Rejected

The clinical presentation of European patients with mild-to-moderate Covid-19 infection is still unknown.

Primary central nervous system lymphoma (PCNSL) occurs frequently in a deep intraparenchymal location. It rarely occurs in the meninges, and bone invasion is uncommon. A 12-year-old boy was admitted to our hospital with a history of headache and seizures. Magnetic resonance imaging showed a 4 cm-sized dural-based mass with osteolytic bone change. Craniotomy and tumor removal were performed. Operative findings showed a dural-based hard tumor including necrosis and hemorrhage, and the skull was focally destroyed by tumor cells. The tumor was completely removed. Pathologically, large atypical cells with pleomorphic nuclei and frequent mitoses were found. The tumor cells were immune-positive for CD30, epithelial cell antigen, and anaplastic lymphoma kinase (ALK). The final diagnosis was ALK-positive anaplastic large cell lymphoma (ALCL). There was no evidence of systemic cancer. The boy underwent chemotherapy following the Non-Hodgkin Lymphoma-Berlin-Frankfurt-Münster protocol. There was no recurrence after a 16-month chemotherapy-off period. ALCL is not a common type of PCNSL, and CNS ALCL frequently involves the dura and meninges compared to PCNSL in general. However, osteolytic bone lesions are rarely seen in ALCL. This case thus represents a rare case of dural based ALCL with bone invasion.

Onabotulinumtoxin type A (BoNTA) is manufactured as powder that requires reconstitution with normal saline prior to injection. Previous literature has suggested that preserved saline (PS) exerts a local anesthetic effect, and reduces the procedure discomfort when used in reconstitution in lieu of preservative-free saline (PFS). However, this was mainly studied in the aesthetics indications of BoNTA, and never in its use for the treatment of chronic migraine. The distinction is important as the population of patients with chronic migraine suffers high incidence of scalp allodynia which makes it more prone to injection site pain. In addition, the pain of the procedure itself may be related to the spike of migraine frequency in the immediate post- procedural period which can occur in up to 5% of patients receiving the treatment. Our trial aimed to study the difference in procedural pain scale, and post-procedural headache rating with the use of PS vs PFS in constitution of BoNTA when used as a treatment for chronic migraine.

Cardiac abnormalities are frequently reported in acute subarachnoid hemorrhage (SAH) patients. However, frank ST-elevation and myocardial dysfunction mimicking acute coronary syndrome is a rare occurrence. Systemic and local catecholamine release mediate myocardial injury and may explain raised troponin levels, concordant regional wall motion abnormalities and systolic dysfunction. These findings can pose a significant problem in the acute setting where "time-is-muscle" paradigm can rush clinicians towards a "rule – in" diagnosis of acute myocardial infarction. We present the case of a 60-year-old male who presented to a regional emergency department with loss of consciousness, chest pain and headache. His ECG showed ST-elevation in precordial leads with corresponding region wall motion abnormalities and dynamically elevated troponin levels which supported a diagnosis of acute myocardial infarction. Percutaneous coronary intervention was attempted but found no hemodynamically significant lesions and the patient was managed conservatively with antithrombotic treatment. Further work-up for his headache led to the diagnosis of aneurysmal SAH and subsequent endovascular coiling. The patient was discharged with a good clinical outcome. We discuss the potential catastrophic consequences of interpreting neurologic myocardial stunning as STEMI. Use of potent antithrombotic therapies, like bridging thrombolysis, in this setting can lead to dismal consequences. Clinical history should still be carefully obtained in the acute setting in this era of sensitive biomarkers.

This study aimed to explore the day-to-day experiences of family caregivers who are caring for children with Osteogenesis Imperfecta (OI).

The E3 ubiquitin ligase Itch has long been appreciated to be a critical suppressor of inflammation, first identified as a regulator of Th2 differentiation and lung inflammation. Recent studies have revealed novel roles for this protein in mouse and human disease, and it is now clear that Itch also limits the function of other lymphocytes, innate immune cells, and nonhematopoietic cells to regulate immunity. In addition to Th2 cells, Itch also regulates Th17 and regulatory T cells. Itch regulates humoral immunity through direct roles in T follicular helper cells and T follicular regulatory cells, and B cells. Furthermore, Itch limits innate immune responses, such as macrophage cytokine production. Through these cell-intrinsic functions, Itch regulates the interplay between innate and adaptive immune cells, resulting in profound autoinflammation in Itch-deficient mice. Whereas Itch deficiency was previously thought to be an extremely rare occurrence humans, whole exome sequencing of patients with unexplained autoimmune disease has revealed at least two additional cases of Itch deficiency in the last year alone, each caused by distinct mutations within the Itch gene. The recent identification of these patients suggests that Itch mutations may be more common than previously thought, and demonstrates the need to understand how this protein regulates inflammation and autoimmune disease.

Aim of the study is to compare macroporous (> 1 mm) polytetrafluoroethylene mesh (LP-PTFE) versus microporous (< 1 mm) polypropylene mesh (SP-PPL) in terms of postoperative acute and chronic discomfort and pain, difficulty in mesh handling and long-term recurrence rate.

Multiple sclerosis (MS) is a chronic disease that is associated with a variety of MS-specific symptoms. Many of these symptoms have a negative impact on health-related quality of life (HRQoL). Until now it is unclear which MS-specific symptoms have the highest impact on the HRQoL.

Capillary lymphatic venous malformations (CLVM) are complex vascular anomalies characterized by aberrant and enlarged lymphatic and blood vessels. CLVM appear during fetal development and enlarge after birth, causing life-long complications such as coagulopathy, pulmonary embolism, chronic pain, and disfigurement. Treatment includes surgical debulking, amputation, and recurrent sclerotherapy. Somatic, mosaic mutations in the 110-kD catalytic α-subunit of phosphoinositide-3-kinase (PIK3CA) gene have been previously identified in affected tissues from CLVM patients; however, the cell population harboring the mutation is still unknown. In this study, we hypothesized that endothelial cells (EC) carry the PIK3CA mutations and play a major role in the cellular origin of CLVM. We isolated EC from the lesions of seven patients with CLVM and identified PIK3CA hotspot mutations. The CLVM EC exhibited constitutive phosphorylation of the PI3K effector AKT as well as hyperproliferation and increased resistance to cell death compared to normal EC. Inhibitors of PIK3CA (BYL719) and AKT (ARQ092) attenuated the proliferation of CLVM EC in a dose-dependent manner. A xenograft model of CLVM was developed by injecting patient-derived EC into the flanks of immunocompromised mice. CLVM EC formed lesions with enlarged lymphatic and vascular channels, recapitulating the patient histology. EC subpopulations were further obtained by both immunomagnetic separation into lymphatic EC (LEC) and vascular EC (VEC) and generation of clonal populations. By sequencing these subpopulations, we determined that both LEC and VEC from the same patient express the PIK3CA mutation, exhibit increased AKT activation and can form lymphatic or vascular lesions in mouse.

Central nervous system (CNS) involvement, including encephalopathy, encephalitis, leptomeningitis, and pachymeningitis, in rheumatoid arthritis (RA) is rather rare. We report the case of a 61-year-old female with a history of RA in remission for 7 years, who presented with numbness, weakness of the left upper limb, dysarthria, and headache. Magnetic resonance imaging (MRI) of the brain showed meningeal enhancement in the frontal, parietal, and temporal lobes. Cerebrospinal fluid (CSF) examination detected high levels of both rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA), with a high ACPA-immunoglobulin G index (> 2.0). She was diagnosed with rheumatoid meningitis. Following combined therapy with oral prednisolone and intravenous infusion of cyclophosphamide, her symptoms promptly improved. After treatment, RF and ACPA levels in the CSF were reduced, and MRI showed improvement of the meningeal structures. This case, along with existing literature, suggests that the ACPA level in the CSF may serve as a useful marker for diagnosing of CNS involvement in RA, as well as an index of effectiveness of the associated treatment.