Appalachian Regional Healthcare

A disease-first off-patent drug-repurposing engine identified dextromethorphan (DXM) as a compound that could lower the risk of post-traumatic stress disorder (PTSD) when administered soon after exposure to severe stress. DXM combines anti-inflammatory activity, N-methyl-D-aspartate (NMDA) receptor antagonism, sigma-1 receptor agonism, and monoamine re-uptake inhibition, a profile that targets several molecular events observed minutes to hours after trauma. Animal studies confirm neuroprotection when DXM is given within two hours of injury, yet no controlled trial has tested this timing in humans. Abuse potential, a narrow therapeutic window, and the historical failure of other NMDA antagonists in neurotrauma limit enthusiasm for large programs until proof-of-concept data emerges.

Abstract Background: Development of acneiform rash in patients with colon cancer treated with anti-EGFR therapies frequently results in dose attenuation or discontinuation, thereby limiting benefits. BRAF inhibitors block the MAPK pathway in BRAF V600 mutant cells, while they paradoxically activate the MAPK pathway in BRAF wild type cells. We hypothesized that a topical formulation of a BRAF inhibitor (LUT014 gel) applied to the areas of acneiform rash would reverse the upstream inhibition of EGFR in skin, thereby reactivating the MAPK pathway and improving the rash and cancer treatment. Methods: Patients with colorectal cancer with grade 2 or non-infected grade 3 acneiform rash while receiving cetuximab or panitumumab were randomized 1:1:1 to: LUT014 gel 0.03%, LUT014 gel 0.1%, or placebo gel. Patients applied the gel to all areas of rash daily for 28 days. Primary endpoint was the proportion of patients who achieved treatment “success” defined as improvement of at least one grade CTCAE score or an improvement of at least 5 for the skin-specific FACT-EGFRI-18 HRQoL. Patients were analyzed via intention to treat (ITT) or as “evaluable pts (EP)” (i.e., those who applied the drug at least once and did not drop out due to reasons besides rash such as disease progression). Sample size calculation was based on an expected treatment success of 20% for the placebo group and 50% for one of the treatment groups. A total of 117 patients were required for a two group ꭕ2 test with a 0.05 two-sided significance and 80% power. Results: The trial enrolled 117 patients from 23 sites. Efficacy is shown in the table. In the ITT as well as the EP, the composite endpoint demonstrated statistically significant rates of success for both LUT014 groups compared to placebo. The table also shows grade 1-5 adverse events (AE) related or suspected to be related to treatment. Conclusion: This is the first placebo-controlled randomized clinical trial demonstrating the benefit and safety of an agent for treatment of the acneiform rash associated with anti-EGFR. Citation Format: Anisha B. Patel, Ofer Purim, Zev A. Wainberg, Nicole LeBoeuf, Iman Imanirad, Efrat Dotan, John Khoury, Veronica Rotemberg, Richard Zuniga, Abhishek Marballi, Esther Tahover, Anil Veluvolu, Samuel Bailey, David Greenberg, Adil Akhtar, Noa Shelach, Benjamin W. Corn, Antoni Ribas, Mario E. Lacouture. A double-blind placebo-controlled randomized phase 2 clinical trial to assess the efficacy of a topical BRAF inhibitor for acneiform rash toxicities from anti-EGFR therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT018.

Abstract Introduction: Mycobacterium malmoense is a slow-growing, non-tuberculous mycobacterium which primarily causes pulmonary disease. M. malmoense is acquired through environmental exposure to contaminated soil or water in individuals with impaired cell immunity. M. malmoense infection may cause extrapulmonary manifestations including cervical adenitis, tenosynovitis, and disseminated disease. Our literature search revealed extremely few cases reported on M. malmoense causing cavitary lesions. We present a case of a patient with hemoptysis and worsening bilateral lung cavitary lesions where sputum culture isolated M. malmoense. Case presentation: A 58-year-old male with a past medical history of hypertension, 80-pack-year smoking history, polysubstance abuse with methamphetamine, cannabis, benzodiazepines, hepatitis C, COPD, and chronic cavitary lung lesions was admitted to the hospital secondary to hemoptysis. He had an initial episode of hemoptysis approximately one year ago which self-resolved after six days. He was scheduled to receive outpatient bronchoscopy for his chronic cavitary lesions though missed follow-up. Two days before the current admission, the patient had worsening cough and bloody sputum. He denied chest pain, night sweats, weight loss, fever, or chills. Computerized tomography (CT) chest showed a new right lower lobe cavitary nodule measuring 3.4 cm x 2.8 cm and unchanged bilateral apical cavitary lung lesions. Our patient was started on IV piperacillin-tazobactam and vancomycin. He had approximately 150 ml of hemoptysis in 24 hours therefore received inhaled tranexamic acid. Sputum smear was positive for acid fast bacilli. Quantiferon TB and HIV testing were negative. Sputum cultures grew Mycobacterium malmoense. Unfortunately, the patient refused any further treatment. Discussion: Mycobacterium species are seen in patients with underlying lung disease or immunocompromised states. Infection is diagnosed by clinical, radiological, and microbiological workup. Microbiological workup includes two separate sputum samples or via transbronchial biopsy or bronchial wash. The most common radiological finding include thick-walled cavitary lung lesions in the upper lobes and underlying pulmonary fibrosis. This Mycobacterium species has high antimicrobial resistance. As per the current ATS and IDSA guidelines, multidrug treatment with macrolides, ethambutol, and rifamycin for a duration of 12 months is indicated. Conclusion: Non-TB Mycobacterium infrequently causes disease, though in susceptible or immunocompromised individuals, it can cause serious respiratory infections. M. malmoense infection still carries a high mortality risk, so careful and early diagnosis is important to improve outcomes. It is important to recognize patients with non-resolving radiographic imaging as well as atypical and persistent infections that do not improve with standard treatment.

Abstract Introduction: Blastomycosis is a dimorphic fungal infection endemic to the Mississippi and Ohio River basins primarily causing pulmonary disease. Cutaneous blastomycosis is a rare manifestation of blastomycosis. Immunocompetent patients may have asymptomatic pulmonary disease, however, chronic fungal shedding may cause disseminated skin lesions. We present a patient with asymptomatic cavitary lung disease who presented with skin lesions that failed to respond to multiple courses of outpatient antibiotics. Case Presentation: A 53-year-old male with diabetes mellitus, coal workers’ pneumoconiosis, and a 20-pack-year smoking history presented to the outpatient clinic for evaluation of ulcerated skin lesions on the abdomen, thigh, and left arm associated with generalized weakness and unintentional weight loss for six months. His lesions failed to respond to courses of mupirocin, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, clindamycin, and doxycycline. Over the next few months, the patient subsequently developed new verrucous lesions on the left eyebrow and bilateral nasal cavity with intermittent episodes of bleeding (figure 1a). He was referred to ENT where he underwent biopsy of the nasal cavity lesion. Computerized tomography (CT) scan of the chest revealed multifocal cavitary lesions scattered throughout both lungs. Urine antigen test for both Histoplasma and Blastomycosis were positive. Pathology showed fungal lesions consistent with Blastomycosis on GMS stain. Bacterial and fungal cultures were negative. He received six months of itraconazole with significant improvement and complete healing of the skin lesions (Figure 1b). The size of asymptomatic pulmonary cavitations also decreased from 4.2 x 3.8 cm to 1.5 x 1.0 cm. Discussion: Cutaneous Blastomycosis may appear like basal cell carcinoma, squamous cell carcinoma, pyoderma gangrenosum, or keratoacanthoma. Urine antigen testing has high sensitivity (92.9%) though low specificity. Histopathology helps to rule-out malignancy and differentiates between Histoplasma and Blastomycosis which can be diagnosed by the presence of broad-based budding. Culture is the most sensitive diagnostic tool and the gold standard for definitive diagnosis. Conclusion: Blastomyces may evade host immune defenses causing asymptomatic disseminated disease. Cutaneous blastomycosis, a rare manifestation, can present as chronic non-healing ulcerative or verrucous lesions. Given skin lesions maybe the only presenting manifestation of disseminated pulmonary blastomycosis, this case highlights the need for including Blastomycosis in the differential diagnosis. With a cure rate of 90-95% with itraconazole, early diagnosis and treatment decreases morbidity and disease burden on patients.

Abstract Introduction: Pulmonary sequestration is a congenital anomaly of the foregut which accounts for 0.15-6.4% of all the congenital lung malformations. It is a nonfunctional lung tissue. It is divided into intra lobar and extra lobar sequestration. Extra-lobar can manifest in infancy and intra-lobar sequestration gets diagnosed in the adult as an incidental finding. Case presentation: Patient is a 50-year-old female with a medical history of asthma presented to the pulmonary Clinic for the incidental lung nodule. On the computerized tomography (CT) of the chest without contrast showed 1.9 cm irregularly shaped nodule in the left lower lobe of the lung. Patient did not have any shortness of breath, cough, no hemoptysis, appetite stable and intentional weight loss of 15 lb over the past 6 months. Patient uses fluticasone salmeterol inhaler every alternate day and as-needed albuterol inhaler. Patient has less than 20 pack years of smoking and quit more than 15 years ago. Based on the solitary pulmonary nodule lung-cancer risk calculator showed patient is moderate risk for malignancy and hence positron emission tomography (PET-CT) was ordered. Subsequently the scan did not reveal any hypermetabolic uptake of the 1.9 cm lung nodule of stable size. During the next office visit, CT angiography of the chest was ordered to rule out any pulmonary arteriovenous malformations. CT angiography of the chest revealed stable size irregular opacity in the left lower lobe is noted and an arterial vessel arising from the left lateral wall of the abdominal aorta coursing into and supplying this opacity, findings compatible with pulmonary sequestration is noted. Discussion: It is a nonfunctional lung tissue in which the segment or lobe of dysplastic lung has no communication with the rest of the tracheobronchial tree and receives anomalous systemic vascular supply. In intra-lobar sequestration, part of lung is within the visceral pleura of the functioning lung and the venous drainage is into the pulmonary vein unlike extra lobar where it has a separate visceral pleura and venous drainage into the systemic vein. Patients usually present with recurrent pneumonia in the same segment of the lung. Diagnosis in the adults is achieved through CT chest with contrast or an alternative being MR angiography, which are done to exclude any other thoracic pathologies and to see abnormal arterial supply. Treatment includes conservative management, treatment of choice is pulmonary lobectomy but recent advancements like endovascular embolization and coiling are provided as alternative management.

The theophylline toxidrome presents with multisystemic involvement that includes cardiovascular, neurologic, metabolic, musculoskeletal, and gastrointestinal manifestations. Considering such a varied spectrum of presentations, it is often difficult to ascertain the diagnosis of this particular toxidrome. Review of home medications is an important step when working with a patient presenting as a toxidrome. The case report is about a 69-year-old female patient who was brought to the emergency room in status epilepticus and atrial fibrillation with rapid ventricular response. She had a prolonged state of drowsiness following an initial antiepileptic therapy and a toxicologic screen positive for toxic levels of theophylline at 59.7 mcg/mL. Emergent dialysis was performed leading to improvement of her overall clinical status. We suspect the patient had built up toxic levels of theophylline due to evolving drug interactions after she discontinued many of her routine home medications following her husband's death. Theophylline is a methylxanthine derivative medication that is used sparingly in the treatment of airway diseases. It has become less favorable over the years due to its narrow therapeutic index and potential for development of toxicity. Monitoring serum drug levels and adjusting the dose frequently to maintain a therapeutic range is essential to prevent toxicity related to theophylline. There is emerging evidence that the drug might have anti-inflammatory properties to aid in treating many chronic airway disorders and pharmacovigilance is necessary for its continued use.

Hypertrophic obstructive cardiomyopathy (HOCM) and subaortic membrane (SAS) are distinct cardiac conditions, but their coexistence presents complex diagnostic challenges. We report the case of a 52-year-old male with HOCM and a concurrent subaortic membrane, highlighting the intricacies of diagnosis and management. The patient's presentation included symptoms of dyspnea and chest tightness, and diagnostic evaluations revealed a unique combination of dynamic left ventricular outflow tract (LVOT) obstruction from HOCM and fixed obstruction from the subaortic membrane. This case emphasizes the importance of a comprehensive diagnostic workup to guide appropriate treatment decisions when managing multiple cardiac abnormalities.

BRASH syndrome, characterized by bradycardia, renal dysfunction, atrioventricular (AV) nodal blockage, shock, and hyperkalemia, is a rare but potentially life-threatening condition resulting from the interplay between AV nodal blockers and hyperkalemia. This complex syndrome poses significant challenges in diagnosis and management, with patients often presenting with bradycardia and high potassium levels. This case report highlights the need for increased awareness of BRASH syndrome, especially in an aging population and evolving cardiovascular treatments. Early recognition and a comprehensive, multidisciplinary approach are crucial for improving outcomes in affected patients.