Symptoms of Anxiety, Depression, and Stress among Families of Critically Ill Patients with COVID-19: A Longitudinal Clinical Trial.

Rationale: Families of critically ill patients with coronavirus disease (COVID-19) may be at particularly high risk for anxiety, depression, and post-traumatic stress disorder after hospital discharge. Objectives: To assess symptoms of anxiety, depression, and stress among families of patients with COVID-19 during and after intensive care unit (ICU) admissions and to use qualitative methods to determine the sources of emotional distress. Methods: Families of patients with COVID-19 who participated in an ICU study were approached for participation in this post-hospital discharge study. Participants completed the Hospital Anxiety and Depression Scale (HADS) and the Impact of Events Scale-Revised (IES-R) at up to three points during the ICU stay and once after the ICU stay. Mixed-effects models were used to compare trajectories of HADS and IES-R scores over the ICU and post-ICU periods. Telephone interviews with participants were evaluated using thematic content analysis. Results: Among the 90 families that participated from September 2020 to April 2021, 47 respective patients were alive and 43 were deceased. Average HADS anxiety, HADS depression, and IES-R scores after hospital discharge were significantly higher (greater symptom burden) among families of deceased versus surviving patients: 9.2 (95% confidence interval [CI], 7.8-10.6) versus 6.3 (95% CI, 4.9-7.6) (P < 0.01), 7.1 (95% CI, 5.7-8.6) versus 3.2 (95% CI, 2.3-4.1) (P < 0.001), and 36.1 (95% CI, 31.0-41.2) versus 20.4 (95% CI, 16.1-24.8) (P < 0.001), respectively. HADS anxiety and HADS depression scores began to diverge during the ICU stay, whereas IES-R scores diverged after the stay for families of surviving versus deceased patients. Qualitative analysis confirmed a higher burden of psychological symptoms among families of deceased patients. Memories from the ICU stay became a focal point for participants who lost their loved ones, whereas families of surviving patients were able to look positively toward the future. In addition, families of deceased patients often viewed friends and family as sources of stress, whereas families of surviving patients typically viewed their community as a source of support. Conclusions: Patient death was associated with symptoms of anxiety, depression, and post-traumatic stress disorder among families of ICU patients with COVID-19. Psychological support interventions may be most beneficial for families of patients who died of COVID-19. Clinical trial registered with www.clinicaltrials.gov (NCT04501445).

Factors associated with future hospitalization among children with asthma: a systematic review.

OBJECTIVE: Asthma is a leading cause of emergency department (ED) visits and hospitalizations in children, though many could be prevented. Our study objective was to identify factors from the published literature that are associated with future hospitalization for asthma beyond 30 days following an initial asthma ED visit. DATA SOURCES: We searched CINAHL, CENTRAL, MEDLINE, and Embase for all studies examining factors associated with asthma-related hospitalization in children from January 1, 1992 to February 7, 2022.Selecting Studies: All citations were reviewed independently by two reviewers and studies meeting inclusion criteria were assessed for risk of bias. Data on all reported variables were extracted from full text and categorized according to identified themes. Where possible, data were pooled for meta-analysis using random effects models. RESULTS: Of 2262 studies, 68 met inclusion criteria. We identified 28 risk factors and categorized these into six themes. Factors independently associated with future hospitalization in meta-analysis include: exposure to environmental tobacco smoke (OR = 1.94 95%CI 0.67-5.61), pets exposure (OR = 1.67 95%CI 1.17-2.37), and previous asthma hospitalizations (OR = 3.47 95% CI 2.95-4.07). Additional related factors included previous acute care visits, comorbid health conditions (including atopy), allergen exposure, severe-persistent asthma phenotype, inhaled steroid use prior to ED visit, poor asthma control, higher severity symptoms at ED presentation, warmer season at admission, longer length of stay or ICU admission, and African-American race/ethnicity. CONCLUSIONS: We identified multiple factors that are consistently associated with future asthma hospitalization in children and could be used to identify those who would benefit from targeted preventative interventions.

Piloting Group-Based Behavioral Activation Therapy for Families of Deceased COVID-19 Patients.

Surrogate decision-making is a stressful process for many family members of critically ill patients. The COVID-19 pandemic may have amplified the risk for anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms in ICU surrogates. OBJECTIVES: This study piloted an online group-based behavioral intervention with family members of deceased COVID-19 patients. Participant engagement, perceptions, and responses related to the intervention were assessed. DESIGN: A single-arm pilot study was conducted with bereaved families. Quantitative analysis of measures of anxiety, depression, and PTSD symptoms was conducted with mixed models. Qualitative data were analyzed to identify themes in surrogates' experiences with the intervention. SETTING: Participants were recruited from ICUs at a tertiary academic medical center. Participants completed the intervention, measures, and interviews online. SUBJECTS: Participants were family members of patients who died from COVID-19. INTERVENTIONS: The intervention involved six online group-based behavioral activation sessions. Sessions covered topics pertinent to grieving and engagement in personally meaningful activities. MEASUREMENTS AND MAIN RESULTS: Semi-structured interviews explored participants' experiences with the intervention. Surrogates also completed measures of anxiety, depression, and PTSD symptoms before and after the intervention. Nineteen of 26 participants (73.1%) completed the study. Thematic analysis suggested that surrogates found the group helpful for overcoming perceived isolation, receiving validation, and developing coping skills. Significant pre-to-post reductions were observed in symptoms of Hospital and Anxiety Disorder Scale (HADS) anxiety (pre-mean = 9.27, sd = 5.30 vs post-mean = 6.80, sd = 4.16; p = 0.0271), HADS depression (pre-mean =6 .65, sd = 4.58 vs post- mean = 4.89, sd = 3.40; p = 0.0436), and Impact of Events Scale-Revised PTSD (pre-mean = 36.86, sd = 16.97 vs post-mean = 24.14, sd = 13.49; p = 0.0008). LIMITATIONS: This was a preliminary study based on qualitative and self-report measures. Future studies should include a control group. CONCLUSIONS: Online group-based behavioral activation therapy appears to be a potentially useful intervention for family members of ICU patients who died from COVID-19.

The economic impact of increased length of stay associated with surgical site infections in liver transplantation on Canadian healthcare costs.

BACKGROUND: Complications after liver transplantation cause additional healthcare costs. The objective of this study was to contrast the length of stay (LOS) costs for recipients with and without surgical site infections (SSIs). METHODS: This retrospective observational cohort study was conducted at a transplant center in Canada, between February 2011 and August 2014. The difference in the LOS costs was assessed by the Mann-Whitney U test, while multiple linear regression analysis was used to identify the variables that may have impacted on the costs. RESULTS: Two hundred and twenty-nine liver transplant recipients were enrolled. Thirty-six recipients developed SSIs (36/229, 15.7%). The median LOS costs in recipients with and without SSIs were $39,456 Canadian dollars (interquartile range $25,696- 59,722) and $31,084 Canadian dollars (interquartile range $22,712-49 610), respectively (p = .072). There was a trend that the costs were higher for those recipients with versus those without SSIs (p = .088). Transfusion of ≥ 5 units of red cells and dialysis before transplantation impacted on cost. CONCLUSION: There was a trend for higher healthcare facility costs for recipients with SSIs. Red cell transfusions and greater dialysis use before transplant were factors associated with the cost. Implementation of cost reduction strategies targeting high-cost recipients is necessary.

Uveitis and cystoid macular oedema secondary to topical prostaglandin analogue use in ocular hypertension and open angle glaucoma.

BACKGROUND: Of the side effects of prostaglandin analogues (PGAs), uveitis and cystoid macular oedema (CME) have significant potential for vision loss based on postmarket reports. Caution has been advised due to concerns of macular oedema and uveitis. In this report, we researched and summarised the original data suggesting these effects and determined their incidence. METHODS: Preferred Reporting Items for Systematic review and Meta-Analyses guidelines were followed. Studies evaluating topical PGAs in patients with ocular hypertension or open angle glaucoma were included. MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, LILACS and ClinicalTrials.gov were searched between 1946 and 2019. Experimental studies, animal studies and randomised studies with other intraocular pressure-lowering eye drops were excluded. RESULTS: 214 studies (28 232 patients) met the inclusion criteria. Using prospective data, the incidence of uveitis and CME among PGA users were 62/28 232 (0.22%) and 25/28 232 (0.09%), respectively. A higher frequency of both uveitis and CME were found among latanoprost users compared with bimatoprost. There were 21 case studies reporting CME including 48 eyes in 43 patients. 47 of 48 eyes (97.9%) had previous incisional ocular surgery. 8 eyes were re-challenged, of which 7 (87.5%) recurred. 7 case studies reported uveitis in 15 eyes of 10 patients. 7 of 15 eyes (46.7%) were either pseudophakic or aphakic. 6 eyes were re-challenged, and all 6 (100%) recurred. CONCLUSIONS: Cases of uveitis or CME revealed a confounding effect of ocular surgery, aphakia or subluxed intraocular lens. PGAs may be used in non-surgical patients without concern of causing CME or uveitis. The incidences of PGA-associated CME and uveitis are rare with limited prospective studies on the cause-effect relationship.

Risk factors for surgical site infection after kidney and pancreas transplantation.

OBJECTIVE: To evaluate the incidence of surgical site infection (SSI) in a cohort of pancreas transplant recipients and assess predisposing risk factors for SSI DESIGN: Retrospective cohort study SETTING: Single transplant center in CanadaPatientsPatients who underwent any simultaneous pancreas and kidney (SPK) or pancreas after kidney (PAK) transplant procedures between January 2000 and December 2015 METHODS: In this retrospective cohort evaluation of SPK or PAK recipients, we assessed the incidence of SSI and risk factors associated with superficial, deep, and organ/space SSI. Multivariate logistic regression was used to identify independent risk factors for SSI in SPK and PAK recipients. RESULTS: In total, 445 adult transplant recipients were enrolled. The median age of these patients was 51 years (range, 19-71 years), and 64.9% were men. SSIs were documented in 108 patients (24.3%). Organ/space SSIs predominated (59 patients, 54.6%), followed by superficial SSIs (47 patients, 43.5%) and deep SSIs (3 patients, 2.8%). Factors predictive of SSIs in the multivariate analysis were cold pancreas ischemic time (odds ratio [OR], 1.002; P=.019) and SPK transplant (compared to PAK transplant recipients; OR, 2.38; P=.038). Patients with SSIs developed graft loss more frequently (OR, 16.99; P<.001). CONCLUSIONS: Organ/space SSIs remain a serious and common complication after SPK and PAK. Prolonged cold ischemic time and SPK transplant were the risk factors predictive of SSIs. Appropriate perioperative prophylaxis in high-risk patients targeting the potential pathogens producing SSIs in kidney and/or pancreas transplant recipients and a reduction in cold ischemia may prove beneficial in reducing these SSIs.

Oncoprotein Stathmin Modulates Sensitivity to Apoptosis in Hepatocellular Carcinoma Cells During Hepatitis C Viral Replication.

Patients with chronic hepatitis C virus (HCV) infection risk complications of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Previously, our proteomic examination of hepatocytes carrying a HCV-replicon revealed that deregulation of cytoskeletal dynamics may be a potential mechanism of viral-induced HCC growth. Here, we demonstrate the effect of HCV replication on the microtubule regulator stathmin (STMN1) in HCC cells. We further explore how the altered activity or synthesis of stathmin affects cellular proliferation and sensitivity to apoptosis in control HCC cells (Huh7.5) and experimental HCV-replicon harboring HCC cells (R-Huh7.5). The HCV-replicon harboring HCC cells (R-Huh 7.5) lack viral structural genes/proteins for acute infectivity and thus is the standard model for in vitro chronic infection study. Knockdown of endogenous stathmin reduced sensitivity to apoptosis in replicon cells. Meanwhile, constitutively active stathmin increased sensitivity to apoptosis in replicon cells. In addition, overexpression of constitutively active stathmin reduced cell proliferation in both control and replicon cells. These findings implicate, for the first time, a novel role for stathmin in viral replication-related apoptosis. Stathmin's potential role in HCV replication and HCC make it a candidate for the future study of viral-induced malignancies.

Complete Genome Sequences of Mycobacteriophages Clautastrophe, Kingsolomon, Krypton555, and Nicholas.

We report here the complete genome sequences of four subcluster L3 mycobacteriophages newly isolated from soil samples, using Mycobacterium smegmatis mc2155 as the host. Comparative genomic analyses with four previously described subcluster L3 phages reveal strong nucleotide similarity and gene conservation, with several large insertions/deletions near their right genome ends.

Surgical Site Infections After Liver Transplantation: Prospective Surveillance and Evaluation of 250 Transplant Recipients in Canada.

OBJECTIVE To evaluate the incidence of surgical-site infections (SSIs) in a cohort of liver transplant recipients and to assess risk factors predisposing patients to these infections. DESIGN Prospective observational cohort study. SETTING Single transplant center in Canada. PATIENTS Patients who underwent liver transplantation between February 2011 and August 2014. METHODS Multivariate logistic regression was used to identify independent risk factors for SSIs in liver transplant patients. RESULTS We enrolled 250 liver transplant recipients. The recipients' median age at the time of transplantation was 56 years (range, 19-70 years), and 166 patients (66.4%) were male. Moreover, 47 SSIs were documented in 43 patients (17.2%). Organ-space, superficial, and deep SSIs were noted in 29, 7, and 3 patients, respectively. In addition, 2 patients developed superficial and organ-space SSIs, and another 2 patients were found to have deep as well as organ-space infections. In total, we identified 33 organ-space SSIs (70.2%), 9 superficial SSIs (19.1%), and 5 deep SSIs (10.6%). Factors predictive of SSIs by multivariate analysis were duct-to-duct anastomosis (odds ratio [OR], 3.88; 95% CI, 1.85-8.13; P<.001) and dialysis (OR, 3.57; 95% CI, 1.02-12.50; P=.046). Of the 66 organisms isolated in both deep and organ-space SSIs, 55 (83%) were resistant to cefazolin. CONCLUSIONS Organ-space SSIs are a common complication after liver transplantation. Duct-to-duct anastomosis and dialysis were independent risk factors associated with SSIs. Appropriate perioperative prophylaxis targeting patients with duct-to-duct anastomosis and dialysis while simultaneously providing optimum coverage for the potential pathogens causing SSIs is warranted. Infect Control Hosp Epidemiol 2017;38:1084-1090.

Rare primary mucosal melanoma of the larynx.

Few cases of primary mucosal melanoma of the larynx have been documented in the literature, so only a limited amount of data exists regarding its diagnosis and treatment. The prognosis is poor, as patients often present at a late stage with regional or distant metastases. We describe the case of a 66-year-old man who presented with hoarseness and dysphagia. Laryngoscopy identified a dark discoloration of the supraglottic larynx and incomplete mobility of the right vocal fold; an excisional biopsy confirmed the diagnosis. We discuss the epidemiology, clinical features, diagnosis, interpretation of imaging findings, and management of this rare malignant melanoma.

Radiology Case of the Month: Gliomatosis Cerebri.

A 71 year-old female with a past medical history significant for hypertension, hyperlipidemia, diabetes, and strokes, presented initially to the stroke service with a sudden onset of right facial droop, right-sided weakness, dysarthria, and seizures that had gotten progressively worse for six weeks.

Phospho-Network Analysis Identifies and Quantifies Hepatitis C Virus (HCV)-induced Hepatocellular Carcinoma (HCC) Proteins Regulating Viral-mediated Tumor Growth.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection are at risk of serious complications of cirrhosis and hepatocellular carcinoma (HCC). Mass spectrometry (MS) is a versatile methodology that produces a global proteomic landscape for analysis of cancer mechanisms. MATERIALS AND METHODS: Using multiplex peptide stable isotopic labeling and immobilized metal affinity chromatography (IMAC), we enriched and quantified the phosphoproteome of HCC, with and without HCV. While raw data identified protein targets based on expression alone, we also used abundance groups for comprehensive functional analysis. RESULTS: Analysis of functional differences highlighted deregulated phosphoprotein networks. This uncovered additional candidates that could be directly derived from the MS data. Cellular processes and pathways that may differ with HCV infection include: cytoskeletal dynamics, insulin response, gene expression, and PI3K/AKT oncogenesis. CONCLUSION: This function-focused workflow provides a simple framework to analyze MS data. Phosphoproteome quantitation with inclusive functional analysis can generate hypotheses for liver cancer research to improve early screening and identification of molecular targets for therapy.

A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C.

The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, in part through inhibition of heat shock proteins. If quercetin demonstrates safety and antiviral activity in patients, then it could be developed into an inexpensive HCV treatment for third world countries or other affected populations that lack financial means to cover the cost of mainstream antivirals. A phase 1 dose escalation study was performed to evaluate the safety of quercetin in 30 untreated patients with chronic HCV infection and to preliminarily characterize quercetin's potential in suppressing viral load and/or liver injury. Quercetin displayed safety in all trial participants. Additionally, 8 patients showed a "clinically meaningful" 0.41-log viral load decrease. There was a positive correlation (r = 0.41, p = 0.03) indicating a tendency for HCV decrease in patients with a lower ratio of plasma quercetin relative to dose. No significant changes in aspartate transaminase and alanine transaminase were detected. In conclusion, quercetin exhibited safety (up to 5 g daily) and there was a potential for antiviral activity in some hepatitis C patients.

Intrathecal trastuzumab: immunotherapy improves the prognosis of leptomeningeal metastases in HER-2+ breast cancer patient.

We describe the clinical and therapeutic course of a 51-year-old woman with HER-2+ breast cancer who developed leptomeningeal (LM) and spinal cord metastases after 8 years of stable disease on combination therapy with intravenous (IV) trastuzumab. Due to progressive CNS disease, intrathecal (IT) trastuzumab was introduced to enhance HER-2+ therapy into the CSF space. A combination HER-2+ targeted approach achieved clinical remission with stable disease in our patient 46 months after she was diagnosed with LM metastases. However, spinal cord C-1 metastasis was not fully controlled with IT trastuzumab, ultimately leading to the patient's respiratory compromise. In our patient, IT trastuzumab immunotherapy improved prognosis and was an effective strategy to manage HER-2+ LM disease. Given alone or alongside other anti-HER-2+ therapeutics with sufficient CNS penetration, IT trastuzumab could extend the lifespan of patients with leptomeningeal and CNS metastases.