Searching for a "Window of Opportunity" in the Treatment of Vulvar Lichen Sclerosus: Evidence for Therapeutic Benefits of an Early Corticosteroid Treatment.

INTRODUCTION: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. METHODS: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. RESULTS: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. CONCLUSION: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment.

Hepatitis C-associated Osteosclerosis (HCAO): Long-Term Follow-Up of a New Case Recovered After Antiviral Treatment.

Hepatitis C-associated osteosclerosis (HCAO) is a very rare condition that can be observed in a small number of patients with Hepatitis C Virus (HCV) infection. HCAO is usually characterized by widespread bone sclerosis, associated with severe bone pain, and increased levels of bone turnover markers, especially alkaline phosphatase (ALP). In this report, we present the case of a 55-year-old woman who was affected by HCV and came to our attention for severe and diffuse bone pain. Radiological studies showed bone sclerosis, and bone mineral density (BMD) was markedly increased, as well as serum ALP levels. The patient was initially treated with intravenous pamidronate, which provided only a transient benefit on clinical symptoms. Then antiviral therapy for HCV (interferon-alfa and ribavirin) was started and it was effective in making the viral load undetectable. After a long follow-up period, we observed a persistent remission of bone pain, a reduction in BMD together with a progressive trend toward the normalization of bone turnover markers. In conclusion, HCAO, although rare, should be considered among the potential causes of increased bone mass in patients with HCV infection, and treatment for the underlying infection may be effective in controlling the manifestations of this disease.

Disorganization and Musculoskeletal Diseases: Novel Insights into the Enigma of Unexplained Bone Abnormalities and Fragility Fractures.

PURPOSE OF REVIEW: Describe the potential contribution of disorganized tissue to the pathogenesis of bone abnormalities and fractures. Especially, fractures that are unexplained by bone loss (osteoporosis) or structural deterioration. RECENT FINDINGS: Currently, bone fragility is primarily viewed as due to loss, or decay (osteoporosis). However, it is also acknowledged that this view is limited because it does not explain many fractures or abnormalities such as necrosis, sclerosis, or infarcts. Atypical femoral fractures (AFFs) during antiresorptive therapy are an example. Hence, it is proposed that another distinct mechanism is responsible for bone diseases. A remarkable bone property distinct from mass and decay is the organization (arrangement) of its components. Components must be perfectly assembled or well-stacked to ensure "the right amount of bone, at the right place". Disorganization is an aberration that is conspicuous in many diseases, more so in conditions poorly associated with bone mass and decay such as osteogenesis imperfecta, hypophosphatasia, and AFFs. However, despite the likely critical role of disorganization, this feature has received limited clinical attention. This review focuses on the potential contribution of disorganization to bone in health and diseases. Particularly, we propose that disorganization, by causing ineffective transfer of loads, may produce not only bone abnormalities (pain, necrosis, infarct, sclerosis, delayed healing) but also fractures, especially AFFs or stress fractures. A disorganized element is one that is where it shouldn't be (improperly stacked elements). Hence, disorganization can be measured by quantifying the extent to which a tissue (pixel within an image) is at an incorrect location.

Primary non-parasitic splenic cyst: US- and fluoroscopy-guided percutaneous management by alcohol sclerosis on six patients.

PURPOSE: This manuscript aims to report on a retrospective analysis of six patients treated with combined US- and fluoroscopic-guided percutaneous alcohol sclerosis for primary non-parasitic splenic cysts. METHODS: In this retrospective analysis, three females and three males affected by primary non-parasitic splenic cysts were included. All except one were symptomatic. Preoperative cyst diameter was in mean 113 mm (range: 67-210 mm). Ethanol 96% was adopted as sclerosant agent; the amount of ethanol injected corresponded to the 20%-30% of the cystic volume. US follow-up was planned at 2/4 weeks; MR follow-up was conducted almost at 6 months after the last treatment session. Technical success was considered as cyst disappearance or reduction of the maximum diameter <50 mm; clinical success, in those symptomatic cases, was considered as symptoms resolution or marked improvement. RESULTS: Eleven procedures had been performed: one in three patients, three in two patients and two in one patient. Technical success was 83.3%; clinical success was 80%. Only one patient, with a preoperative cystic diameter of 210 mm and despite three treatment sessions, had an increase in the cystic size and did not report symptoms improvement. CONCLUSIONS: In this sample, US-guided percutaneous alcohol sclerosis was a safe and effective spleen preserving option to treat primary non-parasitic splenic cysts.

[Pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma].

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

Case Report: Idiopathic Sclerosing Orbital Inflammation.

SIGNIFICANCE: Idiopathic sclerosing orbital inflammation (ISOI) is characterized by insidious, chronic, progressive inflammation and fibrosis that damage ocular structures and produce a mass effect. This case highlights the challenges in diagnosis and management of ISOI, as well as the associated ocular morbidities, including potential vision loss. PURPOSE: The purpose of this study was to provide education regarding a rare condition that exhibits variable presentation and has an unpredictable success rate with regard to treatment paradigm. Improved therapeutic options are promising. Ultimately, early detection and management are key and may allow for better visual outcome. CASE REPORT: A 46-year-old woman presented with complaints of chronic right-sided facial headaches and eye pain and gradual right globe prominence over the previous 6 months. Worsening vision and decreased right peripheral visual field were also noted. Upon examination, an afferent pupillary defect and florid disc edema were evident. Imaging studies revealed an orbital and extraorbital infiltrative mass involving the right orbital apex, inferior orbital fissure, pterygopalatine fossa, and cavernous sinus. Right anterior orbitotomy with biopsy revealed fragments of fibroconnective and adipose tissue with sclerosis and chronic focal inflammation, consistent with ISOI. Treatment included intravenous methylprednisone, followed by oral prednisone, beginning at 60 mg/d with a slow taper thereafter. Signs and symptoms improved dramatically and eventually resolved. Vision significantly improved, and the afferent pupillary defect resolved. The patient remained asymptomatic at 3-month follow-up. CONCLUSIONS: Idiopathic sclerosing orbital inflammation is difficult to diagnose and manage. No large studies exist because of the rare nature of the disease. Slowly progressive, nonspecific signs and symptoms may delay recognition and treatment. Orbital imaging and histopathologic analysis are critical for definitive diagnosis. Conventional treatment with corticosteroids is not uniformly successful, but newer combined therapy options can improve outcomes. Early identification and treatment are key to management and ultimate preservation of function and vision.

Role of vasoactive intestinal peptide in the progression of osteoarthritis through bone sclerosis and angiogenesis in subchondral bone.

OBJECTIVE: Osteoarthritis (OA) is a progressive joint disorder, with abnormal remodeling of subchondral bone linked to the disruption of cartilage metabolism. Nerves also play an important role in bone remodeling in OA progression, and vasoactive intestinal peptide (VIP), one of the neuropeptides, plays an important role in bone metabolism. The aim of this study was to analyze the expression pattern of VIP in subchondral bone, and its potential as a therapeutic target for OA progression. DESIGN: The pattern of VIP expression in the human tibia was histologically evaluated. The effect of VIP on angiogenesis was investigated using human umbilical vein endothelial cells (HUVECs). Knee OA was induced by the resection of the medial meniscotibial ligament in C57BL/6 mice. A VIP receptor antagonist was intraperitoneally administered postoperatively, and therapeutic effects were analyzed at 4 and 8 weeks. RESULTS: VIP expression in the subchondral bone increased as OA progressed in human tibia. VIP was also expressed in the vascular channels into the cartilage layer. The total length and branch points were significantly increased, due to the VIP receptor agonist in HUVECs. In OA mice, the VIP receptor antagonist could prevent cartilage degeneration and subchondral bone sclerosis. The Osteoarthritis Research Society International score in the VIP receptor antagonist group was significantly lower than in the control group. CONCLUSION: VIP is involved in the progression of OA through its effect on subchondral bone sclerosis and angiogenesis. Inhibition of VIP signaling has the potential to be a therapeutic target to prevent OA progression.

Cognitive impairment and drug responsiveness in mesial temporal lobe epilepsy.

OBJECTIVES: Mesial temporal lobe epilepsy (MTLE) is the most common form of partial epilepsies. Seizures of MTLE with hippocampal sclerosis (MTLE-HS) are typically resistant to antiepileptic drug (AED) therapy. Although memory disturbances in patients with MTLE-HS are expected, verbal attention and frontal lobe functions may also be impaired. We aimed to examine the relationship between the clinical features and cognitive functions of patients by comparing cognitive test scores of patients with MTLE with few seizures (drug-responsive group) and those with frequent seizures (pharmacoresistant group). METHODS: Seventy-nine patients with MTLE-HS and 30 healthy controls were enrolled. Thirty-four patients were accepted as the drug-responsive group (DrG), and 45 patients were included in the pharmacoresistant group (PRG). Tests evaluating attention, memory, and executive functions were performed on all participants. RESULTS: Forty-nine (62%) female and 30 (38%) male patients with MTLE-HS, and 14 (46.7%) female and 16 (53.3%) male controls participated in the study. The mean age of the patients and controls was 33.53 ±â€¯9.60 (range, 18-57) years and 35.90 ±â€¯7.98 (range, 18-56) years, respectively. Both the DrG and PRG showed poorer performances in tests evaluating memory and frontal lobe functions when compared with the control group (CG). Additionally, attention test results were significantly worse in the PRG than in the DrG. CONCLUSION: It is reasonable to say that increased seizure frequency is the main causative factor of verbal attention deficit due to the poorer attention test results in the PRG. Poor performances in memory and frontal lobe function tests of all patients with MTLE-HS emphasized the importance of the mutual connection between the temporal lobe and prefrontal cortices.

Fungal fibrosing mediastinitis in pregnancy - Case report with review of literature.

Fibrosing mediastinitis (FM) is characterized by extensive and invasive fibro-inflammatory proliferation, triggered by a delayed hypersensitivity reaction to variety of infective or noninfective stimuli. The infective agents often have a geographic distribution such as Histoplasma capsulatum in North America and Mycobacterium tuberculosis in Asian regions. In few reports, the mediastinitis is caused by fungi, particularly Aspergillus species. We report the first case of possible aspergillous FM in a young pregnant woman.

Benign mesial temporal lobe epilepsy: A clinical cohort and literature review.

OBJECTIVE: We present a single-center retrospective study of benign mesial temporal lobe epilepsy (bMTLE) between 1995 and 2014. METHODS: Hospital records and clinic charts were reviewed. The clinical, Eelectroencephalographic (EEG), imaging features, and response to treatment with antiepileptic drugs (AEDs) were documented. Patients were included in this study if they were seizure-free for a minimum of 24months with or without an AED. RESULTS: Twenty-seven patients were identified. There were 19 (70%) females, mean age at first seizure was 32.2 (range: 15-80years). In all patients, seizures were mild, and seizure freedom was readily achieved with the initiation of AED therapy. Sixteen patients (59%) had mesial temporal sclerosis (MTS). In three patients, we attempted to discontinue AED therapy after a prolonged period of remission (5-8years), but all had seizure recurrence within 2 to 4weeks. SIGNIFICANCE: Not all temporal lobe epilepsy is refractory to medication, despite the presence of MTS. Until clinical trials indicate otherwise, surgery is not indicated but life-long medical treatment is advocated.

Imatinib and dasatinib as salvage therapy for sclerotic chronic graft-vs-host disease.

AIM: To assess the toxicity, tolerance, steroid-sparing capacity, effectiveness, and response rate to imatinib and dasatinib for the treatment of severe sclerotic chronic graft-vs-host disease (scGVHD). METHODS: This retrospective study analyzed 8 consecutive patients with severe refractory scGVHD who received salvage therapy with imatinib. Patients intolerant and/or refractory to imatinib received dasatinib treatment. RESULTS: 7 patients discontinued imatinib treatment (1 achieved complete response, 5 were resistant and/or intolerant, and 1 developed grade IV neutropenia) and 1 patient achieved prolonged partial response, but died due to an infectious complication while on treatment. 5 patients started dasatinib treatment (3 achieved partial responses and discontinued dasatinib, 1 achieved a durable partial response, but died due to a consecutive rapid pulmonary cGVHD progression and 1 with stable disease discontinued treatment due to gastroenteric intolerance). The response rate (partial and/or complete responses) for severe scGVHD was 25% for imatinib and 60% for dasatinib. CONCLUSION: In our series, dasatinib was better tolerated, safer, steroid-sparing, and had a low incidence of infectious complications, which suggests that it may be a more effective therapeutic alternative for patients with refractory scGVHD than imatinib. Treatment of scGVHD with effective antifibrotic drugs such as TKI, which block the kinase fibrotic pathway, may be a safe and effective therapeutic option, but further studies are needed to confirm our findings.

Update on Hippocampal Sclerosis.

The diagnostic hallmarks of hippocampal sclerosis (HS) are severe volume loss of the hippocampus, severe neuronal loss, and reactive gliosis involving primarily two especially vulnerable fields, CA1 and the subiculum. Occasionally, HS may be the only neuropathological change detected in older individuals with dementia and is known as pure HS. In the majority of cases, HS occurs in the setting of other degenerative changes, usually Alzheimer's disease (AD). In these cases, it is classified as combined HS. Although a clinical profile for HS has been identified, its similarities with AD make the diagnosis during life quite challenging; thus, the diagnosis is often made postmortem. The pathogenesis of HS is not completely understood, but the strong association with transactive response DNA-binding protein 43 (TDP-43), in approximately 90%, and the recent discovery of genetic risk factors are important contributions to a better understanding of the disease process.

Non-IgG4-Related Fibrosing Mediastinitis Diagnosed on Core Needle Biopsy and Treated with Steroids: A Case Study and Review of the Differential Diagnoses.

OBJECTIVES: This study aimed to investigate the histological characteristics and treatment efficacy of non-immunoglobulin G4-related fibrosing mediastinitis and discuss differential diagnoses for this rare entity. METHODS: We present a case study of non-immunoglobulin G4-related fibrosing mediastinitis diagnosed on core biopsy and treated with steroids. A total of four 18-gauge core needle biopsy specimens were obtained for surgical pathology. Analysis of the patient's medical history, radiological characteristics of fibrosing mediastinitis, histological features, immunohistochemistry results, the differential diagnosis and treatment efficacy of different types of fibrosing mediastinitis was performed. RESULTS: This report describes a unique presentation of fibrosing mediastinitis (syncope and weight loss) that was concerning for malignancy. Histological, laboratory and radiographical studies confirmed the diagnosis of non-immunoglobulin G4-related fibrosing mediastinitis. The patient received corticosteroid treatment which showed marked improvement after 1 month of treatment. CONCLUSIONS: Fibrosing mediastinitis is an extremely uncommon entity with unknown pathogenesis, and it is more important to rule out malignancy and infection than to delineate between fibrosing mediastinitis and IgG4-related disease. In doing this, we may reasonably initiate a trial of corticosteroids which may prove beneficial, as in this patient. More studies on the pathogenesis of fibrosing mediastinitis are necessary to guide better directed treatments.

[Clinical case of the month. Idiopathic mediastinal fibrosis]. / Fibrose médiastinale idiopathique.

Fibrosing mediastinitis is a rare condition characterized by an excessive growth of dense fibrous tissue within the mediastinum. The etiology of the disease is most often a fungal infection and may in some cases be idiopathic. We present the case of a patient with chronic obstructive pulmonary disease (COPD) suffering from fibrosing mediastinitis of undetermined origin and in whom the diagnosis was established by histopathological analysis after mediastinoscopy.

Sclerosing mesenteritis following immune checkpoint inhibitor therapy.

PURPOSE: Sclerosing mesenteritis (SM), a fibroinflammatory process of the mesentery, can rarely occur after immune checkpoint inhibitor (ICI) therapy; however, its clinical significance and optimal management are unclear. We aimed to assess the characteristics and disease course of patients who developed SM following ICI therapy at a single tertiary cancer center. METHODS: We retrospectively identified 12 eligible adult cancer patients between 05/2011 and 05/2022. Patients' clinical data were evaluated and summarized. RESULTS: The median patient age was 71.5 years. The most common cancer types were gastrointestinal, hematologic, and skin. Eight patients (67%) received anti-PD-1/L1 monotherapy, 2 (17%) received anti-CTLA-4 monotherapy, and 2 (17%) received combination therapy. SM occurred after a median duration of 8.6 months from the first ICI dose. Most patients (75%) were asymptomatic on diagnosis. Three patients (25%) reported abdominal pain, nausea, and fever and received inpatient care and corticosteroid treatment with symptom resolution. No patients experienced SM recurrence after the completion of corticosteroids. Seven patients (58%) experienced resolution of SM on imaging. Seven patients (58%) resumed ICI therapy after the diagnosis of SM. CONCLUSIONS: SM represents an immune-related adverse event that may occur after initiation of ICI therapy. The clinical significance and optimal management of SM following ICI therapy remains uncertain. While most cases were asymptomatic and did not require active management or ICI termination, medical intervention was needed in select symptomatic cases. Further large-scale studies are needed to clarify the association of SM with ICI therapy.

Idiopathic mediastinal fibrosis with involvement of the pulmonary vessels and left main coronary artery.

Idiopathic mediastinal fibrosis (IMF) is an uncommon clinical condition and the manifestations of this disease vary from a relatively benign disorder with minor symptoms to severe pulmonary vascular occlusion leading to mortality, commonly presenting a diagnostic and therapeutic challenge. Here, we present the case of a Taiwanese woman with obstruction of the left pulmonary veins and artery and stenosis of the left main coronary artery (LMCA) resulting from IMF. To our knowledge, this is the first reported case of IMF successfully treated with percutaneous balloon angioplasty with stent placement for the LMCA stenosis.

Immunoglobulin G4-related sclerosing disease: experience with this novel entity in a local hospital.

OBJECTIVE: To review the site of involvement, clinical presentation, and treatment outcome of patients having immunoglobulin G4-related sclerosing disease in a local regional hospital. DESIGN: Retrospective case series. SETTING: Pamela Youde Nethersole Eastern Hospital, Hong Kong. PATIENTS: All patients with a diagnosis of immunoglobulin G4-related sclerosing disease in the hospital diagnosed in the period from April 2008 to March 2010. RESULTS: A total of 12 patients with involvement of various organs were identified. There was a male predominance (male-to-female ratio=5:1). The mean age at diagnosis was 65 years. The salivary glands, biliary tract, pancreas, and cervical lymph nodes were the commonest involved sites. The immunoglobulin G4 level was elevated in 83% of the patients. Patients usually appeared to respond well to steroid treatment. CONCLUSION: Immunoglobulin G4-related sclerosing disease is a systemic disease and can involve various systems.