Disseminated Histoplasmosis in a Patient with Myelofibrosis on Ruxolitinib: A Case Report and Review of the Literature on Ruxolitinib-Associated Invasive Fungal Infections.

Ruxolitinib, a selective inhibitor of Janus kinases, is a standard treatment for intermediate/high-risk myelofibrosis (MF) but is associated with a predisposition to opportunistic infections, especially herpes zoster. However, the incidence and characteristics of invasive fungal infections (IFIs) in these patients remain uncertain. In this report, we present the case of a 59-year-old woman with MF who developed disseminated histoplasmosis after seven months of ruxolitinib use. The patient clinically improved after ten weeks of combined amphotericin B and azole therapy, and ruxolitinib was discontinued. Later, the patient received fedratinib, a relatively JAK2-selective inhibitor, without relapse of histoplasmosis. We also reviewed the literature on published cases of proven IFIs in patients with MF who received ruxolitinib. Including ours, we identified 28 such cases, most commonly due to Cryptococcus species (46%). IFIs were most commonly disseminated (39%), followed by localized lung (21%) infections. Although uncommon, a high index of suspicion for opportunistic IFIs is needed in patients receiving JAK inhibitors. Furthermore, the paucity of data regarding the optimal management of IFIs in patients treated with JAK inhibitors underscore the need for well-designed studies to evaluate the epidemiology, pathobiology, early diagnosis, and multimodal therapy of IFIs in patients with hematological malignancies receiving targeted therapies.

Bias in artificial intelligence algorithms and recommendations for mitigation.

The adoption of artificial intelligence (AI) algorithms is rapidly increasing in healthcare. Such algorithms may be shaped by various factors such as social determinants of health that can influence health outcomes. While AI algorithms have been proposed as a tool to expand the reach of quality healthcare to underserved communities and improve health equity, recent literature has raised concerns about the propagation of biases and healthcare disparities through implementation of these algorithms. Thus, it is critical to understand the sources of bias inherent in AI-based algorithms. This review aims to highlight the potential sources of bias within each step of developing AI algorithms in healthcare, starting from framing the problem, data collection, preprocessing, development, and validation, as well as their full implementation. For each of these steps, we also discuss strategies to mitigate the bias and disparities. A checklist was developed with recommendations for reducing bias during the development and implementation stages. It is important for developers and users of AI-based algorithms to keep these important considerations in mind to advance health equity for all populations.

Infections Simulating Immune Checkpoint Inhibitor Toxicities: Uncommon and Deceptive.

Use of immune checkpoint inhibitors (ICIs), a revolutionary treatment in modern oncology, is frequently complicated by immune-related adverse events (irAEs), which can be confused with infections, and vice versa, thus complicating management decisions. In this study, we review the published cases of infections as simulators of irAEs in cancer patients.

All-cause mortality in cancer patients treated for sepsis in intensive care units: a systematic review and meta-analysis.

PURPOSE: Sepsis is a common complication in patients with cancer, but studies evaluating the outcomes of critically ill cancer patients with sepsis on a global scale are limited. We aimed to summarize the existing evidence on mortality rates in this patient population. METHODS: Prospective and retrospective observational studies evaluating critically ill adult cancer patients with sepsis, severe sepsis, and/or septic shock were included. Studies published from January 2010 to September 2021 that reported at least one mortality outcome were retrieved from MEDLINE (Ovid), Embase (Ovid), and Cochrane databases. Study selection, bias assessment, and data collection were performed independently by two reviewers, and any discrepancies were resolved by a third reviewer. The risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled intensive care unit (ICU), hospital, and 28/30-day mortality rates. The heterogeneity of the data was tested using the chi-square test, with a P value < 0.10 indicating significant heterogeneity. RESULTS: A total of 5464 citations were reviewed, of which 10 studies met the inclusion criteria; these studies included 6605 patients. All studies had a Newcastle-Ottawa scale score of 7 or higher. The mean patient age ranged from 51.4 to 64.9 years. The pooled ICU, hospital, and 28/30 day mortality rates were 48% (95% CI, 43- 53%; I2 = 80.6%), 62% (95% CI, 58-67%; I2 = 0%), and 50% (95% CI, 38- 62%; I2 = 98%), respectively. Substantial between-study heterogeneity was observed. CONCLUSION: Critically ill cancer patients with sepsis had poor survival, with a hospital mortality rate of about two-thirds. The substantial observed heterogeneity among studies could be attributed to variability in the criteria used to define sepsis as well as variability in treatment, the severity of illness, and care across settings. Our results are a call to action to identify strategies that improve outcomes for cancer patients with sepsis.

Cat Scratch Disease as a Mimicker of Malignancy.

Cat scratch disease (CSD) infrequently mimics malignancy. We reviewed 11 such cases at MD Anderson Cancer Center and an additional 36 reported from the literature. Breast cancer, sarcoma, and lymphoma were the most commonly suspected malignancies. Most patients were young, female, had prior cat exposure, and had no systemic symptoms. Regional lymphadenopathy was the most common finding.

Assessment of Intercostal Nerve Block Analgesia for Thoracic Surgery: A Systematic Review and Meta-analysis.

Importance: The use of intercostal nerve block (ICNB) analgesia with local anesthesia is common in thoracic surgery. However, the benefits and safety of ICNB among adult patients undergoing surgery is unknown. Objective: To evaluate the analgesic benefits and safety of ICNB among adults undergoing thoracic surgery. Data Sources: A systematic search was performed in Ovid MEDLINE, Ovid Embase, Scopus, and the Cochrane Library databases using terms for ICNB and thoracic surgery (including thoracic surgery, thoracoscopy, thoracotomy, nerve block, intercostal nerves). The search and results were not limited by date, with the last search conducted on July 24, 2020. Study Selection: Selected studies were experimental or observational and included adult patients undergoing cardiothoracic surgery in which ICNB was administered with local anesthesia via single injection, continuous infusion, or a combination of both techniques in at least 1 group of patients. For comparison with ICNB, studies that examined systemic analgesia and different forms of regional analgesia (such as thoracic epidural analgesia [TEA], paravertebral block [PVB], and other techniques) were included. These criteria were applied independently by 2 authors, and discrepancies were resolved by consensus. A total of 694 records were selected for screening. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data including patient characteristics, type of surgery, intervention analgesia, comparison analgesia, and primary and secondary outcomes were extracted independently by 3 authors. Synthesis was performed using a fixed-effects model. Main Outcomes and Measures: The coprimary outcomes were postoperative pain intensity (measured as the worst static or dynamic pain using a validated 10-point scale, with 0 indicating no pain and 10 indicating severe pain) and opioid consumption (measured in morphine milligram equivalents [MMEs]) at prespecified intervals (0-6 hours, 7-24 hours, 25-48 hours, 49-72 hours, and >72 hours). Clinically relevant analgesia was defined as a 1-point or greater difference in pain intensity score at any interval. Secondary outcomes included 30-day postoperative complications and pulmonary function. Results: Of 694 records screened, 608 were excluded based on prespecified exclusion criteria. The remaining 86 full-text articles were assessed for eligibility, and 20 of those articles were excluded. All of the 66 remaining studies (5184 patients; mean [SD] age, 53.9 [10.2] years; approximately 59% men and 41% women) were included in the qualitative analysis, and 59 studies (3325 patients) that provided data for at least 1 outcome were included in the quantitative meta-analysis. Experimental studies had a high risk of bias in multiple domains, including allocation concealment, blinding of participants and personnel, and blinding of outcome assessors. Marked differences (eg, crossover studies, timing of the intervention [intraoperative vs postoperative], blinding, and type of control group) were observed in the design and implementation of studies. The use of ICNB vs systemic analgesia was associated with lower static pain (0-6 hours after surgery: mean score difference, -1.40 points [95% CI, -1.46 to -1.33 points]; 7-24 hours after surgery: mean score difference, -1.27 points [95% CI, -1.40 to -1.13 points]) and lower dynamic pain (0-6 hours after surgery: mean score difference, -1.66 points [95% CI, -1.90 to -1.41 points]; 7-24 hours after surgery: mean score difference, -1.43 points [95% CI, -1.70 to -1.17 points]). Intercostal nerve block analgesia was noninferior to TEA (mean score difference in worst dynamic panic at 7-24 hours after surgery: 0.79 points; 95% CI, 0.28-1.29 points) and marginally inferior to PVB (mean score difference in worst dynamic pain at 7-24 hours after surgery: 1.29 points; 95% CI, 1.16 to 1.41 points). The largest opioid-sparing effect of ICNB vs systemic analgesia occurred at 48 hours after surgery (mean difference, -10.97 MMEs; 95% CI, -12.92 to -9.02 MMEs). The use of ICNB was associated with higher MME values compared with TEA (eg, 48 hours after surgery: mean difference, 48.31 MMEs; 95% CI, 36.11-60.52 MMEs) and PVB (eg, 48 hours after surgery: mean difference, 3.87 MMEs; 95% CI, 2.59-5.15 MMEs). Conclusions and Relevance: In this study, single-injection ICNB was associated with a reduction in pain during the first 24 hours after thoracic surgery and was clinically noninferior to TEA or PVB. Intercostal nerve block analgesia had opioid-sparing effects; however, TEA and PVB were associated with larger decreases in postoperative MMEs, suggesting that ICNB may be most beneficial for cases in which TEA and PVB are not indicated.

Non-pharmacological sleep interventions for pediatric cancer patients and survivors: a systematic review protocol.

BACKGROUND: Sleep disturbances constitute a common complication in pediatric cancer patients and survivors and are frequently severe enough to warrant treatment. Suboptimal sleep has been associated with decreased emotional well-being and cognitive functioning and increased behavioral problems. Standardized guidelines for non-pharmacological sleep interventions for adults with cancer exist, but no standard of care intervention or standard guidelines are available to guide such intervention in pediatric cancer patients and survivors. Therefore, effective behavioral interventions for improving sleep quality need to be identified. The objective of the review is to evaluate the effect of non-pharmacological sleep interventions on sleep quality in pediatric cancer patients and survivors. METHODS: The review will consider studies that include children and adolescents between 0 and 18 years diagnosed with cancer or who have a history of cancer who have non-respiratory sleep disturbance. We will include experimental and quasi-experimental studies evaluating non-pharmacological interventions such as psychological interventions, technical/device interventions, interventions targeting physical activity, and complementary and alternative medicine interventions (e.g., yoga, massage, music). Interventions involving medications, ingestible supplements, products purported to work through absorption, and medical devices will be excluded. Primary outcome will be sleep quality as measured by methods including retrospective ratings, daily sleep diary, and validated questionnaires. Secondary outcomes will include total sleep time, sleep onset latency, wake after sleep onset, daytime sleepiness, and daytime sleep duration (naps) as measured by retrospective ratings, daily sleep diary, validated questionnaires, and/or actigraphy. Databases will include MEDLINE (Ovid), EMBASE (Ovid), Cochrane Library, CINAHL (Ebsco), and PsycINFO (Ovid) and will be queried from database inception to present. Two reviewers will independently screen all citations, full-text articles, and extract data. The study methodological quality will be assessed using Joanna Briggs Institute (JBI) critical appraisal tools. Data will be extracted and findings pooled and synthesized using a meta-aggregation approach via the JBI System for the Unified Management, Assessment, and Review of Information (SUMARI). If feasible, we will conduct random effects meta-analysis. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., methodological quality, study design, outcome measures). DISCUSSION: This systematic review will synthesize and consolidate evidence on existing non-pharmacological interventions to improve sleep in pediatric cancer patients and survivors. Findings may help inform practitioners working with pediatric cancer patients and survivors experiencing sleep disturbances and is intended to identify gaps and opportunities to improve methodical quality of further non-pharmacological sleep intervention research in this population toward developing an eventual standard of care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020200397 .

Epidemiology and organ specific sequelae of post-acute COVID19: A narrative review.

OBJECTIVES: "Long COVID", a term coined by COVID-19 survivors, describes persistent or new symptoms in a subset of patients who have recovered from acute illness. Globally, the population of people infected with SARS-CoV-2 continues to expand rapidly, necessitating the need for a more thorough understanding of the array of potential sequelae of COVID-19. The multisystemic aspects of acute COVID-19 have been the subject of intense investigation, but the long-term complications remain poorly understood. Emerging data from lay press, social media, commentaries, and emerging scientific reports suggest that some COVID-19 survivors experience organ impairment and/or debilitating chronic symptoms, at times protean in nature, which impact their quality of life. METHODS/RESULTS: In this review, by addressing separately each body system, we describe the pleiotropic manifestations reported post COVID-19, their putative pathophysiology and risk factors, and attempt to offer guidance regarding work-up, follow-up and management strategies. Long term sequelae involve all systems with a negative impact on mental health, well-being and quality of life, while a subset of patients, report debilitating chronic fatigue, with or without other fluctuating or persistent symptoms, such as pain or cognitive dysfunction. Although the pathogenesis is unclear, residual damage from acute infection, persistent immune activation, mental factors, or unmasking of underlying co-morbidities are considered as drivers. Comparing long COVID with other post viral chronic syndromes may help to contextualize the complex somatic and emotional sequalae of acute COVID-19. The pace of recovery of different aspects of the syndrome remains unclear as the pandemic began only a year ago. CONCLUSIONS: Early recognition of long-term effects and thorough follow-up through dedicated multidisciplinary outpatient clinics with a carefully integrated research agenda are essential for treating COVID-19 survivors holistically.

Patient Adherence to Screening for Lung Cancer in the US: A Systematic Review and Meta-analysis.

Importance: To be effective in reducing deaths from lung cancer among high-risk current and former smokers, screening with low-dose computed tomography must be performed periodically. Objective: To examine lung cancer screening (LCS) adherence rates reported in the US, patient characteristics associated with adherence, and diagnostic testing rates after screening. Data Sources: Five electronic databases (MEDLINE, Embase, Scopus, CINAHL, and Web of Science) were searched for articles published in the English language from January 1, 2011, through February 28, 2020. Study Selection: Two reviewers independently selected prospective and retrospective cohort studies from 95 potentially relevant studies reporting patient LCS adherence. Data Extraction and Synthesis: Quality appraisal and data extraction were performed independently by 2 reviewers using the Newcastle-Ottawa Scale for quality assessment. A random-effects model meta-analysis was conducted when at least 2 studies reported on the same outcome. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guideline. Main Outcomes and Measures: The primary outcome was LCS adherence after a baseline screening. Secondary measures were the patient characteristics associated with adherence and the rate of diagnostic testing after screening. Results: Fifteen studies with a total of 16 863 individuals were included in this systematic review and meta-analysis. The pooled LCS adherence rate across all follow-up periods (range, 12-36 months) was 55% (95% CI, 44%-66%). Regarding patient characteristics associated with adherence rates, current smokers were less likely to adhere to LCS than former smokers (odds ratio [OR], 0.70; 95% CI, 0.62-0.80); White patients were more likely to adhere to LCS than patients of races other than White (OR, 2.0; 95% CI, 1.6-2.6); people 65 to 73 years of age were more likely to adhere to LCS than people 50 to 64 years of age (OR, 1.4; 95% CI, 1.0-1.9); and completion of 4 or more years of college was also associated with increased adherence compared with people not completing college (OR, 1.5; 95% CI, 1.1-2.1). Evidence was insufficient to evaluate diagnostic testing rates after abnormal screening scan results. The main source of variation was attributable to the eligibility criteria for screening used across studies. Conclusions and Relevance: In this study, the pooled LCS adherence rate after a baseline screening was far lower than those observed in large randomized clinical trials of screening. Interventions to promote adherence to screening should prioritize current smokers and smokers from minority populations.

Invasive Fungal Infections at Presentation of Untreated Hematologic Malignancies: Rare and Elusive.

Invasive fungal infections (IFIs) are a feared complication of hematologic malignancy (HM) treatment. Infrequently, the diagnosis of a new IFI contemporaneously with a new untreated HM has been sporadically described in case reports. We performed a comprehensive search of published literature and reviewed cases describing this synchronous disease phenomenon.

Insect Bite-Associated Invasive Fungal Infections.

Insect bites are rarely reported to result in myocutaneous mycoses. We reviewed the literature and report 22 cases. Molds were the most common pathogens (15), especially Mucorales (9). Infections were typically misdiagnosed, and 68% had necrotizing features, often requiring amputation or extensive surgery. Both immunocompetent and immunosuppressed patients were affected.

Just-in-Time Feedback in Diet and Physical Activity Interventions: Systematic Review and Practical Design Framework.

BACKGROUND: The integration of body-worn sensors with mobile devices presents a tremendous opportunity to improve just-in-time behavioral interventions by enhancing bidirectional communication between investigators and their participants. This approach can be used to deliver supportive feedback at critical moments to optimize the attainment of health behavior goals. OBJECTIVE: The goals of this systematic review were to summarize data on the content characteristics of feedback messaging used in diet and physical activity (PA) interventions and to develop a practical framework for designing just-in-time feedback for behavioral interventions. METHODS: Interventions that included just-in-time feedback on PA, sedentary behavior, or dietary intake were eligible for inclusion. Feedback content and efficacy data were synthesized descriptively. RESULTS: The review included 31 studies (15/31, 48%, targeting PA or sedentary behavior only; 13/31, 42%, targeting diet and PA; and 3/31, 10%, targeting diet only). All studies used just-in-time feedback, 30 (97%, 30/31) used personalized feedback, and 24 (78%, 24/31) used goal-oriented feedback, but only 5 (16%, 5/31) used actionable feedback. Of the 9 studies that tested the efficacy of providing feedback to promote behavior change, 4 reported significant improvements in health behavior. In 3 of these 4 studies, feedback was continuously available, goal-oriented, or actionable. CONCLUSIONS: Feedback that was continuously available, personalized, and actionable relative to a known behavioral objective was prominent in intervention studies with significant behavior change outcomes. Future research should determine whether all or some of these characteristics are needed to optimize the effect of feedback in just-in-time interventions.

The F-BAR protein CIP4 promotes GLUT4 endocytosis through bidirectional interactions with N-WASp and Dynamin-2.

F-BAR proteins are a newly described family of proteins with unknown physiological significance. Because F-BAR proteins, including Cdc42 interacting protein-4 (CIP4), drive membrane deformation and affect endocytosis, we investigated the role of CIP4 in GLUT4 traffic by flow cytometry in GLUT4myc-expressing L6 myoblasts (L6 GLUT4myc). L6 GLUT4myc cells express CIP4a as the predominant F-BAR protein. siRNA knockdown of CIP4 increased insulin-stimulated (14)C-deoxyglucose uptake by elevating cell-surface GLUT4. Enhanced surface GLUT4 was due to decreased endocytosis, which correlated with lower transferrin internalization. Immunoprecipitation of endogenous CIP4 revealed that CIP4 interacted with N-WASp and Dynamin-2 in an insulin-dependent manner. FRET confirmed the insulin-dependent, subcellular properties of these interactions. Insulin exposure stimulated specific interactions in plasma membrane and cytosolic compartments, followed by a steady-state response that underlies the coordination of proteins needed for GLUT4 traffic. Our findings reveal a physiological function for F-BAR proteins, supporting a previously unrecognized role for the F-BAR protein CIP4 in GLUT4 endocytosis, and show that interactions between CIP4 and Dynamin-2 and between CIP4 and NWASp are spatially coordinated to promote function.