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1.
Medicine (Baltimore). 2019 Sep;98(39):e17345. doi: 10.1097/MD.0000000000017345.

Laryngeal granuloma occurring after surgery for laryngeal cancer treated by surgical removal and immediate post-operative radiotherapy: A case report.

Author information

1
Department of Radiotherapy.
2
Department of Thoracic Oncology, Hubei Cancer Hospital, Wuhan, China.
3
Department of Otolaryngology, First Hospital of Jilin University, Changchun.

Abstract

RATIONAL:

Laryngeal granulomas are benign lesion that rarely occurs after surgery of laryngeal cancer. Until now there has not been standard treatment for it.

PATIENT CONCERN:

The patient was diagnosed with laryngeal neoplasm one and half a month ago. Endoscopic low-temperature plasma knife in the radical excision of left vocal cord was performed under the general anesthesia. Postoperative histopathological examination confirmed left vocal cord tumor was highly differentiated invasive squamous cell carcinoma (SCC). Then the patient suffered unexplained intermittent dyspnea which persisted nearly 1 month after the surgery. Laryngoscope examination showed granulation formation on the glottis.

DIAGNOSES:

The patient was diagnosed with laryngeal granuloma 1 month after the surgery of laryngeal cancer.

INTERVENTIONS:

The patient received resection of the laryngeal mass, and pathological examination confirmed the granuloma. Postoperative radiotherapy (RT) was performed within 24 hours after surgery.

OUTCOMES:

The patient was followed up for 3 years after surgery and the laryngeal granuloma and laryngeal cancer did not recur during follow-up. The symptoms of intermittent dyspnea disappeared and a satisfactory outcome was achieved.

LESSONS:

Usually for primary laryngeal granulomas, surgical treatment alone is not enough, because it is easy to relapse. RT within 24 hours after operation can significantly reduce the recurrence of laryngeal granuloma.

PMID:
31574876
PMCID:
PMC6775417
DOI:
10.1097/MD.0000000000017345
[Indexed for MEDLINE]
Free PMC Article
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2.
Otolaryngol Clin North Am. 2019 Aug;52(4):657-668. doi: 10.1016/j.otc.2019.03.010. Epub 2019 May 11.

Diagnosis and Treatment of Benign Pediatric Lesions.

Author information

1
Harvard Medical School, Tufts University School of Medicine, Massachusetts General Hospital, Center for Laryngeal Surgery & Voice Rehabilitation, One Bowdoin Sq, 11th Floor, Boston, MA 02114, USA.
2
Pediatric Otolaryngology, Connecticut Children's Medical Center, 282 Washington, 2L, Hartford, CT 06106, USA; Department of Otolaryngology-Head and Neck Surgery, University of Connecticut Medical School, Farmington, CT, USA.
3
Pediatric Otolaryngology, Connecticut Children's Medical Center, 282 Washington, 2L, Hartford, CT 06106, USA; Department of Otolaryngology-Head and Neck Surgery, University of Connecticut Medical School, Farmington, CT, USA. Electronic address: lnmurray@connecticutchildrens.org.

Abstract

Dysphonia is common in pediatrics and affects individuals from infancy through their teenage years. Pediatric dysphonia has a variable impact on children, ranging from no impact to a severe social barrier. Although most etiologies are benign, potentially life-threatening causes must be ruled out by direct examination of the larynx. The most common benign lesions of the larynx in pediatrics are vocal nodules, vocal fold polyps, cysts, granulomas, ectasias, sulcus vocalis, and vascular lesions, including hemangioma and postcricoid cushion. Treatment of benign vocal lesions should be tailored to the individual patient and the perceived impact.

KEYWORDS:

Dysphonia; Post-cricoid vascular cushion; Vocal fold cyst; Vocal fold granuloma; Vocal fold polyp; Vocal nodule

PMID:
31088693
DOI:
10.1016/j.otc.2019.03.010
[Indexed for MEDLINE]
Icon for Elsevier Science
3.
Otolaryngol Clin North Am. 2019 Aug;52(4):745-757. doi: 10.1016/j.otc.2019.03.017. Epub 2019 May 8.

Updated Medical and Surgical Treatment for Common Benign Laryngeal Lesions.

Author information

1
Rush Medical College, 600 S. Paulina Street, Suite 202, Chicago, IL 60612, USA.
2
Rush University Medical Center, 1611 West Harrison, Suite 550, Chicago, IL 60612, USA. Electronic address: Inna_husain@rush.edu.

Abstract

Benign laryngeal lesions are often the result of phonotraumatic forces on the vocal folds and thus classically are treated with a combination of voice therapy and phonomicrosurgical techniques to minimize inadvertent additional trauma. Newer management strategies expand on these techniques with the use of the pKTP laser as well as intralesional injections, both in the operating room and in the awake outpatient setting.

KEYWORDS:

Intralesional injection; Vocal fold cyst; Vocal fold nodules; Vocal fold polyp; Vocal process granuloma; pKTP laser

PMID:
31078305
DOI:
10.1016/j.otc.2019.03.017
[Indexed for MEDLINE]
Icon for Elsevier Science
4.
Aust Vet J. 2019 Mar;97(3):81-86. doi: 10.1111/avj.12784. Epub 2019 Feb 17.

Avian mycobacteriosis in captive brolgas (Antigone rubicunda).

Author information

1
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, 250 Princes Highway, Werribee, Victoria 3030, Australia.
2
City University of Hong Kong College of Veterinary Medicine and Life Sciences, Kowloon, Hong Kong.

Abstract

CASE SERIES:

Avian mycobacteriosis is a significant disease of a wide range of bird species worldwide. The most common causative agent, Mycobacterium avium, is reported to also infect a range of mammals, including humans. Of 11 brolgas (Antigone rubicunda) submitted to the University of Melbourne for postmortem examination over a 10-year period, 7 were diagnosed with mycobacteriosis. All were from a wildlife park and kept in permanent enclosures as part of a breeding program. Most of the brolgas with mycobacteriosis were in poor body condition and had widely disseminated granulomas throughout the body, especially within the liver, spleen and gastrointestinal tract. Respiratory tract involvement was common, with all disseminated cases having pulmonary or air sac granulomas. Rare to moderate numbers of acid-fast organisms were detected in granulomas by histological examination. Where examined by appropriate bacteriological examinations, M. avium complex was isolated from affected tissues.

CONCLUSION:

This case series is the first known report of mycobacteriosis in brolgas and highlights the pathological changes seen. The complications in maintaining an avian mycobacteriosis-free breeding program and in eradication of the disease from an enclosed wildlife environment are discussed.

KEYWORDS:

Mycobacterium avium; avian tuberculosis; brolgas

PMID:
30773616
DOI:
10.1111/avj.12784
[Indexed for MEDLINE]
Icon for Wiley
5.
Tuberculosis (Edinb). 2018 Dec;113:130-138. doi: 10.1016/j.tube.2018.10.003. Epub 2018 Oct 10.

A new model for chronic and reactivation tuberculosis: Infection with genetically attenuated Mycobacterium tuberculosis in mice with polar susceptibility.

Author information

1
Laboratory for Immunogenetics, Central Institute for Tuberculosis, Moscow, Russia.
2
Laboratory for Immunogenetics, Central Institute for Tuberculosis, Moscow, Russia; Department of Immunology, School of Biology, Moscow State University, Russia. Electronic address: alexapt0151@gmail.com.

Abstract

TB infection in mice develops relatively rapidly which interferes with experimental dissection of immune responses and lung pathology features that differ between genetically susceptible and resistant hosts. Earlier we have shown that the M. tuberculosis strain lacking four of five Rpf genes (ΔACDE) is seriously attenuated for growth in vivo. Using this strain, we assessed key parameters of lung pathology, immune and inflammatory responses in chronic and reactivation TB infections in highly susceptible I/St and more resistant B6 mice. ΔACDE mycobacteria progressively multiplied only in I/St lungs, whilst in B6 lung CFU counts decreased with time. Condensed TB foci apeared in B6 lungs at week 4 of infection, whilst in I/St their formation was delayed. At the late phase of infection, in I/St lungs TB foci fused resulting in extensive pneumonia, whereas in B6 lungs pathology was limited to condensed foci. Macrophage and neutrophil populations characteristically differed between I/St and B6 mice at early and late stages of infection: more neutrophils accumulated in I/St and more macrophages in B6 lungs. The expression level of chemokine genes involved in neutrophil influx was higher in I/St compared to B6 lungs. B6 lung cells produced more IFN-γ, IL-6 and IL-11 at the early and late phases of infection. Overall, using a new mouse model of slow TB progression, we demonstrate two important features of ineffective infection control underlined by shifts in lung inflammation: delay in early granuloma formation and fusion of granulomas resulting in consolidated pneumonia late in the infectious course.

KEYWORDS:

Chronic infection; Immune response; Inflammation; Lung pathology; Mycobacteria

PMID:
30514495
DOI:
10.1016/j.tube.2018.10.003
[Indexed for MEDLINE]
Icon for Elsevier Science
6.
Front Immunol. 2018 Oct 23;9:2417. doi: 10.3389/fimmu.2018.02417. eCollection 2018.

Human Monocytic Suppressive Cells Promote Replication of Mycobacterium tuberculosis and Alter Stability of in vitro Generated Granulomas.

Author information

1
Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
2
University of Medicine and Pharmacy Craiova, Human Genomics Laboratory, Craiova, Romania.
3
Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, SAMRC Centre for Tuberculosis Research, DST and NRF Centre of Excellence for Biomedical TB Research, Stellenbosch University, Tygerberg, South Africa.
4
Institute of Immunology, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut, Insel Riems, Germany.
5
Faculty of Mathematics and Natural Sciences, University of Greifswald, Greifswald, Germany.

Abstract

Tuberculosis (TB) has tremendous public health relevance. It most frequently affects the lung and is characterized by the development of unique tissue lesions, termed granulomas. These lesions encompass various immune populations, with macrophages being most extensively investigated. Myeloid derived suppressor cells (MDSCs) have been recently identified in TB patients, both in the circulation and at the site of infection, however their interactions with Mycobacterium tuberculosis (Mtb) and their impact on granulomas remain undefined. We generated human monocytic MDSCs and observed that their suppressive capacities are retained upon Mtb infection. We employed an in vitro granuloma model, which mimics human TB lesions to some extent, with the aim of analyzing the roles of MDSCs within granulomas. MDSCs altered the structure of and affected bacterial containment within granuloma-like structures. These effects were partly controlled through highly abundant secreted IL-10. Compared to macrophages, MDSCs activated primarily the NF-κB and MAPK pathways and the latter largely contributed to the release of IL-10 and replication of bacteria within in vitro generated granulomas. Moreover, MDSCs upregulated PD-L1 and suppressed proliferation of lymphocytes, albeit with negligible effects on Mtb replication. Further comprehensive characterization of MDSCs in TB will contribute to a better understanding of disease pathogenesis and facilitate the design of novel immune-based interventions for this deadly infection.

KEYWORDS:

IL-10; Mycobacterium tuberculosis; PD-L1; granuloma; myeloid-derived suppressor cells; tuberculosis

PMID:
30405617
PMCID:
PMC6205994
DOI:
10.3389/fimmu.2018.02417
[Indexed for MEDLINE]
Free PMC Article
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8.
J Immunol. 2018 Nov 1;201(9):2541-2548. doi: 10.4049/jimmunol.1800993.

The End of the Binary Era: Revisiting the Spectrum of Tuberculosis.

Author information

1
Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224; and.
2
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 joanne@pitt.edu.

Abstract

Human Mycobacterium tuberculosis infection was thought to result in either active symptomatic tuberculosis (TB) or latent asymptomatic infection. It is now clear that this binary classification is insufficient to describe the myriad of infection outcomes. In active TB, symptomatic disease can be mild to severe, with a range of lung and thoracic lymph node involvement or extrapulmonary manifestations. Most humans control the infection and develop latent TB infection, with differential risks of reactivation to active TB. However, some frequently exposed persons appear to be resistant to infection, whereas others may initially become infected yet subsequently eliminate all bacilli. The immunologic factors influencing these varied outcomes are still not clear, but likely involve a range of different responses. In this article, we review the data supporting the spectrum of M. tuberculosis infection in humans as well as data in nonhuman primates that allow dissection of the immune responses leading to the varied outcomes of infection.

PMID:
30348659
PMCID:
PMC6217958
DOI:
10.4049/jimmunol.1800993
[Indexed for MEDLINE]
Free PMC Article
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9.
Nanotoxicology. 2018 Nov;12(9):975-991. doi: 10.1080/17435390.2018.1502830. Epub 2018 Oct 14.

Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes.

Author information

1
a Department of Biological Sciences , North Carolina State University , Raleigh , NC , USA.
2
b College of Veterinary Medicine , North Carolina State University , Raleigh , NC , USA.
3
c National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
4
d National Institute for Occupational Safety and Health , Morgantown , WV , USA.

Abstract

The fiber-like shape of multi-walled carbon nanotubes (MWCNTs) is reminiscent of asbestos, suggesting they pose similar health hazards when inhaled, including pulmonary fibrosis and mesothelioma. Mice deficient in the tumor suppressor p53 are susceptible to carcinogenesis. However, the chronic pathologic effect of MWCNTs delivered to the lungs of p53 heterozygous (p53+/-) mice has not been investigated. We hypothesized that p53+/- mice would be susceptible to lung tumor development after exposure to either tangled (t-) or rod-like (r-) MWCNTs. Wild-type (p53+/+) or p53+/- mice were exposed to MWCNTs (1 mg/kg) via oropharyngeal aspiration weekly over four consecutive weeks and evaluated for cellular and pathologic outcomes 11-months post-initial exposure. No lung or pleural tumors were observed in p53+/+ or p53+/- mice exposed to either t- or rMWCNTs. In comparison to tMWCNTs, the rMWCNTs induced the formation of larger granulomas, a greater number of lymphoid aggregates and greater epithelial cell hyperplasia in terminal bronchioles in both p53+/- and p53+/+ mice. A constitutively larger area of CD45R+/CD3+ lymphoid tissue was observed in p53+/- mice compared to p53+/+ mice. Importantly, p53+/- mice had larger granulomas induced by rMWCNTs as compared to p53+/+ mice. These findings indicate that a combination of p53 deficiency and physicochemical characteristics including nanotube geometry are factors in susceptibility to MWCNT-induced lymphoid infiltration and granuloma formation.

KEYWORDS:

Caron nanotubes; cancer; granuloma; immunotoxicology; p53

PMID:
30317900
PMCID:
PMC6379105
DOI:
10.1080/17435390.2018.1502830
[Indexed for MEDLINE]
Free PMC Article
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10.
PLoS One. 2018 Sep 27;13(9):e0204495. doi: 10.1371/journal.pone.0204495. eCollection 2018.

Efficacy of pyrazinoic acid dry powder aerosols in resolving necrotic and non-necrotic granulomas in a guinea pig model of tuberculosis.

Author information

1
Department of Pathology and Laboratory Medicine and Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
2
Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
3
RTI International, Research Triangle Park, North Carolina, United States of America.
4
Department of Biostatistics and North Carolina Translational and Clinical Sciences Institute, University of North Carolina, Chapel Hill, North Carolina, United States of America.
5
Department of Chemistry, University at Albany, Albany, New York, United States of America.

Abstract

New therapeutic strategies are needed to treat drug resistant tuberculosis (TB) and to improve treatment for drug sensitive TB. Pyrazinamide (PZA) is a critical component of current first-line TB therapy. However, the rise in PZA-resistant TB cases jeopardizes the future utility of PZA. To address this problem, we used the guinea pig model of TB and tested the efficacy of an inhaled dry powder combination, referred to as Pyrazinoic acid/ester Dry Powder (PDP), which is comprised of pyrazinoic acid (POA), the active moiety of PZA, and pyrazinoic acid ester (PAE), which is a PZA analog. Both POA and PAE have the advantage of being able to act on PZA-resistant Mycobacterium tuberculosis. When used in combination with oral rifampicin (R), inhaled PDP had striking effects on tissue pathology. Effects were observed in lungs, the site of delivery, but also in the spleen and liver indicating both local and systemic effects of inhaled PDP. Tissue granulomas that harbor M. tuberculosis in a persistent state are a hallmark of TB and they pose a challenge for therapy. Compared to other treatments, which preferentially cleared non-necrotic granulomas, R+PDP reduced necrotic granulomas more effectively. The increased ability of R+PDP to act on more recalcitrant necrotic granulomas suggests a novel mechanism of action. The results presented in this report reveal the potential for developing therapies involving POA that are optimized to target necrotic as well as non-necrotic granulomas as a means of achieving more complete sterilization of M. tuberculosis bacilli and preventing disease relapse when therapy ends.

PMID:
30261007
PMCID:
PMC6160074
DOI:
10.1371/journal.pone.0204495
[Indexed for MEDLINE]
Free PMC Article
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11.
Front Immunol. 2018 Sep 12;9:2069. doi: 10.3389/fimmu.2018.02069. eCollection 2018.

The Synergistic Effects of the Glutathione Precursor, NAC and First-Line Antibiotics in the Granulomatous Response Against Mycobacterium tuberculosis.

Author information

1
Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, United States.
2
College of life Sciences, Hebei University, Baoding, China.
3
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United States.
4
Department of Biological Sciences, California State Polytechnic University, Pomona, CA, United States.
5
Department of Internal Medicine, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United States.
6
Department of Clinical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United States.
7
Public Health Research Institute (PHRI), New Jersey Medical School, Rutgers University, Newark, NJ, United States.

Abstract

Mycobacterium tuberculosis (M. tb), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing M. tb infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to eradicate, and limit the spread of M. tb through the conventional use of first-line antibiotics. Unfortunately, with the emergence of drug resistant and multi-drug resistant strains of M. tb the archetypical antibiotics no longer provide the same ascendancy as they once did. Furthermore, when administered, these first-line antibiotics commonly present severe complications and side effects. The biological antioxidant glutathione (GSH) however, has been demonstrated to have a profound mycobactericidal effect with no reported adverse consequences. Therefore, we examined if N-Acetyl Cysteine (NAC), the molecular precursor to GSH, when supplemented in combination with suboptimal levels of standalone first-line antibiotics would be sufficient to completely clear M. tb infection within in vitro derived granulomas from healthy subjects and individuals with type 2 diabetes (T2DM). Our results revealed that by virtue of immune modulation, the addition of NAC to subprime levels of isoniazid (INH) and rifampicin (RIF) was indeed capable of inducing complete clearance of M. tb among healthy individuals.

KEYWORDS:

Mycobacterium tuberculosis; antibiotics; antitubercular; cytokines; tuberculosis; type 2 diabetes

PMID:
30258443
PMCID:
PMC6144952
DOI:
10.3389/fimmu.2018.02069
[Indexed for MEDLINE]
Free PMC Article
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12.
Laryngoscope. 2019 Feb;129(2):441-447. doi: 10.1002/lary.27492. Epub 2018 Sep 12.

Granulomas of the membranous vocal fold after intubation and other airway instrumentation.

Author information

1
Sean Parker Institute for the Voice, Department of Otolaryngology-Head and Neck Surgery, Weill Cornell Medical College/New York-Presbyterian Hospital, New York, New York, U.S.A.
2
Department of Otolaryngology-Head and Neck Surgery, New York University Langone Medical Center, New York, New York, U.S.A.

Abstract

OBJECTIVES/HYPOTHESIS:

We describe the clinical features of granulomas of the membranous vocal fold secondary to endotracheal intubation, bronchoscopy or esophagogastroduodenoscopy.

STUDY DESIGN:

Retrospective case series.

METHODS:

Review of cases at a single tertiary institution with evaluation of patient demographic characteristics, time to presentation, time to treatment, and clinical outcomes.

RESULTS:

Thirteen adult patients were identified with postintervention granuloma of the membranous vocal fold. All patients were female, with a mean age of 60 years (range, 28-81 years). None noted hoarseness prior to the intervention, and all noted significant hoarseness postoperatively. Conservative treatment with proton pump inhibitors and vocal rest was initially implemented in all patients. Four cases resolved without further intervention. Nine underwent surgical management because of airway symptoms, failure to improve, or patient request. One patient had injury to the contralateral vocal fold upon intubation. None experienced recurrence. Five had complete recovery of voice postoperatively, four did not.

CONCLUSION:

Iatrogenic granulomas of the membranous vocal fold after intubation or other upper airway instrumentation are rare complications presenting in the early postprocedure period with worsening hoarseness. Initial conservative treatment may be sufficient to yield resolution, and surgical treatment is effective for those failing medical management. Permanent voice damage may result from the original injury.

LEVEL OF EVIDENCE:

4 Laryngoscope, 129:441-447, 2019.

KEYWORDS:

Laryngeal granuloma; intubation injury; laryngeal granulation; vocal fold injury; vocal fold scar

PMID:
30208219
DOI:
10.1002/lary.27492
[Indexed for MEDLINE]
Icon for Wiley
13.
ORL J Otorhinolaryngol Relat Spec. 2018;80(5-6):307-316. doi: 10.1159/000492976. Epub 2018 Sep 11.

Conservative Treatment versus Surgery for Laryngeal Contact Granuloma: A Prospective Study.

Chen M1,2, Chen J1,2, Yang Y1,2, Li CJ1,2, Wu HT1,2, Chen L3,4.

Author information

1
Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China.
2
Shanghai Key Clinical Disciplines of Otorhinolaryngology, Shanghai, China.
3
Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, Chinaeentchenglei@163.com.
4
Shanghai Key Clinical Disciplines of Otorhinolaryngology, Shanghai, Chinaeentchenglei@163.com.

Abstract

AIMS:

To confirm the efficacy of conservative treatment for laryngeal contact granuloma and identify factors influencing treatment outcome.

METHODS:

In this prospective study, patients with laryngeal contact granuloma were divided into a group receiving conservative treatment and a group undergoing surgery. Efficacy was assessed by analyzing the complete response after a 48-week follow-up. The association of treatment outcome with clinical factors was then evaluated.

RESULTS:

In total, 61 patients, 43 in the group receiving conservative treatment and 18 in the group undergoing surgery, were analyzed, and the complete response rate was 72.1% and 38.9%, respectively. Both univariate analysis and multivariate analysis revealed that treatment modality (p1 = 0.015, p2 = 0.043), voice abuse (p1 = 0.010, p2 = 0.010), and the size of the granuloma (p1 = 0.031, p2 = 0.020) were significantly associated with the complete response of laryngeal contact granuloma. Kaplan-Meier curves showed that alcohol consumption (p = 0.031), voice abuse (p < 0.001), and granuloma size (p = 0.025) were significantly related to the complete response of conservative treatment.

CONCLUSIONS:

This prospective study strengthens the argument for conservative treatment (instead of surgery) as the first choice for laryngeal contact granuloma. The results also suggest that voice abuse, alcohol consumption, and the size of the granuloma may predict treatment outcome.

KEYWORDS:

Conservative treatment; Laryngeal contact granuloma; Size; Surgery; Voice abuse

PMID:
30205367
DOI:
10.1159/000492976
[Indexed for MEDLINE]
Icon for S. Karger AG, Basel, Switzerland
14.
Int J STD AIDS. 2018 Dec;29(14):1451-1453. doi: 10.1177/0956462418787603. Epub 2018 Aug 16.

Nodular granulomatous Pneumocystis jiroveci pneumonia consequent to delayed immune reconstitution inflammatory syndrome.

Author information

1
1 Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, USA.
2
2 Division of Infectious Diseases, Eastern Virginia Medical School, Norfolk, VA, USA.

Abstract

Although Pneumocystis jiroveci pneumonia (PCP) is a frequent manifestation of acquired immune deficiency syndrome (AIDS), the granulomatous form is uncommon. Here, we present an unusual case of granulomatous PCP consequent to immune reconstitution inflammatory syndrome (IRIS) after highly active antiretroviral therapy. A 36-year-old woman with human immunodeficiency virus (HIV) presented with cough and dyspnea that were attributed to typical PCP associated with AIDS. She was successfully treated with antibiotic, steroid, and antiretroviral therapies. After six months, however, she presented with consolidating lung lesions caused by bronchial obstruction from PCP granulomatous disease. Although antibiotics were ineffective, the effectiveness of steroid therapy suggested a diagnosis of granulomatous IRIS caused by persistent PCP antigens. Physicians should strongly suspect PCP in HIV-positive patients with nodular lung lesions and must remain aware that these lesions, if immune in origin, might not respond to antimicrobial therapy.

KEYWORDS:

HIV; Pneumocystis jiroveci pneumonia; granulomatous Pneumocystis jiroveci pneumonia; immune reconstitution inflammatory syndrome; nodular Pneumocystis jiroveci pneumonia

PMID:
30114992
DOI:
10.1177/0956462418787603
[Indexed for MEDLINE]
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15.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Aug 5;31(15):1217-1220. doi: 10.13201/j.issn.1001-1781.2017.15.020.

[Current status of treatment of laryngeal contact granuloma].

[Article in Chinese]

Abstract

Laryngeal contact granuloma, also known as vocal cord granuloma, is the non-neoplastic inflammatory granulation tissue occurring in the vocal cord around. The cause is unclear, morbidity and cure rate is low, the recurrence rate is high, leading to a poor clinical treatment. But some symptoms of the sound disorder, pharyngeal foreign body sensation seriously affect the quality of life of patients, increase the psychological burden of patients. With the increasing awareness of the disease, the deepening of the research, there have been different treatment methods. This paper reviews the previous literatures, and summarizes LCG treatment for the status.

KEYWORDS:

laryngeal contact granuloma; therapy; vocal cord granuloma

[Indexed for MEDLINE]

Conflict of interest statement

The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

16.
BMC Pulm Med. 2018 May 22;18(1):77. doi: 10.1186/s12890-018-0654-0.

The first case of multiple pulmonary granulomas with amyloid deposition in a dental technician; a rare manifestation as an occupational lung disease.

Author information

1
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryou-machi, Aoba-ku, Sendai, 980-8574, Japan.
2
Department of Respiratory Medicine, Hiraka General Hospital, Yokote, Japan.
3
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryou-machi, Aoba-ku, Sendai, 980-8574, Japan. tnumakura@rm.med.tohoku.ac.jp.
4
Department of Respiratory Medicine, Hiraka General Hospital, Yokote, Japan. tnumakura@rm.med.tohoku.ac.jp.
5
Department of Respiratory Medicine, Nishi-Niigata Chuo National Hospital, Niigata, Japan.
6
Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
7
Department of Respiratory Medicine, Saitama Medical Center Jichi Medical University, Saitama, Japan.

Abstract

BACKGROUND:

Occupational lung diseases, such as pneumoconiosis, are one of the health problems of dental workers that have been receiving increasing interest. Pulmonary amyloidosis is a heterogenous group of diseases, and can be classified into primary (idiopathic) and secondary (associated with various inflammatory diseases, hereditary, or neoplastic). To date, the development of pulmonary amyloidosis in dental workers has not been reported.

CASE PRESENTATION:

A 58-year-old Japanese female presented with chest discomfort and low-grade fever that has persisted for 2 months. She was a dental technician but did not regularly wear a dust mask in the workplace. Chest X ray and computed tomography revealed multiple well-defined nodules in both lungs and fluorodeoxyglucose (FDG)-positron emission tomography revealed abnormal FDG uptake in the same lesions with a maximal standardized uptake value (SUV [max]) of 5.6. We next performed thoracoscopic partial resection of the lesions in the right upper and middle lobes. The histological examination of the specimens revealed granuloma formation with foreign body-type giant cells and amyloid deposition that was confirmed by Congo red staining and direct fast scarlet (DFS) staining that produce apple-green birefringence under crossed polarized light. Because there were no other causes underlying the pulmonary amyloidosis, we performed electron probe X-ray microanalysis (EPMA) of the specimens and the result showed silica deposition in the lesions. Based on these results, we finally diagnosed the patient with pulmonary granulomas with amyloid deposition caused by chronic silica exposure. Afterward, her symptoms were improved and the disease has not progressed for 2 years since proper measures against additional occupational exposure were implemented.

CONCLUSIONS:

Our case presented three important clinical insights: First, occupational exposure to silica in a dental workplace could be associated with the development of amyloid deposition in lung. Second, EPMA was useful to reveal the etiology of amyloid deposition in the lungs. Last, proper protection against silica is important to prevent further progression of the disease. In conclusion, our case suggested that occupational exposure to silica should be considered when amyloid deposition of unknown etiology is found in the lungs of working or retired adults.

KEYWORDS:

Amyloid deposition; Dental technician; Pulmonary granulomas; Silica

PMID:
29788999
PMCID:
PMC5964708
DOI:
10.1186/s12890-018-0654-0
[Indexed for MEDLINE]
Free PMC Article
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17.
Braz J Otorhinolaryngol. 2018 Nov - Dec;84(6):781-789. doi: 10.1016/j.bjorl.2018.03.003. Epub 2018 Apr 14.

Treatment of post-intubation laryngeal granulomas: systematic review and proportional meta-analysis.

Author information

1
Universidade Estadual Paulista (Unesp), Faculdade de Medicina de Botucatu, Departamento de Oftalmologia, Otorrinolaringologia e Cirurgia de Cabeça e Pescoço, Botucatu, SP, Brazil.
2
Universidade Estadual Paulista (Unesp), Faculdade de Medicina de Botucatu, Departamento de Oftalmologia, Otorrinolaringologia e Cirurgia de Cabeça e Pescoço, Botucatu, SP, Brazil. Electronic address: rmartins@fmb.unesp.br.
3
Universidade Estadual Paulista (Unesp), Faculdade de Medicina de Botucatu, Departamento de Cirurgia, Botucatu, SP, Brazil.
4
Universidade de São Paulo (USP), Departamento de Otorrinolaringologia, São Paulo, SP, Brazil.

Abstract

INTRODUCTION:

Laryngeal granulomas post intubation are benign but recurrent lesions. There is no consensus for its treatment.

OBJECTIVE:

To describe the effectiveness of different treatment modalities for primary or recurrent laryngeal granulomas resulting from endotracheal intubation.

METHODS:

Systematic review and proportional meta-analysis. Eligibility criteria - experimental or observational studies with at least five subjects. Outcomes studied - granuloma resolution, recurrence, and time for resolution. Databases used - Pubmed, Embase, Lilacs, and Cochrane. The Stats Direct 3.0.121 program was used.

RESULTS:

Six studies were selected, with 85 patients. The treatments registered were: antireflux therapy, speech therapy, anti-inflammatory drugs, steroids, antibiotics, zinc sulfate and surgery. 85 patients from six studies had primary treatment: surgery±associations (41 patients), resolution chance 75% (95% CI: 0.3-100%, I2=90%), absolute relapse risk 25% (95% CI: 0.2-71%); medical treatment (44 patients), resolution chance 86% (95% CI: 67-97%); and absolute relapse risk 14% (95% CI: 3-33%). There was no significant difference between groups. Three studies, encompassing 19 patients, analyzed secondary treatment (failure or recurrence after primary treatment); three subjects presented new recurrence. The time needed to resolve the lesions varied from immediate, after surgery, to 23 months, for inhaled steroid.

CONCLUSION:

There is no evidence of high quality that proves the efficacy of any treatment for laryngeal granulomas resulting from endotracheal intubation.

KEYWORDS:

Granulomas; Laringe; Larynx; Revisão sistemática; Systematic review; Tratamento; Treatment

PMID:
29699879
DOI:
10.1016/j.bjorl.2018.03.003
[Indexed for MEDLINE]
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18.
PLoS Pathog. 2018 Apr 26;14(4):e1006974. doi: 10.1371/journal.ppat.1006974. eCollection 2018 Apr.

Matrix metalloproteinase inhibitors enhance the efficacy of frontline drugs against Mycobacterium tuberculosis.

Author information

1
Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, United States of America.
2
Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, United States of America.
3
School of Electrical and Computer Engineering, Cornell University, Ithaca, NY, United States of America.
4
Department of Biomedical Engineering, Duke University, Durham, NC, United States of America.
5
Department of Microbiology and Immunology, Cornell University, Ithaca, NY, United States of America.
6
Department of Biomedical Sciences and Cornell Stem Cell Program, Cornell University, Ithaca, NY, United States of America.
7
Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Abstract

Mycobacterium tuberculosis (Mtb) remains a grave threat to world health with emerging drug resistant strains. One prominent feature of Mtb infection is the extensive reprogramming of host tissue at the site of infection. Here we report that inhibition of matrix metalloproteinase (MMP) activity by a panel of small molecule inhibitors enhances the in vivo potency of the frontline TB drugs isoniazid (INH) and rifampicin (RIF). Inhibition of MMP activity leads to an increase in pericyte-covered blood vessel numbers and appears to stabilize the integrity of the infected lung tissue. In treated mice, we observe an increased delivery and/or retention of frontline TB drugs in the infected lungs, resulting in enhanced drug efficacy. These findings indicate that targeting Mtb-induced host tissue remodeling can increase therapeutic efficacy and could enhance the effectiveness of current drug regimens.

PMID:
29698476
PMCID:
PMC5919409
DOI:
10.1371/journal.ppat.1006974
[Indexed for MEDLINE]
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19.
Cell Rep. 2018 Apr 24;23(4):1072-1084. doi: 10.1016/j.celrep.2018.03.125.

Multiplexed Quantitation of Intraphagocyte Mycobacterium tuberculosis Secreted Protein Effectors.

Author information

1
Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, CNRS UMR 3525, 25 rue du Dr. Roux, Paris 75015, France.
2
Institut Pasteur, Unit for Molecular Virology and Vaccinology, 28 rue du Dr. Roux, Paris 75015, France.
3
Université de Lille, CNRS UMR 8204, INSERM U1019, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille (CIIL), 1 rue du Professeur Calmette, 59000 Lille, France.
4
Institut Pasteur, Neonatal Immunity Group, Unit for Human Histopathology and Animal Models, 28 rue du Dr. Roux, Paris 75015, France.
5
Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, CNRS UMR 3525, 25 rue du Dr. Roux, Paris 75015, France; Sorbonne Universités, UPMC University of Paris 06, CIMI-Paris, AP-HP, Hôpital Pitié-Salpêtrière, CNR-MyRMA, Paris, France.
6
Sorbonne Universités, UPMC University of Paris 06, CIMI-Paris, AP-HP, Hôpital Pitié-Salpêtrière, CNR-MyRMA, Paris, France.
7
University of Pisa, Department of Biology, via S. Zeno 35-39, 56127 Pisa, Italy.
8
Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, CNRS UMR 3525, 25 rue du Dr. Roux, Paris 75015, France. Electronic address: laleh.majlessi@pasteur.fr.

Abstract

The pathogenic potential of Mycobacterium tuberculosis largely depends on ESX secretion systems exporting members of the multigenic Esx, Esp, and PE/PPE protein families. To study the secretion and regulation patterns of these proteins while circumventing immune cross-reactions due to their extensive sequence homologies, we developed an approach that relies on the recognition of their MHC class II epitopes by highly discriminative T cell receptors (TCRs) of a panel of T cell hybridomas. The latter were engineered so that each expresses a unique fluorescent reporter linked to specific antigen recognition. The resulting polychromatic and multiplexed imaging assay enabled us to measure the secretion of mycobacterial effectors inside infected host cells. We applied this novel technology to a large panel of mutants, clinical isolates, and host-cell types to explore the host-mycobacteria interplay and its impact on the intracellular bacterial secretome, which also revealed the unexpected capacity of phagocytes from lung granuloma to present mycobacterial antigens via MHC class II.

KEYWORDS:

T-cell hybridomas; bacterial antigen presentation; intracellular bacteria; in vivo antigen presentation; lentiviral vectors; mycobacterial virulence factors; mycobacterium tuberculosis; protein localization; reporter T cells; type VII secretion systems

PMID:
29694886
PMCID:
PMC5946722
DOI:
10.1016/j.celrep.2018.03.125
[Indexed for MEDLINE]
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20.
Tuberculosis (Edinb). 2018 Jan;108:201-210. doi: 10.1016/j.tube.2018.01.001. Epub 2018 Jan 8.

Use of a leukocyte-targeted peptide probe as a potential tracer for imaging the tuberculosis granuloma.

Author information

1
Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, 793 Biomedical Research Tower, 460 W. 12th Avenue, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: Landon.Locke@osumc.edu.
2
Department of Radiology, The Wright Center for Innovation in Biomedical Imaging, Martha Morehouse Medical Plaza, 2050 Kenny Road, The Ohio State University, Columbus, OH 43221, USA. Electronic address: Shankaran.Kothandaraman@osumc.edu.
3
Department of Radiology, The Wright Center for Innovation in Biomedical Imaging, Martha Morehouse Medical Plaza, 2050 Kenny Road, The Ohio State University, Columbus, OH 43221, USA. Electronic address: Michael.Tweedle@osumc.edu.
4
Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus, OH, USA.
5
Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, 793 Biomedical Research Tower, 460 W. 12th Avenue, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: Daniel.Wozniak@osumc.edu.
6
Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, 793 Biomedical Research Tower, 460 W. 12th Avenue, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, TX 78227, USA. Electronic address: LSchlesinger@txbiomed.org.

Abstract

Granulomas are the histopathologic hallmark of tuberculosis (TB), both in latency and active disease. Diagnostic and therapeutic strategies that specifically target granulomas have not been developed. Our objective is to develop a probe for imaging relevant immune cell populations infiltrating the granuloma. We report the binding specificity of Cyanine 3 (Cy3)-labeled cFLFLFK-PEG12 to human leukocytes and cellular constituents within a human in vitro granuloma model. We also report use of the probe in in vivo studies using a mouse model of lung granulomatous inflammation. We found that the probe preferentially binds human neutrophils and macrophages in human granuloma structures. Inhibition studies showed that peptide binding to human neutrophils is mediated by the receptor formyl peptide receptor 1 (FPR1). Imaging the distribution of intravenously administered cFLFLFK-PEG12-Cy3 in the mouse model revealed probe accumulation within granulomatous inflammatory responses in the lung. Further characterization revealed that the probe preferentially associated with neutrophils and cells of the monocyte/macrophage lineage. As there is no current clinical diagnostic imaging tool that specifically targets granulomas, the use of this probe in the context of latent and active TB may provide a unique advantage over current clinical imaging probes. We anticipate that utilizing a FPR1-targeted radiopharmaceutical analog of cFLFLFK in preclinical imaging studies may greatly contribute to our understanding of granuloma influx patterns and the biological roles and consequences of FPR1-expressing cells in contributing to disease pathogenesis.

KEYWORDS:

FPR1; Granuloma; Infection imaging; Mycobacterium tuberculosis; Peptide probe; Phagocytes

PMID:
29623875
PMCID:
PMC6014630
DOI:
10.1016/j.tube.2018.01.001
[Indexed for MEDLINE]
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