Trends of primary liver cancer incidence and mortality in the United States: A population-based study over the last four decades.

BACKGROUND: Primary liver cancer is the third leading cause of cancer deaths worldwide and has one of the worst 5-year survival rates. This study examines US primary liver cancer incidence and incidence-based mortality trends over four decades. RESEARCH DESIGN AND METHODS: The SEER-9 registry was used to study primary liver cancer cases from 1978 to 2018. The incidence and mortality rates were calculated based on gender, age, race, and stage of diagnosis. Joinpoint regression software was used to calculate the annual percent change. RESULTS: The overall incidence rate of primary liver cancer from 1978 to 2018 increased by 2.71%/year (p<0.001). Rates in patients <50 years old began to fall in 2002 at a rate of -3.62%/year (p<0.001). Similarly, the incidence-based mortality rates for primary liver cancer increased by 2.15%/year (p<0.001). Whereas Whites incidence-based mortality rates began to plateau in 2012 (0.18%/year; p = 0.84), Blacks rates have declined since 2010 (-2.93%/year; p = 0.03), and Asian rates have declined since 1999 (-1.30%/year; p<0.001). CONCLUSION: While the overall primary liver cancer incidence and incidence-based mortality have been increasing over the last four decades, there was an observed decline in incidence and incidence-based mortality in recent years, especially among at-risk subgroups.

Higher body mass index is strongly linked to poor outcomes in adult COVID-19 hospitalizations: A National Inpatient Sample Study.

Aims: The coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 6 million deaths worldwide. Studies on the impact of obesity on patients hospitalized with COVID-19 pneumonia have been conflicting, with some studies describing worse outcomes in patients with obesity, while other studies reporting no difference in outcomes. Previous studies on obesity and critical illness have described improved outcomes in patients with obesity, termed the "obesity paradox." The study assessed the impact of obesity on the outcomes of COVID-19 hospitalizations, using a nationally representative database. Materials and Methods: ICD-10 code U071 was used to identify all hospitalizations with the principal diagnosis of COVID-19 infection in the National Inpatient Database 2020. ICD-10 codes were used to identify outcomes and comorbidities. Hospitalizations were grouped based on body mass index (BMI). Multivariable logistic regression was used to adjust for demographic characteristics and comorbidities. Results: A total of 56,033 hospitalizations were identified. 48% were male, 49% were white and 22% were black. Patients hospitalized with COVID-19 pneumonia in the setting of obesity and clinically severe obesity were often younger. Adjusted for differences in comorbidities, there was a significant increase in mortality, incidence of mechanical ventilation, shock, and sepsis with increased BMI. The mortality was highest among hospitalizations with BMI ≥60, with an adjusted odds ratio of 2.66 (95% Confidence interval 2.18-3.24) compared to hospitalizations with normal BMI. There were increased odds of mechanical ventilation across all BMI groups above normal, with the odds of mechanical ventilation increasing with increasing BMI. Conclusion: The results show that obesity is independently associated with worse patient outcomes in COVID-19 hospitalizations and is associated with higher in-patient mortality and higher rates of mechanical ventilation. The underlying mechanism of this is unclear, and further studies are needed to investigate the cause of this.

Epidemiology, characteristics, and outcomes of adult haemophagocytic lymphohistiocytosis in the USA, 2006-19: a national, retrospective cohort study.

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome characterized by an excessive inflammatory response. Limited data exist on adult HLH. Methods: In this national, retrospective cohort study, we analysed data from the US National Inpatient Sample database collected between October 1, 2006 and December 31, 2019. Using the International Classification of Diseases (ICD) codes, we identified all adult patients who were admitted non-electively with the diagnosis of HLH. We described demographic characteristics, triggers, and associated conditions. Trends of diagnosis, treatment, and in-hospital mortality were analysed using joinpoint models. In-hospital mortality rates were compared using multivariable logistic regression models that adjusted for demographic characteristics and associated conditions. Finally, we described resource utilization outcomes including cost of hospitalization and length of stay. Findings: We identified 16,136 non-elective adult HLH admissions. The population pyramid showed a bimodal distribution, with peaks in young adults (16-30 years) and older adults (56-70 years). Joinpoint regression analysis revealed a significant increase in HLH incidence per 100,000 admissions over the study period (Average Annual Percent Change [APC] = 25.3%, p < 0.0001), and no significant change in rates of in-hospital mortality (slope = -0.01; p = 0.95) or administration of in-hospital HLH treatment (slope = 0.46, p = 0.20). The most common associated conditions were malignancy (4953 admissions [30.7%]), infections (3913 admissions [24.3%]), autoimmune conditions (3362 admissions [20.8%]), organ transplant status (639 admissions [4%]), and congenital immunodeficiency syndromes (399 admissions [2.5%]). In-hospital mortality was higher in older adults and males. Furthermore, Congenital immunodeficiency syndromes had the worst in-hospital mortality rate (mortality rate 31.1%, adjusted OR 2.36 [1.56-3.59]), followed by malignancies (mortality rate 28.4%, adjusted OR 1.80 [1.46-2.22]), infections (mortality rate 21.4%, adjusted OR 1.33 [1.10-1.62]), other/no trigger (mortality rate 13.6%, adjusted OR 0.73 [0.58-0.92]), autoimmune (mortality rate 13%, adjusted OR 0.72 [0.57-0.92]), and post-organ transplant status (mortality rate 14.1%, adjusted OR 0.64 [0.43-0.97]). The overall mean length of stay was 14.3 ± 13.9 days, and the mean cost of hospitalization was $54,900 ± 59,800. Interpretation: We provide insight into the burden of adult HLH in the USA. The incidence has been increasing and the outcomes remain dismal. This signifies the growing need for the development of updated diagnosis and treatment protocols that are specific to adult HLH. Funding: None.

Outcomes of therapeutic plasma exchange in severe autoimmune hemolytic anemia hospitalizations: An analysis of the National Inpatient Sample.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is characterized by humoral and/or cellular immune-mediated hemolysis of red blood cells. The role of therapeutic plasma exchange (TPE) in AIHA is unclear. STUDY DESIGN AND METHODS: We queried the National Inpatient Sample (NIS) for 2002-2019 to identify hospitalizations with the primary diagnosis of AIHA. We included hospitalizations with the highest severity subclass identified by All Patient Refined Disease Related Group (APR-DRG). We used multivariate regression analysis to compare in-hospital mortality and other relevant in-hospital outcomes between hospitalizations that received TPE and those that did not. RESULTS: We identified 255 weighted hospitalizations in the TPE group and 4973 in the control group. Those in the control group were older (median age 67 vs. 48 years, p < .001) and had a higher prevalence of most comorbidities. The TPE group had higher odds of all-cause in-hospital mortality (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.11). They also had higher rates of many secondary outcomes, including requiring mechanical ventilation, developing circulatory shock, acute stroke, urinary tract infections, intracranial hemorrhage, acute kidney injury, and requiring new hemodialysis. No significant differences were noted in the rates of acute myocardial infarctions, bacterial pneumonia, sepsis/septicemia, thromboembolic events, and other bleeding events. Furthermore, the TPE group had a higher median length of hospital stay (19 vs. 9 days, p < .001). CONCLUSION: Hospitalizations with severe AIHA that received TPE had higher rates of adverse in-hospital outcomes.

Delay in treatment of adult hemophagocytic lymphohistiocytosis is associated with worse in-hospital outcomes.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled activation of the immune system leading to multiorgan failure. Timely initiation of HLH-specific treatment is believed to be essential and lifesaving. Due to the rarity of the condition in adults, there is no data available in the literature to investigate the effects of treatment delay in this age group. We used data from the National Inpatient Sample (NIS) to evaluate the inpatient practices of HLH treatment initiation over 13 years (2007-2019) and their association with clinically relevant inpatient outcomes. Patients were divided into early treatment group (<6 days) and late treatment group (≥ 6 days). We compared outcomes using multivariate logistic regression models adjusting for age, sex, race, and HLH-triggering conditions. There were 1327 and 1382 hospitalizations in the early and late treatment groups, respectively. Hospitalization in the late treatment group had higher rates of in-hospital mortality (OR 2.00 [1.65-2.43]), circulatory shock (OR 1.33 [1.09-1.63]), requiring mechanical ventilation (OR 1.41 [1.18-1.69]), venous thromboembolism (OR 1.70 [1.27-2.26]), infectious complications (OR 2.24 [1.90-2.64]), acute kidney injury (OR 2.27 [1.92-2.68]), and requiring new hemodialysis (OR 1.45 [1.17-1.81]). Additionally, we observed no significant trend in the mean time to treatment over the study period. This study shows the importance of early initiation of HLH treatment and highlights the adverse outcomes of treatment delay.

Trends of chronic lymphocytic leukemia incidence and mortality in the United States: a population-based study over the last four decades.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults, and its incidence is higher in elderly individuals. This study aims to examine the burden of CLL in the United States (US) by exploring the incidence-based rates (IBR) and incidence-based mortality (IBMR) across four decades. RESEARCH DESIGN AND METHODS: CLL incidence data were obtained from the SEER-8 registry, covering 8.3% of the US population. Cases were identified using specific diagnostic codes and excluded if diagnosed on autopsy or death certificate. Age-standardized IBR and IBMR were calculated based on age, sex, and ethnicity/race. Joinpoint Regression Program was used to analyze changing trends in incidence and mortality. RESULTS: Since 2011, males' and females' IBRs declined by -1.72%/year (p = 0.028) and -1.07%/year (p = 0.222), respectively. IBR of patients > 75 years increased by 4.01%/year (p < 0.001) form 1998-2010, then declined by 2.02%/year (p = 0.011). IBR of Blacks increased by 0.96%/year (p < 0.001) throughout the study period. CLL IBMR stabilized at -0.38%/year (p = 0.457) since 2012. Whites' IBMR plateaued at a rate of -0.10%/year (p = 0.857) form 2012-2019, while blacks' IBMR increased by 1.40%/year (p = 0.056) between 2000-2019. CONCLUSIONS: The analysis revealed a decline in CLL incidence since 2013, with stable mortality rates since 2012, indicating advancements in CLL management.

Hemophagocytic lymphohistiocytosis in inflammatory bowel disease: a nationwide analysis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening immune dysregulation disease. Patients with inflammatory bowel disease (IBD) can become profoundly immunocompromised due to immunosuppressive therapy, hence increasing the risk of viral infections that can trigger HLH. However, data on the association between IBD and HLH remains limited. We used data from the National Inpatient Sample (2012-2019) utilizing International Classification of Diseases (ICD)-9 or ICD-10 codes to identify individuals with IBD, either Crohn's disease (CD) or ulcerative colitis (UC), and HLH. The primary outcome was to compare the prevalence of HLH among patients with IBD with those without IBD. Secondary outcomes included in-hospital mortality, mean hospital length of stay, and description of HLH-associated triggers in IBD patients. A total of 513,322 hospitalizations included a diagnosis of IBD, 188,297 had UC and 325,025 had CD. Compared to the general population, patients with IBD were older (median age of 52 vs. 49 years, p < 0.05), more likely to be male, and of Asian/Pacific Islander descent, and had a higher median household income. There was also a higher prevalence of liver disease, autoimmune diseases, tobacco abuse, and hypothyroidism (all had p-value of < 0.001) in IBD patients. There were 94 hospitalizations identified with a diagnosis of HLH in IBD patients. Compared to patients without IBD, patients with IBD had increased odds of developing HLH (0.02% vs 0.01%, p-value < 0.001). After adjusting for various demographic characteristics, co-morbidities, and HLH-related conditions, IBD was an independent predictor for developing HLH (adjusted OR, 2.3; 95% CI, 1.847-2.866, p-value of < 0.001). There was no statistical difference between CD and UC in the odds of developing HLH. Compared to IBD patients without HLH, patients with IBD and HLH had a lower mean age at diagnosis (38 vs 52, p-value of < 0.001), higher in-hospital mortality (14.9% vs 1.5%, p-value of < 0.001), and longer mean hospital length of stay (days) (17 vs 5.4, p-value of < 0.001). Prevalence of different HLH-associated illnesses was identified in HLH patient's discharge data. Lymphoma was the most common associated malignancy (18.1%) and cytomegalovirus infection was the most common associated infection (16.0%). Our population-based study suggests that IBD is independently associated with developing HLH. Early recognition of IBD patients presenting with features suggestive of HLH is warranted to aide early diagnosis and aggressive treatment.

Cardiac Arrest Secondary to Inferior ST-Segment-Elevation Myocardial Infarction in Patient with Paroxysmal Nocturnal Hemoglobinuria and COVID-19 Infection.

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have transient attacks of complement-mediated hemolysis and thrombosis that can be spontaneous or secondary to precipitating factors such as infections. We present a case of a 63-year-old male patient with a medical history of PNH who presented with typical chest pain, fever, cough, jaundice, and dark-colored urine. On examination, he was hemodynamically stable but had conjunctival icterus. A few minutes after presentation, the patient suffered a ventricular fibrillation cardiac arrest and then achieved a return of spontaneous circulation after receiving two defibrillator shocks. EKG showed inferior wall ST-segment elevation myocardial infarction. Labs showed hemoglobin of 6.4 g/dl, elevated cardiac markers, serum lactate dehydrogenase, and indirect bilirubin. Serum haptoglobin was < 1 mg/dl. His COVID-19 polymerase chain reaction test was positive. Immediately, the patient received 2 units of packed RBCs and underwent a coronary angiogram (CA), which revealed total proximal occlusion of the right coronary artery. He underwent successful percutaneous coronary intervention (PCI), and two drug-eluting stents were placed. His peripheral blood immunophenotyping and flow cytometry showed loss of glycosylphosphatidylinositol-linked antigens and decreased expression of CD 59/14/24. He was started on ravulizumab, a humanized monoclonal antibody complement five inhibitor. Both PNH and COVID-19 increase the risk of thrombosis. Endothelial injury and cytokine storm increase the risk of thrombosis in COVID-19 patients, whereas the activation of the coagulation system and the impairment of the fibrinolytic system by complement cascade leads to thrombosis in PNH patients. Regardless of which pathway leads to coronary artery thrombosis, CA and PCI can be life-saving.

Trends and Outcomes of Transcatheter Tricuspid Valve Repair and Surgical Tricuspid Valve Repair in Patients With Tricuspid Valve Regurgitation; A Population Based Study.

Data on clinical outcomes of transcatheter tricuspid valve repair (TTVR) compared with surgical tricuspid valve repair (STVR) in patients with tricuspid valve regurgitation (TVR) remains limited. Data from the national inpatient sample (2016-2020) and propensity-score matched (PSM) analysis was utilized to determine adjusted odds ratio (aOR) of inpatient mortality and major clinical outcomes of TTVR compated with STVR in patients with TVR. A total of 37,115 patients with TVR were included: 1830 (4.9%) and 35,285 (95.1%) underwent TTVR and STVR, respectively. After PSM, there was no statistically significant difference in baseline characteristics and medical comorbidities between both groups. Compared with STVR, TTVR was associated with lower inpatient mortality (aOR 0.43 [0.31-0.59], P < 0.01), cardiovascular complications (aOR 0.47 [0.3-0.45], P < 0.01), hemodynamic complications (aOR 0.47 [0.4-0.55], P < 0.01), infectious complications (aOR 0.44 [0.34-0.57], P < 0.01), renal complications (aOR 0.56 [0.45-0.64], P < 0.01), and need for blood transfusion. There was no statistically significant difference in odds of major bleeding events (aOR 0.92 [0.64-1.45], P 0.84). Also, TTVR was associated with less mean length of stay (7 days vs 15 days, P < 0.01) and less cost of hospitalization ($59,921 vs $89,618) compared with STVR. There was an increase in the utility of TTVR associated with a decrease in the utility of STVR from 2016 to 2020 (P < 0.01). Our study showed that compared with STVR, TTVR was associated with lower inpatient mortality and clinical events. Nevertheless, further studies are needed to investigate the difference in outcomes between both procedures.

Relapsed chronic lymphocytic leukemia with a cardiac mass: A case report.

Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the USA. Extra-medullary disease is very rare and is not well characterized. In practice, clinically significant cardiac or pericardial involvement by CLL is extremely rare with only a few case reports in literature. We report a 51-year-old male patient with a past medical history of CLL in remission, who presented with fatigue, dyspnea on exertion, night sweats and left supraclavicular lymphadenopathy. Laboratory investigations were notable for leukopenia and thrombocytopenia. Due to high suspicion of an underlying malignant process, a full body computerized tomography (CT) scan was obtained and showed an 8.8 cm soft tissue mass-like lesion occupying the majority of the right atrium and extending into the right ventricle, with probable pericardial involvement. Enlarged left supraclavicular and mediastinal lymph nodes were also present and had a mild mass effect on the traversing left internal thoracic artery and left pulmonary artery. A transesophageal echocardiogram and cardiac magnetic resonance imaging (MRI) were done to better characterize the cardiac mass. They confirmed a large infiltrating mass (measuring 10 × 7.4 cm) in the right atrium and ventricle, extending into the inferior vena cava inferiorly and coronary sinus posteriorly. A left supraclavicular excisional lymph node biopsy was performed and histopathology was consistent with Small Lymphocytic Lymphoma (SLL)/CLL. This case represents one of the few known cases of cardiac extramedullary-CLL presenting with an isolated cardiac mass. Further studies are needed to characterize the course of the disease, prognosis and optimum management along with the role of surgery.

Isolated Tuberculosis of the Cervical Vertebrae.

Tuberculosis (TB) is a highly infectious disease that primarily affects the lungs, but extrapulmonary affection can occur with lymphatic or hematogenous spread. Skeletal affection commonly involves the spine, but cervical vertebral affection is rare. We report a 23-year-old female patient who presented to the hospital with diffuse limb weakness and neck pain as the only complaints. MRI of the cervical spine revealed a peripherally enhancing lesion arising from the posterior aspects of the cervical vertebrae with compressive myelopathy. She underwent surgical decompression and was noted to have caseous drainage during the procedure. She was started promptly on anti-tuberculous therapy after she had a positive interferon-gamma release assay. Late culture results confirmed isolated cervical TB of the vertebrae as the diagnosis. Prompt awareness and initiation of treatment for vertebral TB are necessary as clinical presentation can mimic other infectious and malignant etiologies.

Acute venous thromboembolic events in patients with monoclonal gammopathy of undetermined significance: An analysis of the National Inpatient Sample.

BACKGROUND: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant plasma cell disorder which despite being clinically silent carries an increased risk of venous thromboembolism (VTE). We conducted a population-based study to investigate the risk of VTE in these patients. METHODS: We utilized the National Inpatient Sample (NIS) for the year 2016 to compare the incidence of acute VTE between patients who carry the diagnosis of MGUS and those who don't. We excluded hospitalizations with age < 18 years and those that had a diagnosed lymphoma, leukemia, solid malignancy, or other plasma cell dyscrasia. We utilized the ICD-10-CM coding system to search the database for codes of VTE, MGUS, and other comorbid conditions. Multivariate logistic regression models were used for comparative analysis adjusting for demographic characteristics and comorbidities. Baseline comorbidities were described as frequencies and proportions for categorical variables and as medians with interquartile ranges for continuous variables. RESULTS: A total of 33,115 weighted hospitalizations were included in the MGUS group. These were compared to 27,418,403 weighted hospitalizations without the diagnosis of MGUS. The MGUS group had higher odds of composite venous thromboembolism (adjusted OR 1.33, 95 % CI 1.22-1.44), deep vein thrombosis (adjusted OR 1.46, 95 % CI 1.29-1.65), and pulmonary embolism (adjusted OR 1.22, 95 % CI 1.09-1.37). CONCLUSION: Patients with MGUS had increased odds of developing acute venous thromboembolism compared to patients with no history of MGUS.

Investigating the association of CD36 gene polymorphisms (rs1761667 and rs1527483) with T2DM and dyslipidemia: Statistical analysis, machine learning based prediction, and meta-analysis.

CD36 (cluster of differentiation 36) is a membrane protein involved in lipid metabolism and has been linked to pathological conditions associated with metabolic disorders, such as diabetes and dyslipidemia. A case-control study was conducted and included 177 patients with type-2 diabetes mellitus (T2DM) and 173 control subjects to study the involvement of CD36 gene rs1761667 (G>A) and rs1527483 (C>T) polymorphisms in the pathogenesis of T2DM and dyslipidemia among Jordanian population. Lipid profile, blood sugar, gender and age were measured and recorded. Also, genotyping analysis for both polymorphisms was performed. Following statistical analysis, 10 different neural networks and machine learning (ML) tools were used to predict subjects with diabetes or dyslipidemia. Towards further understanding of the role of CD36 protein and gene in T2DM and dyslipidemia, a protein-protein interaction network and meta-analysis were carried out. For both polymorphisms, the genotypic frequencies were not significantly different between the two groups (p > 0.05). On the other hand, some ML tools like multilayer perceptron gave high prediction accuracy (≥ 0.75) and Cohen's kappa (κ) (≥ 0.5). Interestingly, in K-star tool, the accuracy and Cohen's κ values were enhanced by including the genotyping results as inputs (0.73 and 0.46, respectively, compared to 0.67 and 0.34 without including them). This study confirmed, for the first time, that there is no association between CD36 polymorphisms and T2DM or dyslipidemia among Jordanian population. Prediction of T2DM and dyslipidemia, using these extensive ML tools and based on such input data, is a promising approach for developing diagnostic and prognostic prediction models for a wide spectrum of diseases, especially based on large medical databases.