Search

Ajay S Kasi,1 Hong Li,2 Kelli-Lee Harford,1 Humphrey V Lam,3 Chad Mao,4 April M Landry,5 Sarah G Mitchell,6 Matthew S Clifton,7 Roberta M Leu1 1Department of Pediatrics, Division of Pediatric Pulmonology and Sleep Medicine, Emory University, Children’s Healthcare of Atlanta, Atlanta, GA, USA; 2Department of Human Genetics, Emory University, Children’s Healthcare of Atlanta, Atlanta, GA, USA; 3Division of Pediatric Anesthesiology, Emory University, Children’s Healthcare of Atlanta, Atlanta, GA, USA; 4Department of Pediatrics, Division of Pediatric Cardiology, Emory University, Children’s Healthcare of Atlanta, Atlanta, GA, USA; 5Division of Pediatric Otorhinolaryngology, Emory University, Children’s Healthcare of Atlanta, Atlanta, GA, USA; 6Department of Pediatrics, Division of Pediatric Hematology and Oncology, Emory University, Children’s Healthcare of Atlanta, Atlanta, GA, USA; 7Division of Pediatric Surgery, Emory University, Children’s Healthcare of Atlanta, Atlanta, GA, USACorrespondence: Ajay S Kasi, Department of Pediatrics, Division of Pediatric Pulmonology and Sleep Medicine, Emory University, Children’s Healthcare of Atlanta, 1400 Tullie Road NE, Atlanta, GA, 30329, USA, Tel +1 404 785 5437, Fax +1 404 785 9087, Email ajay.kasi@emory.eduAbstract: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder affecting respiratory control and autonomic nervous system function caused by variants in the paired-like homeobox 2B (PHOX2B) gene. Although most patients are diagnosed in the newborn period, an increasing number of patients are presenting later in childhood, adolescence, and adulthood. Despite hypoxemia and hypercapnia, patients do not manifest clinical features of respiratory distress during sleep and wakefulness. CCHS is a lifelong disorder. Patients require assisted ventilation throughout their life delivered by positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and/or diaphragm pacing. At different ages, patients may prefer to change their modality of assisted ventilation. This requires an individualized and coordinated multidisciplinary approach. Additional clinical features of CCHS that may present at different ages and require periodic evaluations or interventions include Hirschsprung’s disease, gastrointestinal dysmotility, neural crest tumors, cardiac arrhythmias, and neurodevelopmental delays. Despite an established PHOX2B genotype and phenotype correlation, patients have variable and heterogeneous clinical manifestations requiring the formulation of an individualized plan of care based on collaboration between the pulmonologist, otolaryngologist, cardiologist, anesthesiologist, gastroenterologist, sleep medicine physician, geneticist, surgeon, oncologist, and respiratory therapist. A comprehensive multidisciplinary approach may optimize care and improve patient outcomes. With advances in CCHS management strategies, there is prolongation of survival necessitating high-quality multidisciplinary care for adults with CCHS.Keywords: congenital central hypoventilation syndrome, multidisciplinary care, diaphragm pacing, tracheostomy, noninvasive ventilation, CCHS

Introduction: Bladder cancer staging is pivotal for guiding therapeutic decisions. In this study, the primary objective was to assess the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI), The study aimed to classify bladder tumors as either nonmuscle-invasive bladder cancers or muscle-invasive bladder cancers (MIBC) using the Vesical Imaging Reporting and Data System (VI-RADS) scoring. A secondary objective of the study focused on the accuracy of biparametric magnetic resonance imaging (bpMRI) in comparison to mpMRI. Methods: Thirty-three patients with bladder tumors were enrolled and underwent both mpMRI and bpMRI scoring assessments. VI-RADS scores were assigned and subsequently compared with histopathological findings posttransurethral resection of bladder tumor., Statistical measures included sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for VI-RADS scores at cutoff thresholds of ≥4 and 5. Results: MpMRI at a VI-RADS cutoff of ≥4 yielded an 83.33 sensitivity and 100 specificity, with a diagnostic accuracy of 90.91. At a cutoff of 5, sensitivity was 100, specificity was 77.27, and diagnostic accuracy was 84.85. bpMRI at a cutoff of ≥4 showed an 80 sensitivity and 100 specificity, with diagnostic accuracy matching mpMRI at 90.91. Conclusions: This prospective analysis demonstrates that VI-RADS scoring with mpMRI provides reliable diagnostic accuracy for bladder cancer staging. mpMRI exhibits high sensitivity and specificity at a cutoff of ≥ 4, making it a robust tool for MIBC detection. bpMRI is an effective alternative in select patients. The study validates the use of VI-RADS scoring in clinical practice for effective treatment planning., Author(s): Bommireddy V. Reddy [1]; Kasi Viswanath Gali [1]; Arun Chawla (corresponding author) [1]; Anshuman Singh [1]; Sunil Pillai Bhaskara [1]; Padmaraj Hegde [1] INTRODUCTION Bladder cancer ranks as the [...]

Pancreatic and colorectal cancers are often KRAS mutated and are incurable when tumor DNA or protein persists or recurs after curative intent therapy. Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). We treated 25 patients (20 pancreatic and five colorectal) who were positive for minimal residual mKRAS disease (ctDNA and/or serum tumor antigen) after locoregional treatment in a phase 1 study of fixed-dose Amph-Peptides-2P and ascending-dose Amph-CpG-7909; study enrollment is complete with patient follow-up ongoing. Primary endpoints included safety and recommended phase 2 dose (RP2D). The secondary endpoint was tumor biomarker response (longitudinal ctDNA or tumor antigen), with exploratory endpoints including immunogenicity and relapse-free survival (RFS). No dose-limiting toxicities were observed, and the RP2D was 10.0 mg of Amph-CpG-7909. Direct ex vivo mKRAS-specific T cell responses were observed in 21 of 25 patients (84%; 59% both CD4+ and CD8+); tumor biomarker responses were observed in 21 of 25 patients (84%); biomarker clearance was observed in six of 25 patients (24%; three pancreatic and three colorectal); and the median RFS was 16.33 months. Efficacy correlated with T cell responses above or below the median fold increase over baseline (12.75-fold): median tumor biomarker reduction was -76.0% versus -10.2% (P

If you want to enter the professional dance field, it pays to know about rates, resources, and standards

Introduction Bladder cancer staging is pivotal for guiding therapeutic decisions. In this study, the primary objective was to assess the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI), The study aimed to classify bladder tumors as either nonmuscle-invasive bladder cancers or muscle-invasive bladder cancers (MIBC) using the Vesical Imaging Reporting and Data System (VI-RADS) scoring. A secondary objective of the study focused on the accuracy of biparametric magnetic resonance imaging (bpMRI) in comparison to mpMRI. Methods Thirty-three patients with bladder tumors were enrolled and underwent both mpMRI and bpMRI scoring assessments. VI-RADS scores were assigned and subsequently compared with histopathological findings posttransurethral resection of bladder tumor., Statistical measures included sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for VI-RADS scores at cutoff thresholds of ≥4 and 5. Results MpMRI at a VI-RADS cutoff of ≥4 yielded an 83.33% sensitivity and 100% specificity, with a diagnostic accuracy of 90.91%. At a cutoff of 5, sensitivity was 100%, specificity was 77.27%, and diagnostic accuracy was 84.85%. bpMRI at a cutoff of ≥4 showed an 80% sensitivity and 100% specificity, with diagnostic accuracy matching mpMRI at 90.91%. Conclusions This prospective analysis demonstrates that VI-RADS scoring with mpMRI provides reliable diagnostic accuracy for bladder cancer staging. mpMRI exhibits high sensitivity and specificity at a cutoff of ≥ 4, making it a robust tool for MIBC detection. bpMRI is an effective alternative in select patients. The study validates the use of VI-RADS scoring in clinical practice for effective treatment planning.

Introduction: Immune thrombocytopenia (ITP) secondary to durvalumab, a programmed cell death ligand 1 inhibitor, is a rare but clinically significant immune-related adverse event. Herein, we present 2 patients with cholangiocarcinoma who developed ITP immediately post-yttrium-90 radioembolization (Y90-RE) while on durvalumab-based systemic therapy. We hypothesize that given the timing, the immunotherapy and the radioembolization combination led to this event. It is not uncommon given the approval of immunotherapy and its role in locoregional therapies, that patients are treated with a combination of systemic immunotherapy and radioembolization or other forms of radiation, thus signifying the importance of potential complications. Case Presentation: Two patients, a 67-year-old female and a 60-year-old man, with biopsy-proven advanced unresectable cholangiocarcinoma, received a combination of systemic therapy with durvalumab, gemcitabine, and cisplatin and subsequently Y90-RE. Both patients developed ITP following in the immediate post-Y90-RE period. All other causes of ITP were comprehensively ruled out and treatment for ITP was initiated in the form of high-dose steroid and intravenous immunoglobulins. Durvalumab was discontinued, and only gemcitabine/cisplatin-based chemotherapy was continued thereafter. Due to recurrence, one of the patients required longer courses of steroids as well as thrombopoietin receptor agonists. Conclusion: Immunotherapy in the form of durvalumab and now pembrolizumab alongside chemotherapy is an approved first-line standard of care. Furthermore, it is not uncommon for patients to receive Y90-RE to improve patient outcomes. This report highlights the development of ITP in 2 patients who received durvalumab alongside Y90-RE. Awareness of this as a potential immune-mediated event is important to allow for close monitoring of platelet counts and for early intervention/management when this occurs.

Abstract Background Management of high-grade renal trauma is debatable, with the recent evidence embracing a conservative approach in the management of even grade 5 renal injuries. The study aimed to analyze the clinical profile of patients with high-grade renal trauma, assessing their management strategies, outcomes, complications, and need for ancillary procedures. Methods A retrospective analysis of prospectively maintained data was performed involving blunt abdominal trauma patients with high-grade renal injuries (Grade 4 and 5) presenting to our hospital from January 2018 to December 2022. Patient data analyzed included demographics, clinical presentation, injury characteristics, complications, ancillary procedures, and mortality rates. All patients underwent renal functional assessment using an isotope renogram scan at the 3-month follow-up. Data collected were entered into a database and subjected to descriptive analysis using Jamovi version 2.3.28. Results The study included 45 patients with a mean age of 29 years and a male-to-female ratio of 41:4. Most patients (n = 42) were managed conservatively. Thirty-eight patients had grade 4 injuries, and seven had grade 5 injuries. Twenty-six patients suffered renal parenchymal injuries alone, three patients had renal vascular injuries alone, and 16 patients had both parenchymal and vascular injuries. Grade 5 renal injury (p

Ajay S Kasi,1 Iris A Perez,1,2 Sheila S Kun,1 Thomas G Keens1,2 1Division of Pediatric Pulmonology and Sleep Medicine, Children’s Hospital Los Angeles, 2Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA Abstract: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder with failure of central control of breathing and of the autonomic nervous system function due to a mutation in the paired-like homeobox 2B (PHOX2B) gene. Affected patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxemia, and they do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis of CCHS must be confirmed with PHOX2B gene mutation. Generally, the PHOX2B mutation genotype can aid in anticipating the severity of the phenotype. They require ventilatory support for life. Home assisted ventilation options include positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and diaphragm pacing via phrenic nerve stimulation, but each strategy has its associated limitations and challenges. Since all the clinical manifestations of CCHS may not manifest at birth, periodic monitoring and early intervention are necessary to prevent complications and improve outcome. Life-threatening arrhythmias can manifest at different ages and a normal cardiac monitoring study does not exclude future occurrences leading to the dilemma of timing and frequency of cardiac rhythm monitoring and treatment. Given the rare incidence of CCHS, most health care professionals are not experienced with managing CCHS patients, particularly those with diaphragm pacers. With early diagnosis and advances in home mechanical ventilation and monitoring strategies, many CCHS children are surviving into adulthood presenting new challenges in their care. Keywords: congenital central hypoventilation syndrome, PHOX2B, home mechanical ventilation, diaphragm pacing, CCHS

In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed (inside-out (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.

Hepatocellular carcinoma (HCC) is a challenging cancer with high mortality rates, limited predictability, and a lack of effective prognostic indicators. The relationship between small nucleolar RNAs (snoRNAs) and HCC is poorly understood. Based on the literature data, snoRNA studies were primarily focused on viral-related causes of HCC, such as Hepatitis B or C viruses (HBV or HCV). According to these studies, we selected four snoRNAs (snoRA12, snoRA47, snoRA80E, and snoRD126) for exploration in the context of non-viral-related causes, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver diseases (NAFLD), and alcohol steatohepatitis. The primary goal of this study was to gain a deeper understanding of how snoRNA expression affects patient outcomes and whether it can serve as a prognostic tool for non-viral HCC. We conducted a study on tissue samples from 35 HCC patients who had undergone resection at Pilsen University Hospital. SnoRA12, snoRA47, snoRA80E, and snoRD126 were studied by quantitative real-time PCR (qRT-PCR) in tumor and non-tumor adjacent tissue (NTAT) samples. Kaplan-Meier analysis was performed to assess the association of snoRNAs expression levels with patient outcomes: time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS). In tumor tissues, snoRA12, snoRA47 and snoRA80E were upregulated, while snoRD-126 was downregulated compared to NTAT. Low expression of snoRA47 and snoRD126 in patients was associated with longer TTR and DFS. The individual expression of snoRA12 and snoRA80E did not show associations with TTR and DFS. However, a combination of medium expression of snoRD126 and snoRA80E was associated with longer TTR and DFS, while high and low expressions of the combined snoRA126 and snoRA80E showed no significant association with TTR, DFS, and OS. Conversely, a combination of high expression of snoRA12 and snoRD126 was associated with shorter TTR. In conclusion, the results indicate that snoRA47 and snoRD126 exhibit good prognostic power specifically for non-viral related HCC. Both snoRA47 and snoRD126 showed favorable prognostication in single and combined analysis when assessing patient outcomes. Also, in combination analysis, snoRA80E and snoRA12 showed favorable prognosis, but not alone.