Retrospective analysis of the outcomes of endoscopic transsphenoidal surgery for Cushing's disease.

Background: The first-line surgical management of an adrenocorticotropic hormone (ACTH)--secreting pituitary adenoma causing Cushing's disease (CD) is endoscopic transsphenoidal resection of the tumor. This study was performed to assess postoperative (postop) complications and remission in endoscopic surgically resected cases of CD. Methods: Data of patients who underwent endoscopic transsphenoidal surgery (ETSS) for CD were collected from the neurosurgery department at a tertiary care center in a retrospective manner from January 2015 to February 2022 and analyzed. Postoperative remission was categorized as - early morning serum cortisol <138 nmol/L within 7 days of the surgery, as per the Endocrine Society Guidelines, with significant clinical improvement in features of hypercortisolism in the operated patient and strict cutoff rate of <50 nmol/L at postop day 3 was also utilized, to look for the early identification of remission. Results: A total of 41 patients were identified who underwent 44 ETSS during the same timeframe. Preoperative magnetic resonance imaging localized an adenoma in all 41 patients, out of which 32 were microadenoma, and nine were macroadenoma (2 with cavernous sinus invasion). Intrapetrosal sinus sampling was performed in 35 (85%) patients. The rate of remission for the initial surgery was 85.4% using the standard criteria and 68.3% using strict criteria. Three patients underwent early repeat surgery for the persistent disease as the day 3 cortisol was high (306-555 nmol/L). Once the outcome of this surgery was also included, the overall rate of remission was 90.2% (37/41). None of the patients had meningitis, cerebrospinal fluid leakage, visual deterioration, or vascular injury. Permanent and transient diabetes insipidus (DI) occurred in 9.75% and 26.8% following the first ETSS, respectively. We also noted a single case of CD recurrence in 9 months during the total follow-up period of 84 months. Conclusion: ETSS has satisfactory rates of remission for the primary treatment of CD, with rates being higher for microadenomas. A long follow-up period is needed to assess the rates of recurrence. Patients must be counseled regarding the risk of postop DI, whether transient or permanent, as a possible complication.

Effectiveness of biofeedback on blood pressure in patients with hypertension: systematic review and meta-analysis.

Hypertension is the leading modifiable risk factor for cardiovascular disease, but less than 50% have their blood pressure controlled. A possible avenue to support hypertension management is a holistic approach, using non-pharmacological interventions. Since hypertension is mediated in part by dysregulation of the autonomic nervous system (ANS), biofeedback may help improve hypertension management by targeted self-regulation and self-awareness of parameters that regulate the ANS. This systematic review aimed to assess the effectiveness of biofeedback on blood pressure in hypertensive patients. The review was pre-registered on PROSPERO and followed the PICO strategy. A total of 1782 articles were retrieved, 20 met the inclusion criteria. Sample sizes ranged from 15 to 301 participants; with a median age of 49.3 (43.3-55.0) years and 45% were female. There was a significant effect of biofeedback on systolic (-4.52, Z = 2.31, P = 0.02, CI [-8.35, -0.69]) and diastolic blood pressure (-5.19, Z = 3.54, P = 0.0004, CI [-8.07, -2.32]). Six different biofeedback modalities were used, with biofeedback delivered by psychologists, trained therapists and research assistants. There was no publication bias, heterogeneity was rated as substantial and data quality was rated to be poor. This review demonstrated that biofeedback had a significant effect on blood pressure. However, this should be viewed in the context of included studies being limited by heterogeneity and dated literature, meaning the research does not reflect the current biofeedback technology such as wearable devices. Future research should incorporate these technologies with robust methodology to fully understand the effect of biofeedback on hypertension.

Dual-energy CT in differentiating benign gallbladder wall thickening from wall thickening type of gallbladder cancer.

OBJECTIVE: To evaluate the performance of dual-energy computed tomography (DECT) in differentiating non-acute benign from malignant gallbladder wall thickening (GBWT). METHODS: This prospective study comprised consecutive adults with GBWT who underwent late arterial phase (LAP) and portal venous phase (PVP) DECT between January 2022 and May 2023. The final diagnosis was based on histopathology or 3-6 months follow-up imaging. DECT images in LAP and PVP were assessed independently by two radiologists. The demographic, qualitative, and quantitative parameters were compared between two groups Multivariate logistic regression was performed to determine the association between the aforementioned factors and malignant GBWT. RESULTS: Seventy-five patients (mean age 56 ± 12.8 years, 46 females) were included. Forty-two patients had benign, and 33 had malignant GBWT. In the overall group, female gender (p = 0.018), lymphadenopathy (p = 0.011), and omental nodules (p = 0.044) were significantly associated with malignant GBWT. None of the DECT features differed significantly between benign and malignant GBWT in overall group. In the xanthogranulomatous cholecystitis (XGC, n = 9) vs. gallbladder cancer (GBC) (n = 33) subgroup, mean attenuation value at 140 keV LAP VMI was significantly associated with malignant GBWT [p = 0.023, area under curve 0.759 (95%CI 0.599-0.919)]. CONCLUSION: DECT-generated quantitative parameters do not add value in differentiating non-acute benign from malignant GBWT. However, DECT may have a role in differentiating XGC from GBC in a selected subgroup of patients. Further, larger studies may be necessary to confirm these findings. CLINICAL RELEVANCE STATEMENT: In patients with non-acute gallbladder wall thickening in whom there is suspicion of xanthogranulomatous cholecystitis (XGC), DECT findings may allow differentiation of XGC from wall thickening type of gallbladder cancer. KEY POINTS: Differentiation of benign and malignant gallbladder wall thickening (GBWT) at CT is challenging. Quantitative dual energy CT (DECT) features do not provide additional value in differentiating benign and malignant GBWT. DECT may be helpful in a subgroup of patients to differentiate xanthogranulomatous cholecystitis from gallbladder cancer.

Transverse versus longitudinal mucosal incision during POEM for esophageal motility disorders: a randomized trial.

BACKGROUND: Longitudinal incision is the commonly used incision for entry into the submucosal space during peroral endoscopic myotomy (POEM) for esophageal motility disorders. Transverse incision is another alternative for entry and retrospective data suggest it has less operative time and chance of gas-related events. METHODS: This was a single-center, randomized trial conducted at a tertiary care hospital. Patients undergoing POEM for esophageal motility disorders were randomized into group A (longitudinal incision) and group B (transverse incision). The primary objective was to compare the time needed for entry into the submucosal space. The secondary objectives were to compare the time needed to close the incision, number of clips required to close the incision, and development of gas-related events. The sample size was calculated as for a non-inferiority design using Kelsey method. RESULTS: Sixty patients were randomized (30 in each group). On comparing the 2 types of incisions, there was no difference in entry time [3 (2, 5) vs 2 (1.75, 5) min, p = 0.399], closure time [7 (4, 13.5) vs 9 (6.75, 19) min, p = 0.155], and number of clips needed for closure [4 (4, 6) vs 5 (4, 7), p = 0.156]. Additionally, the gas-related events were comparable between the 2 groups (capnoperitoneum needing aspiration-5 vs 2, p = 0.228, and development of subcutaneous emphysema-3 vs 1, p = 0.301). CONCLUSION: This randomized trial shows comparable entry time, closure time, number of clips needed to close the incision, and gas-related events between longitudinal and transverse incisions. REGISTRATION NUMBER: CTRI/2021/08/035829.

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.

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.

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.

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.

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.

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.

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.

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.

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 µm) 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.

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.