Oral squamous cell carcinoma (OSCC) progresses from preneoplastic precursors via genetic and epigenetic alterations. Previous studies have focused on the treatment of terminally developed OSCC. However, the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied. Our study identified lysine-specific demethylase 1 (LSD1) as a crucial promoter of OSCC, demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia. LSD1 inhibition by SP2509 disrupted cell cycle, reduced immunosuppression, and enhanced CD4+ and CD8+ T-cell infiltration. In a feline model of spontaneous OSCC, a clinical LSD1 inhibitor (Seclidemstat or SP2577) was found to be safe and effectively inhibit the STAT3 network. Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling, which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4. Notably, LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422, offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition. This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
STAT3 Transcription Factor/metabolism* ; Animals ; Histone Demethylases/genetics* ; Phosphorylation ; Mouth Neoplasms/immunology* ; Mice ; Carcinoma, Squamous Cell/immunology* ; Disease Progression ; Cyclin-Dependent Kinase-Activating Kinase ; Precancerous Conditions/metabolism* ; Humans ; Cyclin-Dependent Kinases/metabolism* ; Disease Models, Animal

Objective: Optical coherence tomography (OCT) is considered superior to coronary angiography (CA). However, OCT is not widely used, and data are limited in India. In the present study, the efficacy and safety of OCT for guiding percutaneous coronary intervention (PCI) in all-comer patients were evaluated and compared with those of CA. Materials and Methods: In this retrospective study, the data associated with 434 patients who underwent PCI between December 2018 and June 2020 were analyzed. The primary endpoint was major adverse cardiac events (MACEs) at 6 months. Results: The patients were divided into OCT-guided and angiography-guided PCI groups (217 in each group) after propensity matching. The OCT-guided PCI group had a significantly larger proportion of patients with unstable angina (55.7% vs. 43.3%, p=0.009) and non-STelevation myocardial infarction (NSTEMI; 17.5% vs. 10.0%, p=0.02) compared with the angiography-guided PCI group, and the proportion of patients with STEMI was significantly lower in the OCT-guided PCI group than in the angiography-guided PCI group (23.5% vs. 41.5%, p=0.00005). The OCT-guided PCI group had a lower incidence of MACEs at 6 months than the angiography-guided PCI group but without statistical significance (6.9% vs. 9.7%, p=0.296).Incidences of target lesion failure, target vessel myocardial infarction, in-stent restenosis, or stent thrombosis did not occur in either group. On post-PCI OCT, stent underexpansion, tissue prolapse, stent edge dissection, and stent malapposition were observed in 28.5%, 10%, 4.1%, and 3.7% of the cases, respectively. Conclusion When comparing OCT-guided PCI with angiography-guided PCI, OCT-guided PCI showed slightly superior clinical outcomes at 6 months, although the differences were not statistically significant.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

Purpose::Common peroneal nerve palsy is quite disabling and every effort should be made to prevent its injury during the treatment.Methods::We retrospectively reviewed the prospectively collected data of 7 cases of tibial plateau fractures in association with proximal fibula fracture from January 2019 to September 2019 who presented to emergency room of our hospital.Results::In addition to fibular neck fracture, the first case had type 6 tibial plateau displaced fracture and the second case had displaced acetabular fracture with instability of knee with tibial tuberosity avulsion. common peroneal nerve palsy developed following application of distal tibial skeletal traction in both the cases. Other 6 such cases remained neurologically intact as traction was not applied to them.Conclusion::Such iatrogenic complication could have been prevented if the injury pattern of "concomitant medial and lateral columns" of the proximal leg is kept in mind by the treating surgeon before applying skeletal traction.

Methods: A total of 18 mice were divided into injured (n=12) and non-injured (n=6) groups. The disc height index (DHI%) at coccygeal 4–5 level was measured by computed tomography (CT) scan for all mice. Coccygeal 4–5 discs of the injury group were injured using a 32G needle fixed to a novel tool and confirmed by CT. The non-injury group underwent no procedure. DHI% was measured by CT at 2-, 4-, and 6-week post-injury, and all mice tails were sectioned for histopathology grading of disc degeneration at the respective time intervals. Results: The injured group showed significant variation in DHI% at 2, 4, and 6 weeks, whereas there was no change in the noninjured group. Histopathologic evaluation with Safranin O stain showed a worsening of the disc degeneration score at 2, 4, and 6 weeks in the injured group, but in the non-injured group there was no change. Percutaneous needle injury technique with our novel tool provided 100% accuracy and uniform degeneration. Conclusions A simple, easily reproducible mouse model for disc degeneration was created using a simple, cost-effective, novel tool and technique, its advantage being high precision and user friendly.

Background/Aims: The severe acute respiratory syndrome coronavirus 2 pandemic has affected the gastrointestinal (GI) endoscopy units globally owing to the risk of transmission. We present our data on the use of rapid antigen test (RAT) as a screening tool prior to endoscopy to prevent the transmission of coronavirus disease (COVID-19). Methods: This study was a retrospective analysis of patients who underwent any GI endoscopic procedure from July 2020 to October 2020 at a tertiary referral center in New Delhi, India. All patients underwent screening for COVID-19 using RAT, and endoscopy was performed only when the RAT was negative. The data are presented as numbers and percentages. Results: A total of 3,002 endoscopic procedures were performed during the study period. Only one endoscopic procedure was performed in a COVID-19 positive patient. A total of 53 healthcare workers were involved in conducting these procedures. Only 2 healthcare workers (3.8%) were diagnosed COVID-19 positive, presumably due to community-acquired infection, during this period. Conclusions The COVID-19 RAT is easily usable as a simple screening tool prior to GI endoscopy during the COVID-19 pandemic.

Background/Aims: The management of patients with walled-off necrosis (WON) has undergone a paradigm shift from surgical to nonsurgical modalities. Real-world data on the management of symptomatic WON are scarce. Methods: Prospectively collected data of symptomatic WON cases were retrospectively evaluated. The treatment modalities used were medical management alone, percutaneous catheter drainage (PCD) or endoscopic drainage, or a combination of PCD and endoscopic drainage. We compared technical success, clinical success, mortality, readmissions, complications, and length of hospital stay among these modalities. Results: A total of 264 patients were evaluated (predominantly men: n=195, 74%). The mean age was 37.66 (±14.41) years. The etiology of acute pancreatitis was excessive alcohol consumption in 115 (44%) and biliary (gall stone, microlithiasis) in 89 (34%). The most common indications for drainage were pain (n=253, 96%) and fever (n=140, 53%). Of the patients, 74 (28%) were treated with medical therapy alone, 81 (31%) with endoscopic drainage, 98 (37%) with PCD, and 10 (4%) with a combined approach. Technical success and clinical success were achieved in 78 (93%) and 74 (91%) patients in the endoscopic arm and in 88 (90%) and 79 (81%) patients in the PCD arm, respectively (p=0.0004 for clinical success). Lower rates of complications (7% vs. 22%, p=0.005), readmission (20% vs. 34%, p=0.04), and mortality (4% vs. 19%, p=0.0012), and shorter hospital stay (13 days vs. 19 days, p=0.0018) were observed in the endoscopic group than in the PCD group. Conclusions Endoscopic drainage of WON is better than PCD and is associated with lower mortality, fewer complications, and shorter hospitalization.

Methods: A total of 18 mice were divided into injured (n=12) and non-injured (n=6) groups. The disc height index (DHI%) at coccygeal 4–5 level was measured by computed tomography (CT) scan for all mice. Coccygeal 4–5 discs of the injury group were injured using a 32G needle fixed to a novel tool and confirmed by CT. The non-injury group underwent no procedure. DHI% was measured by CT at 2-, 4-, and 6-week post-injury, and all mice tails were sectioned for histopathology grading of disc degeneration at the respective time intervals. Results: The injured group showed significant variation in DHI% at 2, 4, and 6 weeks, whereas there was no change in the noninjured group. Histopathologic evaluation with Safranin O stain showed a worsening of the disc degeneration score at 2, 4, and 6 weeks in the injured group, but in the non-injured group there was no change. Percutaneous needle injury technique with our novel tool provided 100% accuracy and uniform degeneration. Conclusions A simple, easily reproducible mouse model for disc degeneration was created using a simple, cost-effective, novel tool and technique, its advantage being high precision and user friendly.

Background/Aims: The severe acute respiratory syndrome coronavirus 2 pandemic has affected the gastrointestinal (GI) endoscopy units globally owing to the risk of transmission. We present our data on the use of rapid antigen test (RAT) as a screening tool prior to endoscopy to prevent the transmission of coronavirus disease (COVID-19). Methods: This study was a retrospective analysis of patients who underwent any GI endoscopic procedure from July 2020 to October 2020 at a tertiary referral center in New Delhi, India. All patients underwent screening for COVID-19 using RAT, and endoscopy was performed only when the RAT was negative. The data are presented as numbers and percentages. Results: A total of 3,002 endoscopic procedures were performed during the study period. Only one endoscopic procedure was performed in a COVID-19 positive patient. A total of 53 healthcare workers were involved in conducting these procedures. Only 2 healthcare workers (3.8%) were diagnosed COVID-19 positive, presumably due to community-acquired infection, during this period. Conclusions The COVID-19 RAT is easily usable as a simple screening tool prior to GI endoscopy during the COVID-19 pandemic.

Snakebite is a severe medical, economic, and social problem across the world, mostly in the tropical and subtropical area. These regions of the globe have typical of the world's venomous snakes present where access to prompt treatment is limited or not available. Snake venom is a complex mixture of toxin proteins like neurotoxin and cardiotoxin, and other enzymes like phospholipase A2 (PLA2 ), haemorrhaging, transaminase, hyaluronidase, phosphodiesterase, acetylcholinesterase, cytolytic and necrotic toxins. Snake venom shows a wide range of biological effects like anticoagulation or platelet aggregation, hemolysis, hypotension and edema.Phospholipase A2 is the principal constituent of snake venom; it catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid, which is the precursor of eicosanoids including prostaglandins and leukotrienes. The information regarding the structure and function of the phospholipase A2enzyme may help in treating the snakebite victims. This review article constitutes a brief description of the structure, types, mechanism occurrence, and tests of phospholipase A 2 and role of components of medicinal plants used to inhibit phospholipase A2 .