Clostridial Myonecrosis: A Comprehensive Review of Toxin Pathophysiology and Management Strategies.

Clostridial myonecrosis, commonly known as gas gangrene (GG), is a rapidly progressing and potentially fatal bacterial infection that primarily affects muscle and soft tissue. In the United States, the incidence of GG is roughly 1000 cases per year, while, in developing countries, the incidence is higher. This condition is most often caused by Clostridium perfringens, a Gram-positive, spore-forming anaerobic bacterium widely distributed in the environment, although other Clostridium species have also been reported to cause GG. The CP genome contains over 200 transport-related genes, including ABC transporters, which facilitate the uptake of sugars, amino acids, nucleotides, and ions from the host environment. There are two main subtypes of GG: traumatic GG, resulting from injuries that introduce Clostridium spores into deep tissue, where anaerobic conditions allow for bacterial growth and toxin production, and spontaneous GG, which is rarer and often occurs in immunocompromised patients. Clostridium species produce various toxins (e.g., alpha, theta, beta) that induce specific downstream signaling changes in cellular pathways, causing apoptosis or severe, fatal immunological conditions. For example, the Clostridium perfringens alpha toxin (CPA) targets the host cell's plasma membrane, hydrolyzing sphingomyelin and phosphatidylcholine, which triggers necrosis and apoptosis. The clinical manifestations of clostridial myonecrosis vary. Some patients experience the sudden onset of severe pain, swelling, and muscle tenderness, with the infection progressing rapidly to widespread tissue necrosis, systemic toxicity, and, if untreated, death. Other patients present with discharge, pain, and features of cellulitis. The diagnosis of GG primarily involves clinical evaluation, imaging studies such as X-rays, computer tomography (CT) scans, and culture. The treatment of GG involves surgical exploration, broad-spectrum antibiotics, antitoxin, and hyperbaric oxygen therapy, which is considered an adjunctive treatment to inhibit anaerobic bacterial growth and enhance the antibiotic efficacy. Early recognition and prompt, comprehensive treatment are critical to improving the outcomes for patients affected by this severe and life-threatening condition.

Age and Sex in the Development of Hepatic Encephalopathy: Role of Alcohol.

Hepatic encephalopathy (HE) is a neurological condition linked to liver failure. Acute HE (Type A) occurs with acute liver failure, while chronic HE (Type C) is tied to cirrhosis and portal hypertension. HE treatments lag due to gaps in understanding its development by gender and age. We studied how sex and age impact HE and its severity with combined liver toxins. Our findings indicate that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young/aged female rats. However, adding alcohol (ethanol, EtOH) worsens TAA's brain edema in both young and aged females, with females experiencing a more severe effect than males. These patterns also apply to Type A HE induced by azoxymethane (AZO) in mice. Similarly, TAA-induced behavioral deficits in Type C HE were milder in young and aged females than in males. Conversely, EtOH and TAA in young/aged males led to severe brain edema and fatality without noticeable behavioral changes. TAA metabolism was slower in aged males than in young or middle-aged rats. When TAA-treated aged male rats received EtOH, there was a slow and sustained plasma level of thioacetamide sulfoxide (TASO). This suggests that with EtOH, TAA-induced HE is more severe in aged males. TAA metabolism was similar in young, middle-aged, and aged female rats. However, with EtOH, young and aged females experience more severe drug-induced HE as compared to middle-aged adult rats. These findings strongly suggest that gender and age play a role in the severity of HE development and that the presence of one or more liver toxins may aggravate the severity of the disease progression.

Dermatologic Changes in Experimental Model of Long COVID.

The coronavirus disease-19 (COVID-19) pandemic, declared in early 2020, has left an indelible mark on global health, with over 7.0 million deaths and persistent challenges. While the pharmaceutical industry raced to develop vaccines, the emergence of mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains continues to pose a significant threat. Beyond the immediate concerns, the long-term health repercussions of COVID-19 survivors are garnering attention, particularly due to documented cases of cardiovascular issues, liver dysfunction, pulmonary complications, kidney impairments, and notable neurocognitive deficits. Recent studies have delved into the pathophysiological changes in various organs following post-acute infection with murine hepatitis virus-1 (MHV-1), a coronavirus, in mice. One aspect that stands out is the impact on the skin, a previously underexplored facet of long-term COVID-19 effects. The research reveals significant cutaneous findings during both the acute and long-term phases post-MHV-1 infection, mirroring certain alterations observed in humans post-SARS-CoV-2 infection. In the acute stages, mice exhibited destruction of the epidermal layer, increased hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of sebaceous glands. Moreover, the thinning of the panniculus carnosus and adventitial layer was noted, consistent with human studies. A long-term investigation revealed the absence of hair follicles, destruction of adipose tissues, and further damage to the epidermal layer. Remarkably, treatment with a synthetic peptide, SPIKENET (SPK), designed to prevent Spike glycoprotein-1 binding with host receptors and elicit a potent anti-inflammatory response, showed protection against MHV-1 infection. Precisely, SPK treatment restored hair follicle loss in MHV-1 infection, re-architected the epidermal and dermal layers, and successfully overhauled fatty tissue destruction. These promising findings underscore the potential of SPK as a therapeutic intervention to prevent long-term skin alterations initiated by SARS-CoV-2, providing a glimmer of hope in the battle against the lingering effects of the pandemic.

Krokodil-Associated Cutaneous Ulceration, Cardiac Arrhythmia and Thrombi.

Krokodil, the street name for desomorphine, has emerged as a deadly and alarming drug phenomenon in recent years. This report delves into the intricate relationship between krokodil abuse, its adverse effects on the skin and its profound impact on cardiovascular events. Our patient developed a non-healing cutaneous ulceration associated with an acute onset of cardiac arrhythmia, as well as bilateral upper extremity acute deep-vein thrombosis. LEARNING POINTS: The use of Krokodil can lead to chronic non-healing ulcerations.It is important to be aware that new cardiac arrhythmias can arise in individuals using krokodil.Acute bilateral upper extremity thrombosis can occur as a complication in patients using krokodil.

Development of purpura fulminans by Candida glabrata and Mucormycosis infection post-surgery.

Purpura fulminans (PF) is a disorder with multifactorial causes that lead to acute localize skin microvasculature thrombosis. PF can be classified as one of the manifestations of disseminated vascular coagulation (DIC). Although, there are three types of PF including hereditary (autosomal dominant) due to mutations in single nucleotide polymorphisms (PROC and PROS1) and serpin family C member 1 (SERPINC1) genes. Idiopathic or acquired type of PF is complex and the pathophysiology is ambiguous, however, low levels of protein C and S were observed. The acute infectious form of PF occurs post-bacterial infection (e.g., Neisseria). The clinical presentation is limited to skin findings or systematic manifestation (shock, disseminated intravascular coagulation, or death). We are presenting two cases of PF sharing similar clinical manifestations developed within 12 h post-operatively with distinct micro-organisms infection. The first patient's wound culture grew fluffy mold, and the sequencing confirmed a Mucormycosis, Absidia corymbifera species, while the second patient was infected by cutaneous Candida glabrata which led to the development of PF. Our findings suggest that surgery can trigger local immunological responses in susceptible individuals such as concealed protein C and S deficiency or microorganism toxins that initiated the rapidly developing of PF in those patients.

Prior viral infection determines the mode and severity of monkeypox virus.

OBJECTIVES: Monkeypox (MPox) is a zoonotic virus in the genus Orthopoxvirus. It is transmitted from animal to human, and between humans. The clinical presentations vary, starting with a prodrome phase to different skin findings and systemic complications. METHODS: We present two distinctive cases of MPox co-infected with other viruses (hepatitis C virus [HCV] and HIV) by clinical and histopathological analysis. RESULTS: Surprisingly, the MPox patient with a history of HCV developed different skin pathological characteristics (less severe inflammatory changes than the classic patient with HCV or MPox alone). In contrast, patients living with HIV presenting with MPox had severe inflammatory cutaneous changes and distortion of the skin architecture. CONCLUSION: Our findings strongly suggest that MPox infections likely occur in the presence of one or more previous other viral infections, and the prior infection with specific microbes determines the severity of MPox infection.

JAPANESE ENCEPHALITIS VIRUS TRIGGERED OVERLAPPING MILLER FISHER SYNDROME WITH BICKERSTAFF ENCEPHALITIS IN A YOUNG FILIPINO CRUISE LINE WORKER.

Japanese encephalitis virus is an RNA flavivirus and one of the rare pathogens that can cause encephalitis. The main vector is the Culex tritaeniorhynchus mosquito. The virus is very close in pathophysiology and structure to the West Nile and St. Louis encephalitis viruses. It is endemic in Asia and Western Pacific areas, mostly during the summer; only a few cases have been reported outside those regions. We present the case of a young Filipino cruise line male worker with signs and symptoms of Japanese encephalitis concomitantly with Miller Fisher syndrome and Bickerstaff brainstem encephalitis. The patient developed obtundation, ataxia, areflexia, flaccid paralysis, and ophthalmoplegia, which were preceded by a few days of constitutional symptoms (fever, malaise, fatigue and anorexia). Physical examination showed various stages of erythema nodosum on the lower extremities. Analysis of cerebrospinal fluid was positive for anti-GQ1b, West Nile IgG and Japanese encephalitis IgM. Despite the neurological complications and bradyarrhythmia occurring during hospitalization, the patient recovered completely under our regimen. LEARNING POINTS: Insidious onset of bilateral paralysis preceded by fever is most likely encephalitis.Japanese encephalitis virus led to the development of variant forms of Guillain-Barré syndrome in our patient.Supportive care resulted in significant recovery despite the severity of the condition.

Transactivation Response DNA-Binding Protein of 43 (TDP-43) and Glial Cell Roles in Neurological Disorders.

The trans-activation response DNA-binding protein of 43kDa (TDP-43) is involved in the pathogenesis of multiple brain disorders. As scientists are unraveling TDP-43 function and its impact on various diseases, we have begun to subcategorize them into TDP-43 proteinopathies. Furthermore, glial cell dysfunction contributes to various disorders, and TDP-43 is involved with glial cells via multiple pathways (direct or indirect) that aggravate the pathophysiology of such disorders. We are only now discovering and understanding the vast and diverse roles TDP-43 plays on neuronal cells and its effects on gliosis and neurodegenerative pathologies. It has multiple roles: mRNA maturation and splicing, transporting and maintaining mRNA stability, a component of stress granules and ubiquitination of dysfunctional or misfolded proteins, transcription of microtubule "Futsch" protein, and a role in maintaining synapse integrity and possibly more as we continue to research and uncover the labyrinth of the neuronal network. TDP-43 could also have a detrimental impact on glial cell activation and pathophysiology in diseases where TDP-43 is associated with its pathogenesis. We will review the pathophysiology of various neurological disorders that are associated with the alteration of the TDP-43 levels along with glial cell activation. Further, multiple diseases have glial cell participation in the pathogenesis, and the role of TDP-43 has not yet been investigated. We, therefore, explore those disorders in the context of both TDP-43 and glial cells involvement. This step will enhance the understanding of neurodegeneration where further research could prompt curative modalities with the advancement of technology.

A Rare Case of Non-immune Hemolytic Anemia in a Stage IV Breast Cancer Patient Treated With Capecitabine.

Incremental changes in the diagnosis of breast cancer leave drastic impacts on patients. There are detrimental shifts in cost, psychological disorders in terms of depression, and morbidities. Stage IV breast cancer has a high mortality rate and was afflicting our patient who was diagnosed with metastatic breast cancer estrogen receptor/progesterone receptor (ER/PR) positive, human epidermal growth factor receptor 2 (HER-2) neo negative, and low Ki-67. Among the various management modalities and effective treatments, capecitabine was selected because of its benefits; however, there are several commonly known adverse effects when using capecitabine including non-immune hemolytic anemia, a very rare and unexpected side effect despite the many research and clinical trials performed. Immune mediate or Coombs positive hemolytic anemia was reported with the usage of capecitabine, but this patient developed Coombs negative or non-immune hemolytic anemia. Capecitabine, a form of fluoropyrimidine, hypothetically affects the erythrocyte membrane structure resulting in the destruction of these cells. Additionally, discontinuation of capecitabine in the patient led to the resolution of the condition; this made us more aware of the precise diagnosis, also considering that the bone marrow biopsy came back negative.

Pneumocystis jirovecii pneumonia and deep vein thrombosis in a patient with glioblastoma multiforme.

We present a case of disseminated Pneumocystis jirovecii pneumonia in a patient with a medical history of glioblastoma multiforme associated with acute deep-vein thrombosis. The patient presented to the emergency department with clinical features of pulmonary infection, and the chest images showed pneumonia. Antibiotics were initiated (azithromycin, cefepime, and vancomycin) and the patient was transferred to the ward for further management, where the condition of the patient continued to worsen over the second day. The patient developed bilateral lower extremity swelling and the doppler ultrasound revealed bilateral lower extremity acute deep vein thrombosis. Laboratory results showed pancytopenia and transaminitis. However, a repeated chest X-ray showed ground-glass changes and interstitial infiltrates, suggestive of atypical infection. We indeed identified D-glucan which hints to a disseminated form of Pneumocystis jirovecii pneumonia infection in this patient. We further confirmed the Pneumocystis jirovecii pneumonia by polymerase chain reaction test from the fluid obtained via bronchoalveolar lavage. We, therefore, initiated intravenous trimethoprim/ sulfamethoxazole treatment with an anticoagulant, and the patient's condition improved. Our findings strongly suggest a possible link between Pneumocystis jirovecii pneumonia infection and thrombogenesis, with impact in medical practice.

Malignant Hypertension Without End-Organ Damage Secondary to Stressful Condition in a Female.

Malignant hypertension (hypertensive emergency), is an extreme elevation of blood pressure under certain conditions that can lead to organ damage and other serious consequences. It is a common condition that affects about one in three Americans, according to the Centers for Disease Control and Prevention. An elevation of systolic blood pressure above 180 mmHg and diastolic blood pressure above 120 mmHg is considered a hypertensive emergency. This article addresses the case of a 61-year-old female patient who presented to the ER with a semicomatose and gasping condition and response to painful stimuli with an unclear voice. She also had unstable vital signs, with a blood pressure of 370/200 mmHg, a pulse rate of 115, a respiratory rate of 22, and a pulse oximetry of 96%, but no fever. Her son provided a brief history and reported that a stressful condition had occurred at home one hour before; she had begun to scream and been brought to the ER by ambulance in the condition described above. Cardiac monitoring and an electrocardiograph were performed and indicated a normal condition besides the unstable vital signs. Oxygen was administered via a nasal cannula with 20 mg of intravenous hydralazine, and the patient's blood pressure improved progressively. Moreover, she regained consciousness with no end-organ damage. A hypertensive emergency is usually associated with end-organ damage, such as heart, kidney, eye, or brain damage. However, in this case, despite the extreme elevation of her blood pressure, the patient suffered no organ damage. It is essential to manage the extreme elevation of blood pressure as soon as possible and monitor the patient for consequences.

Coronavirus (COVID-19) Fulminant Myopericarditis and Acute Respiratory Distress Syndrome (ARDS) in a Middle-Aged Male Patient.

Myopericarditis remains a prominent infectious inflammatory disorder throughout a patient's lifetime. Moreover, viral pathogens have been proven to be the leading contributors to myopericarditis in the pediatric and adult populations. Despite the current comprehensive knowledge of myocardial injury in viral and post-viral myopericarditis, the cellular and molecular mechanisms of SARS-CoV-2-induced myopericarditis are poorly understood. This report presents a case of coronavirus (COVID-19) fulminant myopericarditis and acute respiratory distress syndrome (ARDS) in a middle-aged male patient: a 51-year-old man with a history of hypertension who arrived to the emergency department with a dry cough, fatigue, dyspnea, and a fever. A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay confirmed a diagnosis of COVID-19 infection, resulting in the patient's admission to the airborne isolation unit for clinical observation. When his condition began to deteriorate, the patient was transferred to the cardiac care unit after electrocardiography detected cardiac injury, demonstrating diffuse ST-segment elevation. Laboratory evaluations revealed elevated troponin T and BNP, with an echocardiogram indicating global left ventricular hypokinesia and a reduced ejection fraction. The patient was treated with hydroxychloroquine, azithromycin, dobutamine, remdesivir, and ventilatory support. This specific case highlights the severity and complications that may arise as a direct result of COVID-19 infection.