Asciminib in chronic myeloid leukemia: a STAMP for expedited delivery?

Asciminib is a novel tyrosine kinase inhibitor (TKI) that specifically targets the myristoyl pocket. It has increased selectivity and potent activity against BCR-ABL1 and the mutants that most frequently prevent the activity of the ATPbinding competitive inhibitors. Results for clinical trials in patients with chronic myeloid leukemia that have received two or more TKI (randomized against bosutinib) or who have a T315I mutation (single arm study) have shown high levels of activity and a favorable toxicity profile. Its approval has offered new options for patients with these disease features. There are, however, a number of unanswered questions that remain to be defined, including the optimal dose, understanding the mechanisms of resistance, and, importantly, how it compares to ponatinib in these patient populations for whom we now have these two options available. Ultimately, a randomized trial is needed to answer questions to which we currently offer speculative informed guesses. The novelty of its mechanism of action and the exciting early data offer the potential for asciminib to address some of the remaining needs in the management of patients with chronic myeloid leukemia, including second-line therapy after resistance to a front-line second-generation TKI and improving successful treatment-free remission. Multiple studies are ongoing in these areas, and one can only hope that the desired randomized trial comparing asciminib to ponatinib will be conducted soon.

Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy.

INTRODUCTION: Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. CASE REPORT: We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome.Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. DISCUSSION: As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.

Cardiovascular risk stratification in diabetic patients following stress single-photon emission-computed tomography myocardial perfusion imaging: the impact of achieved exercise level.

BACKGROUND: Previous studies have demonstrated that diabetic patients undergoing exercise stress single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) have significantly lower cardiac events when compared to the diabetic patients undergoing pharmacologic stress SPECT MPI across all perfusion categories. However, there are limited data on the level of exercise achieved during exercise SPECT MPI among diabetic patients and its impact on cardiovascular outcomes. METHODS: We retrospectively analyzed 14,849 consecutive patients (3,654 diabetics and 11,195 non-diabetics) undergoing exercise stress, combined exercise and pharmacologic stress, and pharmacologic stress SPECT MPI from 1996 to 2005 at a single tertiary care center. Diabetic and non-diabetic patients were categorized into 3 groups based on the metabolic equivalents (METs) achieved: ≥5 METs, <5 METs, and pharmacologic stress groups. All studies were interpreted using the 17-segment ASNC model. The presence, extent, severity of perfusion defects were calculated using the summed stress score (SSS), and patients were classified into normal (SSS < 4), mildly abnormal (SSS 4-8), and moderate-severely abnormal (SSS > 8) categories. Annualized event rates (AER) for the composite end point of non-fatal myocardial infarction and cardiac death were calculated over a mean follow-up period of 2.4 ± 1.4 years with a maximum of 6 years. RESULTS: In moderate-severe perfusion abnormality (SSS > 8) category, diabetic patients who were able to achieve ≥5 METs had significantly lower AER compared to diabetic patients who were unable to achieve ≥5 METs (3% vs 5.5%, P = .04), and non-diabetic patients unable to achieve ≥5 METs (3% vs 4.8%, P < .001). Diabetic patients who achieved a high workload of ≥10 METs had a very low AER of 0.9%. Diabetic patients, who attempted exercise but were unable to achieve ≥5 METs, still had significantly lower AER than diabetics undergoing pharmacologic stress MPI across all perfusion categories [1.5% vs 3.2%, P = .006 (SSS < 4); 2.5% vs 4.9%, P = .032 (SSS 4-8); 5.5% vs 10.3%, P = .003 (SSS > 8)]. After adjustment for cardiovascular risk factors, the percentage decrease in cardiac event rate for every 1-MET increment in exercise capacity was 10% in the overall cohort, 12% in diabetic group, and 8% in non-diabetic group. CONCLUSIONS: Despite significant perfusion defects, diabetic patients who achieve ≥5 METs during stress SPECT MPI have significantly reduced risk for future cardiac events. Diabetic patients who achieve ≥10 METs have a very low annualized event rate. These findings support that exercise capacity obtained during SPECT MPI is a surrogate for outcomes among diabetic patients undergoing nuclear stress testing.

Deep neck space infections in end-stage renal disease patients: Prevalence and mortality.

Deep neck space infections (DNSI) are severe infections within the layers of neck fascia that are known to be associated with underlying immunocompromised states. Although uremia associated with kidney disease is known to cause immune system dysfunction, DNSI in patients with kidney disease has been poorly studied. This study investigated the prevalence of DNSI and the associated risk of mortality within the United States end-stage renal disease (ESRD) population, using a retrospective cohort study design and the United States Renal Data System database of patients (ages 18-100) who initiated dialysis therapy between 2005 and 2019. International Classification of Disease-9 and -10 codes were used to identify the diagnosis of DNSI and comorbid conditions. Of the 705,891 included patients, 2.2% had a diagnosis of DNSI. Variables associated with increased risk of DNSI were female sex, black compared to white race, catheter, or graft compared to arteriovenous fistula (AVF) access, autoimmune disease, chronic tonsillitis, diagnoses in the Charlson Comorbidity Index (CCI), tobacco use, and alcohol dependence. DNSI diagnosis was an independent risk factor for mortality, which was also associated with other comorbidity factors such as older age, catheter or graft compared to AVF access, comorbidities in the CCI, tobacco use, and alcohol dependence. Because of the increased mortality risk of DSNI in the ESRD population, health professionals should encourage good oral hygiene practices and smoking cessation, and they should closely monitor these patients to reduce poor outcomes.

Risk factors and mortality in dialysis patients with abdominal aortic aneurysm: A retrospective cohort study.

In the general population, abdominal aortic aneurysm (AAA) is synonymous with vascular disease and associated with increased mortality. Vascular disease is common in end-stage renal disease (ESRD) patients on dialysis, but there is limited information on AAA in this population. To address this issue, we queried the United States Renal Data System for risk factors associated with a diagnosis of AAA as well as the impact of AAA on ESRD patient survival. Incident dialysis patients from 2005 to 2014 with AAA and other clinical comorbidities were identified using ICD-9 and ICD-10 codes. Time to death was defined using the time from the start of dialysis to the date of death or to December 31, 2015. Cox proportional hazards (CPH) modeling was used to determine the adjusted hazard ratio (aHR) and 95% confidence intervals (CI) for death. From a total cohort of 820,826, we identified 21,631 subjects with a diagnosis of AAA. When compared to patients without AAA, AAA patients were older and more likely to be of white race and male gender, have a higher mean Charlson comorbidity index (CCI), have hypertension as the ESRD etiology, and use tobacco. Although a bivariate CPH model showed that AAA patients had an increased mortality risk compared to patients without the diagnosis, in the final CPH model, AAA patients had a decreased risk of mortality (aHR = 0.83, 95% CI 0.81-0.84) due to confounding with age. These results suggest that AAA is not associated with increased risk of death in ESRD patients after controlling for various demographic and clinical risk factors.

Demographic and clinical risk factors for diagnosis of sleep disorders in ESRD patients.

BACKGROUND: Sleep disturbances in patients with end-stage renal disease (ESRD) are common and more prevalent than in the general population. This study aims to assess the demographic and clinical risk factors for the diagnosis of sleep disorders in ESRD patients. METHODS: This study is a retrospective analysis of the United States Renal Data System (USRDS) to evaluate risk factors for the diagnosis of sleep disorders, including hypersomnolence, insomnia, restless leg syndrome (RLS), or obstructive or central sleep apnea (OSA/CSA). All ESRD subjects enrolled in the USRDS between 2004-2015 were eligible for inclusion. The risk factors analyzed were age, race, sex, ethnicity, access type, dialysis modality, and the Charlson Comorbidity Index (CCI). All statistical analysis was performed using SAS 9.4, and statistical significance was assessed using an alpha level of 0.05. Descriptive statistics on all variables overall and by each sleep diagnosis were determined. RESULTS: Increasing age, black race, other race, and Hispanic ethnicity were associated with decreased risk of each sleep diagnosis while CCI was associated with increased risk. Females were at increased risk of RLS and insomnia while males were at increased risk of OSA/CSA. Catheter and graft access decreased risk of RLS but increased risk of insomnia compared to AVF access. Catheter access increased risk of OSA/CSA compared to graft access. Hemodialysis increased risk of OSA/CSA compared to peritoneal dialysis. CONCLUSIONS: Some ESRD patients are at an increased risk for diagnosis of sleep disorders based on age, race, sex, comorbid health conditions, and dialysis modality.

Cutaneous squamous cell carcinoma and mortality in end-stage renal disease.

BACKGROUND: In the general population, cutaneous squamous cell carcinoma (cSCC) is associated with increased all-cause mortality. Transplant patients have been shown to have an increased risk of developing cSCC, and their cSCC is associated with an increased risk for mortality. In end-stage renal disease (ESRD) patients, there is extensive mortality and immune dysfunction. Because of this immune system dysfunction, we examined whether cSCC is associated with increased risk of all-cause mortality among ESRD patients, as well as the risk factors for cSCC. METHODS: We analyzed ESRD patients in the United States Renal Data System from 2004-2014, excluding organ transplant recipients. We assessed mortality using a Cox Proportional Hazards (CPH) model to control for various demographic and clinical parameters, identified using international classification of diseases (ICD)-9 codes. RESULTS: Of the 1,035,193 patients included, 624 (0.1%) were diagnosed with cSCC. The median survival time for those with cSCC was 3.91 years [95% confidence interval (CI) = 3.67-4.15], versus 2.92 years [95%CI = 2.92-2.93] for patients without cSCC. ESRD patients with cSCC were at lower risk of death [adjusted hazard ratio = 0.75; 95%CI = 0.69-0.82] compared to those without. Decreased risk of death was also associated with parameters such as black race, Hispanic ethnicity, tobacco dependence and actinic keratosis. Increased mortality risk was associated with increasing age, male sex, hemodialysis (versus peritoneal dialysis) and alcohol dependence. CONCLUSIONS: Contrary to expectations, ESRD patients with a cSCC diagnosis showed reduced all-cause mortality risk relative to those without. The reason for this discrepancy remains unclear, suggesting the need for further study.

Association of psoriasis with myocardial infarction in end-stage renal disease patients.

BACKGROUND: Previous research in non-dialysis patients suggests that the inflammatory skin disease psoriasis is associated with an increased risk of severe vascular events like myocardial infarction (MI). Thus, we determined whether psoriasis represents a significant risk factor for MI in end-stage renal disease (ESRD) patients. METHODS: We queried the United States Renal Data System for ESRD patients starting dialysis between 2004 and 2015. ICD-9 and ICD-10 codes were used to identify those with at least two diagnoses of psoriasis, a diagnosis of MI, and other clinical risk factors. Logistic regression was used to examine the association of psoriasis and various risk factors with MI. RESULTS: Of a cohort of 1,062,693, we identified 6823 (0.6%) subjects with psoriasis and 181,960 (17.1%) with MI. Of the 6823 patients with psoriasis, 1671 (24%) developed an MI. Psoriasis was associated with an increased risk of MI in an unadjusted model [odds ratio (OR) = 1.34; confidence interval (CI) = 1.26-1.42]. However, after controlling for demographics, dialysis modality, access type, and various conditions related to the Charlson Comorbidity Index, psoriasis was not associated with MI (OR = 0.95, CI = 0.89-1.01). Confounders of the association of psoriasis with MI included congestive heart failure (OR = 5.26, CI = 5.17-5.36), pulmonary disease (OR = 1.25, CI = 1.23-1.26), and diabetes with complications (OR = 1.82, CI = 1.79-1.85). CONCLUSIONS: Contrary to prior research in the general population, in the ESRD population psoriasis was not associated with an increased risk of MI after controlling for various demographic and clinical parameters. These data emphasize the importance of an integrated approach since comorbidities may influence the choice of therapy for psoriasis and outcomes.

Non-tuberculous mycobacterial infections in patients with end-stage renal disease: Prevalence, risk factors, and mortality.

Non-tuberculous mycobacterial (NTM) disease has increased in prevalence in the USA, however, little is known on NTM in the population with end-stage renal disease (ESRD). Thus, we investigated patients with ESRD to determine risk factors for NTM disease and mortality. We queried the United States Renal Data System from 2005 to 2015 using International Classification of Diseases (ICD)-9/ICD-10 codes to identify NTM and risk factors. Logistic regression was used to examine the association of risk factors with NTM and Cox proportional hazards modeling was used to assess the association of NTM with mortality. Of 1,068,634 included subjects, 3232 (0.3%) individuals were identified with any NTM diagnosis. Hemodialysis versus peritoneal dialysis (OR=0.10, 95% CI=0.08 to 0.13) was protective for NTM, whereas black (OR=1.27, 95% CI=1.18 to 1.37) or other race compared with white race (OR=1.39, 95% CI=1.21 to 1.59) increased the risk of NTM. HIV (OR=15.71, 95% CI=14.24 to 17.33), history of any transplant (OR=4.25, 95% CI=3.93 to 4.60), kidney transplant (OR=3.00, 95% CI=2.75 to 3.27), diabetes (OR=1.32, 95% CI=1.23 to 1.43), rheumatologic disease (OR=1.92, 95% CI=1.77 to 2.08), and liver disease (OR=2.09, 95% CI=1.91 to 2.30) were associated with increased risk for NTM diagnosis. In multivariable analysis, there was a significant increase in mortality with any NTM diagnosis (HR=1.83, 95% CI=1.76 to 1.91, p≤0.0001). Controlling for relevant demographic and clinical risk factors, there was an increased risk of mortality associated with any diagnosis of NTM. Early diagnosis and treatment of NTM infection may improve survival in patients with ESRD.

Association of psoriasis and stroke in end-stage renal disease patients.

BACKGROUND: Previous research in the general population suggests that the inflammatory skin disease psoriasis is associated with an increased risk of vascular events, such as stroke. Thus, psoriasis may also represent a risk factor for stroke in end-stage renal disease (ESRD) patients. METHODS: We queried the United States Renal Data System for incident dialysis patients between 2004 and 2015. Psoriasis was defined as having at least two international classification of disease (ICD)-9 or ICD-10 diagnosis codes. ICD codes were also used to query the outcome of interest, stroke, as well as other clinical risk factors. Logistic regression was used to examine the association of psoriasis and other risk factors with stroke. RESULTS: Of 966,399 ESRD patients, we identified 89,700 (9.3%) subjects with stroke and 6,286 (0.7%) with psoriasis. Of these psoriasis patients, 796 (0.9%) also had a stroke. Psoriasis was associated with an increased risk of stroke in an unadjusted model [odds ratio (OR)=1.16; 95% confidence interval (CI)=1.08-1.25]. However, after controlling for demographic and clinical risk factors, the final adjusted model showed that psoriasis was not associated with stroke (OR=0.96, CI=0.88-1.04). Congestive heart failure [adjusted OR of 1.79 (CI=1.75-1.83)] was a confounder of the association of psoriasis with stroke. CONCLUSIONS: Contrary to prior research in the general population, psoriasis in ESRD patients was not associated with the risk of stroke after controlling for various demographic and clinical parameters. Our finding emphasizes the importance of controlling for a variety of factors in population studies examining associations of diseases and risk factors.

Risk factors and mortality in patients with listeriosis and end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) is a known immunocompromising status that predisposes patients to developing infections. Disease from Listeria monocytogenes may affect any host but tends to be more severe in the immunocompromised. METHODS: We used a large population of patients with ESRD to identify risk factors for listeriosis and mortality. Patients with a diagnosis of Listeria and other risk factors for listeriosis were identified using claims data from the United States Renal Data System database from 2004-2015. Demographic parameters and risk factors associated with Listeria were modeled using logistic regression while association with mortality was assessed with Cox Proportional Hazards modeling. RESULTS: A diagnosis of Listeria was identified in 291 (0.01%) of a total 1,071,712 patients with ESRD. Cardiovascular disease, connective tissue disease, upper gastrointestinal ulcerative disease, liver disease, diabetes, cancer, and human immunodeficiency virus were all associated with an increased risk of Listeria. Patients with Listeria had an increased risk of death relative to patients without Listeria (adjusted hazard ratio=1.79; 95% confidence interval 1.52-2.10). CONCLUSIONS: Incidence of listeriosis in our study population was over 7 times higher than what has been reported for the general population. The independent association of a Listeria diagnosis with increased mortality is also consistent with the disease's high mortality in the general population. Due to limitations with diagnosis, providers should maintain high clinical suspicion for listeriosis when patients with ESRD present with a compatible clinical syndrome. Further prospective study may help precisely quantify the increased risk of listeriosis in patients with ESRD.

Sleep apnea in end-stage renal disease patients: risk factors and mortality.

Sleep apnea (SA) is highly prevalent in the end-stage renal disease (ESRD) population. However, the impact of SA on mortality in ESRD is unclear. This study investigates the relationship between SA and mortality in ESRD. The United States Renal Data System was queried in a retrospective cohort study to identify ESRD patients aged 18-100 years who initiated hemodialysis between 2005 and 2013. Diagnoses of SA and comorbidities were determined from International Classification of Disease-9 codes and demographic variables from Centers for Medicare and Medicaid Services Form-2728. Cox proportional hazards models were used to examine the association of SA with mortality controlling for multiple variables. Of 858,131 subjects meeting inclusion criteria, 587 were found to have central SA (CSA) and 22,724 obstructive SA (OSA). The SA cohort was younger and more likely to be male and Caucasian compared to the non-SA cohort, with more diagnoses of tobacco and alcohol use, hypertension, heart failure, and diabetes. Both CSA (adjusted hazard ratio (aHR) = 1.42, 95% confidence interval (CI): 1.29-1.56) and OSA (aHR = 1.35, 95% CI: 1.32-1.37) were associated with increased mortality. Other variables associated with increased mortality included age, dialysis initiation with a catheter or graft, alcohol use, hypertension, and cardiovascular disease. Factors associated with decreased mortality included female sex, black race, Hispanic ethnicity, diagnosis of heart failure or diabetes, and an ESRD etiology of glomerulonephritis or polycystic kidney disease. Since a diagnosis of either OSA or CSA increases mortality risk, early identification of SA and therapy in this ESRD population may improve survival.

Psoriasis and pneumonia in the end-stage renal disease population.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease associated with an increased risk for acute infections. Because chronic kidney disease is a risk factor for pneumonia, end-stage renal disease (ESRD) patients with psoriasis may have an increased risk for acquiring pneumonia. MATERIAL AND METHODS: A retrospective cohort analysis was performed using the United States Renal Data System, a medical claims database of all ESRD patients undergoing dialysis in the US. Logistic regression analysis was used to investigate the association of psoriasis with pneumonia in ESRD patients. RESULTS: A total of 6841 (0.7%) ESRD patients were diagnosed with psoriasis; 385,976 (36%) ESRD patients had pneumonia. Although simple models showed that psoriasis was associated with an increased risk of pneumonia in the ESRD population (odds ratio (OR) = 1.14), the final multivariable model found that psoriasis was protective for pneumonia (OR = 0.56) when controlling for age, race, sex, ethnicity, dialysis modality, Charlson Comorbidity Index (CCI), multiple sclerosis, tobacco use and alcohol use. This is due to both the CCI and tobacco use being strong confounders of the association of psoriasis and pneumonia. Black, other race and Hispanic ethnicity were also protective for pneumonia, while increasing age and CCI, female sex, hemodialysis, multiple sclerosis and tobacco and alcohol use were associated with increased risk. CONCLUSIONS: When controlling for multiple factors, psoriasis does not increase the risk for pneumonia in ESRD patients. In this cohort, other factors, such as the CCI and tobacco use, were more strongly associated with increased risk for pneumonia than psoriasis.

Incidence and risk factors for mucormycosis in renal transplant patients.

BACKGROUND: Renal transplant patients are at increased risk for mucormycosis. Diabetes, neutropenia, deferoxamine therapy, and immunosuppressive medications have been associated with increased risk of mucormycosis in studies of solid organ transplant recipients. To focus on renal transplant patients, the US Renal Data System (USRDS) was queried to determine the incidence and risk factors for mucormycosis. METHODS: All renal transplant patients in the USRDS from 1988 to 2015 were queried for a diagnosis of mucormycosis after the first transplant date using ICD-9 and ICD-10 codes. The International Classification of Diseases (ICD) codes, which currently exist in the ninth and tenth revisions, are a global system of classification used to code diagnoses, procedures, and symptoms. We defined proven mucormycosis by a histopathologic or fungal stain procedure code within 7 days of the diagnosis code. Logistic regression controlling for person-years at risk was used to examine demographic and clinical diagnosis risk factors for mucormycosis. RESULTS: Of the 306,482 renal transplant patients, 222 (0.07%) had codes consistent with proven mucormycosis. The incidence of mucormycosis increased from 1990 to 2000 (peak 17.6 per 100,000 person-years) and subsequently demonstrated more variability. Hispanic ethnicity (OR=1.45), age 65 years or greater (OR=1.64), other or black race compared with white race (OR=1.96 and 1.74), cadaver or other donor type (OR=2.41), and receiving tacrolimus (OR=2.09) were associated with increased risk. Comorbidities associated with decreased risk of mucormycosis included female sex (OR=0.68), iron overload (OR=0.56), and receiving mycophenolate mofetil (OR=0.67) or azathioprine (OR=0.53). CONCLUSIONS: In renal transplant patients, age, deceased donor graft transplant, tacrolimus administration, race other than white, and Hispanic ethnicity were associated with increased risk of mucormycosis. Unexpectedly, iron overload was protective. Mucormycosis is a rare infection in renal transplant patients which should be considered in patients with the above risk factors after more common infections have been ruled out.

Association of intermittent versus continuous hemodialysis modalities with mortality in the setting of acute stroke among patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) are 8-10 times more likely to suffer from a stroke compared with the general public. Despite this risk, there are minimal data elucidating which hemodialysis modality is best for patients with ESRD following a stroke, and guidelines for their management are lacking. We retrospectively queried the US Renal Data System administrative database for all-cause mortality in ESRD stroke patients who received either intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). Acute ischemic stroke and hemorrhagic stroke were identified using the International Classification of Diseases 9th Revision (ICD-9)/ICD-10 codes, and hemodialysis modality was determined using Healthcare Common Procedure Coding System (HCPCS) codes. Time to death from the first stroke diagnosis was the outcome of interest. Cox proportional hazards modeling was used, and associations were expressed as adjusted HRs. From the inclusion cohort of 87,910 patients, 92.9% of patients received IHD while 7.1% of patients received CRRT. After controlling for age, race, sex, ethnicity, and common stroke risk factors such as hypertension, diabetes, tobacco use, atrial fibrillation, and hyperlipidemia, those who were placed on CRRT within 7 days of a stroke had an increased risk of death compared with those placed on IHD (HR=1.28, 95% CI 1.25 to 1.32). It is possible that ESRD stroke patients who received CRRT are more critically ill. However, even when the cohort was limited to only those patients in the intensive care unit and additional risk factors for mortality were controlled for, CRRT was still associated with an increased risk of death (HR=1.32, 95% CI 1.27 to 1.37). Therefore, further prospective clinical trials are warranted to address these findings.

Septic arthritis in the end-stage renal disease population.

Septic arthritis is important to consider in any patient who presents with joint pain because it is a medical emergency with an 11% fatality rate. Diagnosis and treatment may improve prognosis; however, many patients do not regain full joint function. In patients with end-stage renal disease (ESRD), immune dysfunction due to uremia and chronic vascular access leads to increased risk of infection. We examined the incidence, risk factors and sequelae of septic arthritis in a cohort of hemodialysis patients. The US Renal Data System was queried for diagnoses of septic arthritis and selected sequelae using International Statistical Classification of Diseases and Related Health Problems-9 and Current Procedural Terminology-4 codes in patients who initiated hemodialysis between 2005 and 2010. Multivariable logistic regression was used to determine potential risk factors for septic arthritis and its sequelae. 7009 cases of septic arthritis were identified, an incidence of 514.8 per 100,000 persons per year. Of these patients, 2179 were diagnosed with a documented organism within 30 days prior to or 14 days after the septic arthritis diagnosis, with methicillin-resistant Staphylococcus aureus infections (57.4%) being the most common. Significant risk factors for septic arthritis included history of joint disease, immune compromise (diabetes, HIV, cirrhosis), bacteremia and urinary tract infection. One of the four sequelae examined (joint replacement, amputation, osteomyelitis, Clostridioides difficile infection) occurred in 25% of septic arthritis cases. The high incidence of septic arthritis and the potential for serious sequelae in patients with ESRD suggest that physicians treating individuals with ESRD and joint pain/inflammation should maintain a high clinical suspicion for septic arthritis.

Epidemiology of Non-Hodgkin's Lymphoma.

Non-Hodgins's lymphoma (NHL) is the most common hematological malignancy worldwide, accounting for nearly 3% of cancer diagnoses and deaths. NHL is the seventh most prevalent cancer and has the sixth highest mortality among cancers in the US. NHL accounts for 4% of US cancer diagnoses, and incidence has increased 168% since 1975 (while survival has improved 158%). NHL is more common among men, those >65 years old, and those with autoimmune disease or a family history of hematological malignancies. NHL is a heterogenous disease, with each subtype associated with different risk factors. Marginal zone lymphoma (MZL) is strongly associated with Sjogren's syndrome (SS) and Hashimoto's thyroiditis, while peripheral T-cell lymphoma (PTCL) is most associated with celiac disease. Occupational exposures among farm workers or painters increases the risk of most of the common subtypes. Prior radiation treatment, obesity, and smoking are most highly associated with diffuse large B-cell lymphoma (DLBCL), while breast implants have been rarely associated with anaplastic large cell lymphoma (ALCL). Infection with Epstein-Barr Virus (EBV) is strongly associated with endemic Burkitts lymphoma. HIV and human herpes virus 8 (HHV-8), is predisposed to several subtypes of DLBCL, and human T-cell lymphoma virus (HTLV-1) is a causative agent of T-cell lymphomas. Obesity and vitamin D deficiency worsen NHL survival. Atopic diseases and alcohol consumption seem to be protective against NHL.

Epidemiology, Staging, and Management of Multiple Myeloma.

Multiple myeloma (MM) is a plasma cell disorder that is on the rise throughout the world, especially in the US, Australia, and Western Europe. In the US, MM accounts for almost 2% of cancer diagnoses and over 2% of cancer deaths (more than double the global proportion). Incidence has risen by 126% globally and over 40% in the US since 1990, while global mortality has risen by 94% and US mortality has fallen by 18%. The 5 year survival in the US has more than doubled over the past decades with the introduction of new targeted therapies and transplant techniques. Risk factors for MM include age (average age of diagnosis is 69), race (African Americans are over double as likely to be diagnosed), sex (men are at a 1.5× risk), and family history. Diagnosis includes serum or urine electrophoresis and free light-chain assay but requires bone marrow biopsy. It is distinguished from smoldering myeloma and monoclonal gammopathy of undetermined significance by a high (>3 g/dL) level of M-protein (monoclonal light chains) and the presence of CRAB (Hypercalcemia, Renal failure, Anemia, Bone pain) symptoms, which include hypercalcemia, renal failure, anemia, and bone pain, suggesting an end-organ damage. International staging system staging involves beta 2 microglobulin and albumin levels, while the revised system considers prognostic factors such as lactate dehydrogenase levels and chromosomal abnormalities. Front-line management includes induction regimen, maintenance therapy and hematopoietic cell transplantation for eligible patients and bisphosphonates or bone-stimulating agents for the prevention of skeletal events. Treatment for relapsed disease includes newly approved monoclonal antibodies like the CD38-targeting daratumumab, proteasome inhibitors, immunomodulating agents, and investigational therapies such as B cell maturation antigen Chimeric antigen receptor T cells.

The Impact of Clostridium Difficile Infections on In-Hospital Outcomes of Venous Thromboembolism (Deep Vein Thrombosis or Pulmonary Embolism) Hospitalizations.

Background Clostridium difficile infection (CDI) is associated with high mortality. Studies have shown an increased rate of venous thromboembolism (VTE) in patients with CDI. However, literature regarding the impact of CDI on outcomes of VTE-related hospitalizations is scarce. Our study aimed to assess the impact of CDI on in-hospital outcomes among VTE hospitalizations. Methods The 2016 National Inpatient Sample (NIS) was used to identify all adult hospitalizations in the United States with a primary discharge diagnosis of acute VTE. Hospitalizations with deep vein thrombosis (DVT) or pulmonary embolism (PE) were included under VTE. The sample was stratified based on the presence or absence of active CDI. Chi-square test and weighted Student's t-test were used to analyze categorical and continuous variables, respectively. The adjusted odds ratio (OR) for clinical outcomes were calculated using multivariate logistic regression analysis. Subgroup analyses for DVT and PE hospitalizations were performed. All analyses were completed in SAS (SAS Institute Inc., Cary, NC), and a p-value of <0.05 was considered statistically significant. Results We identified 382,585 weighted hospitalizations for VTE. Among them, 0.8% had concomitant CDI. The presence of CDI was associated with a statistically significant increase in in-hospital mortality (6% vs. 3%), hospitalization cost ($147,356.5 vs. $55,193), and length of stay (13.7 vs. 5.4 days). There were more incidents of bleeding and acute respiratory failure requiring prolonged ventilation in patients with CDI. The odds of stroke were significantly higher in patients with CDI and DVT. Conclusion CDI independently increased in-hospital mortality in VTE. Preventing CDI in the VTE population may mitigate complications, improve in-hospital outcomes, and reduce treatment costs.