Xanthogranulomatous Pyelonephritis in a Neonate Masquerading as Renal Mass.

Xanthogranulomatous pyelonephritis (XGP), a variant of chronic obstructive pyelonephritis, is a very rare diagnosis in neonates with three reported cases to date. It is often misdiagnosed in infancy as it mimics the features of renal mass. Herein, we report a case of 20-day-old neonate with XGP presenting as a renal mass.

Micro-RNAs With Prognostic Significance in Gallbladder Cancer: A Systematic Review and Meta-Analysis.

Gallbladder cancer (GBC) stands out as one of the most widespread malignancies impacting the biliary tract globally. Despite increasing interest, to the best of our knowledge, no meta-analysis has been undertaken to amalgamate the existing data concerning the prognostic significance of micro-RNAs (miRNAs) in GBC in comparison to studies on miRNAs in other cancers. Hence, this systematic review and meta-analysis aimed at determining the prognostic significance of miRNAs in GBC patients. Comprehensive literature searches were conducted across PubMed, Cochrane Library, Ovid, Scopus, and Science Direct databases. Studies that evaluated the association between miRNAs and overall survival in GBC patients were included. Random-effect meta-analysis was employed to pool hazard ratios (HRs) and their 95% confidence intervals (CIs) across studies. A total of 15 studies, encompassing 16 miRs, were included for our analysis. The pooled analysis revealed that a high expression of miR-204, miR-7-2-3p, miR-29c-3p, miR-125b, miR-20a, miR-139-5p, miR-141, miR-92b-3p, miR-335, and miR-372 was significantly associated with poor prognosis and increased risk (HR>1 and the upper bound of the 95% CI>1). Additionally, these miRNAs were associated with the overall survival (HR = 1.56, 95% CI = 0.91-2.20, I2 = 91.82%). Significant heterogeneity was observed and could be attributed to the limited number of studies available on the GBC and significant reliance on quantitative real-time PCR for the detection of miRNAs. In conclusion, specific miRNAs exhibit prognostic significance in GBC, with potential implications for patient stratification and targeted therapeutic interventions. However, due to the heterogeneity among studies, these findings should be interpreted cautiously and validated in larger cohorts.

Clinical acceptance and dosimetric impact of automatically delineated elective target and organs at risk for head and neck MR-Linac patients.

Background: MR-Linac allows for daily online treatment adaptation to the observed geometry of tumor targets and organs at risk (OARs). Manual delineation for head and neck cancer (HNC) patients takes 45-75 minutes, making it unsuitable for online adaptive radiotherapy. This study aims to clinically and dosimetrically validate an in-house developed algorithm which automatically delineates the elective target volume and OARs for HNC patients in under a minute. Methods: Auto-contours were generated by an in-house model with 2D U-Net architecture trained and tested on 52 MRI scans via leave-one-out cross-validation. A randomized selection of 684 automated and manual contours (split half-and-half) was presented to an oncologist to perform a blind test and determine the clinical acceptability. The dosimetric impact was investigated for 13 patients evaluating the differences in dosage for all structures. Results: Automated contours were generated in 8 seconds per MRI scan. The blind test concluded that 114 (33%) of auto-contours required adjustments with 85 only minor and 15 (4.4%) of manual contours required adjustments with 12 only minor. Dosimetric analysis showed negligible dosimetric differences between clinically acceptable structures and structures requiring minor changes. The Dice Similarity coefficients for the auto-contours ranged from 0.66 ± 0.11 to 0.88 ± 0.06 across all structures. Conclusion: Majority of auto-contours were clinically acceptable and could be used without any adjustments. Majority of structures requiring minor adjustments did not lead to significant dosimetric differences, hence manual adjustments were needed only for structures requiring major changes, which takes no longer than 10 minutes per patient.

Assessment of Nutritional Status and Correlation of Factors With Body Mass Index of Cancer Patients: A Cross-Sectional Study.

BACKGROUND: Decreased diet intake and malnourishment have profound implications on cancer patients' quality of life and survival. Malnutrition increases the risk of postoperative complications, increases hospital length stays, reduces patient's tolerance to radiation and chemotherapy treatment, and results in poor response to treatment. In the present study, we intended to assess the nutritional status of cancer patients and find the correlation of body mass index with anthropometric and blood parameters. MATERIAL & METHODS: The study was prospective and cross-sectional, and 104 patients with newly diagnosed solid tumors were included. Patient demographics, symptoms, and anthropometric and blood parameters were collected. The correlation was estimated with Pearson's correlation coefficient. A p-value of less than 0.05 was considered significant. RESULTS: The association between stages of the disease, dental status, type of diet, and BMI was p=0.701, 0.216, and 0.422, respectively, and was not statistically significant. The anthropometric parameters mid upper arm circumference (MUAC cm), mid arm circumference (MAC cm), and triceps skinfold thickness (TSF mm) correlated with body mass index (BMI kg/m2) and had statistically significant p values of 0.0001, 0.0001, and 0.033, respectively. The correlation was assessed between hemoglobin, red cell distribution width, neutrophil-to-lymphocyte ratio, and serum albumin levels with BMI, but except for albumin (p=0.05), no other blood parameter correlated. CONCLUSION: Nutritional assessment is vital in recognizing patients at risk of treatment-associated complications and poor responders to treatment. In this study, BMI correlated with anthropometric parameters MUAC, MAMC, and TSF. Baseline dietary assessments of patients will help focus on the nutritional build-up of patients before starting treatment.

Comparison of block characteristics and outcomes in opioid-free and opioid-based thoracic continuous spinal anaesthesia in patients undergoing major abdominal surgery: A double-blinded randomised controlled trial.

Background and Aims: Thoracic continuous spinal anaesthesia (TCSA) is emerging as the sole anaesthetic for major abdominal surgery due to its better perioperative outcomes. This study was designed to evaluate block characteristics and outcomes in 'opioid-free' and 'opioid-based' TCSA. Methods: After ethical approval, trial registration and written informed consent, 50 adult patients undergoing major abdominal surgery were randomised into 'opioid-free' (bupivacaine alone) and 'opioid-based' (bupivacaine with fentanyl) groups. After confirmation of T4-L1 dermatome level of spinal anaesthesia, sedation by intravenous (IV) midazolam (0.02-0.05 mg/kg), ketamine (0.25 mg/kg) and dexmedetomidine (bolus dose of 1 µg/kg IV over 10 min followed by 0.2-0.7 µg/kg/h infusion) were started. The primary outcome measured was postoperative pain scores for 72 h in both groups. The secondary objectives were rescue opioid requirement, and the dose of bupivacaine required to achieve T4 level. Data were compared using the two-sided Student t-test, Mann-Whitney and Fisher's exact tests. Results: The 'opioid-based' group performed significantly better compared with the 'opioid-free' group concerning pain scores at rest at 0 h (P = 0.023), 18 h (P = 0.023) and 24 h (P = 0.016) postoperatively, decreased intrathecal bupivacaine requirement [(induction (P = 0.012) and maintenance (P = 0.031)], postoperative rescue fentanyl requirement (P = 0.018) and patient satisfaction (P = 0.032) at the cost of increased postoperative nausea and vomiting (P = 0.049). Conclusion: The 'opioid-based' TCSA provided better postoperative analgesia with significantly lesser postoperative pain scores when compared to the 'opioid-free' group in patients undergoing major abdominal surgery.

Calvarial hemangiomas: Series of 6 cases and review of literature.

Calvarial haemangiomas are benign, vascular tumours of the skull involving parietal and frontal bones. Mostly these lesions remain asymptomatic, and present with cosmetic deformity, headache, uncommon neurological symptoms and reported as case reports and case series. The radiological appearance can range from sessile growing intradiploically to globular and the lesions may extend outwards or inwards after eroding the outer and inner tables of the skull. "Sunburst appearance" and "Wagon-wheel sign" are classical radiological findings but the lesions may present simply as a lytic expansile or even sclerotic calvarial mass. Because of varied clinical presentation and atypical radiological characteristics, the final diagnosis can be clinched by histology only. In selected cases where these lesions are not cosmetically acceptable, en bloc resection with tumour free margins followed by cranioplasty is the treatment of choice. Most reports of calvarial haemangiomas in literature are in the form of case reports.

Sildenafil as a Candidate Drug for Alzheimer's Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons.

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease needing effective therapeutics urgently. Sildenafil, one of the approved phosphodiesterase-5 inhibitors, has been implicated as having potential effect in AD. Objective: To investigate the potential therapeutic benefit of sildenafil on AD. Methods: We performed real-world patient data analysis using the MarketScan® Medicare Supplemental and the Clinformatics® databases. We conducted propensity score-stratified analyses after adjusting confounding factors (i.e., sex, age, race, and comorbidities). We used both familial and sporadic AD patient induced pluripotent stem cells (iPSC) derived neurons to evaluate the sildenafil's mechanism-of-action. Results: We showed that sildenafil usage is associated with reduced likelihood of AD across four new drug compactor cohorts, including bumetanide, furosemide, spironolactone, and nifedipine. For instance, sildenafil usage is associated with a 54% reduced incidence of AD in MarketScan® (hazard ratio [HR] = 0.46, 95% CI 0.32- 0.66) and a 30% reduced prevalence of AD in Clinformatics® (HR = 0.70, 95% CI 0.49- 1.00) compared to spironolactone. We found that sildenafil treatment reduced tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic AD patient iPSC-derived neurons. RNA-sequencing data analysis of sildenafil-treated AD patient iPSC-derived neurons reveals that sildenafil specifically target AD related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in AD. Conclusions: These real-world patient data validation and mechanistic observations from patient iPSC-derived neurons further suggested that sildenafil is a potential repurposable drug for AD. Yet, randomized clinical trials are warranted to validate the causal treatment effects of sildenafil in AD.

Correlation of anterior segment optical coherence tomography and ultrasound biomicroscopy in congenital corneal opacity.

PURPOSE: To investigate the correlation between swept-source anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) in congenital corneal opacity (CCO). METHODS: All children with unilateral or bilateral congenital corneal opacities who underwent examination under anesthesia (EUA) and anterior segment optical coherence tomography (AS-OCT) imaging from January 1, 2022, to December 31, 2022, were included. Main outcome measures were corneal and anterior segment evaluation and correlation of UBM and AS-OCT findings. RESULTS: A total of 22 eyes of 15 patients were imaged using both technologies. The age at first EUA ranged from 11 days to 4 years. Different phenotypes were classified based on the clinical examination, UBM, and AS-OCT findings. Fourteen eyes were diagnosed with Peters anomaly, congenital corneal staphyloma was observed in 4 eyes, 2 eyes had coloboma, 1 eye had peripheral sclerocornea, and 1 eye was diagnosed with congenital primary aphakia. AS-OCT and UBM findings were closely correlated in 18 of 22 eyes (82%) but AS-OCT failed to provide detailed information in 4 eyes (18%) where UBM revealed more details. CONCLUSIONS: Although AS-OCT offers valuable preliminary data for initial assessment and counseling, it may not consistently provide precise assessments in all cases. Therefore, UBM should be considered for definitive evaluation.

The Resurgence of Lymphogranuloma Venereum: Changing Presentation of Lymphogranuloma Venereum in the Era of HIV Preexposure Prophylaxis, 2004 to 2022.

BACKGROUND: Before the early 2000s, the sexually transmitted infection lymphogranuloma venereum (LGV) was rare in high-income countries. Initially, most cases in these countries were among symptomatic men who have sex with men (MSM) living with HIV. In the context of widespread HIV preexposure prophylaxis (PrEP), LGV's epidemiology may be changing. We aimed to characterize the epidemiology and clinical presentation of LGV in the PrEP era. METHODS: A retrospective chart review was performed on all LGV cases occurring between November 2004 to October 2022 in British Columbia (BC), Canada. Cases were stratified by having occurred before (2004-2017) or after widespread PrEP availability in BC (2018-2022). Annual rates and test positivity percentages were calculated. Bivariate logistic regression was performed to identify drivers of asymptomatic infection in the PrEP era. RESULTS: Among 545 cases identified, 205 (37.6%) occurred pre-PrEP and 340 (62.4%) occurred during the PrEP era. Most cases were among MSM (97.2%). The estimated rate of LGV has doubled from 2018 to 2022, reaching 1535.2 cases per 100,000 PrEP users. Most PrEP-era cases were among HIV-negative individuals (65.3%), particularly those on PrEP (72.6%). Cases in the PrEP era were often asymptomatic compared with pre-PrEP (38.6% vs. 19.3%; P < 0.001). Users of PrEP were more likely to experience asymptomatic infection compared with HIV-negative PrEP nonusers (odds ratio, 2.07; 95% confidence interval, 1.07-3.99). CONCLUSIONS: In the context of increased asymptomatic testing, LGV may be increasing in BC. Most infections now occur among HIV-negative MSM. A high proportion of infections are asymptomatic.

Effects of ultraviolet radiation on cellular functions of the cyanobacterium Synechocystis sp. PCC 6803 and its recovery under photosynthetically active radiation.

Cyanobacteria are photosynthetic organisms and challenged by large number of stresses, especially by ultraviolet radiation (UVR). UVR primarily impacts lipids, proteins, DNA, photosynthetic performance, which lowers the fitness and production of cyanobacteria. UVR has a catastrophic effect on cyanobacterial cells and eventually leads to cell death. UVR tolerance in the Synechocystis was poorly studied. Therefore, we irradiated Synechocystis sp. PCC 6803 to varying hours of photosynthetically active radiations (PAR), PAR + UV-A (PA), and PAR + UV-A + UV-B (PAB) for 48 h. To study the tolerance of Synechocystis sp. PCC 6803 against different UVR. The study shows that Chl a and total carotenoids content increased up to 36 h in PAR and PA, after 36 h a decrease was observed. PC increased up to 4-fold in 48 h of PA irradiation compared to 12 h. Maximum increase in ROS was observed under 48 h PAB i.e., 5.8-fold. Flowcytometry (FCM) based analysis shows that 25% of cells do not give fluorescence of Chl a and H2DCFH. In case of cell viability 10% cells were found to be non-viable in 48 h of PAB irradiance compared to 12 h. From the above study it was found that FCM-based approaches would provide a better understanding of the variations that occurred within the Synechocystis cells compared to fluorescence microscopy-based methods.

A Case Report on Hendren's Technique for Managing Symptomatic Isolated Urogenital Sinus in an Infant.

Isolated urogenital sinus is a rare anomaly. These cases may have high confluence which adds complexity to surgical correction. There are controversies regarding timing and techniques of management. We present a case report on managing such a case in an infant with bladder outlet obstruction and pyocolpos.

Study of Intrahepatic Biliary Architecture in Patients Operated for Extrahepatic Biliary Atresia using Magnetic Resonance Cholangiopancreatography.

Aim: The aim is to study intrahepatic biliary architecture in patients following Kasai's portoenterostomy for extrahepatic biliary atresia using magnetic resonance cholangiopancreatography (MRCP). Materials and Methods: It is a prospective observational study in a cohort of patients who have survived with a complete jaundice-free period for at least 1 year. MRCP was done to look for various intrahepatic architectural changes during their last visit. Findings were correlated with liver functions and growth and development. Results: Twenty-one patients were included in the study. The male-to-female sex ratio was 1.6:1, the median age at surgery was 75 days (18-140 days), and the median age at magnetic resonance imaging (MRI) was 4 years (18 months-18 years). More than 2 years of follow-up was in seven patients. Left lobe hypertrophy was observed in six patients, right lobe hypertrophy was in three patients, intrahepatic biliary tract dilatation was in five patients, and altered signal intensity between intrahepatic ducts was seen in five patients. In addition, hypointense foci in the spleen were seen in one patient. Twelve children had normal weight for their age, ten children had the normal height for their age, and gamma-glutamyl transferase was elevated in all children. Only four children had a history of fever and jaundice. Conclusions: The patients who survive after successful surgical intervention have near-normal liver gross architecture as on MRI/MRCP. Occasional findings of dilatation and lobar atrophy/hypertrophy are possible, especially in those with a history of cholangitis. The survivors also have acceptable growth parameters and normal liver functions.

Biophysical and Biochemical Characterization of Structurally Diverse Small Molecule Hits for KRAS Inhibition.

We describe six compounds as early hits for the development of direct inhibitors of KRAS, an important anticancer drug target. We show that these compounds bind to KRAS with affinities in the low micromolar range and exert different effects on its interactions with binding partners. Some of the compounds exhibit selective binding to the activated form of KRAS and inhibit signal transduction through both the MAPK or the phosphatidylinositide 3-kinase PI3K-protein kinase B (AKT) pathway in cells expressing mutant KRAS. Most inhibit intrinsic and/or SOS-mediated KRAS activation while others inhibit RAS-effector interaction. We propose these compounds as starting points for the development of non-covalent allosteric KRAS inhibitors.

Rank acquisition impact on radiomics estimation (AсquIRE) in chest CT imaging: A retrospective multi-site, multi-use-case study.

BACKGROUND: Radiomics is a method within medical image analysis that involves the extraction of quantitative data from radiologic scans, often in conjunction with machine learning algorithms to phenotype disease appearance, prognosticate disease outcome, and predict treatment response. However, variance in CT scanner acquisition parameters, such as convolution kernels or pixel spacing, can impact radiomics texture feature values. PURPOSE: The extent to which the parameters influence radiomics features continues to be an active area of investigation. In this study, we describe a novel approach, Acquisition Impact on Radiomics Estimation (AcquIRE), to rank the impact of CT acquisition parameters on radiomic texture features. METHODS: In this work, we used three chest CT imaging datasets (n = 749 patients) from nine sites comprising: i) lung granulomas and adenocarcinomas (D1) (10 and 52 patients, respectively); ii) minimal and frank invasive adenocarcinoma (D2) (74 and 145 patients); and iii) early-stage NSCLC patients (D3) (315 patients). Datasets D2 and D3 were collected from four sites each, and D1 from a single site. For each patient, 744 texture features and nine acquisition parameters were extracted and utilized to evaluate which parameters impact radiomic features the most. The AcquIRE method establishes a relative assessment between acquisition parameters and radiomic texture featuresa through the creation of a classification model, which is then utilized to assess the rank of the acquisition parameters. RESULTS: Across the use cases, CT software version and convolution kernel parameters were found to have the most variance. In D1, it was observed that the Haralick texture feature family was the least affected by variations in acquisition parameters, while the Gabor feature family was the most impacted. However, in datasets D2 and D3, the Gabor features were found to be the least affected. Our findings suggest that the impact on radiomic parameters is as much a function of the problem in question as it is acquisition parameters. CONCLUSIONS: The software version and convolution kernel parameters impacted the radiomics feature the most.

Comparison of HASTE versus EPI-Based DWI for Retinoblastoma and Correlation with Prognostic Histopathologic Parameters.

BACKGROUND AND PURPOSE: Non-EPI-based DWI has shown better performance in head and neck pathologies owing to lesser susceptibility artifacts compared with EPI-DWI. However, only sporadic studies have investigated the feasibility of non-EPI-based DWI in retinoblastoma (RB). We qualitatively and quantitively compared EPI-DWI and HASTE-DWI in RB and correlated the tumor ADC values obtained from these 2 techniques with histopathologic markers. MATERIALS AND METHODS: Twenty-one treatment-naive patients with RB underwent 1.5T orbital MR imaging. EPI-DWI and HASTE-DWI were acquired at 3 b-values (0, 500, and 1000 s/mm2). All patients subsequently underwent surgical enucleation. For qualitative image assessment, scoring of overall image quality, artifacts, tumor sharpness, and tumor conspicuity was done by using a 5-point Likert scale. Quantitative assessment included calculations of SNR, contrast-to-noise ratio (CNR), geometric distortion, and ADC. Qualitative scores were compared by using the Wilcoxon signed-rank test, and quantitative parameters were analyzed with a t test. RESULTS: All 21 patients had unilateral RB; 15 were male and 6 were female with a median age of 36 months (range, 9-72 months). On histopathology, patients had either poorly differentiated (n = 13/21) or moderately differentiated (n = 8/21) RB. Other poor prognostic markers evaluated were optic nerve invasion (n = 10/21), choroidal invasion (n = 12/21), and anterior eye segment enhancement on MRI (n = 6/21). HASTE-DWI demonstrated higher image quality scores than EPI-DWI (P < .01), except for tumor conspicuity score, which was higher for EPI-DWI (P < .001). HASTE-DWI showed lower SNR, CNR, and geometric distortion than EPI-DWI (P < .001). The average acquisition times of EPI-DWI and HASTE-DWI were ∼1 and 14 minutes, respectively. The mean tumor ADC value on EPI-DWI was 0.62 ± 0.14 × 10-3 mm2/s and on HASTE-DWI was 0.83 ± 0.17 × 10-3 mm2/s. A significant correlation between EPI-DWI and HASTE-DWI ADC values (r = 0.8; P = .01) was found. Lower ADC values were found in tumors with poor prognostic markers, but none reached a statistically significant difference. CONCLUSIONS: HASTE-DWI shows improved overall image quality; however, it lacks in terms of tumor conspicuity, SNR, CNR, and longer acquisition time compared with EPI-DWI. ADC values derived from HASTE-DWI show no advantage over EPI-DWI in correlation with histopathologic prognostic markers.