Malak Moones Abedi

Post-hemorrhagic hydrocephalus (PHH) is a serious neurological sequela of severe intraventricular hemorrhage (IVH) in premature infants and remains one of the leading indications for ventriculoperitoneal (VP) shunt placement. Evaluating possible VP shunt-related complications can be challenging because clinical manifestations are often nonspecific, neuroimaging may initially appear unchanged, and microbiological cultures may remain negative. We report the case of a 19-month-old male born at 28 weeks’ gestation who developed Grade IV germinal matrix/intraventricular hemorrhage with bilateral intraparenchymal extension, early periventricular cystic leukomalacia, and post-hemorrhagic communicating hydrocephalus requiring multiple cerebrospinal fluid diversion procedures culminating in long-term VP shunt dependence. His medical history was notable for recurrent neonatal meningitis, secondary epilepsy with previous episodes of status epilepticus, secondary adrenal insufficiency, and severe global developmental delay. He presented with fever, recurrent coffee-ground vomiting, abdominal distension, progressive lethargy, reduced responsiveness, and localized erythematous swelling over the cranial VP shunt reservoir, raising concern for possible shunt-related pathology. During hospitalization, he deteriorated with status epilepticus and respiratory failure, with clinical concern for increased intracranial pressure, requiring admission to the Pediatric Intensive Care Unit (PICU). Laboratory investigations demonstrated leukocytosis, elevated C-reactive protein, cerebrospinal fluid pleocytosis, markedly elevated CSF protein, and CSF glucose of 2.0 mmol/L, for which a paired serum glucose value was unavailable, while repeated blood, urine, wound, and CSF cultures remained negative. Initial computed tomography (CT) demonstrated no significant interval change in the chronic hydrocephalus despite progressive neurological deterioration; however, serial neuroimaging later revealed progressive bilateral extra-axial fluid collections with radiological features suggestive of an evolving subacute subdural hemorrhage. The patient was managed with empirical broad-spectrum intravenous antibiotics, aggressive seizure control, stress-dose corticosteroids, respiratory support, and continuous multidisciplinary monitoring. His neurological and respiratory status subsequently improved, and he returned to his pre-admission neurological baseline before discharge with planned further evaluation at a tertiary pediatric neurosurgical center. This case highlights the diagnostic uncertainty surrounding acute neurological deterioration in a child with shunt-dependent PHH. VP shunt-related infection or malfunction remained important but unconfirmed diagnostic considerations, alongside competing or potentially overlapping contributors including status epilepticus, evolving extra-axial collections, respiratory infection, and endocrine or metabolic decompensation. No single etiology was definitively established. The case emphasizes the importance of serial neurological assessment, consideration of alternative diagnoses, repeat neuroimaging, and multidisciplinary evaluation when initial investigations do not establish the cause of deterioration.

Background/Objectives: Post-hemorrhagic hydrocephalus (PHH) is a major complication of extreme prematurity associated with significant neurodevelopmental morbidity. Although post-hemorrhagic ventricular dilatation (PHVD) is a recognized consequence of intraventricular hemorrhage (IVH), progression from an apparently low-grade IVH to severe shunt-dependent disease with imaging features suggestive—but not diagnostic—of a non-communicating hydrocephalus pattern is uncommon and presents important diagnostic and management challenges. We report such a case. Case Presentation: A male infant born at 26 weeks’ gestation developed an initially documented Grade II intraventricular hemorrhage that subsequently evolved into progressive post-hemorrhagic ventricular dilatation. Serial cranial ultrasonography demonstrated progressive ventriculomegaly, later confirmed by computed tomography showing marked dilatation of the lateral and third ventricles with severe cortical mantle thinning and a relatively preserved fourth ventricle, raising suspicion of a non-communicating hydrocephalus pattern. Clinical deterioration with progressive macrocephaly and neurological manifestations necessitated temporizing ventricular cerebrospinal fluid drainage, followed by ventriculoperitoneal shunt placement after stabilization and management of secondary complications. Management throughout the clinical course relied on serial neuroimaging, multidisciplinary decision-making, and individualized neurosurgical intervention. Conclusions: This case illustrates that an apparently low-grade neonatal intraventricular hemorrhage may evolve into severe shunt-dependent PHVD and emphasizes the importance of serial neuroimaging surveillance, objective assessment of ventricular progression, and cautious interpretation of imaging findings suggestive—but not diagnostic—of a non-communicating hydrocephalus pattern. It further highlights the diagnostic and therapeutic challenges encountered when atypical radiological evolution complicates the management of PHVD in extremely premature infants.

Adenosine has emerged as a central metabolic signal linking cellular stress to systemic physiological adaptation. Under conditions such as hypoxia, ischemia, inflammation, and tissue injury, extracellular adenosine triphosphate (eATP) released from stressed cells is sequentially metabolized by the ectonucleotidases CD39 and CD73, generating adenosine that accumulates in the extracellular microenvironment. This stress-responsive nucleoside activates four G-protein-coupled receptors (A1, A2A, A2B, and A3), triggering intracellular signaling networks including the cyclic adenosine monophosphate–protein kinase A (cAMP–PKA), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase–protein kinase B (PI3K–Akt), and hypoxia-inducible factor-1 alpha (HIF-1α) pathways. Through these integrated mechanisms, adenosine orchestrates diverse physiological processes such as vascular regulation, metabolic adaptation, immune modulation, and cellular survival. In the cardiovascular system, adenosine promotes coronary vasodilation and ischemic preconditioning, limiting reperfusion injury. In pulmonary tissues, it mediates acute anti-inflammatory responses but may also drive chronic fibrotic remodeling. Within the central nervous system, adenosine functions as a neuromodulator regulating neuronal excitability, sleep–wake homeostasis, and neuroprotection. In the tumor microenvironment, hypoxia-driven adenosine accumulation suppresses cytotoxic T cell and natural killer activity, facilitating immune evasion and tumor progression. Collectively, adenosine signaling represents a central integrative network that links metabolic stress sensing to coordinated cellular adaptation while simultaneously emerging as a clinically actionable therapeutic target across cardiovascular, inflammatory, neurological, and oncological diseases.

Background: Glucagon-like peptide-1 (GLP-1)-based therapies offer significant cardiometabolic benefits. Obesity-related heart failure with preserved ejection fraction (HFpEF) arises from a complex interplay of increased lipids, chronic inflammation, and metabolic disturbances. These factors not only exacerbate the disease but also affect GLP-1 pathways, supporting the potential role of GLP-1-based therapies in targeting this condition. Objective: This review aimed to synthesize the current evidence on GLP-1-based therapy in HFpEF, focusing on mechanisms of action, clinical outcomes, and practical significance. Methodology: A narrative review using PubMed and Scopus was conducted, including studies published between January 2020 and March 2026. Evidence from randomized trials, pooled analyses, mechanistic studies, and observational data was incorporated. Results: GLP-1-based therapies, including semaglutide and tirzepatide, demonstrated significant improvements in symptoms, exercise capacity, and quality of life. These benefits are closely linked to weight loss, reduced inflammation, and improved congestion indices. Tirzepatide use has also been associated with a reduction in heart failure-related complications. The underlying mechanisms likely involve coordinated effects on metabolism, inflammation, hemodynamics, and cardiac remodeling. Current evidence suggests that its efficacy in improving morbidity rates is stronger than its efficacy in reducing mortality rates. Conclusions: GLP-1-based therapies offer a promising, phenotypically targeted approach to managing obesity-associated HFpEF. However, their long-term effects on mortality remain unclear, highlighting the need for further research. Further studies should refine patient selection and define optimal clinical integration.

This systematic review aimed to synthesize experimental evidence on the anticancer effects of Lacticaseibacillus rhamnosus (L. rhamnosus) and its derivatives against colorectal cancer (CRC) cell models. Eligible studies investigated probiotics, postbiotics, or bioactive compounds derived from L. rhamnosus with an in vitro component; studies relying solely on in vivo animal models, clinical trials, or observational designs were excluded. PubMed and Scopus were searched to identify relevant studies. Risk of bias was assessed using a modified QUIN tool, and extracted data were tabulated. Owing to incomplete numerical data, meta-analysis was not feasible, and the results were synthesized accordingly. Seventeen studies were included. L. rhamnosus and its derivatives reduced CRC cell proliferation, induced apoptosis, and caused cell cycle arrest. Reported mechanisms included upregulation of Bax, caspase-3/9, and p53; downregulation of Bcl-2/Bcl-xl; inhibition of Wnt/β-catenin signaling; reduced invasion and migration; increased reactive oxygen species; and immunomodulatory effects. Key limitations were heterogeneity in interventions, dosages, exposure periods, and cell lines, along with incomplete reporting, which precluded quantitative synthesis. Overall, preclinical evidence indicates multimodal anticancer effects of L. rhamnosus in CRC models; however, standardized reporting and translational research are required.