Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4+/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. OBJECTIVE: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. METHODS: The 98 patients (63 LRBA-/- and 35 CTLA4+/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. RESULTS: The LRBA-/- patients exhibited a more severe disease course than did the CTLA4+/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. CONCLUSIONS: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.

The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

Comparison of chest computed tomography and 3-T magnetic resonance imaging results in patients with common variable immunodeficiency.

BACKGROUND: Patients with common variable immunodeficiency (CVID) have an increased incidence of pulmonary infections and require frequent follow-up computed tomography (CT) scans. PURPOSE: To evaluate the diagnostic performance of 3-T magnetic resonance imaging (MRI) in patients with CVID. MATERIAL AND METHODS: In this prospective study, 3-T MRI was performed in 20 patients with CVID. The patients were imaged with CT and MRI scans on the same day. The MRI protocol included a T2-weighted HASTE sequence (TR=1400 ms, TE=95 ms, slice thickness (ST)=3 mm), T2-weighted BLADE sequence (TR=5379 ms, TE=100 ms, ST=3 mm), and 3D VIBE sequence (TR=3.9 ms, TE=1.32 ms, ST=3 mm). Mediastinal and parenchymal changes were compared. A modified Bhalla scoring system was used in the evaluation of CT and MRI scans. RESULTS: A total of 17 (85%) patients had parenchymal abnormalities identified by CT or MRI. Similar findings were detected with CT and MRI in the assessment of the severity of bronchiectasis (P=0.083), bronchial wall thickening (P=0.157), and mucus plugging (P=0.250). Consolidations were detected with both modalities in all patients. There was excellent concordance between the two modalities in the evaluation of nodules >5 mm (nodule size 5-10 mm, P=0.317; nodule size >10 mm, P=1). However, MRI failed to detect most of the small nodules (<5 mm). CONCLUSION: 3-T MRI detected mediastinal and parenchymal alterations in patients with CVID and provided findings that correlated well with CT. Despite a few limitations, MRI is a well-suited radiation-free technique for patients requiring longitudinal imaging.

Interdisciplinary Healthcare Team Experience of Carboplatin and Oxaliplatin Desensitizations in a Tertiary Referral University Hospital.

Purpose: Repeated exposure to platinum compounds increases the risk of immunoglobulin E-mediated immediate hypersensitivity reactions (HSR). To date, many different desensitization protocols with varying success rates have been reported. The presented study is aimed at disseminating the real-world experience of an interdisciplinary healthcare team focusing on platin desensitization. Patients and Methods: This is a cross-sectional, retrospective study of 7 female patients with carboplatin- or oxaliplatin-induced HSRs. After a discussion with the oncologist and the patient, desensitization protocols were performed by a team consisting of an allergy and immunology specialist, a clinical pharmacist, and a nurse. Clinical data were extracted from the patients' medical records, and HSRs were reviewed and classified by an allergist according to severity and type. Results: Twenty-five desensitization protocols were carried out for patients with carboplatin- or oxaliplatin-induced HSRs (N=4 and N=3, respectively; age range: 54-66). Two of the patients did not experience any HSR during a total of 8 desensitization cycles. The other patients had grade 1-3 HSRs on 15 cycles, which were successfully managed by oxygen and/or pharmacological interventions and infusions were resumed at a lower rate after stabilization of the patient. Compared to baseline, serum tryptase levels were elevated during HSRs (4.77±0.21 vs 9.50±1.71, P=0.028). Conclusion: All the patients were able to finish the treatment protocol and receive full chemotherapeutic doses. Interdisciplinary teams may facilitate the preparation and administration of platinum-based chemotherapeutics and increase the success rates of desensitization protocols for platin-based chemotherapy, where the concentration and application of drugs differ from standard procedure.

In Vitro Fertilization Using Luteinizing Hormone-Releasing Hormone Injections Resulted in Healthy Triplets without Increased Attack Rates in a Hereditary Angioedema Case.

Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH) is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50-200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH) injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.

Evaluation of Inferior Turbinate Stroma with Ultrasound Elastography in Allergic Rhinitis Patients.

BACKGROUND: Diagnosis of allergic rhinitis is primarily based on history, physical examination and allergy testing. A technique that noninvasively evaluates the soft tissue changes in the nasal mucosa of allergic rhinitis patients has not been defined. AIMS: To assess nasal mucosal changes and measure the submucosal fibrosis in allergic rhinitis patients with sonoelastography. STUDY DESIGN: Case control study. METHODS: Eighty-eight turbinates of 44 patients were included in the study. There were 23 prick test positive allergic rhinitis patients. The control group constituted 21 patients. The rhinitis quality of life questionnaire and the visual analogue scale were applied to the allergic rhinitis patients. A higher visual analogue scale score indicated more severe allergic rhinitis symptoms. Sonoelastographic measurements were made from the lateral nasal wall. The propagation speed of sound waves was recorded in m/s. The presence of asthma and the type of allergic rhinitis (seasonal or perennial) was noted. RESULTS: Ten patients had seasonal allergic rhinitis and thirteen patients had perennial allergic rhinitis. Six patients (26.1%) had accompanying asthma along with allergic rhinitis. The median visual analogue scale score was 7 (3-9) in allergic rhinitis patients. The median symptom duration was 7 (1-24) months. The median quality of life questionnaire score was 3.39 (1.68-5.43) points. The median sonoelastography scores of allergic rhinitis patients and healthy subjects were 2.38 m/s (0.9-4.47) and 2.42 m/s (1.62-3.50), respectively. Sonoelastographic measurements of seasonal and perennial allergic rhinitis patients did not differ significantly (p<0.05). The presence of asthma did not have a significant impact on the elastography measurements (<0.05). However, regression analysis revealed a significant inverse correlation (coefficients: B=0.005, standard error=0.097, beta 0=0.008) between the visual analogue scale and sonoelastography scores (p>0.05). CONCLUSION: Sonoelastography was not suitable as a diagnostic tool in allergic rhinitis. Reduced sonoelastography scores were measured in more symptomatic patients. Higher visual analogue scale scores could be an indicator of disease severity.

The Role of Body Mass Index in Triple Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) has none of the targeted treatment choices due to its distinct biological property, making this subtype a unique disease. In this study, we evaluated the impact of obesity on clinical outcomes of TNBC. METHODS: The data of breast cancer patients admitted to our department were collected. TNBC was defined as lack of estrogen receptor (ER), progesterone receptor (PR) and HER-2. The body mass index (BMI) of 112 TNBC patients was calculated with weight at the time of diagnosis and height. The patients were classified into groups with a BMI of < 25 (normal/underweight), 25-29.9 (overweight) or ≥ 30 (obese). After a mean follow-up of 23.2 ± 15.5 months, there were 12 recurrences (10.71%) and 6 deaths (5.35%). Disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: The survival analyses of all the patients did not demonstrate any differences in OS or DFS in obese as compared to non-obese patients. However, we showed that obesity was associated with a poorer OS for postmenopausal TNBC patients (p < 0.05). CONCLUSION: Obesity is related to a poorer OS in postmenopausal TNBC patients. Due to the heterogeneous disease profile of TNBC, larger randomized studies will be needed to clarify the exact role of obesity in TNBC.