Clinical utility of metagenomic next-generation sequencing in fever of undetermined origin.

Background: Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool increasingly used in the field of infectious diseases. Little guidance is available regarding its appropriate use in different patient populations and clinical syndromes. We aimed to review the clinical utility of mNGS in patients with a specific clinical syndrome and identify factors that may increase its utility. Methods: We retrospectively reviewed charts of 72 non-immunocompromised adults hospitalized with the clinical syndrome of 'fever of undetermined origin' and underwent mNGS testing. Standardized criteria from a previously published study were used to determine the clinical impact of mNGS testing. We applied logistic regression to identify factors associated with a positive clinical impact. Results: Of the 72 patients identified, 62.5% were males with a median age of 56. All patients had a fever at the time of evaluation. At least one organism was identified in 65.3% of cases; most commonly were Epstein-Barr virus (13.9%), cytomegalovirus (12.5%), and Rickettsia typhi (11.1%). Of those determined to have an infectious etiology of their febrile syndrome, 89.5% (n = 34/38) had a positive mNGS. Consistency between the organism(s) on mNGS and the clinically determined infectious etiology was 82.4%. mNGS had a positive clinical impact in 40.3% of cases, a negative impact in 2.8%, and no impact in 56.9% of cases. Besides age, we did not identify other factors associated with a higher likelihood of positive clinical impact. Conclusion: In our review, mNGS had a positive clinical impact in a large proportion of adults with fever of undetermined origin, with minimal negative impact. However, mNGS results should be interpreted carefully given the high rate of detection of pathogens of unclear clinical significance. Randomized clinical trials are needed to assess the clinical utility of this novel diagnostic tool.

Clinical utility of metagenomic next-generation sequencing in fever of undetermined origin In this study, we evaluated the use of a new diagnostic tool, namely, metagenomic next generation sequencing (mNGS), in hospitalized, non-immunocompromised, adult patients with a fever that was otherwise unexplained. We reviewed the clinical utility of this tool in 72 patients and found that at least one organism was found in 65.3% of cases, with the 2 most common organisms being viruses. In patients who were found to have an infection as the cause of their fever, 89.5% had a positive mNGS study. In 82.4% of cases, the infectious organism(s) found on mNGS was the organism thought to be the cause of the fever. Based on definitions from another study, mNGS had a positive clinical impact in 40.3% of cases, a negative impact in 2.8%, and no impact in 56.9% of cases. This study suggests that mNGS has minimal negative impact and can be a useful tool in identifying a causative infectious organism in patients with unexplained fevers. Additional studies are needed to identify patients and clinical conditions that would most benefit from this tool.

COVID-19 Vaccination in Patients With Cancer and Recipients of Cellular Therapy.

COVID-19 continues to disproportionately affect patients with cancer because of their underlying immunocompromised state. Strategies to mitigate the impact of COVID-19 on patients with cancer include vaccination, which has demonstrated some level of protection, at least against serious complications such as respiratory failure and death, with limited safety concerns. In this narrative review, we discuss the current COVID-19 vaccines that are available in the United States, the published data regarding vaccine efficacy and safety in patients with cancer, current vaccination guidelines, and future directions.

The Cost of Breaking Even: a Perspective on the Net Clinical Impact of Adding Aspirin to Antithrombotic Therapies in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

PURPOSE: Outcomes from randomized controlled trials (RCTs) inform the latest recommendations on percutaneous coronary intervention (PCI) management of a short period of oral anticoagulation (OAC), a P2Y12 receptor inhibitor, and aspirin for 1 week or until hospital discharge in patients with atrial fibrillation (AF) undergoing PCI, and up to 4 weeks in individuals considered to be at high-risk for ischemic events, followed by discontinuation of aspirin and continuation of OAC and a P2Y12 inhibitor for up to 12 months. METHODS: We examined and summarized the outcomes of bleeding and major adverse cardiac events (MACEs) from RCTs and meta-analyses, published between 2013 and 2022, comparing therapy with OAC and a P2Y12 inhibitor with and without aspirin in AF patients undergoing PCI with stenting. RESULTS: Data comparing dual therapy with OAC and a P2Y12 inhibitor alone to triple therapy with OAC, a P2Y12 inhibitor, and aspirin with respect to the risks of MACEs, including stent thrombosis within the first 30 days, are underpowered and inconclusive. The addition of aspirin does not appear to be associated with a decreased risk of ischemic events, even in patients with high-risk CHA2DS2-VASc scores, but does significantly increase bleeding hazards. The increased safety of newer generation drug-eluting stents may have further minimized any theoretical anti-ischemic benefits of aspirin. The possible attenuation of the pleiotropic effects of concomitant cardiovascular medications by aspirin may also have been a contributing factor. CONCLUSION: The addition of aspirin to OAC and a P2Y12 inhibitor is likely associated with a net clinical harm in patients with AF who undergo PCI with stenting, even within the first 1-4 weeks after PCI. Revisiting the guideline recommendations to administer aspirin in this timeframe may be warranted.

Clinical outcomes and predictors of complications in patients undergoing leadless pacemaker implantation.

BACKGROUND: Leadless pacemakers have emerged as a viable alternative for traditional transvenous pacemakers to reduce the risk of device-related complications. OBJECTIVE: The purpose of this study was to examine the real-world clinical outcomes and complications associated with the implantation of leadless pacemaker devices. METHODS: Using the National Readmission Database (NRD), we examined patient demographics, and in-hospital and 30-day procedural outcomes after leadless pacemaker implantation from 2016-2018. Our cohort comprised adults (≥18 years) with an ICD-10 procedural code for leadless pacemaker implantation. RESULTS: Our cohort included a total of 7821 patients who underwent leadless pacemaker implantation. Overall immediate procedure-related complications, as defined broadly in this study, occurred in 7.5% of patients. Pericardial effusion without the need for pericardiocentesis occurred in 1.9% of patients, with pericardiocentesis performed in 1.0%. Vascular complications occurred in 2.3% of patients; 0.33% required repair, and device dislodgment occurred in 0.51%. The most significant predictor for procedural complications was end-stage renal disease (odds ratio [OR] 1.65; 95% confidence interval [CI] 1.17-2.32; P = .004), congestive heart failure (OR 1.28; 95% CI 1.01-1.62; P = .04), and coagulopathy (OR 1.77; 95% CI 1.34-2.34; P <.001). All-cause readmission occurred in 17.9% of patients within 30 days from device implant, with 1.36% of readmissions being procedure related. At 30 days postimplant and after discharge, 0.25% of patients needed a new pacemaker, and 0.18% had pericardial complications. CONCLUSION: In our large real-life cohort, we found the rate of serious complications after leadless pacemaker implantation to be relatively low and comparable to prior studies in a high-risk population with multiple comorbid conditions.

Temporal Trends in Outcomes in Patients With Adrenocortical Carcinoma: A Multidisciplinary Referral-center Experience.

CONTEXT: Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies. OBJECTIVE: This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials. METHODS: A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019). RESULTS: A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients with hormonal overproduction. More patients in the late cohort had stage IV disease compared to the early cohort (36.8% vs 23.1%; P < .0001). Resection of the primary tumor was performed in 502 patients (80.8%). Complete resection (R0) was more common in the late cohort (165 [60.2%]) than in the early cohort (100 [44.6%]; P = .0005). Of 475 patients with metastatic disease (stage IV or recurrent metastatic disease), 352 (74.1%) received mitotane, 320 (67.4%) received chemotherapy, and 53 (11.2%) received immunotherapy. In the early cohort, 70 (33%) received 2 or more lines of therapy, whereas in the late cohort, 127 (48%) received 2 or more lines of therapy. The 5-year overall survival (OS) rates were 65%, 58%, 45%, and 10% for stage I, II, III, and IV disease, respectively, whereas the 2-year OS rates in patients with stage IV disease was 24% in the early cohort and 46% in the late cohort (P = .01). CONCLUSION: ACC clinical outcomes improved over the past 2 decades as more patients had complete resection or received more lines of systemic therapy.

Cytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients' Survival.

CONTEXT: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. OBJECTIVE: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. DESIGN AND SETTING: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. INTERVENTION: Performance (or not) of cytoreductive surgery of the primary tumor. MAIN OUTCOME AND MEASURES: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. RESULTS: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). CONCLUSION: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.

High rates of advanced prostate cancer in the Middle East: Analysis from a tertiary care center.

OBJECTIVES: Prostate cancer incidence is increasing in the Middle East (ME); however, the data of stage at the diagnosis and treatment outcomes are lacking. In developed countries, the incidence of de novo metastatic prostate cancer ranges between 4% and 14%. We hypothesized that the rates of presentation with advanced disease are significantly higher in the ME based on clinical observation. This study aims to examine the stage at the presentation of patients with prostate cancer at a large tertiary center in the ME. METHODS: After Institutional Review Board approval, we identified the patients diagnosed with prostate adenocarcinoma and presented to a tertiary care center between January 2010 and July 2015. Clinical, demographic, and pathological characteristics were abstracted. Patients with advanced disease were stratified according to tumor volume based on definitions from practice changing clinical trials. Descriptive and Kaplan-Meier survival analysis was used. RESULTS: A total of 559 patients were identified, with a median age at the diagnosis of 65 years and an age range of 39-94 years. Median prostate-specific antigen (PSA) at the presentation was 10 ng/ml, and almost a quarter of the men (23%) presented with metastatic disease. The most common site of metastasis was the bone (34/89, 38%). High-volume metastasis was present in 30.3%, 9%, and 5.2% of the cohort based on STAMPEDE, CHAARTED, and LATITUDE trial criteria, respectively. CONCLUSION: This is the first report showing the high proportion of men from ME presenting with de novo metastasis. This could be due to many factors, including the highly variable access to specialist multidisciplinary management, lack of awareness, and lack of PSA screening in the region. There is a clear need to raise the awareness about prostate cancer screening and early detection and to address the rising burden of advanced prostate cancer affecting men in the ME region.

Gender disparities in difficulty accessing healthcare and cost-related medication non-adherence: The CDC behavioral risk factor surveillance system (BRFSS) survey.

Ensuring healthcare access is critical to maintain health and prevent illness. Studies demonstrate gender disparities in healthcare access. Less is known about how these vary with age, race/ethnicity, and atherosclerotic cardiovascular disease. We utilized cross-sectional data from 2016 to 2019 CDC Behavioral Risk Factor Surveillance System (BRFSS), a U.S. telephone-based survey of adults (≥18 years). Measures of difficulty accessing healthcare included absence of healthcare coverage, delay in healthcare access, absence of primary care physician, >1-year since last checkup, inability to see doctor due to cost, and cost-related medication non-adherence. We studied the association between gender and these variables using multivariable-adjusted logistic regression models, stratifying by age, race/ethnicity, and atherosclerotic cardiovascular disease status. Our population consisted of 1,737,397 individuals; 54% were older (≥45 years), 51% women, 63% non-Hispanic White, 12% non-Hispanic Black,17% Hispanic, 9% reported atherosclerotic cardiovascular disease. In multivariable-adjusted models, women were more likely to report delay in healthcare access: odds ratio (OR) and (95% confidence interval): 1.26 (1.11, 1.43) [p < 0.001], inability to see doctor due to cost: 1.29 (1.22, 1.36) [p < 0.001], cost-related medication non-adherence: 1.24 (1.01, 1.50) [p = 0.04]. Women were less likely to report lack of healthcare coverage: 0.71 (0.66, 0.75) [p < 0.001] and not having a primary care physician: 0.50 (0.48, 0.52) [p < 0.001]. Disparities were pronounced in younger (<45 years) and Black women. Identifying these barriers, particularly among younger women and Black women, is crucial to ensure equitable healthcare access to all individuals.

Promise and Perils of Telehealth in the Current Era.

PURPOSE OF REVIEW: The concept of telehealth has been around since the early twentieth century and has been used in different healthcare specialties. However, with the recent COVID-19 pandemic necessitating physical distancing, there has been an increased emphasis and utilization of this mode of healthcare delivery. With increasing reliance on telehealth services, data from investigator groups have brought to light several merits as well as failings of telehealth. RECENT FINDINGS: Telehealth services have been associated with improved healthcare outcomes while remaining a cost-effective mode of healthcare delivery. Improving access and timeliness of care has also been observed by multiple telehealth-related studies. Finally, telehealth services are also anticipated to serve as part of emergency preparedness protocol and have shown to reduce provider-patient supply-demand mismatch, prevalent in certain subspecialties. With these benefits come certain challenges that have been highlighted in the literature. Indiscriminate utilization of telehealth services may widen public health disparities among minority groups and may increase overall healthcare expenditure due to overutilization of care, and the digital platform may jeopardize security of patient data. COVID-19 has been a catalyst in increasing utilization of telehealth services. As we move forward from the current pandemic, lessons learned from the studies demonstrating benefits and challenges associated with telehealth should be taken into account when drafting post-pandemic telehealth policies. Special attention should be paid to ensure that telehealth narrows, and not widens, the currently existing disparities in access to healthcare.

Invasive Therapies for Acute Coronary Syndromes in the COVID-19 Era.

PURPOSE OF REVIEW: To identify and address the challenges associated with the care of ACS patients during the coronavirus 2019 pandemic. RECENT FINDINGS: The COVID-19 pandemic has had a considerable global impact with over 2.0 million deaths worldwide so far. There has been considerable evidence suggesting that COVID-19 increases the risk of acute coronary syndromes (ACS). We propose characterizing ACS patients into 3 distinct categories to better assist in appropriate triage and management: critically ill patients, non-critically ill ST elevation myocardial infarction (STEMI) patients, and non-critically ill non-ST elevation myocardial infarction (NSTEMI)/unstable angina (UA) patients. We thoroughly review treatments strategies, management considerations, and current consensus statements for the care of COVID-19 patients with ACS. As we continue to gain more experience with management of COVID-19 in ACS patients and as health-care workers and patients continue to get vaccinated, we must continue to adapt our strategies to treat this high-risk group of patients.

Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma.

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC. METHODS: A retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC. RESULTS: Eight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21-49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2-9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8-not reached) and median duration of therapy was 8.5 months (range 2-22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events. CONCLUSIONS: In our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.

Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with high risk of recurrence despite macroscopically complete surgical resection. The main predictors of ACC recurrence include advanced disease stage, incomplete surgical resection, cortisol production, certain genetic alterations, and high proliferation rate (Ki-67 proliferation index). Mitotane has been the mainstay adjuvant therapy of ACC. However, the use of mitotane is based on retrospective and occasionally conflicting evidence. As mitotane levels can take a few months before reaching therapeutic levels, there is an emerging practice of combining platinum-based chemotherapy with mitotane in the adjuvant setting. Retrospective data indicate that radiotherapy is an option for select patients, particularly those with positive resection margins. There are multiple knowledge gaps in selecting patients for adjuvant therapy. It is of great importance to establish risk calculators to predict recurrence and to implement molecular profiling of ACC to guide adjuvant therapy. The role of immunotherapy in metastatic ACC is emerging and if deemed efficacious, then future studies will be needed to ascertain the role of adjuvant immunotherapy in ACC.

High-Cost Cancer Treatment Across Borders in Conflict Zones: Experience of Iraqi Patients in Lebanon.

PURPOSE: Conflict-induced cross-border travel for medical treatment is commonly observed in the Middle East. There has been little research conducted on the financial impact this has on patients with cancer or on how cancer centers can adapt their services to meet the needs of this population. This study examines the experience of Iraqi patients seeking care in Lebanon, aiming to understand the social and financial contexts of conflict-related cross-border travel for cancer diagnosis and treatment. PATIENTS AND METHODS: After institutional review board approval, 60 Iraqi patients and caregivers seeking cancer care at a major tertiary referral center in Lebanon were interviewed. RESULTS: Fifty-four respondents (90%) reported high levels of financial distress. Patients relied on the sale of possessions (48%), the sale of homes (30%), and vast networks to raise funds for treatment. Thematic analysis revealed several key drivers for undergoing cross-border treatment, including the conflict-driven exodus of Iraqi oncology specialists; the destruction of hospitals or road blockages; referrals by Iraqi physicians to Lebanese hospitals; the geographic proximity of Lebanon; and the lack of diagnostic equipment, radiotherapy machines, and reliable provision of chemotherapy in Iraqi hospitals. CONCLUSION: As a phenomenon distinct from medical tourism, conflict-related deficiencies in health care at home force patients with limited financial resources to undergo cancer treatment in neighboring countries. We highlight the importance of shared decision making and consider the unique socioeconomic status of this population of patients when planning treatment.