Harpreet Singh

Alveolar–pleural or broncho-pleural fistulas, leading to persistent air leaks (PALs), are associated with prolonged hospitalization and substantial morbidity. While guidelines advocate surgical repair as the primary treatment, its efficacy is limited. For patients recently subjected to thoracic surgery or those for whom surgery is contraindicated due to severe illness, viable treatment alternatives have been lacking. This article reviews the newer and less invasive treatment options for PALs. Further research is crucial, including randomized controlled trials comparing these options, and long-term monitoring of intervention outcomes is warranted.

The incidence of colorectal cancer (CRC) in the U.S. is declining in adults 50 years and older; however, recent studies suggest an increasing disease burden among adults under age 50. This study aims to compare the incidence, mortality, and mortality-to-incidence ratios (MIRs) of CRC in EU15+ countries to determine if similar age-stratified occurrences are observed across these countries with similar “Western lifestyle”-related risk factors. Incidence and mortality rates for CRC between 1990 and 2019 were extracted using the Global Burden of Disease database. The data were age-stratified into groups between ages 25–49, 50–69, and greater than 69 years. We observed that the incidence of CRC increased globally for all age groups, with the highest increase observed for males (75.9%) and females (27.7%) aged 25–49. A similar trend was observed in 15 of the 19 EU15+ countries for males and 16 of the 19 EU15+ countries for females aged 25–49. Global mortality rates decreased for all age groups in females but increased for males in all age groups. This raises concerns regarding potentially modifiable risk factors contributing to increased CRC development and underscores the importance of implementing standardized screening at an earlier stage to ensure adequate detection in the younger population.

Hereditary Breast and Ovarian Cancer (HBOC) and Lynch Syndrome (LS) are the most common inherited cancer syndromes identified with genetic testing. Testing, though, commonly reveals variants of uncertain significance (VUSs). This is a retrospective observational study designed to determine the prevalence of pathogenic mutations and VUSs in patients tested for HBOC and/or LS and to explore the characteristics of the VUS population. Patients 18–80 years old that met NCCN criteria for HBOC and/or LS genetic screening were tested between 2006 and 2020 at Mount Auburn Hospital in Cambridge, Massachusetts. A total of 663 patients were included in the study, with a mean age of 50 years old and 90% being females. Pathogenic mutations were identified in 12.5% and VUSs in 28.3%. VUS prevalence was associated with race (p-value = 0.019), being particularly higher in Asian populations. Patients with a personal history of breast cancer or family history of breast or ovarian cancer were more likely to have a VUS (personal breast: OR: 1.55; CI: 1.08–2.25; family breast: OR: 1.68; CI: 1.08–2.60, family ovarian OR: 2.29; CI: 1.04–5.45). In conclusion, VUSs appear to be detected in almost one third patients tested for cancer genetic syndromes, and thus future work is warranted to determine their significance in cancer development.

Cystic fibrosis transmembrane conductance regulator modulators have revolutionized cystic fibrosis (CF) care in the past decade. This study explores the CF-related mortality trends in the US from 1999 to 2020. We extracted CF-related mortality data from the CDC WONDER database. CF age-standardized mortality rates (ASMRs) were identified by ICD-10 code E84 and were stratified by demographic and geographical variables. Temporal trends were analyzed using Joinpoint modeling. CF-related ASMRs decreased from 1.9 to 1.04 per million population (p = 0.013), with a greater reduction in recent years. This trend was replicated in both sexes. The median age of death increased from 24 to 37 years. CF mortality rates decreased across sex, white race, non-Hispanic ethnicity, census regions, and urbanization status. Incongruent trends were reported in non-white races and Hispanic ethnicity. A lower median age of death was observed in women, non-white races, and Hispanic ethnicity. SARS-CoV-2 infection was the primary cause of death in 1.7% of CF decedents in 2020. The national CF-related mortality rates declined and the median age of death among CF decedents increased significantly indicating better survival in the recent years. The changes were relatively slow during the earlier period of the study, followed by a greater decline lately. We observed patterns of sex, ethnic, racial, and geographical disparities associated with the worsening of the gap between ethnicities, narrowing of the gap between races and rural vs. urban counties, and closing of the gap between sexes over the study period.

PURPOSE: Lung cancer is the leading cause of cancer-related deaths in the United States. This study aims to analyze lung cancer incidence, mortality, and related statistics from 1990 to 2019, focusing on national- and state-level trends and exploring potential disparities between sexes. METHODS: The Global Burden of Disease database was used to extract tracheal, bronchus, and lung cancer mortality data from 1990 to 2019 for both males and females and across all states of the United States. Age-standardized incidence rates, age-standardized mortality rates, disability-adjusted life years (DALYs), and mortality-to-incidence indices (MIIs) were studied to assess for gender-based, geographic, and temporal disparities. Joinpoint regression analysis was performed to further evaluate trends. RESULTS: The incidence of these cancers in the United States decreased between 1990 and 2019 by 23.35%, with a more significant decline in males (37.73%) than females (1.41%). Similarly, for mortality, a decrease was observed for both sexes combined (26.83%), but much more significantly for males (40.23%) than females (6.01%). The MIIs decreased overall, but there were variations across states. DALYs decreased for both sexes combined, with males experiencing a larger reduction, but an increase was noted in some states for females. CONCLUSION: This analysis reveals diverse trends pertaining to the incidence, mortality, and disability burden associated with lung cancer by sex and states in the United States, emphasizing the need for targeted interventions to reduce disparities. These findings contribute to our understanding of the current landscape of lung cancer and can inform future strategies for prevention, early detection, and management.

PURPOSE: AML accounts for 80% of acute leukemia in adults. While progress has been made in treating younger patients in the past 2 decades, there has been limited improvement for older patients until recently. This study examines the global and European Union (EU) 15+ trends in AML between 1990 and 2019. METHODS: We extracted age-standardized incidence rates (ASIRs), age-standardized death rates (ASMRs), and disability-adjusted life years, stratified by sex from the Global Burden of Disease Study database, and mortality-to-incidence ratio (MIR) were computed. Trends were compared using Joinpoint regression. RESULTS: The findings show a global increase in AML incidence for both sexes from 1990 to 2019. In the EU15+ countries, most countries exhibited an increase in ASIR for both sexes. Joinpoint revealed that globally for male patients, ASIR steadily increased until 2010, remained stable until 2015 followed by a decline till 2019. Similar trends were observed in female patients. For ASMR, although there was an increase globally and in most EU15+ countries, there was a statistically significant decrease in mortality rates globally and in the majority of EU15+ countries in recent years. MIR improved in both sexes globally. On age stratification, AML burden was highest among older groups (55 years and older), while the lowest rates were observed in younger than 20 years. CONCLUSION: The findings from our study indicate a global rise in AML incidence and mortality in both sexes and decrease in MIR from 1990 to 2019 suggesting a better survival. However, on Joinpoint analysis, there is no change in MIR in women in the past decade and past 4 years in men indicating plateau in survival trends despite recent advances.

Background: Pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality. In the last two decades, significant advances have been made in management of World Health Organization (WHO) group 1 PH. However, there are no approved targeted pharmacotherapies for PH secondary to left-sided heart diseases or chronic hypoxic lung diseases which are thought to account for more than 70–80% of the disease burden. No recent investigation has analyzed and compared the mortality burden related to WHO group 1 PH with the mortality burden with WHO groups 2–5 PH at the national level in the United States (US). We hypothesize that WHO group 1 PH-related mortality has improved over the last two decades in comparison to WHO groups 2–5 PH. Methods: In this study, we used data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) the underlying cause of death database to study age-standardized mortality rates related to PH in the US from 2003 to 2020. Results: A total of 126,526 deaths were recorded from PH in the US between 2003 and 2020. Across the study period, PH-related ASMR increased from 17.81 per million population in 2003 to 23.89 in 2020 with a percentage change (PC) of +34%. However, there are contrasting mortality trends in WHO group 1 PH when compared to WHO groups 2–5 PH. Data demonstrated a decline in mortality from group 1 PH regardless of gender. In contrast, an increase in mortality from WHO groups 2–5 PH was observed, accounting for the major proportion of the overall PH mortality burden in recent years. Conclusions: PH-related mortality continues to an increase primarily due to increase in mortality attributed to WHO groups 2–5 PH. These findings have notable public health implications. Screening and risk assessment tools for secondary PH, risk factor modification, and novel management strategies are vital to improve outcomes.

Introduction: Awake prone positioning (APP) has been widely applied in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure. However, the results from randomised controlled trials (RCTs) are inconsistent. We performed a meta-analysis to assess the efficacy and safety of APP and to identify the subpopulations that may benefit the most from it. Methods: We searched five electronic databases from inception to August 2022 (PROSPERO registration: CRD42022342426). We included only RCTs comparing APP with supine positioning or standard of care with no prone positioning. Our primary outcomes were the risk of intubation and all-cause mortality. Secondary outcomes included the need for escalating respiratory support, length of ICU and hospital stay, ventilation-free days, and adverse events. Results: We included 11 RCTs and showed that APP reduced the risk of requiring intubation in the overall population (RR 0.84, 95% CI: 0.74–0.95; moderate certainty). Following the subgroup analyses, a greater benefit was observed in two patient cohorts: those receiving a higher level of respiratory support (compared with those receiving conventional oxygen therapy) and those in intensive care unit (ICU) settings (compared to patients in non-ICU settings). APP did not decrease the risk of mortality (RR 0.93, 95% CI: 0.77–1.11; moderate certainty) and did not increase the risk of adverse events. Conclusions: In patients with COVID-19-related acute hypoxemic respiratory failure, APP likely reduced the risk of requiring intubation, but failed to demonstrate a reduction in overall mortality risk. The benefits of APP are most noticeable in those requiring a higher level of respiratory support in an ICU environment.