Venetoclax with decitabine or azacitidine in relapsed or refractory acute myeloid leukemia.

Relapsed or refractory acute myeloid leukemia (AML) is associated with poor outcomes and resistance to therapy. The addition of venetoclax, a BCL-2 antagonist, to lower-intensity therapies results in improved survival in the first-line setting compared to monotherapy with a hypomethylating agent or low-dose cytarabine. Despite this, much remains unknown about the performance of venetoclax with a hypomethylating agent following the first-line setting. Additionally, while the ELN 2022 guidelines appear to improve the prognostication of AML, clarification is needed to determine how the revision applies to lower-intensity strategies. To investigate this, we retrospectively analyzed the performance of venetoclax with decitabine or azacitidine in relapsed or refractory AML under the ELN 2022 guidelines. We demonstrated that the ELN 2022 revision is not optimized for lower-intensity venetoclax-based strategies. To refine the prognostication schema, we showed significantly improved response and survival benefits for patients with mutated NPM1 and IDH. Relatively, patients with mutated NRAS, KRAS, and FLT3-ITD were associated with inferior response and survival. Furthermore, there is an unmet clinical need for tools to improve the selection of lower-intensity therapy candidates with borderline functional status. Using an incremental survival computation method, we discovered that a CCI score threshold of 5 distinguishes patients at an elevated risk of death. Together, these novel findings highlight areas of refinement to improve survival in relapsed or refractory AML.

Prediction of Liver Steatosis and Fibrosis Based on Clinical Variables Using a Large National Survey Database.

Background: Vibration-controlled transient elastography (VCTA) and controlled attenuation parameter (CAP) are used more frequently to diagnose liver fibrosis and steatosis among nonalcoholic fatty liver disease patients. However, limited robust data are available on the clinical variables strongly related to these disorders and who needs to be referred for screening. Methods: We used the National Health and Nutritional Examination Survey 2017-2018 database to identify the clinical predictors strongly related to liver steatosis and advanced fibrosis. Baseline comparisons among these groups were made based on widely accepted cutoffs. Linear and logistic regressions were performed to identify the associations between the clinical variables and liver steatosis and fibrosis. We used adaptive lasso regression, gradient-boosted model, and decision trees to determine clinical variables strongly related to these outcomes. A Naïve Byes classifier and decision trees were used to calculate the predicted probabilities of liver steatosis and fibrosis. Results: 32% of our population had evidence of liver steatosis using 294 dB/m as a cutoff. An increase in age, serum triglyceride, and body mass index were associated with a statistically significant increase in liver steatosis; in contrast, females had statistically significantly lower values for liver steatosis by 15 points in the multivariable linear regression model. Serum LDL, smoking, and systolic and diastolic blood pressure are poorly associated with liver steatosis in the adaptive lasso regression. On the other hand, sex, tobacco use, metabolic energy expenditure, and serum triglyceride are the least associated with liver fibrosis based on decision tree analysis and a gradient-boosted model. In decision trees, people with a body mass index above 30 and HbA1c above 5.7 have a 72% likelihood of liver steatosis compared to 14% for people with a body mass index below 30. On the other hand, people with a body mass index above 41 have a 38% likelihood of liver fibrosis. Conclusion: Body mass index, hemoglobin A1c, serum triglyceride level, sex, and age could provide a good prediction for liver steatosis, while body mass index, blood pressure, platelet counts, hemoglobin A1c, serum LDL, or HDL are highly associated with liver fibrosis and should be used as an initial screening tool prior referral for VCTE/CAP.

Venetoclax with decitabine or azacitidine in the first-line treatment of acute myeloid leukemia.

Treatment paradigms for acute myeloid leukemia (AML) have evolved at a rapid pace in recent years. The combination of venetoclax with a hypomethylating agent prolonged survival in clinical trials when compared to hypomethylating agent monotherapy. However, little is known about the performance of venetoclax-based regimens outside of clinical trials, given conflicting safety and efficacy data. Even less is known about the impact of the hypomethylating agent backbone. In this study, we demonstrate that decitabine-venetoclax is associated with a significantly higher rate of grade three or higher thrombocytopenia, but lower rates of lymphocytopenia compared to azacitidine-venetoclax. There was no difference in response or survival across ELN 2017 cytogenetic risk categories in the overall cohort. Significantly more patients succumb to relapsed or refractory disease than death from any other cause. We demonstrated that a Charlson comorbidity index score threshold of seven identifies exceptionally high-risk patients, providing evidence for clinical use to reduce the risk of early treatment-related mortality. Lastly, we provide evidence that measurable residual disease negativity and an IDH mutation predict a significant survival benefit outside clinical trials. Taken together, these data illuminate the real-world performance of venetoclax and decitabine or azacitidine in the treatment of AML.

Predictors of Secondary Lung Cancer Among Hodgkin Lymphoma Survivors: A Nationwide Analysis.

PURPOSE: There is insufficient data regarding the incidence rate of secondary lung cancer among Hodgkin lymphoma (HL) survivors and the predisposing factors. METHODS: We analyzed the data from the cohort of patients who had HL between 1973 and 2015 using the Surveillance Epidemiology and End Results database (SEER). Data on patient's age, gender, year of diagnosis with HL, Ann-Arbor stage, Histology, racial groups, date of last follow-up, date of death, and treatment modalities were collected. RESULTS: We identified a total of 56,856 patients with HL; of those, 862 had secondary lung cancer, with an incidence rate of 157 (95%CI: 147-168) per 100,000 person-years. The median overall survival from time of HL diagnosis for those with secondary lung cancer was 12.1 years (95% CI: 10.7-13) compared to 27.1 years (95% CI: 26.5-27.6) for those who did not develop lung cancer (log-rank P-value of <.01). After propensity score weighting, radiation therapy was associated with a higher risk of secondary lung cancer (hazard ratio (HR): 1.23, 95% CI: 1.002-1.55) with a P-value of 0.048. Older age at the time of HL diagnosis and male gender were associated with higher risk, with an HR of 1.07 (95% CI 1.062-1.073) and an HR of 1.602 (95% CI 1.33-1.94), respectively. Furthermore, chemotherapy increased the risk only among older age groups. CONCLUSION: Older age at the time of HL diagnosis, male gender, radiation therapy, and chemotherapy only among older age groups were associated with higher risk for secondary lung cancer, with 50% of the cases occurring within 9.1 years following HL diagnosis.

Major adverse cardiac events in symptomatic women with non-obstructive CAD on coronary CTA: pooled analysis from PROMISE and SCOT-HEART.

The presence of non-obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA) has been associated with the occurrence of major adverse cardiac events (MACE). However, factors associated with the development of MACE in symptomatic women with non-obstructive CAD on coronary CTA have not been fully elucidated. We sought to examine the influence of risk factors and coronary artery calcification on MACE in symptomatic women with non-obstructive CAD on coronary CTA. Women from PROMISE and SCOT-HEART trials with none or non-obstructive CAD on coronary CTA comprised the study cohort. Baseline characteristics and clinical presentation were assessed. Survival analysis using Kaplan-Meier curves was done to compare outcomes stratified by the atherosclerotic cardiovascular disease (ASCVD) risk score and the Agatston score. The primary endpoint was a composite of all-cause mortality, myocardial infarction, and revascularization. 2597 women had non-obstructive CAD or normal coronary CTA, with a median follow-up of 32 months. Compared to women without MACE, women with MACE had lower high-density lipoprotein cholesterol (HDL-C) levels and higher mean ASCVD risk scores. Further, women with non-obstructive CAD and ASCVD ≥ 7.5% had higher risk of MACE than those with ASCVD < 7.5% [3.2% vs. 1.1%, adjusted HR (aHR) of 3.1 (95% CI 1.32, 7.23), P-value 0.009]. The Agatston calcium score, on the other hand, was not independently associated with MACE among this population of symptomatic women. Symptomatic women with non-obstructive CAD on coronary CTA are at higher risk for MACE, with the ASCVD risk score being independently associated with the occurrence of adverse events.

Prognostic Impact of Cytoreductive Nephrectomy in Patients with Metastatic Renal Cell Carcinoma: Data from a Large Population-Based Database.

PURPOSE: Cytoreductive nephrectomy (CN) was considered a well-established treatment modality for patients with metastatic renal cell carcinoma (RCC) in the interferon era. However, its role after the introduction of multiple targeted therapies is less well established. Herein, We evaluated the effect of CN on overall survival (OS) on patients with RCC who were identified through the Surveillance, Epidemiology, and End Results database (SEER). MATERIALS AND METHODS: A total of 5,483 patients with metastatic RCC were identified from 2010 to 2016 using the SEER database. Factors pertaining to the following variables were collected: presence or absence of CN; age; gender; grade; status of metastasis to bone, liver, lung and brain; tumor stage; nodal status; histological subtypes; and chemotherapy status. Subjects who had CN were matched with those who did not in all previously mentioned covariates using inverse probability weighting. These weights were then used in adjusted Cox regression models to report doubly robust estimates. RESULTS: CN was associated with 67% reduction in the hazards of death. Advanced T-stage, N1 disease, advanced tumor grade, non-clear histology and metastasis to bone, liver, lung or brain are independent risk factors for death. Patients with T4 disease benefited less of CN compared to those with T1 disease, while higher number of metastatic sites didn't predict worse outcome among those who had CN. CONCLUSION: CN could provide a survival advantage in favorable risk patients with RCC in the era of targeted therapy.

Factors Associated with Worse Outcome in Early Stage Gastric Cancer Using the Surveillance, Epidemiology, and End Results (SEER) Database.

Background The benefit of adjuvant treatment in gastric adenocarcinoma patients with involvement of the muscularis propria but not beyond is unclear. We aim to establish a model that identifies the factors that adversely affect the prognosis in these patients. Methods We used the Surveillance, Epidemiology, and End Results (SEER) database to identify subjects with stage T2aN0M0 gastric adenocarcinoma who had tumor resection between 2004 and 2015. Data pertaining to the following variables were collected: age, gender, ethnicity, tumor size, grade, site, number of lymph nodes (LNs) being examined, and extent of surgery. Results A total of 1307 patients met our inclusion criteria. The five-year overall survival (OS) was 65%. The following factors were significantly associated with a shorter OS in univariate analysis. Age > 60 years, non-Hispanic whites and non-Hispanic blacks, patients with less than 15 lymph nodes examined at the time of surgery, tumors at the fundus and cardia of the stomach, and those who underwent endoscopic resection or had partial esophagectomy. On multivariate Cox regression, the following factors were predictors for worse OS: age > 60 years with a hazards ratio (HR) = 2.03 (95% CI: 1.49-2.76), patients with less than 15 lymph nodes examined with HR = 1.72 (95% CI: 1.34-2.20), non-Hispanic whites and non-Hispanic blacks with HR = 1.62 (95% CI: 1.26-2.08), and tumors within the cardia and fundus of the stomach with HR = 1.51 (95% CI: 1.21-1.89). Conclusion Patients with stage T2aN0M0 gastric cancer who had their tumor located at the cardia or fundus of the stomach or those with inadequate lymph nodes resection had inferior survival and could potentially benefit from adjuvant chemotherapy.

A case report of double negative anti-GBM disease.

Goodpasture's disease is a life-threatening autoimmune disease that can lead to end stage renal disease and death. We report a case of 61-year-old female who presented with deteriorating renal function. Initial laboratory investigations were negative for autoimmune antibodies including negative anti-neutrophilic cytoplasm antibodies and anti-glomerular basement membrane (anti-GBM) antibodies using both enzyme-linked immunosorbent assay and indirect immunofluorescence. However, renal biopsy was positive for linear IgG staining. Despite starting plasmapheresis and corticosteroids treatment, her renal functions continued to deteriorate and she was started on regular hemodialysis. This case highlights the challenging presentation and diagnosis of anti-GBM disease, which requires a high clinical suspicion necessarily for early diagnosis and treatment to improve survival rates.

The Effect of Perioperative Bevacizumab on Disease-Free and Overall Survival in Locally Advanced HER-2 Negative Breast Cancer: A Meta-Analysis.

INTRODUCTION: Multiple trials demonstrated that adding Bevacizumab to the standard neoadjuvant chemotherapy in HER-2 negative breast cancer increases pathological complete response. We conducted this meta-analysis to evaluate that effect on survival. METHODS: We performed a systematic search for randomized trials measuring the effect of adding either neoadjuvant or adjuvant Bevacizumab to the standard chemotherapy on disease-free and overall survival in breast cancer surgical candidates. The Mantel-Haenszel method and random effect model were used to analyze the data. A total of 7 randomized controlled trials were included in the analysis with a mean follow-up of 45 months. RESULTS: No statistically significant difference in overall survival was found after adding Bevacizumab to the standard chemotherapy in the overall study population, HR=0.9, 95% CI (90.72-1.13), estrogen/ progesterone positive subgroup, HR=0.99, 95% CI (0.72-1.35), or in triple negative breast cancer, HR=0.88, 95% CI (0.77-1.01). However, there was a small but significant improvement in disease-free survival in triple negative breast cancer with a HR of 0.88, 95% CI (0.78-0.98), but not in estrogen/ progesterone receptor positive tumors, HR=1.01, 95% CI (0.81-1.26). CONCLUSIONS: The addition of Bevacizumab along with the standard chemotherapy would not improve overall survival in breast cancer surgical candidates, however, due to a small but significant improvement on disease-free survival in triple negative breast cancer, that would not eliminate the possibility of a certain subgroup of the latter who might benefit from adding Bevacizumab.

Synchronous endometrial adenocarcinoma and carcinosarcoma in endometrial polyp.

INTRODUCTION: Carcinosarcoma is a rare gynecological malignancy and it usually follows an aggressive clinical course. Rarely, it can be confined to an endometrial polyp or be synchronous with another gynecological malignancy. Herein, we report a rare case of synchronous carcinosarcoma confined to an endometrial polyp and endometrioid endometrial adenocarcinoma arising from a distinct uterine wall site. CASE PRESENTATION: A 57-year-old female patient presented with heavy vaginal bleeding. She underwent hysterectomy with bilateral salpingo-oophorectomy for endometrioid endometrial adenocarcinoma that was diagnosed preoperatively through dilation and curettage. Full histopathological examination of the uterine specimen revealed carcinosarcoma confined to a 4 cm endometrial polyp in addition to a stage IA endometrioid endometrial adenocarcinoma which arose from a distinct uterine wall. CONCLUSION: Having an endometrioid endometrial cancer diagnosis preoperatively through dilation and curettage and at examination of the frozen section specimen following surgical resection should not preclude the standard full histopathological examination of the uterine specimen, since this could reveal an additional uterine malignancy, such as carcinosarcoma. Such a finding would alter the post-operative management, prognosis, and outcome even if it is confined to an endometrial polyp.

Is Peripherally Inserted Central Catheter-Related Thrombosis Associated With ABO Blood Group? A Case-Control Pilot Study.

Peripherally inserted central catheter (PICC) use is associated with many complications including line-related thrombosis. Several studies and meta-analyses confirmed the increased risk to develop venous thromboembolism in non-O blood group individuals. Our pilot study aimed to examine whether PICC-related thrombosis is influenced by ABO blood group. We identified patients admitted to Hurley Medical Center between March 2012 and March 2016 who had PICC placed during their admission, had their ABO blood group identified in their medical record, and had upper extremity venous Doppler ultrasound performed on the same side of PICC. We excluded pregnant women, patients on anticoagulation initiated before PICC insertion, and patients with active cancer. Data of 227 patients who met our criteria were analyzed. Of these patients, 140 (61.7%) patients had PICC-related thrombosis (cases) and 86 (37.9%) patients had O blood group. Controls were patients who had PICC and did not develop PICC-related thrombosis. Multivariate logistic regression revealed no association between PICC-related thrombosis and ABO blood group (adjusted odds ratio: 1.1; 95% confidence interval: 0.6-2.0; P = .733). Therefore, our data suggest that non-O blood group does not increase the odds of having PICC-related thrombosis.

Does acute care for the elderly (ACE) unit decrease the incidence of falls?

To determine whether acute care for the elderly (ACE) units decrease the incidence of patient falls compared to general medical and surgical (GMS) units, a non-concurrent prospective study included individuals aged 65 and older admitted to ACE or GMS units over a 2-year span was done. There were 7069 admissions corresponded to 28,401 patient-days. A total of 149 falls were reported for an overall incidence rate (IR) of 5.2 falls per 1000 patient-days, 95% CI, 4.4/1000-6.1/1000 patient-days. The falls IR ratio for patients in ACE unit compared to those in non-ACE units after adjusting for age, sex, prescribed psychotropics and hypnotics, and Morse Fall Score was 0.27/1000 patient-days; 95% CI, 0.13-0.54; p < 0.001. So, an estimated 73% reduction in patient falls between ACE unit and non-ACE units. Hospitals may consider investing in ACE units to decrease the risk of falls and the associated medical and financial costs.

Primary Idiopathic Osteoarthropathy: Could It Be Related to Alcoholism?

Background. Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by abnormal proliferation of the skin and bony structures at the distal extremities resulting in digital clubbing, periosteal bony reaction, and joint effusion. It can be primary (idiopathic) without any clear identifiable etiology as well as secondary to variety of systemic diseases most notably lung pathology. Case Presentation. We describe a rare case of primary idiopathic osteoarthropathy in a male patient who presented with severe pain and tenderness in his legs. His history was significant for long standing alcoholism. Physical examination showed severe fingers and toes clubbing. He reported similar changes in his mother. Clinical and radiological findings were remarkable for distal leg tenderness and diffuse periosteal bony reactions, respectively. Computerized tomography scan failed to show any pathology apart from fatty liver infiltration. In the absence of obesity or diabetes, this was consistent with alcoholic steatosis. He was started on nonsteroidal anti-inflammatory drug which dramatically improved his symptoms. Conclusion. Primary hypertrophic osteoarthropathy should be considered in a previously healthy person presenting with bony pain and finger clubbing especially after ruling out the common secondary causes. Moreover, alteration of prostaglandin metabolism secondary to alcoholic consumption might be a contributing factor.

Factors associated with short recurrence-free survival in completely resected colon cancer.

Background: Several factors could affect disease recurrence in surgically resected colon cancer. While the role of certain factors such as cancer stage and grade is well established, the role of other factors (e.g., histological subtypes) is yet to be determined. Objective:Therefore, we conducted a study to evaluate the impact of several factors in recurrence-free survival (RFS) in patients who were disease free following surgical resection of the colon cancer. Design/Methods: Data were collected for patients with Stage I-III colon cancer who underwent complete surgical resection of the tumor between January 2010 and December 2015 in our institution. A total of 90 subjects met the inclusion criteria and were included in the study. The following factors were collected at the time of surgical resection of the colonic tumor: patient's age, gender, colon cancer stage, grade and histological subtype, body mass index, hemoglobin A1c, and smoking history. Results: A total of 28 patients (31%) developed recurrence and had a mean follow-up time of 19.8 months (range: 2-54.4 months). Median RFS was 54.4 months with a 5-year RFS of 49%. Advanced colonic cancer stage and mucinous histological subtype were associated with shorter RFS with an HR of 2.37, 95% CI = 1.38-4.06, and 95% CI = 1.02-5.90, respectively. Current smokers or those who quit less than 15 years earlier tended to have worse RFS with an HR of 2.47, 95% CI = 0.98-6.27. Conclusion: Advanced colon cancer stage and mucinous histological subtype are independent risk factors for cancer recurrence and shorter RFS in completely resected colonic tumor.

Azacitidine-induced cryptogenic organizing pneumonia: a case report and review of the literature.

BACKGROUND: Myelodysplasia syndrome is a heterogeneous group of hematological disorders that are characterized by abnormal morphology and cytopenias of bone marrow elements. Azacitidine is a hypomethylating agent that is commonly used in treatment of myelodysplasia syndrome. We present an extremely rare case of cryptogenic organizing pneumonia following therapy with azacitidine and a review of the relevant literature. This is the fifth case of azacitidine-induced interstitial lung disease and the sixth one due to hypomethylating drugs; of interest, this is the first reported case that has occurred after the second cycle. Our case report highlights an important, potentially treatable and rare side effect of azacitidine and hypomethylating agents in general that might be overlooked by oncologists. Furthermore, our review of the literature showed heterogeneity in the clinical outcome which might, in part, be due to delay in initiating corticosteroids treatment. CASE PRESENTATION: A 67-year-old white man presented with worsening shortness of breath and mild productive cough that started 1 week prior to his presentation. An initial chest X-ray showed infiltration of both lung fields. Radiographic findings of computed axial tomography, results of bronchoscopy and a lung biopsy were consistent with cryptogenic organizing pneumonia. The patient showed variable clinical response to steroids and he remained dependent on home oxygen. CONCLUSIONS: We concluded that there is a recognizable potentially life-threatening toxicity due to organizing pneumonia secondary to azacitidine in the setting of myelodysplasia syndrome treatment. This toxicity is not limited to the first cycle as in previous cases; furthermore, pleural effusion can be associated with this toxicity. Health care professionals should be aware of this recognizable side effect. Early recognition and timely management are critical to prevent permanent lung fibrosis.