated with increased morbidity, it does not significantly impact patient survival.

Background: Post-liver transplant biliary strictures are a common cause of morbidity among patients who have undergone living donor liver transplantation (LDLT). Limited data are available concerning the response rates to various treatment modalities and the long-term outcomes for these individuals. Methods: This study was a retrospective analysis of a prospectively collected database, including adult patients aged 18 years or older who underwent LDLT between 2006 and 2022. Results: Between 2006 and 2022, a total of 3,550 patients underwent liver transplantation. After applying exclusion criteria, 2,956 patients were included in the analysis.During the study period, 344 patients (11.6%) developed biliary strictures. Of these, 77.0% underwent endoscopic retrograde cholangiopancreatography as the primary treatment for biliary strictures, while the remainder received percutaneous transhepatic biliary drainage. Identified risk factors for post-liver transplant biliary strictures included the presence of multiple biliary anastomoses, bile leak, and older donor and recipient ages. The overall graft and patient survival rates were comparable between patients with and without biliary strictures, at both 1 year (93.0% vs. 96.3%) and 5 years (82.3% vs. 79.2%). Conclusions Biliary strictures are observed in approximately 11% of recipients following LDLT. While the presence of biliary strictures is associated with increased morbidity, it does not significantly impact patient survival.

Background: Post-liver transplant biliary strictures are a common cause of morbidity among patients who have undergone living donor liver transplantation (LDLT). Limited data are available concerning the response rates to various treatment modalities and the long-term outcomes for these individuals. Methods: This study was a retrospective analysis of a prospectively collected database, including adult patients aged 18 years or older who underwent LDLT between 2006 and 2022. Results: Between 2006 and 2022, a total of 3,550 patients underwent liver transplantation. After applying exclusion criteria, 2,956 patients were included in the analysis.During the study period, 344 patients (11.6%) developed biliary strictures. Of these, 77.0% underwent endoscopic retrograde cholangiopancreatography as the primary treatment for biliary strictures, while the remainder received percutaneous transhepatic biliary drainage. Identified risk factors for post-liver transplant biliary strictures included the presence of multiple biliary anastomoses, bile leak, and older donor and recipient ages. The overall graft and patient survival rates were comparable between patients with and without biliary strictures, at both 1 year (93.0% vs. 96.3%) and 5 years (82.3% vs. 79.2%). Conclusions Biliary strictures are observed in approximately 11% of recipients following LDLT. While the presence of biliary strictures is associated with increased morbidity, it does not significantly impact patient survival.

Background: Post-liver transplant biliary strictures are a common cause of morbidity among patients who have undergone living donor liver transplantation (LDLT). Limited data are available concerning the response rates to various treatment modalities and the long-term outcomes for these individuals. Methods: This study was a retrospective analysis of a prospectively collected database, including adult patients aged 18 years or older who underwent LDLT between 2006 and 2022. Results: Between 2006 and 2022, a total of 3,550 patients underwent liver transplantation. After applying exclusion criteria, 2,956 patients were included in the analysis.During the study period, 344 patients (11.6%) developed biliary strictures. Of these, 77.0% underwent endoscopic retrograde cholangiopancreatography as the primary treatment for biliary strictures, while the remainder received percutaneous transhepatic biliary drainage. Identified risk factors for post-liver transplant biliary strictures included the presence of multiple biliary anastomoses, bile leak, and older donor and recipient ages. The overall graft and patient survival rates were comparable between patients with and without biliary strictures, at both 1 year (93.0% vs. 96.3%) and 5 years (82.3% vs. 79.2%). Conclusions Biliary strictures are observed in approximately 11% of recipients following LDLT. While the presence of biliary strictures is associated with increased morbidity, it does not significantly impact patient survival.

This retrospective case series evaluated the effectiveness of minimally invasive spine surgery-transforaminal lumbar interbody fusion (MIS-TLIF) using the “trial-in-situ ” technique for reducing high-grade spondylolisthesis. The surgical management of grade ≥III spondylolisthesis has been controversial, with various methods documented in the literature, including in-situ fusion, in-situ trans-sacral delta fixation, distraction techniques, and external reduction techniques. Recently, MIS techniques have gained popularity. This study analyzed 18 cases of high-grade spondylolisthesis treated with MIS-TLIF using the “trial-in-situ ” technique. The clinical outcomes were assessed using the Visual Analog Scale (VAS) and the modified Oswestry Disability Index (mODI) scores. The spinopelvic parameters and sagittal balance were also analyzed. Preoperatively, the spinopelvic parameters were deranged, with a mean pelvic tilt of 28.31°, which improved to 13.91° postoperatively. Similarly, the sacral slope improved from 45.65° to 38.01°. VAS and mODI scores improved postoperatively, indicating the effectiveness of the “trial-in-situ ” technique in reducing high-grade spondylolisthesis and achieving a better sagittal profile and spinopelvic parameters. The findings indicate that MIS-TLIF using the “trial-in-situ ” technique is a viable and effective method for treating high-grade spondylolisthesis.

Purpose::Tibial stress fracture associated with knee osteoarthritis is an unusual and difficult clinical scenario. There is no clear existing treatment guideline for this uncommon clinical disease. The aim of this study is to review the impact of various treatment options for patients with advanced knee osteoarthritis associated with proximal tibial stress fracture.Methods::The study was performed using the databases of PubMed and Scopus. Methodological index for non-randomized studies score was used to evaluate the included studies’ bias. The concluded data included the treatment approach, reported outcome measure, and time to fracture union. The literature search was started in December 2021 and accomplished in January 2022. A narrative description of the different methods and comparison of their results were done.Results::Out of total assessed 69 studies, 9 studies were included in our review. The commonest treatment approach used was total knee arthroplasty by long tibial stem extension. The mean preoperative knee society score and knee functional score were 30.62 and 23.17, respectively. The mean postoperative knee society knee score was 86.87, while the functional score was 83.52. The average reported time to achieve fracture union was 4 months (a range of 2.07 - 5.50 months).Conclusion::The optimal clinical outcome for treating either acute or mobile tibial stress fracture in patients with advanced knee osteoarthritis can be achieved with long stem total knee arthroplasty. However, due to heterogeneity of data, comparison of different treatment options for chronic proximal tibial stress fracture mal-union/non-union coexisting with knee osteoarthritic and such inferences need to be judged cautiously.

Background/Aims: Intestinal tuberculosis (ITB) and Crohn’s disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. Methods: Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL.Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. Results: Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55–0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. Conclusions In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.