High-titer rheumatoid factor seropositivity predicts mediastinal lymphadenopathy and mortality in rheumatoid arthritis-related interstitial lung disease.

Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue disease-related ILD (CTD-ILD) associated with high morbidity and mortality. Although rheumatoid factor (RF) seropositivity is a risk factor for developing RA-ILD, the relationship between RF seropositivity, mediastinal lymph node (MLN) features, and disease progression is unknown. We aimed to determine if high-titer RF seropositivity predicted MLN features, lung function impairment, and mortality in RA-ILD. In this retrospective cohort study, we identified patients in the University of Chicago ILD registry with RA-ILD. We compared demographic characteristics, serologic data, MLN size, count and location, and pulmonary function over 36 months among patients who had high-titer RF seropositivity (≥ 60 IU/ml) and those who did not. Survival analysis was performed using Cox regression modeling. Amongst 294 patients with CTD-ILD, available chest computed tomography (CT) imaging and serologic data, we identified 70 patients with RA-ILD. Compared to RA-ILD patients with low-titer RF, RA-ILD patients with high-titer RF had lower baseline forced vital capacity (71% vs. 63%; P = 0.045), elevated anti-cyclic citrullinated peptide titer (122 vs. 201; P = 0.001), CT honeycombing (50% vs. 80%; P = 0.008), and higher number of MLN ≥ 10 mm (36% vs. 76%; P = 0.005). Lung function decline over 36 months did not differ between groups. Primary outcomes of death or lung transplant occurred more frequently in the high-titer RF group (HR 2.8; 95% CI 1.1-6.8; P = 0.028). High-titer RF seropositivity was associated with MLN enlargement, CT honeycombing, and decreased transplant-free survival. RF titer may be a useful prognostic marker for stratifying patients by pulmonary disease activity and mortality risk.

Reasons for initiation of treatment and predictors of response for patients with Rai stage 0/1 chronic lymphocytic leukemia (CLL) receiving first-line therapy: an analysis of the Connect® CLL cohort study.

A 'watch-and-wait' strategy is recommended for most patients with early-stage chronic lymphocytic leukemia (CLL) prior to treatment initiation. In the Connect® CLL registry, a prospective observational cohort study of 1494 patients treated in 199 US centers, median time to first-line treatment initiation was 3.8, 1.5, and 0.6 years for patients with Rai stage 0, 1, and ≥2, respectively. Only 60% of patients with Rai stage 0/1 underwent FISH/cytogenetic testing prior to initiation of a new line of therapy. Lymphocytosis and lymphadenopathy were the most common reasons for treatment initiation. Lymphocytosis as a reason for treatment initiation was associated with inferior event-free survival at Rai stage 0/1. Short treatment duration was associated with inferior overall survival regardless of Rai stage; sensitivity analyses confirmed the association. The Connect CLL registry provides valuable information on a real-world population of patients with CLL, clarifying both the timing and rationale for initiating therapy.

Laparoscopic Lymph Node Biopsy: Efficacy and Advantages.

BACKGROUND: Diagnosis of abdominal lymphadenopathy is challenging when not accompanied by peripheral lymphadenopathy. Computed tomography-guided core-needle biopsy has largely replaced open procedures in recent years, but this approach is limited by access to the anatomic region and the amount of tissue acquired. OBJECTIVES: To demonstrate the feasibility of the laparoscopic approach in obtaining abdominal lymph node biopsies and to evaluate the diagnostic adequacy of the technique. METHODS: We reviewed the data of patients who underwent laparoscopic lymph node biopsy between 2014 and 2014 in our department. Demographics, intra-operative parameters and postoperative course were examined, as were histological reports. Postoperative complications were categorized according to the Clavien-Dindo(CD) classification. RESULTS: Between 2004 and 2014, 57 laparoscopic biopsies were performed for intra-abdominal lymphadenopathy. One case was a repeated attempt due to limited histologic material. The mean age was 49.5 ± 19.6 years. There were two conversions to open laparotomy, one due to small bowel injury and the other due to a sizable mass. Overall, 56 cases had full clinical data: 48 cases (85.7%) had CD=0, six (10.7%) had CD=1, one postoperative severe complication (CD=3) and one mortality (CD=5), which was related to preexisting hepatic insufficiency. Mean hospital stay was 1.6 days. Overall, adequate tissue samples were acquired in 96.7% and only 3 of these cases resulted in inconclusive diagnoses. CONCLUSIONS: Laparoscopic lymph node biopsy is a viable alternative to the currently available methods of tissue retrieval. It provides an access for nodes which are inaccessible percutaneously, and may allow a superior diagnostic yield.

Does the addition of postoperative radiotherapy to adjuvant chemotherapy offer any benefit in patients with non-small cell lung cancer and mediastinal lymphadenopathy?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether the addition of postoperative radiotherapy (PORT) to adjuvant chemotherapy offers any benefit in patients undergoing curative resection for non-small cell lung cancer found to harbour mediastinal lymphadenopathy. A total of 77 papers were identified using the reported search, of which 11 represented the best evidence to answer the clinical question. Only studies reporting on survival data of patients receiving adjuvant chemotherapy with and without PORT were included in this analysis. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. Six studies reported a statistically significant positive impact of PORT on long-term or disease-free survival (DFS) (P = 0.048-0.0001). Five more studies found no difference in terms of survival between patients receiving and not receiving PORT. Among the 11 studies, only two were randomized controlled, with one of them reporting improved disease-free (P = 0.041) but not overall survival (P = 0.073), while the other finding no difference in survival. Furthermore, three more studies reported on DFS and/or locoregional recurrence of the disease. One of these studies reported a significantly improved DFS among patients receiving PORT (P = 0.003), while two of them reported a reduced rate of locoregional recurrence in this group (P = 0.032-0.009). Many studies report a positive effect of PORT when combined in parallel or sequentially with adjuvant chemotherapy in terms of long-term, disease free survival or locoregional control of the disease in patients who have undergone surgical resection of NSCLC and are found to harbour N2 disease. However, these reports are counterbalanced by an almost equal number of studies which show no difference between PORT and no PORT. Only one study reported significantly increased radiation related adverse effects in patients undergoing chemotherapy and PORT.

CXCR5 is critically involved in progression of lupus through regulation of B cell and double-negative T cell trafficking.

The recruitment of immune cells to sites of tissue inflammation is orchestrated by chemokine/chemokine receptor networks. Among these, the CXCL13/CXCR5 axis is thought to be involved critically in systemic lupus erythematosus (SLE) and lupus nephritis pathogenesis. Beyond B cell abnormalities, another hallmark of SLE disease is the occurrence of aberrant T cell responses. In particular, double-negative (DN) T cells are expanded in the peripheral blood of patients with SLE and in lupus-prone mice. DN T cells induce immunoglobulin production, secrete proinflammatory cytokines and infiltrate inflamed tissue, including kidneys. We aimed to investigate how CXCR5 deficiency changes immune cell trafficking in murine lupus. We therefore crossed CXCR5(-/-) mice with B6/lpr mice, a well-established murine lupus model. B cell numbers and B cellular immune responses were diminished in CXCR5-deficient B6/lpr mice. In addition, we observed reduced accumulation of DN T cells in spleen and lymph nodes, paralleled by reduced splenomegaly and lymphadenopathy. In-vivo migration assays revealed reduced migration of CXCR5-deficient DN T cells into lymph nodes, and ex-vivo-activated CXCR5-deficient DN T cells failed to infiltrate kidneys of recipients. Moreover, DN T cells and B cells of CXCR5-deficient B6/lpr mice failed to migrate towards CXCL13 in vitro. We propose that CXCR5 is involved critically in B cell trafficking and germinal cell (GC) formation in murine lupus and in guiding pathogenic DN T cells into lymphoid organs and kidneys, and we therefore describe new pathomechanisms for the CXCL13/CXCR5 axis in SLE.