Ocular Cicatricial Pemphigoid in Young Patients.

PURPOSE: The purpose of this study is to report ocular cicatricial pemphigoid (OCP) occurring in young patients. Relevant literature is also reviewed. METHODS: Medical records of patients aged 30 years or younger who were treated for OCP between August 2021 and May 2023 at a tertiary care eye institute were reviewed. The most common differential diagnoses of cicatrizing conjunctivitis, such as Stevens-Johnson syndrome sequelae, chemical injury, chronic topical/systemic drug use, autoimmune connective tissue disorders, or allergic eye diseases, were ruled out based on clinical history, examination, and the Cicatrizing Conjunctivitis Score described by Shanbhag et al. The diagnosis of OCP was confirmed by positive direct immunofluorescence of oral mucosal and/or conjunctival biopsy in a majority of the patients. RESULTS: Seven patients fulfilled the criteria for a diagnosis of OCP. The mean age at presentation was 21.86 ± 5.25 years (13-28 years). Some of the patients presented with relatively atypical features for OCP such as corneal immune ring infiltrate and bilateral corneal perforation. Six patients exhibited systemic mucosal lesions, and the direct immunofluorescence yield was 85.71%. All patients required aggressive immunosuppressive treatment. CONCLUSIONS: OCP is classically described as a rare disease that occurs in old age. This case series highlights the importance of a higher index of suspicion for diagnosing OCP at a younger age. Early administration of immunosuppressive agents can potentially control severe ocular surface inflammation and its sequelae.

Preoperative topical estrogen application in the management of hypospadias: a systematic review.

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18 years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.

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.

Risk factors and outcome of antenatally diagnosed congenital diaphragmatic hernia following in-utero transfer in a busy public-sector tertiary care center in North India.

We analyzed the risk factors and outcomes of antenatally diagnosed congenital diaphragmatic hernia (CDH) from a tertiary-care children's hospital following in-utero transfer. A total of 41 antenatally detected cases of CDH were included; 30 were live-born and 11 were still-born. The primary outcome was postnatal survival. The secondary outcome was the probable factor affecting survival. No medical termination of the pregnancy was done. The mean gestational age at diagnosis was 23 weeks. The diagnostic accuracy of antenatal ultrasonography was 40/41 (97.5%). Lung-to-head ratio (LHR) was <1 in 20 cases (survived 2), LHR was >1 in 10 cases (survived 8), and LHR was not recorded in 11 cases (survived 4). Overall survival was 14/41 (34.1%). Survival in fetuses with polyhydramnios was 0% (n=3; survived 0), associated anomalies were 33.3% (n=3; survived 1), and liver herniation was 22.2% (n=9; survived 2). Postnatally, significant risk factors included a low Apgar score, the need for ventilation, and neonatal intensive care unit (NICU) management. Survival in live-born cases was 14/30 (46.6%) and in operated cases was 14/19 (73.6%). We concluded that antenatal ultrasound had a high accuracy rate for detecting CDH. Antenatal risk factors affecting outcomes were low LHR, maternal polyhydramnios, liver herniation, and associated malformations. Postnatal risk factors included a low Apgar score, NICU admission, and a need for ventilation. The overall survival rate, as well as the survival rates for live-borns and those undergoing surgery, were 34.1%, 46.6%, and 73.6%, respectively. This data will guide clinicians in counseling the families of antenatally diagnosed CDH.

Ultrasound-guided procedures for postoperative pain management in pediatric patients undergoing abdominal surgeries: A systematic review.

Many ultrasound-guided procedures are available for administering analgesia via peripheral nerve blockade. This systematic review aims to compare different ultrasound-guided procedures to determine which procedure is better suited for pediatric abdominal surgeries. The objective is to understand the efficacy of ultrasound-guided procedures for postoperative pain management in children undergoing abdominal surgeries and to identify which procedure takes less time and is better suited for a particular surgery. A systematic literature search was performed in PubMed, SCOPUS, Central Cochrane Registry of Controlled Trials (The Cochrane Library), and ScienceDirect databases for pediatric abdominal surgeries conducted with ultrasound-guided procedures for administering analgesia. We included studies involving randomized controlled trials (RCTs). Quasi-randomized controlled studies, prospective, retrospective observational studies, case series, case reports, letters, editorials, comments, animal studies, and studies from non-English literature were excluded. We reviewed 13 articles with 910 patients included. Age groups varied from 6 months to 21 years. The most common block used was the transversus abdominis block (47.76%), and the most common surgery performed was hernia and hydrocele (52.10%). Quadratus lumborum block was used in 26.92%, erector spinae block in 8.97%, modified transversus abdominus block and rectus sheath block in 9.62%, and ilioinguinal block in 6.73% of the patients. No complications were reported in any of the studies. Transversus abdominus block is less effective in two of the studies. Each procedure for pediatric postoperative analgesia has specific advantages and limitations, highlighting the complexity of tailoring interventions. Our review focuses on the advancements in ultrasound-guided analgesia for lower abdominal surgeries in pediatric patients while also emphasizing the need for future randomized controlled trials (RCTs) to compare efficacy, standardize practices, and improve patient outcomes.

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.

Measurement and Incorporation of Laryngeal Motion Using cine-MRI on an MR-Linear Accelerator to Generate Radiation Therapy Plans for Early-stage Squamous Cell Cancers of the Glottis.

Purpose: Swallow-related motion of the larynx is most significant in the cranio-caudal directions and of` short duration. Conventional target definition for radical radiation therapy includes coverage of the whole larynx. This study longitudinally examined respiration- and swallow-related laryngeal motions using cine-magnetic resonance imaging. We further analyzed the dosimetry to organs at risk by comparing 3D-conformal radiation therapy (3D-CRT), volumetric modulated arc therapy (VMAT), and intensity modulated radiation therapy (IMRT) techniques. Methods: Fifteen patients with T1-2 N0 glottic squamous cell carcinomas were prospectively recruited for up to 3 cine-MRI scans on the Elekta Unity MR-Linear accelerator, at the beginning, middle, and end of a course of radical radiation therapy. Swallow frequency and motion of the hyoid bone, cricoid and thyroid cartilages, and vocal cords were recorded during swallow and rest. Adapted treatment volumes consisted of gross tumor volume + 0.5-1 cm to a clinical target volume with an additional internal target volume (ITV) for personalized resting-motion. Swallow-related motion was deemed infrequent and was not accounted for in the ITV. We compared radiation therapy plans for 3D-CRT (whole larynx), VMAT (whole larynx), and VMAT and IMRT (ITV for resting motion). Results: Resting- and swallow-related motions were most prominent in the cranio-caudal plane. There were no significant changes in the magnitude of motion over the course of radiation therapy. There was a trend of a progressive reduction in the frequency of swallow. Treatment of partial larynx volumes with intensity modulated methods significantly reduced the dose to carotid arteries, compared with treatment of whole larynx volumes. Robustness analysis demonstrated that when accounting for intrafraction swallow, the total dose delivered to the ITV/planning target volume was maintained at above 95%. Conclusions: Swallow-related motions are infrequent and accounting for resting motion in an ITV is sufficient. VMAT/IMRT techniques that treat more conformal targets can significantly spare critical organs at risk such as the carotid arteries and thyroid gland, potentially reducing the risk of carotid artery stenosis-related complications and other long-term complications.

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.

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.

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.

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.

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.

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.

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.

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.

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.