IgM-MM is predominantly a pre-germinal center disorder and has a distinct genomic and transcriptomic signature from WM.

Immunoglobulin M (IgM) multiple myeloma (MM) is a rare disease subgroup. Its differentiation from other IgM-producing gammopathies such as Waldenström macroglobulinemia (WM) has not been well characterized but is essential for proper risk assessment and treatment. In this study, we investigated genomic and transcriptomic characteristics of IgM-MM samples using whole-genome and transcriptome sequencing to identify differentiating characteristics from non-IgM-MM and WM. Our results suggest that IgM-MM shares most of its defining structural variants and gene-expression profiling with MM, but has some key characteristics, including t(11;14) translocation, chromosome 6 and 13 deletion as well as distinct molecular and transcription-factor signatures. Furthermore, IgM-MM translocations were predominantly characterized by VHDHJH recombination-induced breakpoints, as opposed to the usual class-switching region breakpoints; coupled with its lack of class switching, these data favor a pre-germinal center origin. Finally, we found elevated expression of clinically relevant targets, including CD20 and Bruton tyrosine kinase, as well as high BCL2/BCL2L1 ratio in IgM-MM, providing potential for targeted therapeutics.

ROBO1 Promotes Homing, Dissemination, and Survival of Multiple Myeloma within the Bone Marrow Microenvironment.

The bone marrow (BM) microenvironment actively promotes multiple myeloma (MM) pathogenesis and therapies targeting both cancer cells and the niche are highly effective. We were interested in identifying novel signaling pathways supporting MM-BM crosstalk. Mutations in the transmembrane receptor Roundabout 1 (ROBO1) were recently identified in MM patients, however their functional consequences are uncertain. Through protein structure-function studies, we discovered that ROBO1 is necessary for MM adhesion to BM stromal and endothelial cells and ROBO1 knock out (KO) compromises BM homing and engraftment in a disseminated mouse model. ROBO1 KO significantly decreases MM proliferation in vitro and intra- and extramedullary tumor growth, in vivo. Mechanistically, ROBO1 C-terminus is cleaved in a ligand-independent fashion and is sufficient to promote MM proliferation. Viceversa, mutants lacking the cytoplasmic domain, including the human-derived G674* truncation, act dominantly negative. Interactomic and RNA sequencing studies suggest ROBO1 may be involved in RNA processing, supporting further studies.

Community-acquired pneumonia in patients with chronic obstructive pulmonary disease requiring admission to the intensive care unit: risk factors for mortality.

PURPOSE: The aims of this study are to identify factors predicting mortality in patients with chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia (CAP) requiring intensive care unit (ICU) admission and to examine whether noninvasive ventilation treatment reduces mortality. MATERIALS AND METHODS: An analysis was performed on data from patients with CAP hospitalized in the ICUs of 19 different hospitals in Turkey between October 2008 and January 2011. Predictors of mortality were assessed by both univariate and multivariate statistical analyses. RESULTS: Two hundred eleven patients with COPD and CAP were included. The overall ICU mortality was 23.9%. Noninvasive ventilation treatment (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.03-0.49; P = .003), hypertension (OR, 0.13; 95% CI, 0.02-0.93; P = .042), bilateral infiltration (OR, 13.92; 95% CI, 2.94-65.84; P = .001), systemic corticosteroid treatment (OR, 0.19; 95% CI, 0.35-0.96; P = .045), length of ICU stay (OR, 0.65; 95% CI, 0.47-0.89; P = .007), and duration of invasive mechanical ventilation (OR, 1.11; 95% CI, 1.01-1.22; P = .032) were independent factors related to mortality. CONCLUSION: Noninvasive ventilation, hypertension, systemic corticosteroid treatment, and shorter ICU stay are associated with reduced mortality, whereas bilateral infiltration and longer duration of invasive mechanical ventilation are associated with increased risk of mortality in patients with COPD and CAP requiring ICU admission.

Mortality indicators in community-acquired pneumonia requiring intensive care in Turkey.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is a fatal disease. This study was conducted to describe an outcome analysis of the intensive care units (ICUs) of Turkey. METHODS: This study evaluated SCAP cases hospitalized in the ICUs of 19 different hospitals between October 2008 and January 2011. The cases of 413 patients admitted to the ICUs were retrospectively analyzed. RESULTS: Overall 413 patients were included in the study and 129 (31.2%) died. It was found that bilateral pulmonary involvement (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.1-5.7) and CAP PIRO score (OR 2, 95% CI 1.3-2.9) were independent risk factors for a higher in-ICU mortality, while arterial hypertension (OR 0.3, 95% CI 0.1-0.9) and the application of non-invasive ventilation (OR 0.2, 95% CI 0.1-0.5) decreased mortality. No culture of any kind was obtained for 90 (22%) patients during the entire course of the hospitalization. Blood, bronchoalveolar lavage, and non-bronchoscopic lavage cultures yielded enteric Gram-negatives (n=12), followed by Staphylococcus aureus (n=10), pneumococci (n=6), and Pseudomonas aeruginosa (n=6). For 22% of the patients, none of the culture methods were applied. CONCLUSIONS: SCAP requiring ICU admission is associated with considerable mortality for ICU patients. Increased awareness appears essential for the microbiological diagnosis of this disease.

Ischemia-modified albumin levels in children having seizure.

Convulsions are one of the frequently seen problems for a neurologist in the daily routine. It is difficult to distinguish the seizure from pseudo-seizure because of lack of conclusive tests. The aim of this study is to investigate the relationship between seizure types and seizure periods by studying IMA serum levels in children having seizure. Two groups were included (patients and control) in our study. The patient group consisted of the children admitted to Pediatric Emergency Care during January 2008-January 2010 with seizure and the control group consisted of healthy children. Serum Ischemia modified albumin (IMA) level in the group having seizures was 99.7 and 83.2U/ml in the control group. In the comparison of the patient and control groups, significant differences were found between their IMA values (p=0.000). There was a significant difference between IMA values of the group having generalized tonic-clonic seizures and those of the control group (p=0.001). In comparison of the IMA values of the group having febrile convulsions and those of the control group, a significant difference was determined (p=0.011). It has been shown that if the seizure was prolonged over 5 min, IMA level increased, and there was a significant difference between the groups experiencing over 5 min of seizures and the groups experiencing less than 5 min of seizures (p=0.001). An increase in IMA levels in febrile convulsion supports the hypoxia development in the brain during the seizure. Serum IMA levels increased with the elongation of the seizure period and may be an indicator for status epilepticus.