Intrabronchial Valves for Air Leaks After Lobectomy, Segmentectomy, and Lung Volume Reduction Surgery.

PURPOSE: Air leaks are common after lobectomy, segmentectomy, and lung volume reduction surgery (LVRS). This can increase post-operative morbidity, cost, and hospital length of stay. The management of post-pulmonary resection air leaks remains challenging. Minimally invasive effective interventions are necessary. The Spiration Valve System (SVS, Olympus/Spiration Inc., Redmond, WA, US) is approved by the FDA under humanitarian use exemption for management of prolonged air leaks. METHODS: This is a prospective multicenter registry of 39 patients with air leaks after lobectomy, segmentectomy, and LVRS managed with an intention to use bronchoscopic SVS to resolve air leaks. RESULTS: Bronchoscopic SVS placement was feasible in 82.1% of patients (32/39 patients) and 90 valves were placed with a median of 2 valves per patient (mean of 2.7 ± 1.5 valves, range of 1 to 7 valves). Positive response to SVS placement was documented in 76.9% of all patients (30/39 patients) and in 93.8% of patients when SVS placement was feasible (30/32 patients). Air leaks ultimately resolved when SVS placement was feasible in 87.5% of patients (28/32 patients), after a median of 2.5 days (mean ± SD of 8.9 ± 12.4 days). Considering all patients with an intention to treat analysis, bronchoscopic SVS procedure likely contributed to resolution of air leaks in 71.8% of patients (28/39 patients). The post-procedure median hospital stay was 4 days (mean 6.0 ± 6.1 days). CONCLUSIONS: This prospective registry adds to the growing body of literature supporting feasible and effective management of air leaks utilizing one-way valves.

Regulatory T cell expansion resolves after effective strongyloidiasis treatment in subjects with HTLV-1 co-infection.

BACKGROUND: Regulatory T-cells (Tregs) are increased in patients with HTLV-1/Strongyloides stercoralis co-infection, and they may modify otherwise protective antigen-specific cytokine production. We hypothesized that effective anti-helminthic treatment would decrease Tregs and restore antigen-specific cytokine responses. METHODS/RESULTS: We enrolled 19 patients with Strongyloides larvae in their stool by Baerman's test. Six were positive and 13 negative for antibody to HTLV-1 by ELISA, with positive tests confirmed by immunoblot. Before treatment, co-infected subjects had higher Tregs percentages and lower antigen-stimulated IL-5 levels compared to subjects with Strongyloides without HTLV-1. All patients were treated with ivermectin. After effective treatment, Tregs percentages decreased in patients with HTLV-1; however, antigen-specific IL-5 production remained blunted in co-infected subjects. CONCLUSION: These results suggest that treating strongyloidiasis infection decreases circulating Tregs, but antigen-specific cytokine remains altered. This may reflect blunting of sensitization by Tregs.

Characteristics and Outcomes of Lung Transplant Candidates With Preexisting Renal Dysfunction.

BACKGROUND: The proportion of lung transplant candidates with comorbid renal dysfunction (RD) may rise as sicker patients are being considered for lung transplant (LT). There is lack of data regarding the characteristics and outcome of patients with RD and the role of simultaneous lung-kidney transplant (SLuKi) among these patients. METHODS: The United Network of Organ Sharing database was queried for adult patients (18 years or older) undergoing LT between 1995 and 2014. Pretransplant RD was defined as estimated glomerular filtration rate (eGFR), using the Chronic Kidney Disease Epidemiology Collaboration equation of <60 mL/min/1.73 m2 at the time of transplant listing. The recipient, donor, and procedure-related variables and survival were compared among patients with RD undergoing LT alone (split on the basis of eGFR impairment: 30-60 mL/min/1.73 m2 and ≤ 30 mL/min/1.73 m2) vs those with SLuKi. RESULTS: The frequency of pretransplant RD was 5.42% (n = 1337). Patients with RD have significantly higher 1-year mortality (23.2% vs 15%; P < .001) and 3-year mortality (38.3% vs 28%; P < .001) than patients with eGFR > 60mL/min/1.73 m2. The proportion of patients with RD undergoing SLuKi was 2.84% (38 of 1337). Both the number and proportion of patients undergoing SLuKi progressively increased during the study period, especially in the lung allocation score era (30 of 38 SLuKi patients in the post lung allocation score era (linear R2 = 0.641, P < .001). The patients who underwent SLuKi were significantly younger, had lower body mass index, serum albumin, and listing eGFR (P < .001 for all comparisons). Patients with SLuKi were more likely to have cystic fibrosis or vascular diseases as the underlying diagnosis (29.7% vs 13.8%, P = .004). Despite higher need of early dialysis support after transplant, there was no difference in the 30-day, 1-year, or 3-year survival between the 2 groups. CONCLUSIONS: A significant proportion of LT candidates have a pre-existing RD, and this comorbidity is associated with significantly worse 1- and 3-year survival. Despite being the sicker group at baseline, patients with RD who undergo SLuKi have 1-year outcomes similar to patients with LT alone.

Regulatory T-Cell Dynamics in Cutaneous and Mucocutaneous Leishmaniasis due to Leishmania braziliensis.

To evaluate the dynamics of regulatory T cells (Tregs) during tegumentary leishmaniasis, we assessed peripheral blood and biopsies from 54 patients. Patients with cutaneous leishmaniasis (CL) had a decreased proportion of Tregs in the peripheral blood, but the proportion was higher in the biopsies of lesions. During treatment of CL, circulating Tregs increased reaching normal proportions, whereas antigen-specific interferon-γ responses diminished. By contrast, circulating Tregs from mucosal leishmaniasis patients failed to normalize during treatment. C-C chemokine receptor type 5 was expressed on a large proportion of Tregs at the site of infection. These results demonstrate increased Tregs at the site of infection, possibly homing from the peripheral circulation.

Strongyloides stercoralis infection complicating the central nervous system.

Strongyloides stercoralis is a nematode endemic in humid tropical regions. The life cycle of this parasite is complex and unique due to its capacity to cause autoinfection, resulting in chronic infections. Innate and adaptive immune responses are responsible for clearing the parasite. Many risk factors have been described, but the most important is living in or having visited an endemic area. The clinical presentation of strongyloidiasis is varied and ranges from asymptomatic chronic infection to hyperinfection syndrome. Hyperinfection syndrome is more common in patients with immunosuppresion due to therapy with corticosteroids, coinfection with human T-lymphotropic virus type I (HTLV-1), transplant patients, or patients receiving chemotherapy. Multiplication and migration of large parasite numbers cause worsening of the initial symptoms and leads to a high mortality rate. CNS involvement in strongyloidiasis has only been seen in patients with hyperinfection syndrome. Meningitis is the most common form of CNS involvement and gram-negative bacteria are the more frequent etiology. Repeated stool samples with concentration methods have a good sensitivity and specificity. In patients that are not from endemic areas serum antibody tests may be useful in the diagnosis. Treatment with a single dose of ivermectin is recommended for most patients. In severe or hyperinfection cases repeated doses may be needed.

Are increased Foxp3+ regulatory T cells responsible for immunosuppression during HTLV-1 infection? Case reports and review of the literature.

Research of human T lymphotropic virus type I (HTLV-1)-associated diseases is mostly focused on inflammatory and lymphoproliferative disorders. However, the immunosuppressive consequences of HTLV-1 infection are frequently ignored. In developing countries where exposure to parasitic and other tropical diseases is frequent, the burden of disease is significantly increased by opportunistic infections. Regulatory T cells (Tregs) are a CD4 T-cell subset capable of suppressing effector responses. During HTLV-1 infection, CD4+Foxp3+ cells are increased in HTLV-1-associated leukaemia/lymphoma (ATLL) as well as in non-leukaemic presentations. However, controversy exists regarding the actual regulatory function of these cells. In this report, we present two cases of HTLV-1 ATLL complicated by parasitic organisms and we provide a brief review of the literature regarding FoxP3+ regulatory T cells and their role as a possible mechanism for the immunosuppressive manifestations that take place during HTLV-1 infection.