Efficacy of CytoSorb®: a systematic review and meta-analysis.

INTRODUCTION: Cytokine adsorption using the CytoSorb® adsorber has been proposed in various clinical settings including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery or recovery after cardiac arrest. The aim of this analysis is to provide evidence for the efficacy of the CytoSorb® adsorber with regard to mortality in various settings. METHODS: We searched PubMed, Cochrane Library database and the database provided by Cytosorbents™ (01.1.2010-29.5.2022). We considered randomized controlled trials and observational studies with control groups. The longest reported mortality was defined as the primary endpoint. We computed risk ratios and 95%-confidence intervals and used DerSimonian and Lairds random effects model. We analysed all studies combined and divided them into the subgroups: sepsis, cardiopulmonary bypass surgery (CPB), other severe illness, SARS-CoV-2 infection and recovery from cardiac arrest. The meta-analysis was registered in advance (PROSPERO: CRD42022290334). RESULTS: Of an initial 1295 publications, 34 studies were found eligible, including 1297 patients treated with CytoSorb® and 1314 controls. Cytosorb® intervention did not lower mortality (RR [95%-CI]: all studies 1.07 [0.88; 1.31], sepsis 0.98 [0.74; 1.31], CPB surgery 0.91 [0.64; 1.29], severe illness 0.95 [0.59; 1.55], SARS-CoV-2 1.58 [0.50; 4.94]). In patients with cardiac arrest, we found a significant survival advantage of the untreated controls (1.22 [1.02; 1.46]). We did not find significant differences in ICU length of stay, lactate levels, or IL-6 levels after treatment. Of the eligible 34 studies only 12 were randomized controlled trials. All observational studies showed moderate to serious risk of bias. INTERPRETATION: To date, there is no evidence for a positive effect of the CytoSorb® adsorber on mortality across a variety of diagnoses that justifies its widespread use in intensive care medicine.

"More than just giving them a piece of paper": Interviews with Primary Care on Social Needs Referrals to Community-Based Organizations.

BACKGROUND: Primary care practices are responding to calls to incorporate patients' social risk factors, such as housing, food, and economic insecurity, into clinical care. Healthcare likely relies on the expertise and resources of community-based organizations to improve patients' social conditions, yet little is known about the referral process. OBJECTIVE: To characterize referrals to community-based organizations by primary care practices. DESIGN: Qualitative study using semi-structured interviews with healthcare administrators responsible for social care efforts in their organization. PARTICIPANTS: Administrators at 50 diverse US healthcare organizations with efforts to address patients' social risks. MAIN MEASURES: Approaches used in primary care to implement social needs referral to community-based organizations. RESULTS: Interviewed administrators reported that social needs referrals were an essential element in their social care activities. Administrators described the ideal referral programs as placing limited burden on care teams, providing patients with customized referrals, and facilitating closed-loop referrals. We identified three key challenges organizations experience when trying to implement the ideal referrals program: (1) developing and maintaining resources lists; (2) aligning referrals with patient needs; and (3) measuring the efficacy of referrals. Collectively, these challenges led to organizations relying on staff to manually develop and update resource lists and, in most cases, provide patients with generic referrals. Administrators not only hoped that referral platforms may help overcome some of these barriers, but also reported implementation challenges with platforms including inconsistent buy-in and use across staff; integration with electronic health records; management and prioritization of resources; and alignment with other organizations in their market. CONCLUSION AND RELEVANCE: Referrals to community-based organizations were used in primary care to improve patients' social conditions, but despite strong motivations, interviewees reported challenges providing tailored and up-to-date information to patients.

Renal events in patients receiving neprilysin inhibitors: a systematic review and meta-analysis.

BACKGROUND: While it is well known that angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) increase the risk of acute renal failure, the role of neprilysin inhibition (NEPi) is unclear and some physicians are reluctant to prescribe sacubitril/valsartan because of safety concerns. This meta-analysis aimed to examine the risk for renal events, progression of chronic kidney disease (CKD) or progression to dialysis on combined NEPi and ACEi/ARBs compared with ACEi or ARBs. METHODS: We performed a systematic meta-analysis including 17 randomized controlled trials (study drug sacubitril/valsartan or omapatrilat), involving a total of 23 569 patients, after searching PubMed, Cochrane, ClinicalTrials.org and Embase for eligible studies. From the included trials, all renal endpoints, including long- and short-term outcomes and hyperkalemia, were extracted. Pooled odds ratios (ORs) were calculated using the DerSimonian and Laird method. The study was registered at PROSPERO. RESULTS: Overall, treatment with sacubitril/valsartan or omapatrilat showed a slightly lower risk of any renal event [OR 0.82 (0.7-0.97)] compared with treatment with an ACEi or ARB alone. Also, there was a decreased risk of severe acute renal events [OR 0.8 (0.69-0.93)] and a decrease in estimated glomerular filtration rate decline [mean difference -0.58 mL/min (-0.83 to -0.33 mL/min)]. There was no difference in chronic renal events [OR 0.92 (0.8-1.05)] or hyperkalemia [OR 1.02 (0.84-1.23)]. CONCLUSION: NEPi + ACEi/ARBs are safe in terms of renal adverse events. Longer trials focusing on CKD are needed to evaluate the effect of NEPi on decreasing progression of CKD.

Outpatient Virtual Visits and the "Right" Amount of Telehealth Going Forward.

Background: An exponential increase in outpatient telehealth visits occurred early in the pandemic period that has been followed by volumes that, although lower than peak numbers, are substantially greater than the pre-pandemic period. This provided an opportunity to assess provider perceptions regarding the right prevalence going forward and key obstacles to achieving it. Methods: A 10-question survey was distributed to all outpatient providers within the Dartmouth-Hitchcock Health System. Domains included practice location, specialty, professional degree, experience with telehealth, satisfaction, perception of the amount of telehealth that could be adequately delivered going forward, role of audio-only, and obstacles. Results: Three hundred thirty-six providers completed the survey representing 51 specialties. The most common response regarding the proportion of outpatient visits that could be delivered by video going forward was 21-50% (n = 104) followed by 6-20% (n = 99) and >50% (n = 71). A minority of respondents chose ≤5% (n = 17). In terms of the fraction of video visits for which phone was equally effective, a similar percentage of respondents felt that it was 1/10 (22%), 1/4 (20%), or 1/2 (26%) of visits. Fewer felt that all (7%) or 3/4 (15%) of visits were equally effective, and 10% felt that it was none. Common obstacles identified were the need for a physical exam, unique aspects of providers' patients, patient preference, and issues regarding technology and internet speed/connectivity. Conclusions: After a period of exponential growth in virtual visits due to the pandemic, outpatient providers within an academic health system felt that a substantial portion of future visits could be delivered by this modality.

Assessment of liver ischemia reperfusion injury in mice using hepatic T2 mapping: Comparison with histopathology.

BACKGROUND: Liver ischemia reperfusion injury (IRI) occurs during liver surgery or transplantation resulting in an inflammatory response, tissue damage, and functional impairment of the organ. PURPOSE: To assess the feasibility of T2 mapping for noninvasive quantification of liver edema after partial liver IRI in mice. STUDY TYPE: Prospective, experimental study. ANIMAL MODEL: Partial liver IRI was induced in C57BL/6-mice by transient clamping of the left lateral and median liver lobes for 35 (n = 8), 45 (n = 6), 60 (n = 17), or 90 minutes (n = 5). For comparison, healthy C57BL/6-mice were examined as controls (n = 9). FIELD STRENGTH/SEQUENCE: Functional liver MRI was performed on a 7T scanner using a respiratory-triggered multiecho spin-echo sequence. ASSESSMENT: Healthy control mice and mice with partial liver IRI on day 1 after surgery, and additionally on day 7 in a subgroup with 60 minutes IRI (n = 8) were examined. Maps of T2 relaxation time of liver tissue were used to assess distribution, severity of tissue edema (mean T2 time), and the percentage of edematous liver tissue. STATISTICAL TEST: One-way analysis of variance (ANOVA) with Tukey's honest significant difference (HSD), paired t-tests, Pearson's test for correlation of MRI parameters with levels of liver enzymes, and histopathology, receiver operating characteristic (ROC) analysis. RESULTS: Significant tissue edema induced by liver IRI as compared to the control group was detected by increased mean T2 times in groups with 60 minutes (P < 0.001) and 90 minutes IRI (P < 0.001). The percentage of edematous liver tissue significantly increased with longer ischemia times (controls 3.4 ± 0.4%, 35 minutes 5.3 ± 0.6%, 45 minutes 23.3 ± 7.6%, 60 minutes 39.7 ± 3.6%, 90 minutes 51.3 ± 4.5%). Mean T2 times and the percentage of edematous liver tissue significantly correlated with elevation of liver enzymes (P < 0.001), histological evidence of liver injury (r = 0.80 and r = 0.82, P < 0.001), and neutrophil infiltration (r = 0.70 and r = 0.74, P < 0.001). In the subgroup with follow-up, the severity (P < 0.01) and extent of liver edema decreased significantly over time (P < 0.01). DATA CONCLUSION: T2 mapping allows quantification and follow-up of liver injury in mice. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1586-1594.

Gd-EOB-DTPA-enhanced MRI for quantitative assessment of liver organ damage after partial hepatic ischaemia reperfusion injury: correlation with histology and serum biomarkers of liver cell injury.

OBJECTIVE: To evaluate Gd-EOB-DTPA-enhanced MRI for quantitative assessment of liver organ damage after hepatic ischaemia reperfusion injury (IRI) in mice. METHODS: Partial hepatic IRI was induced in C57Bl/6 mice (n = 31) for 35, 45, 60 and 90 min. Gd-EOB-DTPA-enhanced MRI was performed 1 day after surgery using a 3D-FLASH sequence. A subgroup of n = 9 animals with 60 min IRI underwent follow-up with MRI and histology 7 days after IRI. The total liver volume was determined by manual segmentation of the entire liver. The volume of functional, contrast-enhanced liver parenchyma was quantified by a region growing algorithm (visual threshold) and an automated segmentation (Otsu's method). The percentages of functional, contrast-enhanced and damaged non-enhanced parenchyma were calculated according to these volumes. MRI data was correlated with serum liver enzyme concentrations and histologically quantified organ damage using periodic acid-Schiff (PAS) staining. RESULTS: The percentage of functional (contrasted) liver parenchyma decreased significantly with increasing ischaemia times (control, 94.4 ± 3.3%; 35 min IRI, 89.3 ± 4.1%; 45 min IRI, 87.9 ± 3.3%; 60 min IRI, 68 ± 10.5%, p < 0.001 vs. control; 90 min IRI, 55.9 ± 11.5%, p < 0.001 vs. control). The percentage of non-contrasted liver parenchyma correlated with histologically quantified liver organ damage (r = 0.637, p < 0.01) and serum liver enzyme elevations (AST r = 0.577, p < 0.01; ALT r = 0.536, p < 0.05). Follow-up MRI visualized recovery of functional liver parenchyma (71.5 ± 8.7% vs. 84 ± 2.1%, p < 0.05), consistent with less histological organ damage on day 7. CONCLUSION: We demonstrated the feasibility of Gd-EOB-DTPA-enhanced MRI for non-invasive quantification of damaged liver parenchyma following IRI in mice. This novel methodology may refine the characterization of liver disease and could have application in future studies targeting liver organ damage. KEY POINTS: • Prolonged ischaemia times in partial liver IRI increase liver organ damage. • Gd-EOB-DTPA-enhanced MRI at hepatobiliary phase identifies damaged liver volume after hepatic IRI. • Damaged liver parenchyma quantified with MRI correlates with histological liver damage. • Hepatobiliary phase Gd-EOB-DTPA-enhanced MRI enables non-invasive assessment of recovery from liver injury.

Efficacy of pharmacological and interventional treatment for resistant hypertension: a network meta-analysis.

AIMS: Resistant hypertension is associated with a high risk of cardiovascular disease, chronic kidney disease, and mortality. Yet, its management is challenging. This study aims to establish the comparative effectiveness of pharmacologic and interventional treatments by conducting a network meta-analysis. METHODS AND RESULTS: MEDLINE, Cochrane Register of Controlled Trials, and Web of Science Core Collection were systematically searched in March 2022. Randomized controlled trials comparing treatment options for management of resistant hypertension were included. Outcomes were blood pressure (BP) changes, measured in the office and in 24 h ambulatory BP measurement. We applied a frequentist random effects model to perform a network meta-analysis combining placebo medication and sham procedure as the reference comparator. From 4771 records, 24 studies met the inclusion criteria with 3458 included patients in total. Twelve active treatment alternatives [spironolactone, doxazosin, ß-blocker, clonidine, darusentan, guanfacine, various types of renal sympathetic denervation, lifestyle intervention, continuous positive airway pressure, and baroreflex activation therapy (BAT)] were analysed. Among all comparators, spironolactone had the highest ranking probability and was considered the most effective treatment to reduce office systolic blood pressure (sBP) [-13.30 mmHg (-17.89; -8.72); P < 0.0001] and 24 h sBP [-8.46 mmHg (-12.54; -4.38); P < 0.0001] in patients with resistant hypertension. Lifestyle interventions were the most effective non-pharmacological treatment, lowering office sBP by -7.26 mmHg (-13.73; -0.8), whereas BAT lowered office sBP by -7.0 (-18.59; 4.59). Renal denervation lowered office sBP by -5.64 mmHg (-12.95; 1.66) and -3.79 mmHg (-11.39; 3.8) depending on the type of the procedure. CONCLUSION: Among all pharmacologic and interventional treatments, spironolactone is the most effective treatment in reducing BP in patients with resistant hypertension. More comparative trials and especially trials with long-term follow-up are needed. In the meanwhile, we have to conclude that a combination of spironolactone and lifestyle modification are the most effective treatments in resistant hypertension.

Treatment of diabetic kidney disease. A network meta-analysis.

BACKGROUND: Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis. METHODS: We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others. CONCLUSIONS: As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.

Much improved conditions for the Negishi cross-coupling of iodoalanine derived zinc reagents with aryl halides.

A combination of Pd(2)(dba)(3) and SPhos (1:2 molar ratio) is an excellent precatalyst for the Negishi cross-coupling of the serine-derived organozinc reagent 2 with aryl halides, including previously difficult ortho-substituted examples. In the case of meta- and para-substituted aryl halides, Pd-loadings of 0.5 mol % give satisfactory results. Use of 2-iodoaniline as substrate gives the lactam 12 in good yield.

Comparison of Multidetector Computed Tomography and Flat-Panel Computed Tomography Regarding Visualization of Cortical Fractures, Cortical Defects, and Orthopedic Screws: A Phantom Study.

To compare the visualization of cortical fractures, cortical defects, and orthopedic screws in a dedicated extremity flat-panel computed tomography (FPCT) scanner and a multidetector computed tomography (MDCT) scanner.We used feet of European roe deer as phantoms for cortical fractures, cortical defects, and implanted orthopedic screws. FPCT and MDCT scans were performed with equivalent dose settings. Six observers rated the scans according to number of fragments, size of defects, size of defects opposite orthopedic screws, and the length of different screws. The image quality regarding depiction of the cortical bone was assessed. The gold standard (real number of fragments) was evaluated by autopsy.The correlation of reader assessment of fragments, cortical defects, and screws with the gold standard was similar for FPCT and MDCT. Three readers rated the subjective image quality of the MDCT to be higher, whereas the others showed no preferences.Although the image quality was rated higher in the MDCT than in the FPCT by 3 out of 6 observers, both modalities proved to be comparable regarding the visualization of cortical fractures, cortical defects, and orthopedic screws and of use to musculoskeletal radiology regarding fracture detection and postsurgical evaluation in our experimental setting.

Comparing the image quality of a mobile flat-panel computed tomography and a multidetector computed tomography: a phantom study.

OBJECTIVES: The aim of this study was to compare the image quality of a compact mobile flat-panel computed tomography (FPCT) capable of extremity imaging and a multidetector computed tomography (MDCT) in examinations with the same radiation dose. MATERIAL AND METHODS: Imaging with the FPCT was performed with default settings. Monte Carlo simulations were used to calculate equivalent dose settings for the 320-row MDCT. Simulations were based on and validated by dose measurements. Homogeneity, geometric distortion, artifacts, accuracy of Hounsfield values, contrast, and spatial resolution were evaluated in different imaging phantoms. Whitney-Mann U Test and Spearman ρ were used for statistical analysis. RESULTS: Homogeneity reached 2.5% for the FPCT and 0.5% for the MDCT. Hounsfield values were more accurate and contrast to noise ratios were higher for the MDCT than the FPCT (P ≤ 0.001). The MDCT depicted more rod inserts than the FPCT did. No significant geometric distortion was detected in either modality. The FPCT was more prone to artifacts around Krischner wires with a diameter of 2 mm (P = 0.05-0.001), whereas the MDCT showed a higher amount of artifacts around wires with a diameter of 0.8 mm (P ≤ 0.001). Spatial resolution was 1 lp/mm (xy), 1.7 lp/mm (z) for the FPCT and 1 lp/mm (xy), less than 1 lp/mm (z) for the MDCT. CONCLUSIONS: We compared a mobile FPCT and a 320-row MDCT by using the same radiation dose for scans. We found the spatial resolution to be higher in the FPCT. Hounsfield units were more accurate and homogeneity and contrast resolution were better in MDCT. The MDCT was also less prone to artifacts from thick Kirschner wires but showed comparably more artifacts around thin wires.