Cryoablation in Extra-Abdominal Desmoid Tumors: A 10-Year Experience in Pediatric and Young Adult Patients.

PURPOSE: To determine the efficacy and safety of cryoablation in pediatric and young adult patients with desmoid tumors (DTs) retrospectively over a 10-year period. MATERIALS AND METHODS: Twenty-one patients (age 2-22 years; median 14 years), with 21 desmoid tumors, underwent a total of 34 percutaneous cryoablation procedures between August 2013 and August 2023. All patients, excluding two, had surgical resection, chemotherapy, or a combination of these therapies with failed or suboptimal response. Clinical and imaging outcomes were analyzed for technical success, change in tumor volume, and recurrence of tumor, symptom improvement or recurrence, and procedure-related complications. RESULTS: All procedures were technically successful. The median follow-up duration was 9 months (range, 3-32 months); total symptomatic improvement was achieved in 90% (19/21) patients, noticeable pain relief was seen in 100% (18/18) and 90% (9/10) patients had improved range of motion (ROM), discomfort resolved in 66.7% (2/3) patients. Of the treated tumors, 43% (9/21) showed greater than 75% tumor volume reduction of which 44% (4/9) had no evidence of viable residual tumor at follow-up, and 33% (7/21) had 50-75% volume reduction and 14% (3/21) had greater than 40-50% tumor volume reduction. According to modified response evaluation criteria in solid tumors (mRECIST), 71%( 15/21) had partial response (PR), 19% (4/21) had complete response (CR), and 10% (2/21) had stable disease. Four (12%) treatments were associated with minor complications, which self-resolved. CONCLUSION: In this, predominantly pediatric patient cohort, cryoablation was effective and safe for the local control of extra-abdominal desmoid tumors in short-term follow-up.

Conditional nmy-1 and nmy-2 alleles establish that nonmuscle myosins are required for late Caenorhabditis elegans embryonic elongation.

The elongation of Caenorhabditis elegans embryos allows examination of mechanical interactions between adjacent tissues. Muscle contractions during late elongation induce the remodeling of epidermal circumferential actin filaments through mechanotransduction. Force inputs from the muscles deform circumferential epidermal actin filament, which causes them to be severed, eventually reformed, and shortened. This squeezing force drives embryonic elongation. We investigated the possible role of the nonmuscle myosins NMY-1 and NMY-2 in this process using nmy-1 and nmy-2 thermosensitive alleles. Our findings show these myosins act redundantly in late elongation, since double nmy-2(ts); nmy-1(ts) mutants immediately stop elongation when raised to 25°C. Their inactivation does not reduce muscle activity, as measured from epidermis deformation, suggesting that they are directly involved in the multistep process of epidermal remodeling. Furthermore, NMY-1 and NMY-2 inactivation is reversible when embryos are kept at the nonpermissive temperature for a few hours. However, after longer exposure to 25°C double mutant embryos fail to resume elongation, presumably because NMY-1 was seen to form protein aggregates. We propose that the two C. elegans nonmuscle myosin II act during actin remodeling either to bring severed ends or hold them.

Multifiller-based polymer composites for shielding high energy ionising radiation.

Polydimethyl silicone rubber-based polymer composites filled with molybdenum and bismuth were fabricated using simple open mold cast technique. The physical and chemical structure and gamma shielding parameters like attenuation coefficient, half-value layer (HVL) thickness and relaxation length have been investigated for the said novel materials using X-ray diffraction (XRD), Fourier transform Infrared spectroscopy (FTIR) and gamma ray spectrometer. XRD study reveals the crystalline nature of the composites. It is evident from FTIR studies that there is no chemical interaction between the polymer matrix and filler particles. The results of attenuation studies reveal that the linear attenuation coefficient increases with addition of Bi and Mo and is found to be 0.653, 1.341 and 1.017, 1.793 and 0.102, 0.152 cm-1 for 1MMB and 2MMB polymer composites at 80, 356 and 662 keV gamma rays, respectively. The HVL thickness of the materials is found to be 1.06, 0.51 and 0.68, 0.38 and 6.73, 4.532 cm for 1MMB (20Mo + 10Bi phr) and 2MMB (40Mo + 20Bi phr) at these energies, respectively. The mass attenuation coefficient of the novel composites 1MMB and 2MMB is found to be higher than the conventional materials like lead and barite for 356 keV gamma rays. In addition, the material is found to be light weight and flexible enabling to be molded in required forms, thus being a substitute for the material lead that is known to be heavy and toxic by nature.

Assessment of Biological Damage Induced during Multidetector Computed Tomography (MDCT) Examination.

Computed tomography (CT) is known for its non-invasiveness, fast procedure, and also for providing detailed diagnostic information to physicians. It also utilises low-dose-rate ionising radiation (X-rays) as a source for imaging. Multidetector computed tomography (MDCT) is an advanced system that uses iodinated contrast media for more accurate diagnostic results. Studies suggest using these contrasts will lead to greater radiation adsorption with significant DNA damage. No studies have been taken comparing the physical dose with the biological effect. The present study sheds light on the same by assessing the biological effect of CT with and without contrast intervention. The present study is timebound; thus, 21 participants attending for CT thorax and abdomen with no history of any cancer were included. The same participants underwent both pre-contrast and post-contrast studies. The blood sample was taken before the procedure and used as a control. Physical parameters like DLP and CTDI obtained from the instrument were compared with the MN frequency obtained (CBMN Assay). The study showed a significant increase (p-value < 0.05) in the Physical and MN frequency in the Post-Contrast group compared to the pre-contrast group. Although a positive correlation was observed between pre and post-contrast groups, the results were not found to be statistically significant (p-value < 0.05). The study confirms increased physical dose and MN frequency upon contrast intervention. This study recommends the judicial use of MDCT in disease diagnostics.

Zinner syndrome in pediatric age group: An underdiagnosed entity.

INTRODUCTION: Zinner Syndrome (ZS), a rare congenital malformation of the mesonephric duct, combines seminal vesicle cyst (SVC) with ipsilateral upper urinary tract abnormalities. Typically asymptomatic in childhood, ZS manifests between 2nd to 4th decades with bladder symptoms, perineal pain and infertility. Diagnostic confirmation with additional imaging is needed when either renal or seminal abnormalities are identified. MATERIALS AND METHODS: A retrospective study spanning 22 years identified 20 pediatric ZS cases through clinical analytics. Demographic, clinical, and radiological data were analyzed, including presenting complaints, imaging modalities (ultrasound, CT, MRI), and surgical findings. The study was HIPAA-compliant and IRB-approved. RESULTS: Among 20 cases (mean age: 7.3 years), clinical presentations included asymptomatic cases, urinary symptoms, and abdominal pain. Imaging revealed renal anomalies (agenesis, multicystic dysplastic kidney) and seminal vesicle abnormalities. Surgical interventions (n = 12) addressed symptomatic cases, often involving robotic or laparoscopic procedures. DISCUSSION: ZS, though rare, presents with varied clinical features, necessitating a multidisciplinary approach. Early diagnosis is facilitated by prenatal identification of renal abnormalities. Surgical intervention is reserved for symptomatic cases, with techniques such as vesiculectomy and resection of remnant structures employed. CONCLUSION: This study highlights ZS's diverse clinical and radiological spectrum, emphasizing the need for vigilance in detecting overlapping entities. Timely identification, utilizing advanced imaging techniques, is crucial for accurate diagnosis and appropriate management of Zinner Syndrome in the pediatric population.

ORMDL3 regulates NLRP3 inflammasome activation by maintaining ER-mitochondria contacts in human macrophages and dictates ulcerative colitis patient outcome.

Genome-wide association studies in inflammatory bowel disease have identified risk loci in the orosomucoid-like protein 3/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) gene to confer susceptibility to ulcerative colitis (UC), but the underlying functional relevance remains unexplored. Here, we found that a subpopulation of the UC patients who had higher disease activity shows enhanced expression of ORMDL3 compared to the patients with lower disease activity and the non-UC controls. We also found that the patients showing high ORMDL3 mRNA expression have elevated interleukin-1ß cytokine levels indicating positive correlation. Further, knockdown of ORMDL3 in the human monocyte-derived macrophages resulted in significantly reduced interleukin-1ß release. Mechanistically, we report for the first time that ORMDL3 contributes to a mounting inflammatory response via modulating mitochondrial morphology and activation of the NLRP3 inflammasome. Specifically, we observed an increased fragmentation of mitochondria and enhanced contacts with the endoplasmic reticulum (ER) during ORMDL3 over-expression, enabling efficient NLRP3 inflammasome activation. We show that ORMDL3 that was previously known to be localized in the ER also becomes localized to mitochondria-associated membranes and mitochondria during inflammatory conditions. Additionally, ORMDL3 interacts with mitochondrial dynamic regulating protein Fis-1 present in the mitochondria-associated membrane. Accordingly, knockdown of ORMDL3 in a dextran sodium sulfate -induced colitis mouse model showed reduced colitis severity. Taken together, we have uncovered a functional role for ORMDL3 in mounting inflammation during UC pathogenesis by modulating ER-mitochondrial contact and dynamics.

Positron emission tomography in the diagnosis and management of primary pediatric lung tumors.

Primary pediatric lung tumors are uncommon and have many overlapping clinical and imaging features. In contrast to adult lung tumors, these rare pediatric neoplasms have a relatively broad histologic spectrum. Informed by a single-institution 13-year retrospective record review, we present an overview of the most common primary pediatric lung neoplasms, with a focus on the role of positron emission tomography (PET), specifically 18F-fluorodeoxyglucose (FDG) PET and 68Ga-DOTATATE PET, in the management of primary pediatric lung tumors. In addition to characteristic conventional radiographic and cross-sectional imaging findings, knowledge of patient age, underlying cancer predisposition syndromes, and PET imaging features may help narrow the differential. While metastases from other primary malignancies remain the most commonly encountered pediatric lung malignancy, the examples presented in this pictorial essay highlight many of the important conventional radiologic and PET imaging features of primary pediatric lung malignancies.

Contrast-Enhanced Ultrasound of the Chest in Children and Adolescents: A Pilot Study for Assessment of Added Diagnostic Value.

OBJECTIVES: To determine the added diagnostic value of contrast-enhanced ultrasound (CEUS) in pediatric chest abnormalities by comparing interpretation of CEUS studies and confidence level to conventional US studies. METHODS: CEUS studies in patients with a variety of clinically suspected chest abnormalities performed between 2016 and 2020 were reviewed and compared to same-day conventional US studies. Examinations were independently interpreted by 4 radiologists blinded to clinical and other imaging data. Rater confidence was classified as low, moderate, or high. Diagnostic accuracy was determined by comparing image interpretation to patient outcome as the ground truth. Interobserver agreement was also assessed. RESULTS: Sixteen patients (10 male) with 18 CEUS studies were included. Median rater agreement with ground truth was significantly higher for CEUS (100%) than conventional US (50%; P = .004). Median rater confidence was high (3.0) for CEUS, and low-moderate (1.5) for conventional US (P < .001). CEUS sensitivity (54.6-81.8%) and specificity (63.4-100.0%) were greater than conventional US (45.5-72.7% and 12.5-63.5%, respectively). CEUS false positives (0-4) and false negatives (2-5) were fewer than conventional US (4-7 and 3-6, respectively). Except for one rater pair where agreement was substantial (κ = .78, P < .01), inter-rater agreement for CEUS for all other rater pairs was nonsignificant (κ = .25-0.51, P ≥ .07). Agreement for conventional US was moderate and statistically significant for 3 rater pairs (κ = .55-0.78) and nonsignificant for the remaining 3 rater pairs (P ≥ .06). CONCLUSIONS: CEUS adds diagnostic value to the assessment of a variety of chest abnormalities. The data support further evaluation of the role of CEUS as a non-invasive, problem-solving technique in children.

Cryoablation for Bone and Soft Tissue Lesions in Pediatric Patients: Complications and Preventive Measures.

PURPOSE: To evaluate complications associated with cryoablation in a pediatric population and review preventive measures to mitigate these complications. MATERIAL AND METHODS: Retrospective study including all the image guided cryoablations performed on pediatric population. Immediate and delayed complications were analyzed, and we identified the different protective measures used and the clinical outcomes from follow-up. Point estimates for the percentage of complications were calculated by maximum likelihood, and 95% confidence intervals for the true percentages were calculated using the Clopper-Pearson exact method. RESULTS: Eighty-seven ablations were performed on 68 patients (age range of 2-18 years, mean 12.4 years) for non-neoplastic (70%) and neoplastic (30%) lesions. The percentage of ablations resulting in complications was 18% (95% confidence interval (CI) 11% to 28%). Of these, 5% (95% CI 1% to 11%) were grade 3 complications, and 14% (95% CI 7% to 23%) were grade 2 complications. Thermal protection was performed in 27.6% of ablations (n = 24). The mean clinical follow-up duration was 348 days. CONCLUSION: Cryoablation in pediatric patients is relatively safe, with a major complication rate per ablation of 5%. Thermal protective measures can be considered to mitigate these complications.

CLUH functions as a negative regulator of inflammation in human macrophages and determines ulcerative colitis pathogenesis.

Altered mitochondrial function without a well-defined cause has been documented in patients with ulcerative colitis (UC). In our efforts to understand UC pathogenesis, we observed reduced expression of clustered mitochondrial homolog (CLUH) only in the active UC tissues compared with the unaffected areas from the same patient and healthy controls. Stimulation with bacterial Toll-like receptor (TLR) ligands similarly reduced CLUH expression in human primary macrophages. Further, CLUH negatively regulated secretion of proinflammatory cytokines IL-6 and TNF-α and rendered a proinflammatory niche in TLR ligand-stimulated macrophages. CLUH was further found to bind to mitochondrial fission protein dynamin related protein 1 (DRP1) and regulated DRP1 transcription in human macrophages. In the TLR ligand-stimulated macrophages, absence of CLUH led to enhanced DRP1 availability for mitochondrial fission, and a smaller dysfunctional mitochondrial pool was observed. Mechanistically, this fissioned mitochondrial pool in turn enhanced mitochondrial ROS production and reduced mitophagy and lysosomal function in CLUH-knockout macrophages. Remarkably, our studies in the mouse model of colitis with CLUH knockdown displayed exacerbated disease pathology. Taken together, this is the first report to our knowledge explaining the role of CLUH in UC pathogenesis, by means of regulating inflammation via maintaining mitochondrial-lysosomal functions in the human macrophages and intestinal mucosa.

Imaging evaluation of the pediatric mediastinum: new International Thymic Malignancy Interest Group classification system for children.

Mediastinal masses are commonly identified in the pediatric population with cross-sectional imaging central to the diagnosis and management of these lesions. With greater anatomical definition afforded by cross-sectional imaging, classification of mediastinal masses into the traditional anterior, middle and posterior mediastinal compartments - as based on the lateral chest radiograph - has diminishing application. In recent years, the International Thymic Malignancy Interest Group (ITMIG) classification system of mediastinal masses, which is cross-sectionally based, has garnered acceptance by multiple thoracic societies and been applied in adults. Therefore, there is a need for pediatric radiologists to clearly understand the ITMIG classification system and how it applies to the pediatric population. The main purpose of this article is to provide an updated review of common pediatric mediastinal masses and mediastinal manifestations of systemic disease processes in the pediatric population based on the new ITMIG classification system.

Intrathecal catheter and port placement for nusinersen infusion in children with spinal muscular atrophy and spinal fusion.

BACKGROUND: Spinal administration of medications is challenging in patients with complete posterior spinal fusion. We describe percutaneous image-guided intrathecal port placement for administration of the antisense oligonucleotide nusinersen for children and young adults with spinal muscular atrophy. OBJECTIVE: To describe and present our initial experience with a new technique for administering nusinersen in patients with spinal muscular atrophy and posterior spinal fusion. MATERIALS AND METHODS: We reviewed medical records of 13 patients who received intrathecal ports using DynaCT, biplane fluoroscopy and iGuide from April 2018 through June 2019, and we describe the clinical course over 1 year. RESULTS: Image-guided catheter and port implantation was successful in all cases. Two ports were subsequently removed, one for persistent cerebrospinal fluid leak and one for superficial infection. The other 11 have functioned successfully for a minimum of 23 months. CONCLUSION: We report our experience with image-guided intrathecal port placement in children with complete posterior spine fusion. The implanted port permits dosing in an outpatient setting and avoids the need for multiple future radiologic procedures, and it reduces discomfort, procedural costs and potential risks and sequelae of multiple anesthetics and radiation exposures. Further studies are needed to define the relative risks and benefits of intrathecal ports compared to other approaches such as repeated transforaminal lumbar punctures.

A STUDY ON THE RADIATION DOSE DUE TO DISSOLVED 222RN IN WATER SAMPLES OF MANDYA CITY, KARNATAKA, INDIA.

Measurement of dissolved radon concentrations in the water samples collected from selected borewells (depth ~300 ft), wells (depth ~25 ft) and overhead tanks (height ~30 ft) of Mandya city, Karnataka, India, has been carried out by using Emanometry method. The radon concentrations in the waters of borewell, well and overhead tank ranges from 1.5 ± 0.1 to 102.8 ± 5.1, 1.3 ± 0.1 to 3.8 ± 0.4 and 2.5 ± 0.2 to 9.7 ± 1.1 Bq l-1 with the mean values of 16.8, 2.5 and 6.2 Bq l-1, respectively. Majority of borewell water samples showed higher concentrations of dissolved 222Rn compared to waters of well and overhead tank. The overall mean value of dissolved radon concentration of 12.2 Bq l-1 is found to be close to the maximum contaminant level of 11 Bq l-1 suggested by US Environment Protection Agency. The physicochemical parameters like pH, TDS and conductivity were also measured, and dependence of dissolved 222Rn on these parameters has been studied. Using the mean value of dissolved radon concentration, a new attempt has been made to compute the doses imparted to different organs and tissues of the human body. Dosimetric calculations showed that stomach and small intestine receive greater doses due to dissolved radon compared to other organs.

Telomerase therapy attenuates cardiotoxic effects of doxorubicin.

Doxorubicin is one of the most potent chemotherapeutic agents. However, its clinical use is restricted due to the severe risk of cardiotoxicity, partially attributed to elevated production of reactive oxygen species (ROS). Telomerase canonically maintains telomeres during cell division but is silenced in adult hearts. In non-dividing cells such as cardiomyocytes, telomerase confers pro-survival traits, likely owing to the detoxification of ROS. Therefore, we hypothesized that pharmacological overexpression of telomerase may be used as a therapeutic strategy for the prevention of doxorubicin-induced cardiotoxicity. We used adeno-associated virus (AAV)-mediated gene therapy for long-term expression of telomerase in in vitro and in vivo models of doxorubicin-induced cardiotoxicity. Overexpression of telomerase protected the heart from doxorubicin-mediated apoptosis and rescued cardiac function, which was accompanied by preserved cardiomyocyte size. At the mechanistic level, we observed altered mitochondrial morphology and dynamics in response to telomerase expression. Complementary in vitro experiments confirmed the anti-apoptotic effects of telomerase overexpression in human induced pluripotent stem cell-derived cardiomyocytes after doxorubicin treatment. Strikingly, elevated levels of telomerase translocated to the mitochondria upon doxorubicin treatment, which helped to maintain mitochondrial function. Thus, telomerase gene therapy could be a novel preventive strategy for cardiotoxicity by chemotherapy agents such as the anthracyclines.

Contribution of FDG-PET/CT to the management of esophageal cancer patients at multidisciplinary tumor board conferences.

BACKGROUND: A multidisciplinary team approach to the management of esophageal cancer patients leads to better clinical decisions. PURPOSE: The contribution of CT, endoscopic and laparoscopic ultrasound to clinical staging and treatment selection by multidisciplinary tumor boards (MTB) in patients with esophageal cancer is well documented. However, there is a paucity of data addressing the role that FDG-PET/CT (PET/CT) plays to inform the clinical decision-making process at MTB conferences. The aim of this study was to assess the impact and contribution of PET/CT to clinical management decisions and to the plan of care for esophageal cancer patients at the MTB conferences held at our institution. MATERIALS AND METHODS: This IRB approved study included all the cases discussed in the esophageal MTB meetings over a year period. The information contributed by PET/CT to MTB decision making was grouped into four categories. Category I, no additional information provided for clinical management; category II, equivocal and misguiding information; category III, complementary information to other imaging modalities, and category IV, information that directly changed clinical management. The overall impact on management was assessed retrospectively from prospectively discussed clinical histories, imaging, histopathology, and the official minutes of the MTB conferences. RESULTS: 79 patients (61 males and 18 females; median age, 61 years, range, 33-86) with esophageal cancer (53 adenocarcinomas and 26 squamous cell carcinomas) were included. The contribution of PET/CT-derived information was as follows: category I in 50 patients (63%); category II in 3 patients (4%); category III in 8 patients (10%), and category IV information in 18 patients (23%). Forty-five patients (57%) had systemic disease, and in 5 (11%) of these, metastatic disease was only detected by PET/CT. In addition, PET/CT detected previously unknown recurrence in 4 (9%) of 43 patients. In summary, PET/CT provided clinically useful information to guide management in 26 of 79 esophageal cancer patients (33%) discussed at the MTB. CONCLUSION: The study showed that PET/CT provided additional information and changed clinical management in 1 out of 3 (33%) esophageal cancer cases discussed at MTB conferences. These results support the inclusion whenever available, of FDG-PET/CT imaging information to augment and improve the patient management decision process in MTB conferences.

Non-coding RNAs: Regulators of valvular calcification.

There is currently a growing global burden of valvular heart diseases due to aging populations and changing lifestyles. Valvular heart diseases mainly include the malfunctioning of aortic and mitral valves and are characterized by extensive tissue remodeling, which includes calcification, endothelial dysfunction, and endothelial-mesenchymal transition. These valvular remodeling processes are known to be regulated by protein-coding genes as well as non-coding genes. Here, we have summarized studies highlighting the non-coding RNA mediated regulation of valvular tissue remodeling and their potential therapeutic benefits. Additionally, studies investigating the diagnostic capability of circulating non-coding RNA molecules in valvular diseases are also summarized. Overall, of the various candidates, several studies have highlighted miR-214 and miR-204 as central regulators of valvular calcification.

Eagle's Syndrome: An Underdiagnosed Condition-Case Series in a Tertiary Care Hospital.

To evaluate all the cases of chronic neck pain thoroughly to diagnose eagle's syndrome. Hospital based prospective study done in the department of otorhinolaryngology at our tertiary care hospital from January 2017 to December 2018. We selected 60 subjects in our study who presented to us with complaints of chronic neck pain associated with referred otalgia, along with aggravation of pain with neck movements, odynophagia, throat pain and foreign body sensation in the throat. After thorough clinical examination an orthopantomogram has been done which revealed elongated styloid process. Conservative management with carbamazepine was tried but only temporary relief was noticed in these patients. Hence intra oral tonsillo-styloidectomy was done and patients were followed up to 3 months. Out of 10 patients, 9 were female and 1 was male. 8 patients had bilateral elongated styloid process and 2 patients had unilateral elongation. Orthopantomogram revealed an average elongation of styloid process of 3.5-5 cm and the average length of the removed styloid process ranged from 0.6-3 cm. All patients showed significant improvement post operatively. Eagle's syndrome is not a rarity, but underdiagnosed and missed most of the times. Hence all cases of chronic neck pain should be evaluated thoroughly by taking complete history and proper clinical examination, along with radiological investigations.