-
1.
Clinical and ocular abnormalities in DEGCAGS syndrome-Developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities.
Ali, SM, AlMasri, DA, Prada, CE, Lin, D, Bosley, TM, Kozak, I
Molecular genetics & genomic medicine. 2024;(1):e2329
Abstract
PURPOSE To describe clinical and ocular abnormalities in a case of Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities (DEGCAGS syndrome). METHODS A clinical report. CASE DESCRIPTION An infant born to a consanguineous Middle Eastern family who was delivered by cesarean section because of in utero growth restriction, premature labor, and breech presentation. Post-partum medical problems included hypotension, generalized hypotonia, bradycardia, apnea requiring resuscitation and positive pressure ventilation, facial dysmorphia, skeletal malformations, and disorders of the gastrointestinal, immune, urinary, respiratory, cardiac, and visual systems. The family reported that a previous child had severe hypotonia at birth and was given the diagnosis of hypoxic ischemic encephalopathy; that child remains on a ventilator in a chronic care facility. Our patient was found to be homozygous for a novel pathogenic missense variant in theZNF699 zinc finger gene on chromosome 19p13 causing a syndrome known as Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities (DEGCAGS syndrome). We review this variable syndrome, including abnormalities of the visual system not described previously. CONCLUSIONS We describe the 15th child to be presumably identified with the DEGCAGS syndrome and the first individual with homozygous missense variants in the ZNF699 gene who had complete clinical examination and detailed retinal imaging.
-
2.
Understanding very early onset inflammatory bowel disease (VEOIBD) in relation to inborn errors of immunity.
Hall, CHT, de Zoeten, EF
Immunological reviews. 2024;(1):329-338
Abstract
Inflammatory bowel diseases (IBD) are multifactorial diseases which are caused by the combination of genetic predisposition, exposure factors (environmental and dietary), immune status, and dysbiosis. IBD is a disease which presents at any age, ranging from newborns to the elderly. The youngest of the pediatric IBD population have a more unique presentation and clinical course and may have a different etiology. Very early onset IBD (VEOIBD) patients, designated as those diagnosed prior the age of 6, have distinct features which are more frequent in this patient population including increased incidence of monogenetic causes for IBD (0%-33% depending on the study). This proportion is increased in the youngest subsets, which is diagnosed prior to the age of 2. To date, there are approximately 80 monogenic causes of VEOIBD that have been identified and published. Many of these monogenic causes are inborn errors of immunity yet the majority of VEOIBD patients do not have an identifiable genetic cause for their disease. In this review, we will focus on the clinical presentation, evaluation, and monogenic categories which have been associated with VEOIBD including (1) Epithelial cell defects (2) Adaptive immune defects, (3) Innate Immune/Bacterial Clearance and Recognition defects, and (4) Hyperinflammatory and autoinflammatory disorders. We will highlight differential diagnosis of VEOIBD presentations, as well as evaluation and treatment, which will be helpful for those who study and care for VEOIBD patients outside of the pediatric gastroenterology field. This is a fast-moving field of research which has grown significantly based on knowledge that we gain from our patients. These scientific findings have identified novel mucosal biology pathways and will continue to inform our understanding of gastrointestinal biology.
-
3.
Anti-Gene IGF-I Vaccines in Cancer Gene Therapy: A Review of a Case of Glioblastoma.
Trojan, A, Lone, YC, Briceno, I, Trojan, J
Current medicinal chemistry. 2024;(15):1983-2002
Abstract
OBJECTIVE Vaccines for the deadliest brain tumor - glioblastoma (GBM) - are generally based on targeting growth factors or their receptors, often using antibodies. The vaccines described in the review were prepared to suppress the principal cancer growth factor - IGF-I, using anti-gene approaches either of antisense (AS) or of triple helix (TH) type. Our objective was to increase the median survival of patients treated with AS and TH cell vaccines. METHODOLOGY The cells were transfected in vitro by both constructed IGF-I AS and IGF-I TH expression episomal vectors; part of these cells was co-cultured with plant phytochemicals, modulating IGF-I expression. Both AS and TH approaches completely suppressed IGF-I expression and induced MHC-1 / B7 immunogenicity related to the IGF-I receptor signal. RESULTS This immunogenicity proved to be stronger in IGF-I TH than in IGF-I AS-prepared cell vaccines, especially in TH / phytochemical cells. The AS and TH vaccines generated an important TCD8+ and TCD8+CD11b- immune response in treated GBM patients and increased the median survival of patients up to 17-18 months, particularly using TH vaccines; in some cases, 2- and 3-year survival was reported. These clinical results were compared with those obtained in therapies targeting other growth factors. CONCLUSION The anti-gene IGF-I vaccines continue to be applied in current GBM personalized medicine. Technical improvements in the preparation of AS and TH vaccines to increase MHC-1 and B7 immunogenicity have, in parallel, allowed to increase in the median survival of patients.
-
4.
Coxsackie B virus-induced myocarditis in a patient with a history of lymphoma: A case report and review of literature.
Zhang, Q, Yuan, J, Zhao, W, Ouyang, W, Chen, B, Li, Y, Tao, J, Chen, X, Li, G, Guo, Z, et al
Medicine. 2024;(10):e37248
-
-
Free full text
-
Abstract
INTRODUCTION In rare occasions, coxsackievirus infections can cause serious illness, such as encephalitis and myocarditis. The immunotherapies of cancer could increase the risk of myocarditis, especially when applying immune checkpoint inhibitors. Herein, we report a rare case of Coxsackie B virus-induced myocarditis in a patient with a history of lymphoma. CASE PRESENTATION A 32-year-old woman was admitted to the hospital with recurrent fever for more than 20 days, and she had a history of lymphoma. Before admission, the positron emission tomography/computed tomography result indicated that the patient had no tumor progression, and she was not considered the cancer-related fever upon arriving at our hospital. Patient's red blood cell, platelet count, and blood pressure were decreased. In addition, she had sinus bradycardia and 3 branch blocks, which was consistent with acute high lateral and anterior wall myocardial infarction. During hospitalization, the patient had recurrent arrhythmia, repeated sweating, poor mentation, dyspnea, and Coxsackie B virus were detected in patient's blood samples by pathogen-targeted next-generation sequencing. The creatine kinase, creatine kinase MB, and N-terminal pro-brain natriuretic peptide were persistently elevated. Consequently, the patient was diagnosed with viral myocarditis induced by Coxsackie B virus, and treated with acyclovir, gamma globulin combined with methylprednisolone shock therapy, trimetazidine, levosimendan, sildenan, continuous pump pressors with m-hydroxylamine, entecavir, adefovir, glutathione, pantoprazole, and low-molecular-weight heparin. Her symptoms worsened and died. CONCLUSION We reported a case with a history of lymphoma presented with fever, myocardial injury, who was ultimately diagnosed with Coxsackie B virus-induced myocarditis. Moreover, pathogen-targeted next-generation sequencing indeed exhibited higher sensitivity compared to mNGS in detecting Coxsackie B virus.
-
5.
Immune checkpoint inhibitor-related adrenal hypofunction and Psoriasisby induced by tislelizumab: A case report and review of literature.
Deng, Y, Huang, M, Deng, R, Wang, J
Medicine. 2024;(12):e37562
-
-
Free full text
-
Abstract
RATIONALE Immune-related adverse events following treatment with immune checkpoint inhibitors can affect almost every organ. Tislelizumab, a novel humanized Ig G4 programmed death receptor 1 inhibitor, was started for bladder cancer in 2019, but the adverse effects of this drug may not yet be known due to its short time on the market, and there are still some clinical safety concerns. There are few reports of adrenal insufficiency after tislelizumab treatment, which is easily missed, misdiagnosed and life-threatening. PATIENT CONCERNS A 67-year-old male with bladder cancer who developed rash, water-sodium retention, electrolyte disturbances, hypoalbuminemia, low-grade fever, nausea and vomiting, and fatigue after 2 cycles of tislelizumab. DIAGNOSIS Immune checkpoint inhibitor-related adrenal hypofunction and Psoriasisby. INTERVENTIONS Suspended tislelizumab treatment and continued glucocorticoid therapy. OUTCOMES The patient showed significant improvement in the above symptoms. But bladder cancer reemerged at the same site. CONCLUSIONS The advent of immune-related adverse events has increased the complexity of the application of tislelizumab in the treatment of bladder cancer and further research is needed to develop the best treatment guidelines. Early diagnosis and treatment are crucial since the adverse events could endanger lives.
-
6.
Clinico-Microbiological Correlation in Salmonella Endophthalmitis: Case Series and Review of Literature.
Mitra, S, Meshram, B, Jalali, S, Basu, S
Seminars in ophthalmology. 2024;(4):294-298
Abstract
PURPOSE To report two rare cases of Salmonella endogenous endophthalmitis in an immunocompromised premature baby and an immunocompetent adult and do a brief literature review of related cases. Diagnosis in both cases was confirmed only after the pathogen grew from ocular samples, in the absence of clear signs of enteric fever. METHODS Retrospective analysis of medical and microbiology records. RESULTS Both of our cases of Salmonella endophthalmitis had poor visual outcome, despite timely and aggressive management and irrespective of immune status of the patient. Salmonella infection being a rare cause of endophthalmitis was not initially suspected as the adult had minimal systemic symptoms 2 weeks before presentation, while the preterm baby was still on milk feeds. These were just two microbiologically confirmed cases of Salmonella endophthalmitis at our institute over the past 10 years, though enteric fever due to Salmonella species is endemic in Asian countries. CONCLUSIONS Salmonella endophthalmitis, though rare, leads to poor visual outcomes despite early recognition and aggressive management and may be confused with other infections or non-infectious entities such as necrotizing retinoblastoma in babies, in the absence of clear systemic signs of the disease.
-
7.
Perimyocarditis Associated with Immune Checkpoint Inhibitors: A Case Report and Review of the Literature.
Shalata, W, Steckbeck, R, Abu Salman, A, Abu Saleh, O, Abu Jama, A, Attal, ZG, Shalata, S, Alnsasra, H, Yakobson, A
Medicina (Kaunas, Lithuania). 2024;(2)
Abstract
Patient prognoses have been significantly enhanced by immune checkpoint inhibitors (ICIs), altering the standard of care in cancer treatment. These novel antibodies have become a mainstay of care for metastatic non-small-cell lung cancer (mNSCLC) patients. Several types of adverse events related to ICIs have been identified and documented as a result of the launch of these innovative medicines. We present here a 74-year-old female patient with a stage IV lung adenocarcinoma, treated with nivolumab plus ipilimumab, who developed perimyocarditis two weeks after receiving the third cycle of immune checkpoint inhibitor therapy. The patient was diagnosed using troponin levels, computed tomography (CT) angiography, and echocardiography. After hospitalization, her cardiac condition was successfully resolved with corticosteroids, colchicine, and symptomatic treatment. To the best of our knowledge, this is one of the rarest cases to be reported of perimyocarditis as a toxicity of immunotherapy in a patient treated for adenocarcinoma of the lung.
-
8.
Rare, late onset of immune checkpoint inhibitor-induced type 1 diabetes mellitus in a patient with small-cell lung cancer treated with serplulimab: a case report and review of the literature.
Ning, P, Liu, S, Cao, H
Journal of medical case reports. 2024;(1):51
Abstract
BACKGROUND As a newly approved immune checkpoint inhibitor in China, serplulimab has been widely used in the immunotherapy of tumors. However, the immune-related adverse events of immune checkpoint inhibitors should not be ignored. Although immune checkpoint inhibitor-induced type 1 diabetes mellitus is a rare complication, it may cause diabetic ketoacidosis and endanger the lives of patients. CASE PRESENTATION This case report describes a 55-year-old male of Han nationality from China diagnosed with small-cell lung cancer with multiple metastases who experienced an adverse event of type 1 diabetes mellitus 68 weeks after receiving serplulimab therapy. The patient presented with typical symptoms of diabetic ketoacidosis, including severe thirst, nausea, vomiting, deep respirations, and stupor. Despite the absence of diabetes-related autoantibodies, the patient had extremely low levels of insulin and C-peptide release. Other potential causes of diabetes were ruled out, confirming the condition as serplulimab-induced immune checkpoint inhibitor-induced type 1 diabetes mellitus. After aggressive treatment to correct diabetic ketoacidosis, the patient's blood glucose levels stabilized and symptoms of diabetes improved significantly, although long-term insulin maintenance therapy was necessary. CONCLUSION This case highlights a rare, late-onset adverse event of immune checkpoint inhibitor-induced type 1 diabetes mellitus that may be overlooked during treatment with serplulimab. The monitoring of blood glucose levels and early signs and symptoms of diabetes cannot be relaxed at the late stage of treatment, even if patients do not have elevated blood glucose levels before and during the middle stage of treatment.
-
9.
Association of SARS-CoV-2 infection with neurological impairments in pediatric population: A systematic review.
Kwan, ATH, Portnoff, JS, Al-Kassimi, K, Singh, G, Hanafimosalman, M, Tesla, M, Gharibi, N, Ni, T, Guo, Z, Sonfack, DJN, et al
Journal of psychiatric research. 2024;:90-110
Abstract
Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population. A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged <18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches. A total of 843 no-duplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6985 individuals were included, where 12.8% (n = 892) of hospitalized patients experienced neurocognitive impairments which includes: 1) neurological symptoms (n = 294 of 892, 33.0%), 2) neurological syndromes and neuroimaging abnormalities (n = 223 of 892, 25.0%), and 3) other phenomena (n = 233 of 892, 26.1%). Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%). Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.
-
10.
Pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient: a case report and review of the literature.
Saad, R, Ghaddar, A, Zeenny, RM
Journal of medical case reports. 2024;(1):107
Abstract
BACKGROUND The cardiovascular system is among the least systems affected by immune-related adverse events. We report a rare life-threatening case of pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient. CASE PRESENTATION An 82-year-old Caucasian female with invasive urothelial carcinoma, started on first-line pembrolizumab, was admitted four days after receiving her second dose for severe asthenia, diffuse muscle aches, neck pain, and lethargy. In the emergency department, she had several episodes of bradycardia reaching 40 beats per minute associated with general discomfort and fatigue. Electrocardiography showed a third-degree atrioventricular heart block, while the patient remained normotensive. Cardiac damage parameters were altered with elevated levels of creatine phosphokinase of 8930 U/L, suggestive of immune checkpoint inhibitor-induced myositis, and troponin T of 1.060 ng/mL. Transthoracic echocardiography showed a preserved ejection fraction. Pembrolizumab-induced myocarditis was suspected. Therefore, treatment was initiated with high-dose glucocorticoids for 5 days, followed by a long oral steroid taper. A pacemaker was also implanted. Treatment resulted in the resolution of heart block and a decrease in creatine phosphokinase to the normal range. CONCLUSION Life-threatening cardiac adverse events in the form of myocarditis may occur with pembrolizumab use, warranting vigilant cardiac monitoring. Troponin monitoring in high-risk patients, along with baseline echocardiography may help identify this complication promptly to prevent life-threatening consequences.