Acquired autoimmune Haemophilia following SARS-CoV-2 vaccines: Dual drug effects on blood coagulation and the Scylla and Charybdis phenomenon

Vaccination against the SARS-CoV-2 may lead to immunologic reactions activating the haemostatic system and resulting in both venous and arterial thromboembolism. Aquired autoimmune Haemophilia following SARS-CoV-2 vaccines were now reported 15 to 19 days (or later) after vaccination and resolution of symptoms by adequate treatment of the immunologic reaction. From patients’ point of view, anticoagulants and SARS-CoV-2 vaccines share their capacity to induce thrombosis as well as bleeding and clinicians are subjected to Scylla and Charybdis when they treat patients not only with anticoagulants but also with SARS-CoV-2 vaccines. Careful analysis of coincidence and causality requires attention when reporting on acquired coagulation inhibitors regarding severity, treatments, duration and statistical risk.

Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin

Immunotherapy of bladder cancer is known to have favorable effects, although it is difficult to determine which patients will show a good response because of the different tumor microenvironments (TME). Here, we developed a bladder cancer-on-a-chip (BCOC) to mimic the TME using three-dimensional (3D) bioprinting and microfluidic technology. We fabricated a T24 and a 5637-cell line-based BCOC that also incorporated MRC-5, HUVEC, and THP-1 cells. We evaluated the effects of TME and assessed the immunologic reactions in response to different concentrations of Bacillus Calmette–Guérin (BCG) via live/dead assay and THP-1 monocytic migration, and concentrations of growth factors and cytokines. The results show that cell viability was maintained at 15% filling density in circle-shaped cell constructs at 20 μL/min microfluidic flow rate. A 3D co-culture increased the proliferation of BCOCs. We found that the appropriate time to evaluate the viability of BCOC, concentration of cytokines, and migration of monocytes was 6 h, 24 h, and three days after BGC treatment. Lastly, the immunotherapeutic effects of BCOC increased according to BCG dosage. To predict effects of immunotherapeutic agent in bladder cancer, we constructed a 3D bioprinted BCOC model. The BCOC was validated with BCG, which has been proven to be effective in the immunotherapy of bladder cancer.

Milk-Derived Extracellular Vesicles in Inter-Organism, Cross-Species Communication and Drug Delivery

Milk is considered as more than a source of nutrition for infants and is a vector involved in the transfer of bioactive compounds and cells. Milk contains abundant quantities of extracellular vesicles (EVs) that may originate from multiple cellular sources. These nanosized vesicles have been well characterized and are known to carry a diverse cargo of proteins, nucleic acids, lipids and other biomolecules. Milk-derived EVs have been demonstrated to survive harsh and degrading conditions in gut, taken up by various cell types, cross biological barriers and reach peripheral tissues. The cargo carried by these dietary EVs has been suggested to have a role in cell growth, development, immune modulation and regulation. Hence, there is considerable interest in understanding the role of milk-derived EVs in mediating inter-organismal and cross-species communication. Furthermore, various attributes such as it being a natural source, as well as its abundance, scalability, economic viability and lack of unwarranted immunologic reactions, has generated significant interest in deploying milk-derived EVs for clinical applications such as drug delivery and disease therapy. In this review, the role of milk-derived EVs in inter-organismal, cross-species communication and in drug delivery is discussed.

Persistent Infection Versus Type 2 Immunological Reaction in Lepromatous Leprosy

The distinction between persistent infection and immunologic reactions in leprosy is often difficult but critically important since their management is different. We present the case of a 51-year-old Vietnamese female who presented in 2015 with areas of erythema and skin infiltration on face and chest, as well as edema on her hands and feet. Skin biopsy was consistent with lepromatous leprosy. She was treated with rifampin, clarithromycin, and levofloxacin for 2 years. Her lower extremity edema was attributed to type 2 immunological reaction for which she was started on prednisone and methotrexate, but she was lost to follow-up for 19 months. She presented with new skin lesions and pain on her extremities. New biopsies revealed an intense neutrophilic infiltrate in the dermis and acid-fast bacilli focally within cutaneous nerve twigs. As compared with the initial biopsy, the inflammatory infiltrates were diminished and the bacilli had a degenerating appearance. These findings were consistent with type 2 immunological reaction. The patient was treated with thalidomide with improvement in the appearance of the skin lesions. A follow-up biopsy showed lack of neutrophilic infiltrates and decreased number of bacilli. This case illustrates the importance of differentiating between persistent infection and immunologic reactions in leprosy. Clinicians should be aware of these complications. A high index of suspicion and accurate interpretation of skin biopsy results are essential for appropriate diagnosis.

Treatment for Early, Uncomplicated Coccidioidomycosis: What Is Success?

The care of primary pulmonary coccidioidomycosis remains challenging. Such infections produce a variety of signs, symptoms, and serologic responses that cause morbidity in patients and concern in treating clinicians for the possibility of extrapulmonary dissemination. Illness may be due to ongoing fungal growth that produces acute inflammatory responses, resulting in tissue damage and necrosis, and for this, administering an antifungal drug may be of benefit. In contrast, convalescence may be prolonged by other immunologic reactions to infection, even after fungal replication has been arrested, and in those situations, antifungal therapy is unlikely to yield clinical improvement. In this presentation, we discuss what findings are clinical indicators of fungal growth and what other sequelae are not. Understanding these differences provides a rational management strategy for deciding when to continue, discontinue, or reinstitute antifungal treatments.

Blood clot formation in reinfusion bag with CATSmart: Two case reports

Autologous blood cell salvage reduces the need for postoperative allogeneic blood transfusion and alleviates immunologic reactions, so the technique is commonly used in cardiac surgery. The continuous autotransfusion system is a type of blood cell salvage device. Although the processing program of continuous autotransfusion system includes filtering of several materials from suctioned blood, such as clots, leukocytes, cytokines, and complement, we identified some unexpected blood clots in the reinfusion bag. Pathologic examination revealed that the clots were composed of fibrin, red blood cell aggregates, and histiocytes. We report two cases of these abnormal findings during the use of CATSmart in cardiac surgery.

BULLOUS ERYTHEMA NODOSUM AS INITIAL MANIFESTATION OF LEPROSY

Introduction: Leprosy is a chronic granulomatous infectious disease caused by Mycobacterium leprae with protean manifestations, particularly prone to affect skin and peripheral nerves. The natural course of the disease may be associated with the development of type 1 or type 2 immunologic reactions. These immunologic reactions are reported to be caused by increased activity of the immune system, particularly a cell-mediated immune response against live leprosy bacillus or remnants of dead bacilli. Leprosy is one of the oldest diseases of mankind. Its clinical diagnosis can be challenging due to the varied manifestations. The first description of bullous erythema nodosum was made 1898 and since then there are few recorded reports. Case Report: Here we present a case of bullous erythema nodosum as leprosy first manifestation. A 35 year-woman presented with 1-year history of disseminated blisters on trunk, forearms and thighs, and multiple painful ulcerated nodules on her face. She reported that the lesions in her face became eroded and ulcerated spontaneously. There were no thickened nerves. Blood and Histopathological investigations were made. The treatment instituted was prednisone 1mg/kg without thalidomide. After two weeks with excellent response, specific therapy for Mycobacterium leprae was initiated by the infectious diseases assistant physician with a satisfactory response.