Citations

The immune system’s response to an invading pathogen is the critical determinant in recovery from illness. Here, we hypothesize that the immune response will swiftly follow classical activation and a resolution trajectory in patients with the rapid evolution of symptoms if challenged by a viral pathogen for the first time. Alternatively, a dysregulated response will be signified by a protracted clinical trajectory. Consequently, we enrolled 106 patients during the first wave of COVID-19 and collected their blood within 24 h, 48 h, 7 days, and over 28 days from symptoms onset. The pathogenic burden was measured via serum levels of the S-spike protein and specific immunoglobulin titers against the S and N proteins of SARS-CoV-2. The nonspecific immunological response was gauged using interleukin 6, leukocytosis, and C-reactive protein. Coagulation status was assessed. Several serum biomarkers were used as surrogates of clinical outcomes. We identified four clusters depending on the onset of symptoms (immediate [A], 6 days [B], 12 days [C], and over 21 days [D]). High variability in the S-spike protein in cluster A was present. The corresponding immunoglobulin titer was random. Only procalcitonin differentiated clusters in terms of markers of nonspecific inflammation. Coagulation markers were not significantly different between clusters. Serum surrogates on cardiomyopathy and neuronal pathology exhibited significant variability. Implementation of ECMO or noninvasive ventilation was more prominent in cluster C and D. Interestingly, SOFA or APACHE II scores were not different between nominal (A and B) versus dysregulated clusters (C and D).

Advances in prenatal diagnostics, imaging, and surgical techniques have accelerated maternal-fetal interventions (MFI), fetal care centers, and expanded options for families. Progress in this field has also raised ethical issues surrounding maternal autonomy, informed consent and decision-making, innovation versus research, equitable access, and disability and reproductive rights. We review ethical frameworks to evaluate MFIs, from innovation to research and, ideally, clinical practice. Necessary oversight and resources are summarized to promote ethical, equitable innovation and research while protecting maternal autonomy and supporting the informed consent and decision-making process. Additional implications amidst abortion restrictions are discussed, along with areas for future research.

Background Mechanical thrombectomy (MT) is established as an effective treatment for large vessel occlusion strokes, but its efficacy and safety for medium vessel occlusions (MeVOs) remain less clear. This study examines the impact of periprocedural embolization to a new vascular territory (ENT) on clinical outcomes in patients with MeVO stroke treated with MT. Methods A multicenter, retrospective analysis was conducted using the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry, including 2122 patients with MeVO stroke w­ho underwent MT between September 2017 and July 2023. ENT was defined as filling defects in previously unaffected territories, excluding embolization near the original occlusion, observed on final angiographic runs after retrieval of the primary thrombus. The associations between ENT, procedural variables, and 90-day clinical outcomes were evaluated, including functional independence (modified Rankin Scale (mRS) scores of 0–2), excellent outcomes (mRS 0–1), mortality, and hemorrhagic complications. Results ENT occurred in 2.9% (63/2122) of patients. Longer onset-to-arterial puncture time (adjusted OR 1.03; 95% CI 1.01 to 1.05; P=0.002) and a greater number of passes (adjusted OR 1.15; 95% CI 1.01 to 1.32; P=0.032) were associated with increased ENT risk, while excellent recanalization (thrombolysis in cerebral infarction (TICI) scale score 2c–3) was associated with reduced ENT risk (adjusted OR 0.41; 95% CI 0.23 to 0.72; P=0.002). ENT was not associated with poorer functional independence, mortality, or hemorrhagic complications. Conclusions ENT during MT for MeVO stroke occurs infrequently and does not significantly affect the clinical outcomes. These findings suggest ENT risk should not deter clinicians from performing MT in patients with MeVO. Further prospective studies are needed to validate these results.

When one initially targets the null effect and the point estimate falls close to the null, two challenges exist in rating certainty of evidence. First, when the point estimate is near the null and the data, therefore, suggests little or no effect, rating certainty in a benefit or harm is misleading. Second, since in general the narrower the confidence interval (CI) the more precise the estimate, if the CI is narrow, rating down for imprecision due simply to crossing the null is inappropriate. This paper addresses these issues and provides a solution: to revise the target of certainty rating from a non-zero effect to a little or no effect. This solution requires estimating a range in which the minimal important difference (MID) for benefit and an MID for harm might lie, and thus establishing a range that represents little or no effect. If GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) users are confident that the point estimate represents an effect less than the smallest plausible MID, they will revise their target and rate certainty to a little or no effect. If the entire CI falls within the range of little or no effect, they will not rate down for imprecision. Otherwise (if the CI includes an important effect), they will rate down. Using the solution provided in this paper GRADE users can make an optimal choice of the target of certainty rating.

Key Points Nonimmunologic AKI-related rehospitalizations post–kidney transplant are associated with poorer long-term allograft and recipient outcomes. These data are not reported to United Network for Organ Sharing, and there are no datasets highlighting this important association; thus, our findings are valuable to clinicians. We hope to help the community create a cohort of higher risk transplant patients who need closer monitoring to potentially increase graft longevity Background AKI is associated with an increased risk of CKD and ESKD. However, only limited studies have investigated the effect of AKI episodes on kidney transplant outcomes. This study evaluated the effect of rehospitalization associated with nonimmunologic AKI on long-term outcomes. Data on rehospitalization with AKI after kidney transplant are not reported to United Network for Organ Sharing, and thus, there are no large datasets available to study this association. Methods We completed chart reviews of 989 deceased donor kidney transplant recipients transplanted from 2010 to 2014 at 13 transplant centers in the Deceased Donor Study Consortium. Rehospitalizations up to 5 years post-transplant were included. The cause of rehospitalizations was adjudicated by a transplant nephrologist on the basis of the discharge diagnosis. Primary outcomes were the effect of AKI-related rehospitalization on death-censored graft failure and all-cause mortality. We excluded rehospitalizations because of acute rejection from the primary analysis. The cohort was linked to data from Organ Procurement and Transplantation Network supplied by United Network for Organ Sharing. Time-varying cox-proportional hazard models were used to examine the association between rehospitalization and outcomes. Results We identified 200 (20%) recipients with at least one rehospitalization associated with AKI, 516 (52%) with rehospitalizations without AKI, and 273 (28%) without a rehospitalization post-transplant. Delayed graft function, donor age, and kidney donor profile index score differed between the three groups. We found a higher risk of death censored graft failure adjusted hazard ratio (aHR) 7.5 (95% confidence interval [CI], 4.0 to 13.8), all-cause graft failure aHR 6.7 (95% CI, 4.2 to 10.8), and all-cause mortality aHR 5.7 (95% CI, 2.7 to 11.8) for rehospitalizations associated with AKI compared with no rehospitalization. The non-AKI rehospitalizations also had significantly higher rates of measured outcomes; however, the associations were not as strong. Conclusions AKI rehospitalizations were associated with a significantly increased risk of poorer graft outcomes, and thus, closer follow-up of this high-risk group is warranted.