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Surgical Case Reports Jun 2024Gastrointestinal mucormycosis is a rapidly progressing and often fatal disease, predominantly affecting immunocompromised patients. Surgical intervention, in addition to...
BACKGROUND
Gastrointestinal mucormycosis is a rapidly progressing and often fatal disease, predominantly affecting immunocompromised patients. Surgical intervention, in addition to antifungal therapy, is essential. Herein, we describe the successful management of appendiceal mucormycosis in a patient with acute promyelocytic leukemia through rapid surgical intervention and antifungal therapy.
CASE PRESENTATION
A 29-year-old woman underwent autologous peripheral blood stem cell transplantation for acute promyelocytic leukemia (APL). Subsequently, her condition relapsed, and remission induction therapy was initiated. During the immunosuppressive period, she developed a fever and severe abdominal pain. Computed tomography revealed severe edema of the ileum, cecum, and ascending colon. Despite receiving multiple antibiotics, antivirals, and antifungals, her condition showed no improvement. Consequently, she underwent exploratory laparotomy, with no bowel perforation noted, revealing severe inflammation in the ileum, cecum, and ascending colon, as well as appendiceal necrosis. Appendectomy was performed, and histopathological analysis revealed hyphae in the vessels and layers of the appendiceal wall, suggestive of mucormycosis. The patient was diagnosed with appendiceal mucormycosis, and liposomal amphotericin B was administered. Subsequent monitoring showed no recurrence of mucormycosis. Genetic analysis of the resected tissue revealed Rhizopus microspores as the causative agent.
CONCLUSIONS
Rapid surgical intervention and antifungal drug administration proved successful in managing appendiceal mucormycosis in a patient with APL. Early recognition and aggressive surgical intervention are imperative to improve outcomes in such patients.
PubMed: 38916715
DOI: 10.1186/s40792-024-01958-y -
AJNR. American Journal of Neuroradiology Jun 2024Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors...
BACKGROUND AND PURPOSE
Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors can be challenging on imaging, and preoperative diagnosis can change the neurosurgical approach. We hypothesize that a 'lightbulb sign' on the ASL sequence (diffuse homogenous intense hyperperfusion within the solid component of the tumor) will provide additional imaging finding to differentiate hemangioblastoma from other posterior fossa tumors.
MATERIALS AND METHODS
In this retrospective comparative observational study, we only included pathology-proven cases of hemangioblastoma, while the control group consisted of other randomly selected pathology-proven posterior fossa tumors from January 2022 to January 2024. Two blinded neuroradiologists analyzed all applicable MRI sequences, including ASL sequence if available. ASL was analyzed for the 'lightbulb sign'. Disagreements between the radiologists were resolved by a third pediatric neuroradiologist. Chi-square and Fisher's exact test were used to analyze the data.
RESULTS
95 patients were enrolled in the study; 57 (60%) were male. The median age at diagnosis was 8 years old (IQR: 3-14). Out of the enrolled patients, 8 had hemangioblastoma, and 87 had other posterior fossa tumors, including medulloblastoma (n=31), pilocytic astrocytoma (n=23), posterior fossa ependymoma type A (n=16), and other tumors (n=17). The comparison of hemangioblastoma vs non-hemangioblastoma showed that peripheral edema (p=0.02) and T2 flow void (p=0.02) favors hemangioblastoma, whereas reduced diffusion (low ADC) (p=0.002) and ventricular system extension (p=0.001) favors nonhemangioblastoma tumors.Forty-two cases also had ASL perfusion sequences. While high perfusion favors hemangioblastoma (p=0.03), the lightbulb sign shows a complete distinction since all the ASL series of hemangioblastoma cases (n=4) showed the lightbulb sign, whereas none of the nonhemangioblastoma cases (n=38) showed the sign (p<0.001).
CONCLUSIONS
Lightbulb-like intense and homogenous hyperperfusion patterns on ASL are helpful in diagnosing posterior fossa hemangioblastoma in children.ABBREVIATIONS ASL = Arterial spin labelling; pASL = Pulsed arterial spin labelling; pCASL = Pseudocontinuous arterial spin labelling; DCE = Dynamic contrast-enhanced; DSC = Dynamic susceptibility contrast; VHL = Von Hippel Lindau.
PubMed: 38914433
DOI: 10.3174/ajnr.A8391 -
Frontiers in Genetics 2024Dysferlinopathy is an autosomal recessive disorder caused by mutations in the DYSF gene. This study reported two homozygous adjacent missense mutations in the DYSF...
Dysferlinopathy is an autosomal recessive disorder caused by mutations in the DYSF gene. This study reported two homozygous adjacent missense mutations in the DYSF gene, presenting clinically with bilateral lower limb weakness and calf swelling. Two homozygous adjacent missense mutations in the DYSF gene may be associated with the development of dysferlinopathy, but the exact mechanism needs further investigation. A retrospective analysis of clinical data from a dysferlinopathy-affected family was conducted. Peripheral blood samples were collected from members of this family for whole-exome sequencing (WES) and copy number variation analysis. Sanger sequencing was employed to confirm potential pathogenic variants. The Human Splicing Finder, SpliceAI, and varSEAK database were used to predict the effect of mutations on splicing function. The pathogenic mechanism of aberrant splicing in dysferlinopathy due to two homozygous adjacent missense mutations in the DYSF gene was determined by an splicing assay and an minigene assay. The proband was a 42-year-old woman who presented with weakness of the lower limbs for 2 years and edema of the lower leg. Two homozygous DYSF variants, c.5628C>A p. D1876E and c.5633A>T p. Y1878F, were identified in the proband. Bioinformatics databases suggested that the mutation c.5628C>A of DYSF had no significant impact on splicing signals. Human Splicing Finder Version 2.4.1 suggested that the c.5633A>T of DYSF mutation caused alteration of auxiliary sequences and significant alteration of the ESE/ESS motif ratio. VarSEAK and SpliceAI suggested that the c.5633A>T of DYSF mutation had no splicing effect. Both an splicing assay and an minigene assay showed two adjacent mutations: c.5628C>A p. D1876E and c.5633A>T p. Y1878F in the DYSF gene leading to an Exon50 jump that resulted in a 32-aa amino acid deletion within the protein. Point mutation c.5628C>A p. D1876E in the DYSF gene affected splicing , while point mutation c.5633A>T p. Y1878F in the DYSF gene did not affect splicing function. This study confirmed for the first time that two homozygous mutations of DYSF were associated with the occurrence of dysferlinopathy. The c.5628C>A p. D1876E mutation in DYSF affected the splicing function and may be one of the contributing factors to the pathogenicity.
PubMed: 38903757
DOI: 10.3389/fgene.2024.1404611 -
Cureus May 2024As globalization progresses, cases of sickle cell disease (SCD) are now being seen even in Japan, where SCD did not originally exist. SCD causes not only anemia but also...
As globalization progresses, cases of sickle cell disease (SCD) are now being seen even in Japan, where SCD did not originally exist. SCD causes not only anemia but also peripheral blood flow obstruction, which can lead to systemic complications. This report represents a case of sickle cell retinopathy (SCR) in Japan discovered with the onset of retinal artery occlusion (RAO). The patient, a 20-year-old African-Japanese male, was being monitored for SCD at the Nagoya University Hospital, Pediatrics Department, Nagoya, Japan. Following a chest pain episode, he reported a loss of vision in his right eye and was referred to the ophthalmology department. Examination showed reduced visual acuity in the right eye 20/40 compared to the left 20/20. A Goldman visual field test indicated central vision loss in the right eye, and fundoscopic examination revealed yellow-white lesions centered on the macula and peripheral salmon-patch-like lesions in the right eye, with peripheral black sunburst-like lesions in the left eye. Optical coherence tomography (OCT) of the right eye showed inner retinal edema within the macula, suggesting an SCR accompanied by branch RAO. Six months later, he complained of further vision loss in his right eye. Examination and OCT revealed sub-inner limiting membrane hemorrhage in the right eye, suggesting worsening of the SCR. SCD is exceedingly rare among native Japanese but is likely to be encountered more frequently as globalization progresses. Even in countries where SCD has traditionally been rare, attention must be paid to the occurrence of severe SCR when managing SCD.
PubMed: 38899256
DOI: 10.7759/cureus.60653 -
Journal of Ethnopharmacology Jun 2024In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases.
ETHNOPHARMACOLOGICAL RELEVANCE
In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases.
AIM OF THE STUDY
to evaluate the chemical composition, antinociceptive, and anti-inflammatory activities of Lippia alba essential oil and its major compound geraniol.
MATERIAL AND METHODS
Lippia alba leaves were collected in Pará state, Brazil. The leaf essential oil was obtained using a modified Clevenger-type extractor. Then, the oil was analyzed by GC and GC-MS analyses. To evaluate the toxicity of LaEO and geraniol, the doses of 50, 300, and 2000 mg/kg were used in a mouse model. For antinociception tests, abdominal contortion, hot plate, and formalin tests were used; all groups were treated with LaEO and geraniol at doses of 25, 50, and 100 mg/kg; and to evaluate inflammation using the ear edema model.
RESULTS
The constituents identified in the highest content were oxygenated monoterpenes: geraniol (37.5%), geranial (6.7%) and neral (3.8%). The animals treated with LaEO and geraniol demonstrated atypical behaviors with aspects of lethargy and drowsiness, characteristics of animals in a state of sedation; the relative weights showed no significant difference compared to the controls. In the abdominal contortion test, LaEO at 25 mg/kg, 50 mg/kg doses, and 100 mg/kg reduced the number of contortions, representing a percentage reduction of 84.64%, 81.23%, and 66.21% respectively. In the hot plate test, LaEO and geraniol increased the latency time at doses of 25, 50, and 100 mg/kg in all test periods; there was no statistical difference between LaEO and geraniol. In the first phase of the formalin test, only doses of 25 mg/kg and 100 mg/kg of LaEO showed significant activity, reducing the latency time by 53.40% and 58.90%. LaEO at doses of 25 mg/kg and 100 mg/kg reduced the size of the edema, demonstrating an anti-inflammatory activity of 59.38% (25 mg/kg) and 50% (100 mg/kg).
CONCLUSION
Lippia alba essential oil and geraniol showed central/peripheral analgesic and anti-inflammatory potential and can be used as an alternative or complementary treatment to conventional drugs. More studies are needed to evaluate its action mechanisms and its analgesic effects.
PubMed: 38897034
DOI: 10.1016/j.jep.2024.118459 -
Diagnostics (Basel, Switzerland) May 2024The fact that some SARS-CoV-2 pneumonia patients benefit from changing body position, and some from continuous positive airways pressure (CPAP), indicates the functional...
The fact that some SARS-CoV-2 pneumonia patients benefit from changing body position, and some from continuous positive airways pressure (CPAP), indicates the functional character of hypoxia. We hypothesize that such effects could be explained by the closure of small airways. To prove the hypothesis, we evaluated the patency of small airways in 30 oxygen-dependent, spontaneously breathing patients with SARS-CoV-2 pneumonia during their hospital stay using the FOT method and then compared the results with data obtained three months later. During the acute period, total resistance (R5) and peripheral resistance (R5-20) rose above the upper limit of normal (ULN) in 28% and 50% of all patients, respectively. Reactance indices X5, AX and Fres exceeded ULN in 55%, 68% and 66% of cases. Significant correlations were observed between PaO/FiO, the time spent in the hospital and R5, X5, AX and Fres. After 3 months, 18 patients were re-examined. During the hospital stay, 11 of them had risen above the upper limit of normal (ULN), for both resistance (R5-20) and reactance (X5, AX) values. Three months later, ULN for R5-20 was exceeded in only four individuals, but ULN for X5 and AX was exceeded in five individuals. Lung function examination revealed a combined restrictive/obstructive ventilatory failure and reduced CO transfer factor. We interpret these changes as lung tissue remodeling due to the process of fibrosis. We conclude that during acute period of SARS-CoV-2 pneumonia, dilated pulmonary blood vessels and parenchymal oedema induce functional closure of small airways, which in turn induce atelectasis with pulmonary right-to-left shunting, followed by the resulting hypoxemia.
PubMed: 38893686
DOI: 10.3390/diagnostics14111160 -
The Egyptian Heart Journal : (EHJ) :... Jun 2024Amyloidosis, particularly wild-type transthyretin amyloidosis (ATTRwt), is an increasingly recognized cause of heart failure with preserved ejection fraction in the...
BACKGROUND
Amyloidosis, particularly wild-type transthyretin amyloidosis (ATTRwt), is an increasingly recognized cause of heart failure with preserved ejection fraction in the aging population. The complexity of managing ATTRwt in older patients underscores the necessity for individualized treatment approaches, yet clinical guidelines are lacking. This case report contributes to the understanding of ATTRwt management in the elderly, emphasizing the intricacies of medication tolerance and therapeutic decision-making.
CASE PRESENTATION
An 83-year-old Korean man with a history of hypertension presented with dyspnea and peripheral edema. Investigations including electrocardiography, transthoracic echocardiography, cardiac magnetic resonance, and Technetium pyrophosphate scintigraphy led to a diagnosis of ATTRwt cardiac amyloidosis. Initial management with heart failure medications, including an angiotensin-converting enzyme inhibitor, diuretic, and mineralocorticoid receptor antagonist, was modified due to evolving clinical presentations, such as hypotension and onset of atrial fibrillation. Challenges included intolerance to beta-blockers and bleeding complications from direct oral anticoagulant therapy. The patient's treatment journey highlighted the need for personalized management strategies in older ATTRwt patients.
CONCLUSIONS
This case illustrates the challenges in diagnosing and managing ATTRwt amyloidosis in the elderly, particularly the complexities in medication management due to the patient's age, comorbid conditions, and side effects. It underscores the importance of a tailored approach in managing ATTRwt in older populations and highlights the need for ongoing research and development of treatment strategies tailored to this demographic.
PubMed: 38888709
DOI: 10.1186/s43044-024-00507-0 -
Gene Regulation of Neutrophils Mediated Liver and Lung Injury through NETosis in Acute Pancreatitis.Inflammation Jun 2024Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies, often resulting in self-digestion, edema, hemorrhage, and even necrosis of pancreatic...
Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies, often resulting in self-digestion, edema, hemorrhage, and even necrosis of pancreatic tissue. When AP progresses to severe acute pancreatitis (SAP), it often causes multi-organ damage, leading to a high mortality rate. However, the molecular mechanisms underlying SAP-mediated organ damage remain unclear. This study aims to systematically mine SAP data from public databases and combine experimental validation to identify key molecules involved in multi-organ damage caused by SAP. Retrieve transcriptomic data of mice pancreatic tissue for AP, lung and liver tissue for SAP, and corresponding normal tissue from the Gene Expression Omnibus (GEO) database. Conduct gene differential analysis using Limma and DEseq2 methods. Perform enrichment analysis using the clusterProfiler package in R software. Score immune cells and immune status in various organs using single-sample gene set enrichment analysis (ssGSEA). Evaluate mRNA expression levels of core genes using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Validate serum amylase, TNF-α, IL-1β, and IL-6 levels in peripheral blood using enzyme-linked immunosorbent assay (ELISA), and detect the formation of neutrophil extracellular traps (NETs) in mice pancreatic, liver, and lung tissues using immunofluorescence. Differential analysis reveals that 46 genes exhibit expression dysregulation in mice pancreatic tissue for AP, liver and lung tissue for SAP, as well as peripheral blood in humans. Functional enrichment analysis indicates that these genes are primarily associated with neutrophil-related biological processes. ROC curve analysis indicates that 12 neutrophil-related genes have diagnostic potential for SAP. Immune infiltration analysis reveals high neutrophil infiltration in various organs affected by SAP. Single-cell sequencing analysis shows that these genes are predominantly expressed in neutrophils and macrophages. FPR1, ITGAM, and C5AR1 are identified as key genes involved in the formation of NETs and activation of neutrophils. qPCR and IHC results demonstrate upregulation of FPR1, ITGAM, and C5AR1 expression in pancreatic, liver, and lung tissues of mice with SAP. Immunofluorescence staining shows increased levels of neutrophils and NETs in SAP mice. Inhibition of NETs formation can alleviate the severity of SAP as well as the levels of inflammation in the liver and lung tissues. This study identified key genes involved in the formation of NETs, namely FPR1, ITGAM, and C5AR1, which are upregulated during multi-organ damage in SAP. Inhibition of NETs release effectively reduces the systemic inflammatory response and liver-lung damage in SAP. This research provides new therapeutic targets for the multi-organ damage associated with SAP.
PubMed: 38884700
DOI: 10.1007/s10753-024-02071-w -
Drug Discoveries & Therapeutics Jun 2024Malnutrition is a common problem among hospitalized older patients. Peripheral parenteral nutrition (PN) can improve patient outcomes but can also lead to complications...
Malnutrition is a common problem among hospitalized older patients. Peripheral parenteral nutrition (PN) can improve patient outcomes but can also lead to complications that affect future treatment. Older inpatients, in particular, are expected to be prone to these catheter-related complications. However, the impact of peripheral PN on older inpatients has been rarely investigated. In the current study, the impact of PN on short peripheral catheters (SPCs) was evaluated by comparing signs and symptoms at the time of catheter removal between 22 patients with PN and 27 without. In addition to external clinical assessment, sonographic investigations of the SPC site were performed. The prevalence of external signs and symptoms of complications was similar between the patients (all P > 0.05). However, subcutaneous edema was found by ultrasound in > 80% of patients with PN, compared with 55.6% of those without PN (P = 0.051). Unlike cases without PN, all patients with PN who presented with external signs and symptoms developed subcutaneous edema (P = 0.022). Multivariate analysis demonstrated that administration of PN was independently associated with subcutaneous edema (adjusted odds ratio = 6.88, 95% confidence interval = 1.083-75.486, P = 0.040). For several decades, phlebitis has been the primary focus of complications related to peripheral PN in clinical settings. However, our results imply that peripheral PN causes subcutaneous edema, which can lead to catheter failure in older inpatients. This study contributes to understanding the etiology of catheter failure during peripheral PN in this population.
PubMed: 38880602
DOI: 10.5582/ddt.2024.01029 -
Microvascular Research Jun 2024Ischemic stroke occurs due a blockage in the blood flow to the brain, leading to damage to the nervous system. The prevalent morbidities resulting from stroke include...
Ischemic stroke occurs due a blockage in the blood flow to the brain, leading to damage to the nervous system. The prevalent morbidities resulting from stroke include post-stroke infection, as sepsis. Additionally, oxidative stress is recognized for inducing functional deficits in peripheral organs during sepsis. Therefore, sex differences in stroke exist and we aimed to investigate the peripheral oxidative stress caused by sepsis after stroke in male and female rats. Wistar rats (male and female) were divided into sham+sham, middle cerebral artery occlusion (MCAO) + sham, sham+ cecal ligation and perforation (CLP) and MCAO+CLP groups to males and female rats. Animals were subjected to MCAO or sham and after 7 days, were subjected to sepsis by CLP or sham. After 24 h, serum, total brain, lung, liver, heart, and spleen were collected. Brain edema, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, oxidative damage to lipids and proteins, and catalase activity were evaluated. Brain edema was observed only in male rats in MCAO+CLP group compared to MCAO+sham. Regarding MPO activity, an increase was verified in male in different organs and serum in MCAO+CLP group. For N/N levels, the increase was more pronounced in females submitted to MCAO+CLP. In general, to oxidative stress, an increase was only observed in animals exposed to MCAO+CLP, or with a greater increase in this group compared to the others. The findings provided the first indication that animals exposed to MCAO exhibit a heightened vulnerability to the harmful impacts of sepsis, as evidenced by brain edema and peripheral oxidative stress, and this susceptibility is dependent of sex.
PubMed: 38880383
DOI: 10.1016/j.mvr.2024.104711