KIBRA, MTNR1B, and FKBP5 genotypes are associated with decreased odds of incident delirium in elderly post-surgical patients

Despite the association between cognitive impairment and delirium, little is known about whether genetic differences that confer cognitive resilience also confer resistance to delirium. To investigate whether older adults without postoperative delirium, compared with those with postoperative delirium, are more likely to have specific single nucleotide polymorphisms (SNPs) in the FKBP5, KIBRA, KLOTHO, MTNR1B, and SIRT1 genes known to be associated with cognition or delirium. This prospective nested matched exploratory case–control study included 94 older adults who underwent orthopedic surgery and screened for postoperative delirium. Forty-seven subjects had incident delirium, and 47 age-matched controls were not delirious. The primary study outcome was genotype frequency for the five SNPs. Compared with participants with delirium, those without delirium had higher adjusted odds of KIBRA SNP rs17070145 CT/TT [vs. CC; adjusted odds ratio (aOR) 2.80, 95% confidence interval (CI) 1.03, 7.54; p = 0.04] and MTNR1B SNP rs10830963 CG/GG (vs. CC; aOR 4.14, 95% CI 1.36, 12.59; p = 0.01). FKBP5 SNP rs1360780 CT/TT (vs. CC) demonstrated borderline increased adjusted odds of not developing delirium (aOR 2.51, 95% CI 1.00, 7.34; p = 0.05). Our results highlight the relevance of KIBRA, MTNR1B, and FKBP5 in understanding the complex relationship between delirium, cognition, and sleep, which warrant further study in larger, more diverse populations.

Inpatient Type 1 Thyroplasty Versus Injection Laryngoplasty for Vocal Fold Movement Impairment After Extent type I and II Aortic Repair

Importance: Vocal fold motion impairment (VFMI) due to neuronal injury is a known complication following thoracic aortic repair that can impair pulmonary toilet function and post-operative recovery. Objective: To demonstrate clinical outcomes of patients undergoing inpatient vocal fold medialization for VFMI after aortic surgery. Design: A 15-year retrospective chart review (2005-2019) of 259 patients with postoperative VFMI after thoracic aortic surgery registry was conducted. Data included demographics, surgery characteristics, laryngology exam, and postoperative clinical outcomes. Medialization procedures consisted of type 1 thyroplasty and injection laryngoplasty. Setting: Tertiary care hospital Participants: Two hundred and fifty-nine patients (median age 61, 71% male) with VFMI post-thoracic aortic repair met inclusion criteria; inpatient vocal fold medialization was performed for 203 (78%) patients. One hundred and twenty-six. (49%) received type 1 thyroplasty and 77 (30%) received injection laryngoplasty procedures at a median 7 days (IQR 5-8 days) from extubation. Main Outcomes: Primary study outcome measurements consisted of median LOS, median ICU LOS, complications intra- and postoperatively, and pulmonary complications (post-medialization bronchoscopies, pneumonia, tracheostomy, etc.). Results: Post-medialization bronchoscopy rates were significantly lower in the medialization (n = 11) versus the non-medialization group (n = 8) (5% vs 14%, P = .02) and significantly higher in the injection laryngoplasty group (n = 77) versus thyroplasty group (n = 126) (10% vs 2%, P = .02). Further analysis revealed no significant difference in overall LOS and pulmonary complications between the techniques. Conclusion: Inpatient thyroplasty and injection laryngoplasty are both effective vocal fold medialization techniques after extent I and II aortic repair. Thyroplasty may have a small pulmonary toilet advantage, as measured by need for post-medialization bronchoscopy, compared to injection laryngoplasty.

Peritoneal carcinosis in male germ cell tumor patients: a registry study compiled by the German Testicular Cancer Study Group (GTCSG)

Purpose To report on the clinical characteristics, outcome, and frequency of peritoneal carcinosis (PC) in patients with advanced germ cell tumors (GCT), a multicenter registry analysis was carried out. Methods A multicenter registry analysis was conducted by the German Testicular Cancer Study Group (GTCSG) with international collaborators. Data was collected and analyzed retrospectively. Patients were eligible for inclusion if PC was diagnosed either by radiologic or histopathologic finding during the course of disease. Descriptive and explorative statistical analysis was carried out with cancer-specific survival (CSS) as primary study endpoint. Results Collaborators from ten GCT expert centers identified 28 GCT (0.77%) patients with PC after screening approximately 3767 GCT patient files and one case was contributed from a cancer registry request. Patients were diagnosed from 1997 to 2019 at a median age of 37 years (interquartile range, 13). Two patients (7%) presented with stage I and 27 patients (93%) with synchronous metastatic disease at first diagnosis. The primary histology was seminoma in seven (27%) and non-seminoma in 21 patients (72%). PC was detected after a median of 15.3 months from primary diagnosis (range 0–177) and two consecutive treatment lines (range 0–5), respectively. The median CSS from the time of detection of PC was 10.5 months (95%Confidence Interval 0.47–1.30) associated with an overall 2-year CSS rate of 30%. Conclusion PC represents a rare tumor manifestation in GCT patients and was primarily associated with the occurrence of advanced cisplatin-refractory disease conferring to a dismal prognosis.

Association of Vitamin D Status and COVID-19-Related Hospitalization and Mortality

Background The relationship between vitamin D status and COVID-19-related clinical outcomes is controversial. Prior studies have been conducted in smaller, single-site, or homogeneous populations limiting adjustments for social determinants of health (race/ethnicity and poverty) common to both vitamin D deficiency and COVID-19 outcomes. Objective To evaluate the dose-response relationship between continuous 25(OH)D and risk for COVID-19-related hospitalization and mortality after adjusting for covariates associated with both vitamin D deficiency and COVID-19 outcomes. Design Retrospective cohort study. Patients Veteran patients receiving care in US Department of Veteran Affairs (VA) health care facilities with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and a blood 25(OH)D test between February 20, 2020, and November 8, 2020, followed for up to 60 days. Main Measures Exposure was blood 25(OH)D concentration ascertained closest to and within 15 to 90 days preceding an index positive SARS-CoV-2 test. Co-primary study outcomes were COVID-19-related inpatient hospitalization requiring airborne, droplet, contact, or other isolation and mortality ascertained within 60 days of an index positive SARS-CoV-2 test. Key Results Of 4,599 veterans with a positive SARS-CoV-2 test, vitamin D deficiency (< 20 ng/mL) was identified in 665 (14.5%); 964 (21.0%) were hospitalized; and 340 (7.4%) died. After adjusting for all covariates, including race/ethnicity and poverty, there was a significant independent inverse dose-response relationship between increasing continuous 25(OH)D concentrations (from 15 to 60 ng/mL) and decreasing probability of COVID-19-related hospitalization (from 24.1 to 18.7%, p=0.009) and mortality (from 10.4 to 5.7%, p=0.001). In modeling 25(OH)D as a log-transformed continuous variable, the greatest risk for hospitalization and death was observed at lower 25(OH)D concentrations. Conclusions Continuous blood 25(OH)D concentrations are independently associated with COVID-19-related hospitalization and mortality in an inverse dose-response relationship in this large racially and ethnically diverse cohort of VA patients. Randomized controlled trials are needed to evaluate the impact of vitamin D supplementation on COVID-19-related outcomes.

Real-World Data of Off-Label Drug Use in Patients with Actionable Genomic Alterations on Next-Generation Sequencing

We analyzed the outcomes of patients in our institution treated with off-label drugs targeting actionable genomic alteration based on next-generation sequencing when clinical trials were not available. Our study endpoint was objective tumor response or stable disease at 16 weeks or later after treatment initiation. Sixteen patients were included in this study, 8 were treated with immune checkpoint inhibitors targeting PD-L1 or TP53 mutations and 8 with other drugs. Tumors were analyzed based on PD-L1 expression, TP53 mutation, MSI, TMB, MMR status, and other targetable alterations. Of the 16 patients in the intention-to-treat group, no patients had an objective response after 16 weeks. Eleven patients met the primary study endpoint with stable disease, 8 in the immune checkpoint inhibitors group and 3 in the non-immune checkpoint inhibitors group. Using the log-rank test, the p-value for the difference between groups was 0.008. In this study with off-label drugs, immune checkpoint inhibitors targeting TP53 mutations or PD-L1 expression were superior to the other drugs. This suggests the possibility of off-label use of anti-cancer drugs based on next-generation sequencing to be beneficial for advanced cancer patients without other therapeutic options.

Incidence and Risk Factors for Acute Transient Contrast‐Induced Neurologic Deficit: A Systematic Review With Meta‐Analysis

BACKGROUND After MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) demonstrated that endovascular therapy improved outcomes in patients with stroke, the number of endovascular procedures has risen sharply. We describe acute transient contrast‐induced neurological deficit (ATCIND), a group of neurological syndromes associated with arterial contrast administration during angiography. Our goal is to elucidate the incidence, risk factors, outcomes, pathogenesis, and diagnostic characteristics of ATCIND. Our primary objective is to elucidate the incidence of ATCIND in the setting of coronary or cerebral angiography. Secondary outcomes include potential risk factors, demographics, treatment modalities, and patient recovery. METHODS The data that support the findings of this study are available from the corresponding author on reasonable request. The databases of the Cochrane Library, MEDLINE, Web of Science, and Embase were queried, yielding studies from 1974 to 2021. Inclusion criteria for articles were the following: (1) contrast‐induced encephalopathy, contrast‐induced neurotoxicity, or cortical blindness after contrast administration during angiography were the focus of the article; (2) incidence was reported; (3) studies included ≥3 cases; and (4) follow‐up tests were described to rule out other causes. Exclusion criteria included the following: (1) incidence was not reported; (2) unavailable in the English language; (3) abstracts and unpublished studies; and (4) did not exclude other possible causes, or findings suggested other possible causes, such as worsening ischemic injury. Of 627 articles, 7 were retained. This systematic review with meta‐analysis was performed in accordance with guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) and the Meta‐Analysis of Observational Studies in Epidemiology (MOOSE) checklists. Independent extraction by multiple reviewers was performed. Data were pooled using a random‐effects model. RESULTS The primary study outcome was incidence of ATCIND, which was formulated before data collection began. We hypothesized that the pooled incidence of ATCIND would be similar to that of individual studies. A total of 70 of 21007 patients had the diagnosis of contrast‐induced encephalopathy, contrast‐induced neurotoxicity or angiography‐associated cortical blindness, and ATCIND. The incidence rate of ATCIND is estimated to be 0.51% (CI, 0.3%–1.0%; P <0.001 [ I 2 =29.3]), or 51 per 10 000 patients. Pooled data for risk factors for contrast‐induced encephalopathy were higher contrast dose (odds ratio [OR], 1.072; 95% CI, 0.952–1.192 [ P <0.001]; I 2 =0), and prior stroke (OR, 5.153; CI 1.726–8.581 [ P =0.003]; I 2 =0). Contrast dose >150 mL was a positive, significant predictor of visual disturbance (OR, 7.083; CI, 1.1742–42.793 [ P =0.033]). Full recovery is estimated at 89.5% (95% CI, 76.9%–95.6%; P <0.001 [ I 2 =0]). CONCLUSIONS This study confirms the rare incidence of ATCIND, although it shows moderate heterogeneity, likely reflecting the type of angiography performed. Risk factors include larger contrast dose and prior stroke. Full recovery occurs in the majority of patients. It should remain in the differential diagnosis in patients with certain risk factors for blood–brain barrier compromise.

Advanced catalytic oxidation coupled to biological systems to treat pesticide-contaminated water: A review on technological trends and future challenges

This article had the one and only objective of consolidating the couplings of advanced oxidation processes and biological in the decontamination of wastewater with pesticide content reported in the Scopus and Web of Science databases, through a critical analysis of which have been the most used, what methodologies have been implemented to develop them, identify the objectives of each work, determine the success of the research and where the main niches of knowledge are, which can lead to the generation of new scientific knowledge as well as future trends. A co-occurrence analysis was carried out through the VOSViewer software, to determine the most associated key words with the treatment configurations described above. Fenton and Photo-Fenton processes, heterogeneous photocatalysis TiO2/UV, electrocatalysis, ozonization and a particular case of hydrodynamic-ozone cavitation as main advanced oxidation processes, together with advanced biological processes such as SBR, MBR, MBBR; biodegradability and toxicity tests with bacterial strains and surface wetlands, whose treatment philosophy is activated sludge. The main future trends are the reuse of treated wastewater, the analysis and control of costs towards the efficient use of resources and the primary study of the byproducts generated in advanced oxidation to improve the efficiencies in the coupling.

Decreased Incidence of Michigan Emergency Department Visits for Febrile Neutropenia Observed After Public Health Measures for the COVID-19 Pandemic

Importance: Masking and social distancing appear to decrease the of febrile neutropenia in susceptible populations, especially among patients with hematologic malignancies.Objective: To determine whether COVID-19 infection mitigation efforts, namely masking and social distancing, results in a reduction in the incidence of febrile neutropenia.Design: This was a retrospective cohort study comparing the incidence of FN in the 13 months prior to (Year 0) and 13 months following (Year 1) the public health executive orders (PHEO) in Michigan. Data voluntarily submitted by Michigan emergency departments to the National Syndromic Surveillance Program (NSSP) was queried for all ED visits from April 1st, 2019 to March 31st, 2021.Setting: Population based study.Participants: A population-based sample of patients who reported to a Michigan emergency department and on whom data was captured.Intervention(s): Population based masking and social distancing.Main Outcome(s) and Measure(s): The primary study outcome was the incidence of FN as a proportion of emergency visits in the 13-months before and after COVID-19 mitigations efforts, namely masking and social distancing. We hypothesized that there would be a significant decrease in the incidence of FN in the period following the public health executive orders aimed at reducing the spread of the COVID-19 virus.Results: There was a total of 8,979,221 total ED visits captured during the study period. In Year 0 there were 5,073,081 recorded ED visits and 3,906,140 in Year 1, a decrease of 23%. There was a significant reduction in the proportion of total ED visits with a diagnosis of FN, decreasing 13.3% across periods (0.15% vs. 0.13%, p=0.036). In patients with a hematologic malignancy the incidence of FN was significantly lower in the period following PHEO (22% vs 17%, p=0.02, Table 2).Conclusions and Relevance: Our study found a significant association between social distancing and mask guidelines implemented on a large public scale with decreased rates of FN, particularly in those with a hematologic malignancy. These findings may be useful in the design of clinical trials as well as informing future recommendations for the prevention of FN.

Fremanezumab in the Prevention of High-Frequency Episodic and Chronic Migraine: A 12-Week, Multicenter, Real-Life, Cohort Study (The FRIEND Study).

Background Fremanezumab has demonstrated to be effective, safe, and tolerated in the prevention of episodic or chronic migraine (CM) in randomized, placebo-controlled trials (RCTs). Real-life studies are needed to explore drug effects in unselected patients in routine circumstances and to provide higher generalizability results. This study explores the effectiveness, safety, and tolerability of fremanezumab in a real-life population of individuals affected by high-frequency episodic (HFEM: 8-14 days/month) or CM. Methods This is a 12-week multicenter, prospective, cohort, real-life study. We considered all consecutive patients affected by HFEM or CM visited at 9 Italian headache centers from 28/07/2020 to 11/11/2020. Eligible patients were given subcutaneous fremanezumab at the doses of 225 mg monthly or 675 mg quarterly, according to their preference. Primary study endpoints were the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients at weeks 9-12 compared to baseline. Secondary endpoints encompassed variation in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), HIT-6 and MIDAS scores, and ≥50%, ≥75% and 100% responder rates at the same time intervals. Results 67 migraine patients had received ≥1 subcutaneous fremanezumab dose and were considered for safety analysis, while 53 patients completed 12 weeks of treatment and were included also in the effectiveness analysis. Fremanezumab was effective in both HFEM and CM, inducing at week 12 a significant reduction in MMDs (-4.6, p<0.05), MHDs (-9.4, p<0.001), MAI (-5.7, p<0.05; -11.1, p<0.001), NRS (-3.1, p<0.001; -2.5, p<0.001), and MIDAS scores (-58.3, p<0.05; -43.7; p<0.001). HIT-6 was significantly reduced only in HFEM patients (-18.1, p<0.001). Remission from CM to episodic migraine and from MO to no-MO occurred in 75% and 67.7% of the patients. The ≥50%, ≥75% and 100% responder rates at week 12 were 76.5%, 29.4% and 9.9% in HFEM and 58.3%, 25% and 0% in CM. Younger age emerged as a positive response predictor (OR=0.91; 95% CI 0.85-0.98, p=0.013). Treatment-emergent adverse events were uncommon (5.7%) and mild. No patient discontinued fremanezumab for any reason. Conclusions Fremanezumab seems more effective in real-life than in RCTs. Younger age emerges as a potential response predictor.