Class 3 semaphorins as a therapeutic target

Introduction: The semaphorins were initially described as axon guidance molecules that play important roles in the development of nervous system. Recent studies suggest that semaphorins and their receptors also exert such diverse functions as immune response, control of vascular endothelial cell motility and invasion of many types of cancer cells.

Areas covered: The available results concerning application of class 3 semaphorins and their inhibitors for the treatment in animal disease models.

Expert opinion: Because semaphorins are now recognized as key players in immune, cardiovascular, bone metabolism and neurological system, semaphorins and their receptors are most promising therapeutic targets for various disease states. As semaphorins exert their diverse or even opposing activities in vivo, more elaborate studies on pathophysiology and signal transduction mechanisms of semaphorins are required.     

Immunoblastic lymphadenopathy-like T-cell lymphoma complicated by multiple gastrointestinal involvement

We report a rare case of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma complicated by multiple gastrointestinal involvement, which appeared to be ameliorated by chemotherapy but resulted in perforative peritonitis. A 66-year-old Japanese woman who had generalized lymphadenopathy and eruptions was admitted to our hospital because of bloody stool. Colonoscopic examination revealed hemorrhagic ulcers in the terminal ileum and a saucer-like ulcer in the cecum. Gastrointestinal endoscopy revealed several ulcerative or elevated lesions in stomach and duodenum. Biopsy specimens of these lesions and of a lymph node showed characteristic histological features of IBL-like T-cell lymphoma. The initial treatment with prednisolone (PSL) and cyclophosphamide (CPA) was effective. Six months after the treatment, however, she developed bloody stool again caused by multiple ulcerative lesions in the large intestine. The recurrence of the disease was determined histologically, and four courses of CPA, PSL, vinblastine sulfate and doxorubicin hydrochloride (CHOP) therapy were administered. One month after completing the CHOP therapy, she developed intestinal obstruction and then acute peritonitis resulting from perforation at an ulcer scar in the jejunum. Surgical treatment was successful, and histological examination demonstrated no lymphoma cells in the resected specimen. A gastrointestinal perforation should be recognized as a potential complication of IBL-like T-cell lymphoma, even during remission. (Received: June 24, 1998; accepted: Oct. 23, 1998)     

肥厚性硬脑膜炎病例1例分析并文献复习

目的:探讨肥厚性硬脑膜炎(HCP)的临床特征、影像学表现。方法:报道1例HCP患者的临床资料并结合文献进行回顾性分析。结果:该患者以头痛起病,伴视力下降;血液学检验:ANA(+);腰椎穿刺示:脑脊液压力≥330 mmH_2O;头颅MRI平扫+增强示:大脑镰、小脑幕、双侧额顶叶硬脑膜增厚伴强化;硬脑膜活检病理示:玻璃样变纤维血管组织中散在淋巴细胞、浆细胞,以血管周围较明显;免疫组化:CD138(散在+),IgG(个别细胞+),IgG4(个别细胞+);予以激素治疗,症状明显好转。搜索近5年报道的HCP患者189例,最常见的首发症状为头痛,所有患者头颅磁共振平扫+增强均见不同部位的硬脑膜肥厚伴强化,予以激素、激素联合免疫抑制剂或手术治疗后,90%以上患者症状改善。讨论:HCP临床症状可表现为慢性头痛、颅神经受累、共济失调。需进一步完善血液学检验、头颅磁共振平扫+增强检查,必要时硬脑膜活检以确诊。     

Associations of childhood overweight and obesity with upper-extremity fracture characteristics

Childhood obesity is a growing epidemic in the United States, and is associated with an increased risk of lower-extremity physeal fractures, and fractures requiring operative intervention. However, no study has assessed the risk upper extremity physeal fractures among overweight children. Our purpose was to compare the following upper-extremity fracture characteristics in overweight and obese children with those of normal-weight/underweight children (herein, “normal weight”): mechanism of injury, anatomical location, fracture pattern, physeal involvement, and treatment types. We hypothesized that overweight and obese children would be higher risk for physeal and complete fractures with low-energy mechanisms and would therefore more frequently require operative intervention compared with normal-weight children.We performed a cross-sectional review of our database of 608 patients aged 2 to 16 years, and included patients who sustained isolated upper-extremity fractures at our level-1 pediatric tertiary care center from January 2014 to August 2017. Excluded were patients who sustained pathologic fractures and those without basic demographic or radiologic information. Using body mass index percentile for age and sex, we categorized patients as obese (≥95th percentile), overweight (85th to <95th percentile), normal weight (5th to <85th percentile), or underweight (<5th percentile). The obese and overweight groups were analyzed both separately and as a combined overweight/obese group. Demographic data included age, sex, height, and weight. Fractures were classified based on fracture location, fracture pattern (transverse, comminuted, buckle, greenstick, avulsion, or oblique), physeal involvement, and treatment type. Of the 608 patients, 58% were normal weight, 23% were overweight, and 19% were obese. There were no differences in the mean ages or sex distributions among the 3 groups.Among patients with low-energy mechanisms of injury, overweight/obese patients had significantly greater proportions of complete fractures compared with normal-weight children (complete: 65% vs 55%, P = .001; transverse: 43% vs 27%, P = .006). In addition, the overweight/obese group sustained significantly more upper-extremity physeal fractures (37%) than did the normal-weight group (23%) (P = .007).Compared with those in normal-weight children, upper-extremity fracture patterns differ in overweight and obese children, who have higher risk of physeal injuries and complete fractures caused by low-energy mechanisms.Level of Evidence: Level III, retrospective comparative study.     

Early blood pH as an independent predictor of neurological outcome in patients with out-of-hospital cardiac arrest: A retrospective observational study

Metabolic acidosis is observed in 98% of patients with out-of-hospital cardiac arrest (OHCA). The longer the no-flow or low-flow duration, the more severe is the acidosis in these patients. This study explored whether blood pH in early stages of advanced life support (ALS) was an independent predictor of neurological prognosis in patients with OHCA.We retrospectively enrolled patients with OHCA from January 2012 to June 2018 in a single-medical tertiary hospital in Taiwan. Patients with OHCA whose blood gas analyses within 5 minutes after receiving ALS at the emergency department (ED) were enrolled. Patients younger than 20 years old, with cardiac arrest resulting from traumatic or circumstantial causes, with return of spontaneous circulation (ROSC) before ED arrival, lacking record of initial blood gas analysis, and with do-not-resuscitate orders were excluded. The primary outcome of this study was neurological status at hospital discharge.In total, 2034 patients with OHCA were enrolled. The majority were male (61.89%), and the average age was 67.8 ± 17.0 years. Witnessed OHCA was noted in 571 cases, cardiopulmonary resuscitation was performed before paramedic arrival in 512 (25.2%) cases, and a shockable rhythm was observed in 269 (13.2%). Blood pH from initial blood gas analysis remained an independent predictor of neurological outcome after multivariate regression.Blood pH at early stages of ALS was an independent prognostic factor of post-OHCA neurological outcome. Blood gas analysis on arrival at the ED may provide additional information about the prognosis of patients with OHCA.     

Central nervous system involvement in patients with mantle cell lymphoma

 In small cell lymphomas, central nervous system (CNS) involvement has been considered to be very rare. Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin's lymphomas consisting of small or intermediate lymphatic B-cells. It has a poorer prognosis than the other small cell lymphomas. Only a few MCL patients with CNS involvement have been reported in the literature to date. We analyzed retrospectively the incidence, clinical characteristics, and outcome of CNS involvement in 94 patients with confirmed MCL treated at one center from 1980 to 1997. Four of the 94 patients (4%) developed CNS lymphoma during the median follow-up of 51 months. The diagnosis was based on clinical, cytological and radiological findings. CNS involvement appeared at 4.6, 56, 66, or 86 months from the diagnosis of MCL. All patients had neurological symptoms and a leukemic disease; two cases were seen with a blastoid morphology. Malignant lymphatic cells were detected in spinal fluid in all cases and parenchymal infiltrations in brain in two. All patients were treated with intrathecal chemotherapy, without response. Survival time after diagnosis of CNS lymphoma ranged from 18 to 55 days. At diagnosis, no adverse prognostic factors predictive of CNS lymphoma were found. CNS involvement was associated with a progressive leukemic disease as a late event or a blastoid transformation. The prognosis of MCL patients with CNS involvement is poor. Received: July 30, 1998 / Accepted: November 12, 1998     

The effect of recanalization on long‐term neurological outcome after cerebral venous thrombosis

Essentials

• The role of cerebral venous thrombosis (CVT) recanalization on neurologic outcome is still debated.
• We studied a large cohort of 508 CVT patients with 419 patient years of radiological follow‐up.
• Recanalization rate is high during the first months after CVT and neurologic outcome is favorable.
• High recanalization grade of CVT independently predicts good neurological outcome.

Summary

Background

Studies with limited sample size and with discordant results described the recanalization time‐course of cerebral venous thrombosis (CVT). The neurological outcome after a first episode of CVT is good, but the role of recanalization on neurological dependence is still debated.

Objectives

The aim of the study is to assess the recanalization rate after cerebral venous thrombosis (CVT) and its prognostic role in long‐term neurological outcome.

Patients/Methods

In a retrospective observational multicenter cohort study, patients with an acute first episode of CVT with at least one available imaging test during follow‐up were enrolled. Patency status of the vessels was categorized as complete, partial or not recanalized. Neurological outcome was defined using the modified Rankin scale (mRS) as good (mRS = 0–1) or poor (mRS = 2–6).

Results

Five‐hundred and eight patients (median [IQR] age, 39 [28.5–49] years; 26% male) were included. Complete or partial recanalization was not differently represented in patients undergoing scans at different periods of time (from 28‐day to 3 month‐period up to a 1–3 year‐period). mRS at the time of follow‐up imaging was available in 483 patients; 92.8% of them had a mRS of 0‐1. CVT recanalization (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.59–4.13) was positively associated, whereas cancer (OR, 0.29; 95% CI, 0.09–0.88), and personal history of venous thromboembolism (VTE) (OR, 0.36; 95% CI, 0.14–0.92) were negatively associated as independent predictors of favorable (mRS = 0–1) outcome at follow‐up.

Conclusions

Most patients with a first CVT had complete or partial recanalization at follow‐up. Recanalization was independently associated with a favorable neurological outcome.