Integration of Prior Expectations and Suppression of Prediction Errors During Expectancy-Induced Pain Modulation: The Influence of Anxiety and Pleasantness.

Pain perception arises from the integration of prior expectations with sensory information. Although recent work has demonstrated that treatment expectancy effects (e.g., placebo hypoalgesia) can be explained by a Bayesian integration framework incorporating the precision level of expectations and sensory inputs, the key factor modulating this integration in stimulus expectancy-induced pain modulation remains unclear. In a stimulus expectancy paradigm combining emotion regulation in healthy male and female adults, we found that participants' voluntary reduction in anticipatory anxiety and pleasantness monotonically reduced the magnitude of pain modulation by negative and positive expectations, respectively, indicating a role of emotion. For both types of expectations, Bayesian model comparisons confirmed that an integration model using the respective emotion of expectations and sensory inputs explained stimulus expectancy effects on pain better than using their respective precision. For negative expectations, the role of anxiety is further supported by our fMRI findings that (1) functional coupling within anxiety-processing brain regions (amygdala and anterior cingulate) reflected the integration of expectations with sensory inputs and (2) anxiety appeared to impair the updating of expectations via suppressed prediction error signals in the anterior cingulate, thus perpetuating negative expectancy effects. Regarding positive expectations, their integration with sensory inputs relied on the functional coupling within brain structures processing positive emotion and inhibiting threat responding (medial orbitofrontal cortex and hippocampus). In summary, different from treatment expectancy, pain modulation by stimulus expectancy emanates from emotion-modulated integration of beliefs with sensory evidence and inadequate belief updating.

Effectiveness and safety of early treatment with spironolactone for new-onset acute heart failure.

BACKGROUND: The effectiveness and safety of mineralocorticoid receptor antagonists (MRA) in acute heart failure (HF) is uncertain. We sought to describe the prescription of spironolactone during acute HF and whether early treatment is effective and safe in a real-world setting. METHODS: We performed a retrospective cohort study of adult (≥18 years) nonpregnant patients hospitalized with new-onset HF with reduced ejection fraction (HFrEF, defined by ejection fraction ≤40%) within 15 Kaiser Permanente Southern California medical centers between 2016 and 2021. Early treatment was defined by spironolactone prescription at discharge. The primary effectiveness outcome was a composite of HF readmission or all-cause mortality at 180 days. Safety outcomes were hypotension and hyperkalemia at 90 days. RESULTS: Among 2318 HFrEF patients, 368 (15.9%) were treated with spironolactone at discharge. After 1:2 propensity score matching, 354 early treatment and 708 delayed/no treatment patients were included in the analysis. The median age was 63 (IQR: 52-74) years; 61.6% were male, and 38.6% were White. By 90 days, ~20% had crossed over in the two groups. Early treatment was not associated with the composite outcome at 180 days (HR [95% CI]: 0.81 [0.56-1.17]), but a trend towards benefit by 365 days that did not reach statistical significance (0.78 [0.58-1.06]). Early treatment was also associated with hyperkalemia (subdistribution HR [95% CI]: 2.33 [1.30-4.18]) but not hypotension (0.93 [0.51-1.72]). CONCLUSIONS: Early treatment with spironolactone at discharge for new-onset HFrEF in a real-world setting did not reduce the risk of HF readmission or mortality in the first year after discharge. The risk of hyperkalemia was increased.

Caffeic acid ethanolamide induces antifibrosis, anti-inflammatory, and antioxidant effects protects against bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease; its cause is unknown, and it leads to notable health problems. Currently, only two drugs are recommended for IPF treatment. Although these drugs can mitigate lung function decline, neither can improve nor stabilize IPF or the symptoms perceived by patients. Therefore, the development of novel treatment options for pulmonary fibrosis is required. The present study investigated the effects of a novel compound, caffeic acid ethanolamide (CAEA), on human pulmonary fibroblasts and evaluated its potential to mitigate bleomycin-induced pulmonary fibrosis in mice. CAEA inhibited TGF-ß-induced α-SMA and collagen expression in human pulmonary fibroblasts, indicating that CAEA prevents fibroblasts from differentiating into myofibroblasts following TGF-ß exposure. In animal studies, CAEA treatment efficiently suppressed immune cell infiltration and the elevation of TNF-α and IL-6 in bronchoalveolar lavage fluid in mice with bleomycin-induced pulmonary fibrosis. Additionally, CAEA exerted antioxidant effects by recovering the enzymatic activities of oxidant scavengers. CAEA directly inhibited activation of TGF-ß receptors and protected against bleomycin-induced pulmonary fibrosis through inhibition of the TGF-ß/SMAD/CTGF signaling pathway. The protective effect of CAEA was comparable to that of pirfenidone, a clinically available drug. Our findings support the potential of CAEA as a viable method for preventing the progression of pulmonary fibrosis.

Association Between Coronary Artery Disease Testing in Patients with New-Onset Heart Failure and Heart Failure Readmission and Mortality.

BACKGROUND: In patients with new-onset heart failure (HF), coronary artery disease (CAD) testing remains underutilized. Whether widespread CAD testing in patients with new-onset HF leads to improved outcomes remains to be determined. OBJECTIVE: We sought to examine whether CAD testing, and its timing, among patients hospitalized with new-onset HF with reduced ejection fraction (HFrEF), is associated with improved outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: Adult (≥ 18 years) non-pregnant patients with new-onset HFrEF hospitalized within one of 15 Kaiser Permanente Southern California medical centers between 2016 and 2021. Key exclusion criteria included history of heart transplant, hospice, and a do-not-resuscitate order. MAIN MEASURES: Primary outcome was a composite of HF readmission or all-cause mortality through end of follow-up on 12/31/2022. KEY RESULTS: Among 2729 patients hospitalized with new-onset HFrEF, 1487 (54.5%) received CAD testing. The median age was 66 (56-76) years old, 1722 (63.1%) were male, and 1074 (39.4%) were White. After a median of 1.8 (0.6-3.4) years, the testing group had a reduced risk of HF readmission or all-cause mortality (aHR [95%CI], 0.71 [0.63-0.79]). These results were consistent across subgroups by history of atrial fibrillation, diabetes, renal disease, myocardial infarction, and elevated troponin during hospitalization. In a secondary analysis where CAD testing was further divided to early (received testing before discharge) and late testing (up to 90 days after discharge), there was no difference in late vs early testing (0.97 [0.81-1.16]). CONCLUSIONS: In a contemporary and diverse cohort of patients hospitalized with new-onset HFrEF, CAD testing within 90 days of hospitalization was associated with a lower risk of HF readmission or all-cause mortality. Testing within 90 days after discharge was not associated with worse outcomes.

Telehealth transitional care and 30-day readmission during the COVID-19 pandemic.

Transitional care management (TCM) services after hospital discharge are critical for continuity of care, and the COVID-19 pandemic accelerated the shift to telehealth modes of delivery. This study examined the shift from face-to-face to telehealth care around the start of the pandemic (April-July 2020) compared with the same months in 2019 and 2021 and the corresponding 30-day readmission rates. We compared the rates of face-to-face and telehealth TCM as well as face-to-face and telehealth non-TCM services and observed a dramatic shift to telehealth in 2020 with a slight drop-off in 2021. For TCM services specifically, face-to-face visits made up nearly 90% of visits in 2019, whereas telehealth made up the vast majority in 2020 and 2021 at 97.5% and 84.9%, respectively. Over the same time periods, 30-day readmission rates remained steady at 10% along with no changes in 30-day mortality. Among those who completed TCM visits, 30-day readmission rates remained between 8% and 9% and 30-day mortality remained below 1%. These data indicate that this dramatic systemwide shift from face-to-face to telehealth TCM was not accompanied by concurrent changes in either 30-day readmission or mortality rates. Although the findings may be subject to ecologic bias, the data at hand did not allow for reliable estimation of differences in effects of patient-level service delivery type on readmission risk or mortality due to the extremely low volume of face-to-face visits during the pandemic periods. Future research would be needed to conduct such comparisons.

Rates of diabetic ketoacidosis with empagliflozin use during hospitalization for acute heart failure.

There is concern that sodium-glucose cotransporter-2 inhibitors during hospitalization for acute heart failure (aHF) may precipitate diabetic ketoacidosis (DKA). A retrospective study of all hospitalization encounters for aHF defined by a primary HF International Classification of Diseases (ICD)-10 code in 15 Kaiser Permanente Southern California medical centers hospitalized between January 1, 2021 and August 31, 2023 was performed to describe rates of DKA with empagliflozin use. DKA was defined by the presence of either a DKA ICD-10 code or ketoacidosis lab criteria (bicarbonate <18 mmol/L and urine ketone 1+ or more or elevated serum beta-hydroxybutyrate within 12 h) during hospitalization. Among 21,630 hospital encounters (15,518 patients) for aHF, 1678 (8%) had empagliflozin use. There were 2 (0.1%) probable DKA cases in empagliflozin encounters and 15 (0.1%) in nonexposed encounters. These rates were similar when stratified by diabetes status and ejection fraction. Empagliflozin may be safe during aHF hospitalization.

Technical Refinement of a Bilateral Renal Ischemia-Reperfusion Mouse Model for Acute Kidney Injury Research.

Cardiac arrest poses a large public health burden. Acute kidney injury (AKI) is an adverse marker in survivors of cardiac arrest following the return of spontaneous circulation (ROSC) after successful cardiopulmonary resuscitation. Conversely, recovery of kidney function from AKI is a predictor of favorable neurological outcomes and hospital discharge. However, an effective intervention to prevent kidney damage caused by cardiac arrest after ROSC is lacking, suggesting that additional therapeutic strategies are required. Renal hypoperfusion and reperfusion are two pathophysiological mechanisms that cause AKI after cardiac arrest. Animal models of ischemia-reperfusion-induced AKI (IR-AKI) of both kidneys are comparable with patients with AKI following ROSC in a clinical setting. However, IR-AKI of both kidneys is technically challenging to analyze because the model is associated with high mortality and wide variation in kidney damage, which may affect the analysis. Lightweight mice were chosen, placed under general anesthesia with isoflurane, subjected to surgery with a dorsolateral approach, and their body temperature maintained during operation, thereby reducing tissue damage and establishing a reproducible acute renal IR-AKI research protocol.

Soluble dipeptidyl peptidase-4 induces epithelial-mesenchymal transition through tumor growth factor-ß receptor.

BACKGROUND: Kidney fibrosis is the final manifestation of chronic kidney disease, a condition mainly caused by diabetic nephropathy. Persistent tissue damage leads to chronic inflammation and excessive deposition of extracellular matrix (ECM) proteins. Epithelial-mesenchymal transition (EMT) is involved in a variety of tissue fibrosis and is a process during which epithelial cells transform into mesenchymal-like cells and lose their epithelial functionality and characteristics Dipeptidyl peptidase-4 (DPP4) is widely expressed in tissues, especially those of the kidney and small intestine. DPP4 exists in two forms: a plasma membrane-bound and a soluble form. Serum-soluble DPP4 (sDPP4) levels are altered in many pathophysiological conditions. Elevated circulating sDPP4 is correlated with metabolic syndrome. Because the role of sDPP4 in EMT remains unclear, we examined the effect of sDPP4 on renal epithelial cells. METHODS: The influences of sDPP4 on renal epithelial cells were demonstrated by measuring the expression of EMT markers and ECM proteins. RESULTS: sDPP4 upregulated the EMT markers ACTA2 and COL1A1 and increased total collagen content. sDPP4 activated SMAD signaling in renal epithelial cells. Using genetic and pharmacological methods to target TGFBR, we observed that sDPP4 activated SMAD signaling through TGFBR in epithelial cells, whereas genetic ablation and treatment with TGFBR antagonist prevented SMAD signaling and EMT. Linagliptin, a clinically available DPP4 inhibitor, abrogated sDPP4-induced EMT. CONCLUSIONS: This study indicated that sDPP4/TGFBR/SMAD axis leads to EMT in renal epithelial cells. Elevated circulating sDPP4 levels may contribute to mediators that induce renal fibrosis.

A novel caffeic acid derivative prevents angiotensin II-induced cardiac remodeling.

Differentiation of cardiac fibroblasts into myofibroblasts is a critical event in the progression of cardiac fibrosis that causes pathological cardiac remodeling. Cardiac fibrosis is a hallmark of heart disease and is associated with a stiff myocardium and heart failure. This study investigated the effect of caffeic acid ethanolamide (CAEA), a novel caffeic acid derivative, on cardiac remodeling. Angiotensin (Ang) II was used to induce cardiac remodeling both in cell and animal studies. Treating cardiac fibroblast with CAEA in Ang II-exposed cell cultures reduced the expression of fibrotic marker α-smooth muscle actin (α-SMA) and collagen and the production of superoxide, indicating that CAEA inhibited the differentiation of fibroblast into myofibroblast after Ang II exposure. CAEA protects against Ang II-induced cardiac fibrosis and dysfunction in vivo, characterized by the alleviation of collagen accumulation and the recovery of ejection fraction. In addition, CAEA decreased Ang II-induced transforming growth factor-ß (TGF-ß) expression and reduced NOX4 expression and oxidative stress in a SMAD-dependent pathway. CAEA participated in the regulation of Ang II-induced TGF-ß/SMAD/NOX4 signaling to prevent the differentiation of fibroblast into myofibroblast and thus exerted a cardioprotective effect. Our data support the administration of CAEA as a viable method for preventing the progression of Ang II-induced cardiac remodeling.

Dementia and readmission risk in patients with heart failure participating in a transitional care program.

BACKGROUND: Cognitive impairment is prevalent in patients hospitalized for heart failure (HF). We aimed to generate further evidence on the value of dementia screening in hospitalized HF patients by examining whether and when dementia would be an independent risk factor for 30-day readmission while modeling permutations of known risk factors such as patient demographics, disease burden, prior utilization, and index hospitalization characteristics. METHODS AND RESULTS: A retrospective cohort study was employed, consisting of 26,128 patients (2,075 or 7.9% with dementia) in a transitional care program post HF hospitalization. The overall 30-day all-cause readmission rate was 18.1%. Patients with dementia had higher unadjusted rates of readmission (22.0 vs 17.8%) and death (4.5 vs. 2.2%) within 30 days post hospitalization, compared to those without dementia. Hierarchical multivariable proportional hazards regression results showed that dementia independently predicted readmission when both patient demographics and disease burden variables were controlled for (HR=1.15, p=0.02). However, the association between dementia and readmission was attenuated in the full model when prior utilization and index hospitalization characteristics were added (HR=1.04, p=0.55). For dementia patients, Charlson comorbidity index, prior ED visits, and length of stay were significant risk factors of readmission. CONCLUSIONS: The presence of dementia and the predictors of 30-day readmission in those with dementia may help identify this subset of high-risk HF patients for potential efforts to improve their prognosis.

Pelvic Neoadjuvant Radiotherapy for Stage M1a Rectal Adenocarcinoma Patients Treated With Systemic Therapy Followed by Proctectomy and Metastasectomy: A Nationwide Retrospective Cohort Study.

BACKGROUND/AIM: The effect of pelvic neoadjuvant radiotherapy (nRT) for stage M1a rectal adenocarcinoma patients treated with systemic therapy followed by proctectomy and metastasectomy was scarcely investigated in the literatures. PATIENTS AND METHODS: The eligible rectal cancer patients diagnosed between 2011-2019 were identified via the Taiwan Cancer Registry. In the primary analysis, we used propensity score weighting to balance observable potential confounders and compared the hazard ratio (HR) of death for the nRT group vs. without RT group. We also compared the incidence of rectal cancer mortality (IRCM) and performed various supplementary analyses. RESULTS: Our primary analyses included 145 patients. nRT was associated with improved OS (HR=0.51, p=0.01). The numerical trends remained similar for IRCM and in supplementary analyses. CONCLUSION: nRT was associated with improved OS in our study population.

Photoreactive Mercury-Containing Metallosupramolecular Nanoparticles with Tailorable Properties That Promote Enhanced Cellular Uptake for Effective Cancer Chemotherapy.

A new potential route to enhance the efficiency of supramolecular polymers for cancer chemotherapy was successfully demonstrated by employing a photosensitive metallosupramolecular polymer (Hg-BU-PPG) containing an oligomeric poly(propylene glycol) backbone and highly sensitive pH-responsive uracil-mercury-uracil (U-Hg-U) bridges. This route holds great promise as a multifunctional bioactive nano-object for development of more efficient and safer cancer chemotherapy. Owing to the formation of uracil photodimers induced by ultraviolet irradiation, Hg-BU-PPG can form a photo-cross-linked structure and spontaneously forms spherical nanoparticles in aqueous solution. The irradiated nanoparticles possess many unique characteristics, such as unique fluorescence behavior, highly sensitive pH-responsiveness, and intriguing phase transition behavior in aqueous solution as well as high structural stability and antihemolytic activity in biological media. More importantly, a series of cellular studies clearly confirmed that the U-Hg-U photo-cross-links in the irradiated nanoparticles substantially enhance their selective cellular uptake by cancer cells via macropinocytosis and the mercury-loaded nanoparticles subsequently induce higher levels of cytotoxicity in cancer cells (compared to non-irradiated nanoparticles), without harming normal cells. These results are mainly attributed to cancer cell microenvironment-triggered release of mercury ions from disassembled nanoparticles, which rapidly induce massive levels of apoptosis in cancer cells. Overall, the pH-sensitive U-Hg-U photo-cross-links within this newly discovered supramolecular system are an indispensable factor that offers a potential path to remarkably enhance the selective therapeutic effects of functional nanoparticles toward cancer cells.

Global research trends of peri-implantitis during the last two decades: a bibliometric and visualized study.

Peri-implantitis is one of the most prevalent and impactful complications of dental implant prostheses. This study aimed to identify area focuses and emerging trends in peri-implantitis research. A literature search was conducted in the Web of Science Core Collection (WoSCC), employing a bibliometric approach for data evaluation. VOSviewer and CiteSpace software were used for identifying and analyzing research foci and trends. Between 2001 and 2020, there were 2,346 publications on peri-implantitis. Leaders in number of articles published and collaboration networks were USA and Europe. High-frequency keywords included periodontitis, treatment, prevalence, titanium, follow-up, survival, in vitro, and bone loss. Keyword burst detection analysis revealed epidemiology, outcomes, and impact as emerging research hotspots. The findings suggest a need for more international multicenter clinical studies on peri-implantitis, with future studies likely focusing on prevalence, treatment, and predisposing factors.

Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway.

With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations; however, poor bone condition affects the long-term stability of implant prostheses. This study aimed to investigate the therapeutic effect of quercetin (QR) compared with alendronate (ALN), the primary treatment for PMOP, on mandibular osteoporosis (OP) induced by ovariectomy (OVX) in female rats. Adult female rats were treated with QR (50 mg/kg/day), ALN (6.25 mg/kg/week) by gavage for 8 weeks, chloroquine (CQ, 10 mg/kg/twice a week), and cytokine release inhibitory drug 3 (MCC950, 10 mg/kg/three times a week) by intraperitoneal injection for 8 weeks after bilateral OVX. Blood samples were collected prior to euthanasia; the mandibles were harvested and subjected to micro-computed tomography (micro-CT) and pathological analysis. QR administration controlled weight gain and significantly improved the bone microstructure in OVX rats, increasing bone mass, and bone mineral density (BMD), reducing bone trabecular spacing, and decreasing osteoclast numbers. Western blotting, real-time quantitative PCR (RT-qPCR), and serum markers confirmed that QR inhibited interleukin- 1ß (IL-1ß) and interleukin-18 (IL-18) on the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) pathway thereby inhibiting osteoclast differentiation, immunofluorescence and western blotting also confirmed that QR inhibited autophagy in OVX rats and suppressed the number of tartrate-resistant acid phosphatase (TRAP)-stained positive osteoclasts. The findings suggest that QR may protect the bone structure and prevent bone loss in osteoporotic rats by inhibiting the NLRP3 pathway and autophagy in osteoclasts with comparable effects to ALN, thus QR may have the potential to be a promising alternative supplement for the preventive and therapeutic treatment of PMOP.

Development and validation of the COVID-19 Hospitalized Patient Deterioration Index.

OBJECTIVES: To develop a COVID-19-specific deterioration index for hospitalized patients: the COVID Hospitalized Patient Deterioration Index (COVID-HDI). This index builds on the proprietary Epic Deterioration Index, which was not developed for predicting respiratory deterioration events among patients with COVID-19. STUDY DESIGN: A retrospective observational cohort was used to develop and validate the COVID-HDI model to predict respiratory deterioration or death among hospitalized patients with COVID-19. Deterioration events were defined as death or requiring high-flow oxygen, bilevel positive airway pressure, mechanical ventilation, or intensive-level care within 72 hours of run time. The sample included hospitalized patients with COVID-19 diagnoses or positive tests at Kaiser Permanente Southern California between May 3, 2020, and October 17, 2020. METHODS: Machine learning models and 118 candidate predictors were used to generate benchmark performance. Logit regression with least absolute shrinkage and selection operator and physician input were used to finalize the model. Split-sample cross-validation was used to train and test the model. RESULTS: The area under the receiver operating curve was 0.83. COVID-HDI identifies patients at low risk (negative predictive value [NPV] > 98.5%) and borderline low risk (NPV > 95%) of an event. Of all patients, 74% were identified as being at low or borderline low risk at some point during their hospitalization and could be considered for discharge with or without home monitoring. A high-risk group with a positive predictive value of 51% included 12% of patients. Model performance remained high in a recent cohort of patients. CONCLUSIONS: COVID-HDI is a parsimonious, well-calibrated, and accurate model that may support clinical decision-making around discharge and escalation of care.

Self-Assembled Supramolecular Micelles Based on Multiple Hydrogen Bonding Motifs for the Encapsulation and Release of Fullerene.

Living creatures involve several defense mechanisms, such as protecting enzymes to protect organs and cells from the invasion of free radicals. Developing antioxidant molecules and delivery systems to working with enzymes is vital. In this study, a supramolecular polymer PNI-U-DPy was used to encapsulate C60, a well-known antioxidant that is hard to dissolve or disperse in the aqueous media. PNI-U-DPy exhibits characteristics similar to PNIPAM but could form micelles even when the environment temperature is lower than its LCST. The U-DPy moieties could utilize their strong complementary hydrogen bonding-interaction to create a physically crosslinked network within PNIPAM micelles, thus adjusting its LCST to a value near the physiological temperature. Morphological studies suggested that C60 could be effectively loaded into PNI-U-DPy micelles with a high loading capacity (29.12%), and the resulting complex PNI-C60 is stable and remains temperature responsive. A series of measurements under variable temperatures was carried out and showed that a controlled release process proceeded. Furthermore, PNI-C60 exhibits hydroxyl radicals scavenging abilities at a low dosage and could even be adjusted by temperature. It can be admitted that the micelle system can be a valuable alternative for radical scavengers and may be delivered to the desired position with good dispersibility and thermo-responsivity. It is beneficial to the search progress of scientists for drug delivery systems for chemotherapeutic treatments and biomedical applications.

Comparison of safety and outcomes related to remdesivir treatment among dialysis patients hospitalized with COVID-19.

Background: Patients with end-stage kidney disease (ESKD) are highly susceptible to coronavirus disease 2019 (COVID-19) infection and its complications. Remdesivir has improved outcomes in COVID-19 patients but its use has been limited among ESKD patients due to insufficient data regarding safety outcomes. We sought to evaluate the safety of remdesivir among dialysis patients hospitalized with COVID-19. Methods: This retrospective cohort study was conducted among patients age ≥18 years on maintenance dialysis and hospitalized with COVID-19 between 1 May 2020 and 31 January 2021 within an integrated health system who were treated or not treated with remdesivir. The primary outcome was 30-day all-cause mortality. Secondary outcomes were intensive care unit (ICU) stay, and transaminitis (AST/ALT >5× normal). Pseudo-populations were created using inverse probability of treatment weights with propensity scoring to balance patient characteristics among the two groups. Multivariable Poisson regression with robust error was performed to estimate 30-day mortality risk ratio. Results: A total of 486 (407 hemodialysis and 79 peritoneal dialysis) patients were hospitalized with COVID-19, among which 112 patients (23%) were treated with remdesivir [median treatment four days (interquartile range 2-5)]. The 30-day mortality rate was 24.1% among remdesivir-treated and 27.8% among non-treated patients. The estimated 30-day mortality rate was 0.74 (95% confidence interval 0.52-1.05) among remdesivir treated compared with non-treated patients. Liver injury and ICU admission rates were 1.8% and 14.3% among remdesivir-treated patients compared with 2.4% and 16% among non-treated patients. Conclusion: Among dialysis patients hospitalized with COVID-19, remdesivir was not associated with higher rates of liver injury or ICU admissions, and demonstrated a trend toward lower 30-day mortality.

A Pathophysiological Approach to Reduce Peritumoral Edema with Gamma Knife Radiosurgery for Large Incidental Meningiomas.

BACKGROUND: Peritumoral edema may be a prohibitive side effect in treating large incidental meningiomas with stereotactic radiosurgery. An approach that limits peritumoral edema and achieves tumor control with SRS would be an attractive management option for large incidental meningiomas. METHODS: This is a retrospective cohort study of patients with large incidental meningiomas (≥2 mL in volume and/or 2 cm in diameter) treated with gamma knife radiosurgery (GKRS) between 2000 and 2019 in Taiwan and followed up for 5 years. The outcomes of a pathophysiological approach targeting the dural feeding artery site with a higher marginal dose (18-20 Gy) to enhance vascular damage and the parenchymal margin of the tumor with a lower dose (9-11 Gy) to reduce parenchymal damage were compared with those of a conventional approach targeting the tumor center with a higher dose and tumor margin with a lower dose (12-14 Gy). RESULTS: A total of 53 incidental meningiomas were identified, of which 23 (43.4%) were treated with a pathophysiological approach (4 cases underwent a two-stage approach) and 30 (56.7%) were treated with a conventional approach. During a median follow-up of 3.5 (range 1-5) years, tumor control was achieved in 19 (100%) incidental meningiomas that underwent a single-stage pathophysiological approach compared with 29 (96.7%) incidental meningiomas that underwent a conventional approach (log-rank test: p = 0.426). Peritumoral edema developed in zero (0%) incidental meningiomas that underwent a single stage pathophysiological approach compared to seven (23.3%) incidental meningiomas that underwent a conventional approach (log-rank test: p = 0.023). CONCLUSIONS: Treatment of large incidental meningiomas with a pathophysiological approach with GKRS achieves similar rates of tumor control and reduces the risk of peritumoral edema. GKRS with a pathophysiological approach may be a reasonable management strategy for large incidental meningiomas.