Outcomes and factors influencing prognosis in patients with vascular pythiosis.

OBJECTIVE: Vascular pythiosis, caused by Pythium insidiosum, is associated with a high mortality rate. We reviewed the outcomes and established the factors predicting prognosis of patients treated in our institution with surgery, antifungal therapy, or immunotherapy. METHODS: We undertook a retrospective record review of patients with vascular pythiosis treated in Siriraj Hospital, Bangkok, Thailand, between January 2005 and January 2015. Patient characteristics, type of surgery, adjunctive antifungal treatment, adjunctive immunotherapy, and disease status of surgical arterial and surrounding soft tissue margins were recorded. We calculated the mortality rate and established factors predicting prognosis. RESULTS: The records of 11 patients were reviewed. All patients had thalassemia. Nine patients (81.8%) had a history of contact with contaminated water. The clinical presentations were chronic ulcers (45.5%), toe gangrene (27.3%), pulsatile mass (27.3%), and acute limb ischemia (27.3%). Above-knee amputation was required in 10 patients (90.9%). The mortality rate was 36.4%. Independent variables between survivors and nonsurvivors were lack of an arterial disease-free surgical margin (P = .003), lack of a surrounding soft tissue disease-free surgical margin (P < .05), a suprainguinal lesion (P < .05) and duration of symptoms (P < .05). Adjuvant itraconazole, terbinafine, and Pythium vaccine have a role to play in patients with a disease-free arterial surgical margin but in whom infected surrounding soft tissue could not be completely excised. CONCLUSIONS: Achieving adequate disease-free surgical margins-especially the arterial margin-at amputation or débridement is the most important prognostic factor in patients with vascular pythiosis. Early detection combined with a multidisciplinary approach to treatment, including surgery, antifungal agents, and immunotherapy, allows the best possible outcome to be obtained.

The Influence of VKORC1 Polymorphisms on Warfarin Doses in Thai Patients with Deep Vein Thrombosis.

BACKGROUND: Polymorphisms in cytochrome P450 2C9 and vitamin K epoxide reductase complex, subunit 1 genes (CYP2C9 and VKORC1, respectively) were previously shown to affect the warfarin dose required in anticoagulant therapy of deep vein thrombosis (DVT). However, little is known about the role of these genetic variants in the Thai population. OBJECTIVE: To identify the effect of CYP2C9 and VKORC1 genetic variants on warfarin dosage in the Thai population with DVT. MATERIAL AND METHOD: Genotyping of CYP2C9 (*2 and *3) and VKORC1 promoter (-1 639G>A) variants were carried out in 97 Thai DVT patients receiving constant warfarin therapy and with a stable international normalized ratio using real-time PCR assays. RESULTS: VKORC1 AA, GA, and GG genotype frequencies were found to be 49.5%, 46.4%, and 4.1%, respectively, while those of CYP2C9 genotypes were 88.7% for *1/*1 and 11.3%for *1/*3. The CYP2C9*2 variant was not present in the patients studied. The mean daily warfarin dose required to maintain a therapeutic INR differed significantly according to VKORC1 genotype, with 3.6 mg/day required for AA, 4.7 mg/day for GA, and 7.4 mg/day for GG (p-value < 0.001). The CYP2C9 genotype did not significantly affect the warfarin dosage requirement (p-value = 0.29). CONCLUSION: These findings underline the impact of VKORC1 genotypes on the wide variation in warfarin maintenance dosing in Thai patients with DVT.

Predictors and pathways of in-hospital mortality in active vascular contrast extravasation detected on abdominopelvic CT.

OBJECTIVES: This study aimed to identify factors influencing in-hospital mortality in adult patients with active vascular contrast extravasation (AVCE) on abdominopelvic computed tomography (CT). METHODS: All consecutive patients with AVCE detected on CT between January 2019 and May 2022 were retrospectively included. Their data were compared through uni- and multivariable analyses between patients with and without in-hospital mortality. Path analysis was utilized to clarify the relationships among factors affecting mortality. RESULTS: There were 272 patients (60.2 ± 19.4 years, 150 men) included, of whom 70 experienced in-hospital mortality. Multivariable analysis revealed nonsurgery, chronic kidney disease (CKD) stage 4-5 or dialysis, prolonged partial thromboplastin time (PTT), minimum AVCE length > 8 mm, and a lower rate of packed red cell (PRC) transfusion were identified as independent predictors of in-hospital mortality (p = 0.005-0.048). Path analysis demonstrated direct influences of CKD4-5 or dialysis, prolonged PTT, and minimum AVCE length on mortality (coefficients 0.525-0.616; p = 0.009 to < 0.001). PRC transfusion impacted mortality through nonsurgery (coefficient 0.798, p = 0.003) and intensive care unit (ICU) admission (coefficients 0.025, p = 0.016), leading to subsequent death. Three AVCE spaces (free, loose, and tight) defined on CT were not directly associated with in-hospital mortality. CONCLUSION: In adults with AVCE on CT, AVCE size had a direct independent influence on mortality, highlighting the critical role of radiologists in detecting and characterizing this finding. Additionally, CKD4-5 or dialysis and prolonged PTT also directly influenced mortality, while the lower rate of PRC transfusion impacted mortality through nonsurgery and ICU admission. CLINICAL RELEVANCE STATEMENT: In patients with active vascular contrast extravasation (AVCE) on abdominopelvic CT, larger AVCE directly increased in-hospital mortality. Radiologists' detection and characterization of this finding is crucial, along with recognizing factors like CKD4-5, dialysis, and prolonged PTT to improve patient outcomes. KEY POINTS: Several factors independently predicted in-hospital mortality in patients with abdominopelvic AVCE. Extravasation length > 8 mm was the only imaging marker predictive of in-hospital mortality. Non-imaging factors correlated with in-hospital mortality, and PRC transfusion impacted mortality through nonsurgery and ICU admission pathways.

Myocardial alterations following traumatic hemorrhagic injury.

BACKGROUND: Cardiac dysfunction (CD) has emerged as a key contributor to delayed organ failure and late mortality in patients surviving the initial traumatic hemorrhagic response. Inflammatory processes are implicated in the initial stages of this CD; however, downstream pathways leading to a characteristic rapid fall in stroke volume and cardiac output are not yet fully defined. Currently, no cardioprotective treatments are available. We investigated the role of myocardial oxidative stress in the pathogenesis of CD associated to traumatic hemorrhagic injury, and its related metabolomic profile. METHODS: Ex vivo tissue from a 3-hour murine model of pressure-controlled trauma hemorrhagic shock (THS) was analyzed. Animals were randomized to echocardiography-guided crystalloid fluid resuscitation or a control group (sham: cannulation and anesthesia only, or naïve: no intervention). Trauma hemorrhagic shock and naïve samples were assessed by immunohistochemistry for nuclear 8-hydroxy-2'-deoxyguanosine expression as a marker of oxidative stress. Metabolomic analysis of THS and sham group tissue was performed by LC-MS. RESULTS: 8-Hydroxy-2'-deoxyguanosine expression across the myocardium was significantly higher following THS injury compared to naïve group (33.01 ± 14.40% vs. 15.08 ± 3.96%, p < 0.05). Trauma hemorrhagic shock injury significantly increased lysine ( p = 0.022), and decreased aconitate ( p = 0.016) and glutamate ( p = 0.047) in the myocardium, indicating activation of a catabolic metabolism and oxidative stress response. CONCLUSION: We confirm the acute development of oxidative stress lesions and altered cardiac energy metabolism following traumatic hemorrhage injury, providing insight into the relationship between inflammatory damage and impaired cardiac contractility. These findings may provide targets for development of novel cardioprotective therapeutics aiming to decrease late mortality from trauma.

Modeling Cardiac Dysfunction Following Traumatic Hemorrhage Injury: Impact on Myocardial Integrity.

Cardiac dysfunction (CD) importantly contributes to mortality in trauma patients, who survive their initial injuries following successful hemostatic resuscitation. This poor outcome has been correlated with elevated biomarkers of myocardial injury, but the pathophysiology triggering this CD remains unknown. We investigated the pathophysiology of acute CD after trauma using a mouse model of trauma hemorrhage shock (THS)-induced CD with echocardiographic guidance of fluid resuscitation, to assess the THS impact on myocardial integrity and function. Mice were subjected to trauma (soft tissue and bone fracture) and different degrees of hemorrhage severity (pressure controlled ~MABP < 35 mmHg or <65 mmHg) for 1 h, to characterize the acute impact on cardiac function. In a second study, mice were subjected to trauma and hemorrhage (MABP < 35 mmHg) for 1 h, then underwent two echocardiographic-guided resuscitations to baseline stroke volume at 60 and 120 min, and were monitored up to 180 min to study the longer impact of THS following resuscitation. Naïve and sham animals were used as controls. At 60 min post-THS injury, animals showed a lower cardiac output (CO) and stroke volume (SV) and an early rise of heart fatty acid-binding protein (H-FABP = 167 ± 38 ng/ml; 90% increase from shams, 3.54 ± 3.06 ng/ml), when subjected to severe hemorrhage and injury. Despite resuscitation, these animals maintained lower CO (6 ml/min vs. 23 ml/min), lower SV (10 µl vs. 46 µl; both ~75% decreased), and higher H-FABP (levels (340 ± 115 ng/ml vs. 10.3 ± 0.2 ng/ml; all THS vs. shams, P < 0.001) at 180 min post-THS injury. Histopathological and flow-cytometry analysis of the heart confirmed an influx of circulatory leukocytes, compared to non-injured hearts. Myocardial injury was supported by an increase of troponin I and h-FABP and the widespread ultrastructural disorganization of the morphology of sarcomeres and mitochondria. DNA fragmentation and chromatin condensation driven by leakage of apoptosis-inducing factor (AIF) may suggest a mitochondria-driven progressive cell death. THS modeling in the mouse results in cardiomyocyte damage and reduced myocardial function, which mimics the cardiac dysfunction seen in trauma patients. This CD model may, therefore, provide further understanding to the mechanisms underlying CD and act as a tool for developing cardioprotective therapeutics to improve survival after injury.

Clinical Efficacy Test of Polyester Containing Herbal Extract Dressings in Burn Wound Healing.

Technological advancement has assisted in developing various availabilities of wound products that help in not only in healing and preventing infection but also in providing patients' comfort and pain reduction during application. However, most of advanced wound healing products in Thailand were imported at high costs to patients. Nowadays, there are increased numbers of local researches of herbs that could provide healing environment for successful wound care. Herbal wound products are currently being introduced as alternatives to those imported dressings. The aim of this study was to report the clinical efficacy of using polyester containing herbal extract dressings in healing of second-degree burns. The volunteers were divided by simply randomized method into the study group of patient using polyester containing herbal extract dressing and the control group of patients treating with dressings that are commercially available and common use. The standard treatment protocols were performed at every 3 days of dressing change. Comparative evaluation consisted of time of healing, length of hospital stays, pain analog score assessment, percentage of infection, and descriptive notification of unfavorable clinical symptoms or signs or side effects.