Successful Outcome after Treatment with Cidofovir, Vaccinia, and Extended Course of Tecovirimat in a Newly-Diagnosed HIV Patient with Severe Mpox: A Case Report.

PURPOSE: To report a case of severe mpox in a newly diagnosed HIV patient concerning for Immune Reconstitution Inflammatory Syndrome (IRIS) and/or tecovirimat resistance and to describe the management approach in the setting of refractory disease. CASE: 49-year-old man presented with 2 weeks of perianal lesions. He tested positive for mpox PCR in the emergency room and was discharged home with quarantine instructions. Three weeks later, the patient returned with disseminated firm, nodular lesions in the face, neck, scalp, mouth, chest, back, legs, arms, and rectum, with worsening pain and purulent drainage from the rectum. The patient reported being on 3 days of tecovirimat treatment, which was prescribed by the Florida department of health (DOH). During this admission, he was found to be HIV positive. A pelvic CT scan revealed a 2.5 cm perirectal abscess. Treatment with tecovirimat was continued for 14 days, along with an empiric course of antibiotics for treatment of possible superimposed bacterial infection upon discharge. He was seen in the outpatient clinic and initiated antiretroviral therapy (ART) with TAF/emtricitabine/bictegravir. Two weeks after starting ART, the patient was readmitted for worsening mpox rash and rectal pain. Urine PCR also returned positive for chlamydia, for which the patient was prescribed doxycycline. He was discharged on a second course of tecovirimat and antibiotic therapy. Ten days later, the patient was readmitted for the second time due to worsening symptoms and blockage of the nasal airway from progressing lesions. At this point, there were concerns for tecovirimat resistance, and after discussion with CDC, tecovirimat was reinitiated for the third time, with the addition of Cidofovir and Vaccinia, and showed an improvement in his symptoms. He received three doses of cidofovir and two doses of Vaccinia, and the patient was then discharged to complete 30 days of tecovirimat. Outpatient follow-up showed favorable outcomes and near resolution. CONCLUSION: We reported a challenging case of worsening mpox after Tecovirimat treatment in the setting of new HIV and ART initiation concerning IRIS vs. Tecovirimat resistance. Clinicians should consider the risk of IRIS and weigh the pros and cons of initiating or delaying ART. In patients not responding to first-line treatment with tecovirimat, resistance testing should be performed, and alternative options should be considered. Future research is needed to establish guidance on the role of Cidofovir and Vaccinia immune globulin and the continuation of tecovirimat for refractory mpox.

Indicators for technological, environmental and economic sustainability of ozone contactors.

Various studies have attempted to improve disinfection efficiency as a way to improve the sustainability of ozone disinfection which is a critical unit process for water treatment. Baffling factor, CT10, and log-inactivation are commonly used indicators for quantifying disinfection credits. However the applicability of these indicators and the relationship between these indicators have not been investigated in depth. This study simulated flow, tracer transport, and chemical species transport in a full-scale ozone contactor operated by the City of Tampa Water Department and six other modified designs using computational fluid dynamics (CFD). Through analysis of the simulation results, we found that baffling factor and CT10 are not optimal indicators of disinfection performance. We also found that the relationship between effluent CT obtained from CT transport simulation and baffling factor depends on the location of ozone release. In addition, we analyzed the environmental and economic impacts of ozone contactor designs and upgrades and developed a composite indicator to quantify the sustainability in technological, environmental and economic dimensions.

Impact of sludge layer geometry on the hydraulic performance of a waste stabilization pond.

Improving the hydraulic performance of waste stabilization ponds (WSPs) is an important management strategy to not only ensure protection of public health and the environment, but also to maximize the potential reuse of valuable resources found in the treated effluent. To reuse effluent from WSPs, a better understanding of the factors that impact the hydraulic performance of the system is needed. One major factor determining the hydraulic performance of a WSP is sludge accumulation, which alters the volume of the pond. In this study, computational fluid dynamics (CFD) analysis was applied to investigate the impact of sludge layer geometry on hydraulic performance of a facultative pond, typically used in many small communities throughout the developing world. Four waste stabilization pond cases with different sludge volumes and distributions were investigated. Results indicate that sludge distribution and volume have a significant impact on wastewater treatment efficiency and capacity. Although treatment capacity is reduced with accumulation of sludge, the latter may induce a baffling effect which causes the flow to behave closer to that of plug flow reactor and thus increase treatment efficiency. In addition to sludge accumulation and distribution, the impact of water surface level is also investigated through two additional cases. Findings show that an increase in water level while keeping a constant flow rate can result in a significant decrease in the hydraulic performance by reducing the sludge baffling effect, suggesting a careful monitoring of sludge accumulation and water surface level in WSP systems.

Evaluating hydraulic and disinfection efficiencies of a full-scale ozone contactor using a RANS-based modeling framework.

The capability of predicting hydraulic and disinfection efficiencies of ozone disinfection contactors is essential for evaluating existing contactors and improving future designs. Previous attempts based on ideal and non-ideal models for the hydraulics and simplified mechanisms for chemical reaction modeling have resulted in low accuracy and are restricted to contactors with simple geometries. This manuscript develops a modeling framework for the ozonation process by combining computational fluid dynamics (CFD) with a kinetics-based reaction modeling for the first time. This computational framework has been applied to the full-scale ozone contactor operated by the City of Tampa Water Department. Flow fields, residence time distribution, ozone concentration distribution, and concentration-contact time (CT) distribution within the contactor have been predicted via the computational framework. The predictions of ozone and bromate concentrations at sample points agree well with physical experimental data measured in the contactor. The predicted CT values at the contactor outlet demonstrate that the disinfection performance of the ozone contactor operated by the City of Tampa Water Department is sufficient to meet regulation requirements. The impact of seasonal flow rate change on disinfection performance is found to be significant and deserves attention during the management and operation of a water treatment plant.

Taenia eggs in a stabilization pond system with poor hydraulics: concern for human cysticercosis?

The objective of this study is to compare the removal of Taenia eggs to the removal of Ascaris eggs in a wastewater stabilization pond system consisting of three ponds in series, where the hydraulic residence time distribution has been characterized via a tracer study supported by computational fluid dynamics modeling. Despite a theoretical hydraulic retention time of 30 days, the peak dye concentration was measured in the effluent of the first pond after only 26 hours. The smaller-sized Taenia eggs were detected in higher concentrations than Ascaris eggs in the raw wastewater. Ascaris eggs were not detected in the pond system effluent, but 45 Taenia eggs/L were detected in the system effluent. If some of these eggs were of the species Taenia solium, and if the treated wastewater were used for the irrigation of crops for human consumption, farmers and consumers could potentially be at risk for neurocysticercosis. Thus, limits for Taenia eggs in irrigation water should be established, and precautions should be taken in regions where pig taeniasis is endemic. The results of this study indicate that the theoretical hydraulic retention time (volume/flow) of a pond is not always a good surrogate for helminth egg removal.

Computational fluid dynamic analysis of flow velocity waveform notching in umbilical arteries.

Umbilical artery Doppler velocimetry waveform notching has long been associated with umbilical cord abnormalities, such as distortion, torsion, and/or compression (i.e., constriction). The physical mechanism by which the notching occurs has not been elucidated. Flow velocity waveforms (FVWs) from two-dimensional pulsatile flows in a constricted channel approximating a compressed umbilical cord are analyzed, leading to a clear relationship between the notching and the constriction. Two flows with an asymmetric, semi-elliptical constriction are computed using a stabilized finite-element method. In one case, the constriction blocks 75% of the flow passage, and in the other the constriction blocks 85%. Channel width and prescribed flow rates at the channel inflow are consistent with typical cord diameters and flow rates reported in the literature. Computational results indicate that waveform notching is caused by flow separation induced by the constriction, giving rise to a vortex (core) wave and associated eddies. Notching in FVWs based on centerline velocity (centerline FVW) is directly related to the passage of an eddy over the point of measurement on the centerline. Notching in FVWs based on maximum cross-sectional velocity (envelope FVW) is directly related to acceleration and deceleration of the fluid along the vortex wave. Results show that notching in envelope FVW is not present in flows with less than a 75% constriction. Furthermore, notching disappears as the vortex wave is attenuated at distances downstream of the constriction. In the flows with 75 and 85% constriction, notching of the envelope FVW disappears at ∼3.8 and ∼4.3 cm (respectively) downstream of the constriction. These results are of significant medical importance, given that envelope FVW is typically measured by commercial Doppler systems.

Atherosclerotic plaque composition assessed by virtual histology intravascular ultrasound and cerebral embolization after carotid stenting.

OBJECTIVE: Previous studies have investigated the predictive value of clinical and morphologic parameters for distal embolization during carotid interventions. The composition of the atherosclerotic plaque, using virtual histology intravascular ultrasound (VH-IVUS) imaging obtained with an IVUS catheter that is advanced through the lesion after a filter has been placed distally, has not been evaluated as a marker for cerebral embolization. The purpose of this study was to assess the relationship between atherosclerotic plaque composition determined with VH-IVUS and the occurrence of cerebral embolization after carotid artery stenting (CAS). METHODS: During a 10-month period, 24 patients undergoing CAS procedures using a filter device for embolic protection were prospectively evaluated. All patients underwent VH-IVUS exams at the time of the intervention, transcranial Doppler (TCD) monitoring during CAS, and pre- and 24-hour postprocedural diffusion-weighted magnetic resonance imaging (DW-MRI) exams. Using VH-IVUS, plaque components were characterized as fibrotic, fibrofatty, dense calcium, and necrotic core. The frequency of Doppler-detected microembolic signals (MES) during CAS and the incidence and location of acute postprocedural embolic lesions detected with DW-MRI were assessed to determine cerebral embolization. Univariate and correlation analyses were used to assess the association between plaque composition and frequency of cerebral embolization. RESULTS: No periprocedural transient ischemic attacks, strokes, or deaths occurred within 30 days. Seventeen patients (71%) demonstrated new acute cerebral emboli in DW-MRI. Of these, all revealed ipsilateral lesions and 12 (50%) had contralateral lesions. For the entire study group, the median number of ipsilateral DW-MRI lesions was 1 (range, 0 to 3), and TCD MES counts were 227 (interquartile range, 143-315). Volumetric VH-IVUS analysis revealed that there was a trend for larger median dense calcium volume in patients with ipsilateral subclinical cerebral embolism detected with DW-MRI (33.2±24.5 mm3 vs 11.4±6.1 mm3; P=.08). Scatter plots of plaque components revealed statistically significant correlation between fibrofatty plaque volume (Spearman r=0.49; P=.016) and number of new ipsilateral lesions in DW-MRI. Degree of cerebral embolization during CAS measured with TCD correlated with plaque burden, necrotic core, fibrofatty, and fibrous volumes. CONCLUSIONS: Plaque composition, as determined by VH-IVUS, only weakly correlates with the degree of cerebral embolization after carotid stenting. Specifically, there is a trend for larger dense calcium volume in patients with distal embolization. Of note, the proportion of necrotic core, which has traditionally been considered the main component of a vulnerable or unstable plaque, is not definitely associated with subclinical cerebral embolization after CAS when a filter device for embolic protection is used. The role of VH-IVUS in evaluating plaque composition during CAS remains unestablished and warrants further investigation.