Lipoprotein apheresis: an established therapeutic modality for homozygous familial hypercholesterolemia patients refractory to PCSK9 inhibitors: a case report and literature review.

Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12-14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1-2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality.

An evaluation of different dilution modes on circuit lifespan during continuous veno-venous hemodiafiltration without anticoagulation.

BACKGROUND: Circuit clotting remains a major problem during continuous kidney replacement therapy (CKRT), particularly in patients with contraindications to anticoagulant use. We hypothesized that the different options of alternative replacement fluid infusion sites might affect circuit lifespan. However, research-based evidence supporting an optimal replacement fluid infusion strategy is limited. Therefore, we aimed to evaluate the effect of three dilution modes (pre-dilution, post-dilution, and pre- to post-dilution) on circuit lifespan during continuous veno-venous hemodiafiltration (CVVHDF). METHODS: This prospective cohort study was conducted between December 2019 and December 2020. Patients requiring CKRT were enrolled to receive pre-dilution, post-dilution, or pre- to post-dilution fluid infusion with CVVHDF. The primary endpoint was circuit lifespan, and the secondary outcomes included the clinical parameters of patients, such as changes in serum creatinine (Scr) and blood urea nitrogen (BUN) levels, 28-day all-cause mortality, and length of stay. For all patients included in this study, only the first circuit used was recorded. RESULTS: Among the 132 patients enrolled in this study, 40 were in the pre-dilution mode, 42 were in the post-dilution mode, and 50 were in the pre- to post-dilution mode. The mean circuit lifespan was significantly longer in the pre- to post-dilution group (45.72 h, 95% CI, 39.75-51.69 h) than in the pre-dilution group (31.58 h, 95% CI, 26.33-36.82 h) and the post-dilution group (35.20 h, 95% CI, 29.62-40.78 h). There was no significant difference between the pre- and post-dilution group circuit lifespan (p > 0.05). Kaplan-Meier survival analysis revealed a significant difference between the three dilution modes (p = 0.001). No significant differences were observed in terms of changes in the Scr and BUN levels, admission day, and 28-day all-cause mortality among the three dilution groups (p > 0.05). CONCLUSION: The pre- to post-dilution mode significantly prolonged circuit lifespan but did not reduce Scr and BUN levels, compared with the pre-dilution and post-dilution modes during CVVHDF when no anticoagulants were used.

Sailing between scylla and charybdis-anticoagulation dilemma in a patient with calciphylaxis and mechanical cardiac valve replacement: a case report and literature review.

Calciphylaxis is a rare and life-threatening condition in patients with end-stage kidney disease (ESKD). In this case report, we reported a 72-year-old female who had undergone aortic and mitral mechanical valve replacement 22 years ago due to rheumatic aortic and mitral stenosis. Following the valve replacement, she initiated warfarin treatment. Five years ago, she received a diagnosis of uremia and has since been undergoing regular hemodialysis. Ten months prior to her current admission, she experienced excruciating pain and was diagnosed with calciphylaxis. Additionally, an electrocardiogram revealed atrial fibrillation, while echocardiography indicated that the aortic and mitral mechanical valves were appropriately positioned, with normal perivalvular surroundings and good valve leaflet activity. No noticeable thrombosis was observed in the left atrium or left atrial appendage. Color Doppler imaging showed moderate stenosis in the lower extremity arteries, with no venous thromboembolism present. Extensive eggshell-like calcification within the arterial media was detected. The patient was managed with regular hemodialysis, symptomatic treatments (including anticoagulation and analgesia), and sodium thiosulfate. Unfortunately, symptomatic management provided limited relief, and during the one-month follow-up period, the patient passed away due to septic shock. Currently, there is insufficient conclusive evidence regarding alternative influential anticoagulants or appropriate prosthetic valve selection. For individuals with ESKD receiving maintenance hemodialysis, early identification, diagnosis, and treatment of calciphylaxis are of paramount importance.

Research on a Variable Pressure Driving Method for Soft Robots Based on the Electromagnetic Effect.

This study proposes a novel variable air pressure supply structure based on the electromagnetic effect. This structure can be implemented in various soft robots driven by air pressure, including pneumatic artificial muscles, pneumatic soft grippers, and other soft robots. The structure's main body comprises a hollow circular tube, a magnetic piston arranged in the tube, and an electromagnetic solenoid nested outside the tube. The electromagnetic solenoid is designed with special winding and power supply access modes, generating either an attractive force or a repulsive force on the magnetic piston. This solenoid conforms with the magnetic piston expectation in the tube by changing the polarity direction. The interior of the whole structure is a closed space. The gas is conveyed to the soft robot by the gas guide hoses at the two ends of the structure, and the expansion energy of the compressed gas is fully utilized. Then, the gas supply pressure is controlled to drive the robot. The mathematical model of the structure is established based on the analysis of the electromagnetic force and gas pressure on the piston. The simulation results show that the structure's inherent vibration characteristics under various parameters align with expectations. The real-time automatic optimization of the controller parameters is realized by optimizing the incremental proportional-integral-derivative (PID) controller based on a neural network. The simulation results show that the structure can meet the application requirements. The experimental results show that the proposed gas supply structure can provide a continuous pressure supply curve with any frequency in a specific amplitude range and has an excellent tracking effect on the sinusoidal-like pressure curve.

Phospholipase A2 induces acute kidney injury by complement mediated mitochondrial apoptosis via TNF-α/NF-κB signaling pathway.

OBJECTIVE: Acute kidney injury (AKI) is one of common complications of wasp/bee stings. Phospholipase A2 (PLA2) is a vital pathogenic composition of wasp/bee venom. We aimed to investigate the role of complement mediated mitochondrial apoptosis in PLA2 induced AKI. MATERIALS AND METHODS: PLA2 induced AKI model was established by injecting PLA2 into via tail vein on mice. The pathological changes and the microstructural changes of kidney, complement activation, inflammation and apoptosis were detected in vitro and in vivo respectively. RESULTS: The results showed that PLA2 induced AKI models were successfully established in vivo and vitro. Compared with control, serum creatinine and urea nitrogen levels were elevated. Complement system activation and mitochondrial damage were observed. Expressions of IL-6, TNF-α, cleaved caspase-3 and cleaved caspase-9, and Bax/Bcl-2 increased in PLA2 induced AKI models. TNF-α/NF-κB signaling pathway activation in AKI models. CONCLUSION: In the present study, PLA2 induced AKI model was first successfully established to our knowledge. The role of complement mediated mitochondrial apoptosis pathway in renal tubular epithelial cells in PLA2 induced AKI were verified in vitro and vivo.

Continuous Renal Replacement Therapy With Adsorbing Filter oXiris in Acute Kidney Injury With Septic Shock: A Retrospective Observational Study.

Background and Objective: Sepsis/septic shock-associated acute kidney injury (S-AKI) is associated with prolonged kidney recovery and extremely high mortality. Extracorporeal blood purification therapy for the removal of endotoxin and cytokines might benefit patients with S-AKI. The purpose of this study was to compare the efficacy of adsorbing filter oXiris in the treatment of S-AKI. Design Setting Participants and Measurements: This was a retrospective observational study conducted from September 2017 to June 2020 in ICU. All patients received CRRT for ≥24 h. The primary outcomes were mortality. The secondary outcomes included cardiovascular SOFA score and vasoactive-inotropic score (VIS), the SOFA, the reduction of inflammatory mediators. Results: A total of 136 septic shock patients with AKI were included. The interventional group (oXiris group; n = 70) received CRRT with endotoxic and cytokine adsorption function hemofilter (oXiris), while the control group (ST150 group; n = 66) was treated with the ST150 hemofilter. The early mortality in 7 and 14 days was significantly lower in oXiris group compared with ST150 group (7 days: 47.1 vs. 74.2%, P = 0.007; 14 days: 58.5 vs. 80.3%, P = 0.005), but the difference was not significant in 90-day mortality (71.4 vs. 81.8%, P = 0.160). Additionally, the reduction of the SOFA score in the oXiris group at 24, 48, and 72 h CRRT was significantly faster than that in the controlled group. Meanwhile, the reduction of VIS score in the oXiris group compared with the ST150 group at 24 and 48 h after the initiation of CRRT was statistically significant (P < 0.05). Furthermore, the decreases in procalcitonin were greater in the oXiris group than those in the ST150 group at 24, 48, and 72h after initiation of CRRT. Multivariate Cox regression model demonstrated that oXiris (vs. ST150) played a favorably important role in the prognosis of septic shock patients with a hazard ratio (HR) of 0.500 (95% CI: 0.280-0.892; P = 019). Conclusion: Although no difference was found in 90-day mortality, oXiris might reduce the short-term (<14-day) mortality compared with ST150 groups in septic shock with AKI. Further investigation in randomized controlled trials or high-quality prospective studies is warranted to validate the present findings.

Effect of Dynamic Circuit Pressures Monitoring on the Lifespan of Extracorporeal Circuit and the Efficiency of Solute Removal During Continuous Renal Replacement Therapy.

Objective: To observe the effects of dynamic pressure monitoring on the lifespan of the extracorporeal circuit and the efficiency of solute removal during continuous renal replacement therapy (CRRT). Materials and Methods: A prospective observational study was performed at the West China Hospital of Sichuan University in the ICU. Analyses of the downloaded pressure data recorded by CRRT machines and the solute removal efficiencies, calculated by 2*Ce/(Cpre+Cpost), where Ce, Cpre, and Cpost are the concentrations of the effluent, pre-filter blood, and post-filter blood, respectively, were performed. Samples were collected at 0, 2, 6, 12, and 24 h when continuous veno-venous hemodiafiltration (CVVHDF) was used after the initiation of CRRT. Measurements in concentrations of creatinine, blood urea nitrogen, and ß2-microglobulin in the plasma and effluent were recorded. Results: Extracorporeal circuits characterized by moderate-to-severe (M-S) access outflow dysfunction (AOD) events, defined as access outflow pressure less than or equal to -200 mmHg for more than 5 min, had shorter median lifespans with no anticoagulation (32.3 vs. 10.90 h, P = 0.001) compared with the no M-S AOD events group. The significant outcome also existed in regional citrate anticoagulation (RCA) (72 vs. 42.47 h, P = 0.02). Moreover, Cox regression analysis revealed that the lack of M-S AOD events, RCA, or CVVHDF independently prolonged the circuit lifespan. All tested solutes removal efficiencies started to decline at 12 h. Furthermore, efficiencies of all solutes removal dropped obviously at 24 h when TMP ≥ 150 mmHg. Conclusion: RCA and CVVHDF predicted a longer circuit lifespan. M-S AOD events were associated with a shorter circuit lifespan when RCA or no anticoagulant was used. Replacement of extracorporeal circuit could be considered when running time of filter lasted up to 24 h with TMP ≥ 150 mmHg.