Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study.

BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.

[Clinical characteristics and ultra-structural features of skeletal muscle in mitochondrial cytopathies].

OBJECTIVE: To investigate the ultrastructural features of mitochondrial cytopathies and its diagnostic value. METHODS: Muscle biopsy specimens from 33 cases of mitochondrial cytopathies were examined by routine pathological and electron microscopic examinations. RESULTS: The main pathologic changes included ragged red fibers in modified Gomori staining, hyper-intense staining myofibers in SDH, COX-negative fibers while dark counterstaining with SDH in COX/SDH double staining technique. Ultrastructural findings included subsarcolemmal and intramyofibrillar proliferation of mitochondria and the appearance of abnormal mitochondria, paracrystalline inclusions, concentric dystrophic cristae and excessive subsarcolemmal glycolipid compounds in subsarcolemmal. CONCLUSION: The presence of proliferation and abnormality of mitochondria, electro-dense granule and paracrystalline inclusions in mitochondria provide key diagnostic evidence for the diagnosis of this disease.

[Typing and prognosis of striatocapsular hemorrhage, study of 181 cases].

OBJECTIVE: To analyze the impact of hematoma location and vascular territory on the clinical symptoms and signs, neuroimaging findings, and clinical prognosis of striatocapsular hemorrhage. METHODS: The data of 181 cases of striatocapsular hemorrhage, 124 males and 57 females, aged 28 - 89, including medical history, symptoms, and signs were analyzed. On the basis of hematoma locations and arterial territories, the striatocapsular hemorrhage was divided into six types: anterior type (with the blood supply from Heubner's artery), middle type (with the blood supply from medial lenticulostriate artery), posteromedial type (with the blood supply from anterior choroidal artery), posterolateral type (with the blood supply from posteromedial branches of lateral lenticulostriate artery), lateral type (with the blood supply from the most of lateral branches of lenticulostriate artery), and massive type (with the hematoma occupying the whole or greater part of striatocapsular region). The short-term clinical outcome and prognosis were evaluated by Modified Rankin Scale (MRS). The relationship between the type and outcome was analyzed. RESULTS: There were 22 cases of anterior type, accounting for 12.15%, of which 68.18% showed an excellent outcome (MRS = 0 - 2) and only 1 case died. There were 12 cases of middle type, accounting for 6.63%, of which 6 cases (50%) showed a poor outcome (MRS = 5) but without dead case. There were 19 cases of posteromedial type (10.50%), of which 52.63% had excellent outcome (MRS = 0 - 2) without dead case. There were 19 cases of posterolateral type (18.78%), of which 76.47% were with poor outcome (MRS = 5) and 17.65% died. Accounting for 39.23%, lateral type was the most common condition, of which 38.03% patients had a poor outcome (MRS = 5) and 8.45% cases died. The incidence rate of massive type was also high (12.71%), of which 47.82% showed a poor outcome (MRS = 5) and 47.83% cases died. CONCLUSION: Hematoma location and vascular territory are the determinating factors of prognosis of striatocapsular hemorrhage. The six-type classification system provides a simple and reliable means to predict the clinical outcomes and to guide therapeutic options of striatocapsular hemorrhage.

Vascular involvement in the pathogenesis of mitochondrial encephalomyopathies.

OBJECTIVE: The aim of this study was to perform perfusion CT imaging in the acute phase of myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), to assess whether these patients had cerebral perfusion abnormalities. Furthermore, the pathology of muscle vessel was evaluated, to explore the role of vasculopathy and ischemic events in the pathogenesis of mitochondrial encephalomyopathies. METHODS: Computed tomography perfusion (CTP) imaging was applied to the evaluation of brain perfusion during the symptomatic period of mitochondrial encephalomyopathies. Mitochondria structures in the blood vessels wall within muscle fibers were observed by light and electron microscopy analyses. RESULTS: Neuroimaging studies demonstrated uni- and bilateral lesions predominantly in the occipital and temporal-parietal lobes. Compared with the healthy control subjects, significant decreases in cerebral blood flow and cerebral blood volume were noted in affected brain areas of individuals with MELAS. In particular, mean transit time and the time to peak were prolonged both in lesion and non-lesion brain areas. Muscle pathology showed large granular deposits on vessel wall as demonstrated by succinic acid dehydrogenase staining. Electron microscopy of blood vessels revealed swelling of cristae and a striking increase in the number of mitochondria in the smooth muscle and endothelial cells. CONCLUSION: Insufficient cerebral perfusion or vascular reserve and secondary metabolic dysfunction may represent an important feature of the pathogenesis of the stroke-like episodes in MELAS.