The immunomodulation role of Th17 and Treg in renal transplantation.

Kidney transplantation (KT) is an ultimate treatment of end-stage chronic kidney disease, which can meet a lot of complications induced by immune system. With under-controlled immunosuppression, the patient will obtain a good prognosis. Otherwise, allograft disfunction will cause severe organ failure and even immune collapse. Acute or chronic allograft dysfunction after KT is related to Th17, Treg, and Th17/Treg to a certain extent. Elevated Th17 levels may lead to acute rejection or chronic allograft dysfunction. Treg mainly plays a protective role on allografts by regulating immune response. The imbalance of the two may further aggravate the balance of immune response and damage the allograft. Controlling Th17 level, improving Treg function and level, and adjusting Th17/Treg ratio may have positive effects on longer allograft survival and better prognosis of receptors.

Data science in the intensive care unit.

In this editorial, we comment on the current development and deployment of data science in intensive care units (ICUs). Data in ICUs can be classified into qualitative and quantitative data with different technologies needed to translate and interpret them. Data science, in the form of artificial intelligence (AI), should find the right interaction between physicians, data and algorithm. For individual patients and physicians, sepsis and mechanical ventilation have been two important aspects where AI has been extensively studied. However, major risks of bias, lack of generalizability and poor clinical values remain. AI deployment in the ICUs should be emphasized more to facilitate AI development. For ICU management, AI has a huge potential in transforming resource allocation. The coronavirus disease 2019 pandemic has given opportunities to establish such systems which should be investigated further. Ethical concerns must be addressed when designing such AI.

Recombinant human brain natriuretic peptide ameliorates venous return function in congestive heart failure.

AIMS: Recombinant human brain natriuretic peptide (rh-BNP) is commonly used as a decongestive therapy. This study aimed to investigate the instant effects of rh-BNP on cardiac output and venous return function in post-cardiotomy patients with congestive heart failure (CHF). METHODS AND RESULTS: Twenty-four post-cardiotomy heart failure patients were enrolled and received a standard loading dose of rh-BNP. Haemodynamic monitoring was performed via a pulmonary artery catheter before and after the administration of rh-BNP. The cardiac output and venous return functions were estimated by depicting Frank-Starling and Guyton curves. After rh-BNP infusion, variables reflecting cardiac congestion and venous return function, such as pulmonary artery wedge pressure, mean systemic filling pressure (Pmsf) and venous return resistance index (VRRI), reduced from 15 ± 3 to 13 ± 3 mmHg, from 32 ± 7 to 28 ± 7 mmHg and from 6.7 ± 2.6 to 5.7 ± 1.8 mmHg min m2 /L, respectively. Meanwhile, cardiac index, stroke volume index, and the cardiac output function curve remained unchanged per se. The decline in Pmsf [-13% (-22% to -8%)] and VRRI [-12% (-25% to -5%)] was much greater than that in the systemic vascular resistance index [-7% (-14% to 0%)]. In the subgroup analysis of reduced ejection fraction (<40%) patients, the aforementioned changes were more significant. CONCLUSIONS: rh-BNP might ameliorate venous return rather than cardiac output function in post-cardiotomy CHF patients.

Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

Objective: Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation. Method: 20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group). Results: Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023). Conclusion: The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT04328688).

INFRARED THERMOGRAPHY-BASED BODY-SURFACE THERMAL INHOMOGENEITY MONITORING TO ASSESS THE SEVERITY OF HYPOPERFUSION IN CRITICALLY ILL PATIENTS.

ABSTRACT: Background: Uneven body-surface thermal distribution is a manifestation of hypoperfusion and can be quantified by infrared thermography. Our aim was to investigate whether body-surface thermal inhomogeneity could accurately evaluate the severity of patients at risk of hypoperfusion. Methods: This was a prospective cohort study in which infrared thermography images were taken from unilateral legs of critically ill patients at high risk of hypoperfusion in a cardiac surgical intensive care unit. For each patient, five body-surface thermal inhomogeneity parameters, including standard deviation (SD), kurtosis, skewness, entropy, and low-temperature area rate (LTAR), were calculated. Demographic, clinical, and thermal characteristics of deceased and living patients were compared. The risk of mortality and capillary refill time (CRT) were chosen as the primary outcome and benchmarking parameter for hypoperfusion, respectively. The area under the receiver operating characteristic curve (AUROC) was used to evaluate predictive accuracy. Results: Three hundred seventy-three patients were included, and 55 (14.7%) died during hospital stay. Of inhomogeneity parameters, SD (0.738) and LTAR (0.768) had similar AUROC to CRT (0.757) for assessing mortality risk. Besides, there was a tendency for LTAR (1%-3%-7%) and SD (0.81°C-0.88°C-0.94°C) to increase in normotensive, hypotensive, and shock patients. These thermal parameters are associated with CRT, lactate, and blood pressure. The AUROC of a combined prediction incorporating three thermal inhomogeneity parameters (SD, kurtosis, and entropy) was considerably higher at 0.866. Conclusions: Body-surface thermal inhomogeneity provided a noninvasive and accurate assessment of the severity of critically ill patients at high risk of hypoperfusion.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury.

Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%-15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.

Tailoring glucocorticoids in patients with severe COVID-19: a narrative review.

OBJECTIVE: To discuss the pathogenesis of severe coronavirus disease 2019 (COVID-19) infection and the pharmacological effects of glucocorticoids (GCs) toward this infection. To review randomized controlled trials (RCTs) using GCs to treat patients with severe COVID-19, and investigate whether GC timing, dosage, or duration affect clinical outcomes. Finally. to discuss the use of biological markers, respiratory parameters, and radiological evidence to select patients for improved GC therapeutic precision. BACKGROUND: COVID-19 has become an unprecedented global challenge. As GCs have been used as key immunomodulators to treat inflammation-related diseases, they may play key roles in limiting disease progression by modulating immune responses, cytokine production, and endothelial function in patients with severe COVID-19, who often experience excessive cytokine production and endothelial and renin-angiotensin system (RAS) dysfunction. Current clinical trials have partially proven this efficacy, but GC timing, dosage, and duration vary greatly, with no unifying consensus, thereby creating confusion. METHODS: Publications through March 2021 were retrieved from the Web of Science and PubMed. Results from cited references in published articles were also included. CONCLUSIONS: GCs play key roles in treating severe COVID-19 infections. Pharmacologically, GCs could modulate immune cells, reduce cytokine and chemokine, and improve endothelial functions in patients with severe COVID-19. Benefits of GCs have been observed in multiple clinical trials, but the timing, dosage and duration vary across studies. Tapering as an option is not widely accepted. However, early initiation of treatment, a tailored dosage with appropriate tapering may be of particular importance, but evidence is inconclusive and more investigations are needed. Biological markers, respiratory parameters, and radiological evidence could also help select patients for specific tailored treatments.