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Long Survival and Prolonged Remission after Surgery and Chemotherapy in a Metastatic Mismatch Repair Deficient Pancreatic Neuroendocrine Carcinoma with MLH1/PMS2 Immunodeficiency and Minimal Microsatellite Shift.

Endocr Pathol. 2020 May 09;:

Authors: Vanoli A, Perfetti V, Furlan D, Neri G, Viglio A, Sessa F, Martino M, Di Sabatino A, Solcia E, La Rosa S

Abstract
Pancreatic neuroendocrine carcinomas (NECs) are rare and very aggressive neoplasms with dismal prognosis, especially when metastatic or with negative prognostic factors, such as vascular invasion. To the best of our knowledge, no case of pancreatic NEC with mismatch repair deficiency has been reported to date. We describe a 62-year-old patient who underwent pancreaticoduodenectomy for a NEC located in the pancreatic head, with peripancreatic lymph node metastases. Tumor necrosis was prominent and the Ki67 proliferative index was 60%. One year after the diagnosis, the patient experienced recurrence with a left supraclavicular lymph node metastasis, which was surgically removed, followed by standard cisplatin-etoposide chemotherapy. Neoplastic cells showed combined loss of expression of MLH1 and PMS2 in both primary tumor and lymph node metastasis. Microsatellite instability (MSI) test using a mononucleotide repeats pentaplex PCR (BAT-25, BAT-26, NR-21, NR-22, and NR-24) revealed minimal mononucleotide shifts showing deletion of less than 3 bp at NR-21, BAT-26, NR-24, and NR-22 loci. MLH1 methylation analysis revealed absence of the gene promoter methylation. BRAF and KRAS mutations were not detected. In gut, NECs’ mismatch repair deficiency phenotype has been reported in about 10% of cases, and it represents an independent factor of more favorable outcome. Likewise, our patient is currently alive with a follow-up of more than 12 years after pancreaticoduodenectomy, by itself an unexpected finding for such an aggressive neoplasm.

PMID: 32388775 [PubMed – as supplied by publisher]

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Thoracic Manifestations of Primary Immunodeficiency Disorders.

Indian J Pediatr. 2020 May 08;:

Authors: Sherwani P, Bhalla AS, Jana M, Naranje P, Kabra SK, Gupta AK, Kandasamy D

Abstract
Primary immunodeficiency disorders (PIDD) are a group of disorders presenting with recurrent infections. The authors retrospectively reviewed the imaging records of 24 proven cases of PIDD and correlated the imaging findings with the type of defect. Final diagnoses were categorized in four groups; Group I (humoral immunodeficiency), Group 2 (cell mediated immunodeficiency), Group 3 (phagocytic disorders) and Group 4 (others). Group 3 was the commonest, followed by 1 and 2. Three most common disorders encountered were chronic granulomatous disease (CGD) (7/24), hyper IgE syndrome (5/24) and common variable immunodeficiency (CVID) (4/24). Consolidation (12/24), nodules (10/24), bronchiectasis (9/24) and lymphadenopathy (8/24) were the commonest imaging findings. Although not statistically significant, some definite imaging trends could be established. Presence of consolidation and nodules; with absence of bronchiectasis was the striking finding in Group 3. Group 2 disorders predominantly showed bronchiectasis, whereas presence of consolidation, nodules, bronchiectasis all were very common in Group 1.

PMID: 32385778 [PubMed – as supplied by publisher]

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Long-term efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HyQvia(®)) in immunodeficiency diseases: real-life data from a monocentric experience.

Clin Exp Med. 2020 May 08;:

Authors: Angelotti F, Capecchi R, Giannini D, Mazzarella O, Rocchi V, Migliorini P

Abstract
Humoral immunodeficiency diseases represent a heterogeneous group of disorders that require long-term therapies. Thus, the treatment provided must not only be effective but also safe and well tolerated. In this paper, we report our data on the efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HyQvia(®)) in immunodeficiency patients. We collected retrospective data from 30 patients with primary and secondary immunodeficiency diseases in therapy with fSCIG from September 2014 to December 2019. We evaluated the efficacy of the therapy, taking into account serum IgG values during follow-up and the number of annual infectious events and serious bacterial infections reported by patients. Safety was assessed on the basis of the number and intensity of adverse events (AEs) and local reactions reported. Our real-life data suggest that long-term repeated self-administration of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulins results in a reduced rate of infectious events if compared to the pre-treatment rate. Both AEs and local reactions are mild to moderate and were never reasons for treatment discontinuation. Therapy with HyQvia shows prolonged efficacy and good tolerability; these aspects, together with the possibility of self-administration at home, minimize the impact the illness has on patients.

PMID: 32385734 [PubMed – as supplied by publisher]

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Agammaglobulinemia: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management.

Endocr Metab Immune Disord Drug Targets. 2020 May 08;:

Authors: Pashangzadeh S, Yazdani R, Nazari F, Azizi G, Abolhassani H, Aghamohammadi A

Abstract
Agammaglobulinemia is a type of primary antibody deficiencies, characterized by severe reduction in serum level of all types of immunoglobulins level and absence of B cells in the peripheral blood. X-linked and various autosomal recessive/dominant mutations have been identified underlying the pathogenesis of this disorder. Affected patients present a broad range of clinical manifestations, including respiratory infections, gastrointestinal complications, Enterovirus infections, autoimmunity, and malignancies. This disease can be controlled via different therapeutic strategies. In this review, we describe different aspects of agammaglobulinemia such as epidemiology, pathogenesis, clinical phenotype, diagnosis, management, and prognosis of congenital agammaglobulinemia.

PMID: 32384040 [PubMed – as supplied by publisher]

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Targeting CD4+ Cells with Anti-CD4 Conjugated Mertansine Loaded Nanogels.

Biomacromolecules. 2020 May 08;:

Authors: Canakci M, Singh K, Munkhbat O, Santhalingam S, Mitra A, Gordon M, Osborne BA, Thayumanavan S

Abstract
CD4+ T lymphocytes play an important role in controlling many malignancies. The modulation of CD4+ T cells through immunomodulatory or cytotoxic drugs could change the course of disease progression for disorders such as autoimmunity, immunodeficiency, and cancer. Here, we demonstrate that anti-CD4 conjugated polymeric nanogels can deliver a small molecule cargo to primary CD4+ T cells and a CD4high T cell lymphoma. The antibody conjugation not only increased the uptake efficiency of the nanogel (NG) by CD4+ T cells, but also decreased the non-specific uptake of NG by CD4- lymphocytes. For T lymphoma cell lines, the mertansine-loaded conjugate displayed a dose-dependent cell growth inhibition at 17 ng/mL antibody concentration. On the other hand, antibody-drug conjugate (ADC) type formulation of the anti-CD4 reached similar levels of cell growth inhibition only at the significantly higher concentration of 1.8 µg/mL. NG and antibody conjugates have the advantage of carrying a large payload to a defined target in a more efficient manner, as it needs far less antibody to achieve a similar outcome.

PMID: 32383874 [PubMed – as supplied by publisher]

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Single-cycle rituximab-induced immunologic changes in children: Enhanced in neuroimmunologic disease?

Neurol Neuroimmunol Neuroinflamm. 2020 Jul;7(4):

Authors: Deyà-Martínez A, Gordón Y, Molina-Anguita C, Vlagea A, Piquer M, Juan M, Esteve-Solé A, Antón J, Madrid Á, García-García A, Plaza AM, Armangue T, Alsina L

Abstract
OBJECTIVE: To investigate the immunologic impact of a single cycle of rituximab (RTX) in children and adolescents with immune-mediated disorders, we evaluated B cells and immunoglobulin levels of 20 patients with neuroimmunologic, nephrologic, dermatologic, and rheumatologic disorders treated under recommended guidelines.
METHODS: Retrospective study of immunologic changes in children (aged ≤18 years) diagnosed with immune-mediated disorders in which RTX was prescribed between June 2014 and February 2019. Patients were excluded if they had prior diagnosis of malignant disease or primary immunodeficiency. Patients were clinically and immunologically followed up every 3 months. Only patients having received a single cycle of RTX and with a follow-up greater than 12 months were included in the analysis of persistent dysgammaglobulinemia.
RESULTS: Twenty children were included. Median age at RTX treatment was 12.8 years (interquartile range [IQR] 6.6-15.5 years). Median follow-up was 12.6 months (IQR 10.2-24 months). Of the 14 patients eligible for persistent dysgammaglobulinemia analysis (3 had received RTX retreatment, 2 had <12 months post-RTX follow-up, and in 1 data for this time point was missing), 2/14 (14%) remained with complete B-cell depletion, and 5/14 (36%) had dysgammaglobulinemia. Patients with dysgammaglobulinemia were younger (7.8 vs 15.6 years, p = 0.072), had more underlying neuroimmunologic diseases (5/5 vs 0/9, p < 0.001), and had received more frequently concentrated doses of RTX (3/5 vs 1/9, p = 0.05) than patients without dysgammaglobulinemia. Kinetics of immunoglobulins in the 20 patients revealed a decrease as early as 3 months after RTX in patients with neuroimmunologic disorders.
CONCLUSION: In our cohort, single-cycle RTX-induced dysgammaglobulinemia was enhanced in patients with neuroimmunologic diseases. Further studies are needed to confirm this observation.

PMID: 32376706 [PubMed – in process]

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