Impact of the Timing of Percutaneous Catheter Drainage following Endoscopic Drainage on Outcomes in Acute Necrotizing Pancreatitis.

Background The role of dual-modality drainage of walled-off necrosis (WON) in patients with acute pancreatitis (AP) is established. However, there are no data on the association of clinical outcomes with the timing of percutaneous catheter drainage (PCD). We investigated the impact of the timing of PCD following endoscopic drainage of WON on clinical outcomes in AP. Materials and Methods This retrospective study comprised consecutive patients with necrotizing AP who underwent endoscopic cystogastrostomy (CG) of WON followed by PCD between September 2018 and March 2023. Based on endoscopic CG to PCD interval, patients were divided into groups (≤ and >3 days, ≤ and >1 week, ≤ and >10 days, and ≤ and >2 weeks). Baseline characteristics and indications of CG and PCD were recorded. Clinical outcomes were compared between the groups, including length of hospitalization, length of intensive care unit stay, need for surgical necrosectomy, and death during hospitalization. Results Thirty patients (mean age ± standard deviation, 35.5 ± 12.7 years) were evaluated. The mean CG to PCD interval was 11.2 ± 7.5 days. There were no significant differences in baseline characteristics and indications of CG and PCD between the groups. The mean pain to CG interval was not significantly different between the groups. Endoscopic necrosectomy was performed in a significantly greater proportion of patients undergoing CG after 10 days ( p = 0.003) and after 2 weeks ( p = 0.032). There were no significant differences in the complications and clinical outcomes between the groups. Conclusion The timing of PCD following endoscopic CG does not affect clinical outcomes.

Safety Assessment of Ultra High Dilutions of Camphora officinarum: A Preclinical Investigation.

Background: Camphora officinarum (CO) is a commonly used homeopathic remedy for treating colds, collapse, and recurrent eruptive illnesses. Objective: Due to the non-availability of safety data on CO, the current study intended to determine the oral toxicity of CO in its ethanol-potentized dilutions 6C, 30C, and 200C in Wistar albino rats as per OECD guidelines. Materials and methods: A single oral dose of CO-6C, 30C, and 200C (2000 µl/kg) was administered, and the animals were monitored for behavior and mortality for up to 14 days in an acute toxicity study. In the subacute study, the effects of daily oral administration of CO-6C, 30C, and 200C (200 µl/kg) for 28 days were observed for clinical signs, change in body weight, and mortality. Hematological, biochemical, and histopathological analyses were assessed and organ weights were determined. Results: Results indicate no mortality of CO in its potencies in the acute toxicity study and was found to be safe at 2000 µl/kg dosage in the subacute toxicity study. CO (200 µl/kg/day) did not show any signs of toxicity in the hematological, biochemical, and histopathological analyses, along with organ weights. Conclusion: In conclusion, the findings suggest that CO in potencies of 6C, 30C, and 200C is safe up to a single oral dose of 2000 µl/kg body weight, and the No Observed Adverse Effect Level (NOAEL) was determined to be greater than 200 µl/kg/day.

Anterior segment optical coherence tomography (AS-OCT) in strabismus following trauma.

We describe 3 cases of ocular trauma that presented with strabismus. Anterior segment optical coherence tomography was used to delineate the morphology of extraocular muscle insertions and proved helpful in diagnosis and management.

Modular synthesis of pyrrole-fused heterocycles via glucose-mediated nitro-reductive cyclization.

A novel biomass-derived glucose-mediated one-pot multicomponent nitro-reductive cyclization method is presented for the direct synthesis of diverse pyrrole-fused heterocycles. The process involves two-component reactions of alkyl (NH)-pyrrole-2-carboxylates and 2-fluoronitroarenes, yielding pyrrolo[1,2-a]quinoxalin-4(5H)-ones, as well as three-component reactions utilizing (NH)-pyrroles, nitroarenes, and DMSO as carbon sources, resulting in various pyrrolo[1,2-a]quinoxaline derivatives. High yields were achieved with broad substrate scope and gram-scale synthesis capability, including pharmaceuticals featuring pyrroloquinoxaline scaffolds. The method's key innovation lies in enabling three or four reactions in a single-pot setup, previously unexplored in pyrrole chemistry. The simplicity of nitro group reduction by biomass-derived glucose ensures practical safety during scale-up, while mechanistic insights from control experiments reveal a new paradigm in pyrrole chemistry. The tandem process demonstrates low PMI values and high step and atom economies, aligning well with green chemistry principles.

Deep-learning enabled ultrasound based detection of gallbladder cancer in northern India: a prospective diagnostic study.

Background: Gallbladder cancer (GBC) is highly aggressive. Diagnosis of GBC is challenging as benign gallbladder lesions can have similar imaging features. We aim to develop and validate a deep learning (DL) model for the automatic detection of GBC at abdominal ultrasound (US) and compare its diagnostic performance with that of radiologists. Methods: In this prospective study, a multiscale, second-order pooling-based DL classifier model was trained (training and validation cohorts) using the US data of patients with gallbladder lesions acquired between August 2019 and June 2021 at the Postgraduate Institute of Medical Education and research, a tertiary care hospital in North India. The performance of the DL model to detect GBC was evaluated in a temporally independent test cohort (July 2021-September 2022) and was compared with that of two radiologists. Findings: The study included 233 patients in the training set (mean age, 48 ± (2SD) 23 years; 142 women), 59 patients in the validation set (mean age, 51.4 ± 19.2 years; 38 women), and 273 patients in the test set (mean age, 50.4 ± 22.1 years; 177 women). In the test set, the DL model had sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of 92.3% (95% CI, 88.1-95.6), 74.4% (95% CI, 65.3-79.9), and 0.887 (95% CI, 0.844-0.930), respectively for detecting GBC which was comparable to both the radiologists. The DL-based approach showed high sensitivity (89.8-93%) and AUC (0.810-0.890) for detecting GBC in the presence of stones, contracted gallbladders, lesion size <10 mm, and neck lesions, which was comparable to both the radiologists (p = 0.052-0.738 for sensitivity and p = 0.061-0.745 for AUC). The sensitivity for DL-based detection of mural thickening type of GBC was significantly greater than one of the radiologists (87.8% vs. 72.8%, p = 0.012), despite a reduced specificity. Interpretation: The DL-based approach demonstrated diagnostic performance comparable to experienced radiologists in detecting GBC using US. However, multicentre studies are warranted to explore the potential of DL-based diagnosis of GBC fully. Funding: None.

Role of imaging in evaluating the complications of endoscopic management of pancreatic fluid collections in acute pancreatitis.

Acute pancreatitis is associated with local and systemic complications. Pancreatic fluid collection (PFC) is the most common local complication. Infected or symptomatic PFCs need drainage. Endoscopic drainage (ED) is the first-line procedure for accessible PFCs adjacent to the stomach and duodenum. ED is performed under endoscopic ultrasound (EUS) guidance. The technical and clinical success rates of EUS-guided ED in well-encapsulated PFCs are high. ED of poorly encapsulated PFCs is associated with complications. Bleeding and perforation are the most common complications. Contrast-enhanced computed tomography is critical in planning ED and early detection and management of complications. With the increasing utilization of ED for PFC, the radiologist must be familiar with the ED techniques, types of stents, and the complications related to ED. In this review, we discuss the technical aspects of the ED as well as the imaging findings of ED-related complications.

Effect of Clemizole on Alpha-Synuclein-Preformed Fibrils-Induced Parkinson's Disease Pathology: A Pharmacological Investigation.

Parkinson's disease (PD) is a neurodegenerative disorder associated with mitochondrial dysfunctions and oxidative stress. However, to date, therapeutics targeting these pathological events have not managed to translate from bench to bedside for clinical use. One of the major reasons for the lack of translational success has been the use of classical model systems that do not replicate the disease pathology and progression with the same degree of robustness. Therefore, we employed a more physiologically relevant model involving alpha-synuclein-preformed fibrils (PFF) exposure to SH-SY5Y cells and Sprague Dawley rats. We further explored the possible involvement of transient receptor potential canonical 5 (TRPC5) channels in PD-like pathology induced by these alpha-synuclein-preformed fibrils with emphasis on amelioration of oxidative stress and mitochondrial health. We observed that alpha-synuclein PFF exposure produced neurobehavioural deficits that were positively ameliorated after treatment with the TRPC5 inhibitor clemizole. Furthermore, Clemizole also reduced p-alpha-synuclein and diminished oxidative stress levels which resulted in overall improvements in mitochondrial biogenesis and functions. Finally, the results of the pharmacological modulation were further validated using siRNA-mediated knockdown of TRPC5 channels, which also decreased p-alpha-synuclein expression. Together, the results of this study could be superimposed in the future for exploring the beneficial effects of TRPC5 channel modulation for other neurodegenerative disorders and synucleopathies.

Correlation of clinical and radiological scores for evaluation of activity in patients having thyroid-associated orbitopathy: A prospective observational study.

PURPOSE: To find a correlation between the clinical (vision-inflammation-strabismus-appearance [VISA] score) and radiological (apparent diffusion coefficient [ADC] values) scores for evaluating disease activity in patients with thyroid-associated orbitopathy. DESIGN: A prospective comparative study. METHODS: Our study was performed for consecutively diagnosed thyroid-associated orbitopathy (TAO) patients. Clinical evaluation included the VISA classification system with the basic thyroid workup. An inflammatory score of <4/8 was considered inactive and ≥4/8 as an active disease. Every included patient underwent a diffusion-weighted magnetic resonance imaging (DW-MRI) scan of the orbits. The orbital parameters evaluated on imaging included the proptosis, thickness, as well as the ADC values of extraocular muscles. RESULTS: We studied 33 consecutive patients (23 females, 69.7%) with a mean age of 41.8 years. The majority (n = 27, 81.8%) were hyperthyroid, four were hypothyroid, and two were euthyroid. In the VISA classification, nine patients had active TAO (≥4/8 inflammation score), while 24 had inactive disease. There was a positive correlation between the inflammation score and ADC values of medial rectus (MR), inferior rectus (IR) and lateral rectus (LR). We had nine patients with inflammation scores ≥4. With receiver operating characteristic (ROC) curve analysis, we found that the ADC value of IR can predict disease activity with 68% sensitivity and MR-ADC can predict active TAO with 87% sensitivity. CONCLUSION: The ADC parameters of DW-MRI are objective and less operator dependent than the clinical TAO activity scores like VISA classification. A randomized control trial may provide robust data on this correlation.

Venous Thrombosis in Acute Pancreatitis: What to and Not to Do?

Acute pancreatitis is an acute inflammatory condition of the pancreas that has not only local but systemic effects as well. Venous thrombosis is one such complication which can give rise to thrombosis of the peripheral vasculature in the form of deep vein thrombosis, pulmonary embolism, and splanchnic vein thrombosis. The prevalence of these complications increases with the severity of the disease and adds to the adverse outcomes profile. With better imaging and awareness, more cases are being detected, although many at times it can be an incidental finding. However, it remains understudied and strangely, most of the guidelines on the management of acute pancreatitis are silent on this aspect. This review offers an overview of the incidence, pathophysiology, symptomatology, diagnostic work-up, and management of venous thrombosis that develops in AP.

Contrast Enhanced CT Versus MRI for Accurate Diagnosis of Wall-thickening Type Gallbladder Cancer.

Introduction: Diagnosis of wall-thickening type gallbladder cancer (GBC) is challenging. Computed tomography (CT) and magnetic resonance imaging (MRI) are commonly utilized to evaluate gallbladder wall thickening. However, there is a lack of data comparing the performance of CT and MRI for the detection of wall-thickening type GBC. Aim: We aim to compare the diagnostic accuracy of CT and MRI in diagnosis of wall-thickening type GBC. Materials and methods: This prospective study comprised consecutive patients suspected of wall-thickening type GBC who underwent preoperative contrast-enhanced CT and MRI. The final diagnosis was based on the histopathology of the resected gallbladder lesion. Two radiologists independently reviewed the characteristics of gallbladder wall thickening at CT and MRI. The association of CT and MRI findings with histological diagnosis and the interobserver agreement of CT and MRI findings were assessed. Results: Thirty-three patients (malignancy, 13 and benign, 20) were included. None of the CT findings were significantly associated with GBC. However, at MRI, heterogeneous enhancement, indistinct interface with the liver, and diffusion restriction were significantly associated with malignancy (P = 0.006, <0.001, and 0.005, respectively), and intramural cysts were significantly associated with benign lesions (P = 0.012). For all MRI findings, the interobserver agreement was substantial to perfect (kappa = 0.697-1.000). At CT, the interobserver agreement was substantial to perfect (k = 0.631-1.000). Conclusion: These findings suggest that MRI may be preferred over CT in patients with suspected wall thickening type GBC. However, larger multicenter studies must confirm our findings.

Ophthalmologic profile of patients with systemic sclerosis.

PURPOSE: To study the ophthalmologic manifestations of systemic sclerosis (SSc) and its correlation with autoantibody profile. METHODS: A cross-sectional study on 200 eyes of 100 consecutive adult patients diagnosed with SSc was performed at a tertiary care center in Northern India. The examination of ocular adnexa, anterior segment, and posterior segment with slit-lamp biomicroscopy, tear film break-up time (TBUT), Schirmer's II test, and choroidal thickness measurement by swept-source ocular coherence tomography was done. Autoantibody profile was available for 85 patients, and its statistical association with the ocular examination findings was analyzed. RESULTS: In total, 100 patients (93 females and 7 males) were included. The mean age was 45.11 ± 11.68 years, and the mean disease duration was 6.93 ± 3.68 years. Meibomian gland disease was more commonly found in patients with the diffuse subtype of SSc (P = 0.037). Choroidal thickness was increased in 34% and decreased in 7% (reference range = 307 ± 79 mm) patients. Reduced TBUT, meibomian gland dysfunction, and eyelid stiffness had a statistically significant association with the presence of anti-Scl-70 antibody (P = 0.003, <0.0001, and 0.004, respectively). These patients had ocular fatigue, foreign body sensation, and burning sensation. No significant association was noted with the presence of SS-A/Ro and SS-B/La antibodies. CONCLUSION: This study highlights the need for an active comprehensive ophthalmic evaluation. Approximately 75% of the patients in our cohort had ocular involvement to varying extent. An isolated presence of anti-Scl70 antibody was also found to have a positive association with dry eye disease.

Isolated cavernous venous malformation of the eyelid.

Cavernous hemangioma, currently known as "cavernous venous malformation," is a common, benign, non-infiltrative, slowly progressive vascular malformation of the orbit presenting in adults. We report the case of a 9-year-old girl who presented with a painless palpable mass over the right upper eyelid of 7 years' duration. A computed tomography scan of the orbits revealed a heterogeneously enhancing, well-circumscribed mass in the right upper eyelid with no orbital extension. A transcutaneous excisional biopsy with histopathology disclosed cavernous venous malformation. The majority of cavernous venous malformations are intraconal and present in the fourth to fifth decade of life.

Multifunctional 58S Bioactive Glass/Silver/Cerium Oxide-Based Biocomposites with Effective Antibacterial, Cytocompatibility, and Mechanical Properties.

58S bioactive glass (BG) has effective biocompatibility and bioresorbable properties for bone tissue engineering; however, it has limitations regarding antibacterial, antioxidant, and mechanical properties. Therefore, we have developed BGAC biocomposites by reinforcing 58S BG with silver and ceria nanoparticles, which showed effective bactericidal properties by forming inhibited zones of 2.13 mm (against Escherichia coli) and 1.96 mm (against Staphylococcus aureus; evidenced by disc diffusion assay) and an increment in the antioxidant properties by 39.9%. Moreover, the elastic modulus, hardness, and fracture toughness were observed to be increased by ∼84.7% (∼51.9 GPa), ∼54.5% (∼3.4 GPa), and ∼160% (∼1.3 MPam1/2), whereas the specific wear rate was decreased by ∼55.2% (∼1.9 × 10-11 m3/Nm). X-ray diffraction, high-resolution transmission electron microscopy, and field emission scanning electron microscopy confirmed the fabrication of biocomposites and the uniform distribution of the nanomaterials in the BG matrix. The addition of silver nanoparticles in the 58S BG matrix (in BGA) increased mechanical properties by composite strengthening and bactericidal properties by damaging the cytoplasmic membrane of bacterial cells. The addition of nanoceria in 58S BG (BGC) increased the antioxidant properties by 44.5% (as evidenced by the 2,2-diphenyl-1-picrylhydrazyl assay). The resazurin reduction assay and MTT assay confirmed the effective cytocompatibility for BGAC biocomposites against mouse embryonic fibroblast cells (NIH3T3) and mouse bone marrow stromal cells. Overall, BGAC resulted in mechanical properties comparable to those of cancellous bone, and its effective antibacterial and cytocompatibility properties make it a good candidate for bone healing.

Novel treatment with double scope technique for disconnected pancreatic duct syndrome with external pancreatic fistula.

Background and study aims External pancreatic fistula in association with disconnected pancreatic duct syndrome is a common sequelae of the percutaneous step-up approach for infected pancreatic necrosis and is associated with significant morbidity. The present study aimed to report the initial outcome of a novel technique of two-scope guided tractogastrostomy for management of this condition. Patients and methods The present study was a retrospective analysis of data from patients with external pancreatic fistula and disconnected pancreatic duct syndrome, who underwent two-scope-guided tractogastrostomy. All the patients had a 24F or larger drain placed in the left retroperitoneum. Transgastric echo endoscopy and sinus tract endoscopy were performed simultaneously to place a stent between the gastric lumen and the sinus tract. Technical success was defined as placement of the stent between the tract and the stomach. Clinical success was defined as successful removal of the percutaneous drain without the occurrence of pancreatic fluid collection, ascites, external fistula, or another intervention 12 weeks after the procedure. Results Three patients underwent two scope-guided tractogastrostomy. Technical and clinical success were achieved in all the patients. No procedure-related side effects or recurrence occurred in any of the patients. Conclusions Two-scope-guided tractogastrostomy for treatment of external pancreatic fistula due to disconnected pancreatic duct syndrome is a feasible technique and can be further evaluated.

Applications of artificial intelligence in biliary tract cancers.

Biliary tract cancers are malignant neoplasms arising from bile duct epithelial cells. They include cholangiocarcinomas and gallbladder cancer. Gallbladder cancer has a marked geographical preference and is one of the most common cancers in women in northern India. Biliary tract cancers are usually diagnosed at an advanced, unresectable stage. Hence, the prognosis is extremely dismal. The five-year survival rate in advanced gallbladder cancer is < 5%. Hence, early detection and radical surgery are critical to improving biliary tract cancer prognoses. Radiological imaging plays an essential role in diagnosing and managing biliary tract cancers. However, the diagnosis is challenging because the biliary tract is affected by many diseases that may have radiological appearances similar to cancer. Artificial intelligence (AI) can improve radiologists' performance in various tasks. Deep learning (DL)-based approaches are increasingly incorporated into medical imaging to improve diagnostic performance. This paper reviews the AI-based strategies in biliary tract cancers to improve the diagnosis and prognosis.