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Biomedical Reports Aug 2024During a routine ultrasound examination of the abdomen, a 60-year-old male patient was diagnosed with mass in the tail of the pancreas. However, computed tomography (CT)...
During a routine ultrasound examination of the abdomen, a 60-year-old male patient was diagnosed with mass in the tail of the pancreas. However, computed tomography (CT) suggested that the lesion was an intrapancreatic accessory spleen (IPAS). IPAS is a congenital anomaly, which usually does not present with symptoms. IPAS occurs during embryologic splenic development when a portion of the splenic tissue fails to fuse with the main body of the spleen. IPAS does not require treatment, except when it is combined with idiopathic thrombocytopenic purpura. In the present case, the diagnosis of IPAS was confirmed using magnetic resonance imaging (MRI). On CT and MRI, the IPAS had a density and intensity comparable with that of the spleen in all plain and contrast-enhanced phases. Due to comorbidities, the patient refused further evaluation or surgery. The lesion was periodically monitored using CT every 1-2 years. Since the tumour was stable during the 7-year follow-up, it was concluded that it was an IPAS. In patients that cannot undergo surgery, a characteristic location (near the spleen) and imaging features (such as a 'zebra-patterned' enhancement in the arterial phase on CT and high signal intensity on diffusion-weighted imaging sequences on MRI, which is comparative to that of the normal spleen) may allow for a diagnose of IPAS with a high level of certainty. Being aware of this condition could aid a correct diagnosis of IPAS and prevent unnecessary surgery.
PubMed: 38912170
DOI: 10.3892/br.2024.1801 -
Proceedings (Baylor University. Medical... 2024We describe the case of a 19-year-old woman who presented with abdominal pain, vomiting, and a palpable purpuric rash. The patient subsequently developed dysentery and...
We describe the case of a 19-year-old woman who presented with abdominal pain, vomiting, and a palpable purpuric rash. The patient subsequently developed dysentery and was found to have an infection from Shiga toxin-producing . The patient also met diagnostic criteria for IgA vasculitis (also known as Henoch Schönlein purpura) but had negative immunofluorescence biopsies of the rash. The patient was treated with steroids and achieved recovery. To our knowledge, this is the first documented case of IgA vasculitis in the setting of an enterohemorrhagic infection. This case highlights an atypical presentation of IgA vasculitis and the need to include small vessel vasculitis as a differential diagnosis when treating patients of all ages.
PubMed: 38910806
DOI: 10.1080/08998280.2024.2345555 -
Cureus May 2024An 11-year-old patient presented with the primary complaint of hematuria and vomiting. On further investigation and a series of diagnostic tests, including a biopsy and...
An 11-year-old patient presented with the primary complaint of hematuria and vomiting. On further investigation and a series of diagnostic tests, including a biopsy and thrombotic microangiopathy (TMA) profile, the patient was diagnosed with thrombotic microangiopathy. TMA is a pathological process involving endothelial cell injury, leading to thrombocytopenia and microangiopathic hemolytic anemia. This case highlights the importance of considering TMA in pediatric patients presenting with nonspecific symptoms, such as loss of appetite. Further research is needed to understand the pathophysiology and optimal management strategies for pediatric TMA. This case adds to the growing body of literature on pediatric TMA and underscores the need for a high index of suspicion in similar clinical scenarios.
PubMed: 38910744
DOI: 10.7759/cureus.60872 -
The Journal of Allergy and Clinical... Jun 2024It is currently unclear whether cesarean section increases the risk of allergic diseases in offspring.
BACKGROUND
It is currently unclear whether cesarean section increases the risk of allergic diseases in offspring.
OBJECTIVE
To investigate the association between cesarean section and the risk of allergic diseases in offspring.
METHODS
We searched PubMed, Embase, and the Cochrane Library for relevant studies up to October 12, 2023. Observational studies comparing the risk of allergic diseases in offspring delivered by cesarean section versus those delivered vaginally were included. Most-adjusted estimates from individual studies were synthesized by meta-analysis.
RESULTS
A total of 113 studies were included, 70 of which had a low risk of bias. Compared with offspring delivered vaginally, offspring delivered by cesarean section had significantly greater risks of asthma (odds ratio [OR] 1.20, 95% CI 1.16 to 1.25), allergic rhinitis/conjunctivitis (OR 1.15, CI 1.09 to 1.22), atopic dermatitis/eczema (OR 1.08, CI 1.04 to 1.13), food allergies (OR 1.35, CI 1.18 to 1.54), and allergic sensitization (OR 1.19, CI 1.10 to 1.28). Cesarean section did not significantly increase urticaria risk. Sensitivity analyses including only studies with a low risk of bias, adjusted estimates, prospective data collection, large sample sizes, or outcomes from medical records generally supported these findings. Offspring age, study region latitude, economy type, and cesarean section rate accounted for some of the clinical heterogeneity. No data on allergic purpura were found.
CONCLUSION
Most-adjusted estimates suggest that cesarean section is associated with increased risks of asthma, allergic rhinitis/conjunctivitis, atopic dermatitis/eczema, food allergies, and allergic sensitization in offspring. The impact of cesarean section on urticaria and purpura remains uncertain.
PubMed: 38908434
DOI: 10.1016/j.jaip.2024.06.022 -
Medicine Jun 2024Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated... (Observational Study)
Observational Study
Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated morbidities due to maternal ITP are unclear. The present study aimed to assess the neonatal outcomes of pregnant women with ITP. Fifty-five pregnant women with ITP and their babies, born between January/2013 and April/2021, were retrospectively reviewed. Maternal and neonatal thrombocytopenia cases other than ITP were excluded from the study. Physical examination, blood count, and cranial/abdominal ultrasonography findings of the newborns were recorded. Neonatal thrombocytopenia was defined as a platelet count < 150 × 109/L. Relationship between neonatal thrombocytopenia and maternal factors was investigated. Thrombocytopenia was detected in 17/55 babies (30.9%), and 8/17 (47.1%) had symptoms of bleeding, all but one being mild bleeding. There was a significant correlation between neonatal platelet counts of < 100 × 109/L and maternal splenectomy history. Incidence of moderate and severe thrombocytopenia was higher (statistically insignificant) in neonates of mothers with ITP. No significant correlation was determined between maternal and neonatal platelet counts. There was a weak insignificant correlation between platelet counts of neonates of mothers with or without thrombocytopenia. A significant correlation was found between the presence of splenectomy before delivery in the mother and a platelet count of < 100 × 109/L in the neonate. Moderate and severe thrombocytopenia was higher in neonates of mothers diagnosed with ITP before pregnancy and needed treatment during pregnancy and/or delivery, but the difference was insignificant. Close follow-up of babies born to mothers with ITP after birth is crucial since there is no significant prediction criterion for developing neonatal thrombocytopenia and associated morbidities.
Topics: Humans; Female; Retrospective Studies; Infant, Newborn; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Cross-Sectional Studies; Adult; Platelet Count; Pregnancy Complications, Hematologic; Thrombocytopenia, Neonatal Alloimmune; Splenectomy
PubMed: 38905433
DOI: 10.1097/MD.0000000000038587 -
Retrograde adenosine/A receptor signaling facilitates excitatory synaptic transmission and seizures.Cell Reports Jun 2024Retrograde signaling at the synapse is a fundamental way by which neurons communicate and neuronal circuit function is fine-tuned upon activity. While long-term changes...
Retrograde signaling at the synapse is a fundamental way by which neurons communicate and neuronal circuit function is fine-tuned upon activity. While long-term changes in neurotransmitter release commonly rely on retrograde signaling, the mechanisms remain poorly understood. Here, we identified adenosine/A receptor (AR) as a retrograde signaling pathway underlying presynaptic long-term potentiation (LTP) at a hippocampal excitatory circuit critically involved in memory and epilepsy. Transient burst activity of a single dentate granule cell induced LTP of mossy cell synaptic inputs, a BDNF/TrkB-dependent form of plasticity that facilitates seizures. Postsynaptic TrkB activation released adenosine from granule cells, uncovering a non-conventional BDNF/TrkB signaling mechanism. Moreover, presynaptic ARs were necessary and sufficient for LTP. Lastly, seizure induction released adenosine in a TrkB-dependent manner, while removing ARs or TrkB from the dentate gyrus had anti-convulsant effects. By mediating presynaptic LTP, adenosine/AR retrograde signaling may modulate dentate gyrus-dependent learning and promote epileptic activity.
PubMed: 38905101
DOI: 10.1016/j.celrep.2024.114382 -
Cureus Jun 2024A 65-year-old male with multiple comorbidities and recently diagnosed with diabetic kidney disease developed upper and lower extremity rash following escitalopram...
A 65-year-old male with multiple comorbidities and recently diagnosed with diabetic kidney disease developed upper and lower extremity rash following escitalopram initiation for his depressive mood. Clinical assessment and skin biopsy confirmed cutaneous small-vessel vasculitis (CSVV), prompting drug discontinuation and oral methylprednisolone therapy. The resolution of the rash was achieved within a week. This rare case of CSVV induced by escitalopram highlights the importance of timely recognition and management of drug-induced CSVV and adds to the limited literature on selective serotonin reuptake inhibitor-associated CSVV.
PubMed: 38903979
DOI: 10.7759/cureus.62776 -
Frontiers in Immunology 2024Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other... (Review)
Review
Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other causes including bone marrow suppression induced by chemotherapeutic agents, infection, and progression of cancer; drug-induced thrombocytopenia can easily be misdiagnosed or overlooked. Here, we present a case of an ovarian cancer patient with a history of mixed connective tissue disease who underwent surgery followed by treatment with paclitaxel, cisplatin, and bevacizumab. The patient developed acute isolated thrombocytopenia after the sixth cycle. Serum antiplatelet antibody testing revealed antibodies against glycoprotein IIb. After we analyzed the whole therapeutic process of this patient, drug-induced immune thrombocytopenia was assumed, and bevacizumab was conjectured as the most probable drug. Thrombocytopenia was ultimately successfully managed using recombinant human thrombopoietin, prednisone, and recombinant human interleukin-11. We provide a summary of existing literature on immune thrombocytopenia induced by bevacizumab and discuss related mechanisms and triggers for drug-induced immune thrombocytopenia. The present case underscores the potential of bevacizumab to induce immune-mediated thrombocytopenia, emphasizing the need for heightened vigilance towards autoimmune diseases or an autoimmune-activated state as plausible triggers for rare drug-induced immune thrombocytopenia in cancer therapy.
Topics: Female; Humans; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Mixed Connective Tissue Disease; Ovarian Neoplasms; Purpura, Thrombocytopenic, Idiopathic
PubMed: 38903494
DOI: 10.3389/fimmu.2024.1382964 -
The New England Journal of Medicine Jun 2024Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal...
BACKGROUND
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells.
METHODS
We conducted a phase 1-2, open-label study to evaluate the safety and efficacy of CM313 in adult patients with ITP. CM313 was administered intravenously at a dose of 16 mg per kilogram of body weight every week for 8 weeks, followed by a 16-week follow-up period. The primary outcomes were adverse events and documentation of two or more consecutive platelet counts of at least 50×10 per liter within 8 weeks after the first dose of CM313. The status of peripheral-blood immune cells in patients and changes in the mononuclear phagocytic system in passive mouse models of ITP receiving anti-CD38 therapy were monitored.
RESULTS
Of the 22 patients included in the study, 21 (95%) had two consecutive platelet counts of at least 50×10 per liter during the treatment period, with a median cumulative response duration of 23 weeks (interquartile range, 17 to 24). The median time to the first platelet count of at least 50×10 per liter was 1 week (range, 1 to 3). The most common adverse events that occurred during the study were infusion-related reaction (in 32% of the patients) and upper respiratory tract infection (in 32%). After CD38-targeted therapy, the percentage of CD56CD16+ natural killer cells, the expression of CD32b on monocytes in peripheral blood, and the number of macrophages in the spleen of the passive mouse models of ITP all decreased.
CONCLUSIONS
In this study, anti-CD38 targeted therapy rapidly boosted platelet levels by inhibiting antibody-dependent cell-mediated cytotoxicity on platelets, maintained long-term efficacy by clearing plasma cells, and was associated with mainly low-grade toxic effects. (Funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and others; ClinicalTrials.gov number, NCT05694767).
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Female; Middle Aged; Animals; Mice; Antibodies, Monoclonal; Male; ADP-ribosyl Cyclase 1; Aged; Adult; Platelet Count
PubMed: 38899695
DOI: 10.1056/NEJMoa2400409 -
Journal of Controlled Release :... Jun 2024We report our experience disrupting the blood-brain barrier (BBB) to improve drug delivery in glioblastoma patients receiving temozolomide chemotherapy. The goals of...
PURPOSE
We report our experience disrupting the blood-brain barrier (BBB) to improve drug delivery in glioblastoma patients receiving temozolomide chemotherapy. The goals of this retrospective analysis were to compare MRI-based measures of BBB disruption and vascular damage to the exposure levels, acoustic emissions data, and acoustic simulations. We also simulated the cavitation detectors.
METHODS
Monthly BBB disruption (BBBD) was performed using a 220 kHz hemispherical phased array focused ultrasound system (Exablate Neuro, InSightec) and Definity microbubbles (Lantheus) over 38 sessions in nine patients. Exposure levels were actively controlled via the cavitation dose obtained by monitoring subharmonic acoustic emissions. The acoustic field and sensitivity profile of the cavitation detection system were simulated. Exposure levels and cavitation metrics were compared to the level of BBBD evident in contrast-enhanced MRI and to hypointense regions in T2*-weighted MRI.
RESULTS
Our treatment strategy evolved from using a relatively high cavitation dose goal to a lower goal and longer sonication duration and ultimately resulted in BBBD across the treatment volume with minimal petechiae. Subsonication-level feedback control of the exposure using acoustic emissions also improved consistency. Simulations of the acoustic field suggest that reflections and standing waves appear when the focus is placed near the skull, but their effects can be mitigated with aberration correction. Simulating the cavitation detectors suggest variations in the sensitivity profile across the treatment volume and between patients. A correlation was observed with the cavitation dose, BBBD and petechial hemorrhage in 8/9 patients, but substantial variability was evident. Analysis of the cavitation spectra found that most bursts did not contain wideband emissions, a signature of inertial cavitation, but biggest contribution to the cavitation dose - the metric used to control the procedure - came from bursts with wideband emissions.
CONCLUSION
Using a low subharmonic cavitation dose with a longer duration resulted in BBBD with minimal petechiae. The correlation between cavitation dose and outcomes demonstrates the benefits of feedback control based on acoustic emissions, although more work is needed to reduce variability. Acoustic simulations could improve focusing near the skull and inform our analysis of acoustic emissions. Monitoring additional frequency bands and improving the sensitivity of the cavitation detection could provide signatures of microbubble activity associated with BBB disruption that were undetected here and could improve our ability to achieve BBB disruption without vascular damage.
PubMed: 38897294
DOI: 10.1016/j.jconrel.2024.06.036