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Article ; Online: Hereditary Hemorrhagic Telangiectasia.

Parambil, Joseph G

2016 Volume 37, Issue 3, Page(s) 513–521

Abstract: Hereditary hemorrhagic telangiectasia (HHT) is an underrecognized and underdiagnosed autosomal-dominant angiodysplasia that has an estimated prevalence of 1 in 5000 individuals, with variable clinical presentations even within family members with ... ...

Abstract	Hereditary hemorrhagic telangiectasia (HHT) is an underrecognized and underdiagnosed autosomal-dominant angiodysplasia that has an estimated prevalence of 1 in 5000 individuals, with variable clinical presentations even within family members with identical mutations. The most common manifestations are telangiectasias of the skin and nasal mucosa. However, HHT can often be complicated by the presence of arteriovenous malformations and telangiectasias in the lungs, brain, gastrointestinal tract, and liver that are often silent and can lead to life-threatening complications of stroke and hemorrhage. This article reviews HHT for the pulmonologist, who is not uncommonly the first practitioner to encounter these patients.
MeSH term(s)	Arteriovenous Malformations/etiology ; Arteriovenous Malformations/physiopathology ; Brain Diseases/etiology ; Brain Diseases/physiopathology ; Family ; Gastrointestinal Diseases/etiology ; Gastrointestinal Diseases/physiopathology ; Gastrointestinal Hemorrhage/etiology ; Hemorrhage/etiology ; Humans ; Intracranial Arteriovenous Malformations/etiology ; Intracranial Arteriovenous Malformations/physiopathology ; Intracranial Hemorrhages/etiology ; Liver Diseases/etiology ; Liver Diseases/physiopathology ; Lung Diseases/etiology ; Lung Diseases/physiopathology ; Mutation ; Stroke/etiology ; Telangiectasia, Hereditary Hemorrhagic/complications ; Telangiectasia, Hereditary Hemorrhagic/physiopathology
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	447455-7
ISSN	1557-8216 ; 0272-5231
ISSN (online)	1557-8216
ISSN	0272-5231
DOI	10.1016/j.ccm.2016.04.013
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Article ; Online: Obliterative Bronchiolitis as a Systemic Manifestation of Cutaneous Lupus Erythematosus.

Deshwal, Himanshu / Valeria Arrossi, A / Parambil, Joseph G

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

2018 Volume 27, Issue 8S, Page(s) S595–S597

MeSH term(s)	Bronchiolitis Obliterans/diagnosis ; Bronchiolitis Obliterans/etiology ; Humans ; Lupus Erythematosus, Cutaneous/diagnosis ; Lupus Erythematosus, Discoid ; Lupus Erythematosus, Systemic
Language	English
Publishing date	2018-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1283266-2
ISSN	1536-7355 ; 1076-1608
ISSN (online)	1536-7355
ISSN	1076-1608
DOI	10.1097/RHU.0000000000000962
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Zs.A 4815: Show issues

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Article ; Online: Sclerotherapy Versus Cautery/Laser Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia.

Woodard, Troy D / Yappel-Sinkko, Kathleen B / Wang, Xiaofeng / McCrae, Keith R / Parambil, Joseph G

The Laryngoscope

2021 Volume 132, Issue 5, Page(s) 920–925

Abstract: Objectives/hypothesis: Surgical interventions for epistaxis management in hereditary hemorrhagic telangiectasia (HHT) demonstrate short-term success and require repeated procedures for disease control. Although electrocautery and/or laser ... ...

Abstract	Objectives/hypothesis: Surgical interventions for epistaxis management in hereditary hemorrhagic telangiectasia (HHT) demonstrate short-term success and require repeated procedures for disease control. Although electrocautery and/or laser photocoagulation (C ± L) are most frequently performed, sodium tetradecyl sclerotherapy (STS) is emerging as a promising newer treatment. We hypothesized that in a 24-month time period, STS would require fewer treatments than C ± L to maintain epistaxis severity within the mild range. Study design: Retrospective study. Methods: We retrospectively assessed 67 patients with HHT with moderate and severe epistaxis that were treated periodically with C ± L (34 patients) versus STS (33 patients). The primary outcome was the number of procedures needed to maintain the epistaxis severity score (ESS) as mild. Secondary outcomes assessed for differences in postoperative complications, hemoglobin levels, iron stores, hematologic support, and quality-of-life (QoL) scores. Results: To maintain ESS in the mild range, 1.6 STS procedures (range, 1-4) were performed versus 3.6 C ± L procedures (range, 1-8) (P = .003). Significant postoperative differences included reduction in nasal crusting (3% vs. 32%, P = .001), foul odor (3% vs. 35%, P < .001), and septal perforation (3% vs. 29%, P = .006) after STS. There were no significant differences between the two treatments in hemoglobin levels, iron stores, hematologic support, or QoL scores. Conclusion: STS is able to attain satisfactory epistaxis control with significantly fewer procedures and lower postoperative complications than C ± L. STS should be considered as the initial surgical intervention for epistaxis in patients with HHT. Level of evidence: 4 Laryngoscope, 132:920-925, 2022.
MeSH term(s)	Electrocoagulation/adverse effects ; Epistaxis/etiology ; Epistaxis/surgery ; Hemoglobins ; Humans ; Iron ; Lasers ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; Sclerotherapy/methods ; Telangiectasia, Hereditary Hemorrhagic/therapy
Chemical Substances	Hemoglobins ; Iron (E1UOL152H7)
Language	English
Publishing date	2021-06-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.29701
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Article ; Online: Pazopanib effective for bevacizumab-unresponsive epistaxis in hereditary hemorrhagic telangiectasia.

Parambil, Joseph G / Woodard, Troy D / Koc, Omer N

The Laryngoscope

2018 Volume 128, Issue 10, Page(s) 2234–2236

Abstract: Hereditary hemorrhagic telangiectasia (HHT) most commonly manifests with nasal mucosal telangiectasias, and vascular endothelial growth factor (VEGF) plays a significant role in this angiodysplasia. We describe a patient with HHT with epistaxis ... ...

Abstract	Hereditary hemorrhagic telangiectasia (HHT) most commonly manifests with nasal mucosal telangiectasias, and vascular endothelial growth factor (VEGF) plays a significant role in this angiodysplasia. We describe a patient with HHT with epistaxis recalcitrant to several endonasal procedures and six cycles of intravenous bevacizumab, for which he was dependent on iron infusions and packed red blood cells transfusions. He then started pazopanib at 100 mg with dramatic improvements in epistaxis and normalization of hemoglobin and iron levels, without replenishment needs for 12 months. This is the first report on the efficacy of pazopanib with high selectivity for abrogating VEGF receptor-2 signaling in HHT, and needs to be explored further. Laryngoscope, 128:2234-2236, 2018.
MeSH term(s)	Anemia, Iron-Deficiency/etiology ; Anemia, Iron-Deficiency/therapy ; Angiogenesis Inhibitors/therapeutic use ; Bevacizumab/therapeutic use ; Epistaxis/drug therapy ; Epistaxis/etiology ; Erythrocyte Transfusion/methods ; Hemoglobins/analysis ; Hemoglobins/drug effects ; Humans ; Male ; Middle Aged ; Pyrimidines/therapeutic use ; Sulfonamides/therapeutic use ; Telangiectasia, Hereditary Hemorrhagic/complications ; Telangiectasia, Hereditary Hemorrhagic/drug therapy
Chemical Substances	Angiogenesis Inhibitors ; Hemoglobins ; Pyrimidines ; Sulfonamides ; Bevacizumab (2S9ZZM9Q9V) ; pazopanib (7RN5DR86CK)
Language	English
Publishing date	2018-02-16
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.27129
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Article ; Online: Different efficacy of inhaled and oral medications in pulmonary hypertension.

AbuHalimeh, Batool J / Parambil, Joseph G / Tonelli, Adriano R

Heart & lung : the journal of critical care

2017 Volume 46, Issue 4, Page(s) 334–337

Abstract: Pulmonary arterial hypertension (PAH) is progressive disorder characterized by elevated pulmonary vascular resistance that can lead to right heart failure and death. One of the main therapeutic options for PAH are medications targeting the prostacyclin ... ...

Abstract	Pulmonary arterial hypertension (PAH) is progressive disorder characterized by elevated pulmonary vascular resistance that can lead to right heart failure and death. One of the main therapeutic options for PAH are medications targeting the prostacyclin pathway. Treprostinil is a prostacyclin analogue and selexipag is a selective IP receptor agonist. Treprostinil can be delivered by a variety of routes including oral, inhaled, subcutaneous and intravenous. Selexipag is currently approved as an oral formulation. The impact of the route of delivery and the optimal dosing for transitioning inhaled treprostinil to oral treprostinil or selexipag is unknown. More importantly, given the different selectivity for prostacyclin receptors, it is uncertain whether treprostinil and selexipag can be substituted. We present two patients with PAH who received medications targeting the prostacyclin pathway and were transitioned from inhaled treprostinil to either oral treprostinil or selexipag. In both cases, we noted clinical, functional and hemodynamic deterioration. These cases highlight that the route of delivery (inhaled versus oral) and/or the specific PH medication (treprostinil versus selexipag) matter; therefore close monitoring during transitions is imperative.
MeSH term(s)	Acetamides/administration & dosage ; Administration, Inhalation ; Administration, Oral ; Antihypertensive Agents/administration & dosage ; Blood Pressure/drug effects ; Epoprostenol/administration & dosage ; Epoprostenol/analogs & derivatives ; Epoprostenol/therapeutic use ; Female ; Humans ; Hypertension, Pulmonary/drug therapy ; Hypertension, Pulmonary/physiopathology ; Male ; Middle Aged ; Pyrazines/administration & dosage
Chemical Substances	Acetamides ; Antihypertensive Agents ; Pyrazines ; selexipag (5EXC0E384L) ; Epoprostenol (DCR9Z582X0) ; treprostinil (RUM6K67ESG)
Language	English
Publishing date	2017-07
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	193129-5
ISSN	1527-3288 ; 0147-9563
ISSN (online)	1527-3288
ISSN	0147-9563
DOI	10.1016/j.hrtlng.2017.04.010
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Article ; Online: Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

Mukhopadhyay, Sanjay / Parambil, Joseph G

Seminars in respiratory and critical care medicine

2012 Volume 33, Issue 5, Page(s) 476–485

Abstract: Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of ... ...

Abstract	Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF).
MeSH term(s)	Acute Disease ; Acute Lung Injury/diagnosis ; Acute Lung Injury/physiopathology ; Diagnosis, Differential ; Humans ; Lung Diseases, Interstitial/diagnosis ; Lung Diseases, Interstitial/physiopathology ; Pulmonary Alveoli/pathology ; Pulmonary Fibrosis/diagnosis ; Pulmonary Fibrosis/physiopathology ; Respiratory Distress Syndrome, Adult/diagnosis ; Respiratory Distress Syndrome, Adult/physiopathology
Language	English
Publishing date	2012-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1183617-9
ISSN	1098-9048 ; 1069-3424
ISSN (online)	1098-9048
ISSN	1069-3424
DOI	10.1055/s-0032-1325158
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Zs.A 1555: Show issues

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Article ; Online: Prospective cohort of cryobiopsy in interstitial lung diseases: a single center experience.

Ribeiro Neto, Manuel L / Arrossi, Andrea Valeria / Yadav, Ruchi / Culver, Daniel A / Mukhopadhyay, Sanjay / Parambil, Joseph G / Southern, Brian D / Tolle, Leslie / Pande, Aman / Almeida, Francisco A / Sahoo, Debasis / Glennie, Jessica / Ahmad, Usman / Mehta, Atul C / Gildea, Thomas R

BMC pulmonary medicine

2022 Volume 22, Issue 1, Page(s) 215

Abstract: Rationale: Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to ... ...

Abstract	Rationale: Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. Objectives: To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. Methods: This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. Measurements and main results: Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004). Conclusions: Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.
MeSH term(s)	Biopsy/adverse effects ; Hemorrhage/etiology ; Humans ; Lung Diseases, Interstitial/complications ; Prospective Studies ; Surgical Instruments/adverse effects
Language	English
Publishing date	2022-06-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2059871-3
ISSN	1471-2466 ; 1471-2466
ISSN (online)	1471-2466
ISSN	1471-2466
DOI	10.1186/s12890-022-01990-4
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Article ; Online: Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia.

Parambil, Joseph G / Gossage, James R / McCrae, Keith R / Woodard, Troy D / Menon, K V Narayanan / Timmerman, Kasi L / Pederson, Douglas P / Sprecher, Dennis L / Al-Samkari, Hanny

Angiogenesis

2021 Volume 25, Issue 1, Page(s) 87–97

Abstract: ... Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 ... g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4.77 (3.11-6.44) points (7.20 vs. 2 ...

Abstract	Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25-300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4.77 (3.11-6.44) points (7.20 vs. 2.43 points, P < 0.0001) after 12 months of treatment. Compared with 3 months of pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P < 0.0001) and elemental iron infusion decreased by 92% (median of 4500 vs. 0 mg, P = 0.005) during the first 3 months of treatment; improvements were maintained over time. Pazopanib was well-tolerated: hypertension, lymphocytopenia, and fatigue were the most common TEAEs. In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patients from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial.
MeSH term(s)	Anemia/drug therapy ; Anemia/etiology ; Epistaxis/drug therapy ; Epistaxis/etiology ; Humans ; Indazoles ; Pyrimidines ; Retrospective Studies ; Sulfonamides ; Telangiectasia, Hereditary Hemorrhagic/complications ; Telangiectasia, Hereditary Hemorrhagic/drug therapy
Chemical Substances	Indazoles ; Pyrimidines ; Sulfonamides ; pazopanib (7RN5DR86CK)
Language	English
Publishing date	2021-07-22
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1484717-6
ISSN	1573-7209 ; 0969-6970
ISSN (online)	1573-7209
ISSN	0969-6970
DOI	10.1007/s10456-021-09807-4
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Article: Acute Interstitial Pneumonia (AIP): Relationship to Hamman-Rich Syndrome, Diffuse Alveolar Damage (DAD), and Acute Respiratory Distress Syndrome (ARDS)

Mukhopadhyay, Sanjay / Parambil, Joseph G.

Seminars in Respiratory and Critical Care Medicine

(Orphan Lung Diseases)

2012 Volume 33, Issue 05, Page(s) 476–485

Series title	Orphan Lung Diseases
Abstract	Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from “acute exacerbation of IPF,” a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF).
Keywords	acute interstitial pneumonia ; acute lung injury ; acute respiratory distress syndrome ; diffuse alveolar damage
Language	English
Publishing date	2012-09-21
Publisher	Thieme Medical Publishers
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-0032-1325158
Database	Thieme publisher's database

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Article ; Online: Performance of diagnostic criteria in patients clinically judged to have cardiac sarcoidosis: Is it time to regroup?

Ribeiro Neto, Manuel L / Jellis, Christine / Hachamovitch, Rory / Wimer, Allison / Highland, Kristin B / Sahoo, Debasis / Khabbaza, Joseph E / Pande, Aman / Bindra, Akhil / Southern, Brian D / Parambil, Joseph G / Callahan, Thomas D / Joyce, Emer / Culver, Daniel A

American heart journal

2020 Volume 223, Page(s) 106–109

Abstract: Background: The diagnosis of cardiac sarcoidosis (CS) is challenging. Because of the current limitations of endomyocardial biopsy as a reference standard, physicians rely on advanced cardiac imaging, multidisciplinary evaluation, and diagnostic criteria ...

Abstract	Background: The diagnosis of cardiac sarcoidosis (CS) is challenging. Because of the current limitations of endomyocardial biopsy as a reference standard, physicians rely on advanced cardiac imaging, multidisciplinary evaluation, and diagnostic criteria to diagnose CS. Aims: To compare the 3 main available diagnostic criteria in patients clinically judged to have CS. Methods: We prospectively included patients clinically judged to have CS by a multidisciplinary sarcoidosis team from November 2016 to October 2017. We included only incident cases (diagnosis of CS within 1 year of inclusion). We applied retrospectively the following diagnostic criteria: the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), the Heart Rhythm Society (HRS), and the Japanese Circulation Society (JCS) 2016 criteria. Results: We identified 69 patients. Diagnostic criteria classified patients as follows: WASOG as highly probable (1.4%), probable (52.2%), possible (0%), some criteria (40.6%), and no criteria (5.8%); HRS as histological diagnosis (1.4%), probable (52.2%), some criteria (40.6%), and no criteria (5.8%); JCS as histological diagnosis (1.4%), clinical diagnosis (58%), some criteria (39.1%), and no criteria (1.4%). Concordance was high between WASOG and HRS (κ = 1) but low between JCS and the others (κ = 0.326). Conclusions: A high proportion of patients clinically judged to have CS are unable to be classified according to the 3 main diagnostic criteria. There is low concordance between JCS criteria and the other 2 criteria (WASOG and HRS).
MeSH term(s)	Adult ; Cardiomyopathies/diagnosis ; Diagnostic Techniques, Cardiovascular ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sarcoidosis/diagnosis
Language	English
Publishing date	2020-02-08
Publishing country	United States
Document type	Comparative Study ; Letter
ZDB-ID	80026-0
ISSN	1097-6744 ; 0002-8703
ISSN (online)	1097-6744
ISSN	0002-8703
DOI	10.1016/j.ahj.2020.02.008
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