BACKGROUND: There is little literature on the paraneoplastic value of the absence of long-lasting morning stiffness (MS) at the time of diagnosis of polymyalgia rheumatica (PMR). We investigated whether and to what extent this finding was related to the probability of diagnosing a neoplasia.
METHODS: This was an observational, retrospective, single-center cohort study. We enrolled all patients consecutively referred to our rheumatologic outpatient clinic between January 2015 and December 2020, who could be classified as PMR according to 2012 EULAR/ACR criteria. In particular, we assessed all patients scoring a minimum of five points with a combination of clinical and ultrasound (US) criteria. The exclusion criteria were as follows: (a) follow-up duration RESULTS: 143 patients (108 women; median age: 71.5 years) were enrolled, and 35 of them did not have long-standing MS at the time of PMR diagnosis. In 10 patients (6.9%), a neoplasia was diagnosed in the first 6 months of follow-ups; among these, 7 did not have long-lasting MS. Among the remaining 133 PMR patients without subsequent malignancy, 28 did not have long-lasting MS. The odds of cancer were 0.114 (C.I. 95% 0.028, 0.471). Long-lasting MS was inversely associated with the development of neoplasias. In all eight PMR patients diagnosed with solid cancers during follow-ups, the removal of the neoplastic mass led to a fast disappearance of clinical, ultrasound and laboratory findings, thus supporting the diagnosis of paraneoplastic PMR. Finally, a positive response to glucocorticoids (GCs) was present in 100% of the 28 PMR patients without long-lasting MS at the time of diagnosis and without neoplasia during their follow-ups. On the contrary, a positive response to GCs was present in 71% of PMR patients without long-lasting MS and neoplasias during follow-up. Among the variables we assessed, a positive response to GCs was the only one that was statistically significant (p < 0.0001). These data suggested that an inadequate response to GCs in PMR patients without long-lasting MS at the time of diagnosis should strengthen investigations to rule out neoplasias.
CONCLUSIONS: The absence of long-standing MS at the time of diagnosis can be a paraneoplastic warning in patients classified as PMR. A thorough investigation is therefore needed in this subset of patients to rule out neoplasia, before diagnosing an idiopathic PMR and starting treatment with GCs.

UNASSIGNED: It is unclear whether Guillain-Barré syndrome (GBS) can be a marker of a paraneoplastic syndrome. We examined whether GBS is associated with cancer and whether the prognosis of GBS patients with cancer differs from that of other cancer patients.
UNASSIGNED: We conducted a population-based cohort study of patients diagnosed with GBS between 1978 and 2017 using Danish registry-data. Main outcome measures were cancer incidence and mortality after cancer diagnosis. We calculated absolute risks of a cancer diagnosis, treating death as competing risk, and standardized incidence ratios (SIRs) as measures of relative risk. We matched each GBS cancer patient with up to 10 cancer patients without a GBS diagnosis and examined the six-month survival after cancer diagnosis using Cox regression analysis.
UNASSIGNED: We identified 7897 patients (58% male, median age 57 years) with GBS. During a median follow-up of 9.5 years, the one-year risk of cancer was 2.7% (95% confidence interval (CI), 2.4-3.1). The SIR was increased throughout follow-up, but most noticeably during the first year after diagnosis (SIR: 3.35, 2.92-3.83). SIRs were particularly elevated for hematologic cancers (SIR: 8.67, 6.49-11.34), smoking-related cancers (SIR: 3.57, 2.81-4.47), and cancers of neurological origin (SIR: 8.60, 5.01-13.77). Lung cancer was the main contributor to the overall excess risk, which persisted after 36 months of follow-up (SIR: 1.17, 1.09-1.25). The mortality rate ratio comparing patients diagnosed with any cancer within one year of their GBS diagnosis and matched GBS-free cancer cohort members was 1.56 (95% CI, 1.27-1.90).
UNASSIGNED: GBS patients had a three-fold increased risk of cancer diagnosis in the first year of follow-up. The absolute cancer risk was almost 3.0%. A GBS diagnosis was an adverse prognostic marker for survival following cancer diagnosis. Clinicians should consider occult cancer in patients hospitalized with GBS.

The idiopathic inflammatory myopathies (IIM) are a group of heterogeneous systemic diseases which include as main subtypes: polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM). The key feature of IIMs is the muscle weakness, accompanied by a characteristic skin rash in DM patients. The overall risk for malignancy in IIM is higher compared to the age-and sex-matched general population. Most epidemiologic studies have included only PM and DM patients and reported consistently higher rates of malignancy in DM. Most common types of cancer in DM are adenocarcinoma of the lung, ovary or gastrointestinal tract, melanoma and non-Hodgkins lymphoma. The highest risk for malignancy is seen in the first year after DM diagnosis. Multiple disease features have been linked to the development of cancer in DM. These include: older age, male sex, skin necrosis, Gottron sign, heliotrope rash, dysphagia, low complement C4, lymphocytosis, poor response to corticosteroids and rapid disease progression. Our study included 23 patients with DM, divided into two groups based on the association of malignancy, in order to compare clinical and demographic features, laboratory markers and analyze characteristic of cancer development.

Patients with inflammatory myopathies (IM) are known to have an increased risk of developing malignancies. Autoimmune and inflammatory diseases occur in up to 25% of patients with myelodysplastic syndrome (MDS). This study aimed to describe the rare association between IM and MDS.
We report here the main characteristics, treatment, and outcome of 21 patients (11 national cases and 10 additional cases from a literature review) with IM associated to MDS.
Median age of patients at IM diagnosis was 66 years (range 26 - 78). Diagnosis of the two conditions were concomitant in most patients (n=14/21) whereas MDS diagnosis preceded IM diagnosis in 5 patients. Different types of IM were observed but dermatomyositis was the most frequent (59%). Compared to IM without MDS (IM/MDS-), patients with MDS (IM/MDS+) were older (median 66 vs 55, p=0.3), more frequently male (sex ratio M/F 1.125 vs 0.41, p=0.14) and positive for anti-TIF1γ (24% vs 4%, p=0.0039). Antisynthetase syndrome was never observed among IM/MDS+ patients (0% vs 28%, p=0.01). MDS WHO type was not univocal, but the prognostic score was of low risk in almost all cases. IM was usually steroid sensitive (82% of patients) but often steroid dependent (56% of patients). Overall survival of IM patients with MDS was worse compared to patients with IM without MDS (p=0.0002).
IM associated with MDS are mainly represented by dermatomyositis and/or anti-TIF1γ autoantibodies. Antisynthetase syndrome has not been described in association with MDS. Despite low-risk MDS, overall survival of IM patients with MDS is worse than IM patients without MDS.

暂无摘要。

BACKGROUND: Flow cytometric cerebrospinal fluid (CSF) lymphocyte subset analysis has improved the diagnosis of neuroinflammation and identified multiple markers of inflammation in opsoclonus-myoclonus syndrome (OMS). The aim of this exploratory, retrospective study was to analyze the effect of immunotherapy on these markers to determine which agents are disease modifying.
METHODS: Cross-sectional immunological observations were made in an IRB-approved case-control study, and patients were treated empirically. Ten different CSF lymphocyte subpopulations from 18 children with persistent OMS had been measured by flow cytometry before and after clinical treatment with cyclophosphamide/ACTH/IVIG combination (n = 7) or ACTH/IVIG alone (n = 11). Clinical severity of OMS was scored from videotapes by a blinded observer using the OMS Evaluation Scale.
RESULTS: Only cyclophosphamide combination therapy (mean dose 26 ± 3 mg/kg or 922 ± 176 mg/m2 x 6 cycles) significantly decreased the percentage of CSF B cells. The mean reduction was 65%, with CSF B cell frequency normalized at 7-8 months in 70%. Other abnormalities of the CSF immunophenotype, such as the low CD4/CD8 T cell ratio, persisted, and there were no therapeutic changes in T cell activation/maturation markers. Effects on relative and absolute size of PBMC subsets were similar. Clinical improvement was 70% and 55% in respective treatment groups. The relapse rates of the two groups did not significantly differ.
CONCLUSIONS: The main effect of cyclophosphamide combination therapy on neuroinflammation in OMS was moderate reduction in CSF B cell expansion. Though exploratory, it may provide a steroid sparer option in partially-responsive OMS.

Studies of cerebrospinal fluid (CSF) γδ T cells in children are limited, due especially to the lack of control data. In adults, gamma/delta T cells (TCR-γδ) residing in the intrathecal space are sometimes involved in neuroinflammation. To evaluate the possible role of γδ T cells in paediatric neuroinflammation, we immunophenotyped cerebrospinal fluid (CSF) and blood lymphocytes using flow cytometry in a case-control study of 100 children with non-inflammatory neurological disorders (NIND), 312 with opsoclonus-myoclonus (OMS) and 23 with other inflammatory neurological disorders (OIND). In NIND, the negative correlation between CSF γδ T cell frequency and patient age was striking: median frequency of 27% in infants and 3·3% in teens. Interindividual variations were largest in the youngest. There was no gender effect. In all OMS, after correcting for age, only a small effect of OMS severity remained. Measurement of markers for γδ T cell activation [human leucocyte antigen D-related (HLA-DR)], maturation (CD45RA, CD45RO) or intracellular cytokine staining [interleukin (IL)-4, interferon (IFN)-γ] failed to discriminate OMS and NIND groups. Of seven OMS immunotherapies/combinations, none altered the frequency of total CSF γδ T cells or subsets significantly. In OIND, the CSF γδ T cell frequency was < 10% for single samples of other paraneoplastic disorders [anti-neuronal nuclear antibody (ANNA)-1, PCA-1, teratoma-associated syndrome], cerebellar ataxia (post-infectious, ataxia-telangiectasia), acute disseminated encephalomyelitis, neuroborreliosis and encephalitis. This study provides new insights into CSF γδ T cells in the paediatric population. Although their role in CSF remains elusive, the negative age correlation, resistance to immunotherapy and our age cut-off references for NIND are important findings for the design of future paediatric studies.

Pediatric-onset opsoclonus-myoclonus syndrome (OMS) is a devastating neuroinflammatory, often paraneoplastic, disorder. The objective was to characterize demographic, clinical, and immunologic aspects in the largest cohort reported to date. Cross-sectional data were collected on 389 children in an IRB-approved, observational study at the National Pediatric Myoclonus Center. Non-parametric statistical analysis was used. OMS manifested in major racial/ethnic groups, paralleling US population densities. Median onset age was 1.5 years (1.2-2 interquartile range), inclusive of infants (14%), toddlers (61%), and youngsters (25%). The higher female sex ratio of 1.2 was already evident in toddlers. Time to diagnosis was 1.2 months (0.7-3); to treatment, 1.4 months (0.4-4). Irritability/crying dominated prodromal symptomatology (60%); overt infections in <35%. Acute cerebellar ataxia was the most common misdiagnosis; staggering appeared earliest among 10 ranked neurological signs (P < 0.0001). Some untreated youngsters had no words (33%) or sentences (73%). Remote neuroblastic tumors were detected in 50%; resection was insufficient OMS treatment (58%). Age at tumor diagnosis related to tumor type (P = 0.004) and stage (P = 0.002). A novel observation was that paraneoplastic frequency varied with patient age-not a mere function of the frequency of neuroblastoma, which was lowest in the first 6 months of life, when that of neuroblastoma without OMS was highest. The cerebrospinal fluid (CSF) leukocyte count was minimally elevated in 14% (≤11/mm3) with normal differential, and commercially screened serum autoantibodies were negative, but CSF oligoclonal bands (OCB) and B cells frequency were positive (58 and 93%). Analysis of patients presenting on immunotherapy revealed a shift in physician treatment practice patterns from monotherapy toward multi-agent immunotherapy (P < 0.001); the number of agents/sequences varied. In sum, a major clinical challenge is to increase OMS recognition, prevent initial misdiagnosis, and shorten time to diagnosis/treatment. The index of suspicion for an underlying tumor must remain high despite symptoms of infection. The disparity in onset age of neuroblastoma frequency with that of neuroblastoma with OMS warrants further studies of potential host/tumor factors. OMS neuroinflammation is best diagnosed by CSF OCB and B cells, not by routine CSF or commercial antibody studies.

Thymomas are one of the most common tumors of the cranial mediastinum in dogs; however there is limited information available on the use of radiation therapy for treating this neoplasm. Objectives of the current retrospective observational study were to describe outcomes and side effects of a hypofractionated radiation therapy protocol in a group of dogs with confirmed thymoma. A total of eight dogs were included. To generate individualized treatment plans, we designed the planning target volume according to the limits on mean lung dose and the percentage of the total lung volume exceeding 20 Gy (V20). The total administered dose was 48-49 Gy, with one fraction per week for a total of six to seven fractions. After therapy, two dogs achieved complete responses, two achieved partial responses, and the disease remained stable in two. Two dogs died during the radiation therapy protocol and were not classified. The median mean lung dose and V20 were 6.0 Gy (range: 3.1-15.0 Gy) and 12.4% (range: 2.3-27.5%), respectively. The overall response rate was 50.0%, and the median time to response following treatment initiation was 22 days (range: 14-115 days). Acute and late side effects were common in the skin and/or lung and were self-limiting or asymptomatic. The median survival time was not reached (range: 8-1128 days) and the 1 year survival rate was 75.0%. Hypofractionated radiation therapy was well tolerated in this sample of dogs with thymoma and may be considered when owners decline surgical treatment or the tumor is deemed unresectable.

BACKGROUND: Acute ischemia of the upper limbs is rare in comparison with ischemia of the lower limbs. The origins of this condition are varied.
OBJECTIVE: We retrospectively analyzed cases of acute finger ischemia (Raynaud\'s phenomena was excluded) in a dermatology department between 2008 and 2013 in order to evaluate the etiology and management of this phenomenon.
RESULTS: Thirteen cases of finger ischemia were reported. The mean age was 54 years. Active smoking was noted in 11 cases. Ischemia was acute in 9 cases and subacute in 4 cases. The location was unilateral in 10 cases and bilateral in 2. Etiologies were: dysplasia of the palmar arch, antiphospholipid antibody syndrome, frostbite, distal arteritis linked to smoking, paraneoplastic arteritis, Buerger\'s disease, polyarteritis nodosa, stenosis of the subclavian artery, and 3 cases of embolic origin (ulnar, cardiac, and paraneoplastic aneurysm). In the acute phase, antiplatelets were given in 6 cases, anticoagulants in 10 cases and ilomedin in 6 cases. Sympathectomy was performed in 1 case and amputation in 2 cases.
CONCLUSIONS: This study illustrates the diversity of etiologies of finger ischemia. The etiological test battery should be broad and include immunological and thrombophilia tests, arterial and cardiac investigations, cervical radiography and CT scan (screening for cancer). Close collaboration between dermatologists, hematologists, vascular surgeons and radiologists is essential for the management of these patients.