An unexpected diagnosis: Good's syndrome

Case report Introduction: Good's syndrome (GS) represents an acquired adult-onset immunodeficiency associated with thymoma. GS affects patients over 40 yrs in form of recurrent infections especially with encapsulated bacteria, opportunistic viral and fungal invasions as a result of combined T/B cell deficiency. The imbalanced immunity may also provoke autoimmune phenomena and tumorigenesis. Case report: We present a 40-year- old male with a newly onset of dull thoracic pain and with no history of previous diseases. Chest CT revealed an anterior mediastinal mass in 2021, without lympadenopathy. A CT-guided core biopsy was suggestive for malignant thymoma, so the patient underwent total thymectomy. Histology indicated a thymoma of the AB type (WHO), and stage I. (Masaoka-Koga);(pT1a pNo). After surgery he was readmitted due to recurrent febrile respiratory tract infections, caused by Gram (-) bacteria or fungi;combination therapy of antibiotics and antifungal drugs was used. With suspicion of GS we determined immunoglobulin levels and the distribution of peripheral lymphocyte subsets. Hypogammaglobulinemia (IgG/A/M), and by flow cytometry markedly reduced peripheral B cells, and an inverse ratio of CD4+/CD8+ T cells were detected, confirming the diagnosis. Blast transformation assay indicated decreased T cell proliferation. Thus, following thymectomy, the patient exhibited severe T/B cell alterations with subsequent recurrent infections. Detailed autoantibody and complement analyses indicated no autoimmune laboratory abnormalities so far. There are still no effective protocols for GS therapy, except of antibiotic prophylaxis, preventive vaccination, and regular immunoglobulin replacement, so IVIG was introduced. As part of the follow-up repeated CT indicated no thymoma recurrence or metastasis. In December 2021 the vaccination refusing patient survived a severe bilateral organizing pneumonia secondary to SARS-CoV2. Conclusion(s): Incidence of the thymic epithelial tumor, thymoma is 0.15-0.33 cases/100.000/year. Depending on histology it could be linked to various immunological abnormalities. Appr. 0.2%-6% of thymomas corresponds to GS. GS, with a still elusive pathogenesis is considered as an uncommon combined immunodeficiency of adults with a variable phenotype and certain similarities to CVID. The prevalence is estimated appr. as 1/500.000. Combination of the high infection susceptibility and concomitant autoimmune diseases could make the diagnosis a challenging task.

COMMON PRESENTATION WITH AN UNCOMMON ETIOLOGY: THYMOMA-ASSOCIATED AUTOIMMUNE ENCEPHALITIS INDUCED BY COVID-19 BOOSTER VACCINE

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Thymoma-associated autoimmune encephalitis (TAAE) is an understudied and overlooked diagnosis in patients presenting with abrupt altered mental status. Described as inflammation of brain tissue, autoimmune encephalitis is seen in 5-10 cases per 100,000 across all age groups per year. A rare subtype involves neuronal surface antibodies to alpha-amino-3-hydroxyl-5-methyl-4isoxazolepropionic acid receptors (AMPA-R) encephalitis is seen even less commonly. Given the "unicorn” nature of presenting cases and difficulty of diagnosis, prompt identification and treatment are critical as prolonged courses without treatment are irreversible and deadly. CASE PRESENTATION: A 47-year-old male with no past medical history presented 3 days after a Johnson & Johnson coronavirus-2019 (COVID-19) booster vaccine due to worsening acute altered mental status over the past week. He complained of episodes of fever & chills prior to this. The patient's wife reported abrupt changes in memory and personality. Upon admission, the patient had a Glasgow Coma Scale of 4. The patient was intubated and transferred to the intensive care unit. Intravenous (IV) vancomycin, ceftriaxone and acyclovir was initiated for meningitis. Computed tomography (CT) scan of the head without contrast was unremarkable. Magnetic resonance imaging (MRI) showed enhancements of the right anterior and medial temporal lobe suggesting encephalitis. Cerebrospinal fluid analysis (CSF) revealed lymphocytic pleocytosis. A CT scan of the chest, abdomen and pelvis showed an anterior mediastinal mass measured 1.8 x 2.3 cm (Figure 1). FilmArray Meningitis polymerase chain reaction was negative as well as Herpes Simplex Virus (HSV) 1 and 2. Autoimmune encephalitis antibody was positive for Anti-AMPAR. Pulse dose steroids and intravenous immunoglobulin were initiated but failed. Rituximab was initiated and cardiothoracic surgery completed a thymectomy. DISCUSSION: TAAE is a rare disease, permanently debilitating, and deadly if unrecognized or treatment is delayed. Autoimmune encephalitis is an umbrella disease process seen in 0.00005% of patients per year. AMPA-R positive encephalitis is even less commonly seen with only 22 cases reported between the years 2009 and 2014 [1]. A rapidly progressive cognitive decline or psychiatric disorders are early features of this disease.Our patient had prodromal symptoms of fever and cognitive decline days after receiving his COVID-19 booster vaccine. CONCLUSIONS: Post-vaccine encephalomyelitis has been described in other settings[2]. This patient was free of symptoms prior to the COVID-19 vaccine booster, and demonstrated altered mental status hours after receiving it. This furthers the possibility of an association of the COVID-19 booster vaccine, development of encephalitis, and in this case a thymoma. Despite this, conclusions can not be made on the account of one report, but introduces a new area of focus to study. Reference #1: Höftberger, R., van Sonderen, A., Leypoldt, F., Houghton, D., Geschwind, M., Gelfand, J., Paredes, M., Sabater, L., Saiz, A., Titulaer, M. J., Graus, F., & Dalmau, J. (2015). Encephalitis and AMPA receptor antibodies: Novel findings in a case series of 22 patients. Neurology, 84(24), 2403–2412. https://doi.org/10.1212/WNL.0000000000001682 Reference #2: Huynh, W., Cordato, D. J., Kehdi, E., Masters, L. T., & Dedousis, C. (2008). Post-vaccination encephalomyelitis: literature review and illustrative case. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 15(12), 1315–1322. https://doi.org/10.1016/j.jocn.2008.05.002 DISCLOSURES: No relevant relationships by Matthew Frank No relevant relationships by Justin Ilagan No relevant relationships by Danielle Mahon No relevant relationships by Danielle Mahon No relevant relationships by Harshini Sahani No relevant relationships by Kameron Tavakolian No relevant relationship by Ndausung Udongwo

PROGRESSIVE ASCENDING WEAKNESS AFTER THE PFIZER/BIONTECH COVID-19 VACCINE

SESSION TITLE: Autoimmune Disorders: Both Primary and Secondary SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Myasthenia gravis (MG) occurs sporadically with no known causes. We present a rare case of new onset MG s/p COVID-19 vaccination. CASE PRESENTATION: A healthy 46-year-old female presented with progressing LE weakness for 3 months. Symptoms started 5 days after her initial Pfizer COVID-19 vaccine. Her workup showed negative neuroimaging, bland basic CSF studies from LP, with negative MS profile and AChR Ab. She presented again in 1 month with difficulty rising from a seated position, raising her arms above her head with blurry vision. Exam showed bilateral ptosis that improved with an ice pack test, weakness is worst in proximal muscles, but normal reflexes. Workup was again negative. Pyridostigmine was added after discharge (DC). 2 months after, she was admitted to the ICU for acute progressive fatiguability and dyspnea. EMG/NCS of the ulnar nerve showed 60-70% electrical decrement. She underwent therapeutic PLEX. Prednisone was added at DC followed by mycophenolate. 2 weeks later, she was again admitted with myasthenic crisis. She again underwent PLEX with improvement and intubation was avoided. Biweekly PLEX was started at DC. Testing for AChR, MuSK, and LRP4 Abs were initially negative, but AChR Abs were present 6 months later. She then underwent thymectomy showing hyperplasia. DISCUSSION: MG exacerbations have been attributable to infections (50%) and medications (30%). This has worsened during the COVID-19 pandemic especially when medications such as azithromycin were used to treat acute infections. While vaccine-induced flares or onset of autoimmune diseases have been described in literatures, new onset MG following vaccines is rare, limited to 1 to 3 case reports. No case, to our knowledge, correlated to the 1st dose like our patient. The temporal relationship between the COVID-19 vaccination and onset of MG symptoms in our patient could represent a correlation, but does not prove causality. Perhaps a more plausible theory is that the vaccine may have unmasked a previously unrecognized disease in high-risk patient. We ask if the COVID vaccine induces a similar cytokine storm, which hyperstimulates the immune system to a point that breaks immunologic self-tolerance. Interestingly, our patient was initially seronegative, but the presence of AChR Ab was confirmed after sensitive cell-based assays testing. Our patient may have had pre-existing self-antigens to the AChR that were released after receiving the Pfizer COVID-19 vaccine. CONCLUSIONS: The rate of COVID-19 vaccinations will soon surpass that of infections placing vulnerable individuals at risk for MG onset. Recognizing this risk will open discussions about vaccine safety. In doing so, we can begin to formulate new parameters for post-vaccination monitoring. The risks of and complications from acute COVID-19 still outweigh the rare adverse events from vaccines;thus, eligible patients should be offered the COVID-19 vaccine. Reference #1: Guidon AC, Amato AA. COVID-19 and neuromuscular disorders. Neurology. 2020 Jun 2;94(22):959-969. doi: 10.1212/WNL.0000000000009566. Epub 2020 Apr 13. PMID: 32284362. Reference #2: Tagliaferri AR, Narvaneni S, Azzam MH, Grist W. A Case of COVID-19 Vaccine Causing a Myasthenia Gravis Crisis. Cureus. 2021;13(6):e15581. Published 2021 Jun 10. doi:10.7759/cureus.15581 Reference #3: Chavez A, Pougnier C. A Case of COVID-19 Vaccine Associated New Diagnosis Myasthenia Gravis. Journal of Primary Care & Community Health. January 2021. doi:10.1177/21501327211051933 DISCLOSURES: No relevant relationships by andrew bui No relevant relationships by Sharonya Shrivastava

Immunosuppressive Therapy as Risk Factor for Severe SARS-CoV-2 Infection in Myasthenia Gravis

Importance: Patients with myasthenia gravis (MG) and IST are potentially at increased risk for poor COVID-19 outcome. Objective: To determine whether immunosuppressive therapy (IST) compared to no IST is associated with a higher risk for, first, a symptomatic SARS-CoV-2 infection and, second, a more severe COVID-19 disease course as measured by hospitalization rate and death. Design, setting, and participants: The present study included all available MG patients from the German myasthenia gravis registry, which is a nationwide registry conducted by expert centers since February 2019 (German Clinical Trials Registry DRKS-ID 00024099). Main outcomes and measures: Between May 2020 and June 2021, data were collected on demographics, disease duration, comorbidities, preexistent IST including standard (corticosteroids, azathioprine, mycophenolate mofetil, methotrexate, cyclosporine) and escalation (rituximab, eculizumab) IST, thymectomy, COVID-19 characteristics, and outcomes. COVID-19 was diagnosed with a nasopharyngeal swab by polymerase-chain-reaction. Multiple binary logistic regression models and generalized estimation equation regression models based on matched SARS-CoV-2 infected to non-infected patients were used to estimate the association of IST with SARS-CoV-2 infection. Multiple binary logistic regression models were used to assess the association of IST with outcome of COVID-19 in MG patients. Results: Of 1388 MG patients, 95 (7%) MG patients with a mean age of 58 (SD 18) and median disease duration of 65 months (IQR 27-126) presented with COVID-19. Among them, 39 patients (41%) were male, and 76 (80%) received IST at the time of infection. There were 32 patients (34%) admitted to hospital due to COVID-19, 12 (13%) to the intensive care unit, and a total of 11 patients (12%) died. IST was a risk factor for hospitalization and death in the group of COVID-19 affected MG patients (adjusted odds ratio [OR] 3.04, 95% confi- dence interval [CI] = 1.02-9.06, p=0.046), but not for symptomatic SARS-CoV-2 infection itself in the whole group of MG patients. Conclusions and relevance: In MG patients, preexistent IST was a factor for a severe disease course of COVID-19 but not for the risk for SARS-CoV-2 infection. These data support the consequent implementation of effective strategies to prevent COVID- 19 in this high-risk group.

Myasthenic Crisis

Myasthenia gravis (MG) is an acquired autoimmune disorder of the neuromuscular junction, caused by antibodies that target the post-synaptic membrane. These antibodies most commonly bind to the nicotinic acetylcholine receptor (AChR), but in a smaller proportion of cases, antibodies to muscle specific tyrosine kinase (MuSK)(1-10%) or to lipoprotein receptor-related protein 4 (Lrp-4)(1-3%) can be present instead. These antibodies act on the receptors, prevent neuromuscular transmission and induce weakness of skeletal muscles. In 10-15% of MG patients, no antibodies are detected and these patients are designated as seronegative. Weakness can be generalized or localized, is usually more proximal than distal, and nearly always includes eye muscles, causing diplopia and/or ptosis. The pattern of involvement is usually symmetric, except for the eye involvement, which is mostly markedly asymmetric. The muscle weakness typically increases with exercise and repetitive muscle use (fatigue) and varies over the course of a day and from day to day. Patients commonly present first with ocular manifestations, however, the majority develop generalized muscle weakness, involving the facial and bulbar muscles (dysarthria, dysphagia), the limbs, the neck and axial muscles (dropped head, bent spine), and in severe cases the diaphragmatic and intercostal muscles. MuSK-MG predominantly appears in women, who show weakness in mostly cranial and bulbar muscles, commonly with an acute onset and a tendency to rapid progression in comparison to AchRMG. Myasthenic crisis (MC), the severe end of the disease spectrum, can occur at any age and is potentially life-threatening. This is a clinical emergency that requires management in an intensive care setting. MC is mostly provoked by infections or inadequate treatment. In 15-40% of the reported patients with COVID-19 infection a MC occurred. MC appears in around 15-20% of MG patients in the first 2 years after diagnosis. MC can be the first manifestation of MG. Up to a half of MuSK-MG patients develop a MC in their disease course and it is also common in patients with thymoma-associated disease, or AChR-positive late-onset disease;after surgery (including thymectomy);during or after childbirth;in patients taking a contraindicated medication;at the start of corticosteroid treatment or during the tapering of immunosuppression. In approximately 20% the cause of an exacerbation remains unknown. Characteristic symptoms for the impending MC include rapidly progressive muscle weakness, 'inverse aspiration', dysphagia with choking, and dyspnoea associated with orthopnoea and/or tachypnoea which can result in respiratory insufficiency. The clinical management of MC with mechanical ventilation, extended intensive care management and intravenous immunoglobulins (IVIg) or plasmapheresis (PLEX) or in case of persistent MC escalation with rituximab has led to a significant decline in mortality from around 40% in the early 1960s to 5-22% in recent studies with negative prognostic factors including older age at onset, prolonged intubation, and associated comorbidities. At present IVIg and PLEX are considered the gold standard treating MC. However, it may be conceiv- able that newly developed monoclonal antibody therapy (eculizumab, efgartigimod), could be used as rescue therapy to achieve a significant and rapid clinical improvement.

Anesthetic Management during Robotic-Assisted Minimal Invasive Thymectomy Using the Da Vinci System: A Single Center Experience.

BACKGROUND: Robotic-assisted surgery is gaining more adaption in different surgical specialties. The number of patients undergoing robotic-assisted thymectomy is continuously increasing. Such procedures are accompanied by new challenges for anesthesiologists. We are presenting our primary anesthesiologic experience in such patients. METHODS: This is a retrospective single center study, evaluating 28 patients who presented with thymoma or myasthenia gravis (MG) and undergone minimal invasive robotic-assisted thoracic thymectomy between 01/2020-01/2022. We present our fast-track anesthesia management as a component of the enhanced recovery program and its primary results. RESULTS: Mean patient's age was 46.8 ± 18.1 years, and the mean height was 173.1 ± 9.3 cm. Two-thirds of patients were female (n = 18, 64.3%). The preoperative mean forced expiratory volume in the first second (FEV1) was 3.8 ± 0.7 L, forced vital capacity (FVC) was 4.7 ± 1.1 L, and the FEV1/FVC ratio was 80.4 ± 5.3%. After the creation of capnomediastinum, central venous pressure and airway pressure have been significantly increased from the baseline values (16.5 ± 4.9 mmHg versus 13.4 ± 5.1 mmHg, p < 0.001 and 23.4 ± 4.4 cmH2O versus 19.3 ± 3.9 cmH2O, p < 0.001, respectively). Most patients (n = 21, 75%) developed transient arrhythmias episodes with hypotension. All patients were extubated at the end of surgery and discharged awake to the recovery room. The first 16 (57.1%) patients were admitted to the intensive care unit and the last 12 patients were only observed in intermediate care. Postoperatively, one patient developed atelectasis and was treated with non-invasive ventilation therapy. Pneumonia or reintubation was not observed. Finally, no significant difference was observed between MG and thymoma patients regarding analgesics consumption or incidence of complications. CONCLUSIONS: Robotic-assisted surgery is a rapidly growing technology with increased adoption in different specialties. Fast-track anesthesia is an important factor in an enhanced recovery program and the anesthetist should be familiar with challenges in this kind of operation to achieve optimal results. So far, our anesthetic management of patients undergoing robotic-assisted thymectomy reports safe and feasible procedures.

Myasthenia gravis and coronavirus disease 2019: A report from Iran

Background: Coronavirus disease 2019 (COVID-19) is spreading rapidly and has affected millions of people worldwide. Comorbid diseases have complicated the course of infection and increased mortality. Myasthenia gravis (MG) affects the neuromuscular junctions (NMJs) and can compromise respiratory muscle action, leading to worse clinical outcomes in individuals infected with the COVID-19 theoretically. In this study, the aim is to assess the pattern of COVID-19 infection in patients with MG based on several factors. Methods: This was a prospective cohort study following 150 patients with MG over a six-month period. The patients were monitored for the development of signs and symptoms of the COVID-19 infection. Results: Comparison of the patients infected with COVID-19 with MG and those not infected was performed independently based on age, duration since MG diagnosis, status of thymectomy, and current clinical status of MG disease. Data analysis did not reveal increased susceptibility or increased severity of COVID-19 illness based the criteria assessed. Conclusion: COVID-19 related deaths and susceptibility were not related to age, thymectomy status, and disease duration in patients with MG. © 2021 Iranian Neurological Association, and Tehran University of Medical Sciences Published by Tehran University of Medical Sciences.

Immunocompromised Patients with Prolonged Viral Shedding of SARS-COV-2

Background. Most individuals diagnosed with mild to moderate COVID-19 are no longer infectious after day 10 of symptom onset and those with severe or critical illness from COVID are typically not infection after day 20 day of symptom onset. Recovered persons can continue to test positive for SARS-CoV-2 by PCR via detection of non-viable RNA in nasopharyngeal specimens for up to three months (or longer) after illness onset. It is also know known that severely immunocompromised patients may produce replication-competent virus greater than 20 days from symptom onset and may require, per CDC recommendations, "additional testing and consultation with infectious diseases specialists and infection control experts". We aim to discuss four case studies of severely immunocompromised patients who exhibited signs of persistent COVID-19 infection of COVID and how we managed transmission-based precautions in our hospital through sequencing and evaluation of cycle thresholds (CT) values and subgenomic RNA detection. Methods. Residual nasopharyngeal (NP) samples were collected on patients exhibiting persistent COVID like symptoms. These samples underwent N gene and N gene subgenomic RNA (sgRNA) real-time reverse transcription polymerase chain reaction (rRT-PCR) testing. Results. Analysis of longitudinal SARS-CoV-2 sequence data demonstrated within-patient virus evolution, including mutations in the receptor binding domain and deletions in the N-terminal domain of the spike protein, which have been implicated in antibody escape. See Figures 1 and 2. Figure 1. Timelines of Identified Patients 1 and 2 Patient 1: 46-year-old woman with recently diagnosed stage IV diffuse large B-cell lymphoma for which she was treated with 2 cycles of R-CHOP. Patient 2: 38-year-old woman with history of myelodysplastic syndrome, peripheral blood stem cell transplant with chronic graft versus host disease of the GI tract, skin, and eyes as well as CMV enteritis, and she was maintained on rituximab, mycophenolate mofetil, prednisone, and monthly IVIG without recent changes to her immunosuppression. Figure 2. Timeline of Identified Patients 3 and 4 Patient 3: 44 year-old man with prior history of thymoma s/p thymectomy Patient 4: 46 year-old man who was initially diagnosed with marginal zone lymphoma approximately 2.5 years ago. He was initially treated with bendamustine and rituximab and achieved remission. He was then continued on maintenance rituximab without significant complications for a planned two years. Conclusion. Differentiating between prolonged viral shedding of non-infectious RNA and persistent replicating viable virus can be difficult to determine without full evaluation of a patient's clinical picture and timeline. Consultation between laboratory, infectious diseases, and infection prevention experts to provide appropriate level of guidance for precautions and treatment may be warranted. Testing by PCR and analysis of CT values may provide key findings of viral replication in immunocompromised hosts, indicating the need for evaluation of additional treatment and maintaining isolation status in healthcare settings.

Early Flare-Ups of Myasthenia Gravis After Thoracoscopic Thymectomy in a Patient Recently Receiving BNT162b2 mRNA COVID-19 Vaccination.

Myasthenia gravis (MG) is an autoimmune disorder characterized by abnormal neuromuscular transmission. The thymus is believed to play a key role in the pathogenesis of MG, and thymectomy has been an optional treatment for the disease. Relapse of MG after thymectomy has been reported. Exacerbations and new onset of MG following COVID-19 vaccination have also been documented. This report presents a case of a stable MG patient with recent COVID-19 vaccination experiencing flare-ups of symptoms shortly after video-assisted thoracoscopic (VATS) thymectomy. A 31-year-old female received the second dose of the BNT162b2 mRNA COVID-19 vaccine eight days before thymectomy and developed flare-ups of symptoms four days after the surgery. Although the substantial link between MG exacerbations post-thymectomy and pre-thymectomy COVID-19 vaccination cannot be concluded, this observation warrants further research.

T cell response to influenza vaccination remains intact in adults with congenital heart disease who underwent early thymectomy

Introduction: Thymectomy is routine during surgery for congenital heart defects to access to the heart. T cells developed in the thymus play a key role in immunity. Individuals with thymectomy in infancy have altered T cell populations suggesting early immunosenescence. Hypothesis: Adults with Congenital Heart Disease (ACHD) who underwent thymectomy in the first year of life have an altered response to influenza vaccination due to T cell immunosenescence. Methods: We recruited ACHD with early thymectomy ≤ 1 year of age (ACHD-ET;n = 12), ACHD and no thymectomy (ACHD-NT;n = 8), and healthy controls (HC;n = 14). Peripheral blood was collected prior to influenza vaccine and 4 weeks following administration. Flow cytometry of T cell subsets and intracellular cytokine staining of CD4 T cells was done following in vitro stimulation with influenza viral antigen. Results: Subject's mean age was 34 ± 10.6 years with no difference between the groups. At baseline, the median (IQR) frequency of naïve CD4 T cells was 24.7% (15.9) in ACHD-ET vs. 43.6% (16.9) in HC (P=0.01). Similarly, naïve CD8 T cells were lower with 37.5% (25.7) in ACHDET vs 62.8% (22.9) in HC (P=0.02). This also resulted in a reciprocal increase in memory CD4 and CD8 T Cells in the ACHD-ET group. The ACHD-NT was not significantly different than the other groups. The frequencies of influenza antigen-specific memory CD4 T cells expressing IFN-γ and TNF-α were significantly increased in post-vaccine blood samples compared to pre-vaccine samples across all 3 groups (P<0.05). Conclusions: ACHD-ET have a smaller population of naïve T cells, suggestive of immunosenescence. Despite this they have an equivalent cytokine response suggesting that early thymectomy does not inhibit the response to vaccination in young adulthood. Our findings support the recommendation that preventative vaccination against pathogens including influenza virus and the newly emerging SARS-CoV-2 should continue to be routinely performed in ACHD.

SUPERIOR VENA CAVA RESECTION FOR EXTENDED THYMIC EPITHELIAL TUMORS: SAFETY AND OUTCOMES ANALYSIS

TYPE: TOPIC: Disorders of the Mediastinum PURPOSE: Infiltration of superior vena cava (SVC) is not uncommon in stage III–IVa thymic epithelial tumours (TETs). SVC extent of resection is proportional to width of neoplastic invasion region. Aim: to assess the safety and long-term results of prolonged thymectomy for TETs with and without SVC resection. METHODS: Retrospective review of patients who underwent extended thymectomy for TETs during the preceding two decades, using STROBE method. Kaplan–Meier technique was used to calculate progression-free survival (PFS) and overall survival (OS). To evaluate the factors related to long-term outcomes, a backward stepwise Cox regression multivariate analysis was done. RESULTS: Between January 1998 and April 2019, 78 individuals received surgery for advanced-stage TETs (Masaoka-Koga stages III–IVa). 14 (17.9%) received thymectomy with SVC resection. At multivariate analysis, presence of thymic cancer (HR=2.26;95%CI=1.82–6.18;p=0.038) and SVC resection (HR=1.89;95%CI=1.11–3.96;p=0.041) were found to be unfavourable prognostic variables. All SVC resected patients had median OS=50 months (range: 5–207) and median PFS=31 months (range: 5–151). There was no statistically significant difference in OS (p=0.28) or PFS (p=0.32) between patients with and without SVC resection. CONCLUSIONS: SVC resection is a safe and successful surgery for re-establishing the continuity of the venous system that appears not to influence survival or disease recurrence. CLINICAL IMPLICATIONS: Surgical approaches vary considerably according to extent of SVC infiltration, and issues associated with SVC resection for TETs remain unresolved. SVC resection is a safe and effective operation that appears not to affect survival or recurrence. This surgical technique enables complete resection of locally progressed TETs, even following neoadjuvant treatment. DISCLOSURE: No conflict of interest to declare. This was submitted (ad accepted) in Chest 2020 Bologna withdrawn due to the COVID pandemic. KEYWORD: thymic epithelial neoplasm

Immunity and inflammation: the neglected key players in congenital heart disease?

Although more than 90% of children born with congenital heart disease (CHD) survive into adulthood, patients face significantly higher and premature morbidity and mortality. Heart failure as well as non-cardiac comorbidities represent a striking and life-limiting problem with need for new treatment options. Systemic chronic inflammation and immune activation have been identified as crucial drivers of disease causes and progression in various cardiovascular disorders and are promising therapeutic targets. Accumulating evidence indicates an inflammatory state and immune alterations in children and adults with CHD. In this review, we highlight the implications of chronic inflammation, immunity, and immune senescence in CHD. In this context, we summarize the impact of infant open-heart surgery with subsequent thymectomy on the immune system later in life and discuss the potential role of comorbidities and underlying genetic alterations. How an altered immunity and chronic inflammation in CHD influence patient outcomes facing SARS-CoV-2 infection is unclear, but requires special attention, as CHD could represent a population particularly at risk during the COVID-19 pandemic. Concluding remarks address possible clinical implications of immune changes in CHD and consider future immunomodulatory therapies.