Incidence and Risk Factors of Hypomagnesemia in Patients With Bone Metastasis From Solid Malignancies Treated With Denosumab: A Retrospective Chart Review.

BACKGROUND: Hypomagnesemia is associated with poor clinical outcomes in cancer patients. Patients with bone metastasis from solid malignancies receiving denosumab (Dmab) to prevent skeletal-related events often receive concurrent antineoplastic agents for cancer treatment. The incidence and risk factors of hypomagnesemia in patients receiving Dmab and the optimal frequency of monitoring serum magnesium (Mg) levels have not been studied in these patient populations. OBJECTIVE: The objective is to investigate the incidence and potential risk factors of hypomagnesemia and the optimal frequency of monitoring serum Mg levels. METHODS: A retrospective chart review identified patients with solid malignancies with bone metastases treated with Dmab at the Loma Linda University Cancer Center between January 2013 and February 2024. The incidence of hypomagnesemia was determined using the number of patients with hypomagnesemia and the total number of patients in the study. Univariate and multivariate logistic regression analyses identified risk factors for hypomagnesemia. RESULTS: Hypomagnesemia was observed in 19% (29/153) of patients, the majority of whom were on concurrent antineoplastic agents with ≥15% hypomagnesemia incidence (high-hypomagnesemic antineoplastics) or nonantineoplastic drugs with documented cases or incidence of hypomagnesemia (hypomagnesemic nonantineoplastics) in addition to high-hypomagnesemic antineoplastics. Multivariate analysis showed increased odds of developing hypomagnesemia with high-hypomagnesemic antineoplastics (odds ratio [OR]: 174.93, 95% confidence interval [CI]: 12.82 to 387.43, P < 0.001); hypomagnesemic nonantineoplastics plus high-hypomagnesemic antineoplastics (OR: 210.09, 95% CI: 11.80 to 3740.12, P < 0.001); and Mg level ≤ 0.85 prior to Dmab administration (OR: 16.79, 95% CI: 2.30 to 122.41, P = 0.005). CONCLUSION AND RELEVANCE: This study describes the incidence and potential risk factors for hypomagnesemia in patients with solid malignancies and metastatic bone disease treated with Dmab. This study's findings provide additional clinical insight into potential risk factors for hypomagnesemia and the need for more frequent serum Mg level monitoring of at-risk patients. Future prospective studies are needed to determine the exact frequencies most appropriate in monitoring serum Mg levels in this group of patients.

CT Features of Benign Intrapulmonary Lymph Nodes in Pediatric Patients With Known Extrapulmonary Solid Malignancy.

OBJECTIVE. The purpose of our study was to determine the CT features of benign intrapulmonary lymph nodes in pediatric patients with known extrapulmonary solid malignancy. MATERIALS AND METHODS. A retrospective review of surgical pathology archives was performed to identify consecutive chest CT studies of pediatric patients (≤ 18 years) with extrapulmonary solid malignancy and histologically confirmed benign intrapulmonary lymph nodes between January 1, 2004, and March 15, 2020. CT features of intrapulmonary lymph nodes-including size, shape, margin, type, associated calcification or fat, and location-were independently evaluated by two pediatric radiologist reviewers. The CT features of benign intrapulmonary lymph nodes in pediatric patients were analyzed using summary statistics. Interobserver agreement was measured with the kappa coefficient. RESULTS. There were 36 pathology-confirmed benign intrapulmonary lymph nodes in 27 pediatric patients (18 boys and nine girls; mean age, 12 years; age range, 1-18.2 years). Twenty-three (63.9%) of the benign intrapulmonary lymph nodes were biopsied from the right lung and 13 (36.1%) from the left lung (p = .03). The mean size, determined from CT studies, of benign intrapulmonary lymph nodes was 3.6 mm (SD, 1.4 mm; range, 1.3-7.8 mm). Triangular shape (25/36, 69.4%) was the most common shape of the benign intrapulmonary lymph nodes. Less commonly seen shapes of benign intrapulmonary lymph nodes were oval (6/36, 16.7%), round (3/36, 8.3%), and trapezoidal (2/36, 5.6%). All benign intrapulmonary lymph nodes were smoothly marginated and solid without associated calcification or fat. Of the 36 benign intrapulmonary lymph nodes, 15 (41.7%) were pleura-based; 11 (30.6%), perifissural; and 10 (27.8%), parenchymal. The kappa value for interobserver agreement between the two reviewers was 0.917 (95% CI, 0.825-1.000; standard error, 0.047), which corresponds to near-perfect agreement. CONCLUSION. In pediatric patients with known extrapulmonary solid malignancy, benign intrapulmonary lymph nodes are subcentimeter (mean size, 3.6 mm), smoothly marginated, and solid without containing calcification or fat on CT. In particular, triangular shape was the most commonly encountered shape of a benign intrapulmonary lymph node.

Increased Vancomycin Clearance in Patients with Solid Malignancies.

Vancomycin (VAN) is an anti-microbial agent used to treat a number of bacterial infections, which has a high incidence of nephrotoxicity. We examined the pharmacokinetics of VAN retrospectively based on trough concentrations at large scale and identified pharmacokinetic differences between Japanese patients having solid malignancy and non-malignancy patients. Data were analyzed from 162 solid malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN. We failed to detect differences in values for VAN clearance or shorter elimination half-lives between these two groups. In contrast, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to solid malignancies in each stage. We conclude that VAN clearance in solid malignancy patients is increased and that the blood concentration of VAN becomes lower than expected. These results suggest that early monitoring of VAN levels in solid malignancy patients might be essential for maintaining desired effects without side-effects.

Integration of Tumor-Treating Fields into the Multidisciplinary Management of Patients with Solid Malignancies.

Tumor-treating fields (TTFields) are a noninvasive antimitotic cancer treatment consisting of low-intensity alternating electric fields delivered to the tumor or tumor bed via externally applied transducer arrays. In multiple in vitro and in vivo cancer cell lines, TTFields therapy inhibits cell proliferation, disrupts cell division, interferes with cell migration and invasion, and reduces DNA repair. Human trials in patients with primary glioblastoma showed an improvement in overall survival, and trials in patients with unresectable malignant pleural mesothelioma showed favorable outcomes compared with historical control. This led to U.S. Food and Drug Administration approval in both clinical situations, paving the way for development of trials investigating TTFields in other malignancies. Although these trials are ongoing, the existing evidence suggests that TTFields have activity outside of neuro-oncology, and further study into the mechanism of action and clinical activity is required. In addition, because TTFields are a previously unrecognized antimitotic therapy with a unique mode of delivery, the oncological community must address obstacles to widespread patient and provider acceptance. TTFields will likely join surgery, systemic therapy, and radiation therapy as a component of multimodality management of patients with solid malignancies. IMPLICATIONS FOR PRACTICE: Tumor-treating fields (TTFields) exhibit a broad range of antitumor activities. Clinically, they improve overall survival for patients with newly diagnosed glioblastoma. The emergence of TTFields has changed the treatment regimen for glioblastoma. Clinicians need to understand the practical issues surrounding its use in the multidisciplinary management of patients with glioblastoma. With ongoing clinical trials, TTFields likely will become another treatment modality for solid malignancies.

Genotype 3b of human parvovirus B19 detected from hospitalized children with solid malignancies in a North Indian tertiary care hospital.

Human parvovirus B19 (B19V) infection is known to cause serious consequences in immuno-compromized individuals. The present cross sectional study was designed to estimate the prevalence and genotype distribution of B19V in children receiving chemotherapy for solid malignancies at a tertiary care hospital in North India during October 2013 to May 2015. Serum samples from all the patients were tested for anti-B19V IgM and IgG antibodies and for B19V-DNA as soon as received. Samples testing positive for B19V-DNA were subjected to viral load estimation and to genotype determination by sequencing. Total 96 children were enrolled of which 9 (9.3%), 32 (33.3%), and 25 (26%) tested positive for anti-B19V IgM, anti-B19V IgG, and B19V-DNA, respectively. The viral load of B19V-DNA positive children ranged from 5.5 × 10(2) to 3.5 × 10(12) copies/ml. Accordingly children were divided into three groups: group I, with acute infection (n = 25); group II, previously exposed (n = 27), and group III, negative for B19V infection or with inappropriate antibody response (n = 44). B19V positivity was significantly associated (P-value < 0.0001) with a history of blood transfusion in the past 6 months, severe anemia (hemoglobin levels <6 gm%) and thrombocytopenia (platelets <150,000/cu.mm.). Sequence analysis of 21 of 25 DNA positive samples showed that all of them were Genotype 3b that clustered into three groups. All the sequences within each cluster were identical. The nucleotide identity of the sequences suggests a nosocomial outbreak of B19V during the study period. Children on chemotherapy for solid tumors should be routinely screened for B19V infection by both serology and PCR. J. Med. Virol. 88:1922-1929, 2016. © 2016 Wiley Periodicals, Inc.

Risk of secondary solid malignancies after allogeneic hematopoietic stem cell transplantation and preventive strategies.

The risk of secondary solid malignancies is increased after allogeneic hematopoietic stem cell transplantation (HSCT). The risk starts at about 10 years after HSCT and continues even 20 years later. The most common secondary malignancies include squamous cell carcinoma of skin, genitourinary tract and oral cavity; lung and breast cancers. The use of total body irradiation or conditioning chemotherapy, chronic graft-versus-host disease and duration since HSCT can influence the risk of secondary solid malignancies. Secondary solid malignancies are common causes of nonrelapse mortality in long-term survivors and may account for up to 10% of late deaths. Avoiding smoking, alcohol use and excess sun exposure may reduce the risk. Cancer prevention guidelines are largely consensus-driven and follow the recommendations for general population.

Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review.

BACKGROUND: Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. METHOD: A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. RESULTS: Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. CONCLUSION: Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

Background: Previous studies documented that heparin can inhibit the invasion and metastasis of tumors, but its role on outcomes in patients with solid malignancy complicated sepsis remains unclear. Methods: A retrospective cohort study was conducted in critically ill patients with solid malignancy associated sepsis from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was intensive care unit (ICU) mortality, secondary outcomes were thrombosis and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), cox proportional hazards model, stratification analysis and E-value were used to account for baseline differences, time-varying confounding and unmeasured variables. Results: A total of 1,512 patients with solid malignancy complicated sepsis were enrolled, of which 683 in the heparin group with intensive care unit mortality, thrombosis rate and hospital mortality were 9.7%, 5.4%, 16.1%, and 829 in the non-heparin group with ICU mortality, thrombosis rate and hospital mortality were 14.6%, 12.5%, 22.6%. Similar results were observed on outcomes for patients with PSM (ICU mortality hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41-0.92), thrombosis rate (HR 0.42, 95% confidence interval 0.26-0.68); hospital mortality HR 0.70, 95% CI 0.50-0.99). marginal structural Cox model further reinforced the efficacy of heparin in reducing ICU mortality (HR 0.48, 95% CI 0.34-0.68). Logistic regression and Cox regression model showed heparin use also markedly reduced thrombosis (HR 0.42; 95% CI 0.26-0.68; p < 0.001) and hospital mortality (HR 0.70; 95% CI 0.50-0.99; p = 0.043). Stratification analysis with the MSCM showed an effect only those with digestive system cancer (HR 0.33, 95% CI 0.16-0.69). Conclusion: Early heparin therapy improved outcomes in critically ill patients with solid malignancy complicated sepsis. These results are evident especially in those with digestive system cancer. A prospective randomized controlled study should be designed to further assess the relevant findings.

The prognostic impact of tumor-infiltrating B lymphocytes in patients with solid malignancies: A systematic review and meta-analysis.

This study reviewed the prognostic effect of tumor-infiltrating B lymphocytes (TIBLs) on solid malignancies, to determine the potential role of TIBLs in predicting cancer patient's prognosis and their response to immunotherapy. A total of 45 original papers involving 11,099 individual patients were included in this meta-analysis covering 7 kinds of cancer. The pooled results suggested that high levels of TIBLs were correlated with favorable OS in lung, esophageal, gastric, colorectal, liver, and breast cancer; improved RFS in lung cancer; and improved DFS in gastrointestinal neoplasms. Additionally, TIBLs were significantly correlated with negative lymphatic invasion in gastric cancer, small tumor size in hepatocellular carcinoma, and negative distant metastasis in colorectal cancer. Additionally, TIBLs were reported as a discriminative feature of patients treated with immunotherapy with improved survival. We concluded that TIBLs play a favorable prognostic role among the common solid malignancie, providing theoretical evidence for further prognosis prediction for solid tumors.

The efficacy of selinexor (KPT-330), an XPO1 inhibitor, on non-hematologic cancers: a comprehensive review.

PURPOSE: Selinexor is a novel XPO1 inhibitor which inhibits the export of tumor suppressor proteins and oncoprotein mRNAs, leading to cell-cycle arrest and apoptosis in cancer cells. While selinexor is currently FDA approved to treat multiple myeloma, compelling preclinical and early clinical studies reveal selinexor's efficacy in treating hematologic and non-hematologic malignancies, including sarcoma, gastric, bladder, prostate, breast, ovarian, skin, lung, and brain cancers. Current reviews of selinexor primarily highlight its use in hematologic malignancies; however, this review seeks to summarize the recent evidence of selinexor treatment in solid tumors. METHODS: Pertinent literature searches in PubMed and the Karyopharm Therapeutics website for selinexor and non-hematologic malignancies preclinical and clinical trials. RESULTS: This review provides evidence that selinexor is a promising agent used alone or in combination with other anticancer medications in non-hematologic malignancies. CONCLUSION: Further clinical investigation of selinexor treatment for solid malignancies is warranted.

Laparoscopic Excision of Large Wilms Tumor in Children: A Single-Center Experience from a Resource-Challenged Nation.

Background: In this study, we aim to review the outcomes of children with Wilms tumor (WT) operated through the minimally invasive surgery (MIS) approach at our center. We also intend to highlight essential surgical steps during laparoscopic excision of large WTs. Methods: This retrospective study included children with unilateral WT who had undergone resection for a period of 4 years, w.e.f. July 2013 to July 2017. Simple maneuvers such as tilting the table in different positions and use of blunt metallic cannula to lift the tumor to access the hilar vessels were used to dissect large WT. An extended lumbotomy incision was used for retrieval of tumor and lymph-node sampling. Results: Eleven patients (male:female = 7:4) of WT, all having stage III disease, had undergone laparoscopic tumor resection at our center during the study period. The median age at presentation was 36 months (range = 17 months-5 years) and the median preoperative tumor volume was 1140 (range = 936-1560) cm3. The average length of the lumbotomy incision was 6.3 (range = 5-8.2) cm. The median hospital stay was 6 (range = 5-10) days. Two children developed complications (port-site recurrence and grade III surgical site infection in one each) during the postoperative period. All cases are long-term survivors after a median follow-up of 86 (range = 56-104) months. Conclusion: This study highlights the feasibility and safety of the removal of large WT through the MIS approach. Problems due to large-sized tumors in children can be overcome by simple maneuvers. Also, adequate lymph node sampling is possible with a suitably placed extended lumbotomy incision for tumor removal.

Mediastinal high-grade vasculogenic mesenchymal tumour with seminoma: a case report and literature review.

Germ cell tumours with somatic-type solid malignancy (GCT-STM) are a rare disease of the mediastinum. Recently, a cohort of vasculogenic mesenchymal tumour (VMT)-nonseminoma cases with different prognoses were recognized and reported. Here, we report a case of mediastinal high-grade VMT with a seminoma. A 16-year-old male had a fever, chest tightness and fatigue. Chest CT showed a 7.5 cm×5.3 cm solid mass in the right anterior mediastinum. The serum levels of alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (ß-HCG) and carcinoembryonic antigen (CEA) were within the normal range. Tumorectomy was performed. The tumour was irregular, and no capsule was found. The cut surface was greyish white and greyish brown with medium consistency. There were foci of bleeding and necrosis. Microscopic histology showed prominent vascular proliferation, which was lined by mildly atypical endothelial cells in a cellular stroma with significant cytologic atypia. The vascular spectrum varied from crevice-like or antler-like thin- to thick-walled vessels. Beyond the tumour area, inside the remnant thymus tissues, there were small clusters of polygonal tumour cells with clear cytoplasm, distinct cell membranes, and round to polygonal nuclei with prominent nucleoli that were positive for Oct4, PLAP, SALL4 and CD117. The patient did not receive any treatments pre- or postoperation, and his condition was stable without progression after 14 months of follow-up evaluation. Here, we added a new entity of GCT-STM of the mediastinum composed of VMT and seminoma. A better understanding of the pathological features of GCT-VMT could help pathologists improve their awareness of these rare diseases.

Systematic Review of Available CAR-T Cell Trials around the World.

In this systematic review, we foresee what could be the approved scenario in the next few years for CAR-T cell therapies directed against hematological and solid tumor malignancies. China and the USA are the leading regions in numbers of clinical studies involving CAR-T. Hematological antigens CD19 and BCMA are the most targeted, followed by mesothelin, GPC3, CEA, MUC1, HER2, and EGFR for solid tumors. Most CAR constructs are second-generation, although third and fourth generations are being largely explored. Moreover, the benefit of combining CAR-T treatment with immune checkpoint inhibitors and other drugs is also being assessed. Data regarding product formulation and administration, such as cell phenotype, transfection technique, and cell dosage, are scarce and could not be retrieved. Better tracking of trials' status and results on the ClinicalTrials.gov database should aid in a more concise and general view of the ongoing clinical trials involving CAR-T cell therapy.

Double trouble: Biochemically confirmed bilateral chylothorax with positive pleural fluid cytology due to breast adenocarcinoma.

Although chylothorax is a well-described complication of malignancy, especially lymphoma, breast adenocarcinoma has not been a commonly implicated primary tumor. There has been only one published report of biochemically confirmed bilateral chylothorax in solid malignancy, and this was not associated with breast adenocarcinoma. Likewise, there has been only one published report of bilateral chylothorax in solid malignancy with positive pleural fluid cytology on both sides; again, the primary tumor was not breast adenocarcinoma. Herein we present a case that combines all three of these rarely reported features: a patient with metastatic breast adenocarcinoma who developed biochemically confirmed bilateral chylothorax with documented positive pleural fluid cytology on both sides. This report is accompanied by a literature review of published cases of bilateral chylothorax in solid malignancy.

Incidence and Determinants of Chemotherapy Associated Thromboembolic Events among Ethiopian Patients Treated for Solid Malignancy: A Retrospective Cross-Sectional Study.

Venous thromboembolism is a common problem in patients treated for cancer, although the reported incidence varies widely between studies. This was the first study in its kind in Ethiopia and aimed to assess the incidence and determinants of chemotherapy associated thromboembolic events among patients treated for solid malignancy. An institution-based retrospective cross-sectional study was conducted from 1st March to 1st June, 2019 at adult oncology center of Tikur Anbessa Specialized Hospital. Systematic random sampling technique was employed to recruit 423 study participants. Patients who have received at least a single cycle of any chemotherapy regimen were included in the study. Khorana risk assessment tool was used to predict chemotherapy associated thrombosis. Descriptive statistics were used to summarize the data while multivariable logistic regression was employed to explore associations among variables of interest. The median age of study participants was 43 years, which ranged from 14 to 83 years. Majority of the study participants were treated for breast cancer. Thromboembolic events encountered in 43(10.2%) of patients, from which the commonest one being deep venous thrombosis 36 (85.7%), followed by myocardial infarction 5(11.9%). In multivariable logistic regression, blood transfusion, a primary site of cancer with gastrointestinal malignancy and performance status showed statistically significant association towards the occurrences of thromboembolic events. The incidence of chemotherapy associated thromboembolic events among patients treated for solid malignancy was comparable to other studies. Hence, other prospective randomized trials are needed to see the importance of thrombo-prophylaxis in such high-risk patients.

Hyperprogressive disease in patients suffering from solid malignancies treated by immune checkpoint inhibitors: A systematic review and meta-analysis.

Introduction: Hyperprogressive disease (HPD) is a paradoxically rapid disease progression during or shortly after antitumor treatment, especially immune checkpoint inhibitors (ICIs). Various diagnosis criteria of HPD cause heterogeneous incidence rates in different clinical research, and there is no consensus on potential risk factors associated with HPD occurrence. Hence, we aimed to summarize incidence of HPD in ICI treatment for solid tumors. Clinicopathological factors associated with HPD are also analyzed. Methods: Clinical studies about HPD during/after ICI treatment of solid malignancies are included. Pubmed, Embase, and Cochrane library were searched for eligible studies published before October 7. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Random effect and fixed effect models were, respectively, used for pooling incidence of HPD and analysis of risk factors for HPD. Heterogeneity, subgroup analysis, and publication bias were also analyzed. All meta-analysis was performed via R software (y -40v4.0.2). Results: Forty-one studies with 6009 patients were included. The pooled incidence of HPD was 13.2% (95% CI, 11.2%-15.4%). Head and neck cancer (HNC) had the highest incidence of HPD (18.06%), and melanoma had the lowest (9.9%). Tumor types (P = .0248) and gender ratio (P = .0116) are sources of heterogeneity of pooled incidence of HPD. For five clinicopathological factors associated with HPD, only programmed cell death protein 1 ligand 1 (PD-L1) positivity was a preventive factor (odds ratio = 0.61, P <.05). High lactate dehydrogenase (LDH) level (OR = 1.51, P = .01), metastatic sites >2 (OR = 2.38, P <.0001), Eastern Cooperative Oncology Group Performance Score ≥2 (OR = 1.47, P = .02), and liver metastasis (OR = 3.06, P <.0001) indicate higher risk of HPD. Conclusions: The pooled incidence of HPD was less than 15%, and HNC had the highest incidence of HPD. LDH and PD-L1 are remarkable biomarkers for prediction of HPD in future medical practice.

Comorbidity and survival after admission to the intensive care unit: A population-based study of 41,230 patients.

PURPOSE: To describe the relationship between comorbidities and survival following admission to the intensive care unit. METHODS: Retrospective observational study using several linked routinely collected databases from 16 general intensive care units between 2002 and 2011. Comorbidities identified from hospitalisation in the five years prior to intensive care unit admission. Odds ratios for survival in intensive care unit, hospital and at 30 days, 180 days and 12 months after intensive care unit admission derived from multiple logistic regression models. RESULTS: There were 41,230 admissions to intensive care units between 2002 and 2011. Forty-one percent had at least one comorbidity - 24% had one, 17% had more than one. Patients with comorbidities were significantly older, had higher Acute Physiology and Chronic Health Evaluation II scores and were more likely to have received elective rather than emergency surgery compared with those without comorbidities. After excluding elective hospitalisations, intensive care unit and hospital mortality for the cohort were 24% and 29%, respectively. Asthma (odds ratio 0.79, 95% confidence interval 0.63-0.99) and solid tumours (odds ratio 0.74, 0.67-0.83) were associated with lower odds of intensive care unit mortality than no comorbidity. Intensive care unit mortality was raised for liver disease (odds ratio 2.98, 2.43-3.65), cirrhosis (odds ratio 2.61, 1.9-3.61), haematological malignancy (odds ratio 2.29, 1.85-2.83), chronic ischaemic heart disease (odds ratio 1.53, 1.19-1.98), heart failure (odds ratio 1.79, 1.35-2.39) and rheumatological disease (odds ratio 1.53, 1.18-1.98). CONCLUSIONS: Comorbidities affect two-fifths of intensive care unit admission and have highly variable effects on subsequent outcomes. Information on the differential effects of comorbidities will be helpful in making better decisions about intensive care unit support and understanding outcomes beyond surviving intensive care unit.

Risk of solid malignancies in bullous pemphigoid: A large-scale population-based cohort study.

The association of bullous pemphigoid (BP) with solid malignancies (SM) is a matter of controversy, as previous studies produced inconclusive findings. The aim of this study was to assess the risk of SM among patients with BP and to evaluate whether a history of SM predisposes individuals to develop subsequent BP. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and race-matched control subjects (n = 19 280) with regard to incident cases of SM. Adjusted hazard ratios (HR) and adjusted odds ratios (OR) were estimated by Cox regression and logistic regression, respectively. The incidence of SM was 13.4 (95% confidence interval [CI], 11.6-15.3) and 14.3 (95% CI, 13.5-15.1) per 1000 person-years among patients with BP and controls, respectively. BP was not associated with an increased risk of SM (adjusted HR, 0.90; 95% CI, 0.77-1.05). Additionally, a history of SM was not related to the risk of subsequent BP (adjusted OR, 1.00; 95% CI, 0.90-1.10). In a stratified analysis, patients with BP had an increased risk of uterine cancer (adjusted HR, 2.56; 95% CI, 1.39-4.72) unlike the 18 remaining analyzed types of SM. Relative to BP patients without SM, those with BP and SM were older, had a male predominance, a higher prevalence of smoking, a higher burden of comorbidities and comparable survival rates. Although patients with BP do not experience an overall increased risk of developing SM, they are more likely to have uterine cancer. Our findings argue against routine extended cancer screening for patients with incident BP, but raise the awareness of uterine cancer among females with BP.

Cancer Radiation Therapy May Be Associated With Atrial Fibrillation.

Background: The association of atrial fibrillation (AF) with cancer and cancer types is inconclusive. Similarly, data regarding the association of AF with different cancer therapies are controversial. Objectives: To study the association of AF with cancer subtypes and cancer therapies. Methods: We studied all patients aged 18-89 years who presented to the Feist Weiller Cancer Center, with or without a diagnosis of cancer, between January 2011 and February 2016. Electronic health records were systematically queried for baseline demographics and ICD-9 and ICD-10 codes for specific co-morbidities. Patients with a diagnosis of AF were tabulated based on cross-validation with the ECG database and/or by recorded history. We assessed the prevalence and risk of AF based on cancer diagnosis, specific cancer type, and cancer therapy. Results: A total of 14,600 patients were analyzed. Compared to non-cancer patients (n = 6,801), cancer patients (n = 7,799) had a significantly higher prevalence of AF (4.3 vs. 3.1%; p < 0.001). However, following correction for covariates in a multivariable logistic regression model, malignancy was not found to be an independent risk factor for AF (p = 0.32). While patients with solid tumors had a numerically higher prevalence of AF than those with hematological malignancies (4.3 vs. 4.1%), tumor type was not independently associated with AF (p = 0.13). AF prevalence was higher in patients receiving chemotherapy (4.1%), radiation therapy (5.1%), or both (6.9%) when compared to patients not receiving any therapy (3.6%, p = 0.01). On multivariable logistic regression, radiation therapy remained an independent risk factor for AF for the entire study population (p = 0.03) as well as for the cancer population (p < 0.01). Conclusions: Radiation therapy for cancer is an independent risk factor for AF. The known association between cancer and AF may be mediated, at least in part, by the effects of radiation therapy.

Incidence of venous thromboembolism in patients with solid cancers in Japan: retrospective study of 2735 patients.

BACKGROUND: The incidence of cancer-associated venous thromboembolism (CA-VTE) in Japan has not been fully investigated. METHODS AND RESULTS: Clinicopathological information from patients with solid malignancies who first visited our department between November 2011 and March 2018 were retrospectively reviewed from medical records. The primary outcome was incidence of CA-VTE, defined as deep-vein thrombosis (DVT) and/or pulmonary embolism (PE). On median follow-up of 187 days, 91 of 2735 patients (3.3%) developed CA-VTE during their clinical course, giving an incidence rate of 40.7 per 1000 person-years. Of the 91 patients, 75 (82%) were diagnosed with DVT alone, 6 (7%) with PE alone, and 10 (11%) with both DVT and PE. CA-VTE was most frequent in non-small cell lung cancer (10.8%), followed by cancer of unknown origin (5.8%). Forty-four patients (48%) had one or more symptoms at the initial diagnosis of VTE. Five patients (6%) had a normal D-dimer level (≤ 1.0 µg/mL); of these, 2 were asymptomatic. CONCLUSIONS: In this retrospective study, the incidence of CA-VTE in Japanese patients with cancer was equivalent to that in Western populations. Approximately half of CA-VTE patients were asymptomatic and 6% had normal D-dimer levels, indicating the need for closer attention to occult CA-VTE.