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  1. Article ; Online: Pulmonary toxicity of immune checkpoint immunotherapy.

    Ghanbar, Mohammad I / Suresh, Karthik

    The Journal of clinical investigation

    2024  Volume 134, Issue 2

    Abstract: Cancer remains a leading cause of mortality on a global scale. Lung cancer, specifically non-small cell lung cancer (NSCLC), is a prominent contributor to this burden. The management of NSCLC has advanced substantially in recent years, with ... ...

    Abstract Cancer remains a leading cause of mortality on a global scale. Lung cancer, specifically non-small cell lung cancer (NSCLC), is a prominent contributor to this burden. The management of NSCLC has advanced substantially in recent years, with immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), leading to improved patient outcomes. Although generally well tolerated, the administration of ICIs can result in unique side effects known as immune-related adverse events (irAEs). The occurrence of irAEs involving the lungs, specifically checkpoint inhibitor pneumonitis (CIP), can have a profound effect on both future therapy options and overall survival. Despite CIP being one of the more common serious irAEs, limited treatment options are currently available, in part due to a lack of understanding of the underlying mechanisms involved in its development. In this Review, we aim to provide an overview of the epidemiology and clinical characteristics of CIP, followed by an examination of the emerging literature on the pathobiology of this condition.
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Lung Neoplasms/drug therapy ; Antineoplastic Agents, Immunological/adverse effects ; Pneumonia ; Immunotherapy/adverse effects ; Drug-Related Side Effects and Adverse Reactions
    Chemical Substances Antineoplastic Agents, Immunological
    Language English
    Publishing date 2024-01-16
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI170503
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Review of Pulmonary Manifestations in Antisynthetase Syndrome.

    Ghanbar, Mohammad I / Danoff, Sonye K

    Seminars in respiratory and critical care medicine

    2024  

    Abstract: Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in patients with a triad of myositis, arthritis, and interstitial lung disease (ILD), its presentation can be ... ...

    Abstract Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in patients with a triad of myositis, arthritis, and interstitial lung disease (ILD), its presentation can be diverse. Additional common symptoms experienced by patients with ASyS include Raynaud's phenomenon, mechanic's hand, and fever. Although there is a significant overlap with polymyositis and dermatomyositis, the key distinction lies in the presence of antisynthetase antibodies (ASAs). Up to 10 ASAs have been identified to correlate with a presentation of ASyS, each having manifestations that may slightly differ from others. Despite the proposal of three classification criteria to aid diagnosis, the heterogeneous nature of patient presentations poses challenges. ILD confers a significant burden in patients with ASyS, sometimes manifesting in isolation. Notably, ILD is also often the initial presentation of ASyS, requiring pulmonologists to remain vigilant for an accurate diagnosis. This article will comprehensively review the various aspects of ASyS, including disease presentation, diagnosis, management, and clinical course, with a primary focus on its pulmonary manifestations.
    Language English
    Publishing date 2024-05-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1183617-9
    ISSN 1098-9048 ; 1069-3424
    ISSN (online) 1098-9048
    ISSN 1069-3424
    DOI 10.1055/s-0044-1785536
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Review of Pulmonary Manifestations in Antisynthetase Syndrome

    Ghanbar, Mohammad I. / Danoff, Sonye K.

    Seminars in Respiratory and Critical Care Medicine

    (Pulmonary Complications of Connective Tissue Diseases)

    2024  

    Abstract: Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in patients with a triad of myositis, arthritis, and interstitial lung disease (ILD), its presentation can be ... ...

    Series title Pulmonary Complications of Connective Tissue Diseases
    Abstract Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in patients with a triad of myositis, arthritis, and interstitial lung disease (ILD), its presentation can be diverse. Additional common symptoms experienced by patients with ASyS include Raynaud's phenomenon, mechanic's hand, and fever. Although there is a significant overlap with polymyositis and dermatomyositis, the key distinction lies in the presence of antisynthetase antibodies (ASAs). Up to 10 ASAs have been identified to correlate with a presentation of ASyS, each having manifestations that may slightly differ from others. Despite the proposal of three classification criteria to aid diagnosis, the heterogeneous nature of patient presentations poses challenges. ILD confers a significant burden in patients with ASyS, sometimes manifesting in isolation. Notably, ILD is also often the initial presentation of ASyS, requiring pulmonologists to remain vigilant for an accurate diagnosis. This article will comprehensively review the various aspects of ASyS, including disease presentation, diagnosis, management, and clinical course, with a primary focus on its pulmonary manifestations.
    Keywords antisynthetase syndrome ; antisynthetase antibodies ; interstitial lung disease ; idiopathic inflammatory myopathies ; connective tissue disease ; idiopathic interstitial pneumonia
    Language English
    Publishing date 2024-05-06
    Publisher Thieme Medical Publishers, Inc.
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 1183617-9
    ISSN 1098-9048 ; 1069-3424
    ISSN (online) 1098-9048
    ISSN 1069-3424
    DOI 10.1055/s-0044-1785536
    Database Thieme publisher's database

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  4. Article ; Online: Wernicke's encephalopathy-induced hearing loss complicating sleeve gastrectomy.

    Mohammed, Elaf Abdulnabi / Hajji, Sulaiman Ali / Aljenaee, Khaled / Ghanbar, Mohammad Ibrahim

    BMJ case reports

    2020  Volume 13, Issue 9

    Abstract: A 25-year-old woman brought to the hospital with symptoms of acute confusion, disorientation, diplopia, hearing loss and unsteady gait which started 4 days prior to her presentation with rapid worsening in its course until the day of admission. She had a ...

    Abstract A 25-year-old woman brought to the hospital with symptoms of acute confusion, disorientation, diplopia, hearing loss and unsteady gait which started 4 days prior to her presentation with rapid worsening in its course until the day of admission. She had a surgical history of laparoscopic sleeve gastrectomy 2 months earlier which was complicated by persistent vomiting around one to three times per day. She lost 30 kg of her weight over 2 months and was not compliant to vitamin supplementation. CT of the brain was unremarkable. Brain MRI was done which showed high signal intensity lesions involving the bilateral thalamic regions symmetrically with restricted diffusion on fluid-attenuated inversion recovery imaging. Other radiological investigations, such as magnetic resonance venography and magnetic resonance angiography of the brain were unremarkable. An official audiogram confirmed the sensorineural hearing loss. A diagnosis of Wernicke's encephalopathy due to thiamin deficiency post-sleeve gastrectomy was made based on the constellation of her medical background, clinical presentation and further supported by the distinct MRI findings. Consequently, serum thiamin level was requested and intravenous thiamin 500 mg three times per day for six doses was started empirically, then thiamin 250 mg intravenously once daily given for 5 more days. Marked improvement in cognition, eye movements, strength and ambulation were noticed soon after therapy. She was maintained on a high caloric diet with calcium, magnesium oxide, vitamin D supplements and oral thiamin with successful recovery of the majority of her neurological function with normal cognition, strength, reflexes, ocular movements, but had minimal resolution of her hearing deficit. Serum thiamin level later was 36 nmol/L (67-200).
    MeSH term(s) Adult ; Female ; Gastrectomy/adverse effects ; Gastrectomy/methods ; Hearing Loss/etiology ; Humans ; Postoperative Complications/etiology ; Wernicke Encephalopathy/complications ; Wernicke Encephalopathy/diagnosis
    Language English
    Publishing date 2020-09-15
    Publishing country England
    Document type Case Reports ; Journal Article
    ISSN 1757-790X
    ISSN (online) 1757-790X
    DOI 10.1136/bcr-2019-233144
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Population Pharmacokinetics of Intraperitoneal Gentamicin and the Impact of Varying Dwell Times on Pharmacodynamic Target Attainment in Patients with Acute Peritonitis Undergoing Peritoneal Dialysis.

    Farkas, Andras / Oikonomou, Katerina / Ghanbar, Mohammad / Villasurda, Phillip / Varghese, Julie / Lipman, Jeffrey / Sassine, Joseph / Ranganathan, Dwarakanathan / Roberts, Jason A

    Antimicrobial agents and chemotherapy

    2021  Volume 66, Issue 2, Page(s) e0167921

    Abstract: While the use of intraperitoneal (i.p.) gentamicin is common in the treatment of peritoneal dialysis (PD)-related infections, the ability of these regimens to attain pharmacodynamic target indices of interest in blood and dialysate has not been widely ... ...

    Abstract While the use of intraperitoneal (i.p.) gentamicin is common in the treatment of peritoneal dialysis (PD)-related infections, the ability of these regimens to attain pharmacodynamic target indices of interest in blood and dialysate has not been widely reported. Pharmacokinetic (PK) data were obtained and analyzed from a multiple-dose PK study of i.p. gentamicin with 24 patients who received the drug at 0.6 mg/kg dose of body weight. The probability of target attainment (PTA) for indices of treatment success (i.p. peak/MIC ratio > 10) and toxicity (plasma area under the concentration-time curve [AUC] < 120 mg·h/L) was determined for 0.3- to 1.2-mg/kg i.p. regimens every 24 h for dwell times of 2 to 6 h and for the duration of a 2-week course. In the peritoneum, successful PTA was achieved by all of the simulated regimens up to an MIC of 1 mg/L and by doses equal to or greater than 0.6 mg/kg up to the MIC of 2 mg/L. At the susceptibility breakpoint of 4 mg/L, only the highest dose of 1.2 mg/kg is likely to provide adequate PTA. The probability of achieving exposure below the threshold of 120 mg·h/L in the daily AUC in plasma seems acceptable for all regimens at or below 0.6 mg/kg. Based on the model we developed, a gentamicin dose of 0.6 mg/kg is sufficient to treat organisms with an MIC of ≤2 mg/L without the risk of significant systemic exposure. The 1.2-mg/kg dose necessary to reach the pharmacodynamic target for efficacy at the clinical breakpoint of 4 mg/L is likely to produce early toxic levels of exposure that are expected to be detrimental to the renal system.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Gentamicins/pharmacokinetics ; Gentamicins/therapeutic use ; Humans ; Peritoneal Dialysis/adverse effects ; Peritonitis/drug therapy ; Prospective Studies
    Chemical Substances Anti-Bacterial Agents ; Gentamicins
    Language English
    Publishing date 2021-12-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.01679-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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