Risk of second primary malignancy in patients with primary myelofibrosis: a SEER database study.

Prior studies report a greater incidence of second primary malignancy (SPM) among patients with myeloproliferative neoplasms, although the true risk in primary myelofibrosis (PMF) has not been elucidated. We utilized the Surveillance, Epidemiology, and End Results database to evaluate the risk of SPM in PMF patients and analyzed the effects of sociodemographic factors on the risk of SPM. Out of 5273 patients, 385 patients (7.30%) developed SPM. SPM occurred at SIR of 1.95 (95% CI 1.76-2.15) and AER of 149.01 per 10,000 population. A significantly higher incidence of melanoma (SIR 1.76, 95% CI 1.01-2.86), lymphoma (SIR 3.38, 95% CI 2.28-4.83), and leukemia (SIR 27.19, 95% CI 23.09-31.81) was observed. The risk was significantly higher in patients ≤60 years, males, chemotherapy recipients, within 5 years of PMF diagnosis, and for PMF diagnosed after 2009.

Isocitrate dehydrogenase mutation and risk of venous thromboembolism in glioma: A systematic review and meta-analysis.

BACKGROUND: Patients with malignancies including malignant gliomas have a relatively high risk for venous thromboembolism (VTE). Recent evidence has linked isocitrate dehydrogenase (IDH) mutation with reduced VTE risk in malignant glioma. This meta-analysis aims to quantify the association of IDH mutation status with risks of VTE in patients with glioma. METHODS: We searched PubMed, Google Scholar, Medline OVID, Cochrane library, Cumulative Index to Nursing and Allied Health Literature databases to identify relevant studies. The overall odd ratio (OR) was pooled using the random-effects model. We evaluated the statistical heterogeneity using Cochran's Q statistics and I2 tests. We performed subgroup analyses according to age, tumor, study design, and study quality. RESULTS: A total of 2600 patients from 8 studies were included in the meta-analysis. Patients with IDH mutant-type gliomas had a significantly lower risk of VTE (OR: 0.21, 95 % confidence interval [CI]: 0.09-0.46, I2 = 34 %) compared to patients with IDH wild-type gliomas. Among high-grade (III and IV) glioma, VTE events in IDH-mutant gliomas occurred with an OR of 0.28 (95 % CI: 0.14-0.53). No statistically significant decrease in the VTE risk was observed in grade II gliomas with IDH mutation compared to IDH wild-type gliomas, as indicated by the OR of 0.60 (95 % CI: 0.17-2.11). CONCLUSION: IDH mutation is significantly associated with 79 % lower risk of VTE among patients with high-grade glioma compared to IDH wild-type. Our findings suggest the potential utility of IDH mutation status regarding thromboprophylaxis, and the need for further studies to elucidate the mechanism of the association.

AML with BCR-ABL1 Fusion treated with Imatinib, a Hypomethylating Agent and Venetoclax.

A patient with history of myelodysplastic syndrome (MDS) presented with multifocal pneumonia and was found to have Philadelphia chromosomepositive (Ph+) acute myeloid leukemia (AML). A tyrosine kinase inhibitor (TKI) was added to decitabine and venetoclax combination, providing a molecular and cytogenetic complete response despite additional cytogenetic and molecular abnormalities. She remains in remission after eleven cycles of treatment. Our report describes the tolerability and success of a triplet regimen that incorporates a TKI to a backbone of decitabine and venetoclax in a patient with high-risk disease and with significant comorbidities.

Risk factors for the development of orthostatic hypotension during autologous stem cell transplant in patients with multiple myeloma.

Orthostatic hypotension (OH) is a well-recognized phenomenon occurring in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT), and is associated with significant morbidity and mortality. A retrospective analysis of patients admitted for first ASCT between June 2012 and April 2014 found that 161/222 (73%) patients were diagnosed with OH during the course of ASCT, including 51 patients who were found to have OH on the day of first orthostatic vitals check. Excluding these 51 patients, 110/171 (64%) patients developed OH during the peri-transplant period, at a median of 7 days post ASCT (95% CI: 6.5-8.5). OH did not significantly impact length of hospitalization, progression free and overall survival. Multivariable analysis revealed four risk factors (i.e. ≥0.5% weight loss/day, white race, gabapentin, antihypertensives) and two protective factors (i.e. antihistamine, proton pump inhibitor) associated with the development of peri-transplant OH.

Trends in Primary Gallbladder Cancer Incidence and Incidence-based Mortality in the United States, 1973 to 2015.

OBJECTIVES: Primary gallbladder cancer (GBC) is the most common biliary tract cancer with poor survival despite aggressive treatment. This study aimed to investigate the trends of GBC incidence and incidence-based mortality (IBM) over the last 4 decades. MATERIALS AND METHODS: GBC cases diagnosed between 1973 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Incidence rates, IBM rates, and annual percent changes (APCs) were calculated and stratified according to population and tumor characteristics. RESULTS: The cohort consisted of 10,792 predominantly white (81%) and female (71%) GBC patients. The overall GBC incidence decreased by 1.65% (95% confidence interval [CI]: 1.45% to 1.84%) per year since 1973, but has plateaued since 2002. IBM decreased by 1.69% (95% CI: 1.22% to 2.16%) per year from 1980 to 2015; the rate of decrease in IBM rates was lower during 1997 to 2015 (APC: -1.19%, 95% CI: -1.68% to -0.71%) compared with 1980 to 1997 (APC: -3.13%, 95% CI: -3.68% to -2.58%). CONCLUSIONS: The incidence and IBM rates of GBC have been decreasing over the last 40 years, but the decrease plateaued over the last 2 decades. The effects of treatment modalities, including laparoscopic cholecystectomy, adjuvant chemotherapy, and radiation on the incidence and IBM of GBC need to be further investigated.

Real-World Effectiveness of Tixagevimab and Cilgavimab (Evusheld) in Patients With Hematological Malignancies.

Background: Immunocompromised individuals with hematological malignancy have increased risk for poor outcomes and death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This special population may mount a suboptimal response to vaccination. We assessed the effectiveness of tixagevimab and cilgavimab (Evusheld), a monoclonal antibody combination against SARS-CoV-2, in conjunction with standard preventative measures, at preventing symptomatic incident infection. Methods: Patients aged 18 years and older with hematological malignancy consented to receive Evusheld. Patients were followed longitudinally for development of symptomatic incident SARS-CoV-2 infections. Adverse events were monitored. Results: Two hundred and three patients (94 female) with hematological malignancies and mean age 72 ± 10 years were included. Of the patients, 99.5% had received at least one mRNA vaccination against SARS-CoV-2. Average time of follow-up was 151 ± 50 days. Nineteen patients (9.3%) developed incident symptomatic SARS-CoV-2 infection, with only one (0.5%) requiring hospitalization. During the same follow-up period, local incident rate of infection was 84,123 cases (11.3% of population). Of those, 3,386 cases (4%) of SARS-CoV-2 required hospital admission. The incidence rate ratio was 0.79. No serious adverse events occurred following administration of Evusheld. Conclusion: Patients with hematological malignancy who received Evusheld infrequently developed symptomatic infections or require hospitalization. The high-risk cohort incidence was at least as comparable to the average risk general population. Evusheld appears effective and is well tolerated, and may be administered in conjunction with vaccination and standard prevention measures, at decreasing incident SARS-Co-V2 cases in this high-risk population.

Severe Haemolytic Anaemia Resulting from a Malpositioned Haemodialysis Catheter.

Severe haemolytic anaemia is a rare complication of haemodialysis that is often difficult to recognize, especially when there are other potential differential diagnoses. Here, we present the case of 19-year-old man on haemodialysis who developed severe haemolytic anaemia while recovering from acute renal failure secondary to rhabdomyolysis. Other causes of haemolytic anaemia such as thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome were ruled out. As his blood counts were dropping on days following haemodialysis, haemolysis secondary to the mechanical sheering effect of the catheter was considered and his haemodialysis catheter was exchanged, which led to the resolution of anaemia. LEARNING POINTS: Haemodialysis-related haemolysis can be due to the mechanical sheering effect of the catheter/tubing, and overheating or contamination of the dialysate fluid.Most cases of catheter or faulty tubing-related haemolysis need a high level of suspicion for diagnosis and normally resolve with correction of the underlying mechanical issue.Due to the rarity of the phenomenon, it is very important to rule out other life-threatening causes of haemolytic anaemia, such as disseminated intravascular coagulation and thrombotic thrombocytopenic purpura.

Role of cytokines produced by T helper immune-modulators in dengue pathogenesis: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Modulation of the immune reaction is essential in the development of various diseases, including dengue's "Cytokine Tsunami", an increase in vascular permeability with concomitant severe vascular leakage. We aim to identify the role of T-helper (Th) cells, Th2 and Th7, with their related cytokines in dengue pathogenesis. MATERIAL AND METHODS: Nine electronic databases and manual search were applied to detect available publications. A meta-analysis using a fixed- or random-effect model was performed to measure standardized mean difference (SMD) with 95% confidence interval (CI). The National Institute of Health (NIH) tools for observational cohort, cross-sectional, and case-control studies were used to examine the risk of bias. The protocol was recorded in PROSPERO with CRD42017060230. RESULTS: A total of 38 articles were found including 19 case-control, 11 cross-sectional and 8 prospective cohort studies. We indicated that Th2 cytokines (IL-4, IL-6, IL-8) and Th17 cytokine (IL-17) in dengue patients were notably higher than in a healthy control group in acute phase (SMD = 1.59, 95% CI [0.68, 2.51], p = 0.001; SMD = 1.24, 95% CI [0.41, 2.06], p = 0.003; SMD = 1.13, 95% CI [0.61, 1.66], p<0.0001; SMD = 1.74, 95% CI [0.87, 2.61], p<0.0001), respectively. CONCLUSIONS: This study provides evidence of the significant roles of IL-4, IL-6, IL-8, IL-10 and IL-17 in the pathogenesis of developing a severe reaction in dengue fever. However, to fully determine the association of Th cytokines with dengue, it is necessary to perform further studies to assess kinetic levels during the duration of the illness.

Effect of nitazoxanide on diarrhea: A systematic review and network meta-analysis of randomized controlled trials.

We aimed to systematically review evidence pertaining to the safety and efficacy of nitazoxanide in treating infectious diarrhea. On September 21, 2017, we identified relevant studies using 12 databases. The estimates of the included studies were pooled as a risk ratio (RR). We conducted a network and pairwise random-effects meta-analysis for both direct and indirect comparisons of different organisms that are known to cause diarrhea. The primary and secondary analysis outcomes were clinical response until cessation of illness, parasitological response and adverse events. We included 18 studies in our analysis. In cryptosporidiosis, the overall estimate favored nitazoxanide in its clinical response in comparison with placebo RR 1.46 [95% CI 1.22-1.74; P-value <0.0001]. Network meta-analysis among patients with Giardia intestinalis showed an increase in the probability of diarrheal cessation and parasitological responses in comparison with placebo, RR 1.69 [95% CI 1.08-2.64, P-score 0.27] and RR 2.91 [95% CI 1.72-4.91, P-score 0.55] respectively. In Clostridium difficile infection, the network meta-analysis revealed a non-significantly superior clinical response effect of nitazoxanide to metronidazole 31 days after treatment RR 1.21 [95% CI 0.87-1.69, P-score 0.26]. In Entamoeba histolytica, the overall estimate significantly favored nitazoxanide in parasitological response with placebo RR 1.80 [95% CI 1.35-2.40, P-value < 0.001]. We highlighted the effectiveness of nitazoxanide in the cessation of diarrhea caused by Cryptosporidium, Giardia intestinalis and Entamoeba histolytica infection. We also found significant superiority of NTZ to metronidazole in improving the clinical response to G. intestinalis, thus it may be a suitable candidate for treating infection-induced diarrhea. To prove the superiority of NTZ during a C. difficile infection may warrant a larger-scale clinical trial since its superiority was deemed insignificant. We recommend nitazoxanide as an appropriate option for treating infectious diarrhea.

Efficacy and resistance of different artemisinin-based combination therapies: a systematic review and network meta-analysis.

BACKGROUND: Malaria parasites have developed resistance to most of the known antimalarial drugs in clinical practice, with reports of artemisinin resistance emerging in South East Asia (SEA). We sort to find the status of artemisinin resistance and efficacy of different modalities of the current artemisinin-based combination therapies (ACTs). METHODS: We carried out a systematic search in 11 electronic databases to identify in vivo studies published between 2001 and 2017 that reported artemisinin resistance. This was then followed by A network meta-analysis to compare the efficacy of different ACTs. Quality assessment was performed using the Cochrane Risk of Bias (ROB) tool for randomized controlled trials and National Institute of Health (NIH) tool for cross-sectional studies. The study protocol was registered in PROSPERO under number CRD42018087574. RESULTS: With 8400 studies initially identified, 82 were eligible for qualitative and quantitative analysis. Artemisinin resistance was only reported in South East Asia. K13 mutation C580Y was the most abundant mutation associated with resistance having an abundance of 63.1% among all K13 mutations reported. Although the overall network meta-analysis had shown good performance of dihydroartemisinin piperaquine in the early years, a subgroup analysis of the recent years revealed a poor performance of the drug in relation to recrudescence, clinical failure and parasitological failure especially in the artemisinin resistant regions. CONCLUSION: With report of high resistance and treatment failure against the leading artemisinin combination therapy in South East Asia, it is imperative that a new drug or a formulation is developed before further spread of resistance.

Association between pet ownership and cardiovascular risks and mortality: a systematic review and meta-analysis.

: The aim of the study was to determine the association between pet ownership and cardiovascular risk factors and mortality. Electronic search was conducted through nine databases including PubMed for relevant publications reporting cardiovascular events and mortality among pet owners. Meta-analysis was used to pool the results. Of a total of 2818 reports screened, 26 studies were included in our systematic review and meta-analysis. Higher survival rate was observed in the pet owners group after pooling nonadjusted and adjusted hazard ratios for cardiovascular mortality at 0.73 [95% confidence interval (CI) 0.62-0.86] and 0.81 (0.68-0.97), respectively. A similar trend was observed for the pooled nonadjusted hazard ratio for overall mortality 0.73 (0.62-0.87) but not the adjusted hazard ratio 0.40 (0.04-3.78). Cat owners have a reduction in cardiovascular mortality but not overall mortality after pooling the adjusted hazard ratio 0.79 (0.63-0.99) and 1.04 (0.90-1.21), respectively. However, no significant association between dog owners and survival rate was observed for overall and cardiovascular-specific mortality. Pet owners had significantly lower heart rate (mean difference 95% CI: -2.32 (-3.07 to -1.57), mean arterial pressure -2.60 (-4.25 to -0.95) and SBP -1.69 (-3.06 to -0.31) but not DBP -0.23 (-1.05 to 0.60). No significant difference was observed between pet owners and nonpet owners in prevalence of hypertension. Our study draws attention to the beneficial effects of the human--pet bond; therefore, we recommend pet acquisition for better cardiovascular outcomes after controlling for zoonotics and pet-induced allergies.

Prognostic factors and nomogram for survival prediction in patients with primary pulmonary lymphoma: a SEER population-based study.

Primary pulmonary lymphomas (PPLs) are rare lymphoproliferative malignancies arising from the lungs. The prognostic factors and optimal management of PPL have not been clearly defined due to its rarity. This study sought to characterize the significant prognostic factors and develop a validated nomogram for individualized prediction of survival outcomes in patients with PPL. A total of 2325 patients diagnosed with PPL between 1983 and 2010 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Older age at diagnosis, males, Hispanic race, non-marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue histology, Ann Arbor stage IV were significantly associated with worse OS on multivariable analysis. All treatment modalities, including chemotherapy, surgery, and radiotherapy were independent predictors of survival on univariable analysis. The nomogram built demonstrated good discriminative ability and calibration, with the C-index of 0.690 and 0.730 in the training and validation cohorts, respectively.

Competing Mortality in Patients With Neuroendocrine Tumors.

OBJECTIVES: Patients with neuroendocrine tumors (NETs) are at increased risk of mortality from competing causes in light of the improvement in overall survival over recent decades. The purpose of this study was to explore the competing causes of deaths and the risk factors associated with competing mortality. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with NETs between 1973 and 2015. Risk of competing mortality was estimated by the standardized mortality ratios (SMRs) and by using the Fine and Gray multivariate regression model. RESULTS: Of the 29,981 NET patients, 42.5% of the deaths that occurred during follow-up were attributed to competing causes (83.9% from noncancer causes and 16.1% from second primary neoplasms). Overall SMR of competing mortality was 2.50 (95% confidence interval [CI]: 2.43-2.56). The SMR of noncancer causes was 2.65 (95% CI: 2.58-2.73), with the highest risk present within the first year of diagnosis. The SMR of second primary neoplasms was 1.91 (95% CI: 1.79-2.04), with the highest risk observed after 10-year postdiagnosis. A drastic rise in competing mortality was observed in the last decade between 2005 and 2015. Advanced age, black race, small intestinal and gastric NETs, and surgery were significantly associated with competing mortality. Female, pancreatic and recto-anal NETs, distant and regional spread, chemotherapy and radiotherapy were significantly associated with lower competing mortality. CONCLUSIONS: Competing mortality plays an increasingly significant role over the years and may hamper efforts made to improve survival outcomes in NET patients.

Examined and positive lymph nodes counts and lymph nodes ratio are associated with survival in major salivary gland cancer.

BACKGROUND: We aimed to investigate the prognostic role of examined (dissected) lymph nodes (ELNs), negative LNs (NLNs), and positive (metastatic) LNs (PLNs) counts and LN ratio (LNR = PLNs/ELNs×100) in patients with major salivary gland cancer (SGC). METHODS: Data were retrieved for major SGC patients diagnosed between 1988 and 2011 from Surveillance, Epidemiology, and End Results program. RESULTS: We have included 5446 patients with major SGC. Most patients had parotid gland cancer (84.61%). Patients having >18 ELNs, >4 PLNs, and >33.33% LNR were associated with a worse survival. Moreover, older age, male patients, grade IV, distant stage, unmarried patients, submandibular gland cancer, and received chemotherapy but not received surgery were significantly associated with a worse survival. CONCLUSIONS: We demonstrated that patients with >18 ELNs and >4 PLNs counts, and >33.33% LNR were high-risk group patients. We strongly suggest adding the ELNs and PLNs counts and/or LNR into the current staging system.

Negative Lymph Node Count and Lymph Node Ratio Are Associated With Survival in Male Breast Cancer.

BACKGROUND: Male breast cancer (MBC) is usually diagnosed at late stages and therefore has a worse prognosis than female breast cancer (FBC). MBC is also more likely to have lymph node (LN) involvement than FBC. MATERIALS AND METHODS: We sought to determine the prognostic role of the examined lymph node (LN), negative LN (NLN), and positive LN counts and the LN ratio (LNR), defined as (positive LNs/ENLs), on the survival rate among MBC patients. We performed a large population-based study using the data from the Surveillance, Epidemiology, and End Results program. RESULTS: Older age, black race, stage IV disease, ≤ 1 NLN, and a > 31.3% LNR were significantly associated with worse survival across all prediction models. Moreover, we demonstrated a decreased risk of mortality in MBC patients across the MBC-specific survival model (hazard ratio, 0.98; 95% confidence interval, 0.96-0.998; P = .03) and 10-year MBC-specific survival model (hazard ratio, 0.98; 95% confidence interval, 0.96-0.999; P = .04). CONCLUSION: MBC has had an augmented incidence over the years. We found several independent predictors of MBC survival, including age, race, stage, NLNs, and the LNR. We strongly suggest adding the NLN count and/or LNR into the current staging system. Further studies are needed to provide information on the mechanisms underlying the association between the NLN count and MBC survival and the LNR and MBC survival.