Fibrotic phenotype of IgG4-related disease.

A prompt response to glucocorticoids is a clinical hallmark of IgG4-related disease. However, manifestations characterised by prominent tissue fibrosis on histological examination can be less responsive to glucocorticoid therapy than other types of IgG4-related disease. These manifestations include retroperitoneal fibrosis, fibrosing mediastinitis, Riedel thyroiditis, orbital pseudotumor, and hypertrophic pachymeningitis, among others. To explain this discrepancy, a preliminary distinction into proliferative and fibrotic phenotypes of IgG4-related disease has been proposed on the basis of clinical presentation, pathological features, and response to immunosuppressive therapy. Implications of this classification for patient management remain an important area of investigation. In this Series paper, we aim to dissect the pathophysiology of tissue fibrosis in IgG4-related disease and discuss how clinicians should approach the management of fibrotic manifestations of IgG4-related disease based on the most recent diagnostic and therapeutic developments.

Postoperative mediastinitis and sternal osteitis after cardiac surgery caused by Mycoplasma hominis: A case report.

BACKGROUND: Mediastinitis and sternal osteitis are critical complications in cardiac surgery. Cases of these complications caused by Mycoplasma hominis are extremely rare. CASE PRESENTATION: We present a case of mediastinitis and sternal osteitis caused by M. hominis infection following ascending aortic replacement surgery. Whole gene sequencing analysis suggested the genitourinary tract as the most likely source of this M. hominis infection. Successful infection control was achieved through a regimen of moxifloxacin treatment. Additionally, a notable correlation was observed between serum levels of interleukin-6 and M. hominis infection. CONCLUSIONS: The significance of M. hominis as a potential cause of postoperative infection in cardiac surgery is still not fully recognized. Special attention should be paid to patients with bacteriologically negative infections, as M. hominis should not be disregarded, despite its rarity.

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation.

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

Sclerosing mesenteritis following immune checkpoint inhibitor therapy.

PURPOSE: Sclerosing mesenteritis (SM), a fibroinflammatory process of the mesentery, can rarely occur after immune checkpoint inhibitor (ICI) therapy; however, its clinical significance and optimal management are unclear. We aimed to assess the characteristics and disease course of patients who developed SM following ICI therapy at a single tertiary cancer center. METHODS: We retrospectively identified 12 eligible adult cancer patients between 05/2011 and 05/2022. Patients' clinical data were evaluated and summarized. RESULTS: The median patient age was 71.5 years. The most common cancer types were gastrointestinal, hematologic, and skin. Eight patients (67%) received anti-PD-1/L1 monotherapy, 2 (17%) received anti-CTLA-4 monotherapy, and 2 (17%) received combination therapy. SM occurred after a median duration of 8.6 months from the first ICI dose. Most patients (75%) were asymptomatic on diagnosis. Three patients (25%) reported abdominal pain, nausea, and fever and received inpatient care and corticosteroid treatment with symptom resolution. No patients experienced SM recurrence after the completion of corticosteroids. Seven patients (58%) experienced resolution of SM on imaging. Seven patients (58%) resumed ICI therapy after the diagnosis of SM. CONCLUSIONS: SM represents an immune-related adverse event that may occur after initiation of ICI therapy. The clinical significance and optimal management of SM following ICI therapy remains uncertain. While most cases were asymptomatic and did not require active management or ICI termination, medical intervention was needed in select symptomatic cases. Further large-scale studies are needed to clarify the association of SM with ICI therapy.

Bacteremic necrotizing mediastinitis caused by community-associated clonal complex 398 methicillin-resistant Staphylococcus aureus in a baby aged 4 months.

Invasive community-associated methicillin-resistant Staphylococcus aureus (MRSA) diseases caused by clonal complex 398 MRSA without animal contact have become a new emerging threat. We report a case of bacteremic mediastinitis caused by a Panton-Valentine leukocidin-positive community-associated sequence type 1232 MRSA in a Taiwanese baby aged 4 months without animal contact.

Role of early extraction of odontogenic focus in deep neck infections

Background: Odontogenic deep neck infections remain a common condition that presents a challenging issue due to the complex involvement of the neck and adjacent structures and its potential life-threatening risk. Periapical infection of the second or third molar with spread to the submandibular and parapharyngeal spaces is the most commonly observed scenario. However, the time of dental extraction of the infection focus remains controversial. The aim of this study is to provide an overview of the epidemiology, clinical and radiological features, and management in patients diagnosed with ODNI and to identify the role of early dental extraction on patient outcomes and recovery. Material and methods: This retrospective study included patients over 18 years old with a diagnosis of ODNI who were admitted to the University Hospital "Dr Jose Eleuterio Gonzalez" from January 2017 to January 2022. ODNI diagnosis was based on clinical and radiological evidence of the disease supplemented by dental and maxillofacial evaluation for an odontogenic aetiology. Results: A total of 68 patients were included in the study. The patients' mean age was 40.96 ± 14.9. Diabetes mellitus was the most common comorbidity. The submandibular space was the most common deep neck space involved (n=59, 86.8%). Mediastinitis, marginal nerve injury and orocervical fistula were observed in 7.5% of patients, with no fatality in this series. A delay of >3 days for dental extraction of the involved tooth was associated with an increased rate of mediastinitis (n=3, 100%, p= 0.022), number of surgical interventions (1.45 ± 0.61, p= 0.006), ICU stay (n=8, 40%, p= 0.019), and ICU length of stay (0.85 ± 0.8, p= 0.001). Conclusions: Expedited management with surgical drainage and intravenous antibiotic treatment, along with early extraction of the involved tooth, is mandatory. (AU)

Role of early extraction of odontogenic focus in deep neck infections.

BACKGROUND: Odontogenic deep neck infections remain a common condition that presents a challenging issue due to the complex involvement of the neck and adjacent structures and its potential life-threatening risk. Periapical infection of the second or third molar with spread to the submandibular and parapharyngeal spaces is the most commonly observed scenario. However, the time of dental extraction of the infection focus remains controversial. The aim of this study is to provide an overview of the epidemiology, clinical and radiological features, and management in patients diagnosed with ODNI and to identify the role of early dental extraction on patient outcomes and recovery. MATERIAL AND METHODS: This retrospective study included patients over 18 years old with a diagnosis of ODNI who were admitted to the University Hospital "Dr Jose Eleuterio Gonzalez" from January 2017 to January 2022. ODNI diagnosis was based on clinical and radiological evidence of the disease supplemented by dental and maxillofacial evaluation for an odontogenic aetiology. RESULTS: A total of 68 patients were included in the study. The patients' mean age was 40.96 ± 14.9. Diabetes mellitus was the most common comorbidity. The submandibular space was the most common deep neck space involved (n=59, 86.8%). Mediastinitis, marginal nerve injury and orocervical fistula were observed in 7.5% of patients, with no fatality in this series. A delay of >3 days for dental extraction of the involved tooth was associated with an increased rate of mediastinitis (n=3, 100%, p= 0.022), number of surgical interventions (1.45 ± 0.61, p= 0.006), ICU stay (n=8, 40%, p= 0.019), and ICU length of stay (0.85 ± 0.8, p= 0.001). CONCLUSIONS: Expedited management with surgical drainage and intravenous antibiotic treatment, along with early extraction of the involved tooth, is mandatory.

Gram-negative bacteria as a cause of mediastinitis after cardiac surgery.

PURPOSE OF REVIEW: Poststernotomy mediastinitis (PSM) remains a serious infection and is significantly associated with high morbidity, short-term and long-term mortality. Gram-negative bacteria (GNB) are an underestimated cause of PSM, and there is little information on the risk factors, prevention, diagnosis and management of GNB PSM. RECENT FINDINGS: The pathogenesis of PSM is the result of a complex and multifactorial interplay between intraoperative wound contamination, host-related and surgical host factors but GNB are probably mostly translocated from other host site infections. GNB are frequent cause of PSM (18-38% of cases) and GNB PSM have shown to more frequently polymicrobial (20-44%). GNG PSM has shown to occur earlier than Gram-positive PSM. Early diagnosis is crucial to successful treatment. The management of PSM needs a combination of culture-directed antimicrobial therapy and an early extensive surgical debridement with either immediate or delayed closure of the sternal space. Antibiotic treatment choice and duration should be based on clinical evaluation, evolution of inflammatory markers, microbiological tests and imaging studies. Mortality has shown to be significantly higher with GNB PSM compared with other causes and the inappropriateness of initial antibiotic therapy may explain the worse outcome of GNB PSM. SUMMARY: GNB PSM is usually undervalued in the setting of PSM and have shown to be a frequent cause of inappropriate treatment with adverse prognostic potential. There is a need for efforts to improve knowledge to prevent and adequately treat GNB PSM.

A 51-Year-Old Man With a Large Posterior Mediastinal Mass.

CASE PRESENTATION: A 51-year-old White male never-smoker presented with intermittent cough and progressive dyspnea. His symptoms started after an exposure to bat guano while cleaning his attic approximately 9 months earlier. He has received several courses of antibiotic and corticosteroid for these symptoms, with short-term relief.

Clinical Features of Fibrosing Mediastinitis in Japanese Patients: Two Case Reports and a Literature Review.

Fibrosing mediastinitis (FM) is a rare fibroinflammatory disease of the mediastinum with an etiology and clinical features that vary by world region. The characteristics of FM in Japan are still unknown. We herein report two Japanese patients with FM who were treated with corticosteroids and responded well. We also reviewed the Japanese literature on PubMed® and summarized the characteristics of 27 Japanese FM patients, including our two patients. In Japan, the predominant cases were those without a specific cause, were diffusely distributed, and responded well to corticosteroid therapy.

Late outcome after surgical and topical treatment for Aspergillus mediastinitis after heart transplantation.

The 7-year long-term survival after Aspergillus fumigatus mediastinitis after heart transplantation, an uncommonly described condition, is herein reported. A 66-year-old male developed an infection with A. fumigatus covering the entire thoracic cavity with a fungal turf after orthotopic heart transplantation. Repeated surgical removal of infectious and necrotic tissue together with innovative topical treatment using voriconazole and chlorhexidine combined with systemic antifungal treatment, helped in controlling the infection. Definitive wound closure was achieved by standard sternal refixation and latissimus dorsi muscle flap plasty. Survival after A. fumigatus mediastinitis after heart transplantation was achieved with sequential debridement in combination with topical application of antifungal agents.

Fibrosing Mediastinitis Associated With Tuberculosis in Children.

Two children developed fibrosing mediastinitis following past tuberculosis disease. Both were microbiologically negative for tuberculosis at presentation. One was treated with steroids and supportive therapy, but developed active tuberculosis with complications. He ultimately succumbed to healthcare-associated infection. The other recovered with steroids, administered along with antituberculosis treatment.

Tuberculosis lymphadenopathy: A rare etiology of the superior vena cava syndrome.

Superior vena cava syndrome is the clinical expression of the obstruction of the superior vena cava reducing the blood flow. Malignant etiologies are the most common. Its management is multidisciplinary and despite the progress of endovascular procedures, conventional surgery retains its place in certain indications. Mediastinal fibrosis secondary to tuberculosis lymphadenopathy may be associated with superior vena cava syndrome. In the presence of symptomatic SVCS associated with extensive mediastinal fibrosis compressing the superior vena cava with sub occlusive thrombosis, conventional surgery remains a treatment option, with cavo-venous derivation by prosthetic bypass.

Nocardia beijingensis lung mass in an immunocompetent adult.

A 47-year-old man was referred for ongoing workup of an enlarging lung mass. Extensive workup of the mass had been unrevealing for several months until cultures grew Nocardia beijingensis He was successfully treated with trimethoprim/sulfamethoxazole and then doxycycline with near-complete resolution of the mass on follow-up. This case presents a rare species of N. beijingensis It highlights the importance of considering nocardiosis in immunocompetent adults and the challenge in initiating targeted treatment due to delayed culture results.

Eradication of Staphylococcus aureus Post-Sternotomy Mediastinitis Following the Implementation of Universal Preoperative Nasal Decontamination With Mupirocin: An Interrupted Time-Series Analysis.

BACKGROUND: Although presurgical nasal decontamination with mupirocin (NDM) has been advocated as a measure for preventing postsurgical mediastinitis (PSM) due to Staphylococcus aureus, this strategy is not universally recommended due to lack of robust supporting evidence. We aimed to evaluate the role of preoperative NDM in the annual incidence of S. aureus PSM at our institution. METHODS: An interrupted time-series analysis, with an autoregressive error model, was applied to our single-center cohort by comparing preintervention (1990-2003) and postintervention (2005-2018) periods. Logistic regression was performed to analyze risk factors for S. aureus PSM. RESULTS: 12 236 sternotomy procedures were analyzed (6370 [52.1%] and 5866 [47.9%] in the pre- and postintervention periods, respectively). The mean annual percentage adherence to NDM estimated over the postintervention period was 90.2%. Only 4 of 127 total cases of S. aureus PSM occurred during the 14-year postintervention period (0.68/1000 sternotomies vs 19.31/1000 in the preintervention period; P < .0001). Interrupted time-series analysis demonstrated a statistically significant annual reduction in S. aureus PSM of -9.85 cases per 1000 sternotomies (-13.17 to -6.5; P < .0001) in 2005, with a decreasing trend maintained over the following 5 years and an estimated relative reduction of 84.8% (95% confidence interval [CI], 89.25-74.09%). Chronic obstructive pulmonary disease was the single independent risk factor for S. aureus PSM (odds ratio, 3.7; 95% CI, 1.72-7.93) and was equally distributed in patients undergoing sternotomy during pre- or postintervention periods. CONCLUSIONS: Our experience suggests the implementation of preoperative NDM significantly reduces the incidence of S. aureus PSM.

Sequential antimicrobial therapy in mediastinitis after cardiac surgery: An observational study of 81 cases / Tratamiento antimicrobiano secuencial en mediastinitis poscirugía cardiaca: estudio observacional de 81 casos

INTRODUCTION: Mediastinitis is an infrequent but serious complication of cardiac surgery. Antimicrobial treatment guidelines are not well established. The aim was to describe the efficacy of sequential intravenous to oral therapy in selected post-surgical mediastinitis patients. METHODS: A retrospective observational study including cases of mediastinitis after cardiac surgery, defined according to CDC criteria, at a third-level university hospital between January 2002 and December 2016. Sequential antimicrobial therapy was proposed in clinically stable patients. Rates of cure, relapse, and hospital stay were compared between patients who received sequential intravenous to oral therapy and those who received therapy exclusively by the intravenous route. RESULTS: Eighty-one cases were included. Sequential intravenous to oral therapy was performed in 48 (59.3%) patients on median day 15. No differences in baseline characteristics or causal microorganisms were found between the two cohorts. The average duration of antibiotic therapy was 41.2 ± 10.09 days. The most commonly used drugs in sequential therapy were quinolones in 31 (64.6%) cases and rifampicin, always in association with another antibiotic, in 25 (52.1%). Hospital stay was shorter in the sequential therapy group (57.57 ± 34.03 vs. 84.35 ± 45.67; P = 0.007). Cure was achieved in 77 (92.8%) patients. Overall in-hospital mortality was less frequent in the group that received sequential therapy (2.1% vs. 15.2%; P = 0.039). There were no differences in relapse between the two cohorts (4.2% vs 9.1%; P = 0.366). CONCLUSION: Sequential antimicrobial treatment in selected patients with post-surgical mediastinitis may be as effective as exclusively intravenous treatment, reducing risks, hospital stay and associated costs

INTRODUCCIÓN: La mediastinitis es una complicación grave pero infrecuente de la cirugía cardiaca. Las pautas de tratamiento antimicrobiano no han sido bien definidas. El objetivo es describir la eficacia del tratamiento antimicrobiano secuencial, de intravenoso a oral, en pacientes seleccionados con mediastinitis. MÉTODO: Estudio observacional retrospectivo en el que se incluyeron los casos de mediastinitis relacionados con la cirugía cardiaca, según criterios del CDC, en un hospital universitario entre enero de 2002 y diciembre de 2016. Una vez estabilizados los pacientes, se propuso completar el tratamiento antimicrobiano de forma secuencial, pasando de la vía intravenosa a la oral. Se compararon las tasas de curación, las recidivas y la estancia hospitalaria entre los pacientes que recibieron ambos regímenes. RESULTADOS: Se incluyeron 81 casos. El tratamiento antimicrobiano secuencial se utilizó en 48 (59,3%) pacientes, en una media de 15 días. No se encontraron diferencias respecto a las características basales y microorganismos causales en ambos grupos. La duración media del tratamiento antibiótico fue de 41,2 ± 10,09 días. Los antimicrobianos más utilizados en el tratamiento secuencial fueron quinolonas en 31 (64,6%) y rifampicina, siempre asociada a otro antibiótico, en 25 (52,1%). La estancia hospitalaria fue menor en el grupo con tratamiento secuencial (57,57 ± 34,03 vs. 84,35 ± 45,67; p = 0,007). En conjunto, curaron 77 (92,8%) pacientes. La mortalidad hospitalaria fue inferior en el grupo tratado secuencialmente (2,1% vs. 15,2%; p = 0,039). No hubo diferencias en recidivas entre ambos grupos (4,2% vs 9,1%; p = 0,366). CONCLUSIÓN: El tratamiento antimicrobiano secuencial en pacientes con mediastinitis posquirúrgica seleccionados puede tener una eficacia similar al tratamiento exclusivamente intravenoso, permitiendo reducir riesgos y costes asociados

Spontaneous community-acquired PVL-producing Staphylococcus aureus mediastinitis in an immunocompetent adult - a case report.

BACKGROUND: Mediastinitis caused by hematogenous spread of an infection is rare. We report the first known case of community-acquired mediastinitis from hematogenous origin in an immunocompetent adult. This rare invasive infection was due to Panton-Valentine Leucocidin-producing (PVL+) methicillin-susceptible Staphylococcus aureus (MSSA). CASE PRESENTATION: A 22-year-old obese man without other medical history was hospitalized for febrile precordial chest pain. He reported a cutaneous back abscess 3 weeks before. CT-scan was consistent with mediastinitis and blood cultures grew for a PVL+ MSSA. Intravenous clindamycin (600 mg t.i.d) and cloxacillin (2 g q.i.d.), secondary changed for fosfomycin (4 g q.i.d.) because of a related toxidermia, was administered. Surgical drainage was performed and confirmed the presence of a mediastinal abscess associated with a fistula between the mediastinum and right pleural space. All local bacteriological samples also grew for PVL+ MSSA. In addition to clindamycin, intravenous fosfomycin was switched to trimethoprim-sulfamethoxazole after 4 weeks for a total of 10 weeks of antibiotics. CONCLUSIONS: We present the first community-acquired mediastinitis of hematogenous origin with PVL+ MSSA. Clinical evolution was favorable after surgical drainage and 10 weeks of antibiotics. The specific virulence of MSSA PVL+ strains played presumably a key role in this rare invasive clinical presentation.

Acute mediastinitis associated with tracheobronchial tuberculosis and aspergillosis: a case report and literature review.

Acute mediastinitis (AM) is a rare but life-threatening disease. Here, we report a case of AM secondary to endobronchial tuberculosis (EBTB) and pseudomembranous Aspergillus tracheobronchitis (PMATB) co-infection. EBTB was confirmed by tissue culture for Mycobacterium tuberculosis and GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) detection (simultaneous detection of M. tuberculosis and resistance to rifampin) using endobronchial biopsies; PMATB was confirmed by histopathology. Even with antibiotic treatment and systemic support treatment, the patient died of massive hemoptysis on day 10 after admission. When immunocompromised hosts have AM, especially with central airway involvement, EBTB and aspergillosis should be considered potential causes. Bronchoscopy is helpful for rapid diagnosis and administering precise treatment.

Superior vena cava stenting in IgG4-associated mediastinal fibrosis.

We report a rare case of IgG4-associated mediastinal fibrosis with complete superior vena cava (SVC) obstruction successfully managed by thrombolysis and stenting in a 33-year-old male. The patient presented with a mediastinal mass lesion with clinical findings of SVC obstruction. Surgical biopsy of the mediastinal mass lesion with histology and immunohistochemistry staining established the diagnosis of IgG4 associated mediastinal fibrosis. The patient was treated with a systemic steroid and rituximab, but despite treatment, SVC obstruction and thromboses persisted, surgical intervention was declined by the thoracic surgeon due to extensive mediastinal fibrosis and an expected poor outcome. Percutaneous SVC angioplasty, intravascular thrombolysis with tissue plasminogen activator and afterward stent placement was done by the interventional radiology service. This intervention is rare and possibly was lifesaving as it restored complete patency of the SVC. Our case is probably the first with IgG4 mediastinitis and SVC complete obstruction relieved by intravascular thrombolysis and SVC stent placement. It demonstrates that SVC stenting can relieve SVC obstruction in patients with a high risk of surgery either due to medical comorbidities or an expected high surgical risk like bleeding in the mediastinal fibrosis, which in our case of SVC obstruction was due to a nonoperable mediastinal tumor. SIMILAR CASES PUBLISHED: None to our knowledge.