The impact on thirty day readmissions for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease admitted to an observation unit versus an inpatient medical unit: A retrospective observational study.

OBJECTIVES: We aimed to evaluate the utility of an Observation Unit (OU) in management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and to identify the clinical characteristics of patients readmitted within 30-days for AECOPD following index admission to the OU or inpatient floor from the OU. METHODS: This is a retrospective observational study of patients admitted from January to December 2017 for AECOPD to an OU in an urban-based tertiary care hospital. Primary outcome was rate of 30-day readmission after admission for AECOPD for patients discharged from the OU versus inpatient service after failing OU management. Regression analyses were used to define risk factors. RESULTS: 163 OU encounters from 92 unique patients were included. There was a lower readmission rate (33%) for patients converted from OU to inpatient care versus patients readmitted after direct discharge from the OU (44%). Patients with 30-day readmissions were more likely to be undomiciled, with history of congestive heart failure (CHF), pulmonary embolism (PE), or had previous admissions for AECOPD. Patients with >6 annual OU visits for AECOPD had higher rates of substance abuse, psychiatric diagnosis, and prior PE; when these patients were excluded, the 30-day readmission rate decreased to 13.5%. CONCLUSION: Patients admitted for AECOPD with a history of PE, CHF, prior AECOPD admissions, and socioeconomic deprivation are at higher risk of readmission and should be prioritized for direct inpatient admission. Further prospective studies should be conducted to determine the clinical impact of this approach on readmission rates.

Anti-aquaporin-4 immune complex stimulates complement-dependent Th17 cytokine release in neuromyelitis optica spectrum disorders.

Proinflammatory cytokines, such as (IL: interleukin) IL-6 and IL-17A, and complement fixation are critical in the immunopathogenesis of neuromyelitis optica spectrum disorders (NMOSD). Blocking the IL-6 receptor or the C5 complement pathway reduces relapse risk. However, the role of interleukin (IL)-6 and complement in aquaporin-4 (AQP4) autoimmunity remains unclear. To investigate the role of the anti-AQP4 immunoglobulin (AQP4-IgG)/AQP4 immunocomplex on the induction and profile of ex vivo cytokine and surface marker expression in peripheral blood mononuclear cells (PBMC) culture. Isolated PBMCs obtained from 18 patients with AQP4-IgG-seropositive-NMOSD (8 treatment-naive, 10 rituximab-treated) or ten healthy controls were cultured with AQP4-immunocomplex with or without complement. Changes in PBMC surface markers and cytokine expression were profiled using flow cytometry and ELISA. PBMCs derived from treatment-naive NMOSD patients stimulated with a complex mixture of serum complement proteins produced significant elevations of IL-17A and IL-6. Rituximab-treated patients also exhibited higher IL-6 but not IL-17A release. IL-6 and IL-17A elevations are not observed without complement. Co-stimulation of PBMCs with AQP4-IgG/AQP4 immunocomplex and complement prompts a Th17-biased response consistent with the inflammatory paradigm observed in NMOSD. A possible inflammation model is proposed via antigen-specific autoreactive peripheral blood cells, including NK/NKT cells.

Biometric magnetic resonance imaging analysis of fetal brain development in Down syndrome.

OBJECTIVES: To assess brain development in living fetuses with Down syndrome (DS) by biometric measurements on fetal brain magnetic resonance images (MRI). METHODS: We scanned 10 MRIs of fetuses with confirmed trisomy 21 at birth and 12 control fetal MRIs without any detected anomalies. Fetal brain MRIs were analyzed using 14 fetal brain and skull biometric parameters. We compared measures between DS and controls in both raw MRIs and motion-corrected and anterior-posterior commissure-aligned images. RESULTS: In the reconstructed images, the measured values of the height of the cerebellar vermis (HV) and anteroposterior diameter of the cerebellar vermis (APDV) were significantly smaller, and the anteroposterior diameter of the fourth ventricle (APDF) was significantly larger in fetuses with DS than controls. In the raw MRIs, the measured values of the right lateral ventricle were significantly larger in fetuses with DS than in controls. Logistic regression analyses revealed that a new parameter, the cerebellar-to-fourth-ventricle ratio (i.e., (APDV * Height of the vermis)/APDF), was significantly smaller in fetuses with DS than controls and was the most predictive to distinguish between fetuses with DS and controls. CONCLUSIONS: The study revealed that fetuses with DS have smaller cerebellums and larger fourth ventricles compared to the controls.

Vascular access for transcatheter aortic valve replacement: A network meta-analysis.

BACKGROUND: The choice of an alternative access for transcatheter aortic valve replacement (TAVR) remains controversial when transfemoral (TF) access is not feasible. METHODS: We conducted a network meta-analysis to compare the outcomes of TAVR via various peripheral vascular accesses. MEDLINE and EMBASE were searched through July 2022 to identify studies that investigated outcomes in patients who underwent TAVR via TF, trans-subclavian (Tsc), transcarotid (TC), or transcaval (Tcav) access. A network meta-analysis was conducted via random-effects model. Outcomes of interest were major or life-threatening bleeding, stroke, major vascular complication, and 30-day mortality. RESULTS: No randomized trial was identified. Our analysis included 33 observational studies that enrolled a total of 43,455 patients who underwent TAVR via TF (n = 36,202), Tsc (n = 3869), TC (n = 3066), or Tcav (n = 318) access. The risk of major or life-threatening bleeding was higher via Tsc compared with TF [odds ratio (OR); 95 % confidence interval (CI) =1.51 (1.03-2.23), p = 0.034]. The risk of stroke was higher via Tsc compared with TF and Tcav [OR (95 % CI) =2.00 (1.14-3.52), p = 0.018, OR (95 % CI) =2.43 (1.03-5.74), p = 0.044, respectively]. The risk of major vascular complications was lower via TC compared with Tsc, and Tcav and higher with Tcav compared with TF and Tsc. 30-day mortality was higher via Tsc compared with TF. Tsc was associated with higher risk of major or life-threatening bleeding compared with TF, and higher risk of stroke compared to TF and Tcav. Tcav had the highest risk of major vascular complications. CONCLUSION: In patients who underwent TF, Tsc, TC, or Tcav TAVR, Tsc had a higher rate of stroke compared to TF and Tcav, and major or life-threatening bleeding compared to TF. The rate of major vascular complications in Tcav was the highest among the four approaches.

Outcomes of Simultaneous Heart and Kidney Transplantation.

BACKGROUND: Simultaneous heart-kidney transplantation has been increasingly performed in end-stage heart failure patients with concurrent kidney dysfunction despite limited evidence supporting its indications and utility. OBJECTIVES: The purpose of this study was to investigate the effects and utility of simultaneously implanted kidney allografts with various degrees of kidney dysfunction during heart transplantation. METHODS: Using the United Network for Organ Sharing registry, long-term mortality was compared in recipients with kidney dysfunction who underwent heart-kidney transplantation (n = 1,124) vs isolated heart transplantation (n = 12,415) in the United States between 2005 and 2018. In heart-kidney recipients, contralateral kidney recipients were compared for allograft loss. Multivariable Cox regression was used for risk adjustment. RESULTS: Long-term mortality was lower among heart-kidney recipients than among heart-alone recipients when recipients were on dialysis (26.7% vs 38.6% at 5 years; HR: 0.72; 95% CI: 0.58-0.89) or had a glomerular filtration rate (GFR) of <30 mL/min/1.73 m2 (19.3% vs 32.4%; HR: 0.62; 95% CI: 0.46-0.82) and GFR of 30 to 45 mL/min/1.73 m2 (16.2% vs 24.3%; HR: 0.68; 95% CI: 0.48-0.97) but not in GFR of 45 to 60 mL/min/1.73 m2. Interaction analysis showed that the mortality benefit of heart-kidney transplantation continued up to GFR 40 mL/min/1.73 m2. The incidence of kidney allograft loss was higher among heart-kidney recipients than among contralateral kidney recipients (14.7% vs 4.5% at 1 year; HR: 1.7; 95% CI: 1.4-2.1). CONCLUSIONS: Heart-kidney transplantation relative to heart transplantation alone provided superior survival for dialysis-dependent recipients and non-dialysis-dependent recipients up to a GFR of approximately 40 mL/min/1.73 m2 but at the cost of almost twice the risk of kidney allograft loss than contralateral kidney allograft recipients.

Effect of cooling methods and target temperature on outcomes in comatose patients resuscitated from cardiac arrest: Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Targeted temperature management (TTM) has been recommended after cardiac arrest (CA), however the specific temperature targets and cooling methods (intravascular cooling (IVC) versus surface cooling (SC)) remain uncertain. METHODS: PUBMED and EMBASE were searched until October 8, 2022 for randomized clinical trials (RCTs) investigating the efficacy of TTM after CA. The randomized treatment arms were categorized into the following 6 groups: 31..C to 33..C IVC, 31..C to 33..C SC, 34..C to 36..C IVC, 34..C to 36..C SC, strict normothermia or fever prevention (Strict NT or FP), and standard of care without TTM (No-TTM). The primary outcome was neurological recovery. P-score was used to rank the treatments, where a larger value indicates better performance. RESULTS: We identified 15 RCTs, involving 5,218 patients with CA. Compared to No-TTM as the reference, the other therapeutic options significantly improved neurological outcomes (vs No-TTM; 31..C to 33.. C IVC: RR = 0.67, 95% CI 0.54 to 0.83; 31..C to 33..C SC RR = 0.73, 95% CI 0.61 to 0.87; 34..C to 36.. C IVC: RR = 0.66, 95% CI 0.51 to 0.86; 34..C to 36..C SC: RR = 0.73, 0.59 to 0.90; Strict NT or FP: RR = 0.75, 95% CI 0.62 to 0.90). Overall, 31-33..C IVC had the highest probability to be the best therapeutic option to improve outcomes (the ranking P-score of 0.836). As a subgroup analysis, the ranking P-score showed that IVC might be a better cooling method compared to SC (IVC vs SC P-score: 0.960 vs 0.670). CONCLUSIONS: Hypothermia (31..C to 36..C IVC and SC) and active normothermia (Strict-NT and Strict-FP) were associated with better neurological outcomes compared to No-TTM, with IVC having a greater probability of being the better cooling method than SC.

Characterization of Immune Checkpoint Inhibitor-Induced Myasthenia Gravis Using the US Food and Drug Administration Adverse Event Reporting System.

Myasthenia gravis (MG) is a rare but fatal adverse event of immune checkpoint inhibitors (ICIs). We assessed whether patient characteristics differed between those with ICI-related myasthenia gravis and those with idiopathic myasthenia gravis. Reports from the US Food and Drug Administration Adverse Event Reporting System were analyzed. Multivariate analyses were conducted to evaluate the associations between age, sex, and ICI treatment and the reporting rate of myasthenia gravis. Among 5 464 099 cases between 2011 and 2019, 53 447 were treated with ICIs. Myasthenia gravis was reported more often in ICI users. Multiple logistic regression analyses showed that the reporting rate of ICI-related myasthenia gravis did not differ significantly between men and women; however, it was higher in older people than in younger people (adjusted odds ratio, 2.4 [95%CI, 1.84-3.13]). We also investigated useful signs for the early detection of myositis and myocarditis, which are fatal when overlapping with ICI-related myasthenia gravis. Patients with elevated serum creatine kinase or troponin levels were more likely to have concurrent myositis and myocarditis. Unlike idiopathic myasthenia gravis, there was no sex difference in the development of ICI-related myasthenia gravis, which may be more common in older people. Considering the physiological muscle weakness that occurs in the elderly, it may be necessary to monitor ICI-related myasthenia gravis more closely in older people.

Impact of time from symptom onset to operation on outcome of repair of acute type A aortic dissection with malperfusion.

OBJECTIVES: We analyzed patients with acute type A aortic dissection complicated by malperfusion syndrome to establish whether the timing of operative treatment and the location of malperfusion are factors in determining outcomes. METHODS: A total of 331 patients with acute type A aortic dissection were treated surgically between August 2003 and May 2019. Eighty-four patients (25%) presented with preoperative malperfusion syndrome. Fifty-eight patients with malperfusion syndrome (69%) were transferred to the operating room within 5 hours of the onset of symptoms (immediate repair); 26 patients (31%) were transferred after 5 hours (later repair). We analyzed the effects of immediate aortic repair on surgical outcomes. RESULTS: There was no significant difference in the early mortality rates between patients with immediate and later aortic repair, which were 20.0% (n = 11/58) and 26.9% (n = 7/19), respectively (P = .12). Preoperative coronary malperfusion was the only predictor of early mortality. The cumulative 5-year survivals of patients with malperfusion syndrome in the immediate and later repair groups were 76.7% and 45.4%, respectively. A significant difference was noted in the long-term outcomes between the 2 groups (P = .02). On multivariable Cox survival analysis, coronary malperfusion and shock on arrival were associated with increased long-term mortality (P < .01 and P = .04). Conducting surgery within 5 hours of the onset of symptoms was a significant predictor of favorable long-term outcome (P = .03). CONCLUSIONS: Although preoperative coronary malperfusion and shock on arrival worsened the long-term outcomes in patients undergoing aortic repair for acute type A aortic dissection with preoperative malperfusion syndrome, conducting an operation within 5 hours of the onset of symptoms significantly improved their long-term outcomes.

Upregulated complement receptors correlate with Fc gamma receptor 3A-positive natural killer and natural killer-T cells in neuromyelitis optica spectrum disorder.

BACKGROUND AND OBJECTIVES: Inhibition of terminal complement in neuromyelitis optica spectrum disorder (NMOSD) using eculizumab helps prevent relapses, but the exact mechanism of action of the drug remains unclear. Similarly, genetic variants in the Fc Gamma receptor 3A (FCGR3A), also known as CD16, are correlated with outcomes in NMOSD, but the immune cells expressing those CD16 are unknown. We compared CD16 expression on immune cells modulated by complement activity in natural killer (NK) cells and natural killer-T (NKT) cells in NMOSD to disease and normal-healthy controls. METHODS: Peripheral blood cell (PBMC) samples from 45 patients with NMOSD with aquaporin 4 (AQP4)-IgG, 18 disease controls, and 19 normal controls were analyzed for CD16 expression and complement receptors in vitro. RESULTS: At baseline, the number of NKT cells was increased in NMOSD (p < 0.001), but the proportion that was CD16 positive was lower compared to normal and disease controls (p = 0.0012). NK cell count was normal, but the ratio that was CD16 positive was also significantly lower (p < 0.001). In both NK cells and NKT cells from NMOSD, C5 complement receptor expression was much higher than normal and disease controls (p < 0.001 for both). We also evaluated activation markers CD69 and CD83, which were also significantly higher in NK and NKT cells from NMOSD patients. FCGR3A p158 V/V genotype group in NMOSD patients showed decreased NK cell proportion with activation, and fewer CD16-expressing NKT cells than the F/F genotype group. DISCUSSION: Our results support an immunopathogenesis model in which complement pathway activation in NK/NKT cells upregulates CD16 expression that binds to antibody/antigen complexes. In the context of NMOSD, these complement-sensitive cells may be responsible for the escalating autoimmune activity.

Mechanical Thrombectomy and Intravenous Thrombolysis in Patients with Acute Stroke: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: The benefit and risk of administration of tissue plasminogen activator (tPA) before endovascular mechanical thrombectomy (E-MT) in acute stroke has been actively debated. We therefore aimed to investigate the efficacy and safety of three therapeutic strategies for acute stroke: direct E-MT, E-MT with pre-administration of tPA, and tPA alone with a network meta-analysis. MATERIALS AND METHODS: PUBMED and EMBASE were searched from September to November 2021 for randomized control trials that compared direct E-MT, E-MT with tPA, and tPA alone therapies in acute stroke. The primary outcome was functional independence, defined as modified Rankin Scale score of 0-2, at 90 days. All-cause mortality, symptomatic intracranial hemorrhage, and successful revascularization were also evaluated. RESULTS: We identified 11 randomized controlled trials with a total of 3,640 patients with acute stroke. Compared to E-MT with tPA, direct E-MT provided comparable outcomes regarding functional independence (relative risk (RR): 1.02; 95% confidence interval (CI): 0.88-1.19, I2 = 36.6%) and all-cause mortality (RR: 1.05; 95% CI: 0.85-1.31, I2 = 0%). The incidence of symptomatic intracranial hemorrhage was not significantly different between direct E-MT and E-MT with tPA (RR: 0.83; 95% CI: 0.57-1.20, I2 = 0%). Direct E-MT had favorable functional independence (RR: 1.41; 95% CI: 1.15-1.74, I2 = 36.6%) and higher successful revascularization rate (RR: 1.60; 95% CI: 1.33-1.93, I2 = 61.2%) than tPA alone. CONCLUSIONS: Direct E-MT alone led to acceptable outcomes even in comparison to E-MT with tPA, whereas additional tPA did not cause higher risk of symptomatic intracranial hemorrhage.

Association of Donor Brain Death Due to Stroke With Prognosis After Heart Transplantation.

BACKGROUND: The proximate cause of donor brain death is not considered a conventional risk factor in modern heart transplantation. OBJECTIVES: This study aimed to investigate the effect of the cause of donor brain death on recipients. METHODS: Using the United Network for Organ Sharing registry, long-term mortality and allograft failure were compared in recipients who underwent heart transplantation in the United States from 2005 through 2018 between allograft recipients from donors with stroke as the cause of brain death (n = 3,761) vs nonstroke causes (n = 14,677). Inverse probability weighting was used for risk adjustment. Interactions were investigated between the cause of brain death and other conventional donor risk factors for recipient mortality. RESULTS: There was an interaction between the cause of brain death and donor age (Pinteraction = 0.008). When allografts were procured from donors aged 40 years or younger, stroke as the cause of brain death was associated with an increased risk of mortality (23% vs 19% at 5 years; HR: 1.17; 95% CI: 1.02-1.35) and allograft failure (HR: 1.30; 95% CI: 1.04-1.63). When donors were older than 40 years, the cause of brain death was not associated with outcomes. CONCLUSIONS: As the cause of donor brain death, stroke had a substantially different effect on recipient and allograft survival depending on donor age. In the case of younger donor ages, stroke was associated with higher recipient mortality and allograft failure than other causes of brain death. The strength of this association decreased with increasing donor age such that the increased hazard was no longer present in donors older than approximately 40 years.

Machine learning prediction model of acute kidney injury after percutaneous coronary intervention.

Acute kidney injury (AKI) after percutaneous coronary intervention (PCI) is associated with a significant risk of morbidity and mortality. The traditional risk model provided by the National Cardiovascular Data Registry (NCDR) is useful for predicting the preprocedural risk of AKI, although the scoring system requires a number of clinical contents. We sought to examine whether machine learning (ML) techniques could predict AKI with fewer NCDR-AKI risk model variables within a comparable PCI database in Japan. We evaluated 19,222 consecutive patients undergoing PCI between 2008 and 2019 in a Japanese multicenter registry. AKI was defined as an absolute or a relative increase in serum creatinine of 0.3 mg/dL or 50%. The data were split into training (N = 16,644; 2008-2017) and testing datasets (N = 2578; 2017-2019). The area under the curve (AUC) was calculated using the light gradient boosting model (GBM) with selected variables by Lasso and SHapley Additive exPlanations (SHAP) methods among 12 traditional variables, excluding the use of an intra-aortic balloon pump, since its use was considered operator-dependent. The incidence of AKI was 9.4% in the cohort. Lasso and SHAP methods demonstrated that seven variables (age, eGFR, preprocedural hemoglobin, ST-elevation myocardial infarction, non-ST-elevation myocardial infarction/unstable angina, heart failure symptoms, and cardiogenic shock) were pertinent. AUC calculated by the light GBM with seven variables had a performance similar to that of the conventional logistic regression prediction model that included 12 variables (light GBM, AUC [training/testing datasets]: 0.779/0.772; logistic regression, AUC [training/testing datasets]: 0.797/0.755). The AKI risk model after PCI using ML enabled adequate risk quantification with fewer variables. ML techniques may aid in enhancing the international use of validated risk models.

Neuroimmunological adverse events associated with immune checkpoint inhibitor: a retrospective, pharmacovigilance study using FAERS database.

PURPOSE: To investigate the characteristics and risk factors for neurologic adverse events (AEs) induced by immune checkpoint inhibitors (ICIs). METHODS: An observational, retrospective, and pharmacovigilance study based on the FAERS database collected between January 2014 and December 2019 was conducted. ICI-related AEs were defined as adverse reactions in patients using anti-PD-1 (nivolumab and pembrolizumab), anti-PD-L1 (atezolizumab, avelumab, and durvalumab), and anti-CTLA-4 (ipilimumab and tremelimumab). Neurologic AEs previously reported to be associated with ICI were evaluated in the disproportionality analysis using the reporting odds ratio (ROR). RESULTS: Among 50,406 ICI-related reports, 3619 (7.2%) neurological case was found: 1985 with anti-PD-1, 372 with anti-PD-L1, 366 with anti-CTLA-4, and 896 with the combination of ICIs. In comparison to non-ICI drug use, ICI use demonstrated higher risk for neurologic complication, including hypophysitis/hypopituitarism, myasthenia gravis, encephalitis/myelitis, meningitis, Guillain-Barre syndrome, vasculitis, and neuropathy. The risk of neurologic AEs associated with ICI combination therapy was as high as or even higher than ICI monotherapy, most significantly in hypophysitis/hypopituitarism. The proportion of serious neurological events and death related to combination therapy has been decreasing in recent years. Older age, male and female sex, and metastasis were not significant risk factors for the incidence of neurologic ICI-related AEs. Patients at older age, with melanoma or non-small cell lung cancer, or on dual ICI therapy may be at higher risk of fatal neurologic AEs. CONCLUSION: ICI use is associated with a higher risk of neurological complications, with dual ICI therapy posing a higher risk, while older age, sex, or metastasis were not. Patients at older age, with certain cancer types, or on dual ICI therapy may be at higher risk of fatal neurologic AEs.

Effect of Hepatitis C Virus Infection on Heart Transplants in the Current Era.

BACKGROUND: The effect of hepatitis C virus (HCV) infection in recipients or donors on heart transplants is less known in the current era after the introduction of direct-acting antiviral agents (DAAs) in 2011. METHODS: Using the United Network for Organ Sharing registry, 24 871 adult heart transplant recipients between 2005 and 2019 were identified. The trend in prevalence of HCV-infected recipients and in utilization of HCV-infected donors and their effect on the transplant outcomes were investigated in the past era versus the current era separated by 2011, using Cox proportional hazard regression. RESULTS: HCV antibody-positive recipients (n = 520, 2.1%) had stable prevalence (P = 0.18). They had a lower survival estimate when compared with HCV antibody-negative recipients in the past era (55.3% versus 70.9% at 7 y; hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.27-1.91; P < 0.001), however not in the current era (73.1% versus 71.5% at 7 y; HR, 1.00; 95% CI, 0.75-1.32; P = 0.98) (Pinteraction < 0.001). Organ use from HCV antibody-positive donors (n = 371, 1.5%) was concentrated in the recent years (P < 0.001) and provided the similar survival estimate up to 2 y (84.2% versus 87.6%; HR, 0.97; 95% CI, 0.65-1.44; P = 0.87). The similar findings were confirmed with a subgroup cohort with positive nucleic acid amplification test. CONCLUSIONS: Positive HCV antibody in recipients did not adversely affect the long-term transplant outcomes in the current era. Graft utilization from positive HCV antibody or nucleic acid amplification test-positive donors are rapidly more prevalent and appeared to be promising up to 2 y posttransplant.

The Risk Factors Associated with Immune Checkpoint Inhibitor-Related Pneumonitis.

BACKGROUND: Pneumonitis is a serious adverse event in patients treated with immune checkpoint inhibitors (ICIs), with a mortality rate of up to 20%. The risk factors for ICI-related pneumonitis remain unclear due to the scarce data and infrequent event rate of 0-10% for all grades in patients using ICIs. OBJECTIVES: This study evaluated the risk factors for ICI-related pneumonitis using the United States Food and Drug Administration (US FDA) Adverse Event Reporting System (FAERS) database. METHOD: To investigate the association between pneumonitis and ICIs, the FAERS database, which contains spontaneous adverse event reports submitted to the US FDA, was utilized. Data between January 2014 and December 2019 were collected. Univariate logistic regression analysis with covariates, including age, sex, and ICI use, was performed to assess the risk of ICI-related pneumonitis. The relative risk of pneumonitis was estimated using by the odds ratio. RESULTS: We identified 4,248,808 reports, including 51,166 cases of those who received eight different ICIs. Nivolumab was the most common ICI (n = 27,273 of 51,166 [53.3%] patients). Reporting rates of pneumonitis were significantly high in ICI users (odds ratio 29.48; 95% confidence interval [CI], 27.49-31.62). Univariate logistic regression analysis showed that pneumonitis risk was significantly associated with age. Age ≤60 years old was associated with an increase in the reported frequency of pneumonitis. CONCLUSIONS: Our data suggest that the risk of ICI-related pneumonitis may increase in certain populations, including younger age (age <60 years) and ICIs users. These patients require careful monitoring.

Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis.

BACKGROUND: Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients. METHODS: We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized. RESULTS: Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95% CI]; 0.85 [0.75-0.96] and 0.68 [0.59-0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80-1.04] and 0.86 [0.72-1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78-1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63-0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69-0.95]), while exendin-4 analogues did not (RR 1.03 [0.88-1.20]). CONCLUSIONS: In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not.

Association of decreasing hemoglobin levels with the incidence of acute kidney injury after percutaneous coronary intervention: a prospective multi-center study.

Acute kidney injury (AKI) is common in patients undergoing percutaneous coronary intervention (PCI). One risk factor for AKI is periprocedural hemoglobin drop level (> 3 g/dL); however, whether the relationship between hemoglobin drop and AKI is linear or nonlinear remains unknown. We aimed to investigate the relationship between periprocedural hemoglobin drop and AKI after PCI. We evaluated 14,273 consecutive patients undergoing PCI between September 2008 and March 2019. AKI was defined as an absolute or a relative increase in serum creatinine level of 0.3 mg/dL or 50%, respectively. Restricted cubic spline was constructed to assess the association between hemoglobin drop and AKI by logistic regression and machine learning (ML) models, which were used to predict the risk of AKI. The patients' mean age was 68.4 ± 11.6 years; the AKI incidence was 10.5% (N = 1499). An absolute > 3 g/dL or 20% relative decrease in hemoglobin level was an independent predictor of AKI incidence (odds ratio, OR [95% confidence interval, CI]: 2.24 [1.92-2.61], P < 0.001; 2.35 [2.04-2.71], P < 0.001, respectively). An adjusted restricted cubic spline demonstrated that absolute/relative decrease in hemoglobin was linearly associated with AKI. Logistic and ML models with absolute/relative hemoglobin changes were comparable while estimating the risk of AKI (absolute area under the curve [AUC] (logistic):0.826, AUC (ML): 0.820; relative AUC (logistic): 0.818, AUC (ML): 0.816). An absolute/relative decrease in periprocedural hemoglobin after PCI was linearly associated with AKI. Detection of a relative/absolute decrease in hemoglobin may help clinicians identify individuals as high risk for AKI after PCI.

Risk Factors for Mortality in Patients with COVID-19 in New York City.

BACKGROUND: New York City emerged as an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To describe the clinical characteristics and risk factors associated with mortality in a large patient population in the USA. DESIGN: Retrospective cohort study. PARTICIPANTS: 6493 patients who had laboratory-confirmed COVID-19 with clinical outcomes between March 13 and April 17, 2020, who were seen in one of the 8 hospitals and/or over 400 ambulatory practices in the New York City metropolitan area MAIN MEASURES: Clinical characteristics and risk factors associated with in-hospital mortality. KEY RESULTS: A total of 858 of 6493 (13.2%) patients in our total cohort died: 52/2785 (1.9%) ambulatory patients and 806/3708 (21.7%) hospitalized patients. Cox proportional hazard regression modeling showed an increased risk of in-hospital mortality associated with age older than 50 years (hazard ratio [HR] 2.34, CI 1.47-3.71), systolic blood pressure less than 90 mmHg (HR 1.38, CI 1.06-1.80), a respiratory rate greater than 24 per min (HR 1.43, CI 1.13-1.83), peripheral oxygen saturation less than 92% (HR 2.12, CI 1.56-2.88), estimated glomerular filtration rate less than 60 mL/min/1.73m2 (HR 1.80, CI 1.60-2.02), IL-6 greater than 100 pg/mL (HR 1.50, CI 1.12-2.03), D-dimer greater than 2 mcg/mL (HR 1.19, CI 1.02-1.39), and troponin greater than 0.03 ng/mL (HR 1.40, CI 1.23-1.62). Decreased risk of in-hospital mortality was associated with female sex (HR 0.84, CI 0.77-0.90), African American race (HR 0.78 CI 0.65-0.95), and hydroxychloroquine use (HR 0.53, CI 0.41-0.67). CONCLUSIONS: Among patients with COVID-19, older age, male sex, hypotension, tachypnea, hypoxia, impaired renal function, elevated D-dimer, and elevated troponin were associated with increased in-hospital mortality and hydroxychloroquine use was associated with decreased in-hospital mortality.

Marijuana-related Reversible Cerebral Vasoconstriction Syndrome.

The legalization of recreational marijuana in some countries has been accompanied by an increased number of case reports of serious cardiovascular and cerebrovascular complications. However, there have been few studies describing the detailed clinical course of reversible cerebral vasospasm syndrome (RCVS) associated with marijuana use. We herein report a unique case of recurrent bi-fronto-parietal subcortical (watershed) infarction in the setting of chronic daily marijuana use for several years, with evidence of bilateral anterior cerebral artery vasoconstriction. The quick resolution of symptoms with treatment and the normalization of cerebral vasoconstriction on follow-up imaging lend high certainty to the diagnosis of RCVS.