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Lung Matters
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Since chemotherapy does not specifically target cancer cells, many healthy cells are killed in the process of treatment, particularly fast-growing cells such as the hair follicles, gut, mouth and blood. The most common side effects include low red and white blood cell counts, loss in appetite, nausea, vomiting, diarrhea, hair loss and mouth sores, among many others (Alder, 2017). It is clear that many options are available to patients; however, their success is limited and comes at a price of often severe side effects. The liver is the primary site of metabolism for many of these drugs. All of the mentioned therapies can cause damage to the liver known as hepatotoxicity. The clinical presentations of hepatotoxicity can vary from asymptomatic to an increase of liver chemistries and evident cholestatic hepatitis. This damage can progress to fibrosis and cirrhosis, malignant transformation, veno-occlusive disease/sinusoidal obstruction and even fulminant hepatic failure (Grigorian and Brien, 2014).
Mucosal manifestations of immunodeficiencies
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Scott Snapper, Jodie Ouahed, Luigi D. Notarangelo
Veno-occlusive disease with immunodeficiency is an autosomal recessive, rare disorder characterized by profound immunodeficiency, liver fibrosis and veno-occlusive disease. Patients present with severe symptoms within the first year of life. The disease has been reported predominantly in patients of Lebanese origin and is due to mutations of the SP110 gene that encodes for a nuclear protein of unclear function. Patients show profound hypogammaglobulinemia and a lack of germinal centers in the lymph nodes. T lymphocytes are present in normal numbers, but opportunistic infections (P. jiroveci pneumonia, cytomegalovirus infection, persistent candidiasis) are observed in most patients, indicative of a severe defect in cell-mediated immunity. Hepatomegaly and abnormalities of liver enzymes are often the first signs of severe liver disease that may progress to veno-occlusive disease and terminal liver failure. Liver biopsy shows sinusoidal congestion or obstruction and narrowing of terminal hepatic venules. Ultrasonography demonstrates hepatosplenomegaly, increased portal vein diameter, reduced hepatic vein diameter, ascites, and recanalization of the ligamentum teres due to shunting of blood flow from the liver. Doppler ultrasonography shows reduced portal venous flow and increased resistance in the hepatic artery. Prognosis is dismal, and most patients die in the first years of life.
Ursodeoxycholic Acid Treatment of Vanishing Bile Duct Syndromes
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Chronic graft-versus-host-disease (GVHD) frequendy involves the liver. It is a classical VBDS with liver biopsies showing a reduction or absence of small bile ducts with cholestasis.83 Since the pathophysiology is similar to that observed in PBC, UDCA therapy was evaluated in patients with liver GVHD, because UDCA is safe and may exert beneficial effects in addition to those induced by immunosuppressive therapy. UDCA was used in combination with cyclosporine and methotrexate in 67 patients after bone marrow transplantation.84 The development of veno-occlusive disease was significantly reduced in patients treated with UDCA, resulting in a decreased 100-day mortality. However, larger trials are needed to confirm the positive preliminary results of UDCA treatment and to assess the long-term efficacy, which is currently unknown.
Improving outcomes and quality of life for patients with transfusion-dependent β-thalassemia: recommendations for best clinical practice and the use of novel treatment strategies
Published in Expert Review of Hematology, 2021
Ali T. Taher, Rayan Bou-Fakhredin, Antonis Kattamis, Vip Viprakasit, Maria Domenica Cappellini
Eligible patients ≥ 12 years of age must have hemoglobin levels ≥ 11 g/dL for 30 days prior to mobilization and during myeloablation; creatinine clearance ≤ 70 mL/min/1.73 m2; normal liver function tests; negative serology HIV-1/2; and cardiac T2*-weighted magnetic resonance imaging (T2*MRI) ≥ 10 msec. If MRI liver iron concentration is ≥ 15 mg/g, liver biopsy should be performed to confirm absence of fibrosis, cirrhosis, or active hepatitis. Negative serum pregnancy tests must be provided before mobilization and conditioning, and before beti-cel infusion. Beti-cel is not recommended for women who are breastfeeding. Ova and semen cryopreservation are recommended before treatment. Anti-retroviral medications and/or hydroxyurea should be stopped ≥ 1 month prior to and until ≥ 7 days after conditioning and ICT must be stopped ≥ 7 days before conditioning. It is recommended that patients receive prophylaxis to prevent veno-occlusive disease and prophylaxis against seizures should also be considered.
Pulmonary tumor thrombotic microangiopathy: A systematic review of the literature
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2021
L. V. Morin-Thibault, D. Wiseman, P. Joubert, R. Paulin, S. Bonnet, S. Provencher
In the context of severe PH of unknown origin, few patients were anticoagulated (n = 39), received thrombolytics (n = 5) or were treated with PH-targeted treatments (n = 27) including phosphodiesterase-5 inhibitors (n = 15), endothelin receptor antagonists (n = 12), prostanoids (n = 11), stimulator of soluble guanylate cyclase (n = 1) and inhaled nitric oxide (n = 1) (Supplementary Table S2). One patient quickly developed hypoxic respiratory failure after the initiation of epoprostenol. Interestingly, on autopsy, this patient showed signs of pulmonary veno-occlusive disease. Of the 5 patients who received thrombolysis, one had a concomitant massive PE and one had a subsegmental PE and DVT. Reasons for thrombolysis in the three other cases are unknown. One intracranial bleed was reported.11 Among the 29 patients with an antemortem diagnosis of PTTM, 4 did not receive any treatment, 16 received anticoagulants, 11 were treated with PH-specific therapies and 10 received either oral or IV corticosteroids. Moreover, 1 patient underwent an oncological surgery, 1 patient received percutaneous cardiorespiratory support and 1 patient underwent a cardiopulmonary transplant. Finally, 21 patients received conventional chemotherapy and 6 patients received imatinib (Table 4).12–17
Immune-checkpoint inhibitors to treat cancers in specific immunocompromised populations: a critical review
Published in Expert Review of Anticancer Therapy, 2018
Hélène Babey, Gilles Quéré, Renaud Descourt, Ronan Le Calloch, Luca Lanfranco, Jean-Baptiste Nousbaum, Divi Cornec, Alice Tison, Christos Chouaid
The results of a study [57] on patients allografted after having received an anti-PD-1 monoclonal antibody showed the risk of accrued toxicity, especially veno-occlusive disease and GVHD. In that study on 39 heavily pretreated (median 4 (2–8) previous treatment lines) patients (31 Hodgkin lymphomas and 8 non-Hodgkin lymphomas), the median age was 34 years; 82% had received autografts and relapsed a median of 23 (range 2–132) months thereafter; 24 had already received brentuximab. The patients were given a median of 8 (range 3–27) anti-PD1 infusions. The ORR was 62% (74% of Hodgkin lymphoma patients), including 36% complete responses. Safety was acceptable, with 44% of the patients experiencing grade 1 GVHD at 1 year and 13 had grade 4 GVHD that was fatal for 3. A fourth patient died of veno-occlusive disease. The authors concluded that allografting after anti-PD-1 seems possible with a low relapse rate. However, an accrued risk of early immune toxicity could exist, which might reflect long-duration immune changes induced by prior anti-PD-1 use.