Candida Dublinensis Meningitis in an Immunocompetent Host: A Case Report and Review of the Literature.

Objectives: This study presents a case of Candida dubliniensis meningitis in an immunocompetent injection drug user and provides a literature review of CNS infections related to C dubliniensis. Methods: A 32-year-old man with a history of opioid use disorder presented with seizures and underwent extensive diagnostic evaluations, including imaging, lumbar puncture, and tissue biopsies. Treatment consisted of antifungal therapy and placement of ventriculoperitoneal shunt (VPS). Results: C dublinensis meningitis was identified on culture from a posterior fossa arachnoid sample. The patient demonstrated leptomeningeal enhancement on imaging, which resolved following 20 weeks of fluconazole. The development of hydrocephalus necessitated placement of VPS. Additional published cases of C dublinensis meningitis revealed varying presentations, diagnostic methods, and treatment regimens. Discussion: C dublinensis meningitis is a rare condition affecting both immunocompromised and immunocompetent individuals, particularly those with intravenous drug use. The diagnosis can be challenging, often requiring repeat lumbar punctures, extensive CSF sampling, or meningeal biopsy. Treatment involves a combination of antifungal agents, such as amphotericin B and fluconazole. Intracranial hypertension and hydrocephalus may necessitate surgical intervention. In conclusion, C dublinensis meningitis should be considered as a potential etiology of meningitis, particularly in those with a history of injection drug use.

Splanchnic vein thrombosis in acute pancreatitis: a review of treatment indications, methods, and outcomes in a single institution.

BACKGROUND: Splanchnic vein thrombosis (SVT) is a well-recognized complication of acute pancreatitis. The question of whether or not to treat SVT with systemic therapeutic anticoagulation (STA) remains to be seen. The universal use of anticoagulation may lead to an increased risk of bleeding complications associated with acute pancreatitis. Literature on this subject is sparse and there is no clear guideline on how to treat SVT. Our research demonstrates local practice where therapeutic anticoagulation in SVT varies. METHODS: A retrospective review of patients presenting with acute pancreatitis admitted over a five-year period to a single tertiary hospital with splanchnic vein thrombosis was performed. RESULTS: Of the 1408 patients admitted with acute pancreatitis, 42 were diagnosed with splanchnic vein thrombosis, with a male dominance of 34 (81%). A total of 25 patients received anticoagulation. The use of anticoagulation was dependent on the location of the thrombus, P < 0.01. Anticoagulation use was most common in cases of combination mesenteric, splenic, and portal vein thrombus (100%), isolated mesenteric vein (100%), isolated portal vein (89%), combination portal and splenic vein (87%), and combination mesenteric and splenic vein (75%). The rate of anticoagulation use was lowest in isolated splenic vein thrombus (23%). CONCLUSION: The early commencement of STA in patients with acute pancreatitis and triple-vessel SVT or with portal vein involvement is supported by our data. Isolated splenic vein thrombus does not require systemic therapy. Further research is needed to establish a clear clinical guideline.

Persistent coagulopathy after gunshot traumatic brain injury: the importance of INR and the SPIN score.

INTRODUCTION: Penetrating ballistic brain injury (gunshot traumatic brain injury or GTBI) is associated with a high mortality. Admission Glascow Coma Scale (GCS), injury severity score and neurological findings, cardiopulmonary instability, coagulopathy and radiological finding such as bullet trajectory and mass effect are shown to predict survival after GTBI. We aimed to examine the dynamics of the observed coagulopathy and its association with outcome. METHODS: In this single-centered retrospective cohort study, we examined 88 patients with GTBI between 2015 and 2021. Variables analyzed include patient age; temperature, hemodynamic and respiratory variables, admission Glasgow Coma Scale (GCS); injury severity score (ISS); head abbreviated injury scale (AIS); Marshall, Rotterdam, SPIN and Baylor scores, and laboratory data including PTT, INR and platelet count. Receiver operating characteristic analysis was conducted to evaluate the performance of the predictive models. RESULTS: The average age of our sample was 28.5 years and a majority were male subjects (92%). Fifty-four (62%) of the patients survived to discharge. The GCS score, as well as the motor, verbal, and eye-opening sub-scores were higher in survivors (P < 0.001). As was expected, radiologic findings including the Marshall and Rotterdam Scores were also associated with survival (P < 0.001). Although the ISS and Head AIS scores were higher (P < 0.001), extracranial injuries were not more prevalent in non-survivors (P= 0.567). Non-survivors had lower platelet counts and elevated PTT and INR (P < 0.001) on admission. PTT normalized within 24 h but INR continued to increase in non-survivors. SPIN score, which includes INR, was a better predictor for mortality than Rotterdam, Marshall, and Baylor etc. CONCLUSION: Progressively increasing INR after GTBI is associated with poor outcome and may indicate consumption coagulopathy from activation of the extrinsic pathway of coagulation and metabolic derangements that are triggered and sustained by the brain injury. The SPIN score, which incorporates INR as a major survival score component, outperforms other available prediction models for predicting outcome after GTBI.

Splanchnic venous thrombosis: aetiologies and a review of the literature.

BACKGROUND: Splanchnic vein thrombosis (SVT) is an uncommon yet potentially life-threatening manifestation of venous thromboembolism. The aim of this study was to present a retrospective analysis of a cohort of Western Australian patients diagnosed with SVT on imaging study, and a review of the literature surrounding the aetiology, location, anticoagulation treatment and outcomes of SVT. METHODS: All patients diagnosed with SVT over a five-year period from 2015 to 2020 in three tertiary hospitals in Western Australia were identified by using an electronic search engine of imaging reports. Collected data included patient demographics and co-morbidity, presentation data, location of thrombus, aetiology of thrombus, treatment with anti-coagulation, length of stay and outcome data including mortality. RESULTS: A total of 164 patients met inclusion criteria. The 90-day mortality was 20.1%; 64% of whom were those with portal vein thrombosis. Aetiology was grouped into haematological conditions (4 patients), non-haematological conditions (130 patients), a combination of factors (17 patients) and idiopathic (13 patients). The majority of deaths were due to malignancy, severe pancreatitis or decompensated liver cirrhosis. CONCLUSION: Whilst the prevalence of SVT is rising with the increase in accessibility to radiological studies, it remains a diagnostic and therapeutic challenge for clinicians. With no consensus guidelines available to direct treatment, the management of patients with SVT should be individualized and considered carefully. The potential complications of venous thrombosis, SVT recurrence or extension and the risk of bleeding need to be evaluated before the commencement of anticoagulation therapy.

Large spontaneous median sacral artery pseudoaneurysm masquerading as hip pain.

We report the case of an 81-year-old man who presented with severe right hip pain and reduced physical function secondary to a large spontaneous median sacral artery pseudoaneurysm measuring 83.5 × 55.4 mm. The patient had no history of recent trauma, infective or inflammatory disease, or any recent procedures. The patient was taking apixaban for atrial fibrillation. Percutaneous coil embolization was used to occlude the pseudoaneurysm. This case describes a novel disease, spontaneous median sacral artery pseudoaneurysm, presenting with hip pain.

Multicentre Covariate Adjustment Analysis of Short-Term and 5-Year Outcomes after Endovascular Repair according to Sex.

BACKGROUND: Several studies have reported worse outcomes in women compared to men after endovascular aneurysm repair (EVAR). This study aimed to evaluate sex-specific short-term and 5-year outcomes after EVAR. METHODS: A total of 409 consecutive patients underwent elective EVAR from 2004 to 2017 at two tertiary hospitals in Western Australia. Baseline, intraoperative, and postoperative variables were examined retrospectively according to sex. The primary outcome was 30-day mortality (death within 30 days after EVAR). Secondary outcomes were 30-day composite endpoint, length of stay after EVAR, 5-year survival, freedom from reintervention, residual aneurysm size after EVAR, and major adverse event rate at 5-year follow-up. RESULTS: A cohort of 409 patients, comprising 57 women (14%) and 352 men (86%), was analysed. Female patients were older (median age, 76.8 versus 73.5 years, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%. CONCLUSION: This study found no significant differences in 30-day and 5-year outcomes between female and male patients treated with EVAR, implying that EVAR remains a safe treatment choice for female patients.

Portal venous gas: different aetiologies and their respective outcomes.

BACKGROUND: Historically finding of portal venous gas (PVG) has been considered as an ominous sign and an indication for emergency surgery and reportedly has a high mortality rate. However, with the recent increasing use of imaging studies, cases of PVG associated with benign and non-life-threatening causes are increasing. The purpose of our study was to investigate the different aetiologies associated with PVG and their respective outcomes. METHODS: A consecutive series of patients with PVG was identified in our group of tertiary hospitals in Western Australia over a 10-year period. Collected data included patients' demographic data, comorbidities, blood tests results, underlying aetiology of the PVG, patients' management and their outcomes. RESULTS: During the study period of 2008 to 2018, 164 patients met the inclusion criteria. Male : Female 90 versus 74. Average age was 65.6. A diverse range of underlying causes identified broadly divided into thromboembolic events (n = 70), mechanical bowel obstruction (n = 29), inflammatory conditions (n = 37) and a wide range of other pathologies (n = 28). The overall mortality was 47.5%, however, varied depending on the underlying aetiology (14.3-72.8%). CONCLUSION: Our study demonstrates that PVG is not always a fatal sign and that mortality varies significantly depending on the aetiology. Both the patient's presenting history and the clinical findings have to be considered to recognize benign aetiology of PVG on computed tomography imaging and the treatment should be directed to the underlying disease with consideration of the high mortality rate of PVG associated with ischaemic bowel.

VEGF Requires the Receptor NRP-1 To Inhibit Lipopolysaccharide-Dependent Dendritic Cell Maturation.

To stimulate a productive T cell response, dendritic cells (DC) must undergo maturation characterized by heightened cell surface expression of MHC and costimulatory molecules as well as cytokine production. Conversely, the inhibition of DC maturation is a central mechanism of immune tolerance. The control of the DC maturation process relies on the integration of several cellular stimulatory or inhibitory signals. The soluble factors and their receptors controlling this central aspect of DC biology are incompletely characterized. We show that murine bone marrow-derived DC (BMDC) maturation induced by LPS, as opposed to polyinosinic:polycytidylic acid or cytosine-phosphate-guanine, is robustly inhibited by vascular endothelial growth factor (VEGF), a previously identified immunosuppressive cytokine. Using BMDC from wild type and conditional knockout mice, we show that neuropilin-1 (NRP-1), a known receptor of VEGF, is necessary to suppress LPS-dependent BMDC maturation. The absence of NRP-1 had no ostensible effects on the biology of BMDC in the absence of VEGF. However, NRP-1-deficient BMDC remained completely insensitive to the VEGF-dependent inhibition of BMDC maturation in culture. In the presence of VEGF, NRP-1 directly interacted with the LPS receptor TLR4 and suppressed downstream signaling through ERK and NF-κß, resulting in a sharp inhibition of MHC class II and costimulatory molecules (CD40, CD86) expression as well as proinflammatory cytokine production. Consequently, we identify NRP-1 as a target to optimize DC maturation within environments that are rich in VEGF, such as tumors.

Durability of the balloon-expandable covered versus bare-metal stents in the Covered versus Balloon Expandable Stent Trial (COBEST) for the treatment of aortoiliac occlusive disease.

OBJECTIVE: The Covered vs Balloon Expandable Stent Trial (COBEST) is the first multicenter trial to investigate the patency of covered stents (CSs) and bare-metal stents (BMSs) in the treatment of aortoiliac arterial disease. The short-term results demonstrated that CSs were superior to BMSs in maintaining patency for TransAtlantic Inter-Society Consensus (TASC) C and D lesions at 18 months and were equivalent to BMSs for TASC B lesions. The current study was conducted to determine if the initial patency advantage of CSs over BMSs was sustained at the 5-year follow-up. METHODS: A retrospective post hoc analysis of COBEST was performed. Originally, 125 patients with 168 iliac arteries were prospectively enrolled and randomly assigned to receive a CS or BMS. In this study, 77 of the 125 patients (61.6%; 119 limbs) were assessed at 60 months for the primary and secondary end points, with particular attention paid to the outcomes stratified according to TASC lesion severity. The primary end point was the rate of binary stenosis or freedom from stent occlusion of the treated area, as determined by ultrasound imaging or quantitative visual angiography. RESULTS: The 5-year results of the COBEST showed that the CS had a significantly higher patency rate than the BMS at 18, 24, 48, and 60 months (95.1%, 82.1%, 79.9%, 74.7% for CS vs 73.9%, 70.9%, 63% and 62.5% for BMS; log-rank test, P = .01). On multivariate analysis, the type of stent used (hazard ratio [HR], 2.797; 95% confidence interval [CI], 1.471-5.318; P = .002) and the Rutherford classification (HR, 2.019; 95% CI, 1.278-3.191; P = .026) significantly affected the adjusted primary patency. On subgroup analysis, the CS showed significantly higher patency and a survival benefit compared with the BMS in TASC C and D lesions (HR, 8.639; 95% CI, 54.253-75.753; P = .003). Moreover, fewer patients received target limb revascularization in the CS group than in the BMS group (odds ratio, 2.32; 95% CI, 1.47-3.36; P = .02); however, there was no statistically significant difference in the rate of amputations between the groups. CONCLUSIONS: The 5-year results of the COBEST demonstrated that the CS has an enduring patency advantage over the BMS in both the short and long terms. Furthermore, the CS showed acceptable patency rates for the treatment of more severe TASC C and D lesions, and patients who received a CS required fewer revascularization procedures. However, the choice of stent did not affect the rate of major limb amputations.

Migraine prophylaxis, ischemic depolarizations, and stroke outcomes in mice.

BACKGROUND AND PURPOSE: Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression (SD) are implicated in the pathogenesis of both migraine and stroke. Spontaneous SD waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced SD susceptibility facilitates anoxic depolarizations and peri-infarct SDs and accelerates infarct growth, suggesting that susceptibility to SD is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses SD susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome. METHODS: We measured the cortical susceptibility to SD and ischemic depolarizations, and determined tissue and neurological outcomes after middle cerebral artery occlusion in wild-type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing. RESULTS: Chronic treatment with topiramate or lamotrigine reduced the susceptibility to KCl-induced or electric stimulation-induced SDs as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes were improved. Notably, treatment with a single dose of either drug was ineffective. CONCLUSIONS: These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury.

Chronic lithium administration ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats; potential role for adenosine triphosphate sensitive potassium channels.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is a multi-factorial disease with an unknown etiology characterized by oxidative stress, leukocyte infiltration and a rise in inflammatory cytokines. This study was conducted to investigate lithium in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic model of experimental IBD, and the contribution of potassium channels as a possible underlying mechanism. METHODS: Experimental IBD was induced in rats by a single colonic administration of 10 mg of TNBS. Lithium, Glibenclamide (a potassium channel blocker), Lithium + Glibenclamide, Cromakalim or Lithium+Glibenclamide+ Cromakalim were given twice daily for 7 successive days. At the end of the experiment, macroscopic and histopathologic scores, colonic malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) level, and myeloperoxidase (MPO) activity as well as plasma lithium level were assessed. RESULTS: Both macroscopic and histological features of colonic injury were markedly ameliorated by lithium. Likewise, the elevated amounts of MPO and MDA were diminished as well as those of TNF-α (P < 0.05). Glibenclamide reversed the effect of lithium on these markers, Addition of cromakalim abrogated the effects mediated by glibenclamide and markedly decreased MPO activity, MDA level and TNF-α content (P < 0.0.05). Macroscopic and microscopic scores and biochemical markers were significantly decreased in Cromakalim-treated animals. No significant difference was observed between TNBS and Glibenclamide groups. CONCLUSION: Lithium exerts prominent anti-inflammatory effects on TNBS-induced colitis in rats. Potassium channels contribute to these beneficial properties.

Tropisetron ameliorates ischemic brain injury in an embolic model of stroke.

Tropisetron is widely used to counteract chemotherapy-induced emesis. Evidence obtained from human and animal studies shows that tropisetron possesses anti-inflammatory properties. In this study, we assessed the effect of tropisetron on brain damage in a rat thromboembolic model of stroke. Stroke was rendered in rats by introduction of an autologous clot into the middle cerebral artery (MCA). Tropisetron (1 or 3mg/kg); m-chlorophenylbiguanide (mCPBG), a selective 5-HT(3) receptor agonist (15 mg/kg); tropisetron (3mg/kg) plus mCPBG (15 mg/kg); granisetron (3mg/kg); tacrolimus (1mg/kg); or tacrolimus (1mg/kg) plus tropisetron (3mg/kg) were administered intraperitoneally 1h prior to embolization. Behavioral scores and infarct volume as well as myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-α) level were determined in the ipsilateral cortex 4h and 48 h following stroke induction. Forty-eight hours after embolization, tropisetron (1 or 3mg/kg), tropisetron (3mg/kg) plus mCPBG (15 mg/kg), tacrolimus (1mg/kg), or tacrolimus (1mg/kg) plus tropisetron (3mg/kg) significantly curtailed brain infarction, improved behavioral scores, diminished elevated tissue MPO activity, and reduced TNF-α levels compared to control group (n=6; P<0.05). mCPBG or granisetron had no effect on the mentioned parameters. Tropisetron attenuates brain damage after a thromboembolic event. Beneficial effects of tropisetron in this setting are receptor independent.

Adenosine A2A receptors and uric acid mediate protective effects of inosine against TNBS-induced colitis in rats.

Inflammatory bowel disease comprises chronic recurrent inflammation of gastrointestinal tract. This study was conducted to investigate inosine, a potent immunomodulator, in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced chronic model of experimental colitis, and contribution of adenosine A(2A) receptors and the metabolite uric acid as possible underlying mechanisms. Experimental colitis was rendered in rats by a single colonic administration of 10 mg of TNBS. Inosine, potassium oxonate (a hepatic uricase inhibitor), SCH-442416 (a selective adenosine A(2A) receptor antagonist), inosine+potassium oxonate, or inosine+SCH-442416 were given twice daily for 7 successive days. At the end of experiment, macroscopic and histopathologic scores, colonic malondialdehyde (MDA), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-1beta (IL-1ß) levels, and myeloperoxidase (MPO) activity were assessed. Plasma uric acid level was measured throughout the experiment. Both macroscopic and histological features of colonic injury were markedly ameliorated by either inosine, oxonate or inosine+oxonate. Likewise, the elevated amounts of MPO and MDA abated as well as those of TNF-α and IL-1ß (P<0.05). SCH-442416 partially reversed the effect of inosine on theses markers, while inosine+oxonate showed a higher degree of protection than each treatment alone (P<.0.05). No significant difference was observed between TNBS and SCH-442416 groups. Uric acid levels were significantly higher in inosine or oxonate groups compared to control. Inosine+oxonate resulted in an even more elvelated uric acid level than each treatment alone (P<0.05). Inosine elicits notable anti-inflammatory effects on TNBS-induced colitis in rats. Uric acid and adenosine A(2A) receptors contribute to these salutary properties.

Granisetron ameliorates acetic acid-induced colitis in rats.

Inflammatory bowel disease (IBD) is a chronically relapsing inflammation of the gastrointestinal tract, of which the definite etiology remains ambiguous. Considering the adverse effects and incomplete efficacy of currently administered drugs, it is indispensable to explore new candidates with more desirable therapeutic profiles. 5-HT( 3) receptor antagonists have shown analgesic and anti-inflammatory properties in vitro and in vivo. This study aims to investigate granisetron, a 5-HT( 3) receptor antagonist, in acetic acid-induced rat colitis and probable involvement of 5-HT(3) receptors. Colitis was rendered by instillation of 1 mL of 4% acetic acid (vol/vol) and after 1 hour, granisetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5-HT( 3) receptor agonist, or granisetron + mCPBG was given intraperitoneally. Twenty-four hours following colitis induction, animals were sacrificed and distal colons were assessed macroscopically, histologically and biochemically (malondialdehyde, myeloperoxidase, tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6). Granisetron or dexamethasone significantly (p < .05) improved macroscopic and histologic scores, curtailed myeloperoxidase activity and diminished colonic levels of inflammatory cytokines and malondialdehyde. The protective effects of granisetron were reversed by concurrent administration of mCPBG. Our data suggests that the salutary effects of granisetron in acetic acid colitis could be mediated by 5-HT(3) receptors.

Protective effects of lithium on acetic acid-induced colitis in rats.

Inflammatory bowel disease (IBD) is a multifactorial disease with unknown etiology characterized by oxidative stress, leukocyte infiltration, and rise in inflammatory cytokines such as tumor necrosis factor (TNF-alpha). Lithium, as a therapeutic agent for bipolar disorder, exerts some anti-inflammatory properties. In this study we have investigated the effects of lithium on acetic-acid-induced colitis in rats. Lithium (5, 10, and 20 mg/kg) was administered 1 h before the introduction of acetic acid. Colonic status was investigated 24 h following colitis induction through macroscopic, histological, and biochemical analyses. Lithium (20 mg/kg) ameliorated macroscopic and microscopic scores. These observations were accompanied by a reduction in the degree of both neutrophil infiltration, indicated by decreased myeloperoxidase activity, and lipid peroxidation, as measured by a decline in malondialdehyde content in inflamed colon as well as a decrease in TNF-alpha levels. These findings suggest that lithium exerts beneficial effects on experimental colitis and therefore might be useful in the treatment of IBD.

H. pylori infection and reflux oesophagitis: a case-control study.

AIM: To examine the relationship between H. pylori and gastro-oesophageal reflux disease (GORD) in Iran. METHODS: In this study 51 GORD patients (referred to endoscopy at Taleghani hospital) were compared with 49 age-sex matched controls. Diagnosis of H. pylori was made by gastric mucosal biopsy and rapid urease test (positive if the result of one or both diagnostic methods was positive). Updated Sydney system was used to report histopathological changes. RESULTS: The frequency of H. pylori infection based on rapid urease test and histology was 88.2% (45) in patients and 77.6% (38) in controls, which showed no significant difference. The frequency of H. pylori infection was significantly higher in the antrum than in the corpus and cardia. The mean activity, inflammation, and gastritis scores were also higher in the antrum of patients than in the antrum of controls. The mean scores were significantly higher in the corpus of controls than in the corpus of patients. Diffuse active gastritis was observed in a significantly larger number of controls, while the frequency of diffuse chronic gastritis was higher in patients. There was no significant difference in the frequency of other histological findings between patients and controls. CONCLUSION: H. pylori infection cannot prevent GORD in this region.