Temporal Relationship and Clinical Outcomes of Acute Kidney Injury Following Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVES: Conduct a systematic review and meta-analysis to assess prevalence and timing of acute kidney injury (AKI) development after acute respiratory distress syndrome (ARDS) and its association with mortality. DATA SOURCES: Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO database, Scopus, and Web of Science thought April 2023. STUDY SELECTION: Titles and abstracts were screened independently and in duplicate to identify eligible studies. Randomized controlled trials and prospective or retrospective cohort studies reporting the development of AKI following ARDS were included. DATA EXTRACTION: Two reviewers independently extracted data using a pre piloted abstraction form. We used Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) and Open Meta software (Brown University, Providence, RI) for statistical analyses. DATA SYNTHESIS: Among the 3646 studies identified and screened, 17 studies comprising 9359 ARDS patients met the eligibility criteria and were included in the meta-analysis. AKI developed in 3287 patients (40%) after the diagnosis of ARDS. The incidence of AKI at least 48 hours after ARDS diagnosis was 20% (95% CI, 0.18-0.21%). The pooled risk ratio (RR) for the hospital (or 30-d) mortality among ARDS patients who developed AKI was 1.93 (95% CI, 1.71-2.18). AKI development after ARDS was identified as an independent risk factor for mortality in ARDS patients, with a pooled odds ratio from multivariable analysis of 3.69 (95% CI, 2.24-6.09). Furthermore, two studies comparing mortality between patients with late vs. early AKI initiation after ARDS revealed higher mortality in late AKI patients with RR of 1.46 (95% CI, 1.19-1.8). However, the certainty of evidence for most outcomes was low to very low. CONCLUSIONS: While our findings highlight a significant association between ARDS and subsequent development of AKI, the low to very low certainty of evidence underscores the need for cautious interpretation. This systematic review identified a significant knowledge gap, necessitating further research to establish a more definitive understanding of this relationship and its clinical implications.

Acetazolamide for acute kidney injury in patients undergoing high dose methotrexate therapy: a systematic review and meta-analysis.

BACKGROUND: Urine alkalization is one of the standard treatments to prevent acute kidney injury in patients receiving high-dose methotrexate. Carbonic anhydrase inhibitors are promising adjuvants/substitutes with advantages such as faster urine alkalization time and prevention of fluid overload. However, there is limited and contradictory evidence on its efficacy and safety. We aimed to compare the efficacy and safety of carbonic anhydrase inhibitors to standard treatments in adult patients receiving high-dose methotrexate. METHODS: The protocol was registered at PROSPERO (CRD42022352802) in August 2021. We evaluated the use of carbonic anhydrase inhibitors in combination with standard treatment compared to standard treatment alone. We excluded articles irrelevant to the efficacy and safety of acetazolamide in patients receiving high dose methotrexate and/or did not provide sufficient data regarding doses, recruitment criteria, and follow-up period. Two authors performed the data extraction independently. RESULTS: Among 198 articles retrieved, six observational studies met all eligibility criteria. Four studies with five datasets (totaling 558 patients/cycles) had enough data to be included in the meta-analysis. We independently report the results from the two remaining studies. The results did not show a significant difference between acetazolamide versus standard treatment in acute kidney injury (AKI) rate (OR = 0.79, 95% CI 0.48-1.29, P = 0.34, I2 = 0%). Regarding the time to urine pH goal, there was no significant time difference between the two groups (Mean Difference = 0.07, 95% CI - 1.9 to 2.04, P = 0.95, I2 = 25%). Furthermore, our meta-analysis showed that acetazolamide did not reduce length of stay (Mean Difference = 0.75, 95% CI - 0.8 to 2.31, P = 0.34, I2 = 0%). In one study, the only reported side effect of acetazolamide was hypokalemia (nearly 50% in the acetazolamide group). CONCLUSIONS: This systematic review showed no significant difference between acetazolamide and standard care treatment regarding urine alkalinization time and AKI rate in adult patients receiving high dose methotrexate. We suggest performing a large blinded, randomized, controlled trial to evaluate the potential benefits of this low-cost medication.

The Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Diagnosing Pneumocystis Pneumonia: A Systemic Review and Meta-analysis.

Background: Pneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests' performance in detecting PCP. Methods: Five databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used. Results: Eleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90-0.99), and specificity was 0.96 (95% CI, 0.92-0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01-0.05) and 19.31 (95% CI, 10.26-36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78-0.99) and 0.93 (95% CI, 0.80-0.98) and a specificity of 0.96 (95% CI, 0.88-0.99) and 0.98 (95% CI, 0.76-1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90-0.98) and 0.94 (95% CI, 0.84-0.98), respectively. The overall confidence in the estimates was low. Conclusions: Despite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

Synthesis by deamination reaction and crystal structure at 120†K of (16Z,19E)-18-oxo-N-(pyridin-2-yl)-6,7,9,10-tetra-hydro-18H-dibenzo[h,o][1,4,7]trioxa-cyclo-hexa-decine-17-carboxamide.

The title compound, C27H24N2O5, is a product of the deamination reaction from aza-14-crown-4 ether containing the γ-piperidone subunit. The title mol-ecule contains a 16-membered macrocycle with the conformation of the C-O-C-C-O-C-C-O-C polyether chain being t-g (-)-t-t-g (+)-t (t = trans, 180°; g = gauche, ±60°). The dihedral angle between the planes of the benzene rings fused to the aza-14-crown-4-ether moiety is 31.11 (14)°. The cavity size inside the macrocycle is 4.72 Å. The macrocycle is significantly flattened as a result of the extended conjugated system. Steric repulsion between the pyridyl-carboxamide fragment and the benzene ring results in a slight deviation of macrocycle from planarity. The structure also features intra-molecular hydrogen bonding, which results in a deviation of the angle between the planes of amide and pyridyl groups from planarity: this angle is 16.32 (18)°. In the crystal, the mol-ecules are linked into infinite zigzag chains via inter-molecular C-H⋯π contacts. The chains are bound into layers parallel to (100) by weak inter-molecular C-H⋯O hydrogen bonds.

Unexpected synthesis and crystal structure of N-{2-[2-(2-acetyl-ethen-yl)phen-oxy]eth-yl}-N-ethenyl-4-methyl-benzene-sulfonamide.

The title compound, C21H23NO4S, obtained by alkaline treatment of 1,5-bis-(1-phen-oxy)-3-aza-pentane at moderate heating, is a N-tosyl-ated secondary vinyl-amine. An intra-molecular S=O⋯H-C hydrogen bond generates a 13-membered ring. The benzalacetone moiety adopts a trans conformation with respect to the C=C double bond, which is slightly longer than usual due to the conjugation with a neighbouring acetyl group. Theoretical predictions of potential biological activities were performed, suggesting that the title compound can inhibit gluconate 2-de-hydrogenase (85% probability), as well as to act as a mucomembranous protector (73%).

One-pot synthesis of (1RS,21SR)-diethyl 2-[23-amino-22-eth-oxy-carbonyl-8,11,14-trioxa-25-aza-tetra-cyclo-[19.3.1.02,7.015,20]penta-cosa-2,4,6,15(20),16,18,22-heptaen-25-yl]but-2-endioate.

The title compound, C30H34N2O9 (4), is a product of the Michael reaction of aza-crown ether with dimethyl acetyl-enedi-carboxyl-ate modified by an addition of NH3 (aq.) at 298 K. The aza-14-crown-4-ether ring adopts a bowl conformation. The dihedral angle between the planes of the benzene rings fused to the aza-14-crown-4-ether moiety is 8.65 (5)°. The tetra-hydro-pyridine ring has a boat conformation. The mol-ecular conformation is supported by one N-H⋯O and two C-H⋯O intra-molecular hydrogen bonds. Both heterocyclic and amino N atoms have essentially planar configurations (sums of the bond angles are 359.35 and 358.00°). Compound 4 crystallizes as a racemate consisting of enanti-omeric pairs of the 1R,21S diastereomer. In the crystal, mol-ecules of 4 are connected by N-H⋯O hydrogen bonds, forming chains along [100]. According to the PASS program (computer prediction of biological activities), compound 4 may exhibit anti-allergic (72% probability) and anti-asthmatic (67%) activity, as well as be a membrane permeability inhibitor (65%).

Crystal structure of 22,24,25-trimethyl-8,11,14-trioxa-25-aza-tetra-cyclo-[19.3.1.02,7.015,20]penta-cosa-2,4,6,15(20),16,18-hexaen-23-one.

The title compound, C24H29NO4, is the product of a Petrenko-Kritchenko condensation of 1,5-bis-(2-formyl-phen-oxy)-3-oxa-pentane, pentan-3-one and methyl-ammonium acetate in ethanol. The mol-ecule has mirror symmetry. The aza-14-crown-3 ether ring adopts a bowl conformation stabilized by a weak intra-molecular C-H⋯O hydrogen bond. The conformation of the C-O-C-C-O-C-C-O-C polyether chain is t-g+-t-t-g--t (t = trans, 180°; g = gauche, ±60°). The dihedral angle between the benzene rings fused to the aza-14-crown-4-ether moiety is 72.68 (4)°. The piperidinone ring adopts a chair conformation. The nitro-gen atom has a trigonal-pyramidal geometry, the sum of the bond angles being 335.9°. In the crystal, the mol-ecules are linked by weak C-H⋯O inter-actions, forming zigzag chains propagating along the [100] direction.

Crystal structure of 26-(4-methyl-phen-yl)-8,11,14,17-tetra-oxa-28-aza-tetra-cyclo[22.3.1.0(2,7).0(18,23)]hexa-cosa-2,4,6,18(23),19,21,24(1),25,27-nona-ene.

The title compound, C30H29NO4, is a tetra-cyclic system containing a 4-aryl-pyridine fragment, two benzene rings and an aza-17-crown-5 ether moiety, in a bowl-like arrangement. The pyridine ring is inclined to the 4-methyl-phenyl ring by 26.64 (6)°, and by 57.43 (6) and 56.81 (6)° to the benzene rings. The benzene rings are inclined to one another by 88.32 (6)°. In the crystal, mol-ecules are linked by pairs of C-H⋯N hydrogen bonds, forming inversion dimers with an R 2 (2)(14) ring motif. The dimers are linked via a number of C-H⋯π inter-actions, forming a three-dimensional architecture.