Single-Center Study of 72 Patients with Severe Combined Immunodeficiency: Clinical and Laboratory Features and Outcomes

Journal of Clinical Immunology - Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various...     

High-dose thiotepa,melphalan and carboplatin (TMCb) followed by autologous stem cell transplantation in patients with advanced breast cancer: a retrospective evaluation

This study was conducted to evaluate the efficacy of high-dose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m(2)), melphalan (100 mg/m(2)) and carboplatin (1200-1350 mg/m(2)). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n=2) or early death due to transplant-related complications (n=3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%),(10) are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n=17) and responsive (n=10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR(*) following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR(*) following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.     

Potential Animal Reservoirs of Toscana Virus and Coinfections with Leishmania infantum in Turkey

Toscana virus (TOSV), a sandfly-borne phlebovirus, is an important agent of human meningoencephalitis in the Mediterranean region, for which vertebrates acting as reservoirs have not yet been determined. This study investigates TOSV and Leishmania infections in dogs, cats, sheep, and goats from Adana and Mersin provinces in southeastern Turkey. TOSV neutralizing antibodies were demonstrated in 40.4% of the dog and 4% of the goat samples. TOSV RNA was detected in 9.9% of the 252 samples that mainly comprise dogs (96%). Thus, canine species can be suggested as the candidate reservoirs of TOSV. Partial sequences revealed the activity of TOSV genotypes A and B. In two dogs presenting with symptoms of canine leishmaniasis, infections of TOSV genotype B and Leishmania infantum have been documented, describing the first report of coinfections with these agents.     

Evaluation of purified antigen fraction in the immunodiagnosis of cystic echinococcosis

Echinococcus granulosus antigen B fraction (AgB) was evaluated for its prognostic value in the serological follow-up of cystic echinococcosis (CE), compared to crude hydatid fluid (HF) as well as soluble somatic Echinococcus multilocularis antigen (Em). The sensitivity and specificity of enzyme-linked immunosorbent assays (ELISA) were compared examining 177 sera from patients with different clinical courses and outcome of CE and with other parasitic infections. AgB-ELISA in comparison to confirmed cystic echinococcosis has 96.4 % sensitivity and 97.2 % specificity, with 93.1 % positive predictive value and 98.6 % negative predictive value. The HF-ELISA was more sensitive than the AgB-ELISA, but its specificity was lower. Our results indicate that AgB-ELISA was more satisfactory for seroconfirmation of acute echinococcosis than HF-ELISA. Moreover, the AgB-ELISA has a potential key role in control measures implemented in patients undergoing surgery. In sera of patients more than 3 months after the treatment, no antibody response to antigen B was detected; however, with conventionally used HF-ELISA, they were still positive. The AgB is recommended for the confirmatory diagnosis. AgB-WB allocated low background with typical “triplet” bands at 8-12-16 kDa.     

Approach to patients with chylothorax complicating pulmonary resection

Mediastinal lymph node dissection, an important part of surgery for non-small cell lung cancer, is associated with a risk of chylothorax. Although mortality has significantly decreased in recent years, it still worries thoracic surgeons. In this report we reviewed our experience on chylothorax with 26 cases and assessed the outcomes after conservative and surgical approaches. Between January 2000 and June 2010, twenty-six patients developed chylothorax after pulmonary resection performed for non-small cell lung cancer. Initially, all cases were treated conservatively with cessation of oral intake and the application of talc poudrage. If the conservative method failed, a surgical approach was used, which consisted either of suturing the leak or of mass ligation. The mean age of patients was 56 ± 9.05 years, and 3 were female. Chylothorax was more common on the right side, in lobectomy cases, in cases with adenocarcinoma, and in patients with advanced stage lung cancer, but the difference did not reach statistical significance. Conservative treatment was successful in 19 of 26 (73 %) patients, four of whom had undergone pneumonectomy. Seven out of 26 cases (27%) required thoracotomy to control the chylous leak. Though thoracotomy was required mostly for the right side (6 right vs. 1 left, p = 0.15), and in patients who had had pneumonectomy as their first operation (4 patients vs. 3, p = 0.18), this did not reach statistical significance. No patient died as a result of surgical intervention. In conclusion, chylothorax is not rare after pulmonary resection performed for lung cancer. But it is not as dangerous as it used to be. Talc pleurodesis has increased the success of conservative management and minimized the need for surgical intervention. In cases of high output leak the surgeon should not hesitate to perform surgery. VATS can be performed instead of open surgery in suitable cases.     

Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy

PurposeExcision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy.Materials and methodsThirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival.ResultsPathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012–0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2–11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. ≤60 years) (HR 3.4, 95% CI 1.2–9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014–0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9–19.9, P = 0.002) were significantly associated with OS.ConclusionsOur results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer.     

The pulmonary involvement in rheumatic diseases: pulmonary effects of ankylosing spondylitis and its impact on functionality and quality of life

Rheumatic diseases are chronic inflammatory diseases which cause mild to severe functional loss and disability due to articular and extra-articular manifestations. One common form -ankylosing spondylitis (AS)- affects mainly the axial skeleton and sacroiliac joints, and certain extra-articular organs. The pulmonary involvement is a known manifestation of AS and emerges either in the form of interstitial lung disease or in the form of restricted pulmonary functions. The aim of this study is to determine the pulmonary functions in AS patients and to assess its relationship with quality of life, functionality and disease activity. Thirty-six AS patients and 34 healthy volunteers were recruited for the study. A detailed examination, pulmonary function tests, smoking inquiry and quality of life questionnaire were performed on all participants. Also patients were requested to complete functionality and disease activity indexes. The outcomes showed that 15 (41.7%) AS patients had pulmonary involvement: twelve patients with restrictive patterns, one with obstructive pattern, and two with both restrictive and obstructive patterns. Decreased forced expiratory volume in one second was associated with deteriorated functionality (p < 0.05). Decreased chest expansion was also accompanied with decreased forced vital capacity (p < 0.05). There was no statistically significant difference between the smoking and non-smoking patients in regard to disease activity, functionality and pulmonary function test variables (p > 0.05). In conclusion, the pulmonary involvement is common in AS and might have disturbed functionality and the quality of life in AS patients.     

Assessment of left ventricular diastolic function with Doppler tissue imaging: effects of preload and place of measurements

Mitral inflow velocities are widely used for the evaluation of left ventricular (LV) diastolic function. However, they are closely affected by other factors such as preload. The purpose of this study was to evaluate the usefulness of tissue Doppler velocities obtained from the mitral annulus for the evaluation of ventricular relaxation in patients under different loading conditions. We also evaluated the effect of preload at different sides on the mitral annulus. The study population consisted of 62 consecutive patients (38 male, 24 female with a mean age of 42 ± 13 years) who have undergone hemodialysis. Both mitral inflow velocities (E wave, A wave, E wave deceleration time and isovolumetric relaxation time) and mitral annulus tissue Doppler velocities (E, A) from the septal, lateral, anterior, posterolateral and inferior sides of the mitral annulus were measured immediately before and after hemodialysis. Mitral inflow E and A wave velocities and E/A ratio decreased significantly (p < 0.001, p = 0.007, p < 0.001, respectively) after hemodialysis. Mitral annulus E wave velocities and E/A ratios obtained from five different sides of the annulus also changed significantly (p < 0.001 for all); however, there was no change in the A wave velocity (p > 0.05 for all) after hemodialysis. The decrease in E wave and E/A ratio in mitral inflow measurements and E velocities and E/A ratios in tissue Doppler measurements were correlated with the amount of fluid extracted (for mitral inflow E wave, r = 0.392, p = 0.002 and E/A ratio, r = 0.280 and p = 0.027; for lateral side E, r = 0.329, p = 0.009 and E/A ratio, r = 0.286, p = 0.04; for septal side E, r = 0.376, p = 0.003 and E/A ratio, r = 0.297, p = 0.019; for anterior side E, r = 0.342, p = 0.007 and E/A ratio, r = 0.268, p = 0.035; for posterolateral side E, r = 0.423, p = 0.001 and E/A ratio, r = 0.343, p = 0.007; and for inferior side E, r = 0.326, p = 0.01 and E/A ratio, r = 0.278, p = 0.029). We conclude that mitral annular velocities obtained by tissue Doppler are preload dependent parameters for the evaluation of LV diastolic function.