Rejected

Osteonecrosis associated with the use of glucocorticoids is a severe, potentially debilitating complication. In broader terms, it commonly involves the femoral head with secondary hip osteoarthritis. Osteonecrosis can also be caused by trauma and other non-traumatic factors besides steroid treatment. Nonetheless, glucocorticoid use is frequently observed in clinical settings in which this represents a common therapeutic option, including general practice, rheumatology and clinical immunology, among others. The pathogenesis involves genetic components, vascular impairment, adipocyte hypertrophy, and increased intraosseous pressure, ultimately leading to marrow and bone ischemia and necrosis and the process rapidly becomes irreversible. Osteonecrosis manifests with pain and impaired motility while the diagnosis is usually made with magnetic resonance imaging allowing early detection and potentially (dependent on the patient's needs for steroids and stage) timely management with conservative options, followed by joint replacement at late stages. In this review we discuss the pathogenesis, risk factors, diagnosis, staging, and management of this complication associated with glucocorticoid treatment.

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a urologic, chronic pelvic pain syndrome characterized by pelvic pain, pressure, or discomfort with urinary symptoms. Symptom exacerbation (flare) is common with multiple, perceived triggers including stress. Multiple transient receptor potential (TRP) channels (TRPA1, TRPV1, TRPV4) expressed in the bladder have specific tissue distributions in the lower urinary tract (LUT) and are implicated in bladder disorders including overactive bladder (OAB) and BPS/IC. TRPV4 channels are strong candidates for mechanosensors in the urinary bladder and TRPV4 antagonists are promising therapeutic agents for OAB. In this perspective piece, we address the current knowledge of TRPV4 distribution and function in the LUT and its plasticity with injury or disease with an emphasis on BPS/IC. We review our studies that extend the knowledge of TRPV4 in urinary bladder function by focusing on (i) TRPV4 involvement in voiding dysfunction, pelvic pain, and non-voiding bladder contractions in NGF-OE mice; (ii) distention-induced luminal ATP release mechanisms and (iii) involvement of TRPV4 and vesicular release mechanisms. Finally, we review our lamina propria studies in postnatal rat studies that demonstrate: (i) the predominance of the TRPV4+ and PDGFRα+ lamina propria cellular network in early postnatal rats; (ii) the ability of exogenous mediators (i.e., ATP, TRPV4 agonist) to activate and increase the number of lamina propria cells exhibiting active Ca events; and (iii) the ability of ATP and TRPV4 agonist to increase the rate of integrated Ca activity corresponding to coupled lamina propria network events and the formation of propagating wavefronts.

Primary brain calcification (PBC) is a rare and intractable neurodegenerative disease. SLC20A2 and PDGFB are two major causative genes. As there is no effective treatment to avoid further progression or to prevent the onset of the disease, the patients may experience psychological distress. There is a qualitative study on the experiences of patients with primary brain calcification with SLC20A2 variants. However, the experiences of patients with PDGFB variants of the disease have not been explored. The purpose of this study is to identify the experiences of patients with PDGFB variants after diagnosis.

Some people experience prolonged symptoms following an acute COVID-19 infection including fatigue, chest pain and breathlessness, headache and cognitive impairment. When symptoms persist for over 12 weeks following the initial infection, and are not explained by an alternative diagnosis, the term post-COVID-19 syndrome is used, or the patient-defined term of Long Covid. Understanding the lived experiences of Long Covid is crucial to supporting its management. However, research on patient experiences of Long Covid is currently not ethnically diverse enough. The study aim is to explore the lived experience of Long Covid, using qualitative interviews and art-based methods, among people from ethnically diverse backgrounds (in the UK), to better understand wider systems of support and healthcare support needs. Co-created artwork will be used to build on the interview findings. A purposive sampling strategy will be used to gain diverse experiences of Long Covid, sampling by demographics, geographic locations and experiences of Long Covid. Individuals (aged >18 years) from Black and ethnic minority backgrounds, who self-report Long Covid symptoms, will be invited to take part in a semi-structured interview. Interviews will be analysed thematically. A sub-sample of participants will be invited to co-create visual artwork to further explore shared narratives of Long Covid, enhance storytelling and increase understanding about the condition. A patient advisory group, representing diversity in ethnicity and experiences of Long Covid, will inform all research stages. Stakeholder workshops with healthcare professionals and persons, systems or networks important to people's management of Long Covid, will advise on the integration of findings to inform management of Long Covid. The study will use patient narratives from people from diverse ethnic backgrounds, to raise awareness of Long Covid and help inform management of Long Covid and how wider social systems and networks may inform better healthcare service access and experiences.

Cavernoma is the second most common cerebrovascular lesion. Cavernoma involving the cranial nerves is very rare. Only 15 cases of cavernoma presenting with trigeminal neuralgia (TN) have been previously reported. Here, we report a rare case of cavernoma manifesting with TN. A young female patient with a 15-day history of right-sided lancinating pain in the face, difficulty in opening the mouth, and hearing dysesthesia. Magnetic resonance imaging (MRI) revealed a well-demarcated lesion in the cerebellopontine angle related closely to the root of the trigeminal nerve. The initial impression was that of a neurinoma. The lesion was surgically resected the retrosigmoid approach, postoperative pathological analysis confirmed the diagnosis of cavernoma, and the patient's pain and difficulty in opening the mouth resolved completely. We presented the 16 documented case of cavernoma with TN. Although cavernoma involving the trigeminal nerve is extremely rare, this diagnosis should be taken into consideration when a lesion in the cerebellopontine angle is detected on MRI, and the clinical manifestation is consistent with that of secondary TN. Specialized MRI sequences, such as susceptibility weighted imaging (SWI), gradient echo T2, and constructive interference in steady-state (CISS)-weighted imaging, aid in establishing the diagnosis. Resection craniotomy may be the primary management strategy for cavernoma causing TN. In addition, gamma knife radiosurgery (GKRS) and percutaneous balloon compression (PBC) may ameliorate the pain to some extent.

We aimed to assess factors influencing the occurrence of delayed hyponatremia after transsphenoidal surgery in patients with Rathke's cleft cysts (RCCs).

It is widely known that carbon dioxide (CO) arc welding generates carbon monoxide (CO). However, to the best of our knowledge, no case reports have been published regarding CO poisoning in CO arc welders. Therefore, we aimed to report a case of CO poisoning-induced encephalopathy in a CO arc welder in the Republic of Korea to inform about the dangers of CO exposure among COarc welders.

Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). However, effective therapeutic drugs for IDD remain to be further explored. Inflammatory cytokines play a pivotal role in the onset and progression of IDD. Dihydroartemisinin (DHA) has been well reported to have powerful anti-inflammatory effects, but whether DHA could ameliorate the development of IDD remained unclear. In this study, the effects of DHA on extracellular matrix (ECM) metabolism and cellular senescence were firstly investigated in nucleus pulposus cells (NPCs) under tumor necrosis factor alpha (TNF)-induced inflammation. Meanwhile, AKT agonist sc-79 was used to determine whether DHA exerted its actions through regulating PI3K/AKT and NF-B signaling pathways. Next, the therapeutic effects of DHA were tested in a puncture-induced rat IDD model. Finally, we detected the activation of PI3K/AKT and NF-B signaling pathways in clinical degenerative nucleus pulposus specimens. We demonstrated that DHA ameliorated the imbalance between anabolism and catabolism of extracellular matrix and alleviated NPCs senescence induced by TNF. Further, we illustrated that DHA mitigated the IDD progression in a puncture-induced rat model. Mechanistically, DHA inhibited the activation of PI3K/AKT and NF-B signaling pathways induced by TNF, which was undermined by AKT agonist sc-79. Molecular docking predicted that DHA bound to the PI3K directly. Intriguingly, we also verified the activation of PI3K/AKT and NF-B signaling pathways in clinical degenerative nucleus pulposus specimens, suggesting that DHA may qualify itself as a promising drug for mitigating IDD.

Case 1, a 6-year-old, spayed female Pug, presented with severe systemic urticaria, edema, and erythema. The dog had received a famotidine injection as a treatment for repeated vomiting in another hospital. On physical examination, hyperthermia was observed. Moderate pancytopenia, hypoalbuminemia, and increased CRP and D-dimer were also observed in blood tests. Hyposthenuric proteinuria, pulmonary interstitial infiltration, and hepatomegaly were found in other tests. In the histology of the skin, dermal edema and infiltration of inflammatory cells were observed. Therefore, she was diagnosed with acute systemic hypersensitivity. Case 2, a 13-month-old, neutered male Pembroke welsh corgi, presented with severe and patchy systemic ulcerative skin lesions. The dog had a history of soft feces and pain around the anus 2 days before. Thrombocytopenia, and increased CRP and D-dimer were observed in blood tests. In histology, epidermal necrolysis, separation of the epidermis and dermis, and infiltration of inflammatory cells were observed. Therefore, he was diagnosed with an immune-mediated disease with necrolysis dermatitis. Case 3, a 12-year-old, spayed female Pomeranian, presented with severe systemic alopecia, pustule, and crust on the skin. The dog had received an infection treatment from a local hospital. Severe regenerative anemia (hematocrit 15.3%, negative saline agglutination test, negative slide agglutination test, negative Coomb's test, prominent spherocytes) elevated liver enzymes, and increased CRP and D-dimer were observed in blood tests. On histopathology of the skin, pustules, acantholytic cells, and inflammatory cells were observed in the keratin layer of the epithelium. Therefore, she was diagnosed with concurrent with immune-mediated hemolytic anemia. The 3 cases were diagnosed with fatal immune-mediated skin disease concurrently with hematological and systemic abnormalities. All the cases were treated with immune-suppressive drugs, prednisolone, and cyclosporine. In cases 2 and 3, the dogs also received human intravenous immunoglobulin as an immune modulator. The treatment was successful with significant improvements in all the 3 cases.

We report the case of an 8-year-old child with a complex neurodevelopmental disorder, including severe developmental coordination disorder with dysgraphia, anxiety and depression, mild social functioning impairments, headache and chronic musculoskeletal pain, secondary to Ehlers-Danlos syndrome (EDS) hypermobility type. We explored whether wearing whole-body compressive garments (CGs) could improve his motor skills assessed through standardized and experimental procedures. In addition to the effectiveness of CGs on pain, we found partial improvements in his motor skills, specifically postural control, hand movements, and body schema representation, after wearing CGs for 15 days. During an experimental motor imitation task with a virtual tightrope walker, we found improvements in interpersonal synchronization with performances closer to those of typical developing (TD) controls. We conclude that CGs appear to be an innovative and interesting adjuvant treatment for motor skill impairments in children with multidimensional impairments involving EDS. These promising results require confirmation by further evidence-based research.