Successful use of therapeutic plasma exchange for the management of acute lung transplant rejection secondary to immune checkpoint inhibitor therapy.

The use of immune checkpoint inhibitors (ICIs) in individuals with a history of solid organ transplantation is fraught with the emergence of solid organ transplantation rejection (SOTR). The current recommendations for the management of SOTRs secondary to ICI include the use of high-dose steroids along with the escalation of immunosuppressive therapy. Therapeutic Plasma Exchange (TPE) has been described to be effective in managing various immune-related toxicities, however, the data for using TPE in the setting of acute SOTRs induced by ICIs are limited. Herein, we describe the successful use of TPE in a patient with a history of bilateral lung transplantation who developed an episode of mixed acute cellular and antibody-mediated lung transplant rejection after a single dose of PD-1 inhibitor Pembrolizumab for the treatment of underlying melanoma.

Rare capture: The detection of synchronous diffuse large B-cell lymphoma and lung adenocarcinoma diagnosed by effusion cytology.

The diagnosis of two primary synchronous malignancies in a single pleural effusion cytology specimen is exceedingly rare. We describe, to the best of our knowledge, the first reported case of lung adenocarcinoma and suspected relapse of Diffuse Large B-Cell Lymphoma (DLBCL) diagnosed from a solitary effusion sample.

Setting Up a Teleneurology Clinic during COVID-19 Pandemic: Experience from an Academic Practice.

The declaration of the COVID-19 pandemic necessitated rapid implementation of telehealth across all neurological subspecialties. Transitioning to telehealth technology can be challenging for physicians and health care facilities with no prior experience. Here, we describe our experience at the Neurology and Sleep Disorders Clinic at the University of Missouri-Columbia of successful transition of all in-person clinic visits to telehealth visits within a span of 2 weeks with a collaborative effort of clinic staff and the leadership. Within a month of launch, 18 clinic providers with no prior telehealth experience conducted 1451 telehealth visits, which was the 2nd highest number of telehealth visits conducted by any department at the University of Missouri-Columbia Health Care system. Lack of connectivity, poor video/audio quality, and unavailability of smart devices among rural populations were the important shortcomings identified during our telehealth experience. Our study highlighted the need for expansion of high-speed internet access across rural Missouri. We hope our experience will help other health care facilities to learn and incorporate telehealth technology at their facilities, overcome the associated challenges, and serve patient needs while limiting the spread of the COVID-19.

Indwelling Pleural Catheter (IPC) for the Management of Hepatic Hydrothorax: The Known and the Unknown.

BACKGROUND: Hepatic hydrothorax (HH) is described as pleural effusion secondary to liver cirrhosis after ruling out other etiologies. We aim to assess the efficacy of an indwelling pleural catheter (IPC) placement in refractory HH in this systematic review and meta-analysis. METHODS: A comprehensive search of literature was performed from inception to December 2020. The authors reviewed, selected, and abstracted the data from eligible studies into Covidence, a systematic review software. Cochrane criteria was used to rate each study for the risk of bias. The data abstracted were described using a random-effects model. Heterogeneity was evaluated using the I2 test. RESULTS: Ten studies involving a total of 269 patients were included. The studies were analyzed for the proportion of pleurodesis achieved, the average time to pleurodesis, total complication rate, pleural infection rate, and mortality. A proportion of 47% of the total subjects included achieved spontaneous pleurodesis in an average duration of 104.3 days. The frequency of total complication rate was noted to be 30.36%. The incidence of pleural cavity infection was described to be 12.4% and death resulting from complications of IPC was 3.35%. CONCLUSION: The current management options for the refractory pleural effusion in HH include repeated thoracenteses, transjugular intrahepatic portosystemic shunt, surgical repair of defects in the diaphragm, and liver transplantation. However, the cost, eligibility, and availability can be some of the major concerns with these treatment modalities. With this meta-analysis, we conclude that IPCs can provide an alternative therapeutic option for spontaneous pleurodesis.

Adverse Side Effects Associated with Corticosteroid Therapy: A Study in 39 Patients with Generalized Myasthenia Gravis.

BACKGROUND The tolerability of high-dose oral corticosteroids in patients with generalized myasthenia gravis (gMG) has not been systematically assessed. We evaluated adverse side effects (ASEs) of corticosteroid treatment in patients with gMG. MATERIAL AND METHODS Retrospective analysis was conducted of ASEs reported as being related to corticosteroid treatment in 39 patients with gMG who were treated with oral corticosteroids for ≥1 year. RESULTS Median (interquartile range [IQR]) age was 60 (21) years, 53.8% of patients were women, and 66.7% were aged ≤65 years. Median (IQR) prednisone treatment duration was 14 (2) months; median (IQR) daily dose was 40 (15) mg. The median number of ASEs reported as corticosteroid-related was 2/patient (IQR, 1). Pre-diabetes and weight gain were most common (each 43.6% of patients). Bruising, insomnia, and osteoporosis were more prevalent in patients aged >65 years, while irritability, osteopenia, and pre-diabetes were more common in patients aged £65 years, although differences were not statistically significant. Irritability and weight gain were more prevalent in women (P=0.010 for irritability); osteoporosis and pre-diabetes more common in men (P=0.015 for osteoporosis). ASEs were generally more common in the high-dose prednisone group (>30 mg/day), but were only statistically significant for irritability (P=0.001). CONCLUSIONS Corticosteroid-related ASEs were common in patients with gMG. Some of these ASEs can have serious medical consequences, and certain ASEs appeared to be associated with specific patient characteristics. Demographics and comorbidities of patients with gMG must be carefully considered before corticosteroid initiation. Potential ASEs, such as unanticipated osteoporosis in men, require extra vigilance.

A case of hemothorax secondary to intrapleural fibrinolytic therapy: Considerations for use of fibrinolytics in high-risk patients.

Indwelling Pleural Catheters (IPC) are increasingly being used for management of recurrent pleural effusions (RPEs). Use of IPC for management of both malignant and non-malignant recurrent pleural effusions has been associated with complications such as dysfunctional or nonfunctioning IPCs. Alteplase, a tissue plasminogen activator (tPA) is often used to restore flow of non-draining IPC in symptomatic patients. We present a case of a sixty-eight-year old patient with life-threatening pleural hemorrhage following intrapleural catheter instillation of tPA that was managed successfully by thoracotomy. Our case describe the importance of individualizing the fibrinolytic dose, frequency and the indwelling time in high risk patients. We have reviewed the current literature and recommendations for use of fibrinolytic therapy for IPC in high risk patients on anticoagulation.

Disease and Patient Characteristics Contributing to Diagnostic Delays in Patients With Guillain-Barré Syndrome.

Introduction: Diagnosis of Guillain Barre syndrome (GBS) is often made clinically. Certain patient and disease characteristics can cause delays in diagnosis and management. Methods: Observational retrospective study of forty-four patients diagnosed with GBS either clinically, cerebrospinal fluid analysis, and/or by electro-diagnostic criteria at a teaching hospital (University of Missouri Hospital) in Columbia, Mid-Missouri between 2011 and 2017. Results: Patients with coexisting neurological conditions had statistically significant delay in diagnosis of GBS [Mean (SD); 13 ± 5 vs. 9.39 ± 4.7; p = 0.03]. Patients presenting with motor + symptoms (sensory and/or autonomic, in addition to motor), compared to those with only motor symptoms had statistically significant delay in diagnosis of GBS [Mean (SD); 11.90 ± 5 vs. 8.58 ± 4; p = 0.04]. Discussion: Presence of co-existing neurological conditions, and motor + symptoms can delay timely diagnosis and management of GBS.

Diffuse Gonococcal Infection (DGI) in a Patient with Treatment-Refractory Acetylcholine Receptor Antibody-Positive (AChR+) Generalized Myasthenia Gravis (gMG) Treated with Eculizumab.

Patients receiving complement inhibitor, eculizumab, are at high risk for infections with encapsulated organisms such as Neisseria due to impaired opsonophagocytic activity. Impaired complement immunity may increase the risk for dissemination of asymptomatic Neisseria gonorrhoeae. Disseminated Gonococcal Infection (DGI) is a rare but potentially life-threatening complication associated with eculizumab. Physicians should obtain adequate sexual histories from the patients and educate them on safe sexual practices. Here, we describe a case of DGI in a 32-year-old African American female patient with acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (gMG), receiving eculizumab.

Clinical experience with maintenance therapeutic plasma exchange in refractory generalized myasthenia gravis.

BACKGROUND: Despite the availability of several immunomodulatory therapies, about 20% of myasthenia gravis (MG) patients remain refractory to conventional treatments. There is limited evidence to support the use of maintenance therapeutic plasma exchange (TPE) therapy for refractory generalized MG. METHODS: Retrospective chart review of 14 patients with refractory generalized MG treated for 12 months with maintenance TPE therapy. Outcome measures were myasthenia gravis composite (MGC) score, myasthenia gravis activities of daily living (MG-ADL), number of acute exacerbations, medication changes, and adverse events. Data were collected at 3 monthly intervals for 12 months before and after initiation of TPE therapy. RESULTS: Clinically meaningful reductions in mean MG-ADL (>2 points) (mean MG-ADL score: 9.9 ± 0.5; 12-month pre-TPE to 5.2 ± 0.9; 12-month post-TPE) and MGC (>3 points) (mean MGC score: 25.2 ± 1.6; 12-month pre-TPE to 11.7 ± 1.4; 12-month post-TPE) were observed at 3 months following initiation of TPE and were maintained up to 12 months in all patients. After 12 months of TPE therapy, all patients had a significant reduction in daily prednisone and pyridostigmine use. Patients previously on IVIG or rituximab therapy were successfully weaned off both treatments. There was a significant reduction in acute MG exacerbations; 7.8 ± 1.1 mean exacerbations/patient (12-month pre-TPE) to 2 ± 1.1 mean exacerbations/patient (12-month post-TPE). CONCLUSION: Over a period of 12 months, maintenance TPE therapy improved MG-ADL, and MGC with decreased immunosuppressant requirement, while being well-tolerated.

Eculizumab in the Treatment of Aquaporin-4 Seronegative Neuromyelitis Optica Spectrum Disorder: A Case Report.

Objective: To report the case of a 35-year-old woman with treatment-resistant aquaporin-4 (AQP-4) immunoglobulin G (IgG) seronegative neuromyelitis optica spectrum disorder (NMOSD) successfully treated with eculizumab (a terminal complement inhibitor). Methods: The investigational procedures and treatment regimens the patient received were documented over 8 years [2012 (first presentation) to 2020]. Results: The patient presented with subacute onset of lower-limb weakness and numbness, gait imbalance, and urinary incontinence. Magnetic resonance imaging (MRI) showed abnormalities in the thoracic spine from T7 to T10, but brain and cervical spine scans, visual evoked potential latencies, and IgG index were normal; cerebrospinal fluid pleocytosis and oligoclonal bands were both present. After treatment with intravenous methylprednisolone 1 g/day for 5 days, the patient was discharged without medication to acute rehabilitation but experienced relapses from 2012 to 2014. She was treated with oral prednisone (initiated at 40 mg/day in 2014; the dose was halved in 2015 due to weight gain) and mycophenolate mofetil (MMF) 1 g twice daily (from June 2015), but between 2014 and 2019 experienced 4-5 relapses/year, requiring treatment with intravenous methylprednisolone, with added maintenance plasma exchange from 2018 onwards. Although the patient tested negative for antibodies to AQP-4 and myelin oligodendrocyte glycoprotein, she was diagnosed with NMOSD in February 2017, based on recurrent episodes of longitudinal extensive transverse myelitis, MRI changes, and area postrema syndrome. By 2018 the patient needed a cane to walk. Prednisone and MMF were discontinued mid-2018, and rituximab was prescribed from July 2018 (maintenance regimen two 1 g doses 2 weeks apart every 6 months) but discontinued in July 2019 owing to lack of significant improvement. From July 2019 eculizumab was prescribed for 6 months (900 mg weekly for the first four doses, then 1200 mg every 2 weeks). The patient had no relapses or adverse events during and after eculizumab treatment (as of August 2020) and was able to walk unaided; her Expanded Disability Status Scale score improved from 4-5 during 2015-2018 to 2 in 2020 following eculizumab treatment. Conclusion: Eculizumab shows promise as a treatment for AQP-4 IgG-seronegative NMOSD and further studies are warranted.

Clinical Experience with Eculizumab in Treatment-Refractory Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis.

BACKGROUND: Although established therapies are effective in most patients with generalized myasthenia gravis (gMG), some patients do not respond or they experience intolerable adverse events, highlighting the need for better tolerated, targeted therapies for treatment-refractory gMG. OBJECTIVE: To describe real-world experience with eculizumab in patients with treatment-refractory acetylcholine receptor antibody-positive (AChR+) gMG. METHODS: Retrospective chart review of 15 patients with treatment-refractory AChR+ gMG treated for 12 months with eculizumab (900 mg/week for 4 weeks then 1200 mg every 2 weeks). Outcome measures were Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores, number of exacerbations, single-breath count test (SBCT) score, medication changes, selected Quantitative Myasthenia Gravis (QMG) evaluations, and adverse events. Data collected at 3-monthly intervals for 12 months before and after eculizumab initiation were analyzed. RESULTS: Clinically meaningful reductions in total MG-ADL scores were observed at 3 months following eculizumab initiation and maintained up to 12 months in all patients. After 12 months' eculizumab treatment, there was a significant reduction in the number of acute exacerbations; mean (SD) SBCT score improved from 28.13 (0.33) to 50.26 (2.86); all patients achieved a 'none' or 'mild' rating for QMG evaluations; all patients reduced their daily prednisone dose; and nine patients had discontinued pyridostigmine. At the end of treatment, intravenous immunoglobulin was discontinued in all six patients receiving this therapy at eculizumab initiation. Eculizumab was well tolerated. CONCLUSIONS: This real-world study demonstrated improvement in outcome measures and decreased concomitant drug requirement within 12 months of eculizumab initiation in patients with treatment-refractory AChR+ gMG.

Epstein-Barr virus (EBV) induced pneumonitis in an immunocompetent adult: A case report.

Epstein Barr Virus (EBV) is one of the herpes viruses that is responsible for causing infectious mononucleosis, lymphomas, and carcinomas primarily in immunocompromised individuals. We present a case of EBV-induced pneumonitis in an immunocompetent female, successfully treated with steroids. The patient is a 70 year-old female with a history of infectious mononucleosis in her teens who presented to the emergency room with worsening shortness of breath, associated with cough and fever. She underwent extensive work up and her serologic workup revealed positive anti-EBV antibodies, pointing towards the diagnosis of EBV induced pneumonitis. EBV-induced Pneumonitis is a very rare entity and is especially hardly seen among immunocompetent individuals. This interesting case shows that in this new era of viral pneumonias, EBV induced pneumonitis should be considered among differentials when dealing with lung infections. Prompt initiation of treatment with steroids or antiviral medication may result in complete recovery. The choices among treatment options can be individualized according to the severity of disease, course of disease progression, and side effect profile of medications. In our case we were able to successfully treat the patient with high dose steroids only.

Seizure and COVID-19: Association and review of potential mechanism.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, this highly transmissible virus has since spread rapidly around the world. Though respiratory complication is the primarily reported manifestation though rare, yet serious neurological complications are being frequently reported in the literature. In selected coronavirus disease-2019 (COVID-19) cases neurologic complications may manifest as seizures. In this paper, we have reviewed current literature on seizures linked with SARS- COV 2 infection including published or pre-print original articles, review articles, and case reports. We have discussed the electroencephalogram (EEG), imaging, and Cerebrospinal fluid (CSF) findings in patients with COVID-19 presenting with seizure. We will be concluding the paper by briefly discussing the three mechanisms by which seizures can develop in patients infected with SARS- COV 2 - (a) Direct Mechanism (b) Indirect Mechanism and (c) Exacerbation of Seizure in Patients with Epilepsy (PWE). Our aim is to update the physicians working with COVID-19 patients about this potential complication and hope that understanding of these proposed mechanisms can provide an opportunity for the physicians for early diagnosis or even better, help prevent this complication.

Neuromuscular Complications With SARS-COV-2 Infection: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases were first reported in Wuhan, Hubei province of China in December, 2019. SARS- COV-2 primarily affects the cardio-respiratory system. Over the last few months, several studies have described various neurological sequelae of SARS-COV-2 infection. Neurological complications are more frequent in patients with severe respiratory infections. In this review, we have analyzed the current literature on neuromuscular complications associated with SARS-COV-2 and highlighted possible mechanisms of neuromuscular invasion. We reviewed 11 studies describing 11 cases of Guillain Barre syndrome (GBS), and 1 case each of Miller Fisher syndrome, Polyneuritis Cranialis, Acute myelitis, Oculomotor paralysis and Bell's Palsy associated with SARS-COV-2 infection. Mean age of patients with GBS was 61.54 years, with standard deviation (SD) 14.18 years. Majority patients had fever and cough as the first symptom of SARS COV-2 infection. Mean time for onset of neurological symptoms from initial symptoms in 11 patients was 8.18 days, with SD of 2.86 days. Mean time to performing electrodiagnostic study from onset of neurological symptom was 6 days with standard deviation of 3.25. Six patients had demyelinating pattern, three had acute sensory motor axonal neuropathy, and one had acute motor axonal neuropathy on electrodiagnostic studies.

Miliary Tuberculosis in a Young Patient? Let's Not Forget the Lung Adenocarcinoma!

Lung cancer is one of the most common cancers diagnosed every year and accounts for a major percentage of cancer incidence and mortality annually, especially in men. Lung adenocarcinoma is a subtype of non-small cell lung cancer (NSCLC), which is the most common type of lung cancer found in smokers and nonsmokers alike. It is known to have diverse CT chest findings ranging from: ground-glass opacities (GGOs) with partially solid nodules, to single or multiple solid nodules that can be either central or peripheral, to thin-walled cystic lesions. Lesions are usually solitary but may be multifocal. Rarely, these lesions can be calcified or demonstrate cavitation, which can make it difficult to distinguish from an infectious disease like tuberculosis, pneumonia, or even fungal infections. Here, we present a case of a 36-year-old Asian male with no significant past medical history, except a 16-pack-year smoking history and recent deployment to Afghanistan, that initially presented with a chief complaint of cough of three-week duration. His CT scan showed innumerable bilateral pulmonary nodules within both lung fields with a miliary type appearance that ultimately turned out to be adenocarcinoma.

Bilateral pneumothorax as possible atypical presentation of coronavirus disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19) is most frequently associated with a mild presentation of fever, cough, and shortness of breath. Typical radiographic findings of COVID-19 are bilateral ground-glass opacities on computed tomography (CT) scans. However, there have been instances of pneumothorax, giant bulla, and pneumomediastinum, mainly in elderly COVID-19 patients and predominately occurring at least one week after symptom onset. Here, we report a case where a healthy, young Hispanic man presented with three days of fever, cough, and dyspnea. On admission to the emergency department, he was found to have bilateral pneumothoraces, pneumomediastinum, and pneumopericardium requiring bilateral chest tubes. The patient had no predisposing risk factors for pneumothorax, such as a history of trauma, smoking, past intubations, asthma, high pressure oxygen delivery, or a history of prior pneumothorax. The only positive diagnostic test was a SARS-CoV-2 test by real-time reverse transcriptase-polymerase chain reaction assay. This case highlights the potential atypical presentation of a COVID-19 infection and is the first reported case, to our knowledge, that features bilateral spontaneous pneumothoraces, pneumomediastinum, and pneumopericardium as a probable rare presentation of COVID-19.

Journey of the Nasal Septum Into the Lungs: A Unique Complication of Cocaine Abuse.

Cocaine is a powerful addictive stimulant drug which is known to have a wide range of adverse effects across the spectrum of organ systems. Pulmonary complications have been widely reported. Intranasal inhalation has its own sequelae of complications. It is also quite common that patients who use cocaine also use other drugs. Polysubstance abuse may result in varying detrimental effects. Here, we report a unique case of nasal septal aspiration as a complication of intranasal cocaine inhalation with concomitant alcohol abuse. It is hypothesized the patient perforated his nasal septum due to chronic intranasal inhalation of cocaine and he subsequently aspirated his septum as a result of central nervous system depression secondary to alcohol intoxication.

A Case of Acute Esophageal Necrosis from Unruptured Thoracic Aortic Aneurysm.

Acute esophageal necrosis (AEN), also known as black esophagus due to its appearance on endoscopy, classically involves the distal esophagus (97% of cases). AEN affecting the midesophagus with sparing of the distal esophagus is rare and usually occurs in patients with thoracic aortic aneurysmal (TAA) rupture or aortic dissection. Herein, we report a unique case of AEN in the midesophagus in a patient with an unruptured and undissected TAA.