A case of TAFRO syndrome after vaccination, successfully treated with cyclosporine.

BACKGROUND: TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine. CASE PRESENTATION: An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission. CONCLUSIONS: Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights.

Safety-Catch Linkers for Solid-Phase Peptide Synthesis.

Solid-phase peptide synthesis (SPPS) is the preferred strategy for synthesizing most peptides for research purposes and on a multi-kilogram scale. One key to the success of SPPS is the continual evolution and improvement of the original method proposed by Merrifield. Over the years, this approach has been enhanced with the introduction of new solid supports, protecting groups for amino acids, coupling reagents, and other tools. One of these improvements is the use of the so-called "safety-catch" linkers/resins. The linker is understood as the moiety that links the peptide to the solid support and protects the C-terminal carboxylic group. The "safety-catch" concept relies on linkers that are totally stable under the conditions needed for both α-amino and side-chain deprotection that, at the end of synthesis, can be made labile to one of those conditions by a simple chemical reaction (e.g., an alkylation). This unique characteristic enables the simultaneous use of two primary protecting strategies: tert-butoxycarbonyl (Boc) and fluorenylmethoxycarbonyl (Fmoc). Ultimately, at the end of synthesis, either acids (which are incompatible with Boc) or bases (which are incompatible with Fmoc) can be employed to cleave the peptide from the resin. This review focuses on the most significant "safety-catch" linkers.

Assessment of friction in aged soft contact lenses by an innovative method.

In the present research work, we intend to evaluate the effect of aging of CL (contact lenses) on friction and, in case there are alterations in the value of the coefficient of friction after aging, to understand which modifications in the material incite these variations. For this, a simulation of the aging process to which the CL are subject in vivo is carried out and the friction and stiffness of the CL are characterized, before and after aging. The aging procedure of SCLs (soft contact lenses) was simulated by a cycling process considering that the main parameter influencing the material surface is the transition between the closed and open eye and the exposure to environmental aggressions, particularly ultraviolet radiation. The values of the coefficient of friction and elastic modulus before and after the aging process were compared and was verified the increase of both parameters for all contact lenses. The hydrogel lens was the least affected by aging and the silicone - hydrogel lens based on delefilcon A was the one that showed the least stability of properties.

Case report: Clinical experience of treating pembrolizumab-induced systemic capillary leak syndrome (SCLS) in one patient with metastatic gastroesophageal junction squamous cell carcinoma.

Systemic capillary leak syndrome (SCLS) is a rare and complex adverse effect of immune checkpoint inhibitors (ICIs). The diagnosis of drug-induced SCLS is based on diffuse infusions of exudative fluid into the interstitial areas and the exclusion of other causes. The best management of ICIs-induced SCLS is not settled, though proper supportive care and corticosteroids were commonly applied as the first-line treatment. In our patient with advanced gastroesophageal junction squamous cell carcinoma, although ICIs-induced SCLS was successfully controlled with corticosteroids, the patient soon experienced cancer progress and died of pulmonary infections. Based on our experience and the reported cases by other hospitals, different stages of SCLS might respond differently to the same treatment. Therefore, a grading of ICIs-induced SCLS might help to stratify the patient for different treatment strategies. Besides, corticosteroids-sensitive patients, though waived from deadly SCLS, might be at higher risk of cancer progress and subsequent infections due to the application of corticosteroids. Considering that the inflammatory factors should be closely involved in the development of ICIs-induced SCLS, targeted therapy against the driver inflammatory cytokine might offer treatment regimens that are more effective and safer.

Bilateral choroidal effusions and angle closure in the setting of systemic capillary leak syndrome from HLA-directed vaccine and pembrolizumab therapy for squamous cell carcinoma.

Purpose: Immunotherapy has become an important addition to oncology treatment plans in recent years. As these therapies become more widely employed, many unique side effects have been reported. In ophthalmology the most well-documented side effects of immune checkpoint inhibitors (ICI) include uveitis, macular edema and dry eye syndrome. This manuscript describes a rare case of bilateral choroidal effusions and secondary angle narrowing in the setting of systemic capillary leak syndrome (SCLS) from an HLA-directed vaccine and an ICI, pembrolizumab, for the treatment of stage IV squamous cell carcinoma (SCC) of the lung. Observations: A 67-year-old male with a history of stage IV SCC of the lung status-post pneumonectomy presented to the emergency department due to functional decline, anasarca, and dyspnea after receiving an HLA-directed vaccine in combination with pembrolizumab. Extensive workup revealed that his symptoms were secondary to SCLS. Ophthalmology was consulted due bilateral choroidal detachments seen on magnetic resonance imaging. B-scan ultrasound and ultrasound biomicroscopy revealed large, non-appositional choroidal effusions with anterior rotation of the ciliary body. Given minimal response to oral steroid therapy, sub-Tenon's triamcinolone acetonide, atropine, and intraocular pressure-lowering eyedrops were initiated with a good response. Conclusions and Importance: Choroidal effusions and secondary angle closure can be rare complications of SCLS in the setting of ICIs. Clinicians must be aware of the potentials side effects of ICI therapy, as these medications become more commonly used.

[Necrotizing myositis of the thigh : Cause or result of a systemic capillary leak syndrome?] / Nekrotisierende Myositis des Oberschenkels : Ursache oder Folge eines systemischen "Capillary-leak"-Syndroms?

Infectious diseases of the musculoskeletal system are in trauma surgery sometimes the symptoms that most severely impair patients and are a challenge to surgeons, hospitals and the economy of the public healthcare system. The systemic capillary leak syndrome (SCLS) is a rare idiopathic syndrome that can provoke a fulminant life-threatening progress even if the primary infection is trivial. In addition to a clearly arranged description of the SCLS we report on an affected patient who developed a necrotizing myositis of the right thigh due to an unstable scar.

An unusual presentation of recurrent COVID-19 associated systemic capillary leak syndrome in a patient with multi-system inflammatory syndrome in adults (MIS-A) due to prior COVID-19 infection: Case report and literature review.

Introduction: and importance: Systemic capillary leak syndrome (SCLS) and multisystem inflammatory syndrome in adults (MIS-A) are very rare multifactorial etiology disorders associated with COVID-19 infection. Both conditions are thought to be manifested by the inflammatory state induced by COVID-19 infection. Recurrent COVID-19-associated concomitant/successive manifestations of both disorders have not been reported yet. Case presentation: We report a 38-year-old Asian gentleman who presented initially with fever, cough, shortness of breath, body aches, dizziness, and epigastric pain due to COVID-19 infection. A few days before this presentation, the same patient developed multisystem inflammatory syndrome in adults (MIS-A). Later, based on clinical and laboratory investigations, he was diagnosed with new-onset systemic capillary leak syndrome (SCLS). Despite resuscitative measures, the patient passed away. Clinical discussion: The increased risk of inflammatory complications associated with COVID-19 infection is an emerging concern. Our case report signifies the importance of COVID-19 awareness in less educated and underserved areas with fewer information resources. Rare and fatal manifestations should also be advertised and discussed with the general masses with equal emphasis. Conclusion: This case signifies the importance of understanding the pathophysiology of new-onset systemic capillary leak syndrome in a patient with recurrent COVID-19 infection and utilizing clinical knowledge and decision-making to manage such rare and complex disorders.

Systemic capillary leak syndrome following granulocyte colony-stimulating factor therapy in a T-lymphoblastic leukemia/lymphoma patient: a case report.

Introduction: Systemic capillary leak syndrome (SCLS) is a rare and often fatal clinical entity used to describe a generalized increase in vascular permeability leading to fluid extravasation toward the interstitial compartment. SCLS could be an idiopathic disease or secondary to infections, malignancies or drugs. Case: We present a case of presumably granulocyte colony-stimulating factor (G-CSF)-induced SCLS in a 21-year-old man diagnosed with T­lymphoblastic leukemia/lymphoma. He received the 6th cycle (part B) of the hyper-CVAD chemotherapeutic regimen followed by the initiation of neutropenic fever prophylaxis protocol which included antibiotics and G­CSF. In a course of hours, the patient became dyspneic, hypotensive, and edematous which required intensive care unit admission and was stabilized accordingly. In the following days the patient's anasarca progressively increased which was associated with hypoalbuminemia, hypotension and anemia with pericardial and bilateral plural effusions. As a diagnosis of exclusion augmented by the acuity of such clinical event, observed concomitantly with the administration of the prophylaxis protocol, the suspicion of G­CSF-induced SCLS was established. Consequently, G­CSF was discontinued and treatment with dexamethasone and intravenous immunoglobulins (IVIG) was started. The patient's condition improved significantly illustrated by hemodynamic stability in addition to improvement regarding the anasarca, hypoalbuminemia, and anemia. Follow-up scans suggest resolution of the pericardial and plural effusions. Conclusion: SCLS remains a serios and potentially fatal complication of G­CSF administration which should be taken into consideration, since such medication is widely utilized in oncology wards.

Nivolumab-induced systemic capillary leak syndrome as an ultra rare life-threatening phenomenon of late toxicity and intravenous immunoglobulin efficacy.

Systemic capillary leak syndrome (SCLS) is a life-threatening disease. It is characterized by severe capillary hyperpermeability to proteins resulting in hemoconcentration, hypoalbuminemia and hypovolemic shock. Its treatment remains supportive, and the prognosis is generally poor. We report on a 51-year old male with melanoma treated with nivolumab for 1 year. 1 month following the completion of the treatment, the patient presented with signs of hypovolemic shock, anasarca, hemoconcentration and hypoalbuminemia. After excluding other diseases, a diagnosis of nivolumab-induced systemic capillary leak syndrome was made. A high dose of intravenous steroid therapy was promptly initiated without any significant clinical improvement. Intravenous immunoglobulin therapy was then administered with normalization of blood pressure, hemoconcentration and complete resolution of anasarca. Intravenous immunoglobulin should be considered a first-line treatment option for this rare phenomenon.

Lay abstract Systemic capillary leak syndrome (SCLS) is a life-threatening disease with a high fatality rate. Patients present with low blood pressure, widespread edema and rapid weight gain. Labs show low albumin levels with highly concentrated blood, seen as high hematocrit and hemoglobin levels. Current treatments aim to support the acute crisis. We are presenting on a 51-year old patient with melanoma, treated with nivolumab for 1 year who developed signs of SCLS 1-month following medication discontinuation. He was first treated with high-dose steroids without symptom resolution. He was then administered immune proteins called intravenous immunoglobulins, resolving all his symptoms. Due to the patient's complete response, we suggest intravenous immunoglobulins as the initial treatment in patients taking nivolumab presenting with SCLS.

Cardiac magnetic resonance in recovering COVID-19 patients. Feature tracking and mapping analysis to detect persistent myocardial involvement.

BACKGROUND: Post-COVID-19 patients may incur myocardial involvement secondary to systemic inflammation. Our aim was to detect possible oedema/diffuse fibrosis using cardiac magnetic resonance imaging (CMR) mapping and to study myocardial deformation of the left ventricle (LV) using feature tracking (FT). METHODS: Prospective analysis of consecutively recruited post-COVID-19 patients undergoing CMR. T1 and T2 mapping sequences were acquired and FT analysis was performed using 2D steady-state free precession cine sequences. Statistical significance was set to p < 0.05. RESULTS: Included were 57 post-COVID-19 patients and 20 healthy controls, mean age 59 ± 15 years, men 80.7%. The most frequent risk factors were hypertension (33.3%) and dyslipidaemia (36.8%). The contact-to-CMR interval was 81 ± 27 days. LV ejection fraction (LVEF) was 61 ± 10%. Late gadolinium enhancement (LGE) was evident in 26.3% of patients (19.3%, non-ischaemic). T2 mapping values (suggestive of oedema) were higher in the study patients than in the controls (50.9 ± 4.3 ms vs 48 ± 1.9 ms, p < 0.01). No between-group differences were observed for native T1 nor for circumferential strain (CS) or radial strain (RS) values (18.6 ± 3.3% vs 19.2 ± 2.1% (p = 0.52) and 32.3 ± 8.1% vs 33.6 ± 7.1% (p = 0.9), respectively). A sub-group analysis for the contact-to-CMR interval (<8 weeks vs ≥ 8 weeks) showed that FT-CS (15.6 ± 2.2% vs 18.9 ± 2.6%, p < 0.01) and FT-RS (24.9 ± 5.8 vs 33.5 ± 7.2%, p < 0.01) values were lower for the shorter interval. CONCLUSIONS: Post-COVID-19 patients compared to heathy controls had raised T2 values (related to oedema), but similar native T1, FT-CS and FT-RS values. FT-CS and FT-RS values were lower in post-COVID-19 patients undergoing CMR after < 8 weeks compared to ≥ 8 weeks.