Trends in pulmonary tuberculosis mortality between 1985 and 2018: an observational analysis.

BACKGROUND: Pulmonary tuberculosis (TB) is a major source of global morbidity and mortality. Latent infection has enabled it to spread to a quarter of the world's population. The late 1980s and early 1990s saw an increase in the number of TB cases related to the HIV epidemic, and the spread of multidrug-resistant TB. Few studies have reported pulmonary TB mortality trends. Our study reports and compares trends in pulmonary TB mortality. METHODS: We utilized the World Health Organization (WHO) mortality database from 1985 through 2018 to analyze TB mortality using the International Classification of Diseases-10 codes. Based on the availability and quality of data, we investigated 33 countries including two countries from the Americas; 28 countries from Europe; and 3 countries from the Western Pacific region. Mortality rates were dichotomized by sex. We computed age-standardized death rates per 100,000 population using the world standard population. Time trends were investigated using joinpoint regression analysis. RESULTS: We observed a uniform decrease in mortality in all countries across the study period except the Republic of Moldova, which showed an increase in female mortality (+ 0.12 per 100,000 population). Among all countries, Lithuania had the greatest reduction in male mortality (-12) between 1993-2018, and Hungary had the greatest reduction in female mortality (-1.57) between 1985-2017. For males, Slovenia had the most rapid recent declining trend with an estimated annual percentage change (EAPC) of -47% (2003-2016), whereas Croatia showed the fastest increase (EAPC, + 25.0% [2015-2017]). For females, New Zealand had the most rapid declining trend (EAPC, -47.2% [1985-2015]), whereas Croatia showed a rapid increase (EAPC, + 24.9% [2014-2017]). CONCLUSIONS: Pulmonary TB mortality is disproportionately higher among Central and Eastern European countries. This communicable disease cannot be eliminated from any one region without a global approach. Priority action areas include ensuring early diagnosis and successful treatment to the most vulnerable groups such as people of foreign origin from countries with a high burden of TB and incarcerated population. Incomplete reporting of TB-related epidemiological data to WHO excluded high-burden countries and limited our study to 33 countries only. Improvement in reporting is crucial to accurately identify changes in epidemiology, the effect of new treatments, and management approaches.

An observational epidemiological study to analyze intracerebral hemorrhage across the United States: Incidence and mortality trends from 1990 to 2017.

OBJECTIVES: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variations remain unknown. Our study reports updated trends of ICH incidence, mortality, and mortality to incidence ratio (MIR) across the US. MATERIALS AND METHODS: Observational study to evaluate the incidence and mortality from ICH across the US. Data was obtained from Global Burden of Disease (GBD) database. Age-Standardized Incidence (ASIRs) and Death (ASDRs) Rates, as well as the Mortality- to-Incidence ratios (MIRs) for ICH in the US overall and state-wise from 1990-2017. Joinpoint regression analysis was used, with presentation of estimated annual percentage changes (EAPCs). RESULTS: Overall decrease in ASIRs, ASDRs, and MIRs in the US for both sexes. The 2017 mean ASIR was 25.67/100,000 for men and 19.17/100,000 for women, whereas mean ASDR was 13.96/100,000 for men and 11.35/100,000 for women. District of Columbia had greatest decreases in ASIR EAPCs for both men and women at -41.25% and -40.58%, respectively, and greatest decreases in ASDR EAPCs for men and women at -55.38% and -48.51%, respectively. MIR between 1990-2017 decreased in men by -12.12% and women by -7.43%. MIR increased in men from 2014-2017 (EAPC +2.2%) and in women from 2011-2017 (EAPC +1.0%). CONCLUSION: Decreasing trends in incidence, mortality, and MIR. No significant trends in mortality were found in the last 6 years of the study period. MIR worsened in males from 2014-2017 and females from 2011-2017, suggesting decreased ICH-related survival lately.

Prevalence of Variants of Uncertain Significance in Patients Undergoing Genetic Testing for Hereditary Breast and Ovarian Cancer and Lynch Syndrome.

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.

Patent Foramen Ovale and Ascending Aortic Dilatation Causing Platypnea-Orthodeoxia Syndrome.

Platypnea-orthodeoxia syndrome (POS) is an underdiagnosed clinical syndrome characterized by dyspnea (platypnea) and hypoxemia (orthodeoxia) in the upright position that resolves when recumbent. POS is often due to an underlying right-to-left shunt. Four broad mechanisms for the shunt have been described: intracardiac shunts, intrapulmonary shunts, hepatopulmonary syndrome, and pulmonary ventilation-perfusion mismatch. A 68-year-old male with a past medical history of chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, ascending aortic dilation (3.9 cm), myelofibrosis, and status post stem cell transplant complicated by graft versus host disease was found hypoxemic (oxygen saturation: 82%) on routine visit prompting hospitalization. Hypoxemia initially responded to 40% FiO2 but subsequently progressed to refractory hypoxemia on 100% FiO2. A chest computed tomography (CT) scan showed evidence of multiple segmental pulmonary emboli with patent central pulmonary arteries. Hypoxemia out of proportion to pulmonary embolism clot burden and examination findings consistent with orthodeoxia prompted further investigations. Nuclear medicine scan showed radiotracer activity in both brain and kidneys consistent with a small right-to-left shunt (5.9%). Transesophageal echocardiography (TEE) revealed a patent foramen ovale (PFO) with a right-to-left shunt across the atrial septum, with a maximum opening of 3.5 mm and tunnel length of 25 mm. Right heart catheterization (RHC) is consistent with the right-to-left shunt and normal right heart pressures. The degree of the shunt was not significant enough to explain the degree of hypoxemia, but all the diagnostic studies were performed in a supine position, possibly underestimating the degree of the shunt. PFO closure with transcatheter 30-mm Gore device (GORE® CARDIOFORM, Arizona, USA) decreased supplemental oxygen requirement from 75% high-flow nasal cannula (NC) to room air (RA) immediately after the procedure. The patient was subsequently discharged home on a baseline oxygen requirement of 2 L NC at nighttime. POS should be suspected when a patient develops severe hypoxemia after changing from a recumbent position to a sitting or standing position. The identification and correction of the shunting or mismatch often allow complete resolution of POS. Transthoracic echocardiography with agitated saline, TEE, and RHC are the diagnosis modalities of choice. Left heart cardiac catheterization remains the gold standard, which would demonstrate a mismatch in oxygen saturation between the pulmonary vein and the aorta. Our patient's PFO was successfully closed by a percutaneous transcatheter closure device leading to the complete resolution of hypoxemia immediately.

Nodule net: A centralized prospective lung nodule tracking and safety-net program.

BACKGROUND: Inadequate follow-up of suspicious lung nodules can result in diagnostic delays and potential progression to advanced lung cancer. In 2015, a multidisciplinary lung nodule management program, Nodule Net, was implemented to increase the timely follow-up rate. In this study, we sought to evaluate the effectiveness of the program. METHODS: 2398 chest CT reports were reviewed for the presence of a lung nodule. Baseline demographics, nodule characteristics, and follow-up recommendations were collected. For reports that did not include structured recommendations, Fleischner Society guidelines were applied if appropriate. The rate of follow-up imaging was recorded and compared with historical rates. RESULTS: Lung nodules were reported on 1367 (57%) of scans. Of the 632 participants with recommendations for follow-up, the Nodule Net nurse navigator was notified on 523 (83%). Of these, 408 (78%) completed follow-up, compared to 57/109 (52%) in those who were not reported to Nodule Net tracking system (risk ratio: 1.49, 95% CI: 1.24-1.79, p-value < 0.05). Out of these 408, nodule net outreach was required to prompt the follow-up in 116 (28%). Of these, a lung malignancy was diagnosed in 4 (4%). CONCLUSIONS: Management of lung nodules is a complex process. Implementation of a lung nodule tracking program led to a significant increase in the completion of recommended follow-up imaging compared with usual care. Developing a comprehensive lung nodule program using an automated software system rather than manual processes to refer and track incidental findings may further reduce barriers to completion of follow-up.

Longstanding Phenytoin Use as a Cause of Progressive Dyspnea.

CASE PRESENTATION: A 54-year-old South African man with a medical history of type 2 diabetes mellitus, seizure disorder, OSA, and latent TB presented to the ER with gradually progressive dyspnea over months. He also reported occasional dry cough and fatigue at presentation but denied fever, chills, chest pain, leg swelling, palpitations, or lightheadedness. He was treated with a course of levofloxacin for presumed community-acquired pneumonia as an outpatient without improvement and had tested negative for COVID-19. He denied occupational or environmental exposures or sick contacts, though he had traveled back to South Africa 1 year before presentation. He had complex partial seizures for the past 22 years, which had been well controlled on phenytoin (300 mg daily). His other home medications included dulaglutide, sertraline, and atorvastatin and had no recent changes. He quit smoking 30 years ago after smoking one pack per day for 10 years.

Food Coma: Hyperammonemic Encephalopathy From Refeeding Syndrome.

Hyperammonemic encephalopathy (HAE) from extrahepatic causes is increasingly being recognized. Refeeding syndrome is characterized by severe fluid and electrolyte shifts following the reintroduction of nutrition. We describe the case of a 67-year-old man with bilateral maxillary sinus squamous cell carcinoma on nivolumab who became comatose after initiation of enteral feeding. Initial workup was notable for severe hypophosphatemia (<1 mg/dL) and markedly elevated ammonia (226 µmol/L). Neuroimaging was unrevealing. Correction of hypophosphatemia did not improve mental status. Ammonia levels briefly decreased while holding enteral feeding but worsened again on resumption. High-volume continuous renal replacement therapy was recommended but deferred in accordance with family wishes. We hypothesize that HAE may have been precipitated by a combination of refeeding-induced high nitrogen burden and limited detoxification via the urea cycle and extrahepatic pathways in the setting of severe protein-energy malnutrition and underlying malignancy. Nivolumab could have contributed as well.

A rare etiology of pulmonary nodules.

INTRODUCTION: Pulmonary nodules are a frequent finding on chest imaging studies, with differential including multiple benign entities, but malignancy is often also a concern. Computed Tomography (CT) and Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) scans have improved the characterization of pulmonary nodules. However, many nodules remain indeterminate and require periodic monitoring. Here we report two nodular pulmonary amyloidosis cases as a rare etiology of enlarging pulmonary nodules with FDG avidity. CASE PRESENTATION: Case 1: 75-year-old woman with a history of asthma, emphysema, bronchiectasis, and a 48 pack-year smoking history was found to have subcentimeter groundglass pulmonary nodules in the right lower lobe (RLL). Follow-up imaging demonstrated an increased solid component of a RLL bulla associated with mild FDG uptake on PET scan. A CT-guided biopsy revealed amyloid deposition. Case 2: 77-year-old man with a history of interstitial lung disease, asbestos exposure, prior tobacco use, and atrial fibrillation treated with amiodarone was found to have a 1.6cm RLL nodule. Follow-up imaging identified an interval increase to 2.0cm associated with moderate FDG uptake on PET scan. Transthoracic biopsy identified amyloid deposition. DISCUSSION: Nodular pulmonary amyloidosis is a rare form of amyloidosis which may present as an enlarging pulmonary nodule with FDG avidity, raising concern for malignancy. A CT-guided biopsy is a safe way to establish a diagnosis. Recent studies have demonstrated an association between nodular pulmonary amyloidosis and marginal zone lymphomas, which warrants longitudinal follow-up for evolution to lymphoproliferative disorder.

Trends of HIV Mortality between 2001 and 2018: An Observational Analysis.

Since the beginning of the epidemic in the early 1980s, HIV-related illnesses have led to the deaths of over 32.7 million individuals. The objective of this study was to describe current mortality rates for HIV through an observational analysis of HIV mortality data from 2001 to 2018 from the World Health Organization (WHO) Mortality Database. We computed age-standardized death rates (ASDRs) per 100,000 people using the World Standard Population. We plotted trends using locally weighted scatterplot smoothing (LOWESS). Data for females were available for 42 countries. In total, 31/48 (64.60%) and 25/42 (59.52%) countries showed decreases in mortality in males and females, respectively. South Africa had the highest ASDRs for both males (467.7/100,000) and females (391.1/100,000). The lowest mortalities were noted in Egypt for males (0.2/100,000) and in Japan for females (0.01/100,000). Kyrgyzstan had the greatest increase in mortality for males (+6998.6%). Estonia had the greatest increase in mortality for females (+5877.56%). The disparity between Egypt (the lowest) and South Africa (the highest) was 3042-fold for males. Between Japan and South Africa, the disparity was 43,454-fold for females. Although there was a decrease in mortality attributed to HIV among most of the countries studied, a rising trend remained in a number of developing countries.

Trends in Breast Cancer Mortality Between 2001 and 2017: An Observational Study in the European Union and the United Kingdom.

PURPOSE: Breast cancer is the most common cancer in women worldwide, representing 25.4% of the newly diagnosed cases in 2018. The past two decades have seen advancements in screening technologies, guidelines, and newer modalities of treatment. Our study reports and compares trends in breast cancer mortality in the European Union and the United Kingdom. MATERIALS AND METHODS: We used the WHO Mortality Database. We extracted breast cancer mortality data from 2001 to 2017 on the basis of the International Classification of Diseases, 10th revision system. Crude mortality rates were dichotomized by sex and reported by year. We computed age-standardized death rates (ASDRs) per 100,000 population using the world standard population. Breast cancer mortality trends were compared using joinpoint regression analysis. RESULTS: We analyzed data from 24 EU countries, including the United Kingdom. For women, breast cancer mortality was observed to be downtrending in all countries except Croatia, France, and Poland. For the most recent female data, the highest ASDR for breast cancer was identified in Croatia (19.29 per 100,000), and the lowest ASDR was noted in Spain (12.8 per 100,000). Denmark had the highest change in ASDR and the highest estimated annual percentage change of -3.2%. For men, breast cancer mortality decreased in 18 countries, with the largest relative reduction observed in Denmark with an estimated annual percentage change of -27.5%. For the most recent male data, the highest ASDR for breast cancer was identified in Latvia (0.54 per 100,000). CONCLUSION: Breast cancer mortality rates have down trended in most EU countries between 2001 and 2017 for both men and women. Given the observational nature of this study, causality to the observed trends cannot be reliably ascribed. However, possible contributing factors should be considered and subject to further study.

Qualitative emphysema and risk of COPD hospitalization in a multicenter CT lung cancer screening cohort study.

BACKGROUND: In the United States, 9 to 10 million Americans are estimated to be eligible for computed tomographic lung cancer screening (CTLS). Those meeting criteria for CTLS are at high-risk for numerous cardio-pulmonary co-morbidities. The objective of this study was to determine the association between qualitative emphysema identified on screening CTs and risk for hospital admission. STUDY DESIGN AND METHODS: We conducted a retrospective multicenter study from two CTLS cohorts: Lahey Hospital and Medical Center (LHMC) CTLS program, Burlington, MA and Mount Auburn Hospital (MAH) CTLS program, Cambridge, MA. CTLS exams were qualitatively scored by radiologists at time of screening for presence of emphysema. Multivariable Cox regression models were used to evaluate the association between CT qualitative emphysema and all-cause, COPD-related, and pneumonia-related hospital admission. RESULTS: We included 4673 participants from the LHMC cohort and 915 from the MAH cohort. 57% and 51.9% of the LHMC and MAH cohorts had presence of CT emphysema, respectively. In the LHMC cohort, the presence of emphysema was associated with all-cause hospital admission (HR 1.15, CI 1.07-1.23; p < 0.001) and COPD-related admission (HR 1.64; 95% CI 1.14-2.36; p = 0.007), but not with pneumonia-related admission (HR 1.52; 95% CI 1.27-1.83; p < 0.001). In the MAH cohort, the presence of emphysema was only associated with COPD-related admission (HR 2.05; 95% CI 1.07-3.95; p = 0.031). CONCLUSION: Qualitative CT assessment of emphysema is associated with COPD-related hospital admission in a CTLS population. Identification of emphysema on CLTS exams may provide an opportunity for prevention and early intervention to reduce admission risk.