COVID-19-Associated Nonocclusive Fibrin Microthrombi in the Heart.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection. METHODS: Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction. RESULTS: Male sex was more common in the COVID-19 group (P=0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (P=0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (P=0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (P=0.69, P=1.00, P=0.46, P=0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations. CONCLUSIONS: This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.

Cyto-histologic correlation of crystal-storing histiocytosis: Rare presentation in breast, predating diagnosis of B-cell lymphoma by two years.

Crystal-storing histiocytosis (CSH) is a rare disorder characterized by the accumulation of crystalized immunoglobulins within the cytoplasm of histiocytes. It is often associated with an underlying lymphoproliferative or plasma cell disorder. Most patients with CSH are asymptomatic in regard to the disease and are incidentally discovered. Herein we present cyto-histologic correlation of a rare example of CSH presenting with a two-year interval between original diagnosis of CSH and confirmation of a low-grade B-cell lymphoma.

Disseminated blastomycosis in a kidney transplant recipient.

Disseminated blastomycosis in solid organ transplant is uncommon. The diagnosis is usually challenging due to vague clinical presentations, which could lead to a devastating outcome. We reported a unique case of disseminated blastomycosis with laryngeal involvement in a kidney transplant recipient who presented with hoarseness. The diagnosis was made by histopathology and culture of laryngeal mass.

Viral panniculitis in a patient with disseminated opportunistic Enterovirus infection.

Infection-induced panniculitis has been described in association with a broad range of microorganisms. Among those, viral panniculitis represents a minor category, with only a few anecdotal reports in the literature documenting viral infection in the subcutaneous fat. Herein, we report a woman in her 30s with seropositive rheumatoid arthritis on rituximab and prednisone, who presented with a 6-month history of progressive multisystem manifestations, including unintentional weight loss, fever, fatigue, myopathy, pancreatitis, and sensorineural hearing loss. She had indurated plaques on her thighs characterized by predominantly lobular panniculitis with chronic lymphohistiocytic inflammation. Molecular studies performed at the Centers for Disease Control and Prevention identified evidence of Enterovirus group with the highest identity of Coxsackievirus A9. Enterovirus RNA was also detected in the cerebrospinal fluid and muscle. Based on the findings, a diagnosis of disseminated enteroviral infection in the setting of B-cell depletion was rendered. To the best of our knowledge, this represents the first reported case of viral panniculitis with documentation of Coxsackievirus A9 in the skin. Since rituximab may be used for the treatment of autoimmune dermatological diseases, familiarity of the potential occurrence of severe enteroviral infections in the setting of immunosuppressive treatment is important for dermatopathologists.

Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology.

We report the neuropathological findings of a patient who died from complications of COVID-19. The decedent was initially hospitalized for surgical management of underlying coronary artery disease. He developed post-operative complications and was evaluated with chest imaging studies. The chest computed tomography (CT) imaging results were indicative of COVID-19 and he was subsequently tested for SARS-CoV-2, which was positive. His condition worsened and he died after more than 2 weeks of hospitalization and aggressive treatment. The autopsy revealed a range of neuropathological lesions, with features resembling both vascular and demyelinating etiologies. Hemorrhagic white matter lesions were present throughout the cerebral hemispheres with surrounding axonal injury and macrophages. The subcortical white matter had scattered clusters of macrophages, a range of associated axonal injury, and a perivascular acute disseminated encephalomyelitis (ADEM)-like appearance. Additional white matter lesions included focal microscopic areas of necrosis with central loss of white matter and marked axonal injury. Rare neocortical organizing microscopic infarcts were also identified. Imaging and clinical reports have demonstrated central nervous system complications in patients' with COVID-19, but there is a gap in our understanding of the neuropathology. The lesions described in this case provide insight into the potential parainfectious processes affecting COVID-19 patients, which may direct clinical management and ongoing research into the disease. The clinical course of the patient also illustrates that during prolonged hospitalizations neurological complications of COVID may develop, which are particularly difficult to evaluate and appreciate in the critically ill.

Disseminated Mycobacterium avium Complex Infection Following CD3/CD20 Bispecific Antibody Therapy in a Patient With Follicular Lymphoma.

Infections remain a major concern following bispecific antibody therapy but are not well described in pivotal trials. We present the first well-documented case of a classic but rare opportunistic infection, disseminated Mycobacterium avium complex, in a patient receiving bispecific antibody therapy.

Non-tuberculous mycobacteria infection presenting as a hepatic allograft abscess.

Nontuberculous mycobacteria (NTM) are mycobacterial species other than Mycobacterium tuberculous and Mycobacterium leprae [1]. They are environmental organisms which have been implicated in a wide array of clinical syndromes. Here we describe a case of a Mycobacterium fortuitum complex liver abscess in a liver transplant recipient.

Persistent aortic inflammation in patients with giant cell arteritis.

OBJECTIVES: To investigate the clinicopathologic features of patients with giant cell arteritis (GCA) who had thoracic aorta aneurysm or dissection surgery. METHODS: Patients who had thoracic aorta surgery between January 1, 2000, and December 31, 2021, at the Mayo Clinic, Rochester, Minnesota, were identified with current procedural terminology (CPT) codes. The identified patients were screened for a prior diagnosis of GCA with diagnostic codes and electronic text search. The available medical records of all the patients of interest were manually reviewed. Thoracic aorta tissues obtained during surgery were re-evaluated in detail by pathologists. The clinicopathologic features of these patients were analyzed. Overall observed survival was compared with lifetable rates from the United States population. RESULTS: Of the 4621 patients with a CPT code for thoracic aorta surgery, 49 had a previous diagnosis of GCA. Histopathologic evaluation of the aortic tissue revealed active aortitis in most patients with GCA (40/49, 82%) after a median (IQR) of 6.0 (2.6-10.3) years from GCA diagnosis. All patients were considered in clinical remission at the time of aortic surgery. The overall mortality compared to age and sex-matched general population was significantly increased with a standardized mortality ratio of 1.55 (95% CI, 1.05-2.19). CONCLUSION: Histopathologic evaluation of the thoracic aorta obtained during surgery revealed active aortitis in most patients with GCA despite being considered in clinical remission several years after GCA diagnosis. Chronic, smoldering aortic inflammation likely contributes to the development of aortic aneurysm and dissection in GCA.

Sarcina ventriculi in an Endoscopic Ultrasound-Guided Fine Needle Aspiration of a Perigastric Lymph Node with Metastatic Pancreatic Adenocarcinoma: A Carry-Through Contaminant Bacterial Microorganism from the Stomach.

Sarcina ventriculi is a rare gram-positive coccus increasingly reported in patients with a history of delayed gastric emptying or gastric outlet obstruction and is sometimes seen in association with emphysematous gastritis and perforation. We report a case of a 67-year-old male who presented with epigastric pain. CT imaging and cholangiopancreatography were concerning for pancreatic neoplasia. Upper endoscopic ultrasound-guided fine needle aspiration cytology of a perigastric lymph node confirmed metastatic adenocarcinoma of pancreatic origin, and cocci arranged in a tetrad fashions characteristic of Sarcina ventriculi were noted. To our knowledge, this is the first reported case of Sarcina ventriculi in an FNA of metastatic pancreatic carcinoma in a perigastric lymph node. These organisms likely represent carry-through contaminants from the transgastric approach of the endoscopic FNA.

Activity of Various Essential Oils Against Clinical Dermatophytes of Microsporum and Trichophyton.

Dermatophytoses account for nearly a quarter of all fungal infections worldwide. These difficult to treat infections of the skin, hair, and nails, are growing more resistant to conventional antifungal treatments, and when treatable, often require prolonged therapeutic regimens. For centuries, essential oils have been used to treat a variety of ailments. In this study, we evaluated the clinical effects in vitro of 65 essential oils and 21 essential oil blends against various clinical species/strains of dermatophytes from two primary genera, Microsporum and Trichophyton. Our aim: To determine the overall activity of a wide range of essential oils against a number of clinical strains of dermatophytes. For all assays, 16 clinically derived species/strains of dermatophytes were used. The activity of each essential oil was assessed using a modified disk-diffusion assay over a period of 21 days of incubation vs. standard antifungal drugs. Subsequently, we determined the minimum inhibitory dilution possible for the most potent essential oils and performed combination testing to determine if synergy could be demonstrated with sub-inhibitory concentrations. We also assessed the effect of repeated vs. single applications. Of all the essential oils tested, cassia, cilantro, cinnamon, thyme, and oregano were the most potent along with one blend, DDR Prime; all genera/species tested were completely inhibited for 21 days following a single application. Many of the other oils tested exhibited temporal differences in activity where significant inhibition was observed ≤10 days of incubation which declined by day 21. Synergistic combinations were achieved with oregano and cilantro, cassia, or cinnamon bark; rose and cassia were also synergistic. Repeat application maintained complete inhibition for citronella, lemon myrtle, and litsea out to 21 days, but not lemon grass or On Guard. More study is necessary to understand the ways essential oils inhibit the growth of dermatophytes. Comprehensive research aimed at understanding the mechanism of action of essential oils and their components may provide the basis for a natural alternative to topical antifungal drugs. Such research could be envisioned to target optimal combinations and determine the timing between applications to provide for maximum inhibition of recurrence or growth.

Cryptococcal Meningitis Presenting as New-Onset Seizures in an Immunocompetent Patient.

This report describes a 30-year-old immunocompetent male with new-onset seizures, later found on imaging to have 2 enhancing lesions in the brain. The patient underwent a left parietal craniectomy with resection of one of the masses, which demonstrated focal areas of necrosis and many small cystic structures positive for periodic acid-Schiff and Gomori's methenamine silver special stain. Numerous laboratory examinations, including HIV test, rapid plasma reagin, toxoplasma immunoglobulin G and immunoglobulin M, Lyme, cytomegalovirus, tuberculosis, cysticercosis, and Echinococcus serology, were all negative. Despite negative cerebrospinal fluid (CSF) culture and several negative CSF antigen tests, continued investigation, and follow-up, CSF antigen testing ultimately revealed Cryptococcus as the causative agent. In light of the mysterious and unusual presentation, the authors discuss potential infectious differential diagnoses in patients with atypical clinical presentation, laboratory tests, and surgical pathology.

Malignant Mesothelioma of the Tunica Vaginalis Testis-A Malignancy Associated With Asbestos Exposure and Trauma: A Case Report and Literature Review.

In this article, we report an unusual case of a malignant mesothelioma of the testis, presenting as hydrocele. The patient has a known medical history of trauma and occupational exposure to asbestos. The clinical features of this injury are discussed together with its immunohistochemistry. Surgical intervention is discussed due to the nature of this pathology.

A survey of antimicrobial resistance in Enterobacteriaceae isolated from the Chesapeake Bay and adjacent upper tributaries.

In recent years, the rise in antimicrobial resistance (AR) in the healthcare setting as well as the environment has been recognized as a growing public health problem. The Chesapeake Bay (CB) and its upper tributaries (UT) is a large and biologically diverse estuary. This pilot study evaluated the presence of AR of gram-negative bacteria isolated from water samples collected at various sites of the Chesapeake Bay. Bacterial organisms were identified and antimicrobial susceptibility testing was performed by phenotypic and genotypic methods. Ninety-two distinctly different gram-negative bacteria were identified; Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, and Escherichia coli were most often isolated. Serratia marcescens was more frequently isolated in samples from the UT compared to the CB. Antimicrobial resistance was more frequently detected in organisms from the CB by phenotypic and genotypic methods. Antimicrobial resistance to ampicillin, imipenem, tetracycline, and chloramphenicol were the most frequently observed resistance patterns. ACT-1, CMY, and SHV genes were the most frequently detected resistance genes, with predominance in organism isolated from the CB. The results from this study emphasize the importance for further developing comprehensive surveillance programs of AR in bacterial isolates in the various environments, such as recreational and other water systems.

An unusual antibiotic susceptibility pattern in a Mycobacterium Cosmeticum strain isolated from the chesapeake bay.

OBJECTIVE/BACKGROUND: Mycobacterium cosmeticum, first described in 2004, was recovered from a patient undergoing a cosmetic procedure. Subsequently, this species was associated with an outbreak in a nail salon. In all cases, the isolates were susceptible to all antibiotics tested. Recently, however, we recovered a strain of M. cosmeticum from the Chesapeake Bay, resistant to 11 of 14 antimicrobials. The objective of this work was to present our findings on the resistance and susceptibility of this isolate to various antibiotics. MATERIALS AND METHODS: Surface water samples were collected from 10 sites in the Chesapeake Bay and upper tributaries to assess microbial diversity and antibiotic resistance. Site selection was based on proximity to agricultural runoff, industrial contaminants, and sewage effluents. Samples were processed and recovered organisms were identified and subjected to antimicrobial-susceptibility testing. RESULTS: One nontuberculous species, identified as M. cosmeticum, was recovered from Sandy Point State Park. Resistance was detected to several antibiotics: doxycycline (16 µg/mL), tigecycline (≥4 µg/mL), clarithromycin (8 µg/mL), trimethoprim/sulfamethoxazole (≥8/152 µg/mL), imipenem (32 µg/mL), cefoxitin (32 µg/mL), ethionamide (≥20 µg/mL), and streptomycin (16 µg/mL). Of the 14 antibiotics tested, only the fluoroquinolones, linezolid, and amikacin demonstrated potent activity with susceptible minimum inhibitory concentrations. CONCLUSION: The antimicrobial resistance identified in this M. cosmeticum isolates from the Chesapeake Bay raises some important concerns: (a) why is the susceptibility pattern in this isolate so different from the previously published reports, (b) how did resistance emerge in this isolate,

Potent Inhibition of Pseudogymnoascus destructans, the Causative Agent of White-Nose Syndrome in Bats, by Cold-Pressed, Terpeneless, Valencia Orange Oil.

The causative agent of White-nose Syndrome (WNS), Pseudogymnoascus destructans, has been shown to be fatal to several species of bats in North America. To date, no compounds or chemical control measures have been developed which eliminates the growth of the fungus in the environment or in affected animals. In the current study, we evaluated the activity of cold-pressed, terpeneless orange oil (CPT) against multiple isolates of P. destructans in vitro. For all assays, a modified Kirby-Bauer disk diffusion assay was used. Standardized spore suspensions were prepared, adjusted to a specific optical density, and used to plate fungal lawns. Plates were incubated at either 15°C or 4°C for up to 6 months and checked at regular intervals for growth. Once controls had grown, zones of inhibition were measured (mm) on test plates and compared to those obtained using current antifungal drugs. All P. destructans isolates were completely inhibited by 100% CPT (10 µL) at 1 month of incubation regardless of temperature (4°C and 15°C). Complete inhibition persisted up to 6 months following a single exposure at this concentration. Of the standard antifungals, only amphotericin B demonstrated any activity, resulting in zone diameters ranging from 58 mm to 74 mm. CPT, at the highest concentration tested (100%), had no significant effect against a variety of other environmental organisms including various filamentous fungi, bacteria and aerobic actinomycetes. Given that CPT is relatively non-toxic, the possibility exists that the all-natural, mixture could be used as an environmental pre-treatment to eradicate P. destructans from bat habitats. Additional studies are needed to assess any undesirable effects of CPT on bat behavior and health and overall impacts on other members of the interconnected ecosystem(s).

Detection of heteroplasmic mitochondrial DNA in single mitochondria.

BACKGROUND: Mitochondrial DNA (mtDNA) genome mutations can lead to energy and respiratory-related disorders like myoclonic epilepsy with ragged red fiber disease (MERRF), mitochondrial myopathy, encephalopathy, lactic acidosis and stroke (MELAS) syndrome, and Leber's hereditary optic neuropathy (LHON). It is not well understood what effect the distribution of mutated mtDNA throughout the mitochondrial matrix has on the development of mitochondrial-based disorders. Insight into this complex sub-cellular heterogeneity may further our understanding of the development of mitochondria-related diseases. METHODOLOGY: This work describes a method for isolating individual mitochondria from single cells and performing molecular analysis on that single mitochondrion's DNA. An optical tweezer extracts a single mitochondrion from a lysed human HL-60 cell. Then a micron-sized femtopipette tip captures the mitochondrion for subsequent analysis. Multiple rounds of conventional DNA amplification and standard sequencing methods enable the detection of a heteroplasmic mixture in the mtDNA from a single mitochondrion. SIGNIFICANCE: Molecular analysis of mtDNA from the individually extracted mitochondrion demonstrates that a heteroplasmy is present in single mitochondria at various ratios consistent with the 50/50 heteroplasmy ratio found in single cells that contain multiple mitochondria.